Correction: Limitations of rapid diagnostic tests in malaria surveys in areas with varied transmission intensity in Uganda 2017-2019: Implications for selection and use of HRP2 RDTs.

[This corrects the article DOI: 10.1371/journal.pone.0244457.].

Plasmodium falciparum genetic diversity and multiplicity of infection based on msp-1, msp-2, glurp and microsatellite genetic markers in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: In sub-Saharan Africa (SSA), Plasmodium falciparum causes most of the malaria cases. Despite its crucial roles in disease severity and drug resistance, comprehensive data on Plasmodium falciparum genetic diversity and multiplicity of infection (MOI) are sparse in SSA. This study summarizes available information on genetic diversity and MOI, focusing on key markers (msp-1, msp-2, glurp, and microsatellites). The systematic review aimed to evaluate their influence on malaria transmission dynamics and offer insights for enhancing malaria control measures in SSA. METHODS: The review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Two reviewers conducted article screening, assessed the risk of bias (RoB), and performed data abstraction. Meta-analysis was performed using the random-effects model in STATA version 17. RESULTS: The review included 52 articles: 39 cross-sectional studies and 13 Randomized Controlled Trial (RCT)/cohort studies, involving 11,640 genotyped parasite isolates from 23 SSA countries. The overall pooled mean expected heterozygosity was 0.65 (95% CI: 0.51-0.78). Regionally, values varied: East (0.58), Central (0.84), Southern (0.74), and West Africa (0.69). Overall pooled allele frequencies of msp-1 alleles K1, MAD20, and RO33 were 61%, 44%, and 40%, respectively, while msp-2 I/C 3D7 and FC27 alleles were 61% and 55%. Central Africa reported higher frequencies (K1: 74%, MAD20: 51%, RO33: 48%) than East Africa (K1: 46%, MAD20: 42%, RO33: 31%). For msp-2, East Africa had 60% and 55% for I/C 3D7 and FC27 alleles, while West Africa had 62% and 50%, respectively. The pooled allele frequency for glurp was 66%. The overall pooled mean MOI was 2.09 (95% CI: 1.88-2.30), with regional variations: East (2.05), Central (2.37), Southern (2.16), and West Africa (1.96). The overall prevalence of polyclonal Plasmodium falciparum infections was 63% (95% CI: 56-70), with regional prevalences as follows: East (62%), West (61%), Central (65%), and South Africa (71%). CONCLUSION: The study shows substantial regional variation in Plasmodium falciparum parasite genetic diversity and MOI in SSA. These findings suggest a need for malaria control strategies and surveillance efforts considering regional-specific factors underlying Plasmodium falciparum infection.

The clinical utility of cystatin C based eGFR in assessing renal function among HIV/AIDs patients on ART at Mildmay Uganda.

BACKGROUND: In clinical practice, Measurement of estimated glomerular filtration rates (eGFR) is the gold standard assessing renal function the glomerular filtration rate often estimated from plasma creatinine. Several studies have shown Cystatin C based eGFR (Cys C) to be a better parameter for the diagnosis of impaired renal function. Cystatin C based eGFR has been proposed as a potential renal function marker but its use in HIV&AIDS patients has not been well evaluated. METHODS: A cross sectional study was carried out on 914 HIV&AIDS patients on antiretroviral therapy (ART) attending Mildmay Uganda for care and treatment between January to March 2015. Serum Cystatin C based eGFR was measured using the particle enhanced immunoturbidimetric assay. Creatinine was analyzed using enzymatic Creatinine PAP method and creatinine clearance was calculated according to C&G. RESULTS: The sensitivity of Cystatin C based eGFR was 15.1% (95% CI = 8.4, 24) with specificity 99.3% (95% CI = 98- 99.7). The positive and negative predictive values were 70.0% (95% CI 45.7-88.1) and 91.2% (95% CI 98.11-92.94) respectively. The positive likelihood ratio was 18.81 and negative likelihood ratio was 0.85. Cystatin C based eGFR had diagnostic accuracy of 90.7 and area under curve was 0.768. CONCLUSION: Cystatin C based eGFR exhibited a high specificity and a high positive likelihood ratio in diagnosis of kidney disease among HIV&AIDS patients. Cystatin C based eGFR can be used as a confirmatory test.

HIV pre-exposure prophylaxis uptake, retention and adherence among female sex workers in sub-Saharan Africa: a systematic review.

