Co-development of a training programme on disability for healthcare workers in Uganda.

BACKGROUND: Approximately 1.3 billion people worldwide face barriers in accessing inclusive healthcare due to disabilities, leading to worse health outcomes, particularly in low and middle-income countries (LMIC). However, there is a lack of training of healthcare workers about disability, both globally and in Uganda. OBJECTIVES: To use mixed research methods to develop a comprehensive training program with standardisedelements for healthcare workers in Uganda, focusing on improving their knowledge, attitudes, and skills inproviding care for people with disabilities. METHODS: The Medical Research Council (MRC) approach was employed to guide the development of the training intervention. We conducted an umbrella review to gather relevant literature on disability training for healthcare workers. Interviews were conducted with international experts to gain insights and perspectives on the topic. Additionally, interviews were undertaken with people with disabilities and healthcare workers in Uganda to understand their experiences and needs. A participatory workshop was organised involving key stakeholders, to collaboratively design the training material based on the findings from these data sources. RESULTS: Eight review articles examined training programs for healthcare workers on disability. Training settings ranged from specialised clinical settings to non-clinical settings, and the duration and evaluation methods of the training varied widely. Lectures and didactic methods were commonly used, often combined with other approaches such as case studies and simulations. The impact of the training was assessed through healthcare worker reports on attitudes, knowledge, and self-efficacy. Interviews emphasised the importance of involving people with disabilities in the training and improving communication and understanding between healthcare providers and people with disabilities. Five themes for a training on disability for healthcare workers were generated through the workshop, including responsibilities and rights, communication, informed consent, accommodation, and referral and connection, which were used to guide the development of the curriculum, training materials and training approach. CONCLUSION: This study presents a novel approach to develop a training program that aims to enhance healthcare services for people with disabilities in Uganda. The findings offer practical insights for the development of similar programs in LMICs. The effectiveness of the training program will be evaluated through a pilot test, and policy support is crucial for its successful implementation at scale.

KEY MESSAGES: 1. Healthcare workers require training to effectively address the health concerns of people with disabilities, yet this is rarely included in curricula worldwide. 2. Uganda recognises the importance of addressing this issue and is taking steps to improve training programs about disability for healthcare workers. 3. We used multiple research methods (umbrella review, semi-structured interviews, participatory research and collaborative design) to co-develop a comprehensive training program with standardised elements for healthcare workers in Uganda, focusing on improving their knowledge, attitudes, and skills in providing care for people with disabilities. 4. The developed training material could be adapted for healthcare workers in other resource-limited settings, and policy support is needed to ensure its implementation at scale.

Bacterial microbiome and host inflammatory gene expression in foreskin tissue.

The penile epithelial microbiome remains underexplored. We sequenced human RNA and a segment of the bacterial 16S rRNA gene from the foreskin tissue of 144 adolescents from South Africa and Uganda collected during penile circumcision after receipt of 1-2 doses of placebo, emtricitabine + tenofovir disoproxil fumarate, or emtricitabine + tenofovir alafenamide to investigate the microbiome of foreskin tissue and its potential changes with antiretroviral use. We identified a large number of anaerobic species, including Corynebacterium acnes, which was detected more frequently in participants from South Africa than Uganda. Bacterial populations did not differ by treatment received, and no differentially abundant taxa were identified between placebo versus active drug recipients. The relative abundance of specific bacterial taxa was negatively correlated with expression of genes downstream of the innate immune response to bacteria and regulation of inflammation. Our results show no difference in the tissue microbiome of the foreskin with short-course antiretroviral use but that bacterial taxa were largely inversely correlated with inflammatory gene expression, consistent with commensal colonization.

Moving forward through consensus: a national Delphi approach to determine the top research priorities in prostate cancer in Uganda.

