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Background: Hormonal contraception has been associated with a reduced risk of vaginal dysbiosis, which in turn has been associated with reduced prevalence of sexually transmitted infections (STIs), including HIV. Vaginal rings are used or developed as delivery systems for contraceptive hormones and antimicrobial drugs for STI and HIV prevention or treatment. We hypothesized that a contraceptive vaginal ring (CVR) containing oestrogen enhances a lactobacilli-dominated vaginal microbial community despite biomass accumulation on the CVR’s surface. Methods: We enrolled 120 women for 12 weeks in an open-label NuvaRing® study at Rinda Ubuzima, Kigali, Rwanda. Vaginal and ring microbiota were assessed at baseline and each ring removal visit by Gram stain Nugent scoring (vaginal only), quantitative PCR for Lactobacillus species, Gardnerella vaginalis and Atopobium vaginae, and fluorescent in situ hybridization to visualize cell-adherent bacteria. Ring biomass was measured by crystal violet staining. Results: Bacterial vaginosis (BV) prevalence was 48% at baseline. The mean Nugent score decreased significantly with ring use. The presence and mean log10 concentrations of Lactobacillus species in vaginal secretions increased significantly whereas those of G. vaginalis and presence of A. vaginae decreased significantly. Biomass accumulated on the CVRs with a species composition mirroring the vaginal microbiota. This ring biomass composition and optical density after crystal violet staining did not change significantly over time. Conclusions: NuvaRing® promoted lactobacilli-dominated vaginal microbial communities in a population with high baseline BV prevalence despite the fact that biomass accumulated on the rings. [ABSTRACT FROM AUTHOR]

Background: Contraceptive vaginal rings could play a role in expanding the contraceptive method mix and in preparing communities for the introduction of HIV prevention and multipurpose rings. Methods: We conducted an open label single-centre randomised clinical trial of intermittent versus continuous use of NuvaRing® in Kigali, Rwanda, in 2013–2014. We randomised 120 HIV-negative women 1:1 to intermittent use (three rings with a ring-free week in between rings) or continuous use (four rings without ring-free weeks). Women underwent an interview, counselling, and a speculum examination, and were tested for pregnancy, bacterial vaginosis (BV) by Nugent scoring, yeasts and trichomonads on wet mount, and sexually transmitted infections. Findings: Only one woman withdrew early. Deliberate ring removals were rare, but spontaneous ring expulsions occurred during 14% of ring use periods. There were no incident pregnancies, serious adverse events, serious social harms, or early discontinuations for safety reasons. Systemic side effects were uncommon, and local side effects were not significantly differently distributed between groups except for lower abdominal pain (P = 0.013). The incidence of vaginal yeasts during ring use was high: 22% of intermittent users and 27% of continuous users had incident vaginal yeasts at one or multiple ring removal visits (P = 0.666), and symptomatic vaginal yeast cases were more common in the continuous than intermittent users (P = 0.031). In contrast, mean Nugent scores improved over time in both groups. Conclusions: Intermittent and continuous NuvaRing® use were safe in Rwandan women and improved Nugent scores over time. However, attention should be paid to ring expulsions and to a potential increased risk of vaginal candidiasis. [ABSTRACT FROM AUTHOR]

