Protocol for the Adolescent Menstrual Experiences and Health Cohort (AMEHC) Study in Khulna, Bangladesh: A Prospective cohort to quantify the influence of menstrual health on adolescent girls' health and education outcomes.

BACKGROUND: Menstrual health is essential for gender equity and the well-being of women and girls. Qualitative research has described the burden of poor menstrual health on health and education; however, these impacts have not been quantified, curtailing investment. The Adolescent Menstrual Experiences and Health Cohort (AMEHC) Study aims to describe menstrual health and its trajectories across adolescence, and quantify the relationships between menstrual health and girls' health and education in Khulna, Bangladesh. METHODS AND ANALYSIS: AMEHC is a prospective longitudinal cohort of 2016 adolescent girls recruited at the commencement of class 6 (secondary school, mean age=12) across 101 schools selected through a proportional random sampling approach. Each year, the cohort will be asked to complete a survey capturing (1) girls' menstrual health and experiences, (2) support for menstrual health, and (3) health and education outcomes. Survey questions were refined through qualitative research, cognitive interviews and pilot survey in the year preceding the cohort. Girls' guardians will be surveyed at baseline and wave 2 to capture their perspectives and household demographics. Annual assessments will capture schools' water, sanitation and hygiene, and support for menstruation and collect data on participants' education, including school attendance and performance (in maths, literacy). Cohort enrolment and baseline survey commenced in February 2023. Follow-up waves are scheduled for 2024, 2025 and 2026, with plans for extension. A nested subcohort will follow 406 post-menarche girls at 2-month intervals throughout 2023 (May, August, October) to describe changes across menstrual periods. This protocol outlines a priori hypotheses regarding the impacts of menstrual health to be tested through the cohort. ETHICS AND DISSEMINATION: AMEHC has ethical approval from the Alfred Hospital Ethics Committee (369/22) and BRAC James P Grant School of Public Health Institutional Review Board (IRB-06 July 22-024). Study materials and outputs will be available open access through peer-reviewed publication and study web pages.

Childhood and adolescent factors shaping vulnerability to underage entry into sex work: a quantitative hierarchical analysis of female sex workers in Nairobi, Kenya.

OBJECTIVE: To explore factors associated with early age at entry into sex work, among a cohort of female sex workers (FSWs) in Nairobi, Kenya. BACKGROUND: Younger age at sex work initiation increases the risk of HIV acquisition, condom non-use, violence victimisation and alcohol and/or substance use problems. This study aimed to understand factors in childhood and adolescence that shape the vulnerability to underage sex work initiation. DESIGN: Building on previous qualitative research with this cohort, analysis of behavioural-biological cross-sectional data using hierarchical logistic regression. PARTICIPANTS AND MEASURES: FSWs aged 18-45 years were randomly selected from seven Sex Workers Outreach Programme clinics in Nairobi, and between June and December 2019, completed a baseline behavioural-biological survey. Measurement tools included WHO Adverse Childhood Experiences, Alcohol, Smoking and Substance Involvement Screening Test and questionnaires on sociodemographic information, sexual risk behaviours and gender-based violence. Descriptive statistics and logistic regression were conducted using hierarchical modelling. RESULTS: Of the 1003 FSWs who participated in the baseline survey (response rate 96%), 176 (17.5%) initiated sex work while underage (<18 years). In the multivariable analysis, factors associated with entering sex work while underage included incomplete secondary school education (aOR=2.82; 95% CI=1.69 to 4.73), experiencing homelessness as a child (aOR=2.20; 95% CI=1.39 to 3.48), experiencing childhood physical or sexual violence (aOR=1.85; 95% CI=1.09 to 3.15), young age of sexual debut (≤15 years) (aOR=5.03; 95% CI=1.83 to 13.79) and being childless at time of sex work initiation (aOR=9.80; 95% CI=3.60 to 26.66). CONCLUSIONS: Lower education level and childhood homelessness, combined with sexual violence and sexual risk behaviours in childhood, create pathways to underage initiation into sex work. Interventions designed for girls and young women at these pivotal points in their lives could help prevent underage sex work initiation and their associated health, social and economic consequences.

