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Background: People with disabilities frequently experience barriers in seeking healthcare that lead to poorer health outcomes compared to people without disabilities. To overcome this, it is important to assess the accessibility of primary health facilities – broadly defined to include a disability-inclusive service provision – so as to document present status and identify areas for improvement. We aimed to identify, adapt and pilot test an appropriate tool to assess the accessibility of primary health facilities in Luuka District, Uganda. Methods: We conducted a rapid literature review to identify appropriate tools, selecting the Disability Awareness Checklist (DAC) on account of its relative brevity and development as a sensitization and action tool. We undertook three rounds of adaptation, working together with youth researchers (aged 18–35) with disabilities who then underwent 2 days of training as DAC facilitators. The adapted tool comprised 71 indicators across four domains and 12 sub-domains. We also developed a structured feedback form for facilitators to complete with healthcare workers. We calculated median accessibility scores overall, per domain and per sub-domain, and categorised feedback form suggestions by type and presumed investment level. We pilot-tested the adapted tool in 5 primary health facilities in one sub-district of Luuka, nested within a pilot healthcare worker training on disability. Results: The median overall facility accessibility score was 17.8% (range 12.3–28.8). Facility scores were highest in the universal design and accessibility domain (25.8%, 22.6–41.9), followed by reasonable accommodation (20.0%, 6.7–33.3). Median scores for capacity of facility staff (6.67%, 6.7–20.0), and linkages to other services were lower (0.0%, 0–25.0). Within the feedback forms, there were a median of 21 suggestions (range 14–26) per facility. Most commonly, these were categorised as minor structural changes (20% of suggestions), with a third categorised as no (2%) or low (33%) cost, and the majority (40%) medium cost. Conclusions: Overall accessibility scores were low, with many opportunities for low-cost improvement at the facility level. We did not identify any issues with the implementation of the tool, suggesting few further adaptations are required for its future use in this setting. [ABSTRACT FROM AUTHOR]

Background: There are 1.3 billion people with disabilities globally, and they frequently face barriers to accessing healthcare, contributing to their worse health and higher mortality. However, little research has explored patient-reported approaches to improve healthcare for persons with disabilities. Consequently, this study aimed to explore possible solutions and recommendations to address the existing barriers to access to healthcare for persons with disabilities in rural Uganda. Methods: We conducted 27 semi-structured interviews with individuals with various disabilities in rural Luuka district, Eastern Uganda, between September and November 2022. The participants included individuals with visual impairment (n = 5), physical impairment (n = 5), hearing impairment (n = 6), multiple impairments (n = 5), intellectual/cognitive impairment (n = 5), and albinism (n = 1). Interviews were recorded, transcribed verbatim, and thematically analysed. We categorized the solutions using the Missing Billion disability-inclusive health systems framework. Results: Our findings, framed within the health systems framework, revealed several critical themes. On the demand side, suggested solutions emphasized advocacy and sensitization for persons with disabilities, their communities, and caregivers about healthcare needs. Socio-economic empowerment and community-based health services were also highlighted as essential. On the supply side, participants stressed the importance of training healthcare workers on disability, facilitating dialogue and experience-sharing sessions, and employing health workers with disabilities. Additional recommendations included improving accessibility and reasonable accommodation, organizing inclusive services like special clinic days and outreaches, ensuring representation in health facility management, and establishing comprehensive rehabilitation services with affordable assistive devices. Conclusion: The multifaceted solutions proposed by persons with disabilities highlight the complex challenges they face in accessing healthcare services and highlight the necessity for comprehensive, sustainable interventions. The call to action for policymakers and healthcare providers is to prioritise the incorporation of disability-inclusive practices and explore multi-dimensional approaches that foster a more inclusive healthcare environment that adequately meets the needs of persons with disabilities. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Uganda adopted the HIV Test and Treat in 2016. There is paucity of data about its implementation among hospitalized patients. We aimed to determine the proportion of patients initiating anti-retroviral therapy (ART) during hospitalization, barriers and mortality outcome. Methods: In this mixed methods cohort study, we enrolled hospitalized patients with a recent HIV diagnosis from three public hospitals in Uganda. We collected data on clinical characteristics, ART initiation and reasons for failure to initiate ART, as well as 30 day outcomes. Healthcare workers in-depth interviews were also conducted and data analyzed by sub-themes. Results: We enrolled 234 patients; females 140/234 (59.8%), median age 34.5 years (IQR 29–42), 195/234 (83.7%) had WHO HIV stage 3 or 4, and 74/116 (63.8%) had CD4 ≤ 200 cell/μL. The proportion who initiated ART during hospitalization was 123/234 (52.6%) (95% CI 46.0–59.1), of these 35/123 (28.5%) initiated ART on the same day of hospitalization, while 99/123 (80.5%) within a week of hospitalization. By 30 days 34/234 (14.5%) (95% CI 10.3–19.7) died. Patients residing ≥ 35 kilometers from the hospital were more likely not to initiate ART during hospitalization, [aRR = 1.39, (95% CI 1.22–1.59). Inadequate patient preparation for ART initiation and advanced HIV disease were highlighted as barriers of ART initiation during hospitalization. Conclusion: In this high HIV prevalence setting, only half of newly diagnosed HIV patients are initiated on ART during hospitalization. Inadequate pre-ART patient preparation and advanced HIV are barriers to rapid ART initiation among hospitalized patients in public hospitals. [ABSTRACT FROM AUTHOR]

