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PubMedDate not supplied

Human immunodeficiency virus transmission and the role of other sexually transmitted diseases. Measures of association and study design.

BACKGROUND: Studies have reported that infection with certain sexually transmitted diseases (STD), such as chancroid, gonorrhea, and genital herpes, enhances the probability of human immunodeficiency virus (HIV) transmission by sexual contact with an infected partner. Epidemiologic studies vary in design from longitudinal to cross-sectional, with varying periods of follow-up or retrospective history of exposure to STD. The major difficulty in assessing the results of past work centers on the validity and precision of widely used measures of association, such as relative risk (RR) and odds ratio (OR), in situations in which common behavior (e.g., different facets of sexual behavior) underpins the acquisition of both the STD cofactor and HIV. GOAL: To evaluate the quality of the cumulative incidence ratio (CIR), the hazard rate ratio (HRR), and the prevalence ratio (PR) as measures of association to estimate and test the increase in HIV transmission probabilities caused by the STD. STUDY DESIGN: The study is based on a proportional hazard stochastic model of concomitant HIV and STD cofactor transmission. Analysis was performed using Monte-Carlo simulation. RESULTS: Estimates of the HIV-STD association by the CIR, HRR, and PR, adjusted and nonadjusted for sexual activity, are shown to have poor validity and great variability. The adjusted CIR, HRR, and PR tend to underestimate the strength of the true association (specified in the model) in both longitudinal and cross-sectional designs. In the absence an HIV-STD association, the PR tends to overestimate the magnitude, whereas the CIR and HRR may either underestimate or overestimate it in longitudinal studies. These results have direct consequences on the reliability of the test of association showing both a lack of specificity (empirical type I error) and sensitivity (empirical power). Some reasons contributing to the bias in the estimates of the measures of association are the presence of confounding variables, namely the frequency of change of sex partner and the mixing pattern between sexual activity classes, as well as the adopted definition of exposure to the STD cofactor and the prevalence of both HIV and the STD cofactor. CONCLUSIONS: The precision of estimates and reliability of the test of HIV-STD association could be improved through longitudinal studies using more careful definition and measurement of exposure to the STD cofactor and larger sample sizes permitting finer stratification of sexual behavior and a sufficient number of persons per stratum.

Bias↗
PubMed2002

Can behavior change explain increases in the proportion of genital ulcers attributable to herpes in sub-Saharan Africa? A simulation modeling study.

BACKGROUND: The proportion of cases of genital ulcer disease attributable to herpes simplex virus type 2 (HSV-2) appears to be increasing in sub-Saharan Africa. GOAL: To assess the contributions of HIV disease and behavioral response to the HIV epidemic to the increasing proportion of genital ulcer disease (GUD) attributable to HSV-2 in sub-Saharan Africa. STUDY DESIGN: Simulations of the transmission dynamics of ulcerative sexually transmitted diseases (STDs) and HIV with use of the model STDSIM. RESULTS: In simulations, 28% of GUD was caused by HSV-2 before a severe HIV epidemic. If HIV disease was assumed to double the duration and frequency of HSV-2 recurrences, this proportion rose to 35% by year 2000. If stronger effects of HIV were assumed, this proportion rose further, but because of increased HSV-2 transmission this would shift the peak in HSV-2 seroprevalence to an unrealistically young age. A simulated 25% reduction in partner-change rates increased the proportion of GUD caused by HSV-2 to 56%, following relatively large decreases in chancroid and syphilis. CONCLUSION: Behavioral change may make an important contribution to relative increases in genital herpes.

Adult↗
PubMed2002

Epidemic Lymphogranuloma venereum during epidemics of crack cocaine use and HIV infection in the Bahamas.