OBJECTIVE: To evaluate oral pre-exposure prophylaxis (PrEP) uptake, retention and adherence among female sex workers (FSWs) receiving care through community and facility delivery models in sub-Saharan Africa (SSA). DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched online databases (PubMed, MEDLINE, SCOPUS, EMBASE, Google Scholar, Cochrane Database of Systematic Reviews and Web of Science) between January 2012 and 3 April 2022. ELIGIBILITY CRITERIA FOR STUDIES: Randomised controlled trials, cohort studies, cross-sectional studies and quasi-experimental studies with PrEP uptake, adherence and retention outcomes among FSWs in SSA. DATA EXTRACTION AND SYNTHESIS: Seven coders extracted data. The framework of the Cochrane Consumers and Communication Review Group guided data synthesis. The Risk of Bias In Non-Randomized Studies of Interventions tool was used to evaluate the risk of bias. Meta-analysis was conducted using a random-effects model. A narrative synthesis was performed to analyse the primary outcomes of PrEP uptake, adherence and retention. RESULTS: Of 8538 records evaluated, 23 studies with 40 669 FSWs were included in this analysis. The pooled proportion of FSWs initiating PrEP was 70% (95% CI: 56% to 85%) in studies that reported on facility-based models and 49% (95% CI: 10% to 87%) in community-based models. At 6 months, the pooled proportion of FSWs retained was 66% (95% CI: 15% to 100%) for facility-based models and 83% (95% CI: 75% to 91%) for community-based models. Factors associated with increased PrEP uptake were visiting a sex worker programme (adjusted OR (aOR) 2.92; 95% CI: 1.91 to 4.46), having ≥10 clients per day (aOR 1.71; 95% CI: 1.06 to 2.76) and lack of access to free healthcare in government-run health clinics (relative risk: 1.16; 95% CI: 1.06 to 1.26). CONCLUSIONS: A hybrid approach incorporating both facility-based strategies for increasing uptake and community-based strategies for improving retention and adherence may effectively improve PrEP coverage among FSWs. PROSPERO REGISTRATION NUMBER: CRD42020219363.

Perspectives of female sex workers on HIV pre-exposure prophylaxis delivery in Uganda: A qualitative study.

Background: HIV pre-exposure prophylaxis (PrEP) is underutilized by cisgender female sex workers (FSW) despite its proven effectiveness. This study aimed to understand the experiences of FSW with PrEP services in Uganda to inform HIV programming for this key population. Methods: We conducted qualitative interviews with 19 FSW between June and July 2022 at the Most at Risk Populations Initiative clinic, Mulago Hospital, Kampala, to explore experiences with accessing PrEP Indepth interviews explored: (1) descriptions of where and how PrEP was obtained; (2) perspectives on current approaches for accessing PrEP; and (3) individual encounters with PrEP services. Data were analyzed through inductive thematic analysis. Results: Three key themes emerged for FSW perspectives on PrEP service delivery. FSW highlighted the positive impact of a welcoming clinic environment, which motivated FSW to initiate PrEP and fostered a sense of connectedness within their community. They also reported feeling accepted, secure, and free from prejudice when accessing PrEP through facility-based services. The second explores the obstacles faced by FSW, such as lengthy wait times at clinics, inadequate provider support, and lack of sensitivity training which hindered their access to PrEP The third sheds light on how HIV-related stigma negatively impacted the delivery of community-based PrEP for FSW. While community-based distribution offered convenience and helped mitigate stigma, clinic-based care provided greater anonymity and was perceived as offering higher-quality care. Overall, FSWs emphasized the critical role of friendly healthcare providers, social support, and non-stigmatizing environments in promoting successful utilization of PrEP. Conclusion: The study findings offer insights that can support HIV programs in optimizing PrEP delivery for FSW. Establishing easily accessible drug pick-up locations, prioritizing privacy, addressing and improving health workers' attitudes, and providing regular reminders could enhance PrEP access for FSW and decrease HIV acquisition.

Health provider perspectives of Village Health Team-delivered oral HIV self-testing among men in Central Uganda: a qualitative evaluation using RE-AIM framework.

