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PubMed1993

Treatment of bacterial sexually transmitted diseases.

Sexually transmitted diseases (STD) cause significant morbidity in the industrialized nations and, even more so in third world countries. Genital ulcerative STD such as herpes genitalis, syphilis, and chancroid have been identified as important risk factors for the spread of human immunodeficiency virus infection. Efficient and safe therapeutic regimen are therefore essential to cure the individual and to prevent spread of STD in the community. In this review, the current treatment guidelines for the bacterial STD gonorrhoea, chlamydial infections, syphilis, and chancroid are summarized and recent therapeutic developments are discussed.

Anti-Bacterial Agents↗
PubMed1995

Simple algorithms for the management of genital ulcers: evaluation in a primary health care centre in Kigali, Rwanda.

A cross-sectional study was conducted among 395 patients presenting with genital ulcers at a primary health care centre in Kigali, Rwanda. Using clinical data and the results of a rapid plasma reagin (RPR) test, we simulated the diagnostic outcome of two simple WHO flowcharts for the management of genital ulcers. These outcomes and a clinical diagnosis were then compared with the laboratory diagnosis based on culture for genital herpes and Haemophilus ducreyi and serology for syphilis. The prevalence of HIV infection was high (73%) but there was no difference between HIV-positive and HIV-negative patients in the clinical presentation and etiology of genital ulcer disease. The proportion of correctly managed chancroid and/or syphilis cases was 99% using a syndromic approach, 82.1% using a hierarchical algorithm including an RPR test, and 38.3% with a clinical diagnosis. In situations where no laboratory support is available, a simple syndromic approach is preferable to the clinical approach for the management of genital ulcer. If an RPR test can be included in the diagnostic strategy, patients with a reactive RPR test should be treated for both syphilis and chancroid infection.

Algorithms↗
PubMed1994

A socioeconomic, clinical and serological study in an African city of prostitutes and women still married to their first husband.

The aim of this paper was to compare women involved in prostitution with a group of women still married to their first husband and reporting having had only one sexual partner, in order to ascertain what factors if any contributed to women going into prostitution or staying still married to their first husband, their only sexual partner, and thereafter to compare clinical and serological aspects of the gynaecological conditions of the women in these two groups. The role of prostitutes in transmission of sexually transmitted diseases (STD) is widely recognised. Socioeconomic factors determining whether a woman will drift into prostitution or have a stable first marriage are largely unknown as are prevalence rates of STD, pelvic inflammatory disease (PID) and cervical cancer in these women. A socioeconomic, clinical and serologic study is reported for 2111 Ethiopian women attending teaching hospitals and maternal and child health clinics in Addis Ababa, analysing basic demographic data of three groups of women: (i) 278 engaged in prostitution, (ii) 730 still married to their one and only sexual partner, and (iii) 1103 single, widowed, divorced or married to their second or subsequent partner. Thereafter groups (i) and (ii) were compared and contrasted with regard to further socioeconomic, clinical and serological associations. The most significant socioeconomic associations for women in prostitution were low income (95% had < 50 Ethiopian birr [< U.S. $25] per month), ethnic group, and the timing of first coitus in relation to the menarche (81% were first married by age 15), in that order. Women still married to their first sexual partner had higher income, higher age at first marriage and longer duration of marriage. Sero-prevalence rates of STD in prostitutes were high: gonorrhoea 88%, genital chlamydiae 78%, syphilis (TPHA) 62%, HSV2 and HBV 46%, and chancroid 19%: 67% had PID and 2.9% cervical cancer. In comparison, rates for women married to their first and only sexual partner were: gonorrhoea 40%, genital chlamydiae 54%, syphilis (TPHA) 19%, HSV2 33%, HBV 35%, chancroid 13%, PID 47% and cervical cancer 1%. While the very high prevalence of STD in women involved in prostitution is not so unexpected, the high rate of STD in women still married to their first and only sexual partner is indicative of male promiscuity. Control of prostitution and diseases spread by it, together with education of both men and women is a national priority.

Adolescent↗
PubMedDate not supplied

Results of treatment with quinolones of sexually transmitted diseases in the Far East: a brief summary.