BACKGROUND: Since the early 1980s, the Bahamas has experienced sequential epidemics of freebase/crack cocaine use, genital ulcer-inguinal adenopathy disease (GUD), and heterosexual HIV infection. GOAL: To prospectively define the etiology of GUD in patients at the Princess Margaret Hospital during outbreaks of crack cocaine use, GUD, and HIV infection in the Bahamas. STUDY DESIGN: In Nassau, 47 consecutive patients with GUD underwent serologic testing for syphilis and for infections with HIV, herpes simplex virus type 2 (HSV-2), and Chlamydia trachomatis. Genital ulcer specimens were tested by culture and/or polymerase chain reaction (PCR) assay for Haemophilus ducreyi; by PCR and/or antigen assay for HSV; and by PCR for C trachomatis. Lymph node aspirates were tested by PCR for C trachomatis and H ducreyi. RESULTS: Twenty patients (43%) had HIV infection; eight had lymphogranuloma venereum (LGV), confirmed by PCR detection of C trachomatis sequences consistent with the L2 serovar; and nine others had possible LGV, on the basis of serum microimmunofluorescent C trachomatis antibody titers > or =256. Inguinal lymphadenopathy or bubo was present in 15 of 17 patients, who thus met the laboratory criteria for definite or possible LGV, and in 7 of 30 who did not meet such laboratory criteria (P < 0.001). Thirteen patients had confirmed genital herpes, seven had confirmed chancroid, and four had probable or possible primary syphilis. CONCLUSIONS: The epidemics in the Bahamas of crack use, heterosexual HIV infection, and GUD apparently included epidemic transmission of LGV.

Adult↗
PubMed2007

Male circumcision as a preventive measure against HIV and other sexually transmitted diseases.

PURPOSE OF REVIEW: In 2005, 4.1 million people were infected with HIV. There is an urgent need to intensify and expand HIV prevention methods. Male circumcision is one of several potential approaches. This review summarizes recent evidence for the potential of male circumcision to prevent HIV and other sexually transmitted infections. RECENT FINDINGS: The first randomized controlled trial of adult male circumcision found a highly significant 60% reduction in HIV incidence among men in the intervention arm. Modelling this effect predicts that widespread implementation of male circumcision could avert 2 million HIV infections over the next decade in sub-Saharan Africa. The biological rationale is that the foreskin increases risk of HIV infection due to the high density of HIV target cells and lack of keratinization of the inner mucosal surface. SUMMARY: There is strong evidence that male circumcision reduces risk of HIV, syphilis and chancroid. If results are confirmed by two ongoing trials in sub-Saharan Africa, provision of safe male circumcision could be added to HIV prevention packages in high-incidence settings. This would also provide an opportunity for HIV-prevention education and counselling to young men at high risk of infection.

Circumcision, Male↗
PubMed1995

Localisation and immunological properties of a 24-kDa surface protein of Haemophilus ducreyi.

The cell wall and outer structures of Haemophilus ducreyi bacteria were investigated. The 24-kDa outer protein from two strains was purified with an SDS-PAGE preparative continuous-elution electrophoresis cell. The protein was further characterised by SDS-PAGE and immunoblotting, and the immunological properties were investigated by ELISA. Localisation on the bacterial surface was investigated by immuno-electron-microscopy with a polyclonal antiserum raised against the purified protein. A triple-laminar cell wall typical of gram-negative bacteria, close cellular contact between bacterial cells and outer blebs were seen on thin sections. An additional high mol. wt band of c. 165 kDa was seen when not treated by heating to 100 degrees C. A high density fibrilla-like material was detected on the bacterial cell and in the environment by negative staining and immuno-electron-microscopy with antisera specific for the 24-kDa protein. The surface localisation of the 24-kDa protein was confirmed by an ELISA technique with the specific antiserum and whole bacterial cells as antigen. The presence of antibodies to the 24-kDa protein was demonstrated in antisera to 13 strains of H. ducreyi, indicating antigenic identity or within-species cross-reactivity. Low titres of antibodies to this protein were also detected in 19 antisera raised against different strains of gram-negative bacteria, indicating cross-reactivity with other species. Antibody response to the 24-kDa protein in rabbits immunised subcutaneously with live bacteria resulted in a secondary IgG response. Of 28 sera from patients with culture-verified chancroid, 26 manifested high titres of IgG antibodies to the 24-kDa protein, thus indicating the involvement of this antigen in the disease process in man.

Amino Acid Sequence↗
PubMed2002

Rising incidence of genital herpes over two decades in a sexually transmitted disease clinic in north India.