Background: HIV self-testing (HIVST) is a practical and effective way to provide HIV testing services to at-risk and underserved populations, particularly men. Utilizing Village Health Teams (VHTs) could enhance community-based delivery of oral HIVST to reach the last un-tested individuals who may be at-risk of infection. However, little is known about what VHTs and facility-based healthcare workers think about facilitating oral HIVST and delivery of subsequent HIV services. We investigated the views of health providers on oral HIVST delivered by VHTs among men in rural communities in Central Uganda. Methods: We conducted a qualitative study in Mpigi district, interviewing 27 health providers who facilitated oral HIV self-testing among men. The providers consisting of 15 VHTs and 12 facility-based health workers were purposively selected. All interviews were audio-recorded, transcribed verbatim, and translated to English for a hybrid inductive-deductive thematic analysis. We used the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) Implementation Science framework to generate and categorize open codes. Results: In terms of reaching men with HIV testing services, the providers considered HIVST to be a fast and convenient method, which could boost HIV testing. However, they also had concerns about its accuracy. In terms of effectiveness, HIVST was perceived as a reliable, user-friendly, and efficient approach to HIV testing. However, it depended on the user's preference for testing algorithms. Regarding adoption, HIVST was considered to enhance autonomy, well-suited for use in the community, and offered opportunities for linkage and re-linkage into care. However, at times HIVST faced hesitance. As for Implementation, VHTs had various support roles in HIVST but had concerns about social insecurities and delays in seeking subsequent facility-based services after HIVST. Regarding Maintenance, providers recommended several ways to improve oral HIVST including; optimizing tracking of HIVST distribution and use, improving linkage and retention in care after HIVST, diversifying HIVST for combined HIV prevention packages and including more languages, broadening sensitization among potential HIVST users and health providers, differentiating distribution models, and prioritizing targeted HIVST efforts. Conclusion: HIVST has the potential to increase testing rates and engagement of men in HIV services. However, for it to be implemented on a population-wide scale, continuous sensitization of potential users and health providers is necessary, along with streamlined structures for tracking kit distribution, use, and reporting of results. Further implementation research may be necessary to optimize the role of health providers in facilitating HIVST.

Acceptability of short message service reminders as the support tool for PrEP adherence among young women in Mukono district, Uganda.

Adolescent girls and young women (AGYW) have a disproportionately high incidence of HIV compared to males of the same age in Uganda. AGYW are a priority sub-group for daily oral Pre-Exposure Prophylaxis (PrEP), but their adherence has consistently remained low. Short Message Service (SMS) reminders could improve adherence to PrEP in AGYW. However, there is paucity of literature about acceptability of SMS reminders among AGYW using PrEP. We assessed the level of acceptability of SMS reminders as a PrEP adherence support tool and the associated factors, among AGYW in Mukono district, Central Uganda. We consecutively enrolled AGYW using PrEP in Mukono district in a cross sectional study. A structured pre-tested questionnaire was administered to participants by three trained research assistants. Data were analyzed in STATA 17.0; continuous variables were summarized using median and interquartile range (IQR) while categorical variables were summarized using frequencies and percentages. Acceptability of SMS was defined as willingness to accept SMS reminders to support PrEP adherence and was assessed using the seven constructs of the theoretical framework of acceptability. The relationship between the outcome and independent variables was assessed using a modified Poisson regression with robust standard errors. During the month of August 2022, 142 AGYW with median age 22 years (IQR; 18, 24) of whom 80.3% owned a personal mobile phone were assessed. SMS reminders were highly acceptable [90.9%, 95% Confidence Interval (CI) [84.9, 95.0]]. Rural residence was negatively associated with acceptability of SMS reminders (aPR: 0.92, 95% CI (0.84, 0.99)) and having belief that SMS cannot breach individual's privacy (aPR: 1.40, 95% CI (1.07, 1.84)) was positively associated with acceptability of SMS reminders. The acceptability of SMS reminders was high in this sub-population. SMS reminder can be leveraged to support AGYW to adhere to PrEP but should be designed in a way that maintains confidentiality, and supports AGYW living in rural settings.

Village health team-delivered oral HIV self-testing increases linkage-to-care and antiretroviral-therapy initiation among men in Uganda.

Targeted strategies are central to increasing HIV-status awareness and progress on the care cascade among men. We implemented Village-Health-Team (VHT)-delivered HIV self-testing (HIVST) among men in a peri-urban Ugandan district and assessed linkage to confirmatory-testing, antiretroviral-therapy (ART) initiation and HIV-status disclosure following HIVST. We conducted a prospective cohort study from November 2018 to June 2019 and enrolled 1628 men from 30-villages of Mpigi district. VHTs offered each participant one HIVST-kit and a linkage-to-care information leaflet. At baseline, we collected data on demographics, testing history and risk behavior. At one-month, we measured linkage to confirmatory-testing and HIV-status disclosure, and at three months ART-initiation if tested HIV-positive. We used Poisson regression generalized estimating equations to evaluate predictors of confirmatory-testing. We found that 19.8% had never tested for HIV and 43% had not tested in the last 12-months. After receiving HIVST-kits, 98.5% self-reported HIVST-uptake in 10-days, 78.8% obtained facility-based confirmation in 30-days of HIVST with 3.9% tested HIV-positive. Of the positives, 78.8% were newly diagnosed, 88% initiated ART and 57% disclosed their HIV-status to significant others. Confirmatory testing was associated with having a higher level of education and knowing a partner's HIV-status. VHT-delivered HIVST may be effective for boosting testing, ART-initiation and HIV-status disclosure among men.

