Meningococcus

Cesk Epidemiol Mikrobiol Imunol, 1993 Dec, 42(4), 165 - 71
{Increased incidence of invasive meningococcal disease caused by C:2a:P1.2 meningococci in certain regions of the Czech Republic}; Krizova-Kuzemenska P et al.; In the first half of 1993 an increased incidence of invasive meningococcal disease was recorded in the Czech Republic . In the CR a total of 59 cases were revealed, incl . 10 fatal ones . This high lethality (16.9%) is markedly higher than that from 036 recorded in this country during previous years . The highest incidence and death rate was recorded in the North Moravian region and in the age group from 15-19 years . Based on active surveillance of the invasive meningococcal disease by epidemiologists, microbiologists and infectiologists of the entire Czech Republic, it may be concluded that the sulphonamide sensitive strain Neisseria meningitidis C:2a:P1.2 caused in the North Moravian region a local epidemic of invasive meningococcal disease in the army and civilian population . In other regions of the CR the epidemiological situation in the first half of 1993 did not differ from the previous period: sporadic incidence of meningococcal disease, prevalence of the serological group B, highest incidence in the youngest age groups . The meningococcus C:2a:P1.2 was not detected in the CR before 1993 . This uncommon epidemiological situation was resolved by immunization, aimed from the antigenic aspect and with regard to age and locality.

Zhonghua Liu Xing Bing Xue Za Zhi, 1993 Dec, 14(6), 366 - 70
{Application of SP-RIA in the antibody surveillance and serologic diagnosis of epidemic cerebrospinal meningitis}; Chen X; This paper reports the effectiveness of SP-RIA in the antibody surveillance on population, the observation of immune persistence after vaccination with Group A Neisseria meningococcal capsular polysaccharide vaccine, as well as its use in the serological diagnosis of Neisseria meningitis . In comparison with other assays used presently, SP-RIA might be better and more sensitive for quantitative assay of the antibody . The results showed the practical value of SP-RIA in the study of epidemiology and serology of epidemic cerebrospinal meningitis.

Acta Paediatr, 1993 Dec, 82(12), 1053 - 6
Prognostic factors in meningococcal disease and a new scoring system; Tuysuz B et al.; One-hundred-and-forty patients diagnosed as having meningococcal disease have been investigated retrospectively with respect to prognostic factors . The overall mortality was 8.6%, the mortality rate of the infants under 6 months of age being higher than that of the other groups . In cases where there was no meningitis or leucocytosis, the presence of hypotension, disturbed consciousness and diffuse petechiae increased the mortality rate significantly . High fever did not have any effect on mortality . We propose a new practical and reliable scoring system for meningococcal disease for determining the influence of prognostic factors on mortality.

J Public Health Med, 1993 Dec, 15(4), 315 - 9
Reliability of notification data for childhood bacterial meningitis; Fortnum H et al.; This study reports the notification rates over ten years (1980-1989) for 232 children with documented bacterial meningitis in Nottingham District Health Authority . The average notification rate was approximately 50 per cent of known cases . It was higher for meningococcal infections (57/84, 68 per cent) than for any other type (45/148, 30 per cent), and lower in neonates (1/29, 3 per cent) than in any other age group (101/203, 50 per cent) . The results show that the notification rates required to be adjusted during the decade of the study (1980-1989) . The achievement of better notification rates may now be more feasible since implementation of the recommendations of the Committee of Inquiry into the Future Development of the Public Health Function for the control of communicable diseases . This paper provides a baseline upon which to measure the impact of such changes.

Ceylon Med J, 1993 Dec, 38(4), 170 - 1
Improving child survival through immunisation; Lamabadusuriya SP; PIP: UNICEF decided to achieve the 1977 World Health Organization objective Health For All By The Year 2000 through primary health care, utilizing growth monitoring, oral rehydration therapy, breast-feeding, immunization, family planning, and education of women . Since the 1960s BCG (bacillus Calmette-Guerin) vaccination, DPT (diphtheria, pertussis, tetanus) and OPV (oral polio vaccine) have been available in Sri Lanka . The expanded program of immunization has almost eliminated diphtheria, pertussis, neonatal tetanus, and poliomyelitis . Tuberculous meningitis, bone and joint tuberculosis, measles, and miliary tuberculosis have become very rare . Among other vaccine-preventable diseases, mumps is the commonest cause of aseptic meningitis and viral encephalitis in children . Maternal rubella in the first trimester causes abortion or gross teratogenic effects including congenital heart disease . Safe vaccines may be used to prevent mumps and rubella . In recent years there has been a resurgence of measles in North America among school children, and presently a 2nd dose of vaccine is recommended for children . Japanese B encephalitis has a mortality rate of over 30% and half the survivors have residual brain damage . The Ministry of Health has immunized susceptible children in some of the prevalent areas . This vaccine also gives partial protection against dengue hemorrhagic fever . In Hong Kong, Singapore, and Taiwan hepatitis B vaccine is part of the national immunization schedule because of the common occurrence of primary hepatoma of the liver . At present this vaccine is recommended for health workers in Sri Lanka . Meningococcal meningitis occurs in some Middle East countries such as Saudi Arabia, thus Haj pilgrims are advised to be vaccinated against it before the pilgrimage . In Sri Lanka beta-thalassemia major is prevalent, and as most of these patients are subjected to splenectomy, pneumococcal vaccine should be given to them . Currently research work is being carried out for development of vaccines against rotavirus, streptococcal, and hepatitis A infection .

Ir J Med Sci, 1993 Dec, 162(12), 495 - 6
Endophthalmitis as a presentation of meningococcal septicaemia; Abousaesha F et al.; Meningococcal infections can present in diverse clinical forms ranging from fulminant, occult, chronic meningococcaemia to meningitis . Rare presentations may include conjunctivitis, sinusitis, pneumonia, pericarditis, arthritis, and osteomyelitis . We present a very unusual case of meningococcaemia presented as an endophthalmitis.

Bull Acad Natl Med, 1993 Dec, 177(9), 1539 - 45; discussion 1545-8
{Realities of immunizations in the armed forces: necessity of continued adaptation of vaccinations against cerebrospinal meningitis, typhoid and hepatitis A}; Meyran M et al.; The history of military medicine has always been closely linked with that of vaccinations . Doctors of Armed Forces, doctors of collectivities, have contributed to vaccination progresses in large amounts . But evolutions are often rapid here: epidemiological modifications, improvements in the existing vaccines or creation of new vaccines, diversification of military specificities . Three recent modifications in the vaccination schedule of the Armed Forces show this necessary adaptation: Systematization of the meningococcal A + C vaccination during the incorporation, because of the modification of the disease's epidemiological profile: increase of the frequency in serogroup C with a mortality increase (9 cases of death out of 10 observed between 1991 and 1992) . Cancellation of antityphoid vaccination for recruits serving in home country . Indeed the disease has become rare in France, and this is often due to imported cases (3 cases in the Armed Forces in 1992) . Introduction in 1994 of vaccination against viral hepatitis A, systematic under the age of 25 years and after a serological selection above for servicemen having to serve overseas or for outside operations . These 3 examples show the necessity to have updated and adaptable vaccination schedules.

Mol Microbiol, 1993 Dec, 10(5), 1013 - 28
Pilus-facilitated adherence of Neisseria meningitidis to human epithelial and endothelial cells: modulation of adherence phenotype occurs concurrently with changes in primary amino acid sequence and the glycosylation status of pilin; Virji M et al.; Adherence of capsulate Neisseria meningitidis to endothelial and epithelial cells is facilitated in variants that express pili . Whereas piliated variants of N . meningitidis strain C311 adhered to endothelial cells in large numbers (> 150 bacteria/cell), derivatives containing specific mutations that disrupt pilE encoding the pilin subunit were both non-piliated and failed to adhere to endothelial cells (< 1 bacterium/cell) . In addition, meningococcal pili recognized human endothelial and epithelial cells but not cells originating from other animals . Variants of strain C311 were obtained that expressed pilins of reduced apparent M(r) and exhibited a marked increase in adherence to epithelial cells . Structural analysis of pilins from two hyper-adherent variants and the parent strain were carried out by DNA sequencing of their pilE genes . Deduced molecular weights of pilins were considerably lower compared with their apparent M(r) values on SDS-PAGE . Hyper-adherent pilins shared unique changes in sequence including substitution of Asn-113 for Asp-113 and changes from Asn-Asp-Thr-Asp to Thr-Asp-Ala-Lys at residues 127-130 in mature pilin . Asn residues 113 and 127 of 'parental' pilin both form part of the typical eukaryotic N-glycosylation motif Asn-X-Ser/Thr and could potentially be glycosylated post-translationally . The presence of carbohydrate on pilin was demonstrated and when pilins were deglycosylated, their migration on SDS-PAGE increased, supporting the notion that variable glycosylation accounts for discrepancies in apparent and deduced molecular weights . Functionally distinct pilins produced by two fully piliated variants of a second strain (MC58) differed only in that the putative glycosylation motif Asn-60-Asn-61-Thr-62 in an adherent variant was replaced with Asp-60-Asn-61-Ser-62 in a non-adherent variant . Fully adherent backswitchers obtained from the non-adherent variant always regained Asn-60 but retained Ser-62 . We propose, therefore, that functional variations in N . meningitidis pili may be modulated in large part by primary amino acid sequence changes that ablate or create N-linked glycosylation sites on the pilin subunit.

J Immunol, 1993 Nov 1, 151(9), 4782 - 9
Protective immunity in baboons vaccinated with a recombinant antigen or radiation-attenuated cercariae of Schistosoma mansoni is antibody-dependent; Soisson LA et al.; Mice vaccinated with radiation-attenuated cercariae of Schistosoma mansoni exhibit high levels of resistance to challenge infection . We have previously shown that sera from these mice recognize polypeptides that are expressed on the surface of newly transformed schistosomula . We have cloned and sequenced a cDNA that encodes a 62-kDa portion of one of these polypeptides . Vaccination of mice with this 62-kDa polypeptide (designated rlrV-5) elicits high antibody titers and significant resistance to challenge infection . We report here the results of a vaccination trial in baboons with the rlrV-5 or radiation-attenuated cercariae . rlrV-5 was presented either in the form of protein micelles or complexed with the outer membrane protein of meningococcus to form proteosomes . The level of protection achieved in these groups ranged from 0 to 54%, with a mean of 27.7% . In baboons exposed to radiation-attenuated cercariae the level of protection was very high, with a mean of 84% . The resistance observed after vaccination with rlrV-5 or radiation-attenuated cercariae was reflected in the overall histopathology . Vaccination of baboons with rlrV-5 or radiation-attenuated cercariae elicited an antibody response against epitopes exposed on the surface of newly transformed schistosomula . In the case of baboons vaccinated with radiation-attenuated cercariae, this response was not limited to epitopes encompassed by rlrV-5 . Analysis of individual baboon sera by ELISA demonstrated that there was a direct correlation between the anti-rlrV-5 titer and resistance to challenge worm burden, suggesting that the immunoprotective mechanism is antibody-dependent.

Infect Immun, 1993 Nov, 61(11), 4734 - 42
Humoral immune response to the class 3 outer membrane protein during the course of meningococcal disease; Guttormsen HK et al.; We have determined the amounts of specific anti-class 3 outer membrane protein antibodies of immunoglobulin G (IgG), IgM, and IgA isotypes in patient sera during the course of meningococcal disease by using purified class 3 protein as the sensitizing antigen in an enzyme-linked immunosorbent assay . The class 3 protein was obtained from a variant of strain 44/76 (B:15:P1.7,16) lacking class 1 and class 4 outer membrane proteins . Serum samples from 25 patients with systemic meningococcal disease caused by organisms of various serotypes were collected during the course of disease . Seven of these patients had been immunized with a meningococcal outer membrane vesicle vaccine made from strain 44/76 prior to disease . An increase in specific anti-class 3 (type 15) outer membrane protein IgG antibodies was demonstrated in 22 of 25 patients (88%), regardless of the serotype of the infecting strain . This indicates that the specific anti-class 3 antibodies were reacting in part with epitopes not determined by the monoclonal antibodies used for serotyping . A considerable heterogeneity in antibody levels and IgG subclass response was seen . Most patients had low levels of anti-class 3 antibodies during the acute illness, with antibodies peaking during the second week of disease and returning to near baseline in sera collected 6 to 12 months after the onset of the disease . The majority of the specific anti-class 3 IgG antibodies were shown to bind to surface-exposed epitopes on the whole bacteria and to belong to IgG1 and IgG3 . The highest anti-class 3 IgG peak levels were seen in patients infected with strains of the homologous serotype after vaccination with the meningococcal outer membrane vesicle vaccine, suggesting an anamnestic response . However, these patients were not protected from meningococcal disease after immunization.

Infect Immun, 1993 Nov, 61(11), 4724 - 33
Molecular characterization of the 98-kilodalton iron-regulated outer membrane protein of Neisseria meningitidis; Pettersson A et al.; When grown under iron limitation, Neisseria meningitidis expresses several additional outer membrane proteins (OMPs), which were studied to assess their vaccine potential . Two monoclonal antibodies were obtained against a 98-kDa OMP of strain 2996 (B:2b:P1.2) . Cross-reactivity studies revealed that the two antibodies reacted with 44 and 42 of 74 meningococcal strains, respectively . The antibodies did not block the binding of transferrin or lactoferrin to intact cells . The structural gene for the protein, tentatively designated iroA, was isolated and sequenced . Computer analysis revealed homology to the ferric siderophore receptors in the outer membrane of Escherichia coli and to gonococcal transferrin-binding protein 1 (TbpA) . The high degree of cross-reactivity and the results of Southern blot analyses, which showed that the iroA gene is also present in strains that did not react with the monoclonal antibodies, suggest that the 98-kDa OMP is well conserved among meningococci and that it is a suitable vaccine candidate . However, the antibodies were not bactericidal in an in vitro assay with human complement.

Pediatr Allergy Immunol, 1993 Nov, 4(4), 214 - 6
Chronic meningococcemia in a child with a deficiency of the sixth component of complement; Fasano MB et al.; Chronic meningococcemia represents an uncommon manifestation of meningococcal disease . Microbial and host factors which may predispose to this form of meningococcal disease are not understood . Although acute meningococcal disease is frequently found in patients with terminal complement deficiencies, the relationship of chronic meningococcemia to complement deficiencies is unclear . We present a case report and a review of the literature describing chronic meningococcemia in association with deficiencies of the complement system . A total of eight cases were identified, all of whom were male . Six of the eight patients were children and two of the eight had a previous history of meningococcal disease . This case report, in conjunction with the previously reported cases, suggests an association between complement deficiencies and chronic meningococcemia.

Neurologia, 1993 Nov, 8(9), 283 - 7
{The validity of the system of obligatory disease declaration for the epidemiologic surveillance of meningococcal meningitis}; Ara JR et al.; In Spain meningococcic meningitis is a disease of obligatory declaration which is declared under the name of "Meningococcic infection" . In this section other process are also included with the declaration being made under suspicion, with no knowledge of the degree of fulfillment and the significance of the official data . To know this the clinical history of meningitis patients of all the hospitals in Aragon from January 1985 to December 1988 were reviewed comparing the results with those from the system of obligatory disease declaration . The degree of fulfillment for meningococcic meningitis was 90% with the annual rates of incidence of meningococcic meningitis being 1.11 to 2.13 fold higher, according to hospitalary data, higher than the rates of the obligatory disease declaration system.

Medicine (Baltimore), 1993 Nov, 72(6), 374 - 92
Meningococcal disease in patients with late complement component deficiency: studies in the U.S.S.R; Platonov AE et al.; The purpose of this study was to examine the occurrence of late complement component deficiency (LCCD) states in the USSR . Thirty deficient individuals were detected: 27 with C8 beta and 3 with C7 deficiency . Among individuals with a first episode of meningococcal infection, about 1% had LCCD, whereas among patients with recurrent bacterial meningitis the prevalence of LCCD rose to approximately 50% . This corresponds to a prevalence for LCCD of approximately 12 per 100,000 in the general population . The individuals with LCCD identified in this study experienced about 77 episodes of meningococcal disease and acute bacterial meningitis . Mathematical analysis of the morbidity from meningococcal disease in individuals with LCCD demonstrated that the probability of disease did not change with the age of the patient and was not affected by prior episodes of infection . This finding suggest that in contrast to the situation in the general population, prior infection fails to protect the deficient individual from recurrent disease . In comparison to complement-sufficient persons, the course of disease in individuals with LCCD is less severe, as shown by a reduction in the number of episodes of endotoxic shock and mortality as well as their more rapid recovery . These findings suggest that exuberant complement activation and concomitant formation of membrane attack complexes during meningococcal infection in complement-sufficient patients plays an important role in the activation and injury of peripheral blood cells and endothelial cells during endotoxic shock.

Crit Care Med, 1993 Nov, 21(11), 1699 - 705
Fatal course in severe meningococcemia: clinical predictors and effect of transfusion therapy; Busund R et al.; OBJECTIVE: To investigate whether the administration of fresh-frozen plasma to patients with systemic meningococcal disease is associated with an increased mortality rate compared with the administration of plasma substitutes . DESIGN: Seventeen-year case-control study . SETTING: Intensive care units and departments of internal medicine and pediatrics of one university hospital and one local hospital . PATIENTS: A total of 336 patients with culture-proven meningococcemia or symptoms characteristic of meningococcemia who were admitted to two hospitals in northern Norway between 1974 and 1991 . MEASUREMENTS AND MAIN RESULTS: High-risk patients were selected on the basis of two different scoring systems (Niklasson's score and clinical score) and classified according to the type of intravenous fluid regimen (fresh-frozen plasma, blood, or colloids) . For comparison between groups, analysis of variance and chi-square tests were used . Assessments of adjusted effects on mortality rate were done by multiple logistic regression . Administration of blood or plasma was significantly associated with a fatal course, both in the total patient population (p < .01) and in the high-risk group (p = .02), while using colloids alone was negatively associated with death, although not reaching statistical significance . A significantly lower mortality rate was found in one of the hospitals where colloids were used instead of plasma or blood in the last part of the period studied (p < .05) . CONCLUSION: The results support our hypothesis that the use of fresh-frozen plasma may negatively influence outcome in systemic meningococcal disease.

Surg Neurol, 1993 Nov, 40(5), 378 - 82
Meningitis following fractures of the paranasal sinuses: accurate, non-invasive localization of the dural defect by direct coronal computed tomography; Farrell VJ et al.; A consecutive series of 30 patients admitted with non-meningococcal meningitis is presented . In all there was a history of preceding head injury . All 30 patients were investigated by direct coronal computed tomography (CT) scan to determine whether or not a site of fracture into a paranasal air sinus could be demonstrated . We postulated that such a fracture would correspond to the site of a dural tear . Direct coronal CT demonstrated a fracture in all patients, and this corresponded to the site of a dural tear at operation in every case in which an operation was carried out (28 out of the 30 patients) . We propose that this method of investigation is superior to other techniques that have been, or are currently, employed in this clinical situation.

Haematologica, 1993 Nov-Dec, 78(6 Suppl 2), 73 - 7
Fulminant sepsis in adults splenectomized for Hodgkin's disease; Frezzato M et al.; BACKGROUND AND METHODS . Laparotomy with splenectomy still remains important for staging Hodgkin's disease (HD) . The risk of fulminant sepsis (FS) after splenectomy is well known, but the incidence of FS in splenectomized HD adult patients has not been accurately assessed . In this study we have tried to assess this risk and its duration and to evaluate the role of HD "per se" in causing FS . RESULTS . Six cases of FS were traced in a group of 226 splenectomized adults, with a crude incidence of 2.65% . Age at the time of the event ranged from 23 to 41 years and time after splenectomy from 46 to 98 months . Four patients were disease-free when sepsis occurred . In 4 cases the causative agent was isolated (3 Streptococcus Pneumoniae, 1 Streptococcus alpha Haemolyticus) . The mortality rate was 66%, while net probability of death (life table) at 10 years was 2.6% . M/F rate was 0/6 (P = 0.01) . The incidence of FS was 0.33 cases per 100 patient-years (I.C . 95% = 0.12-0.72) . There seems to be no relationship to histological type, clinical stage or age at splenectomy . No case of sepsis occurred in a control group of 281 non-splenectomized HD adults (P = < 0.01), despite the more advanced disease present in these cases on the average . CONCLUSIONS . The frequency of FS, the causative agents, the mortality rate, the duration of risk are similar to those previously reported . Prompt treatment of any febrile disease in HD splenectomized patients and a policy of antipneumococcal (and possibly of anti-meningococcal) vaccination seem advisable.

Mol Microbiol, 1993 Nov, 10(3), 499 - 510
Meningococcal Opa and Opc proteins: their role in colonization and invasion of human epithelial and endothelial cells; Virji M et al.; Neisseria meningitidis (Nm) isolates from disease or during carriage express, on their outer membranes, one or more of a family of closely related proteins designated Opa proteins . In this study, we have examined the potential roles of Nm Opa proteins in bacterial attachment and invasion of endothelial as well as epithelial cells and compared the influence of Opa proteins with that of Opc protein, which has been previously shown to increase bacterial interactions with eukaryotic cells . Several variants expressing different Opa proteins (A, B, D) or Opc were selected from a culture of capsule-deficient non-piliated bacteria of strain C751 . Although the Opa proteins increased bacterial attachment and invasion of endothelial cells, Opc was the most effective protein in increasing bacterial interactions with these cells . In contrast, attachment to several human epithelial cells was facilitated at least as much by OpaB as Opc protein . OpaA was largely without effect whereas OpaD conferred intermediate attachment . OpaB also increased invasion of epithelial cells; more bacteria were internalized by Chang conjunctival cells compared with Hep-2 larynx carcinoma or A549 lung carcinoma cells . Monoclonal antibody reacting with OpaB inhibited bacterial interactions with the host cells . Opa-mediated interactions were also eliminated or significantly reduced in variants expressing capsule or those with sialylated lipopolysaccharide . These data are consistent with the notion that environmental factors controlling capsule and lipopolysaccharide phenotype may modulate bacterial interactions mediated by these OM proteins . In permissive microenvironments, some Opa proteins may be important in bacterial colonization and translocation in addition to Opc . The data also support the notion that Nm Opa may confer tissue tropism.

Microb Pathog, 1993 Nov, 15(5), 359 - 66
Demonstration of lipooligosaccharide immunotype and capsule as virulence factors for Neisseria meningitidis using an infant mouse intranasal infection model; Mackinnon FG et al.; Using an infant mouse intranasal infection model, we have compared the virulence of 17 epidemiologically related isolates of Neisseria meningitidis associated with an outbreak of meningococcal disease in Gloucestershire, UK, and one German isolate . The isolates were all of serotype 15 subtype P1:7, 16 and were identical by restriction fragment length polymorphism analysis, but differed in either (i) whether they were isolated from a case or a carrier, (ii) the presence or absence of group B capsule, or (iii) their lipooligosaccharide (LOS) immunotype . The results indicate that capsule is a major virulence determinant and is required for colonization and hence for invasion . In addition, the LOS L3,7,9 immunotype, when compared to the L1,8,10 immunotype, is a secondary virulence factor which enhances colonization of nasal passages and invasion of the blood stream by both case and carrier isolates . Two case isolates which were unusual in possessing the L1,8,10 immunotype, established invasive infection, but this was associated with a switch to the L3,7,9 immunotype . The results confirm that LOS is a virulence factor for N . meningitidis and that immunotype L3,7,9 is associated with invasive disease.

Ugeskr Laeger, 1993 Oct 25, 155(43), 3456 - 9
{Meningococcal disease 1987-1989 . Outbreak of serogroup B:15:P1.16 in the county of Frederiksborg}; Ege PP et al.; Epidemiological features of an outbreak of group B:15:P1.16 meningococcal disease in Frederiksborg County 1987-1989 were investigated . The study comprised 149 cases notified during the outbreak and the two preceding years . One hundred and fifteen were confirmed by the isolation of Neisseria meningitidis . In 1989 the incidence had increased to 14.1 per 100,000 population . Among group B strains, B:15:P1.16 . accounted for 80% . The overall mortality rate was 10% . Regarding cases due to group B:15:P1.16 strains, a significant time-space clustering was demonstrated, occurring exclusively within the 10-19 year-old group . The prophylactic measures used included administration of rifampicin to household contacts . During the outbreak the proportion of secondary cases was high (six to fifteen percent) . All secondary cases occurred outside the household, indicating that the household had been protected.

Ugeskr Laeger, 1993 Oct 25, 155(43), 3452 - 5
{Purulent meningitis among adults in the county of Frederiksborg . Therapeutic results in the period 1 January 1980--31 December 1990}; Handberg J et al.; A review of 158 cases of bacterial meningitis and meningococcal sepsis in adults is presented . The patients were admitted during a 11-year period, from 1980-1990 . The incidence was 5.5/100,000 adults per year, which is high . The area had epidemics of meningococcal disease in the years 1987 and 1989 . The bacterial agent was meningococci in 40.5%, pneumococci in 21.5% and unknown in 27.2% . The overall lethality was 13.9%, highest (26%) in patients who were infected by pneumococci . The meningococcal relative lethality was 14% . In the period of high meningococcal incidence 1986-1989, we found a relative lethality of 17% . The overall local hospital lethality was 18.3%, which has to be compared with 11.2% among patients primarily admitted to the County hospital . The lethality among patients who underwent emergency transfer from one of the local hospitals to the County hospital was 20%, which is as high as in the group of patients treated locally . Neither of these trends lethality are statistically significant at the level of 5%, tested by chi square tests.

J Bacteriol, 1993 Oct, 175(20), 6382 - 91
Oxidation of D-lactate and L-lactate by Neisseria meningitidis: purification and cloning of meningococcal D-lactate dehydrogenase; Erwin AL et al.; Neisseria meningitidis was found to contain at least two lactate-oxidizing enzymes . One of these was purified 460-fold from spheroplast membranes and found to be specific primarily for D-lactate, with low-affinity activity for L-lactate . The gene for this enzyme (dld) was cloned, and a dld mutant was constructed by insertional inactivation of the gene . The mutant was unable to grow on D-lactate but retained the ability to grow on L-lactate, providing evidence for a second lactate-oxidizing enzyme with specificity for L-lactate . High-affinity L-lactate-oxidizing activity was detected in intact bacteria of both the dld+ and dld mutant strains . This L-lactate-oxidizing activity was also seen in sonicated bacteria but was reduced substantially on detergent solubilization or on preparation of spheroplast membranes.

Neuropediatrics, 1993 Oct, 24(5), 274 - 80
Infantile spasms: infectious disorders; Riikonen R; Infections were considered to be etiological factors in 29 patients (10%) with infantile spasms; congenital CMV (n = 5), congenital or acquired CMV (n = 1), acquired CMV (n = 5), congenital rubella (n = 2), herpes simplex virus (n = 5), enterovirus (n = 1), adenovirus (n = 1), viral encephalitis of unknown agent (n = 3), meningococcus (n = 4), pneumococcus (n = 1) and pertussis (n = 1) . The children with congenital infections had long-lasting tremor and convulsions from birth . Early EEG pattern was characteristic for children with herpes encephalitis but not for other patients . Infantile spasms appeared only some weeks after viral encephalitis . One patient with enterovirus and another with probable adenovirus infection had necrotic changes in their brain CT resembling those of herpes encephalitis . The response to ACTH was poor (38%) compared to the whole series (60%) . The long-term outcome was also poor compared to the whole series; mental retardation in 90%, convulsions in 62%, abnormal EEG in 89% . Four children died during the follow-up of 7 years . Autopsy showed disseminated CMV infection in one patient and chronic CMV infection in another . The outcome of children with infectious etiology appears to be particularly poor . Thus, the prevention and specific diagnosis and treatment are important . Steroid therapy should be avoided in children with a history of herpes virus encephalitis (CMV, herpes simplex) in the past.

Eur J Clin Microbiol Infect Dis, 1993 Oct, 12(10), 766 - 8
Ceftriaxone versus penicillin G in the short-term treatment of meningococcal meningitis in adults; Marhoum el Filali K et al.; Short-term treatment with ceftriaxone 2 g once daily for two days (group 1) was compared to treatment with a standard regimen of penicillin G (group 2) for six days in adults with meningococcal meningitis . Thirty-six patients were allocated in a randomized fashion to a treatment group: 16 to group 1 and 20 to group 2 . The clinical and microbiological results were comparable in the two treatment groups . In both groups cultures of cerebrospinal fluid were sterile after 24 hours . One patient in each group died . In group 1 one case of fulminant meningococcemia and one case of brain abscess required further antibiotic treatment . It is concluded that short-term treatment with ceftriaxone is feasible but patients with severe forms of meningitis would not be eligible for treatment with this regimen, and careful follow-up of the patients receiving ceftriaxone is necessary.

Pediatr Infect Dis J, 1993 Oct, 12(10), 808 - 11
Deafness, complement deficiencies and immunoglobulin status in patients with meningococcal diseases due to uncommon serogroups; Mayatepek E et al.; The prevalence of deafness and complement deficiencies in association with meningococcal disease caused by uncommon serogroups of meningococci was studied in 30 patients (Group A) and 30 controls with Serogroup B disease (Group B) . In Group A 8 patients (26.6%) had hearing impairment in contrast to only 1 patient (3.3%) in Group B (P < 0.01) . Complement deficiency was detected in 8 patients (26.6%) of Group A whereas none of the Group B patients showed a defect in the complement system (P < 0.01) . Association between complement deficiencies and meningococcal disease was detected for Serogroups Y (n = 5; 16.6%) and W135 (n = 3; 10.0%) . Localization of the defects revealed only complement deficiencies of the classical pathway (C8-beta or C7 defects) . The levels of Ig and IgG subclasses were found to be within the normal range for all patients . Our results suggest that meningococcal diseases caused by uncommon serogroups are more often associated with deafness and late complement component defects.

APMIS, 1993 Oct, 101(10), 791 - 4
ABH secretor status, as judged by the Lewis phenotypes, in Norwegian survivors from meningococcal disease; Kornstad L et al.; Survivors from meningococcal disease (serogroups B and C) and a control series (blood donors) were examined for their ability to secrete ABH blood group substance . The examination was done indirectly by determining their Lewis phenotypes . There was no significant difference in the secretor status between the two groups.

Mol Microbiol, 1993 Oct, 10(1), 13 - 23
Analysis in Neisseria meningitidis and other Neisseria species of genes homologous to the FKBP immunophilin family; McAllister CF et al.; The immunophilin family of FK506-binding proteins (FKBPs), involved in eukaryotic protein-folding and cell regulation, have recently been found to have prokaryotic homologues . Genes with sequences homologous to those encoding human FKBPs were examined in Neisseria species . An FKBP DNA sequence was present, as shown by the polymerase chain reaction and Southern blotting experiments, in the chromosome of Neisseria meningitidis (14 strains) and in all 11 different commensal Neisseria spp . studied, but was not found in Neisseria gonorrhoeae (11 strains tested) or in Moraxella catarrhalis . The nucleotide and predicted protein sequences of the FKBP-encoding domain from five of the meningococcal strains were highly conserved (e.g . > or = 97% homologous) . The meningococcal nucleotide sequence was > or = 93% homologous and the consensus meningococcal protein sequence was > or = 97% homologous to FKBP sequences found in seven different commensal Neisseria spp . The meningococcal nucleotide and predicted protein sequences were > or = 59% homologous to the conserved C-terminus of the human FKBP gene family . The FKBP nucleotide sequence was present as a single copy in the chromosome of commensal Neisseria spp . and in most strains of N . meningitidis . The FKBP gene was linked to the silent pilin locus, pilS, in class II-piliated meningococcal strains . In meningococcal strains expressing class I pili, the FKBP gene was linked to one of several pilS loci but not the pilE locus present in these strains . FKBP genes found in commensal Neisseria spp . were not linked to known pilin loci.

Mol Microbiol, 1993 Oct, 10(2), 299 - 310
Deletions of Tn916-like transposons are implicated in tetM-mediated resistance in pathogenic Neisseria; Swartley JS et al.; Using the tetM-containing conjugative transposon Tn916 as a mutagenesis tool, we identified two distinct classes of transposon insertions in the meningococcal chromosome . Class I insertions have an intact copy of Tn916 that appears to have transposed by a novel recombinational mechanism, similar to the transposition of conjugative transposons in Gram-positive bacteria . Class II insertions were characterized by deletions of Tn916 but preservation of the tetM determinant . In addition, we identified Class II Tn916-like insertions in the naturally occurring 25.2 MDa tetM-containing plasmids of both Neisseria meningitidis and Neisseria gonorrhoeae . The turncated Tn916-like insertions appeared to be present in the same site in these two plasmids; however, the deletions of the transposon were different . Plasmid sequence adjacent to the truncated transposon in the 25.2 MDa plasmids was found in a tetracycline-sensitive N . gonorrhoeae 24.5 MDa conjugative plasmid . These data suggest that the 25.2 MDa plasmids are the result of one or a series of Class II Tn916-like insertions into 24.5 MDa conjugative plasmids . Class II insertions of Tn916-like transposons are implicated in the dissemination of tetM resistance in pathogenic Neisseria.

J Clin Microbiol, 1993 Oct, 31(10), 2594 - 8
Characterization of Neisseria meningitidis by polymerase chain reaction and restriction endonuclease digestion of the porA gene; Kertesz DA et al.; Subtype classification based on the use of monoclonal antibodies to the class 1 outer membrane protein combined with techniques such as multilocus enzyme electrophoresis remains the standard method of characterizing isolates during outbreaks of invasive meningococcal disease . We developed a rapid typing method based on the restriction fragment length polymorphisms (RFLPs) within the polymerase chain reaction (PCR) product of the porA gene, which encodes the class 1 outer membrane protein, reflecting genotypic rather than phenotypic variability between strains . Forty-five isolates of invasive Neisseria meningitidis obtained from October 1990 to April 1992 were studied after randomization and coding . Included among these were isolates from a local outbreak that resulted in a mass vaccination program . PCR amplification for each isolate was followed by restriction digestion with the following enzymes in the indicated sequence: HaeIII, RsaI, HinfI, HpaII, and AluI . Eighteen different patterns were demonstrated on the basis of RFLPs, whereas only seven groups were identified after standard subtyping . The most common isolate identified by serosubtyping was serogroup C, serotype 2a, subtype P1.2 (C:2a:P1.2) (38%) . Thirteen (76%) of these group C isolates shared a common RFLP pattern after digestion with the five restriction enzymes . We were able to further differentiate strains of C:2a:P1.2 with electrophoretic type 5 from electrophoretic types 1, 9, and 15 that occurred during an apparent outbreak . We were also able to characterize 15 isolates (33%) which could not be subtyped with monoclonal antibodies . Our method offers a convenient alternative to standard subtyping procedures and is particularly useful in outbreak situations in which rapid characterization of N . meningitidis is essential so that rational public health policy regarding preventative measures can be formulated.

Infect Immun, 1993 Oct, 61(10), 4217 - 24
Use of transformation to construct antigenic hybrids of the class 1 outer membrane protein in Neisseria meningitidis; van der Ley P et al.; The class 1 protein of Neisseria meningitidis is an important component of candidate outer membrane vaccines against meningococcal meningitis . This porin protein contains two variable regions which determine subtype specificity and provide binding sites for bactericidal monoclonal antibodies . To determine the contribution of each of these variable regions in the induction of bactericidal antibodies, a set of isogenic strains differing only in their class 1 epitopes was constructed . This was done by transformation of meningococcal strain H44/76 with cloned class 1 genes and selection of the desired epitope combinations in a colony blot with subtype-specific monoclonal antibodies . When used for the immunization of mice, outer membrane complexes induced bactericidal antibodies only against meningococcal strains sharing at least one of their class 1 epitopes . The results demonstrate that the P1.2 and P1.16 epitopes, normally located in the fourth exposed loop of the protein, efficiently induce bactericidal antibodies independently of the particular sequence in the first variable region . The P1.5 and P1.7 epitopes, normally located in the first exposed loop, were found to induce lower bactericidal titers . Hybrid class 1 outer membrane proteins were constructed by inserting oligonucleotides encoding the P1.7 and P1.16 epitopes into the porA gene . In this way, we obtained a set of strains which carry the P1.5 epitope in loop 1, P1.2 in loop 4, and P1.7 and P1.16 (separately or in combination) in either loop 5 or loop 6 . The additional epitopes were found to be exposed at the cell surface . Outer membrane complexes from several of these strains were found to induce a bactericidal response in mice against the inserted epitopes . These results demonstrate that it is feasible to construct meningococcal strains carrying multivalent class 1 proteins in which multiple subtype-specific epitopes are present in different cell surface-exposed loops.

