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Abstract Background Following the World Health Organization’s declaration of COVID-19 as a global pandemic, several countries implemented population-wide lockdowns. However, these responses to COVID-19 caused severe healthcare system disruptions to service delivery. The TB case notification rate in Uganda decreased by 22% between January and April 2020, which coincided with a lockdown and an increase in COVID-19 cases. In this study, we tested the effect of screening all patients with both COVID-19-positive and negative symptom screen for TB at a National Referral Hospital. Design/Methods Following our formative assessment, we identified potential barriers to and facilitators of integrating screening for COVID-19 and TB at Kiruddu National Referral Hospital. To address the barriers, in February 2021 we trained healthcare providers on integrated COVID-19-TB screening tools and provided COVID-19/TB screening tools/Standard operating procedures and personal protective equipment. From March 1, 2021, to June 30, 2021, we screened patients presenting to the emergency and outpatient departments for COVID-19 symptoms, and subsequently, we performed TB symptom screening for both patients with COVID-19 positive and negative symptom screen using the intensified tuberculosis case-finding (ICF) guide. We then compared the outcomes of TB symptom screening for patients initially with a positive COVID-19 symptom screen with those who initially had a negative COVID-19 symptom screen. Results From March 2021 to June 2021, we screened 1464 patients (44.3% male and 55.7% female) for COVID-19 symptoms. Out of these participants, 1252 (85.5%) screened positive for COVID-19 symptoms, while 212 (14.5%) screened negative. The majority of patients with a positive COVID-19 symptom screen, 717 (57.3%), also screened positive for TB symptoms compared to 19 (8.9%) among patients with a negative COVID-19 symptom screen. Out of the total 736 presumptive TB cases identified, 717 (97.4%) initially screened positive for COVID-19 symptoms. TB was diagnosed in 110 individuals including 104 who had positive COVID-19-symptom screen and six who had a negative COVID-19 symptom screen. All of the 110 newly diagnosed TB cases were linked to TB treatment. Conclusions Patients who screen positive for COVID-19 symptoms should be routinely screened for TB to mitigate missed opportunities for TB case identification.

Abstract Introduction Community Client-Led ART Delivery (CCLAD) is a community HIV care model. In this model, a group of persons living with HIV (PLHIV) in a specific location, take turns going to the HIV clinic to pick up Antiretroviral Treatment refills for members. The uptake of this model, however, remains low despite its improvements in patient retention. In this study, we explored PLHIV’s perceptions of this model and identified the factors associated with its low uptake. Methods This was a mixed methods study based on a retrospective review of records of PLHIV and in-depth interviews. We reviewed the medical records of people receiving ART to determine their current model of ART delivery and conducted in-depth interviews with 30 participants who were eligible to be enrolled in the CCLAD model at the Mulago ISS clinic. We performed logistic regression to identify factors associated with the uptake of the CCLAD model and inductive thematic analysis to explore PLHIV’s perceptions of the CCLAD model. Results A total of 776 PLHIV were sampled for the study, 545 (70.2%) of whom were female. The mean age (standard deviation) was 42 (± 9.3) years. Overall, 55 (7.1%) received ART using the CCLAD model. Compared to other ART-delivery models, CCLAD was associated with being on ART for at least eight years (AOR 3.72; 95% CI: 1.35–10.25) and having no prior missed clinic appointments (AOR 10.68; 95% CI: 3.31–34.55). Mixed perceptions were expressed about the CCLAD model. Participants interviewed appreciated CCLAD for its convenience and the opportunities it offered members to talk and support each other. Others however, expressed concerns about the process of group formation, and feeling detached from the health facility with consequences of lack of confidentiality. Conclusion The current uptake of the CCLAD model is lower than the national recommended percentage of 15%. Its uptake was associated with those who had been in care for a longer period and who did not miss appointments. Despite CCLAD being perceived as convenient and as promoting support among members, several challenges were expressed. These included complexities of group formation, fear of stigma and feelings of detachment from health facilities among others. So, while CCLAD presents a promising alternative ART delivery model, more attention needs to be paid to the processes of group formation and improved patient monitoring to address the feelings of detachment from the facility and facility staff.

