J Antimicrob Chemother, 1995 Jul, 36(1), 215 - 8 In-vitro activity of a new quinolone (CP-99,219) compared with ciprofloxacin, pefloxacin, azithromycin and penicillin against Neisseria gonorrhoeae; van Rijsoort-Vos JH et al.; The in-vitro activities of CP-99, 219, ciprofloxacin, pefloxacin, azithromycin and penicillin was tested against 114 Neisseria gonorrhoeae strains . The MIC90s were: 0.008 mg/L (MIC range 0.001-0.06 mg/L) for CP-99, 219, 0.008 mg/L (MIC range 0.001-0.25 mg/L) for ciprofloxacin, 0.12 mg/L (MIC range 0.008-4 mg/L) for pefloxacin, 0.25 mg/L (MIC range 0.03-1 mg/L) for azithromycin and 16 mg/L (MIC range 0.015-16 mg/L) for penicillin . The activity of CP-99,219 against various N . gonorrhoeae isolates was comparable to ciprofloxacin. J Infect Dis, 1995 Jul, 172(1), 186 - 91 Inflammatory cytokines produced in response to experimental human gonorrhea; Ramsey KH et al.; Inflammatory cytokine production in men was examined after intraurethral challenge of volunteers with Neisseria gonorrhoeae MS11mkA or MS11mkC . Increased interleukin (IL)-8, IL-6, and tumor necrosis factor-alpha (TNF-alpha) were detected in urine before the onset of symptoms and peaked simultaneously with the detection of IL-1 beta at the onset of symptoms . Urine cytokine levels returned to baseline or near baseline within 48 h after antibiotic therapy . In plasma, IL-8, TNF-alpha, IL-1 beta, and IL-6 were elevated at the onset of symptoms in 9, 5, 4, and 3 of 10 subjects, respectively, and returned to near normal within 48 h after treatment . IL-1 alpha and granulocyte-macrophage colony-stimulating factor were not consistently detected in urine or plasma after challenge . Cytokine mRNA transcripts in peripheral blood mononuclear cells were not altered by the infection . The findings suggest that IL-8, IL-6, and possibly TNF-alpha were produced at the local site of infection, whereas IL-1 beta was derived from infiltrating leukocytes. J Infect Dis, 1995 Jul, 172(1), 180 - 5 Experimental human gonococcal urethritis: 250 Neisseria gonorrhoeae MS11mkC are infective; Schneider H et al.; Neisseria gonorrhoeae MS11mkA (mkA) expresses one 3.6-kDa lipooligosaccharide (LOS) . Variant MS11mkC (mkC), expressing four larger LOSs, occurs in vitro among mkA at a frequency of 10(-3) . Infectivity of these variants was compared in 2 groups of volunteers inoculated with approximately 40,000 piliated, Opa- gonococci of either strain . The mkC variant infected 5 of 5 while mkA infected only 2 (40%) of 5 . Gonococci recovered from the mkA infections showed a transition toward the mkC LOS phenotype . The mkA inoculum contained approximately 40 mkC gonococci . These data confirmed earlier studies and suggested that small numbers of mkC gonococci would be infective . This hypothesis was tested in three more experiments . In two, volunteers were inoculated with 250 or 1250 mkC, infecting 3 of 7 in each group, and in the third, 1600 mkC infected 2 of 6, resulting in a total of 8 of 20 infected by < or = 1600 mkC . Gonococci shed by infected volunteers maintained the mkC LOS phenotype but shifted from Opa- to Opa+ . Thus, LOS and opacity protein, as well as pilus, are gonococcal virulence factors. Infect Immun, 1995 Jul, 63(7), 2773 - 5 Phenotypic modulation of gonococcal lipooligosaccharide in acidic and alkaline culture; Pettit RK et al.; Neisseria gonorrhoeae infects a diverse array of niches in its human host, which expose the organism to dramatic variations in pH . We examined growth and lipooligosaccharide expression of two gonococcal strains in liquid and solid cultures under acidic, neutral, and alkaline conditions . Growth rates in broth were similar under the three conditions, and the pH remained fairly constant throughout the growth cycle . Altered lipooligosaccharide expression at the different pHs was noted in both plate- and broth-grown organisms. Infect Immun, 1995 Jul, 63(7), 2508 - 15 Microheterogeneity of Neisseria lipooligosaccharide: analysis of a UDP-glucose 4-epimerase mutant of Neisseria meningitidis NMB; Lee FK et al.; Neisseria meningitidis is the etiologic agent of epidemic bacterial meningitis . Lipooligosaccharide (LOS) is a principal virulence factor associated with the organism, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of LOS has demonstrated that there is considerable microheterogeneity in the molecule . To begin our understanding of the nature of this heterogeneity, we identified a Tn916-generated LOS mutant of N . meningitidis NMB (serotype L3, monoclonal antibodies 3F11+, 6B4+, and 4C4-) that was designated NMB-SS3 (monoclonal antibodies 3F11-, 6B4-, and 4C4+) . The transposon insertion was localized to the amino terminus of the functional copy of the UDP-Glc 4-epimerase gene (galE) . UDP-Glc 4-epimerase (EC 5.1.3.2) activity was present in N . meningitidis NMB but not in NMB-SS3, indicating that the Tn916 insertion had abolished this activity . Mass spectrometric analysis of the LOS from strain NMB revealed multiple species of LOS, which is consistent with extensive microheterogeneity . While the most predominant structure was consistent with a terminal lacto-N-neotetrose structure found in other strains of N . meningitidis, Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1-->4Glc-->(GlcNAc)-->Hep2PEA-->KDO2 (where Hep is heptose, PEA is phosphoethanolamine, and KDO is 2-keto-3-deoxymannooctulosonic acid), structures containing repetitive hexoses which are not precursors of this structure were also identified . Compositional analysis of LOS from strain NMB-SS3 revealed that there were no galactoses present in the structure . Mass spectrometric analysis of O-deacylated LOS revealed the presence of multiple species, with the predominant LOS species in this mutant strain formed by the Hex-->(HexNAc)-->Hep2PEA-->KDO2 (where Hex is hexose and HexNAc is N-acetylhexosamine) structure . However, LOS structures with repetitive hexoses, e.g., Hexn-->(HexNAc)-->Hep2PEA-->KDO2 (n = 2, 3, or 4), emanating from one or both heptoses were also identified . Since this mutant cannot synthesize UDP-Gal, these structures must repetitive glucoses . These data suggest that NMB has a glycosyltransferase capable of polymerizing glucose moieties as an alternative biosynthetic pathway to the wild-type lacto-N-neotetrose structure. Clin Orthop, 1995 Jul, (316), 221 - 6 Obturator internus pyomyositis . A case report; Birkbeck D et al.; Pyomyositis appears to be increasing in prevalence in temperate climates, and often the orthopaedist is integral in the decision making and care of these patients . This is the first reported case of spontaneous bacterial pyomyositis involving the obturator internus muscle . Deep pelvic infections involving the psoas, iliacus, piriformis, and obturator internus can be a significant cause of morbidity and mortality . The infection subsequently may exit the pelvis, and conceivably may progress to a septic hip, bursitis, or lower extremity cellulitis . Improvements in noninvasive imaging such as ultrasound, computed tomography, and magnetic resonance imaging have produced finer resolution of tissue planes . Because of the pathology's deep location within the pelvis of the patient described here, all 3 tests were integral in the surgical planning, exposure, and proper diagnosis . Although 95% of pyomyositis cases are caused by Staphylococcus aureus, cases of pyomyositis with negative cultures have been described . Consideration should be made of disseminated Neisseria gonorrhoeae in sexually active individuals, and cultures should include Thayer-Martin agar to decrease the likelihood of a false-negative culture result. J Bacteriol, 1995 Jul, 177(14), 4162 - 5 Transcriptional control of the mtr efflux system of Neisseria gonorrhoeae; Hagman KE et al.; The capacity of Neisseria gonorrhoeae to resist structurally diverse hydrophobic agents (HAs) because of the mtr (multiple transferable resistance) efflux system was found to be regulated at the level of transcription by two distinct mechanisms . This was surmised because a deletion that removed > 90% of the coding sequence of the mtrR (multiple transferrable resistance regulator) gene or a single-base-pair deletion within a 13-bp inverted repeat sequence located in its promoter resulted in altered expression of the mtrC gene; mtrC encodes a 44-kDa membrane lipoprotein essential for the efflux of HAs . However, the single-base-pair deletion had the more significant impact on gene expression since it resulted in the loss of expression of mtrR and a threefold increase in the expression of mtrC . Hence, the mtr efflux system in gonococci is subject to both MtrR-dependent and MtrR-independent regulation, and the levels of mtrC mRNA correlate well with HA resistance levels in gonococci. J Bacteriol, 1995 Jul, 177(13), 3781 - 7 The pilE gene of Neisseria gonorrhoeae MS11 is transcribed from a sigma 70 promoter during growth in vitro; Fyfe JA et al.; Type 4 pili are essential for virulence in Neisseria gonorrhoeae . The gonococcal pilin subunit is encoded by pilE, upstream of which three putative promoter sequences (P1, P2, and P3) have been identified . P1 and P2 are sigma 70-like promoters and are functional when a PpiE::cat transcriptional fusion is expressed in Escherichia coli DH5 alpha . P3 is sigma 54 dependent and overlaps the P1 sequence . Site-directed mutagenesis of the pilE promoters followed by transcriptional analysis in E . coli indicated that in the absence of an appropriate activator protein, binding of RNA polymerase-sigma 54 to P3 inhibits transcription from P1 on the order of 30-fold . Transcription from P3 was undetectable in E . coli . However, PilR-dependent, P3-associated expression was detected in Pseudomonas aeruginosa PAK containing a PpilE::cat fusion, with P3 the only intact promoter . A similar analysis was performed on gonococcal reporter strains containing wild-type and mutated PpilE::cat cassettes recombined into the chromosome . In such piliated gonococcal recombinants cultured in vitro, P1 was responsible for cat expression and almost certainly for transcription of pilE . Transcription from P2 and P3 was not detectable under these conditions . Inhibition of transcription from P1 by sigma 54 binding to P3 was not apparent in N . gonorrhoeae MS11-A, suggesting that sigma 54 was either absent or unable to bind to P3 in these cells. J Clin Pathol, 1995 Jul, 48(7), 658 - 61 Value of screening for oro-pharyngeal Chlamydia trachomatis infection; Jebakumar SP et al.; AIMS--To determine whether oro-pharyngeal colonisation by Chlamydia trachomatis occurs in patients at risk of genital chlamydia infection; to determine whether screening pharyngeal specimens by polymerase chain reaction (PCR) increases detection of C trachomatis compared with isolation and the immune dot blot test; and to correlate the detection of C trachomatis and Neisseria gonorrhoeae in the pharynx with a history of oro-genital contact . METHODS--Thirteen homosexuals and 11 heterosexuals were included in the study . Urogenital and pharyngeal specimens were tested for C trachomatis and N gonorrhoeae using standard clinical diagnostic procedures . Two different PCR methodologies were also used to detect C trachomatis in the pharyngeal specimens . Results were correlated with the mode of sexual practice . RESULTS--Oro-genital sexual contact was practised by 64.9% (72/111) of heterosexuals in addition to penetrative penovaginal intercourse . Additionally, 62.1% (77/124) of all patients did not use any form of barrier protection . Of those who admitted to oro-genital sexual contact, 17.6% of patients with a genital chlamydial infection and 36.4% of those with genital gonorrhoea also had asymptomatic pharyngeal colonisation . C trachomatis was detected in three of 124 (2.4%) pharyngeal specimens by PCR which were reported as negative by chlamydial culture; one was positive by the immune dot blot test . CONCLUSION--The majority of patients practised unprotected oro-genital contact and significant pharyngeal colonisation by C trachomatis and N gonorrhoeae occurred if genital infection was present . Despite the use of PCR in a population at high risk of sexually transmitted disease, the prevalence of chlamydia in the pharynx was very low . This indicates that transmission of C trachomatis to the oro-pharynx does not pose a serious health risk and that screening of patients for oro-pharyngeal C trachomatis is not worthwhile. Int J STD AIDS, 1995 Jul-Aug, 6(4), 273 - 7 Sexually transmitted diseases and human immunodeficiency virus infection among women with genital infections in Burkina Faso; Meda N et al.; This study reports the prevalence of sexually transmitted diseases (STDs) among gynaecological outpatients presenting at the Bobo-Dioulasso Hospital (Burkina Faso) with genital infections and examines the factors associated with HIV infection in this population . Of 245 eligible non-pregnant women, 220 consented to participate in the study . Seventy-seven per cent had sexually transmitted infections . The most common were: Trichomonas vaginalis (28%), Chlamydia trachomatis (27%), bacterial vaginosis (20%), Candida albicans (17%), Neisseria gonorrhoeae (11%) . The prevalence of HIV infection was 42% (95% c.i . 35.3, 48.3) . Logistic regression analyses revealed Neisseria gonorrhoeae to be the only STD significantly associated with infection with HIV (P = 0.04) . A sedimentation rate greater than or equal to 100 mm in the first hour was also associated with HIV infection (P < 0.001) . Women consulting for genital infections constitute a high risk group for HIV infection and other STDs . Management of these women should focus on the early diagnosis and treatment of STDsPIP: During May-October 1992 in the gynecology and obstetrics department at the National Central Hospital Souro Sanou in Bobo-Dioulasso, Burkina Faso, physicians conducted a physical examination of and took vaginal smears from 220 nonpregnant women of reproductive age who consented to take part in this study and who had clinical signs of a genital infection . The researchers wanted to determine the prevalence of sexually transmitted diseases (STDs) and the factors associated with HIV infection . 