Introduction: Sub‐Saharan Africa (SSA) carries the burden of the HIV epidemic, especially among adolescents and young people (AYP). Little is known about pre‐exposure prophylaxis (PrEP) uptake and preferences among AYP in SSA. We describe preferences for daily and on‐demand PrEP among AYP in South Africa, Uganda and Zimbabwe. Methods: A cross‐sectional survey was conducted in 2019 among 13‐ to 24‐year olds, capturing socio‐demographics, HIV risk behaviours and preferences for daily or on‐demand PrEP. Logistic regression models were used to estimate odds ratios, adjusting for site, sex and age. Results and discussion: A total of 1330 participants from Cape Town (n = 239), Johannesburg (n = 200), Entebbe (n = 491) and Chitungwiza (n = 400) were enrolled; 673 (51%) were male, and the median age was 19 years (interquartile range 17–22 years). Of 1287 participants expressing a preference, 60% indicated a preference for on‐demand PrEP with differences by site (p < 0.001), sex (p < 0.001) and age group (p = 0.003). On‐demand PrEP was most preferred in Entebbe (75%), among males (65%) versus females (54%) and in older participants (62% in 18‐ to 24‐year‐olds vs. 47% in 13‐ to 15‐year‐olds). After adjusting for site, sex and age group, preference for on‐demand PrEP decreased as sex frequency over the past month increased (p‐trend = 0.004) and varied with the number of partners in the last 6 months, being least popular among those reporting four or more partners (p = 0.02). Participants knowing further in advance that they were likely to have sex were more likely to prefer on‐demand PrEP (p‐trend = 0.02). Participants having a larger age gap with their most recent partner and participants whose last partner was a transactional sex partner or client were both less likely to prefer on‐demand compared to daily PrEP (p = 0.05 and p = 0.09, respectively). Participants who knew their most recent partner was living with HIV or who did not know the HIV status of their most recent partner were less likely to prefer on‐demand PrEP (p = 0.05). Conclusions: Our data show that AYP in four SSA communities prefer on‐demand over daily PrEP options, with differences seen by site, age and sex. PrEP demand creation needs to be reviewed, optimized and tailored to socio‐demographic differences and designed in conjunction with AYP. [ABSTRACT FROM AUTHOR]

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-a; 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. [ABSTRACT FROM AUTHOR]

Pre-exposure prophylaxis (PrEP) is an HIV-prevention strategy recommended for those at high-risk of infection, including adolescents and young people (AYP). We explored how PrEP roll-out could influence sexual risk behaviour among AYP in East and southern Africa. Twenty-four group discussions and 60 in-depth interviews were conducted with AYP between 13 and 24 years old, recruited from community settings in Uganda, Zimbabwe and South Africa, from September 2018 to January 2019. Participants perceived that PrEP availability could change sexual behaviour among AYP, influencing: (1) condom use (increased preference for condomless sex, reduced need and decrease in use of condoms, relief from condom use discomfort, consistent condom use to curb sexually transmitted infections and pregnancies); (2) sexual activities (increase in sexual partners and sexual encounters, early sexual debut, sexual experimentation and peace of mind during risky sex, sexual violence and perversion); (3) HIV risk perception (neglect of other HIV prevention strategies, unknown sexual partner HIV status, adoption of PrEP). PrEP initiation may be associated with increased interest in sexual activities and risky sexual behaviour among AYP. PrEP should be included as part of a combination package of HIV prevention strategies for AYP with methods to prevent other sexually transmitted infections and unwanted pregnancies. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has brought many health systems in low resource settings to their knees. The pandemic has had crippling effects on the already strained health systems in provision of maternal and newborn healthcare. With the travel restrictions, social distancing associated with the containment of theCOVID-19 pandemic, healthcare providers could be faced with challenges of accessing their work stations, and risked burnout as they offered maternal and newborn services. This study sought to understand the experiences and perceptions of healthcare providers at the frontline during the first phase of the lockdown as they offered maternal and newborn health care services in both public and private health facilities in Uganda with the aim of streamlining patient care in face of the current COVID-19 pandemic and in future disasters. Methods: Between June 2020 and December 2020, 25 in-depth interviews were conducted among healthcare providers of different cadres in eight Public, Private-Not-for Profit and Private Health facilities in Kampala, Uganda. The interview guide primarily explored the lived experiences of healthcare providers as they offered maternal and newborn healthcare services during the COVID-19 pandemic. All of the in depth interviews were audio recorded and transcribed verbatim. Themes and subthemes were identified using both inductive thematic and phenomenological approaches. Results: The content analysis of the in depth interviews revealed that the facilitators of maternal and newborn care service delivery among the healthcare providers during the COVID-19 pandemic included; salary bonuses, the passion to serve their patients, availability of accommodation during the pandemic, transportation to and from the health facilities by the health facilities, teamwork, fear of losing their jobs and fear of litigation if something went wrong with the mothers or their babies. The barriers to their service delivery included; lack of transport means to access their work stations, fear of contracting COVID-19 and transmitting it to their family members, salary cuts, loss of jobs especially in the private health facilities, closure of the non-essential services to combat high patient numbers, inadequate supply of Personal Protective equipment (PPE), being put in isolation or quarantine for two weeks which meant no earning, brutality from the security personnel during curfew hours and burnout from long hours of work and high patient turnovers. Conclusion: The COVID-19 Pandemic has led to a decline in quality of maternal and newborn service delivery by the healthcare providers as evidenced by shorter consultation time and failure to keep appointments to attend to patients. Challenges with transport, fears of losing jobs and fear of contracting COVID-19 with the limited access to personal protective equipment affected majority of the participants. The healthcare providers in Uganda despite the limitations imposed by the COVID-19 pandemic are driven by the inherent passion to serve their patients. Availability of accommodation and transport at the health facilities, provision of PPE, bonuses and inter professional teamwork are critical motivators that needed to be tapped to drive teams during the current and future pandemics. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Severe anaemia is a common clinical problem among young children in sub-Saharan Africa. However, the effect of severe anaemia on neurodevelopment of these children is not well described. Therefore, we assessed the neurodevelopmental performance of preschool children diagnosed with severe anaemia in Northern Uganda. Methods: We conducted a prospective cohort study among children < 5 years of age 14 days post discharge after an episode of severe anaemia (Hb < 5.0 g/dl; n = 171; mean Hb = 3.9g/dl) at Lira Regional Referral Hospital, Uganda. Neurodevelopmental outcomes (cognitive, language and motor) were assessed using Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III). Age-adjusted z-scores for each domain were calculated using scores from healthy community control children (n = 88) recruited from the same environment for each age category. Multiple linear regression was used to compare z-scores in the cognitive, language and motor scales between the two groups after adjusting for weight-for-age z-score, socioeconomic status, mother's education, and father's employment on all the scales. Results: The prevalence of neurodevelopmental impairment was 2.3% (95% CI: 0.8–6.1) for cognition, 1.7% (95%: 0.6–5.3) for language and 3.5% (95% CI: 1.6–7.6) for motor scales and 4.6% (95% CI: 2.3–9.1) for deficits in ≥1 area of neurodevelopment. Significant differences were observed between the two groups with the SA group performing worse on cognition [adjusted mean score, (Standard error, SE), P-value] [-0.20, (0.01) vs. 0.00, (0.01), P = 0.02]; language [-0.25, (0.01) vs. 0.00, (0.01), P< 0.001]; and motor [-0.17, (0.01) vs. 0.00, (0.01), P = 0.05] scales. Conclusion: In children < 5 years of age, severe anaemia was associated with neurocognitive (cognition, language and motor) deficits in the immediate period post treatment. Further research is needed to identify risk factors and determine the long-term effects of poor neurodevelopment in young children with severe anaemia. [ABSTRACT FROM AUTHOR]

