Effects of schistosomes on host anti-viral immune response and the acquisition, virulence, and prevention of viral infections: A systematic review.

Although a growing number of studies suggest interactions between Schistosoma parasites and viral infections, the effects of schistosome infections on the host response to viruses have not been evaluated comprehensively. In this systematic review, we investigated how schistosomes impact incidence, virulence, and prevention of viral infections in humans and animals. We also evaluated immune effects of schistosomes in those coinfected with viruses. We screened 4,730 studies and included 103. Schistosomes may increase susceptibility to some viruses, including HIV and Kaposi's sarcoma-associated herpesvirus, and virulence of hepatitis B and C viruses. In contrast, schistosome infection may be protective in chronic HIV, Human T-cell Lymphotropic Virus-Type 1, and respiratory viruses, though further research is needed. Schistosome infections were consistently reported to impair immune responses to hepatitis B and possibly measles vaccines. Understanding the interplay between schistosomes and viruses has ramifications for anti-viral vaccination strategies and global control of viral infections.

Associations between age of menarche, early sexual debut and high-risk sexual behaviour among urban Tanzanian schoolgirls: A cross-sectional study.

OBJECTIVES: This cross-sectional survey aimed to explore associations between age of menarche, early sexual debut and high-risk sexual behaviour among urban Tanzanian schoolgirls. METHODS: Secondary schoolgirls aged 17-18 years from Mwanza, Tanzania, participated in structured face-to-face questionnaire-based interviews, conducted by nurses and clinicians. Age of menarche was evaluated in categories of 11-12, 13-14, 15-16 or ≥17 years. Primary outcome measures were self-reported early sexual debut (first vaginal sex at <16 years) and high-risk sexual behaviour, including non-use of condoms, having sex for gifts/money, having older sexual partners and/or other risky behaviours. RESULTS: Of 401 girls enrolled, 174 (43.4%) reported prior vaginal sex. Prevalence of early sexual debut was 14.2% but pressured/forced sex and risky sexual behaviours were common. Adjusted for potential confounding, younger age at menarche was associated with early sexual debut (adjusted odds ratio for linear trend: 1.88 per category, 95% confidence interval: 1.21-2.92, p = 0.005). This association remained after excluding girls with first sex at <8 years or experiencing pressure or force at first sex. Further, adjusted for potential confounding (including ever experiencing forced sex), early sexual debut was associated with high-risk sexual behaviour (adjusted odds ratio: 2.85, 95% confidence interval: 1.38-5.88, p = 0.004). CONCLUSIONS: Among urban Tanzanian school girls, younger age of menarche was associated with early sexual debut, and early sexual debut was associated with high-risk sexual behaviour. Researchers and public health professionals developing and delivering interventions aimed at preventing adverse sexual health outcomes should consider the impact of these early biological and sexual exposures.

Prevalence of G6PD deficiency and submicroscopic malaria parasites carriage in malaria hotspot area in Northwest, Tanzania.

BACKGROUND: The use of primaquine for mass drug administration (MDA) is being considered as a key strategy for malaria elimination. In addition to being the only drug active against the dormant and relapsing forms of Plasmodium vivax, primaquine is the sole potent drug against mature/infectious Plasmodium falciparum gametocytes. It may prevent onward transmission and help contain the spread of artemisinin resistance. However, higher dose of primaquine is associated with the risk of acute haemolytic anaemia in individuals with a deficiency in glucose-6-phosphate dehydrogenase. In many P. falciparum endemic areas there is paucity of information about the distribution of individuals at risk of primaquine-induced haemolysis at higher dose 45 mg of primaquine. METHODS: A retrospective cross-sectional study was carried out using archived samples to establish the prevalence of G6PD deficiency in a malaria hotspot area in Misungwi district, located in Mwanza region, Tanzania. Blood samples collected from individuals recruited between August and November 2010 were genotyped for G6PD deficiency and submicroscopic parasites carriage using polymerase chain reaction. RESULTS: A total of 263 individuals aged between 0 and 87 were recruited. The overall prevalence of the X-linked G6PD A- mutation was 83.7% (220/263) wild type, 8% (21/263) heterozygous and 8.4% (22/263) homozygous or hemizygous. Although, assessment of the enzymatic activity to assign the phenotypes according to severity and clinical manifestation as per WHO was not carried out, the overall genotype and allele frequency for the G6PD deficiency was 16.4% and 13. 2%, respectively. There was no statistically significant difference in among the different G6PD genotypes (p > 0.05). Out of 248 samples analysed for submicroscopic parasites carriage, 58.1% (144/248) were P. falciparum positive by PCR. G6PD heterozygous deficiency were associated with carriage of submicroscopic P. falciparum (p = 0.029). CONCLUSIONS: This study showed that 16.4% of the population in this part of North-western Tanzania carry the G6PD A- mutation, within the range of 15-32% seen in other parts of Africa. G6PD gene mutation is widespread and heterogeneous across the study area where primaquine would be valuable for malaria control and elimination. The maps and population estimates presented here reflect potential risk of higher dose of primaquine being associated with the risk of acute haemolytic anaemia (AHA) in individuals with a deficiency in glucose-6-phosphate dehydrogenase and call further research on mapping of G6PD deficiency in Tanzania. Therefore, screening and education programmes for G6PD deficiency is warranted in a programme of malaria elimination using a higher primaquine dose.