77% had an STD . The most common STDs were Trichomonas vaginalis (28%) and Chlamydia trachomatis (27%) . 42% were HIV positive . HIV-positive women were significantly more likely than HIV-negative women to be infected with Neisseria gonorrhoeae (30.4% vs . 24.2%; p = 0.03) . Risk factors associated with HIV infection among women presenting with genital infections included young age (25.5 vs . 27.5 years; p = 0.03), low gravidity (2 vs . 2.7; p = 0.04), a higher sedimentation rate in the first hour (75.3 vs . 54; p 0.001), and a low hemoglobin level (11.7 vs . 12.2 g/dl; p = 0.01) . These findings indicate that women with genital infections are a group at high risk of HIV and other STDs and a target population for preventive interventions . Physicians should focus on detection and treatment of STDs when they manage cases with genital infections, and they should give appropriate advice on the prevention of HIV to all women presenting with genital infections . Curr Opin Rheumatol, 1995 Jul, 7(4), 310 - 4 Bacterial arthritis; Goldenberg DL; A number of experimental models of bacterial arthritis demonstrated that immune factors, especially directed cytokines, play an important role in cartilage destruction . The most important studies in bacterial arthritis were a review of the clinical manifestations of gonococcal arthritis and two reports of the use of polymerase chain reaction to detect Neisseria gonorrhoeae DNA in synovial fluid . Polymerase chain reaction may be an important diagnostic test in culture-negative cases and may be very helpful in understanding the pathophysiology of gonococcal arthritis. Antimicrob Agents Chemother, 1995 Jul, 39(7), 1606 - 8 Activities of three investigational fluoroquinolones (BAY y 3118, DU-6859a, and clinafloxacin) against Neisseria gonorrhoeae isolates with diminished susceptibilities to ciprofloxacin and ofloxacin; Carlyn CJ et al.; Between 1 January 1992 and 31 December 1993, our laboratory, as part of the Gonococcal Isolate Surveillance Project, found that 39 of 673 isolates of Neisseria gonorrhoeae from one local sexually transmitted diseases clinic demonstrated decreased susceptibilities to both ciprofloxacin and ofloxacin . The MICs of BAY y 3118, DU-6859a, and clinafloxacin at which 90% of the gonococci with decreased susceptibility to ciprofloxacin and ofloxacin were inhibited were all 0.016 microgram/ml, which was eightfold higher than those for ciprofloxacin-susceptible gonococci . Our report substantiates prior observations that diminished susceptibility to one quinolone is often associated with diminished susceptibility to other quinolones. Sex Transm Dis, 1995 Jul-Aug, 22(4), 244 - 52 Male urethritis with and without discharge: a clinical and microbiological study; Janier M et al.; BACKGROUND: The definition of male urethritis in the absence of urethral discharge has not been well established . The sensitivity of urethral swabs and first-catch urine is controversial . GOAL OF THIS STUDY: To correlate clinical data (discharge or not), urethral swabs, and first-catch urine examinations with the microorganisms found within the urethra in a cohort of men attending the sexually transmitted disease clinic of Hopital Saint Louis (Paris) for treatment of urethral symptoms with or without discharge . STUDY DESIGN: Two-hundred-seventy-three consecutive male patients entered this prospective study between October 1, 1992 and November 30, 1992 . Fifty-two patients were excluded because they had been treated with antibiotics in the previous 3 months . All patients were screened for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, Ureaplasma urealyticum, Mycoplasma hominis, and Candida albicans . RESULTS: Two-hundred-nineteen patients were eligible for the study (122 with discharge and 97 with no discharge) . The prevalence of microorganisms was as follows: Chlamydia trachomatis in 13%, Neisseria gonorrhoeae in 11%, Ureaplasma urealyticum in 7%, Mycoplasma genitalium in 17%, Trichomonas vaginalis in 1%, and indeterminate pathogens alone in 20% . All major pathogens and Mycoplasma genitalium were more common in patients with discharge . Stratification of results according to the presence of polymorphonuclear leukocytes on the urethral swab and first-catch urine showed a low sensitivity of both tests for Chlamydia trachomatis (29%), Mycoplasma genitalium (50% and 62%), and Ureaplasma urealyticum (33%) in patients with no discharge . CONCLUSION: A specific and sensitive search for Chlamydia trachomatis should be done in every patient with urethral symptoms whether or not the classic symptoms of urethritis are present (discharge, presence of polymorphonuclear leukocytes in the urethra or first-catch urine). Sex Transm Dis, 1995 Jul-Aug, 22(4), 236 - 43 Spectrum of genital human papillomavirus infection in a female adolescent population; Jamison JH et al.; BACKGROUND: Human papillomavirus infection is a sexually transmitted disease associated with cervical dysplasia and carcinoma . GOAL OF THIS STUDY: To determine prevalence rates of cervical human papillomavirus infection compared with other sexually transmitted diseases and risk factors associated with human papillomavirus infection among adolescent women, we evaluated 634 patients attending three urban adolescent clinics . STUDY DESIGN: Patient evaluation included Pap smears; screening for chlamydia, gonorrhea, and trichomoniasis; and testing of cervical swab samples for human papillomavirus DNA . RESULTS: Cervical human papillomavirus was the most common STD in our population (15.6%), followed by infection with Chlamydia trachomatis (11.0%), Neisseria gonorrhoeae (7.1%), and Trichomonas vaginalis (5.4%) . The most prevalent human papillomavirus types were 16/18 (7.3%), followed by 31/33/35 (4.7%) and 6/11 (3.5%) . When genital warts on exam, low-grade squamous intraepithelial lesions on cytology, or cervical human papillomavirus DNA were considered as indicators of genital human papillomavirus infection, 24% of patients had any manifestation of infection, including 15% with clinically apparent infection (genital warts), 36% with cytologically apparent infection without warts, and 49% with subclinical infection only (cervical human papillomavirus DNA without low-grade squamous intraepithelial lesions or warts) . Factors associated with detection of cervical human papillomavirus DNA by multivariate analysis included number of lifetime sexual partners and genital warts on exam . CONCLUSION: Cervical human papillomavirus infection was the most prevalent sexually transmitted disease among an ethnically diverse group of urban adolescent females, with a large proportion of infections neither clinically nor cytologically apparent . The strong association with lifetime sexual partners substantiates that cervical human papillomavirus is acquired predominantly by sexual contact and often soon after the onset of sexual activityPIP: The study was conducted at three urban adolescent clinics administered by the Denver Department of Health and Hospitals.The population was derived predominantly from inner city, low-income adolescents 12-18 years old during the period of May 1989 to January 1990 . A questionnaire regarding sexual and STD history, contraceptive use, and substance use was administered to each patient . Specimens for laboratory studies included collection of vaginal fluid swabs for pH determination and wet mount microscopy; sequential cervical swabs for testing for Neisseria gonorrhea, Chlamydia trachomatis, and HPV DNA; and endocervical swabs and ectocervical scrapes for cytology . A total of 634 were included . The population was ethnically mixed: 167 (26%) were Black, 287 (45%) were Hispanic, 174 (28%) were White, 1 (0.2%) was Asian, and 3 (10.5%) were of other ethnic groups . The mean age was 16.8 years, with a range of 12-18 years . Cervical HPV infection was the most prevalent STD in the population, detected in 99 (15.6%) subjects, followed by infection with C . trachomatis in 69 (11.0%), N . gonorrhea in 45 (7.1%), and T . vaginalis in 34 (5.3%) . Overall, 188 (30.3%) subjects had any of the 4 STDs detected . The most prevalent, higher-risk HPV types were 16/18, either as single or mixed infections, which were detected in 46 (7.2%) patients . Infection with HPV types 31/33/35 or 6/11 occurred in an additional 31 (4.9%) and 23 (3.6%) subjects, respectively . Overall, 152 (24%) patients had any manifestation of genital HPV infection, 23 (15%) with clinically apparent infection (external genital warts), an additional 54 (36%) with cytologically apparent infection (low-grade squamous intraepithelial lesions or LSIL) without warts, and 69 (49%) with subclinical cervical infection (with neither warts nor LSIL) . The relative risk of cervical HPV DNA for those with 2 or more partners was 2.7 (p 0.001) . By multivariate analysis, the independent predictors of cervical HPV DNA included the number of lifetime sexual partners (2 or more partners: OR, 1.9) and current genital warts (OR, 5.1) . Pathol Biol (Paris), 1995 Jun, 43(6), 542 - 6 {Azithromycin and genital infections}; Micoud M et al.; The lower genital tract infections due to Chlamydia trachomatis are frequent, essentially occurring in young patients, with possible complications and severe sequela, particularly in women where the sterility risk is one of the major consequences . If an effective treatment could be systematically proposed, a good compliance (easy administration and good toleration) is one of the key factor to success . In this context, the azithromycin displays numerous advantages . The azithromycin in vitro activity on Chl . trachomatis strains is permanent with MIC comprised between 0.06 and 0.125 micrograms/ml, with an activity equivalent to those of other macrolides, to tetracyclines and quinolones . Different animal models allow to demonstrate the curative activity of the azithromycin administered as a single dose, at dosage regimen equivalent to those used in man, and a prophylactic activity on the salpingitis onset in provoked Chl . trachomatis infections . Several comparative clinical studies with azithromycin administered as a 1 g single dose displayed very satisfactory results with 98% of bacterial eradication, identical to those obtained with reference treatment . On the other hand, restrictions to the product use are a less constant activity against Neisseria gonorrhoeae and a lack of efficacy on Mycoplasma hominis . The efficacy on Treponema pallidum remains to be clinically tested. Br J Biomed Sci, 1995 Jun, 52(2), 87 - 92 Gonococcal serovar patterns in Glasgow: 1990-1992; Ross JD et al.; Using monoclonal antibodies directed against protein 1 (major outer membrane protein) in the cell wall of Neisseria gonorrhoeae it is possible to serotype the gonococcus into different sub-groups . This study was designed to analyse the distribution of such serovars in Glasgow, Scotland, and report associations between serovars and clinical features of infection . N . gonorrhoeae isolated from all patients with a diagnosis of gonorrhoea attending genitourinary medicine clinics in Glasgow were serotyped between January 1990 and December 1992 . The results were then correlated with sexual orientation of patients, penicillin sensitivity, site of infection, location of acquisition of infection and presence of symptoms . Six hundred and four episodes of gonococcal infection were analysed and an association between certain serovars with sexual orientation, penicillin sensitivity and asymptomatic infection was found . No association between serovar type and locality of acquisition of infection was apparent . Although there was a decreasing trend in the incidence of gonorrhoea overall, infections in homosexual men increased over the three-year study period . The associations between serovars and other features of gonococcal infection are discussed . The observed increase in homosexually-acquired infection has implications with regard to the spread of human immunodeficiency virus infection in this area, and suggests that attempts to promote safer sex in this group are failing. Infect Immun, 1995 Jun, 63(6), 2201 - 5 Characterization of the structural elements in lipid A required for binding of a recombinant fragment of bactericidal/permeability-increasing protein rBPI23; Gazzano-Santoro H et al.; Both human bactericidal/permeability-increasing protein (BPI) and a recombinant amino-terminal fragment of BPI (rBPI23) have been shown to bind with high affinity to the lipid A region of lipopolysaccharide (LPS) (H . Gazzano-Santoro, J . B . Parent, L . Grinna, A . Horwitz, T . Parsons, G . Theofan, P . Elsbach, J . Weiss, and P . J . Conlon, Infect . Immun . 