Genital herpes, which was considered to be a minor sexually transmitted disease (STD) in the past in developing countries, is rapidly increasing; in contrast, bacterial STDs are declining. This changing trend of various STDs prompted us to analyze our data retrospectively to see whether a similar change is occurring in this part of India as well. The records of sexually transmitted diseases (STDs) clinic attendees from January 1977 to December 2000 were analyzed. The demographic profile of patients with genital herpes was also considered for analysis. STDs were diagnosed clinically and by appropriate laboratory tests wherever applicable. VDRL test was done in all patients, and HIV antibody detection was performed from 1987 onwards. The incidences of chancroid, donovanosis, and gonorrhea were 12.2%, 6.3%, and 16.9%, respectively, from January 1977 to December 1985. The figures for the same decreased to 2.5%, 0.9%, and 2.3%, respectively, from January 1993 to December 2000. The decreasing incidence of the above bacterial STDs is statistically significant (p<0.001). However, there was an approximately two-fold increase in the incidence of genital herpes in recent years (20.5%) in comparison to the figures from the late 70s (11.4%). Molluscum contagiosum also showed an upward trend (1% in 1977-85 vs. 9.8% in 1993-2000). Condylomata accuminata remained almost unchanged (21.4% in 1977-85 vs. 20% in 1993-2000). To conclude, a significant increase in the number of viral STDs and a decline in the bacterial diseases were observed in recent years in comparison to the figures from the late 70s. This may be due to awareness of HIV, success of control programs, syndromic management of STDs, and adoption of safer sexual practices, which prevent bacterial STDs more efficiently than viral ones.

Adolescent↗
PubMed1997

Distribution, cloning, characterisation and mutagenesis of sodC, the gene encoding copper/zinc superoxide dismutase, a potential determinant of virulence, in Haemophilus ducreyi.

The sodC gene encoding the periplasmic enzyme copper/zinc superoxide dismutase (CuZnSOD) has been cloned from Haemophilus ducreyi, the causative agent of the genital ulcer disease, chancroid. Examination of a collection of diverse strains indicates that it is present throughout the species. Cloned sodC has been expressed in E. coli and shown to encode active enzyme. Insertional mutagenesis was used to construct a non-functional version of the gene. This has been transferred into the chromosome of the parent H. ducreyi strain by electroporation and homologous recombination, in preparation for studies of the role of this enzyme in the interactive biology of the organism with its host, perhaps in protecting bacteria from superoxide radicals and their reactive progeny generated by neutrophils in the context of host defence.

Amino Acid Sequence↗
PubMed1998

Facile construction of mutations in Haemophilus ducreyi using lacZ as a counter-selectable marker.

Haemophilus ducreyi is a Gram-negative bacterium which is the causative agent of chancroid, an ulcerative sexually transmitted disease. In order to understand the pathogenesis of H. ducreyi disease, studies designed to identify potential virulence determinants and construct mutants deficient in the elaboration of these determinants have been undertaken in several laboratories. At the present time, construction of isogenic mutants is accomplished by electroporation of linearized DNA containing insertionally inactivated H. ducreyi genes followed by selection for the resistance marker encoded on the inactivated gene. In our experience, certain mutants are difficult to construct using this procedure. In the construction of strains containing lacZ as a reporter gene, we observed that the growth of lacZ expressing H. ducreyi was inhibited in the presence of X-gal. We have exploited this observation to develop a new strategy for the construction of isogenic H. ducreyi mutants.

Alleles↗
PubMed1979

Plasmid-mediated ampicillin resistance in Haemophilus ducreyi.

Three of 19 strains of Haemophilus ducreyi, isolated during a recent outbreak of chancroid, were found to produce beta-lactamase and to harbor a 6.0 x 10(6)-dalton plasmid. Escherichia coli transformed with this plasmid acquired beta-lactamase-mediated resistance to ampicillin. The guanine-plus-cytosine content of the plasmid was found to be 41 mol%. Restriction endonuclease digestion studies suggest that a relatively large portion of the Tn1 translocon is carried by this plasmid. Whereas this plasmid could not be transferred to H. influenzae by mating on membrane filters, a strain of H. ducreyi was able to receive and donate a 30 x 10(6)-dalton ampicillin resistance plasmid from H. influenzae. The ability of H. ducreyi to receive and donate conjugative plasmids may result in the appearance of multiply resistant strains.