The emergence of penicillinase-producing Neisseria gonorrhoeae (PPNG) strains in 1976 and the increasing frequency of chromosomally mediated resistance to penicillin has resulted in a decline in the effectiveness of penicillin for the treatment of gonorrhea. In Hong Kong, the emergence of bacterial resistance to kanamycin or tetracycline has also been observed. Quinolones were first introduced in Hong Kong in 1985, and since then the percentage of PPNG-related cases of gonorrhea has dropped dramatically. The use of quinolones for the treatment of nongonococcal urethritis has not been as successful as that for gonorrhea. Haemophilus ducreyi (the causative organism of chancroid) is sensitive to quinolones, and the occurrence of chancroid since 1985 has decreased from 628 to (in 1987) 184.

4-Quinolones↗
PubMed1997

Prospective analysis of genital ulcer disease in Brooklyn, New York.

We prospectively studied 82 men and women with first episodes of genital ulceration. By using newer diagnostic techniques, a definite microbial etiology of 84 infections in 65 of the 82 patients evaluated was found. There were 33 cases of definite primary syphilis, 27 of definite chancroid, and 24 of definite genital herpes simplex. Conclusive evidence of more than one microbial etiology was found for 19 (23%) of the patients. Simultaneous primary syphilis and chancroid was the third most common ulcer infection. This finding underscores the need for both clinical suspicion of multiple infections in patients with genital ulcers and comprehensive testing for all suspicious etiologies.

Adolescent↗
PubMed1988

Genital ulceration as a risk factor for human immunodeficiency virus infection.

Among 115 heterosexual men who presented with genital ulcers to a sexually transmitted disease clinic in Nairobi, Kenya, the prevalence of serum antibody to HIV was 16.5%. A past history of genital ulcers was reported by 12 (63%) of 19 men with antibody to HIV versus 30 (31%) of 96 without antibody (P = 0.008). HIV infection was also positively associated with lack of circumcision, but was not associated with the etiology of the current genital ulcer. Logistic regression analysis (adjusted for age, number of recent sex partners, recent prostitute contact, circumcision, tribal ethnic identity, past history of urethritis, and current diagnoses) confirmed only the association between prior history of genital ulcer disease and HIV infection; (P = 0.04, odds ratio 2.35, 95% confidence limits, 1.01-5.47). The incidence of genital ulcers, particularly chancroid, is much higher in parts of Africa than in Europe or North America. This may contribute to the increased risk of heterosexual transmission of HIV in Africa. Aggressive control of chancroid and syphilis may offer one very feasible approach to reducing transmission of HIV in this region.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Laboratory diagnosis of sexually transmitted diseases in facilities within the United States. Results of a national survey.

BACKGROUND AND OBJECTIVES: The diagnosis of many sexually transmitted diseases (STD) requires laboratory testing. The authors assessed the effects of the introduction of new tests and regulations on STD testing. STUDY DESIGN: A questionnaire survey was mailed to a random sample of facilities listed in the STD Referral Database inquiring about tests offered, changes in testing, and reasons for changes. RESULTS: Responses from 405 facilities were analyzed. Most responding facilities collected specimens for nontreponemal tests for syphilis (352 of 405 [86.9%]). Since each facility's information was last updated, the number reporting testing for Chlamydia trachomatis rose from 160 of 405 (39.5%) to 288 of 405 (71.1%), but testing for gonorrhea and chancroid decreased (365 of 405 [90.1%] to 328 of 405 [81%], and 182 of 405 [44.9%] to 32 of 405 [7.9%], respectively). Of 364 responses to a question on changes in tests performed in the last 2 years, 249 (68.4%) reported no change, 81 (22.3%) reported an increase, and 37 (10.2%) reported a decrease. The most frequently added tests were nonculture tests for C. trachomatis (34 of 81 [42%]) and the most frequent reason for adding tests was targeted funding (25 of 81 [30.9%]). The most frequently discontinued tests were cultures and gram stains for gonorrhea (15 of 37 [40.5%]) and other in-house tests (9 of 37 [24.3%]). Most facilities that discontinued testing cited the Clinical Laboratory Improvement Act as the reason (34 of 37 [91.9%]; 95% confidence interval = 78.1%, 98.3%). CONCLUSIONS: The number of facilities testing for C. trachomatis has increased with funding and with the availability of nonculture tests, but the number of those testing for chancroid and gonorrhea has decreased. Implementation of the Clinical Laboratory Improvement Act may be associated with a decrease in the number of facilities performing tests for STD.