MICROS: Asthma Control App for School Adolescents in a Low Resource Setting - A Cluster Randomized Controlled Trial Protocol.

Introduction: Poor asthma control in adolescents is partly attributed to inadequate asthma education for self-management. This study is set to determine the effectiveness of the "KmAsthma" self-management app in improving the control of asthma among adolescents in a low-resource setting. Methods: The two-arm 6-month cluster randomized controlled trial, will aim at enrolling 120 day scholars aged 12-19 years in secondary schools with a clinician's diagnosis and self-reported uncontrolled asthma in Kampala City Uganda. The primary endpoint of asthma control will be measured as a change in mean Asthma Control Test (ACT) scores. Asthma quality of life, adherence to medications, and self-efficacy will also be assessed. The iMprovIng the ContROl of aSthma (MICROS) study will employ the "KmAsthma" app for self-management education. The intervention group will receive the app on their smartphones and training on its eight sections: the profile, asthma history, goals, inspirations, reminders, connect, information about asthma, and emergency support. Participants will navigate these sections to set asthma control goals, schedule medication reminders, log daily symptoms, and receive guidance for attacks. All participants will be encouraged to seek routine care. A study nurse will follow up with each participant via the phone six weeks post-intervention. The MICROS study was approved by the Makerere University School of Medicine Research and Ethics Committee and the Uganda National Council of Science and Technology. This protocol is registered on Clinicaltrials.gov (NCT05850806). Conclusion: The MICROS study will provide comprehensive insights into how effective a mHealth intervention can be an aid for adolescents in a low-resource setting in managing their asthma. The findings of this study will contribute to filling the gap leading to unsatisfactory asthma control in adolescents.

Uptake and perceptions of oral HIV self-testing delivered by village health teams among men in Central Uganda: A concurrent parallel mixed methods analysis.

The World Health Organization (WHO) recommends HIV self-testing (HIVST) to increase access to and utilization of HIV services among underserved populations. We assessed the uptake and perceptions of oral HIVST delivered by Village Health Teams (VHTs) among men in a peri-urban district in Central Uganda. We used a concurrent parallel mixed methods study design and analyzed data from 1628 men enrolled in a prospective cohort in Mpigi district, Central Uganda between October 2018 and June 2019. VHTs distributed HIVST kits and linkage-to-care information leaflets to participants in 30 study villages allowing up-to 10 days each to self-test. At baseline, we collected data on participant socio-demographics, testing history and risk behavior for HIV. During follow-up, we measured HIVST uptake (using self-reports and proof of a used kit) and conducted in-depth interviews to explore participants' perceptions of using HIVST. We used descriptive statistics to analyze the quantitative data and a hybrid inductive, and deductive thematic analysis for the qualitative data and integrated the results at interpretation. The median age of men was 28 years, HIVST uptake was 96% (1564/1628), HIV positivity yield was 4% (63/1564) and reported disclosure of HIVST results to sexual partners and significant others was 75.6% (1183/1564). Men perceived HIVST as a quick, flexible, convenient, and more private form of testing; allowing disclosure of HIV test results to sexual partners, friends and family, and receiving social support. Others perceived it as an opportunity for knowing or re-confirming their sero-status and subsequent linkage or re-linkage to care and prevention. Utilizing VHT networks for community-based delivery of HIVST is effective in reaching men with HIV testing services. Men perceived HIVST as highly beneficial but needed more training on performing the test and the integrating post-test counseling support to optimize use of the test for diagnosing HIV.

Factors associated with isoniazid preventive treatment interruption and completion among PLHIV in Gombe Hospital, Uganda, 2017-2019.

