Higher organism load associated with failure of azithromycin to treat rectal chlamydia.

Repeat rectal chlamydia infection is common in men who have sex with men (MSM) following treatment with 1 g azithromycin. This study describes the association between organism load and repeat rectal chlamydia infection, genovar distribution, and efficacy of azithromycin in asymptomatic MSM. Stored rectal chlamydia-positive samples from MSM were analysed for organism load and genotyped to assist differentiation between reinfection and treatment failure. Included men had follow-up tests within 100 days of index infection. Lymphogranuloma venereum and proctitis diagnosed symptomatically were excluded. Factors associated with repeat infection, treatment failure and reinfection were investigated. In total, 227 MSM were included - 64 with repeat infections [28·2%, 95% confidence interval (CI) 22·4-34·5]. Repeat positivity was associated with increased pre-treatment organism load [odds ratio (OR) 1·7, 95% CI 1·4-2·2]. Of 64 repeat infections, 29 (12·8%, 95% CI 8·7-17·8) were treatment failures and 35 (15·4%, 95% CI 11·0-20·8) were reinfections, 11 (17·2%, 95% CI 8·9-28·7) of which were definite reinfections. Treatment failure and reinfection were both associated with increased load (OR 2·0, 95% CI 1·4-2·7 and 1·6, 95% CI 1·2-2·2, respectively). The most prevalent genovars were G, D and J. Treatment efficacy for 1 g azithromycin was 83·6% (95% CI 77·2-88·8). Repeat positivity was associated with high pre-treatment organism load. Randomized controlled trials are urgently needed to evaluate azithromycin's efficacy and whether extended doses can overcome rectal infections with high organism load.

Duration of syphilis symptoms at presentations in men who have sex with men in Australia: are current public health campaigns effective?

The rapid rise in syphilis cases has prompted a number of public health campaigns to assist men who have sex with men (MSM) recognize and present early with symptoms. This study aimed to investigate the temporal trend of the duration of self-report symptoms and titre of rapid plasma reagin (RPR) in MSM with infectious syphilis. Seven hundred and sixty-one syphilis cases in MSM diagnosed at the Melbourne Sexual Health Centre (MSHC) from 2007-2013 were reviewed. Median duration of symptoms and RPR titres in each year were calculated. The median durations of symptoms with primary and secondary syphilis were 9 [interquartile range (IQR) 6-14] days and 14 (IQR 7-30) days, respectively. The overall median titre of RPR in secondary syphilis (median 128, IQR 64-256) was higher than in primary syphilis (median 4, IQR 1-32) and in early latent syphilis (median 32, IQR 4-64). The median duration of symptoms for primary syphilis, secondary syphilis and titre of RPR level did not change over time. Public health campaigns were not associated with a significant shorter time from onset of symptoms to treatment. Alternative strategies such as more frequent testing of MSM should be promoted to control the syphilis epidemic in Australia.

Routine CD4 cell count monitoring seldom contributes to clinical decision-making on antiretroviral therapy in virologically suppressed HIV-infected patients.

OBJECTIVES: In Australia, CD4 cell count is monitored approximately every 6 months in HIV-infected patients during antiretroviral therapy (ART). The aim of this study was to determine if routine CD4 monitoring contributed to decisions on changes to ART, and to estimate how reduced CD4 monitoring could contribute to cost savings in Australia. METHODS: We conducted a retrospective cohort analysis investigating all HIV-infected patients who attended the Melbourne Sexual Health Centre (MSHC) in Australia from 1 April 2011 to 1 October 2013. We reviewed the electronic medical records of all patients who changed or stopped antiretroviral regimens during this time period to determine whether CD4 cell count could have contributed to this clinical decision. RESULTS: Among 1004 patients with HIV infection on ART, none [95% confidence interval (CI) 0-2.3%] of the 162 clinical decisions to change or stop treatment were influenced by CD4 cell counts. Reducing the current biannual CD4 monitoring strategy to annually could potentially save ∼AU$ 1.5 million (US$ 1.4 million) each year in Australia [i.e. ∼AU$ 74 700 (US$ 67 700) could be saved per 1000 HIV-infected patients during ART]. CONCLUSIONS: Routine CD4 monitoring in HIV-infected patients during ART could be reduced from biannually to annually, as it rarely influences clinical decisions in patients' management. Not only could this avoid patients being unnecessarily anxious about normal fluctuations in their CD4 counts but it would also result in cost savings.