Clinical Laboratory Techniques↗
PubMed2006

Empirical observations underestimate the proportion of human immunodeficiency virus infections attributable to sexually transmitted diseases in the Mwanza and Rakai sexually transmitted disease treatment trials: Simulation results.

BACKGROUND AND OBJECTIVES: Population attributable fractions (PAF) from observational studies may under- or overestimate the contribution of cofactor sexually transmitted disease (STD) to human immunodeficiency virus (HIV) spread. Empirical PAF estimates from the Mwanza and Rakai trials indicated the proportion of HIV infections attributable to STDs was higher in Mwanza than Rakai. GOAL OF THIS STUDY: Estimate the "true" proportion (PAFM) of HIV infections attributable to STDs in the Mwanza and Rakai STD trial populations and explore how the evaluated interventions prevented HIV infections. STUDY DESIGN: The STDSIM model was used to simulate the 2 populations at the baseline of the trials (with no STD treatment interventions) and counterfactual scenarios in which STD cofactor effects on HIV spread were removed either at the start of the trials or 2, 10, and 20 years into the HIV epidemics. Similar methods were used to quantify the contribution of the cure of each STD to overall HIV impact in each site. RESULTS: : In Mwanza, the highest PAFM for the effect of any single STD over the 2 years of the trial was due to chancroid (40%). The PAFM for all curable STD was 65%. In Rakai, herpes simplex virus type 2 (HSV-2) was the most important STD (PAFM = 23%); the PAFM for curable STD was 20%. In both sites, the proportion of new infections due to treatable STD decreased over time. The decrease was greater for Rakai, where a behavioral risk reduction that preceded the trial reduced STD prevalence. In both sites, the importance of HSV-2 increased later in the HIV epidemics and STD increased transmission of HIV more than acquisition of HIV. In the Mwanza trial, treatment of chancroid contributed most to preventing new HIV infections. CONCLUSIONS: PAFs calculated from empirical data underestimated the contribution of STD to HIV spread in the Mwanza and Rakai trial populations because STD effects on HIV transmission (as opposed to acquisition) were not captured in the observationally based studies.

Computer Simulation↗
PubMed1992

Identification of highly conserved and species-specific polypeptides of Haemophilus ducreyi.

Chancroid is a sexually transmitted diseased caused by Haemophilus ducreyi. The pathological manifestations of chancroid are unique among Haemophilus species and the virulence factors of H. ducreyi that account for these features have not been identified. Some of these virulence factors may be unique components of H. ducreyi, but attempts to identify H. ducreyi-specific components have been unsuccessful. Four polypeptides--A, B, C and D of 83, 77, 56 and 28 kDa, respectively--were identified with a panel of nine H. ducreyi-specific monoclonal antibodies (MAbs). Polypeptide C was one of the five major proteins in H. ducreyi and demonstrated micro-heterogeneity in SDS-PAGE. Polypeptides A, B and D were present in only small amounts in whole-cell lysates of H. ducreyi. The relative amounts of A and B varied, suggesting that they may be precursor molecules. The unique polypeptides C and D were not exposed on the surface. Polypeptide C was highly soluble and did not appear to be membrane-bound, whereas polypeptide D appeared to partition with the cytoplasmic membrane and was soluble in Sarkosyl. All four polypeptides appeared to be unique to H. ducreyi since MAbs directed against them did not cross-react with H. influenzae, H. parainfluenzae or Neisseria gonorrhoeae. The mol. wts of all of these polypeptides were conserved throughout 35 clinical isolates collected from 15 cities in eight countries and one reference strain of H. ducreyi that were tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1998

Haemophilus ducreyi is susceptible to protegrin.

