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Background: The introduction of antiretroviral therapy (ART) and the implementation of the human immunodeficiency virus (HIV) universal test and treat (UTT) policy have led to a decline in the incidence of opportunistic infections. However, oropharyngeal and oral candidiasis remain prevalent and continue to pose challenges among people living with human immunodeficiency virus (PLHIV) in Africa, indicating the need for a better understanding of the distribution of Candida species responsible for these infections. This systematic review and meta-analysis aimed to determine the distribution of Candida species isolated from PLHIV with oropharyngeal and oral candidiasis in Africa in the era of UTT policy., Methods: The review followed the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. A comprehensive search was conducted to identify eligible studies to be included in the meta-analysis and analysed using a random effects model in STATA version 17. The risk of bias was assessed using the Joanna Briggs Institute quality assessment tool., Results: Fourteen studies with 4281 participants were included in the review. Overall, 2095 Candida isolates were reported, 78.7% (1650/2095) of which were C. albicans, 19.6% (410/2095), non-albicans Candida (NAC), and 1.7% (35/2095) could not be identified to the Candida specific species level. The most prevalent NAC species were C. glabrata (26.3%), followed by C. tropicalis (24.9%), C. krusei (15.6%), C. parapsilosis (11%), and C. dubliniensis (6.3%). The pooled prevalence of oropharyngeal and oral candidiasis was 48% (95% CI 34-62%). The prevalence of oropharyngeal candidiasis was higher in the pre-UTT era, at 56% (95% CI 40-72%, p < 0.001), than in the post-UTT era, at 34% (95% CI 10-67%, p < 0.001). The risk of bias assessment revealed that 71.4% (10/14) of the included studies had a low risk of bias and that 28.6% (4/14) had a moderate risk of bias., Conclusions: While C. albicans remain, the predominant species causing oropharyngeal and oral candidiasis among PLHIV in Africa, NAC species also contribute significantly to the infection burden. Despite ART and UTT policies, oropharyngeal candidiasis remains prevalent, emphasizing the need for targeted interventions., Competing Interests: Declarations. Ethics approval and consent to participate: Although ethical approval was obtained from the Makerere University School of Biomedical Sciences Research Ethics Committee (Reference number: SBS-2022–254) for the larger study, this systematic review analysed published studies without identifiable patient data; as such, ethical approval was not needed. Consent for publications: Not applicable. Competing interests: The author(s) declare no potential conflicts of interest concerning the research, authorship, and/or publication of this article., (© 2024. The Author(s).)

Background: The incidence of oropharyngeal candidiasis among people living with human immunodeficiency virus in Africa is on the rise. Oropharyngeal candidiasis is mainly caused by C.albicans ; however, a shift in the etiology towards non- Candida albicans species is increasing. In addition, there are variations in the epidemiological distribution of Candida species causing oropharyngeal candidiasis among people living with human immunodeficiency virus in Africa., Objective: This review aimed to determine the prevalence of oropharyngeal candidiasis and the distribution of Candida species among people living with human immunodeficiency virus in Africa., Materials and Methods: This systematic review protocol was registered in the base PROSPERO database prior to its conduct (CRD42021254473). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol guidelines (PRISMA-P) were followed for this study. The PubMed, Scopus and EMBASE databases were searched to identify published studies published between 1 st January 2000 and 8 th October 2022. The eligible studies were included in the meta-analysis and analyzed using a random effects model. The risk of bias of the included studies was assessed using the Joanna Briggs Institute quality assessment tool for prevalence studies., Results: The database search yielded 370 titles from PubMed (n=192), EMBASE (n=162) and SCOPUS (n=16). Fourteen studies with a total of 3,863 participants were included in the meta-analysis. The pooled prevalence of oropharyngeal candidiasis was 49.0% (95% CI: 37% - 62%). A total of 2,688 Candida isolates were reported; approximately 76.6% (n=2,060) were C. albicans , and 21.7% (n=582) were non- C. albicans . Among the non- Candida albicans species, C . glabrata was the most common isolate (29.6%), followed by C . tropicalis (27.7%), C . krusei (17.0%), C . parapsilosis (8.1%) and C . dubliniensis (5.2%). Out of 14 studies, 7 (50.0%) had a low risk of bias, 5 (35.7%) had a moderate risk of bias, and 2 (14.3%) had a high risk of bias., Conclusion: Almost half of people living with HIV in Africa have oropharyngeal candidiasis, and C. albicans remains the most frequent cause of oropharyngeal candidiasis., Competing Interests: Declaration of Competing interests The author(s) declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Studies suggest a need for new diagnostic approaches for cervical cancer including microRNA technology. In this review, we assessed the diagnostic accuracy of microRNAs in detecting cervical cancer and Cervical Intraepithelial Neoplasia (CIN). We performed a systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analysis guideline for protocols (PRISMA-P). We searched for all articles in online databases and grey literature from 01st January 2012 to 16th August 2022. We used the quality assessment of diagnostic accuracy studies tool (QUADAS-2) to assess the risk of bias of included studies and then conducted a Random Effects Meta-analysis. We identified 297 articles and eventually extracted data from 24 studies. Serum/plasma concentration miR-205, miR-21, miR-192, and miR-9 showed highest diagnostic accuracy (AUC of 0.750, 0.689, 0.980, and 0.900, respectively) for detecting CIN from healthy controls. MicroRNA panels (miR-21, miR-125b and miR-370) and (miR-9, miR-10a, miR-20a and miR-196a and miR-16-2) had AUC values of 0.897 and 0.886 respectively for detecting CIN from healthy controls. For detection of cervical cancer from healthy controls, the most promising microRNAs were miR-21, miR-205, miR-192 and miR-9 (AUC values of 0.723, 0.960, 1.00, and 0.99 respectively). We report higher diagnostic accuracy of upregulated microRNAs, especially miR-205, miR-9, miR-192, and miR-21. This highlights their potential as stand-alone screening or diagnostic tests, either with others, in a new algorithm, or together with other biomarkers for purposes of detecting cervical lesions. Future studies could standardize quantification methods, and also study microRNAs in higher prevalence populations like in sub-Saharan Africa and South Asia. Our review protocol was registered in PROSPERO (CRD42022313275)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.We, the authors declare that we do not have any competing interests., (© 2024 The Author(s).)

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., (© 2024. The Author(s).)

Background: Children exposed to severe malaria may recover with gross neurologic deficits (GND). Several risk factors for GND after cerebral malaria (CM), the deadliest form of severe malaria, have been identified in children. However, there is inconsistency between previously reported and more recent findings. Although CM patients are the most likely group to develop GND, it is not clear if other forms of severe malaria (non-CM) may also contribute to the malaria related GND. The aim of this systematic review is to synthesize evidence on the prevalence and risk factors for GND in children following CM and map the changes in patterns over time. In addition, this review will synthesize evidence on the reported prevalence and risk factors of gross neurologic deficits following other forms of severe malaria., Methods: The systematic review will be conducted according to recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols (PRISMA-P). Relevant research articles will be identified using relevant search terms from the following databases: MEDLINE, Embase, Web of Science and Global Index Medicus (GIM). The articles will be screened at title and abstract, then at full text for inclusion using a priori eligibility criteria. Data extraction will be done using a tool developed and optimized in Excel spreadsheet. Risk of bias assessment will be done using appropriate tools including ROBINS-E ('Risk Of Bias In Non-randomized Studies of Exposure') tool, while publication bias will be assessed using funnel plot. A random-effects meta-analysis and structured narrative synthesis of the outcomes will be performed and results presented., Discussion: Findings from this systematic review will inform policy makers on planning, design and implementation of interventions targeting the treatment and rehabilitation of GND following severe malaria in children., Systematic Review Registration: The protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42022297109., Competing Interests: Competing interests The authors declare that they have no competing interest.