Unmet need for modern contraception by HIV status: findings from community-based studies implemented before and after earlier ART initiation program in rural Tanzania.

BACKGROUND: Tanzania Health policy insists on the need to provide all women access to contraception despite HIV status. We used data from two HIV epidemiologic serological surveys carried out at different periods of ART provision in rural Tanzania to assess the level of unmet need for modern contraception by HIV status and associated factors. METHODS: We performed secondary data analysis of two surveys conducted at the Magu Health and Demographic Surveillance System site, in Mwanza, Tanzania. Information on unmet need for modern contraception was derived from fertility desire and contraception use. Unmet need, HIV status, and socioeconomic and demographic variables were analysed. The percentage of women with unmet needs for modern contraception by HIV status is presented for the 2012 and 2017 surveys. Bivariate and multivariate analyses using logistic regression were used to investigate associated factors showing adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs). RESULTS: Data from 3352 and 3196 women aged 15-49 years collected in the 2012 and 2017 surveys, respectively, were analysed. The percentages of women with unmet needs for modern contraception in the 2012 and 2017 surveys were 30.9% (95% CI 29.4-32.6) and 31.6% (95% CI 30.0-33.3), respectively. The unmet need for modern contraception was 26% lower in HIV-uninfected women in 2012 (aOR = 0.74; 95% CI 0.569-0.973); p = 0.031). Risk factors for unmet need for modern contraception in 2012 were HIV uninfected (adjusted OR = 0.74; 95% CI 0.569-0.973); p = 0.031), married marital status (adjusted OR = 0.768; 95% CI 0.743-0.794); p < 0.0001), higher education (adjusted OR = 0.768; 95% CI 0.743-0.794); p < 0.0001), and taking alcohol (adjusted OR = 0.768; 95% CI 0.743-0.794); p < 0.0001). Only two factors were associated with unmet need for modern contraception in 2017: married marital status (adjusted OR = 0.46; 95% CI 0.305-0.722); p = 0.001) and women who earned for their families (aOR = 0.66; 95% CI 0.494-0.887); p = 0.006). DISCUSSION: Nearly one-third of women had an unmet need for modern contraception, which was lower in HIV-uninfected women than in WLHIV-infected women. The study has identified women whose demand for contraception has not been met: WLHIV, post marital women, women with low education and women who were reported to earn money for their families. Family planning interventions should be tailored to these groups of women.

Primary resistance against integrase strand transfer inhibitors in integrase strand transfer inhibitor-naive patients failing first- and second-line ART in Tanzania.

INTRODUCTION: Sub-Saharan African countries are introducing integrase strand transfer inhibitors (INSTIs) in their ART programmes as the preferred first-line regimen, and dolutegravir is the INSTI of choice due to its potency, tolerability and high genetic barrier to resistance. Dolutegravir was introduced into the first-line ART regimen in Tanzania in 2019. However, there is a paucity of data on the occurrence of mutations in HIV lineages circulating in Tanzania. This study aimed to determine the prevalence of INSTI primary resistance mutations in Tanzanian patients exposed to ART but not INSTIs. METHODS: Plasma samples from 50 INSTI-naive patients failing first- or second-line ART [median (IQR) age: 40 (21.93-46.41) years; 68% women] were subjected to Sanger sequencing of the HIV integrase gene. Participants had been on ART for a median (IQR) duration of 7.32 (4.73-9.29) years, with 80% and 20% failing first- and second-line ART, respectively. RESULTS: No major INSTI mutations were found, but 2 (4%) participants had the accessory mutation T97A. Using the REGA HIV-1 subtyping tool, HIV subtype A1 (53.1%) was found to be dominant, followed by subtypes C (30.6%) and D (16.3%). CONCLUSIONS: This study found no current evidence for transmitted resistance against INSTIs among unexposed patients failing ART and supports the scale-up of INSTI-based regimens. However, the presence of accessory mutations calls for the surveillance of INSTI resistance mutations to ensure that the anticipated long-term desired outcomes are achieved.

Population pharmacokinetics of liposomal amphotericin B in adults with HIV-associated cryptococcal meningoencephalitis.