Background: Tuberculosis (TB) is the leading cause of death in persons living with HIV (PLHIV). PLHIV carry a disproportionate burden of TB infection with risks 20-37 times greater than HIV-negative populations. While isoniazid preventive treatment (IPT) is regarded as a crucial component of HIV care to prevent active TB, the uptake among PLHIV remains very poor. Studies on the factors associated with IPT interruption and completion among PLHIV in Uganda are scarce. Thus, in Gombe Hospital in Uganda, this study assessed the factors associated with IPT interruption and completion among PLHIV. Methods: This was a hospital-based cross-sectional study that used both quantitative and qualitative methods of data collection from January 3rd, 2020 to February 28th, 2020. We reviewed the medical records of 686 PLHIV who received IPT at Gombe Hospital from January 1st, 2017 to December 31st, 2019. Binary logistic and modified Poisson regression were used to analyze factors associated with IPT completion and interruption. We conducted 7 key informant interviews and 14 in-depth interviews. Results: Second-line antiretroviral therapy (AOR = 46, p < 0.001) and age ≥ 45 years (AOR = 0.2, p = 0.040) were significantly associated with IPT interruption, while attending routine ART counseling sessions (APR = 1.5, p < 0.001) and prescription for ≥ 2 months at the start of IPT (APR = 1.1, p = 0.010) were associated with IPT completion. Barriers to IPT completion included pill burden, forgetfulness, poor integration of IPT in HIV healthcare services, and lack of awareness of IPT, while facilitators were easy accessibility of IPT and support from implementing partners. Conclusions: Side effects and pill burden were the major barriers to the long-term completion of IPT. Supplying ≥ 2 months IPT drugs, using IPT drugs with fewer side effects, and counseling during IPT could improve IPT completion and reduce IPT interruption.

Co-Surveillance of Rotaviruses in Humans and Domestic Animals in Central Uganda Reveals Circulation of Wide Genotype Diversity in the Animals.

Rotavirus genotypes are species specific. However, interspecies transmission is reported to result in the emergence of new genotypes. A cross-sectional study of 242 households with 281 cattle, 418 goats, 438 pigs, and 258 humans in Uganda was undertaken between 2013 and 2014. The study aimed to determine the prevalence and genotypes of rotaviruses across co-habiting host species, as well as potential cross-species transmission. Rotavirus infection in humans and animals was determined using NSP3 targeted RT-PCR and ProSpecT Rotavirus ELISA tests, respectively. Genotyping of rotavirus-positive samples was by G- and P-genotype specific primers in nested RT-PCR assays while genotyping of VP4 and VP7 proteins for the non-typeable human positive sample was done by Sanger sequencing. Mixed effect logistic regression was used to determine the factors associated with rotavirus infection in animals. The prevalence of rotavirus was 4.1% (95% CI: 3.0-5.5%) among the domestic animals and 0.8% (95% CI: 0.4-1.5%) in humans. The genotypes in human samples were G9P[8] and P[4]. In animals, six G-genotypes, G3(2.5%), G8(10%), G9(10%), G11(26.8%), G10(35%), and G12(42.5%), and nine P-genotypes, P[1](2.4%), P[4](4.9%), P[5](7.3%), P[6](14.6%), P[7](7.3%), P[8](9.8%), P[9](9.8%), P[10](12.2%), and P[11](17.1%), were identified. Animals aged 2 to 18 months were less likely to have rotavirus infection in comparison with animals below 2 months of age. No inter-host species transmission was identified.

Mortality among non-severely under nourished children with pneumonia globally: protocol for a systematic review and meta-analysis.

Background: Pneumonia remains the commonest cause of ill health and mortality among children worldwide. Severe undernutrition increases the mortality risk among children with pneumonia. While children with pneumonia are at increased risk of developing malnutrition, the impact of pneumonia on mortality and nutritional status of non-severely undernourished children is not well described. The impact of nutritional supplementation on mortality and nutritional status in this population is not well understood. This review will collate available evidence on the all-cause mortality and anthropometric indices outcomes following pneumonia, as well as the impact of nutritional supplementation on mortality and anthropometry among non-severely malnourished children with pneumonia. Methods: The review will be done using a priori criteria developed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Data will be obtained from data bases, grey literature, and bibliographies. An experienced librarian will conduct article search in PUBMED, MEDLINE, EMBASE, Web of Science, Google scholar, and Scopus. Retrieved articles will be entered in Endnote ver 9.0, duplicates removed, and transferred to Epi-reviewer for screening and data abstraction. Risk of bias in the included articles will be assessed using standard criteria. Heterogeneity will be assessed using I 2-statistic and sub-group analysis will be done. Data will be analysed using both narrative and quantitative synthesis. Quantitative synthesis will be done using DeSimonian and Laird Random-effects model in STATA ver 15.0. Conclusions: The results will provide baseline information about the mortality and anthropometric outcomes of pneumonia among non-severely malnourished children as well as the potential effect of nutritional supplementation on these outcomes. This will provide a basis to explore the potential for nutritional supplementation improving clinical outcomes like mortality and occurrence of severe acute malnutrition among children with severe pneumonia worldwide. Registration: The review has been registered in PROSPERO (CRD42021257272; 15 July 2021).