Comparison of a TaqMan-based real-time polymerase chain reaction with conventional tests for the detection of Trichomonas vaginalis.

OBJECTIVE: To compare a TaqMan-based real-time polymerase chain reaction (PCR) with conventional PCR, culture, and wet-mount microscopy for the diagnosis of trichomoniasis in women. METHODS: Vaginal swabs from 119 women were tested for Trichomonas vaginalis by wet mount and culture. Paired vaginal lavage and urine specimens were tested by conventional and real-time PCR. RESULTS: Using an expanded "gold standard", defined as a positive culture result using vaginal swabs and/or a positive PCR test using TVK3/7 primers, the overall prevalence of T vaginalis in the study population was 65.5% (78/119). The detection rate of T vaginalis was 65.5% (78/119) and 36.9% (44/119) by conventional PCR using vaginal washings and urine specimens, respectively; 68.9% (82/119) by real-time PCR using vaginal washings and 61.3% (73/119) by real-time PCR using urine specimens. The sensitivities of conventional PCR using vaginal washings and urine and real-time PCR using vaginal washings and urine, compared with the gold standard were 100%, 56.4%, 100% and 76.7%, and the specificities of these tests were 100%, 97.6%, 82.9% and 97%, respectively. CONCLUSIONS: The real-time PCR test proved to be significantly more sensitive than culture and wet-mount microscopy, although its specificity was slightly lower than these tests. In addition, it was more sensitive, rapid and less time consuming than conventional PCR for the detection of T vaginalis.

Observations on the microbiology of urethritis in black South African men.

The occurrence of Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium was determined by molecular techniques in urine specimens from 182 black South African men who had symptoms and/or overt signs of urethritis. Eighty-six (47.3%) of these men were infected with N. gonorrhoeae. There were 185 men without overt evidence of urethritis, 16 (8.6%) of whom were also infected with N. gonorrhoeae. Of the 96 men who had non-gonococcal urethritis, 14 (14.6%) were infected with C. trachomatis, 16 (16.7%) with M. genitalium and only one with both microorganisms. In comparison, 15 (8.9%) of 169 men without overt urethritis and without N. gonorrhoeae were infected with C. trachomatis and 15 (8.9%) with M. genitalium, proportions that were about half the size of those in the group with overt urethritis.

Molecular typing of Treponema pallidum in South Africa: cross-sectional studies.

We evaluated a molecular subtyping system for Treponema pallidum for its ability to differentiate between strains obtained from male patients with primary syphilis in South Africa. Of 201 T. pallidum-positive specimens, 161 were typeable, revealing 35 subtypes. The unique subtypes identified in Durban, Cape Town, and Carletonville and the total number of subtypes suggested that the strain population was very diverse and varied geographically.

HIV infection among youth in a South African mining town is associated with herpes simplex virus-2 seropositivity and sexual behaviour.

OBJECTIVES: To determine the seroprevalence of HIV and herpes simplex virus-2 (HSV-2) by age and gender among young people aged 14--24 years in a South African town and to identify risk factors for HIV infection. DESIGN: A community-based, cross-sectional study was conducted on a random sample of men (n = 723) and women (n = 784) living in a township in the Carletonville district of South Africa. METHODS: Potential demographic and behavioural risk factors associated with HIV were recorded by questionnaire and biological tests were performed on serum and urine. Data analysis was performed using multivariate logistic regression. RESULTS: Among men and women the prevalence of HIV infection was 9.4 and 34.4%, respectively, and of positive HSV-2 serology was 17.0 and 53.3%, respectively. Among 24-year-old women the prevalence of HIV was 66.7% [95% confidence interval (CI), 54.6--77.3%]. HSV-2 seropositivity was a strong independent risk factor for HIV infection with odds ratios of 5.3 (95% CI, 2.7--10.3) for men and 8.4 (95% CI, 4.9--14.2) for women. There was no independent effect of age at first sex or serological markers of other sexually transmitted infections on HIV infection. CONCLUSIONS: HIV infection among young women increases rapidly after the onset of sexual activity and reaches extremely high levels by 24 years of age. These findings suggest that rates of HIV transmission from men to women are high and that HSV-2 plays a major role in the spread of HIV in this population.