Background: Wounds inflict pain and affect human health causing high expenditure on treatment and management. Herbal crude extracts are used in traditional medicine as a treatment for wounds and other illnesses. However, the progress in the use of plants has been deterred due to their poor solubility and poor bioavailability requiring administration at high doses. It has been established that nanoencapsulation of herbal products in nanocarriers (size 1 nm to 100 nm) such as nanofibers, nanoparticles, nanospheres, and nanoliposomes greatly improves their efficacy. Due to their small and large surface area, nanocarriers are more biologically active, improve bioavailability, protect the drug from deterioration, and release it to the targeted site in a sustainable manner., Aim: The review aims to collate and appraise evidence on the efficacy of nano encapsulated herbal extracts in the treatment of induced wounds in animal models., Methods: The review will be protocol-driven and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Protocols (PRISMA-P) and protocol guidelines for systematic review and meta-analysis for animal intervention studies. The final review will be conducted and reported with reference to PRISMA 2020 statement. Studies will be searched in Pub Med, ProQuest, Web of Science, Medline Ovid, EMBASE, and Google Scholar. The PRISMA flow criteria will be followed in screening the articles for inclusion. Data extraction form will be designed in Excel spreadsheet 2013 and data extracted based on the primary and secondary outcomes. Risk of bias assessment will be done using SYRCLE's risk of bias tool for animal studies. Data analysis will be done using narrative and quantitative synthesis., Expected Results: We hope to make meaningful comparisons between the effectiveness of the herb-loaded nanomaterials and other interventions (controls) in the selected studies, based on the primary and secondary outcome measures. We expect that these findings to inform clinical practice on whether preclinical studies show enough quality evidence on the efficacy and safety of herbal-loaded nanomaterials that can be translated into clinical trials and further research., Systemic Review Registration: PROSPERO 330330. The protocol was submitted on the 11th of May 2022., (© 2023. The Author(s).)

Introduction: The practice of creating large databases has become increasingly common by combining research participants' data into larger repositories. Funders now require that data sharing be considered in newly funded research project, unless there are justifiable reasons not to do so. Access to genomic data brings along a host of ethical concerns as well as fairness and equity in the conduct of collaborative research between researchers from high- income and low-and middle-income countries., Materials and Methods: This systematic review protocol will be developed in line with PRISMA -guidelines which refers to Open Science Framework, registered in PROSPERO (https://www.crd.york.ac.uk/prospero/) record CRD42022297984 and published in a peer reviewed journal. Data sources will include PubMed, google scholar, EMBASE, Web of science and MEDLINE. Both published and grey literature will be searched. Subject matter experts including bioethicists, principal investigators of genomic research projects and research administrators will be contacted. After de-duplication, titles and abstracts will be screened for eligibility. Data extraction will be undertaken using a piloted form designed in EPPI-Reviewer software before conducting risk of bias assessments by a pair of reviewers, acting independently. Any discrepancies will be resolved by consensus. Analysis will be done using a structured narrative synthesis and where feasible metanalysis. This review will attempt to highlight the context of data sharing practices in the global North-South and South-South collaborative human genomic research in low- and middle-income countries. This review will enhance the body of evidence on ethical, legal and social implications of data sharing in international collaborative genomic research setting criteria for data sharing. The full report will be shared with relevant stakeholders including universities, civil society, funders, and departments of genomic research to ensure an adequate reach in low-and middle-income countries (LMICs)., Competing Interests: The authors have declared that no competing interest exists., (Copyright: © 2023 Ekusai-Sebatta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The One Health approach is key in implementing International Health Regulations (IHR, 2005) and the Global Health Security Agenda (GHSA). Uganda is signatory to the IHR 2005 and in 2017, the country conducted a Joint External Evaluation (JEE) that guided development of the National Action Plan for Health Security (NAPHS) 2019-2023., Aim: This study assessed the contribution of the One Health approach to strengthening health security in Uganda., Methods: A process evaluation between 25th September and 5th October 2020, using a mixed-methods case study. Participants were Subject Matter Experts (SMEs) from government ministries, departments, agencies and implementing partners. Focus group discussions were conducted for five technical areas (workforce development, real-time surveillance, zoonotic diseases, national laboratory systems and emergency response operations), spanning 18 indicators and 96 activities. Funding and implementation status from the NAPHS launch in August 2019 to October 2020 was assessed with a One Health lens., Results: Full funding was available for 36.5% of activities while 40.6% were partially funded and 22.9% were not funded at all. Majority (65%) of the activities were still in progress, whereas 8.6% were fully implemented and14.2% were not yet done. In workforce development, several multisectoral trainings were conducted including the frontline public health fellowship program, the One Health fellowship and residency program, advanced field epidemiology training program, in-service veterinary trainings and 21 district One Health teams' trainings. Real Time Surveillance was achieved through incorporating animal health events reporting in the electronic integrated disease surveillance and response platform. The national and ten regional veterinary laboratories were assessed for capacity to conduct zoonotic disease diagnostics, two of which were integrated into the national specimen referral and transportation network. Multisectoral planning for emergency response and the actual response to prioritized zoonotic disease outbreaks was done jointly., Conclusions: This study demonstrates the contribution of 'One Health' implementation in strengthening Uganda's health security. Investment in the funding gaps will reinforce Uganda's health security to achieve the IHR 2005. Future studies could examine the impacts and cost-effectiveness of One Health in curbing prioritized zoonotic disease outbreaks., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: To evaluate the support from the available guidance on reporting of health equity in research for our candidate items and to identify additional items for the Strengthening Reporting of Observational studies in Epidemiology-Equity extension., Study Design and Setting: We conducted a scoping review by searching Embase, MEDLINE, CINAHL, Cochrane Methodology Register, LILACS, and Caribbean Center on Health Sciences Information up to January 2022. We also searched reference lists and gray literature for additional resources. We included guidance and assessments (hereafter termed "resources") related to conduct and/or reporting for any type of health research with or about people experiencing health inequity., Results: We included 34 resources, which supported one or more candidate items or contributed to new items about health equity reporting in observational research. Each candidate item was supported by a median of six (range: 1-15) resources. In addition, 12 resources suggested 13 new items, such as "report the background of investigators"., Conclusion: Existing resources for reporting health equity in observational studies aligned with our interim checklist of candidate items. We also identified additional items that will be considered in the development of a consensus-based and evidence-based guideline for reporting health equity in observational studies., Competing Interests: Declaration of Competing Interest Although Luis Gabriel Cuervo is an official of the Pan American Health Organization, the views expressed in this publication are his sole responsibility and do not necessarily represent the decisions or policies of the Pan American Health Organization (PAHO/WHO)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Diseases addressed by surgical, obstetric, trauma and anaesthesia (SOTA) care are rising globally due to an anticipated rise in the burden of non-communicable diseases and road traffic accidents. Low- and middle-income countries (LMICs) disproportionately bear the brunt. Evidence-based policies and political commitment are required to reverse this trend. The Lancet Commission of Global Surgery proposed National Surgical and Obstetric and Anaesthesia Plans (NSOAPs) to alleviate the respective SOTA burdens in LMICs. NSOAPs success leverages comprehensive stakeholder engagement and appropriate health policy analyses and recommendations. As Uganda embarks on its NSOAP development, policy prioritisation in Uganda remains unexplored. We, therefore, seek to determine the priority given to SOTA care in Uganda's healthcare policy and systems-relevant documents., Methods and Analysis: We will conduct a scoping review of SOTA health policy and system-relevant documents produced between 2000 and 2022 using the Arksey and O'Malley methodological framework and additional guidance from the Joanna Briggs Institute Reviewer's manual. These documents will be sought from the websites of SOTA stakeholders by hand searching. We shall also search from Google Scholar and PubMed using well-defined search strategies. The Knowledge Management Portal for the Ugandan Ministry of Health, which was created to provide evidence-based decision-making data, is the primary source. The rest of the sources will include the following: other repositories like websites of relevant government institutions, international and national non-governmental organisations, professional associations and councils, and religious and medical bureaus. Data retrieved from the eligible policy and decision-making documents will include the year of publication, the global surgery specialty mentioned, the NSOAP surgical system domain, the national priority area involved and funding. The data will be collected in a preformed extraction sheet. Two independent reviewers will screen the collected data, and results will be presented as counts and their respective proportions. The findings will be reported narratively using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for scoping reviews., Ethics and Dissemination: This study will generate evidence-based information on the state of SOTA care in Uganda's health policy, which will inform NSOAP development in this nation. The review's findings will be presented to the Ministry of Health planning task force. The study will also be disseminated through a peer-reviewed publication; oral and poster presentations at local, regional, national and international conferences and over social media., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: With the rising resistance to artemisinin-based combination treatments, there is a need to hasten the discovery and development of newer antimalarial agents. Herbal medicines are key for the development of novel drugs. Currently, herbal medicine usage in communities for treatment of malaria symptoms is common as an alternative to conventional (modern) antimalarial agents. However, the efficacy and safety of most of the herbal medicines has not yet been established. Therefore, this systematic review and evidence gap map (EGM) is intended to collate and map the available evidence, identify the gaps and synthesise the efficacy of herbal antimalarial medicines used in malaria affected regions globally., Methods and Analysis: The systematic review and EGM will be done following PRISMA and Campbell Collaboration guidelines respectively. This protocol has been registered in PROSPERO. Data sources will include PubMed, MEDLINE Ovid, EMBASE, Web of Science, Google Scholar and grey literature search. Data extraction will be done in duplicate using a data extraction tool tailored in Microsoft Office excel for herbal antimalarials discovery research questions following the PICOST framework. The Risk of Bias and overall quality of evidence will be assessed using Cochrane risk of bias tool (clinical trials), QUIN tool (in vitro studies), Newcastle-Ottawa tool (observational studies) and SYRCLE's risk of bias tool for animal studies (in vivo studies). Data analysis will be done using both structured narrative and quantitative synthesis. The primary review outcomes will be clinically important efficacy and adverse drug reactions. Laboratory parameters will include Inhibitory Concentration killing 50% of parasites, IC 50; Ring Stage Assay, RSA 0-3 hou; Trophozoite Survival Assay, TSA 50. ETHICS AND DISSEMINATION: The review protocol was approved by the School of Biomedical Science Research Ethics Committee, Makerere University College of Health Sciences (SBS-2022-213)., Prospero Registration Number: CRD42022367073., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite the discovery of vaccines, the control, and prevention of Coronavirus disease 2019 (COVID-19) relied on non-pharmaceutical interventions (NPIs). This article describes the development and application of the Public Health Act to implement NPIs for COVID-19 pandemic control in Uganda., Methods: This is a case study of Uganda's experience with enacting COVID-19 Rules under the Public Health Act Cap. 281. The study assessed how and what Rules were developed, their influence on the outbreak progress, and litigation. The data sources reviewed were applicable laws and policies, Presidential speeches, Cabinet resolutions, statutory instruments, COVID-19 situation reports, and the registry of court cases that contributed to a triangulated analysis., Results: Uganda applied four COVID-19 broad Rules for the period March 2020 to October 2021. The Minister of Health enacted the Rules, which response teams, enforcement agencies, and the general population followed. The Presidential speeches, their expiry period and progress of the pandemic curve led to amendment of the Rules twenty one (21) times. The Uganda Peoples Defense Forces Act No. 7 of 2005, the Public Finance Management Act No. 3 of 2015, and the National Policy for Disaster Preparedness and Management supplemented the enacted COVID-19 Rules. However, these Rules attracted specific litigation due to perceived infringement on certain human rights provisions., Conclusions: Countries can enact supportive legislation within the course of an outbreak. The balance of enforcing public health interventions and human rights infringements is an important consideration in future. We recommend public sensitization about legislative provisions and reforms to guide public health responses in future outbreaks or pandemics., (© 2023. The Author(s).)