OBJECTIVE: To identify key areas for research in prostate cancer (PC) in the Ugandan context by establishing the major health system, socioeconomic and clinical barriers to seeking, reaching and receiving high-quality cancer care. DESIGN: Modified Delphi Technique. SETTING: Government and private-not-for-profit hospitals. METHODS: We applied a two-stage modified Delphi technique to identify the consensus view across cancer experts. In round 1, experts received a questionnaire containing 21 statements drawn from a systematic review identifying the reason for the delay in accessing cancer care. Each statement was scored out of 20. Statements scoring ≥15 from over 70% of participants were prioritised for inclusion while statements for which <30% of participants gave a score of ≥15 were excluded. Sixteen statements were included in round 2 as they did not receive consensus for inclusion or exclusion. RESULTS: We found that the top six research priority areas arise from challenges including: (1) lack of diagnostic services-ultrasound, laboratory tests and biopsy facilities; (2) high costs of services, for example, surgery, radiotherapy, hormone therapy are unaffordable to most patients, (3) lack of essential medicines, (4) limited radiotherapy capacity, (5) lack of awareness of cancer as a disease and low recognition of symptoms, (6) low healthcare literacy. The lack of critical surgical supplies, high diagnostic and treatment costs were ranked highest in order of importance in round 1. Round 2 also revealed lack of diagnostic services, unavailability of critical medicines, lack of radiotherapy options, high costs of treatments and lack of critical surgical supplies as the top priorities. CONCLUSION: These research priority areas ought to be addressed in future research to improve prompt PC diagnosis and care in Uganda. There is need to improve the supply of high-quality affordable anticancer medicines for PC patients so as to improve the survivorship from the cancer.

Understanding the social and physical menstrual health environment of secondary schools in Uganda: A qualitative methods study.

Adolescent girls face social, psychological, and physical problems managing menstruation in schools in low-resource settings. This study aimed to evaluate the social and physical menstrual health environment of secondary schools in Wakiso and Kalungu districts, Uganda, in preparation for a subsequent menstrual health intervention trial to improve education, health and wellbeing. We conducted a qualitative rapid assessment in 75 secondary schools in Uganda. This involved conducting in-depth interviews with 150 head/senior teachers and 274 students, 26 Focus Group Discussions with students, and 13 transect walks to observe school Water, Sanitation and Hygiene (WASH) facilities between May and October 2021. Due to COVID-19 related school closures, face-to-face research activities were halted and in-depth interviews were conducted over phone and replaced focus group discussions. We employed a thematic framework analysis approach using the social-ecological model (which focuses on the complex interplay between individual, interpersonal, institutional, and societal factors) to generate themes and key concepts. Participants described the social and physical menstrual health environment of secondary schools at the individual level (knowledge gaps on menstruation before menarche, negative norms and beliefs about menstrual health); interpersonal level (limited psycho-social support, myths and misconceptions about the disposal of sanitary materials and pain relief, menstrual hygiene management (MHM) support from school nurses, peers and senior teachers); institutional level (non-implementation of Government circulars on MHM, lack of school-level guidelines policies and programs on MHM and poor WASH facilities, i.e. lack of soap, safe water and unclean toilets); and societal level (MHM programmes provided by civil society groups, health workers, and students' school associations). The findings showed individual, societal and institutional burdens related to menstrual experiences. Multi-level evidence-based interventions aimed at improving the social and physical environment for menstrual health among school-going girls are needed.

"She gives it to her child who doesn't even talk": a qualitative exploration of alcohol and drug use among primary school-age children in Uganda.

BACKGROUND: There is little research on alcohol and other drugs (AOD) use by school-age children in low-resource settings like Uganda. Including the voices of children in research can inform prevention and early intervention efforts for those at risk of AOD use. The aim of this study was to understand the perspectives of children aged 6 to 13 years regarding AOD in Uganda. METHODS: This qualitative study was conducted in Mbale district, Uganda from February to March 2020. Eight focus group discussions (FGDs) were conducted with 56 primary school-age children, stratified by age (6-9 and 10-13 years), sex (male and female), and school status (in school and out of school). All FGDs were conducted in either Lumasaaba or Luganda. The FGDs were audio-recorded, transcribed verbatim, and translated into English. Data were coded, and overarching themes were identified using thematic framework analysis. RESULTS: Two themes identified were (1) Children's perceptions and experiences with AODs. The participants understood alcohol by its consistency, colour, odour, and by brand/logo. They described the types and quantities of AOD consumed by school-age children, brewing processes for homemade alcoholic drinks, and short and long-term consequences of the use of alcohol. (2) Contributing factors to childhood drinking included: Stress relief for children who experienced multiple adversities (orphaned, poverty-stricken, and hailing from broken homes), fitting in with friends, influence from families, and media exposure that made alcohol look cool. Children would start drinking at an early age) or were given alcohol by their parents, sometimes before they could start talking. In the community, alcohol and other drugs were cheap and available and children could drink from anywhere, including in the classroom. CONCLUSIONS: Children eligible for primary education in Uganda can easily access and use AOD. Several factors were identified as contributing to alcohol and other drug use among children, including availability and accessibility, advertising, lack of parental awareness and supervision, peer influence, adverse childhood experiences, socioeconomic factors, and cultural norms. There is a need for multi-sectoral action for awareness of childhood AOD use and deliberate consideration of children in the planning, design, and implementation of research, policies, and programs for prevention and early intervention.