Evidence of declining STD prevalence in a South African mining community following a core-group intervention.

OBJECTIVES: To reduce the prevalence of curable sexually transmitted diseases (STDs) in a South African mining community through provision of STD treatment services, including periodic presumptive treatment and prevention education to a core group of high-risk women living in areas around the mines. METHODS: Women at high risk for STDs attended a mobile clinic monthly for examination and counseling, and were treated presumptively for bacterial STDs with a directly observed 1-g dose of azithromycin. Gonococcal and chlamydial infection rates were measured by urine ligase chain reaction, and genital ulcers were assessed by clinical examination. Changes in STD prevalence among local miners were assessed through comparison of prevalence in two cross-sectional samples of miners taken 9 months apart, and through routine disease surveillance at mine health facilities. RESULTS: During the first 9 months of the intervention, 407 women used the services. Baseline prevalence of Neisseria gonorrhoeae and/or Chlamydia trachomatis in women was 24.9%; 9.7% of these women had clinical evidence of genital ulcer disease (GUD). The proportion of women with incident gonococcal or chlamydial infections at the first monthly return visit (69% follow-up rate) was 12.3%, and genital ulcers were found in 4.4% of these women. In the miner population, the prevalence of N gonorrhoeae and/or C trachomatis was 10.9% at baseline and 6.2% at the 9-month follow-up examination (P<0.001). The prevalence of GUD by clinical examination was 5.8% at baseline and 1.3% at follow-up examination (P< 0.001). Rates of symptomatic STDs seen at mine health facilities decreased among miners in the intervention area compared with miners living farther from the site and with less exposure to the project. DISCUSSION: Provision of STD treatment services to a core group of high-risk women may significantly reduce their burden of disease, and may contribute to a reduction in community STD prevalence. In the absence of sensitive and affordable screening tests for STDs in women, periodic presumptive treatment coupled with prevention education is a feasible approach to providing STD services in this population.

PIP: This intervention-linked study was conducted to reduce the prevalence of curable sexually transmitted diseases (STDs) in a South African mining community through provision of STD treatment services, including periodic presumptive treatment and prevention education to a core group of high-risk women living in areas around the mines. In this article, the impact of such an intervention is assessed on the women as well as the male migrant community in the intervention area. During the 9 months of the intervention, 407 women used the services. Baseline prevalence of gonococcal or chlamydial infections in women was 24.9%; 9.7% of these women had clinical evidence of genital ulcer disease (GUD). At the first monthly return, baseline for gonococcal or chlamydial infected women was 12.3%, and genital ulcers were found in 4.4% of the women. In the miner population, the overall result was similar to the result observed in the women: a decrease in rate of baseline prevalence of gonococcal or chlamydial infections and GUD was noted. In addition, rates of symptomatic STDs seen at mine health facilities decreased more among miners living closer within the intervention area than among those living farther away. In conclusion, provision of STD treatment services to a core group of high-risk women may significantly reduce their burden of disease, and may contribute to a reduction in community STD prevalence.

Human immunodeficiency virus infection and genital ulcer disease in South Africa: the herpetic connection.