Background: Cervical cancer remains a public health problem worldwide, especially in sub-Saharan Africa. There are challenges in timely screening and diagnosis for early detection and intervention. Therefore, studies on cervical cancer and cervical intraepithelial neoplasia suggest the need for new diagnostic approaches including microRNA technology. Plasma/serum levels of microRNAs are elevated or reduced compared to the normal state and their diagnostic accuracy for detection of cervical neoplasms has not been rigorously assessed more so in low-resource settings such as Uganda. The aim of this systematic review was therefore to assess the diagnostic accuracy of serum microRNAs in detecting cervical cancer., Methods: We will perform a systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. We will search for all articles in MEDLINE/PubMed, Web of Science, Embase, and CINAHL, as well as grey literature from 2012 to 2022. Our outcomes will be sensitivity, specificity, negative predictive values, positive predictive values or area under the curve (Nagamitsu et al, Mol Clin Oncol 5:189-94, 2016) for each microRNA or microRNA panel. We will use the quality assessment of diagnostic accuracy studies (Whiting et al, Ann Intern Med 155:529-36, 2011) tool to assess the risk of bias of included studies. Our results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy studies (PRISMA-DTA). We will summarise studies in a flow chart and then describe them using a structured narrative synthesis. If possible, we shall use the Lehmann model bivariate approach for the meta analysis USE OF THE REVIEW RESULTS: This systematic review will provide information on the relevance of microRNAs in cervical cancer. This information will help policy makers, planners and researchers in determining which particular microRNAs could be employed to screen or diagnose cancer of the cervix., Systematic Review Registration: This protocol has been registered in PROSPERO under registration number CRD42022313275., (© 2023. The Author(s).)

Background: Globally, 13% of the youth are not in education, employment or training (NEET). Moreover, this persistent problem has been exacerbated by the shock of Covid-19 pandemic. More youth from disadvantaged backgrounds are likely unemployed than those from better off backgrounds. Thus, the need for increased use of evidence in the design and implementation of youth employment interventions to increase effectiveness and sustainability of interventions and outcomes. Evidence and gap maps (EGMs) can promote evidence-based decision making by guiding policy makers, development partners and researchers to areas with good bodies of evidence and those with little or no evidence. The scope of the Youth Employment EGM is global. The map covers all youth aged 15-35 years. The three broad intervention categories included in the EGM are: strengthening training and education systems, enhancing labour market and, transforming financial sector markets. There are five outcome categories: education and skills; entrepreneurship; employment; welfare and economic outcomes. The EGM contains impact evaluations of interventions implemented to increase youth employment and systematic reviews of such single studies, published or made available between 2000 and 2019., Objectives: The primary objective was to catalogue impact evaluations and systematic reviews on youth employment interventions to improve discoverability of evidence by decision makers, development patterners and researchers, so as to promote evidence-based decision making in programming and implementation of youth employment initiatives., Search Methods: Twenty databases and websites were searched using a validated search strategy. Additional searches included searching within 21 systematic reviews, snowballing 20 most recent studies and citation tracking of 10 most recent studies included in the EGM., Selection Criteria: The study selection criteria followed the PICOS approach of population, intervention, relevant comparison groups, outcomes and study design. Additional criterion is; study publication or availability period of between 2000 and 2021. Only impact evaluations and systematic reviews that included impact evaluations were selected., Data Collection and Analysis: A total of 14,511 studies were uploaded in EPPI Reviewer 4 software, upon which 399 were selected using the criteria provided above. Coding of data took place in EPPI Reviewer basing on predefined codes. The unit of analysis for the report is individual studies where every entry represents a combination of interventions and outcomes., Main Results: Overall, 399 studies (21 systematic reviews and 378 impact evaluations) are included in the EGM. Impact evaluations ( n  = 378) are much more than the systematic reviews ( n  = 21). Most impact evaluations are experimental studies ( n  = 177), followed by non-experimental matching ( n  = 167) and other regression designs ( n  = 35). Experimental studies were mostly conducted in both Lower-income countries and Lower Middle Income countries while non-experimental study designs are the most common in both High Income and Upper Middle Income countries. Most evidence is from low quality impact evaluations (71.2%) while majority of systematic reviews (71.4% of 21) are of medium and high quality rating. The area saturated with most evidence is the intervention category of 'training', while the underrepresented are three main intervention sub-categories: information services; decent work policies and; entrepreneurship promotion and financing. Older youth, youth in fragility, conflict and violence contexts, or humanitarian settings, or ethnic minorities or those with criminal backgrounds are least studied., Conclusions: The Youth Employment EGM identifies trends in evidence notably the following: Most evidence is from high-income countries, an indication of the relationship between a country's income status and research productivity.The most common study designs are experimental.Most of the evidence is of low quality. This finding serves to alert researchers, practitioners and policy makers that more rigorous work is needed to inform youth employment interventions. Blending of interventions is practiced. While this could be an indication that blended intervention could be offering better outcomes, this remains an area with a research gap., Competing Interests: The authors declare that there are no conflict of interests., (© 2022 The Authors. Campbell Systematic Reviews published by John Wiley & Sons Ltd on behalf of The Campbell Collaboration.)

