Search

Objective: To estimate the association between (1) visual impairment (VI) and (2) eye disease and 6-year mortality risk within a cohort of elderly Kenyan people., Design, Setting and Participants: The baseline of the Nakuru Posterior Segment Eye Disease Study was formed from a population-based survey of 4318 participants aged ≥50 years, enrolled in 2007-2008. Ophthalmic and anthropometric examinations were undertaken on all participants at baseline, and a questionnaire was administered, including medical and ophthalmic history. Participants were retraced in 2013-2014 for a second examination. Vital status was recorded for all participants through information from community members. Cumulative incidence of mortality, and its relationship with baseline VI and types of eye disease was estimated. Inverse probability weighting was used to adjust for non-participation., Primary Outcome Measures: Cumulative incidence of mortality in relation to VI level at baseline., Results: Of the baseline sample, 2170 (50%) were re-examined at follow-up and 407 (10%) were known to have died (adjusted risk of 11.9% over 6 years). Compared to those with normal vision (visual acuity (VA) ≥6/12, risk=9.7%), the 6-year mortality risk was higher among people with VI (<6/18 to ≥6/60; risk=28.3%; risk ratio (RR) 1.75, 95% CI 1.28 to 2.40) or severe VI (SVI)/blindness (<6/60; risk=34.9%; RR 1.98, 95% CI 1.04 to 3.80). These associations remained after adjustment for non-communicable disease (NCD) risk factors (mortality: RR 1.56, 95% CI 1.14 to 2.15; SVI/blind: RR 1.46, 95% CI 0.80 to 2.68). Mortality risk was also associated with presence of diabetic retinopathy at baseline (RR 3.18, 95% CI 1.98 to 5.09), cataract (RR 1.26, 95% CI 0.95 to 1.66) and presence of both cataract and VI (RR 1.57, 95% CI 1.24 to 1.98). Mortality risk was higher among people with age-related macular degeneration at baseline (with or without VI), compared with those without (RR 1.42, 95% CI 0.91 to 2.22 and RR 1.34, 95% CI 0.99 to 1.81, respectively)., Conclusions: Visual acuity was related to 6-year mortality risk in this cohort of elderly Kenyan people, potentially because both VI and mortality are related to ageing and risk factors for NCD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Importance: Half of all the cases of blindness worldwide are associated with cataract. Cataract disproportionately affects people living in low- and middle-income countries and persons of African descent., Objective: To estimate the 6-year cumulative incidence of visually impairing cataract in adult participants in the Nakuru Eye Disease Cohort Study in Kenya., Design, Setting, and Participants: This secondary analysis of the Nakuru Eye Disease Cohort Study was conducted from February 2016 to April 2016. This cohort comprised citizens of Nakuru, Kenya, aged 50 years or older who consented to participate in the initial or baseline survey from January 2007 to November 2008, as well as the follow-up conducted from January 2013 to March 2014. All participants at baseline (n = 4364) and follow-up (n = 2159) underwent ophthalmic examination., Main Outcomes and Measures: Six-year cumulative incidence of visually impairing cataract, risk factors of incidence, population estimates, and required cataract surgical rates to manage incident visually impairing cataract., Results: In total, 4364 individuals (with a mean [SD] age of 63.4 [10.5] years and with 2275 women [52.1%]) had complete eye examinations at baseline, and 2159 participants (with a mean [SD] age of 62.5 [9.3] years and with 1140 men [52.8%]) were followed up 6 years later. The 6-year cumulative incidence of visually significant cataract in either eye was 251.9 per 1000 (95% CI, 228.5-276.8), with an increase with age from 128.9 (95% CI, 107.9-153.2) per 1000 for the group aged 50 to 59 years to 624.5 (95% CI, 493.1-739.9) per 1000 for the group aged 80 years or older. This equated to an annual incidence of visually significant cataract of 45.0 per 1000 people aged 50 years or older. Multivariable analysis showed alcohol consumption (risk ratio [RR], 1.4; 95% CI, 1.1-1.8), diabetes (RR, 1.7; 95% CI, 1.3-2.3), educational level, and increasing age (RR, 3.8; 95% CI, 2.6-5.5 for those aged ≥80 years) were associated with incident visually impairing cataract. Extrapolations to all people aged 50 years or older in Kenya indicated that 148 280 (95% CI, 134 510-162 950) individuals might develop new visually impairing cataract in either eye (visual acuity <6/18 in the worse-seeing eye) and that 9540 (95% CI, 6610-13 750) might become cataract blind in both eyes (visual acuity <3/60 in better-seeing eye)., Conclusions and Relevance: Adults in Kenya appeared to have a high incidence of visually impairing cataract, making cataract a priority for blindness prevention programs in the region; surgical interventions and awareness of these services are also required.

Background: High attrition and irregular testing for human immunodeficiency virus (HIV) in cohort studies for high-risk populations can bias incidence estimates. We compare incidence trends for high-risk women attending a dedicated HIV prevention and treatment clinic, using common methods for assigning when seroconversion occurs and whether seroconversion occurs among those with attrition., Methods: Between April 2008 and May 2009, women were enrolled into cohort 1 and from January 2013 into cohort 2, then scheduled for follow-up once every 3 months. Incidence trends based on assuming a midpoint in the seroconversion interval were compared with those of assigning a random-point. We also compared estimates based on the random-point with and without multiple imputation (MI) of serostatuses for participants with attrition., Results: By May 2017, 3084 HIV-negative women had been enrolled with 18,364 clinic visits. Before attrition, 27.6% (6990 of 25,354) were missed visits. By August 2017, 65.8% (426 of 647) of those enrolled in cohort 1 and 49.0% (1194 of 2437) in cohort 2 were defined with attrition. Among women with 1 or more follow-up visit, 93 of 605 in cohort 1 and 77 of 1601 in cohort 2 seroconverted. Periods with longer seroconversion intervals appeared to have noticeable differences in incidences when comparing the midpoint and random-point values. The MI for attrition is likely to have overestimated incidence after escalated attrition of participants. Based on random-point without MI for attrition, incidence at end of observation was 3.8/100 person-years in cohort 1 and 1.8/100 in cohort 2., Conclusions: The random-point approach attenuated variation in incidence observed using midpoint. The high incidence after years of ongoing prevention efforts in this vulnerable population should be investigated to further reduce incidence.

Background: Few studies have evaluated the acceptability of self-collected vaginal swabs among young women in sub-Saharan Africa, including in school settings. We evaluated the acceptability of 2 conditions for the self-collection of swabs in secondary schools in Entebbe, Uganda., Methods: Assenting girls with parental consent from 3 secondary schools were provided instructions for sampling, and randomly allocated to self-collection of vaginal swabs with or without nurse assistance to help with correct placement of the swab. Swabs were tested for bacterial vaginosis by Gram stain. Participants were followed up after 1 to 2 days and 1 to 2 weeks and invited for a qualitative interview., Results: Overall 96 girls were enrolled (median age, 16 years; interquartile range, 15-17 years). At the first follow-up visit, participants in both arms reported that instructions for sample collection were easy to understand, and they felt comfortable with self-collection. Girls in the nurse assistance arm reported feeling less relaxed (27% vs. 50%, P = 0.02) than those in the arm without nurse assistance, but more confident that they collected the sample correctly (96% vs. 83%, P = 0.04). About half (47%) of participants agreed that self-sampling was painful, but almost all (94%) would participate in a similar study again. Qualitative data showed that participants preferred self-collection without nurse assistance to preserve privacy. Bacterial vaginosis prevalence was 14% (95% confidence interval, 8-22)., Conclusions: In this setting, self-collection of vaginal swabs in secondary schools was acceptable and feasible, and girls preferred self-collection without nurse assistance. Self-collection of swabs is an important tool for the detection, treatment and control of reproductive tract infections in girls and young women.

Voluntary medical male circumcision (VMMC) is effective in reducing the risk of human immunodeficiency virus (HIV). However, countries like Tanzania have high HIV prevalence but low uptake of VMMC. We conducted a discrete-choice experiment to evaluate the preferences for VMMC service attributes in a random sample of 325 men aged 18 years or older from the general population in 2 Tanzanian districts, Njombe and Tabora. We examined the preference for financial incentives in the form of a lottery ticket or receiving a guaranteed transport voucher for attendance at a VMMC service. We created a random-parameters logit model to account for individual preference heterogeneity and a latent class analysis model for identifying groups of men with similar preferences to test the hypothesis that men who reported sexually risky behaviors (i.e., multiple partners and any condomless sex in the past 12 months) may have a preference for participation in a lottery-based incentive. Most men preferred a transport voucher (84%) over a lottery ticket. We also found that offering a lottery-based financial incentive may not differentially attract those with greater sexual risk. Our study highlights the importance of gathering local data to understand preference heterogeneity, particularly regarding assumptions around risk behaviors.

Increased coverage of voluntary medical male circumcision (VMMC) is needed in countries with high HIV prevalence. We applied an HIV-prevention cascade to identify gaps in male circumcision coverage in Zambia. We used survey data collected in 2013 and 2014/15 to describe circumcision coverage at each time-point, and prevalence of variables related to demand for and supply of VMMC. We explored whether circumcision coverage in 2014/15 was associated with demand and supply among uncircumcised men in 2013. Results show that circumcision coverage was 11.5% in 2013 and 18.0% in 2014/15. Levels of having heard of circumcision and agreeing with prevention benefits was similar at both time-points (79.8% vs 83.2%, and 49.7% vs 50.7%, respectively). In 2013, 39.3% of men perceived services to be available compared to 54.7% in 2014/15. Levels of having heard of circumcision in 2013 was correlated with and higher perceived service availability associated with coverage in 2014/15. VMMC coverage was low in these study sites. Knowledge of prevention tools and of service availability are necessary to increase coverage but alone are insufficient.

Objective: We assessed feasibility of an HIV-combination-prevention trial among fishing communities in Uganda., Design: Cluster randomised trial in four fishing communities on Lake Victoria, Uganda. Two intervention communities received a combination-prevention-package (behaviour change communication, condom promotion, HIV testing, voluntary male medical circumcision and referral for anti-retroviral therapy if HIV-positive). All four communities received routine government HIV care services., Methods: Using household census data we randomly selected a cohort of consenting residents aged ≥18 years. A baseline sero-survey in July 2014 was followed by two repeat surveys in March and December 2015. We measured uptake of HIV prevention methods, loss-to-follow-up and HIV incidence, accounting for multistage survey design., Results: A total of 862 participants were enrolled and followed for 15 months. Participation was 62% and 74% in the control and intervention arms respectively; Overall loss to follow up (LTFU) was 21.6% and was similar by arm. Self-reported abstinence/faithfulness increased between baseline and endline in both arms from 53% to 73% in the control arm, and 55% to 67% in the intervention arm. Reported condom use throughout the study period was 36% in the intervention arm vs 28% in the control arm; number of male participants reporting circumsicion in both arms from 58% to 79% in the intervention arm, and 39% to 46% in the control arm. Independent baseline predictors of loss-to-follow-up were: being HIV positive, residence in the community for <1 year, younger age, living in an urban area, and being away from the area for >1 month/year., Conclusions: Recruitment and retention of participants in longitudinal trials in highly mobile HIV fishing communities is challenging. Future research should investigate modes for locating and retaining participants, and delivery of HIV-combination prevention., Competing Interests: The authors have declared that no competing interests exist.