60:4754-4761, 1992) . In the present study, lipid A preparations derived from bacterial LPS as well as synthetic lipid A's and various lipid A analogs were used to determine the structural elements required for rBPI23 binding . rBPI23 bound in vitro to a variety of synthetic and natural lipid A preparations (both mono- and diphosphoryl forms), including lipid A's prepared from Escherichia coli and Salmonella, Neisseria, and Rhizobium species . Binding does not require that the origin of negative charge be phosphate, since rBPI23 bound with high affinity to lipid A's isolated from Rhizobium species that contain carboxylate (Rhizobium trifolii) or sulfate (Rhizobium meliloti) anionic groups and lack phosphate . Lipid A acyl chains are important, since rBPI23 did not bind to four synthetic variants of the beta(1-6)-linked D-glucosamine disaccharide lipid A head group, all devoid of acyl chains . rBPI23 also bound weakly to lipid X, a monosaccharide lipid precursor of LPS corresponding to the reducing half of lipid A . Lipid IVA, a precursor identical to E . coli lipid A except that it lacks the 2' and 3' acyl chains, was the simplest structure identified in this study that rBPI23 bound with high affinity . These results demonstrate that rBPI23 has a binding specificity for the lipid A region of LPS and binding involves both electrostatic and hydrophobic components. Enferm Infecc Microbiol Clin, 1995 Jun-Jul, 13(6), 345 - 55 {Bacteremia in 13 general hospitals of the province of Barcelona . Prospective study of 1,674 episodes . Group of Microbiologists of the County Hospitals of Catalonia}; Matas L et al.; BACKGROUND: Clinical and microbiological description of bacteremias seen in 13 regional hospitals of Barcelona . METHODS: From January to December of 1991 a multicenter prospective study of bacteremia in regional hospitals was performed . The filiation, clinical findings and microbiological results were registered according to a common protocol . RESULTS: We studied 1674 episodes of bacteremia (13.8 per 1000 admissions) . Patients were distributed into 3 groups according to age: under 14: 204 patients, between 14 to 65: 759 and over 65: 711 patients . Men account for 55% and women for 45% of episodes . The bacteremia was hospital-acquired in 24.4% of cases . The most common foci of infection were: urinary tract (32%), respiratory tract (14%), intestinal tract (8%), intravascular catheter (7%), biliary tract (7%) and unknown (10%) . The most commonly isolated strains were: Escherichia coli 544 cases, Streptococcus pneumoniae 212, Staphylococcus aureus 139, coagulase negative staphylococi 85, Non-typhoid Salmonella 66, Neisseria meningitidis 63, Pseudomonas sp . 59, Enterococcus sp . 59 and Bacteroides sp . 58 . Polimicrobial bacteremia was detected in 83 episodes (5%) . Related mortality rate was 9.6% (161 patients). Genitourin Med, 1995 Jun, 71(3), 176 - 9 Neutrophil enzymes in urine for the detection of urethral infection in men; Fraser PA et al.; OBJECTIVES--To determine if assaying the neutrophil enzymes, neutrophil elastase (NE) and myeloperoxidase (MPO) in the urine of men attending a genitourinary medicine clinic could identify those with Neisseria gonorrhoeae or Chlamydia trachomatis infections, and those with urethritis (with or without an identified infection with either organism), and to compare the new assays with the performance of the leucocyte esterase test (LET) . METHOD--100 men had urethral specimens taken for Gram-stained urethral smear, culture for N gonorrhoeae, and for C trachomatis testing by enzyme immunoassay . First-voided urines were tested for leucocyte esterase by commercial dipstick (positives were defined as greater than "trace") and then frozen at -20 degrees C prior to being assayed for NE and MPO . RESULTS--Five patients had gonorrhoea, six had chlamydia and none had both . Evidence of urethritis (> 5 polymorphonuclear leucocytes in four x 1000 fields) was found in 29 men . The results of the urine assays showed MPO levels to be non-discriminatory; however NE levels were significantly elevated in patients with proven infection or urethritis or both . Using NE values from men with no infection or urethritis an upper limit for normal was defined . Utilising this, the sensitivity of the elastase assay was calculated and found to be superior to the sensitivity of LET for detecting proven infection (64% vs 36%) and urethritis (52% vs 31%) . CONCLUSIONS--Further studies of neutrophil elastase in the pathogenesis, diagnosis and treatment of urethritis are indicated. Genitourin Med, 1995 Jun, 71(3), 163 - 8 Lower genital tract infections in infertile Nigerian women compared with controls; Okonofua FE et al.; OBJECTIVE--To investigate the possibility that infertile Nigerian women have a higher rate of cervical colonisation with pathogenic and facultative organisms than fertile controls . DESIGN--The prevalence of common microorganisms in the vagina and endocervical canals of infertile women was compared with that of pregnant controls . SETTING--The Obafemi Awolowo University Hospital Maternity Centre . SUBJECTS--92 infertile women were compared with 86 pregnant controls . MAIN OUTCOME MEASURES--rates of isolation of Neisseria gonorrhoeae, Candida albicans, Trichomonas vaginalis and other facultative organisms in cases and controls . RESULTS--The rate of isolation of Neisseria gonorrheae was 17.4% among infertile women compared with 10.5% in the group of pregnant women (p > 0.05) . There was no significant difference between the groups in the rate of isolation of Candida albicans, Trichomonas vaginalis and other facultative organisms . High rates of isolation of microorganisms were observed in both groups . However, women with secondary infertility had higher rate of carriage of Neisseria gonorrheae, Candida albicans and Staphylococcus aureus as compared with women with primary infertility . Nearly 15% of infertile women had previous episodes of pelvic inflammatory disease and 26% had had induced abortions . A positive history of vaginal discharge was a poor predictor of vagina and endocervical carriage of microorganisms . CONCLUSIONS--High rates of pathogenic organisms exist in the lower genital tract of infertile women and controls . Women with secondary infertility are more likely to have pathogenic organisms than women with primary infertility . A policy of routinely screening women for lower genital tract infections should be pursued in this population because of the high rate of infection. Genitourin Med, 1995 Jun, 71(3), 155 - 7 Sexually transmitted diseases including HIV infection in women with Bartholin's gland abscesses; Hoosen AA et al.; OBJECTIVES--The aim of this study was to establish the prevalence of sexually transmitted infections including human immunodeficiency virus (HIV) infection in women with Bartholin's gland abscess . SETTING--Gynaecology Clinic of King Edward VIII Hospital, a large urban, referral hospital for the province of Kwa-Zulu Natal, serving an underprivileged population . METHODS--Thirty consecutive women presenting with unruptured Bartholin's gland abscesses were studied . Prior to surgical drainage, aspirates from the abscess cavity and swab specimens from the vagina and endocervix were collected for microbiological investigations . In addition peripheral venous blood samples were obtained for syphilis and HIV antibody testing . RESULTS--Antibody to HIV was detected in 9 of the 30 (30%) patients studied . Recognised sexually transmitted pathogens were detected in both aspirates and endocervical specimens: Chlamydia trachomatis was detected in 3 aspirate and 2 endocervical specimens whilst Neisseria gonorrhoeae was cultured in 5 aspirate and 7 endocervical specimens . When comparing microorganisms isolated from HIV antibody positive and negative women, only Bacteroides species yielded a significantly higher growth (p = 0.01) in the antibody positive women . CONCLUSION--Our findings show that women with Bartholin's gland abscesses have a high prevalence of HIV antibody . Furthermore, this is the only study that demonstrates a role for C trachomatis in the aetiology of Bartholin's gland abscesses . Health workers should be aware of the need for appropriate counselling, and comprehensive treatment of sexually transmitted infections including C trachomatis in women with Bartholin's gland abscesses. Genitourin Med, 1995 Jun, 71(3), 145 - 9 Resolution of clonal subgroups among Neisseria gonorrhoeae IB-2 and IB-6 serovars by pulsed-field gel electrophoresis; Poh CL et al.; OBJECTIVE--Analysis of macrorestriction patterns by PFGE to resolve the relatedness of clonal subgroups amongst N gonorrhoeae IB-2 and IB-6 serovar strains . MATERIALS AND METHODS--Nineteen IB-2 and eight IB-6 serovar strains that differed in either auxotype or penicillin sensitivity were isolated over a two and a half-year period from patients attending several STD clinics in Sydney . During this period, a major clone, Wt/IB-2 (FS), established on epidemiological grounds, was circulating amongst homosexual males . The genetic relation of this major clone to the other strains present in the community was determined by pulsed-field gel electrophoretic (PFGE) analysis of DNA restriction fragments . Genomic DNA from the 27 isolates were prepared, digested with SpeI and BglII and the restriction patterns were analysed by contour-clamped homogeneous electric field electrophoresis (CHEF) in a CHEF DRIII equipment . RESULTS--Phenotypic characterisation of the 27 isolates by the combined use of auxotype, serological characterisation and penicillin sensitivity indicated the presence of subgroups within each of the two serovars . In the present study, PFGE analysis of SPeI and BglII-generated genomic DNA restriction patterns from six of the ten Wt/IB-2 (FS) correlated well with phenotypic characterisation of this major clone . Four of the ten Wt/IB-2 (FS) were found to be clonally-derived variants of this major clone as minor genome variations (less than 3 DNA fragments) were observed . Distinct clones were represented by three Wt/IB-2 (LS) isolates as the DNA fingerprints generated from these were unrelated to the major clone . Analysis of PFGE patterns of 6 Pro/IB-2 isolates showed that one was genotypically identical to the major clone, two were clonal variants and three had significantly different patterns to indicate that they were genotypically unrelated . Wt/IB-6 isolates had heterogenous PFGE patterns that were clearly unrelated to the Wt/IB-2 serovar strains . Within the IB-6 serovar, there were three isolates with the Wt/IB-6 (FS) phenotype that could be considered as clonal variants whilst the rest were genotypically distinct . CONCLUSIONS--PFGE analysis of macrorestriction patterns generated from SpeI- and BglII-cleavage of genomic DNA has enabled the establishment of clonal origins of strains present in the Sydney community during the period of study . The delineation of strains belonging to major A/S groups by PFGE analysis presents a clearer epidemiological picture than phenotypic characterisation alone. Genitourin Med, 1995 Jun, 71(3), 141 - 4 Rapid decline in penicillinase-producing Neisseria gonorrhoeae in Hong Kong associated with emerging 4-fluoroquinolone resistance; Kam KM et al.; OBJECTIVE--To study the changes in penicillinase-producing (PPNG) and high-level tetracycline resistant (TRNG) Neisseria gonorrhoeae isolated in Hong Kong associated with emerging quinolone resistance (QRNG) over a two year period from November 1992 to October 1994 . MATERIALS AND METHODS--Four thousand and eighty-six strains of Neisseria gonorrhoeae isolated, of which 432 were PPNG, were examined for susceptibilities to penicillin and tetracycline by an agar dilution method using the breakpoint minimum inhibitory concentrations (MICs) of 1 and 10 mg/1 respectively . Ofloxacin susceptibility was done using 0.1 and 1 mg/l . Penicillinase production was detected by performing the chromogenic cephalosporin nitrocefin test on all penicillin resistant (MIC > 1 mg/l) strains . RESULTS--Three thousand and eighty (75.4%) and 79 (1.9%) strains were found to be penicillin resistant and TRNG (MIC > 10 mg/l) respectively . Sixty-nine strains (1.7%) were resistant to both, of which 54 (1.3%) were PPNG . Three strains were multiply-resistant to penicillin, tetracycline and ofloxacin; however, none was PPNG . While the percentage of penicillin resistant strains remained stable (mean 75.5%, SD 7.0), TRNG decreased from 4.5% to 2.1% . The most dramatic change was the sharp decline of PPNG from 25.5% in January 1993 to 4.3% in October 1994, concurrent with a linear increase in strains with ofloxacin MIC > 0.1 mg/l . Significant clinical failure was seen in strains having ofloxacin MIC > 1 mg/l (QRNG), which increased drastically from 0.5% to 10.4% during the study period . Selection against PPNG and TRNG strains appeared to occur only when fully quinolone-susceptible strains first become less susceptible (MIC > 0.1 mg/l), but not when these less susceptible strains become fully resistant (MIC > 1 mg/l) . CONCLUSION--PPNG is now no longer hyperendemic in Hong Kong . Emergence of QRNG is associated with rapid decline of both PPNG and TRNG . This is the first report of plasmid-curing effect of the 4-fluoroquinolones occurring on an ecological scale. Clin Infect Dis, 1995 Jun, 20 Suppl 2, S271 - 5 Role of bacterial vaginosis in pelvic inflammatory disease; Sweet RL; Pelvic inflammatory disease (PID) is a frequent infection in sexually active young women and results in adverse sequelae, including tubal-factor infertility and ectopic pregnancy . In the 1970s investigations using culdocentesis demonstrated that anaerobic bacteria played an important role in the etiology of PID . This finding has subsequently been confirmed by studies utilizing laparoscopy and/or endometrial biopsy to obtain specimens directly from the upper genital tract (uterine cavity and fallopian tube) of patients with acute PID . Recently, several investigations have shown an association between bacterial vaginosis and the development of acute PID . The microorganisms associated with bacterial vaginosis include anaerobes such as Prevotella bivia, other Prevotella species, and Peptostreptococcus species . These studies that have demonstrated the presence of bacterial vaginosis-associated bacteria in addition to the sexually transmitted organisms Neisseria gonorrhoeae and Chlamydia trachomatis suggest that treatment of acute PID must be broad spectrum in nature and effective against anaerobic bacteria as well as N . gonorrhoeae and C . trachomatis. Infect Immun, 1995 Jun, 63(6), 2347 - 51 Synthetic peptides representing two protective, linear B-cell epitopes of outer membrane protein F of Pseudomonas aeruginosa elicit whole-cell-reactive antibodies that are functionally pseudomonad specific; Gilleland LB et al.; Peptide 9 (TDAYNQKLSERRAN) and peptide 10 (NATAEGRAINRRVE) represent