Preferences for oral PrEP dosing among adolescent boys and young men in three sub-Saharan African countries.

BACKGROUND: HIV remains a leading contributor to the disease burden in sub-Saharan Africa, with adolescents and young people disproportionately affected. Optimising pre-exposure prophylaxis (PrEP) uptake has predominantly focused on women and adult men who have sex with men. We explore adolescent boys and young men's PrEP uptake preferences in South Africa, Uganda, and Zimbabwe. METHODS: A cross-sectional sequential exploratory mixed-methods study amongst males aged 13-24 years was conducted between April and September 2019 as part of the CHAPS trial. Group discussions (GDs) and In-Depth Interviews (IDIs) focused on motivations and hindrances for HIV testing, PrEP preference, and reasons for the uptake of PrEP. A thematic approach was used to analyse the qualitative data. A quantitative survey following the qualitative work covered questions on demographics, HIV risk and PrEP preferences (on-demand vs. daily). For quantitative analysis, we fitted logistic regression models to determine factors associated with on-demand vs daily PrEP preference. RESULTS: Overall, 647 adolescent boys and young men (median age 20, IQR: 17-22) were enrolled. Of these, 422 (65.22%) preferred on-demand PrEP (South Africa 45.45%, Uganda 76.80%, Zimbabwe 70.35%; p<0.001). Factors independently associated with on-demand PrEP included country (South Africa, adjusted odds ratio (aOR) = 0.19 [95%CI:0.1-0.3] compared to Uganda) and advanced planning of sex [>24 hours in advance aOR = 1.4 (0.9-2.3) compared to <2 hours]. Qualitatively, participants commonly believed they were not at risk of HIV acquisition most of the time and thought that on-demand PrEP would be suitable as they tend to plan sexual activity in advance. CONCLUSION: Preference for on-demand PrEP is high in young males. The qualitative data support a preference for on-demand PrEP in those who plan sex in advance. HIV intervention programs should offer both on-demand and daily PrEP to engage more adolescent boys and young men in HIV prevention practices.

Attitudes, Practices and Understanding of health workers and caregivers regarding the relationship between severe pneumonia and malnutrition in children: A Qualitative Study.

Background: Severe Pneumonia is still the leading cause of morbidity and mortality among children worldwide. Many children with severe pneumonia are reported to die in hospital as well as following discharge due to malnutrition. Severe pneumonia is a catabolic illness, which predisposes to severe malnutrition. WHO and United Nations Children's Fund (UNICEF), recommend 'continued' feeding but do not give any specific recommendations for nutritional support. This could influence health workers' and caregivers' attitudes, practices and understanding regarding the topic. This study aimed to explore the attitudes, practices and understanding of health workers regarding the relationship between severe pneumonia and malnutrition. Methods: We conducted an exploratory qualitative study among health workers and caregivers of children hospitalized with severe pneumonia at Mulago National Referral Hospital in Uganda. Data were collected using focus-groups involving caregivers and key informant interviews with health workers and analysed using the content-thematic analysis approach. Both manual coding and Atlas Ti software were used to support the analysis. Results: Some of the health workers and caregivers were aware of the relationship between severe pneumonia and malnutrition to various degrees, citing reduced appetite, difficulty in breathing and persistent vomiting as pathways to malnutrition in patients with severe pneumonia, which called for a balanced diet and more frequent breastfeeding. Suppressed immunity in malnourished children was mentioned as the pathway to severe pneumonia. Some caregivers confessed not knowing anything about the relationship between the two conditions. Conclusion: Attitudes, practices and understanding regarding the deadly relationship between severe pneumonia and malnutrition among care givers could further be improved by health education and mass sensitization. Clarifying practice guidelines could further enhance attitudes and practices of health workers to reduce preventable pneumonia deaths.

Barriers to childhood asthma care in sub-Saharan Africa: a multicountry qualitative study with children and their caregivers.