Abstract Background Limited diagnostic capabilities, resources and health worker skills have deterred the advancement of birth defects surveillance systems in most low- and middle-income countries (LMICs). Empowering health workers to identify and diagnose major external birth defects (BDs) is crucial to establishing effective hospital-based BD surveillance. Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration BD Surveillance System consists of three diagnostic levels: (1) surveillance midwives, (2) MU-JHU clinical team, and (3) U.S. Centers for Disease Control and Prevention (CDC) birth defects subject matter experts (SMEs) who provide confirmatory diagnosis. The diagnostic concordance of major external BDs by surveillance midwives or MU-JHU clinical team with CDC birth defects SMEs were estimated. Methods Study staff went through a series of trainings, including birth defects identification and confirmation, before surveillance activities were implemented. To assess the diagnostic concordance, we analyzed surveillance data from 2015 to 2021 for major external BDs: anencephaly, iniencephaly, encephalocele, spina bifida, craniorachischisis, microcephaly, anophthalmia/microphthalmia, anotia/microtia, cleft palate alone, cleft lip alone, cleft lip with cleft palate, imperforate anus, hypospadias, talipes equinovarus, limb reduction, gastroschisis, and omphalocele. Positive predictive value (PPV) as the proportion of BDs diagnosed by surveillance midwives or MU-JHU clinical team that were confirmed by CDC birth defects SMEs was computed. PPVs between 2015 and 2018 and 2019–2021 were compared to assess the accuracy of case diagnosis over time. Results Of the 204,332 infants examined during 2015–2021, 870 infants had a BD. Among the 1,245 BDs identified, 1,232 (99.0%) were confirmed by CDC birth defects SMEs. For surveillance midwives, PPV for 7 of 17 BDs was > 80%. For the MU-JHU clinical team, PPV for 13 of 17 BDs was > 80%. Among surveillance midwives, PPV improved significantly from 2015 to 2018 to 2019–2021, for microcephaly (+ 50.0%), cleft lip with cleft palate (+ 17.0%), imperforate anus (+ 30.0%), and talipes equinovarus (+ 10.8%). Improvements in PPV were also observed among MU-JHU clinical team; however, none were significant. Conclusion The diagnostic accuracy of the midwives and clinical team increased, highlighting that BD surveillance, by front-line health care workers (midwives) in LMICs is possible when midwives receive comprehensive training, technical support, funding and continuous professional development.

Abstract Background An estimated 300,000 babies are born with sickle cell anaemia (SCA) annually. Affected children have chronic ill health and suffer premature death. Febrile illnesses such as malaria commonly precipitate acute crises in children with SCA. Thus, chemoprophylaxis for malaria is an important preventive strategy, but current regimes are either sub-optimally effective (e.g. monthly sulphadoxine-pyrimethamine, SP) or difficult to adhere to (e.g. daily proguanil). We propose dihydroartemisinin-piperaquine (DP) as the agent with the most potential to be used across Africa. Methods This will be a randomised, double-blind, parallel-group superiority trial of weekly single-day courses of DP compared to monthly single-day courses of SP in children with SCA. The study will be conducted in eastern (Uganda) and southern (Malawi) Africa using randomisation stratified by body weight and study centre. Participants will be randomised using an allocation of 1:1 to DP or SP. We will investigate the efficacy, safety, acceptability and uptake and cost-effectiveness of malaria chemoprevention with weekly courses of DP vs monthly SP in 548 to 824 children with SCA followed up for 12–18 months. We will also assess toxicity from cumulative DP dosing and the development of resistance. Participant recruitment commenced on 30 April 2021; follow-up is ongoing. Discussion At the end of this study, findings will be used to inform regional health policy. This manuscript is prepared from protocol version 2.1 dated 1 January 2022. Trial registration The trial was registered at ClinicalTrials.gov, NCT04844099 . Registered on 08 April 2021.

Abstract Background Following the first wave of the COVID-19 outbreak, Uganda experienced a 40% drop in tuberculosis (TB) screening by June 2020. We sought to identify barriers to and facilitators of integrated COVID-19 and TB screening from the perspective of healthcare providers (HCPs) at a National Referral Hospital in Kampala, Uganda. Design/methods We conducted a cross-sectional study using in-depth interviews with 12 HCPs involved in TB activities in the outpatient and emergency departments at Kiruddu National Referral Hospital, Kampala, Uganda. We explored the HCP experiences at work in the setting of COVID-19, HCP perceived effect of COVID-19 on TB screening activities at the hospital, and perceptions about social and contextual factors that might influence the willingness of HCP to integrate screening of COVID-19 and TB. We analyzed the data using an inductive thematic approach and we denoted the emergent themes as barriers to and facilitators of COVID-19/TB integrated screening. We then mapped the themes to the Capability, Opportunity, Motivation, and Behavior (COM-B) model. Results The facilitators to integrated COVID-19 and TB screening included the availability of TB focal persons and already existing training forums at the hospital that could be utilized to strengthen the capacity of HCP to integrate COVID-19 and TB screening. The barriers included HCP’s inadequate knowledge on how to integrate screening of COVID-19 and TB, the absence of simple easy-to-use standard operating procedures and data collection tools for integrated screening, inconsistent supply of personal protective equipment (PPE), understaffing, and fear of contracting COVID-19 infection. The identified intervention functions to address the facilitators or barriers included education, persuasion, enablement, and training. Conclusions These findings provided a basis for designing contextually appropriate interventions targeting factors that are likely to influence HCP decisions and willingness to conduct TB screening in the context of COVID-19. Future studies should evaluate the effect of addressing these barriers to the integration of COVID-19 and TB as well as the effect of this on TB case finding in high-burden TB settings.

