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Background: Sub-Saharan Africa (SSA) has the highest sexually transmitted infection (STI) prevalence globally, but information about trends and geographic variation is limited by sparse aetiologic studies, particularly among men. This systematic review assessed chlamydia, gonorrhoea, and trichomoniasis prevalence by sex, sub-region, and year, and estimated male-to-female prevalence ratios for SSA., Methods: We searched Embase, MEDLINE, Global Health, PubMed, and African Index Medicus for studies measuring STI prevalence among general populations from January 1, 2000, to September 17, 2024. We adjusted observations for diagnostic test performance and used log-binomial mixed-effects meta-regressions to estimate prevalence trends and sex-prevalence ratios., Findings: Of 5202 records identified, we included 211 studies from 28 countries. In 2020, estimated prevalence among 15-49-year-olds in SSA for chlamydia was 6.6% (95%CI: 5.0-8.2%, n=169 observations) among females and 4.7% (3.4-6.1%, n=33) among males, gonorrhoea was 2.4% (1.4-3.3%, n=171) and 1.7% (0.7-2.6%, n=31), and trichomoniasis was 6.8% (3.6-9.9%, n=188) and 1.7% (0.7-2.7%, n=19). Male-to-female ratio estimates were 0.61 (0.53-0.71) for chlamydia, 0.81 (0.61-1.09) for gonorrhoea, and 0.23 (0.18-0.28) for trichomoniasis. From 2010-2020, chlamydia prevalence increased by 34.5% (11.1-62.9%) in SSA, while gonorrhoea and trichomoniasis trends were not statistically significant. Chlamydia and gonorrhoea prevalence were highest in Southern and Eastern Africa, whereas trichomoniasis was similar across sub-regions., Interpretation: SSA has a high, geographically varied STI burden, with increasing prevalence of chlamydia. Region-specific sex-prevalence ratios differed from existing global ratios and should be considered in future burden estimates. Enhanced sex-stratified surveillance is crucial to guide national programmes and reduce STI prevalence in SSA., Funding: Gates Foundation, Imperial College London, NIH, UKRI.

Many critical advances in research utilize techniques that combine high-resolution with high-content characterization at the single cell level. We introduce the MICS (MACSima Imaging Cyclic Staining) technology, which enables the immunofluorescent imaging of hundreds of protein targets across a single specimen at subcellular resolution. MICS is based on cycles of staining, imaging, and erasure, using photobleaching of fluorescent labels of recombinant antibodies (REAfinity Antibodies), or release of antibodies (REAlease Antibodies) or their labels (REAdye_lease Antibodies). Multimarker analysis can identify potential targets for immune therapy against solid tumors. With MICS we analysed human glioblastoma, ovarian and pancreatic carcinoma, and 16 healthy tissues, identifying the pair EPCAM/THY1 as a potential target for chimeric antigen receptor (CAR) T cell therapy for ovarian carcinoma. Using an Adapter CAR T cell approach, we show selective killing of cells only if both markers are expressed. MICS represents a new high-content microscopy methodology widely applicable for personalized medicine., (© 2022. The Author(s).)

Background: Sexually transmitted infections (STIs) can be transmitted from mother to neonate. We determined the frequency of mother-to-child transmission (MTCT) of Chlamydia trachomatis , Neisseria gonorrhoeae , and Trichomonas vaginalis to the newborn nasopharynx., Methods: This study was nested in a cohort study of etiologic testing versus syndromic management for STIs among pregnant women living with human immunodeficiency virus in South Africa. Mothers were tested for STIs using the GeneXpert platform within 60 days after delivery. Nasopharyngeal swabs were obtained from newborns of mothers with a positive STI test; these were then tested by Xpert® on the same day based on the maternal STI diagnosis., Results: We tested nasopharyngeal swabs from 85 STI-exposed newborns; 74 (87%) were tested within 2 weeks after birth (median five; range 2-12 days). MTCT frequency of any STI was 30/74 (41%); 43% (23/53) for C. trachomatis , 29% (2/7) for N. gonorrhoeae , and 24% (6/25) for T. vaginalis . Also, 4/11 (36%) swabs obtained between 14 and 60 days after delivery tested positive for STI., Conclusions: There was a high frequency of MTCT of STIs to the nasopharynx of newborns in our setting. The impact of nasopharyngeal colonization and the benefits of STI testing on newborn health remain to be determined.

Aim: To review the current literature and publications to assess the clinical features, recommended investigations and treatment for ocular tuberculosis in HIV infected patients. Methods: Literature review. Results: The human immunodeficiency virus (HIV) epidemic affects as many as 37.9 million people. Mycobacterium tuberculosis infection is common in HIV infection and is a leading cause of death and morbidity. Common clinical presentations include anterior uveitis (granulomatous or otherwise), choroidal granulomas/tubercles, chorioretinitis, subretinal abscess, panophthalmitis, retinal detachment and vasculitis. The majority of clinical findings were in the posterior segment, appeared primarily infective (tubercles/chorioretinitis/abscess) and were largely seen in the context of pulmonary tuberculosis or disseminated disease. Current investigational patterns include corroborative tests such as tuberculin skin test or Interferon-γ release assay. Systemic testing includes Computed Tomography, MRI or PET/CT scans. Newer Molecular techniques such as GeneXpert MTB/RIF assay and Line Probe assays (LPA) are increasingly important. Apart from standard ocular anti-inflammatory protocols, anti-tubercular treatment as per the clinical staging (latent or active) needs to be initiated. Initiation of anti-retroviral therapy (ART) is important and can be started soon after ATT. Conclusions: Ocular manifestations within this group are distinct and unique investigational and therapeutic approaches are needed.

Introduction: Although pre-exposure prophylaxis (PrEP.) is an efficacious HIV prevention strategy, its preventive benefit has not been shown among young women in sub-Saharan Africa, likely due to non-adherence. Adherence may be improved with the use of injectable long-acting PrEP methods currently being developed. We hypothesize that providing long-acting PrEP to women using injectable contraceptives, the most frequently used contraceptive method in South Africa, could improve adherence to PrEP, result in a reduction of new HIV infections, and be a relatively easy-to-reach target population. In this modelling study, we assessed the epidemiological impact and cost-effectiveness of providing long-acting PrEP to injectable contraceptive users in Limpopo, South Africa., Methods: We developed a deterministic mathematical model calibrated to the HIV epidemic in Limpopo. Long-acting PrEP was provided to 50% of HIV negative injectable contraceptive users in 2018 and scaled-up over two years. We estimated the number of HIV infections that could be averted by 2030 and the drug price of long-acting PrEP for which this intervention would be cost-effective over a time horizon of 40 years, from a healthcare payer perspective. In the base-case scenario we assumed long-acting PrEP is 75% effective in preventing HIV infections and 85% of infected individuals are on antiretroviral drug therapy (ART) by 2030. In sensitivity analyses we adjusted PrEP effectiveness and ART coverage. Costs between $519 and $1119 per disability-adjusted life-year (DALY) averted were considered potentially cost-effective, and <$519 as cost-effective., Results: Without long-acting injectable PrEP, 224,000 (interquartile range 176,000 to 271,000) new infections will occur by 2030; use of long-acting injectable PrEP could prevent 21,000 (17,000 to 26,000) or 9.8% (8.9% to 10.6%) new HIV infections by 2030 (including 6000 (4000 to 7000) in men). Long-acting PrEP would prevent 34,000 (29,000 to 39,000) or 12,000 (8000 to 15,000) at 75% and 95% ART coverage by 2030 respectively. To be considered potentially cost-effective the annual long-acting PrEP drug price should be <$16, and/or ART coverage remains at <85% in 2030., Conclusions: Providing long-acting PrEP to injectable contraceptive users in Limpopo is only potentially cost-effective when long-acting PrEP drug prices are low. If low prices are not feasible, providing long-acting PrEP only to women at high risk of HIV infection will become important., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

We report a case of management failure of male urethritis syndrome due to macrolide-resistant Mycoplasma genitalium in South Africa. We detected mutations in 23S rRNA and one of the quinolone resistance-determining regions. This report confirms that drug-resistant M. genitalium infection can undermine the effectiveness of syndromic management in Africa.