Ampicillin↗
PubMed1982

Plasmid-mediated sulfonamide resistance in Haemophilus ducreyi.

Clinical isolates of Haemophilus ducreyi from patients with chancroid were shown to have one or more 4.9- to 7.0-megadalton non-self-transferable plasmids and to have in vitro resistance to sulfonamides. Transformation of Escherichia coli to sulfonamide resistance was associated with the acquisition of a 4.9-megadalton plasmid, which did not confer linked resistance to streptomycin. The guanine-plus-cytosine content of this plasmid was found to be 57%. Filter-blot hybridization and restriction endonuclease digestion studies suggested a relationship of this plasmid to RSF1010. Electron microscope heteroduplex analysis confirmed this relationship. The identification in H. ducreyi of a plasmid closely related to plasmids found in enteric species, rather than transposition of a resistance determinant to an indigenous plasmid, suggests that further dissemination of the enteric plasmid pool to this genus is possible since plasmid transfer between certain Haemophilus species is readily demonstrated.

Endonucleases↗
PubMed1984

Plasmid-mediated tetracycline resistance in Haemophilus ducreyi.

Clinical isolates of Haemophilus ducreyi were shown to be resistant to tetracycline. Resistance was associated in some strains with a 30-megadalton plasmid capable of transferring resistance in conjugative matings with other strains of H. ducreyi and other species of Haemophilus. Restriction endonuclease digestion patterns suggest a relationship between H. ducreyi plasmids and other tetracycline resistance plasmids in Haemophilus. The presence of plasmid-mediated resistance to the tetracyclines limits the use of these agents for the treatment of chancroid.

Conjugation, Genetic↗
PubMed1984

Common beta-lactamase-specifying plasmid in Haemophilus ducreyi and Neisseria gonorrhoeae.

Eighty-nine strains of Haemophilus ducreyi from a chancroid epidemic in Orange County, California, were examined for plasmid content. Seventy-eight (88%) of these isolates were found to contain a plasmid of 3.2 megadaltons which conferred beta-lactamase production. Restriction endonuclease digests indicated that this was the same plasmid that was found in some strains of beta-lactamase-producing Neisseria gonorrhoeae.

DNA, Bacterial↗
PubMed1987

In vitro activity of ceftriaxone, cefetamet (Ro 15-8074), ceftetrame (Ro 19-5247; T-2588), and fleroxacin (Ro 23-6240; AM-833) versus Neisseria gonorrhoeae and Haemophilus ducreyi.

We examined 300 strains of Neisseria gonorrhoeae and 100 strains of Haemophilus ducreyi to determine their in vitro susceptibility to two new cephalosporins, cefetamet (Ro 15-8074) and ceftetrame (Ro 19-5247; T-2588), and a new fluroquinolone, fleroxacin (Ro 23-6240; AM-833). Their activity was compared with that of ceftriaxone, penicillin, spectinomycin, tetracycline, and erythromycin. Cefetamet, ceftetrame, and fleroxacin had excellent in vitro activity against both groups of microorganisms. beta-Lactamase production did not significantly affect the MICs of these agents. The Mtr phenotype of N. gonorrhoeae raised the MICs two- to fourfold, but the MICs remained within the range of achievable levels in serum. These newer compounds have a distinct advantage over existing therapeutic agents in that they can be administered orally. Clinical trials are warranted to assess their usefulness in the therapy of gonorrhea and chancroid.

Cefmenoxime↗
PubMed2006

Identification of genes involved in the expression of atypical lipooligosaccharide structures from a second class of Haemophilus ducreyi.