Significant hyperbilirubinemia among well neonates due for discharge at Kawempe-Mulago Hospital, prevalence, factors associated, and accuracy of transcutaneous bilirubinometry for screening.

Background: Neonates in low resource settings with a lack of pre-discharge screening and early intervention are at risk for complications associated with significant hyperbilirubinemia (SHB). Objectives: To determine the prevalence, factors associated and performance of transcutaneous bilirubin (TCB) in identifying well neonates with SHB. Methods: Over a one month period 235 well neonates 24 to 72 hours of age due for discharge at Kamempe-Mulago Hospital were enrolled in this study. Visual inspection using Kramer rule, transcutaneous bilirubin over the sternum using Draeger JM103 bilirubinometer, and serum bilirubin were determined. Neonates with SHB (total serum bilirubin warranting treatment) were referred for treatment. Relevant data were analyzed. A P-value of <0.05 was considered significant at 95% confidence interval. Results: Thirty two (13.6%) of the neonates had SHB and three (1.3%) had levels above exchange transfusion threshold. Significant hyperbilirubinemia was independently associated with CRP ≥ 10mg/l (AOR 3.96, CI 1.23-12.73, p 0.021), ABO discordance (AOR 3.67, CI 1.28-10.49, p 0.015), jaundice in a previous sibling (AOR 3.565, CI 1.10-11.51, p 0.034) and time of first feed > 1 hour (AOR 2.74, CI 1.10-6.90, p 0.007). The sensitivity, specificity, positive and negative predictive values of TCB were 96.5%, 84.6%, 47.5% and 99.4% respectively compared to 31.2%, 98.5%, 76.9% and 90% respectively for visual assessment (Kramer grading). Conclusions: A significant number of well neonates have SHB. Transcutaneous bilirubinometry is a suitable screening tool in this setting. Early initiation of feeding should be promoted. The cause for high CRP among well neonates with SHB needs to be studied further.

Effectiveness of the Med Safety mobile application in improving adverse drug reaction reporting by healthcare professionals in Uganda: a protocol for a pragmatic cluster-randomised controlled trial.

INTRODUCTION: Combination antiretroviral therapy (cART) has massively reduced HIV mortality. However, long-term cART increases the risk of adverse drug reactions (ADRs), which can lead to higher morbidity, mortality and healthcare costs for people living with HIV (PLHIV).Pharmacovigilance-monitoring the effects of medicines-is essential for understanding real-world drug safety. In Uganda, pharmacovigilance systems have only recently been developed, and rates of ADR reporting for cART are very low. Thus, the safety profile of medicines currently used to treat HIV and tuberculosis in our population is poorly understood.The Med Safety mobile application has been developed through the European Union's Innovative Medicines Initiative WEB-Recognising Adverse Drug Reactions project to promote digital pharmacovigilance. This mobile application has been approved for ADR-reporting by Uganda's National Drug Authority. However, the barriers and facilitators to Med Safety uptake, and its effectiveness in improving pharmacovigilance, are as yet unknown. METHODS AND ANALYSIS: A pragmatic cluster-randomised controlled trial will be implemented over 30 months at 191 intervention and 191 comparison cART sites to evaluate Med Safety. Using a randomisation sequence generated by the sealed envelope software, we shall randomly assign the 382 prescreened cART sites to the intervention and comparison arms. Each cART site is a cluster that consists of healthcare professionals and PLHIV receiving dolutegravir-based cART and/or isoniazid preventive therapy. Healthcare professionals enrolled in the intervention arm will be trained in the use of mobile-based, paper-based and web-based reporting, while those in the comparison arm will be trained in paper-based and web-based reporting only. ETHICS AND DISSEMINATION: Ethical approval was given by the School of Biomedical Sciences Research and Ethics Committee at Makerere University (SBS-REC-720), and administrative clearance was obtained from Uganda National Council for Science and Technology (HS1366ES). Study results will be shared with healthcare professionals, policymakers, the public and academia. TRIAL REGISTRATION NUMBER: PACTR202009822379650.

Screening PLHIV for depression using PHQs: A RCT comparing non-selective with selective screening strategy within a primary health care facility in Uganda.