This study from South Africa highlights the importance of rectal Trichomonas vaginalis infection as a sexually transmitted infection among men who have sex with men (MSM). We report seven MSM presenting with rectal T. vaginalis infection. Two men presented with symptoms of proctitis; 5/7 had urethral coinfection with T. vaginalis. Rectal T. vaginalis infection should be considered in MSM in areas where genital infection is endemic.

Chlamydia trachomatis and Neisseria gonorrhoeae constitute major public health problems among women, but the burden of infection in sub-Saharan Africa is poorly documented. We conducted a structured review of the prevalence and incidence of genital, oral and anal C. trachomatis and N. gonorrhoeae infection in women in sub-Saharan Africa. We searched Medline, EMBASE and Web of Science over a 10-year period for studies on epidemiology of genital, oral and anal chlamydial infection and gonorrhoea in women in all countries of sub-Saharan Africa. We assessed geographic and demographic differences in prevalence and incidence of infection; weighted mean prevalence estimates were calculated with a random-effect model. A total of 102 study results were included, with data available for 24/49 of sub-Saharan countries. The weighted prevalence of chlamydial infection was lower among women in community-based studies (3.9%; 95% CI: 2.9-5.1%) than for women recruited at primary healthcare facilities (6.0%; 95% CI: 4.2-8.4%, p < 0.001); the same was observed for gonorrhoea (2.2%; 95% CI: 1.2-4.0% vs. 4.2%; 95% CI: 3.2-5.6%, p < 0.001). Prevalence of Chlamydia among sex workers was 5.5% (95% CI: 4.2-7.3%) and gonorrhoea 7.6% (95% CI: 5.4-11%). Seven studies reported on incidence which varied between 0.75-28 and 2.8-17 per 100 person-years-at-risk for chlamydial infection and gonorrhoea, respectively. Only two studies reported on anal infections and one on oral infection. This overview underscores the considerable incidence and prevalence of genital C. trachomatis and N. gonorrhoeae in women in different settings in sub-Saharan Africa. Better control strategies are warranted to reduce the burden of infection and to prevent long-term complications of these infections.

Background: Chlamydia trachomatis (CT) , Neisseria gonorrhoeae (NG) , and Trichomonas vaginalis (TV) infections may increase the risk of vertical transmission of the human immunodeficiency virus (HIV). In resource-limited settings, symptomatic screening, and syndromic management of sexually transmitted infections (STIs) during pregnancy continue to be the standard of care. In the absence of diagnostic testing, asymptomatic infections in pregnant women go untreated., Objective: To describe the acceptability and feasibility of integrating diagnostic STI screening into first antenatal care visits for HIV-infected pregnant women., Methods: HIV-infected pregnant women were recruited during their first antenatal care visit from three antenatal care clinics in Tshwane District, South Africa, between June 2016 and October 2017. Self-collected vaginal swabs were used to screen for CT, NG, and TV with a diagnostic point-of-care (POC) nucleic acid amplification test. Those with STIs were provided treatment per South African national guidelines., Results: Of 442 eligible women, 430 (97.3%) agreed to participate and were tested. Of those with a positive STI test result ( n = 173; 40.2%), 159 (91.9%) received same-day results and treatment; 100% of STI-infected women were treated within seven days., Conclusions: Integration of POC diagnostic STI screening into first-visit antenatal care services was feasible and highly acceptable for HIV-infected pregnant women.

There is a lack of evidence on the burden of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) among HIV-infected pregnant women in South Africa. We conducted a cross-sectional analysis of HIV-infected pregnant women in two healthcare facilities in a South African township to determine the prevalence of CT, NG and TV. HIV-infected pregnant women were recruited during the first antenatal care visit for their current pregnancy and requested to self-collect vulvovaginal swab specimens. Specimens were tested for CT, NG and TV using the Xpert® assay (Cepheid, Sunnyvale, CA). Of 247 tested for CT, NG and TV, 47.8% tested positive for at least one organism; CT = 36.8%, TV = 23.9%, NG = 6.9%. Forty three (17.4%) had multiple infections, of which 42 included CT as one of the infecting organisms. Of the 118 participants who tested positive for at least one sexually transmitted infection (STI), 23.7% reported STI-like symptoms. Among women who tested positive for CT, 29.7% reported symptoms while 47.1 and 27.1% of those who tested positive for NG and TV, respectively, reported symptoms. The high STI prevalence coupled with the low symptom prevalence among infected individuals justifies the use of diagnostic screening approaches rather than syndromic management of STIs in this setting.

Background: Recently, we reported that toll-like receptor (TLR)2 and TLR4 localized on the glomerular endothelium in the glomeruli of streptozotocin (STZ)-induced type 1 diabetic mice and high fat diet feed-induced type 2 diabetic mice, and that periodontal pathogen Porphyromonas gingivalis LPS (Pg-LPS) administration lowered the survival rate of diabetic mice. The present study aims to examine the effect of TLR4 blocking on the suppression of Pg-LPS-induced diabetic nephropathy., Methods: The survival rate and morphological/biochemical features for streptozotocin-induced diabetic mice with Pg-LPS and TLR4 blocker eritoran administration were investigated by reporter gene assay, urine and blood analysis, immunohistochemistry, and real time-PCR., Results and Conclusions: All of the diabetic mice administered Pg-LPS were euthanized within the survival period of almost all of the diabetic mice. The blood urea nitrogen and creatinine, expression of TLR2 and TGF-b, and type 1 collagen accumulation, in the diabetic mice increased significantly with the Pg-LPS administration. In spite of the limited TLR4 activation with Pg-LPS, the TLR4 blocker eritoran decreased blood urea nitrogen and creatinine, and raised the survival rate of the Pg-LPS-administered diabetic mice slightly. The high expression levels of TLR2, TGF-b, and type 1 collagen in Pg-LPS-administered diabetic mice decreased with eritoran. Nuclear STAT3 which enhances TLR2 expression was detected in the TLR2-expressing glomeruli of diabetic mice. The TLR2 and STAT3 gene expression increased by the Pg-LPS administration but decreased with eritoran. These may suggest that Pg-LPS-induced diabetic nephropathy is mainly dependent on TLR2 signaling on glomerular endothelial cells, and that TLR4 blocker eritoran may play a role to slow the progress of diabetic nephropathy.