BACKGROUND: Single, high-dose liposomal amphotericin B (LAmB; AmBisome, Gilead Sciences) has demonstrated non-inferiority to amphotericin B deoxycholate in combination with other antifungals for averting all-cause mortality from HIV-associated cryptococcal meningitis. There are limited data on the pharmacokinetics (PK) of AmBisome. The aim of this study was to describe population PK of AmBisome and conduct a meta-analysis of the available studies to suggest the optimal dosing for cryptococcal meningoencephalitis. METHODS: Data from a Phase II and Phase III trial of high-dose, short-course AmBisome for cryptococcal meningoencephalitis were combined to develop a population PK model. A search was conducted for trials of AmBisome monotherapy and meta-analysis of clinical outcome data was performed. RESULTS: A two-compartment model with first-order clearance of drug from the central compartment fitted the data best and enabled the extent of inter-individual variability in PK to be quantified. Mean (SD) population PK parameter estimates were: clearance 0.416 (0.363)  L/h; volume of distribution 4.566 (4.518) L; first-order transfer of drug from central to peripheral compartments 2.222 (3.351)  h-1, and from peripheral to central compartment 2.951 (4.070)  h-1. Data for the meta-analysis were insufficient to suggest optimal dosing of AmBisome for cryptococcal meningoencephalitis. CONCLUSIONS: This study provides novel insight into the PK of AmBisome at the population level and the variability therein. Our analysis also serves to highlight the paucity of data available on the pharmacodynamics (PD) of AmBisome and underscores the importance of thorough and detailed PK/PD analysis in the development of novel antifungals, by demonstrating the challenges associated with post hoc PK/PD analysis.

HIV testing attitudes and practices amongst 'wealthy men': qualitative evidence from Tanzania.

Evidence from nationally representative surveys conducted in sub-Saharan Africa shows that significant proportions of men in the wealthiest quintile report never having tested for HIV. Despite high prevalence rates in this quintile, no research has been conducted on the HIV testing attitudes and practices of wealthier men. This article reports findings from qualitative research conducted with 23 wealthy men in Tanzania. Whilst wealthy men reported barriers to and enablers of HIV testing previously reported by the general population, concerns around loss of social status and community standing were amplified for members of this demographic. Furthermore, HIV stigma among members of this group remains high. However, enhanced access to HIV testing through private clinics, regular healthcare appointments, health insurance schemes and the means to travel to other countries enables wealthy men to avoid stigma. In settings such as the workplace, wealthy men were able to test in public in their roles as 'leaders' to encourage others to test. Future interventions to increase testing amongst men should target settings in which these leadership roles can be taken advantage of. HIV services also need integrating into the health system to remove the need for testing and treatment to be accessed at separate clinics.

Adolescent Health Series: HPV infection and vaccination in sub-Saharan Africa: 10 years of research in Tanzanian female adolescents - narrative review.

Cervical cancer is the leading cause of cancer-related morbidity and mortality in many sub-Saharan African (SSA) countries, including Tanzania. Most cervical cancer cases worldwide are attributable to infection of the cervix with Human Papillomavirus (HPV), a vaccine-preventable sexually transmitted infection (STI). Over the past 10 years, we have conducted a programme of HPV research in pre-adolescents and adolescents in Mwanza, the second-largest city in Tanzania, which is situated in a malaria-endemic region. In this narrative review article, we summarise the contribution of our work, alongside work of others, to improve the understanding of HPV epidemiology in SSA and development of setting-appropriate, evidence-based intervention strategies. We present evidence for very high prevalence and incidence of HPV infection among female SSA adolescents around the time of sexual debut, describe risk factors for HPV acquisition, and discuss associations between HPV, HIV and other STIs, which are also highly prevalent within this population. We summarise findings from early clinical trials of HPV vaccines in SSA, the first of which was an immunogenicity and safety trial conducted in Mwanza, Tanzania, and Dakar, Senegal. Within the trial, we evaluated for the first time the potential impact of malaria and helminth infection on vaccine-induced antibody responses in Tanzanian girls. We describe research evaluating optimal HPV vaccine delivery strategies within this setting, perceived requirements for and barriers to vaccine implementation among key informants from LMIC, vaccine acceptability among girls and parents, and opportunities for co-delivery of interventions alongside HPV vaccination to an adolescent population. Finally, we discuss country-level barriers to vaccine uptake in LMIC, and ongoing studies in Tanzania and other SSA countries of reduced-dose HPV vaccination schedules that may alleviate cost and logistical barriers to vaccine implementation.

ß-cell dysfunction and insulin resistance in relation to pre-diabetes and diabetes among adults in north-western Tanzania: a cross-sectional study.