Background: Recently, a 3-month (12-dose) regimen of weekly isoniazid and rifapentine (3HP) was recommended by the World Health Organization for the prevention of tuberculosis (TB) among people living with HIV (PLHIV) on common antiretroviral therapy regimens. The best approach to delivering 3HP to PLHIV remains uncertain.Methods: We developed a three-armed randomized trial assessing optimized strategies for delivering 3HP to PLHIV. The trial will be conducted at the Mulago Immune Suppression Syndrome (i.e., HIV/AIDS) clinic in Kampala, Uganda. We plan to recruit 1656 PLHIV, randomized 1:1 to each of the three arms (552 per arm). Using a hybrid type 3 effectiveness-implementation design, this pragmatic trial aims to (1) compare the acceptance and completion of 3HP among PLHIV under three delivery strategies: directly observed therapy (DOT), self-administered therapy (SAT), and informed patient choice of either DOT or SAT (with the assistance of a decision aid); (2) to identify processes and contextual factors that influence the acceptance and completion of 3HP under each delivery strategy; and (3) to estimate the costs and compare the cost-effectiveness of three strategies for delivering 3HP. The three delivery strategies were each optimized to address key barriers to 3HP completion using a theory-informed approach. We hypothesize that high levels of treatment acceptance and completion can be achieved among PLHIV in sub-Saharan Africa and that offering PLHIV an informed choice between the optimized DOT and SAT delivery strategies will result in greater acceptance and completion of 3HP. The design and planned evaluation of the delivery strategies were guided by the use of implementation science conceptual frameworks.Discussion: 3HP-one of the most promising interventions for TB prevention-will not be scaled up unless it can be delivered in a patient-centered fashion. We highlight shared decision-making as a key element of our trial design and theorize that offering PLHIV an informed choice between optimized delivery strategies will facilitate the highest levels of treatment acceptance and completion.Trial Registration: ClinicalTrials.gov: NCT03934931 ; Registered 2 May 2019. [ABSTRACT FROM AUTHOR]