The research question guiding the production of the youth employment evidence and gap map (EGM) is stated as follows: What is the nature and extent of the evidence base of impact evaluations and systematic reviews on youth employment programmes in the world? The primary objective of is to catalogue impact evaluations and systematic reviews on youth employment interventions to enhance discoverability of evidence by decision makers, development patterners and researchers, so as to promote evidence-based decision making in programming and delivery of youth employment initiatives. This evidence gap map is also a primary input into the implementation of Mastercard Foundation's strategy titled "Africa Works: Mastercard Foundation Strategy 2018-2030", which points out sharing of evidence-based knowledge and innovation with stakeholders as a key strategy to be used (Mastercard Foundation). The time frame for the development of the youth EGM will run from the last quarter of 2019 to December 2020. The five secondary objectives are: (i) To construct a framework for the classification of youth employment effectiveness studies. The objective will be achieved through the development of an intervention and outcome framework using an engaged consultative process involving the review team, Mastercard Foundation and other stakeholders. (ii) To identify available evidence, and clusters of evidence, including its quality rating. This will involve activities such as identification of studies using a standardised study search strategy, screening and coding of studies in EPPI Reviewer 4, which is a web-based software program for production of reviews. (iii) To create a map of youth employment effectiveness studies equipped with an appealing user-friendly web-based search content visualisation using interactive mapping software. To achieve this object, data coded in EPPI Reviewer 4 will be exported to another software (EPPI mapper) which is designed for generating EGMs. (iv) To produce a narrative report of the youth employment EGM. This will be achieved through analysis of data in EPPI Reviewer 4 and report writing. To disseminate the EGM to users to increase awareness to support evidence-informed decision-making across countries. We will achieve this objective by organising dissemination workshops, participating in conferences and hosting the evidence and gap on our websites., Competing Interests: No conflict of interest., (© 2021 The Authors. Campbell Systematic Reviews published by John Wiley & Sons Ltd on behalf of The Campbell Collaboration.)

Introduction: Accurate and affordable laboratory testing is key to timely diagnosis and appropriate management of patients with COVID-19. New laboratory test protocols are released into the market under emergency use authorisation with limited evidence on diagnostic test accuracy. As such, robust evidence on the diagnostic accuracy and the costs of available tests is urgently needed to inform policy and practice especially in resource-limited settings. We aim to determine the diagnostic test accuracy, cost-effectiveness and utility of laboratory test strategies for COVID-19 in low-income and middle-income countries., Methods and Analysis: This will be a multistaged, protocol-driven systematic review conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for diagnostic test accuracy studies. We will search for relevant literature in at least six public health databases, including PubMed, Google Scholar, MEDLINE, Scopus, Web of Science and the WHO Global Index Medicus. In addition, we will search Cochrane Library, COVID-END and grey literature databases to identify additional relevant articles before double-screening and abstraction of data. We will conduct a structured narrative and quantitative synthesis of the results guided by the Fryback and Thornbury framework for assessing a diagnostic test. The primary outcome is COVID-19 diagnostic test accuracy. Using the GRADE approach specific to diagnostic accuracy tests, we will appraise the overall quality of evidence and report the results following the original PRISMA statement. The protocol is registered with the International Prospective Register of Systematic Reviews (PROSPERO; https://www.crd.york.ac.uk/prospero/)., Ethics and Dissemination: Ethical review was done by the School of Biomedical Sciences Research Ethics Committee and the Uganda National Council for Science and Technology. The published article will be accessible to policy and decision makers. The findings of this review will guide clinical practice and policy decisions and highlight areas for future research. PROSPERO registration number CRD42020209528., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A large proportion of postgraduate students the world over complete a research thesis in partial fulfilment of their degree requirements. This study identified and evaluated support mechanisms for research generation and utilization for masters' students in health institutions of higher learning in Uganda., Methods: This was a self-administered cross-sectional survey using a modified self-assessment tool for research institutes (m-SATORI). Postgraduate students were randomly selected from four medical or public health Ugandan universities at Makerere, Mbarara, Nkozi and Mukono and asked to circle the most appropriate response on a Likert scale from 1, where the "situation was unfavourable and/or there was a need for an intervention", to 5, where the "situation was good or needed no intervention". These questions were asked under four domains: the research question; knowledge production, knowledge transfer and promoting use of evidence. Mean scores of individual questions and aggregate means under the four domains were computed and then compared to identify areas of strengths and gaps that required action., Results: Most of the respondents returned their questionnaires, 185 of 258 (71.7%), and only 79 of these (42.7%) had their theses submitted for examination. The majority of the respondents were male (57.3%), married or cohabiting (58.4%), and were medical doctors (71.9%) from Makerere University (50.3%). The domain proposal development for postgraduate research project had the highest mean score of 3.53 out of the maximum 5. Three of the four domains scored below the mid-level domain score of 3, that is, the situation is neither favourable nor unfavourable. Areas requiring substantial improvements included priority-setting during research question identification, which had the lowest mean score of 2.12. This was followed by promoting use of postgraduate research products, tying at mean scores of 2.28 each. The domain knowledge transfer of postgraduate research products had an above-average mean score of 2.75., Conclusions: This study reports that existing research support mechanisms for postgraduate students in Uganda encourage access to supervisors and mentors during proposal development. Postgraduate students' engagement with research users was limited in priority-setting and knowledge transfer. Since supervisors and mentors views were not captured, future follow-on research could tackle this aspect., (© 2021. The Author(s).)

Emerging highly transmissible viral infections such as SARS-CoV-2 pose a significant global threat to human health and the economy. Since its first appearance in December 2019 in the city of Wuhan, Hubei province, China, SARS-CoV-2 infection has quickly spread across the globe, with the first case reported on the African continent, in Egypt on February 14 th , 2020. Although the global number of COVID-19 infections has increased exponentially since the beginning of the pandemic, the number of new infections and deaths recorded in African countries have been relatively modest, suggesting slower transmission dynamics of the virus on the continent, a lower case fatality rate, or simply a lack of testing or reliable data. Notably, there is no significant increase in unexplained pneumonias or deaths on the continent which could possibly indicate the effectiveness of interventions introduced by several African governments. However, there has not yet been a comprehensive assessment of sub-Saharan Africa's (SSA) preparedness and response to the COVID-19 pandemic that may have contributed to prevent an uncontrolled outbreak so far. As a group of early career scientists and the next generation of African scientific leaders with experience of working in medical and diverse health research fields in both SSA and resource-rich countries, we present a unique perspective on the current public health interventions to fight COVID-19 in Africa. Our perspective is based on extensive review of the available scientific publications, official technical reports and announcements released by governmental and non-governmental health organizations as well as from our personal experiences as workers on the COVID-19 battlefield in SSA. We documented public health interventions implemented in seven SSA countries including Uganda, Kenya, Rwanda, Cameroon, Zambia, South Africa and Botswana, the existing gaps and the important components of disease control that may strengthen SSA response to future outbreaks., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Umviligihozo G et al.)

Introduction: Several studies of neuropsychological measures have been undertaken in patients with psychotic disorders from low- and middle-income countries (LMICs). It is, however, unclear if the measures used in these studies are appropriate for cognitive screening in clinical settings. We undertook a systematic review to determine if measures investigated in research on psychotic disorders in LMICs meet the clinical utility criteria proposed by The Working Group on Screening and Assessment., Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses were employed. We determined if tests had been validated against a comprehensive test battery, the duration and scope of the tests, the personnel administering the tests, and the means of administration., Results: A total of 31 articles were included in the review, of which 11 were from Africa. The studies included 3254 participants with psychosis and 1331 controls. 3 studies reported on the validation of the test against a comprehensive cognitive battery. Assessments took 1 h or less to administer in 6/31 studies. The average number of cognitive domains assessed was four. Nonspecialized staff were used in only 3/31 studies, and most studies used pen and paper tests (17/31)., Conclusion: Neuropsychological measures used in research on psychotic disorders in LMICs typically do not meet the Working Group on Screening and Assessment clinical utility criteria for cognitive screening. Measures that have been validated in high-income countries but not in LMICs that do meet these criteria, such as the Brief Assessment of Cognition in Schizophrenia, therefore deserve further study in LMIC settings., Competing Interests: Dr. Robbins is supported by funding from the US 10.13039/100000002National Institutes of Health (P30-MH43520; PI: Robert H. Remien; R01-HD095256; PI: Reuben N. Robbins; R21-HD098035; PI: Reuben N. Robbins). The other authors declare no conflict of interest., (© 2020 Published by Elsevier Inc.)