OBJECTIVE: Studies on phenotypes of diabetes in Africa are inconsistent. We assessed the role of ß-cell dysfunction and insulin resistance on pre-diabetes and diabetes. METHODS: We included 1890 participants with mean age of 40.6 (SD11.9) years in a cross-sectional study among male and female adults in Tanzania during 2016 to 2017. Data on C-reactive protein (CRP), alpha-acid glycoprotein (AGP), HIV, oral glucose tolerance test (OGTT), body composition and insulin were collected. Insulinogenic index and HOMA-IR were used to derive an overall marker of ß-cell dysfunction and insulin resistance which was categorised as follows: normal ß-cell function and insulin sensitivity, isolated ß-cell dysfunction, isolated insulin resistance, and combined ß-cell dysfunction and insulin resistance. Pre-diabetes and diabetes were defined as 2-hour OGTT glucose between 7.8-11.0 and ≥ 11.1 mmol/L, respectively. Multinomial regression assessed the association of ß-cell dysfunction and insulin resistance with outcome measures. RESULTS: ß-cell dysfunction, insulin resistance, and combined ß-cell dysfunction and insulin resistance were associated with higher pre-diabetes risk. Similarly, isolated ß-cell dysfunction (adjusted relative risk ratio (aRRR) 4.8 (95% confidence interval (CI) 2.5, 9.0), isolated insulin resistance (aRRR 3.2 (95% CI 1.5, 6.9), and combined ß-cell dysfunction and insulin resistance (aRRR 35.9 (95% CI 17.2, 75.2) were associated with higher diabetes risk. CRP, AGP and HIV were associated with higher diabetes risk, but fat mass was not. 31%, 10% and 33% of diabetes cases were attributed to ß-cell dysfunction, insulin resistance, and combined ß-cell dysfunction and insulin resistance, respectively. CONCLUSIONS: ß-cell dysfunction seemed to explain most of diabetes cases compared to insulin resistance in this population. Cohort studies on evolution of diabetes in Africa are needed to confirm these results.

Performance evaluation of the highly sensitive histidine-rich protein 2 rapid test for plasmodium falciparum malaria in North-West Tanzania.

BACKGROUND: Precise detection of Plasmodium infections in community surveys is essential for effective malaria control. Microscopy and rapid diagnostic tests (RDTs) are the major techniques used to identify malaria infections in the field-based surveys. Although microscopy is still considered as the gold standard, RDTs are increasingly becoming versatile due to their rapid and adequate performance characteristics. METHODS: A malaria prevalence cross-sectional survey was carried out in north-western Tanzania in 2016, aimed at appraising the performance of high sensitivity Plasmodium falciparum (HSPf) tests compared to SD Bioline Pf and microscopy in detecting P. falciparum infections. A total of 397 individuals aged five years and above were tested for P. falciparum infections. The sensitivity, specificity, positive, and negative predictive values (PPV and NPV) of microscopy, Pf RDT and HSPf RDT was determined using PCR as the gold standard method. RESULTS: The prevalence of P. falciparum infections determined by microscopy, SD Bioline Pf, HSPf and PCR was 21.9, 27.7, 33.3 and 43.2%, respectively. The new HSPf RDT had significantly higher sensitivity (98.2%) and specificity (91.6%) compared to the routinely used SD Bioline Pf RDT(P < 0.001). The positive predictive value (PPV) was 81.8% and the negative predictive value (NPV) was 99.2% for the routinely used SD Bioline Pf RDT. Moreover, HSPf RDT had sensitivity of 69% and specificity of 76.8% compared to microscopy. The PPV was 45.5% and the NPV was 89.8% for microscopy. Furthermore, the analytical sensitivity test indicated that the newly developed HSPf RDT had lower detection limits compared to routinely used SD Bioline RDT. CONCLUSIONS: HSPf RDT had better performance when compared to both microscopy and the currently used malaria RDTs. The false negativity could be associated with the low parasite density of the samples. False positivity may be related to the limitations of the expertise of microscopists or persistent antigenicity from previous infections in the case of RDTs. Nevertheless, HS PfRDT performed better compared to routinely used Pf RDT, and microscopy in detecting malaria infections. Therefore, HS Pf RDT presents the best alternative to the existing commercial/regularly available RDTs due to its sensitivity and specificity, and reliability in diagnosing malaria infections.

HPV prevalence around the time of sexual debut in adolescent girls in Tanzania.