surface-exposed epitopes of outer membrane protein F of Pseudomonas aeruginosa . Rats immunized with four intramuscular inoculations on days 0, 14, 28, and 42 with either peptide 9 or peptide 10 conjugated to keyhole limpet hemocyanin were afforded protection against pulmonary lesions when examined 7 days subsequent to challenge (day 56) via intratracheal inoculation of P . aeruginosa-containing agar beads . Peptide 9 shares considerable homology with other OmpA-related outer membrane proteins in various bacteria, whereas peptide 10 displays little homology with these other proteins . Antisera directed to peptide 9 reacted weakly with cell envelope proteins from the various other OmpA-associated bacteria upon immunoblot analysis . However, antisera directed to peptide 10 reacted only with Neisseria gonorrhoeae cell envelope proteins upon immunoblot analysis . Antisera to both peptides 9 and 10 reacted at minimal titers with whole cells of the various other bacteria in a whole-cell enzyme-linked immunosorbent assay (ELISA) but antisera to each of the peptides reacted at high titers when various strains of P . aeruginosa were used as the ELISA antigen . Antibodies to peptides 9 and 10 were protective, reactive to all strain of P . aeruginosa tested except for a protein F-deficient mutant, and functionally specific against pseudomonads. Infect Immun, 1995 Jun, 63(6), 2164 - 72 A lipooligosaccharide-binding site on HepG2 cells similar to the gonococcal opacity-associated surface protein Opa; Porat N et al.; The lacto-N-neotetraose-containing lipooligosaccharide (LOS) present on the surface of most Neisseria gonorrhoeae organisms may serve many important functions in gonococcal pathogenesis . This surface glycolipid contains the cross-reactive epitope to human paragloboside and can be sialylated by gonococci grown in the presence of CMP-N-acetylneuraminic acid . Another possible role for this glycolipid could be to mimic human asialocarbohydrates and act as a ligand for asialoglycoprotein receptors contained on numerous human cells . The most noted of this large family of receptors is that expressed on the surface of hepatic cells . In a model cell system, using the hepatoma tissue culture cell line HepG2, we wanted to investigate if the presence of this asialoglycoprotein receptor influenced the adherence and/or invasion of gonococci expressing the lacto-N-neotetraose structure . Piliated variants of the gonococcal wild-type strain 1291 and its isogeneic LOS mutant 1291E were used in adherence-invasion assays . This gonococcal strain is somewhat unusual in that it expresses large amounts of predominantly one species of LOS, thus reducing the complexity of interpreting the data . The data from these assays suggested that the Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)Glc carbohydrate structure on the wild-type LOS affected the adherence-invasion of gonococci into the HepG2 cells . In studies to determine whether the major hepatic asialoglycoprotein receptor was involved in these interactions, we found that the HepG2 cells contained two receptors which bound gonococcal LOS . One of these was the asialoglycoprotein receptor, and the data concerning this receptor will be reported elsewhere . The data on the second receptor are reported here . Purified, 125I-labeled gonococcal LOS was used to identify specific high-affinity LOS-binding sites . These binding experiments revealed one major binding site corresponding to a protein with a molecular mass of 70 kDa (p70) . Several lines of evidence in this study suggested that the oligosaccharide region of LOS played an important role in LOS binding to the p70 of HepG2 cells . In addition, we show that this human LOS receptor has some similarities to the gonococcal Opa proteins. Mol Microbiol, 1995 Jun, 16(5), 847 - 53 Molecular mechanisms and implications for infection of lipopolysaccharide variation in Neisseria; van Putten JP et al.; The lipopolysaccharides of the pathogenic Neisseria species are subject to structural variation owing to a combination of intrinsic changes in lipopolysaccharide (LPS) biosynthesis and external modification of the LPS molecule with sialic acid . This variation appears to control bacterial behaviour by altering their ability to interact with human cells and to evade host immune defences . This interconversion of LPS phenotypes, which is also observed during the natural infection, is probably due to environmental regulation of LPS biosynthesis superimposed on spontaneous changes in the DNA of distinct LPS loci . LPS variation may be a common strategy of mucosal pathogens to colonize and persist within the human host. Gene, 1995 May 19, 157(1-2), 19 - 22 Restriction and modification systems of Neisseria gonorrhoeae; Stein DC et al.; An individual strain of Neisseria gonorrhoeae may produce up to 16 different DNA methytransferases (MTases) . We have used a novel cloning system that is able to detect MTase clones in the absence of direct selection {Piekarowicz et al., Nucleic Acids Res . 19 (1991) 1831-1835} to identify 14 different MTase clones . Initial characterization of these clones indicates that at least seven of these MTases are linked to restriction endonuclease (ENase) systems . Six of these systems have been characterized by DNA sequence analysis, and the open reading frames encoding each of these systems have been identified . The recognition sequences for the cloned systems have the following specificities: S.NgoI, RGCGCY; S.NgoII, GGCC; S.NgoIV, GCCGCC; S.NgoV, GGNNCC; S.NgoVII, GCSGC; S.NgoVIIIA, GGTGA; and S.NgoVIIIC, TCACC . Of those systems that have been cloned, NgoI-NgoVII are typical type II R-M systems, with each encoding a DNA MTase that methylates cytosine in position 5 . NgoVIII is a type IIS system, containing an ENase and two different MTases . One of these is a cytosine MTase (NgoVIIIC) and the other is an adenine MTase (NgoVIIIA) . Although most of our clones encodes both the ENase and the MTase, none of the six R-M systems are genetically linked on the chromosome. Gene, 1995 May 19, 157(1-2), 101 - 2 Purification and characterization of a new DNA methyltransferase from Neisseria gonorrhoeae; Piekarowicz A et al.; A new DNA methyltransferase, M.NgoBVII, was isolated from Neisseria gonorrhoeae strain WR302 . M.NgoBVII recognizes the sequence 5'-GCNGC-3'. EMBO J, 1995 May 15, 14(10), 2144 - 54 Binding of syndecan-like cell surface proteoglycan receptors is required for Neisseria gonorrhoeae entry into human mucosal cells; van Putten JP et al.; Bacterial invasion of human mucosal cells is considered to be a primary event in the pathogenesis of a gonococcal infection . Here we report that cell surface heparan sulfate proteoglycans may play a role in the establishment of an infection, by functioning as receptors for the invasion-promoting gonococcal opacity protein adhesin . Chemical modification and enzymatic removal of proteoglycan receptors from cultured epithelial cells abolished opacity protein-associated gonococcal invasion, and mutant cell lines defective in proteoglycan synthesis were poor substrates for gonococcal attachment . The addition of purified receptor and receptor analogues totally blocked gonococcal entry into the cells . Heparin-affinity chromatography and receptor binding assays using recombinant bacteria producing defined opacity proteins and reconstituted receptor or purified receptor fragments as probes, identified one particular member of the opacity protein family (MS11-Opa30) as the primary ligand for this novel class of receptors for bacteria . Heparan sulfate proteoglycans with gonococcal binding activity were purified from various cell types derived from target tissues of gonococcal infection, including ME-180 endocervical cells and primary cultures of human corneal epithelium . The physico-chemical properties of the receptor indicate that it may belong to the syndecan proteoglycan family. J Med Chem, 1995 May 12, 38(10), 1666 - 72 Antineoplastic agents . 291 . Isolation and synthesis of combretastatins A-4, A-5, and A-6(1a) Pettit GR, Singh SB, Boyd MR, Hamel E, Pettit RK, Schmidt JM, Hogan F. The antineoplastic constituents of Combretum caffrum (Eckl . and Zeyh) Kuntze (Combretaceae family), a species indigenous to South Africa, have been investigated . Subsequently we isolated a series of closely related bibenzyls, stilbenes, and phenanthrenes from C . caffrum . Some of the stilbenes proved to be potent antimitotic agents which inhibited both tubulin polymerization and the binding of colchicine to tubulin . Combretastatin A-4 has been shown to be the most potent cancer cell growth inhibitor of the series . Presently this cis-stilbene is the most effective inhibitor of colchicine binding to tubulin and the simplest natural product yet described with such potent antitubulin effects . Combretastatin A-4, A-5, and A-6 were also found to inhibit growth of Neisseria gonorrhoeae . Details of the isolation and syntheses of combretastatins A-4 (2a), A-5 (2c), and A-6 (3a) have been described. Enferm Infecc Microbiol Clin, 1995 May, 13(5), 283 - 7 {Evaluation of the E test method in the antimicrobial sensitivity of Neisseria meningitidis to penicillin}; Gene A et al.; BACKGROUND: The E test (AB Biodisk, Solna, Sweden) is a rather new method for performing antimicrobial susceptibility test--their results are generated directly as MICs . Due to its simplicity, is available in nearly all laboratories . The present study evaluates the effectiveness of the E test for susceptibility studies of Neisseria meningitidis to penicilline . METHODS: The MICs of penicilline of 55 strains of Neisseria meningitidis, studied by E test and by microdilution method, were compared to those obtained by agar dilution using both Mueller-Hinton (MH) and Mueller-Hinton with a 5% of sheep blood (MH+S) as test culture bases . RESULTS: The concordance rate (+/- 1 log2 of dilutions) was 100% in all cases, except for the E test on MH+S which yielded a 98.2% value . The Pearson's correlation coefficients were 0.95 and 0.84 for the E test and 0.88 and 0.85 for microdilution, using MH and MH+S . Roughly 70% of strains were considered susceptible to penicillin using MH for the in vitro tests, whereas only 40% of them were so considered using MH+S . CONCLUSIONS: The E test can be considered a good alternative to agar dilution method when testing susceptibility of N . meningitidis to penicilline, and MH is the best culture base for these assays. Microbiology, 1995 May, 141 ( Pt 5), 1183 - 91 Organization of carbamoyl-phosphate synthase genes in Neisseria gonorrhoeae includes a large, variable intergenic sequence which is also present in other Neisseria species; Lawson FS et al.; The carbamoyl-phosphate synthase (CPS) enzyme in prokaryotes is a heterodimer, encoded by genes commonly called carA and carB . In most prokaryotes examined, these genes are separated by up to 24 bp and are cotranscribed . In Pseudomonas aeruginosa, carA and carB are also co-transcribed, but are separated by 682 bp . We have determined the complete DNA sequence of the carA and carB genes of Neisseria gonorrhoeae strain CH811 . carA (1125 bp) and carB (3237 bp) are similar in size and sequence to other prokaryotic CPS genes, however they are separated by an intervening sequence of 3290 bp which has no similarity to the intervening sequence between other CPS genes; furthermore, putative transcription terminators are found downstream of both carA and carB . Several neisserial repetitive sequences were identified within the 9 kb sequenced, as well as novel 120 and 150 bp repeats (designated RS6 and RS7, respectively) which were found within the intervening sequence between carA and carB . To determine whether the intervening sequence observed in N . gonorrhoeae CH811 was not unusual, the sequence between carA and carB was amplified by PCR from 30 isolates of N . gonorrhoeae . The intervening sequence was found to vary in size, from approximately 2.2 to 3.7 kb, although the carA and carB genes themselves did not vary in size in isolates with functional CPS enzyme . A similar large, variably sized intervening sequence was also found between the carA and carB genes of 12 isolates of N . meningitidis and 18 commensal Neisseria isolates comprising nine species . This unexpected organization of the CPS genes in N . gonorrhoeae is therefore widespread throughout the genus Neisseria. Mol Biol Evol, 1995 May, 12(3), 363 - 70 Sequence evolution of the porB gene of Neisseria gonorrhoeae and Neisseria meningitidis: evidence of positive Darwinian selection; Smith NH et al.; Protein 1 (PI) is a major porin of Neisseria gonorrhoeae and Neisseria meningitidis and is encoded by a single locus, porB . Alleles of the porB locus of N . gonorrhoeae are assigned to two homology groups, PI(A) and PI(B), on the basis of immunological and structural similarity . In a like manner, alleles of the porB locus of the closely related bacterium, N . meningitidis, are allocated into class 2 and class 3 homology groups . An individual strain of N . gonorrhoeae or N . meningitidis expresses either one or other of these porin homology groups but never both, and the antigenic reactions of these highly diverse outer membrane proteins form part of the N . gonorrhoeae and N . meningitidis serotyping schemes . A comparison of the number of synonymous and nonsynonymous substitutions per site between the two most divergent alleles of each of these four groups of porB alleles shows that PI(A) alleles have accumulated significantly more nonsynonymous substitutions per site than synonymous substitutions . In contrast the distribution of synonymous and nonsynonymous substitutions between alleles of class 2 and class 3 porins are not significantly different from random . We localize the regions of the PI(A) alleles with an excess of amino acid changes to the surface-exposed loops of these outer membrane proteins and suggest that positive