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 s