OBJECTIVES: This study identifies barriers and provides recommendations to improve asthma care in children across sub-Saharan Africa, where qualitative data is lacking despite high rates. DESIGN: One of the aims of our National Institute for Health Research global health research group 'Achieving Control of Asthma in Children in Africa' was to use qualitative thematic analysis of transcribed audio recordings from focus group discussions (FGDs) to describe barriers to achieving good asthma control. SETTING: Schools in Blantyre (Malawi), Lagos (Nigeria), Durban (South Africa), Kampala (Uganda) and Harare (Zimbabwe). PARTICIPANTS: Children (n=136), 12-14 years with either asthma symptoms or a diagnosis and their caregivers participated in 39 FGDs. All were recruited using asthma control questions from the Global Asthma Network survey. RESULTS: There were four key themes identified: (1) Poor understanding, (2) difficulties experienced with being diagnosed, (3) challenges with caring for children experiencing an acute asthma episode and (4) suboptimal uptake and use of prescribed medicines. An inadequate understanding of environmental triggers, a hesitancy in using metred dose inhalers and a preference for oral and alternate medications were identified as barriers. In addition, limited access to healthcare with delays in diagnosis and an inability to cope with expected lifestyle changes was reported. Based on these findings, we recommend tailored education to promote access to and acceptance of metred dose inhalers, including advocating for access to a single therapeutic, preventative and treatment option. Furthermore, healthcare systems should have simpler diagnostic pathways and easier emergency access for asthma. CONCLUSIONS: In a continent with rapidly increasing levels of poorly controlled asthma, we identified multiple barriers to achieving good asthma control along the trajectory of care. Exploration of these barriers reveals several generalisable recommendations that should modify asthma care plans and potentially transform asthma care in Africa. TRIAL REGISTRATION NUMBER: 269211.

A cross-country qualitative analysis of teachers' perceptions of asthma care in sub-Saharan Africa.

Asthma is the most common chronic respiratory disease among school-going adolescents worldwide. However, the burden of severe asthma is highest in Sub-Saharan Africa. This study aimed to explore teachers' perceptions of asthma care across six African countries. We conducted focus group discussions (FGDs) using a semi-structured interview guide. Interviews were audio-recorded, transcribed verbatim and analysed thematically. FGDs were conducted in Kumasi(Ghana), Blantyre (Malawi), Lagos (Nigeria), Durban (South Africa), Kampala (Uganda), and Harare (Zimbabwe) between 01 November 2020 and 30 June 2021. We identified two key themes related to asthma care; barriers to asthma care and suggestions to improve the care of adolescents with asthma. Barriers reported by teachers included a lack of knowledge and skills among themselves, adolescents, and caregivers. In addition, some traditional beliefs of teachers on asthma exacerbated challenges with asthma care in schools. Regarding suggestions, most teachers identified a need for all-inclusive asthma training programmes for teachers, adolescents and caregivers, focusing on acute episodes and mitigating triggers. Utilising teachers with personal experiences with asthma to advocate and support these initiatives was suggested. Further suggestions included the need for annual screening to enable early identification of adolescents with asthma and clarify restrictions on teachers administering asthma medications. Teachers across African schools identify multiple barriers to asthma care. Structured school education programs and annual asthma screening are key to addressing some barriers to care.

Is it feasible to implement a community-based participatory group programme to address issues of access to healthcare for people with disabilities in Luuka district Uganda? A study protocol for a mixed-methods pilot study.

INTRODUCTION: On average, people with disabilities face many difficulties in accessing healthcare and experience worse health outcomes. Yet, evidence on how to overcome these barriers is lacking. Participatory approaches are gaining prominence as they can generate low-cost, appropriate and scalable solutions. This study protocol is for the pilot testing of the co-created Participatory Learning and Action for Disability (PLA-D) groups to assess feasibility. METHODS AND ANALYSIS: We will pilot test PLA-D in five groups in Luuka district, Uganda during 2023. Each group will include approximately 20 members (people with disabilities, family members, carers) who will meet every 2-3 weeks over a 9-11 month period. The groups, guided by a trained facilitator, will identify issues about health and healthcare access and plan and implement locally generated solutions (eg, raising awareness of rights, advocacy and lobbying, establishing health savings and financing schemes). We will collect diverse sources of data to assess feasibility: (1) in-depth interviews and focus group discussions with group participants, non-participants and group facilitators; (2) monitoring of group activities; (3) direct observation of groups and (4) quantitative survey of group participants at baseline and endline. Data analyses will be undertaken to assess feasibility in terms of: acceptability, demand, implementation and practicality. We will develop and refine evaluation tools in preparation for a future trial. ETHICS AND DISSEMINATION: Ethical approval for the study has been received by the London School of Hygiene & Tropical Medicine and the Uganda Virus Research Institute ethics committees. Informed consent will be obtained from all study participants, making adaptations for people with disabilities as necessary. We will reach different groups for our dissemination activities, including (1) people with disabilities (eg, community meetings); (2) policy and programme stakeholders in Uganda and international (eg, individual meetings, evidence briefs) and (3) academics (journal articles, conference/seminar presentations).