Darwinian selection for diversity, driven by the human immune system, can most easily explain the allelic polymorphism and the pattern of synonymous and nonsynonymous substitutions. J Bacteriol, 1995 May, 177(9), 2497 - 504 Interaction of the Neisseria gonorrhoeae PilA protein with the pilE promoter involves multiple sites on the DNA; Arvidson CG et al.; PilA is the putative DNA-binding component of a two-component system that regulates transcription of the pilin expression locus (pilE) of Neisseria gonorrhoeae . Here we report the purification of the PilA protein and characterization of its DNA-binding activity . PilA was overproduced in Escherichia coli with an isopropyl-beta-D-thiogalactopyranoside (IPTG)-inducible expression vector . Cell extracts were prepared by sonication and fractionated by anion-exchange chromotography, followed by dye affinity chromatography with Cibacron Blue . Proteins were eluted by using a gradient of KCl, and PilA-containing fractions were identified by immunoblot analysis with a polyclonal anti-PilA antiserum . Purified PilA was judged to be > 90% pure, as determined by Coomassie blue staining and sodium dodecyl sulfate-polyacrylamide gel electrophoresis . PilA purified in this manner was used to develop a gel retardation assay with a 301-bp fragment containing the pilE promoter (PpilE) and upstream sequences as a probe . A fragment of similar size containing the E . coli aroH promoter was used as a negative control . Competition experiments using a 100- to 1,000-fold excess of unlabelled DNA fragments confirmed the specificity of PilA binding to the pilE promoter . To localize the PilA binding site within the 301-bp PpilE fragment, stepwise deletions were generated by PCR and the fragments were examined in the gel shift assay . The results of these experiments show that there are two regions upstream of PpilE that are required for binding by PilA . Taken together, these data indicate that while PilA binds specifically to the upstream region of the pilE gene, this interaction is complex and likely involves multiple regions of this DNA sequence. J Bacteriol, 1995 May, 177(9), 2321 - 7 A mutation in the Neisseria gonorrhoeae rfaD homolog results in altered lipooligosaccharide expression; Drazek ES et al.; The gonococcal lsi-6 locus was cloned and shown by DNA sequence analysis to have homology with the E . coli rfaD gene, which encodes ADP-L-glycero-D-mannoheptose epimerase . This enzyme is involved in the biosynthesis of the lipopolysaccharide precursor ADP-L-glycero-D-mannoheptose . A site-directed frameshift mutation in lsi-6 was constructed by PCR amplification and introduced into the chromosome of Neisseria gonorrhoeae MS11 P+ by transformation . The lipooligosaccharides (LOS) of mutant and parental strains were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) . The lsi-6 mutant produced LOS components with apparent molecular masses of 2.6 and 3.6 kDa as compared with a 3.6-kDa band of the MS11 P+ strain . The parental LOS phenotype was expressed when a revertant was constructed by transformation of the cloned wild-type gene into the lsi-6 mutant . The immunoreactivity of LOS from parental and constructed strains was examined by SDS-PAGE and Western blotting . Only the parental and reconstructed wild-type strains produced a 3.6-kDa LOS component that reacted with monoclonal antibody 2-1-L8 . These results suggest that the lsi-6 locus is involved in gonococcal LOS biosynthesis and that the nonreactive mutant 3.6-kDa LOS component contains a conformational change or altered saccharide composition that interferes with immunoreactivity. Infect Immun, 1995 May, 63(5), 1790 - 5 Heparin protects Opa+ Neisseria gonorrhoeae from the bactericidal action of normal human serum; Chen T et al.; The pathobiological significance of lipooligosaccharide (LOS) and outer membrane opacity protein (Opa) changes in gonorrheal disease are poorly understood . We assessed variants of strain MS11mk with different LOS and Opa phenotypes for their liability to killing by normal human sera . LOS differences correlated with strikingly disparate susceptibilities to serum killing; LOSa variants were serum resistant, LOSb variants were serum sensitive, and sialylation of LOSb variants enhanced their survival (as reported previously) . Opa phenotype had little influence on the killing of serum-sensitive LOSb cells that were incubated directly in normal human sera, but preincubation of Opa+ LOSb variants in heparin increased their serum resistance whereas Opa- LOSb variants showed no change . Some Opa proteins conferred slightly higher resistance than others, but heparin preincubation increased serum resistance for variants expressing each of seven Opa proteins . These in vitro phenomena may relate to conditions within the male urethra where sulfate-containing proteoglycans are abundant and where antibody and complement may transude from blood plasma . The results suggest that the selective advantage for Opa+ Neisseria gonorrhoeae bacteria observed in vivo may reflect their ability to utilize host cell components to resist killing by host defenses. Sex Transm Dis, 1995 May-Jun, 22(3), 155 - 9 Plasmid-mediated antimicrobial resistance in Neisseria gonorrhoeae in Kingston, Jamaica: 1990-1991; Knapp JS et al.; BACKGROUND AND OBJECTIVES: Gonococcal infections caused by antimicrobial-resistant strains of Neisseria gonorrhoeae have spread into many geographic areas and have increased in prevalence since the mid 1970s . Surveillance of antimicrobial-resistant gonococcal strains of Jamaica from 1981 to 1983 indicated that fewer than 3% of strains of produced beta-lactamase (penicillinase-producing Neisseria gonorrhoeae); approximately 4% of strains were resistant to penicillin, and 12% were resistant to tetracycline . GOAL OF THIS STUDY: To measure the frequency and nature of antimicrobial resistance in Neisseria gonorrhoeae isolates in Kingston, Jamaica, from 1990 to 1991 and to assess the effectiveness of prescribed treatment regimens . STUDY DESIGN: Urethral isolates of Neisseria gonorrhoeae from 116 heterosexual men with uncomplicated gonorrhea, representing 7.1% (116/1633) men attending the STD Comprehensive Health Centre from October 1990 through March 1991 who had positive Gram-stained smears, were characterized by auxotype, serovar, presence of the TetM determinant, and plasmid content . Antimicrobial susceptibilities to penicillin, cefoxitin, ceftriaxone, ciprofloxacin, tetracycline, and spectinomycin were determined by an agar dilution method . RESULTS: A total of 80.2% (93/116) of the isolates exhibited plasmid-mediated resistance to penicillin, tetracycline, or both: penicillinase-producing Neisseria gonorrhoeae (13/116; 11.2%), tetracycline-resistant Neisseria gonorrhoeae (25/116; 21.6%), and penicillinase-producing/tetracycline-resistant Neisseria gonorrhoeae, (55/116;47.4%) . Isolates with chromosomally mediated resistance to penicillin, tetracycline, or both, accounted for 5.2% (6/116) of the isolates . Penicillinase-producing Neisseria gonorrhoeae, tetracycline-resistant Neisseria gonorrhoeae, and penicillinase-producing/tetracycline-resistant Neisseria gonorrhoeae belonging to multiple auxotype/serovar classes were isolated repeatedly through the study period . CONCLUSIONS: Infections caused by Neisseria gonorrhoeae exhibiting plasmid-mediated resistance to penicillin, tetracycline, or both, have become prevalent and endemic in Kingston, Jamaica . Therefore, all gonococcal infections should be treated with antimicrobial therapies known to be active against penicillin-resistant and tetracycline-resistant organisms to reduce gonorrhea transmission. Sex Transm Dis, 1995 May-Jun, 22(3), 145 - 8 Time required for elimination of Neisseria gonorrhoeae from the urogenital tract in men with symptomatic urethritis: comparison of oral and intramuscular single-dose therapy; Haizlip J et al.; BACKGROUND AND OBJECTIVES: The spread of sexually transmitted diseases (STDs), including gonorrhea, is affected by the duration of infection . Oral antibiotic therapy for gonococcal infection has been shown to be as effective as conventional intramuscular injection with ceftriaxone . Rapid cure would be expected to limit further spread of gonorrhea . However, the speed with which Neisseria gonorrhoeae is eliminated from the urogenital tract has not been evaluated . GOAL OF THIS STUDY: To determine the time required for elimination of Neisseria gonorrhoeae for the urine, mucosa, and semen in male subjects after treatment with ceftriaxone (250 mg intramuscularly), ciprofloxacin (500 mg by mouth, single dose) or cefixime (400 mg by mouth, single dose.) RESULTS: In 14 subjects, gonococci were eliminated from the urine within 4 hours of therapy and the mucosa within 24 hours after therapy . In 9 additional subjects, gonococci were eliminated from the semen by 24 hours after therapy . CONCLUSIONS: These results support the efficacy of single-dose oral therapy for gonorrhea and suggest that earlier follow-up for proof of cure in clinical trials of new antibiotics for gonorrhea may be acceptable . Rapid elimination of gonorrhea reduces the risk for continued transmission of the organism. Trends Microbiol, 1995 May, 3(5), 198 - 201 Recognition and control of neisserial infection by antibody and complement; Jarvis GA; Immunity to neisserial infection involves complex interactions between antibody, complement and bacterial cell-surface molecules . Neisseria species express polysaccharide and glycolipid membrane components, which downregulate complement activation . The pathogenic potential of Neisseria depends on evasion of the complement cascade. J Clin Microbiol, 1995 May, 33(5), 1141 - 4 Quality assurance study of bacterial antigen testing of cerebrospinal fluid; Kiska DL et al.; Bacterial antigen testing (BAT) of cerebrospinal fluid (CSF) by latex agglutination is a low-yield procedure in patients whose CSF specimens have normal laboratory parameters . Between August 1992 and August 1994, we evaluated 287 bacterial antigen (BA) test requests to determine whether yields could be improved and whether patient costs could be reduced by cancelling BAT for those patients with normal CSF parameters (cell count, protein, glucose) after consultation with physicians . A total of 171 (68%) BA tests were canceled by this approach . None of these CSF specimens was culture positive for an organism detectable by BAT . Of the remaining 116 CSF specimens tested, only 3 were positive by BAT, one each for Neisseria meningitidis, Streptococcus pneumoniae, and group B streptococcus . Only 43 of the CSF specimens tested had at least two abnormal parameters; the 3 positive CSF specimens were included in this group . In light of the low rate of positivity, the number of BA tests can be further reduced by establishing criteria that must be met before a CSF specimen is accepted for BAT . After review of our data and the literature concerning this topic, we concluded that only specimens with leukocyte counts of > or = 50 cells per mm3 should be tested . Of 287 specimens evaluated in our study, only 36 met this criterion, including the 3 BA-positive specimens . Enacting such a restriction would have reduced the total number of BA tests by 251 (87%) without compromising patient care . A laboratory cost savings of $6,500 per year would have been realized, with a substantial reduction in the cost per positive test . Patient charges would have been reduced by $12,500 per year. Br J Obstet Gynaecol, 1995 May, 102(5), 407 - 14 Clinical, laparoscopic and microbiological findings in acute salpingitis: report on a United Kingdom cohort; Bevan CD et al.; OBJECTIVE: To determine the clinical features and microbial aetiology of acute salpingitis in women attending an inner city teaching hospital . DESIGN: Prospective, longitudinal cohort study . SUBJECTS: One hundred and forty-seven women presenting consecutively with acute abdominal pain and clinical signs of acute salpingitis were evaluated microbiologically and laparoscopically . RESULTS: One hundred and four women (70.7%) had acute salpingitis diagnosed at laparoscopy . Other pathological conditions were identified in 20 women (13.6%) . No visually identifiable pathology was found in 23 (15.6%) . Thirty-five women with acute salpingitis had evidence of pelvic adhesions (33.7%) . Bilateral tubal occlusion was present in 6 (5.8%) cases . Chlamydia trachomatis was identified in the genital tract in 40 (38.5%) of the women with acute salpingitis and Neisseria gonorrhoeae in 15 (14.4%) . A dual infection was present in eight cases (7.7%) . Serological evidence suggested that a further seven women (6.7%) had acute chlamydial infections at the time of diagnosis . C . trachomatis was identified in the genital tract of 5/23 (21.7%) of the women who had no laparoscopic evidence of intra-abdominal pathology . CONCLUSIONS: The responsible care of women with suspected acute salpingitis depends on establishing an accurate diagnosis, so that appropriate therapy can be instigated . This study provides evidence to challenge the outpatient management of acute salpingitis on clinical grounds alone as potentially inadequate . Early laparoscopy in hospitalised women improves diagnostic precision and accurately determines disease severity, providing prognostic information for future fertility . In this urban population, sexually transmitted micro-organisms were the commonest pathogens found in the genital tract of women with acute salpingitis . The high prevalence of C . trachomatis in these women suggests that appropriate chemotherapy for acute salpingitis should always include a specific antichlamydial agent. Kansenshogaku Zasshi, 1995 May, 69(5), 511 - 6 {Quinolone-resistant mutations in Neisseria gonorrhoeae}; Onodera S et al.; For 10 strains of Neisseria gonorrhoeae exhibiting decreased susceptibility to new quinolones (MIC, > or = 0.1 microgram/ml) isolated