Abstract Background The World Health Organization (WHO) recommends the use of pre-exposure prophylaxis (PrEP) in key populations at elevated risk for exposure to HIV. If used effectively, PrEP can reduce annual HIV incidence to below 0.05%. However, PrEP is not acceptable among all communities that might benefit from it. There is, therefore, a need to understand perceptions of PrEP and factors associated with willingness to use PrEP among key populations at risk of HIV, such as members of communities with exceptionally high HIV prevalence. Objective To examine the perceptions and factors associated with willingness to use oral PrEP among members of fishing communities in Uganda, a key population at risk of HIV. Methods We conducted an explanatory sequential mixed-methods study at Ggaba fishing community from February to June 2019. Survey data were collected from a systematic random sample of 283 community members in which PrEP had not been rolled out yet by the time of we conducted the study. We carried out bivariate tests of association of willingness to use PrEP with demographic characteristics, HIV risk perception, HIV testing history. We estimated prevalence ratios for willingness to use PrEP. We used backward elimination to build a multivariable modified Poisson regression model to describe factors associated with willingness to use PrEP. We purposively selected 16 participants for focus group discussions to contextualize survey findings, analysing data inductively and identifying emergent themes related to perceptions of PrEP. Key results We enrolled 283 participants with a mean age of 31 ± 8 years. Most (80.9%) were male. The majority of participants had tested for HIV in their lifetime, but 64% had not tested in the past 6 months. Self-reported HIV prevalence was 6.4%. Most (80.6, 95%CI 75.5–85.0) were willing in principle to use PrEP. Willingness to use PrEP was associated with perceiving oneself to be at high risk of HIV (aPR 1.99, 95%CI 1.31–3.02, P = 0.001), having tested for HIV in the past 6-months (aPR 1.13, 95%CI 1.03–1.24, P = 0.007), and completion of tertiary education (aPR 1.97, 95%CI 1.39–2.81, P

Community antiretroviral groups (CAGs) is one of the innovative and efficient differentiated service delivery models (DSDM) for reaching persons needing human immunodeficiency virus (HIV) treatment in the community. Since DSDM adoption in Uganda, evidence suggests better care outcomes for patients in DSDM compared to counterparts in routine health facility care. However, uptake of CAG models for eligible community groups of persons living with HIV (PLHIV) has been slow in Arua district, Uganda and stakeholders' perceptions regarding its implementation unexplored. The objective of the study was to determine the uptake, barriers and facilitators influencing CAG model implementation in Arua district, Uganda. We conducted a parallel convergent mixed-methods study from March 2020 to December 2020 at Adumi health centre IV and Kuluva hospital in Arua district. We enrolled and extracted data for every fifth virally suppressed participant on antiretroviral therapy (ART) at the two health facilities. Data were analysed using STATA 13.0. Uptake was determined as the proportion of eligible PLHIV that were enrolled into a group. We performed logistic regression to determine factors associated with uptake. We conducted one focus group discussion per facility among healthcare workers involved in the management of PLHIV. We also conducted 7 focus group discussions among PLHIV across the two facilities. Thematic analysis was used to describe the data. A total of 399 PLHIV were eligible for CAG, 61.6% were female, and 44.9% were on dolutegravir (DTG) based regimen. Uptake was 6.8%, 95% CI (4.7-9.7) and was found to be significantly associated with being divorced or separated in a marriage (OR; 0.14, 95%CI; 0.02-0.92, P = 0.014). Members picking drugs in turns, comforting and encouraging others to take the drugs, and health workers advising them to join and stay with other group members were perceived as facilitators to uptake of community antiretroviral group delivery model. Having few and distant eligible members in the local area to form a group, lack of transport among the member to pick the drugs when it's their turn, misunderstandings and lack of confidentiality amongst the members, and lack of partner disclosure were perceived as barriers to uptake of community antiretroviral group delivery model. Uptake of community antiretroviral group delivery model in Arua district is very low. There may be a need to support community antiretroviral group delivery models with income- generating activities, transport facilitation, closer community drug pick-up points and improved partner disclosure support mechanisms among married group members.