Background: Complex health interventions must incorporate user preferences to maximize their potential effectiveness. Discrete choice experiments (DCEs) quantify the strength of user preferences and identify preference heterogeneity across users. We present the process of using a DCE to supplement conventional qualitative formative research in the design of a demand creation intervention for voluntary medical male circumcision (VMMC) to prevent HIV in Tanzania., Methods: The VMMC intervention was designed within a 3-month formative phase. In-depth interviews (n = 30) and participatory group discussions (n = 20) sought to identify broad setting-specific barriers to and facilitators of VMMC among adult men. Qualitative results informed the DCE development, identifying the role of female partners, service providers' attitudes and social stigma. A DCE among 325 men in Njombe and Tabora, Tanzania, subsequently measured preferences for modifiable VMMC service characteristics. The final VMMC demand creation intervention design drew jointly on the qualitative and DCE findings., Results: While the qualitative research informed the community mobilization intervention, the DCE guided the specific VMMC service configuration. The significant positive utilities (u) for availability of partner counselling (u = 0.43, p < 0.01) and age-separated waiting areas (u = 0.21, p < 0.05) led to the provision of community information booths for partners and provision of age-separated waiting areas. The strong disutility of female healthcare providers (u = - 0.24, p < 0.01) led to re-training all providers on client-friendliness., Conclusion: This is, to our knowledge, the first study documenting how user preferences from DCEs can directly inform the design of a complex intervention. The use of DCEs as formative research may help increase user uptake and adherence to complex interventions.

Background: The Thinking Healthy Programme (THP) is a psychological intervention recommended for the treatment of perinatal depression. However, efforts to integrate the intervention at scale into the routines of community health workers who delivered the THP when it was first evaluated were compromised by the competing responsibilities of community health workers. We aimed to assess the effectiveness and cost-effectiveness of THP peer-delivered (THPP) in Goa, India., Methods: In this single-blind, individually randomised controlled trial, we recruited pregnant women aged 18 years or older who scored at least 10 on the Patient Health Questionnaire-9 (PHQ-9) from antenatal clinics in Goa. Participants were randomly allocated (1:1) to receive enhanced usual care (EUC; so-called because, in India, perinatal depression is not typically treated) only (control group) or THPP in addition to EUC (intervention group) in randomly sized blocks that were stratified by area of residence (urban or rural). Group allocations were concealed from participants and researchers before assignments were made by use of sequentially numbered opaque envelopes. The primary outcomes were the severity of depressive symptoms (assessed by PHQ-9 score) and the prevalence of remission (defined as a PHQ-9 score of less than 5) in participants with available data 6 months after childbirth, which was assessed by researchers who were masked to treatment allocations. We analysed outcomes by intention to treat, adjusting for covariates that were defined a priori or that showed imbalance at baseline. The trial is registered with ClinicalTrials.gov, number NCT02104232., Findings: Between Oct 24, 2014, and June 24, 2016, we assessed 118 260 women for their eligibility for screening, of whom 111 851 (94·6%) women were ineligible. 6409 (5·4%) women were eligible for screening and 6369 (99·4%) of these women consented to be screened with the PHQ-9 (40 women did not consent), of whom 333 (5·2%) screened positive for depression (defined as a PHQ-9 score of at least 10). We enrolled 280 (84·1%) women with perinatal depression; 140 women were assigned to the THPP and EUC group and 140 women to the EUC only group. The final treatment was given on May 27, 2017. The final 6-month outcome assessment was completed on June 9, 2017. At 6 months after birth, 122 (87%) women in the THPP and EUC group and 129 (92%) women in the EUC only group were assessed for the primary outcome. There was a higher prevalence of remission at 6 months after birth in the THPP and EUC group compared with the EUC only group (89 [73%] women in the intervention group vs 77 [60%] women in the control group; prevalence ratio 1·21, 95% CI 1·01 to 1·45; p=0·04), but there was no evidence of a difference in symptom severity between the groups (mean PHQ-9 score 3·47 [SD 4·49] in the intervention group vs 4·48 [5·11] in the control group; standardised mean difference -0·18, 95% CI -0·43 to 0·07; p=0·16). There was no evidence of significant differences in serious adverse events between the groups., Interpretation: THPP had a moderate effect on remission from perinatal depression over the 6-month postnatal period. THPP is relatively cheap to deliver and is cost-saving through reduced health-care, time and productivity costs., Funding: National Institute of Mental Health (USA)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The Thinking Healthy Programme (THP), which is endorsed by WHO, is an evidence-based intervention for perinatal depression. We adapted THP for delivery by volunteer peers (laywomen from the community) to address the human resource needs in bridging the treatment gap, and we aimed to assess its effectiveness and cost-effectiveness in Rawalpindi, Pakistan., Methods: In this cluster randomised controlled trial, we randomly assigned 40 village clusters (1:1) to provide either THP peer-delivered (THPP) and enhanced usual care (EUC; intervention group) or EUC only (control group) to the participants within clusters. These villages were randomly selected from eligible villages by an independent researcher. The participants were pregnant women aged 18 years or older who had scored at least 10 on the Patient Health Questionnaire-9 (PHQ-9), who we recruited from households within communities in Rawalpindi, Pakistan. The research teams who were responsible for recruiting trial participants were masked to treatment allocations. Participants attended follow-up visits at 3 and 6 months after childbirth. The primary outcomes were the severity of depressive symptoms (assessed by PHQ-9 score) and the prevalence of remission (defined as a PHQ-9 score of less than 5) in participants with available data 6 months after childbirth, which was assessed by researchers who were masked to treatment allocations. We analysed outcomes by intention to treat, adjusting for covariates that were defined a priori or that showed imbalance at baseline. The trial was registered with ClinicalTrials.gov, number NCT02111915., Findings: Between April 15 and July 30, 2014, we randomly selected 40 of 46 eligible village clusters for assessment, as per sample size calculations. Between Oct 15, 2014, and Feb 25, 2016, we identified and screened 971 women from 20 village clusters that had been randomly assigned to the THPP and EUC group and 939 women from 20 village clusters that had been randomly assigned to the EUC only group. In the intervention group, 79 women were ineligible for inclusion, 11 women refused screening, 597 women screened negative on the PHQ-9, and one woman did not consent to participate. In the control group, 75 women were ineligible for inclusion, 14 women refused screening, 562 women screened negative on the PHQ-9, and one woman did not consent to participate. We enrolled 283 (29%) women in the intervention group and 287 (31%) women in the control group. At 6 months after childbirth, 227 (80%) women in the THPP and EUC group and 226 (79%) women in the EUC only group were assessed for the primary outcome. The severity of depression (assessed by PHQ-9 scores; standardised mean difference -0·13, 95% CI -0·31 to 0·06; p=0·07) and prevalence of remission (49% in the intervention group vs 45% in the control group; prevalence ratio 1·12, 95% CI 0·95 to 1·29; p=0·14) did not significantly differ between the groups 6 months after childbirth. There was no evidence of significant differences in serious adverse events between the groups., Interpretation: THPP had no effect on symptom severity or remission from perinatal depression at 6 months after childbirth, but we found that it was beneficial on some other metrics of severity and disability and that it was cost-effective. THPP could be a step towards use of an unused human resource to address the treatment gap in perinatal depression., Funding: National Institute of Mental Health (USA)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Very little is known about the barriers and facilitators to antiretroviral therapy (ART) access and adherence among older Africans. Most studies on ART have focused on individuals who are 15-49 years of age., Methods: We used in-depth interviews with 40 persons living with HIV, aged 50 to 96 years, who had either initiated ART (n = 26) or were waiting to initiate ART (n = 14), to explore barriers and facilitators to ART access and adherence in rural Uganda., Results: Guided by the Andersen Behavior Model, thematic content analysis highlighted 21 primary factors related to environment, patient and health behavior. Nine of the factors were common to both access and adherence, the remaining 12 were evenly split between access and adherence. Transportation costs, food insecurity, and healthcare workers' knowledge, attitudes and behaviors were key barriers., Conclusions: These barriers were similar to those outlined for younger populations in other studies, but were compounded by age. Despite barriers, either due to the exceptional nature of HIV care or overreporting, both ART access and self-reported adherence were better than expected. Older persons living with HIV highlighted health care needs for non-HIV-related illnesses, suggesting while HIV care is adequate, care for the ailments of "old age" is lagging.