and preserved from patients with gonococcal urethritis during the period from February 1991 through January 1992 . We investigated the mechanisms for development of resistance to new quinolones . After selecting 3 PCG-sensitive and new quinolone-resistant strains from among these strains, we first carried out transformation experiments of N . gonorrhoeae using a plasmid carrying the E . coli gyrA gene . We then determined the base sequence on the N . gonorrhoeae gyrA gene by PCR method . Of the 3 strains in which transformation experiments were carried out, 2 strains yielded transformants, one of which was 8 times more sensitive to norfloxacin (NFLX) than the original strain, and it was assumed that this strain has a mutation in the gyrA gene . In our study of the base sequence on the N . gonorrhoeae gyrA gene using the PCR method, both strains had the mutation of Ser 83 (TCC)-->Phe (TTC), and in addition to this mutation of Ser-->Phe, one other strain had the mutation of Asp-87 (GAC)-->Gly (GGC) . This type of mutation of quinolone-resistant N . gonorrhoeae on the gyrA gene has high homology with the mutations reported for Escherichia coli and other strains and there appears to be a close correlation between the increasing frequency of use of the new quinolones in this country and the spread of such resistant strains of N . gonorrhoeae. Mol Microbiol, 1995 May, 16(3), 451 - 64 Identification and characterization of pilG, a highly conserved pilus-assembly gene in pathogenic Neisseria; Tonjum T et al.; Expression of type IV pili appears to be a requisite determinant of infectivity for the strict human pathogens Neisseria gonorrhoeae and Neisseria meningitidis . The assembly of these colonization factors is a complex process . This report describes a new pilus-assembly gene, pilG, that immediately precedes the gonococcal (Gc) pilD gene encoding the pre-pilin leader peptidase . The nucleotide sequence of this region revealed a single complete open reading frame whose derived polypeptide displayed significant identities to the pilus-assembly protein PilC of Pseudomonas aeruginosa and other polytopic integral cytoplasmic membrane constituents involved in protein export and competence . A unique polypeptide of M(r) 38 kDa corresponding to the gene product was identified . A highly related gene and flanking sequences were cloned from a group B polysaccharide-producing strain of N . meningitidis (Mc) . The results indicate that the pilG genes and genetic organization at these loci in Gc and Mc are extremely conserved . Hybridization studies strongly suggest that pilG-related genes exist in commensal Neisseria species and other species known to express type IV pili . Defined genetic lesions were created by using insertional and transposon mutagenesis and moved into the Gc and Mc chromosomes by allelic replacement . Chromosomal pilG insertion mutants were devoid of pili and displayed dramatically reduced competence for transformation . These findings could not be ascribed to pilin-gene alterations or to polarity exerted on pilD expression . The results indicated that PilG exerts its own independent role in neisserial pilus biogenesis. Obstet Gynecol, 1995 Apr, 85(4), 499 - 503 Value of wet mount and cervical cultures at the time of cervical cytology in asymptomatic women; Eltabbakh GH et al.; OBJECTIVE: To correlate Papanicolaou smear findings with the wet mount and cervical culture results in asymptomatic patients, and to review the value of doing wet mount and/or cervical cultures in these patients at the time of Papanicolaou smear . METHODS: Asymptomatic women presenting for routine Papanicolaou smears at Sinai Samaritan Medical Center, Milwaukee, Wisconsin, between January 1991 and January 1994 were studied by preparing wet mount (saline and potassium hydroxide preparations) and cervical cultures for Chlamydia trachomatis and Neisseria gonorrhoeae at the same visit . Fisher exact test and Pearson chi 2 statistics were applied . RESULTS: Nine hundred sixty-three patients were studied . Nearly 50% of our asymptomatic young urban women had a vaginal and/or cervical infection . Papanicolaou smears with inflammation were associated with bacterial vaginosis (P < .0001), excess white blood cells (P < .0001), trichomoniasis (P < .0001), abnormal wet mounts in general (P < .0001), and positive cervical cultures for C trachomatis and/or N gonorrhoeae (P < .001) . Papanicolaou smears showing atypical cells of undetermined significance were associated with bacterial vaginosis (P < .001) and abnormal wet mounts in general (P < .03) . Seventy-five percent of patients with positive cervical cultures had abnormal wet mounts . Eighty-three percent of the patients whose initial Papanicolaou smear showed inflammation and whose initial wet mount was abnormal had a normal Papanicolaou smear when the wet mount became normal . CONCLUSION: Preparing wet mounts at the time of Papanicolaou smear in asymptomatic young urban women will help in the interpretation of minimally abnormal smears and will probably decrease the need for repeat smears and colposcopy . Simultaneous cervical cultures would not add much information for such interpretation. Infect Immun, 1995 Apr, 63(4), 1498 - 506 Neisseria gonorrhoeae utilizes and enhances the biosynthesis of the asialoglycoprotein receptor expressed on the surface of the hepatic HepG2 cell line; Porat N et al.; One of the lipooligosaccharide (LOS) structures of Neisseria gonorrhoeae contains a terminal Gal(beta 1-4)GlcNAc residue which is a good candidate to serve as a ligand for human asialoglycoprotein receptors (ASGP-R) . These receptors have been shown to be present on macrophages, sperm cells, and hepatocytes . The human tissue culture cell line used most often to study this receptor, HepG2, was used in our investigations only as a model . We also chose N . gonorrhoeae 1291 for these studies because, unlike many other gonococcal strains, this strain expresses one main species of LOS . The LOS structure expressed by this strain has also been fully characterized . Using well-established assays for the utilization of the ASGP-R, we found that incubation of HepG2 cells with gonococci expressing the terminal Gal(beta 1-4)GlcNAc asialo-LOS carbohydrate structure competitively inhibited the ASGP-R from binding to one of its well-known ligands, asialo-alpha-acid-1-glycoprotein . The inhibition was specific to the ASGP-R, since binding of two other ligands to their specific receptors in the same model cell system was not affected . Immunoblot analysis for the ASGP-R suggested that gonococci seemed to stimulate the HepG2 cells to increase the expression of the major (46-kDa) receptor species . This observation was confirmed both by functional analysis, which showed that the concentration of total receptor molecules, as well as surface receptors, was about 60% higher after incubation with gonococci than in control cells and by Northern (RNA) blot analysis using a cDNA probe of the major human H1 subunit . Poly(A) RNA purified from control and HepG2 cells exposed to gonococci indicated the presence of increased amounts of mRNA coding for the ASGP-R after incubation with gonococci . This result supports the idea that the molecular mechanism controlling the receptor level after gonococcal exposure is under transcriptional regulation. Infect Immun, 1995 Apr, 63(4), 1434 - 9 Gonococcal opacity: lectin-like interactions between Opa proteins and lipooligosaccharide; Blake MS et al.; Previous evidence from our laboratory suggested that the tight intercellular adhesions between the outer membranes of gonococci displaying the opacity colony phenotype occurred because Opa proteins expressed on one gonococcus adhered to the lipooligosaccharide (LOS) of the opposing bacterium (M.S . Blake, p . 51-66, in G . G . Jackson and H . Thomas, ed., The Pathogenesis of Bacterial Infections, 1985, and M . S . Blake and E . C . Gotschlich, p . 377-400, in M . Inouye, ed., Bacterial Outer Membranes as Model Systems, 1986) . A noncompetitive inhibition assay used previously to determine the carbohydrate structures recognized by the major hepatic asialoglycoprotein receptor was modified to determine the gonococcal LOS structures that bind Opa proteins (R . T . Lee, Targeted Diagn . Ther . Ser . 4:65-84, 1991) . The LOS carbohydrates used in these assays were LOS structures purified from pyocin LOS mutants of Neisseria gonorrhoeae 1291 described by K . C . Dudas and M . A . Apicella (Infect . Immun . 56:499-504, 1988) and further characterized by C . M . John et al . (J . Biol . Chem . 266:19303-19311, 1991) . Purified gonococcal Opa proteins were incubated with each of the parent and mutant LOS, and the amount of binding of Opa proteins was measured by a direct enzyme-linked immunosorbent assay using the Opa-specific monoclonal antibody 4B12 . The affinities of the Opa proteins for each of the LOS were determined indirectly by measuring the concentrations of Opa proteins that noncompetitively inhibited 50% of the binding of LOS-specific monoclonal antibodies . This concentration is inversely proportional to the affinity of the inhibitor (R . T . Lee, Targeted Diagn . Ther . Ser . 4:65-84, 1991) . Our data suggest that the gonococcal Opa proteins tested had the highest affinity for the Gal beta 1-4GlcNAc residue present on the gonococcal lactoneoseries LOS . This affinity was comparable to that reported for the binding of the major hepatic asialoglycoprotein receptor to glycoconjugates containing terminal galactose and N-acetylgalactosamine (R . T . Lee, Targeted Diagn . Ther . Ser . 4:65-84, 1991) . After sialylation of the lactoneoseries LOS, presumably on the terminal galactose residue, the interaction with the Opa proteins was ablated . Therefore, the gonococcal Opa-LOS and mammalian epithelial cell asialoglycoprotein receptor-carbohydrate interactions have quite similar specificities. Clin Infect Dis, 1995 Apr, 20 Suppl 1, S47 - 65 Drugs of choice for the treatment of uncomplicated gonococcal infections; Moran JS et al.; Resistance of Neisseria gonorrhoeae to antimicrobial agents continues to spread and intensify . Choosing an antimicrobial regimen requires knowledge of the comparative efficacy of candidate regimens, as delineated in properly conducted clinical trials; their activity against N . gonorrhoeae in vitro; and their pharmacokinetics and toxicity . We tabulated the results of trials of single-dose antimicrobial therapy for uncomplicated gonococcal infection published after 1980 . Thirty regimens comprising 21 antimicrobial drugs have been shown to be highly effective for rectal and urogenital infections; the agents involved are cefixime, cefodizime, cefotaxime, cefoxitin, ceftizoxime, ceftriaxone, cefuroxime, cefuroxime axetil, ciprofloxacin, fleroxacin, norfloxacin, ofloxacin, pefloxacin, temafloxacin, azithromycin, aztreonam, netilmicin, rifampin plus erythromycin stearate, sisomicin, and spectinomycin . Few regimens have been shown to be highly effective against pharyngeal infections . Among those antimicrobial agents available for the treatment of uncomplicated gonococcal infections in the United States, ceftriaxone (125 mg), cefixime (400 mg), ciprofloxacin (500 mg), and ofloxacin (400 mg) appear to offer the best balance of proven efficacy and safety. J Clin Microbiol, 1995 Apr, 33(4), 1039 - 41 Differentiation of Neisseria gonorrhoeae isolates requiring proline, citrulline, and uracil by plasmid content, serotyping, and pulsed-field gel electrophoresis; Ng LK et al.; A combination of DNA macrorestriction analysis using pulsed-field gel electrophoresis and a serotyping method using three panels of monoclonal antibody was used to discriminate 43 epidemiologically unrelated Neisseria gonorrhoeae isolates requiring proline, citrulline, and uracil (PCU-) into 35 groups . This indicates that PCU- isolates of N . gonorrhoeae are not clonal. Drugs, 1995 Apr, 49(4), 496 - 515 Drug therapies for sexually transmitted diseases . Clinical and economic considerations; Bowie WR; Sexually transmitted diseases (STDs) are common, and result in immense social and economic costs . In some countries they have a major demographic impact . Because many STDs facilitate the transmission of HIV, the consequences of STDs are further increasing . At the same time, this association between STDs and HIV provides one of the ways in which drug therapy should be very cost effective . The perspective taken in this article is a societal one, and broader issues than those directly related to drug costs and benefits are discussed . However, it is the availability of drugs that has the potential to most quickly and most reliably make a major difference to overall health sector and societal costs as they relate to STDs . For those STDs for which curative therapy is available (particularly Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, and Trichomonas vaginalis) there have been large decreases in prevalence in many parts of the world . In contrast, those STDs for which curative therapy is not available (particularly HIV, genital herpes and genital human papillomavirus infection) have had stable or increasing prevalence . For these latter infections, each new case increases the overall prevalence . Numerous features of STDs make clinical and economic evaluation difficult . These include the sensitive nature of the topic, the changing epidemiology and drug susceptibility of individual STDs, the fact that a large proportion of those infected are asymptomatic, difficulties in making specific diagnoses, the fact that often consequences are recognised late, sexual re-exposure and reinfection, and inadequate data on which to do clinical and economic evaluations . Furthermore, risk of acquiring an STD roughly correlates inversely with socioeconomic status, and countries or places with the highest rates of STDs may have the least ability to deal effectively with their diagnosis and management . Most of the direct and indirect costs are incurred by women, since they experience the vast majority of the complications of STDs . Many of these only become apparent years later, which makes it very hard to attribute costs and benefits to a specific episode of infection, and to its treatment . The late and indirect costs, plus the costs of prevention, are hard to quantify . That the major burden of STDs is in adolescents and young adults, socioeconomically disadvantaged groups and women has important implications, including for pharmacoeconomic studies.