Background: Chloroquine, a previous highly efficacious, easy to use and affordable anti-malarial agent was withdrawn from malaria endemic regions due to high levels of resistance. This review collated evidence from published-reviewed articles to establish prevalence of Pfcrt 76T and Pfmdr-1 86Y alleles in malaria affected countries following official discontinuation of chloroquine use., Methods: A review protocol was developed, registered in PROSPERO (#CRD42018083957) and published in a peer-reviewed journal. Article search was done in PubMed, Scopus, Lilacs/Vhl and Embase databases by two experienced librarians (AK, RS) for the period 1990-to-Febuary 2018. Mesh terms and Boolean operators (AND, OR) were used. Data extraction form was designed in Excel spread sheet 2007. Data extraction was done by three reviewers (NL, BB and MO), discrepancies were resolved by discussion. Random effects analysis was done in Open Meta Analyst software. Heterogeneity was established using I 2 -statistic., Results: A total of 4721 citations were retrieved from article search (Pubmed = 361, Lilac/vhl = 28, Science Direct = 944, Scopus = 3388). Additional targeted search resulted in three (03) eligible articles. After removal of duplicates (n = 523) and screening, 38 articles were included in the final review. Average genotyping success rate was 63.6% (18,343/28,820) for Pfcrt K76T and 93.5% (16,232/17,365) for Pfmdr-1 86Y mutations. Prevalence of Pfcrt 76T was as follows; East Africa 48.9% (2528/5242), Southern Africa 18.6% (373/2163), West Africa 58.3% (3321/6608), Asia 80.2% (1951/2436). Prevalence of Pfmdr-1 86Y was; East Africa 32.4% (1447/5722), Southern Africa 36.1% (544/1640), West Africa 52.2% (1986/4200), Asia 46.4% (1276/2217). Over half, 52.6% (20/38) of included studies reported continued unofficial chloroquine use following policy change. Studies done in Madagascar and Kenya reported re-emergence of chloroquine sensitive parasites (IC 50  < 30.9 nM). The average time (years) since discontinuation of chloroquine use to data collection was 8.7 ± 7.4. There was high heterogeneity (I 2  > 95%)., Conclusion: The prevalence of chloroquine resistance alleles among Plasmodium falciparum parasites have steadily declined since discontinuation of chloroquine use. However, Pfcrt K76T and Pfmdr-1 N86Y mutations still persist at moderate frequencies in most malaria affected countries.

Background: While several individual studies addressing research productivity of post-graduate students are available, a synthesis of effective strategies to increase productivity and the determinants of productivity in low-income countries has not been undertaken. Further, whether or not this research from post-graduate students' projects was applied in evidence-informed decision-making was unknown. Therefore, we conducted a systematic review of literature to identify and assess the effectiveness of approaches that increase productivity (proportion published) or the application (proportion cited) of post-graduate students' research, as well as to assess the determinants of post-graduate students' research productivity and use., Methods: We conducted a systematic review as per our a priori published protocol, also registered in PROSPERO (CRD42016042819). We searched for published articles in PubMed/MEDLINE and the ERIC databases through to July 2017. We performed duplicate assessments for included primary studies and resolved discrepancies by consensus. Thereafter, we completed a structured narrative synthesis and, for a subset of studies, we performed a meta-analysis of the findings using both fixed and random effects approaches. We aligned our results to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement., Results: We found 5080 articles in the PubMed (n = 3848) and ERIC (n = 1232) databases. After excluding duplicates (n = 33), we screened 5047 articles, of which 5012 were excluded. We then retrieved 44 full texts and synthesised 14, of which 4 had a high risk of bias. We did not find any studies assessing effectiveness of strategies for increasing publication nor citations of post-graduate research projects. We found an average publication proportion of 7% (95% CI 7-8%, Higgins I-squared 0.0% and Cochran's Q p < 0.01) and 23% (95% CI 17-29%, Higgins I-squared of 98.4% and Cochran's Q, p < 0.01) using fixed effects and random effects models, respectively. Two studies reported on the citation of post-graduate students' studies, at 17% (95% CI 15-19%) in Uganda and a median citation of 1 study in Turkey (IQR 0.6-2.3). Only one included study reported on the determinants of productivity or use of post-graduate students' research, suggesting that younger students were more likely to publish and cohort studies were more likely to be published., Conclusions: We report on the low productivity of post-graduate students' research in low- and middle-income countries, including the citation of post-graduate students' research in evidence-informed health policy in low- and middle-income countries. Secondly, we did not find a single study that assessed strategies to increase productivity and use of post-graduate students' research in evidence-informed health policy, a subject for future research.

Background: World over, stakeholders are increasingly concerned about making research useful in public policy-making. However, there are hardly any reports linking production of research by students at institutions of higher learning to its application in society. We assessed whether and how post-graduate students' research was used in evidence-informed health policies., Methods: This is a multiple case study of master's students' dissertations at Makerere University College of Health Sciences (MakCHS) produced between 1996 and 2010. In a structured review, we applied a theoretical framework of 'research use' and used content analysis to map how research was used in public policy documents. We categorised content of these documents according to the health-related Millennium Development Goals (MDG). We defined a case of 'use' as citation of research products from a master's student's dissertation in a public policy-related document., Results: We found 22 cases of research use in policy-related documents (0.5%) out of a total 4230 citations from 16 of 1172 total dissertations (1.4%). Additionally, research was mostly cited in primary studies (95.4%), systematic reviews (3%), narrative reviews (0.8%) and cost-effectiveness analyses (0.2%). Research was predominantly used instrumentally, to either frame the problem (burden of disease or health condition) or select an intervention (treatment or diagnostic option) and rarely symbolically to justify strategies already selected. The bulk of the cases of research use addressed child health (MDG 4), focusing on infectious diseases (MDG 6), mainly in international clinical or public health guidelines, working papers, a consensus statement and a global report. We distilled 'synergistic relationships' among organisations or interest groups, 'globalisation of local evidence', 'trade-offs' in the use of research and use of 'negative results' from the documents and text content., Conclusions: Research from dissertations of post-graduate students at MakCHS is used in evidence-informed health policies, particularly for infectious diseases in child health. Further, we have delineated pathways of research use in the global arena and highlighted the importance of 'negative results' from dissertations of post-graduate students at MakCHS.

Background: Malaria remains one of the leading causes of morbidity and mortality in most low- and middle-income countries. Chloroquine is a previously cheap and effective antimalarial agent whose loss to resistance resulted in more than doubling of malaria-related mortality in malaria-endemic countries. Recently, chloroquine sensitivity is re-emerging among Plasmodium falciparum parasites which gives hope for malaria control and treatment efforts globally. The aim of the current review is to establish the prevalence of chloroquine resistance alleles among P. falciparum parasites in malaria-endemic areas after change in malaria treatment policy., Methods/design: The articles will be obtained from search of MEDLINE via PubMed, SCOPUS, and EMBASE data bases. The Mesh terms will be used in article search. Boolean operators ("AND," "OR") will be used in article search. The article search will be done independently by two librarians. The PRISMA-P statement will be used to guide the conduct and reporting of the systematic review. STREGA guideline will be used in developing data abstraction form for the review. Data abstraction will be done by two independent reviewers, Kappa statistic will be calculated, and any discrepancies resolved by discussion. Data analysis will be done using STATA ver 13.0. The level of heterogeneity in the articles will be established by using the I 2 -statistic. Publication bias will be assessed using funnel plot. Random effects analysis will be used., Discussion: The review seeks to establish the extent of chloroquine resistance reversal in malaria-endemic countries. The evidence generated from this review will help guide policy makers on the potential re-emerging role of chloroquine in malaria treatment., Systematic Review Registration: The systematic review protocol has been registered in PROSPERO with registration number CRD42018083957.