Protegrins, potent antimicrobial peptides found in porcine leukocytes, have activity against the sexually transmitted pathogens Neisseria gonorrhoeae, Chlamydia trachomatis, and human immunodeficiency virus type 1. We tested synthetic protegrin 1 (PG-1) for activity against nine isolates of Haemophilus ducreyi, the etiologic agent of chancroid. The test organisms included CIP 542 (the type strain), 35000HP (a human-passaged variant of 35000), 35000HP-RSM2 (an isogenic D-glycero-D-manno-heptosyltransferase mutant of 35000HP), and six clinical isolates. The isolates were epidemiologically unrelated, represented three HindIII ribotypes, and had varying antimicrobial resistance patterns. In bactericidal assays, five isolates were rapidly killed by synthetic PG-1. In radial diffusion assays, all nine isolates were exquisitely sensitive to PG-1. These data highlight the potential of protegrins for development as topical agents to prevent many sexually transmitted diseases, including chancroid.

Anti-Bacterial Agents↗
PubMed1994

Use of pyocin to select a Haemophilus ducreyi variant defective in lipooligosaccharide biosynthesis.

Haemophilus ducreyi, a cause of genital ulcer disease in developing countries, appears to facilitate the heterosexual transmission of the human immunodeficiency virus in Africa. Despite an increase in studies of this gram-negative human pathogen, little is known about the pathogenesis of chancroid. Our studies have shown that the lipooligosaccharides (LOS) of H. ducreyi may play an important role in ulcer formation. Monoclonal antibody and mass spectrometric analyses identified a terminal trisaccharide present on H. ducreyi LOS that is immunochemically similar to human paragloboside. This epitope is present on the LOS of Neisseria gonorrhoeae, and it may be the site of attachment for pyocin lysis. We have used pyocin, produced by Pseudomonas aeruginosa, to select LOS variants with sequential saccharide deletions from N. gonorrhoeae. On the basis of the similarities between N. gonorrhoeae and H. ducreyi LOS, we employed the same technique to determine if H. ducreyi strains were susceptible to pyocin lysis. In this study, we report the generation of a pyocin N-resistant H. ducreyi strain which synthesizes a truncated version of the parental LOS. Further studies have shown that this H. ducreyi variant has lost the terminal LOS epitope defined by monoclonal antibody 3F11. This report demonstrates that H. ducreyi is sensitive to pyocins and that this technique can be used to generate H. ducreyi LOS variants. Such variants could be used in comparative studies to relate LOS structure to biologic function in the pathogenesis of chancroid.

Carbohydrate Sequence↗
PubMed1996

Characterization of a novel lipoprotein expressed by Haemophilus ducreyi.

Pooled sera from patients with chancroid contain antibodies to a Haemophilus ducreyi antigen with an approximate molecular weight of 28,000 (28K). Rabbit polyclonal serum that reacts to a 28K protein can be used to detect H. ducreyi in clinical samples. A monoclonal antibody, designated 5C9, bound to a 28K outer membrane protein and to 35 of 35 H. ducreyi isolates with diverse geographic origins and did not bind to many species of the families Pasteurellaceae, Neisseriaceae, and Enterobacteriaceae or to Corynebacterium and Candida species strains. A 5C9-reactive phage was recovered from a genomic library, and the gene encoding the 28K protein was localized to a 626-bp open reading frame, designated hlp, for H. ducreyi lipoprotein. Translation of hlp predicted a 23K polypeptide that contained a lipoprotein processing site. Escherichia coli transformed with a plasmid containing hlp expressed a novel, membrane-associated protein that could be labeled with [3H]palmitic acid. In H. ducreyi, processing of Hlp was inhibited by globomycin. Database searches found no homologies to hlp or to the predicted Hlp amino acid sequence. Restriction enzyme analysis indicated that hlp was conserved among H. ducreyi isolates. Serum samples from patients with chancroid and other genital ulcer diseases and from normal subjects contained antibodies that bound to purified, recombinant Hlp. Although monoclonal antibody 5C9 recognizes a species-specific epitope of a unique H. ducreyi lipoprotein, the presence of serum antibodies to Hlp may not indicate previous infection with H. ducreyi.