Background WHO guidelines recommend concurrent iron and antimalarial treatment in children with malaria and iron deficiency, but iron may not be well absorbed or utilized during a malaria episode. Objectives We aimed to determine whether starting iron 28 d after antimalarial treatment in children with severe malaria and iron deficiency would improve iron status and lower malaria risk. Methods We conducted a randomized clinical trial on the effect of immediate compared with delayed iron treatment in Ugandan children 18 mo–5 y of age with 2 forms of severe malaria: cerebral malaria (CM; n  = 79) or severe malarial anemia (SMA; n  = 77). Asymptomatic community children (CC; n  = 83) were enrolled as a comparison group. Children with iron deficiency, defined as zinc protoporphyrin (ZPP) ≥ 80 µmol/mol heme, were randomly assigned to receive a 3-mo course of daily oral ferrous sulfate (2 mg · kg–1 · d–1) either concurrently with antimalarial treatment (immediate arm) or 28 d after receiving antimalarial treatment (delayed arm). Children were followed for 12 mo. Results All children with CM or SMA, and 35 (42.2%) CC, were iron-deficient and were randomly assigned to immediate or delayed iron treatment. Immediate compared with delayed iron had no effect in any of the 3 study groups on the primary study outcomes (hemoglobin concentration and prevalence of ZPP ≥ 80 µmol/mol heme at 6 mo, malaria incidence over 12 mo). However, after 12 mo, children with SMA in the delayed compared with the immediate arm had a lower prevalence of iron deficiency defined by ZPP (29.4% compared with 65.6%, P  = 0.006), a lower mean concentration of soluble transferrin receptor (6.1 compared with 7.8 mg/L, P  = 0.03), and showed a trend toward fewer episodes of severe malaria (incidence rate ratio: 0.39; 95% CI: 0.14, 1.12). Conclusions In children with SMA, delayed iron treatment did not increase hemoglobin concentration, but did improve long-term iron status over 12 mo without affecting malaria incidence. This trial was registered at clinicaltrials.gov as NCT01093989. [ABSTRACT FROM AUTHOR]

Background: The appropriate use of the Partograph allows early identification of labour related complications and prevents deaths. We, therefore, sought to determine the level of Partograph completion and healthcare worker perspectives towards its utilization.Methods: This study had two components; a hospital-based cross-sectional descriptive chart review at the Mulago National Referral Hospital, Kampala, Uganda and a qualitative study involving four Focus Group Discussions (FGDs) with ward nurses, midwives and postgraduate residents. Data from the FGDs were analyzed using thematic -content analysis in Open Code software. The quantitative data were summarized using descriptive statistical analysis, means and proportions.Results: Among the 355 Partographs reviewed, 79.1% had incomplete documentation of age, 52.7% gravidity, and 3.2% parity. In about 61%, the specific parameters for fetal monitoring, maternal monitoring and labour progress were incomplete. From the FGDs, the healthcare workers reported being unable to complete the Partographs due to the overwhelming numbers of expectant mothers and other staff responsibilities. Congestion in the maternity ward reduced the Partograph completion rates. The availability of other monitoring tools, limitation in skills, inadequate equipment and supplies, and the state of the mother at the presentation to the hospital all made Partograph use and completion challenging.Conclusions: The majority of Partographs started by health workers were incomplete. The time required to document, health system challenges, status of mother at presentation, and the high workload undermined completion of the Partograph at this high volume facility. [ABSTRACT FROM AUTHOR]

Background: The provision of iron with antimalarial treatment is the standard of care for concurrent iron deficiency and malaria. However, iron that is given during a malaria episode may not be well absorbed or used, particularly in children with severe malaria and profound inflammation. Objectives: We aimed to 1) determine baseline values of iron and inflammatory markers in children with severe malarial anemia (SMA), children with cerebral malaria (CM), and community children (CC) and 2) compare markers in iron-deficient children in each group who received 28 d of iron supplementation during antimalarial treatment with those in children who did not receive iron during treatment.. Design: Seventy-nine children with CM, 77 children with SMA, and 83 CC who presented to Mulago Hospital, Kampala, Uganda, were enrolled in a 28-d iron-therapy study. Children with malaria received antimalarial treatment. All children with CM or SMA, as well as 35 CC, had zinc protoporphyrin (ZPP) concentrations ≥80 µmol/mol heme and were randomly assigned to receive a 28-d course of iron or no iron. We compared iron markers at day 0 among study groups (CM, SMA, and CC groups) and at day 28 between children in each group who were randomly assigned to receive iron or to not receive iron. Results: At day 0, children with CM and SMA had greater values of C-reactive protein, ferritin, and hepcidin than those of CC. At day 28, interactions between study and treatment group were NS. Children in the no-iron compared with iron groups had similar mean values for hemoglobin (115 compared with 113 g/L, respectively; P = 0.73) and ZPP (124 compared with 124 µmol/mol heme, respectively; P = 0.96) but had lower median ferritin [101.0 µg/L (95% CI: 84.2, 121.0 µg/L) compared with 152.9 µg/L (128.8, 181.6 µg/L), respectively; P ≤ 0.001] and hepcidin [45.8 ng/mL (36.8, 56.9 ng/mL) compared with 83.1 ng/mL (67.6, 102.2 ng/mL), respectively; P < 0.011]. Conclusions: Severe inflammation is a characterization of children with CM and SMA. The withholding of iron from children with severe malaria is associated with lower ferritin and hepcidin at day 28 but not a lower hemoglobin concentration. This trial was registered at clinicaltrials.gov as NCT01093989. [ABSTRACT FROM AUTHOR]