Mol Microbiol, 1993 Oct, 10(1), 203 - 13
Expression of meningococcal epitopes in LamB of Escherichia coli and the stimulation of serosubtype-specific antibody responses; McCarvil J et al.; The class 1 outer membrane protein (OMP), a major variable surface antigen of Neisseria meningitidis, is a component of novel meningococcal vaccines currently in field trials . Serological variants of the protein are also used to serosubtype meningococci . Most of the amino acid changes that give rise to antigenic variants of the protein occur in two variable regions (VR1 and VR2) that are thought to form loops on the cell surface . The polymerase chain reaction (PCR) was used to amplify the nucleotide sequences encoding VR1 and VR2 from the chromosomal DNA of N . meningitidis strain M1080 . These were cloned in frame into the lamB gene of the Escherichia coli expression vector pAJC264 . Whole-cell enzyme-linked immunosorbent assays (ELISAs), using monoclonal antibodies, and SDS-PAGE confirmed that, upon induction, strains of E . coli carrying these constructs expressed hybrid LamB proteins containing the N . meningitidis surface loops . These strains were used to immunize rabbits and the resultant polyclonal antisera reacted specifically with the class 1 OMP of reference strain M1080 (P1.7) . Immunogold labelling of meningococcal cells and whole-cell dot-blot analyses with these antisera showed that the variable epitopes were exposed on the cell surface and confirmed that this approach could be used to obtain serosubtype-specific antisera . The binding profiles of the antisera were determined from their reactions with overlapping synthetic peptides and their reactivity compared with that of relevant serosubtype-specific monoclonal antibodies . This approach was used successfully to raise antisera against two other class 1 OMP VR2s . A fourth antiserum raised against a VR2, including the P1.1 epitope, was not subtype specific.

Tidsskr Nor Laegeforen, 1993 Sep 30, 113(23), 2933 - 7
{Meningococcal project Telemark . Experiences after 5 years with contact tracing and eradication of the pathogenic bacteria in near contacts of the patients with meningococcal disease}; Kristiansen BE et al.; Since 1987 we have analysed throat samples from 1,086 healthy contacts of 32 patients with meningococcal disease . The disease-causing strain was found in contacts of 17 out of the 32 patients . 161 (18%) of the contacts carried meningococci, and 30 (3%) of them were carriers of the disease-causing strain as determined by DNA fingerprinting . The carrier strain was eradicated in 29 of these 30 contacts by treatment with rifampicin . No secondary case of meningococcal disease was observed . During the four-year period 1984-87, there were 39 confirmed cases of meningococcal disease, including 12 verified and four suspected secondary cases of meningococcal disease . Therefore identification and eradication of the disease-causing strain seems to prevent secondary cases . A change in the Norwegian recommendations for preventing secondary cases of meningococcal disease should be discussed.

J Clin Microbiol, 1993 Sep, 31(9), 2506 - 8
Genomic fingerprinting of Neisseria meningitidis associated with group C meningococcal disease in Canada; Strathdee CA et al.; A single electrophoretic type (ET15) of Neisseria meningitidis has been associated with an increased incidence of group C meningococcal disease in Canada . Genomic fingerprinting through pulsed-field gel electrophoresis of chromosomal DNA was used to characterize the clonal relationship among meningococcal isolates of different electrophoretic types and among isolates within ET15 . The genomic fingerprints of the ET15 isolates, while similar as a group, were sufficiently distinct to confirm linkage for four pairs of strains from focal outbreaks and differed markedly from those of the other common electrophoretic types, ET5, ET9, and ET21.

Clin Exp Immunol, 1993 Sep, 93(3), 377 - 81
Immunogenicity of the meningococcal stress protein MSP63 during natural infection; Pannekoek Y et al.; Acute- and convalescent-phase sera from 40 patients with meningococcal disease were evaluated for immunoreactivity with the meningococcal member of the hsp60 stress protein family . The IgG response was measured by ELISA, using bacterial cell lysate of the corresponding patients' strain, and purified hsp60 proteins from Neisseria meningitidis (MSP63), Escherichia coli (GroEL) and Mycobacterium bovis BCG (65K) as antigens . Analysis of the antibody responses revealed that 24/35 patients (69%) with elevated anti-meningococcal titres, generated anti-MSP63 antibodies during the time course of infection . Twelve of these patients generated antibodies specific for MSP63, in six patients anti-MSP63 levels exceeded anti-GroEL/65K antibodies . In the remaining six patients, equal levels of anti-MSP63 and anti-GroEL/65K were measured . We conclude that MSP63 is expressed and immunogenic during natural meningococcal infection, and that individual subjects have a restricted response to the antigen, resulting in the recognition of Neisseria-specific hsp60 epitopes and/or cross-reactive hsp60 determinants.

Brain Dev, 1993 Sep-Oct, 15(5), 340 - 5
Brainstem auditory evoked potentials following meningitis in children; Duclaux R et al.; The report concerns findings for brainstem auditory evoked potentials (BAEPs) recorded in 116 children, aged between a few days and 7 years, having suffered from bacterial meningitis . 26% of cases occurred between birth and 6 months, 55% between 6 months and 2 years, and 19% after 2 years of age . Hemophilus was the most common bacteria (49%), followed by Pneumococcus (22%) and Meningococcus (15%) . Neurological complications were found in 30% of the meningitis cases and accounted for 85% of all complications found . 29% of BAEPs were abnormal, of which 47% revealed transmission, 32% endocochlear and 21% retrocochlear impairment . Transmission impairment mainly occurred before the age of 2 years (88%), most frequently in meningococcus meningitis cases (44%), and independently of neurological complications . Retrocochlear impairment was found in association with neurological complications in 71% of cases . Endocochlear BAEP damage was found in 9.5% of cases, half of which were bilateral and total, representing cophosis: it was found at all ages, and without any particular associated neurological complication . Hemophilus was the commonest bacterial agent in endocochlear cases overall, with Pneumococcus underlying 50% of cophosis cases . The study shows BAEP recording in association with a clinical ear examination is useful following childhood bacterial meningitis, screening for definitive endocochlear and deafness, distinguishing total from partial hearing-loss and indicating suitable treatment.

Vaccine, 1993 Sep, 11(12), 1199 - 204
GD3/proteosome vaccines induce consistent IgM antibodies against the ganglioside GD3; Livingston PO et al.; The gangliosides of melanoma and other tumours of neuroectodermal origin are suitable targets for immune intervention with tumour vaccines . The optimal vaccines in current use contain ganglioside plus bacillus Calmette-Guerin and induce considerable morbidity . We have screened a variety of new adjuvants in the mouse, and describe one antigen-delivery system, proteosomes, which is especially effective . Highly hydrophobic Neisserial outer membrane proteins (OMP) form multimolecular liposome-like vesicular structures termed proteosomes which can readily incorporate amphiphilic molecules such as GD3 ganglioside . The optimal GD3/proteosome vaccine formulation for induction of GD3 antibodies in the mouse is determined . Interestingly, the use of potent immunological adjuvants in addition to proteosomes augments the IgM and IgG antibody titres against OMP in these vaccines but GD3 antibody titres are unaffected . The application of proteosomes to enhance the immune response to GD3 extends the concept of the proteosome immunopotentiating system from lipopeptides to amphipathic carbohydrate epitopes such as cell-surface gangliosides . The demonstrated safety of meningococcal OMP in humans and the data in mice presented here suggest that proteosome vaccines have potential for augmenting the immunogenicity of amphipathic tumour antigens in humans.

An Esp Pediatr, 1993 Sep, 39(3), 214 - 8
{Acute meningococcal disease . Its prognostic assessment}; Bermudez de la Vega JA et al.; We have studied 50 children affected with acute meningococcal disease (AMD) . The ages of the children varied between 4 months and 12.58 years, with a mean age of 4.58 years . By using the shock state and DIC syndrome, both of which are indications of the severity of the illness, an evaluation of the discriminatory capacity was done with regard to significantly associate variables and 3 scores, Bjorvatn, Leclerc and PRISM, throughout 8 intervals within the first 48 hours of hospital treatment . We observed a very high survival rate (98%) associated with the early treatment for shock . Leukopenia and disseminated purpura were the best variables in order to discriminate shock and DIC, respectively . The greatest capacity for the diagnosis of the shock state and DIC syndrome were registered during the 0-6 hour period and the 0-12 hour period, respectively . The prognosis improved if the child remained alive 12 hours after the treatment had begun.

Eur J Clin Microbiol Infect Dis, 1993 Sep, 12(9), 683 - 9
Plasmid carriage and antibiotic susceptibility of Neisseria meningitidis strains isolated in Sweden 1981-1990; Backmann A et al.; A random selection of Neisseria meningitidis strains isolated in Sweden in the period 1981-1990 were investigated for plasmid carriage and susceptibility to antimicrobial agents commonly used for treatment and prophylaxis of meningococcal disease . The MICs were determined by the agar dilution method for penicillin V, penicillin G, rifampicin, sulfadiazine, erythromycin and tetracycline . In 13% of the invasive strains the MIC of penicillin V was > or = 0.5 mg/l which may cause concern regarding the usefulness of penicillin V in prophylaxis . In strains isolated from the urogenital tract the MICs of penicillin V and penicillin G were higher than in the invasive strains . In about 82% of the strains isolated in 1987-1988 the MIC of tetracycline was > or = 0.5 mg/l whereas no such strains were found in 1981-1982 . Plasmids were found in 2 of 119 invasive strains, in 1 of 50 strains from the respiratory tract and in 1 of 19 strains from the urogenital tract . The plasmid sizes were 1.3, 2.6, 25 and 40 Mda . None of these strains were beta-lactamase producing and no relation to a high degree antibiotic resistance was observed.

Br J Biomed Sci, 1993 Sep, 50(3), 174 - 7
Neisseria meningitidis: serotyping and subtyping by whole cell ELISA; Prakash K et al.; Twenty strains of Neisseria meningitidis isolated from clinically diagnosed cases of meningococcal disease were subjected to serogrouping, employing slide agglutination followed by serotyping and serosubtyping by whole cell ELISA using monoclonal typing antisera . All isolates were from sporadic cases of meningitis during a period of two years from various hospitals in Delhi . All 20 isolates were grouped as serogroup A and typed as serotype 4, except one strain which was untypable . On serosubtyping the isolates were found to belong to P1.9 (7 strains) followed by P1.1 (5), P1.9 (2), P1.16,1 (2), P1.6,10 (2), P1.10,7,1 (1) and non-subtypable (1).

Acta Paediatr, 1993 Sep, 82(9), 729 - 33
Variation in serum C-reactive protein across the clinical spectrum of meningococcal disease; Marzouk O et al.; In a multicentre prospective study, 124 cases of meningococcal disease were classified into the clinical categories, meningitis alone (n = 15), meningitis and septicaemia (n = 79) and septicaemia alone (n = 30) . A further 60 children referred with other illnesses served as controls . Serial measurements of serum C-reactive protein (admission, day 1, day 2, days 5-7) were compared . Children with septicaemia had significantly lower C-reactive protein levels on admission than those with meningitis alone or meningitis and septicaemia which were unexplained by differences in the duration of the presenting illness or severity of the disease . Within each clinical category of meningococcal disease, significant changes in C-reactive protein concentration occurred during the course of the disease . Four control children had other types of septic meningitis: admission C-reactive protein concentrations did not differ from those with meningitis or meningitis and septicaemia, but were significantly higher than those with septicaemia alone . The other 56 patients had a significantly lower admission C-reactive protein concentration compared with all cases of meningococcal disease . For the diagnosis of meningococcal disease, admission C-reactive protein levels of > or = 40 mg/l had a sensitivity of 79%, specificity of 80% and positive predictive value of 87% . For the prognostic prediction of death in meningococcal disease (or meningococcal disease with shock) CRP < 100 mg/l on admission had a sensitivity of 69% (69%), specificity of 50% (56%) and positive predictive value of 18% (53%) . In children with suspected meningococcal disease, serum C-reactive protein, measured on admission, has diagnostic value but not prognostic value.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimicrob Agents Chemother, 1993 Sep, 37(9), 2024 - 6
Use of single-dose ofloxacin to eradicate tonsillopharyngeal carriage of Neisseria meningitidis; Gilja OH et al.; After an outbreak of three cases of serogroup B meningococcal disease at a Norwegian college, 84 of 392 (21%) subjects were tonsillopharyngeal carriers of Neisseria meningitidis . To eradicate meningococcal carriage, 80 volunteers received a single dose of 400 mg of ofloxacin . Three days after treatment, all 75 evaluable volunteers were culture negative for N . meningitidis, and after 7 days none carried the strain that they carried initially, as judged by DNA fingerprinting . A single dose of ofloxacin was found to be 97.2% effective in eradicating carriage of N . meningitidis for a period of 33 days . The carriage acquisition rate among treated students was four times higher than that among nontreated noncarriers (P = 0.02) . After ofloxacin treatment, no case of meningococcal disease occurred for 6 months . Ofloxacin may thus prevent the outbreak and spread of meningococcal disease.

Zh Mikrobiol Epidemiol Immunobiol, 1993 Sep-Oct, (5), 50 - 5
{A system for the mass combined vaccination of the adult population against influenza, viral hepatitis, typhoid, meningitis and diphtheria}; Gapochko KG et al.; A safe, moderately reactogenic and immunologically effective scheme of complex (combined) immunization against meningitis A, diphtheria, typhoid fever, viral hepatitis A and influenza has been developed as the result of experimental and clinico-immunological studies . Depending on the epidemiological situation, the newly developed scheme can be used in two variants . According to the first variant of this scheme, the following preparations are injected subcutaneously into three different sites: a mixture of group A meningococcal vaccine and diphtheria toxoid, typhoid vaccine and influenza vaccine . The second variant of the scheme differs from its first variant in using intramuscular injection of normal human immunoglobulin instead of injection of influenza vaccine . Moreover, in practical realization these variants may be altered by excluding vaccines, unnecessary under present conditions . The newly developed scheme of vaccinal prophylaxis is recommended for practical use.

Microb Pathog, 1993 Sep, 15(3), 197 - 205
A new variant of serosubtype P1.16 in Neisseria meningitidis from Norway, associated with increased resistance to bactericidal antibodies induced by a serogroup B outer membrane protein vaccine; Rosenqvist E et al.; Based on differences in reaction pattern with monoclonal antibodies against the P1.16 epitope, a new variant of the class 1 protein in Neisseria meningitidis serogroup B was identified in Norway . A single amino acid deletion was revealed when the part of the gene region encoding the second variable region of the protein was sequenced . This new variant was designated P1.16c . About 5% of the B:15:P1.7,16 strains in Norway from the time period 1987-1991 were P1.16c . In a localized area in Southern Norway, 5/8 (62%) of the P1.7,16 strains were P1.16c . The P1.16b mutant, recently described in England, was not found among the Norwegian meningococcal isolates . Strains carrying the P1.16c mutation showed increased resistance to bactericidal killing, not only by P1.16-specific monoclonal antibodies, but also by the sera from individuals immunized with a vaccine based on outer membranes from a B:15:P1.7,16 strain.

Commun Dis Rep CDR Rev, 1993 Aug 13, 3(9), R129 - 31
Meningococcal infections in England and Wales: 1992; Jones DM et al.; Fewer cases of meningococcal infection were identified in England and Wales during 1992 than in 1991 . The 1301 isolates received by the PHLS Meningococcal Reference Unit represented a decrease of 7%, continuing the trend of the last two years . Most regions saw a reduction in cases, but increased numbers of isolates were received from some regions, notably Northern (up 22%), East Anglia (up 25%) and South West Thames (up 50%) . Group C infections (down 17%) contributed disproportionately to the decrease; the numbers of isolates of this organism being the lowest since 1986 . Serology is a reliable diagnostic method in cases where no isolate is obtained.

J Pediatr Nurs, 1993 Aug, 8(4), 211 - 6
Nursing care of a child with meningococcemia; Holland JA et al.; This case presentation will discuss the pathophysiology of a child in septic shock due to Neisseria meningitidis . The most prevalent nursing care concerns of this case encountered during the pediatric intensive care unit (PICU) and during the general floor stay will be addressed . The nursing skill required for identifying problems and planning care that clearly fall under the nursing domain also will be covered . In addition, the complexities of this case demonstrate that collaboration between the PICU nurse and the general pediatric nurse is imperative for successful patient outcome . A.W . was a 5 1/2-month-old infant transported to our PICU from a referral hospital in the state . Diagnosis at time of admission was meningococcemia, disseminated intravascular coagulopathy, septic shock, respiratory failure, and purpura fulminans . There was a 2- to 3-day history of a runny nose, cough, and vomiting . On the day of admission, A.W . had three seizures and developed a fever and a purpuric rash.

Clin Infect Dis, 1993 Aug, 17(2), 254 - 61
Epidemic meningococcemia and purpura fulminans with induced protein C deficiency; Powars D et al.; Patients with epidemic infections caused by Neisseria meningitidis serogroup C were studied to assess the relationship of abnormal coagulation parameters to prognosis . Patients were categorized into stages within the first hour of observation according to severity of illness . During the epidemic years 1986 through 1991, 113 patients with bacteriologically proven N . meningitidis infection were observed, 15 of whom died . Purpura fulminans was seen in 28 patients, of whom 14 (50%) died . Among the 14 surviving patients who had purpura fulminans, 10 suffered gangrene with deforming autoamputation secondary to the dermal microvascular thrombosis and hemorrhagic necrosis . Evaluation of the induced diffuse intravascular coagulation in 59 patients included studies of the naturally occurring anticoagulants, focusing on protein C and protein S . The magnitude of the declining levels of protein C, the degree of thrombocytopenia, and the presence of fibrin split products are directly related to the clinical severity of the illness (P = .0053) . Thus, in individuals with severe disease expression, the risk of purpura fulminans with death or deformity was significantly increased when the platelet count was < 50,000 cells/mm3 (P = .0001) and protein C levels were low (P = .0158) . The immaturity of the protein C system in children who are < 4 years of age may contribute to the rapid and more frequent pathogenesis of purpura fulminans . Therapy directed at replacement of the naturally occurring anticoagulants, such as protein C, may ultimately improve the prognosis for individuals with purpura fulminans.

An Esp Pediatr, 1993 Aug, 39(2), 102 - 4
{Estimation of Neisseria meningitidis carriers among healthy subjects in contact with patients with meningococcal sepsis in the Madrid area}; Calle Puron EM et al.; We have studied 238 asymptomatic school children which had come in contact with one of 5 cases of meningococcal sepsis, which occurred between January 1992 to May 1992 . The study was performed at the corresponding schools and oropharynx samples were immediately put into Thayer-Martin agar plates . The cases were identified as serotype C in three occasions and type B in two cases . The total carrier prevalence was 1.68%, all of which were serotype B . We did not find a significant relationship between asymptomatic carriers and meningococcal sepsis cases . In addition, all contacts were treated with rifampin . Control cultures were made after 15 days of the treatment and 100% of the carriers had negative cultures.

Antimicrob Agents Chemother, 1993 Aug, 37(8), 1728 - 9
Isolation of moderately penicillin-susceptible strains of Neisseria meningitidis in Argentina; Lopardo HA et al.; Four strains that were moderately susceptible to penicillin and/or ampicillin were found among 54 consecutive isolates of meningococci recovered from patients in one pediatric hospital in Argentina from October 1991 to December 1992 . Disk diffusion tests performed with 2 U of penicillin failed to detect one strain . These findings suggest that attention should be paid to changes in the susceptibility patterns of meningococci in order to anticipate therapeutic failures in the future.

J Gen Microbiol, 1993 Aug, 139 ( Pt 8), 1729 - 38
Immunization with synthetic peptides containing epitopes of the class 1 outer-membrane protein of Neisseria meningitidis: production of bactericidal antibodies on immunization with a cyclic peptide; Christodoulides M et al.; The class 1 outer-membrane protein of Neisseria meningitidis is the target for subtype-specific, bactericidal monoclonal antibodies (mAbs) . The epitopes recognized by these antibodies have been mapped previously to linear peptides corresponding to the sequences thought to be exposed at the apices of surface-exposed loops of the protein . In this work several synthetic peptides containing the subtype Pl.16b epitope have been synthetized with the aim of inducing a polyclonal immune response resembling the reactivity of the mAbs . Initially, peptides of 9 and 15 amino acid residues were synthesized and used for immunization after coupling to a carrier protein . The reactivity of the resulting antisera, with synthetic linear decapeptides, resembled that seen in previous epitope mapping experiments with the protective mAbs . However, despite the induction of antibodies having the desired specificity, the antisera reacted poorly with the native protein in outer membranes, and were non-bactericidal . A 36mer peptide, consisting of the entire surface-exposed loop 4 of the class 1 protein was then synthesized and used for immunization as (i) free peptide, (ii) peptide coupled to carrier and (iii) peptide subjected to cyclization, in an attempt to restrict it to conformations that might more closely resemble the native loop structure . In contrast to antisera raised against linear peptides, antibodies raised by immunization with the 36mer cyclic peptide, did not react with linear peptides recognized by the mAbs, but instead appeared to recognize conformational determinants . This antiserum promoted complement-mediated bactericidal killing of the homologous meningococcal strain, demonstrating the potential of synthetic peptide immunogens for inducing a protective immune response against group B meningococci.

Ned Tijdschr Geneeskd, 1993 Jul 24, 137(30), 1505 - 8
{Secondary cases of meningococcal disease in The Netherlands, 1989-1990; a reappraisal of chemoprophylaxis}; Scholten RJ et al.; OBJECTIVE . To assess the secondary attack rate (SAR) of meningococcal disease among the household contacts of primary patients and to describe the use of chemoprophylaxis in the Netherlands . DESIGN . Descriptive, nation-wide survey . METHODS . Information was collected of patients with meningococcal disease, reported between April 1st, 1989 and April 30th, 1990, and their household contacts . A household contact suffering from meningococcal disease between 24 hours and 1 month after hospital admission of the primary patient, was considered to be a secondary case . Chemoprophylaxis was considered appropriate if rifampicin or minocycline had been prescribed to all household contacts within a maximum of one day after admission of the primary patient . RESULTS . There were 5 secondary cases (SAR: 0.3%) . Chemoprophylaxis was prescribed to 627 of 1130 household contacts (55%) . Of those the prophylaxis was considered appropriate in 46% . 2 secondary cases were not given any prophylaxis, 2 received penicillin and 1 rifampicin . Of the primary patients, 6% were given prophylaxis during their hospital stay . All meningococci, isolated from pairs of secondary and primary patients, were rifampicin sensitive . CONCLUSIONS . The SAR of meningococcal disease in the Netherlands is similar to that in other countries . Although prescription of chemoprophylaxis is not recommended by the government, it is prescribed to 55% of the household contacts, and in almost half of these instances it was considered to be appropriate . Chemoprophylaxis is rarely prescribed to primary patients . Recommendations concerning chemoprophylaxis in the Netherlands are in need of reappraisal . Based on the results from this study and the literature, the prescription of chemoprophylaxis to all household contacts of a patient with meningococcal disease, and to the index patient, is recommended.

J Biol Chem, 1993 Jul 5, 268(19), 14146 - 52
Structure of the sialylated L3 lipopolysaccharide of Neisseria meningitidis; Pavliak V et al.; The L3 immunotype lipopolysaccharide (LPS) of Neisseria meningitidis was subjected to degradation procedures, which produced a number of different oligosaccharide fragments . The high resolution 1H and 13C NMR spectroscopic analyses of these oligosaccharides yielded structural information on a number of different regions of the LPS . For example, from one oligosaccharide, it was found that the endogenous sialylation of the meningococcal LPS occurs at O-3 of the terminal beta-D-galactopyranosyl residue of its lacto-N-neotetraose antenna in the alpha-D-configuration . From another, it was also established that the dominant structural feature responsible for L3 epitope specificity is the presence of a phosphorylethanolamine substituent at O-3 of the penultimate heptopyranosyl residue of its other antenna . In addition from information obtained with another oligosaccharide the structure of the 3-deoxy-D-manno-octulosonic acid disaccharide region of the L3 LPS was also elucidated . From all the above cumulative data plus some published data, it was then possible to reconstruct the complete structure of the entire native L3 LPS.

J Infect Dis, 1993 Jul, 168(1), 227 - 31
Vaccination and the role of capsular polysaccharide antibody in prevention of recurrent meningococcal disease in late complement component-deficient individuals; Andreoni J et al.; This study sought to quantitate the response of late complement component-deficient (LCCD) individuals to the meningococcal vaccine, to examine antibody persistence, and to investigate the contribution of these antibodies to meningococcal killing in complement- and phagocyte-dependent bactericidal assays . The mean concentration of antibody to group A and C capsular polysaccharide after vaccination was similar in 8 LCCD, 11 family members, and 7 unrelated normal individuals . LCCD individuals had a greater percentage decline in antibody concentration to group C polysaccharide and had lower concentrations of antibody to group Y polysaccharide 2.0-2.5 years after vaccination than did normal and heterozygous deficient persons . Antibody to subcapsular antigens was minimally effective in mediating complement-dependent killing and had no effect in the opsonophagocytic assay . In contrast, antibody to capsular polysaccharide promoted meningococcal killing in both assays . These data support vaccination as a preventive measure in LCCD individuals and lend credence to the idea that these individuals are critically dependent on capsular antibody for protection against meningococcal disease.

Infect Immun, 1993 Jul, 61(7), 2906 - 11
The RTX cytotoxin-related FrpA protein of Neisseria meningitidis is secreted extracellularly by meningococci and by HlyBD+ Escherichia coli; Thompson SA et al.; Neisseria meningitidis produces proteins (FrpA and FrpC) related to the RTX cytotoxin family . In meningococcal strain FAM20 these proteins were both localized in the outer membrane and secreted into the extracellular medium . An Escherichia coli strain with wild-type hemolysin secretion genes hlyB and hlyD and containing a cloned frpA gene secreted FrpA, whereas an isogenic hlyBD mutant strain did not . Low-stringency DNA hybridization revealed hlyBD-like sequences in N . meningitidis FAM20, suggesting that a similar RTX secretion system exists in meningococci . Structural features found at the C termini of other RTX proteins and thought to be important for their secretion were also found at the C terminus of FrpA . The secretion of FrpA from E . coli by heterologous RTX transport proteins further demonstrates the relation of the FrpA protein to RTX toxins.

Eur J Clin Microbiol Infect Dis, 1993 Jul, 12(7), 505 - 11
Re-emergence of meningococcal carriage on three-year follow-up of a kibbutz population after whole-community chemoprophylaxis; Block C et al.; A long-term study was conducted to determine the rate of re-emergence of throat carriage of meningococci in a semi-closed kibbutz community after the administration of chemoprophylaxis to all its members . Serotype B:4 was selected as marker organism since it was isolated from a fatal case and was the most frequently occurring strain (80%) among serogroup B isolates, which themselves comprised 54% of all meningococci . The carriage rate among Israeli residents (volunteer workers were analyzed separately) before treatment was 6.6% (49/748) overall, with 4.3% group B strains . Three weeks after treatment, in most cases with rifampicin (whereby three persistently positive persons were retreated with minocycline), no meningococci were recovered . Six months later, 1.9% of a population sample aged < or = 30 years were positive, while before treatment and one and three years later, 9.4%, 8.6% and 4.6% respectively were positive in this age group . Serotype B:4 comprised 81.3% of group B strains before prophylaxis, 5.3% after one year, and 28.6% after three years, thus possibly re-establishing itself as the single dominant serotype . The marked suppression of carriage after mass chemoprophylaxis appeared to last at least six months, with the meningococcal population being re-established within a year.

J Infect, 1993 Jul, 27(1), 83 - 8
Age incidence of meningococcal infection England and Wales, 1984-1991; Jones DM et al.; The age incidence of meningococcal infections occurring between 1984 and 1991 in England and Wales was determined from data submitted with isolates to the Meningococcal Reference Laboratory for England and Wales . The incidence was maximum at 6 months of age and thereafter declined sharply to the age of 4 years . It was followed by a small secondary peak at 17-18 years . There was a relative excess of group B infections in the early months of life and, although group B and group C infections both peaked at 6 months of age, the latter did not decline until after the age of 9 months . Certain strains of meningococci were more likely to be associated with disease in older children and young adults.

J Pediatr Orthop, 1993 Jul-Aug, 13(4), 447 - 51
Use of bone scan in management of patients with peripheral gangrene due to fulminant meningococcemia; Hamdy RC et al.; Technetium bone scintigraphy was performed in four patients with fulminant meningococcemia and extensive peripheral gangrene . The bone scans showed variable levels of absent uptake in all extremities of the four patients who subsequently required quadrimembral amputations . In 13 limbs, the level of amputation was determined primarily by the bone scan findings, and operation was successful in 84% of those limbs . These findings suggest that bone scanning is a useful adjunct in differentiating viable from nonviable tissues in patients with extensive peripheral gangrene secondary to fulminant meningococcemia and thus helps determine the appropriate level of amputation in such patients.

Clin Infect Dis, 1993 Jul, 17(1), 126 - 32
Forty years of meningococcal disease in Israel: 1951-1990; Block C et al.; Meningococcal disease accounts for approximately 20% of cases of bacterial meningitis in Israel . During the period 1951-1990, the annual incidence of meningococcal disease rarely exceeded two cases per 100,000 persons and was generally higher among non-Jews (largely the Arab population) than among Jews; there were some notable peaks of disease activity during 1963-1967, 1975, and 1987-1988 . The highest incidence was among infants and young children, with a slight male predominance . The main period of disease activity was from January to April, but an unusual secondary peak in July coincided with the onset of peak summer temperatures . Monthly disease frequencies were significantly correlated with relative humidity . Incidence rates varied between regions and were lower in cities than in smaller settlements . Overall case-fatality rates decreased to approximately 11% for the period 1981-1990 . Outbreaks were infrequent and tended to be small . Meningococci of serogroup B have dominated since the mid-1970s . Group A meningococci were isolated significantly more commonly from Arabs (26.26%) than from Jews (1.03%; P < .000001) . The frequency with which group A organisms occurred among clinical isolates appeared to follow a more or less cyclical pattern.

Zh Mikrobiol Epidemiol Immunobiol, 1993 Jul-Aug, (4), 21 - 5
{The antilysozyme activity of the meningococci isolated from bacterial carriers in closed collectives with different epidemiological situations}; Mil'dzikhova IB et al.; The degree of the antilysozyme activity (ALA) of 430 Neisseria meningitidis strains isolated from 379 healthy carriers in 11 closed groups with different epidemiological situation and in 3 family foci was studied by the method of delayed antagonism . 87% of the strains exhibited ALA in a concentration of lysozyme between 1 and 10 micrograms per ml of the medium; about 11% of them were highly active, inactivating 20 and 25 micrograms of lysozyme per ml . ALA was shown to be the constant sign of carriership . The ALA of 39 strains isolated in cases of prolonged carriership (exceeding 2 weeks) was essentially higher than the ALA of 20 strains obtained in a single isolation . N . meningitidis strains of groups A, B and C, mostly responsible for the appearance of the generalized forms of diseases, were essentially less active than N . meningitidis strains of groups X, Y, Z, 29E, W-135, as well as strains not classified with any group . No correlation between ALA and the presence or absence of hyaluronidase was noted . Analysis of the data obtained in this study revealed that the ALA of N . meningitidis strains isolated in closed groups and families was not linked with the presence or absence of morbidity in the generalized forms of meningococcal infection and the spread of carriership in these groups, but reflected only differences in the serological picture of strains circulating there . The role of ALA in the formation of prolonged N . meningitidis carriership requires further study.

Tidsskr Nor Laegeforen, 1993 Jun 20, 113(16), 1994 - 7
{Meningitis and septic shock as acute, fatal conditions}; Brandtzaeg P; Meningitis and septic shock represent an acute inflammatory response in the subarachnoid space and the vascular tree respectively . Specific molecules in the bacterial outer membrane and exotoxins induce the inflammatory response through various mediator systems . The septic shock is caused by reduced vascular resistance and capillary leakage . Meningitis leads to altered brain metabolism, oedema and circulatory disturbance, which ultimately cause hypoxia . The general practitioner should be aware of the atypical symptomatology of meningitis in infants . Septic shock is related to meningococcal infections, pneumococcal infections in splenectomized persons and toxic shock syndromes . The authors give various advice concerning diagnosis, initial treatment and transport before admission to hospital.

Br J Hosp Med, 1993 Jun 16-Jul 13, 50(1), 42 - 9
Management of meningococcal infections; Klein NJ et al.; The last 5 years has seen an increase in the number of cases of meningococcal infection . Despite the availability of highly active antibiotics, the mortality from this infection remains at 10%, rising to 40% in patients presenting in severe shock . Here we describe the spectrum and pathophysiology of meningococcal infections, and the most important aspects of treatment and management.

Ned Tijdschr Geneeskd, 1993 Jun 5, 137(23), 1147 - 52
{Complement deficiencies and meningococcal disease in The Netherlands}; Swart AG et al.; OBJECTIVE . To determine the prevalence of complement system deficiencies in patients who have survived a Neisseria meningitidis infection . DESIGN . Retrospective . SETTING . Reference laboratory for bacterial meningitis of the University of Amsterdam and the National Institute of Public Health and Environmental Protection . METHOD . Out of the files of the laboratory 187 patients who had experienced a meningococcal infection in the Netherlands between 1959-1990 were selected in two groups according to the infecting bacterial strain: 97 patients with a serogroup X, Y, Z, W135, 29E, or non-groupable strains and 90 patients with an infection due to serogroup A or C . The patients were asked for their cooperation by their family doctor and one of us visited the patients at home to take blood samples . The complement activity was studied with a haemolysis in gel test and with an assay of haemolytic activity in free solution . RESULTS . Complement deficiency was present in 18% of the 187 patients who had experienced a meningococcal infection . The highest prevalence was found in patients older than 10 years who had developed infections due to serogroups X, Y, W135, or non-groupable strains (45%) . Of the patients with a serogroup A or C infection, 3% had an complement deficiency . Of the complement deficiencies, 42% concerned a component of the alternative pathway, 12% a deficiency of C3, and 46% a component of the terminal route . The most commonly found deficiencies were properdin deficiency (39%) and C8 deficiency (18%) . 30% of the complement deficient patients reported other family members having experienced meningitis . Recurrent meningitis was only observed in patients with terminal route deficiencies . CONCLUSION . We recommend that patients with a meningococcal infection due to serogroups X, Y, W135 or non-groupable strains should be screened for complement deficiency.

Ned Tijdschr Geneeskd, 1993 Jun 5, 137(23), 1152 - 4
{Arthritis as complication of acute meningococcal infection}; Postema RR et al.; The incidence of meningococcal disease appears to be increasing in the Netherlands . Numerous complications, mostly involving the central nervous system, have been reported . We focus attention on arthritis by describing the case history of a 2-year-old boy who developed oligoarthritis 8 days after a disease onset characterised by general malaise, fever, signs of meningeal irritation and positive cultures of Neisseria meningitidis in CSF, blood and nasopharynx . The arthritis was probably immune complex mediated . He recovered after antibiotic therapy . There are three forms of arthritis as a complication of meningococcal disease: primary meningococcal arthritis, purulent metastatic arthritis, and immune complex arthritis.

MMWR CDC Surveill Summ, 1993 Jun 4, 42(2), 21 - 30
Laboratory-based surveillance for meningococcal disease in selected areas, United States, 1989-1991; Jackson LA et al.; Problem/Condition: Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia in the United States . Accurate surveillance for meningococcal disease is required to detect trends in patient characteristics, antibiotic resistance, and serogroup-specific incidence of disease . Reporting Period Covered: January 1989 through December 1991 . Description of System: A case of meningococcal disease was defined by the isolation of N . meningitidis from a normally sterile site, such as blood or cerebrospinal fluid, in a resident of a surveillance area . Cases were reported by personnel in each hospital laboratory in the surveillance areas . The surveillance areas consisted of three counties in the San Francisco metropolitan area, eight counties in the Atlanta metropolitan area, four counties in Tennessee, and the entire state of Oklahoma . Results: Age- and race-adjusted projections of the U.S . population suggest that approximately 2,600 cases of meningococcal disease occurred annually in the United States . The case-fatality rate was 12% . Incidence declined from 1.3/100,000 in 1989 to 0.9/100,000 in 1991 . Seasonal variation occurred, with the highest attack rates in February and March and the lowest in September . The highest rates of disease were among infants, with 46% of cases affecting those < or = 2 years of age . Males accounted for 55% of total cases, with an incidence of 1.2/100,000, compared with 1.0/100,000 among females (relative risk (RR) = 1.3, 95% confidence interval (CI) 1.0-1.6) . The incidence was significantly higher among blacks (1.5/100,000) than whites (1.1/100,000) (RR = 1.4 {95% CI 1.1-1.8}) . Serogroup B caused 46% of cases and serogroup C, 45% Thirty-eight percent of isolates were reported to be resistant to sulfa; none were reported to be resistant to rifampin . Interpretation: The decline in incidence of meningococcal disease from 1989 through 1991 cannot be explained by any change in public health control measures; this trend should be monitored by continued surveillance . The age, sex, and race distribution and seasonality of cases are consistent with previous reports . The proportion of N . meningitidis isolates resistant to sulfa continues to be substantial . A relatively small proportion of cases is potentially preventable by the use of the currently available polysaccharide vaccine, which induces protection against serogroups, A, C, Y, and W135 and is effective only for persons > 2 years of age . Actions Taken: Current recommendations against the use of sulfa drugs for treatment or prophylaxis of meningococcal disease unless the organism is known to be sensitive to sulfa should be continued . Since resistance to rifampin is rarely reported, it continues to be the drug of choice for prophylaxis . The development of vaccines effective for infants and vaccines inducing protection against serogroup B would be expected to have a substantial impact on disease.

J Infect Dis, 1993 Jun, 167(6), 1320 - 9
Antigenic and epidemiologic properties of the ET-37 complex of Neisseria meningitidis; Wang JF et al.; A special collection of 336 Neisseria meningitidis strains was established that spanned the genetic variability, as defined by multilocus enzyme electrophoresis, of the ET-37 complex (228 strains isolated in different continents between the 1960s and the 1980s) and of other serogroup C meningococci (108 strains) . Of the strains in the ET-37 complex, 90% were serogroup C and 10% were serogroup B . Most ET-37 complex strains were serotype 2a and serosubtype P1.5,2 or P1.5,y; most expressed class IIb pilin . Twenty-six Opa proteins differing in electrophoretic mobility or reactivity with monoclonal antibodies were variably expressed by different members of the ET-37 complex, although only four opa genes were detected in individual strains . Despite this overall diversity, most isolates from any one outbreak were fairly homogeneous.