Background: School environments affect health and academic outcomes. With increasing secondary school retention in low-income and middle-income countries, promoting quality school social environments could offer a scalable opportunity to improve adolescent health and wellbeing., Methods: We did a cluster-randomised trial to assess the effectiveness of a multi-component whole-school health promotion intervention (SEHER) with integrated economic and process evaluations in grade 9 students (aged 13-14 years) at government-run secondary schools in the Nalanda district of Bihar state, India. Schools were randomly assigned (1:1:1) to three groups: the SEHER intervention delivered by a lay counsellor (the SEHER Mitra [SM] group), the SEHER intervention delivered by a teacher (teacher as SEHER Mitra [TSM] group), and a control group in which only the standard government-run classroom-based life-skills Adolescence Education Program was implemented. The primary outcome was school climate measured with the Beyond Blue School Climate Questionnaire (BBSCQ). Students were assessed at the start of the academic year (June, 2015) and again 8 months later at the end of the academic year (March, 2016) via self-completed questionnaires. This study is registered with ClinicalTrials.gov, number NCT02484014., Findings: Of the 112 eligible schools in the Nalanda district, 75 were randomly selected to participate in the trial. We randomly assigned 25 schools to each of the three groups. One school subsequently dropped out of the TSM group, leaving 24 schools in this group. The baseline survey included a total of 13 035 participants, and the endpoint survey included 14 414 participants. Participants in the SM-delivered intervention schools had substantially higher school climate scores at endpoint survey than those in the control group (BBSCQ baseline-adjusted mean difference [aMD] 7·57 [95% CI 6·11-9·03]; effect size 1·88 [95% CI 1·44-2·32], p<0·0001) and the TSM-delivered intervention (aMD 7·57 [95% CI 6·06-9·08]; effect size 1·88 [95% CI 1·43-2·34], p<0·0001). There was no effect of the TSM-delivered intervention compared with control (aMD -0·009 [95% CI -1·53 to 1·51], effect size 0·00 [95% CI -0·45 to 0·44], p=0·99). Compared with the control group, participants in the SM-delivered intervention schools had moderate to large improvements in the secondary outcomes of depression (aMD -1·23 [95% CI -1·89 to -0·57]), bullying (aMD -0·91 [95% CI -1·15 to -0·66]), violence victimisation (odds ratio [OR] 0·62 [95% CI 0·46-0·84]), violence perpetration (OR 0·68 [95% CI 0·48-0·96]), attitude towards gender equity (aMD 0·41 [95% CI 0·21-0·61]), and knowledge of reproductive and sexual health (aMD 0·29 [95% CI 0·06-0·53]). Similar results for these secondary outcomes were noted for the comparison between SM-delivered intervention schools and TSM-delivered intervention schools (depression: aMD -1·23 [95% CI -1·91 to -0·55]; bullying: aMD -0·83 [95% CI -1·08 to -0·57]; violence victimisation: OR 0·49 [95% CI 0·35-0·67]; violence perpetration: OR 0·49 [95% CI 0·34-0·71]; attitude towards gender equity: aMD 0·23 [95% CI 0·02-0·44]; and knowledge of reproductive and sexual health: aMD 0·22 [95% CI -0·02 to 0·47]). However, no effects on these secondary outcomes were observed for the TSM-delivered intervention schools compared with the control group (depression: aMD -0·03 [95% CI -0·70 to 0·65]; bullying: aMD -0·08 [95% CI -0·34 to 0·18]; violence victimisation: OR 1·27 [95% CI 0·93-1·73]; violence perpetration: OR 1·37 [95% CI 0·95-1·95]; attitude towards gender equity: aMD 0·17 [95% CI -0·09 to 0·38]; and knowledge of reproductive and sexual health: aMD 0·06 [95% CI -0·18 to 0·32])., Interpretation: The multi-component whole-school SEHER health promotion intervention had substantial beneficial effects on school climate and health-related outcomes when delivered by lay counsellors, but no effects when delivered by teachers. Future research should focus on the evaluation of the scaling up of the SEHER intervention in diverse contexts and delivery agents., Funding: John D. and Catherine T. MacArthur Foundation, USA and the United Nations Population Fund India Office., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Knowledge of HIV status remains below target in sub-Saharan Africa, especially among men and adolescents. HIV self-testing (HIVST) is a novel approach that enables unique distribution strategies, with potential to be highly decentralised and to provide complementary coverage to facility-based testing approaches. However, substantial gaps in evidence remain on the effectiveness and cost-effectiveness of HIVST, particularly in rural settings, and on approaches to facilitate linkage to confirmatory HIV testing, prevention, and treatment services. This protocol describes two cluster-randomized trials (CRT) included within the UNITAID/PSI HIV Self-Testing Africa (STAR) project., Methods: Two independent CRTs were designed around existing reproductive health programmes in rural Malawi and rural/peri-urban Zambia. Common features include use of constrained randomisation to allocate health clinic catchment areas to either standard HIV testing (SOC) or SOC plus community-based distribution of OraQuick HIV Self Tests (Bethlehem, PA USA, assembled in Thailand) by trained lay distributors selected by the community. Community-based distribution agents will be trained (3-day curriculum) to provide brief demonstration of kit use and interpretation, information and encouragement to access follow up services, and management of social harm. The primary outcome of both CRTs is the proportion of the population aged 16 years and older who tested for HIV within the 12-month intervention period. Secondary outcomes in both trials include lifetime HIV testing, antiretroviral therapy (ART) initiation and ART use. Circumcision status among males will be a secondary outcome in Zambia and clinic-level demand for ART will be a secondary outcome in Malawi. Outcomes will be measured using cross-sectional household surveys, and routine data extraction from participating clinics. Costing studies will be used to evaluate the cost-effectiveness of the intervention arm. Qualitative research will be used to guide distribution and explore reasons for testing and linkage to onward care., Discussion: The STAR-Malawi and STAR-Zambia trials will provide rigorous evidence of whether community-based lay HIVST distribution is an effective and cost-effective approach to increasing coverage of HIV testing and demand for follow-on HIV services in rural and peri-urban communities in sub-Saharan Africa., Trial Registration: Clinicaltrials.gov, Malawi: NCT02718274 , 18 March 2016; Zambia: NCT02793804 , 3 June 2016. Protocol date: 21 February 2018.

Introduction: A simple cost-effective strategy to pre-screen for targeted HIV testing can have substantial benefit in high burden and resource limited settings. A 4-item (previous hospitalisation, orphanhood, poor health status, and recurring skin problems) screening tool to identify adolescents living with HIV has previously shown high sensitivity in healthcare facility settings. We validated this screening tool in a community setting, in Harare, Zimbabwe in a community-based HIV prevalence survey., Methods: A community-based HIV prevalence survey was conducted among individuals aged 8-17 years with guardian consent and child assent and residing in 7 communities during the period February 2015 to December 2015. Participants without previously diagnosed HIV were evaluated for the probability of having HIV using the screening tool. HIV status was defined using an anonymous HIV test which was done using Oral Mucosal Transudate (OMT). A questionnaire was also administered to ascertain self-reported HIV status and screening tool items. The validity of a 4-item screening tool was tested. Sensitivity and specificity of the screening tool was assessed against the HIV status based on OMT result., Results: Prevalence survey participants were 5386 children who had an HIV test result, aged 8-17 years. However, 5384, who did not report testing HIV positive and responded to all screening tool item questions were included in the validation. Their median age was 12 (IQR: 10-15) years, 2515 (46.7%) were male. HIV prevalence was 1.3% (95% CI:1.0-1.8%). The 4-item screening tool had poor accuracy with an area under the receiver operating curve of 0.65(95% CI: 0.60-0.72) at a cut-off score≥1. Its sensitivity was 56.3% (95% CI:44.0-68.1%) and specificity of 75.1% (95% CI:73.9-76.3%), PPV of 2.9% (95% CI:2.1-3.9%) and a NPV of 99.2% (95% CI:98.9-99.5%). The number needed to test to diagnose one child using the screening tool was 55% lower than universal testing for HIV., Conclusion: Use of the 4-item screening tool could be a strategy that can be adopted to identify children living with HIV in a community setting in resource limited settings by reducing the number needed to test compared to universal testing since it is inexpensive, easy to administer and not harmful. However, screening items adapted to a community setting need to be explored to improve the performance of the screening tool., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To evaluate associations of DNA methylation of the human tumour suppressor gene EPB41L3 with high-grade cervical intraepithelial neoplasia (CIN2+) and HIV-related factors among women living with HIV-1 (WLHIV) in Burkina Faso and South Africa., Design: Case-control study of WLHIV aged 25-50 with histology-determined CIN2+ (cases, N = 152) and ≤CIN1 (controls, N = 210)., Methods: EPB41L3 methylation was measured by pyrosequencing of bisulphite converted DNA from exfoliated cervical specimens at baseline and 16 months later. Median methylation levels were compared across CIN grades using the Mann-Whitney test and Cuzick test for trend. EPB41L3 methylation levels were dichotomized into 'high' and 'low' using the 66.7 percentile point of the distribution in the controls. Associations of EPB41L3 methylation with HIV-related factors were estimated by logistic regression., Results: Among 94 WLHIV in Burkina Faso and 268 in South Africa, median methylation levels at baseline for EPB41L3 increased with increasing CIN grade in both countries (P-trend <0.001).'High' methylation was more frequent among women with a longer time since HIV diagnosis in Burkina Faso [>5 years vs. ≤5 years; adjusted odds ratio (aOR) = 4.15, 95% CI 1.09-15.83, adjusted for age, CD4 count, high-risk HPV and CIN status], with low CD4 count in both countries (CD4 ≤200 vs. ≥350 cells/μl: aOR = 7.14, 95% CI 1.44-35.37 in Burkina Faso; aOR = 2.55, 95% CI 1.07-6.07 in South Africa), and with prolonged ART use in South Africa (ART >2 years vs. ART-naïve: aOR = 2.40, 95% CI: 1.23-4.69)., Conclusion: Methylation of EPB41L3 DNA is elevated among WLHIV with CIN2+ and independently associated with lower CD4 count and ART use.

Background: Human papillomavirus (HPV) serodynamics following infection has never been evaluated prospectively among women living with HIV (WLHIV). We determined HPV seroprevalence, seroconversion, and cervical HPV-DNA acquisition among WLHIV., Methods: Prospective study of 604 WLHIV in Johannesburg, South Africa aged 25-50 years. At baseline and 16 months (endline), HPV type-specific antibodies (HPV6/11/16/18/31/33/35/39/45/52/56/58/59/68/73) were measured using HPV-pseudovirions and cervical HPV-DNA genotypes using INNO-LiPA., Results: Seroprevalence of any-HPV was 93.2% and simultaneous seropositivity for HPV types of the bivalent (HPV16/18), quadrivalent (HPV6/11/16/18), and nonavalent (HPV6/11/16/18/31/33/45/52/58) vaccines were 21.4%, 10.9%, and 2.8%. Among 219 women with cervical HPV-DNA, same-type seronegative and without high-grade cervical intraepithelial neoplasia at baseline, 51 (23.3%) had type-specific seroconversion at endline. Risk of type-specific seroconversion was higher among recent antiretroviral therapy users (ART ≤2 years vs ART naive: adjusted OR [aOR] = 2.39; 95% CI, 1.02-5.62), and lower among women with low CD4+ at endline (≤350 vs >350 cells/mm3: aOR = 0.51; 95% CI, 0.24-1.07). Risk of cervical HPV-DNA acquisition was lower in women seropositive for HPV18, 35, and 58 at baseline., Conclusion: WLHIV have evidence of seroconversion in response to baseline HPV-DNA, dependent on CD4+ count and ART. Baseline HPV seropositivity confers limited protection against some HPV types.

Background: Community-based rehabilitation (CBR), or community-based inclusive development, is an approach to address the complex health, social and economic needs of people with schizophrenia in low and middle-income countries. Formative work was undertaken previously to design a culturally appropriate CBR intervention for people with schizophrenia in Ethiopia. The current study explored the acceptability and feasibility of CBR in practice, as well as how CBR may improve functioning among people with schizophrenia., Methods: This mixed methods pilot study took place in rural Ethiopia between December 2014 and December 2015. Ten people with schizophrenia who were unresponsive to treatment with medication alone, and their caregivers, participated in CBR. CBR was led by lay workers with five weeks training and involved home visits (education, family intervention and support returning to work) and community mobilisation. Theory of change was used to guide the pilot evaluation. Qualitative and quantitative data were collected at baseline, six months and 12 months. Forty in-depth interviews and two focus group discussions were conducted with 31 individuals comprising people with schizophrenia, caregivers, CBR workers, supervisors, health officers and community members., Results: The RISE CBR intervention may have a positive impact on functioning through the pathways of enhanced family support, improved access to health care, increased income and improved self-esteem. CBR was acceptable to CBR workers, community leaders and health officers. Some CBR workers found it challenging to accept the choices of people with schizophrenia. These concerns were felt to be resolvable with supplementary training for CBR workers. The intervention was feasible but further evaluation is needed on a larger scale., Conclusion: In low and middle-income countries, CBR may be an acceptable and feasible adjuvant approach to facility-based care for people with schizophrenia. However, contextual factors, including poverty and inaccessible anti-psychotic medication, remain substantial challenges. There were indications that CBR can impact on functioning but the RISE trial will determine effectiveness.