BACKGROUND AND OBJECTIVES: While genital ulcers are a risk factor in HIV infection, the association of specific agents of genital ulcer disease (GUD) with HIV infection may vary. GOAL: To determine the etiology of GUD in HIV-infected and HIV-uninfected men attending sexually transmitted disease (STD) clinics in Durban, Johannesburg, and Cape Town, South Africa, and the association of previous and current sexually transmitted infections with HIV infection in men with ulcerative and nonulcerative STDs. STUDY DESIGN: A cross-sectional study of 558 men with genital ulcers and 602 men with urethritis. RESULTS: Patients with GUD were more likely to be infected with HIV than patients with urethritis (39.4% versus 21.4%, P< or =0.001). Herpes simplex virus 2 (HSV-2) was the most common agent identified in ulcer specimens (35.9%), and was detected in a significantly higher proportion of ulcer specimens from HIV-infected patients than in specimens from HIV-uninfected patients (47.4% versus 28.2%, P< or =0.001). Patients infected with HIV-1 were significantly more likely to have HSV-2 infection, as measured by the presence of the antibody to glycoprotein G-2, than patients not infected with HIV (63.1% versus 38.5%, P< or =0.001). Patients infected with HIV-1 were also significantly more likely to have initial HSV-2 infection than HIV-uninfected patients with GUD (50.0% versus 31.6%, P = 0.007). Haemophilus ducreyi was detected in 31.7% of ulcer specimens; prevalence did not vary by HIV-infection status. Treponema pallidum DNA was detected significantly less frequently in ulcer specimens from patients infected with HIV than in specimens from patients not infected with HIV (10.2% versus 26%, P< or =0.001); no association was found between HIV-infection status and fluorescent treponemal antibody absorption test seroreactivity, even when men with M-PCR-positive syphilis lesions were excluded from the analyses. CONCLUSION: The authors found that HSV-2 is a more common etiology of GUD than has been suggested by previous studies conducted in South Africa; serologic evidence of HSV-2 infection and current cases of genital herpes are strongly associated with HIV infection among men who present to STD clinics with GUD or urethritis.

Comparison of clinically directed, disease specific, and syndromic protocols for the management of genital ulcer disease in Lesotho.

OBJECTIVE: To evaluate two protocols for the syndromic management of genital ulcer disease (GUD) in Lesotho, southern Africa and to compare the performance of these protocols with that of a conventional disease specific approach. METHODS: A cross sectional study was conducted among consecutive patients with GUD attending an STD clinic in Maseru, Lesotho. The clinical diagnoses were made by using predefined criteria at the initial visit before the performance of laboratory tests. Attempts were made to detect the specific aetiology of the genital ulcers using PCR assays and syphilis serology. The results of PCR assays and syphilis serology were used as the gold standard against which the performance of the management approaches were applied. RESULTS: Of 100 patients initially recruited into the study, Haemophilus ducreyi infection was detected in 56%, herpes simplex virus in 26%, Treponema pallidum in 23%, and lymphogranuloma venereum in 7%. No pathogens were detected in 6% of patients. 17% of patients had mixed infections. Sensitivity, specificity, positive and negative predictive values of the three management protocols for GUD were compared after applying each to the study population. Theoretically, the lowest correct treatment rate would have been obtained by using the disease specific protocol (62%) compared with more than 90% in both syndromic management protocols. Considerable overtreatment for primary syphilis would occur following application of both syndromic protocols. This would be the result of the overdiagnosis of chancroid, in particular the misdiagnosis of genital herpes as chancroid, which would receive treatment for syphilis unnecessarily. The HIV seroprevalence among these patients was 36%. A significantly higher rate of HIV seropositivity was detected among the patients with herpes simplex virus infection when compared with those patients having other causes of genital ulcer disease (58% v 27%; odds ratio 3.73; 95% CI 1.26-11.26; p = 0.01). CONCLUSIONS: Poor sensitivity, specificity, and predictive values were recorded when the disease specific protocol was applied to the study population. In contrast, the syndromic management protocols provided adequate treatment for more than 90% of patients with GUD. Protocol C, which identified a minority of cases of genital herpes, was found to have an advantage when compared with protocol B (all patients with genital ulcer disease treated for both syphilis and chancroid) in that 29% of genital herpes cases would receive appropriate counselling.

Comparison of clinical diagnosis and standard laboratory and molecular methods for the diagnosis of genital ulcer disease in Lesotho: association with human immunodeficiency virus infection.