Association of severe malaria with cognitive and behavioural outcomes in low- and middle-income countries: a meta-analysis and systematic review.

BACKGROUND: Malaria affects 24 million children globally, resulting in nearly 500,000 child deaths annually in low- and middle-income countries (LMICs). Recent studies have provided evidence that severe malaria infection results in sustained impairment in cognition and behaviour among young children; however, a formal meta-analysis has not been published. The objective was to assess the association between severe malaria infection with cognitive and behavioural outcomes among children living in LMICs. METHODS: Six online bibliographic databases were searched and reviewed in November 2022. Studies included involved children < 18 years of age living in LMICs with active or past severe malaria infection and measured cognitive and/or behaviour outcomes. The quality of studies was assessed. Definitions of severe malaria included cerebral malaria, severe malarial anaemia, and author-defined severe malaria. Results from all studies were qualitatively summarized. For studies with relevant data on attention, learning, memory, language, internalizing behaviour and externalizing behaviour, results were pooled and a meta-analysis was performed. A random-effects model was used across included cohorts, yielding a standardized mean difference between the severe malaria group and control group. RESULTS: Out of 3,803 initial records meeting the search criteria, 24 studies were included in the review, with data from 14 studies eligible for meta-analysis inclusion. Studies across sub-Saharan Africa assessed 11 cohorts of children from pre-school to school age. Of all the studies, composite measures of cognition were the most affected areas of development. Overall, attention, memory, and behavioural problems were domains most commonly found to have lower scores in children with severe malaria. Meta-analysis revealed that children with severe malaria had worse scores compared to children without malaria in attention (standardized mean difference (SMD) -0.68, 95% CI -1.26 to -0.10), memory (SMD -0.52, 95% CI -0.99 to -0.06), and externalizing behavioural problems (SMD 0.45, 95% CI 0.13-0.78). CONCLUSION: Severe malaria is associated with worse neuropsychological outcomes for children living in LMICs, specifically in attention, memory, and externalizing behaviours. More research is needed to identify the long-term implications of these findings. Further interventions are needed to prevent cognitive and behavioural problems after severe malaria infection. TRIAL REGISTRATION: This systematic review was registered under PROSPERO: CRD42020154777.

"I abandoned my job to look after my baby." Understanding the unpriced cost of care of a preterm infant: Caregivers' lived experiences.

BACKGROUND: Preterm birth is associated with life-long cost implications on the infant, family, health system, and society at large. The costs related to lost productivity at contributions at work during care of preterm infants are difficult to measure. We aimed to explore and document the unpriced costs parents incur following birth of a preterm infant in the first year of life in a low resource setting. METHODS: Thirty-nine mothers and five fathers of preterm infants who had ever attended the preterm follow-up clinic after discharge from Mulago National Referral Hospital, were included in a qualitative study between November 2019 and February 2020. Participants were purposively selected, and data were collected using four focused group discussions with mothers and in-depth interviews with the fathers lasting 30-70 minutes each. These were audio-recorded, transcribed and translated. The data were manually analysed using the thematic approach. FINDINGS: Three themes were generated: i) complex nature of the infant, ii) time to care for the infant, iii) mother as the predominant caregiver. The parents perceived preterm infants as delicate, complicated and their care more costly compared to those born at term. Expressions of need for time to care for their infants, frequent hospital visits and readmission were raised. Availability of the mother as the predominant caregiver some of whose roles cannot be delegated and their experiences following return to work after birth of a preterm were cited by the participants. CONCLUSION: The results highlight the unpriced costs incurred by the parents through disruption of the work pattern due to the actual and perceived needs of a preterm infant and time to care in a low resource setting. We recommend guidance on financial planning, development of policies and programs on social and financial support for parents and future studies on indirect costs of preterm care.

A qualitative study to explore daily versus on-demand oral pre-exposure prophylaxis (PrEP) in young people from South Africa, Uganda and Zimbabwe.