Background: North-west Ethiopia faces the highest burden world-wide of visceral leishmaniasis (VL) and HIV co-infection. VL-HIV co-infected patients have higher (initial) parasitological failure and relapse rates than HIV-negative VL patients. Whereas secondary prophylaxis reduces the relapse rate, parasitological failure rates remain high with the available antileishmanial drugs, especially when administered as monotherapy. We aimed to determine the initial effectiveness (parasitologically-confirmed cure) of a combination of liposomal amphotericin B (AmBisome) and miltefosine for treatment of VL in HIV co-infected patients. Methodology/Principal findings: We conducted a retrospective cohort study at a Médecins Sans Frontières—supported health center in north-west Ethiopia. We included VL-HIV co-infected adults, treated for VL between January 2011 and August 2014, with AmBisome infusion (30 mg/kg total dose) and miltefosine orally for 28 days (100 mg/day). Proportions of initial treatment outcome categories were calculated. Predictors of initial parasitological failure and of death were determined using multivariable logistic regression. Of the 173 patients included, 170 (98.3%) were male and the median age was 32 years. The proportion of patients with primary VL (48.0%) and relapse VL (52.0%) were similar. The majority had advanced HIV disease (n = 111; 73.5%) and were on antiretroviral therapy prior to VL diagnosis (n = 106; 64.2%). Initial cure rate was 83.8% (95% confidence interval [CI], 77.6–88.6); death rate 12.7% (95% CI, 8.5–18.5) and parasitological failure rate 3.5% (95% CI, 1.6–7.4). Tuberculosis co-infection at VL diagnosis was predictive of parasitological failure (adjusted odds ratio (aOR), 8.14; p = 0.02). Predictors of death were age >40 years (aOR, 5.10; p = 0.009), hemoglobin ≤6.5 g/dL (aOR, 5.20; p = 0.002) and primary VL (aOR, 8.33; p = 0.001). Conclusions/Significance: Initial parasitological failure rates were very low with AmBisome and miltefosine combination therapy. This regimen seems a suitable treatment option. Knowledge of predictors of poor outcome may facilitate better management. These findings remain to be confirmed in clinical trials. [ABSTRACT FROM AUTHOR]

The epidemiology of hepatitis C in Cambodia is not well-known. We evaluated the prevalence of hepatitis C virus (HCV) and risk factors in the HIV cohort of Sihanouk Hospital Center of Hope in Phnom Penh to strengthen the evidence for suitable HCV testing strategies among people living with HIV (PLWH) in Cambodia. All consenting adult PLWH without a history of HCV treatment were tested for HCV between November 2014 and May 2016 according to the CDC algorithm (HCV antibody II electro-chemiluminescence immunoassay, followed by COBAS® AmpliPrep/COBAS® TaqMan® HCV PCR and INNO-LIA® HCV Score immunoblot end-testing). Genotyping was performed using the line probe assay Versant HCV genotype 2.0®. The study enrolled a total of 3045 patients (43% males, median age: 42.5 years, <1% high-risk). HCV antibodies were detected in 230 (7.6%; 95% confidence interval [CI] 6.6–8.5). Upon further testing, HCV antibodies were confirmed in 157 (5.2%; 95% CI 4.4–6.0) and active HCV in 106 (3.5%; 95% CI 2.8–4.2). Viremic prevalence peaked among men aged 50–55 years (7.3%) and women aged >55 years (11.2%). Genotype 1b (45%) and 6 (41%) were predominant. Coinfected patients had a higher aspartate-to-platelet ratio index, lower platelets, a lower HBsAg positivity rate and more frequent diabetes. Based on logistic regression, blood transfusion antecedents (adjusted odds ratio 2.9; 95% CI 1.7–4.9), unsafe medical injections (2.0; 1.3–3.2), and partner (3.4; 1.5–7.6) or household member (2.4; 1.3–3.2) with liver disease were independently associated with HCV in women. However, having a tattoo/scarification (1.9; 1.1–3.4) and household member (3.1; 1.3–7.3) with liver disease were associated with HCV in men. Thus, our study found intermediate endemicity of active hepatitis C in a large Cambodian HIV cohort and provides initial arguments for targeted HCV screening (>50 years, partner/household member with liver disease, diabetes, increased aspartate-to-platelet ratio index) as efficient way forward. [ABSTRACT FROM AUTHOR]