J Infect Dis, 1993 Jun, 167(6), 1314 - 9
Cross-reacting serum opsonins to meningococci after vaccination; Guttormsen HK et al.; The opsonic activity of sera from healthy volunteers immunized with an outer membrane vesicle vaccine prepared from a Neisseria meningitidis (class 3, 44/76, B:15:P1.7,16), characteristic of the present Norwegian epidemic, has been examined . A marked increase in the phagocytosis of class 3 and nontypeable strains of different serogroups, serotypes, and serosubtypes was demonstrated in the presence of postvaccination sera . Sera from vaccinees also caused a significant increase in leukocyte oxidative metabolism as measured by luminol-enhanced chemoluminescence during phagocytosis of class 3 and nontypeable meningococci . An increase in serum opsonins cross-reacting with class 2 (type 2a) meningococci of different serogroups was not observed, suggesting that future meningococcal outer membrane vesicle vaccine preparations should contain both class 2 and class 3 porins in geographic areas where both class 2 and class 3 strains cause disease.

Int J Dev Biol, 1993 Jun, 37(2), 327 - 36
Expression of polysialylated neural cell adhesion molecule (PSA-N-CAM) in developing, adult and regenerating caudal spinal cord of the urodele amphibians; Caubit X et al.; The patterns of expression of polysialylated ("embryonic") form of Neural Cell Adhesion Molecule (PSA/E-N-CAM) and of all N-CAM isoforms were investigated by indirect immunofluorescence and immunoblotting during the development of the Central Nervous System (CNS) and during the regeneration of the caudal Spinal Cord (SC) of the amphibian urodeles Pleurodeles waltl (Pw) and Notophthalmus viridescens (Nv) . In this study, a monoclonal antibody to group B Meningococcus (anti-Men-B) which recognizes alpha-2,8-linked sialic units of PSA-N-CAM, and polyclonal anti-total N-CAM antibodies were used . Total-N-CAM immunoreactivities were consistently detected throughout the CNS of developing and adult newts . PSA-N-CAM expression predominated in "embryonic" developing CNS and was reduced to certain CNS areas in the adult urodeles . In the case of SC, the expression level of this isoform of N-CAM dramatically decreased to become low and nearly restricted to some ependymoglial cell surfaces . Interestingly, during newt tail regeneration, PSA-N-CAM was intensely reexpressed in regenerating SC, at the surface of ependymoglial cell processes and in axonal compartments . Expression was maximal at 4 to 6 weeks following amputation, and then gradually returned to a normal adult low level in well differentiated SC . These findings strongly supported the view that the expression of PSA-N-CAM was associated with the properties of plasticity shown by the SC ependymoglial tissue in newts, during tail regeneration . On the other hand, the high level of PSA-N-CAM expression in axonal compartments of regenerating as well as developing SC suggested that these isoforms of N-CAM could be implicated in axonal outgrowth within the "tunnels" defined by the radial ependymoglial processes . This transient PSA-N-CAM expression could therefore be considered both as a negative modulator of cell-cell and cell-substrate interactions and as a permissive factor for neuron differentiation.

Crit Care Nurse, 1993 Jun, 13(3), 71 - 6
Epidural sympathetic blockade to relieve vascular insufficiency in an infant with purpura fulminans; Chiafery MC et al.; The patient in septic shock who develops vascular insufficiency secondary to purpura fulminans is a challenge to the healthcare team . Initial management is directed toward reversing the disease process by administering antibiotics immediately and initiating life-support measures . Emergency measures include optimizing oxygenation and ventilation, reestablishing and/or maintaining circulation and end-organ perfusion and correcting electrolyte imbalances and coagulopathies . After the emergent life-saving needs of the patient have been addressed, attention may be directed toward saving extremities . Epidural sympathetic blockade proved to be successful as an essential adjunctive intervention in preserving the lower extremities of our patient . We encourage other healthcare providers to consider this treatment to help decrease the morbidity of vascular insufficiency secondary to meningococcal purpura fulminans.

FEMS Microbiol Lett, 1993 Jun 1, 110(1), 51 - 7
Identification of two major families of transferrin receptors among Neisseria meningitidis strains based on antigenic and genomic features; Rokbi B et al.; The transferrin receptor or transferrin-binding proteins (Tbps) of 50 strains of Neisseria meningitidis belonging to different serogroups were examined by Western blotting using two rabbit antisera raised against Tbp purified from N . meningitidis strains B16B6 and M982 . On the basis of the reactivity of Tbp2 with the antisera two patterns were observed and allowed the classification of 74% of the strains in group I (M982-like strains) and 26% in group II (B16B6-like strains) . Southern blot analysis was performed on the genomic DNA of 16 meningococcal strains and showed that under stringent conditions, the tbp2 probes were specific for each group identified . Both immunological and genomic analyses have led to the identification within N . meningitidis strains of two major families distinguished on the basis of the characteristics of Tbp2 molecules, independently of serogroup, type or subtype.

Scand J Immunol, 1993 Jun, 37(6), 644 - 50
Antibody response to meningococcal polysaccharides A and C in patients with complement defects; Biselli R et al.; Patients with defects of terminal complement components are particularly exposed to the risk of developing neisserial infections and seem to respond poorly to meningococcal capsular polysaccharide (PS) C via natural immunization . The sole meningococcal PSC is, on the other hand, an excellent immunogen in normal people . Considering the great importance of vaccine prophylaxis for the prevention of meningococcal infections in patients with complement defects, it is crucial to study the antibody response to the sole meningococcal PS in these patients . We therefore analysed the levels of anti-PSA and PSC antibodies in the members of four families including patients with homozygous and heterozygous defects of C7, C8 or factor H, before and after vaccination with the sole PSA + C . Surprisingly, we found the highest levels of antibodies before vaccination in homozygous subjects, followed by heterozygous and normal controls, whereas, after vaccination, homozygous subjects showed the lowest increase of specific antibodies, indicating their relative incapability to respond to sole meningococcal PS . In conclusion, this study demonstrates (1) the capacity to respond to meningococcal PS via natural immunization by patients with total complement defects, and (2) the low responsiveness to meningococcal PS via vaccine immunization by the same patients . We propose that vaccination should be given to patients lacking specific antibodies and their serological response should be assessed . In addition this study confirms previous observations on a likely lower immunogenic power of meningococcal serogroup C via natural immunization compared with the better immunogenicity of the sole PSC.

Rev Saude Publica, 1993 Jun, 27(3), 221 - 6
{Immune response to anti-meningococcal vaccines}; Milagres LG et al.; In view of a recent epidemic of meningococcal disease caused by serogroup B N . meningitidis in the Greater S . Paulo area (Brazil), a review of the epidemics that occurred in Brazil during the period from 1900 to 1990 is presented . The current status of vaccines against N . meningitidis A.C.Y . and W135 is analysed . The recent advances in the development and effectiveness of B . meningococci vaccines are discussed.

BMJ, 1993 May 8, 306(6887), 1229 - 32
Rapid diagnosis of acute meningococcal infections by needle aspiration or biopsy of skin lesions; van Deuren M et al.; OBJECTIVES--To evaluate the usefulness of Gram staining and culture of skin lesions in patients with acute meningococcal infections . DESIGN--Retrospective study . SETTING--Community hospital and intensive care unit of a teaching hospital . SUBJECTS--51 patients admitted from 1989 to 1993 with proved meningococcal infections and microbiological examination of specimens from skin lesions . INTERVENTIONS--Needle aspiration of a skin lesion before start of antibiotic treatment in 26 patients in the community hospital; punch biopsy of skin lesion after start of antibiotic treatment in 25 patients in the teaching hospital . MAIN OUTCOME MEASURES--Detection of meningococci by Gram staining of specimens from skin lesions according to category of infection (meningococcaemia, meningitis, meningitis with shock, or septic shock without meningitis) . RESULTS--Bacteria were detected in the specimen from haemorrhagic skin lesions by culture or Gram staining, or both in 32 (63%) patients . The sensitivity of the Gram stain was 51% and did not differ significantly from its sensitivity in detecting bacteria in cerebrospinal fluid . In meningococcal sepsis, however, a Gram stained skin lesion was significantly more sensitive (72%) than Gram stained cerebrospinal fluid (22%) . In patients with meningitis skin lesions gave positive results on staining more often if shock was present . The results for punch biopsy specimens were not affected by antibiotics as Gram staining gave positive results up to 45 hours after the start of treatment and culture gave positive results up to 13 hours . CONCLUSION--Microbiological examination of skin lesions is informative, especially in patients with sepsis and inconclusive results from cerebrospinal fluid, and may provide a diagnosis in such patients within 45 minutes . It differentiates well between meningitis with and without haemodynamic complications, and the result is not affected by previous antibiotic treatment.

J Infect, 1993 May, 26(3), 245 - 52
Cerebrospinal fluid lactate in meningitis and meningococcaemia; Cameron PD et al.; Cerebrospinal fluid (CSF) lactate values were measured in 26 children with meningitis (12 bacterial, 9 aseptic, 5 partially treated) and five children with meningococcaemia without meningitis . A reference range (0.5-3.2 mmol/l) was established from 100 control children . Amounts of lactate were significantly raised in bacterial meningitis (mean 6.5, range 4.5-10.2) compared with aseptic meningitis (mean 2.6, range 1.1-4.0) but this finding gave little practical help as the bacterial origin of the meningitis was clear from other CSF findings . High values (5.7) in a case of tuberculous meningitis (TBM) suggest that the test may be helpful when other CSF findings are inconclusive . Unless the CSF lactate is raised, the test is of minimal value in partially treated meningitis (mean 3.4, range 1.4-6.2) . The previously unobserved finding of increased CSF lactate in meningococcaemia without meningitis (mean 3.9, range 3.1-5.0) supports the view that raised CSF lactate values in bacterial meningitis are not solely due to the presence of neutrophils . Literature relating to CSF lactate is reviewed.

J Infect Dis, 1993 May, 167(5), 1212 - 6
Decline in meningococcal antibody levels in African children 5 years after vaccination and the lack of an effect of booster immunization; Ceesay SJ et al.; Antibodies to group A meningococcal polysaccharide were measured by hemagglutination (HA) and by ELISA in sera obtained from Gambian children before vaccination and 3 weeks, 2 years, and 5 years after vaccination with a group A + group C meningococcal capsular polysaccharide vaccine . Children were 1-4 years old at the time of vaccination . Most showed a good initial response to vaccination, including those aged 1-2 years . However, antibody titers declined progressively during follow-up, and 5 years after vaccination, antibody titers measured by both HA and ELISA had returned to prevaccination levels . This decline was not influenced significantly by a booster dose of vaccine given 2 years after initial immunization . Administration of malaria chemoprophylaxis reduced the rate at which antibody levels fell after initial immunization . Sustained protection of children against group A meningococcal disease will require the development of vaccines that are immunogenic in infants and that can induce T cell memory.

J Infect Dis, 1993 May, 167(5), 1065 - 73
The 5C protein of Neisseria meningitidis is highly immunogenic in humans and induces bactericidal antibodies; Rosenqvist E et al.; The 5C protein is expressed by the strain of Neisseria meningitidis (44/76) used for production of the Norwegian meningococcal group B outer membrane vesicle vaccine and is included in the final formulation of this vaccine . The immunoglobulin G antibody response to 5C stimulated by vaccination, systemic meningococcal disease, and carriage was measured using ELISAs with synthetic liposomes as antigen and by immunoblotting . Increased levels of IgG were found in paired sera from all three groups . The antibodies were bactericidal to meningococci of serogroups A and B that expressed large amounts of 5C but not to meningococci expressing smaller amounts . There was a linear correlation between bactericidal titer and units of IgG to 5C.

Crit Care Med, 1993 May, 21(5), 706 - 11
Coagulopathy as a predictor of outcome in meningococcal sepsis and the systemic inflammatory response syndrome with purpura; McManus ML et al.; OBJECTIVE: To identify simple, contemporary predictors of both morbidity and mortality in pediatric patients with purpuric sepsis syndrome in order to provide a basis for future study of innovative interventions . DESIGN: Retrospective study . SETTING: An 18-bed multidisciplinary intensive care unit (ICU) in a large pediatric hospital . PATIENTS: A total of 53 patients, ranging in age from 18 days to 17 yrs (mean 4.9 yrs) with either culture-proven meningococcal sepsis or the systemic inflammatory response syndrome with purpura, who were admitted to the ICU during the period from January 1, 1982 through March 15, 1992 . METHODS: A computerized database was constructed containing the characteristics of these patients at presentation, during the first 24 hrs of hospitalization, and on discharge . Single variables were screened for significance between "good" (intact survival) and "poor" (mortality or survival with significant morbidity) outcome groups . Those variables found to be most significant were then tested for sensitivity, specificity, and predictive value . The best predictors identified in this manner were then compared with the two most-cited prognosticating strategies as applied to these patients . MEASUREMENTS AND MAIN RESULTS: Coagulopathy (defined as a partial thromboplastin time > 50 secs or serum fibrinogen concentration < 150 mg/dL {4.4 mumol/L}) at the referral site or on ICU admission was identified as an excellent predictor of poor outcome: sensitivity, specificity, positive and negative predictive values of a low serum fibrinogen value, being 81%, 95%, 93%, and 88%, and of prolonged partial thromboplastin time, being 95%, 90%, 86%, and 97%, respectively . Classical prognosticating strategies were found to be inadequately associated with mortality, yet comparable with coagulopathy in identifying patients destined for clinically important morbidity . CONCLUSIONS: We conclude that: a) outcome of pediatric patients with meningococcal sepsis or the systemic inflammatory response syndrome with purpura can be predicted rapidly, more easily, and with overall accuracy superior to classical prognostication strategies by the simple presence or absence of coagulopathy; b) when applied to a contemporary population, classical prognostication strategies lack value for prediction of mortality, yet remain valid for prediction of "poor outcome" (significant morbidity + mortality); c) when evaluating treatment strategies for such patients, the presence of serious coagulopathy may potentially be useful as an index of illness severity.

Infect Immun, 1993 May, 61(5), 1873 - 80
Preparation, characterization, and immunogenicity of meningococcal lipooligosaccharide-derived oligosaccharide-protein conjugates; Gu XX et al.; A method was developed for coupling carboxylic acid-containing oligosaccharides (OS) to proteins . An OS was isolated from Neisseria meningitidis group A strain A1 lipooligosaccharide (LOS) . This LOS has no human glycolipid-like lacto-N-neotetraose structure and contains multiple immunotypes, including L8, found in group B and C strains . The carboxylic acid at 2-keto-3-deoxyoctulosonic acid of the OS was linked through adipic acid dihydrazide to tetanus toxoid . The molar ratio of the OS to tetanus toxoid in three conjugates ranged from 11:1 to 19:1 . The antigenicity of the OS was conserved in these conjugates, as measured by an enzyme-linked immunosorbent assay (ELISA) and an inhibition ELISA with polyclonal and monoclonal antibodies to A1 LOS . These conjugates induced immunoglobulin G antibodies to A1 LOS in mice and rabbits . The immunogenicity of the conjugates in rabbits was enhanced by use of monophosphoryl lipid A plus trehalose dimycolate as an adjuvant . The resulting rabbit antisera cross-reacted with most of 12 prototype LOSs and with LOSs from two group B disease strains, 44/76 and BB431, in an ELISA and in Western blotting (immunoblotting), which revealed a 3.6-kDa reactive band in these LOSs . The rabbit antisera showed bactericidal activity against homologous strain A1 and heterologous strains 44/76 and BB431 . These results indicate that conjugates derived from A1 LOS can induce antibodies against many LOS immunotypes from different organism serogroups, including group B . OS-protein conjugates derived from meningococcal LOSs may therefore be candidate vaccines to prevent meningitis caused by meningococci.

Mol Microbiol, 1993 May, 8(5), 891 - 901
The role of galE in the biosynthesis and function of gonococcal lipopolysaccharide; Robertson BD et al.; Lipopolysaccharide is an essential component of the outer membrane of Gram-negative bacteria and an important virulence factor of many pathogens, such as Neisseria gonorrhoeae . We have cloned the gonococcal galE gene which was found to be located in the gonococcal homologue of the meningococcal capsule gene complex region D . Sequence alignment indicated extensive homology with the Escherichia coli and Salmonella GalE proteins . Mutants with insertions in the galE gene were used as a tool to characterize the structure and function of gonococcal lipopolysaccharide . They displayed deep rough phenotypes, and chemical analysis confirmed the loss of galactose from the mutant lipopolysaccharide . Functional analysis indicated that the terminal oligosaccharides contain galactose and that these are lost in galE mutants . The importance of these oligosaccharides in gonococcal biology is clear from the fact that they contain the epitopes that are the targets for killing by normal human serum, and the acceptor site for sialic acid, which acts to protect the gonococcus from this killing . Furthermore, infection experiments in vitro indicate that the galE mutants exhibit unaltered intergonococcal adhesion as well as adhesion to, and invasion of, epithelial cells.

Zhonghua Yu Fang Yi Xue Za Zhi, 1993 May, 27(3), 160 - 1
{Changes in epidemic features of epidemic cerebrospinal meningitis after vaccination with purified meningococcal polysaccharide vaccine group A in Zhengzhou}; Wiu JJ; The authors studied the epidemic features of epidemic cerebrospinal meningitis before and after mass vaccination with Purified meningococcal polysaccharide vaccine group A . After the mass vaccination, the morbidity rate of epidemic cerebrospinal meningitis fell considerably year after year . The epidemic cycle changed for the first time . The ratio of the number of cases in the city to those in the countryside was reduced . The phenomenon that the infectious disease spread along traffic lines from city to countryside disappeared . The cases mainly occurred in the remote mountain village . The morbidity rate in the group of 0-3 years relatively increased . The level of antibody titers in population obviously increased . The carrier rate of meningococci and constituent ratio of group A reduced . The epidemic group was group A, but cases of group C occurred for the first time.

Riv Eur Sci Med Farmacol, 1993 May-Aug, 15(3-4), 127 - 9
Use of antigenic markers and genomic fingerprinting to study epidemiology of meningococcal disease; Falk ES; The usefulness of the restriction enzyme fingerprinting was investigated for epidemiological studies of meningococci isolated from three patients who fell ill in meningococcal disease within a short period of time . The strains belonged to serogroup B and had similar serotype patterns . Epidemiological connections could not be excluded but genomic fingerprinting showed that the strains were probably of different origin . It is concluded that genomic fingerprinting is a potential and sensitive tool for epidemiological studies.

Br J Plast Surg, 1993 Apr, 46(3), 243 - 6
The management of skin infarction after meningococcal septicaemia in children; Hudson DA et al.; The clinical course and management of 21 children (12 females, 9 males; mean age 2.4 years) with skin necrosis secondary to meningococcal septicaemia is described . Skin necrosis was most commonly sited in the lower limbs (20 patients) . Sixteen patients had multiple areas of involvement and amputation of the digits was required in 5 patients . One required an above knee amputation . Small areas of skin necrosis were managed conservatively (4 patients) but larger areas required debridement and grafting . Skin grafting was delayed in 15 patients and graft loss occurred in 8 . Multiple grafting procedures were required in 6 patients . Scar revision was required in 6 patients . Nutritional support is also an important component of management.

Scand J Immunol, 1993 Apr, 37(4), 487 - 9
Low prevalence of complement deficiencies among patients with meningococcal disease in Norway; Hogasen K et al.; Sera from 98 individuals who had survived meningococcal disease were analysed for classical and alternative pathway haemolytic activity and the complement components C3, C4 and properdin . No complete deficiency was found . However, median properdin concentration was only 86% in the disease group compared with the controls (P < 0.001) . Properdin was also significantly lower in serogroup C disease (median 76%) compared with serogroup B disease (median 90%, P = 0.005) . Severe properdin deficiency is an established risk factor for meningococcal disease . The present data may indicate that even moderately reduced properdin level can increase the risk of developing meningococcal disease.

Scand J Immunol, 1993 Apr, 37(4), 468 - 70
A low serum concentration of mannan-binding protein is not associated with serogroup B or C meningococcal disease; Garred P et al.; The mammalian C-type serum lectin, mannan-binding protein (MBP), may induce C1q- and antibody-independent activation of the classical pathway of complement . Accordingly, MBP is considered as a member of the complement system . Complement deficiencies have been found with increased frequency in patients with meningococcal disease . Therefore, we investigated the MBP levels in patients with meningococcal disease . Ninety-nine Norwegian individuals (age 12-21 years) who survived severe systemic disease caused by serogroup B or C meningococci were investigated . No significant differences were observed in the MBP concentration between patients with serogroup B (n = 76) or C (n = 25) disease and healthy blood donor controls (n = 40) (P > 0.05) . The frequency of patients with low levels of MBP (< 100 micrograms/l) was 10.1% . This was not different from controls (12.5%) . Thus, low MBP concentrations do not appear to predispose to serogroup B or C meningococcal disease.

Infect Immun, 1993 Apr, 61(4), 1474 - 81
Complement component C5 modulates the systemic tumor necrosis factor response in murine endotoxic shock; Barton PA et al.; Patients with disseminated Neisseria meningitidis infections (meningococcemia) suffer from a fulminant shock syndrome that is accompanied by extraordinarily high concentrations in serum of tumor necrosis factor (TNF) . People with homozygous deficiencies of late complement components (C5, C6, C7, and C8) experience a high incidence of disseminated neisserial infections yet suffer from an attenuated form of the disease . The mechanisms that account for this disparity in host response are unclear, but they may in part be related to differences in the systemic TNF response that are modulated by terminal complement components (C5 to C9) . The role of C5 in the modulation of the systemic endotoxin-induced TNF response was studied with matched strains of C5-deficient (B10 D2/Osn) and complement-sufficient (B10 D2/Nsn) mice . Following lipopolysaccharide (LPS) administration, complement-sufficient mice exhibited more rapid increases in pulmonary and hepatic vascular permeabilities than did C5-deficient controls . Complement-sufficient mice developed acute passive hepatic congestion, they appeared more ill than C5-deficient mice, and they exhibited a twofold greater rise in serum TNF activity compared with that by C5-deficient mice . C5-deficient mice reconstituted with normal serum before an LPS injection exhibited pulmonary and hepatic vascular permeability increases and serum TNF levels approaching those observed in complement-sufficient mice . Alveolar and peritoneal macrophages isolated from complement-sufficient and C5-deficient mice and incubated in heat-inactivated serum did not exhibit differences in TNF mRNA expression or secreted TNF activity following stimulation with LPS . However, incubation of macrophages in complement-sufficient mouse serum (before LPS stimulation) resulted in increased TNF mRNA expression and TNF activity compared with those in cells incubated in C5-deficient serum . In vitro studies employing human complement components and peripheral blood monocytes revealed that recombinant C5a, in the presence or absence of LPS, can induce increased concentrations of TNF and that C5b to C9 had no additional modulatory effect on the TNF response . These data suggest that C5 modulates the endotoxin-triggered TNF response . The role of complement components distal to C5 (i.e., C5b to C9) in the endotoxin-triggered TNF response remains unclear.

Microb Pathog, 1993 Apr, 14(4), 315 - 27
Distribution of a lipooligosaccharide-specific sialyltransferase in pathogenic and non-pathogenic Neisseria; Mandrell RE et al.; Sialyltransferase activity has been detected in Triton X100 extracts of all examined strains of pathogenic Neisseria as well as in 17 out of 18 Neisseria lactamica isolates . The enzyme was detected both in strains able to synthesize the 4.5 kDa lipooligosaccharide (LOS) component known to be sialylated in vivo and in vitro by cytidine 5'-monophospho-N-acetylneuraminic acid, and in some strains which lack this component . Exogenous 4.5 kDa+ LOS was required to detect the sialyltransferase activity in strains which lacked the LOS component . Sialyltransferase activity in a serogroup A, L11 (4.5 kDa-) meningococcal strain sialylated exogenous purified LOS from gonococci . The meningococcal serogroup B and C strain sialyltransferases active with LOS acceptors appeared to be distinct from the sialyltransferase required for the synthesis of the meningococcal polysialic acid capsule.

Turk J Pediatr, 1993 Apr-Jun, 35(2), 87 - 91
Comparative therapeutic results of penicillin plus chloramphenicol versus ampicillin plus sulbactam in childhood meningococcemia; Kanra G et al.; Fifty-seven cases of meningococcemia were evaluated retrospectively . The age of the patients ranged between 2 and 17 years . Of the 57 patients investigated for the efficacy of antibiotic treatment, 31 (54.4%) were treated with benzylpenicillin plus chloramphenicol and 26 (45.6%) with ampicillin plus sulbactam . Patients with criteria for a poor prognosis (presence of disseminated intravascular coagulation, low arterial blood pressure, and altered consciousness) were divided equally into two treatment groups . There were no statistically significant differences between the two treatment groups except for the higher incidence of convulsion in the group given penicillin plus chloramphenicol . The mortality rate was 19.3 percent for patients treated with benzylpenicillin plus chloramphenicol and 7.6 percent for patients treated with ampicillin plus sulbactam (p = 0.19; overall mortality rate 14%).

Roum Arch Microbiol Immunol, 1993 Apr-Jun, 52(2), 121 - 9
Bacteriological study of Neisseria strains isolated in Romania 1971-1992; Levenet I et al.; 1496 Neisseria strains isolated from patients and carriers from 24 counties in Romania and Bucharest in 1971-1992 were studied . Serogroup A identified in 84.5% in 1987 shows a remarkable decrease in pre- and post-epidemic periods when serogroups B and C reach rates varying from 0 to 66.6% in 1975 for B and 38.8% in 1974 for C . Non-groupable strains were more frequently isolated in inter-epidemic periods, especially in carriers . Sensitivity to antibiotics of the meningococcal strains revealed a law rate of resistant strains, the most active antibiotics in decreasing order being: penicillin, chloramphenicol, tetracycline, ampicillin, rifampicin and erythromycin . Serogroup A was the most resistant to sulfamides as compared to the other serogroups, its resistance rate rising from 18.1% strains resistant to sulfathiazole in 1980-1985 to 60.7% in 1987 and to 83.3% in 1988.

J Infect Dis, 1993 Apr, 167(4), 966 - 70
The immune response of children to meningococcal lipooligosaccharides during disseminated disease is directed primarily against two monoclonal antibody-defined epitopes; Estabrook MM et al.; A human inhibition monoclonal ELISA (HIMELISA) was used to investigate the immune response of infants and children to meningococcal lipooligosaccharide (LOS) . Convalescence from disseminated meningococcal disease significantly increased the inhibition by sera of monoclonal antibody (MAb) binding to two of six defined epitopes on the LOS of meningococcal strain 126E, a strain previously shown to express immunogenic LOS epitopes . The inhibited epitopes were defined by MAbs D6A and 6B7, and both were expressed on the 3.6-kDa LOS of strain 126E . The inhibition of the binding of both MAbs by the convalescent sera was similar to that from children who were meningococcal carriers and greater than that by sera obtained from healthy children . These results support the conclusion that the 3.6-kDa LOS molecule of strain 126E expresses two conserved epitopes that are immunogenic in infants and children; this LOS may serve as a vaccine candidate.

Schweiz Med Wochenschr, 1993 Mar 20, 123(11), 480 - 91
{Cytokines and antagonists in septic shock}; Girardin E et al.; During septic shock, cytokines produced by host cells play an important role in the pathogenesis of hemodynamic involvement and cellular lesions . Recently, natural inhibitory substances able to neutralize the biological activity of tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) were described . These inhibitory molecules are involved in the regulation of the production of these cytokines . Thus, an understanding of these mechanisms could lead to new treatments for septic shock . A review of the interactions of TNF alpha with macrophages, neutrophils and endothelium underlines the key role of TNF alpha in 3 important events of septic shock: neutrophil adherence to endothelium, capillary leak syndrome, and development of disseminated intravascular coagulopathy . In clinical studies, circulating TNF alpha concentrations were elevated and correlated with the severity of the disease . Soluble TNF receptors (TNF-sRI and TNF-sRII) neutralize the biological effect of TNF alpha . Their circulating levels are also increased in meningococcemia, but an imbalance between TNF alpha and TNF-sR was found at the beginning of the disease which could determine the severity of the shock in these patients . The IL-1 system is composed of IL-1 alpha and IL-1 beta, two forms of precursors, two distinct receptors, two soluble fragments of the extramembranous regions of these receptors, and a natural antagonist of IL-1 receptors (IL-1 ra) which could be secreted or remain intracellular . IL-1 ra improved the outcome in some experimental diseases (endotoxemic shock, cerebral malaria arthritis, graft-versus-host reaction) . The treatment of septic shock with IL-1 ra is currently being assessed in phase I and II clinical studies . Blockade of cytokines by antibodies or naturally occurring inhibitory molecules could lead to new therapies for septic shock.

J Immunol Methods, 1993 Mar 15, 160(1), 35 - 47
Selective biotinylation of Neisseria meningitidis group B capsular polysaccharide and application in an improved ELISA for the detection of specific antibodies; Diaz Romero J et al.; A method is described for the selective biotinylation of meningococcal capsular polysaccharide from Neisseria meningitidis group B and its application to an enzyme-linked immunoabsorbent assay (ELISA) to detect specific antibodies by immobilization on streptavidin-coated microtiter wells . Capsular polysaccharide from Neisseria meningitidis B has been biotinylated by specific periodate oxidation of terminal residues and condensation of the resulting aldehydes with biotin hydrazide, using a spin-column technique in the intermediate purification steps . The ELISA was optimized employing an extended reaction time between the label alkaline phosphatase and its most common substrate, p-nitrophenyl phosphate, together with evaluation of blocking agents to minimize non-specific binding . Specificity was demonstrated by a direct competitive enzyme immunoassay (EIA).

APMIS, 1993 Mar, 101(3), 201 - 6
Homology between cryptic plasmid from Neisseria gonorrhoeae and genomic DNA from Neisseria meningitidis; Grimholt U et al.; The human pathogenic Neisseria species N . gonorrhoeae and N . meningitidis are closely related . In contrast to N . meningitidis, however, almost all clinical isolates of N . gonorrhoeae harbour a phenotypically cryptic plasmid . In some gonococcal strains regions of the cryptic plasmid have been found in the gonococcal genome and it has been suggested that large segments of the cryptic plasmid can be integrated into the gonococcal chromosome of both plasmid-bearing and plasmid-free strains . Here we report homology between parts of the cryptic gonococcal plasmid and genomic DNA from four different N . meningitidis strains from systemic disease isolates in which no plasmids have been found with the applied methods . Serogroup B strains, causing many of the cases of meningococcal disease in Norway, hybridized strongly to the cryptic plasmid probe, in contrast to serogroup A and C strains . Clones hybridizing to the cryptic plasmid were isolated from a meningococcal genomic lambda EMBL3 DNA library and characterized by restriction mapping . When using one such clone as a probe the parts of the cryptic plasmid showing homology to the genomic meningococcal DNA were confined to two small separate regions of 420 and 88 bp.

J Burn Care Rehabil, 1993 Mar-Apr, 14(2 Pt 1), 155 - 7
Acute adrenal insufficiency in the patient with burns; Murphy JF et al.; Acute adrenal insufficiency is an uncommon but devastating complication of severe burn injury . The diagnosis is rarely made antemortem . Acute, fatal, adrenal insufficiency developed in three patients among 807 critically ill patients with burns treated at this institution during the past 6 years . Thermal injuries elevate corticosteroid secretion for weeks after injury, severely stressing the adrenal glands . Overload of the hypothalamic-pituitary-adrenal axis is thought to make this system unusually vulnerable to acute infarction . Although the actual mechanism of adrenal hemorrhage is not clear, the combination of excessive adrenocorticotropic hormone stimulation and hemodynamic instability have been implicated in its evolution . Survival may be too short for characteristic Addisonian metabolic changes to develop . Acute adrenal insufficiency is a rare event that is historically associated with meningococcemia, although any life-threatening illness may precipitate this catastrophe . Therefore, when a sudden deterioration in the patient with thermal injuries is encountered, adrenal insufficiency must be considered.

FEMS Microbiol Lett, 1993 Mar 1, 107(2-3), 191 - 7
A NheI macrorestriction map of the Neisseria meningitidis B1940 genome; Bautsch W; A macrorestriction map of the Neisseria meningitidis strain B1940 genome was constructed by two-dimensional pulsed-field gel electrophoresis (2D-PFGE) techniques . Digestion of the genomic DNA with the restriction endonuclease NheI revealed 15 fragments between 10 kb and 450 kb . The sum of the fragments and resolution of the linearized chromosome yielded a total genome size of about 2.3 Mbp . By overlapping methylation with the AluI-methylase six NheI recognition sites could be blocked . Fragments were ordered by partial/complete 2D-PFGE of genomic DNA with and without prior AluI methylation, respectively . All nine AluI-methylase/NheI and 14 NheI restriction sites could be mapped on a single circular chromosome . This map will serve as a useful tool for further genetic analysis of meningococci and exemplifies the power of non-radioactive 2D-PFGE techniques to construct large physical genome maps with a single restriction enzyme.

Microbiol Rev, 1993 Mar, 57(1), 34 - 49
Meningococcal lipopolysaccharides: virulence factor and potential vaccine component; Verheul AF et al.; Lipopolysaccharides (LPS) are surface components of the outer membrane of Neisseria meningitidis . Today, 12 different types of meningococcal LPS (immunotypes) are known, of which 3 are prevalent in the western world . The differences between these immunotypes are in the oligosaccharide part of the LPS molecule and consist of small differences in the oligosaccharide structure, the amount and location of phosphoethanolamine groups, and the degree of O acetylation of individual monosaccharides . Although the differences between the various immunotypes are small, they have a profound influence on the immunochemical and immunological properties of these molecules . Furthermore, each individual strain synthesizes a number of different LPS molecules . The expression of the various components (protective epitopes) is influenced by growth conditions and growth phase . Meningococci can endogenously sialyate their LPS, which constitutes one of the mechanisms by which N . meningitidis can evade the response of the human host . Meningococcal LPS play a key role in the induction of septic shock and can probably enhance the invasiveness of meningococcal strains and shield protective epitopes . Therefore, incorporation of (detoxified) LPS or oligosaccharide components derived therefrom might be very beneficial for the efficacy of a vaccine against group B meningococci . An overview of the development of vaccines against group B meningococci is given, and the status and potential of meningococcal LPS-derived (synthetic) oligosaccharide-protein conjugate vaccines are discussed.

Crit Care Med, 1993 Mar, 21(3), 447 - 52
Predictors of outcome in acute meningococcal infection in children; Algren JT et al.; OBJECTIVES: To develop a rapid and sensitive method for identification of patients at risk for organ system failure and death due to acute meningococcal infection, and to evaluate the reliability of the Pediatric Risk of Mortality score in predicting mortality rates from acute meningococcal infection . DESIGN: A prospective study which followed a retrospective analysis . SETTING: The Emergency Department and pediatric intensive care unit (ICU) of a university-affiliated children's hospital . PATIENTS: The hospital records of 86 pediatric patients with acute meningococcal infection during a 5-yr period (group 1) were reviewed . Twenty-two ICU patients (group 2) were then prospectively evaluated, and the occurrence rate of organ system failure was compared with that rate predicted by the model developed from the analysis of group 1 . INTERVENTIONS: The occurrence of prognostic factors was compared with the development of organ system failure and death by Fisher's exact test and logistic regression analysis for patients in group 1 . The mortality rates for groups 1 and 2 were compared with those rates that were predicted by the use of the Pediatric Risk of Mortality score . MAIN RESULTS: Eighteen of 86 patients in group 1 developed organ system failure, and seven (8.1%) patients died . Logistic regression analysis found that the combination of circulatory insufficiency, peripheral WBC counts of < 10,000 cells/mm3, and coagulopathy best predicted organ system failure . Ten of 22 patients in group 2 developed organ system failure, and two died . All patients with organ system failure exhibited > or = 1 of three identified prognostic factors . The probability of organ system failure occurring was > .5 for nine of ten patients with organ system failure . A total of nine patients in groups 1 and 2 developed multiple organ system failure, and all nine patients died . Based on Pediatric Risk of Mortality scoring, the mortality risk for nonsurvivors ranged from 27% to 94%, compared with 1% to 48% for survivors . The overall mortality rate was consistent with that rate predicted by the Pediatric Risk of Mortality scoring system . CONCLUSIONS: Patients with acute meningococcal infection who exhibit signs of circulatory insufficiency, a peripheral WBC count of < 10,000 cells/mm3, or a coagulopathy have a high probability of developing organ system failure . Death is highly probable when multiple organ system failure develops, and the overall mortality rate is accurately predicted by the Pediatric Risk of Mortality score.

Minerva Pediatr, 1993 Mar, 45(3), 123 - 6
{The persistence after clinical recovery and the suspension of therapy of altered ESR values in a case of meningococcal sepsis and septic shock}; Zecca G et al.; The paper describes a case of meningococcal sepsis and septic shock treated with Ceftriazone, Dexamethosone, plasma and heparin . It was observed that contrary to other hematological parameters, ESR levels remained high for one month after the suspension of antibiotic therapy and complete clinical recovery . The authors relate this alteration of ESR values to the administration of plasma during the acute phase of the disease.