Background: Childhood visual impairment is a major public health concern that requires effective screening and early intervention. We investigated the effectiveness of Peek school eye health, a smartphone-based sight test and referral system (comprising Peek Acuity test, sight simulation referral cards, and short message service [SMS] reminders), versus standard care (Snellen's Tumbling-E card and written referral)., Methods: We initially compared the performance of both the Snellen Tumbling-E card and the Peek Acuity test to a standard backlit EDTRS LogMAR visual acuity test chart. We did a cluster randomised controlled trial to compare the Peek school eye health system with standard school screening care, delivered by school teachers. Schools in Trans Nzoia County, Kenya, were eligible if they did not have an active screening programme already in place. Schools were randomly allocated (1:1) to either the Peek school eye health screening and referral programmes (Peek group) or the standard care screening and referral programme (standard group). In both groups, teachers tested vision of children in years 1-8. Pupils with visual impairment (defined as vision less than 6/12 in either eye) were referred to hospital for treatment. Referred children from the standard group received a written hospital referral letter. Participants and their teachers in the Peek group were shown their simulated sight on a smartphone and given a printout of this simulation with the same hospital details as the standard referral letter to present to their parent or guardian. They also received regular SMS reminders to attend the hospital. The primary outcome was the proportion of referred children who reported to hospital within 8 weeks of referral. Primary analysis was by intention to treat, with the intervention effect estimated using odds ratios. This trial is registered with Pan African Clinical Trial Registry, number PACTR201503001049236., Findings: Sensitivity was similar for the Peek test and the standard test (77% [95% CI 64·8-86·5] vs 75% [63·1-85·2]). Specificity was lower for the Peek test than the standard test (91% [95% CI 89·3-92·1] vs 97·4% [96·6-98·1]). Trial recruitment occurred between March 2, 2015, and March 13, 2015. Of the 295 eligible public primary schools in Trans Nzoia County, 50 schools were randomly selected and assigned to either the Peek group (n=25) or the standard group (n=25). 10 579 children were assessed for visual impairment in the Peek group and 10 284 children in the standard group. Visual impairment was identified in 531 (5%) of 10 579 children in the Peek group and 366 (4%) of 10 284 children in the standard care group. The proportion of pupils identified as having visual impairment who attended their hospital referral was significantly higher in the Peek group (285 [54%] of 531) than in the standard group (82 [22%] of 366; odds ratio 7·35 [95% CI 3·49-15·47]; p<0·0001)., Interpretation: The Peek school eye health system increased adherence to hospital referral for visual impairment assessment compared with the standard approach among school children. This indicates the potential of this technology package to improve uptake of services and provide real-time visibility of health service delivery to help target resources., Funding: Seeing is Believing, Operation Eyesight Universal, Queen Elizabeth Diamond Jubilee Trust, and Wellcome Trust., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: HIV infection in a family may affect optimum child development. Our hypothesis is that child development outcomes among HIV-exposed infants will be improved through a complex early childhood stimulation (ECS) programme, and income and loans saving programme for HIV positive parents., Methods: The study was a cluster-randomized controlled trial in 30 clinic sites in two districts in Zimbabwe. Clinics were randomised in a 1:1 allocation ratio to the Child Health Intervention for Development Outcomes (CHIDO) intervention or Ministry of Health standard care. The CHIDO intervention comprises three elements: a group ECS parenting programme, an internal savings and lending scheme (ISALS) and case-management home visits by village health workers. The intervention was aimed at caregiver-child dyads (child aged 0-24 months) where the infant was HIV exposed or infected. The primary outcomes were cognitive development (assessed by the Mullen Scales of Early Learning) and retention of the child in HIV care, at 12 months after enrolment. A comprehensive process evaluation was conducted., Discussion: The results of this cluster-randomised trial will provide important information regarding the effects of multi-component interventions in mitigating developmental delays in HIV-exposed infants living in resource-limited environments., Trial Registration: This trial is registered with the Pan African Clinical Trials Registry ( www.pactr.org ), registration number PACTR201701001387209; the trial was registered on 16th January 2017 (retrospectively registered).

Background: Although voluntary medical male circumcision (VMMC) reduces the risk of HIV acquisition, demand for services is lower among men in most at-risk age groups (ages 20-34 years). A randomized controlled trial was conducted to assess the effectiveness of locally-tailored demand creation activities (including mass media, community mobilization, and targeted service delivery) in increasing uptake of campaign-delivered VMMC among men aged 20-34 years. We conducted an economic evaluation to understand the intervention's cost and cost-effectiveness., Setting: Tanzania (Njombe and Tabora regions)., Methods: Cost data were collected on surgery, demand creation activities, and monitoring and supervision related to VMMC implementation across clusters in both trial arms, as well as start-up activities for the intervention arms. The Decision Makers' Program Planning Tool was used to estimate the number of HIV infections averted and related cost savings, given the total VMMCs per cluster. Disability-adjusted life years were calculated and used to estimate incremental cost-effectiveness ratios., Results: Client load was higher in the intervention arms than in the control arms: 4394 vs. 2901 in Tabora and 1797 vs. 1025 in Njombe, respectively. Despite additional costs of tailored demand creation, demand increased more than proportionally: mean costs per VMMC in the intervention arms were $62 in Tabora and $130 in Njombe, and in the control arms $70 and $191, respectively. More infections were averted in the intervention arm than in the control arm in Tabora (123 vs. 67, respectively) and in Njombe (164 vs. 102, respectively). The intervention dominated the control because it was both less costly and more effective. Cost savings were observed in both regions stemming from the antiretroviral treatment costs averted as a result of the VMMCs performed., Conclusions: Spending more to address local preferences as a way to increase uptake of VMMC can be cost-saving.

This study examines the cognitive profiles of infants born to HIV positive mothers in Zimbabwe. Caregivers with HIV exposed infants delivered in 30 clinics in two areas of Zimbabwe were recruited to the study. Of the 574 study participants, 562 caregiver-infant dyads with a biological HIV +ve mother and infant aged 0-24 months were interviewed. All infants were tested by a trained administrator for cognitive development on the Mullen Scales of Early Learning (MSEL). The Edinburgh Postnatal Depression Scale and Parental Stress Index-Short Form were completed by the mothers together with infant and caregiver socioeconomic characteristics. Linear regression models were used to relate cognitive development scores to maternal stress scores, maternal depression scores and infant HIV status adjusting for infant and caregiver characteristics, as well as socioeconomic factors. Higher maternal depression scores were associated with lower overall infant cognitive scores (adjusted mean difference (aMD) = -0.28; CI 95%:-0.50 to -0.06; p = 0.01) and in the expressive language (aMD = -0.14; CI 95%:-0.27 to -0.01; p = 0.04), fine motor skills (aMD = -0.17; CI 95%: -0.33 to -0.01; p = 0.03), gross motor (aMD = -0.22; CI 95%:-0.40 to -0.04; p = 0.02), and visual reception (aMD = -0.22; CI 95%:-0.40 to -0.05; p = 0.01) domains. Higher maternal stress was associated with poorer overall infant cognitive scores (aMD = -0.11; CI 95%:-0.20 to -0.02; p = 0.02) and in the specific domains of expressive language (aMD = -0.07; CI 95%:-0.12 to -0.01; p = 0.01), gross motor skills (aMD = -0.12; CI 95%:-0.18 to -0.05; p < 0.01) and visual reception (aMD = -0.09; CI 95%:-0.16 to -0.02; p = 0.02). Comparisons between the small number of HIV positive infants (n = 16) and the HEU infants (n = 381) showed the latter to have higher mean gross motor scores (50.3 vs. 40.6; p = 0.01). There was no evidence of difference by HIV status in the other MSEL domains or overall mean cognitive scores. Our findings demonstrate the association between maternal mood and stress levels and child cognitive functioning, particularly in expressive language and visual reception development. Although cross sectional data cannot shed light on the direction of this association, the study suggests that interventions to address maternal stress and depression symptoms may prove to be beneficial.

Purpose: Glaucoma is a leading cause of blindness in people of African descent. Minimal data is available from African population-based cohort studies. The primary aims of this study were to describe the normative distribution of glaucoma features to enable glaucoma classification and to assess risk factors for those with glaucoma at follow-up among people aged 50 years and above in Kenya., Materials and Methods: Random cluster sampling with probability proportionate to size was used to select a representative cross-sectional sample of adults aged 50 years and above in 2007 to 2008 in Nakuru District, Kenya. A 6-year follow-up was undertaken in 2013 to 2014. Comprehensive ophthalmic examination included visual acuity, digital retinal photography, visual fields, intraocular pressure, optical coherence tomography, and independent grading of optic nerve images. We report glaucoma features, prevalence and predictors for glaucoma based on the International Society for Geographical & Epidemiological Ophthalmology (ISGEO) criteria. Measures were estimated using a Poisson regression model and including inverse-probability weighting for loss to follow-up., Results: At baseline, 4414 participants aged 50 years and above underwent examination. Anterior chamber optical coherence tomography findings: mean anterior chamber angle of 36.6 degrees, mean central corneal thickness of 508.1 μm and a mean anterior chamber depth of 2.67 mm. A total of 2171 participants were examined at follow-up. The vertical cup to disc ratio distribution was 0.7 and 0.8 at the 97.5th and 99.5th percentiles, respectively. A total of 88 (4.3%, 95% confidence interval, 3.5%-5.9%) of participants at follow-up had glaucoma consistent with ISGEO criteria. A relative afferent pupillary defect and raised intraocular pressure were associated with the diagnosis., Conclusions: Glaucoma is a public health challenge in low-resource settings. Research into testing and treatment modalities in Africa is needed.

Purpose: The purpose of this study was to assess whether non-chlamydial bacterial infection is associated with progression of trachomatous scarring in adults., Methods: This was a cohort study involving 800 participants in northern Tanzania who underwent clinical examination, photography, and conjunctival swab collection for microbiology over a 24-month period. Samples for microbiology were inoculated onto blood and chocolate agar, and Chlamydia trachomatis was detected by PCR. Progression was determined by comparison of baseline to 24-month photographs., Results: C. trachomatis was detected in only four participants at baseline. At 24 months, 617 participants (77.1%) were followed up. Of those seen at 24 months, 452 could be reliably assessed. Definite scarring progression (progressors) was seen in 345 (55.9%); there was no progression (nonprogressors) in 107 (17.3%). Using combined baseline and 12-month microbiology results, progressors had significantly higher levels of commensal and pathogenic bacterial organisms detected compared with nonprogressors. After adjusting for age, baseline scarring, and ethnicity, there was weak evidence (P = 0.07) that the bacteria category was associated with scarring progression (commensal organisms only: odds ratio [OR] = 1.61; 95% confidence interval [CI]: 0.90 to 2.89; pathogenic organisms either with or without commensal: OR = 2.39; 95% CI: 1.10 to 5.16)., Conclusion: The findings were consistent with the possibility that trachomatous scarring in adults is associated with the presence of non-chlamydial bacterial organisms, particularly pathogenic organisms. C. trachomatis was detected very infrequently and may not be an important factor in the pathogenesis of scarring progression in adults. This has implications for trachoma control programs, which largely concentrate on reducing C. trachomatis levels and transmission.