Background: In Ethiopia, case fatality rates among subgroups of visceral leishmaniasis (VL) patients are high. A clinical prognostic score for death in VL patients could contribute to optimal management and reduction of these case fatality rates. We aimed to identify predictors of death from VL, and to develop and externally validate a clinical prognostic score for death in VL patients, in a high HIV co-infection burden area in Ethiopia. Methodology/Principal findings: We conducted a retrospective cohort study in north west Ethiopia. Predictors with an adjusted likelihood ratio ≥1.5 or ≤0.67 were retained to calculate the predictor score. The derivation cohort consisted of 1686 VL patients treated at an upgraded health center and the external validation cohort consisted of 404 VL patients treated in hospital. There were 99 deaths in the derivation cohort and 53 deaths in the external validation cohort. The predictors of death were: age >40 years (score +1); HIV seropositive (score +1); HIV seronegative (score -1); hemoglobin ≤6.5 g/dl (score +1); bleeding (score +1); jaundice (score +1); edema (score +1); ascites (score +2) and tuberculosis (score +1). The total predictor score per patient ranged from -1 to +5. A score of -1, indicated a low risk of death (1.0%), a score of 0 an intermediate risk of death (3.8%) and a score of +1 to +5, a high risk of death (10.4–85.7%). The area under the receiver operating characteristic curve was 0.83 (95% confidence interval: 0.79–0.87) in derivation, and 0.78 (95% confidence interval: 0.72–0.83) in external validation. Conclusions/Significance: The overall performance of the score was good. The score can enable the early detection of VL cases at high risk of death, which can inform operational, clinical management guidelines, and VL program management. Implementation of focused strategies could contribute to optimal management and reduction of the case fatality rates. [ABSTRACT FROM AUTHOR]

Bacterial vaginosis (BV) is a difficult-to-treat recurrent condition in which health-associated lactobacilli are outnumbered by other anaerobic bacteria, such as Gardnerella vaginalis. Certain genotypes of G. vaginalis can produce sialidase, while others cannot. Sialidase is known to facilitate the destruction of the protective mucus layer on the vaginal epithelium by hydrolysis of sialic acid on the glycans of mucous membranes. This process possibly facilitates adhesion of bacterial cells on the epithelium since it has been linked with the development of biofilm in other pathogenic conditions. Although it has not been demonstrated yet, it is probable that G. vaginalis benefits from this mechanism by attaching to the vaginal epithelium to initiate biofilm development. In this study, using vaginal specimens of 120 women enrolled in the Ring Plus study, we assessed the association between the putative G. vaginalis sialidase A gene by quantitative polymerase chain reaction (qPCR), the diagnosis of BV according to Nugent score, and the occurrence of a BV-associated biofilm dominated by G. vaginalis by fluorescence in situ hybridisation (FISH). We detected the putative sialidase A gene in 75% of the G. vaginalis-positive vaginal specimens and found a strong association (p<0.001) between the presence of a G. vaginalis biofilm, the diagnosis of BV according to Nugent and the detection of high loads of the G. vaginalis sialidase A gene in the vaginal specimens. These results could redefine diagnosis of BV, and in addition might guide research for new treatment. [ABSTRACT FROM AUTHOR]