Rural South African men who have sex with men (MSM) are likely to be underserved in terms of access to relevant healthcare and HIV prevention services. While research in urban and peri-urban MSM populations has identified a range of factors affecting HIV risk in South African MSM, very little research is available that examines HIV risk and prevention in rural MSM populations. This exploratory study begins to address this lack by assessing perceptions of HIV risk among MSM in rural Limpopo province. Using thematic analysis of interview and discussion data, two overarching global themes that encapsulated participants' understandings of HIV risk and the HIV risk environment in their communities were developed. In the first theme, "community experience and the rural social environment", factors affecting HIV risk within the broad risk environment were discussed. These included perceptions of traditional value systems and communities as homophobic; jealousy and competition between MSM; and the role of social media as a means of meeting other MSM. The second global theme, "HIV/AIDS knowledge, risk and experience", focused on factors more immediately affecting HIV transmission risk. These included: high levels of knowledge of heterosexual HIV risk, but limited knowledge of MSM-specific risk; inconsistent condom and lubricant use; difficulties in negotiating condom and lubricant use due to uneven power dynamics in relationships; competition for sexual partners; multiple concurrent sexual partnerships; and transactional sex. These exploratory results suggest that rural South African MSM, like their urban and peri-urban counterparts, are at high risk of contracting HIV, and that there is a need for more in-depth research into the interactions between the rural context and the specific HIV risk knowledge and behaviours that affect HIV risk in this population.

Background: The involvement of Global Health Initiatives (GHIs) in delivering health services in low and middle income countries (LMICs) depends on effective collaborative working at scales from the local to the international, and a single GHI is effectively constructed of multiple collaborations. Research is needed focusing on how collaboration functions in GHIs at the level of health service management. Here, collaboration between local implementing agencies and departments of health involves distinct power dynamics and tensions. Using qualitative data from an evaluation of a health partnership in South Africa, this article examines how organisational power dynamics affected the operation of the partnership across five dimensions of collaboration: governance, administration, organisational autonomy, mutuality, and norms of trust and reciprocity., Results: Managing the tension between the power to provide resources held by the implementing agency and the local Departments' of Health power to access the populations in need of these resources proved critical to ensuring that the collaboration achieved its aims and shaped the way that each domain of collaboration functioned in the partnership., Conclusions: These findings suggest that it is important for public health practitioners to critically examine the ways in which collaboration functions across the scales in which they work and to pay particular attention to how local power dynamics between partner organisations affect programme implementation.

South Africa's paediatric antiretroviral therapy (ART) programme is managed using a monitoring and evaluation tool known as TIER.Net. This electronic system has several advantages over paper-based systems, allowing profiling of the paediatric ART programme over time. We analysed anonymized TIER.Net data for HIV-infected children aged <15 years who had initiated ART in a rural district of South Africa between 2005 and 2014. We performed Kaplan-Meier survival analysis to assess outcomes over time. Records of 5461 children were available for analysis; 3593 (66%) children were retained in care. Losses from the programme were higher in children initiated on treatment in more recent years (P < 0·0001) and in children aged ≤1 year at treatment initiation (P < 0·0001). For children aged <3 years, abacavir was associated with a significantly higher rate of loss from the programme compared to stavudine (hazard ratio 1·9, P < 0·001). Viral load was suppressed in 48-52% of the cohort, with no significant change over the years (P = 0·398). Analysis of TIER.Net data over time provides enhanced insights into the performance of the paediatric ART programme and highlights interventions to improve programme performance.

Aims: To determine the burden of disease in a unique sample of patients with uveitis from a rural South African setting., Methods: Data in this cross-sectional study were collected from patients presenting with uveitis (n=103) at the ophthalmology outpatient department of three hospitals in rural South Africa. Demographic and clinical data were collected, and laboratory analysis of aqueous humour, serological evaluation and routine diagnostics for tuberculosis (TB) were performed., Results: Sixty-six (64%) participants were HIV infected. Uveitis was predominantly of infectious origin (72%) followed by idiopathic (16%) and autoimmune (12%). Infectious uveitis was attributed to herpes virus (51%), Mycobacterium tuberculosis (24%) and Treponema pallidum (7%) infection. HIV-infected individuals were more likely to have infectious aetiology of uveitis compared with HIV-uninfected individuals (83% vs 51%; p=0.001)., Conclusions: Microbial aetiology of uveitis is common in areas where HIV and TB are endemic. In these settings, a high index of suspicion for infectious origin of uveitis is warranted., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To evaluate the performance of three different guidelines for the management of vaginal discharge syndrome (VDS) for women living in a rural setting in South Africa., Methods: We conducted a secondary analysis of data from a cross-sectional study in Mopani District, South Africa. The 2015 and 2008 guidelines of the South African Department of Health (DoH) and the most recent WHO guidelines were evaluated for adequate treatment of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and Trichomonas vaginalis infection., Results: Of the 489 women included in this analysis, 35% presented with VDS according to the DoH and 30% per WHO definition of VDS. Fifty-six per cent of the women with VDS would be treated adequately for these STI when using the 2015 DoH guideline, whereas 76% (P = 0.01) and 64% (P = 0.35) would receive adequate treatment with the 2008 DoH and WHO guidelines, respectively. Of the symptomatic women who tested negative for all four STI, STI treatment would have been indicated for 36% as per 2015 DoH guideline vs. 69% (P < 0.001) per 2008 DoH and 67% (P < 0.001) per WHO guidelines., Conclusion: A considerable proportion of symptomatic women infected with these common curable STI would receive adequate treatment when using a syndromic management approach, and significant differences exist between the three guidelines. Many symptomatic women without these STI receive broad-spectrum antibiotics, so new approaches are needed to improve syndromic STI control., (© 2016 John Wiley & Sons Ltd.)

The purpose of this investigation was to determine the clinical and corneal microbial profile of infectious keratitis in a high human immunodeficiency virus (HIV) prevalence setting in rural South Africa. Data in this cross-sectional study were collected from patients presenting with symptoms of infectious keratitis (n = 46) at the ophthalmology outpatient department of three hospitals in rural South Africa. Corneal swabs were tested for herpes simplex virus type 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV) and adenovirus DNA by real-time polymerase chain reaction (PCR) and for bacteria and fungi by culture. Based on clinical history, disease characteristics and laboratory results, 29 (63 %) patients were diagnosed as viral keratitis, including 14 (48 %) viral keratitis cases complicated by bacterial superinfection, and 17 (37 %) as bacterial keratitis. VZV and HSV-1 DNA was detected in 11 (24 %) and 5 (11 %) corneal swabs, respectively. Among clinically defined viral keratitis cases, a negative viral swab was predominantly (93 %) observed in cases with subepithelial inflammation and was significantly associated with an increased duration of symptoms (p = 0.003). The majority of bacteria cultured were Gram-positive (24/35), including Staphylococcus epidermidis and S. aureus. Viral aetiology was significantly associated with a history of herpes zoster ophthalmicus (p < 0.001) and a trend was observed between viral aetiology and HIV infection (p = 0.06). Twenty-one (47 %) keratitis cases were complicated by anterior uveitis, of which 18 (86 %) were HIV-infected cases with viral keratitis. The data implicate a high prevalence of herpetic keratitis, in part complicated by bacterial superinfection and/or uveitis, in HIV-infected individuals presenting with infectious keratitis in rural South Africa.