Objective: To report the prevalence and incidence of low-risk human papillomavirus infection (LR-HPV) and anogenital warts (AGW) among women living with HIV (WLHIV) in Burkina Faso (BF) and South Africa (SA), and to explore HIV-related factors associated with these outcomes., Methods: We enrolled 1238 WLHIV (BF = 615; SA = 623) aged 25-50 years and followed them at three time points (6, 12 and 16 months) after enrolment. Presence of AGW was assessed during gynaecological examination. Cervico-vaginal swabs for enrolment and month 16 follow-up visits were tested for HPV infection by Inno-LiPA® genotyping. Logistic regression was used to assess risk factors for prevalent infection or AGW. Cox regression was used to assess risk factors for incident AGW., Results: Women in SA were more likely than those in BF to have prevalent LR-HPV infection (BF: 27.1% vs. SA: 40.9%; p<0.001) and incident LR-HPV infection (BF: 25.8% vs. SA: 31.6%, p = 0.05). Prevalence of persistent LR-HPV was similar in the two countries (BF: 33.3% vs. SA: 30.4%; p = 0.54), as were prevalence and incidence of AGW (Prevalence: BF: 7.5% vs. SA: 5.7%; p = 0.21; Incidence: BF: 2.47 vs. SA: 2.33 per 100 person-years; p = 0.41). HPV6 was associated with incident AGW (BF: adjusted Hazard Ratio (aHR) = 4.88; 95%CI: 1.36-17.45; SA: aHR = 5.02; 95%CI: 1.40-17.99). Prevalent LR-HPV (BF: adjusted Odds Ratio [aOR = 1.86]; 95%CI: 1.01-3.41; SA: aOR = 1.75; 95%CI: 0.88-3.48); persistent LR-HPV (BF: aOR = 1.92; 95%CI: 0.44-8.44; SA: aOR = 2.81; 95%CI: 1.07-7.41) and prevalent AGW (BF: aOR = 1.53; 95%CI: 0.61-3.87; SA: aOR = 4.11; 95%CI: 1.20-14.10) were each associated with low CD4+ counts (i.e. <200 vs. >500 cells/μL). Duration of ART and HIV plasma viral load were not associated with any LR-HPV infection or AGW outcomes., Conclusion: LR-HPV infection and AGW are common in WLHIV in sub-Saharan Africa. Type-specific HPV vaccines and effective ART with immunological reconstitution could reduce the burden of AGW in this population.

Background: Trachomatous trichiasis is treated surgically to prevent sight loss. Unfavourable surgical outcomes remain a major challenge. We investigated the hypothesis that doxycycline might reduce the risk of postoperative trichiasis following surgery in patients with trachomatous trichiasis through anti-matrix metalloproteinase and anti-inflammatory activity., Methods: In this randomised, double-blind, placebo-controlled trial, adults (aged >18 years) with upper lid trachomatous trichiasis in association with tarsal conjunctive scarring were recruited through community-based screening and surgical outreach campaigns in Ethiopia. Individuals who had previously had eyelid surgery were excluded. Participants were randomly assigned (1:1), with random block sizes of four or six, to receive oral doxycycline (100 mg once a day) or placebo for 28 days immediately after trichiasis surgery. Randomisation was stratified by surgeon. Patients, investigators, surgeons, and all other study team members were masked to study group allocation and treatment. Participants were examined at 10 days, and 1, 6, and 12 months after surgery. The primary outcome was the cumulative proportion of individuals who developed postoperative trichiasis by 12 months. Primary analyses were done in all participants who attended at least one of the four follow-up assessments. Safety analyses were done in all participants who attended either the 10 day or 1 month follow-up assessments. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201512001370307., Findings: Between Dec 21, 2015, and April 6, 2016, 1000 patients with trichiasis were enrolled and randomly assigned to treatment (499 patients to doxycycline, 501 patients to placebo). All but one participant attended at least one follow-up assessment. Thus, 999 participants were assessed for the primary outcome: 498 in the doxycycline group and 501 in the placebo group. By month 12, 58 (12%) of 498 patients in the doxycycline group and 62 (12%) of 501 patients in the placebo group had developed postoperative trichiasis (adjusted odds ratio 0·91, 95% CI 0·61 to 1·34, p=0·63), with a risk difference of -0·5% (-4·5% to 3·5%). Significantly more patients in the doxycycline group had an adverse event than in the placebo group (18 [4%] of 498 vs six [1%] of 501; odds ratio 3·09, 95% CI 1·21-7·84; p=0·02). The most frequent adverse events in the doxycycline group were gastritis symptoms (n=9), constipation (n=4), and diarrhoea (n=4)., Interpretation: Doxycycline did not reduce the risk of postoperative trichiasis and is therefore not indicated for the improvement of outcomes following trachomatous trichiasis surgery. Surgical programmes should continue to make efforts to strengthen surgical training and supervision to improve outcomes., Funding: The Wellcome Trust., (Copyright © 2018 The author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Emerging HIV epidemics have been documented among people who inject drugs (PWID) in the Middle East and North Africa (MENA). This study estimates the HIV incidence among PWID due to sharing needles/syringes in MENA. It also delineates injecting drug use role as a driver of the epidemic in the population, and estimates impact of interventions., Methods: A mathematical model of HIV transmission among PWID was applied in seven MENA countries with sufficient and recent epidemiological data and HIV prevalence ≥1% among PWID. Estimations of incident and/or prevalent infections among PWID, ex-PWID and sexual partners of infected current and ex-PWID were conducted., Results: The estimated HIV incidence rate for 2017 among PWID ranged between 0.7% per person-year (ppy) in Tunisia and 7.8% ppy in Pakistan, with Libya being an outlier (24.8% ppy). The estimated number of annual new infections was lowest in Tunisia (n = 79) and Morocco (n = 99), and highest in Iran and Pakistan (approximately n = 6700 each). In addition, 20 to 2208 and 5 to 837 new annual infections were estimated across the different countries among sexual partners of PWID and ex-PWID respectively. Since epidemic emergence, the number of total ever acquired incident infections across countries was 706 to 90,015 among PWID, 99 to 18,244 among sexual partners of PWID, and 16 to 4360 among sexual partners of ex-PWID. The estimated number of prevalent infections across countries was 341 to 23,279 among PWID, 119 to 16,540 among ex-PWID, 67 to 10,752 among sexual partners of PWID, and 12 to 2863 among sexual partners of ex-PWID. Increasing antiretroviral therapy (ART) coverage to the global target of 81% - factoring in ART adherence and current coverage - would avert about half of new infections among PWID and their sexual partners. Combining ART with harm reduction could avert over 90% and 70% of new infections among PWID and their sexual partners respectively., Conclusions: There is considerable HIV incidence among PWID in MENA. Of all new infections ultimately due to injecting drug use, about 75% are among PWID and the rest among sexual partners. Of all prevalent infections ultimately attributed to injecting drug use as epidemic driver, about half are among PWID, 30% among ex-PWID and 20% among sexual partners of PWID and ex-PWID. These findings call for scale-up of services for PWID, including harm reduction as well as testing and treatment services., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Background: Little is understood of Ebola virus disease (EVD) transmission dynamics and community compliance with control measures over time. Understanding these interactions is essential if interventions are to be effective in future outbreaks. We conducted a mixed-methods study to explore these factors in a rural village that experienced sustained EVD transmission in Kailahun District, Sierra Leone., Methods: We reconstructed transmission dynamics using a cross-sectional survey conducted in April 2015, and cross-referenced our results with surveillance, burial, and Ebola Management Centre (EMC) data. Factors associated with EVD transmission were assessed with Cox proportional hazards regression. Following the survey, qualitative semi-structured interviews explored views of community informants and households., Results: All households (n = 240; 1161 individuals) participated in the survey. 29 of 31 EVD probable/confirmed cases died (93·5% case fatality rate); six deaths (20·6%) had been missed by other surveillance systems. Transmission over five generations lasted 16 weeks. Although most households had ≤5 members there was a significant increase in risk of Ebola in households with > 5 members. Risk of EVD was also associated with older age. Cases were spatially clustered; all occurred in 15 households. EVD transmission was better understood when the community experience started to concord with public health messages being given. Perceptions of contact tracing changed from invading privacy and selling people to ensuring community safety. Burials in plastic bags, without female attendants or prayer, were perceived as dishonourable. Further reasons for low compliance were low EMC survival rates, family perceptions of a moral duty to provide care to relatives, poor communication with the EMC, and loss of livelihoods due to quarantine. Compliance with response measures increased only after the second generation, coinciding with the implementation of restrictive by-laws, return of the first survivor, reduced contact with dead bodies, and admission of patients to the EMC., Conclusions: Transmission occurred primarily in a few large households, with prolonged transmission and a high death toll. Return of a survivor to the village and more effective implementation of control strategies coincided with increased compliance to control measures, with few subsequent cases. We propose key recommendations for management of EVD outbreaks based on this experience.

Background: Suicidal ideation may lead to deliberate self-harm which increases the risk of death by suicide. Globally, the main cause of deliberate self-harm is depression. The aim of this study was to explore prevalence of, and risk factors for, suicidal ideation among men and women with common mental disorder (CMD) symptoms attending public clinics in Zimbabwe, and to determine whether problem solving therapy delivered by lay health workers can reduce common mental disorder symptoms among people with suicidal ideation, using secondary analysis of a randomised controlled trial., Methods: At trial enrolment, the Shona Symptom Questionnaire (SSQ) was used to screen for CMD symptoms. In the intervention arm, participants received six problem-solving therapy sessions conducted by trained and supervised lay health workers, while those in the control arm received enhanced usual care. We used multivariate logistic regression to identify risk factors for suicidal ideation at enrolment, and cluster-level logistic regression to compare SSQ scores at endline (6 months follow-up) between trial arms, stratified by suicidal ideation at enrolment., Results: There were 573 participants who screened positive for CMD symptoms and 75 (13.1%) reported suicidal ideation at baseline. At baseline, after adjusting for confounders, suicidal ideation was independently associated with being aged over 24, lack of household income (household income yes/no; adjusted odds ratio 0.52 (95% CI 0.29, 0.95); p = 0.03) and with having recently skipped a meal due to lack of food (adjusted odds ratio 3.06 (95% CI 1.81, 5.18); p < 0.001). Participants who reported suicidal ideation at enrolment experienced similar benefit to CMD symptoms from the Friendship Bench intervention (adjusted mean difference - 5.38, 95% CI -7.85, - 2.90; p < 0.001) compared to those who had common mental disorder symptoms but no suicidal ideation (adjusted mean difference - 4.86, 95% CI -5.68, - 4.04; p < 0.001)., Conclusions: Problem-solving therapy delivered by trained and supervised lay health workers reduced common mental disorder symptoms among participants with suicidal thoughts who attended primary care facilities in Zimbabwe., Trial Registration: pactr.org ldentifier: PACTR201410000876178.