Background: Rates of major depression among people living with HIV (PLWH) are substantially higher than those seen in the general population and this may adversely affect antiretroviral treatment outcomes. Several unique clinical and psychosocial factors may contribute to the development and persistence of depression in PLWH. Given these influences, it is unclear if antidepressant therapy is as effective for PLWH as the general population., Objectives: To assess the efficacy of antidepressant therapy for treatment of depression in PLWH., Search Methods: We searched The Cochrane Common Mental Disorders Group's specialised register (CCMD-CTR), the Cochrane Library, PubMed, Embase and ran a cited reference search on the Web of Science for reports of all included studies. We conducted additional searches of the international trial registers including; ClinicalTrials.gov, World Health Organization Trials Portal (ICTRP), and the HIV and AIDS - Clinical trials register. We searched grey literature and reference lists to identify additional studies and contacted authors to obtain missing data. We applied no restrictions on date, language or publication status to the searches, which included studies conducted between 1 January 1980 and 18 April 2017., Selection Criteria: We included randomized controlled trials of antidepressant drug therapy compared to placebo or another antidepressant drug class. Participants eligible for inclusion had to be aged 18 years and older, from any setting, and have both HIV and depression. Depression was defined according to Diagnostic and Statistical Manual of Mental Disorders or International Statistical Classification of Diseases criteria., Data Collection and Analysis: Two review authors independently applied the inclusion criteria and extracted data. We presented categorical outcomes as risk ratios (RR) with 95% confidence intervals (CIs). Continuous outcomes were presented mean (MD) or standardized mean differences (SMD) with standard deviations (SD). We assessed quality of evidence using the GRADE approach., Main Results: We included 10 studies with 709 participants in this review. Of the 10 studies, eight were conducted in high income countries (USA and Italy), seven were conducted prior to 2000 and seven had predominantly men. Seven studies assessed antidepressants versus placebo, two compared different antidepressant classes and one had three arms comparing two antidepressant classes with placebo.Antidepressant therapy may result in a greater improvement in depression compared to placebo. There was a moderate improvement in depression when assessed with the Hamilton Depression Rating Scale (HAM-D) score as a continuous outcome (SMD 0.59, 95% CI 0.21 to 0.96; participants = 357; studies = 6; I 2 = 62%, low quality evidence). However, there was no evidence of improvement when this was assessed with HAM-D score as a dichotomized outcome (RR 1.10, 95% CI 0.89 to 1.35; participants = 434; studies = 5; I 2 = 0%, low quality evidence) or Clinical Global Impression of Improvement (CGI-I) score (RR 1.28, 95% CI 0.93 to 1.77; participants = 346; studies = 4; I 2 = 29%, low quality evidence). There was little to no difference in the proportion of study dropouts between study arms (RR 1.28, 95% CI 0.91 to 1.80; participants = 306; studies = 4; I 2 = 0%, moderate quality evidence).The methods of reporting adverse events varied substantially between studies, this resulted in very low quality evidence contributing to a pooled estimate (RR 0.88, 95% CI 0.64 to 1.21; participants = 167; studies = 2; I 2 = 34%; very low quality evidence). Based on this, we were unable to determine if there was a difference in the proportion of participants experiencing adverse events in the antidepressant versus placebo arms. However, sexual dysfunction was reported commonly in people receiving selective serotonin reuptake inhibitors (SSRIs). People receiving tricyclic antidepressants (TCAs) frequently reported anticholinergic adverse effects such as dry mouth and constipation. There were no reported grade 3 or 4 adverse events in any study group.There was no evidence of a difference in follow-up CD4 count at study termination (MD -6.31 cells/mm 3 , 95% CI -72.76 to 60.14; participants = 176; studies = 3; I 2 = 0%; low quality evidence). Only one study evaluated quality of life score (MD 3.60, 95% CI -0.38 to 7.58; participants = 87; studies = 1; very low quality evidence), due to the poor quality evidence we could not draw conclusions for this outcome.There were few studies comparing different antidepressant classes. We are uncertain if SSRIs differ from TCAs with regard to improvement in depression as evaluated by HAM-D score (MD -3.20, 95% CI -10.87 to 4.47; participants = 14; studies = 1; very low quality evidence). There was some evidence that mirtazapine resulted in a greater improvement in depression compared to an SSRI (MD 9.00, 95% CI 3.61 to 14.39; participants = 70; studies = 1; low quality evidence); however, this finding was not consistent for all measures of improvement in depression for this comparison.No studies reported on virological suppression or any other HIV specific outcomes.The studies included in this review had an overall unclear or high risk of bias due to under-reporting of study methods, high risk of attrition bias and inadequate sequence generation methods. Heterogeneity between studies and the limited number of participants, and events lead to downgrading of the quality of the evidence for several outcomes., Authors' Conclusions: This review demonstrates that antidepressant therapy may be more beneficial than placebo for the treatment of depression in PLWH. The low quality of the evidence contributing to this assessment and the lack of studies representing PLWH from generalized epidemics in low- to middle-income countries make the relevance of these finding in today's context limited. Future studies that evaluate the effectiveness of antidepressant therapy should be designed and conducted rigorously. Such studies should incorporate evaluation of stepped care models and health system strengthening interventions in the study design. In addition, outcomes related to HIV care and antiretroviral therapy should be reported.

Background: The prevalence of HIV in Uganda is 7.3%, and yet nearly 40% of people living with HIV are unaware of their status. The current HIV testing policy which is strictly blood-based poses several challenges including: a need for high level laboratory skills, stringent waste disposal needs, and painful sample collection. It is envisaged that introduction of a rapid, painless HIV oral fluid test as a potential alternative is likely to increase the number of people testing. The aim of this study was to determine the diagnostic accuracy and acceptability of rapid HIV oral testing among adults attending Kisenyi Health Centre IV in Kampala., Methods and Findings: We conducted a cross-sectional study among 440 adults recruited consecutively at Kisenyi Health Centre IV from January to March 2016. The diagnostic accuracy of the HIV oral test was assessed by comparing to the national HIV serial testing algorithm. We also assessed for acceptability among patients and health care workers (HCWs) by triangulating responses from a structured questionnaire, three focus group discussions and seven key informant interviews. Acceptability was defined as willingness to take the test at the time of the study and intention for future use of the test if it was availed. The prevalence of HIV infection among study participants was 14.8%. The HIV oral fluid test was highly accurate with sensitivity of 100% (95% CI; 94.5-100.0), specificity of 100% (95% CI; 99.0-100.0), positive predictive value (PPV) of 100% (95% CI; 94.5-100.0) and negative predictive value (NPV) of 100% (95% CI; 99.0-100.0). Acceptability of HIV oral testing was also high at 87.0% (95% CI; 83.6-89.9). Participants preferred HIV oral testing because it was: pain free (91%, n = 399) and did not require blood draw (82%, n = 360)., Conclusion: The HIV oral fluid test has high diagnostic accuracy and acceptability. HIV oral testing is a suitable addition to the national HIV testing strategies with the potential of increasing access to HIV testing services in Uganda.

Background: Research is a core business of universities globally, and is crucial in the scientific process as a precursor for knowledge uptake and use. We aimed to assess the academic productivity of post-graduate students in a university located in a low-income country., Methods: This is an observational retrospective documentary analysis using hand searching archives, Google Scholar and PubMed electronic databases. The setting is Makerere University College of Health Sciences, Uganda. Records of post-graduate students (Masters) enrolled from 1996 to 2010, and followed to 2016 for outcomes were analysed. The outcome measures were publications (primary), citations, electronic dissertations found online or conference abstracts (secondary). Descriptive and multivariable logistic regression analyses were performed using Stata 14.1., Results: We found dissertations of 1172 Masters students over the 20-year period of study. While half (590, 50%) had completed clinical graduate disciplines (surgery, internal medicine, paediatrics, obstetrics and gynaecology), Master of Public Health was the single most popular course, with 393 students (31%). Manuscripts from 209 dissertations (18%; 95% CI, 16-20%) were published and approximately the same proportion was cited (196, 17%; 95% CI, 15-19%). Very few (4%) policy-related documents (technical reports and guidelines) cited these dissertations. Variables that remained statistically significant in the multivariable model were students' age at enrolment into the Masters programme (adjusted coefficient -0.12; 95% CI, -0.18 to -0.06; P < 0.001) and type of research design (adjusted coefficient 0.22; 0.03 to 0.40; P = 0.024). Cohort studies were more likely to be published compared to cross-sectional designs (adjusted coefficient 0.78; 95% CI, 0.2 to 1.36; P = 0.008)., Conclusions: The productivity and use of post-graduate students' research conducted at the College of Health Sciences Makerere University is considerably low in terms of peer-reviewed publications and citations in policy-related documents. The need for effective strategies to reverse this 'waste' is urgent if the College, decision-makers, funders and the Ugandan public are to enjoy the 'return on investment' from post-graduate students research.