Community antiretroviral groups (CAGs) is one of the innovative and efficient differentiated service delivery models (DSDM) for reaching persons needing human immunodeficiency virus (HIV) treatment in the community. Since DSDM adoption in Uganda, evidence suggests better care outcomes for patients in DSDM compared to counterparts in routine health facility care. However, uptake of CAG models for eligible community groups of persons living with HIV (PLHIV) has been slow in Arua district, Uganda and stakeholders’ perceptions regarding its implementation unexplored. The objective of the study was to determine the uptake, barriers and facilitators influencing CAG model implementation in Arua district, Uganda. We conducted a parallel convergent mixed-methods study from March 2020 to December 2020 at Adumi health centre IV and Kuluva hospital in Arua district. We enrolled and extracted data for every fifth virally suppressed participant on antiretroviral therapy (ART) at the two health facilities. Data were analysed using STATA 13.0. Uptake was determined as the proportion of eligible PLHIV that were enrolled into a group. We performed logistic regression to determine factors associated with uptake. We conducted one focus group discussion per facility among healthcare workers involved in the management of PLHIV. We also conducted 7 focus group discussions among PLHIV across the two facilities. Thematic analysis was used to describe the data. A total of 399 PLHIV were eligible for CAG, 61.6% were female, and 44.9% were on dolutegravir (DTG) based regimen. Uptake was 6.8%, 95% CI (4.7–9.7) and was found to be significantly associated with being divorced or separated in a marriage (OR; 0.14, 95%CI; 0.02–0.92, P = 0.014). Members picking drugs in turns, comforting and encouraging others to take the drugs, and health workers advising them to join and stay with other group members were perceived as facilitators to uptake of community antiretroviral group delivery model. Having few and distant eligible members in the local area to form a group, lack of transport among the member to pick the drugs when it’s their turn, misunderstandings and lack of confidentiality amongst the members, and lack of partner disclosure were perceived as barriers to uptake of community antiretroviral group delivery model. Uptake of community antiretroviral group delivery model in Arua district is very low. There may be a need to support community antiretroviral group delivery models with income- generating activities, transport facilitation, closer community drug pick-up points and improved partner disclosure support mechanisms among married group members.

Abstract Background We aimed to determine how emerging evidence over the past decade informed how Ugandan HIV clinicians prescribed protease inhibitors (PIs) in HIV patients on rifampicin-based tuberculosis (TB) treatment and how this affected HIV treatment outcomes. Methods We reviewed clinical records of HIV patients aged 13 years and above, treated with rifampicin-based TB treatment while on PIs between1st—January -2013 and 30th—September—2018 from twelve public HIV clinics in Uganda. Appropriate PI prescription during rifampicin-based TB treatment was defined as; prescribing doubled dose lopinavir/ritonavir- (LPV/r 800/200 mg twice daily) and inappropriate PI prescription as prescribing standard dose LPV/r or atazanavir/ritonavir (ATV/r). Results Of the 602 patients who were on both PIs and rifampicin, 103 patients (17.1% (95% CI: 14.3–20.34)) received an appropriate PI prescription. There were no significant differences in the two-year mortality (4.8 vs. 5.7%, P = 0.318), loss to follow up (23.8 vs. 18.9%, P = 0.318) and one-year post TB treatment virologic failure rates (31.6 vs. 30.7%, P = 0.471) between patients that had an appropriate PI prescription and those that did not. However, more patients on double dose LPV/r had missed anti-retroviral therapy (ART) days (35.9 vs 21%, P = 0.001). Conclusion We conclude that despite availability of clinical evidence, double dosing LPV/r in patients receiving rifampicin-based TB treatment is low in Uganda’s public HIV clinics but this does not seem to affect patient survival and viral suppression.