Syndemic of factors that shape the early lives of women who enter into sex work: a qualitative methods study from Nairobi, Kenya.

OBJECTIVE: To explore the structural and social co-factors that shape the early lives of women who enter sex work in Nairobi, Kenya. DESIGN: Thematic analysis of qualitative data collected as part of the Maisha Fiti study among female sex workers (FSWs) in Nairobi. PARTICIPANTS AND MEASURES: FSWs aged 18-45 years were randomly selected from seven Sex Workers Outreach Programme clinics in Nairobi and participated in baseline behavioural-biological surveys. Participants in this qualitative study were randomly selected from the Maisha Fiti study cohort and were interviewed between October 2019 and July 2020. Women described their lives from childhood, covering topics including sex work, violence and financial management. RESULTS: 48 out of 1003 Maisha Fiti participants participated in the in-depth qualitative interviews. FSWs described how physical and sexual violence, poverty and incomplete education in their childhood and adolescence intertwined with early pregnancy, marriage, intimate partner violence and relationship breakdown in their adolescence and early adulthood. The data analysis found clear syndemic relationships between these risk factors, particularly childhood violence, poverty and incomplete education and highlighted pathways leading to financial desperation and caring for dependents, and subsequent entry into sex work. Women perceived sex work as risky and most would prefer alternative work if possible, but it provided them with some financial independence and agency. CONCLUSIONS: This is the first study in Kenya to qualitatively explore the early lives of sex workers from a syndemic perspective. This method identified the pivotal points of (1) leaving school early due to poverty or pregnancy, (2) breakdown of early intimate relationships and (3) women caring for dependents on their own. Complex, multi-component structural interventions before these points could help increase school retention, reduce teenage pregnancy, tackle violence, support young mothers and reduce entry into sex work and the risk that it entails by expanding livelihood options.

Exploring Perceived Barriers and Facilitators of PrEP Uptake among Young People in Uganda, Zimbabwe, and South Africa.

Pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy. Few studies have explored adolescents and young people's perspectives toward PrEP. We conducted 24 group discussions and 60 in-depth interviews with males and females aged 13-24 years in Uganda, Zimbabwe, and South Africa between September 2018 and February 2019. We used the framework approach to generate themes and key concepts for analysis following the social ecological model. Young people expressed a willingness to use PrEP and identified potential barriers and facilitators of PrEP uptake. Barriers included factors at individual (fear of HIV, fear of side effects, and PrEP characteristics), interpersonal (parental influence, absence of a sexual partner), community (peer influence, social stigma), institutional (long waiting times at clinics, attitudes of health workers), and structural (cost of PrEP and mode of administration, accessibility concerns) levels. Facilitators included factors at individual (high HIV risk perception and preventing HIV/desire to remain HIV negative), interpersonal (peer influence, social support and care for PrEP uptake), community (adequate PrEP information and sensitization, evidence of PrEP efficacy and safety), institutional (convenient and responsive services, provision of appropriate and sufficiently resourced services), and structural (access and availability of PrEP, cost of PrEP) levels. The findings indicated that PrEP is an acceptable HIV prevention method. PrEP uptake is linked to personal and environmental factors that need to be considered for successful PrEP roll-out. Multi-level interventions needed to promote PrEP uptake should consider the social and structural drivers and focus on ways that can inspire PrEP uptake and limit the barriers.

Exclusion of enrolled participants in randomised controlled trials: what to do with ineligible participants?