Background: Severe anaemia is a global public health challenge commonly associated with morbidity and mortality among children < 5 years of age in Sub-Saharan Africa. However, less is known about the behavioural performance of children < 5 years surviving severe anaemia in low resource settings. We investigated social-emotional and adaptive behaviour in children < 5 years diagnosed with severe anaemia in Northern Uganda. Methods: We conducted a hospital based prospective cohort study among children 6—42 months who were treated for severe anaemia (n = 171) at Lira Regional Referral Hospital, Uganda. Socio-emotional and adaptive behaviour were assessed 14 days post discharge using the Bayley Scales of Infant and Toddler Development, 3rd edition. Age-adjusted z-scores for each domain were calculated using scores from healthy community children (n = 88) from the same environment for each age category. Multiple linear regression was used to compare z-scores in the social-emotional and adaptive behaviour scales between the two groups after adjusting for weight-for-age z-score, social economic status, mother's education, father's education and father's employment on all the scales. Results: Compared with healthy community controls, children with severe anaemia had poorer [adjusted mean scores (standard error)], socio-emotional [− 0.29, (0.05) vs. 0.01, (0.08), P = 0.002]; but not overall/ composite adaptive behaviour [− 0.10, (0.05) vs. − 0.01, (0.07), P = 0.343]. Within the adaptive behaviour subscales, children with SA displayed significantly poorer scores on the community use [adjusted mean score (standard error)], [− 0.63, (0.10) vs. − 0.01, (0.13), P < 0.001]; and leisure [− 0.35, (0.07) vs. − 0.02, (0.07), P = 0.036] skills. Conclusion: This study suggests that severe anaemia in children < 5 years is associated with poor social-emotional scores in the short-term post clinical recovery in Northern Uganda. We recommend long-term follow-up to determine the course of these problems and appropriate interventions to reduce the behavioural burden among children < 5 years surviving severe anaemia in Uganda. [ABSTRACT FROM AUTHOR]

The article discusses the cross-sectional study on the possible causes of neonatal deaths in rural Uganda. It details how the study was conducted which involved World Health Organization's verbal autopsy tool that was modified for infant death. The results reportedly revealed that 30% of neonatal deaths has occurred during the first week of life and that the top causes of death include sepsis and birth asphyxia.

Introduction: Tight junctions (TJs) serve as permeability filters between the internal and external cellular environment. A large number of proteins have been identified to be localized at the TJs. Due to limitations in tissue collection, TJs in the male genital tract have been understudied., Methods: We analysed the transcriptomics of 132 TJ genes in foreskin tissue of men requesting voluntary medical male circumcision (VMMC) and enrolled in the Combined HIV Adolescent Prevention Study (CHAPS) trial conducted in South Africa and Uganda (NCT03986970). The trial evaluated the dose requirements for event-driven HIV pre-exposure prophylaxis (PrEP) with emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during insertive sex. A total of 144 participants were randomized to either control arm or one of 8 PrEP arms (n=16/arm), receiving oral FTC-TDF or FTC-TAF over one or two days. Following in vivo oral PrEP dosing and VMMC, the expression level of three important TJ proteins (CLDN-1, OCN and ZO-1) was measured ex vivo in foreskin tissue by Western blot. The expression of cytokine genes implicated in TJ regulation was determined. Non-parametric Kruskal-Wallis tests were used to compare TJ gene expression and protein levels by type of PrEP received, and Spearman's correlation coefficients were calculated to assess whether TJ gene expression levels were related to cytokine gene levels or to PrEP drug concentrations and their active intracellularly phosphorylated metabolites., Results: A high level of expression in foreskin tissue was found for 118 (of 132) TJ genes analysed; this finding contributed to create a map of TJ components within the male genital tract. Importantly, PrEP regimens tested in the CHAPS trial did not affect the expression of TJ genes and the analysed proteins in the foreskin; thus, further supporting the safety of this prevention strategy against HIV-1 transmission during insertive sex. Additionally, we identified the level of several cytokines' genes to be correlated to TJ gene expression: among them, IL-18, IL-33 and VEGF., Discussion: TJs can limit viral entry into target cells; to affect this biological function viruses can reduce the expression of TJ proteins. Our study, on the expression and regulation of TJs in the foreskin, contribute important knowledge for PrEP safety and further design of HIV-1 prophylaxis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Webb, Petkov, Yun, Else, Lebina, Serwanga, Pillay, Seiphetlo, Mugaba, Namubiru, Odoch, Opoka, Ssemata, Kaleebu, Khoo, Martinson, Fox, Gray, Herrera and Chiodi.)

Objective: The aim of the research was to explore the barriers to healthcare access for persons with various disabilities in rural Luuka district of Uganda. The findings will assist in appreciating the challenges persons with disabilities face in accessing Healthcare in a rural setting. These insights will contribute to the development of an intervention to improve healthcare access that is affordable, timely and acceptable., Design and Participants: This qualitative study formed the exploratory formative phase of the 'Missing Billion' project. A total of 27 participants with disabilities-visual impairment (n=5), physical impairment (n=5), multiple impairments (n=6) and intellectual/ cognitive impairment (n=5) were purposively selected to participate in in-depth interviews conducted by two experienced researchers. Participants were identified through contact lists provided by the district disability focal person and local disability associations, with additional participants identified through snowball sampling. Interviews with persons with hearing impairment (n=6) were conducted by a researcher with hearing impairment. The interviews were audio/video recorded and transcribed to facilitate thematic data analysis. We used the disability-inclusive health 'Missing Billion' framework to map and inform the barriers., Setting: The study was conducted between September and November 2022 in rural communities in Luuka district, Eastern Uganda., Findings: On the demand side, challenges revolved around autonomy and awareness, limited access to health information, lack of financial capacity and dependence on caregivers for healthcare choices left persons with disabilities feeling disempowered. On the supply side, discrimination and negative attitudes from healthcare workers were reported as prevalent. Absence of healthcare workers and service delivery delays impacted on healthcare access, resulting in poor care. Inaccessible healthcare facilities compounded issues, as they had limited accessibility features., Conclusions: Complex and interconnected barriers underscore the pressing need for systemic changes to ensure equitable healthcare access for persons with disabilities in rural Uganda., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

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., (© 2024. The Author(s).)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

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)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

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., (© 2023. Springer Nature Limited.)