Plain English Summary Adolescent pregnancies are a global problem occurring in high-, middle-, and low-income countries with Uganda having one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes, including major external birth defects, between adolescents, (age 12–19 years) and mothers (age 20–34 years) in four urban hospitals. All informative births, including live births, stillbirths, and spontaneous abortions; regardless of gestational age, delivered at four selected hospitals in Kampala from August 2015 to December 2018 were examined. Demographic data were obtained by midwives through maternal interviews and review of hospital patient notes. Of the 100,189 births, 11.0% were among adolescent mothers and 89.0% among mothers (20–34 years). Adolescent mothers were more likely than mothers (20–34 years) to have an infant with preterm delivery, low birth weight, early neonatal death, and major external birth defects. Adolescent pregnancies were also associated with an increased risk of gastroschisis when compared to mothers (20–34 years). In conclusion, this study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20–34 years. Research on the potential underlying causes or mechanisms for these adverse outcomes among adolescent births is necessary to identify possible interventions.

Sustainable birth defects surveillance systems provide countries with estimates of the prevalence of birth defects to guide prevention, care activities, and evaluate interventions. We used free and open-source software (Open Data Kit) to implement an electronic system to collect data for a hospital-based birth defects surveillance system at four major hospitals in Kampala, Uganda. We describe the establishment, successes, challenges, and lessons learned from using mobile tablets to capture data and photographs. After intensive training, surveillance midwives collected data using Android tablets with inbuilt logic checks; another surveillance midwife checked the quality of the data in real-time before data were securely uploaded onto a local server. Paper forms were used when needed as a backup for the electronic system. We experienced several challenges implementing the surveillance system, including forgotten passwords, unstable network, reduced tablet speed and freezing, loss of touch-screen sensitivity, decreased battery strength, and repetitive extensive retraining. We addressed these challenges by backing up and removing all photos from the tablet, uninstalling irrelevant applications to the study to increase storage space and speed, and monitoring and updating the system based mainly on feedback from the midwives. From August 2015 to December 2018, surveillance midwives documented information on 110,752 births at the participating hospitals. Of these, 110,573 (99.8%) were directly entered into the electronic data system and 179 (0.2%) were captured on paper forms. The use of mobile tablets for real-time data collection was successful in a hospital-based birth defects surveillance system in a resource-limited setting. Extensive training and follow-up can overcome challenges and are key to preparing staff for a successful data collection system.

Awareness of HIV serostatus helps individuals calibrate behaviour or link to care. Globally, young people (15-24years) contribute over 30% of new HIV infections. Despite progress in enhancing access to HIV services, HIV testing among young people in Uganda is below target. We determined the prevalence and factors influencing HIV testing among young people in a peri-urban district with the highest proportion of young people. We conducted a nested explanatory sequential mixed-methods study from March to May 2019 in Wakiso district. We used stratified cluster random sampling to select 397 rural and 253 urban young people from eight parishes. We collected data using questionnaires and subsequently conducted in-depth interviews with 16 purposively selected survey participants. The prevalence of testing for HIV was 80.2%. Young people related their decisions about HIV testing to self-evaluation of their risk and perceived ability to manage the consequences of a positive result. Participants reported high levels of support for HIV testing from peers, partners, and family members. They perceived health facilities as confusing, distant, expensive, and staffed by judgmental, older health workers as barriers. They felt that mobile testing points solved some of these problems, but introduced less privacy and greater confidentiality concerns. The prevalence of HIV testing among young people in Wakiso district was low compared to the UNAIDS 2030 target but among the highest in sub-Saharan Africa. Community-based programs resolve many concerns about testing at health facilities. However, there is a need to make these programs more comfortable and private.

Awareness of HIV serostatus helps individuals calibrate behaviour or link to care. Globally, young people (15-24years) contribute over 30% of new HIV infections. Despite progress in enhancing access to HIV services, HIV testing among young people in Uganda is below target. We determined the prevalence and factors influencing HIV testing among young people in a peri-urban district with the highest proportion of young people. We conducted a nested explanatory sequential mixed-methods study from March to May 2019 in Wakiso district. We used stratified cluster random sampling to select 397 rural and 253 urban young people from eight parishes. We collected data using questionnaires and subsequently conducted in-depth interviews with 16 purposively selected survey participants. The prevalence of testing for HIV was 80.2%. Young people related their decisions about HIV testing to self-evaluation of their risk and perceived ability to manage the consequences of a positive result. Participants reported high levels of support for HIV testing from peers, partners, and family members. They perceived health facilities as confusing, distant, expensive, and staffed by judgmental, older health workers as barriers. They felt that mobile testing points solved some of these problems, but introduced less privacy and greater confidentiality concerns. The prevalence of HIV testing among young people in Wakiso district was low compared to the UNAIDS 2030 target but among the highest in sub-Saharan Africa. Community-based programs resolve many concerns about testing at health facilities. However, there is a need to make these programs more comfortable and private.