OBJECTIVE: Post-randomisation exclusions in randomised controlled trials are common and may include participants identified as not meeting trial eligibility criteria after randomisation. We report how a decision might be reached and reported on, to include or exclude these participants. We illustrate using a motivating scenario from the BREATHE trial (Trial registration ClinicalTrials.gov, NCT02426112) evaluating azithromycin for the treatment of chronic lung disease in people aged 6-19 years with HIV in Zimbabwe and Malawi. KEY POINTS: Including all enrolled and randomised participants in the primary analysis of a trial ensures an unbiased estimate of the intervention effect using intention-to-treat principles, and minimises the effects of confounding through balanced allocation to trial arm. Ineligible participants are sometimes enrolled, due to measurement or human error. Of 347 participants enrolled into the BREATHE trial, 11 (3.2%) were subsequently found to be ineligible based on lung function criteria. We assumed no safety risk of azithromycin treatment; their inclusion in the trial and subsequent analysis of the intervention effect therefore mirrors clinical practice. Senior trial investigators considered diurnal variations in the measurement of lung function, advantages of retaining a higher sample size and advice from the Data Safety and Monitoring Board and Trial Steering Committee, and decided to include these participants in primary analysis. We planned and reported analyses including and excluding these participants, and in our case the interpretation of treatment effect was consistent. CONCLUSION: The decision, by senior investigators, on whether to exclude enrolled participants, should reflect issues of safety, treatment efficacy, statistical power and measurement error. As long as decisions are made prior to finalising the statistical analysis plan for the trial, the risk of exclusions creating bias should be minimal. The decision taken should be transparently reported and a sensitivity analysis can present the opposite decision.

Topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in Nepal: rationale and design of a randomised controlled non-inferiority trial.

INTRODUCTION: Fungal infections of the cornea, fungal keratitis (FK), are challenging to treat. Current topical antifungals are not always effective and are often unavailable, particularly in low-income and middle-income countries where most cases occur. Topical natamycin 5% is usually first-line treatment, however, even when treated intensively, infections may progress to perforation of the eye in around a quarter of cases. Alternative antifungal medications are needed to treat this blinding disease.Chlorhexidine is an antiseptic agent with antibacterial and antifungal properties. Previous pilot studies suggest that topical chlorhexidine 0.2% compares favourably with topical natamycin. Full-scale randomised controlled trials (RCTs) of topical chlorhexidine 0.2% are warranted to answer this question definitively. METHODS AND ANALYSIS: We will test the hypothesis that topical chlorhexidine 0.2% is non-inferior to topical natamycin 5% in a two-arm, single-masked RCT. Participants are adults with FK presenting to a tertiary ophthalmic hospital in Nepal. Baseline assessment includes history, examination, photography, in vivo confocal microscopy and cornea scrapes for microbiology. Participants will be randomised to alternative topical antifungal treatments (topical chlorhexidine 0.2% and topical natamycin 5%; 1:1 ratio, 2-6 random block size). Patients are reviewed at day 2, day 7 (with reculture), day 14, day 21, month 2 and month 3. The primary outcome is the best spectacle corrected visual acuity (BSCVA) at 3 months. Primary analysis (intention to treat) will be by linear regression, with treatment arm and baseline BSCVA prespecified covariates. Secondary outcomes include epithelial healing time, scar/infiltrate size, ulcer depth, hypopyon size, perforation and/or therapeutic penetrating keratoplasty (corneal transplant), positive reculture rate (day 7) and quality of life (EuroQol-5 dimensions, WHO/PBD-VF20, WHOQOL-BREF). ETHICS AND DISSEMINATION: The Nepal Health Research Council, the Nepal Department of Drug Administration and the London School of Hygiene and Tropical Medicine ethics committee have approved the trial. The results will be presented at local and international meetings and submitted to peer-reviewed journals for publication. TRIAL REGISTRATION NUMBER: ISRCTN14332621; pre-results.

The effect of co-morbid anxiety on remission from depression for people participating in a randomised controlled trial of the Friendship Bench intervention in Zimbabwe.