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., Competing Interests: Competing interests: The author(s) declare that they have no financial or personal relationship(s) that may have inappropriately influenced them in writing this article. The funder did not influence the results and compiling of the manuscript. JG reports personal fees from GSK, personal fees from Novartis, personal fees and a grant to QMUL from OM Pharma, personal fees and payment to QMUL from AstraZeneca, personal fees from Omron, outside the submitted work, and is supported by an NIHR Senior Investigator Award. RM reports consultancy and advisory board membership from AstraZeneca, Boehringer and Organon., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

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., (© 2022. The Author(s).)

Introduction: Cognitive impairment is common in first-episode psychosis patients and often associated with poor quality of life and functional impairment. However, most literature on this association is from high income countries and not low resource countries like Uganda. We aimed to determine the association between cognitive impairment with quality of life and functional impairment in Ugandan first-episode psychosis patients., Methods: At Butabika national psychiatric hospital of Uganda, we enrolled 94 first-episode psychosis patients aged 18-60 years with a confirmed first-episode of psychosis and no previous treatment with antipsychotic medication. Neuropsychological assessment was performed using the MATRICS consensus cognitive battery (MCCB). Quality of life and functional impairment were assessed using the brief version of the World Health Organisation Quality of Life scale (WHOQOL-BREF) and the MINI International Neuropsychiatric Inventory (MINI) respectively. Linear regression analyses determined the association between impairment in different cognitive domains with various quality of life and functional impairment domains while controlling for age, gender and level of education., Results: High scores in the reasoning and problem solving cognitive domain were associated with better quality of life in the psychological domain of WHOQOL-BREF (p = 0.029). For functional impairment, high cognitive scores in the domains of speed of processing (p = 0.018), reasoning and problem solving (p = 0.015), working memory (p = 0.017) and visual learning and memory (p = 0.002) were associated with psychosis "having a greater impact on other members of the family" on the MINI. Higher scores in the social cognition domain were associated with "less aggressive and disruptive behaviour" (p = 0.003)., Conclusion: Cognitive impairment in Ugandan first-episode psychotic patients is associated with both poorer quality of life and functional impairment. Remediation of cognitive function may be a plausible intervention to improve outcomes in Ugandan first-episode psychosis patients., (© 2022. The Author(s).)

Introduction: HIV self-testing (HIVST) across sub-Saharan African countries may be acceptable as it overcomes significant barriers to clinic-based HIV testing services such as privacy and confidentiality. There are a number of suggested HIVST distribution models. However, they may not be responsive to the testing service needs of adolescents and young people (AYP). We will investigate the knowledge, acceptability and social implications of a peer-to-peer distribution model of HIVST kits on uptake of HIV prevention including pre-exposure prophylaxis, condoms, and voluntary medical male circumcision and testing services and linkage to anti-retroviral therapy among AYP aged 15-24 in Zambia and Uganda., Methods and Analysis: We will conduct an exploratory mixed methods study among AYP aged 15-24 in Uganda and Zambia. Qualitative data will be collected using audio-recorded in-depth interviews (IDIs), focus group discussions (FGDs), and participant observations. All IDIs and FGDs will be transcribed verbatim, coded and analysed through a thematic-content analysis. The quantitative data will be collected through a structured survey questionnaire derived from the preliminary findings of the qualitative work and programme evaluation quantitative data collected on uptake of services from a Zambian trial. The quantitative phase will evaluate the number of AYP reached and interested in HIVST and the implication of this on household social relations and social harms. The quantitative data will be analysed through bivariate analyses. The study will explore any social-cultural and study design barriers or facilitators to uptake of HIVST., Ethics and Dissemination: This study is approved by the Uganda Virus Research Institute Research and Ethics committee, Uganda National Council for Science and Technology, University of Zambia Biomedical Ethics Committee, Zambia National Health Research Authority and the London School of Hygiene and Tropical Medicine. Dissemination activities will involve publications in peer-reviewed journals, presentations at conferences and stakeholder meetings in the communities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: It is not known whether post-traumatic stress disorder (PTSD) increases HIV-risk behaviours among young people in sub-Saharan Africa. We assessed associations of PTSD symptoms with sexual behaviour, HIV risk perception, and attitudes towards PrEP among young people taking part in the CHAPS community survey. We hypothesised that PTSD symptoms would increase sexual behaviours associated with HIV risk, hinder PrEP uptake and influence preference for daily versus on-demand PrEP., Methods: Young people without HIV, aged 13-24 years, were purposively recruited in Johannesburg and Cape Town in South Africa, Wakiso in Uganda, and Chitungwiza in Zimbabwe, and surveyed on socio-demographic characteristics, PrEP knowledge and attitudes, sexual behaviour, HIV perception and salience, and mental health. PTSD symptoms were measured using the Primary Care PTSD Screen for the Diagnostic and Statistical Manual of Mental Disorders 5 (PC-PTSD-5). Logistic and ordinal logistic regression was used to assess associations between PC-PTSD-5 score and socio-demographic characteristics, sexual behaviour, HIV risk perception, PrEP attitudes, and substance use, adjusting for age, sex, setting, depression and anxiety., Results: Of 1330 young people (51% male, median age 19 years), 522 (39%) reported at least one PTSD symptom. There was strong evidence that having a higher PC-PTSD-5 score was associated with reported forced sex (OR 3.18, 95%CI: 2.05-4.93), self-perception as a person who takes risks (OR 1.12, 95%CI: 1.04-1.20), and increased frequency of thinking about risk of HIV acquisition (OR 1.16, 95%CI: 1.08-1.25). PTSD symptoms were not associated with willingness to take PrEP, preference for on-demand versus daily PrEP, or actual HIV risk behaviour such as condomless sex., Conclusions: Symptoms consistent with probable PTSD were common among young people in South Africa, Uganda and Zimbabwe but did not impact PrEP attitudes or PrEP preferences. Evaluation for PTSD might form part of a general assessment in sexual and reproductive health services in these countries. More work is needed to understand the impact of PTSD on HIV-risk behaviour, forced sex and response to preventive strategies including PrEP., (© 2022. The Author(s).)