Amino Acid Sequence↗
PubMed2002

The cytolethal distending toxin of Haemophilus ducreyi inhibits endothelial cell proliferation.

Haemophilus ducreyi, the etiologic agent of the sexually transmitted disease chancroid, produces a cytolethal distending toxin (HdCDT) that inhibits mammalian cell proliferation. We investigated the effects of HdCDT on normal human endothelial cells and on tubule formation in an in vitro model of angiogenesis. Endothelial cells were arrested in the G2 phase of the cell cycle, and tubule formation was inhibited in a dose-dependent manner. The antiproliferative activities of HdCDT on endothelial cells might contribute to the characteristic slow healing and persistence of chancroid ulcers.

Adult↗
PubMed2002

Haemophilus ducreyi requires the flp gene cluster for microcolony formation in vitro.

Haemophilus ducreyi, the etiologic agent of chancroid, has been shown to form microcolonies when cultured in the presence of human foreskin fibroblasts. We identified a 15-gene cluster in H. ducreyi that encoded predicted protein products with significant homology to those encoded by the tad (for tight adhesion) locus in Actinobacillus actinomycetemcomitans that is involved in the production of fimbriae by this periodontal pathogen. The first three open reading frames in this H. ducreyi gene cluster encoded predicted proteins with a high degree of identity to the Flp (fimbria-like protein) encoded by the first open reading frame of the tad locus; this 15-gene cluster in H. ducreyi was designated flp. RT-PCR analysis indicated that the H. ducreyi flp gene cluster was likely to be a polycistronic operon. Mutations within the flp gene cluster resulted in an inability to form microcolonies in the presence of human foreskin fibroblasts. In addition, the same mutants were defective in the ability to attach to both plastic and human foreskin fibroblasts in vitro. An H. ducreyi mutant with an inactivated tadA gene exhibited a small decrease in virulence in the temperature-dependent rabbit model for experimental chancroid, whereas another H. ducreyi mutant with inactivated flp-1 and flp-2 genes was as virulent as the wild-type parent strain. These results indicate that the flp gene cluster is essential for microcolony formation by H. ducreyi, whereas this phenotypic trait is not linked to the virulence potential of the pathogen, at least in this animal model of infection.

Amino Acid Sequence↗
PubMed2003

Mutations in the lspA1 and lspA2 genes of Haemophilus ducreyi affect the virulence of this pathogen in an animal model system.

Haemophilus ducreyi 35000HP contains two genes, lspA1 and lspA2, whose predicted protein products have molecular weights of 456,000 and 543,000, respectively (C. K. Ward, S. R. Lumbley, J. L. Latimer, L. D. Cope, and E. J. Hansen, J. Bacteriol. 180:6013-6022, 1998). We have constructed three H. ducreyi 35000HP mutants containing antibiotic resistance cartridges in one or both of the lspA1 and lspA2 open reading frames. Western blot analysis using LspA1- and LspA2-specific monoclonal antibodies indicated that the wild-type parent strain 35000HP expressed LspA1 protein that was readily detectable in culture supernatant fluid together with a barely detectable amount of LspA2 protein. The lspA2 mutant 35000HP.2 expressed LspA1 protein that was detectable in culture supernatant fluid and no LspA2 protein. In contrast, the H. ducreyi lspA1 mutant 35000HP.1, which did not express the LspA1 protein, expressed a greater quantity of the LspA2 protein than did the wild-type parent strain. The lspA1 lspA2 double mutant 35000HP.12 expressed neither LspA1 nor LspA2. The three mutant strains adhered to human foreskin fibroblasts and to a human keratinocyte cell line in vitro at a level that was not significantly different from that of the wild-type strain 35000HP. Lack of expression of the LspA1 protein by both the lspA1 mutant and the lspA1 lspA2 double mutant was associated with an increased tendency to autoagglutinate. When evaluated in the temperature-dependent rabbit model for chancroid, the lspA1 lspA2 double mutant was substantially less virulent than the wild-type strain 35000HP. The results of these studies indicated that H. ducreyi requires both the LspA1 and LspA2 proteins to be fully virulent in this animal model for experimental chancroid.