BACKGROUND: Adolescents in sub-Saharan Africa (SSA) remain vulnerable to HIV infection. While pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV transmission as a daily or on-demand regimen, tailored approaches are necessary. The Combined HIV Adolescent PrEP and Prevention Study (CHAPS) is a mixed-methods research program investigating the acceptability and feasibility of implementing daily and on-demand PrEP among young people in SSA. It also aims to determine an on-demand dosing schedule for insertive sex. For this paper, we explored preferences for daily versus on-demand PrEP amongst adolescents as part of CHAPS. METHODS: Purposive sampling was used to recruit participants from Soweto and Cape Town (South Africa), Wakiso district (Uganda) and Chitungwiza (Zimbabwe). At the time of the study in 2018/2019, Uganda had not rolled out PrEP to the general population; in Zimbabwe, PrEP for young people was only available at selected sites with one located within the study recruitment area. In South Africa, PrEP was made available to selected high-risk groups. We conducted 60 in-depth interviews and 24 group discussions amongst young people aged 13-24 without HIV in South Africa, Uganda, and Zimbabwe. All in-depth interviews and group discussions were audio-recorded, transcribed verbatim and translated to English. Data were analysed using framework analysis. The main themes were centered around preferences for daily and on-demand PrEP. RESULTS: Reasons for on-demand preferences included stigma, pill fatigue, adherence and side effects. Reasons for daily PrEP preferences included factors related to sexual risk behaviour, continuous protection against incidents of unintentional exposure, and the increased efficacy of a daily dose. Participants at all sites preferring daily PrEP identified the same reasons, with more males than females citing inadvertent blood contact or perceived increased efficacy. Similarly, participants at all sites preferring on-demand PrEP gave the same reasons for their preferences for on-demand PrEP; the exception was South Africans who did not mention the hope of having fewer side effects by not taking daily PrEP. Additionally, more males than females cited intermittent sex as a reason for opting for on-demand PrEP. CONCLUSIONS: Our study is the first known to explore and describe youth preferences for daily versus on-demand PrEP. While the choice is clear-cut, the reasons cited in the different options provide invaluable insights into their decisions, and the actual and perceived facilitators and barriers to access to PrEP. Further education is needed amongst young people, not only about PrEP but also in other areas of comprehensive sexuality education. Exploring all options of HIV prevention is crucial to provide a tailored, one-size-does-not-fit-all approach to adolescent care in SSA to reduce and, the continued and increasing risk of this preventable infection.

A randomized clinical trial of on-demand oral pre-exposure prophylaxis does not modulate lymphoid/myeloid HIV target cell density in the foreskin.

OBJECTIVES: As topical pre-exposure prophylaxis (PrEP) has been shown to cause immune modulation in rectal or cervical tissue, our aim was to examine the impact of oral PrEP on lymphoid and myeloid changes in the foreskin in response to dosing and timing of drug administration. DESIGN: HIV-negative male individuals ( n  = 144) were recruited in South Africa and Uganda into an open-label randomized controlled trial in a 1 : 1 : 1 : 1 : 1 : 1 : 1 : 1 : 1 ratio to control arm (with no PrEP) or one of eight arms receiving emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) at one of two different doses, 5 or 21 h before undergoing voluntary medical male circumcision (VMMC). METHODS: After dorsal-slit circumcision, foreskin tissue sections were embedded into Optimal Cutting Temperature media and analysed, blinded to trial allocation, to determine numbers of CD4 + CCR5 + , CD1a + cells and claudin-1 expression. Cell densities were correlated with tissue-bound drug metabolites and p24 production after ex-vivo foreskin challenge with HIV-1 bal . RESULTS: There was no significant difference in CD4 + CCR5 + or CD1a + cell numbers in foreskins between treatment arms compared with the control arm. Claudin-1 expression was 34% higher ( P  = 0.003) in foreskin tissue from participants receiving PrEP relative to controls, but was no longer statistically significant after controlling for multiple comparisons. There was neither correlation of CD4 + CCR5 + , CD1a + cell numbers, or claudin-1 expression with tissue-bound drug metabolites, nor with p24 production after ex-vivo viral challenge. CONCLUSION: Oral doses and timing of on-demand PrEP and in-situ drug metabolite levels in tissue have no effect on numbers or anatomical location of lymphoid or myeloid HIV target cells in foreskin tissue.

Dose finding study for on-demand HIV pre-exposure prophylaxis for insertive sex in sub-Saharan Africa: results from the CHAPS open label randomised controlled trial.