Neurol Neurochir Pol, 1993 Mar-Apr, 27(2), 187 - 96
{Ultrastructural location of enzymes in peripheral blood neutrophils and in cerebrospinal fluid neutrophils in neuroinfections}; Skotarczak B; Using cytochemical methods the location and activity were determined of alkaline phosphatase, ATP-ase and succinate dehydrogenase as representative enzymes for the metabolic processes in neutrophils isolated from blood and cerebrospinal fluid (CSF) of patients with meningococcal meningoencephalitis as compared with peripheral blood neutrophils in a control group . The study showed presence of phosphatase on the membranes of many intracellular structures . The activity of the enzymes was higher than in the control group in the membranes of neutrophils in blood and CSF . This is explained as an effect of action of the chemotactic factor on the cell membrane and activation of the cell to movements and phagocytosis . ATP-ase activity in peripheral blood neutrophils in controls was found in all membranous structures in the cell . However, in peripheral blood neutrophils and CSF neutrophils in the acute stage of the disease the active enzyme was noted, in the first place, in cell membranes and digesting vacuoles, which reflected probably the direction of metabolic processes for phagocytosis and destroying of bacteria . The activity of succinate dehydrogenase was found in mitochondrial membranes . Peripheral blood and CSF neutrophils showed a high activity of the enzyme . In the CSF cells in acute phase atypical sites of succinate dehydrogenase activity were noted, which was explained as a sign of cell destruction.

Zh Mikrobiol Epidemiol Immunobiol, 1993 Mar-Apr, (2), 92 - 9
{The biochemical and immunochemical characteristics of the protein preparations obtained by different methods from a biomass of Neisseria meningitidis serogroup B}; Karabak VI et al.; Protein preparations containing group B N . meningitidis outer membrane peptides of classes 1 (44-47 kD), 2 (40-42 kD) and 5 (26-30 kD) have been obtained from the biomass of group B N . meningitidis, grown in a fermenter in a synthetic medium under the conditions of controlled cultivation with regulated oxygen content and the intermittent drainage and filling of the fermenter and with the use of different extraction methods (lithium chloride extraction by the method of C . E . Frasch et al.; sodium deoxycholate and potassium thiocyanate extraction) . The chemical composition of these preparations and their peptide content have been shown to depend on the method of extraction; the preparation containing the least amount of contaminating substances is obtained by extraction with potassium thiocyanate . High-molecular fractions of these protein preparations, studied by the method of immunoblotting, contain antigens cross-reacting with meningococcal sera, groups A and C.

Med J Aust, 1993 Mar 1, 158(5), 336 - 40
Epidemic meningococcal meningitis in central Australia, 1987-1991; Patel MS et al.; OBJECTIVE: To describe an outbreak of meningococcal meningitis and the impact of rifampicin chemoprophylaxis on secondary attack rates among Aboriginal people in central Australia . DESIGN: Prospective study of patients admitted to hospital between September 1987 and May 1991 . SETTING: The Alice Springs Health Region of the Northern Territory and the Anangu Pitjantjatjara Lands of South Australia, covering a population of 13,228 Aboriginal people . SUBJECTS: Patients admitted to the Alice Springs Hospital with clinical signs or autopsy findings of meningococcal disease . Rifampicin chemoprophylaxis was given to close contacts of all cases . Mencevax AC vaccine was offered to children aged 1 to 15 years in the Region . MAIN OUTCOME MEASURES: Blood or cerebrospinal fluid (CSF) with Neisseria meningitidis, or a positive result of latex agglutination testing on CSF . Positive isolates were serogrouped . RESULTS: Seventy-seven cases of meningococcal disease were diagnosed in Aboriginal people over four years compared with one to two cases per year previously; of these, 60 were definite, 7 probable and 10 suspected cases . Seventy-six subjects had meningitis, of whom one also had the clinical features of meningococcal septicaemia; one other subject had positive blood cultures with a mild febrile illness without features of meningitis . The annual attack rate of meningococcal disease in the Aboriginal population was 1.6/1000 . The relative risk for secondary cases was estimated to be between 0.3 (95% confidence interval {CI}, 0.09-0.92) and 0.5 (95% CI, 0.15-1.53) . The annual attack rate in the non-Aboriginal population was 0.04/1000 . CONCLUSIONS: The epidemic closely resembled those in sub-Saharan Africa, and in socioeconomically marginalised groups in developed countries . The relative risk for secondary cases was lower than generally reported, and was attributed to chemoprophylaxis for close contacts and the mass vaccination program for children . Until there are major improvements in living conditions, infectious diseases such as those transmitted by airborne droplets will continue to occur in Aboriginal communities.

Clin Infect Dis, 1993 Feb, 16(2), 237 - 46
Meningococcal disease in The Netherlands, 1958-1990: a steady increase in the incidence since 1982 partially caused by new serotypes and subtypes of Neisseria meningitidis; Scholten RJ et al.; In order to explain a threefold increase in the incidence of meningococcal disease in the Netherlands during the 1980s, we serotyped and subtyped Neisseria meningitidis isolates recovered between 1958 and 1990 from > 3,000 patients with systemic disease . No single strain could be held responsible for the increase . Apart from the newly introduced strain B:4:P1.4, which became the most prevalent phenotype in 1990 (21% of all isolates), the majority of the cases in 1990 were caused by many different strains that were already present in the Netherlands before 1980 . For the period 1980-1990, a shift in the age distribution of patients with meningococcal disease from younger to older age categories was found, particularly with regard to cases due to meningococci of serogroup B; this shift is explained by the changing distribution of serotypes and subtypes within serogroup B . A polyvalent group B, class 1 outer-membrane-protein vaccine of a stable composition could theoretically have prevented approximately 80% of all group B meningococcal infections in the Netherlands during the past 30 years.

J Bacteriol, 1993 Feb, 175(3), 811 - 8
Neisseria meningitidis produces iron-regulated proteins related to the RTX family of exoproteins; Thompson SA et al.; A monoclonal antibody (A4.85) which reacted with Fe-regulated proteins of Neisseria meningitidis, was used to isolate a lambda gt11 clone from N . meningitidis FAM20 . Chromosomal fragments flanking the fragment expressing the A4.85 epitope were cloned, and their DNA sequences revealed a 3,345-bp open reading frame predicting a 122-kDa protein . This gene was named frpA (Fe-regulated protein) . A computer similarity search of GenBank revealed high levels of similarity to members of the RTX family of cytotoxins, especially in a region of tandem 9-amino-acid repeats . These repeats are found in all members of the RTX family; similar repeats were present 13 times in the predicted FrpA protein . Antigenic relatedness between the meningococcal proteins and the RTX proteins was demonstrated by the reactivity of A4.85 with Escherichia coli hemolysin (HlyA) and Bordetella pertussis adenylate cyclase-hemolysin (CyaA) . Similarly, FrpA was recognized by 9D4, a monoclonal antibody directed against B . pertussis CyaA . In addition to the frpA gene, a second gene (frpC) produced a larger RTX-related protein . The frpA and frpC loci were mutagenized in strain FAM20, resulting in the loss of RTX-related proteins . A 120-kDa protein was expressed from the reconstructed frpA gene in E . coli . The biological function of FrpA is unknown, but its similarity to other RTX toxins suggests that it may play an important role in the pathogenesis of meningococcal infection.

Infect Immun, 1993 Feb, 61(2), 751 - 9
Localization of the meningococcal receptors for human transferrin; Ala'Aldeen DA et al.; The interaction between gold-labelled human transferrin (Au-HTF) with live meningococci after growth in vivo or in different in vitro conditions was examined by electron microscopy to localize and quantify the numbers of HTF-binding sites on the cell surface . It was clearly demonstrated that HTF binds to the surface of live meningococci (of different serogroups and serotypes) after growth in either iron-sufficient or iron-restricted cultures, although the degree of labelling was always higher (2- to 35-fold) in the latter case . The commensal Neisseria polysaccharea behaved similarly . Ultrathin sections showed that Au-HTF was localized predominantly on the outer membrane of the cells and vesicles, with hardly any internalization . Au-HTF labelling on meningococci was significantly reduced after incubation with unlabelled HTF or with rabbit antiserum containing antibodies against transferrin-binding proteins (TBPs), demonstrating the specificity of the interaction . These sera also blocked binding between HTF and outer membrane proteins on Western immunoblots . Direct evidence of the expression of the TBPs (Western blots) and localization of the HTF receptor (electron microscopy) on in vivo-grown meningococci was obtained from organisms derived without laboratory culturing from the cerebrospinal fluid of a patient . There was considerable cell-to-cell variation in the amount of labelling present on cells of the same sample (in vitro- or in vivo-grown organisms) and between different strains . The degree of binding varied with time of incubation of the cells with Au-HTF . The gold particles frequently formed discrete circles on the cell surfaces of the in vitro-grown organisms; these circles appear to be associated with outer membrane vesicle formation . The results show that the TBPs, which form part of the active components of the HTF receptor(s), are expressed in vivo and are surface exposed and immunogenic and that antibodies against them can interfere with the HTF binding of the meningococcal cells, which may affect iron utilization . This study further supports the concept of regarding the TBPs as future vaccine candidates.

J Infect Dis, 1993 Feb, 167(2), 471 - 5
Interleukin-8 in serum and cerebrospinal fluid from patients with meningococcal disease; Halstensen A et al.; To evaluate the role of interleukin (IL)-8 in meningococcal disease, a solid-phase double-ligand ELISA was used to quantitate IL-8 in sera and cerebrospinal fluid (CSF) from patients with meningococcal meningitis, bacteremia, or both with or without septic shock . IL-8 was demonstrated in sera from 28 of 62 patients; levels were significantly higher in patients with septic shock without meningitis (median, 36.1 ng/mL) than in patients with other manifestations (median, < 0.02 ng/mL), and 4 of 5 patients who died had high levels . IL-8 was detected in all 27 CSF samples . Serum IL-8 levels correlated highly significantly with those of IL-6 (r = .83) and tumor necrosis factor (TNF; r = .64), while the correlations between corresponding CSF levels were less pronounced (r = .43 and r = .38, respectively) but still significant . Serum IL-8 levels were highest in patients with a symptom history < 12 h . The elimination rate of IL-8 from serum varied and was similar to that of IL-6 and TNF . IL-8 appears to participate in the complex cytokine network during the initial phase of systemic meningococcal infections.

J Infect Dis, 1993 Feb, 167(2), 347 - 55
Pneumococcal capsular polysaccharide-meningococcal outer membrane protein complex conjugate vaccines: immunogenicity and efficacy in experimental pneumococcal otitis media; Giebink GS et al.; Vaccines composed of pneumococcal capsular polysaccharides (PS) conjugated to outer membrane protein complex (OMPC) from Neisseria meningitides group B bacteria were tested in the chinchilla otitis media model . Monovalent (types 6B and 23F), bivalent (6B+23F), and tetravalent (6B+14+19F+23F) PS-OMPC conjugate vaccines elicited significant total serum antibody responses against all four PS . Type 6B vaccine elicited IgG, IgM, and IgA antibodies after a single dose and an anamnestic IgG response after a second vaccine dose on day 28 . Type 6B and 19F vaccines prevented or greatly attenuated pneumococcal otitis media after direct middle ear challenge with the immunizing serotype, type 14 vaccine was not protective by this challenge route, and type 23F pneumococci were not sufficiently virulent in chinchillas to test vaccine effectiveness . The promising results with two serotypes suggest the PS-OMPC conjugates may be useful in human infants.

J Infect Dis, 1993 Feb, 167(2), 475 - 9
Effect of the (alpha 2-->8)-linked polysialic acid capsule on adherence of Neisseria meningitidis to human mucosal cells; Stephens DS et al.; The effect of (alpha 2-->8)-linked polysialic acid on the adherence of Neisseria meningitidis to human mucosal cells was examined using a serogroup B-encapsulated strain and a capsule-defective (Cap-) mutant of this strain . The Cap- mutant contains a single truncated insert of Tn916 in a 3.8-kb HaeIII chromosomal fragment . The Tn916 insert was shown to be responsible for the phenotype by linkage studies and by demonstration that loss of the insert restored encapsulation . The Cap- mutant consistently adhered to human buccal epithelial cell in greater numbers than the encapsulated parent, but the increase in adherence was less than twofold . Adherence of the Cap- mutant during infection of human nasopharyngeal organ cultures was 1.3- to 6.5-fold greater than that of the encapsulated parent . However, specificity of adherence of meningococci for nonciliated nasopharyngeal epithelial cells and the ability to be internalized by these cells was not due to the (alpha 2-->8)-linked polysialic acid capsule.

Curr Opin Pediatr, 1993 Feb, 5(1), 60 - 7
Immunizations in children; Nicoll A et al.; In 1992, there was a setback in measles vaccination for developing countries as high-titre vaccines were withdrawn following reports of excess mortality in vaccine recipients . The importance of continuing polio vaccination in industrialized countries was emphasized by an outbreak of paralytic polio among an unimmunized community in the Netherlands . Immunization programs are now increasingly using the Jeryl Lynn strain of mumps vaccine following reports of meningoencephalitis associated with the Urabe strain . A hepatitis A vaccine has become generally available and hepatitis B vaccine is being introduced into more childhood programs in countries where the disease is highly prevalent . Trials of group B meningococcal meningitis vaccines have yielded disappointing estimates of efficacy, particularly in younger children . Earlier reports of invasive bacterial infections after pertussis immunization have not been confirmed.

Pediatr Allergy Immunol, 1993 Feb, 4(1), 6 - 9
Systemic meningococcal infections in patients with acquired complement deficiency; Garty BZ et al.; Congenital deficiency of the late components of the complement may predispose the individual to systemic meningococcal infection . Assuming that patients with acquired complement deficiencies may also have an increased risk of contracting meningococcal infections, a retrospective and prospective study to assess this association was conducted . Over 20 years (1970-1989), 30 patients with meningococcemia or meningococcal meningitis, proven by blood or CSF culture, were treated at the Beilinson Medical Center . Only one patient died of the infection . Risk factors were found in three patients (10%) . One had a congenital deficiency of C7, and two had acquired complement deficiency due to systemic lupus erythematosus (SLE) and membranoproliferative glomerulonephritis (MPGN) . These latter two patients had low serum concentration of C3 and C4 and reduced complement hemolytic activity before onset of the infection . Since the incidence of culture-proven systemic meningococcal infection in the Jewish population in central Israel is 1/100,000, and the prevalence of SLE and MPGN is, at most, 250/100,000, the finding of two patients with meningococcal infection and these rare disorders is over 100 times the expected incidence . We conclude that patients with acquired complement deficiency are at significant risk of meningococcal infection.

Arch Fr Pediatr, 1993 Feb, 50(2), 111 - 7
{Value of dexamethasone in purulent meningitis in children . Apropos of a comparative study of 85 children}; Marguet C et al.; BACKGROUND . The beneficial effect of dexamethasone plus antibiotic therapy in bacterial meningitis is still controversial . PATIENTS AND METHODS . Eighty-five children, aged 1 month to 14 years, were admitted between 1987 and 1990 for bacterial meningitis . They received the same antibiotic therapy for 10 days (7 days in meningococcal meningitis) . The 44 children admitted since March 1989 were also given dexamethasone (0.15 mg/kg/6 hours for 4 days); the first injection was given before antibiotic therapy . Clinical (fever, neurological findings, audition) and laboratory data {CSF proteins, glucose, lactate, cell and bacterial counts; blood C-reactive protein (CRP), hemoglobin, leukocytes and platelets} were analyzed statistically . RESULTS . The group treated with antibiotics plus dexamethasone showed decreases significantly greater in CSF protein and lactate levels after 48 hours than the children given antibiotics alone and an early (6 hours after the start of treatment) increase in CSF glucose . The blood CRP level of the dexamethasone plus antibiotics group decreased significantly within 48 hours . The numbers of neurological sequelae and deaths in this group were clearly lower than for the antibiotic group, but the risk of deafness did not appear to be altered . CONCLUSIONS . These results confirm the beneficial effect of dexamethasone reported earlier . The relatively frequent transient recurrences of fever and increased CRP when dexamethasone was interrupted suggest that the dose and/or duration of dexamethasone treatment should be modified.

Pathol Biol (Paris), 1993 Feb, 41(2), 164 - 8
Risk factors for death in meningococcal disease; Olivares R et al.; Of 2.139 cases of meningococcal infections notified in France from 1985 to 1989, 10% died . The risk factors for death and for purpura fulminans (extensive purpuric rash associated with cardiovascular collapsus) were studied using multifactorial analysis . The purpura fulminans was the major risk factor for death (representing 22% of the cases and 77% of the deaths in our study) . In the absence of purpura fulminans, significant risk factors for death were: serogroup A or infrequent serogroup infection, an age over 50 years, and the occurrence of a septicaemia . In the presence of purpura fulminans, significant risk factors for death were an age under one year or over 10 years, and an infection with negative cultures from blood and cerebrospinal fluid . The main risk factor for purpura fulminans was the occurrence of septicaemia . Purpura fulminans appears to be a simple and specific clinical entity reflecting the high level of endotoxin released during meningococcal septicaemia.

Mol Microbiol, 1993 Feb, 7(4), 505 - 14
Class 1 outer membrane protein of Neisseria meningitidis: epitope analysis of the antigenic diversity between strains, implications for subtype definition and molecular epidemiology; McGuinness BT et al.; The VR1 and VR2 regions of the class 1 protein have been sequenced from a number of meningococcal strains, including non-subtypable strains and strains of apparently identical subtype . The amino acid sequences have been used to construct synthetic peptides for mapping subtype-specific epitopes . The majority of epitopes was found to be located in VR2 at the apex of a predicted surface-exposed loop . A single amino acid change within an epitope, or an amino acid deletion outside an epitope, were both associated with loss of subtype specificity, resulting from a change in the predicted conformation at the apex of the loop structure . Analysis of the sequence information combined with knowledge of defined epitopes also revealed considerable additional information not demonstrated by current subtyping procedures.

N Z Med J, 1993 Jan 27, 106(948), 3 - 6
Control of epidemic group A meningococcal disease in Auckland; Lennon D et al.; AIM . To study group A meningococcal vaccine delivery to infants less than 2 years of age in Auckland in 1987 to control epidemic disease . METHODS . Mechanisms of vaccine delivery and its facilitation are described . A detailed audit of delivery of vaccine to children less than two years using signed consent forms determined delivery source . This was the age group at highest risk, and poorly covered by routine childhood vaccines . Primary health care source of children presenting with disease was determined by telephone . RESULTS . The epidemic of group A meningococcal disease in the winters of 1985 and 1986 abated most likely due to the vaccination of high risk children (3 months-13 years) in 1987 . 90% of the target population were vaccinated . In south Auckland the majority (92%) of vaccine doses for children less than two years of age was delivered by the Plunket Society with Department of Health backing aided by community health workers . By contrast delivery by, general practitioners was greater in north-west and central Auckland (approximately 25%, of dose 1), especially after the publicity over possible side effects (approximately 50% of dose 2) . Coverage for dose 1 of children < 2 years was similar (89%) in south Auckland . Of children presenting with meningococcal disease 1 in 4 did not have an identifiable general practitioner . CONCLUSIONS . Vaccines to prevent serious paediatric illness are known to be highly cost effective . The best method of delivery of vaccinations may vary from area to area . Major community involvement including community health workers for the Maori and Pacific Island communities may have facilitated the dissemination of information in this campaign.

Bull Hosp Jt Dis, 1993-95, 53(4), 13 - 6
Restoration of apposition function in residual hand by the Ilizarov method: a case report; Samchukov ML et al.; A five-year-old boy is presented with multiple finger and toe amputations, secondary to meningococcemia . The child developed a bimanual use pattern of the upper extremities with a significant amount of soft tissue scarring . The left hand was reconstructed according to Ilizarov's method by a combination of distraction lengthening of the metacarpals with two mini-Hoffman distractors and gradual interdigital space widening with web deepening accompanied by a modified Ilizarov apparatus . One year after removal of the external fixation frame, the web space is preserved and the child is adapting to the pincer-like function of his hands.

Scand J Infect Dis Suppl, 1993, 87, 1 - 72
Serum factors and polymorphonuclear leukocytes in human host defence against Neisseria meningitidis . Studies of interactions with special reference to a chemiluminometric technique; Fredlund H; Luminol enhanced chemiluminescence (CL) was used to study the interactions of various serogroups of opsonized or nonopsonized meningococci (MC) with polymorphonuclear leukocytes (PMNL), and the results were compared with those of functional (serum bactericidal activity = SBA, phagocytic killing = PK) and nonfunctional (EIA and IFL) antibody tests . The inherent problems of inter-assay and day-to-day variations of the CL technique were solved by indexing the responses with the use of an international serogroup X reference MC strain (NCTC 10790) . When opsonized with serum from healthy adults without a history of meningococcal (MC) disease, the pathogenic MC strains of serogroups A, B, C, Y (Orebro variant) and W-135 gave significantly lower CL indexes than the apathogenic ones of serogroups Y, Z, and 29E and of nongroupable strains (p < 0.001) . The same patterns were obtained when the strains were opsonized with serum from Swedish children 1-3 years old and also with serum A Sudanese children . Higher levels of antibodies against MC serogroup A polysaccharide were found in sera from Sudanese children than in those of Swedish ones . Correspondingly, the CL indexes for MC of serogroup A were somewhat higher for the Sudanese children than for the Swedish ones . In spite of this an MC epidemic due to a serogroup A strain could not be avoided in Sudan, but could in Sweden, where the same strain was introduced, indicating that other factors than serum immunity are of importance for avoidance of an MC serogroup A epidemic . In various series of experiments it was shown that the CL technique, like the SBA and PK tests, can discriminate between functional and nonfunctional antibodies in healthy individuals, in patients during and after MC disease and before and after vaccination, whereas EIA and IFL tests cannot . It was also shown that in the presence of serum from healthy individuals without a history of MC disease, both the classical and alternative complement pathways are activated to kill or to induce phagocytosis of apathogenic MC, whereas only the classical pathway is activated for the pathogenic ones . In the presence of serum from an individual vaccinated with MC capsular polysaccharide vaccine (high levels of anti-MC capsular polysaccharide antibodies), the pathogenic MC activate both the classical and alternative complement pathways for induction of phagocytosis . It is concluded that the standardized CL indexing technique for pathogenic and apathogenic MC has several advantages over the laborious and cumbersome SBA and PK assays in demonstrating and measuring the presence of functional anti-MC antibodies . It also has the capacity to discriminate pathogenic from apathogenic MC, and under certain circumstances it might be used as a diagnostic tool.

Vaccine, 1993, 11(5), 578 - 81
Dramatic reduction of meningococcal meningitis among military recruits in Italy after introduction of specific vaccination; Biselli R et al.; Meningococcal meningitis is still a serious infectious disease with a mortality rate that can be as high as 10% even in developed countries . Military recruits are generally a high-risk group for meningococcal disease, with a reported incidence of four to ten times greater than that of the general population . In Italy the results of the National Meningitis Surveillance Programme showed a high attack rate of the disease among recruits in 1985 as well as in 1986, with 92 and 95% of the cases, respectively, caused by serogroup C and thus preventable . These findings led to the authorities' decision to make vaccination against meningococcal disease mandatory for recruits starting from January 1987 . After almost 5 years from the introduction of meningococcal vaccination, we here sum up the epidemiological and immunological effects of the vaccination . From the epidemiological point of view we have observed a dramatic reduction of the prevalence of the disease . In 1987, the year in which we had 150,000 unvaccinated and 150,000 vaccinated recruits, the protective efficacy was 91.2% . From the immunological point of view, vaccination is highly effective, as seroconversion against polysaccharide (PS) A and C is 84 and 91%, respectively . The spectrotypic analysis of the sera before and after vaccination shows that the type of response is mainly oligoclonal, like the majority of the responses to PSs, and the antibodies induced by a sole PS are not qualitatively different from the antibodies induced by natural immunization . In addition, the efficacy is not modified by environmental factors like hypoxia, as demonstrated during permanence at 16,174 feet for 20 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Intensive Care Med, 1993, 19(2), 115 - 6
Rapid recovery of acquired purpura fulminans in a patient with familial C4bBP deficiency; Lemesle FG et al.; A 32-year-old pregnant woman developed meningococcemia associated purpura fulminans and quickly improved with therapy . After this disease C4b-Binding Protein (C4bBP) plasma levels remained very low while protein S activity was in the normal range . Familial investigation proved a hereditary C4bBP deficiency . This observation points out the role of the protein C-protein S system during acquired purpura fulminans.

Scand J Infect Dis, 1993, 25(1), 137 - 9
Septicaemia caused by an unusual Neisseria meningitidis species following dental extraction; Pedersen LM et al.; Dental procedures are frequently followed by transient bacteraemia . Bacteria obtained in the blood cultures are similar to bacteria of the normal mouth flora such as oral streptococci . The potential risk of bacteraemia following dental manipulations is infective endocarditis . We report here a rare case of septicaemia following dental extraction in a 84-year-old woman . Neisseria meningitidis group B type 1P1.9 was cultured from the blood . Postextraction septicaemia caused by meningococci has not been described before . Meningococcaemia as a rare complication of dental extraction is emphasized.

Monatsschr Kinderheilkd, 1993 Jan, 141(1), 7 - 9
{The 150th birthday of Otto Heubner 21 January 1993}; Oehme J; Otto Heubner can be counted among the fathers of pediatry . Beginning as an autodidact, he became pediatrist by chance, holding the first university chair in Germany (1884) exclusively devoted to pediatry; he needed no Dr . med . habil . thesis . Observing the little patients was his primary interest; for the infants treated in the hospital he introduced "aseptic environments" . Heubners main scientific achievements were the treatment of infectious and stomach-intestinal diseases . He described "Endarteritis syphilitica" and found Meningococci in the cerebrospinal fluid . "Serious deficiency of digestion" (Coeliac disease) became known through his work . Together with his friend M . Rubner he created the notion of EQ (Nutrition Quotient) . Also, he realized the functional effects of orthotic albuminuria . Heubners centers of activity were Leipzig and Berlin, where he had a large community of followers; his successor, recommended by him, was A . Czerny.

Int Arch Allergy Immunol, 1993, 100(2), 135 - 43
Serum bactericidal activity and induction of chemiluminescence of polymorphonuclear leukocytes: complement activation pathway requirements in defense against Neisseria meningitidis; Fredlund H et al.; Serum bactericidal activity and chemiluminescence (CL) responses of polymorphonuclear leukocytes (PMNL) to pathogenic Neisseria meningitidis serogroups B and W-135 and to nonpathogenic serogroup 29E were examined with pooled normal human serum depleted of the complement proteins C1q, factor D, properdin and C5 . Purified C1q, factor D, properdin and C5 were added alone or in combination . For investigation of serogroup W-135 meningococci, a C1q, factor D and properdin-depleted postvaccination serum with high concentrations of anticapsular antibodies was also used . Serogroup B and W-135 cultured to log phase were resistant to the bactericidal activity of pooled normal human serum but were efficiently killed through the classical pathway alone when the bacteria were cultured to stationary phase . Nonpathogenic serogroup 29E meningococci in log or stationary growth phases were efficiently killed in serum, predominantly through the classical pathway . Serogroup W-135 meningococci grown to log phase were resistant to classical pathway-mediated bactericidal activity in postvaccination serum but were killed on addition of alternative pathway proteins . Stationary phase serogroup W-135 meningococci were killed through both pathways in the postvaccination serum . In the pooled normal human serum CL responses of PMNL were consistently more pronounced with fully reconstituted C1q, factor D, properdin, C5-depleted serum than with serum reconstituted with C1q, factor D and properdin suggesting contribution of actions related to terminal components . In the absence of C1q, serogroup W-135 meningococci in postvaccination serum induced a significant but delayed alternative pathway-mediated CL response . CL responses induced by serum-opsonized meningococci, in contrast to serum bactericidal activity, were not influenced by culture conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS, 1993 Jan, 7(1), 87 - 90
Disseminated meningococcal infection in HIV-seropositive patients; Nitta AT et al.; OBJECTIVE: Although increasing numbers of infections due to various bacterial pathogens have been described in HIV-infected individuals, there have been few reports to date of disseminated Neisseria meningitidis infections in such individuals . We describe here the presentation and clinical course of systemic meningococcal infection in two HIV-1-seropositive men and the response to meningococcal vaccine in one . DESIGN AND METHODS: Retrospective analysis of case reports of two patients identified in a municipal hospital in Denver, Colorado, USA, and evaluation by enzyme-linked immunosorbent assay of antibody response to quadrivalent (A, C, Y, W-135) meningococcal vaccine . RESULTS: A 27-year-old HIV-seropositive man with bacteremic group Y meningococcal pneumonia and a 45-year-old man with AIDS and group B meningococcal arthritis both responded to short-term antibiotic therapy without recurrence . The second patient responded to meningococcal vaccination with seroconversion to all four serogroups . CONCLUSIONS: Disseminated meningococcal infection, although rare in HIV-infected individuals, may present with a variety of clinical manifestations and responds well to antibiotic therapy . Meningococcal vaccine appears to be immunogenic in such individuals.

Bull World Health Organ, 1993, 71(1), 117 - 8, 123-5
Long-acting chloramphenicol for bacterial meningitis; Epidemic meningococcal meningitis in children . A retrospective analysis of cases admitted to ESCH (1988); Hiwot Fana General Hospital, Harer, EthiopiaOne hundred twenty four cases of meningococcal meningitis were seen at the Ethio-Swedish Children's Hospital (ESCH) during the epidemic period December 1, 1987 to January 31, 1989 . Data on demographic and clinical profile of patients were collected and analyzed . Two thirds of patients were above 5 years of age . Fifty percent of the patients came from the "mercato area" of the city of Addis Abeba, Higher 3, 4, 5 & 6 . Thirteen cases were from outside Addis Abeba . The main clinical presentations were fever and vomiting in all age groups and headache in those above 5 years of age . The classical meningeal signs were rare in those below 5 years of age . The most common neurological deficit was loss of hearing . Mortality was very low (only 3 deaths) . Continuous surveillance of demographic and clinical indicators is recommended as they could be useful early warning signs of an epidemic.

Int J STD AIDS, 1993 Jan-Feb, 4(1), 8 - 12
Anogenital non-gonococcal neisseriae: prevalence and clinical significance; McKenna JG et al.; Over a 13-year period non-gonococcal neisseriae (NGN) were isolated from 114 of 88,670 patients (0.13%) screened for anogenital gonorrhoea at a Genitourinary Medicine Unit . During the same period there were approximately 9000 anogenital gonococcal infections (10%) . The prevalence of NGN was 0.09% (27/31,500) in women, 0.04% (20/52,800) in heterosexual men and 1.5% (67/4370) in homosexual men: the differences in prevalence between women and heterosexual men (P < 0.01) and between heterosexual patients and homosexual men (P < 0.001) are highly significant . Neisseria meningitidis was isolated most frequently and accounted for 85% (99/114) of the NGN . Whenever possible, N . meningitidis was serogrouped and its occurrence correlated with patient symptoms . Eleven of 18 heterosexual men who had meningococci isolated from their urethras had urethritis but co-existing chlamydial infection was excluded in only 5 . None of 9 women with cervical colonization had clinical evidence of pelvic inflammation . Only one of 49 men with rectal colonization had proctitis . The management of anogenital NGN infection is discussed in relation to our findings and those of previously published studies . Within each patient group the prevalence and incidence of anogenital NGN were similar at the beginning and end of the study period indicating that levels have not been influenced by the advent of AIDS.

J Clin Invest, 1993 Jan, 91(1), 99 - 102
Carrier detection in families with properdin deficiency by microsatellite haplotyping; Kolble K et al.; Human properdin deficiency is an X-linked disorder strongly predisposing to meningococcal disease which has been recorded in over 50 cases of various ethnic origins . Immunochemically, total deficiency (type I), partial deficiency (type II), and deficiency due to a dysfunctional molecule (type III) can be differentiated . It is therefore most likely that the causative molecular defects will show considerable genetic heterogeneity . Analysis of the properdin locus at Xp11.3-Xp11.23 has led to the characterization of two polymorphic (dC-dA)n.(dG-dT)n repeats located approximately 15 kb downstream from the structural gene . Three families (two Scottish Caucasoid, one Tunisian Sephardic) with seven deficient individuals were investigated immunochemically and using a nonradioisotopic polymerase chain reaction-based method for microsatellite detection . Probable and definite carriers frequently showed properdin levels which were in the normal range . No recombinants between the microsatellite loci and properdin deficiency were detected, thus allowing identification of the defective allele through the generations in all three pedigrees . Haplotyping for these highly polymorphic microsatellites in close physical linkage to the properdin gene can provide rapid and nonradioactive detection of carrier status and prenatal diagnosis without extensive sequencing analysis.

J Med Microbiol, 1993 Jan, 38(1), 19 - 22
Serogroups, serotypes and subtypes of Neisseria meningitidis isolated from patients and carriers in Greece; Tzanakaki G et al.; The increase in the number of cases of meningococcal disease reported to the Ministry of Health in Athens since 1989 prompted the present study to determine if isolates from patients or carriers expressed the same phenotypic characters as those in other parts of Europe . None of the isolates from patients (31) or carriers (547) expressed the antigenic combinations associated with outbreaks in northern Europe, i.e., B:15:P1.16 or B:4:P1.15 . The majority of the Greek isolates did not react with any of the six monoclonal serotype reagents tested; however, most reacted with one or more of the 11 monoclonal subtype antibodies . The results suggest that additional serotype reagents are needed for epidemiological studies in southeastern Europe and that vaccines based on serotype antigens developed against outbreak strains in northern Europe would not be effective in Greece.

Infect Immun, 1993 Jan, 61(1), 187 - 96
Meningococcal lipopolysaccharide (LPS)-derived oligosaccharide-protein conjugates evoke outer membrane protein- but not LPS-specific bactericidal antibodies in mice: influence of adjuvants; Verheul AF et al.; Meningococcal lipopolysaccharide (LPS)-derived oligosaccharides (OS) were coupled to tetanus toxoid (TT) and purified P1.7,16 outer membrane proteins (OMP) . The immunogenicities of the conjugates with and without the addition of the adjuvant Quil A or the nonionic block polymer L121 were studied in mice . Immunotype L2 and L3,7,9 OS-TT conjugates induced immunoglobulin G (IgG) responses that were strongly augmented by Quil A and L121 . These adjuvants not only enhanced the amount of IgG evoked but also shifted the IgG subclass distribution from mainly IgG1 toward the complement-activating subclasses IgG2a and IgG2b . The antibodies induced were directed against the OS part of meningococcal LPS . They were not bactericidal for group B meningococci . Both the L3,7,9 OS-P1.7,16 OMP conjugate and purified P1.7,16 OMP evoked a strong IgG response against the P1.7,16 OMP but not against the L3,7,9 LPS . These anti-OMP IgG responses were comparable to the IgG OMP-specific responses induced by the H44/76 or HIII-5 outer membrane vesicles but still did not lyse group B meningococcal strains . The IgG response evoked with OS-OMP or purified OMP consisted mainly of the IgG1 subclass, whereas the H44/76 or HIII-5 outer membrane vesicles induced high amounts of bactericidal IgG2a and IgG2b antibodies next to the IgG1 antibodies . The addition of the adjuvant Quil A or L121 to OS-OMP or OMP resulted in the induction of high levels of bactericidal anti-P1.7,16-specific OMP antibodies, as reflected by the presence of substantial amounts of IgG2a and IgG2b antibodies . These results indicate that (i) mouse anti-LPS antibodies evoked by LPS-derived OS-protein conjugates are not bactericidal for group B meningococci, (ii) extensive purification of P1.7,16 OMP can lead to the loss of the intrinsic adjuvant properties of outer membrane vesicle preparations, and (iii) the addition of suitable adjuvants restores the ability of these purified P1.7,16 OMP to induce bactericidal antibodies.

Acta Clin Belg, 1993, 48(1), 42 - 7
Recurrent meningococcal infections in a patient with congenital C5 deficiency; Bols A et al.; A congenital C5 deficiency was the cause of recurrent meningococcal disease in a 27-year-old man . The lack of serum bactericidal activity accounts for the higher incidence and the different course of Neisseria infections in patients with a deficiency of the late complement components . Early antibiotic treatment and vaccination with a capsular polysaccharide meningococcal vaccine (A,C,Y,W-135) should be considered.

Scand J Infect Dis, 1993, 25(3), 331 - 9
Comparative studies on pharyngeal carriage of Neisseria meningitidis during a localized outbreak of serogroup C meningococcal disease; Ronne T et al.; An outbreak involving 20 cases of serogroup C meningococcal disease, predominantly among teenagers, occurred over a 7-month period in the Randers area of Denmark . The cases were caused by serogroup C:2a:P1.2 sulphonamide-resistant strains . The available evidence was against the transmission being related to particular schools . The outbreak was experienced as 3 clusters . At 2 schools involved in the first and the third cluster of the outbreak, 351 students were examined regarding pharyngeal carriage of meningococci, 282 of whom were tested again 17 weeks later; 308 students attending two similar schools in a nearby area were examined once . The majority of strains isolated from group C carriers in the high-risk area were serologically indistinguishable from the outbreak strain (13/14 = 95%), but less often sulphonamide-resistant (5/13 = 38%) . In both areas, the overall rate (30%), the overall group C rate (3%), the carrier rate for the outbreak strain (1%) were the same . The attack rate for the outbreak strain differed significantly: 1/40 in the high-risk area versus 1/2,500 in the normal risk area . No conditions that might explain this difference were revealed . Immediately after recognition of the first and the third cluster, 780 and 13,300 students, respectively, were vaccinated with meningococcal polysaccharide vaccine A+C . It was concluded that the definition of target groups for vaccination should be liberal, because the "at risk" population may be difficult to recognize at the onset of an outbreak.