(ABSTRACT TRUNCATED AT 400 WORDS) Chin Med J (Engl), 1995 Apr, 108(4), 269 - 72 Identification and classification of Neisseria gonorrhoeae by RAPD fingerprinting; Zhu X et al.; Using the RAPD method, we identified and classified Neisseria gonorrhoeae on the basis of the DNA level . Except OPG20 the other 19 primers of OPG arbitrary primer kit showed informative arrays of amplified prominent segments . Most of the segments were common to all three Neisseria gonorrhoeae groups; some segments were amplified from two groups or only one group so that the fingerprint maps of different Neisseria gonorrhoeae groups were distinctive . Based on these findings, i.e . on the genomic level, we can classify the three Neisseria gonorrhoeae groups . Using OPG10 and OPG11 to amplify the five Neisseria species, we found marked diversity among them, which made it easy for us to identify Neisseria gonorrhoeae from four other Neisseria species . The use of the RAPD method needs some special reaction conditions, e.g . annealing temperature that should not be too low or too high and should be consistently stable . The quality of Taq polymerase is also very important . The reproducibility of the results under these conditions was very good. Antimicrob Agents Chemother, 1995 Apr, 39(4), 987 - 9 In vitro activity of a new fluoroquinolone, CP-99,219, against strains of Neisseria gonorrhoeae; Knapp JS et al.; The susceptibilities of 216 strains of Neisseria gonorrhoeae to a new fluoroquinolone, CP-99,219 were determined . For strains for which the MICs of ciprofloxacin were < or = 0.06 microgram/ml, the MICs at which 90% of the isolates are inhibited (MIC90s) of CP-99,219, ciprofloxacin, and ofloxacin were 0.008, 0.015, and 0.03 microgram/ml, respectively . For strains for which the MICs of ciprofloxacin were 0.125 to 0.5 microgram/ml, the MIC90s of CP-99,219, ciprofloxacin, and ofloxacin were 0.06, 0.25, and 0.5 microgram/ml, respectively . For strains for which the MICs of ciprofloxacin and ofloxacin were 2.0 micrograms/ml, the MIC of CP-99,219 was 0.25 microgram/ml. Antimicrob Agents Chemother, 1995 Apr, 39(4), 917 - 20 Trends in susceptibility of Neisseria gonorrhoeae to ceftriaxone from 1985 through 1991; Schwebke JR et al.; The antimicrobial susceptibilities of 16,441 gonococcal isolates from Seattle-King County were determined for ceftriaxone, cefoxitin, penicillin G, and tetracycline . From 1985 to 1989, ceftriaxone, in combination with doxycycline, was increasingly used for treatment of gonorrhea, and by 1989, it was used as therapy for > 80% of cases in Seattle-King County . MICs of ceftriaxone correlated significantly (P < 0.001) with those of the other beta-lactam antibodies included in this study . Geometric mean MICs of penicillin G for isolates that did not produce beta-lactamase increased from 1985 to 1991 . The geometric mean MICs of cefoxitin, ceftriaxone, and tetracycline began to decline in 1987 but increased in 1990 and 1991 . The percentage of strains with decreased susceptibility to ceftriaxone (MIC, 0.06 to 0.25 microgram/ml) rose from 0.3% in 1985 to 5.3% in 1987 but subsequently declined steadily to 2.6% in 1991, despite increased use of ceftriaxone as routine therapy for gonorrhea . Changes in patterns of antimicrobial susceptibility may be related not only to antimicrobial selection pressures but also to less well understood population shifts among Neisseria gonorrhoeae strains within a community. Hinyokika Kiyo, 1995 Apr, 41(4), 279 - 87 {Consecutive annual changes in minimum inhibitory concentration in clinically isolated Neisseria gonorrhoeae strains}; Takai K et al.; Between 1983 and 1991, 465 gonococcal strains isolated in the urological department of Japanese Red Cross Medical Center . The minimum inhibitory concentration (MIC) of these isolates to 22 kinds of antibiotics including penicillins (PC), cephems, tetracyclins (TC) and new quinolons (NQ) were determined and the annual difference of MIC was studied . The annual incidence of penicillinase producing neisseria gonorrhoeae (PPNG) of these 9 years were distributed in 3 to 17% and increasing tendency was not observed . As for Penicillin G, the MIC 90 of PPNG was seven fold higher than that of non-PPNG . No remarked difference was observed between MIC 90 of Cephems, TC and NQ of PPNG and non-PPNG . No annual difference was observed in MIC of PC, Cephems and SPCM . However the rising tendency of MIC was observed in NQ. Bol Oficina Sanit Panam, 1995 Apr, 118(4), 295 - 301 {Humoral immune response to the capsular polysaccharide of Neisseria meningitidis serogroup C in an antimeningococcal BC vaccination trial in Antioquia, Colombia}; Echeverry Uribe ML et al.; As a complement to studying humoral immune response to the proteins of an antimeningococcal vaccine (VA-MENGOC-BC) against serogroups B and C, the humoral immune response to polysaccharide C of the vaccine was also evaluated in 142 children from 1 to 5 years of age in an area of the Department of Antioquia, Colombia . Paired pre-(T0) and post-vaccination (T1) sera were tested for IgG response by means of ELISA and for serum lytic capacity against a strain of serogroup C by means of the bactericidal antibodies test (BAT) . Response to the vaccine was statistically significant (P < 0.01) by both techniques . PAB demonstrated seroconversion (T1/T0 > or = 4) in 88% (95% confidence interval, CI95%: 80% to 95%) of all those who were seronegative before vaccination . The proportion of seroconversion in children 2, 3, and 4 years of age was 86% or more . Of all the sera tested with ELISA, 93% (CI95%: 89% to 97%) showed response to the vaccine (T1/T0 > or = 2), and 98% (CI95%: 94% to 100%) of the subjects with T0 < or = 500 U/mL seroconverted . In this sample, the vaccine stimulated a specific and protective response as measured by ELISA and BAT, the latter test being utilized to evaluate protection status. FEMS Microbiol Lett, 1995 Apr 1, 127(3), 249 - 54 C-terminal glycine-histidine tagging of the outer membrane protein Iga beta of Neisseria gonorrhoeae; Strauss A et al.; A glycine-histidine tag (Gly3His6) was added to the C-terminus of a fusion protein consisting of the cholera toxin B-subunit (CtxB) and the IgA protease beta-domain (Iga beta) . The aim was to facilitate single-step purification and to create a suitable tool for kinetic and structural studies on Iga beta-driven protein translocation across the outer membrane of Gram-negative bacteria . We demonstrate that the glycine-histidine tag does not interfere with the assembly of Iga beta in the outer membrane and that the translocator function of the modified Iga beta is maintained . The applicability of the new construct for the dissection of the Iga beta mediated translocation process and general aspects of C-terminal histidine tagging of outer membrane proteins are discussed. FEMS Microbiol Lett, 1995 Apr 1, 127(3), 223 - 8 Identification and characterization of auxotrophs of Neisseria meningitidis produced by Tn916 mutagenesis; Erwin AL et al.; Fourteen Tn916 mutants of Neisseria meningitidis strain NMB were identified as auxotrophs . Among these were eight amino acid auxotrophs, with five different phenotypes, and three isolates restricted in carbon source utilization, growing in the presence of glucose but not on L-lactate, D-lactate, pyruvate, or casamino acids as principal carbon sources. Genitourin Med, 1995 Apr, 71(2), 126 - 8 A case cluster of possible tissue invasive gonorrhoea; Brook MG et al.; OBJECTIVE--To describe a cluster of patients presenting with severe symptoms and infected with an unusual strain of Neisseria gonorrhoeae . SETTING--A north London Department of Sexual Health . PATIENTS--Five patients were linked by reported sexual contact or other epidemiological evidence as part of a cluster of gonococcal infection . Cultured N gonorrhoea were subtyped by serological (serovar) and cultural (auxotype) methods and antibiotic sensitivities measured by minimum inhibitory concentration (MIC) . RESULTS--Four of the patients had severe gonorrhoea-related systemic or extragenital symptoms: disseminated gonococcal infection with oligoarthritis (1 patient), acute pelvic inflammatory disease (1 patient, who was also chlamydia positive) and tender inguinal adenopathy (2 patients) . The fifth patient was asymptomatic . N gonorrhoeae was isolated in four of the patients . All four organisms had identical MICs . Three of the organisms were subtyped and found to be the same rare strain (serovar 1A1, auxotype NR) . CONCLUSION--This case cluster provides evidence for strain-related virulence in an uncommon gonococcal subtype. J Bacteriol, 1995 Apr, 177(8), 2041 - 9 Cloning, sequencing, and characterization of the gene encoding FrpB, a major iron-regulated, outer membrane protein of Neisseria gonorrhoeae; Beucher M et al.; FrpB (for Fe-regulated protein B) is a 76-kDa outer membrane protein that is part of the iron regulon of Neisseria gonorrhoeae and Neisseria meningitidis . The frpB gene from gonococcal strain FA19 was cloned and sequenced . FrpB was homologous to several TonB-dependent outer membrane receptors of Escherichia coli as well as HemR of Yersinia enterocolitica and CopB of Moraxella catarrhalis . An omga insertion into the frpB coding sequence caused a 60% reduction in 55Fe uptake from heme, but careful analysis suggested that this effect was nonspecific . While FrpB was related to the family of TonB-dependent proteins, a function in iron uptake could not be documented. J Bacteriol, 1995 Apr, 177(8), 1952 - 8 A promoter associated with the neisserial repeat can be used to transcribe the uvrB gene from Neisseria gonorrhoeae; Black CG et al.; A recombinant plasmid capable of restoring UV resistance to an Escherichia coli uvrB mutant was isolated from a genomic library of Neisseria gonorrhoeae . Sequence analysis revealed an open reading frame whose deduced amino acid sequence displayed significant similarity to those of the UvrB proteins of E . coli, Micrococcus luteus, and Streptococcus pneumoniae . A gonococcal uvrB mutant was constructed and found to be extremely sensitive to UV radiation . Transcriptional fusions between portions of the gonococcal uvrB upstream region and a reporter gene were used to localize promoter activity, and the transcriptional start point of the gonococcal uvrB gene was mapped in E . coli by primer extension . A corresponding sigma 70 promoter was identified within a copy of the 26-bp neisserial repeat, and this identification provided the first evidence of a promoter associated with this repetitive element in N . gonorrhoeae. J Trop Med Hyg, 1995 Apr, 98(2), 95 - 100 Single-dose ampicillin/sulbactam versus ceftriaxone as treatment for uncomplicated gonorrhoea in a Ugandan STD clinic population with a high prevalence of PPNG infection; Hellmann NS et al.; During the period November 1989 to March 1991 a total of 330 patients (269 males and 61 females) with signs and symptoms of uncomplicated lower genital tract infections with Neisseria gonorrhoeae were treated at a sexually transmitted disease clinic in Kampala, Uganda . Patients were randomized for treatment with either intramuscular ampicillin/sulbactam (1 g ampicillin/0.5 g sulbactam), plus 1 g probenecid orally, or ceftriaxone (250 mg) . In those cases where N . gonorrhoeae was isolated and the patients returned for a follow-up visit, 70/74 (95%) of the patients treated with ampicillin/sulbactam and 71/72 (99%) of those treated with ceftriaxone had favourable clinical outcomes . All 24 patients with penicillinase-producing N . gonorrhoeae (PPNG) treated with ampicillin/sulbactam had a favourable clinical outcome compared with 95% (20/21) of those with PPNG treated with ceftriaxone . The infecting pathogen was eradicated in 65/71 (92%) of the evaluable patients treated with ampicillin/sulbactam and in 60/63 (95%) of the ceftriaxone group . Both drug regimens were well tolerated and there were no reports of adverse drug effects . In summary, in a predominantly male group of clinic patients in Kampala, Uganda, ampicillin/sulbactam was as safe and effective as ceftriaxone in treating uncomplicated gonococcal infections of the lower genital tract caused by either PPNG or non-PPNG strains. Gastroenterol Clin Biol, 1995 Apr, 19(4), 346 - 9 {Risk of transmission of hepatitis C virus by digestive endoscopy}; Rey JF et al.; OBJECTIVE--In 30 to 50% of cases, the route of transmission of virus C remains unknown . The aim of this study was to investigate the effectiveness of manual cleaning and disinfection procedures after endoscopic examinations in highly infected patients . METHODS--In 39 patients with chronic hepatitis C and a high level of replication, a gastroscopy with biopsy was performed with a fully submersible endoscope . Cleaning and disinfection were carried out with the following protocol: cleaning with detergent solution (Sekulyse), rinsing, 3 to 5 min immersion into a glutaraldehyde disinfectant solution (Sekucid) and final rinsing . One hundred mL of sterile water was flushed through the biopsy channel immediately after removal of the endoscope (T1), after cleaning (T2), and after final disinfection (T3) . These 100 mL were collected in aliquots for viral and bacterial screening . Virus C particles were searched for in the effluent of the biopsy channel using two methods of polymerase chain reaction . RESULTS--Virus