BACKGROUND: The efficacy of on-demand HIV pre-exposure prophylaxis (PrEP) for men in sub-Saharan Africa has not been evaluated, and the on-demand PrEP dosing requirement for insertive sex remains unknown. METHODS: HIV-negative males 13-24 years, requesting voluntary medical male circumcision (VMMC), were enrolled into an open-label randomised controlled trial (NCT03986970), and randomised 1:1:1:1:1:1:1:1:1 to control arm or one of eight arms receiving emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) over one or two days, and circumcised 5 or 21 h thereafter. The primary outcome was foreskin p24 concentrations following ex vivo HIV-1BaL challenge. Secondary outcomes included peripheral blood mononuclear cell (PBMC) p24 concentration, and drug concentrations in foreskin tissue, PBMCs, plasma and foreskin CD4+/CD4-cells. In the control arm, post-exposure prophylaxis (PEP) activity of non-formulated tenofovir-emtricitabine (TFV-FTC) or TAF-FTC was assessed with ex vivo dosing 1, 24, 48 or 72 h post-HIV-1 challenge. FINDINGS: 144 participants were analysed. PrEP with F/TDF or F/TAF prevented ex vivo infection of foreskins and PBMCs both 5 and 21 h after PrEP dosing. There was no difference between F/TDF and F/TAF (p24day15 geometric mean ratio 1.06, 95% confidence interval: 0.65-1.74). Additional ex vivo dosing did not further increase inhibition. In the control arm, PEP ex vivo dosing was effective up to 48 post-exposure diminishing thereafter, with TAF-FTC showing prolonged protection compared to TFV-FTC. Participants receiving F/TAF had higher TFV-DP concentrations in foreskin tissue and PBMCs compared with F/TDF, irrespective of dose and sampling interval; but F/TAF did not confer preferential TFV-DP distribution into foreskin HIV target cells. FTC-TP concentrations with both drug regimens were equivalent and ∼1 log higher than TFV-DP in foreskin. INTERPRETATION: A double dose of either F/TDF or F/TAF given once either 5 or 21 h before ex vivo HIV-challenge provided protection across foreskin tissue. Further clinical evaluation of pre-coital PrEP for insertive sex is warranted. FUNDING: EDCTP2, Gilead Sciences, Vetenskapsrådet.

Delays in seeking, reaching and access to quality cancer care in sub-Saharan Africa: a systematic review.

OBJECTIVES: Late presentation and delays in diagnosis and treatment consistently translate into poor outcomes in sub-Saharan Africa (SSA). The aim of this study was to collate and appraise the factors influencing diagnostic and treatment delays of adult solid tumours in SSA. DESIGN: Systematic review with assessment of bias using Risk of Bias in Non-randomised Studies of Exposures (ROBINS-E) tool. DATA SOURCES: PubMed and Embase, for publications from January 1995 to March 2021. ELIGIBILITY CRITERIA: Inclusion criteria: quantitative or mixed-method research, publications in English, on solid cancers in SSA countries. EXCLUSION CRITERIA: paediatric populations, haematologic malignancies, and assessments of public perceptions and awareness of cancer (since the focus was on patients with a cancer diagnosis and treatment pathways). DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted and validated the studies. Data included year of publication; country; demographic characteristics; country-level setting; disease subsite; study design; type of delay, reasons for delay and primary outcomes. RESULTS: 57 out of 193 full-text reviews were included. 40% were from Nigeria or Ethiopia. 70% focused on breast or cervical cancer. 43 studies had a high risk of bias at preliminary stages of quality assessment. 14 studies met the criteria for full assessment and all totaled to either high or very high risk of bias across seven domains. Reasons for delays included high costs of diagnostic and treatment services; lack of coordination between primary, secondary and tertiary healthcare sectors; inadequate staffing; and continued reliance on traditional healers and complimentary medicines. CONCLUSIONS: Robust research to inform policy on the barriers to quality cancer care in SSA is absent. The focus of most research is on breast and cervical cancers. Research outputs are from few countries. It is imperative that we investigate the complex interaction of these factors to build resilient and effective cancer control programmes.

Short-term oral pre-exposure prophylaxis against HIV-1 modulates the transcriptome of foreskin tissue in young men in Africa.