Bull World Health Organ, 1993, 71(3-4), 311 - 5
{Effect of 2 vaccination strategies on developments during the epidemic of meningococcal A meningitis in N'Djamena (Chad) in 1988}; Spiegel A et al.; From February till May 1988, during an epidemic of group-A meningococcal disease, 4542 cases of meningitis were reported in N'Djamena, the capital of Chad (550,000 inhabitants) . A first selective vaccination campaign was carried out between 5 and 14 March; 156,500 vaccine doses (polyvalent: group A and C: Institut Merieux) were given using jet injectors . The target population for this first campaign consisted of groups such as school-children and the armed forces . As the epidemic continued, a mass vaccination campaign was implemented one month later between 8 and 14 April 1988; this was targeted at the whole population above 1 year of age, not previously immunized, and 266,738 doses of vaccine were injected . One week after the start of the second campaign, the number of reported cases fell sharply and, within four weeks, the epidemic was halted . The vaccination coverage rate, evaluated by a WHO cluster survey method in people above one year of age, was 95.5% . These results show (i) the failure of selective vaccination, restricted to only at-risk groups, to halt the epidemic; (ii) the efficacy of the mass vaccination campaign aimed at the whole population; and (iii) the feasibility in tropical Africa of such a mass campaign which must be carried out in a few days.

Rev Epidemiol Sante Publique, 1993, 41(3), 241 - 9
{Evaluation of the exhaustiveness and representativeness of a surveillance system using the capture-recapture method . Application to the surveillance of meningococcal infections in France in 1989 and 1990}; Hubert B et al.; If surveillance data is to be correctly interpreted, the degree of exhaustiveness and representativeness of the surveillance system must be known . The capture-recapture method, which can be used for this evaluation - provided that at least two data sources are available - was applied to the surveillance of meningococcal infections in France . To identify those cases common to both surveillance systems, cases of the disease occurring in 1989 and 1990 and appearing on detailed Mandatory Notification (MN) records (702 cases) or reported to the National Reference Centre (NRC) (727 cases) were compared . The total number of cases of meningococcal infection was estimated at 1,367, using the capture-recapture method . Exhaustiveness rates, which did not differ for the various bacterial strains, were 51% for MN and 53% for NRC, although large regional differences were found for both systems . More cases were notified to MN in the age group 5-24 (60%), than in other age groups (49%) . Quarterly exhaustiveness rates were unrelated to incidence of the disease . A district by district analysis of the correlation between exhaustiveness rates for each system suggests that the two data sources were probably independent . Scrupulous identification of common cases and study of the independence of the two systems are indispensable prerequisites for using this method, which provides a good alternative to exhaustive studies.

Immunol Res, 1993, 12(3), 295 - 311
Complement deficiency states and meningococcal disease; Figueroa J et al.; Analysis of complement deficiency states has supported the role of complement in host defense and elucidated diseases associated with defective complement function . Although neisserial infection plays a prominent role in these deficiency states, examination of individuals with late complement component deficiency (LCCD) reveals a particular propensity for recurrent meningococcal disease and provides important clues to the role of complement in neisserial infections . In response to meningococcal disease, LCCD individuals produce significantly greater amounts of antilipooligosaccharide (LOS) antibody which can kill group B meningococcus in a complement-sufficient in vitro system . Further studies of antibody cross-reactivity to other meningococci has led to a clearer understanding of its epitopic specificity . Nevertheless, epidemiologic evidence is consistent with the relative absence of protective immunity in LCCD persons following an episode of infection and supported by quantitation of antibody to capsular polysaccharide . However, compared to anti-LOS antibodies, anticapsular antibodies can offer immune protection to LCCD individuals via complement-dependent opsonophagocytosis--the only form of complement-mediated killing available to these persons . Thus vaccination of LCCD persons with capsular antigens is considered an important means of protecting these high-risk individuals against meningococcal disease.

Scand J Infect Dis, 1993, 25(5), 585 - 94
Endotoxin liberation from Neisseria meningitidis correlates to their ability to induce procoagulant and fibrinolytic factors in human monocytes; Schlichting E et al.; Endotoxin released from different strains of Neisseria meningitidis were studied for their ability to induce procoagulant (tissue factor, TF), fibrinolytic (plasminogen activator, PA) and antifibrinolytic (plasminogen activator inhibitor 2, PAI-2) factors in human monocytes . Two meningococcal strains that liberate endotoxin (E+; 270+ and 840+) and 2 non-liberating (E-; 270- and 840-) strains were used . The endotoxin activity in culture filtrates of these strains was monitored with the Limulus amoebocyte lysate (LAL) test . There was a marked difference between E+ and E- strains in their ability to liberate endotoxin . Suspensions of whole bacteria of all 4 strains induced a significant (14-19-fold) increase in monocyte TF expression when present in concentrations > 10(5) CFU/ml . At lower concentrations (10(4) CFU/ml), E+ strains were clearly more potent stimulators of TF synthesis than E- strains . Culture filtrates of E+ strains were up to 10(4)-fold more potent in inducing TF synthesis than filtrates from E- strains . This marked difference in inducing potency between E+ and E- strains was also observed when monocyte PAI-2 synthesis was examined . The PA expression, on the other hand, was suppressed when monocytes were incubated in the presence of culture filtrates, especially filtrates from the E+ strains . The increased procoagulant and antifibrinolytic activity, together with reduced profibrinolytic activity of monocytes, was closely correlated to the amount of endotoxin measured in the culture filtrates . These changes may contribute substantially to the coagulopathic state seen during systemic meningococcal disease.

Pediatr Radiol, 1993, 23(6), 429 - 31
MRI evaluation and follow-up of bone necrosis after meningococcal infection and disseminated intravascular coagulation; Damry N et al.; Disseminated intravascular coagulation (DIC) is a serious complication of meningococcal septicaemia . It often results in infarction of various tissues namely the skin, adrenal glands, kidneys, brain and, much less commonly, bones . We describe a patient who presented bone lesions after meningococcal septicaemia . In addition to plain radiography and scintigraphy the lesions were evaluated with MRI and have proved to be extensive and still progressive, approximately 18 months after the onset of the disease.

Roum Arch Microbiol Immunol, 1993 Jan-Mar, 52(1), 57 - 65
Epidemiology of meningococcal meningitis in Romania 1971-1991; Mihalcu F et al.; The paper describes the endemic epidemic picture of meningococcal meningitis in Romania over 1971-1991 period . After the epidemic of 1970 with 1051 cases and a morbidity of 5.2 %000, the incidence of the disease suddenly decreased; thus in 1972-1984 the number of cases ranged from 191 to 534 per year, corresponding to a morbidity rate of 0.9 - 2.3 %000 . Starting with the autumn of 1985 the incidence of meningococcal meningitis increased rapidly, reaching a maximum value in 1987 (2623 cases) and a morbidity rate of 11.4 %000 . A spectacular decrease to 250-270 cases per year in 1990-1991 and a morbidity rate of 1.1 - 1.2 %000 were reported . Mortality followed closely the morbidity curve with a maximum in 1987 (0.4 %000) . By contrast, lethality was higher in endemic periods with a maximum of 7.9% (1972), 8.9% (1975) and 6.3% (1990-1991), in the remaining years the lowest index being 1.4% (1980) . The meningococcal meningitis epidemic of 1987 was due to group A Neisseria meningitidis identified in 84.5% of isolates from patients, the same serogroup decreasing in endemic periods to 0 (1991) or 5.5% (1974).

Arkh Patol, 1993, 55(5), 16 - 22
{Morphologic aspects of hemostasis disturbances in meningococcemia in children}; Anisimova IuN et al.; 21 children who died from meningococcemia were studied . Shock disturbances of the microcirculation and thrombocytic part of hemostasis prevailed within first hours of the disease in the form of adrenal hemorrhages and brain edema as immediate cause of death . With an increase of the disease duration, aggregational thrombocytopenia, generalized microthrombosis, coagulopathy, fibrinolysis activation resulted in massive hemorrhages in a number of organs and tissues and manifested in the syndrome of polyorganic failure . No significant differences were found depending upon treatment.

Arkh Patol, 1993, 55(5), 12 - 6
{Morphology of recent meningococcal infections in children}; Shvets OL et al.; An analysis of 108 cases of children's death which occurred in 1981-1991 from hypertoxic meningococcal infection (MI) in St . Petersburg is presented . Serogroup B meningococcus as a causative agent was found in 44% of the cases . The role in the thanatogenesis of inflammatory and immune reactions, viral-bacterial associations was shown on the basis of detailed study of 47 cases . Hemorrhagic adrenal necrosis was diagnosed in 94.7% of the cases . Two clinicomorphological variants of the disease are distinguished: 1) variant with a moderate hemorrhagic eruption without pronounced kidney lesion, 2) variant with an abundant confluent rash and pronounced kidney lesions and choroid plexus immune lesions.

Scand J Infect Dis, 1993, 25(6), 757 - 61
Plasmapheresis in the treatment of primary septic shock in humans; Gardlund B et al.; 14 patients (mean age 25.5 yrs) with life-threatening primary septic shock were eligible for treatment with acute plasmapheresis in a prospective study . They had a short history of sepsis and had no severe underlying disease . 10/14 patients had systemic meningococcal disease . All patients were severely ill with a mean APACHE II score of 25.0 . 12/14 patients were treated with plasmapheresis exchanging 1 plasma volume within hours of admission . 11/14 patients survived without major sequelae and 3 (21%) died of irreversible septic shock . This mortality is lower than that predicted from the APACHE II scores (55.2%) . A subgroup of plasmapheresis-treated patients with septic shock and extensive petechiae were compared to a historical control group . The mortality in the treatment group was 1/7 (14%) versus 8/21 (38%) in the control group . We conclude that acute plasmapheresis may be a therapeutic option in the early stages of severe primary non-surgical septic shock.

Med Pregl, 1993, 46(5-6), 188 - 90
{Meningococcal sepsis and difficulties in differential diagnosis--case report}; Madle-Samardzija N et al.; We report a case of meningococcal sepsis in a healthy immunocompetent sixteen year old boy who had developed upper respiratory tract acute infection 10 days before the admittance . Clinical manifestations were similar to those found in allergic hemorrhagic purpura (Schonlein's form of the disease) . The clinical course of these two diseases is usually different but sometimes they cannot be easily differentiated . The acute onset of polyarthritis, temperature and skin manifestations in the form of erythematous maculopapular exanthema which within several hours evolved into hemorrhagic purpura is typical for the sepsis caused by Neisseria meningitides but these characteristics might be found in allergic Henoch-Schonlein' purpura as well . In our case the accurate diagnosis was set by the identification of the group C Neisseriae meningitides from the patient's blood . The first choice was penicillin therapy.

Ann Trop Paediatr, 1993, 13(2), 147 - 52
Fatal meningococcal disease in childhood: an autopsy study of 86 cases; Neveling U et al.; A retrospective study of the pathology in 86 consecutive autopsies of fatal meningococcal infection in children, performed at the Red Cross War Memorial Children's Hospital during the 19-year period from 1973 to 1991, was undertaken . The most prominent pathological changes found at autopsy were those of an overwhelming bacterial infection with evidence of disseminated intravascular coagulopathy in many organs of the body . The skin, adrenal glands and central nervous system were most commonly involved . Acute myocarditis occurred in 23 cases (27%) and was diagnosed almost exclusively histologically . In only one case was it diagnosed clinically . In addition, the nutritional status and the morphological expression of immune reactivity of our hospital population was better than expected.

Eur J Immunol, 1993 Jan, 23(1), 232 - 9
Microheterogeneity in the recognition of a HLA-DR2-restricted T cell epitope from a meningococcal outer membrane protein; Wiertz E et al.; The trimolecular interaction of T cell receptor (TcR), antigen and major histocompatibility complex (MHC) class II was analyzed using a panel of HLA-DR2-restricted T cell clones recognizing the 49-61 region of a meningococcal class I outer membrane protein (OMP) . The clones, all CD3+CD4+CD8-TcR alpha/beta+, were selected by restimulation with the synthetic peptide OMP(49-61), which contains an immunodominant T helper determinant . Using a series of peptides that were sequentially truncated from the N or C terminus, four different epitope fine-specificity patterns were identified . Furthermore, each clone was found to exhibit a distinct recognition pattern for a panel of 20 single-residue substitution analogues of the minimal epitope OMP(50-58) . Most substitutions that were not tolerated in the nonamer were allowed when the analogues were prepared departing from the native peptide OMP(49-61) . Obviously, the residues outside the minimal epitope contribute to stabilization of the trimolecular complex . These findings suggest that defining the minimal size of T cell determinants may be of limited value . By performing proliferation competition assays putative MHC and TcR contact residues were identified in the peptide . Most likely, Ile 51 and Phe 54 act as MHC-anchoring residues, whereas Asp 53 represents a critical TcR contact residue for all of the clones . MHC anchoring may be provided by other residues as well, since Ile 51 and Phe 54 can be substituted by conservative residues {as OMP(50-58) and OMP(49-61) analogues} and with Ala {as OMP(49-61) analogues only} . Some evidence was found for interaction of particular side chains at other positions with TcR molecules, but this contribution was not equally important for all clones . Apparently, the clonotypic TcR can see a single epitope in different ways in the context of the same MHC restriction element . Since most clones use different V alpha and V beta genes (which encompass the putative MHC-binding regions first and second complementarity-determining regions, CDR1 and CDR2) different modes of interaction with the HLA-DR2 molecule indeed are likely to occur.

J Med Microbiol, 1993 Jan, 38(1), 23 - 8
Expression of an inaccessible P1.7 subtype epitope on meningococcal class 1 proteins; Wedege E et al.; Dot-blot analysis of whole-cell suspensions of meningococci showed that 81% of B:15:P1.16 strains from patients reacted with a monoclonal antibody (MAb) against subtype P1.7 . The remaining strains, which did not react on dot-blots or in ELISA, demonstrated the P1.7 subtype epitope on immunoblots after denaturation of the cells with sodium dodecyl sulphate . The monomeric class 1 proteins of the two P1.16 subtype variants had slightly different mol . wts, but bound the P1.7 antibody equally well . These results were explained by a deletion of three codons in the gene encoding the first variable region of the P1.16 class 1 protein . The deletion accounted for the non-exposure of the P1.7 epitope on native cells . Other patient strains, with subtypes P1.3, P1.9 or without any known subtype, also showed a binding site for the P1.7 MAb, which became available only after denaturation . Demonstration of inaccessible epitopes may have consequences for subtype designations and vaccine development.

Lancet, 1992 Dec 12, 340(8833), 1432 - 4
Polymerase chain reaction for diagnosis of meningococcal meningitis; Ni H et al.; Meningococcal disease is normally suspected on clinical grounds but confirmed by isolation of Neisseria meningitidis from blood or cerebrospinal fluid (CSF), or by detection of gram-negative diplococci in CSF . After parenteral antibiotics are started the isolation rate of meningococci from blood cultures drops from 50% to less than 5% and the chances of CSF being positive by culture or microscopy are also reduced . We used the polymerase chain reaction (PCR) in a blinded study to detect meningococcal DNA in 54 CSF samples from patients with meningococcal disease or from controls . The PCR primers were specific for the meningococcal insertion sequence IS1106 . The sensitivity and specificity of this PCR for diagnosis of meningococcal meningitis were both 91% . Sensitivity was not affected by prior antibiotic treatment . The IS1106 PCR is a rapid and sensitive test for confirmation of the diagnosis of meningococcal meningitis.

Lancet, 1992 Dec 5, 340(8832), 1379 - 81
Meningococcal septicaemia in a C6-deficient patient and effects of plasma transfusion on lipopolysaccharide release; Lehner PJ et al.; Patients whose blood is deficient in the terminal component of complement have an increased susceptibility to meningococcal infection . However, mortality from meningococcal infection is lower in these patients than in immunocompetent subjects . We studied a C6-deficient patient with meningococcal sepsis who received fresh frozen plasma (FFP) . The patient's initial plasma endotoxin, C6, and terminal-complement-complex concentrations were low, but rose sharply after treatment with FFP . Samples of the patient's serum taken shortly after admission did not cause endotoxin release from Escherichia coli J5 in vitro, but endotoxin-releasing activity was restored in serum samples taken after infusion of FFP . It is possible that C6-deficient patients have reduced mortality from meningococcal infection because their serum cannot cause acute release of endotoxin from the invading organism and extensive tissue damage is thus avoided.

J Gen Microbiol, 1992 Dec, 138 ( Pt 12), 2647 - 56
Identification of an outer-membrane haemoglobin-binding protein in Neisseria meningitidis; Lee BC et al.; Although Neisseria meningitidis can use haemoglobin as an iron source in vitro, the mechanism of haemoglobin-iron uptake is unknown . Using a biotinylated human haemoglobin probe in a solid-phase dot-binding assay, haemoglobin-binding activity was detected in total membranes derived from meningococci grown under iron-limited but not iron-sufficient conditions . In competition binding experiments, bovine and human haemoglobin could abrogate binding . In contrast, no binding inhibition was seen with ferric nitrate, protoporphyrin IX, and iron-loaded human transferrin . The ability of both haemin and catalase, a nonhaemoglobin haem-containing compound, to inhibit binding competitively suggested that the ligand recognized by the binding protein is the haem moiety . Scatchard plot analysis revealed a heterogeneous receptor population . Limited proteolysis with proteinase K abolished binding activity, suggesting a haemoglobin-protein interaction . Detection of activity in a whole-cell binding assay demonstrated that this haemin-binding protein was surface exposed . In a limited survey of meningococcal strains, the presence of haemoglobin-binding activity in all isolates indicated that expression of this binding protein is not serogroup specific.

Cutis, 1992 Dec, 50(6), 417 - 8
Large erythematous patch as the presenting manifestation of meningococcemia; Weiss PJ et al.; Meningococcemia commonly presents with a petechial rash and a transient macular or papular rash is sometimes present . This report describes a patient with meningococcemia who presented with an atypical erythematous patch over the right hemithorax, petechial rash, and a normal platelet count . The patient was treated with broad-spectrum antibiotics and his condition rapidly improved . He was discharged showing complete resolution of his rash with no neurologic sequelae.

Epidemiol Infect, 1992 Dec, 109(3), 445 - 52
Secretor status and humoral immune responses to Neisseria lactamica and Neisseria meningitidis; Zorgani AA et al.; Non-secretors of ABO blood group antigens are over-represented among patients with meningococcal diseases . Lower levels of secretory IgA reported for non-secretors have been suggested to compromise mucosal defences . Total serum and salivary IgG, IgA and IgM and levels of these isotypes specific for Neisseria lactamica and five isolates of meningococci were determined by ELISA for 357 pupils and staff of a secondary school in which an outbreak of meningitis occurred . There were no differences in total or specific levels of serum IgG, IgA or IgM or salivary IgG or IgA of secretors compared with non-secretors . Non-secretors had significantly lower levels of salivary IgM (P = 0.022) . A similar pattern was observed for levels of IgM specific for N . lactamica and five meningococcal isolates . The significance of these results is discussed with reference to the role of secretory IgM in protection of mucosal surfaces in infants.

Infect Immun, 1992 Dec, 60(12), 5267 - 82
Clonal and antigenic analysis of serogroup A Neisseria meningitidis with particular reference to epidemiological features of epidemic meningitis in the People's Republic of China; Wang JF et al.; Representative strains of serogroup A Neisseria meningitidis were chosen from all major meningitis epidemics worldwide since 1960 and subjected to analysis for the electrophoretic variation of 15 cytoplasmic allozymes and four outer membrane proteins . The 290 strains defined 84 unique electrophoretic types which were classified in nine subgroups . Tests with monoclonal antibodies specific for conserved pilin epitopes showed that the class I, IIa, and IIb epitopes were uniform within the subgroups . Similarly, the subgroups were uniform for expression of different variable regions of class 1 outer membrane protein, with a few minor exceptions . Many of the bacteria tested were isolated in the People's Republic of China, and the epidemiology of Chinese epidemics of meningococcal meningitis is described . The analysis approaches a global description of epidemic meningitis caused by serogroup A meningococci in the past 30 years.

Infect Immun, 1992 Dec, 60(12), 4977 - 83
Immunogenicity of conjugate vaccines consisting of pneumococcal capsular polysaccharide types 6B, 14, 19F, and 23F and a meningococcal outer membrane protein complex; Vella PP et al.; In an effort to prepare pneumococcal (Pn) capsular polysaccharide (Ps) vaccines that would be immunogenic in infants, covalent conjugates were prepared for Pn types 6B, 14, 19F, and 23F . Each Ps type was covalently bound to an outer membrane protein complex from Neisseria meningitidis serogroup B and evaluated for immunogenicity in mice and infant monkeys . The conjugates induced specific anti-Ps antibody responses in mice and in infant rhesus and African green monkeys; a conjugate of 6B and outer membrane protein complex was immunogenic at Ps doses as low as 20 ng . Although low levels of the Pn group-common cell wall polysaccharide were present in all type-specific Ps preparations, anti-cell wall polysaccharide responses induced by covalent conjugates were < 1% of the total anti-Ps response after two doses of vaccine . In contrast, the anti-cell wall polysaccharide response of a noncovalent conjugate represented 41% of the anti-Ps response after two doses . Relative T-cell dependence, a requirement for the human target population of infants less than 18 months old, was demonstrated for all four Pn Ps conjugates in an athymic mouse model . Therefore, these Pn Ps-outer membrane protein complex conjugate vaccines are excellent candidates for evaluation in human infants.

J Infect Dis, 1992 Dec, 166(6), 1316 - 21
Antibodies against IgA1 protease are stimulated both by clinical disease and asymptomatic carriage of serogroup A Neisseria meningitidis; Brooks GF et al.; IgA1 protease was purified from a strain of serogroup A Neisseria meningitidis subgroup IV-1, representative of bacteria that caused an epidemic of meningococcal meningitis in The Gambia in 1982-1983 . ELISAs and immunoblot assays were done using this protease as antigen with paired acute- and convalescent-phase sera from patients from that epidemic and from one in Finland caused by other serogroup A meningococci . Paired sera were also tested from healthy Gambians who were persistent nasopharyngeal carriers, persistent noncarriers, or persons who became carriers after the first serum sample was taken . The results correlated well between the two methods: Antibodies were stimulated by disease or acquisition of carriage, and they remained at a constant level upon continued carriage.

J Immunol, 1992 Dec 1, 149(11), 3612 - 20
Induction of protective immunity in mice using a 62-kDa recombinant fragment of a Schistosoma mansoni surface antigen; Soisson LM et al.; Mice exposed to radiation-attenuated cercariae of Schistosoma mansoni are highly resistant to challenge infection, and sera from these mice can confer partial resistance when transferred to naive recipients . These sera recognize Ag present in schistosomular and adult worms, among them an Ag of 200 kDa . A cDNA encoding a 62-kDa portion of this Ag was cloned; the deduced amino acid sequence of this cDNA clone shares homology with myosins of other species . To assess the immunoprophylactic potential, we carried out vaccination trials in mice using the recombinant polypeptide expressed as a fusion protein with beta-galactosidase presented in the form of proteosome complexes with the outer membrane protein of meningococcus . The level of protection achieved was 32%, and this level could be increased to 75% by removal of those amino acids included in the fusion protein that were derived from the vector to yield a polypeptide, designated rIrV-5 . A similar level of protection was achieved when mice were immunized with the same dose of rIrV-5 in the form of protein complexes but without outer membrane protein, suggesting that protection did not require the use of adjuvant . However, at least three immunizations were necessary to achieve protection . Using mAb and sera from mice vaccinated with rIrV-5, we demonstrated that the native protein recognized by antibodies against rIrV-5 is a 200-kDa protein that is expressed on the surface of newly transformed schistosomula . The protection achieved with rIrV-5 in mice encourages additional studies of its potential as a vaccine candidate for the prevention of schistosomiasis.

J Infect, 1992 Nov, 25(3), 321 - 8
Meningococcal disease in Wales: clinical features, outcome and public health management; Palmer SR et al.; In Wales, in 1988, 119 patients with meningococcal disease were identified, so giving a crude annual incidence of 4.2 patients per 100,000 population . The combined classical clinical features of fever, vomiting, neck stiffness, headache and purpuric rash were identified in only 9% of patients . Fever and vomiting were the commonest symptoms, both being present in 60% of patients . A rash was noted in 77% of patients but neck stiffness in only 39% . Rash was more common in children, headache and photophobia in adults . A total of 13 patients died, the fatality rare increasing with age from 3% in infants to 20% in older teenagers and adults . Only 15% of 75 patients admitted to hospital by general practitioners were known to have received intravenous or intramuscular penicillin before admission as recommended by the Chief Medical Officers of the Health Departments in the U.K . Only 24% of patients received rifampicin to clear nasopharyngeal carriage before or at discharge from hospital . Altogether, 375 household contacts of patients were identified . At least 84% of them received chemoprophylaxis.

Pediatr Nurs, 1992 Nov-Dec, 18(6), 629 - 34
Fulminant meningococcemia in pediatric patients: nursing considerations; Jenkins TL; The mortality rate of children with fulminant meningococcemia is high, and early recognition and intervention by the health care team is crucial for patient survival . Critical care nurses who have knowledge in the cause and treatment of this catastrophic disease and current trends in therapy will be able to provide essential care to these patients.

An Esp Pediatr, 1992 Nov, 37(5), 387 - 90
{Acute meningococcal disease . Study of auditive sequelae}; Bermudez de la Vega JA et al.; We have examined the auditory function in 49 children that have survived an acute meningococcal disease (AMD) . Functional auditory exploration consisted of: ABR; tonal liminal audiometry or behavioral audiometry (Peep-show method, Suzuki-Ogiba ROC) depending on the age and collaboration of the patient; and impedanciometrical techniques (tympanometry, ipsi and contra-lateral stapedial reflex) . Three months later, altered tests were repeated in patients that had been evaluated at a time greater than 90 days after their first day of hospitalization (n = 18) . All tests were repeated in those patients that had been evaluated before 90 days from the first day of hospitalization (n = 31) . No transmission or neurosensory hearing impairments were detected as a result of AMD . We consider the absence of neurosensory hearing impairment, despite the presence of significant risk factors, an important finding . These results suggest that the risk of hearing impairment could be reduced to a minimum by the early establishment of antibiotic treatment.

An Esp Pediatr, 1992 Nov, 37(5), 348 - 50
{Fever and petechial exanthema in children}; Soult Rubio JA et al.; In an attempt to determine clinical and analytical predictive parameters of a possible grave disease, we have carried out a retrospective study of 172 children admitted to our hospital with fever and petechiae as initial symptoms . The ages ranged between 1 month and 10 years . Even though we have not found a clinical symptom or analysis sufficiently sensitive as to predict all grave diseases, the general clinical state of the child associated with either a high or low white cell count and an abnormal coagulation study should be alert signals for a serious infectious disease . On the contrary, if the clinical and analytical parameters are within normal limits the risk of a grave disease is low . We emphasize the high incidence of meningococcal disease (26%).

J Clin Microbiol, 1992 Nov, 30(11), 2835 - 41
Identification of meningococcal serosubtypes by polymerase chain reaction; Maiden MC et al.; The polymerase chain reaction was used as the basis of a novel typing method for Neisseria meningitidis . Southern hybridization experiments demonstrated that it was possible to identify genes encoding different serological variants of the meningococcal class 1 outer membrane protein by probing with polymerase chain reaction products corresponding to known epitopes . A set of 14 defined variable regions was prepared in bacteriophage M13mp19 by the cloning of polymerase chain reaction products . The phage were dot blotted onto membrane filters, which were used as targets for hybridization of radiolabeled amplified class 1 outer membrane protein genes . Thus, the presence of many different subtype-specific epitopes could be investigated in one experiment . This technique was evaluated with a set of serological reference strains, mainly of serogroup B organisms, and provided an alternative, rapid, and comprehensive typing system that was capable of distinguishing known serosubtypes and also of defining currently untypeable strains independently of sodium dodecyl sulfate-polyacrylamide gel electrophoresis or serological analysis . An additional advantage of this technique was that in the case of an unknown serosubtype (i.e., one that did not hybridize with any of the known samples), the DNA amplified from the original sample could be used to determine the nucleotide sequence of the novel serosubtype and to clone the corresponding variable region into bacteriophage M13 . It may be possible to develop this procedure for the diagnostic detection and typing of meningococci directly from clinical samples even when culture is not possible because of antibiotic treatment of an acute case.

J Clin Epidemiol, 1992 Nov, 45(11), 1289 - 93
Diagnostic problems with meningococcal disease in general practice; Sorensen HT et al.; Based on general practitioners' referral letters and hospital records, we made a retrospective analysis of a cohort of 177 consecutive cases of meningococcal disease that occurred during a period of 10 years in the County of North Jutland, Denmark . The analysis concerned diagnostic problems in general practice, prognosis, pre-hospital antibiotic treatment and its effect on subsequent cultures, and degree of obligatory notification . The referring doctor suspected meningococcal disease/central nervous infection in 123 patients (69.5%) . Neck stiffness and petechiae were related to a correct referral diagnosis, in contrast to the occurrence of a non-petechial rash . The presence of disseminated intravascular coagulation was associated with the mortality rate, which was 0.062 . The therapeutic recommendations of the Danish Health Authorities were followed in only 25 of the 98 patients who fulfilled the criteria for pre-hospital parenteral antibiotic treatment . Pre-hospital antibiotic treatment was related to negative culture of spinal fluid or blood . Seven of the 177 patients were not notified according to the rules . Difficulties in pre-hospital diagnosis seem not to influence the lethal course of the disease.

J Clin Invest, 1992 Nov, 90(5), 2031 - 7
Leukemia inhibitory factor levels are elevated in septic shock and various inflammatory body fluids; Waring P et al.; Leukemia inhibitory factor (LIF) has many biological actions which parallel those of IL-1, IL-6 and tumor necrosis factor-alpha, but its role in the pathogenesis of human disease is unknown . A specific radioreceptor competition assay capable of detecting LIF at concentrations above 1 ng/ml (45 pM) was developed . To identify disease states in which LIF might be involved, a cross-sectional survey of serum and body fluids from approximately 1,500 subjects with a variety of diseases was performed using the LIF radioreceptor competition assay . Serum LIF concentrations were transiently elevated (2-200 ng/ml) in six subjects with meningococcal or Gram-negative septic shock, and in a subject with idiopathic fulminant hepatic failure . Moderately elevated LIF concentrations (> 10 ng/ml) were detected in cerebrospinal fluid from subjects with bacterial meningitis, in effusions associated with pneumonia and peritonitis, and in amniotic fluid from a woman with chorioamnionitis . Low LIF concentrations (1-10 ng/ml) were present in synovial fluid from subjects with inflammatory arthritis, amniotic fluid from women in labor, and some reactive, chronic inflammatory and malignant effusions and cyst fluids, but rarely in transudates . These initial findings suggest that LIF might be involved in the pathogenesis of inflammation and septic shock.

J Infect Dis, 1992 Nov, 166(5), 1079 - 88
Sialylation and human neutrophil killing of group C Neisseria meningitidis; Estabrook MM et al.; This study describes the association of lipooligosaccharide (LOS) and capsule sialylation with the survival of 25 serogroup C meningococcal strains in phagocytosis assays . Eleven strains isolated from children were of diverse protein serotypes or were nontypeable; 14 were serotype 2b:P1.2 and were isolated from children during or immediately after a focal epidemic in Texas . Degree of endogenous LOS sialylation and amount of sialic acid capsule were associated with each other and with susceptibility to killing by neutrophils for the non-2b:P1.2 strains . The 2b:P1.2 strains as a group had significantly greater survival in the presence of neutrophils than did the non-2b:P1.2 strains . The susceptibility of these strains to killing by neutrophils was not associated with endogenous LOS sialylation or amount of capsule . These data suggest that many virulent strains evade neutrophil killing, either by sialylation or another mechanism . Evasion of neutrophil killing might enhance a strain's epidemic potential.

Infect Immun, 1992 Nov, 60(11), 4510 - 6
Antibodies to meningococcal class 1 outer membrane proteins in South African complement-deficient and complement-sufficient subjects; Orren A et al.; Inhibition assays were used to investigate human serum antibodies to the meningococcal class 1 outer membrane proteins . We adapted the whole-cell enzyme-linked immunosorbent assay technique to determine the ability of sera to inhibit the binding of murine subtyping monoclonal antibodies . Serum samples from 33 South African subjects with a deficiency in the sixth component of complement as well as serum samples from various groups of complement-sufficient subjects were investigated . Subjects were subdivided according to whether they were (i) convalescent from Neisseria meningitidis infections, (ii) nonconvalescent, or (iii) controls . Preliminary subtyping investigations had shown that P1.2 was present on 36% of meningococcal clinical isolates from Cape Province, South Africa . Assays with the anti-P1.2 antibodies showed the presence of high antibody levels in many deficient sera and moderately elevated levels in some sera from the complement-sufficient convalescent patients . P1.2, P1.4, P1.15, and P1.16 are epitopes situated on loop 4 of the class 1 outer membrane proteins, whereas P1.7 is on loop 1 . Inhibition assays showed that human sera that inhibited binding by P1.2 monoclonal antibodies tended to inhibit the other monoclonal antibodies directed to loop 4 epitopes . This suggests that the epitopes recognized by the human antibodies are not exactly the same as the epitopes recognized by the murine monoclonal antibodies and raises the possibility of the importance of other epitopes.

Neurol Neurochir Pol, 1992 Nov-Dec, 26(6), 815 - 26
{Ultrastructural studies of cells in peripheral blood and cerebrospinal in meningococcal cerebrospinal meningitis}; Skotarczak B; Cells of peripheral blood and cerebrospinal fluid were studied in cases of meningococcal meningitis, and in peripheral blood of healthy controls . In the acute phase of the disease the neutrophils in cerebrospinal fluid showed evidence of phagocytosis activation with presence, among other signs, of numerous cytoplasmic processes . Stages of degeneration of these cells were observed with cytoplasm bulging into the nucleus, strong concentration of nuclear chromatin . In the light of a comparative assessment of cellular structures it was found that the population of neutrophils in peripheral blood is a more stable population showing no morphotic evidence of degeneration . In cerebrospinal fluid eosinophils three types of specific granules were found evidencing hydrolysis stimulation in these cells . In the acute phase of the disease the monocytes in the cerebrospinal fluid showed evidence of transformation, and during convalescence signs of degeneration appeared . Lymphocytes rarely found in the cerebrospinal fluid had features of metabolic stimulation (increased number of mitochondria, lysosomes and pinocytic vacuoles).

J Gen Microbiol, 1992 Nov, 138 ( Pt 11), 2321 - 8
Antibodies recognizing a variety of different structural motifs on meningococcal Lip antigen fail to demonstrate bactericidal activity; Tinsley CR et al.; The neisserial Lip antigen is a conserved antigen associated with the pathogenic Neisseria species, and is composed of multiple repeats of a consensus pentapeptide . A series of monoclonal antibodies reacting with meningococcal Lip antigen were subjected to epitope mapping, using solid-phase synthetic peptides based on the consensus repeat sequence . The antibodies were found to recognize different continuous epitopes based on the consensus sequence . One monoclonal antibody was utilized in affinity chromatography to obtain purified Lip antigen and the antigen was used for immunization of mice . The resulting antisera did not recognize Lip antigen on Western blots but reacted specifically with Lip antigen in immune precipitation experiments, indicating that the predominant polyclonal immune response was directed against conformational epitopes . Despite the diversity of both continuous and conformational epitopes recognized by the antibodies produced, none of the antibodies demonstrated the ability to promote complement-mediated bactericidal activity . Thus despite its initial apparent promise as a potential vaccine candidate the case for the inclusion of Lip antigen in vaccine formulation cannot be supported at present.