BACKGROUND: There is a lack of data from low- and middle-income countries on whether anxiety independently predicts a more chronic course for depression. METHODS: We undertook secondary data analysis of a cluster randomised controlled trial in Zimbabwe which had tested the effectiveness of the Friendship Bench intervention for common mental disorders compared to enhanced usual care. Inclusion for the current study was participants from the trial who had probable major depression at baseline, defined as scoring => 11 on the locally validated Patient Health Questionnaire (PHQ9). This emerged to be 354 of the original 573 (61.78%) of the original trial sample. Anxiety was measured using the locally validated cut-point on the Generalised Anxiety Disorder scale (GAD-7). Persistent depression was defined as scoring => 11 on the PHQ-9 at six-months follow-up. Analysis in Stata 15 used random-effects logistic regression to adjust for clustering by clinic. OUTCOMES: Of the 354 participants who were eligible for treatment, 329 (92·9%) completed 6-month follow-up assessment. 37% of the trial sample had persistent depression at 6-months follow-up; 59% in the control arm and 17% in the intervention arm. Co-morbid anxiety present at trial baseline was independently associated with persistent depression after adjusting for age, gender and baseline depression severity (adjusted OR = 2·83, 95% CI 1·32-6·07). There was no evidence of effect modification by trial arm. Baseline depression severity also predicted persistent depression. Interpretation Treatment for depression in low and middle-income countries (LMIC) should be directed towards those with greatest need. This includes people with co-morbid anxiety and greater depression severity at initial assessment who are less likely to remit at six months. Advice on coping with anxiety, psychological treatments which target common anxiety symptoms such as fear, avoidance, excessive worry and intrusive thoughts, and Selective Serotonin Reuptake Inhibitors (SSRIs) should be made more widely available in LMIC and offered to those with persistent mixed depression and anxiety.

INTREPID II: protocol for a multistudy programme of research on untreated psychosis in India, Nigeria and Trinidad.

INTRODUCTION: There are few robust and directly comparable studies of the epidemiology of psychotic disorders in the Global South. INTREPID II is designed to investigate variations in untreated psychotic disorders in the Global South in (1) incidence and presentation (2) 2-year course and outcome, (3) help-seeking and impact, and (4) physical health. METHODS: INTREPID II is a programme of research incorporating incidence, case-control and cohort studies of psychoses in contiguous urban and rural areas in India, Nigeria and Trinidad. In each country, the target samples are 240 untreated cases with a psychotic disorder, 240 age-matched, sex-matched and neighbourhood-matched controls, and 240 relatives or caregivers. Participants will be followed, in the first instance, for 2 years. In each setting, we have developed and are employing comprehensive case-finding methods to ensure cohorts are representative of the target populations. Using methods developed during pilot work, extensive data are being collected at baseline and 2-year follow-up across several domains: clinical, social, help-seeking and impact, and biological. ETHICS AND DISSEMINATION: Informed consent is sought, and participants are free to withdraw from the study at any time. Participants are referred to mental health services if not already in contact with these and emergency treatment arranged where necessary. All data collected are confidential, except when a participant presents a serious risk to either themselves or others. This programme has been approved by ethical review boards at all participating centres. Findings will be disseminated through international conferences, publications in international journals, and through local events for key stakeholders.

Menstrual health intervention and school attendance in Uganda (MENISCUS-2): a pilot intervention study.

OBJECTIVES: Achieving good menstrual health and hygiene (MHH) is a public health challenge and there is little evidence to inform interventions. The aim of this study was to pilot test an intervention to improve MHH and school attendance in Uganda, in preparation for a future cluster-randomised trial. DESIGN: Longitudinal study with pre-post evaluation of a pilot intervention. SETTING: Two secondary schools in Entebbe, Uganda. PARTICIPANTS: Of the 473 eligible students in secondary 2 (S2) at baseline, 450 (95.1%; 232 girls and 218 boys) consented/assented. 369 students (188 girls; 81.0%; and 181 boys; 83.0%) participated in the endline survey. INTERVENTION: The intervention comprised training teachers to improve delivery of government guidelines for puberty education, training in use of a menstrual kit and pain management, a drama skit, provision of analgesics and improvements to school water and sanitation hygiene facilities. PRIMARY AND SECONDARY OUTCOME MEASURES: Feasibility and acceptability of delivering the intervention. Baseline and endline quantitative surveys were conducted, with qualitative interviews conducted at endline. School attendance was assessed using self-completed daily diaries among a nested cohort of 100 female students. RESULTS: There were high levels of uptake of the individual and behavioural intervention components (puberty education, drama skit, menstrual hygiene management (MHM) kit and pain management). The proportion of girls reporting anxiety about next period decreased from 58.6% to 34.4%, and reported use of effective pain management increased from 76.4% to 91.4%. Most girls (81.4%) reported improved school toilet facilities, which improved their comfort managing menstruation. The diary data and qualitative data indicated a potential intervention impact on improving menstrual-related school absenteeism. CONCLUSIONS: The pilot study showed that the multicomponent MHM intervention was acceptable and feasible to deliver, and potentially effective in improving menstruation knowledge and management. A cluster-randomised trial is needed to evaluate rigorously the intervention effects on MHM and school attendance. TRIAL REGISTRATION NUMBER: NCT04064736; Pre-results.