OBJECTIVES: Cervical cancer is the leading cause of cancer-related mortality among women in sub-Saharan Africa (SSA). Data on human papillomavirus (HPV) epidemiology in adolescent girls in SSA are essential to inform HPV vaccine policy recommendations for cervical cancer prevention. We assessed the burden of HPV infection, and risk factors for infection, among adolescent girls around the time of sexual debut. METHODS: Cross-sectional study of secondary school girls aged 17-18 years in Tanzania. Consenting participants provided samples for HPV and STI testing. Vaginal swabs were tested for 37 HPV genotypes by Roche Linear Array. Logistic regression was used to identify factors associated with HPV infection. Y chromosome was tested as a marker of recent condomless sex. RESULTS: 163/385 girls (42.3%) reported previous penetrative sex. HPV was detected in 125/385 (32.5%) girls, including 84/163 (51.5%) girls reporting previous sex and 41/222 (18.5%) reporting no previous sex. High-risk (HR) genotypes were detected in 70/125 (56.0%) girls with HPV infection. The most common HR genotype was HPV-16 (15/385; 3.9%). The prevalence of other HR HPV vaccine genotypes was between 0.8% and 3.1%. Among 186 girls who reported no previous sex, were negative for Y chromosome, and had no STI, 32 (17%) had detectable HPV. Lactobacillus sp and bacterial vaginosis-associated bacteria were negatively and positively associated, respectively, with HPV. CONCLUSIONS: HPV prevalence among adolescent girls around the time of sexual debut was high. However, prevalence of most vaccine genotypes was low, indicating that extending the age range of HPV vaccination in this region may be cost-effective.

Cascade of care for HIV-seroconverters in rural Tanzania: a longitudinal study.

We examined the HIV care cascade in a community-based cohort study in Kisesa, Magu, Tanzania. We analyzed the proportion achieving each stage of the cascade - Seroconversion, Awareness of HIV status, Enrollment in Care and Antiretroviral therapy (ART) initiation - and estimated the median and interquartile range for the time for progression to the next stage. Modified Poisson regression was used to estimate prevalence risk ratios for enrollment in care and initiation of ART. From 2006 to 2017, 175 HIV-seroconverters were identified. 140 (80%) knew their HIV status, of whom 97 (69.3%) were enrolled in HIV care, and 87 (49.7%) had initiated ART. Time from seroconversion to awareness of HIV status was 731.3 [475.5-1345.8] days. Time from awareness to enrollment was 7 [0-64] days, and from enrollment to ART initiation was 19 [3-248] days. There were no demographic differences in enrollment in care or ART initiation. Efforts have been focusing on shortening time from seroconversion to diagnosis, mostly by increasing the number of testing clinics available. We recommend increased systematic testing to reduce time from seroconversion to awareness of status, and by doing so speed up enrollment into care. Interventions that increase enrollment are likely to have the most impact in achieving UNAIDS targets.

The psychometric properties of PHQ-4 anxiety and depression screening scale among out of school adolescent girls and young women in Tanzania: a cross-sectional study.

BACKGROUND: Literature suggests that most mental disorders have their onset in childhood and adolescence, but go undiagnosed until adulthood. Shorter versions of the screening tools such as the Patient Health Questionnaire with four items (PHQ-4) may help to improve screening coverage. This study assessed the psychometric properties of the PHQ-4 in screening for core symptoms of depression and anxiety among out of school adolescent girls and young women (AGYW). METHODS: This is a cross-sectional analysis of data from a cluster randomized controlled trial conducted among AGYW between June and July 2018 in North-West Tanzania. Two thousand four hundred twenty-six out-of-school AGYW aged 15 to 23 years were included. Data were collected on tablets using audio computer-assisted self-interviews (ACASI). Cronbach's α was used to measure the reliability of the PHQ-4 while confirmatory factor analysis (CFA) and principal components analysis (PCA) were used for construct validity assessment. In CFA, three criteria were used to assess how well the model fits the data: Standardized Root Mean Square Residual (SRMR), the Comparative Fit Index (CFI), the Root Mean Square Error of Approximation (RMSEA) and 90% confidence interval for RMSEA. RESULTS: Of the 2426 participants, 33.8 and 35.5% screened positive for core symptoms of anxiety (GAD-2 ≥ 3) and depression (PHQ-2 ≥ 3), respectively. Cronbach's α of the PHQ-4 was 0.81. Both items-correlation and corrected items-correlation of the PHQ-4 had total correlations above 0.5 (p < 0.01). CFA showed that all items loaded significantly onto the single factor, and loadings were strong, ranging from 0.67 to 0.77 (p < 0.01). CFA indicates that the PHQ-4 scale stand for a unidimensional construct with good model fit (CFI = 0.995, SRMR = 0.013, RMSEA = 0.054 and 90% CI for RMSEA (0.031-0.079)). PCA confirmed two distinct components; GAD-2 (anxiety) and PHQ-2 (depression). Those who reported having suicidal thoughts and social function problems had significantly higher scores on PHQ-2, GAD-2, and PHQ-4 screening items (p < 0.01). CONCLUSIONS: The findings suggest that the PHQ-4 scale can reliably and validly screen for core symptoms of depression and anxiety among out of school AGYW. This tool is short and easy to administer. Thus, the PHQ-4 scale can be very useful in screening for anxiety and depression symptoms in the community, primary health facilities, research and programmatic settings.