Lancet, 1992 Oct 31, 340(8827), 1074 - 8
Protective efficacy of a serogroup B meningococcal vaccine in Sao Paulo, Brazil; de Moraes JC et al.; Serogroup B Neisseria meningitidis is the most common cause of epidemic meningococcal disease in developed countries . Until recently no vaccine has been available for prevention of infection with this organism . In an attempt to control epidemic serogroup B meningococcal disease in greater Sao Paulo, Brazil, during 1989 and 1990, a Cuban-produced outer-membrane-protein-based serogroup B meningococcal vaccine was given to about 2.4 million children aged from 3 months to 6 years . We have done a case-control study to estimate the efficacy of the vaccine in greater Sao Paulo . Microbiologically confirmed cases of serogroup B meningococcal disease were identified through hospital-based surveillance . Controls were matched by neighbourhood and age . Vaccination status was confirmed by inspection of vaccination cards . Between June, 1990, and June, 1991, 112 patients and 409 matched controls with confirmed vaccine status were enrolled . Estimated vaccine efficacy varied by age: 48 months or older = 74% (95% Cl 16 to 92%), 24 to 47 months = 47% (-72 to 84%), and less than 24 months = -37% (< -100 to 73%) . Our results suggest that the Cuban-produced vaccine may be effective for prevention of serogroup B meningococcal disease in older children and adultsPIP: In 1990, researchers compared data on 112 3 month-6 year old children who received a Cuban produced, outer-membrane-protein-based serogroup B meningococcal vaccine (cases) and lived in greater Sao Paulo, Brazil with data on 409 age and neighborhood matched controls to determine the protective efficacy of the vaccine against serogroup B meningococcal disease (Neisseria meningitidis) . Health workers began administering the vaccine in 1989 to control an epidemic of serogroup B meningococcal disease in the area . In fact, in mid-1989 and early 1990, the rates of serogroup B meningococcal disease in 1-6 year old children in Sao Paulo were 2.07/100,000 and 2.3/100,000, respectively . Even though only 44% of serogroup B meningococcal isolates corresponded with the vaccine type strain (B:4:P1:15), many isolates had man of the same serotype or subtype antigens as the vaccine type strain . Thus the vaccine was able to protect against some other serogroup B meningococcal strains other than the vaccine type strain . Vaccine efficacy for 4-year old children was 74%, but was much lower for 24-47 month old children (47%) and 24-month old children (-37%) . The change in the log odds ratio for vaccination by age was linear and significant (p=.057) . The researchers suggested that poor vaccine efficacy among younger children may reflect a need for more boosting to achieve protective levels of immunity . The results showed that the Cuban-produced vaccine could contribute to control of outbreaks of serogroup B meningococcal disease by protecting older children and adults from the disease . Researchers need to conduct additional studies of the vaccine and other possible serogroup B meningococcal vaccines .

Lik Sprava, 1992 Oct, (10), 55 - 7
{The treatment of meningococcemia by preserving immune homeostasis}; Lutsik BD; A study is presented of the cellular-humoral immunity in patients with typical meningococcemia complicated by infectious-toxic shock . Obtained data evidence significant changes of the cellular-humoral immunity in meningococcemias, especially those accompanied by infectious-toxic shock along with traditional methods the authors propose immunoregulatory and pathogenetic treatment: human immunoglobulin, aminocaproic acid, sodium, ethamsilate or dicinon, thymalin or T-activin, dopamin, rifampycin . The dosage of these drugs should be individual . The indications and efficiency should be controlled immunologically.

Blood Coagul Fibrinolysis, 1992 Oct, 3(5), 673 - 7
Meningococcaemia in an adult with hereditary C4b-binding protein deficiency: study of the variations of the protein S system; Gris JC et al.; Serial studies of the plasma protein C-protein S system were performed during the clinical course of a pregnant woman with meningococcaemia who recovered under therapy . The patient had limited purpura fulminans skin lesions and hereditary C4b-binding protein deficiency was suspected . This diagnosis was confirmed in the patient 1 year after delivery and also by family studies . During the meningococcaemia, an initial mild and transient acquired protein C deficiency was seen but no protein S deficiency was observed despite consumption of the latter protein . As C4b-binding protein partial deficiency is associated with high free protein S and protein S activity, this may have protected against acquired protein S deficiency during meningococcaemia.

Arch Dis Child, 1992 Oct, 67(10 Spec No), 1219 - 20
Neonatal meningococcal conjunctivitis associated with meningococcal meningitis; Ellis M et al.; Two infants are described in whom identical strains of meningococcus were isolated from both the eyes and the cerebrospinal fluid . This suggests that the eye may be a portal of entry in at least some cases of perinatally acquired neonatal meningococcal disease and has important implications for the management of purulent conjunctivitis in the newborn.

Mol Microbiol, 1992 Oct, 6(19), 2785 - 95
Expression of the Opc protein correlates with invasion of epithelial and endothelial cells by Neisseria meningitidis; Virji M et al.; Whereas capsulate strains of Neisseria meningitidis are dependent on pili for adhesion to human endothelial and epithelial cells, strains which lacked assembled pili and were partially capsule-deficient adhered to and invaded human endothelial and epithelial cells if they expressed the Opc protein . Bacteria expressing low or undetectable levels of Opc protein failed to adhere to or invade eukaryotic cells . In addition, the presence of OpaAC751 protein on the surface of bacteria did not increase bacterial interactions with host cells . Association of Opc-expressing bacteria was inhibited by antibodies against Opc . Invasion was dependent on the host-cell cytoskeletal activity and was inhibited by cytochalasin D . In some cells, infected at the apical surface, bacteria emerging from basal surface were detected by electron microscopy . Opc is found in diverse meningococci and may represent a common virulence factor which facilitates adherence and invasion by these bacteria.

Surg Gynecol Obstet, 1992 Oct, 175(4), 373 - 87
The wandering spleen; Buehner M et al.; Wandering spleen is an unusual entity, occurring in both sexes and at any age, but is more frequent in women of reproductive age and in children . Wandering spleen is probably most often a result of congenital anomalies of development of the dorsal mesogastrium, but acquired factors may have a role in certain instances . Patients present most commonly with an asymptomatic mass, mass and subacute abdominal or gastrointestinal complaints or with acute abdominal findings . Clinical diagnosis can be difficult, but noninvasive imaging procedures, such as sonography, nuclear scintigraphy, computed tomography and magnetic resonance imaging are usually diagnostic . Laboratory tests are usually nonspecific, but may occasionally reveal evidence of hypersplenism or functional splenia . Symptoms may remain limited or absent for long periods of time, but complications related to torsion or compression of abdominal organs by the spleen or the pedicle are quite common . Splenomegaly is usually a result of torsion of the pedicle and splenic sequestration . Significant morbidity and mortality rates seem to be considerably less than described in 1933 and limited primarily to patients presenting initially with acute abdominal findings . Management recommendations have varied, but recognition of a significant risk of postsplenectomy sepsis supports a conservative approach . Patients with limited symptomatology may be medically managed until they exhibit worsening symptoms indicating progressive splenic torsion or gastrointestinal compression . Detorsion and splenopexy may be considered a reasonable surgical option even in patients presenting with acute abdomen, if there is no evidence of infarction, thrombosis or hypersplenism . Splenic preservation is especially recommended in extremely young patients who are at particular risk for postsplenectomy sepsis . However, it should be noted that follow-up evaluation data on splenopexy patients are notably lacking . Splenectomy is ideally reserved for patients presenting with acute abdomen and splenic infarction or thrombosis or with hypersplenism and patients in whom splenopexy is technically unfeasible . Subtotal splenectomy and splenic autotransplantation may be of limited value . Pneumococcal, Hemophilus and meningococcal vaccines are indicated before elective splenectomy and shortly after nonelective splenectomy . Antibiotic prophylaxis is recommended for those at particular risk . Prospective studies are unlikely, but extended follow-up information on patients already reported, particularly those managed expectantly or with conservative surgical measures, is needed.

South Med J, 1992 Oct, 85(10), 1030 - 1
Recurrence of neisserial meningococcemia due to deficiency of terminal complement component; Morris JT et al.; Recurrent infections with Neisseria meningitidis are attributed to deficiencies of terminal complement components . The serotype most commonly responsible for recurrent N meningitidis infections is serotype Y . We have reported a case of recurrent meningitis due to N meningitidis in a patient who was found to be deficient in the sixth component of complement . Complement deficiencies should be considered in any patient with recurrent infections caused by N meningitidis.

J Bacteriol, 1992 Oct, 174(20), 6386 - 93
Transformational exchanges in the dihydropteroate synthase gene of Neisseria meningitidis: a novel mechanism for acquisition of sulfonamide resistance; Radstrom P et al.; The nucleotide sequences of the chromosomal dihydropteroate synthase (dhps) genes in sulfonamide-susceptible and sulfonamide-resistant strains of Neisseria meningitidis of serogroups A, B and C were determined . The molecular weights and the amino acid sequences showed similarity to those of all other known dihydropteroate synthase polypeptides . Sequence comparison of the N . meningitidis dhps genes indicated horizontal transfer of DNA segments rather than point mutations as the cause for resistance in meningococci . The dhps genes in three of four sulfonamide-resistant meningococci contained identical central regions of 424 bp . Compared with the corresponding genes in susceptible strains, each central region included an insert of 6 bp . In one of the sulfonamide-resistant strains, the dhps gene was similar to the corresponding genes in the sensitive strains in its NH2-terminal and C-terminal parts . Its central region, however, was identical to the corresponding regions of two of the other resistant genes, and thus it could be seen as a hybrid dhps gene . Transformation experiments and mapping of transformed dhps genes indicated the existence of a novel mechanism for the dissemination of sulfonamide resistance in N . meningitidis . The origin of the resistance-mediating segment of the gene is unknown, but hybridization results showed the presence of homologous dhps genes in Neisseria gonorrhoeae and N . lactamica but not in N . subflava or Branhamella catarrhalis.

Epidemiol Infect, 1992 Oct, 109(2), 241 - 53
Transmission of Neisseria meningitidis among asymptomatic military recruits and antibody analysis; Caugant DA et al.; Following the occurrence of a case of systemic meningococcal disease in a military camp in Norway, throat cultures and blood samples were collected from 33 healthy individuals belonging to the same troop as the patient (troop A) and from 29 individuals from a different troop (troop B) in the same camp . Serological studies showed that 91% of the recruits had bactericidal antibodies against the disease-causing strain . The isolates of Neisseria meningitidis recovered from the throat cultures were serogrouped, serotyped, and assigned to a clone on the basis of an analysis of the electrophoretic mobilities of 14 metabolic enzymes . None of the 23 carriers in troop A harboured the clone responsible for the case of disease, but 6 carried isolates of the same electrophoretic type, ET-7, which was not identified in any of the 19 carriers of troop B . Individuals in troop A were resampled 2 and 17 weeks after the meningococcal disease episode . Five of the carriers had acquired different clones and one of them changed clone twice in that period . Four of the six newly acquired clones had previously been identified in other carriers of troop A, demonstrating transmission of clones among individuals living and working in close proximity.

Epidemiol Infect, 1992 Oct, 109(2), 227 - 39
Phylogenetic and epidemiological analysis of Neisseria meningitidis using DNA probes; Ni H et al.; The genetic relationships between various serotypes and serogroups of meningococcal strains were investigated by restriction fragment-length polymorphism (RFLP) analysis using a number of random DNA probes and a probe containing a truncated copy of the meningococcal insertion sequence IS1106 . The data were used to estimate genetic distance between all pairs of strains and to construct phylogenetic trees for meningococcal strains . B15:P1.16R strains isolated from cases of systemic meningococcal disease in two health districts with a high incidence of disease were clonal in contrast to similar strains from cases occurring in other parts of the UK . Strains from these areas, which contain a similar genomic deletion, were found to be derived from two distinct lineages within the B15:P1.16R phylogenetic group . RFLP data demonstrated that present serological typing systems for the meningococcus do not necessarily reflect true genetic relationships.

Indian J Pathol Microbiol, 1992 Oct, 35(4), 340 - 4
Meningococcal meningitis in Ludhiana; Kumar R et al.; A retrospective study was carried out at Dayanand Medical College & Hospital, Ludhiana (Punjab) during the period from January 1985 to June 1990 to know the incidence of meningococcal meningitis . Meningococcal etiology was established in 170 (49.41%) cases out of 344 cases of bacterial meningitis . Out of 170 cases of meningococcal meningitis, 74 (43.52%) were positive only by smear examination, 90 (52.94%) were positive both by smear as well as culture and there were six (3.52%) cases which were positive only by culture . The organisms were sensitive to most of the common antibiotics including penicillin, chloramphenicol, ampicillin and sulphadiazine.

Antibiot Khimioter, 1992 Oct, 37(10), 42 - 4
{Comparative effectiveness of various antibiotics in the treatment of patients with meningococcal meningitis}; Vasil'ev VS et al.; The results of treating 322 patients with various forms of meningococcal infection accepted to a hospital within a year are presented . The patients were divided into 3 groups by the character of etiotropic therapy . The patients of group I were treated with benzylpenicillin and those of group 2 were treated with levomycetin sodium succinate . Group 3 included the patients, the therapy of whom with the above two antibiotics failed and they were subjected to treatment with cefazolin, cefotaxime, amikacin and other broad spectrum antibiotics . Benzylpenicillin generally proved to be the drug of choice in the antibacterial therapy of meningococcal infection . In comparison to levomycetin (chloramphenicol) it provide more rapid clinical recovery of the patients and normalization of the indices of the cerebrospinal fluid . Only failure of benzylpenicillin therapy was considered as an indication to the broad-spectrum antibiotics to be in the complex treatment of the patients . As additional methods for estimating the efficacy of antibacterial therapy it was recommended to employ calculation of the integral indices of hemograms (the leukocyte index of intoxication and the hematologic index of intoxication).

Antibiot Khimioter, 1992 Oct, 37(10), 32 - 4
{Assessment of the sensitivity of Neisseria meningitidis strains to benzylpenicillin using the disc diffusion method}; Il'ina TV; The sensitivity of 235 N . meningitidis strains to 5 antibiotics was estimated by the diameter of growth inhibition zones according to the criteria recommended by a Laboratory (Marseilles, France) collaborating with the WHO . All the strains proved to be sensitive to benzylpenicillin when disks containing 10 and 2 IU of the antibiotic were used . The strains were also shown to be sensitive to chloramphenicol and tetracycline . 95.7 and 7.7 per cent of the strains were sensitive to rifampicin and oleandomycin, respectively . When the strain sensitivity was assayed with the disks containing 10 and 2 IU of benzylpenicillin by the more severe criteria recommended by J . Saez-Nieto et al., significant changes were detected: meningococci with relative resistance to benzylpenicillin were detected in various regions of this country and the number of such strains was found to have a tendency to slightly increase.

FEMS Microbiol Lett, 1992 Sep 15, 75(2-3), 161 - 6
Sequence and functional analysis of the cloned Neisseria meningitidis CMP-NeuNAc synthetase; Edwards U et al.; The CMP-N-acetylneuraminic acid (CMP-NeuNAc) synthetase gene of Neisseria meningitidis group B is located on a 2.3-kb EcoRI fragment within the cps gene cluster . Nucleotide sequence determination of the gene encoding the CMP-NeuNAc synthetase revealed a 515-bp open reading frame that can encode a 18.9-kDA protein . A computer data base scan revealed a 59.4% identity to the CMP-NeuNAc synthetase gene of E . coli K1 . Enzymatic activity was confirmed in vitro and in vivo . Transformation of the CMP-NeuNAc defective E . coli K1 strain EV5 with the meningococcal CMP-NeuNAc synthetase could complement the defect in E . coli.

Clin Infect Dis, 1992 Sep, 15(3), 424 - 30
Plasma and whole blood exchange in meningococcal sepsis; van Deuren M et al.; The present study describes the effect of plasma exchange or whole blood exchange (PEBE) on the survival rate among patients with fulminant meningococcal sepsis and on the level of circulating endotoxin . Since 1989 all patients with meningococcal disease and hypotension who were admitted to our intensive care unit were treated with PEBE . Results for our patients were compared with those for a historical control group conventionally treated between 1984 and 1989 (n = 10; mortality rate, 60%); the expected mortality rate, which was based on the Niklasson prognostic score and was calculated for seven patients in this control group, was 73% . A total of 15 patients were treated with PEBE, three (20%) of whom died, whereas the prognostic score (calculated for 14 patients) for this group was 62% . In two of the fatal cases, PEBE was started after a delay of greater than or equal to 40 hours . In the remaining 13 patients, PEBE was started within 5-30 hours after the first hospital admission . The mortality rate among this group was 8% (one of 13 patients); this rate was significantly different from that among the control group (P = .025) . For seven patients treated with PEBE, plasma endotoxin concentrations were sequentially measured . The overall half-life (+/- SEM) of endotoxin was 181 +/- 18 minutes . This is approximately the same as reported values for patients who were not treated with PEBE . It is concluded that early initiation of PEBE may improve the rate of survival among patients with meningococcal infection and hypotension but that the mechanism of the beneficial effect is most likely not based on the elimination of endotoxin.

J Infect Dis, 1992 Sep, 166(3), 650 - 2
Compartmentalization of lipopolysaccharide production correlates with clinical presentation in meningococcal disease; Brandtzaeg P et al.; Lipopolysaccharide (LPS, endotoxin) was quantified in plasma and cerebrospinal fluid (CSF) collected simultaneously from patients with systemic meningococcal disease . High levels (median, 3800 ng/L; range, 750-14,000) were present in plasma and low levels (median, 40 ng/L; range, less than 25-165) in CSF of patients with fulminant septicemia . Conversely, high levels (median, 2500 ng/L; range, less than 25-500,000) in CSF and low or undetectable levels (median, less than 25 ng/L; range, less than 25-210) in plasma were associated with meningitis without septic shock . Levels of LPS were significantly correlated with protein levels in CSF (r = .50, P = .01) and inversely correlated with the ratio of glucose in CSF to that in blood (r = -.62, P = .0005) . LPS level in CSF greater than 800 ng/L was significantly associated with greater than or equal to 10(9) leukocytes/L, protein levels greater than 0.5 g/L, and a glucose ratio less than 0.5 . Thus, quantification of LPS levels in the plasma and CSF in systemic meningococcal disease is a better predictor of pathophysiologic events than is demonstrating the presence of live bacteria as in conventional culture.

J Infect Dis, 1992 Sep, 166(3), 542 - 5
Meningococcal disease and influenza-like syndrome: a new approach to an old question; Hubert B et al.; The temporal and spatial association of meningococcal disease and influenza-like syndrome (ILS) was assessed from surveillance data on these diseases in France for a 6-year period (1985-1990) . Using time series methods to account for the usual seasonal pattern meningococcal disease, the incidence of meningococcal disease in a given week was found to be linked to incidence of ILS in the 5 previous weeks but not to that in subsequent weeks . Geographic spread of meningococcal disease correlated with spread of ILS . This study also suggests that meningococcal disease is more severe for a 2-month period during and after an ILS epidemic: The proportion of cases with purpura fulminans increased by 24% and those resulting in death by 26% during this period . No shift in the age distribution was observed . When an ILS epidemic is identified, medical practitioners should be informed of the likelihood of an increased incidence and severity of meningococcal disease.

Infect Immun, 1992 Sep, 60(9), 3897 - 903
Toxicity and immunogenicity of Neisseria meningitidis lipopolysaccharide incorporated into liposomes; Petrov AB et al.; To obtain nontoxic and highly immunogenic lipopolysaccharide (LPS) for immunization, we incorporated Neisseria meningitidis LPS into liposomes . Native LPS and its salts were incorporated by the method of dehydration-rehydration of vesicles or prolonged cosonication . The most complete incorporation of LPS into liposomes and a decrease in toxicity were achieved by the method of dehydration-rehydration of vesicles . Three forms of LPS (H+ form, Mg2+ salt, and triethanolamine salt) showed different solubilities in water, the acidic form of LPS, with the most pronounced hydrophobic properties, being capable of practically complete association with liposomal membranes . An evaluation of the activity of liposomal LPS in vitro (by the Limulus amoebocyte test) and in vivo (by monitoring the pyrogenic reaction in rabbits) revealed a decrease in endotoxin activity of up to 1,000-fold . In addition, the pyrogenic activity of liposomal LPS was comparable to that of a meningococcal polysaccharide vaccine . Liposomes had a pronounced adjuvant effect on the immune response to LPS . Thus, the level of anti-LPS plaque-forming cells in the spleens of mice immunized with liposomal LPS was 1 order of magnitude higher and could be observed for a longer time (until day 21, i.e., the term of observation) than in mice immunized with free LPS . The same regularity was revealed in a study done with an enzyme-linked immunosorbent assay . This study also established that antibodies induced by immunization belonged to the immunoglobulin M and G classes, which are capable of prolonged circulation . Moreover, liposomal LPS induced a pronounced immune response in CBA/N mice (defective in B lymphocytes of the LyB-5+ subpopulation) . The latter results indicate that the immunogenic action of liposomal LPS occurs at an early age.

Infect Immun, 1992 Sep, 60(9), 3620 - 9
Molecular analysis of the serotyping antigens of Neisseria meningitidis; Feavers IM et al.; Molecular approaches to the rapid analysis of the serotyping antigens of Neisseria meningitidis, the class 2 and 3 outer membrane proteins (OMPs), were developed, evaluated, and used to study 12 antigenic variants of these proteins . A primer set for the polymerase chain reaction (PCR) amplification of the genes encoding these antigens was devised . Low-stringency amplification of meningococcal chromosomal DNA with this primer set resulted in the amplification of two products from each strain, whereas at higher stringencies only one product was amplified in most strains . Southern hybridization techniques and restriction analyses were used to differentiate the PCR products amplified at high stringencies from strains expressing class 2 or class 3 OMPs; these PCR products were further characterized by the determination of their nucleotide sequences, confirming that they represented the amplified class 2 and class 3 OMP genes . Analyses of these and other nucleotide sequences enabled the construction of a phenogram illustrating the interrelationships between Neisseria OMP genes . The comparative analysis of deduced amino acid sequences revealed conserved and variable regions of the proteins; the latter probably correspond to surface loops on the protein and hence are potentially exposed to the immune system . Further analyses of the primary structures of these related porins from Neisseria species enabled construction of models of the secondary structure of these antigens and comparison of these models with those previously published . The methods reported in the present work are rapid reproducible procedures for the analysis of antigenic variants of these proteins.

Eur J Epidemiol, 1992 Sep, 8(5), 737 - 42
Clusters of meningococcal disease in France (1987-1988); Olivares R et al.; We analyzed 814 cases of meningococcal disease notified in 1987 and 1988 to the Ministry of Health . Data were obtained by report forms including informations about possible additional cases among contacts . Coprimary cases (occurring within 24 hours after the index case) and secondary cases (occurring more than 24 hours after index case) were all reviewed . Twenty eight clusters of meningococcal disease were identified involving 65 cases (8% of total cases) . Twelve of the 814 cases (1.5%) were coprimary cases of an index case and 25 (3%) were secondary cases . The secondary attack rate was 530/100,000 among household contacts and 31/100,000 among school contacts . Seventy two per cent of the secondary cases occurred in the first week after index case . Thirty-eight percent of the secondary cases occurred in the 15-20 age group as opposed to 15% of single cases . Serogroup A was more often found in coprimary (33%) and secondary cases (17%) than in single cases (6%) . In France, prophylaxis of secondary cases is administered to the classroom contacts of a case of meningococcal infection but is not required for the entire school except under epidemic conditions.

Mol Microbiol, 1992 Sep, 6(17), 2499 - 506
The class 1 outer membrane protein of Neisseria meningitidis produced in Bacillus subtilis can give rise to protective immunity; Nurminen M et al.; The class 1 outer membrane protein of Neisseria meningitidis B:15:P1.7,16 was expressed in Bacillus subtilis in high yield as intracellular aggregates . These were easy to isolate and the protein (called BacP1) could be solubilized under denaturing conditions . Sera of mice immunized with thus-solubilized BacP1 contained high titres of antibodies that reacted with the class 1 protein of the meningococcal envelope in immunoblots but did not react with native meningococcal envelope in enzyme immunoassays (EIA) or with intact meningococci in bactericidal assays . However, when the BacP1 protein was complexed with heterologous (Salmonella) lipopolysaccharide, the ensuing sera reacted with meningococcal envelope preparations in both EIA and immunoblots, showed subtype-specific bactericidal activity, and were protective in an infant rat meningitis model.

Eur J Pediatr, 1992 Sep, 151(9), 676 - 9
Complement component deficiencies and infection: C5, C8 and C3 deficiencies in three families; Sanal O et al.; Three families are described with complement component deficiencies . In one family, five children had C5 deficiency; in a second family, two children had C8 deficiency and one child in a third family had C3 deficiency . The index cases were identified during screening of patients with recurrent pyogenic infections, recurrent meningitis and meningococcaemia . Two of the five C5 deficient patients had recurrent meningitis and meningococcaemia, two had recurrent respiratory tract infections and otitis and one was healthy . One of the C8 deficient patients had meningitis, meningococcaemia and pneumonia, whereas his sibling with the same deficiency was healthy . The patient with C3 deficiency had four episodes of meningitis and recurrent otitis.

AIDS, 1992 Sep, 6(9), 971 - 6
High HIV seroprevalence and increased HIV-associated mortality among hospitalized patients with deep bacterial infections in Dar es Salaam, Tanzania; Pallangyo K et al.; OBJECTIVES: To correlate deep bacterial infections with HIV infection and evaluate the influence of HIV on clinical picture and outcome in patients with meningitis, pneumonia or pyomyositis . DESIGN: Case-control comparison of HIV seroprevalence between patients and an age- and sex-matched control group in a prospective cross-sectional study of hospitalized patients . PARTICIPANTS: One hundred and sixty-five patients admitted to hospital with either purulent meningitis, pneumonia or pyomyositis and 165 age- and sex-matched controls from orthopaedic/trauma wards . SETTING: University Hospital, Dar es Salaam, Tanzania . OUTCOME MEASURES: Differences in HIV seroprevalence and mortality . RESULTS: Of 78 patients with purulent meningitis, 19 (24%) were HIV-seropositive, compared with 13 (17%) in the control group (P = 0.345) . Of 36 patients with meningitis seen before a meningococcal epidemic affected Dar es Salaam, there was a statistically significant association with HIV infection (P = 0.013) . Ten out of 19 (53%) HIV-seropositives died, compared with nine out of 59 (15%) seronegatives (P = 0.028) . Of patients with pneumococcal meningitis, five out of six (83%) seropositives died, compared with two out of 12 (17%) seronegatives (P = 0.013) . Fifteen out of 45 (33%) patients with pneumonia were HIV-seropositive, compared with four (9%) in the control group (P = 0.001) . There was no difference in mortality between seropositive and seronegative patients with pneumonia . HIV seroprevalence was 62% among 42 patients with pyomyositis and 12% among 42 controls (P less than 0.0001) . Eighteen out of 25 (72%) seropositive patients with pyomyositis fulfilled the World Health Organization (WHO) clinical case definition for AIDS . Response to recommended antibiotic treatment was satisfactory among patients with pneumonia and pyomyositis . CONCLUSIONS: These results show a strong association between pyomyositis, pneumonia and HIV infection . They also indicate an increased mortality associated with HIV infection in patients with pyogenic meningitis, especially pneumococcal meningitis . Pyomyositis should be considered an indicator of stage III HIV disease in the proposed WHO clinical staging systemPIP: This study sought to correlate deep bacterial infection with HIV infection and evaluate the influence of HIV on clinical practice and outcome in patients with meningitis, pneumonia, or pyomyositis . At University Hospital, Dar es Salaam, Tanzania, 165 patients were admitted to the hospital with purulent meningitis, pneumonia, or pyomyositis and were evaluated in a prospective, cross-sectional study along with 165 age- and sex-matched controls from orthopedic/trauma wards to determine HIV seroprevalence . Of the 78 patients with purulent meningitis, 19 (24%) were HIV-seropositive, as compared with 13 (17%) in the control group (p=0.345) . Of 36 patients with meningitis seen before a meningococcal epidemic affected Dar es Salaam, there was a statistically significant association with HIV infection (p=0.013) . 10 of 19 (53%) HIV-seropositives died, compared with 9 of 59 (15%) seronegatives (p=0.028) . Of patients with pneumococcal meningitis, 5 of 6 (83%) seropositives died, compared with 2 of 12 (17%) seronegatives (p=0.013) . 15 of 45 (33%) patients with pneumonia were HIV-seropositive compared with 4 (9%) in the control group (p=0.001) . There was no difference in mortality between seropositive and seronegative patients with pneumonia . HIV seroprevalence was 62% among 42 patients with pyomyositis and 12% among 42 controls (p0.0001) . 18 of 25 (72%) seropositive patients with pyomyositis fulfilled the WHO clinical case definition of AIDS . Response to recommended antibiotic treatment was satisfactory among patients with pneumonia and pyomyositis . These results show a strong association between pyomyositis, pneumonia, and HIV infection . They also indicate an increased mortality associated with HIV infection in those patients with pyogenic meningitis, especially pneumococcal meningitis . Pyomyositis should be considered an indicator of stage III HIV disease in the proposed WHO clinical staging system . author's modified

Microb Pathog, 1992 Sep, 13(3), 219 - 24
The lipooligosaccharide immunotype as a virulence determinant in Neisseria meningitidis; Jones DM et al.; We have studied the antigenic (immunotype) and physical characteristics of the lipooligosaccharide (LOS) of epidemiologically related Neisseria meningitidis case (36) and carrier (76) isolates associated with a virulent clone of meningococci (ET-5 complex) . LOS immunotypes were determined by dot blotting using immunotype specific monoclonal antibodies and physical characteristics were determined from silver stained SDS-PAGE following proteinase K digestion . The genetic similarity of the different isolates was confirmed by analysis of the restriction fragment length polymorphisms . An association between LOS immunotype expression and invasive disease was found; 97% of case isolates expressed the L3,7,9 immunotype, of which 13% additionally expressed the L1,8,10 determinant . The LOS immunotypes of carrier strains were much more heterogeneous . The predominant immunotype was L1,8,10 (70%) and only 24% expressed L3,7,9 alone . Genotypically related case isolates from Norway (6) and Austria (18) expressed the L3,7,9 immunotype with similar frequency to the U.K . isolates . The combination of LOS immunotype and capsule expression appears to be related to the virulence of these meningococcal strains.

Clin Immunol Immunopathol, 1992 Aug, 64(2), 98 - 105
Immunological evaluation of late complement component-deficient individuals; Platonov AE et al.; The possible contribution of additional immunologic variables to the susceptibility of late complement component-deficient individuals to meningococcal disease has not been systematically examined in previous studies . Thus, we studied three groups of patients: (1) 24 healthy individuals, (2) 8 complement-sufficient individuals with a history of recurrent bacterial meningitis, and (3) 19 complement-deficient individuals with prior meningococcal infection . No statistical differences were noted among the three groups for the following parameters: the absolute number and the percentage of lymphocytes; CD3+, CD4+, CD8+, CD20+, and CD16+ cells; and the CD4+/CD8+ ratio . The concentration of C4 and circulating immune complexes was also similar among the groups . The concentrations of IgG, IgM, and IgA were slightly, but significantly, decreased in the complement-deficient individuals . Of interest, the coefficient of spontaneous and lipopolysaccharide-stimulated activation of neutrophils was significantly depressed in the deficient individuals . We hypothesize that the terminal complement components may participate in maximal neutrophil activation.

Infect Immun, 1992 Aug, 60(8), 3156 - 61
Construction of a multivalent meningococcal vaccine strain based on the class 1 outer membrane protein; Van Der Ley P et al.; Outer membrane complexes (OMCs) are promising vaccine candidates for protection against meningococcal disease . However, a major obstacle to this approach is the fact that the protective antibodies induced are generally type specific . In an attempt to overcome this problem, we have investigated the possibility of constructing a multivalent vaccine strain by insertion of an additional class 1 outer membrane protein-encoding gene . Starting with a derivative of strain H44/76 deficient in class 3 outer membrane protein, a second class 1 gene was inserted into the chromosome, through homologous recombination with a suicide plasmid carrying the class 1 gene from strain 2996 placed within a class 5 gene . In this way, a strain was obtained in which a class 3 protein was in effect replaced by a class 1 protein from another subtype, i.e . P1.5,2 in addition to the P1.7,16 protein of H44/76 . Immunization of mice with such OMCs resulted in high bactericidal titers against both H44/76 and 2996, where normally only strain-specific antibodies are induced . Mutational removal of class 3 protein from the immunizing OMCs had no detectable effect on the bactericidal titer against H44/76, whereas removal of class 1 protein led to a strong reduction . These results demonstrate the dominant role of the subtype-specific sequences of class 1 protein in the induction of bactericidal antibodies and show that construction of a multivalent OMC-based vaccine should be feasible.

J Infect Dis, 1992 Aug, 166(2), 359 - 64
Epidemic meningococcal disease in Nairobi, Kenya, 1989 . The Kenya/Centers for Disease Control (CDC) Meningitis Study Group; Pinner RW et al.; An epidemic of meningococcal disease occurred in Nairobi, Kenya, during 1989, outside the "meningitis belt" of sub-Saharan Africa . About 3800 cases occurred between April and November (250/100,000 population) . The case-fatality rate was 9.4% among hospitalized patients . Areas that included Nairobi's largest slums had particularly high attack rates . The epidemic displayed an unusual age distribution, with high attack rates among those 20-29 years old . A vaccination campaign was conducted . By early January, the weekly case count had fallen to 25 from a high of 272 (in September) . A case-control study estimated the vaccine efficacy to be 87% (95% confidence interval, 67%-95%) . A model estimated that the vaccination campaign reduced the number of cases by at least 20% . Multilocus enzyme electrophoretic typing demonstrated that the strain responsible for this large epidemic is closely related to strains that caused other recent epidemics, documenting further spread of what may be a particularly virulent clonal complex of group A Neisseria meningitidis.

Pediatr Infect Dis J, 1992 Aug, 11(8), 617 - 23
Successful intervention in a group A meningococcal outbreak in Auckland, New Zealand; Lennon D et al.; During two consecutive winter seasons (1985 and 1986) Auckland, New Zealand, experienced epidemic rates of Group A meningococcal disease, a pattern not previously recognized in New Zealand . The overall rate was 8.3/100,000/year . The highest annual rate (64.7) occurred in children 0 to 23 months of age . A city-wide vaccine campaign commencing in May, 1987, was conducted over 6 weeks among children 3 months to 13 years of age with special emphasis on reaching populations at highest risk (Maori and Pacific Island Polynesian children in certain geographic regions of Auckland) . Children from 2 to 13 years of age received a single dose of monovalent Group A meningococcal vaccine . Children ages 3 to 23 months received two doses at least 1 month apart . Overall approximately 130,000 doses were delivered; coverage was approximately 90% in the single dose target group . Among the younger children approximately 89% received the primary dose . Only approximately 26% received the recommended "booster" dose . After 2 1/2 years of active surveillance (1987 to 1989) there were no cases of invasive Group A meningococcal disease in children appropriately vaccinated for age . In contrast to this 100% efficacy the efficacy of a single dose of monovalent Group A meningococcal vaccine to prevent illness in the youngest children during the 1987 epidemic period was 52% (95% confidence interval (-330%, 95%)) falling to 16% (95% confidence interval, (-538%, 90%)) after 1 year . Four cases that occurred in infants 3 to 7 weeks before the scheduled "booster" campaign supports limited true efficacy . However, the prescribed 1 to 3-month interval between the two doses in infants may be too long.(ABSTRACT TRUNCATED AT 250 WORDS)

J Epidemiol Community Health, 1992 Aug, 46(4), 329 - 31
Auditing and improving notification and chemoprophylaxis in bacterial meningitis; Harvey I et al.; STUDY OBJECTIVE--The aim was to audit, against agreed standards, the control of bacterial meningitis, in particular completeness of notification and appropriateness of distribution of chemoprophylaxis to contacts; and to implement appropriate changes and monitor their impact . DESIGN--The first phase involved determination, for the years 1983 and 1984, of completeness of notification by comparison with a comprehensive case register . Information about chemoprophylaxis was obtained from case notes, questionnaires to general practitioners and other records . The second phase involved introducing a programme of clinician education in the hospital with the poorest observed notification performance and re-examining performance during 1988 . Districtwide education regarding chemoprophylaxis was undertaken and the situation re-examined in 1988 . SETTING--The study took place in Mid Glamorgan Health Authority (population 536,000), with four acute hospitals . POPULATION--Consisted of all the residents of Mid Glamorgan Health Authority . MAIN RESULTS--During the first phase of the audit only 28 out of 79 cases of bacterial meningitis were notified (35%) . Performance in one hospital was significantly worse than in the other three . Chemoprophylaxis was distributed to 20 out of 26 (77%) cases of meningococcal meningitis but inappropriate drugs were used in four cases and prophylaxis was distributed more widely than is recommended in 10 cases . In the phase 2 re-examination, a significant improvement in notification was observed in the hospital where special measures were taken, with no change in a "control" hospital . Chemoprophylaxis improved throughout the District, although rifampicin continued to be distributed too widely . CONCLUSIONS--As a result of this audit, measurable improvements in both infectious disease notification and chemoprophylaxis practice were obtained by the education of clinicians . The study provides a good example of a completed audit cycle in public health medicine.

Mol Microbiol, 1992 Aug, 6(15), 2135 - 46
Sequence diversity within the argF, fbp and recA genes of natural isolates of Neisseria meningitidis: interspecies recombination within the argF gene; Zhou J et al.; Studies of natural populations of Neisseria meningitidis using multilocus enzyme electrophoresis have shown extensive genetic variation within this species, which, it has been proposed, implies a level of sequence diversity within meningococci that is greater than that normally considered as the criterion for species limits in bacteria . To obtain a direct measure of the sequence diversity among meningococci, we obtained the nucleotide sequences of most of the argF, recA and fbp genes of eight meningococci of widely differing electrophoretic type (from the reference collection of Caugant) . Sequence variation between the meningococcal strains ranged from 0-0.6% for fbp, 0-1.3% for argF, and 0-3.3% for recA . These levels of diversity are no greater than those found within Escherichia coli 'housekeeping' genes and suggest that multilocus enzyme electrophoresis may overestimate the extent of nucleotide sequence diversity within meningococci . The average sequence divergence between the Neisseria meningitidis strains and N . gonorrhoeae strain FA19 was 1.0% for fbp and 1.6% for recA . The argF gene, although very uniform among the eight meningococcal isolates, had a striking mosaic structure when compared with the gonococcal argF gene: two regions of the gene differed by greater than 13% in nucleotide sequence between meningococci and gonococci, whereas the rest of the gene differed by less than 1.7% . One of the diverged regions was shown to have been introduced from the argF gene of a commensal Neisseria species that is closely related to Neisseria cinerea . The source of the other region was unclear.