Background: Investing in research that is not accessible or used is a waste of resources and an injustice to human subject participants. Post-graduate students' research in institutions of higher learning involves considerable time, effort and money, warranting evaluation of the return on investment. Although individual studies addressing research productivity of post-graduate students are available, a synthesis of these results in low-income settings has not been undertaken. Our first aim is to identify the types of approaches that increase productivity and those that increase the application of medical post-graduate students' research and to assess their effectiveness. Our second aim is to assess the determinants of post-graduate students' research productivity., Methods: We propose a two-stage systematic review. We will electronically search for published and grey literature in PubMed/MEDLINE and the ERIC databases, as well as contact authors, research administration units of universities, and other key informants as appropriate. In stage one, we will map the nature of the evidence available using a knowledge translation framework adapted from existing literature. We will perform duplicate screening and selection of articles, data abstraction, and risk of bias assessments for included primary studies as described in the Cochrane handbook for systematic reviews. Our primary outcome is publication output as a measure of research productivity, whilst we defined research use as citations in peer-reviewed journals or policy-related documents as our secondary outcome. In stage two, we will perform a structured narrative synthesis of the findings and advance to quantitative meta-analysis if the number of studies are adequate and their heterogeneity is low. Adapting the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach, we will assess the overall quality of evidence for effects, and report our results in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement., Discussion: We will share our findings with universities, other training institutions, civil society, funders as well as government departments in charge of education and health particularly in low- and middle-income countries.

Background: The Intensified Case Finding (ICF) tool was approved for TB screening in 2011; however there is still paucity of robust data comparing yields of the different ICF screening modalities. We compared yields of three different screening modalities for TB among Patients Living with HIV (PLHIV) in Uganda in order to inform National TB Programs on the most effective TB screening method., Methods: This was a retrospective quasi-experimental study conducted at an Out-Patient HIV/AIDS clinic in Uganda. We set out to determine yields of three different TB screening modalities at three time periods: 2006/07 where Passive Case Finding (PCF) was used. Here, no screening questions were administered; the clinician depended on the patient's self report. In 2008/09 embedded Intensified Case Finding Tool (e-ICF) was used; here a data capture field was added to the patient clinical encounter forms to compel clinicians to screen for TB symptoms. In 2010/11 Independent Intensified Case Finding Tool (i-ICF) was used; here a screening data collection form, was used, it had the same screening questions as e-ICF. Routine clinical data, including TB status, were collected and entered into an electronic clinical care database. Analysis was done in STATA and the main outcome estimated was the proportional yield of TB cases for each screening modality., Results: The overall yield of TB cases was 11.18 % over the entire period of the study (2006 - 2011). The intervention-specific yields were 1.86 % for PCF, 14.95 % for e-ICF and 12.47 % for i-ICF. Use of either e-ICF (OR: 9.2, 95 % CI: 4.81-17.73) or i- ICF (OR: 7.7, 95 % CI: 4.02-14.78) significantly detected more TB cases compared to PCF (P <0.001). While the yields of the Active Case Finding modalities (e-ICF & i-ICF) were not significantly different (OR: 0.98, 95 % CI 0.76-1.27, P = 0.89)., Conclusion: The active screening modalities (e-ICF & i-ICF) had a comparable TB yield and were eight to nine times more efficient in identifying TB cases when compared to the PCF. Cost effectiveness studies would be informative.

Background: There is clinical equipoise regarding post-operative management of patients with patent ductus arteriosus (PDA) without insertion of a chest drain. This study evaluated post operative outcomes of chest closure with or without a drain following Patent Ductus Arteriosus ligation among childen at Uganda Heart Instritute (UHI)., Methods: This was an open label randomized controlled trial of 62 children 12 years of age and below diagnosed with patent ductus arteriosus at Mulago National Teaching and Referral Hospital, Uganda. Participants were randomized in the ratio of 1:1 with surgical ligation of patent ductus arteriosus to either thoracotomy closure with a chest tube or without a chest tube. All participants received standard care and were monitored hourly for 24 hours then until hospital discharge. The combined primary endpoint consisted of significant pleural space accumulation of fluid or air, higher oxygen need or infection of the surgical site. Analysis was conducted by multivariable logistic regression analysis at 5 % significance level., Results: We enrolled 62 participants, 46 (74 %) of whom were females. Their median age was 12 months (IQR: 8-36). Participants in the no-drain arm significantly had less post-operative complications compared to the drain arm (Unadjusted odds ratio [uOR]: 0.21, 95 % CI: 0.06-0.73, p = 0.015). This "protective effect" remained without statistical significance in the multivariable regression model (Adjusted odds ratio [aOR]: 0.07, 95 % CI: 0.00-2.50, p = 0.144)., Conclusion: Children aged below 6 years with patent ductus arterious can safely and effectively have thoracotomy closure without using a drain in uncomplicated surgical ligation of the PDA. Chest drain was associated with post-operative complications., Trial Registration: The trial was registered in the Pan African Clinical Trials registry on 1st/July/2012, retrospectively registered. Identifier number PACTR201207000395469 .

Background: WHO recommends regular viral load (VL) monitoring of patients on antiretroviral therapy (ART) for timely detection of virological failure, prevention of acquired HIV drug resistance (HIVDR) and avoiding unnecessary switching to second-line ART. However, the cost and complexity of routine VL testing remains prohibitive in most resource limited settings (RLS). We evaluated a simple, low-cost, qualitative viral-failure assay (VFA) on dried blood spots (DBS) in three clinical settings in Uganda., Methods: We conducted a cross-sectional diagnostic accuracy study in three HIV/AIDS treatment centres at the Joint Clinical Research Centre in Uganda. The VFA employs semi-quantitative detection of HIV-1 RNA amplified from the LTR gene. We used paired dry blood spot (DBS) and plasma with the COBASAmpliPrep/COBASTaqMan, Roche version 2 (VLref) as the reference assay. We used the VFA at two thresholds of viral load, (>5,000 or >1,000 copies/ml)., Results: 496 paired VFA and VLref results were available for comparative analysis. Overall, VFA demonstrated 78.4% sensitivity, (95% CI: 69.7%-87.1%), 93% specificity (95% CI: 89.7%-96.4%), 89.3% accuracy (95% CI: 85%-92%) and an agreement kappa = 0.72 as compared to the VLref. The predictive values of positivity and negativity among patients on ART for >12 months were 72.7% and 99.3%, respectively., Conclusions: VFA allowed 89% of correct classification of VF. Only 11% of the patients were misclassified with the potential of unnecessary or late switch to second-line ART. Our findings present an opportunity to roll out simple and affordable VL monitoring for HIV-1 treatment in RLS.

Background: Antimicrobial self-medication is common in most low and middle income countries (LMICs). However there has been no systematic review on non-prescription antimicrobial use in these settings. This review thus intended to establish the burden, risk factors and effects of antimicrobial self-medication in Low and Middle Income Countries., Methods: In 2012, we registered a systematic review protocol in PROSPERO (CRD42012002508). We searched PubMed, Medline, Scopus, and Embase databases using the following terms; "self-medication", "non-prescription", 'self-treatment', "antimicrobial", "antimalarial", "antibiotic", "antibacterial" "2002-2012" and combining them using Boolean operators. We performed independent and duplicate screening and abstraction of study administrative data, prevalence, determinants, type of antimicrobial agent, source, disease conditions, inappropriate use, drug adverse events and clinical outcomes of antibiotic self-medication where possible. We performed a Random Effects Meta-analysis., Results: A total of thirty four (34) studies involving 31,340 participants were included in the review. The overall prevalence of antimicrobial self-medication was 38.8 % (95 % CI: 29.5-48.1). Most studies assessed non-prescription use of antibacterial (17/34: 50 %) and antimalarial (5/34: 14.7 %) agents. The common disease symptoms managed were, respiratory (50 %), fever (47 %) and gastrointestinal (45 %). The major sources of antimicrobials included, pharmacies (65.5 %), leftover drugs (50 %) and drug shops (37.5 %). Twelve (12) studies reported inappropriate drug use; not completing dose (6/12) and sharing of medicines (4/12). The main determinants of antimicrobial self-medication include, level of education, age, gender, past successful use, severity of illness and income. Reported negative outcomes of antimicrobial self-medication included, allergies (2/34: 5.9 %), lack of cure (4/34: 11.8 %) and causing death (2/34: 5.9 %). The commonly reported positive outcome was recovery from illness (4/34: 11.8 %)., Conclusion: The prevalence of antimicrobial self-medication is high and varies in different communities as well as by social determinants of health and is frequently associated with inappropriate drug use.