Background: HIV testing is the important entry point for HIV care and prevention service, but uptake of HIV testing and thus coverage of antiretroviral therapy are much lower in older children and adolescents than in adults. We investigated the effect of economic incentives provided to caregivers of children aged 8-17 years on uptake of HIV testing and counselling in Harare, Zimbabwe., Methods: This randomised controlled trial was nested within a household HIV prevalence survey of children aged 8-17 years in Harare. Households with one or more survey participants whose HIV status was unknown were eligible to participate in the trial. Eligible households were randomly assigned (1:1:1) to either receive no incentive, receive a fixed US$2 incentive, or participate in a lottery for $5 or $10 if the participant presented for HIV testing and counselling at a local primary health-care centre. The survey fieldworkers who enrolled participants were not blinded to trial arm allocation, but the statistician was blinded for analysis of outcome. The primary outcome was the proportion of households in which at least one child had an HIV test within 4 weeks of enrolment. HIV test uptake in the incentivised groups was compared with uptake in the non-incentivised group using logistic regression, adjusting for community and number of children as fixed effects and research assistant as a random effect. All analyses were by intention to treat. The trial is registered with the Pan African Clinical Trials Registry, number PACTR201605001615280., Findings: Between Aug 4, and Dec 18, 2015, 2050 eligible households were enrolled in the prevalence survey. 649 (32%) households were assigned no incentive, 740 (34%) households were assigned a $2 incentive, and 661 (32%) households were assigned to lottery participation. Children were unavailable in 148 households in the no-incentive group, 63 households in the $2 incentive group, and 81 households in the lottery group. 1688 households had at least one child with unknown HIV status and were enrolled into the trial. 22 households had no undiagnosed child, and one household refused consent. The primary outcome of HIV testing was assessed in 472 (28%) households in the no-incentive group, 654 (39%) households in the $2 incentive group, and 562 (33%) households in the lottery group. At least one child was HIV tested in 93 (20%) households in the no-incentive group, in 316 (48%) households in the $2 incentive group (adjusted odds ratio 3·67, 95% CI 2·77-4·85; p<0·0001), and in 223 (40%) of 562 households in the lottery group (2·66, 2·00-3·55; p<0·0001). No adverse events were reported., Interpretation: Fixed incentives and lottery-based incentives increased the uptake of HIV testing by older children and adolescents, a key hard-to-reach population. This strategy would be sustainable in the context of vertical HIV infection as repeated testing would not be necessary until sexual debut., Funding: Wellcome Trust., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Management of menstruation can present substantial challenges to girls in low-income settings. In preparation for a menstrual hygiene intervention to reduce school absenteeism in Uganda, this study aimed to investigate menstruation management practices, barriers and facilitators, and the influence of menstruation on school absenteeism among secondary school students in a peri-urban district of Uganda., Methods: Qualitative and quantitative studies were conducted among consenting girls and boys aged 14-17 years in four secondary schools in Entebbe sub-District, Uganda. Methods included group and in-depth interviews with students, a quantitative cross-sectional questionnaire, a prospectively self-completed menstrual diary, key informant interviews with policy makers, and observations of school water, sanitation and hygiene facilities. Multiple logistic regression was used to assess factors associated with school absenteeism during the most recent menstrual period., Results: Girls reported substantial embarrassment and fear of teasing related to menstruation in the qualitative interviews, and said that this, together with menstrual pain and lack of effective materials for menstrual hygiene management, led to school absenteeism. All policy makers interviewed reported poverty and menstruation as the key factors associated with school attendance. The 352 girls with questionnaire data had a median age of 16 (inter-quartile range (IQR) = 15,16) years, with median age at menarche of 13 (IQR = 13,14) years. Of these, 64 girls (18.7%) reported having stained their clothes and 69 (19.7%) reported missing at least 1 day of school, during their most recent period. Missing school during the most recent period was associated with physical symptoms (headache (odds ratio (OR) = 2.15, 95%CI:1.20, 3.86), stomach pain (OR = 1.89, 95%CI:0.89, 4.04), back pain (OR = 1.75, 95%CI:0.97, 3.14), and with changing protection 4 or more times per 24 h period (OR = 2.08, 95%CI:1.06, 4.10). In the diary sub-study among 40 girls, school absence was reported on 28% of period-days, compared with 7% of non-period days (adjusted odds ratio = 5.99, 95%CI:4.4, 8.2; p < 0.001)., Conclusion: In this peri-urban Ugandan population, menstruation was strongly associated with school attendance. Evaluation of a menstrual management intervention that address both psychosocial (e.g. self-confidence, attitudes) and physical (e.g. management of pain, use of adequate menstrual hygiene materials, improved water and sanitation facilities) aspects of menstruation are needed.

Background: The interactions between antiretroviral therapy (ART) and high-risk human papillomavirus (HPV) and cervical lesions in women living with HIV are poorly understood. We reviewed the association of ART with these outcomes., Methods: We did a systematic review and meta-analysis by searching MEDLINE and Embase databases for cross-sectional or cohort studies published in English between Jan 1, 1996, and May 6, 2017, which reported the association of ART with prevalence of high-risk HPV or prevalence, incidence, progression, or regression of histological or cytological cervical abnormalities, or incidence of invasive cervcal cancer. Studies were eligible if they reported the association of combination ART or highly active ART use with the following outcomes: high-risk HPV prevalence; squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN) prevalence, incidence, progression, or regression; and invasive cervical cancer incidence among women living with HIV. We did random-effects meta-analyses to estimate summary statistics. We examined heterogeneity with the I 2 statistic. This review is registered on the PROSPERO database at the Centre of Reviews and Dissemination, University of York, York, UK (registration number CRD42016039546)., Findings: We identified 31 studies of the association of ART with prevalence of high-risk HPV (6537 women living with HIV) and high grade cervical lesions (HSIL-CIN2+; 9288 women living with HIV). Women living with HIV on ART had lower prevalence of high-risk HPV than did those not on ART (adjusted odds ratio [aOR] 0·83, 95% CI 0·70-0·99; I 2 =51%, adjusted for CD4 cell count and ART duration), and there was some evidence of association with HSIL-CIN2+ (0·65, 0·40-1·06; I 2 =30%). 17 studies reported the association of ART with longitudinal cervical lesion outcomes. ART was associated with a decreased risk of HSIL-CIN2+ incidence among 1830 women living with HIV (0·59, 0·40-0·87; I 2 =0%), SIL progression among 6212 women living with HIV (adjusted hazard ratio [aHR] 0·64, 95% CI 0·54-0·75; I 2 =18%), and increased likelihood of SIL or CIN regression among 5261 women living with HIV (1·54, 1·30-1·82; I 2 =0%). In three studies among 15 846 women living with HIV, ART was associated with a reduction in invasive cervical cancer incidence (crude HR 0·40, 95% CI 0·18-0·87, I 2 =33%)., Interpretation: Early ART initiation and sustained adherence is likely to reduce incidence and progression of SIL and CIN and ultimately incidence of invasive cervical cancer. Future cohort studies should aim to confirm this possible effect., Funding: UK Medical Research Council., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Children and adolescents have poorer HIV treatment outcomes than adults. We aimed to assess the effect of community-based support for caregivers of HIV-infected children and adolescents, who are key mediators to children engaging with care, on treatment outcomes., Methods: In this open-label, randomised contolled trial, we recruited children aged 6-15 years with newly-diagnosed HIV attending primary health-care clinics in Harare, Zimbabwe. Children were randomly assigned to receive decentralised primary health-care clinic-based HIV care (control group), according to national guidelines for 18 months, or decentralised care plus structured support visits by trained community health workers (intervention group) according to national guidelines for 18 months. Primary outcomes were the proportion of participants who died or had an HIV viral load of 400 copies per mL or higher at 12 months after antiretroviral therapy (ART) initiation (among those who started ART within 6 months of enrolment); and the proportion who missed two or more scheduled clinic visits by 18 months post-enrolment (among all participants). Analyses were complete-case, modified-intention-to-treat. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201212000442288., Findings: Between January, 2013, and January, 2015, 470 participants tested HIV-positive at seven study primary health-care clinics and were screened for eligibility. Of the 334 eligible children and adolescents, 166 were randomly assigned to the intervention group and 168 to the control group. The median age of participants was 11 years (IQR 8-13) and 178 (53%) were girls. Among the 238 participants who started ART within 6 months of enrolment, the proportion who died or had a viral load of 400 copies/mL or higher at 12 months post-ART initiation was significantly lower in the intervention group than in the control group (31 [33%] of 94 participants vs 42 [49%] of 86 participants, respectively, adjusted odds ratio [aOR] 0·46, 95% CI 0·23-0·89; p=0·02). The proportion of children missing two or more scheduled visits was similar in the intervention group and control group (27 [17%] of 155 vs 30 [18%] of 165, aOR 0·92, 95% CI 0·49-1·74; p=0·79). One participant withdrew from the trial 240 days after enrolment and 12 died during follow-up (five in the intervention group; seven in the control group)., Interpretation: Community-based support for caregivers has high potential for scalability and could have a substantial effect on HIV virological suppression in children and adolescents, a group with disproportionately poor treatment outcomes., Funding: Wellcome Trust.

Background: World Health Organization (WHO) adolescent HIV-testing and treatment guidelines recommend community-based interventions to support antiretroviral therapy (ART) adherence and retention in care, while acknowledging that the evidence to support this recommendation is weak. This cluster randomized controlled trial aims to evaluate the effectiveness and cost-effectiveness of a psychosocial, community-based intervention on HIV-related and psychosocial outcomes., Methods/design: We are conducting the trial in two districts. Sixteen clinics were randomized to either enhanced ART-adherence support or standard of care. Eligible individuals (HIV-positive adolescents aged 13-19 years and eligible for ART) in both arms receive ART and adherence support provided by adult counselors and nursing staff. Adolescents in the intervention arm additionally attend a monthly support group, are allocated to a designated community adolescent treatment supporter, and followed up through a short message service (SMS) and calls plus home visits. The type and frequency of contact is determined by whether the adolescent is "stable" or in need of enhanced support. Stable adolescents receive a monthly home visit plus a weekly, individualized SMS. An additional home visit is conducted if participants miss a scheduled clinic appointment or support-group meeting. Participants in need of further, enhanced, support receive bi-weekly home visits, weekly phone calls and daily SMS. Caregivers of adolescents in the intervention arm attend a caregiver support group. Trial outcomes are assessed through a clinical, behavioral and psychological assessment conducted at baseline and after 48 and 96 weeks. The primary outcome is the proportion who have died or have virological failure (viral load ≥1000 copies/ml) at 96 weeks. Secondary outcomes include virological failure at 48 weeks, retention in care (proportion of missed visits) and psychosocial outcomes at both time points. Statistical analyses will be conducted and reported in line with CONSORT guidelines for cluster randomized trials, including a flowchart., Discussion: This study provides a unique opportunity to generate evidence of the impact of the on-going Zvandiri program, for adolescents living with HIV, on virological failure and psychosocial outcomes as delivered in a real-world setting. If found to reduce rates of treatment failure, this would strengthen support for further scale-up across Zimbabwe and likely the region more widely., Trial Registration: Pan African Clinical Trial Registry database, registration number PACTR201609001767322 (the Zvandiri trial). Retrospectively registered on 5 September 2016.

The Ugandan government is committed to scaling-up proven HIV prevention strategies including safe male circumcision, and innovative strategies are needed to increase circumcision uptake. The aim of this study was to assess the acceptability and feasibility of implementing a soccer-based intervention ("Make The Cut") among schoolboys in a peri-urban district of Uganda. The intervention was led by trained, recently circumcised "coaches" who facilitated a 60-minute session delivered in schools, including an interactive penalty shoot-out game using metaphors for HIV prevention, sharing of the coaches' circumcision story, group discussion and ongoing engagement from the coach to facilitate linkage to male circumcision. The study took place in four secondary schools in Entebbe sub-district, Uganda. Acceptability of safe male circumcision was assessed through a cross-sectional quantitative survey. The feasibility of implementing the intervention was assessed by piloting the intervention in one school, modifying it, and implementing the modified version in a second school. Perceptions of the intervention were assessed with in-depth interviews with participants. Of the 210 boys in the cross-sectional survey, 59% reported being circumcised. Findings showed high levels of knowledge and generally favourable perceptions of circumcision. The initial implementation of Make The Cut resulted in 6/58 uncircumcised boys (10.3%) becoming circumcised. Changes made included increasing engagement with parents and improved liaison with schools regarding the timing of the intervention. Following this, uptake improved to 18/69 (26.1%) in the second school. In-depth interviews highlighted the important role of family and peer support and the coach in facilitating the decision to circumcise. This study showed that the modified Make The Cut intervention may be effective to increase uptake of safe male circumcision in this population. However, the intervention is time-intensive, and further work is needed to assess the cost-effectiveness of the intervention conducted at scale.