Cesk Epidemiol Mikrobiol Imunol, 1992 Aug, 41(3), 129 - 38
{Genotypes of Neisseria meningitidis strains isolated from patients in the Czech Republic}; Kuzemenska P et al.; A group of 75 strains of Neisseria meningitidis isolated from patients with meningococcal meningitis in the Czech Republic during 1980-1988 was characterized by assessment of serogroups, serotypes, serosubtypes and genotypes . Twelve strains belonged into serogroup A, 27 into serogroup B and 36 into serogroup C . The most frequently found serotype was 4, subserotype P1.2 . The authors identified 48 different enzyme genotypes among which four genetically related groups were assessed . Strains of Neisseria meningitidis of the same genotype were found more frequently during the period of 1980-1984, when a rise of meningococcal meningitis in the Czech Republic was recorded . During this period 73% of the strains belonged into three genetically related groups, while during the subsequent period (1985-1988) these genetically related groups comprised only 47% of the strains . Only one strain of Neisseria meningitidis (878/85) represented a genetic clone ET-5 complex responsible for an epidemic of meningococcal meningitis in western European countries from the mid-seventies.

J Clin Microbiol, 1992 Aug, 30(8), 2047 - 53
Production and characterization of monoclonal antibodies to type 8 lipooligosaccharide of Neisseria meningitidis; Gu XX et al.; Eight monoclonal antibodies (MAbs) to lipooligosaccharides (LOSs) of Neisseria meningitidis were produced by immunizing mice with purified LOS from group A meningococcal strain A1 . The specificities of the MAbs were examined by enzyme-linked immunosorbent assay (ELISA), immunodot assay, and ELISA inhibition by using the homologous A1 LOS, 12 immunotype LOSs of N . meningitidis (L1 through L12), and LOSs or lipopolysaccharides from other gram-negative bacteria . Two of the MAbs, 4385G7 (immunoglobulin G2b {IgG2b}) and 4387A5 (IgG2a), had the strongest reactivities with the homologous A1 LOS, moderate reactivities with the M978 (L8) LOS, but no reactivity with other LOSs . The other six MAbs (4 IgM and 2 IgG3) reacted with the A1 LOS and with several or many of the 12 LOSs . ELISA inhibition at 50% showed that the inhibitory activities of the LOSs from strains A1 and BB431 (a group B strain) to the specific MAb 4387A5 were about 10 to 20 times greater than that of the M978 (L8) LOS . When compared with MAb 2-1-L8 (L8) by Western blot (immunoblot) analysis and ELISA inhibition, the two specific MAbs recognized a different epitope in the 3.6-kDa LOSs of strains A1 and BB431 . We propose that the new epitope is L8a, since the MAbs also reacted with the M978 (L8) LOS . The expression of the L8a epitope in the A1 LOS requires a few monosaccharide residues in its oligosaccharide moiety, and the fatty acid residues in its lipid A moiety also play a role . In a whole-cell ELISA, the two specific MAbs bound specifically to the homologous strain A1 and the L8 prototype strain M978 but not to any other LOS prototype strains . These results suggest that the two specific MAbs can be used for LOS typing of N . meningitidis.

BMJ, 1992 Jul 18, 305(6846), 143 - 7
Early treatment with parenteral penicillin in meningococcal disease; Cartwright K et al.; OBJECTIVE--To measure the effect of parenteral antibiotics given before admission to hospital on mortality and on bacteriological investigations in meningococcal disease . DESIGN--Retrospective review of hospital notes and laboratory and public health medicine department records . SETTING--Three health districts in south west England . SUBJECTS--Patients with meningococcal disease in Gloucester district presenting between 1 January 1982 and 31 December 1991 (n = 190); patients with meningococcal disease in Plymouth (n = 118) and Bath (n = 73) districts presenting between 1 January 1988 and 31 December 1991 (total = 381) . MAIN OUTCOME MEASURE--Number of deaths from meningococcal disease . RESULTS--Parenteral antibiotic given by general practitioners was associated with a substantial reduction in mortality (from 9% to 5%; relative risk 0.6, 95% confidence interval 0.2 to 1.5); patients with a rash were more likely to be given parenteral antibiotics, and mortality was further reduced (from 12% to 5%; 0.5, 0.2 to 1.4) . In a district where such treatment was regularly encouraged its use increased from 5% to 40% of cases over 10 years (p = 0.00001) . Treatment with parenteral antibiotics before admission made isolation of meningococci from blood and cerebrospinal fluid less likely but did not affect nasopharyngeal cultures . CONCLUSIONS--General practitioners should carry benzylpenicillin in their emergency bags at all times and should administer it promptly, preferably intravenously, whenever meningococcal disease is suspected, unless the patient has had an anaphylactic reaction to penicillin . Specimens for culture should include a nasopharyngeal swab.

BMJ, 1992 Jul 18, 305(6846), 141 - 3
Meningococcal infections: reducing the case fatality rate by giving penicillin before admission to hospital; Strang JR et al.; OBJECTIVE--To determine whether parenteral penicillin given before admission to hospital reduces the case fatality rate in patients with meningococcal disease . DESIGN--Retrospective analysis of 46 consecutive patients admitted to hospital with meningococcal disease from January 1986 to March 1991 . SETTING--District general hospital . MAIN OUTCOME MEASURE--Hospital case fatality rate . RESULTS--None of the 13 patients given parenteral penicillin by the referring doctor before admission died, compared with eight deaths (24%) in 33 patients admitted without such treatment . CONCLUSION--Parenteral penicillin given before admission probably contributed to a reduction in the case fatality rate from meningococcal disease, and primary care physicians should be encouraged to give such treatment immediately on suspicion of the diagnosis before transferring the patient to hospital . Public health physicians are well placed to inform and alert general practitioners of the potential benefit of this action.

FEMS Microbiol Lett, 1992 Jul 15, 73(3), 283 - 9
Sequence analysis and relationships between meningococcal class 3 serotype proteins and other porins from pathogenic and non-pathogenic Neisseria species; Ward MJ et al.; The presence of highly conserved regions within previously determined porin gene sequences from Neisseria meningitidis and Neisseria gonorrhoeae permitted the construction of oligonucleotide primers for PCR amplification of other neisserial porin genes . Although two separate porin genes (porA and porB) are present in N . meningitidis only a single fragment, corresponding to porB, could be amplified from this species . The amplified porB genes from four different meningococcal serotypes, which express the class 3 outer membrane protein, were sequenced . Amplified fragments corresponding to porin genes from N . lactamica and N . sicca were also sequenced . In common with the known neisserial porins, models of the organisation of the predicted proteins indicated trans-membrane structures with eight surface exposed loops . In the meningococcal class 3 proteins the main regions of sequence variation, which must be responsible for serotype specificity, were located on loops 5 and 7 . A phylogenetic analysis of the family of porins from the Neisseria confirmed the close relationship of the meningococcal class 3 protein with the gonococcal PIA protein, while the gonococcal PIB protein was shown to be closely related to the N . lactamica porin . The close relationship seen between porins of the pathogenic and non-pathogenic Neisseriae identified no obvious virulence-associated regions in the proteins, but did suggest that the current nomenclature for neisserial porin genes may need reviewing.

Public Health Rep, 1992 Jul-Aug, 107(4), 474 - 6
Timeliness of notification in infectious disease cases; Dominguez A et al.; Records of notification in cases of eight infectious diseases in the "Servei Territorial de Salut Publica" of the Province of Barcelona, Spain, between 1982 and 1986 were reviewed . Time from onset of symptoms to notification, time from notification to completion of data collection, and time from onset to completion of the case investigation were analyzed . For the period from onset to notification, the shortest mean was registered for meningococcal infection (6.31 days) and the longest was for pulmonary tuberculosis (54.79 days) . For time from notification to complete investigation, the shortest value was for pulmonary tuberculosis (12.20 days) and the longest for rickettsioses (35.79 days) . Time from onset to completion of data collection was 22.87 days for meningococcal infection and 72.34 days for tuberculosis of other organs (probably because of the long period of time that elapses between the onset of the first symptoms and notification) . It would appear that both physicians and the general population must be educated so that lay-men can identify early signs and symptoms of disease and physicians can realize that statutory notification of infectious diseases is strongly linked to community health care.

J Clin Microbiol, 1992 Jul, 30(7), 1734 - 8
Ongoing group B Neisseria meningitidis epidemic in São Paulo, Brazil, due to increased prevalence of a single clone of the ET-5 complex; Sacchi CT et al.; Beginning in 1988, the incidence of meningococcal disease in the area of greater Sao Paulo began to surpass the upper confidence limit of an 8-year average incidence (from 1979 to 1986), thus characterizing a new epidemic in the region of greater Sao Paulo . This epidemic, which extended to 1990, was different from previous epidemics in that it was caused by serogroup B . The increased incidence of meningococcal disease was paralleled by an increased prevalence of a single group B clone, B:4:P1.15, of the ET-5 complex . ET-5 strains have been present in the greater Sao Paulo area since 1979; however, they have been associated with a high percentage of the group B disease only from 1987 to the present . On the basis of the increased incidence of group B disease in Sao Paulo, a mass vaccination program with a serotype 4:P1.15 meningococcal protein vaccine was undertaken . The impact of this vaccination program is under analysis.

Infect Immun, 1992 Jul, 60(7), 2887 - 92
Immunogenicity and antigenic heterogeneity of a human transferrin-binding protein in Neisseria meningitidis; Ferron L et al.; Growing Neisseria meningitidis on an iron restriction medium induces the synthesis of new outer membrane proteins, some of them true iron-regulated outer membrane proteins (IROMPs) and others synthesized because of the stress produced by the iron restriction . Some of these proteins are antigenic and can be considered for the development of vaccines; this is especially desirable in the case of N . meningitidis serogroup B, for which polysaccharide vaccines are not efficient . The antigenicity of N . meningitidis 37- and 70-kDa IROMPs has been studied previously; in this work, we studied the immunogenicity and antigenic heterogeneity of another IROMP, the human transferrin-binding protein 2 (TBP2), which seems to be indispensable for meningococcal growth inside the host . Mice were inoculated with purified outer membrane vesicles (blebs) from 5 selected N . meningitidis strains, and the five serum samples obtained were analyzed for anti-TBP2 antibodies by using the homologous strain and for cross-reactivity with the TBP2 of the 4 other selected strains and another 35 heterologous N . meningitidis strains . The TBP2s of the 5 strains tested were all immunogenic in mice to various degrees depending on the strain, and all five TBP2s shared one or more epitopes with heterologous strains (as shown by the cross-reactivities of the five serum samples), although the number of cross-reacting strains was very variable, ranging from 2 for strain V002 to 35 for strain P391 . This suggests that the TBP2 epitopes of different strains differ in nature or in their accessibility to the immune system . Under the iron restriction conditions used, all strains synthesized a non-TBP2 antigenic 56-kDa protein thought to be a stress protein.

Infect Immun, 1992 Jul, 60(7), 2777 - 83
Cross-reacting serum opsonins in patients with meningococcal disease; Guttormsen HK et al.; We have examined the opsonic activity of sera from patients with Neisseria meningitidis (B:15:P1.16) infections against different meningococcal strains, using flow cytometry and luminol-enhanced chemiluminescence . A marked increase in the phagocytosis of ethanol-fixed meningococcal strains of different serogroups, serotypes, and serosubtypes was demonstrated in the presence of convalescence sera compared with acute sera . Convalescence sera also caused a significant increase of leukocyte oxidative metabolism during phagocytosis, as measured by luminol-enhanced chemiluminescence . The sera contained a broad range of opsonins cross-reacting with serogroup A, B, C, W-135, and Y meningococci of different serotypes and serosubtypes, indicating that the cross-reacting opsonins recognized surface epitopes other than those determined by current serotyping schemes.

Clin Genet, 1992 Jul, 42(1), 8 - 12
Linkage analysis in properdin deficiency families: refined location in proximal Xp; Wadelius C et al.; Properdin is a component of the alternative activation pathway of the complement system . Deficiency or dysfunction of the protein is inherited in an X-linked recessive manner . Affected males have an increased risk of developing meningococcal disease . Six multi-generation families with different types of properdin deficiency were analyzed using microsatellite and other polymorphisms on the X chromosome . Based on multipoint data, it was found that the disease gene maps close to DXS255 (Zmax = 13.3 at theta max = 0.00) and DXS426 (Zmax = 12.9 at theta max = 0.00) on the Xp-arm near the centromere . There was no indication of genetic heterogeneity among the six families analyzed . Thus it is now possible to perform accurate DNA-based determination of the inheritance of the mutation in affected families.

Ethiop Med J, 1992 Jul, 30(3), 135 - 42
Epidemic meningococcal meningitis in adult Ethiopians in Addis Abeba, Ethiopia, 1988; Fekade D et al.; 278 patients with pyogenic meningitis admitted to the Tikur Anbessa Teaching Hospital in Addis Abeba, Ethiopia, between January and December 1988 were studied prospectively to describe the epidemiology, microbiology, clinical features and outcome of infection . Fifty-nine per cent of the patients were admitted in the hot dry season between January and the end of June . About half of the patients (57%) were in the age group 15 to 19 years; the male to female ratio was 1.8:1 . Two hundred sixty-two specimens (94%) were examined by Gram stain/or culture . N . Meningitidis was cultured from 161 of 243 CSF specimens (65%) and the Gram stain was diagnostic in 108 of 140 CSF specimens (77%) . Both Gram stain and culture were negative in 90 of 262 specimens (34%) . Thirty-five of the isolates were sero-grouped and all were found to belong to serogroup A . All 30 isolates tested for drug sensitivity were resistant to sulfadiazine but sensitive to penicillin . Forty-three of 204 patients died of their infection, a case fatality rate of 21%: 60% of the deaths occurred in the first 24 hours after admission . Eleven of 13 patients with meningococcaemia expired . The case fatality rates for meningitis and meningococcaemia were 16% and 85% respectively . Nine patients (4%) developed neurologic sequelae: 4 hemiplegia, 3 nerve deafness, 2 cranial nerve palsies . This high morbidity and mortality from meningococcal infection demonstrates the need for a national surveillance programme for the prevention and control of meningococcal disease in the country.

J Exp Med, 1992 Jul 1, 176(1), 79 - 88
Identification of T cell epitopes occurring in a meningococcal class 1 outer membrane protein using overlapping peptides assembled with simultaneous multiple peptide synthesis; Wiertz EJ et al.; The meningococcal class 1 outer membrane protein (OMP) plays an important role in the development of protective immunity against meningococcal infection, and is therefore considered to be a promising candidate antigen (Ag) for a meningococcal vaccine . The induction of an effective antibody response entirely depends upon T helper cells . To identify T cell epitopes of the OMP, we prepared 45 overlapping synthetic peptides representing the entire sequence of the class 1 protein of reference strain H44/76 . Fully automated simultaneous multiple peptide synthesis (SMPS) was used to assemble the 45 twenty mer which overlapped by 12 amino acid residues on a 12 mumol scale . The peptides were tested for recognition by peripheral blood mononuclear cells (PBMC) obtained from 34 volunteers . Surprisingly, all synthetic peptides induced proliferative responses of PBMC isolated from one or more human histocompatibility leukocyte antigen (HLA)-typed immune adults . With PBMC from seven nonimmune donors, no proliferative response was observed . Immunodominant regions were found, recognized by PBMC from many volunteers, irrespective of their HLA type . Most of the immunodominant T cell epitopes are located outside the variable regions and, thus, will be conserved among different meningococcal (and gonococcal) strains . Furthermore, the overlapping peptides could be used to identify the epitopes recognized by OMP-specific T cell clones with known HLA restriction . It is interesting that the epitopes defined with the clones occur in highly conserved areas, shared by all neisserial porin proteins . In summary, this analysis of the T cell response to the meningococcal class 1 OMP constitutes a complete study of reactivity to a foreign protein, and illustrates some important features of Ag recognition by T cells . Our data demonstrate unexpected diversity in the T cell recognition of the OMP, and imply that the T cell repertoire against foreign Ag may be greater than previously assumed . This observation is supported by recent data on the interaction of peptide and major histocompatibility complex (MHC) class II, the latter being much less selective than MHC class I . Finally, a comparative analysis pointed out the limitations of algorithms predicting T cell determinants, and the importance of the empirical methodology provided by SMPS.

Rom J Morphol Embryol, 1992 Jul-Dec, 38(3-4), 107 - 14
Up-to-date aspects of meningoencephalitis . Anatomo-clinical researches; Laky D et al.; The anatomo-clinical study of the deaths caused by meningoencephalitis at the Infectious Diseases Clinics in Bucharest in 1986 and 1987 showed the increase of morbidity, 194 lethal cases being registered . The most affected age group was up to 1 year, followed by older persons, then by children between 1 and 10 years, the male sex prevailing . The most incriminated pathogenic agents were meningococcus, pneumococcus, as well as negative Gram germs, Escherichia coli, whereas the favouring factors were especially malnutrition, premature birth, dystrophies, focal infections . The lesional pictures are described, underlying the frequency of vascular lesions, ventriculitis cerebral abscesses, as well as the role of demyelinizations and of the glial reactions in pathogenesis.

Yale J Biol Med, 1992 Jul-Aug, 65(4), 293 - 315
Immunizations for foreign travel; Hill DR; One of the most important aspects of preparing travelers for destinations throughout the world is providing them with immunizations . Before administering any vaccines, however, a careful health and immunization history and travel itinerary should be obtained in order to determine vaccine indications and contraindications . There are three categories of immunizations for foreign travel . The first category includes immunizations which are routinely recommended whether or not the individual is traveling . Many travelers are due for primary vaccination or boosting against tetanus-diphtheria, measles-mumps-rubella, pneumococcal pneumonia, and influenza, for example, and the pre-travel visit is an ideal time to administer these . The second category are immunizations which might be required by a country as a condition for entry; these are yellow fever and cholera . The final category contains immunizations which are recommended because there is a risk of acquiring a particular disease during travel . Typhoid fever, meningococcal disease, rabies, and hepatitis are some examples . Travelers who are pregnant or who are infected with the human immunodeficiency virus require special consideration . Provision of appropriate immunizations for foreign travel is an important aspect of preventing illness in travelers.

Biochemistry, 1992 Jun 2, 31(21), 4996 - 5004
Helical epitope of the group B meningococcal alpha(2-8)-linked sialic acid polysaccharide; Brisson JR et al.; The immunological properties of the group B meningococcal alpha(2-8)-linked sialic acid polysaccharide have been rationalized in terms of a model where the random coil nature of the polymer can be described by the presence of local helices . The conformational versatility of the alpha NeuAc(2-8)alpha NeuAc linkage has been explored by NMR studies at 600 MHz in conjunction with potential energy calculations for colominic acid, an alpha(2-8)NeuAc polymer, and the trisaccharide alpha NeuAc(2-8)alpha NeuAc(2-8)beta NeuAc . Potential energy calculations were used to estimate the energetically favorable conformers and to describe the wide range of helices which the polymer can adopt . No unique conformer was found to satisfy all NMR constraints, and only ensemble averaged nuclear Overhauser enhancements could correctly simulate the experimental data . Conformational differences between the polymer and the trisaccharide could be best explained in terms of slight changes in the relative distribution of conformers in solution . Similar helical parameters for the alpha(2-8)NeuAc polymer and poly(A) were proposed as the basis for their cross-reactivity to a monoclonal antibody IgMNOV . The unusual length dependency for binding of oligosaccharide to group B specific antibodies was postulated to arise from the recognition of a high-order local helix with an extended conformation which was not highly populated in solution.

Epidemiol Infect, 1992 Jun, 108(3), 449 - 55
Antibiotic sensitivities of Neisseria meningitidis isolates from patients and carriers in Greece; Tzanakaki G et al.; Usage of antibiotics in southern Europe is less well regulated than in northern countries . The proportion (48%) of meningococci in Spain insensitive to pencillin (MIC greater than or equal to 0.1 mg/l) prompted this investigation of antibiotic sensitivities of isolates from Greek patients with meningitis (31) and carriers (47 school-children and 472 recruits) . The agar dilution method was used to determine MIC to penicillin G (PN), sulphamethoxazole (SU), rifampicin (RF), cefaclor (CF) and ciprofloxacin (CP) . The proportion of isolates insensitive to PN was 48% for isolates from patients, 19% from school-children and 36.6% from recruits . Resistance to SU (MIC greater than or equal to 16 mg/l) was found in 16% of those from patients, 10.6% from children and 40% from recruits . None of the isolates from patients was resistant to RF (greater than or equal to 1 mg/l) but 6% of those from carriers were . Resistance to CF (greater than or equal to 4 mg/l) was found in 9.2% of patient isolates, 6.4% from children and 23.7% from recruits . All isolates except one were sensitive to CP (MIC range less than 0.0015-0.125 mg/l) . Resistances to PN, SU and RF were analysed by serogroup, serotype and subtype of the bacteria . The proportion of resistant isolates showed some variation between different areas of Greece, but it was not statistically significant.

Epidemiol Infect, 1992 Jun, 108(3), 441 - 8
Factors affecting carriage of Neisseria meningitidis among Greek military recruits; Blackwell CC et al.; Greek military recruits (993) were examined for carriage of meningococci during July 1990 . Blood, saliva and throat swab specimens were obtained and each recruit answered a questionnaire providing information on age, education (a measure of socioeconomic level), place of residence, smoking habits and recent infections . The overall carriage rate was 25% but differed between the two camps: 79/432 (18%) in Camp A and 168/561 (30%) in Camp B (P less than 0.0005) . In Camp B, there were significantly higher proportions of recruits who were non-secretors (P less than 0.0005), and/or heavy smokers (P less than 0.0005) . They were also younger (less than 19 years old) (P less than 0.001), and on the whole had fewer years of education (P less than 0.0005) . By univariate analysis, carriage was significantly associated with smoking . By multiple logistic regression analysis, carriage was associated with smoking (P less than 0.001), age (P less than 0.01) and the camp in which the recruits were based (P less than 0.01) . Among recruits in Camp B, 15/38 (40%) of those with recent viral infections were carriers compared with 30% for the camp in general.

Eur J Immunol, 1992 Jun, 22(6), 1365 - 72
Mycobacterial heat-shock proteins as carrier molecules . II: The use of the 70-kDa mycobacterial heat-shock protein as carrier for conjugated vaccines can circumvent the need for adjuvants and Bacillus Calmette Guérin priming; Barrios C et al.; In a recent work, we have shown that mycobacterial heat-shock proteins (hsp) of 65-kDa (GroEL-type) and 70-kDa (DnaK-type) acted as carrier molecules in mice, previously primed with Mycobacterium tuberculosis var . bovis (bacillus Calmette-Guerin, BCG), for the induction of high and long-lasting titers of IgG against the repetitive malaria synthetic peptide (NANP)40 . Anti-peptide antibodies were induced when the malaria peptide, conjugated to the mycobacterial hsp, was given in the absence of any adjuvants (Lussow et al., Eur . J . Immunol . 1991 . 87:2960) . In this report, we show that mice immunized with peptides or oligosaccharides conjugated to the 70-kDa hsp produced high titers of IgG antibodies in the absence of any previous priming with BCG . The anti-peptide antibody response persisted for at least 1 year . This adjuvant-free carrier effect of the 70-kDa hsp was T cell dependent, since no anti-peptide nor anti-70-kDa IgG antibodies were induced in athymic nu/nu mice . Previous immunization of mice with the 65-kDa or 70-kDa hsp did not have any negative effect on the induction of anti-peptide IgG antibodies after immunization with hsp-peptide conjugates in the absence of adjuvants . Furthermore, preimmunization with the 65-kDa hsp could substitute for BCG in providing an effective priming for the induction of anti-(NANP) antibodies . Finally, both the 65-kDa and 70-kDa hsp acted as carrier molecules for the induction of IgG antibodies to group C meningococcal oligosaccharides, in the absence of adjuvants . These findings strongly suggest that the use of hsp as carriers in conjugated constructs for the induction of anti-peptide and anti-oligosaccharide antibodies could be of value in the design of new vaccines for eventual use in humans.

Crit Care Med, 1992 Jun, 20(6), 816 - 22
Effect of a human immunoglobulin preparation for intravenous use in a rabbit model of meningococcal endotoxin-induced shock; Saladino R et al.; BACKGROUND AND METHODS: Endotoxin shock is mediated by various cytokines, including tumor necrosis factor . Treatment of patients with i.v . immunoglobulin has been shown to reduce the concentration of circulating cytokines . The purpose of this study was to determine the protective effects of immunoglobulin for i.v . use on meningococcal endotoxin-induced shock in a rabbit model . Experimental animals were challenged with i.v . meningococcal endotoxin (lipo-oligosaccharide) 10 micrograms/kg, and treated with either a 2-hr i.v . immunoglobulin infusion (400 mg/kg) or a similar saline infusion that was initiated 30 mins before endotoxin challenge . Control animals were challenged with saline alone . RESULTS: Compared with untreated control animals, pulse rate increased (p less than .007) and mean arterial pressure and serum bicarbonate concentrations decreased (p less than .02) in both experimental groups, but did not differ between immunoglobulin-treated and saline-treated animals (p greater than .05) at any time after the endotoxin challenge . Geometric mean serum endotoxin concentrations were significantly (p less than .03) lower in the immunoglobulin-treated animals at 60, 120, 180, 240, 300, and 360 mins after the endotoxin challenge . The geometric mean serum tumor necrosis factor level at 1 hr after the endotoxin challenge in the immunoglobulin-treated experimental animals was lower than in saline-treated animals (5.53 vs . 8.47 tumor necrosis factor enzyme-linked immunosorbent assay U/mL), but not significantly so (p greater than .05) . Mortality rate was similar in both experimental groups; eight (67%) of 12 saline-treated experimental rabbits and seven (70%) of ten immunoglobulin-treated rabbits died . All untreated control animals survived 24 hrs . CONCLUSIONS: In this model of circulatory shock in rabbits, i.v . immunoglobulin: a) does not significantly alter the physiologic responses to endotoxin challenge; b) significantly reduces endotoxin concentrations; c) reduces tumor necrosis factor concentrations, but not significantly; and d) does not improve survival rate.

Microb Pathog, 1992 Jun, 12(6), 415 - 20
Intranasal infection of infant mice with Neisseria meningitidis; Mackinnon FG et al.; In human meningococcal infection the mechanism of the transition from asymptomatic carriage to invasive disease is unknown, partly due to the lack of an effective animal model that mimics all stages of the human disease . Therefore, we have endeavoured to develop a model for the human infection by instilling a suspension of Neisseria meningitidis into the nostrils of infant mice and subsequently determining the numbers of organisms in the nasal passages, lungs, blood and brains . Intranasal (i.n.) instillation resulted in consistent nasal colonisation which usually developed into a lung infection . In many cases the lung infection preceded bacteraemia, which occasionally resulted in death of the mice . The severity of the infection and the transition to bacteraemia were enhanced by intraperitoneal (i.p.) treatment of the mice with iron dextran or human transferrin . A N . meningitidis strain that was avirulent in an i.p . infection was also avirulent following i.n . infection . The requirement for lung colonisation to precede bacteraemia and the need for i.p . injection of iron compounds limit the use of i.n . infection of the infant mouse as a model for human meningococcal disease . However, various aspects of meningococcal virulence can be examined using this model.

Immunol Rev, 1992 Jun, 127, 221 - 30
Different role of cytokine mediators in septic shock related to meningococcal disease and surgery/polytrauma; Waage A et al.; So far, there has been a tendency towards a uniform concept of the role and kinetics of TNF and other cytokines in septic shock . However, our comparison of data from different groups of shock patients clearly demonstrates marked differences . On the one hand, the cytokine pattern in experimental septic shock and meningococcal disease has similarities which include early burst releases of TNF and IL-6 . On the other hand, intensive care unit patients which includes patients with polytrauma, surgery, burns and other underlying diseases have a completely different pattern of appearance of TNF and IL-6 in the circulation . We have not been able to detect bioactive TNF in the circulation of these patients, whereas others have measured elevated levels of immunoreactive TNF . Bioactive IL-6 can be detected in serum; however, the levels are often fluctuating and there is no common pattern of appearance . These differences probably reflect differences in the release of endotoxin and the immunological status of the patients . TNF inhibitors and soluble TNF receptors probably play an important role . Experimental models for septic shock most commonly use administration of live bacteria or endotoxin to anesthesized healthy animals . This appears to be a good model for meningococcal disease, but not for intensive care unit patients.

Mol Microbiol, 1992 Jun, 6(11), 1565 - 73
Identification and characterization of a novel insertion sequence, IS1106, downstream of the porA gene in B15 Neisseria meningitidis; Knight AI et al.; Examination of Neisseria meningitidis strains associated with endemic meningococcal disease demonstrated differences in the number of copies of a repetitive sequence . Characterization of a copy of this repetitive sequence present in B15 strains has revealed the presence of a novel insertion sequence (IS1106) located within a complex repetitive region downstream of the gene for the major surface antigen (porA) . IS1106 has a length of 1137 bp and is flanked by 36bp inverted repeats . Two open reading frames (ORF1 and ORF2) are present in opposite strands in codon-codon register with ORF2 entirely located within ORF1 . The predicted protein from ORF1 demonstrates homology with the 5A protein of IS5 (Kroger and Hobom, 1982) . Strains from two independent outbreaks of B15 meningococcal disease in the UK were found to contain the same genomic deletion removing a copy of IS1106 downstream of the porA gene.

Commun Dis Rep CDR Rev, 1992 May 22, 2(6), R64 - 5
A survey of emergency penicillin treatment for meningitis; Rouse AR; The case fatality rate for meningococcal meningitis has changed little in recent years . A study of persons admitted to hospital in Bristol with suspected meningitis found that only five of the 41 cases admitted in 1991 were given penicillin prior to admission . Possible reasons for this include lack of awareness of the need, reluctance to give injections to children, uncertainty about dosage, failure to carry injectable penicillin and diagnostic uncertainty.

Commun Dis Rep CDR Rev, 1992 May 22, 2(6), R61 - 3
Meningococcal infections in England and Wales: 1991; Jones DM et al.; There were fewer reports of cases of meningococcal infection in England and Wales during 1991 than in 1990 . The number of isolates received at the Meningococcal Reference Laboratory decreased by 102 (7%), largely due to fewer strains being received from South West Thames, North East Thames and North Western regions . Group C infections showed a greater decrease than group B, with 16% fewer strains reported in 1991 than in 1990 . Eight per cent of the strains received during 1991 showed reduced susceptibility to penicillin (MIC > 0.16mg/l).

J Am Osteopath Assoc, 1992 May, 92(5), 633 - 7
The varied clinical presentations of meningococcal infection; Sellick JA Jr et al.; The clinical presentation of Neisseria meningitidis may include bacteremia, septic shock, or meningitis . The polysaccharide capsule of the organism appears to be the major determinant and is necessary for specific immunity . Colonization of the nasopharynx is required for invasion, and persons with complement component deficiencies are particularly at risk of infection . The organism can be detected by culture of blood or spinal fluid, or by antigen detection in spinal fluid . Prompt therapy with penicillin G is necessary for a good outcome . The occurrence of secondary cases requires that prophylactic therapy be administered to close contacts of index cases . The cases presented herein illustrate a variety of manifestations of meningococcal infection, and all of the patients initially were seen in primary care settings . It is important for physicians to be vigilant for these infections so that appropriate therapy may be instituted rapidly.

Pediatr Nephrol, 1992 May, 6(3), 239 - 43
Mesangiocapillary glomerulonephritis associated with meningococcal meningitis, C3 nephritic factor and persistently low complement C3 and C5; Hulton SA et al.; We report two unusual cases in which mesangiocapillary glomerulonephritis occurred in association with meningococcal infection . C3 nephritic factor, an autoantibody to alternate pathway C3 convertase, was present . Low serum complement C3 and C5 levels were also noted . The depressed complement levels, in conjunction with terminal complement complexes at the upper limit of normal, suggest activation of the early and late complement cascade . We suggest that children presenting with meningococcal infection should have a regular urine examination, as well as full complement measurements performed, in view of the association with hypocomplementaemic mesangiocapillary glomerulonephritis . Similarly, prophylactic penicillin should be prescribed for patients with mesangiocapillary glomerulonephritis and persistently low C5 levels to prevent meningococcal complications.

Fukuoka Igaku Zasshi, 1992 May, 83(5), 201 - 8
{The association between deficiency of terminal complement components and the occurrence of meningococcal meningitis}; Nishizaki M; Seventeen patients with sporadic meningococcal meningitis, registered in Fukuoka city, were studied for complement deficiency . Four of the seventeen had a selective deficiency of the ninth component of the complement (C9), four had a deficiency of the seventh component of the complement (C7), and one had a deficiency of the fifth component of the complement (C5) as determined by both hemolytic and antigenic assay . Family studies suggested that these complement deficiencies in the present study were hereditary . Based on the incidence (0.036% of homozygous C9 deficiency in Fukuoka (171 C9 deficient individuals of 475, 886 blood donors), we have concluded that patients with C9 deficiency are more susceptible to meningococcal meningitis than normal individuals (p less than 0.001) . In addition, the present study further supports that complement deficiency is common in patients with sporadic meningococcal meningitis.

APMIS, 1992 May, 100(5), 449 - 54
Early development in healthy children of serum opsonins against nonpathogenic Neisseria meningitidis; Fredlund H et al.; In an earlier study, with the use of chemiluminescence (CL) and phagocytic killing, we could show that in the presence of serum from healthy adults polymorphonuclear leukocytes (PMNL) efficiently handle nonpathogenic Neisseria meningitidis strains, in sharp contrast to those associated with clinical disease . The major part of this difference was dependent on serum factors . In the present study 84 serum samples from children 1-3, 4-6, 7-9, and 10-14 years old were studied by the CL technique according to their ability to opsonize meningococci . There was a highly significant difference (p less than 0.001) in all four age groups when the CL indexes obtained with the pathogenic meningococci of the serogroups A, B and C were compared with those of the nonpathogenic menigococci: serogroup 29E and nongroupable meningococci . These findings imply that the ability to opsonize so-called nonpathogenic meningococci is developed early in life and may explain why they are only occasionally able to cause disease.

J Clin Microbiol, 1992 May, 30(5), 1282 - 6
Emergence of a new clone of serogroup C Neisseria meningitidis in São Paulo, Brazil; Sacchi CT et al.; Serogroup C isolates of Neisseria meningitidis recovered from 121 patients with meningitis or septicemia in Greater Sao Paulo, Brazil, between 1976 and 1990 were analyzed with respect to serotype and multilocus enzyme genotype . The distribution of serotypes has changed since 1989 when serotype 2b started to replace serotype 2a . There were 48 distinct multilocus genotypes (electrophoretic types {ETs}) and 13 distinct complexes . Among the 41 serotype C:2b:- strains analyzed, 38 (93%) were found in complex 11 . The percentage of complex 11 increased from 8% in 1988 to 50 and 66% in 1989 and 1990, respectively . Although we have been in an epidemic situation due to serogroup B:4:P1.15 ET-5 complex since 1988, the appearance and increase of a new unrelated strain, C:2b:- of ET-11 complex, in 1989 and 1990 provide enough data to conclude that the presence of two different complexes, ET-5 and -11, of N . meningitidis were responsible for the high levels of meningococcal disease in Greater Sao Paulo during this period.

Scand J Immunol, 1992 May, 35(5), 589 - 95
Complement deficiency and antibody profile in survivors of meningococcal meningitis due to common serogroups in Italy; D'Amelio R et al.; A collaborative survey was carried out in Italy on a group of 59 subjects with a past history of meningococcal meningitis . The aim was to evaluate the prevalence of complement deficiencies, the serogroup of meningococci responsible for the disease and other possible immune abnormalities associated with the infection . Complement analysis allowed the detection of 10 cases (17%) with deficiencies of the terminal components, and in particular six cases of C8 beta, three of C7 and one of C6 defect . Half of the subjects with complement deficiencies had recurrences of meningitis and developed the infection at an older age in comparison with the control group with normal complement activity . The meningococcal C strain was the most diffuse (68%) and infected all the complement-deficient subjects . Evaluation of the antibody response to meningococcal capsular polysaccharides (PS) showed that only 42.5% of the individuals with group C had antibodies as opposed to 83% and 100% of the patients with meningitis due to group A and B, respectively . In all 59 subjects serum Ig as well as IgG subclasses were present, at normal levels for the age . Vaccination of seven out of the 24 subjects without detectable anti-meningococcal PS antibodies with the sole PS A+C induced a normal response in six of them, including a subject with complement defect . In the subject who did not respond to the antigen, the antibodies against the ubiquitous pneumococcal PS type 14 were also lacking, whereas anti-tetanus toxoid (TT) antibodies were normally present . From these data we may conclude the following: (1) the high prevalence (17%) of late complement components defect among survivors of meningococcal meningitis is also confirmed in the Italian population; (2) the serogroup C, responsible for the infections in all the cases with late complement components defect, is highly recirculating in Italy and apparently less immunogenic; (3) specific vaccination with meningococcal PS is a valid prophylaxis in subjects with lack of specific antibodies as well as in subjects with complement defect.