Female sex workers perspectives and concerns regarding HIV self-testing: an exploratory study in Tanzania.

BACKGROUND: HIV testing is a gateway to HIV care and treatment for people diagnosed with HIV and can link those with negative results to HIV preventive services. Despite the importance of HIV testing services (HTS) in HIV control, uptake of HTS among female sex workers (FSWs) across sub-Saharan Africa (SSA) remains sub-optimal. Concerns about stigma associated with sex work and fear of loss of livelihood if HIV status becomes known, are some of the restrictions for FSWs to utilize HTS offered through health care facilities. Introduction of HIV self-testing (HIVST) may mitigate some of the barriers for the uptake of HTS. This study explored the acceptability of FSWs towards the introduction of HIVST in Tanzania. METHODS: We conducted an exploratory study employing in-depth interviews (IDI) and participatory group discussions (PGD) with FSWs in selected regions of Tanzania. Study participants were recruited through snowball sampling. Data were thematically analysed by two analysts using NVivo software. The analysis was informed by the social-ecological model and focused on factors associated with the acceptability of HIVST. RESULTS: We conducted 21 PGD sessions involving 227 FSWs. Twenty three IDIs were conducted to complement data collected through PGD. Our study has demonstrated that FSWs are enthusiastic toward HIVST. Convenience (time and cost saved), and belief that HIVST will increase privacy and confidentiality motivated participants' support for the self-testing approach. Participants did express concerns about their ability to interpret and trust the results of the test. Participants also expressed concern that HIVST could cause personal harm, including severe distress and self-harm for individuals with a reactive test. Very likely, concern about adverse effects of HIVST was linked to the study participants' lay perception that HIVST would be provided only through unassisted modality. CONCLUSIONS: FSWs demonstrated high enthusiasm to use the HIVST once it becomes available. Expectations for increased confidentiality, autonomy, and reduced opportunity costs were among the leading factors that attracted FSWs to HIVST. The major obstacles to the acceptability of HIVST included fear of HIV reactive test and not trusting self-diagnoses. Our findings underscore the importance of providing adequate access to counselling and referral services in conjunction with HIVST.

Short-course High-dose Liposomal Amphotericin B for Human Immunodeficiency Virus-associated Cryptococcal Meningitis: A Phase 2 Randomized Controlled Trial.

Background: We performed a phase 2 noninferiority trial examining the early fungicidal activity (EFA) of 3 short-course, high-dose liposomal amphotericin B (L-AmB) regimens for cryptococcal meningitis (CM) in Tanzania and Botswana. Methods: Human immunodeficiency virus (HIV)-infected adults with CM were randomized to (i) L-AmB 10 mg/kg on day 1 (single dose); (ii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on day 3 (2 doses); (iii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on days 3 and 7 (3 doses); or (iv) L-AmB 3 mg/kg/day for 14 days (control). All patients also received oral fluconazole 1200 mg/day for 14 days. Primary endpoint was mean rate of clearance of cerebrospinal fluid cryptococcal infection (EFA). Noninferiority was defined as an upper limit of the 2-sided 95% confidence interval (CI) of difference in EFA between intervention and control <0.2 log10 colony-forming units (CFU)/mL/day. Results: Eighty participants were enrolled. EFA for daily L-AmB was -0.41 log10 CFU/mL/day (standard deviation, 0.11; n = 17). Difference in mean EFA from control was -0.11 (95% CI, -.29 to .07) log10 CFU/mL/day faster with single dose (n = 16); -0.05 (95% CI, -.20 to .10) log10 CFU/mL/day faster with 2 doses (n = 18); and -0.13 (95% CI, -.35 to .09) log10 CFU/mL/day faster with 3 doses (n = 18). EFA in all short-course arms was noninferior to control. Ten-week mortality was 29% (n = 23) with no statistical difference between arms. All arms were well tolerated. Conclusions: Single-dose 10 mg/kg L-AmB was well tolerated and led to noninferior EFA compared to 14 days of 3 mg/kg/day L-AmB in HIV-associated CM. Induction based on a single 10 mg/kg L-AmB dose is being taken forward to a phase 3 clinical endpoint trial. Clinical Trials Registration: ISRCTN 10248064.

Human papillomavirus DNA detected in fingertip, oral and bathroom samples from unvaccinated adolescent girls in Tanzania.