Background: The Xpert(®) MTB/RIF assay is widely used for Mycobacterium tuberculosis detection. However, specimen transport remains a challenge. PrimeStore Molecular Transport Medium(®) (PS-MTM) inactivates specimens and stabilizes DNA/RNA at ambient temperature for subsequent molecular detection., Objective: To compare the detection of M. tuberculosis concentrations in PS-MTM using Xpert and real-time polymerase chain reaction (RT-PCR), and smear-positive sputum specimens collected using a flocked swab., Methods: Dilutions of M. tuberculosis in PS-MTM and phosphate buffered saline (PBS) were analyzed using the Xpert assay and commercial RT-PCR. Smear-positive (1+ to 3+) sputum specimens (n = 17) were transferred by flocked swab into PS-MTM and PBS, and were compared to standard 1.0 ml sputum Xpert analysis., Results: Using the Xpert assay, cycle threshold values from high M. tuberculosis concentrations in PS-MTM (>10(3) colony forming units [cfu]/ml) were increased compared to control. In contrast, M. tuberculosis samples containing <10(3) cfu/ml, i.e., low concentrations, suspended in PS-MTM resulted in detection down to 10 cfu/ml. Xpert detection efficiency in PS-MTM treated samples (63.2%) was improved compared to PBS controls (34.9%). Xpert detected M. tuberculosis in all sputum specimens collected by flocked swabs in PS-MTM, and correlated with routine Xpert detection., Conclusions: PS-MTM enhances M. tuberculosis detection at low concentrations of M. tuberculosis, and provides a simplified and efficient collection method for Xpert detection.

Background: Sexual behaviour is a core determinant of the HIV and sexually transmitted infection (STI) epidemics in women living in rural South Africa. Knowledge of sexual behaviour in these areas is limited, but constitutes essential information for a combination prevention approach of behavioural change and biomedical interventions., Methods: This descriptive study was conducted in rural Mopani District, South Africa, as part of a larger study on STI. Women of reproductive age (18-49 years) who reported sexual activity were included regardless of the reason for visiting the facility. Questionnaires were administered to 570 women. We report sexual behaviour by age group, ethnic group and self-reported HIV status., Results: Young women (<25 years) were more likely to visit bars, practice fellatio, have concurrent sexual partners and report a circumcised partner than older women (>34 years); there was no difference for condom use during last sex act (36 % overall). Sotho women were more likely to report concurrent sexual partners whereas Shangaan women reported more frequent intravaginal cleansing and vaginal scarring practice in our analysis. HIV-infected women were older, had a higher number of lifetime sexual partners, reported more frequent condom use during the last sex act and were more likely to have a known HIV-infected partner than women without HIV infection; hormonal contraceptive use, fellatio, and a circumcised partner were less often reported., Conclusions: This study provides insight into women's sexual behaviour in a rural South African region. There are important differences in sexual behaviour by age group and ethnicity and HIV status; these should be taken into account when designing tailor-made prevention packages.

Objectives: To assess the performance of an innovative method of transporting sputum to centralised facilities for molecular detection of Mycobacterium tuberculosis: using a swab to inoculate sputum in a transport medium, PrimeStore(®) Molecular Transport Medium (PS-MTM)., Methods: Two sputum specimens were obtained from suspected patients with tuberculosis (TB) at rural healthcare facilities in South Africa. A swab was taken from each specimen and placed into PS-MTM, prior to it being processed by either liquid culture or Xpert MTB/RIF assay (Xpert)., Results: A total of 141 patients (including 47 with laboratory-confirmed TB) were included in this analysis. M. tuberculosis was detected at 29% by culture and 29% by Xpert, whereas 31% tested positive by IS6110 real-time PCR of PS-MTM from the culture and 36% from the Xpert-paired specimen. Concordance between the method under evaluation with culture was 82% (McNemar, P = 0.55) and 84% (McNemar, P = 0.05) for Xpert. Stratified by culture result, the detection rate by IS6110 real-time PCR of PS-MTM was similar to Xpert for patients with positive culture (P = 0.32), but significantly higher if culture was negative (P = 0.008)., Conclusions: These results suggest that swab collection of sputum into PS-MTM for transport is a promising method for diagnosis of TB in rural healthcare settings, thereby potentially improving the options available for molecular diagnosis of TB in countries incapable of applying decentralised high-tech molecular testing., (© 2016 John Wiley & Sons Ltd.)

Objectives: To describe the spectrum of ocular complications of herpes zoster ophthalmicus (HZO) in rural South Africa., Methods: Patients presenting with visual complaints and active or healed HZO at the ophthalmology outpatient department of three hospitals in rural South Africa were included in this study. Demographic and clinical data were collected, and HIV status was determined for all participants., Results: Forty-eight patients were included, and 81% were HIV infected. Poor vision was reported by 94% of patients, painful eye by 79% and photophobia by 63%. A diverse spectrum of ocular complications was observed with corneal inflammation and opacification in 77% followed by anterior uveitis in 65%. The majority (65%) presented with late-stage ocular complications associated with irreversible loss of vision whereas early-stage complications, such as punctate epithelial keratitis and anterior uveitis, were less common. Blindness of the affected eye was observed in 68% of patients with late-stage complications. There was a considerable delay between onset of symptoms and first presentation to the ophthalmology outpatient department (median time 35 days; range 1-2500 days), and longer delay was associated with late-stage ocular complications (P = 0.02)., Conclusions: HZO patients present with relatively late-stage ocular complications, and blindness among these patients is common. The delayed presentation to the ophthalmology outpatient department of hospitals in our rural setting is of concern, and efforts to improve ocular outcomes of HZO are urgently needed., (© 2015 John Wiley & Sons Ltd.)

We report a case of progressive, cephalosporin-susceptible, Neisseria gonorrhoeae conjunctivitis despite successful treatment of male urethritis syndrome. We hypothesize that conjunctival infection progressed due to insufficient penetration of cefixime and azithromycin and point out that extragenital infection and male urethritis may not be cured simultaneously in settings where the syndromic approach is used.