Background: The Healthy Activity Programme (HAP), a brief behavioural intervention delivered by lay counsellors, enhanced remission over 3 months among primary care attendees with depression in peri-urban and rural settings in India. We evaluated the sustainability of the effects after treatment termination, the cost-effectiveness of HAP over 12 months, and the effects of the hypothesized mediator of activation on clinical outcomes., Methods and Findings: Primary care attendees aged 18-65 years screened with moderately severe to severe depression on the Patient Health Questionnaire 9 (PHQ-9) were randomised to either HAP plus enhanced usual care (EUC) (n = 247) or EUC alone (n = 248), of whom 95% completed assessments at 3 months, and 91% at 12 months. Primary outcomes were severity on the Beck Depression Inventory-II (BDI-II) and remission on the PHQ-9. HAP participants maintained the gains they showed at the end of treatment through the 12-month follow-up (difference in mean BDI-II score between 3 and 12 months = -0.34; 95% CI -2.37, 1.69; p = 0.74), with lower symptom severity scores than participants who received EUC alone (adjusted mean difference in BDI-II score = -4.45; 95% CI -7.26, -1.63; p = 0.002) and higher rates of remission (adjusted prevalence ratio [aPR] = 1.36; 95% CI 1.15, 1.61; p < 0.009). They also fared better on most secondary outcomes, including recovery (aPR = 1.98; 95% CI 1.29, 3.03; p = 0.002), any response over time (aPR = 1.45; 95% CI 1.27, 1.66; p < 0.001), higher likelihood of reporting a minimal clinically important difference (aPR = 1.42; 95% CI 1.17, 1.71; p < 0.001), and lower likelihood of reporting suicidal behaviour (aPR = 0.71; 95% CI 0.51, 1.01; p = 0.06). HAP plus EUC also had a marginal effect on WHO Disability Assessment Schedule score at 12 months (aPR = -1.58; 95% CI -3.33, 0.17; p = 0.08); other outcomes (days unable to work, intimate partner violence toward females) did not statistically significantly differ between the two arms. Economic analyses indicated that HAP plus EUC was dominant over EUC alone, with lower costs and better outcomes; uncertainty analysis showed that from this health system perspective there was a 95% chance of HAP being cost-effective, given a willingness to pay threshold of Intl$16,060-equivalent to GDP per capita in Goa-per quality-adjusted life year gained. Patient-reported behavioural activation level at 3 months mediated the effect of the HAP intervention on the 12-month depression score (β = -2.62; 95% CI -3.28, -1.97; p < 0.001). Serious adverse events were infrequent, and prevalence was similar by arm. We were unable to assess possible episodes of remission and relapse that may have occurred between our outcome assessment time points of 3 and 12 months after randomisation. We did not account for or evaluate the effect of mediators other than behavioural activation., Conclusions: HAP's superiority over EUC at the end of treatment was largely stable over time and was mediated by patient activation. HAP provides better outcomes at lower costs from a perspective covering publicly funded healthcare services and productivity impacts on patients and their families., Trial Registration: ISRCTN registry ISRCTN95149997.

Aims: The aim of this study was to examine trajectories of Alcohol Use Disorders (AUD) over a 6 year period and compare the bio-psycho-social correlates between these trajectories., Methods: Community-based cohort of 1899 adult men were interviewed in 2006-2008 and 2012-2014. AUD were assessed using the Alcohol Use Disorder Identification Test, and potential correlates including psycho-social problems, morbidity and physiological parameters were measured at follow-up. Logistic regression was conducted to estimate odds ratios (ORs) for the association of persistent and incident AUD, respectively, with the potential correlates. Analyses were weighted to account for sampling design, number of adults aged 18-49 years in the household and non-response., Results: Compared with men who had recovered from AUD, there was strong evidence (P < 0.001) that men with persistent AUD were more likely to have marital problems, tobacco use, and raised Gamma Glutamyl Transferase (GGT) and strong evidence (0.001 < P < 0.01) that they were more likely to have workplace problems, social problems, increased healthcare contact and raised Mean Corpuscular Volume (MCV). Compared with men who did not have AUD at baseline and follow-up, there was strong evidence (P < 0.001) that men with incident AUD were more likely to have workplace problems, social problems, marital problems, tobacco use, and raised GGT and strong evidence (0.001 < P < 0.01) that they were more likely to have hypertension, accident and injuries and Common Mental Disorders (CMD)., Conclusion: This community-based longitudinal study of AUD, the first from a low and middle income country, clearly demonstrates significant health and social consequences of AUD in men and highlights the need for interventions for their treatment and prevention., Short Summary: Compared to persistent AUD, recovery from AUD has several benefits in health and social domains. Compared to developing new AUD, not having AUD has several benefits in health and social domains. Sustaining the state of not having AUD or recovery can lead to accumulation of health and social capital over time., (© The Author 2017. Medical Council on Alcohol and Oxford University Press.)

African adolescents and young adults remain at substantial risk of infection with HIV and other sexually transmitted infections (STIs), and AIDS is the leading cause of death among African adolescents (10-19 years). Sexual partnership patterns influence transmission risk of sexually transmitted infections. We describe patterns reported by youth (15-30y) in a community-based survey in Tanzania. Among participants reporting multiple partners, we investigated factors associated with reported concurrency. Female (N = 6513) and male (N = 7301) participants had median ages of 21 and 22 years, respectively. Most participants (92%) reported having previously been sexually active, of whom 15% of males and <1% of females reported ≥4 partners in the past year. The point prevalence of concurrency was 2.3% (95%CI 1.9-2.9) for females and 10.6% (95%CI 9.3-12.1) for males. High levels of multiple and concurrent partnerships were reported by those previously married. Females were more likely than males to report having spousal/regular partners and longer partnership lengths. Compared to males, the partnerships reported by females were less likely to be new partnerships, and more likely to be defined by the respondent as still 'ongoing'. Females reporting younger sexual debut were more likely to report concurrent sexual partners. Far fewer young women reported multiple and concurrent partnerships, but we cannot definitively conclude that concurrency was uncommon for women, because stigma towards women's multiple sexual partnerships might contribute to substantial under-reporting, as was found in extensive qualitative research in the study population. This study provides one of the most comprehensive quantitative descriptions of partnership patterns of young people in an African setting. Interventions addressing sexual risk among youth should involve male partners, empower women to protect themselves within different types of partnerships, and encourage a greater openness about young people's sexual relationships.

Background: Trachomatous trichiasis (TT) may lead to disability, impeding productive activities, resulting in loss of income. This study was conducted to determine if trichiasis surgery improves participation in productive and leisure activities, and ability to perform activities without difficulty or assistance. Methods: We recruited 1000 adults with trichiasis (cases) and 200 comparison participants, matched to every fifth trichiasis case on age (+/- two years), sex and location. The 'Stylised Activity List' tool, developed for the World Bank Living Standard Measurement Survey, was adapted to collect data on activity in the last week (participation in activity, difficulty with activity, requirement of assistance for activity), at baseline and 12 months later. All trichiasis cases received trichiasis surgery at baseline. Random effect logistic regression was used to compare cases and comparison participants. Results: There was strong evidence that trichiasis surgery substantially improves the ability of trichiasis cases to perform all the productive and leisure activities investigated without difficulty, with large increases in processing agricultural products, 21.1% to 87.0% (p<0.0001), farming, 19.1% to 82.4% (p<0.0001), and fetching wood, 25.3% to 86.0% (p<0.0001). Similarly, there was a significant increase in the proportion of cases who could perform activities without assistance, with the largest increases in animal rearing 54.2% to 92.0% (p<0.0001) and farming 73.2% to 96.4% (p<0.0001). There was no change in the proportion of comparison participants performing activities without difficulty or assistance. The change in most of the activities in cases was independent of visual acuity improvement and recurrent TT at 12 months. One year after trichiasis surgery, the proportion of cases reporting ocular pain reduced from 98.9% to 33.7% (p<0.0001). Conclusions: Eyelid surgery for TT improves functional capabilities regardless of vision gains. These data lend strong support to the view that TT surgery improves function and contributes to improved household income and wealth., Competing Interests: Competing interests: No competing interests were disclosed.

Purpose: Unfavorable outcomes after trachomatous trichiasis (TT) surgery are undermining the global trachoma elimination effort. This analysis investigates predictors of postoperative TT (PTT), eyelid contour abnormalities (ECAs), and granuloma in the 2 most common TT surgery procedures: posterior lamellar tarsal rotation (PLTR) and bilamellar tarsal rotation (BLTR)., Design: Secondary data analysis from a randomized, controlled, single-masked clinical trial., Participants: A total of 1000 patients with TT, with lashes touching the eye or evidence of epilation, in association with tarsal conjunctival scarring., Methods: Participants were randomly allocated and received BLTR (n = 501) or PLTR (n = 499) surgery. Disease severity at baseline, surgical incisions, sutures, and corrections were graded during and immediately after surgery. Participants were examined at 6 and 12 months by assessors masked to allocation., Main Outcome Measures: Predictors of PTT, ECA, and granuloma., Results: Data were available for 992 (99.2%) trial participants (496 in each arm). There was strong evidence that performing more peripheral dissection with scissors in PLTR (odd ratio [OR], 0.70; 95% confidence interval [CI], 0.54-0.91; P = 0.008) and BLTR (OR, 0.83; 95% CI, 0.72-0.96; P = 0.01) independently protected against PTT. Baseline major trichiasis and mixed location lashes and immediate postoperative central undercorrection independently predicted PTT in both surgical procedures. Peripheral lashes in PLTR (OR, 5.91; 95% CI, 1.48-23.5; P = 0.01) and external central incision height ≥4 mm in BLTR (OR, 2.89; 95% CI, 1.55-5.41; P = 0.001) were independently associated with PTT. Suture interval asymmetry of >2 mm (OR, 3.18; 95% CI, 1.31-7.70; P = 0.01) in PLTR and baseline conjunctival scarring in BLTR (OR, 1.72; 95% CI, 1.06-2.81; P = 0.03) were independently associated with ECA. Older age was independently associated with ECA in both PLTR (P value for trend < 0.0001) and BLTR (P value for trend = 0.03). There was substantial intersurgeon variability in ECA rates for both PLTR (range, 19.0%-36.2%) and BLTR (range, 6.1%-28.7%) procedures. In PLTR surgery, irregular posterior lamellar incision at the center of the eyelid (OR, 6.72; 95% CI, 1.55-29.04; P = 0.01) and ECA (OR, 3.08; 95% CI, 1.37-6.94; P = 0.007) resulted in granuloma formation., Conclusions: Poor postoperative outcomes in TT surgery were associated with inadequate peripheral dissection, irregular incision, asymmetric suture position and tension, inadequate correction, and lash location. Addressing these will improve TT surgical outcomes., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Children living with HIV who are not diagnosed in infancy often remain undiagnosed until they present with advanced disease. Provider-initiated testing and counselling (PITC) in health facilities is recommended for high-HIV-prevalence settings, but it is unclear whether this approach is sufficient to achieve universal coverage of HIV testing. We aimed to investigate the change in community burden of undiagnosed HIV infection among older children and adolescents following implementation of PITC in Harare, Zimbabwe., Methods and Findings: Over the course of 2 years (January 2013-January 2015), 7 primary health clinics (PHCs) in southwestern Harare implemented optimised, opt-out PITC for all attendees aged 6-15 years. In February 2015-December 2015, we conducted a representative cross-sectional survey of 8-17-year-olds living in the 7 communities served by the study PHCs, who would have had 2 years of exposure to PITC. Knowledge of HIV status was ascertained through a caregiver questionnaire, and anonymised HIV testing was carried out using oral mucosal transudate (OMT) tests. After 1 participant taking antiretroviral therapy was observed to have a false negative OMT result, from July 2015 urine samples were obtained from all participants providing OMTs and tested for antiretroviral drugs to confirm HIV status. Children who tested positive through PITC were identified from among survey participants using gender, birthdate, and location. Of 7,146 children in 4,251 eligible households, 5,486 (76.8%) children in 3,397 households agreed to participate in the survey, and 141 were HIV positive. HIV prevalence was 2.6% (95% CI 2.2%-3.1%), and over a third of participants with HIV were undiagnosed (37.7%; 95% CI 29.8%-46.2%). Similarly, among the subsample of 2,643 (48.2%) participants with a urine test result, 34.7% of those living with HIV were undiagnosed (95% CI 23.5%-47.9%). Based on extrapolation from the survey sample to the community, we estimated that PITC over 2 years identified between 18% and 42% of previously undiagnosed children in the community. The main limitation is that prevalence of undiagnosed HIV was defined using a combination of 3 measures (OMT, self-report, and urine test), none of which were perfect., Conclusions: Facility-based approaches are inadequate in achieving universal coverage of HIV testing among older children and adolescents. Alternative, community-based approaches are required to meet the Joint United Nations Programme on HIV/AIDS (UNAIDS) target of diagnosing 90% of those living with HIV by 2020 in this age group.