Arthritis Rheum, 1992 May, 35(5), 580 - 6
Hereditary dysfunction of the third component of complement associated with a systemic lupus erythematosus-like syndrome and meningococcal meningitis; Nilsson UR et al.; OBJECTIVE . We describe a dysfunction of C3 in a patient with a systemic lupus erythematosus (SLE)-like syndrome . Alternative pathway complement function was absent, but classical pathway complement function was partially intact . METHODS . We used functional, preparative, and immunochemical techniques in the study . RESULTS . The patient's C3 proved normally susceptible to trypsin proteolysis and partially resistant to classical pathway, but completely resistant to alternative pathway, convertase-dependent cleavage . CONCLUSION . The dysfunction, thus, was caused by a failure of C3 to interact with the C3 convertases, rather than by a lack of a proteinase-sensitive cleavage site in the deficient protein.

Plast Reconstr Surg, 1992 May, 89(5), 878 - 81
Extremity amputations in meningococcemia-induced purpura fulminans; Genoff MC et al.; Six children with meningococcemia-induced purpura fulminans were followed . Five of the six required amputations of 14 limb segments . Eight of these amputations required revisions to higher levels.

Antimicrob Agents Chemother, 1992 May, 36(5), 1028 - 31
Discriminative criteria for Neisseria meningitidis isolates that are moderately susceptible to penicillin and ampicillin; Campos J et al.; The prevalence of Neisseria meningitidis isolates that are moderately susceptible to penicillin and ampicillin has increased very quickly in Spain; the current prevalences in our hospital are 48.4 and 55.6%, respectively . We studied the reliability of the disk diffusion method for discriminating between fully susceptible (MIC, less than or equal to 0.06 microgram/ml) and moderately susceptible (MICs, 0.12 to 1.0 microgram/ml) isolates . Thirty-eight isolates (12 Pen(s) Amp(s), 18 Penr Ampr, and 8 Pen(s) Ampr) were assayed by the disk diffusion and plate dilution methods by use of disks of 1, 2, 5, and 10 U of penicillin, 2 and 10 micrograms of ampicillin, and 1 microgram of oxacillin on Mueller-Hinton agar with or without 5% sheep blood . Breakpoints were generated, and their discriminative values were determined with a collection of 195 meningococcal strains isolated consecutively from cerebrospinal fluid or blood . None of the strains produced beta-lactamase . Penicillin- and ampicillin-susceptible strains (MIC, less than or equal to 0.06 microgram/ml) had oxacillin inhibition zones of greater than or equal to 11 mm on blood agar . Moderate susceptibility to ampicillin and penicillin was suggested by an inhibition zone of less than or equal to 10 mm around the 1-microgram disk and an inhibition zone of less than or equal to 26 mm around the 2-U penicillin disk . We conclude that discrimination between fully susceptible and moderately susceptible populations of N . meningitidis can be accomplished by the disk diffusion method by use of Mueller-Hinton agar plus 5% sheep blood with the 1-microgram oxacillin disk (which is especially suited for screening methods) and the 2-U penicillin disk . The lack of an oxacillin inhibition zone indicates moderate susceptibility to either penicillin or ampicillin or both.

Immunology, 1992 May, 76(1), 20 - 3
Imbalance between tumour necrosis factor-alpha and soluble TNF receptor concentrations in severe meningococcaemia . The J5 Study Group; Girardin E et al.; The extracellular domain of tumour necrosis factor-alpha (TNF-alpha) receptors have inhibitory properties against TNF-alpha . The relative ratio between ligand and ligand inhibitors may influence the outcome of meningococcaemia . To test this hypothesis, levels of TNF-alpha and of each of the soluble inhibitory fragments originating from two distinct TNF-alpha receptors (sTNF-RI and sTNF-RII) were measured in sera of children with severe meningococcaemia . On admission to the hospital the levels of sTNF-RI, -RII and TNF-alpha were markedly increased and all three correlated with the outcome of the disease . A correlation was found between TNF-alpha and sTNF-RI (P less than 0.001 by Pearson rank correlation coefficient) or sTNF-RII (P = 0.012) . For TNF-alpha concentrations below 500 pg/ml, the increase of TNF-alpha was proportional to that of sTNF-RI and RII; however, when TNF-alpha levels exceeded 500 pg/ml, sTNF-RI and RII concentrations did not increase proportionally . At admission, in patients with fatal outcome, the ratios TNF-alpha/sTNF-RI and -RII were higher than in survivors . During the first 6 hr, the kinetics of TNF-alpha, sTNF-RI and -RII were different . Naturally occurring TNF-alpha inhibitors may play an important role in modulating the biological activity of TNF-alpha in severe meningococcaemia.

Rev Clin Esp, 1992 Apr, 190(6), 311 - 3
{Cutaneous vasculitis during bacteremia caused by Meningococcus serogroup B}; Garcia-Patos V et al.; We report a patient with an upper respiratory tract infection who presented outbreaks of erythematosus-purpuric macules and papules (the pathological substrate of which was a leukocytoclastic vasculitis with numerous intravascular thrombi) coinciding with two autolimited febrile episodes . In serial hemocultures B meningococcus was identified oral antibiotic treatment was given achieving a good clinical evolution . Although both episodes could be considered as a meningococcemia without sepsis, they could also correspond to the initial phase of a chronic meningococcemia . The possible etiopathogenesis of the cutaneous lesions is discussed and the therapeutic and prognostic repercussion of an early identification of these forms of meningococcal disease, which are poorly expressed clinically, are highlighted.

Neurochem Int, 1992 Apr, 20(3), 365 - 70
Study of brain and vascular plexus gangliosides in meningoencephalitis of various etiology; Karpova OB et al.; The content of brain and vascular plexus gangliosides and their composition have been studied in 15 cases of meningoencephalitis of various etiology and degree of disease . The most pronounced decrease of ganglioside concentration was found in brain of children, who died from herpes virus infection . Decrease of ganglioside content was revealed in brain grey matter of patients with influenza virus or meningococcus infection, but not in cases of mycoplasma infection . These data provide evidence of nerve cell destruction due to meningoencephalitis of various etiology . The biochemical data obtained are in good agreement with the results of the brain of children infection by herpes virus (increase of GD1b content in grey matter) . Ganglioside content in vascular plexes of patients with meningoencephalitis was found to be, on the contrary, much higher (ca 4 times) than in the controls . The higher the lesion of choroid plexes in meningoencephalitis is, the higher the ganglioside content in them is.

Proc Natl Acad Sci U S A, 1992 Mar 15, 89(6), 2120 - 4
Molecular polymorphism and epidemiology of Neisseria meningitidis immunoglobulin A1 proteases; Lomholt H et al.; Neisseria meningitidis is one of several important bacterial pathogens that secrete a specific protease capable of cleaving human immunoglobulin A1 (IgA1) in the hinge region . To obtain further information on this putative virulence factor, we examined the IgA1 protease and iga gene region of 133 isolates of N . meningitidis assigned to 88 multilocus enzyme genotypes and representing major epidemics and carrier strains from 19 countries . Of the two IgA1 cleavage specificities previously observed, isolates associated with epidemics of meningococcal disease showed exclusively type 1 IgA1 protease activity . Considerable heterogeneity of the N . meningitidis IgA1 protease was demonstrated at both the protein and gene levels . Thus, five different forms of IgA1 protease were detected with enzyme-neutralizing antibodies raised in rabbits . An antiserum raised against a single type 2 IgA1 protease inhibited the enzyme activity of all strains examined, a finding of potential significance for the possible application of IgA1 protease in a vaccine against meningococcal disease . Examination of the iga gene region with restriction endonucleases revealed a high degree of polymorphism among strains belonging to some multilocus enzyme genotypes . The different iga gene types did not correlate with cleavage type or inhibition of the IgA1 protease . Our findings indicate that horizontal genetic exchange occurs in vivo with considerably different frequency in different clones of meningococci.

Aten Primaria, 1992 Mar 15, 9(4), 193 - 5
{An analysis of the obligatory reporting of meningitis in a pediatric area}; Pascual J et al.; AIMS . To find out the validity, reliability and quality of the epidemiological information which comes from the System of Statutory Declarations . The example used is the incidence of Meningitis . DESIGN . Descriptive study of the coverage of the Declaration, with the help of the EDO (Illnesses requiring a Statutory Declaration) index, of the pediatric (up to 14 years old) cases of meningitis attended in our Area between 1984 and 1989 . We analysed how the Declaration had been filled in and the agreement between the information gathered through the notification system and clinical records . SITE . The whole network of epidemiological vigilance: hospitals, provincial epidemiological services and primary care services . PATIENTS . All the cases of child meningitis (120 cases) seen in the Mother and Child Hospital in our area between 1984 and 1989 . MAIN MEASUREMENTS AND RESULTS . The meningitis declaration covered 47.5% of the total number of cases seen . In the cases declared, the diagnosis of meningococcal meningitis on the EDO index was 89.5%, whereas the rate in the clinical reports was only 20% . Thus agreement in the diagnosis does not exceed what could be produced by chance (Kappa = 2.5%; p = NS), as agreement for all diagnoses is 7.1% . CONCLUSIONS . Our results demonstrate a low level of declaration, poor standard of compliance and scant agreement between the Statement of Declaration and the clinical report . The validity and reliability of this information is extremely low and suggests a need to re-consider the usefulness of this vigilance system for health-service practice, especially in Primary Health Care.

Pathol Biol (Paris), 1992 Mar, 40(3), 230 - 3
The chemoprophylaxis of cerebrospinal meningitis using rifampin in a military population; Chapalain JC et al.; Since February 5th 1990, the prevention of secondary cases of cerebrospinal meningitis (CSM) in France has been obtained by the use of rifampin . Following the detection of a case of N . meningitidis of antigenic formula B:NT:P1.15,16 in a military population, 89 contacts subjects received 600 mg rifampin twice a day during 2 days . Meningococcal carriage rate was investigated by nasopharyngeal swab sampling of the 89 subjects and 62 non-contact controls from the same community . Twenty-three days after the initial case of meningitis, carriage rate was 5.6% for treated subjects and 37.1 for controls . Sero-grouping, serotyping and subtyping failed to detect the initial virulent strain; it demonstrated the heterogeneity of circulating strains . Since rifampin-resistant mutants may occur, two strains in the treated group, it is essential that chemoprophylaxis in a community be limited strictly to the contact subjects.

Int J Biometeorol, 1992 Mar, 36(1), 18 - 29
Weather conditions prior to major outbreaks of meningococcal meningitis in the United Kingdom; Collier CG; Meningitis has been a notifiable disease in the United Kingdom for some 70 years . Only in recent years, stimulated by the work of the Meningitis Trust, has there been a more general awareness of the geographical distribution of cases, with certain locations being more prone than others to episodic outbreaks of the disease . In this paper we consider weather conditions prior to major outbreaks of meningitis in Hereford and Worcester, and Cleveland and the northwest Midlands . Possible causal links to air quality and large temporal changes of relative humidity are found from analysis of case data . However, whilst the diagnostic studies reported are encouraging, an independent test of the relative humidity gradient criterion using independent data for Gloucester was not successful . It is clear that meteorological and air quality data actually of the area from which the disease is reported must be analysed more fully to sustain or overrule the hypothesis proposed . In addition, the need for further clinical research into the likelihood of disease triggers generated by atmospheric smoke, dust and moisture is identified.

APMIS, 1992 Mar, 100(3), 209 - 20
Monocyte phagocytosis of opsonized Neisseria meningitidis serogroup B; Sjursen H et al.; The chemiluminescence (CL) was examined when peripheral blood monocytes were incubated with opsonized Neisseria meningitidis, serogroup B, serotype 15:P1.16 or serotype 2a:P1.2 . The monocytes were separated from a mononuclear cell suspension by an immunomagnetic negative selection technique using magnetic polystyrene microspheres coated with monoclonal antibodies specific for T and B lymphocytes . More than 90% of the lymphocytes were removed, yielding a suspension containing 93% monocytes . Optimal sensitivity for phagocytosis was obtained using 1% serum (10 microliters), 72 bacteria per monocyte cell, and 7.5 min opsonization and incubation time during continuous agitation at 37 degrees C . The CL was amplified by lucigenin . Preliminary experiments suggest that convalescent sera from patients with group B meningococcal disease induced increased CL responses compared to acute sera . Sera from volunteers immunized with an outer membrane complex vaccine from serogroup B, serotype 15:P1.16 or 2a:P1.2 meningococci also induced increased CL activity compared to preimmune sera . No such response was shown when a group B capsular polysaccharide vaccine was given . This response pattern was also demonstrated by a flow cytometric phagocytosis technique (FCM) . Internalization of meningococci by monocytes was demonstrated by a FCM quenching technique and by transmission electron microscopy . CL and FCM represent rapid and reproducible methods for the measurement of opsonophagocytosis of meningococci by monocytes and may be performed with minute amounts of sera.

J Perinatol, 1992 Mar, 12(1), 78 - 80
An interesting case presentation: peripartum meningococcal meningitis; Finan MA et al.; Meningococcal disease during pregnancy is extremely rare . A single reported case occurred more than 20 years ago in England . We present the case of a young woman who just hours after delivery of her baby developed fulminant meningococcal meningitis with its classic findings . Our experience illustrates the importance of early diagnosis and appropriate therapy of meningococcal disease in the gravid as well as in the nongravid population.

Mol Microbiol, 1992 Mar, 6(5), 591 - 7
Tumour necrosis factor alpha antibody protects against lethal meningococcaemia; Nassif X et al.; Tumour necrosis factor alpha (TNF-alpha) has been shown to be the principal mediator of Gram-negative bacterial endotoxin-induced shock . Nevertheless, evidence suggests that TNF-alpha plays a beneficial role in controlling bacterial infections when multiplication of the microorganism is required to kill the host . Using an infant rat model of Neisseria meningitidis infection, we found that blood TNF-alpha concentration reaches a peak three hours after intraperitoneal injection of 3 x 10(6) bacteria . Thereafter, the level of TNF-alpha decreased and was undetectable six to eight hours after infection . A correlation was observed between the magnitude of initial TNF-alpha response and a fatal outcome . Pretreatment of the animals with polyclonal anti-TNF antiserum significantly reduced mortality relative to animals pretreated with control serum . However, pretreatment of animals with anti-TNF antibody did not alter the bacterial invasion of the cerebrospinal fluid . Injection of heat-killed bacteria did not cause death and induced lower TNF-alpha levels than the same number of live bacteria . This excludes the possibility that the role of TNF-alpha is to mediate a shock induced by the endotoxin component of the bacterial inoculum . These results indicate that TNF-alpha has a deleterious effect in this model of bacteraemia . Identification of the critical factors that determine the action of TNF-alpha during lethal bacteraemia will lead to a better understanding of these diseases and the development of appropriate therapeutic intervention.

J Bacteriol, 1992 Mar, 174(6), 1793 - 800
Structural characterization of the lipid A component of pathogenic Neisseria meningitidis; Kulshin VA et al.; The lipid A component of meningococcal lipopolysaccharide was structurally characterized by using chemical modification methods, methylation analysis, 31P nuclear magnetic resonance, and laser desorption mass spectroscopy . It was shown that Neisseria meningitidis lipid A consists of a 1,4'-bisphosphorylated beta(1'----6)-linked D-glucosamine disaccharide (lipid A backbone), both phosphate groups being largely replaced by O-phosphorylethanolamine . This disaccharide harbors two nonsubstituted hydroxyl groups at positions 4 and 6', the latter representing the attachment site of the oligosaccharide portion in lipopolysaccharide . In addition, it is substituted by up to six fatty acid residues . In the major lipid A component, representing a hexaacyl species, the hydroxyl groups at positions 3 and 3' carry (R)-3-hydroxydodecanoic acid {12:0(3-OH)}, whereas the amino groups at positions 2 and 2' are substituted by (R)-3-(dodecanoyloxy)tetradecanoic acid {3-O(12:0)-14:0} . A minor portion was present as a tetraacyl lipid A component lacking either dodecanoic acid (12:0) or 12:0 and 12:0(3-OH) . N . meningitidis lipid A, therefore, significantly differs from Escherichia coli lipid A by the nature and locations of fatty acids and the substitution of O-phosphorylethanolamine for the nonglycosyl (4'-P) and glycosyl phosphate.

Mayo Clin Proc, 1992 Mar, 67(3), 288 - 92
Prophylactic use of antimicrobial agents in adult patients; Van Scoy RE et al.; The prophylactic use of antimicrobial agents is recommended for prevention of numerous infections, including tuberculosis, endocarditis, rheumatic fever, recurrent cellulitis and lymphangitis in patients with lymphedema, meningococcal meningitis, and bite wounds . In addition, the prophylactic use of antimicrobial agents has proved effective in certain surgical procedures such as various abdominal operations, hysterectomy, and major operations that involve the head and neck . Except for oral bowel preparations, antimicrobial prophylaxis should be limited, in general, to the operative period . Prolonged perioperative prophylaxis has not been shown to enhance effectiveness and may result in increased toxicity, resistant superinfections, and inflated costs . The investigation of antimicrobial prophylaxis necessitates adequate evaluation of the potential advantages and disadvantages in a prospective, double-blind fashion.

J Clin Invest, 1992 Mar, 89(3), 816 - 23
Meningococcal endotoxin in lethal septic shock plasma studied by gas chromatography, mass-spectrometry, ultracentrifugation, and electron microscopy; Brandtzaeg P et al.; We have compared gas chromatography and mass spectrometry (GC-MS) analysis with the Limulus amebocyte lysate (LAL) assay to quantify native meningococcal lipopolysaccharides (LPS) in five patient plasmas containing greater than 5 micrograms/liter by LAL . 3-Hydroxy lauric acid (3-OH-12:0) was used as a specific lipid A marker of neisserial LPS . The quantitative LAL results were confirmed by GC-MS (r = 0.98, P = 0.006) . Seven patient plasmas were centrifuged at 103,000 g and the sedimentation behavior of native LPS compared with reference plasma proteins and with apo A1 and apo B100 representing high and low density lipoproteins . After 15 min of centrifugation, 84 +/- 2% (mean +/- SE) of the recovered LPS were found in the lower one-third of the centrifuged volume, whereas 6 +/- 1% remained in the upper one-third volume, indicating that meningococcal endotoxin circulates as complexes with high sedimentation coefficients . Bacterial outer membrane fragments were detected in the bottom fractions of three patient plasmas examined by means of electron microscopy . In three patient plasmas ultracentrifuged for 60 min at 103,000 g, the levels of apo A1 and apo B100 revealed minor changes, whereas only 1 +/- 1% of the recovered LPS remained in the upper one-third and 91 +/- 2% were found in the lower one-third volume . Few bioreactive LPS appear to be complexed with high and low density lipoproteins in meningococcal septic shock plasma.

Infect Immun, 1992 Mar, 60(3), 762 - 7
Ability of gonococcal and meningococcal lipooligosaccharides to clot Limulus amebocyte lysate; Roth RI et al.; We investigated whether the striking difference in severity of coagulopathy observed between bacterial sepsis involving Neisseria meningitidis and Neisseria gonorrhoeae species is related to species-dependent abilities to directly activate coagulation . Using lipooligosaccharide (LOS)-activated gelation of Limulus amebocyte lysate, we compared the relative abilities of outer membrane LOS of 10 N . meningitidis and 10 N . gonorrhoeae strains to initiate coagulation . A wide range of procoagulant potencies was observed for each species, and there was significant overlap of potencies between species . Relative biological activities did not correlate with the oligosaccharide components as defined by LOS molecular weight or specific antigenic epitopes . Purified lipid A of two LOS strains of different potency demonstrated relative procoagulant biological activities similar to those of their parent LOSs . When these lipid A preparations were further separated by thin-layer chromatography, the most polar component of each lipid A possessed the majority of the procoagulant activity . We concluded that the ability of neisserial LOS to initiate coagulation of Limulus lysate is a property of the lipid A portion of the molecule and is most likely determined by fine structural differences in the lipid A which are independent of species.

J Infect Dis, 1992 Mar, 165(3), 494 - 500
Limulus antilipopolysaccharide factor protects rabbits from meningococcal endotoxin shock; Alpert G et al.; Limulus antilipopolysaccharide factor (LALF), an 11.8-kDa peptide isolated from amebocytes of Limulus polyphemus, neutralizes meningococcal lipooligosaccharide (LOS)-induced gelation of limulus amebocyte lysate . Rabbits challenged with an LD90 of LOS (10 micrograms/kg) premixed with LALF in vitro (n = 10) had significantly higher mean arterial pressure, arterial pH, serum bicarbonate concentrations, and survival (90% vs . 8%, P = .005) than did rabbits challenged with LOS alone . Relative to untreated controls, rabbits pretreated with LALF intravenously (iv) at 1.2 mg/kg (n = 21) also had significant improvements in physiologic measurements and higher survival (52% vs . 8%, P = .003) . Even when LALF (1.2 mg/kg iv) was given 1/2 h after LOS challenge, animals showed significant improvements in physiologic measurements and survival (33% vs . 8% in untreated controls P = .028) . LALF-treated animals also had significantly lower circulating endotoxin activity and tumor necrosis factor concentrations . Thus, LALF attenuates the toxic effects of meningococcal LOS in rabbits even when administered after LOS challenge and deserves further evaluation as a potential therapeutic agent for treating gram-negative septic shock.

Infect Immun, 1992 Mar, 60(3), 798 - 803
Conserved outer membrane protein of Neisseria meningitidis involved in capsule expression; Frosch M et al.; In Neisseria meningitidis, translocation of capsular polysaccharides to the cell surface is mediated by a transport system that fits the characteristics of ABC (ATP-binding cassette) transporters . One protein of this transport system, termed CtrA, is located in the outer membrane . By use of a CtrA-specific monoclonal antibody, we could demonstrate that CtrA occurs exclusively in N . meningitidis and not in other pathogenic or nonpathogenic Neisseria species . Nucleotide sequence comparison of the ctrA gene from different meningococcal serogroups indicated that CtrA is strongly conserved in all meningococcal serogroups, independent of the chemical composition of the capsular polysaccharide . Secondary structure analysis revealed that CtrA is anchored in the outer membrane by eight membrane-spanning amphipathic beta strands, a structure of proteins that function as porins.

J Gen Microbiol, 1992 Mar, 138 ( Pt 3), 523 - 31
Analysis of the clonal relationships between strains of Neisseria meningitidis by pulsed field gel electrophoresis; Bygraves JA et al.; Fingerprint patterns were generated from strains of Neisseria meningitidis by digestion of chromosomal DNA samples with 'rare-site' restriction endonucleases and resolution of the resultant fragments by pulsed field gel electrophoresis (PFGE) . The potential of this technique for the rapid establishment of the clonal relationships between different isolates of the meningococcus was investigated . The fingerprint patterns from various serogroup A strains, previously assigned to clonal subgroups on the basis of their electrophoretic types (ETs), were compared . Fingerprints generated with the endonucleases SfiI, SpeI and NheI each gave distinctive patterns for the clonal subgroups I-IV of serogroup A . Further, the endonucleases SpeI and, particularly, NheI were capable of resolving differences between various subgroup III strains isolated at different times and geographical locations . Strains isolated during the 'new wave' pandemic, which was associated with the Haj, from Europe, America, and Africa, had a characteristic fingerprint pattern and appeared to be distinct from 'old wave' pandemic strains . The PFGE technique is a relatively rapid and sensitive method for establishing clonal relationships among epidemic strains of N . meningitidis.

Harefuah, 1992 Feb 16, 122(4), 221 - 3
{Meningococcal disease in western Galilee}; Greif Z et al.; 79 patients with meningococcal disease were evaluated retrospectively between 1972-1986 . All the neisseria isolated were sensitive to penicillin but resistant to sulphonamides . Most of the infections (54%) were caused by serogroup B strains . Clinical features included fever (98%), vomiting (65%), and headache (60%) . Purpura appeared in 95% and severe neurological features in 25% . Most patients (83%) were children less than 10 years old . The incidence was 1.4/100,000 in the non-Jewish population and 2.3/100,000 in the Jewish population . The overall mortality was 23%, but about 50% in the Jewish population (10 deaths in 18 cases) . In kibbutzim the incidence (7.5/100,000) and mortality were especially high . The need for awareness of the disease and the importance of early diagnosis and aggressive treatment are emphasized.

Schweiz Med Wochenschr, 1992 Feb 15, 122(7), 224 - 8
{Typing and sensitivity of meningococci isolated in Switzerland 1988-1990}; Rohner P et al.; Since 1906 severe infections due to Neisseria meningitidis have been reported in Switzerland . The clinical application of antimicrobial agents reduced the mortality rate due to meningococcal infections from 82% before 1939 to 22% after 1942 . However, the annual incidence remained at about 1.5 cases per 100,000 inhabitants . During the years 1988 to 1990, 177 strains isolated in Switzerland have been typed with a dot ELISA using 15 different monoclonal antibodies . The distribution of serogroups was as follows: A (0.6%), B (70.6%), C (22.6%), and W135 (0.6%), while 5.6% could not be assigned to a serogroup . The most common associations of serogroup, serotype and subtype were: B:15:P1.16 (15.3%), B:4:P1.15 (13.6%), and C:2a:P1.2 (9.0%) . The susceptibility of 174 strains was determined by an agar-dilution procedure . All strains were susceptible to cefuroxime, ceftriaxone, ciprofloxacin, minocycline and spiramycin . One strain showed reduced sensitivity to penicillin (MIC = 0.25 mg/l), while another strain was resistant to rifampicin, 3% were resistant of erythromycin and 75% to sulfadiazine.

Circ Shock, 1992 Feb, 36(2), 104 - 12
Effect of meningococcal endotoxin in a rabbit model of shock; Caputo GL et al.; Endotoxin in the form of a lipooligosaccharide (LOS) plays a key role in the development of shock in meningococcal sepsis . To examine hemodynamic and biochemical alterations during meningococcal endotoxic shock, we established a rabbit model . Thirty-nine rabbits, weighing 2.5-4.4 kg, were studied . After anesthesia with intramuscular ketamine (20 mg/kg) and xylazine (4 mg/kg), femoral venous and arterial catheters were inserted . Control animals received only saline, while rabbits in each of four additional groups were given LOS in 10-fold increments from 0.1 microgram/kg to 100 microgram/kg . Mean arterial pressure (MAP), heart rate (HR), respirations (RR), temperature (T), urine output, and arterial blood gases (pH, PCO2, PO2, and bicarbonate) were determined at baseline and hourly . Endotoxin levels and TNF levels were measured at 30, 60, 120, 180, 240, 300, and 360 min post-LOS . Survival was recorded . One-way analysis of variance (ANOVA) and the Scheffe procedure, paired samples t-test, two-tailed t-test, and Fisher's exact test were used . Pearson's coefficients were calculated . Animals receiving meningococcal LOS developed tachycardia and compensated metabolic acidosis with an initially normal pH and MAP . With progression of the shock state, the pH decreased and hypotension ensued . Maximal levels of endotoxin were measured 30 min after LOS injection and declined during the ensuing 6 hr . TNF rose from undetectable to markedly elevated levels and peaked at 60-120 min post-LOS . Increasing the amount of injected endotoxin produced more profound degrees of shock until a dose of 10.0 micrograms/kg was reached . There was no correlation between serum TNF at 60 min and survival at 6 hr or 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Postgrad Med J, 1992 Feb, 68(796), 129 - 31
Hyperpyrexia due to meningococcal septicaemia treated with cold peritoneal lavage; Khan IH et al.; An 18 year old male presented with fulminant meningococcal septicaemia and renal failure . He subsequently developed hyperpyrexia which failed to respond to conventional methods of treatment . Cold peritoneal lavage was employed which resulted in rapid lowering of his core temperature and helped manage his renal failure . The possible causes of the late onset of hyperpyrexia and the use of cold peritoneal lavage to treat refractory hyperpyrexia are discussed.

Mol Microbiol, 1992 Feb, 6(4), 489 - 95
Role of horizontal genetic exchange in the antigenic variation of the class 1 outer membrane protein of Neisseria meningitidis; Feavers IM et al.; The nucleotide sequences of the genes encoding the class 1 outer membrane protein of Neisseria meningitidis (PorA) from 15 meningococcal isolates have been examined . These strains, isolated over a number of years, represented a variety of serological types, clonal groups, and geographical locations . Analysis of the aligned nucleotide sequences showed that the known serological relationships between these proteins were not necessarily reflected throughout the nucleotide sequences of their genes . The uneven distribution of base substitutions, revealed by a comparison of the informative bases, suggested that these genes possessed a mosaic structure . This structure probably resulted from the horizontal transfer of DNA between strains and would have contributed to both the generation and the spread of novel antigenic variants of the protein . In addition, the nucleotide differences between porA genes from different strains were not consistent with the nucleotide sequence divergence of the whole chromosome, as indicated by pulsed-field gel electrophoresis (PFGE) fingerprinting techniques: some strains with divergent PFGE fingerprints shared porA genes with extensive regions of nucleotide sequence identity and, conversely, some strains with similar chromosome structures possessed porA genes with different nucleotide sequences and serological properties . This suggested that entire genes had been exchanged between strains . Given that the meningococcal class 1 OMP is a major component in novel vaccines, some of which are currently undergoing field trials, the potential of horizontal genetic exchange to generate antigenic diversity has implications for the design of such vaccines.

Clin Infect Dis, 1992 Feb, 14(2), 515 - 25
Meningococcal meningitis in sub-Saharan Africa: a model for the epidemic process; Moore PS; Epidemic group A meningococcal meningitis follows a unique and distinctive pattern in sub-Saharan Africa . Advances in molecular and field epidemiology have begun to elucidate the mechanisms of meningococcal meningitis epidemics . Epidemics result from a complex combination of host, organism, and environmental risk factors . Recent studies suggest that "antigenic shifts" in group A meningococcal clones may trigger an outbreak of disease by suddenly decreasing herd immunity within a population . Although the introduction of new group A meningococcal strains into a susceptible population contributes to the likelihood of an epidemic, the presence of additional environmental factors, such as low humidity and coincident respiratory tract infections, are also necessary for an epidemic to occur . Despite the unique behavior of group A meningococcal disease in sub-Saharan Africa, the application of similar methods of epidemiological analysis may be useful for determining epidemic processes for other diseases.

Clin Infect Dis, 1992 Feb, 14(2), 394 - 402
Epidemiology and molecular basis of penicillin-resistant Neisseria meningitidis in Spain: a 5-year history (1985-1989); Saez-Nieto JA et al.; Penicillin-resistant (penr) clinical isolates of Neisseria meningitidis, which do not produce beta-lactamase, were first identified in Spain in 1985; the frequency of their recovery, which has been increasing in the past few years, reached 20% in 1989 . Serogrouping, determination of serotypes and subtypes, and multilocus enzyme electrophoresis of the penr strains showed an extensive diversity . Resistance is due, at least in part, to a decreased affinity of penicillin-binding protein (PBP) 2 for penicillin . Similar low-affinity forms of PBP 2 are also found in penr isolates of Neisseria lactamica, Neisseria polysaccharea, and Neisseria gonorrhoeae . Genetic transformation of an N . meningitidis type strain to low-level penicillin resistance with DNA from resistant meningococci and other Neisseria species resulted in transformants that possessed low-affinity forms of PBP 2 . These altered forms of PBP 2 have been shown to arise from recombinational events that replace parts of the PBP 2 gene with the corresponding regions from the PBP 2 genes of commensal Neisseria species.

Epidemiol Infect, 1992 Feb, 108(1), 19 - 30
An outbreak of serogroup B:15:P1.16 meningococcal disease, Frederiksborg County, Denmark, 1987-9; Samuelsson S et al.; Epidemiological features of an outbreak of group B:15:P1.16 meningococcal disease (MD) in Frederiksborg county, Denmark, 1987-9, were investigated . The study comprised 149 cases notified during the outbreak and the two preceding years; 115 were confirmed by the isolation of Neisseria meningitidis . In 1989 the incidence had increased to 14.1 per 100,000 population . Among group B strains, B:15:P1.16 accounted for 80% (77/97) . The overall mortality rate was 10% (15/149) . Regarding cases due to group B:15:P1.16 strains a significant time-space clustering, which exclusively occurred within the 10-19 years age group, was demonstrated . The link between cases within clusters was indirect or unknown, except for ten patients with contact to one particular school . The prophylactic measures used included administration of rifampicin to household contacts . During the outbreak the proportion of secondary cases was high (6-15%) . All secondary cases occurred outside the household indicating that the household had been protected.

Int J Epidemiol, 1992 Feb, 21(1), 155 - 62
Detection of meningitis epidemics in Africa: a population-based analysis; Moore PS et al.; Portions of sub-Saharan Africa are subject to major epidemics of meningococcal meningitis that require early detection and rapid control . We evaluated the usefulness of weekly meningitis rates derived from active surveillance data in Burkina Faso for detecting a meningitis epidemic . By analysing the rates of disease in 40 x 40km2 areas within a study region of Burkina Faso, we found that a threshold of 15 cases/100,000/week averaged over 2 weeks was 72-93% sensitive and 92-100% specific in detecting epidemics exceeding 100 cases/100,000/year . During epidemic periods, the positive predictive value of this threshold approached 100% for detecting local epidemics . Additionally, meningitis incidence was proportional to village size, with villages greater than 8000 having the highest disease rates during a major group A meningococcal epidemic in 1983-1984 . Despite the rudimentary nature of surveillance data available in many developing countries, these data can be used to detect the early emergence of meningitis epidemics . Additional studies are needed to determine the relevance of this approach for detecting epidemics.

J Clin Microbiol, 1992 Jan, 30(1), 154 - 9
Multicenter comparison of levels of antibody to the Neisseria meningitidis group A capsular polysaccharide measured by using an enzyme-linked immunosorbent assay; Carlone GM et al.; There is no standard immunoassay for evaluating immune responses to meningococcal vaccines . We developed an enzyme-linked immunosorbent assay to measure total levels of antibody to Neisseria meningitidis group A capsular polysaccharide . Five laboratories measured the antibody levels in six paired pre- and postvaccination serum samples by using the enzyme-linked immunosorbent assay . Methylated human serum albumin was used to bind native group A polysaccharide to microtiter plate surfaces . The between-laboratory coefficients of variation for pre- and postvaccination sera had ranges of 31 to 91 and 17 to 31, respectively . The mean laboratory coefficients of variation for pre- and postvaccination sera, respectively, were 17 and 11 (Molecular Biology Laboratory, Centers for Disease Control), 12 and 15 (Immunodiagnostic Methods Laboratory, Centers for Disease Control), 22 and 19 (Dana-Farber Cancer Institute), 38 and 38 (Bacterial Polysaccharide Laboratory, U.S . Food and Drug Administration), and 11 and 10 (Praxis Biologics, Inc.) . Standardization of this enzyme-linked immunosorbent assay should allow interlaboratory comparison of meningococcal vaccine immunogenicity, thus providing a laboratory-based assessment tool for evaluating meningococcal vaccines.

Scand J Infect Dis, 1992, 24(2), 165 - 73
Preventing secondary cases of meningococcal disease by identifying and eradicating disease-causing strains in close contacts of patients; Kristiansen BE et al.; In Norway, the use of chemoprophylaxis after cases of meningococcal disease is not recommended . Instead, household members less than 15 years are treated with penicillin for 7 days . Failures of this treatment have been reported . We therefore used DNA fingerprinting to identify the disease-causing strain in healthy contacts combined with selective rifampicin prophylaxis to these carriers to prevent secondary cases . During a 2-year period (1987-89) there were 13 cases of meningococcal disease in the County of Telemark (165000 inhabitants) . 65 (14.7%) out of 441 contacts to these 13 patients harbored meningococci in their throat; 16 (3.6%) carried the disease-causing strain . Only 1 carrier fulfilled the criteria for being treated with penicillin; 8 were adults and the remaining 7 were not household members . No secondary cases of meningococcal disease occurred during the study period or the following 12 months . During the 4-year period (1984-87) preceding the study period there were 39 cases of meningococcal disease in Telemark; 7 of them were index cases for 12 bacteriologically verified and 4 clinically suspected secondary cases of meningococcal disease . We conclude that selective prophylaxis with rifampicin seems to be more efficient that penicillin treatment of household members less than 15 to prevent secondary cases of meningococcal disease.

Bull World Health Organ, 1992, 70(3), 359 - 62
{Comparative study of 3 bacteriological tests of cerebrospinal meningitis during the epidemiological period}; Sperber G et al.; During an outbreak of group A meningococcal meningitis in Chad in 1988, a comparative study of three bacteriological techniques (direct microscopic examination, latex agglutination, and culture) was conducted with 120 samples of cerebrospinal fluid (CSF) for diagnosis . The results correlated well with cloudy or purulent CSF specimens . Direct microscopic examination was as good a diagnostic indicator as the other tests . The authors recommend using direct microscopic examination, which is easy to perform under field conditions and accurate enough for a rapid diagnosis of cerebrospinal meningitis during an epidemic . However, complete identification of the first cases in the epidemic is important in order to establish control measures as soon as possible.

Klin Med (Mosk), 1992 Jan, 70(1), 90 - 2
{Hyperbaric oxygenation in the combined therapy of infectious diseases}; Ivanov KS et al.; Hypoxia plays an important role in pathogenesis of infectious diseases . Therefore, its correction is an essential factor in pathogenetic antibacterial treatment . Hyperbaric oxygenation (HBO) as a leading method in current antihypoxic therapy was studied in combined medication for typhoid, diphtheria, meningococcal infection, viral hepatitis . HBO sessions were given to 331 patients, 363 controls did not receive HBO . Utilization of HBO provided much better saturation of blood with oxygen, eliminated metabolic disorders, warranted favorable course and outcomes of the diseases.

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