We analyzed data of 263 women with at least one genital or anorectal sexually transmitted infection from a cross-sectional study conducted in rural South Africa. We provide new insights concerning the concurrence of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis infections as well as the characteristics of bacterial loads., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

The technical limitations of common tests used for detecting pyrazinamide (PZA) resistance in Mycobacterium tuberculosis isolates pose challenges for comprehensive and accurate descriptions of drug resistance in patients with multidrug-resistant tuberculosis (MDR-TB). In this study, a 606-bp fragment (comprising the pncA coding region plus the promoter) was sequenced using Ion Torrent next-generation sequencing (NGS) to detect associated PZA resistance mutations in 88 recultured MDR-TB isolates from an archived series collected in 2001. These 88 isolates were previously Sanger sequenced, with 55 (61%) designated as carrying the wild-type pncA gene and 33 (37%) showing mutations. PZA susceptibility of the isolates was also determined using the Bactec 460 TB system and the Wayne test. In this study, isolates were recultured and susceptibility testing was performed in Bactec 960 MGIT. Concordance between NGS and MGIT results was 93% (n = 88), and concordance values between the Bactec 460, the Wayne test, or pncA gene Sanger sequencing and NGS results were 82% (n = 88), 83% (n = 88), and 89% (n = 88), respectively. NGS confirmed the majority of pncA mutations detected by Sanger sequencing but revealed several new and mixed-strain mutations that resolved discordancy in other phenotypic results. Importantly, in 53% (18/34) of these isolates, pncA mutations were located in the 151 to 360 region and warrant further exploration. In these isolates, with their known resistance to rifampin, NGS of pncA improved PZA resistance detection sensitivity to 97% and specificity to 94% using NGS as the gold standard and helped to resolve discordant results from conventional methodologies., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Objectives: Recently, we reported a high prevalence (16%) of urogenital Chlamydia trachomatis infections among women in a rural setting in South Africa. Molecular epidemiological studies on C. trachomatis infections could provide insights into the characteristics of this epidemic, yet such data are not available. The objective of this study was therefore to assess the distribution of C. trachomatis strains among women from a South African rural community, the Mopani district, and to compare it with strains from Amsterdam, the Netherlands., Methods: High-resolution multilocus sequence typing (hr-MLST) was used to study urogenital C. trachomatis infections in women visiting primary healthcare facilities across rural Mopani District in Limpopo Province, South Africa. Sequence types (STs) were compared with 100 strains from women visiting the sexually transmitted infection clinic in Amsterdam, the Netherlands., Results: Full hr-MLST data were obtained for C. trachomatis infection in 43 women from Mopani district. Using the complete hr-MLST profile of all 43 women from Mopani district, 26 STs could be identified, of which 18 (69%) were novel to the hr-MLST database. The remaining STs clustered together with strains from Amsterdam., Conclusions: Hr-MLST data revealed a diverse molecular epidemiology with novel STs and a specific cluster for the Mopani district. Also C. trachomatis types that occur worldwide were detected., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Urogenital Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most prevalent bacterial STIs worldwide. Molecular tests are the standard for the detection of CT and NG, as these are difficult to culture. The recently introduced CE-IVD marked GMT Presto assay promises to be a valuable addition in CT and NG diagnostics. The advantage of the Presto assay is that it works on many PCR systems and the DNA can be isolated by any system.We compared the Presto assay to the widely used Roche cobas® 4800 CT/NG test for the detection of CT and NG in 612 vaginal and rectal dry collected swabs. Discrepant samples were tested by the TIB MOLBIOL Lightmix Kit 480 HT CT/NG assay. The alloyed gold standard was defined as two concurring Presto and cobas® 4800 results, or, with discrepant Presto and cobas® results, two concurring results of either test together with the Lightmix Kit 480 HT CT/NG assay. For the Presto assay,we observed 77 CT positive (13%) and 22 NG positive (3,6%) vaginal samples, and 41 CT positive (6,7%) and 11 NG positive (1,8%) rectal samples. For the cobas® 4800 assay,we observed 77 CT positive (13%) and 21NG positive (3,4%) vaginal samples, and 39 CT positive (6,4%) and 11 NG positive (1,8%) rectal samples. Ten CT samples were discrepant between Presto and cobas® 4800 CT/NG assays, while two NG samples were discrepant. CT sensitivity in both assays was 100% compared to the alloyed gold standard. The sensitivity was 100% for both vaginal and rectal dry swabs, underlining the suitability of these sample types for detection of CT and NG. The Presto assay is therefore valuable for molecular detection of CT and NG in dry vaginal and rectal swabs.

Background: Modern molecular-based approaches for the detection of Mycobacterium tuberculosis in sputum samples promise quicker and more accurate detection of cases. However, processing sputum samples at central diagnostic facilities provides a diagnostic approach, but requires a safe and efficient system that is not affected by transport delays and ambient temperature to be feasible. We evaluated the technical properties of PrimeStore®-Molecular Transport Medium (PS-MTM) for its ability to inactivate mycobacteria, ensuring stability of DNA over time at ambient temperatures and to assess the compatibility of the transport medium with DNA extraction systems., Methods: Assessment of the transport medium for application of sputum samples processed for the detection of M. tuberculosis included the inactivation of M. tuberculosis in spiked sputum samples, compatibility of the medium with three commercial nucleic extraction systems and stability of DNA in the medium at ambient temperature over 28 days. We further performed a clinical laboratory evaluation on 256 sputum specimens sent for tuberculosis investigation., Results: Complete inactivation of M. tuberculosis occurred within 30 min of exposure at a ratio of 1:3 for sputum to PS-MTM. Sputum specimen in PS-MTM showed very good compatibility with automated bead-based extraction systems, producing high DNA output (estimated lower limits of detection: ~170 CFU/ml). Furthermore, PS-MTM samples remained stable over 28 days at ambient temperature displaying no significant change over time in Ct-values (<5% on a mean starting value of 22.47). Of the 256 clinical sputum specimens, 10.2% were culture positive and 11.0% were positive by real-time PCR of PS-MTM samples., Conclusions: Collecting and transporting sputum from TB suspects in PS-MTM offer safe transport at ambient temperature, DNA stability for extended periods without cooling and specimens directly suitable for molecular testing. This novel approach may support introduction and further scale-up of molecular diagnostics for TB in resource-limited settings., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: A pragmatic three-tiered approach to monitor the world's largest antiretroviral treatment (ART) programme was adopted by the South African National Department of Health in 2010. With the rapid expansion of the programme, the limitations of the paper-based register (tier 1) were the catalyst for implementation of the stand-alone electronic register (tier 2), which offers simple digitisation of the paper-based register. This article engages with theory on implementation to identify and contextualise enabling and constraining factors for implementation of the electronic register, to describe experiences and use of the register, and to make recommendations for implementation in similar settings where standardisation of ART monitoring and evaluation has not been achieved., Methods: We conducted a qualitative evaluation of the roll-out of the register. This comprised twenty in-depth interviews with a diverse sample of stakeholders at facility, sub-district, and district levels of the health system. Facility-level participants were selected across five sub-districts, including one facility per sub-district. Responses were coded and analysed using a thematic approach. An implementation science framework guided interpretation of the data., Results & Discussion: We identified the following seven themes: 1) ease of implementation, 2) perceived value of an electronic M&E system, 3) importance of stakeholder engagement, 4) influence of a data champion, 5) operational and logistical factors, 6) workload and role clarity, and 7) importance of integrating the electronic register with routine facility monitoring and evaluation. Interpreting our findings through an implementation theory enabled us to construct the scaffolding for implementation across the five facility-settings. This approach illustrated that implementation was not a linear process but occurred at two nodes: at the adoption of the register for roll-out, and at implementation at facility-level., Conclusion: In this study we found that relative advantage of an intervention and stakeholder engagement are critical to implementation. We suggest that without these aspects of implementation, formative and summative outcomes of implementation at both the adoption and coalface stages of implementation would be negatively affected.