Whilst short-term oral pre-exposure prophylaxis (PrEP) with antiretroviral drugs in men who have sex with men has shown protection against HIV-1 infection, the impact of this regimen on the in vivo foreskin transcriptome is unknown. We collected foreskin tissue after voluntary medical male circumcision from 144 young men (72 from Uganda and 72 from South Africa) randomized to one to two doses of either oral tenofovir (TFV) disoproxil fumarate (FTC-TDF) or tenofovir alafenamide (FTC-TAF) or no drug (untreated controls). This novel approach allowed us to examine the impact of short-term oral PrEP on transcriptome of the male genital tract. A single dose of FTC-TDF did not affect the foreskin transcriptome in relation to control arm, however one dose of FTC-TAF induced upregulation of four genes AKAP8, KIAA0141, HSCB and METTL17. Following two doses of either FTC-TDF or FTC-TAF, there was an increase in 34 differentially expressed genes for FTC-TDF and 15 for FTC-TAF, with nine DEGs in common: KIAA0141, SAFB2, CACTIN, FXR2, AKAP8, HSCB, CLNS1A, DDX27 and DCAF15. Functional analysis of differentially expressed genes revealed modulation of biological processes related to mitochondrial stress (KIAA0141, HSCB and METTL17), anti-viral and anti-inflammatory pathways (CACTIN and AKAP8). Our results show that short-course on-demand oral PrEP in men modulates genes in foreskin tissue which are likely unfavorable to HIV acquisition and replication. We also describe an upregulated expression of genes involved in diverse mitochondria biology which may potentially result in worsened mitochondria-related. These results warrant further studies to assess the role of short-course and prolonged oral PrEP on biological processes of the foreskin mucosa.

Menstrual health interventions, schooling, and mental health problems among Ugandan students (MENISCUS): study protocol for a school-based cluster-randomised trial.

BACKGROUND: Menstrual health is an increasingly recognised public health issue, defined as complete physical, mental, and social well-being in relation to the menstrual cycle. The MENISCUS trial aims to assess whether a multi-component intervention addressing physical and emotional aspects of menstrual health improves educational attainment, mental health problems, menstrual management, self-efficacy, and quality of life among girls in secondary school in Uganda. METHODS: The study is a parallel-arm cluster-randomised controlled trial with 60 schools (clusters) in Wakiso and Kalungu districts, with a mixed-methods process evaluation to assess intervention fidelity and acceptability and economic and policy analyses. The schools will be randomised 1:1 to immediate intervention or to optimised usual care with delayed intervention delivery. The intervention includes creation of a Menstrual Health Action Group at schools and NGO-led training of trainers on puberty education, development of a drama skit, delivery of a menstrual health kit including reusable pads and menstrual cups, access to pain management strategies including analgesics, and basic improvements to school water, sanitation, and hygiene facilities. Baseline data will be collected from secondary 2 students in 2022 (median age ~15.5 years), with endline after 1 year of intervention delivery (~3600 females and a random sample of ~900 males). The primary outcomes assessed in girls are (i) examination performance based on the Mathematics, English, and Biology curriculum taught during the intervention delivery (independently assessed by the Uganda National Examinations Board) and (ii) mental health problems using the Total Difficulties Scale of the Strengths and Difficulties 25-item questionnaire. Secondary outcomes are menstrual knowledge and attitudes in girls and boys and, in girls only, menstrual practices, self-efficacy in managing menstruation, quality of life and happiness, prevalence of urogenital infections, school and class attendance using a self-completed menstrual daily diary, and confidence in maths and science. DISCUSSION: The trial is innovative in evaluating a multi-component school-based menstrual health intervention addressing both physical and emotional aspects of menstrual health and using a "training of trainers" model designed to be sustainable within schools. If found to be cost-effective and acceptable, the intervention will have the potential for national and regional scale-up. TRIAL REGISTRATION: ISRCTN 45461276 . Registered on 16 September 2021.

Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa.

HIV-1 pre-exposure prophylaxis (PrEP) relies on inhibition of HIV-1 replication steps. To understand how PrEP modulates the immunological environment, we derived the plasma proteomic profile of men receiving emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during the CHAPS trial in South Africa and Uganda (NCT03986970). The CHAPS trial randomized 144 participants to one control and 8 PrEP arms, differing by drug type, number of PrEP doses and timing from final PrEP dose to sampling. Blood was collected pre- and post-PrEP. The inflammatory profile of plasma samples was analyzed using Olink (N=92 proteins) and Luminex (N=33) and associated with plasma drug concentrations using mass spectrometry. The proteins whose levels changed most significantly from pre- to post-PrEP were CCL4, CCL3 and TNF-α; CCL4 was the key discriminator between pre- and post-PrEP samples. CCL4 and CCL3 levels were significantly increased in post-PrEP samples compared to control specimens. CCL4 was significantly correlated with FTC drug levels in plasma. Production of inflammatory chemokines CCL4 and CCL3 in response to short-term PrEP indicates the mobilization of ligands which potentially block virus attachment to CCR5 HIV-1 co-receptor. The significant correlation between CCL4 and FTC levels suggests that CCL4 increase is modulated as an inflammatory response to PrEP.