C particles were found in 2 of 39 patients in T1 aliquots collected before washing . Routine cleaning with a detergent eliminated all viral particles, as tests were negative at T2 and T3 . The usual bacteria (Pseudomonas, Streptococcus, Neisseria...) were detected at T1 and had disappeared after total disinfection at T3 . CONCLUSION--Virus C hepatitis could be transmitted during endoscopic examination, but cleaning and disinfection procedures effectively eliminated all viral particles. Patol Fiziol Eksp Ter, 1995 Apr-Jun, (2), 3 - 6 {Specificity of the action of anti-cholinoceptor antibodies}; Burlakov GV; The effect of different anti-cholinoceptive (Ach) antibodies (5 types) on the contractile effect of intestinal smooth muscles under the action of acetylcholine (A) and histamine (H) was examined in experiments on the isolated small bowel sections . Ach-antibodies were demonstrated to have virtually no influence on the effect of the tested dosage of A and H on the intestinal smooth muscles of intact guinea-pigs . Animal sensitization with egg albumin, timophy (Phleum sp.) pollen allergen and Neisseria perflava antigen made Ach-antibodies substantially alter the sensitivity of the isolated small bowel sections to the tested dosages of A and H . The Ach-antibodies under study were also shown to be able to drastically reduce the extent of anaphylactic contractures of the intestine under the influence of challenge doses of a specific allergen . The specificity of the action of ASch-antibodies, the relationship of choline and histamine receptors, and the involvement of Ach-antibodies in allergic reactions are discussed in the paper. Proteins, 1995 Apr, 21(4), 303 - 6 A lipoamide dehydrogenase from Neisseria meningitidis has a lipoyl domain; Bringas R et al.; A protein of molecular weight of 64 kDa (p64k) found in the outer membrane of Neisseria meningitidis shows a high degree of homology with both the lipoyl domain of the acetyltransferase and the entire sequence of the lipoamide dehydrogenase, the E2 and E3 components of the dehydrogenase multienzyme complexes, respectively . The alignment of the p64k with lipoyl domains and lipoamide dehydrogenases from different species is presented . The possible implications of this protein in binding protein-dependent transport are discussed . This is the first lipoamide dehydrogenase reported to have a lipoyl domain. Pathol Biol (Paris), 1995 Apr, 43(4), 281 - 3 {Comparative activity of azithromycin against 100 strains of Neisseria gonorrhoeae}; Chevalier B et al.; Azithromycin is a new semisynthetic, acid stable C15 macrolid . In our study, we compared in vitro activity of azithromycin with 6 other antibiotics usually recommended for treatment of N . gonorrhoeae infections: erythromycin, ampicillin, amoxicillin, ceftriaxone, spectinomycin, ciprofloxacin . 100 strains have been selected: 95 clinical strains with different resistance patterns: 60 susceptible to beta-lactams, 25 PPNG, 10 chromosomal decreased susceptibility to beta-lactams . Among these strains, 13 had a decreased susceptibility to erythromycin (MIC: 2 and 4 mg/l) and 5 WHO reference strains: A: spectinomycin resistance, B: wild phenotype, C: chromosomal decreased susceptibility to penicillin and tetracycline, D: chromosomal resistance to penicillin and erythromycin+chromosomal decreased susceptibility to chloramphenicol, E: beta-lactamase producing strain (PPNG) and decreased susceptibility to tetracycline . MICs have been determined by GC agar dilution method . Azithromycin is more active than erythromycin on all N . gonorrhoeae patterns with a two log 10 difference for MIC50 and MIC90 (p < 0.0001) . Because of pharmacokinetic properties and activity against Chlamydia trachomatis and urogenital mycoplasms often associated with N . gonorrhoeae, azithromycin is a good alternative for the treatment of genital infections. Microbiology, 1995 Apr, 141 ( Pt 4), 913 - 20 Effect of sialylation of lipopolysaccharide of Neisseria gonorrhoeae on recognition and complement-mediated killing by monoclonal antibodies directed against different outer-membrane antigens; de la Paz H et al.; Growth of gonococci in the presence of CMP-N-acetylneuraminic acid (CMP-NANA) has previously been shown to induce resistance to the bactericidal effect of normal human serum and is accompanied by sialylation of the gonococcal lipopolysaccharide (LPS) . We have used monoclonal antibodies (mAbs) to compare the effect of LPS sialylation on recognition of gonococci and complement-mediated killing by antibodies directed either against LPS or against defined epitopes on outer-membrane protein PI . Despite differences in binding to sialylated LPS on Western blots, all three mAbs directed against LPS showed considerably reduced binding to gonococci grown in the presence of CMP-NANA and a concomitant reduction in ability to promote complement-mediated killing . In contrast, mAbs directed against previously defined epitopes on a surface exposed loop of PI showed little difference in binding between sialylated and non-sialylated gonococci and promoted killing of the sialylated gonococci . Similarly a mAb directed against an epitope on a loop of the outer-membrane Rmp protein, which had previously been shown to block killing by antibodies directed against other surface antigens, also exerted a blocking effect with sialylated gonococci . Thus in the present study the continued biological effect of mAbs was correlated with the ability of the antibody to recognize surface-exposed epitopes on sialylated gonococci . Despite the presence of the sialylation which is likely to occur in vivo, it should be possible to induce complement-mediated killing by focusing the immune response to those surface-exposed epitopes which are least susceptible to the potential inhibitory effect of LPS sialylation. Commun Dis Rep CDR Rev, 1995 Mar 31, 5(4), R56 - 7 Brucella melitensis: an unexpected isolate from cerebrospinal fluid; Wheat PF et al.; A specimen of cerebrospinal fluid was initially handled with 'category 3' precautions because the patient came from Somalia, where tuberculosis and HIV infection are endemic . An isolate from the specimen, initially thought to be a Neisseria species, was subsequently handled on the open bench . It was later identified as Brucella melitensis . Laboratory procedures should allow for the possibility of brucella in such specimens until a positive identification has been made. Gene, 1995 Mar 21, 155(1), 101 - 6 Shuttle mutagenesis: a mini-transposon for producing PhoA fusions with exported proteins in Neisseria gonorrhoeae; Boyle-Vavra S et al.; Shuttle mutagenesis is a method for producing stable mini-transposon (mTn) insertions into the genome of Neisseria gonorrhoeae (gonococcus, Gc) and other microbes . Using an mTn3 derivative, we have produced an mTn (mTnCmPhoA) which contains a phoA' gene lacking its N-terminal signal sequence useful for isolating genes which encode exported proteins . mTnCmPhoA was characterized in Gc and Escherichia coli using a cloned target containing the Gc genes, opaE1, pilA and pilB . PhoA+ Gc containing pilB::mTnCmPhoA insertions confirm that PilB is an exported protein in Gc . This system will be useful for isolating and characterizing extracytoplasmic virulence factors from Gc and other bacterial pathogens. N Engl J Med, 1995 Mar 2, 332(9), 562 - 6 A controlled trial of povidone-iodine as prophylaxis against ophthalmia neonatorum; Isenberg SJ et al.; BACKGROUND . Neonatal conjunctivitis (ophthalmia neonatorum) continues to cause blindness because the agents used prophylactically to prevent this condition are not completely effective and are not widely available in many parts of the world . Povidone-iodine ophthalmic solution is an effective antibacterial agent with broad antibacterial and antiviral activity to which no bacteria are known to be resistant, and it is far less expensive and less toxic than the agents currently used to prevent neonatal conjunctivitis . METHODS . We conducted a masked, prospective trial involving 3117 infants born over a period of 30 months in a hospital in Kenya . Shortly after birth each infant received a 2.5 percent solution of povidone-iodine (n = 1076), a 1 percent solution of silver nitrate (n = 929), or 0.5 percent erythromycin ointment (n = 1112) in both eyes . Randomization was achieved by rotating the three medications after each was used for a week . RESULTS . Of the neonates treated with povidone-iodine, 13.1 percent had infectious conjunctivitis, as compared with 17.5 percent of those treated with silver nitrate (P < 0.001) and 15.2 percent of those treated with erythromycin (P = 0.01) . Povidone-iodine was more effective against Chlamydia trachomatis than was silver nitrate (P < 0.001) or erythromycin (P = 0.008) . There were 104 cases of noninfectious conjunctivitis (9.7 percent) in the povidone-iodine group, as compared with 129 in the silver nitrate group (13.9 percent, P < 0.001) and 148 in the erythromycin group (13.3 percent, P = 0.004) . Many cases of noninfectious conjunctivitis were probably due to a toxic reaction to the treatment itself . The incidence of Neisseria gonorrhoeae and Staphylococcus aureus infections was similar in the three groups . CONCLUSIONS . A 2.5 percent ophthalmic solution of povidone-iodine as prophylaxis against ophthalmia neonatorum is more effective than treatment with silver nitrate or erythromycin, and it is less toxic and costs less. Am J Obstet Gynecol, 1995 Mar, 172(3), 919 - 25 The impact of human immunodeficiency virus infection on pelvic inflammatory disease: a case-control study in Abidjan, Ivory Coast; Kamenga MC et al.; OBJECTIVE: Our purpose was to assess the impact of human immunodeficiency virus infection on pelvic inflammatory disease . STUDY DESIGN: A case-control study was performed in Abidjan, Ivory Coast, women with pelvic inflammatory disease, 57 seropositive and 113 seronegative for the human immunodeficiency virus . Women underwent an interview, physical examination, pelvic ultrasonography, and laboratory testing . RESULTS: Seropositive women more often had an oral temperature > or = 38 degrees C (odds ratio 2.5, confidence interval 1.0 to 6.4), a genital ulcer (odds ratio 7.8, confidence interval 1.8 to 45.4), and a tuboovarian mass on ultrasonography (odds ratio 2.6, confidence interval 1.1 to 6.4) and were more likely to require surgery (odds ratio 6.5, confidence interval 1.1 to 67.5) and hospitalization (odds ratio 3.5, confidence interval 0.9 to 14.3) . The mean clinical severity score was significantly higher among seropositive than among seronegative patients (17.4 vs 15.4 p = 0.01) . Gonorrhea was detected in 50 (29.4%) and chlamydia in 16 (9.4%) of the 170 patients, and neither infection was significantly correlated with human immunodeficiency virus infection . After therapy similar proportions of seropositive and seronegative patients (95% and 93%) reported symptomatic improvement within 4 days, and none had persistent fever at day 4 or 14 of follow-up . CONCLUSIONS: Human immunodeficiency virus infection was associated with more severe clinical manifestations of pelvic inflammatory disease but did not affect microbial cause or response to therapyPIP: During October 1992 to July 1993 in Abidjan, Ivory Coast, health workers conducted interviews, physical examinations, pelvic ultrasonography, and laboratory testing with 170 women with pelvic inflammatory disease (PID) at the University Hospital of Treichville and four primary care clinics . They compared clinical and microbiological characteristics and the response to PID therapy in 57 HIV seropositive women (cases) and in 113 HIV seronegative women (controls) . Cases were more likely than controls to have a temperature of at least 38 degrees Celsius (odds ratio {OR} = 2.5), a genital ulcer (OR = 7.8), and a tuboovarian mass on ultrasonography (OR = 2.6) and to need surgery (OR = 6.5) and hospitalization (OR = 3.5) . They also had a higher clinical severity score than did the controls (17.4 vs . 15.4; p = 0.01) . Cases with a lower CD4 count (14%) were significantly more likely than cases with a higher CD4 count to have a temperature of at least 38 degrees Celsius (56% vs . 13-19%; p = 0.03) and dysuria (78% vs . 33-41%; p = 0.05) . They also tended to have a genital ulcer and a tuboovarian mass, but not significantly so . Among all 170 women, the most common pathogenic organisms responsible for PID were Neisseria gonorrhoeae (29.4%) and Chlamydia trachomatis (9.4%) . Neither infection was significantly related to HIV infection . Yet, the cause of PID in cases with the highest CD4 count was less likely to be N . gonorrhea than that of cases with lower CD4 counts (13% vs . 44%; p = 0.07) . Among the 162 women who received oral antibiotics, 95% of the 40 cases and 93% of the controls responded to antibiotic therapy within four days . On days 4 and 14, none of these women still had a fever . These findings suggest that HIV infection affected clinical manifestations of PID but did not affect the cause of PID or response to therapy . J Bacteriol, 1995 Mar, 177(5), 1299 - 306 Identification of an iron-regulated outer membrane protein of Neisseria meningitidis involved in the utilization of hemoglobin complexed to haptoglobin; Lewis LA et al.; Hemoglobin complexed to the plasma protein haptoglobin can be used by Neisseria meningitidis as a source of iron to support growth in vitro . An N meningitidis mutant, DNM2E4, was generated by insertion of the mini-Tn3erm transposon into the gene coding for an 85-kDa iron-regulated outer membrane protein . Membrane proteins prepared from DNM2E4 were identical to those of the wild-type strain except that the 85-kDa protein was not produced . This mutant was unable to use hemoglobin-haptoglobin complexes as an iron source to support growth and was also impaired in the utilization of free hemoglobin . The mutant failed to bind free hemoglobin,