Setting: Mopani District, South Africa., Objective: To explore remote, molecular detection of Mycobacterium tuberculosis from sputum transported using PrimeStore(®) Molecular Transport Medium (PS-MTM) compared to settings where microscopy or Xpert(®) MTB/RIF is used as the baseline test., Design: Two sputum specimens were collected from patients with cough of ⩾ 2 weeks at clinics in rural South Africa. Shortly after expectoration and before processing using Xpert, microscopy and liquid culture, a flocked swab was swirled in each of these specimens and placed in PS-MTM. Swabs were stored and transported to the United States at ambient temperature for real-time PrimeMix(®) polymerase chain reaction (PM-PCR)., Results: Of 132 patients, 23 (17%) were positive on microscopy, 39 (30%) on Xpert and 44 (33%) by PS-MTM/PM-PCR. Concordance of PS-MTM/PM-PCR with positive microscopy and Xpert was respectively 96% and 85%. Of 107 microscopy-negative samples, 22 (21%) were positive using PS-MTM/PM-PCR, while 11/91 (12%) Xpert-negative samples were PS-MTM/PM-PCR-positive. PS-MTM/PM-PCR positivity was significantly higher than smear microscopy positivity (P < 0.001), but similar to Xpert (P = 0.33)., Conclusion: PCR testing of specimens transported in PS-MTM would enhance TB diagnosis in settings where smear microscopy is the baseline diagnostic test, and could provide an alternative in settings where Xpert testing is not available.

Remnant specimens from 601 women obtained in a cross-sectional study from rural South Africa were tested for Mycoplasma genitalium. Overall, 10.8% of women were infected with M. genitalium either in the vagina or in the rectum. Macrolide resistance, although of low prevalence, in M. genitalium is described for the first time in Sub-Saharan Africa.

Staphylococcus aureus is a versatile pathogen of medical significance, using multiple virulence factors to cause disease. A prophylactic S. aureus 4-antigen (SA4Ag) vaccine comprising capsular polysaccharide (types 5 and 8) conjugates, clumping factor A (ClfA) and manganese transporter C (MntC) is under development. This study was designed to characterize S. aureus isolates recovered from infected patients and also to investigate approaches for examining expression of S. aureus vaccine candidates and the host response during human infection. Confirmation of antigen expression in different disease states is important to support the inclusion of these antigens in a prophylactic vaccine. Hospitalized patients with diagnosed S. aureus wound (27) or bloodstream (24) infections were enrolled. Invasive and nasal carriage S. aureus isolates were recovered and characterized for genotypic diversity. S. aureus antigen expression was evaluated directly by real-time, quantitative, reverse-transcriptase PCR (qRT-PCR) analysis and indirectly by serology using a competitive Luminex immunoassay. Study isolates were genotypically diverse and all had the genes encoding the antigens present in the SA4Ag vaccine. S. aureus nasal carriage was detected in 55% of patients, and in those subjects 64% of the carriage isolates matched the invasive strain. In swab samples with detectable S. aureus triosephosphate isomerase housekeeping gene expression, RNA transcripts encoding the S. aureus virulence factors ClfA, MntC, and capsule polysaccharide were detected by qRT-PCR. Antigen expression was indirectly confirmed by increases in antibody titer during the course of infection from acute to convalescent phase. Demonstration of bacterial transcript expression together with immunological response to the SA4Ag antigens in a clinically relevant patient population provides support for inclusion of these antigens in a prophylactic vaccine.

Religion has substantial - positive and negative - influence on South Africa's HIV context. This qualitative study explored possibilities for positive church engagement in paediatric HIV care in a rural district in Limpopo Province, South Africa. Opinions, attitudes and experiences of various stakeholders including religious leaders, healthcare workers and people infected/affected with/by HIV were investigated through participant observation, semi-structured interviews and focus group discussions. During the research the original focus on paediatric HIV care shifted to HIV care in general in reaction to participant responses. Participants identified three main barriers to positive church engagement in HIV care: (a) stigma and disclosure; (b) sexual associations with HIV and (c) religious beliefs and practices. All participant groups appreciated the opportunity and relevance of strengthening church involvement in HIV care. Opportunities for positive church engagement in HIV care that participants identified included: (a) comprehensive and holistic HIV care when churches and clinics collaborate; (b) the wide social reach of churches and (c) the safety and acceptance in churches. Findings indicate that despite barriers great potential exists for increased positive church engagement in HIV care in rural South Africa. Recommendations include increased medical knowledge and dialogue on HIV/AIDS within church settings, and increased collaboration between churches and the medical sector.

Mycobacterium tuberculosis infection is an important cause of sight-threatening chorioretinitis in HIV-infected individuals living in M. tuberculosis endemic areas. We present a case of tuberculous chorioretinitis in a HIV-infected man after recent initiation of antiretroviral therapy in rural South Africa, who had nearly complete resolution of clinical signs and symptoms after standard tuberculosis treatment. His presentation was most likely associated with immune reconstitution inflammatory syndrome.

Healthy eyes and good vision are important determinants of populations' health across the globe. Sub-Saharan Africa is affected by simultaneous epidemics of ocular infections and human immunodeficiency virus (HIV). Ocular infection and its complications, along with cataract and ocular trauma, are common conditions in this region with great impact on daily life. In this review, we discuss the epidemiology, clinical manifestations and microbial aetiology of the most important infectious ocular conditions in sub-Saharan Africa: conjunctivitis, keratitis and uveitis. We focus specifically on the potential association of these infections with HIV infection, including immune recovery uveitis. Finally, challenges and opportunities for clinical management are discussed, and recommendations made to improve care in this neglected but very important clinical field., (© 2014 John Wiley & Sons Ltd.)

Unlabelled: Peripheral neuropathy is a well-known side effect of antiretroviral therapy (ART) in adult patients and is particularly related to the use of nucleoside reverse transcriptase inhibitors. This class of drugs is included in all first-line paediatric ART regimens in Africa, but data on the prevalence of neuropathy in children are scarce. In this cross-sectional study, 182 HIV-infected children on ART in rural South Africa were assessed for peripheral neuropathy using the neuropathy symptom score (NSS) and neuropathy disability score (NDS). Peripheral neuropathy was defined as NSS ≥ 5 or NDS ≥ 3. Neurological assessment was completed for 174 children (96 %). Symptoms of neuropathy were reported in NSS by 48 children (28 %; 95 % confidence interval (CI) 21-34 %), and signs were observed in NDS in 25 children (14 %; 95 % CI 12-16 %). A diagnosis of peripheral neuropathy was established in 42 children (24 %; 95 % CI 18-30 %). Independent risk factors for peripheral neuropathy were co-trimoxazole prophylaxis (adjusted odds ratio 0.45; 95 % CI 0.21-0.95, p = 0.036) and didanosine use (adjusted odds ratio 12; 95 % CI 1.3-116, p = 0.030)., Conclusion: Peripheral neuropathy as determined by clinical assessment is a common condition in African children on ART.