Background: In light of the limitations of the current case finding strategies and the global urgency to improve tuberculosis (TB) case-detection, a renewed interest in active case finding (ACF) has risen. The WHO calls for more evidence on innovative ways of TB screening, especially from low-income countries, to inform global guideline development. We aimed to assess the feasibility of community-based ACF for TB among the urban poor in Cambodia and determine its impact on case detection, treatment uptake and outcome. Methods: Between 9/2/2012-31/3/2013 the Sihanouk Hospital Center of HOPE conducted a door-to-door survey for TB in deprived communities of Phnom Penh. TB workers and community health volunteers performed symptom screening, collected sputum and facilitated specimen transport to the laboratories. Fluorescence microscopy was introduced at three referral hospitals. The GeneXpert MTB/RIF assay (Xpert) was performed at tertiary level for individuals at increased risk of HIV-associated, drug-resistant or smear-negative TB. Mobile phone/short message system (SMS) was used for same-day issuing of positive results. TB workers contacted diagnosed patients and referred them for care at their local health centre. Results: In 14 months, we screened 315.874 individuals; we identified 12.201 aged ≥15 years with symptoms suggestive of TB; 84% provided sputum. We diagnosed 783, including 737 bacteriologically confirmed, TB cases. Xpert testing yielded 41% and 48% additional diagnoses among presumptive HIV-associated and multidrug-resistant TB cases, respectively. The median time from sputum collection to notification (by SMS) of the first positive (microscopy or Xpert) result was 3 days (IQR 2–6). Over 94% commenced TB treatment and 81% successfully completed it. Conclusion: Our findings suggest that among the urban poor ACF for TB, using a sensitive symptom screen followed by smear-microscopy and targeted Xpert, contributed to improved case detection of drug-susceptible and drug-resistant TB, shortening the diagnostic delay, and successfully bringing patients into care. [ABSTRACT FROM AUTHOR]

Background: Although malaria rapid diagnostic tests (RDT) are simple to perform, they remain subject to errors, mainly related to the post-analytical phase. We organized the first large scale SMS based external quality assessment (EQA) on correct reading and interpretation of photographs of a three-band malaria RDT among laboratory health workers in the Democratic Republic of the Congo (DR Congo). Methods and Findings: High resolution EQA photographs of 10 RDT results together with a questionnaire were distributed to health facilities in 9 out of 11 provinces in DR Congo. Each laboratory health worker answered the EQA by Short Message Service (SMS). Filled-in questionnaires from each health facility were sent back to Kinshasa. A total of 1849 laboratory health workers in 1014 health facilities participated. Most frequent errors in RDT reading were i) failure to recognize invalid (13.2–32.5% ) or negative test results (9.8–12.8%), (ii) overlooking faint test lines (4.1–31.2%) and (iii) incorrect identification of the malaria species (12.1–17.4%). No uniform strategy for diagnosis of malaria at the health facility was present. Stock outs of RDTs occurred frequently. Half of the health facilities had not received an RDT training. Only two thirds used the RDT recommended by the National Malaria Control Program. Performance of RDT reading was positively associated with training and the technical level of health facility. Facilities with RDT positivity rates >50% and located in Eastern DR Congo performed worse. Conclusions: Our study confirmed that errors in reading and interpretation of malaria RDTs are widespread and highlighted the problem of stock outs of RDTs. Adequate training of end-users in the application of malaria RDTs associated with regular EQAs is recommended. [ABSTRACT FROM AUTHOR]

Background: HIV prevalence differs by more than an order of magnitude between South Africa's racial groups. Comparing the sexual behaviors and other risk factors for HIV transmission between the different races may shed light on the determinants of South Africa's generalized HIV epidemic. Methods: Five nationally representative and one city-representative population-based surveys of sexual behavior were used to assess the extent to which various risk factors co-varied with HIV prevalence by race in South Africa. Results: In 2004, the prevalence of HIV was 0.5%, 1%, 3.2% and 19.9% in 15–49 year old whites, Indians, coloureds and blacks respectively. The risk factors which co-varied with HIV prevalence by race in the six surveys were age of sexual debut (in five out of five surveys for men and three out of six surveys for women), age gap (zero surveys in men and three in women), mean number of sex partners in the previous year (five surveys in men and three in women) and concurrent partnerships (five surveys in men and one in women). Condom usage and circumcision were both more prevalent in the high HIV prevalence groups. The reported prevalence of concurrency was 6 to 17 times higher in the black as opposed to the white men in the five surveys. Conclusions: The differences in sexual behavior in general, and the prevalence of concurrency and the number of sexual partners in particular, offer a plausible and parsimonious cause to explain a part of the differing prevalences of HIV between South Africa's racial groups. [ABSTRACT FROM AUTHOR]