Haemophilus ducreyi is a gram-negative bacterium that is the causative agent of chancroid. Strain 35000HP has been well characterized and is representative of the majority of H. ducreyi strains. Strain 35000HP produces a lipooligosaccharide (LOS) that contains D-glycero-D-manno-heptose in the main oligosaccharide chain extension; the lbgB gene has been shown to encode the DD-heptosyltransferase. The lbgB gene is found in a gene cluster together with the lbgA gene, which encodes for the galactosyltransferase I. These two genes are flanked by two housekeeping genes, rpmE and xthA, encoding the ribosomal protein L31 and the exonuclease III, respectively. Recently, a second group of H. ducreyi strains have been identified. Strain 33921, a representative of the class II strains, produces an LOS that lacks DD-heptose in the oligosaccharide portion of its LOS. To better understand the biosynthesis of the DD-heptose-deficient 33921 LOS, we cloned and sequenced the corresponding lbgAB genomic region from strain 33921. Similar to strain 35000HP, the 33921 genome contains xthA and rpmE. However, between these two genes we identified genes encoding two putative glycosyltransferases that were not highly homologous to the 35000HP lbgAB genes. In this study, we demonstrate that the product of one of these genes encodes a galactosyltransferase. In addition, dot blot hybridization determined that 3 of 35 strains tested had the atypical transferases present, as did 4 strains characterized as class II strains by other criterion. These data indicate that the lbgAB genes can serve as one indicator of the classification of H. ducreyi strains.

Amino Acid Sequence↗
PubMed1992

Molecular analysis of the Haemophilus ducreyi groE heat shock operon.

Chancroid is a sexually transmitted genital ulcer disease caused by Haemophilus ducreyi. Previously, we developed diagnostic DNA probes for H. ducreyi (L. M. Parsons, M. Shayegani, A. L. Waring, and L. H. Bopp, J. Clin. Microbiol. 27:1441-1445, 1989). In the present study, DNA sequencing of one of the diagnostic probes revealed two adjacent open reading frames (ORFs). These H. ducreyi ORFs and the encoded proteins show significant homology with the groE genes and GroES and GroEL heat shock proteins from several bacterial pathogens and with conserved eukaryotic 60-kDa heat shock proteins. The first H. ducreyi ORF (groES) is preceded by sequences similar to those of the Escherichia coli consensus heat shock promoters and is 288 nucleotides long and is capable of encoding a protein of 10.3 kDa. The second ORF (groEL) is 1,641 nucleotides long and is capable of encoding a protein of 57.8 kDa. Northern (RNA blot) analysis demonstrated the presence of a high level of groE mRNA in exponential-phase H. ducreyi grown in hemin broth at the organism's optimal growth temperature (33 degrees C), with increased levels seen following heat shock. Heat shock also increased the thermostability of the organisms, since stressed cells were more resistant to the lethal effects of rapid chilling. Electrophoretic analysis and immunoblots demonstrated that the predominant protein produced by exponential-phase H. ducreyi was a heat-inducible, immunoreactive protein of approximately 60 kDa (GroEL). Also, H. ducreyi groE mRNA and GroEL were expressed and inducible by heat in E. coli. This is the first report describing the cloning, sequencing, and expression of H. ducreyi protein-encoding genes.

Amino Acid Sequence↗
PubMed1992

Haemophilus ducreyi, a cytotoxin-producing bacterium.

An extra- and an intracellular product from the bacterium Haemophilus ducreyi were shown to have a cytotoxic effect on cell lines of epithelial origin, e.g., HEp-2 and HeLa cells. The cytotoxic effect appeared on cells within 24 h and resulted in cell death and morphologically changed cells. The cytotoxic activity was heat and pronase sensitive. The activity could be removed by incubation with the target cells, suggesting attachment of the agent to the cells. The cytotoxic products were secreted into the environment during exponential growth of bacteria and produced by most of the H. ducreyi strains tested. The activity was neutralized by homologous rabbit immune serum but not by the corresponding preimmune serum. The results indicate that strains of H. ducreyi produce a cytotoxin which may be of importance to the pathogenesis of chancroid.

Animals↗
PubMed1994

Identification of a hemolytic activity elaborated by Haemophilus ducreyi.

Haemophilus ducreyi is the causative agent of the sexually transmitted disease chancroid. We have identified a hemolytic activity expressed by H. ducreyi. This activity is most readily detected when horse erythrocytes are used as a target; however, low levels of activity can be detected with sheep, human, or rabbit erythrocyte targets. The activity is heat labile and protease sensitive.

Animals↗