Background: Epidemiological data of genital chlamydia and gonorrhea, required to inform design and implementation of control programs, are limited for rural Africa. There are no data on the prevalence of rectal or pharyngeal infections among African women., Methods: A cross-sectional study of 604 adult women visiting 25 primary health care facilities in rural South Africa was conducted. Vaginal, anorectal, and oropharyngeal swabs were tested for Chlamydia trachomatis and Neisseria gonorrhoeae., Results: Prevalence of genital chlamydia was 16% and that of gonorrhea was 10%; rectal chlamydial infection was diagnosed in 7.1% and gonococcal in 2.5% of women. One woman had pharyngeal chlamydia. Most women with genital chlamydia (61%) and gonorrhea (57%) were asymptomatic. Independent risk factors for genital chlamydia were younger age (adjusted odds ratio [aOR], 0.96 per year; 95% confidence interval [CI], 0.93-0.98), hormonal contraceptive use (aOR, 2.2; 95% CI, 1.3-3.7), pregnancy (aOR, 2.4; 95% CI, 1.3-4.4), and intravaginal cleansing (aOR, 1.7; 95% CI, 1.04-2.8). Intravaginal cleansing was associated with genital gonorrhea (aOR, 1.9; 95% CI, 1.1-3.3)., Conclusions: Genital and rectal, but not pharyngeal, chlamydia and gonorrhea are highly prevalent and frequently asymptomatic in women in rural South Africa. Young women attending health care facilities for antenatal care or family planning should be prioritized in control efforts.

Seroprevalence data of human herpesviruses (HHVs) are limited for sub-Saharan Africa. These are important to provide an indication of potential burden of HHV-related disease, in particular in human immunodeficiency virus (HIV)-infected individuals who are known to be at increased risk of these conditions in the Western world. In this cross-sectional study among 405 HIV-infected and antiretroviral therapy naïve individuals in rural South Africa the seroprevalence of HHVs was: herpes simplex virus type 1 (HSV-1) (98%), herpes simplex virus type 2 (HSV-2) (87%), varicella zoster virus (VZV) (89%), and 100% for both Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Independent factors associated with VZV seropositivity were low educational status and having children. Lack of in-house access to drinking water was independently associated with positive HSV-1 serostatus, whereas Shangaan ethnicity was associated with HSV-2 seropositivity. Increasing age was associated with higher IgG titres to both EBV and CMV, whereas CD4 cell count was negatively associated with EBV and CMV IgG titres. Moreover, IgG titres of HSV-1 and 2, VZV and CMV, and CMV and EBV were positively correlated. The high HHV seroprevalence emphasises the importance of awareness of these viral infections in HIV-infected individuals in South Africa.

Objectives: To investigate the potential synergy of IL-7-driven T cell-dependent and TLR7-mediated B cell activation and to assess the additive effects of monocyte/macrophages in this respect., Methods: Isolated CD19 B cells and CD4 T cells from healthy donors were co-cultured with TLR7 agonist (TLR7A, Gardiquimod), IL-7, or their combination with or without CD14 monocytes/macrophages (T/B/mono; 1 : 1 : 0,1). Proliferation was measured using 3H-thymidine incorporation and Ki67 expression. Activation marker (CD19, HLA-DR, CD25) expression was measured by FACS analysis. Immunoglobulins were measured by ELISA and release of cytokines was measured by Luminex assay., Results: TLR7-induced B cell activation was not associated with T cell activation. IL-7-induced T cell activation alone and together with TLR7A synergistically increased numbers of both proliferating (Ki67+) B cells and T cells, which was further increased in the presence of monocytes/macrophages. This was associated by up regulation of activation markers on B cells and T cells. Additive or synergistic induction of production of immunoglobulins by TLR7 and IL-7 was associated by synergistic induction of T cell cytokines (IFNγ, IL-17A, IL-22), which was only evident in the presence of monocytes/macrophages., Conclusions: IL-7-induced CD4 T cell activation and TLR7-induced B cell activation synergistically induce T helper cell cytokine and B cell immunoglobulin production, which is critically dependent on monocytes/macrophages. Our results indicate that previously described increased expression of IL-7 and TLR7 together with increased numbers of macrophages at sites of inflammation in autoimmune diseases like RA and pSS significantly contributes to enhanced lymphocyte activation.

We studied blood lactate levels in 253 South African children on antiretroviral therapy. The prevalence of hyperlactatemia was 68% and severity was mild in most cases (69%). There was no association of symptoms and/or signs with hyperlactatemia. Independent predictors were lipo-dystrophy, time on antiretroviral therapy and baseline CD4 count. Increased awareness of hyperlactatemia in African children on antiretroviral therapy is warranted.

Introduction: Blood-stream infection (BSI) is one of the principle determinants of the morbidity and mortality associated with advanced HIV infection, especially in sub-Saharan Africa. Over the last 10 years, there has been rapid roll-out of anti-retroviral therapy (ART) and cotrimoxazole prophylactic therapy (CPT) in many high HIV prevalence African countries., Methods: A prospective cohort of adults with suspected BSI presenting to Queen's Hospital, Malawi was recruited between 2009 and 2010 to describe causes of and outcomes from BSI. Comparison was made with a cohort pre-dating ART roll-out to investigate whether and how ART and CPT have affected BSI. Malawian census and Ministry of Health ART data were used to estimate minimum incidence of BSI in Blantyre district., Results: 2,007 patients were recruited, 90% were HIV infected. Since 1997/8, culture-confirmed BSI has fallen from 16% of suspected cases to 10% (p<0.001) and case fatality rate from confirmed BSI has fallen from 40% to 14% (p<0.001). Minimum incidence of BSI was estimated at 0.03/1000 years in HIV uninfected vs. 2.16/1000 years in HIV infected adults. Compared to HIV seronegative patients, the estimated incidence rate-ratio for BSI was 80 (95% CI:46-139) in HIV-infected/untreated adults, 568 (95% CI:302-1069) during the first 3 months of ART and 30 (95% CI:16-59) after 3 months of ART., Conclusions: Following ART roll-out, the incidence of BSI has fallen and clinical outcomes have improved markedly. Nonetheless, BSI incidence remains high in the first 3 months of ART despite CPT. Further interventions to reduce BSI-associated mortality in the first 3 months of ART require urgent evaluation.

The prevalence of Chlamydia trachomatis varies between ethnic groups in The Netherlands. It is, however, unknown whether this is associated with specific serogroups. The objective of this study was to determine whether serogroup distribution is associated with ethnic origin in the region of The Hague, The Netherlands. Serogroups of 370 microbiologically confirmed C. trachomatis-positive samples were analysed. The samples were obtained from 247 women and 123 men between January and October 2008, of self-reported Dutch Caucasian, Dutch Antillean, Surinamese, N. African/Turkish or other descent. We observed a difference in serogroup distribution comparing Dutch Caucasian women to Dutch Antillean women (χ2 for distribution P = 0·035). Serogroup C was more common in Dutch Antillean women, whereas serogroup B was less common (P = 0·03). This difference was not observed for Dutch Antillean men. The observed difference in distribution of C. trachomatis serogroups between ethnic groups is relevant for further transmission studies.