BACKGROUND: Depression is rarely screened for among People Living with Human Immunodeficiency Virus (PLHIV) although it is 2 to 3 times more prevalent among PLHIV than in the general population. In instances where depression is screened for using screening tools, it usually follows noticing depression risk factors. This practice of selectively screening for depression could be leaving some cases of depression unattended to. On the other hand, subjecting every client to screening tools (non-selective screening) offers every patient an opportunity to be managed for depression. However, this could require additional resources as compared to selective screening. We present and discuss results on whether non-selective and selective screening strategies differ in depression case detection, and in addition, we also present perceptions of the stake holders on the two screening strategies. METHODS: The study was conducted in Princess Diana Memorial Health Centre IV HIV clinic using a randomized controlled trial with a qualitative component. To determine whether there was a difference in depression case detection, consecutively sampled participants were randomly allocated to either non-selective or selective screening strategy. Participants allocated to selective screening were screened for depression using the patient health questionnaire (s) (PHQs) if they were at "crisis points". While those allocated to non-selective screening were screened regardless of whether the "crisis points" were noticed or not. The PHQ-2 and PHQ-9 were used in sequence. 326 PLHIV participated in the study. Outcomes of the MINI evaluation were analyzed for those with PHQ-9 scores of 10 or more to confirm major depressive disorder (MDD). Data was analyzed using the two sample Z-test for proportions with Stata 2013 software. To explore the perceptions of the stake holders, key informant interviews were performed with six stakeholders that experienced the study. RESULTS: Cases of depression (PHQ-9 score ≥ 5) were more likely to be detected by the non-selective screening strategy 30.2% (49/162) compared to the selective screening strategy 19.5% (32/164) (difference in proportions 0.107, 95% confidence interval 0.014-0.200, Cohen's h = 0.25, P = 0.03). The stake holders thought it was important to screen for depression among PLHIV with preference to non-selective screening strategy. CONCLUSION: Evidence from this data suggests that more cases of depression (PHQ-9 score ≥ 5) are likely to be detected with non-selective screening as opposed to selective screening. TRIAL REGISTRATION: PACTR201802003141213 (name: comparison of routine versus selective screening for depression strategies among PLHIV attending Princess Diana Memorial Health Centre iv Soroti).

Adherence to malaria management guidelines by health care workers in the Busoga sub-region, eastern Uganda.

BACKGROUND: Appropriate malaria management is a key malaria control strategy. The objective of this study was to determine health care worker adherence levels to malaria case management guidelines in the Busoga sub-region, Uganda. METHODS: Health facility assessments, health care worker (HCW), and patient exit interview (PEI) surveys were conducted at government and private health facilities in the sub-region. All health centres (HC) IVs, IIIs, and a sample of HC IIs, representative of the tiered structure of outpatient service delivery at the district level were targeted. HCWs at these facilities were eligible for participation in the study. For PEIs, 210 patients of all ages presenting with a history of fever for outpatient care at selected facilities in each district were targeted. Patient outcome measures included testing rates, adherence to treatment, dispensing and counselling services as per national guidelines. The primary outcome was appropriate malaria case management, defined as the proportion of patients tested and only prescribed artemether-lumefantrine (AL) if positive. HCW readiness (e.g., training, supervision) and health facility capacity (e.g. availability of diagnostics and anti-malarials) to provide malaria case management were also assessed. Data were weighted to cater for the disproportionate representation of HC IIs in the study sample. RESULTS: A total of 3936 patients and 1718 HCW from 392 facilities were considered in the analysis. The median age of patients was 14 years; majority (63.4%) females. Most (70.1%) facilities were HCIIs and 72.7% were owned by the government. Malaria testing services were available at > 85% of facilities. AL was in stock at 300 (76.5%) facilities. Of those with a positive result, nearly all were prescribed an anti-malarial, with AL (95.1%) accounting for most prescriptions. Among those prescribed AL, 81.0% were given AL at the facility, lowest at HC IV (60.0%) and government owned (80.1%) facilities, corresponding to AL stock levels. Overall, 86.9% (95%CI 79.7, 90.7) of all enrolled patients received appropriate malaria case management. However, only 50.7% (21.2, 79.7) of patients seen at PFPs received appropriate malaria management. CONCLUSION: Adherence levels to malaria case management guidelines were good, but with gaps noted mainly in the private sector. The supply chain for AL needs to be strengthened. Interventions to improve practise at PFP facilities should be intensified.

High burden of pulmonary tuberculosis and missed opportunity to initiate treatment among children in Kampala, Uganda.