OBJECTIVE: Human papillomavirus (HPV) DNA has been detected in vaginal samples from adolescent girls who report no previous sex and, in high-income settings, from fingertips, raising the possibility of non-sexual transmission. No such studies originate from East Africa which bears among the highest cervical cancer incidence and HPV prevalence worldwide. HPV-related oral cancer incidence is increasing, but oral HPV prevalence data from East Africa are limited. We aimed to describe the HPV DNA prevalence in genital and non-genital sites and in the bathroom of unvaccinated adolescent girls, and examine genotype concordance between sites. METHODS: We nested a cross-sectional study of HPV in genital and extragenital sites within a cohort study of vaginal HPV acquisition. Unvaccinated girls age 16-18 years in Tanzania, who reported ever having had sex, were consented, enrolled and tested for the presence of HPV DNA in vaginal samples collected using self-administered swabs, oral samples collected using an oral rinse, and on fingertips and bathroom surfaces collected using a cytobrush. RESULTS: Overall, 65 girls were enrolled and 23 (35%, 95% CI 23% to 47%) had detectable vaginal HPV. Adequate (ß-globin positive) samples were collected from 36 girls' fingertips and HPV was detected in 7 (19%, 95% CI 6% to 33%). 63 girls provided adequate oral samples, 4 (6%, 95% CI 0% to 13%) of which had HPV DNA detected. In bathroom samples from 58 girls, 4 (7%, 95% CI 0% to 14%) had detectable HPV DNA. Of the 11 girls with extragenital HPV, six had the same genotype in >1 site. CONCLUSION: We found a high prevalence of HPV in non-genital sites in adolescent girls and in their bathrooms, in this region with a high cervical cancer incidence. Concordance of genotypes between sites supports the possibility of autoinoculation.

Results from a cross-sectional sexual and reproductive health study among school girls in Tanzania: high prevalence of bacterial vaginosis.

OBJECTIVES: Bacterial vaginosis (BV) increases women's susceptibility to sexually transmitted infections (STIs) and HIV and may partly explain the high incidence of STI/HIV among girls and young women in East and southern Africa. The objectives of this study were to investigate the association between BV and sexual debut, to investigate other potential risk factors of BV and to estimate associations between BV and STIs. METHODS: Secondary school girls in Mwanza, aged 17 and 18 years, were invited to join a cross-sectional study. Consenting participants were interviewed and samples were obtained for STI and BV testing. Factors associated with prevalent BV were analysed using multivariable logistic regression. Y-chromosome was tested as a biomarker for unprotected penile-vaginal sex. RESULTS: Of the 386 girls who were enrolled, 163 (42%) reported having ever had penile-vaginal sex. Ninety-five (25%) girls had BV. The prevalence of BV was 33% and 19% among girls who reported or did not report having ever had penile-vaginal sex, respectively. BV was weakly associated with having ever had one sex partner (adjusted odds ratio (aOR) 1.59;95% CI 0.93 to 2.71) and strongly associated with two or more partners (aOR = 3.67; 95% CI 1.75 to 7.72), receptive oral sex (aOR 6.38; 95% CI 1.22 to 33.4) and having prevalent human papillomavirus infection (aOR = 1.73; 95% CI 1.02 to 2.95). Of the 223 girls who reported no penile-vaginal sex, 12 (5%) tested positive for an STI and 7 (3%) tested positive for Y-chromosome. Reclassifying these positive participants as having ever had sex did not change the key results. CONCLUSIONS: Tanzanian girls attending school had a high prevalence of BV. Increasing number of sex partner was associated with BV; however, 19% of girls who reported no penile-vaginal sex had BV. This suggests that penile-vaginal sexual exposure may not be a prerequisite for BV. There was evidence of under-reporting of sexual debut.

Determinants of access to HIV testing and counselling services among female sex workers in sub-Saharan Africa: a systematic review.

BACKGROUND: HIV testing and counselling (HTC) is an essential component for HIV prevention and a critical entry point into the HIV continuum of care and treatment. Despite the importance of HTC for HIV control, access to HTC services among female sex workers (FSWs) in sub-Saharan Africa (SSA) remains suboptimal and little is known about factors influencing FSWs' access to HTC. Guided by the client-centred conceptual framework, we conducted a systematic review to understand the facilitators and barriers influencing FSWs in SSA to access HTC services. METHODS: A systematic search was conducted in MEDLINE, POPLINE and Web of Science databases for literature published between January 2000 and July 2017. References of relevant articles were also searched. We included primary studies of any design, conducted in SSA and published in the English language. Studies conducted in multi-sites inclusive of SSA were included only if data from sites in SSA were separately analysed and reported. Similarly, studies that included other subpopulations were only eligible if a separate analysis was done for FSWs. This review excluded papers published as systematic reviews, editorial comments and mathematical modelling. The protocol for this review is registered in the Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42017062203. RESULTS: This review shows that factors related to approachability, acceptability, availability, affordability and appropriateness of the services are crucial in influencing access to HTC services among FSWs in SSA. These factors were mediated by individual attributes such as HIV risk perceptions, awareness of the availability of HTC, and perceptions of the importance and quality of HTC services. The decision to utilise HTC was predominantly hampered by discriminatory social norms such as HIV stigma and criminalisation of sex work. CONCLUSIONS: FSWs' access to HTC is facilitated by multiple factors, including individual awareness of the availability of HTC services, and perceived quality of HTC especially with regard to assured confidentiality. Concerns about HIV stigma and fear about discrimination due to community intolerance of sex work acted as major barriers for FSWs to seek HTC services from the facilities offering health services to the general population.