Agglutination↗
PubMed1993

Antigen detection and immunological typing of Haemophilus ducreyi with a specific rabbit polyclonal serum.

A rabbit polyclonal serum was raised against the 29-kDa species-specific marker, as well as the 30- to 34-kDa immunotype-specific markers of Haemophilus ducreyi described elsewhere (E. Roggen, S. De Breucker, E. Van Dyck, and P. Piot, Infect. Immun. 60:590-595, 1992). These antigens were purified from a cocktail of H. ducreyi isolates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The immune serum reacted in enzyme-linked immunosorbent assay (ELISA) preferentially with H. ducreyi, at a titer as high as 50,000. To make it specific to H. ducreyi, nonspecific antibodies were removed by adsorption on a mixture of Haemophilus spp., Escherichia coli, Candida albicans, and Corynebacterium spp. In the 29- to 34-kDa region of immunoblot profiles from H. ducreyi isolates (n = 450), the adsorbed serum revealed essentially the same antigens as did a pool of well-characterized human sera. Yet, eight different immunotypes were observed. With this rabbit polyclonal serum, an ELISA-based antigen detection test was developed. The adsorbed serum reacted specifically with all H. ducreyi isolates tested (n = 450), but not with other bacterial species (n = 15). This test was evaluated with a limited number of clinical specimens from African patients with culture-proven chancroid and no evidence for any other ulcerating etiology (n = 10) and a number of chancroid-negative control patients from Belgium (n = 20). Within this context, the test yielded a sensitivity and specificity of 100%.

Animals↗
PubMed1996

Ribosomal DNA typing of Haemophilus ducreyi strains: proposal for a novel typing scheme.

Local strains of Haemophilus ducreyi were characterized by ribosomal DNA fingerprinting in order to develop a typing scheme for this organism. Chromosomal DNAs from 30 strains were extracted, and restriction fragments were separated by agarose gel electrophoresis after cleavage with BglII, HindIII, HindII, and BstEII. Of the 30 local strains studied, nine BglII, eight HindIII, six HindII, and five BstEII ribotype patterns were observed. In order to develop a typing scheme, we correlated the ribotype patterns obtained with each of the four enzymes for each strain. By this scheme, 13 ribotypes designated b to n were defined among the local strains. This study demonstrates that there is a diversity of ribotypes among H. ducreyi strains in our area, which emphasizes that there are many strains responsible for chancroid. This novel typing scheme provides a useful tool for further epidemiological studies of chancroid.

Bacterial Typing Techniques↗
PubMed2006

Molecular characterization of Haemophilus ducreyi isolates from different geographical locations.

The technique of random amplified polymorphic DNA (RAPD) was adapted and optimized to study Haemophilus ducreyi isolates. A panel of 43 strains isolated from chancroid patients from different countries in Africa, Europe, North America, and Asia were characterized. The strains were also studied with respect to lipooligosaccharide (LOS) migration and immunoblotting patterns and the presence of cytolethal distending toxin genes. The RAPD method with the OPJ20 primer generated nine banding patterns (1 to 9). The majority of the isolates were clustered into two major profiles, 14 and 13 strains into profiles 1 and 2, respectively, and just a few strains revealed patterns 3 and 4. The isolates from Thailand were exceptional in that they showed greater diversity and were represented by six different RAPD patterns, i.e., patterns 3 and 5 to 9. The LOS migration and immunoblotting analyses revealed two different patterns, which indicated long and short forms of LOS; the former was found in 20/23 tested strains. Two strains that expressed the short form of LOS were grouped into RAPD pattern 4. The absence of cdtABC genes was observed in only 4/23 strains, and three of these isolates were assigned to RAPD pattern 4. Our results showed limited genotypic and phenotypic variations among H. ducreyi strains, as supported by the conserved RAPD and LOS profiles shared by the majority of the studied strains. However, the RAPD method identified differences between strains, including those from different geographic areas, which indicate the potential of RAPD as an epidemiological tool for the typing of H. ducreyi isolates in countries where chancroid is endemic.

Bacterial Toxins↗