Background: HIV remains a major public health issue, especially in Eastern and Southern Africa. Pre-exposure prophylaxis is highly effective when adhered to, but its effectiveness is limited by cost, user acceptability and uptake. The cost of a non-inferiority phase III trial is likely to be prohibitive, and thus, it is essential to select the best possible drug, dose and schedule in advance. The aim of this study, the Combined HIV Adolescent PrEP and Prevention Study (CHAPS), is to investigate the drug, dose and schedule of pre-exposure prophylaxis (PrEP) required for the protection against HIV and the acceptability of PrEP amongst young people in sub-Saharan Africa, and hence to inform the choice of intervention for future phase III PrEP studies and to improve strategies for PrEP implementation., Methods: We propose a mixed-methods study amongst young people aged 13-24 years. The first component consists of qualitative research to identify the barriers and motivators towards the uptake of PrEP amongst young people in South Africa, Uganda and Zimbabwe. The second component is a randomised clinical trial (ClinicalTrials.gov NCT03986970, June 2019) using a novel ex vivo HIV challenge method to investigate the optimal PrEP treatment (FTC-TDF vs FTC-TAF), dose and schedule. We will recruit 144 amongst HIV-negative uncircumcised men aged 13-24 years from voluntary male medical circumcision clinics in two sites (South Africa and Uganda) and randomise them into one of nine arms. One group will receive no PrEP prior to surgery; the other arms will receive either FTC-TDF or FTC-TAF, over 1 or 2 days, and with the final dose given either 6 or 20 h prior to surgery. We will conduct an ex vivo HIV challenge on their resected foreskin tissue., Discussion: This study will provide both qualitative and quantitative results to help decide the optimum drug, dose and schedule for a future phase III trial of PrEP. The study will also provide crucial information on successful strategies for providing PrEP to young people in sub-Saharan Africa., Trial Registration: ClinicalTrials.gov NCT03986970 . Registered on 14 June 2019.

Background: Malaria and iron deficiency (ID) in childhood are both associated with cognitive and behavioral dysfunction. The current standard of care for children with malaria and ID is concurrent antimalarial and iron therapy. Delaying iron therapy until inflammation subsides could increase iron absorption but also impair cognition., Methods: In this study, Ugandan children 18 months to 5 years old with cerebral malaria (CM, n = 79), severe malarial anemia (SMA, n = 77), or community children (CC, n = 83) were enrolled and tested for ID. Children with ID were randomized to immediate vs. 28-day delayed iron therapy. Cognitive and neurobehavioral outcomes were assessed at baseline and 6 and 12 months (primary endpoint) after enrollment., Results: All children with CM or SMA and 35 CC had ID (zinc protoporphyrin concentration ≥80 μmol/mol heme). No significant differences were seen at 12-month follow-up in overall cognitive ability, attention, associative memory, or behavioral outcomes between immediate and delayed iron treatment (mean difference (standard error of mean) ranged from -0.2 (0.39) to 0.98 (0.5), all P ≥ 0.06)., Conclusions: Children with CM or SMA and ID who received immediate vs. delayed iron therapy had similar cognitive and neurobehavioral outcomes at 12-month follow-up., Impact: The optimal time to provide iron therapy in children with severe malaria is not known. The present study shows that delay of iron treatment to 28 days after the malaria episode, does not lead to worse cognitive or behavioral outcomes at 12-month follow-up. The study contributes new data to the ongoing discussion of how best to treat ID in children with severe malaria.