Background: There is uncertainty about the actual burden of childhood TB in Uganda, but underestimation is acknowledged. We aimed at determining prevalence, factors associated with PTB among children attending PHC facilities in Kampala. Methods: This was a cross-sectional study of 255 children, with presumed TB, attending six health facilities in Kampala, Uganda, in March 2015. Socio-demographic, clinical, and laboratory data were collected using a questionnaire. TB was diagnosed using "Desk Guide" algorithms. Sputum based on ZN/FM and/or Gene-Xpert. Logistic regression was used to assess associations with outcomes. Results: Overall, prevalence of PTB 13.7 % (2.6 - 24.8). Among HIV-positive, the prevalence of PTB was 41.7%, while among malnourished children, 21.7% and contacts, 89.3%. The factors that influenced PTB included: tobacco smoker at home (OR = 1.6, 95 % CI: 1.07 - 6.86), stunting (OR = 2.2, 95 % CI: 1.01 - 4.15). Only 5.3% of the smear-negative TB children and 81.3% of the smear-positive children were initiated on treatment within a month of diagnosis. Conclusion: Clinical TB among children is underdiagnosed and undertreated. There is a need for more sensitive and specific diagnostic tests, need ways to disseminate and promote uptake of standardized clinical algorithms. Also, contact TB tracing should be strengthened so that such cases can be actively detected even at community level.

The burden of drug resistant tuberculosis in a predominantly nomadic population in Uganda: a mixed methods study.

BACKGROUND: Emergence of drug resistant tuberculosis (DR-TB) has aggravated the tuberculosis (TB) public health burden worldwide and especially in low income settings. We present findings from a predominantly nomadic population in Karamoja, Uganda with a high-TB burden (3500 new cases annually) and sought to determine the prevalence, patterns, factors associated with DR-TB. METHODS: We used mixed methods of data collection. We enrolled 6890 participants who were treated for tuberculosis in a programmatic setting between January 2015 and April 2018. A cross sectional study and a matched case control study with conditional logistic regression and robust standard errors respectively were used to the determine prevalence and factors associated with DR-TB. The qualitative methods included focus group discussions, in-depth interviews and key informant interviews. RESULTS: The overall prevalence of DR-TB was 41/6890 (0.6%) with 4/64,197 (0.1%) among the new and 37/2693 (1.4%) among the previously treated TB patients respectively. The drug resistance patterns observed in the region were mainly rifampicin mono resistant (68.3%) and Multi Drug-Resistant Tuberculosis (31.7%). Factors independently associated with DR-TB were previous TB treatment, adjusted odds ratio (aOR) 13.070 (95%CI 1.552-110.135) and drug stock-outs aOR 0.027 (95%CI 0.002-0.364). The nomadic lifestyle, substance use, congested homesteads and poor health worker attitudes were a great challenge to effective treatment of TB. CONCLUSION: Despite having the highest national TB incidence, Karamoja still has a low DR-TB prevalence. Previous TB treatment and drug stock outs were associated with DR-TB. Regular supply of anti TB medications and health education may help to stem the burden of TB disease in this nomadic population.

Assessment of the accuracy of malaria microscopy in private health facilities in Entebbe Municipality, Uganda: a cross-sectional study.

BACKGROUND: Although microscopy remains the gold standard for malaria diagnosis, little is known about its accuracy in the private health facilities in Uganda. This study evaluated the accuracy of malaria microscopy, and factors associated with inaccurate smear results at private health facilities in Entebbe Municipality, Uganda. METHODS: Between April and May 2018, all patients referred for a malaria smear in 16 private health facilities in Entebbe municipality were screened, and 321 patients were enrolled. A questionnaire was administered to collect demographic and clinical information, facility-based smear results were recorded from the participant's consultation notes, and a research slide was obtained for expert microscopy during exit interview. A health facility assessment was conducted, and information on experience in performing malaria microscopy was collected from all facility personnel reading smears and the data was linked to the participant's clinic visit. RESULTS: The test positivity rate of malaria parasitaemia was 15.0% by expert microscopy. The sensitivity, specificity and negative predictive value of the facility-based microscopy were high (95.8%, 90.1 and 99.2%, respectively). However; the positive predictive value (PPV) was low with 27/73 (63%) patients diagnosed with malaria not having the disease. Majority of the inaccurate results were from 2 of the 23 laboratory personnel reading the smears. The factors associated with inaccurate smear readings included being read by a technician; (1) who had less than 5 years' experience in reading malaria smears (adjusted Odds Ratio [aOR] = 9.74, 95% confidence interval [CI] (1.06-89.5), p-value = 0.04), and (2) who was examining less than 5 smears a day (aOR = 38.8, 95% CI 9.65-156, p-value < 0.001). CONCLUSIONS: The accuracy of malaria microscopy in this setting was high, although one third of the patients diagnosed with malaria did not have the disease. Majority of the errors in smear readings were made by two laboratory personnel, with the main factor associated with inaccurate smear results being low experience in malaria microscopy. In-service training may be sufficient to eliminate inaccurate smear results in this setting, and these private facilities would be ideal model facilities to improve the quality of malaria microscopy in Uganda especially in the public sector where accuracy is still poor.