Background: In Africa, accessing eye health services is a major challenge. Ocular surface squamous neoplasia (OSSN) is a substantial ocular health problem in Africa related to solar UV light exposure and HIV infection among other risk factors. The disease causes visual loss and even death in advanced cases. This study was conducted to assess referral pathway and treatment delay for patients with OSSN in Kenya., Methods: Adults with conjunctival lesions presenting to four eye centres were asked about their occupations, when they noticed the growth, health facilities visited in seeking care, cost of consultation, surgery, medicines and histopathology and dates at each step. The time-to-presentation was divided into quartiles and correlates analysed using ordinal logistic regression., Results: We evaluated 158 first-time presenters with OSSN. Most were women (102 [65%]), living with HIV (78/110 tested [71%]), with low to medium income (127 [80%]). Most of the HIV patients (49/78 [63%]) were in antiretroviral care programs. About half (88/158, [56%]) presented directly to the study centres while the rest were referred. Indirect presenters sought care earlier than direct presenters (median 2.0 months vs 5.5 months) and travelled a shorter distance to the first health facility (median 20 km vs 30 km) but had surgery later (median 12.5 months vs 5.5 months). Visits beyond the first health facility for indirect presenters markedly increased delay (median 7.3, 29.0, 37.9, and 32.0 months for 1-4 facilities, respectively). Delay was associated with number of health facilities visited (adjusted ordered OR = 9.12; 95%CI 2.83-29.4, p < 0.001) and being female (adjusted ordered OR = 2.42; 95%CI 1.32-4.44, p = 0.004). At the time of presentation at the study centres for surgery the median tumour diameter in both directly and indirectly presenting patients was 6 mm (p = 0.52) and the histological spectrum of OSSN was similar between the groups (p = 0.87)., Conclusions: Referral delays definitive treatment for OSSN. Women were more likely to experience delay. Despite regular contact with the health system for those with known HIV infection, delays occurred. Early detection and referral of OSSN in the HIV service might reduce delays, but reassuringly delay did not give rise to a larger proportion with more advanced grade of OSSN.

Importance: The incidence of age-related macular degeneration (AMD) is unknown in Africa., Objective: To estimate the 6-year cumulative incidence and progression of AMD in older adults (≥50 years old) in Nakuru, Kenya., Design, Setting, and Participants: This study assessed a population-based cohort with 6-year follow-up of 4414 participants who had a complete assessment. Random cluster sampling with probability proportionate to size procedures was used to select a representative, cross-sectional sample of adults 50 years and older from January 26, 2007, through November 11, 2008. A 6-year follow-up was undertaken from January 7, 2013, through March 12, 2014. On both occasions, a comprehensive ophthalmic examination was performed that included logMAR visual acuity, digital retinal photography, and grading of images at Moorfields Eye Hospital Reading Centre. Data were collected on general health and risk factors., Main Outcomes and Measures: Incident AMD in participants with no AMD at baseline and progression from early to late AMD., Results: A total of 1453 of the 2900 individuals (50.1%) at risk for AMD were followed up after 6 years (mean [SD] age, 60.7 [8.2] years; 635 female [49.5%]; 799 Kikuyu [62.3%], 324 Kalenjin [25.3%], and 159 other [12.4%]); 1282 had data on AMD status at follow-up. Of these, 202 developed early AMD, and no participants developed late AMD. The 6-year weighted (for loss to follow-up) cumulative incidence of early AMD was 164.2 per 1000 persons (95% CI, 136.7-195.9 per 1000 persons). Two individuals with baseline early AMD from the 142 at risk had developed late AMD at follow-up, with a 6-year cumulative incidence of progression from early to late AMD of 24.5 per 1000 persons (95% CI, 5.0-111.7 per 1000 persons). Cumulative incidence of AMD increased with age (≥80 years old vs 50-59 years old: 1.8; 95% CI, 0.9-3.5) and was higher in women (female vs male: 1.6; 95% CI, 1.2-2.1) and persons with diabetes (diabetes vs no diabetes: 1.7; 95% CI, 1.0-2.8)., Conclusions and Relevance: In Kenya, more than 100 000 estimated new cases of AMD, mainly early AMD, will develop every year in individuals 50 years or older, although a 50% loss to follow-up and wide CIs for progression to late AMD limit definitive conclusions from these findings.

Data on the course of major depressive disorder (MDD) among people living with HIV (PLWH) are needed to inform refinement of screening and interventions for MDD. This paper describes the incidence and persistence rate of MDD in PLWH in Uganda. 1099 ART-naïve PLWH attending HIV clinics in Uganda were followed up for 12 months. MDD was assessed using the DSM IV based Mini-International Neuropsychiatric Interview with a prevalence for MDD at baseline of 14.0 % (95 % CI 11.7-16.3 %) reported. Multivariable logistic regression was used to determine predictors of incident and persistent MDD. Cumulative incidence of MDD was 6.1 per 100 person-years (95 % CI 4.6-7.8) with significant independent predictors of study site, higher baseline depression scores and increased stress. Persistence of MDD was 24.6 % (95 % CI 17.9-32.5 %) with independent significant predictors of study site, higher baseline depression scores, and increased weight. Risks of incident and persistent MDD observed in this study were high. Potentially modifiable factors of elevated baseline depressive scores and stress (only for incident MDD) were important predictors of incident and persistent MDD.

Objective: We evaluated a demand-creation intervention to increase voluntary medical male circumcision (VMMC) uptake among men aged 20-34 years in Tanzania, to maximise short-term impact on HIV incidence., Methods: A cluster randomized controlled trial stratified by region was conducted in 20 outreach sites in Njombe and Tabora regions. The sites were randomized 1 : 1 to receive either a demand-creation intervention package in addition to standard VMMC outreach, or standard VMMC outreach alone. The intervention package included enhanced public address messages, peer promotion by recently circumcised men, facility setup to increase privacy, and engagement of female partners in demand creation. The primary outcome was the proportion of VMMC clients aged 20-34 years., Findings: Overall, 6251 and 3968 VMMC clients were enrolled in intervention and control clusters, respectively. The proportion of clients aged 20-34 years was slightly greater in the intervention than control arm [17.7 vs. 13.0%; prevalence ratio = 1.36; 95% confidence intervals (CI):0.9-2.0]. In Njombe region, the proportion of clients aged 20-34 years was similar between arms but a significant two-fold difference was seen in Tabora region (P value for effect modification = 0.006). The mean number of men aged 20-34 years (mean difference per cluster = 97; 95% CI:40-154), and of all ages (mean difference per cluster = 227, 95% CI:33-420) were greater in the intervention than control arm., Conclusion: The intervention was associated with a significant increase in the proportion of clients aged 20-34 years in Tabora but not in Njombe. The intervention may be sensitive to regional factors in VMMC programme scale-up, including saturation.

Stigma associated with schizophrenia significantly affects family caregivers, yet few studies have examined the nature and determinants of family stigma and its relationship to their knowledge about the condition. This paper describes the experiences and determinants of stigma reported by the primary caregivers of people living with schizophrenia (PLS) in India. The study used mixed methods and was nested in a randomised controlled trial of community care for people with schizophrenia. Between November 2009 and October 2010, data on caregiver stigma and functional outcomes were collected from a sample of 282 PLS-caregiver dyads. In addition, 36 in-depth-interviews were conducted with caregivers. Quantitative findings indicate that 'high caregiver stigma' was reported by a significant minority of caregivers (21%) and that many felt uncomfortable to disclose their family member's condition (45%). Caregiver stigma was independently associated with higher levels of positive symptoms of schizophrenia, higher levels of disability, younger PLS age, household education at secondary school level and research site. Knowledge about schizophrenia was not associated with caregiver stigma. Qualitative data illustrate the various ways in which stigma affected the lives of family caregivers and reveal relevant links between caregiver-stigma related themes ('others finding out', 'negative reactions' and 'negative feelings and views about the self') and other themes in the data. Findings highlight the need for interventions that address both the needs of PLS and their family caregivers. Qualitative data also illustrate the complexities surrounding the relationship between knowledge and stigma and suggest that providing 'knowledge about schizophrenia' may influence the process of stigmatisation in both positive and negative ways. We posit that educational interventions need to consider context-specific factors when choosing anti-stigma-messages to be conveyed. Our findings suggest that messages such as 'recovery is possible' and 'no-one is to blame' may be more helpful than focusing on bio-medical knowledge alone., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To describe associations of high-risk human papillomavirus (HR-HPV) with high-grade cervical intraepithelial neoplasia (CIN2+) in women living with HIV (WLHIV) in Burkina Faso (BF) and South Africa (SA)., Methods: Prospective cohort of WLHIV attending HIV outpatient clinics and treatment centres. Recruitment was stratified by ART status. Cervical HPV genotyping using INNO-LiPA and histological assessment of 4-quadrant cervical biopsies at enrolment and 16 months later., Results: Among women with CIN2+ at baseline, the prevalence of any HR-HPV genotypes included in the bi/quadrivalent (HPV16/18) or nonavalent (HPV16/18/31/35/45/52/58) HPV vaccines ranged from 37% to 90%. HPV58 was most strongly associated with CIN2+ (aOR = 5.40, 95%CI: 2.77-10.53). At 16-months follow-up, persistence of any HR-HPV was strongly associated with incident CIN2+ (aOR = 7.90, 95%CI: 3.11-20.07), as was persistence of HPV16/18 (aOR = 5.25, 95%CI: 2.14-12.91) and the additional HR types in the nonavalent vaccine (aOR = 3.23, 95%CI: 1.23-8.54)., Conclusion: HR-HPV persistence is very common among African WLHIV and is linked to incident CIN2+. HPV vaccines could prevent between 37-90% of CIN2+ among African WLHIV.