Background: In resource limited settings, there is variability in the level of adherence to clinical guidelines in the inpatient management of children with common conditions like severe anemia. However, there is limited data on the effect of adherence to clinical guidelines on inpatient mortality in children managed for severe anemia., Methods: We analyzed data from an uncontrolled before and after in-service training intervention to improve quality of care in Lira and Jinja regional referral hospitals in Uganda. Inpatient records of children aged 0 to 5 years managed as cases of 'severe anemia (SA)' were reviewed to ascertain adherence to clinical guidelines and compare inpatient deaths in SA children managed versus those not managed according to clinical guidelines. Logistic regression analysis was conducted to evaluate the relationship between clinical care factors and inpatient deaths amongst patients managed for SA., Results: A total of 1,131 children were assigned a clinical diagnosis of 'severe anemia' in the two hospitals. There was improvement in the level of care after the in-service training intervention with more children being managed according to clinical guidelines compared to the period before, 218/510 (42.7%) vs 158/621 (25.4%) (p < 0.001). Overall, children managed according to clinical guidelines had reduced risk of inpatient mortality compared to those not managed according to clinical guidelines, [OR 0.28, (95%, CI 0.14, 0.55), p = 0.001]. Clinical care factors associated with decreased risk of inpatient death included, having pre-transfusion hemoglobin done to confirm diagnosis [OR 0.5; 95% CI 0.29, 0.87], a co-morbid diagnosis of severe malaria [OR 0.4; 95% CI 0.25, 0.76], and being reviewed after admission by a clinician [OR 0.3; 95% CI 0.18, 0.59], while a co-morbid diagnosis of severe acute malnutrition was associated with increased risk of inpatient death [OR 4.2; 95% CI 2.15, 8.22]., Conclusion: Children with suspected SA who are managed according to clinical guidelines have lower in-hospital mortality than those not managed according to the guidelines. Efforts to reduce inpatient mortality in SA children in resource-limited settings should focus on training and supporting health workers to adhere to clinical guidelines., Competing Interests: The authors have declared that no competing interests exist.

Background: Severe anaemia (SA) is a common reason for hospitalisation of children in sub-Saharan Africa but the extent to which blood transfusion is used appropriately in the management of severe anemia has hitherto remained unknown. We report on the use of blood transfusion in the management of anemic children in two hospitals in Uganda., Methods: Inpatient records of children 0-5 years of age admitted to Lira and Jinja regional referral hospitals in Uganda were reviewed for children admitted on selected days between June 2016 and May 2017. Data was extracted on the results, if any, of pre-transfusion hemoglobin (Hb) level, whether or not a blood transfusion was given and inpatient outcome for all children with a diagnosis of 'severe anemia'. Qualitative data was also collected from health workers to explain the reasons for the clinical practices at the two hospitals., Results: Overall, 574/2275 (25.2%) of the children admitted in the two hospitals were assigned a diagnosis of SA. However 551 (95.9%) of children assigned a diagnosis of SA received a blood transfusion, accounting for 551/560 (98.4%) of the blood transfusions in the pediatric wards. Of the blood transfusions in SA children, only 245 (44.5%) was given appropriately per criteria (Pre-transfusion Hb ≤ 6 g/dL), while 306 (55.5%) was given inappropriately; (pre-transfusion Hb not done, n = 216, or when a transfusion is not indicated [Hb > 6.0 g/dl], n = 90). SA children transfused appropriately per Hb criteria had lower inpatient mortality compared to those transfused inappropriately, (7 (2.9%) vs. 22 (7.2%), [OR 0.4, 95% CI 0.16, 0.90]). Major issues identified by health workers as affecting use of blood transfusion included late presentation of SA children to hospital and unreliable availability of equipment for measurement of Hb., Conclusion: More than half the blood transfusions given in the management of anemic children admitted to Lira and Jinja hospitals was given inappropriately either without pre-transfusion Hb testing or when not indicated. Verification of Hb level by laboratory testing and training of health workers to adhere to transfusion guidelines could result in a substantial decrease in inappropriate blood transfusion in Ugandan hospitals.

Background: Exposure to environmental heavy metals is common among African children. Although many of these metals are known neurotoxicants, to date, monitoring of this exposure is limited, even in countries such as Uganda that are undergoing rapid industrialization. An assessment of the burden and potential causes of metal exposure is a critical first step in gauging the public health burden of metal exposure and in guiding its elimination., Methods: In May 2016, we enrolled 100 children between the ages of 6 and 59 months living in the Katanga urban settlement of Kampala, Uganda. We measured whole blood concentrations of antimony, arsenic, barium, cadmium, cesium, chromium, cobalt, copper, lead, manganese, nickel, selenium, and zinc. Applying reference cutoffs, we identified metals whose prevalence of elevated blood concentrations was > 10%. We also administered an environmental questionnaire to each child's caregiver to assess potential exposures, including source of drinking water, cooking location and fuel, materials used for roof, walls, and floor, and proximity to potential pollution sources such as main roads, garbage landfills, and fuel stations. We compared log-transformed blood metal concentrations by exposure category, using t-test for dichotomous comparisons and ANOVA for comparisons of three categories, using Tukeys test to adjust for multiple comparisons., Results: The prevalence of high blood levels was elevated for six of the metals: antimony (99%), copper (12%), cadmium (17%), cobalt (19.2%), lead (97%), and manganese (36.4%). Higher blood manganese was significantly associated with having cement walls (p = 0.04) or floors (p = 0.04). Cadmium was greater among children who attended school (< 0.01), and cobalt was higher among children who lived near a garbage landfill (p = 0.01)., Conclusions: Heavy metal exposure is prevalent in the Katanga settlement and may limit neurodevelopment of children living there. Future studies are needed to definitively identify the sources of exposure and to correct potential nutritional deficiencies that may worsen metal absorption.