A multiplex polymerase chain reaction (M-PCR) assay for Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus (HSV) was compared with clinical and standard laboratory methods for the diagnosis of genital ulcer disease (GUD) in 105 patients; 36% were human immunodeficiency virus (HIV)-seropositive. Chancroid (80%), syphilis (8%), and genital herpes (8%) were the most frequent diagnoses. H. ducreyi and HSV were isolated from ulcers of 43% and 18% of patients, respectively; in 35%, all cultures were negative and the laboratory diagnosis indeterminate. M-PCR detected H. ducreyi, T. pallidum, and HSV in 56%, 23%, and 26% of patients, respectively; (no definitive diagnosis, 6%). The proportion of patients with more than one agent was 4% by culture and 17% by M-PCR (P = .002). Resolved sensitivities of M-PCR for H. ducreyi and HSV cultures were 95% and 93%, respectively. The sensitivities of H. ducreyi and HSV cultures were 75% and 60%, respectively. HSV, detected in 47% of specimens from HIV-infected versus 16% from HIV-uninfected patients (P < .001), may be emerging as a more frequent cause of GUD.

Evidence for naturally occurring recombination in the gene encoding the major outer membrane protein of lymphogranuloma venereum isolates of Chlamydia trachomatis.

The nucleotide sequence of the major outer membrane protein gene (omp1) was determined for three geographically distinct lymphogranuloma venereum isolates which were serologically untypeable. The three omp1 sequences were hybrids of serovars L1 and L2, containing a putative DNA recombination site in variable segment 2. Efforts to manipulate the chlamydial genome in vitro by recombination should be intensified.

Accuracy of clinical diagnosis of genital ulcer disease.

In Africa, establishment of an accurate clinical diagnosis in cases of genital ulcer disease is difficult owing to atypical presentation of ulcerations and mixed infections. This is compounded by the frequent lack of suitable laboratory facilities. In 240 cases of genital ulcer disease among mineworkers in Carletonville, South Africa, this study endeavored to correlate the clinical diagnosis with laboratory findings. Clinical accuracy and positive and negative predictive values were determined for each type of genital ulcer disease encountered. Overall, the accuracy of clinical diagnosis was 68% for single infections, 80% for chancroid, 55% for primary syphilis, 27% for lymphogranuloma venereum (LGV), and 22% for genital herpes. Adequate laboratory facilities are indispensible for the establishment of an accurate etiologic diagnosis of genital ulcer disease and thus the institution of appropriate antimicrobial therapy.

Soluble interleukin-2 receptors in serum and urine of patients with chancroid and their response to therapy.

To investigate cell-mediated immune response in chancroid, soluble interleukin-2 receptor levels in serum and urine samples of healthy individuals and patients were measured by an enzyme-linked immunosorbent assay. Increased levels both in serum and in urine were observed in cases of Haemophilus ducreyi infection. In patients showing a prolonged incubation period, urine levels exceeded serum values. Therapy led to a reduction of elevated interleukin-2 receptor levels in serum and in urine.

Causes and treatment of sexually acquired genital ulceration in southern Africa.

The cause of sexually acquired genital ulceration was studied in 240 consecutive migrant mineworkers attending a sexually transmitted disease clinic in Carletonville, Transvaal. Chancroid proved to be the most common cause of genital ulcer disease, with Haemophilus ducreyi being isolated from 164 patients (68%). In 60% of cases the disease was locally acquired and in the remaining 40%, the infection was acquired in Lesotho, Botswana, Natal, Transkei and Malawi. Syphilis was diagnosed in 62 patients (26%), lymphogranuloma venereum in 16 (7%), genital herpes in 8 (3%) and granuloma inguinale in 1. No cause of ulceration could be found in 31 patients (13%). Mixed infections were documented in 41 patients (17%). Diagnosis of the cause of genital ulcer disease is not possible without relatively sophisticated laboratory support; however, simplified strategies for management and treatment have been developed.

In vitro activity of A-56619 (difloxacin), A-56620, and other new quinolone antimicrobial agents against genital pathogens.

The in vitro activities of two new carboxyquinolones, A-56619 (difloxacin) and A-56620, were compared with those of ciprofloxacin, norfloxacin, and ofloxacin against genital tract pathogens. All the quinolones were highly active against Neisseria gonorrhoeae. A-56619 had the lowest MICs against Chlamydia trachomatis (MIC range, 0.125 to 0.25 micrograms/ml) and Haemophilus ducreyi (MIC for 90% of isolates tested, 0.1 micrograms/ml).