Participants' accrual and delivery of HIV prevention interventions among men who have sex with men in sub-Saharan Africa: a systematic review.

BACKGROUND: Across sub-Saharan Africa (SSA), HIV disproportionately affects men-who-have-sex-with-men (MSM) compared with other men of the same age group in the general population. Access to HIV services remains low among this group although several effective interventions have been documented. It is therefore important to identify what has worked well to increase the reach of HIV services among MSM. METHODS: We searched MEDLINE, POPLINE and the Web of Science databases to collect published articles reporting HIV interventions among MSM across sub-Saharan Africa. Covidence was used to review the articles. The review protocol was registered in International Prospective Register of Systematic Reviews (PROSPERO) - CRD42017060808. RESULTS: The search identified 2627 citations, and following removal of duplicates and inclusion and exclusion criteria, only 15 papers were eligible for inclusion in the review. The articles reported various accrual strategies, namely: respondent driven sampling, known peers identified through hotspot or baseline surveys, engagement with existing community-based organizations, and through peer educators contacting MSM in virtual sites. Some programs, however, combined some of these accrual strategies. Peer-led outreach services were indicated to reach and deliver services to more MSM. A combination of peer outreach and mobile clinics increased uptake of health information and services. Health facilities, especially MSM-friendly facilities attract access and use of services by MSM and retention into care. CONCLUSIONS: There are various strategies for accrual and delivering services to MSM across SSA. However, each of these strategies have specific strengths and weaknesses necessitating combinations of interventions and integration of the specific context to inform implementation. If the best of intervention content and implementation are used to inform these services, sufficient coverage and impact of HIV prevention and treatment programs for MSM across SSA can be optimized.

Dysglycemia associations with adipose tissue among HIV-infected patients after 2 years of antiretroviral therapy in Mwanza: a follow-up cross-sectional study.

BACKGROUND: Data on the burden of dysglycemia among HIV-infected patients on antiretroviral therapy (ART) in Africa are limited. We determined the prevalence of pre-diabetes and diabetes among HIV-infected patients who started ART when malnourished 2 to 3 years previously and investigated the association of dysglycemia with body composition. METHODS: Malnourished (body mass index (BMI) < 18.5 kg/m2) HIV-infected patients who were enrolled in the Nutritional Support for Africans Starting Antiretroviral Therapy (NUSTART) trial from 2011 to 2013 were followed-up from March to August 2015. Anthropometric, fat mass and fat-free mass by bioelectrical impedance, and C-reactive protein (CRP) data were collected at baseline and follow-up. At follow-up, we defined fasting glucose of 6.1-6.9 mmol/L as impaired fasting glucose (IFG) and 2-h oral glucose tolerance test (OGTT) glucose of ≥7.8 to <11.1 mmol/L as impaired glucose tolerance (IGT). Both of these were considered pre-diabetes. Fasting glucose of ≥7.0 mmol/L or impaired glucose tolerance of ≥11.1 mmol/L was defined as diabetes mellitus. The relation of pre-diabetes and diabetes with body composition was assessed using logistic regression. RESULTS: Two hundred seventy-three (57%) of 478 patients who were alive at trial conclusion were followed-up. The mean age was 41.5 (SD 9.8) years and 65.2% (178) were females. The mean follow-up BMI was 19.9 (SD 2.8) kg/m2, 12 (4.4%) were either overweight or obese, and 61 (22.3%) patients had pre-diabetes or diabetes. In multiple regression, upper tertiles of baseline hip circumference (OR: 0.41, 95% CI: 0.2, 0.8) and fat mass index (OR: 0.20 (0.1, 0.5), and upper tertiles of follow-up waist circumference (OR: 0.22 (0.1, 0.5), BMI (OR: 0.32 (0.1, 0.7), fat mass index (OR: 0.19 (0.1, 0.5) and the middle tertile of follow-up fat-free mass (OR: 0.36, 95% CI: 0.1, 0.8) were associated with lower risk of pre-diabetes and diabetes (P < 0.05 for all). Baseline and follow-up CRP were not predictors. CONCLUSIONS: Low rather than high measures of adipose tissue were associated with increased risk of pre-diabetes and diabetes. Additional studies are needed to further investigate the role of body composition and control of glucose metabolism in the pathogenesis of diabetes among persons living with HIV in Africa.