Background: Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection (STI) worldwide. A strong link between C. trachomatis serogroup/serovar and serological response has been suggested in a previous preliminary study. The aim of the current study was to confirm and strengthen those findings about serological IgG responses in relation to C. trachomatis serogroups and serovars., Methods: The study population (n = 718) consisted of two patient groups with similar characteristics of Dutch STI clinic visitors. We performed genotyping of serovars and used titre based and quantitative commercially available ELISA kits (medac Diagnostika) to determine specific serum IgG levels. Optical density (OD) values generated by both tests were used to calculate the IgG titres (cut-off 1:50). Analyses were conducted stratified by gender., Results: We observed very significant differences when comparing the median IgG titres of three serogroups, B, C and I: in women for B vs. C: p < 0.0001 (median titres B 200 vs. C <50); B vs. I: p < 0.0001 (200 vs. 50), and in men for B vs. C: p = 0.0006 (150 vs. <50); B vs. I: p = 0.0001 (150 vs. <50); C vs. I was not significant for both sexes. Serovars D and E of serogroup B had the highest median IgG titres compared to the other serovars in both men and women: 200 and 200 vs. ≤ 100 for women and 100 and 200 vs. ≤ 75 for men, respectively., Conclusions: This study shows that B group serovars induce higher serological responses compared to the C and I group serovars in vivo in both men and women.

Background: Prepubertal gynecomastia is a rare condition and most frequently classified as idiopathic. In HIV-infected adults gynecomastia is a recognised but infrequent side-effect of antiretroviral treatment (ART) and mostly attributed to efavirenz use. Gynecomastia should be distinguished from pseudogynecomastia as part of the lipodystrophy syndrome caused by Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to avoid incorrect substitution of drugs. In the medical literature only five cases of prepubertal gynecomastia in children taking ART are described and underlying pathogenesis was unknown. The occurrence of adverse effects of ART may interfere with therapy adherence and long-term prognosis and for that reason requires attention. We report the first case of prepubertal gynecomastia in a young girl attributed to efavirenz use., Case Presentation: A seven-year-old African girl presented with true gynecomastia four months after initiation on ART (abacavir, lamivudine, efavirenz). History, physical examination and laboratory tests excluded known causes of gynecomastia and efavirenz was considered as the most likely cause. Six weeks after withdrawal of efavirenz the breast enlargement had completely resolved., Conclusions: Efavirenz-induced gynecomastia may occur in children as well as in adults. With the increasing access to ART, the possibility of efavirenz-exposure and the potential occurrence of its associated side-effects may be high. In resource-poor settings, empirical change from efavirenz to nevirapine may be considered, providing no other known or alarming cause is identified, as efavirenz-induced gynecomastia can resolve quickly after withdrawal of the drug. Timely recognition of gynecomastia as a side-effect of efavirenz is important in order to intervene while the condition may still be reversible, to sustain adherence to ART and to maintain the sociopsychological health of the child.

Objectives: The aims of this study were: to determine the incidence of concurrent infections on a serovar level; to determine the incidence of multiple anatomical infected sites on a detection and genotyping level and analyse site-specific serovar distribution; to identify tissue tropism in urogenital versus rectal specimens., Methods: Chlamydia trachomatis-infected patients in two populations were analysed: 75 visiting the outpatient department of obstetrics and gynaecology of the MC Haaglanden, and 358 visiting the outpatient sexually transmitted disease clinic, The Hague, The Netherlands. The PACE 2 assay (Gen-Probe) was used to detect C trachomatis from urethral, cervical, vaginal, oropharyngeal and anorectal swabs. C trachomatis genotyping was performed on all C trachomatis positive samples, using the CT-DT genotyping assay., Results: Samples from 433 patients (256 female and 177 male) with confirmed C trachomatis infection were analysed. In 11 patients (2.6%), concurrent serovars in one anatomical sample site were present. In 62 (34.1%) female and four (9.3%) male patients, multiple sample site infections were found. A substantial percentage of women tested at the cervical/vaginal and rectal site were found to be positive at both sites (36.1%, 22/61). In men, D/Da and G/Ga serovars were more prevalent in rectal than urogenital specimens (p=0.0081 and p=0.0033, respectively), while serovar E was more prevalent in urogenital specimens (p=0.0012)., Conclusions: The prevalence of multiple serovar infections is relatively low. Significant differences in serovar distribution are found in rectal specimens from men, with serovar G/Ga being the most prominent, suggesting tissue tropism.

Background: The relevance of screening of oropharynx and anorectum in addition to endocervical tests for detection of Chlamydia trachomatis and Neisseria gonorrhoeae infection is unclear in women, while there is a documented benefit of this approach in men who have sex with men., Methods: Female visitors to the sexually transmitted disease (STD) clinic were asked about their sexual practice as a part of the routine electronic patient file. In addition to tests for endocervical infection, swabs were taken from the oropharynx and anorectum to test for C. trachomatis and N. gonorrhoeae based on the history of sexual contact. Routinely, all electronic patient files are anonymously included in a database for surveillance purposes. In this observational study, we analyzed all consultations in the database over an 18 months period., Results: A total of 4299 consultations were registered; 10% of women had endocervical chlamydia and 1.1% had gonorrhea. The detection rates for C. trachomatis and N. gonorrhoeae from oropharyngeal samples were 1.9% and 0.8%, and from anorectal samples 8.7% and 1.7%, respectively. Except for 2 cases of pharyngeal gonorrhea, all oropharyngeal and anorectal infections were asymptomatic. Inclusion of oropharyngeal and anorectal tests in the screening protocol was associated with a percentage increase in prevalence of chlamydia by 9.5% and gonorrhea by 31%, relative to tests for endocervical tests alone. The percentage increase in prevalence was higher than that for the symptom-based approach (3.7% and 10.4%, respectively)., Conclusions: Inclusion of oropharyngeal and anorectal tests in the STD screening protocol increases the prevalence of chlamydia and gonorrhea in women. Screening of anatomical sites based on sexual history is preferred over a symptom-based protocol.

Background: Sexually transmitted infection (STI) screening programmes are implemented in many countries to decrease burden of STI and to improve sexual health. Screening for Chlamydia trachomatis and Neisseria gonorrhoeae has a prominent role in these protocols. Most of the screening programmes concerning men having sex with men (MSM) are based on opportunistic urethral testing. In The Netherlands, a history-based approach is used. The aim of this study is to evaluate the protocol of screening anatomic sites for C. trachomatis and N. gonorrhoeae infection based on sexual history in MSM in routine practice in The Netherlands., Methods: All MSM visiting the clinic for STI in The Hague are routinely asked about their sexual practice during consulting. As per protocol, tests for urogenital, oropharyngeal and anorectal infection are obtained based on reported site(s) of sexual contact. All consultations are entered into a database as part of the national STI monitoring system. Data of an 18 months period were retrieved from this database and analysed., Results: A total of 1455 consultations in MSM were registered during the study period. The prevalence of C. trachomatis and N. gonorrhoeae per anatomic site was: urethral infection 4.0% respectively and 2.8%, oropharynx 1.5% and 4.2%, and anorectum 8.2% and 6.0%. The majority of chlamydia cases (72%) involved a single anatomic site, which was especially manifest for anorectal infections (79%), while 42% of gonorrhoea cases were single site. Twenty-six percent of MSM with anorectal chlamydia and 17% with anorectal gonorrhoea reported symptoms of proctitis; none of the oropharyngeal infections were symptomatic. Most cases of anorectal infection (83%) and oropharyngeal infection (100%) would have remained undiagnosed with a symptom-based protocol., Conclusions: The current strategy of sexual-history based screening of multiple anatomic sites for chlamydia and gonorrhoea in MSM is a useful and valid guideline which is to be preferred over a symptom-based screening protocol.