Evaluating the effectiveness and cost-effectiveness of health facility-based and community-based index-linked HIV testing strategies for children: protocol for the B-GAP study in Zimbabwe.

INTRODUCTION: The number of new paediatric infections per year has declined in sub-Saharan Africa due to prevention-of-mother-to-child HIV transmission programmes; many children and adolescents living with HIV remain undiagnosed. In this protocol paper, we describe the methodology for evaluating an index-linked HIV testing approach for children aged 2-18 years in health facility and community settings in Zimbabwe. METHODS AND ANALYSIS: Individuals attending for HIV care at selected primary healthcare clinics (PHCs) will be asked if they have any children aged 2-18 years in their households who have not been tested for HIV. Three options for HIV testing for these children will be offered: testing at the PHC; home-based testing performed by community workers; or an oral mucosal HIV test given to the caregiver to test the children at home. All eligible children will be followed-up to ascertain whether HIV testing occurred. For those who did not test, reasons will be determined, and for those who tested, the HIV test result will be recorded. The primary outcome will be uptake of HIV testing. The secondary outcomes will be preferred HIV testing method, HIV yield, prevalence and proportion of those testing positive linking to care and having an undetectable viral load at 12 months. HIV test results will be stratified by sex and age group, and factors associated with uptake of HIV testing and choice of HIV testing method will be investigated. ETHICS AND DISSEMINATION: Ethical approval for this study was granted by the Medical Research Council of Zimbabwe, the London School of Hygiene and Tropical Medicine and the Institutional Review Board of the Biomedical Research and Training Institute. Study results will be presented at national policy meetings and national and international research conferences. Results will also be published in international peer-reviewed scientific journals and disseminated to study communities at the end of study.

Mortality during 6 years of follow-up in relation to visual impairment and eye disease: results from a population-based cohort study of people aged 50 years and above in Nakuru, Kenya.

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.

Association of Mycoplasma genitalium and HIV infection: a systematic review and meta-analysis.

OBJECTIVE: To systematically review studies of Mycoplasma genitalium and the association with HIV infection in adults and to summarize the findings in a meta-analysis. DESIGN: A systematic review and meta-analysis. METHODS: Epidemiological studies of the association of M. genitalium and HIV infection published prior to June 2008 were identified in a systematic review of the published literature. A random-effects meta-analysis was used to calculate the summary odds ratio (OR) and 95% confidence interval (CI). Further analyses stratified by geographical area and type of control population, and sensitivity analyses were conducted to assess between-study heterogeneity and publication bias. RESULTS: Nineteen eligible studies were identified. The prevalence of M. genitalium ranged from 3.1% to 47.5%. Seventeen studies found that participants with M. genitalium were more likely to be HIV infected, and this association was statistically significant in 12 studies. The summary odds ratio (OR) was 2.01 [95% confidence interval (CI) = 1.44-2.79]. The association was stronger in sub-group analyses among studies in sub-Saharan Africa (OR = 2.60, 95% CI = 2.17-3.11) and studies with healthy control populations (OR = 2.57, 95% CI = 2.05-3.22). There was strong evidence of between-study heterogeneity among all studies combined; however, between-study heterogeneity was substantially reduced in sub-group analyses. There was no statistical evidence of publication bias. CONCLUSION: The strong association between M. genitalium and HIV infections in these primarily cross-sectional observational studies highlights the need for longitudinal studies to understand the temporal association between these infections. Testing and treatment of M. genitalium-positive individuals in high-risk populations should be investigated as a potential HIV prevention strategy.