Background: Depression is one of the commonest neuropsychiatric disorders in patients with diabetes mellitus (DM) and is associated with poor glycaemic control, vascular complications, a low quality of life and increased health care expenditure. Co-morbid DM and depression remains poorly identified and inadequately treated in sub-Saharan Africa., Methods: We conducted a cross-sectional survey of 437 patients with DM at 3 DM clinics in Uganda. Participants were assessed for depression, blood sugar levels, diabetic neuropathy, quality of life, and health care expenditures., Results: The prevalence of depression was 34.8%. Depressed participants were more likely to be suicidal [OR=3.81, (CI 2.87-5.04)], younger [OR=3.98 CI (1.20-13.23)], un-employed [OR=1.99(CI 1.04-3.81)], and having lost a spouse [OR=2.36 (CI 1.29-4.31)]. Overall quality of life was poor [OR=0.67 (CI 0.47-0.96)], they scored poorer in the physical [OR=0.97, (CI 0.95-0.99)], psychological [OR=1.05 (CI 1.03-1.07)], and environmental [OR=0.97, (CI 0.95-0.99)] domains. They had an increased likelihood of incurring direct out-of-pocket payments for health care services [OR=1.56 (CI 1.03-2.36)], and were more likely to be impoverished [OR=1.52 (CI 1.01-2.28)]., Limitation: The cross sectional nature of this study makes it difficult to examine causation. More studies are required in order to better understand the associations and impact of the factors examined above on patient outcomes., Conclusions: Depression is highly prevalent among patients with DM in Uganda, and is associated with a number of adverse outcomes. A holistic approach that focuses on the depression management among patients with diabetes is recommended., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Despite 10 to% of persons living with HIV in sub-Saharan Africa having clinical depression, and the consequences of depression for key public health outcomes (HIV treatment adherence and condom use), depression treatment is rarely integrated into HIV care programs. Task-shifting, protocolized approaches to depression care have been used to overcome severe shortages of mental health specialists in developing countries, but not in sub-Saharan Africa and not with HIV clients. The aims of this trial are to evaluate the implementation outcomes and cost-effectiveness of a task-shifting, protocolized model of antidepressant care for HIV clinics in Uganda., Methods/design: INDEPTH-Uganda is a cluster randomized controlled trial that compares two task-shifting models of depression care--a protocolized model versus a model that relies on the clinical acumen of trained providers to provide depression care in ten public health HIV clinics in Uganda. In addition to data abstracted from routine data collection mechanisms and supervision logs, survey data will be collected from patient and provider longitudinal cohorts; at each site, a random sample of 150 medically stable patients who are depressed according to the PHQ-2 screening will be followed for 12 months, and providers involved in depression care implementation will be followed over 24 months. These data will be used to assess whether the two models differ on implementation outcomes (proportion screened, diagnosed, treated; provider fidelity to model of care), provider adoption of treatment care knowledge and practices, and depression alleviation. A cost-effectiveness analysis will be conducted to compare the relative use of resources by each model., Discussion: If effective and resource-efficient, the task-shifting, protocolized model will provide an approach to building the capacity for sustainable integration of depression treatment in HIV care settings across sub-Saharan Africa and improving key public health outcomes., Trial Registration: INDEPTH-Uganda has been registered with the National Institutes of Health sponsored clinical trials registry (3 February 2013) and has been assigned the identifier NCT02056106.

Objective: Clinical and immunological data about HIV in older adults from low and middle income countries is scarce. We aimed to describe differences between younger and older adults with HIV starting antiretroviral therapy in two low-income African countries., Setting: HIV clinics in Uganda and Zimbabwe., Design: Secondary exploratory cross-sectional analysis of the DART randomized controlled trial., Outcome Measures: Clinical and laboratory characteristics were compared between adults aged 18-49 years (younger) and ≥ 50 years (older), using two exploratory multivariable logistic regression models, one with HIV viral load (measured in a subset pre-ART) and one without., Results: A total of 3316 eligible participants enrolled in DART were available for analysis; 219 (7%) were ≥ 50 years and 1160 (35%) were male. Across the two adjusted regression models, older adults had significantly higher systolic blood pressure, lower creatinine clearance and were consistently less likely to be females compared to younger adults with HIV. Paradoxically, the models separately suggested that older adults had statistically significant (but not clinically important) higher CD4+ cell counts and higher plasma HIV-1 viral copies at initiation. Crude associations between older age and higher baseline hemoglobin, body mass index, diastolic blood pressure and lower WHO clinical stage were not sustained in the adjusted analysis., Conclusions: Our study found clinical and immunological differences between younger and older adults, in a cohort of Africans starting antiretroviral therapy. Further investigations should explore how these differences could be used to ensure equity in service delivery and affect outcomes of antiretroviral therapy.

Background: Treatment of multidrug-resistant or extensively drug-resistant tuberculosis (DR-tuberculosis) is challenging because commonly used second-line drugs are poorly efficacious and highly toxic. Although World Health Organization group 5 drugs are not recommended for routine use because of unclear activity, some may have untapped potential as more efficacious or better tolerated alternatives., Methods: We conducted an exhaustive review of in vitro, animal, and clinical studies of group 5 drugs to identify critical research questions that may inform their use in current treatment of DR-tuberculosis and clinical trials of new DR-tuberculosis regimens., Results: Clofazimine may contribute to new short-course DR-tuberculosis regimens. Beta-lactams merit further evaluation-specifically optimization of dose and schedule. Linezolid appears to be effective but is frequently discontinued due to toxicity. Thiacetazone is too toxic to warrant further evaluation. Mycobacterium tuberculosis has intrinsic inducible resistance to clarithromycin., Conclusions: Clofazimine and beta-lactams may have unrealized potential in the treatment of DR-tuberculosis and warrant further study. Serious toxicities or intrinsic resistance limit the utility of other group 5 drugs. For several group 5 compounds, better understanding of structure-toxicity relationships may lead to better-tolerated analogs.

Objective: The HIV/AIDS epidemic has evolved with an increasing burden in older adults. We assessed for knowledge about aging and HIV/AIDS, among clinicians in Kampala district, Uganda., Methods: A cross-sectional survey of 301 clinicians complemented by 9 key-informant interviews between May and October 2011. Data was analyzed by multivariable logistic regression for potential determinants of clinician knowledge about HIV/AIDS in older adults, estimating their adjusted Odds Ratios (aOR) and 95% confidence intervals (95% CI) using Stata 11.2 software., Results: Two-hundred and sixty-two questionnaires (87.7%) were returned. Respondents had a median age of 30 years (IQR 27-34) and 57.8% were general medical doctors. The mean knowledge score was 49% (range 8.8%-79.4%). Questions related to co-morbidities in HIV/AIDS (non-AIDS related cancers and systemic diseases) and chronic antiretroviral treatment toxicities (metabolic disorders) accounted for significantly lower scores (mean, 41.7%, 95% CI: 39.3%-44%) compared to HIV/AIDS epidemiology and prevention (mean, 65.7%, 95% CI: 63.7%-67.7%). Determinants of clinician knowledge in the multivariable analysis included (category, aOR, 95% CI): clinician age (30-39 years; 3.28∶1.65-9.75), number of persons with HIV/AIDS seen in the past year (less than 50; 0.34∶0.14-0.86) and clinical profession (clinical nurse practitioner; 0.31∶0.11-0.83). Having diploma level education had a marginal association with lower knowledge about HIV and aging (p = 0.09)., Conclusion: Our study identified gaps and determinants of knowledge about HIV/AIDS in older adults among clinicians in Kampala district, Uganda. Clinicians in low and middle income countries could benefit from targeted training in chronic care for older adults with HIV/AIDS and long-term complications of antiretroviral treatment.

Depressive disorders are highly prevalent in Africa where diseases such as HIV/AIDS are common. The aim of this study was to assess the validity of commonly used depression screening instruments in a setting characterized by low literacy, where patients may not be able to self-administer depression scales. We explored the validity of the Patient Health Questionaire-9 (PHQ-9), Centre for Epidemiological Surveys for Depression (CES-D), and the Kessler-10 (K-10), using the Mini International Neuropsychiatric Instrument (MINI) as a gold standard in 368 persons living with HIV/AIDS (PLWHA) in Uganda. The shorter versions of the K-10 and PHQ-9 were extracted to assess their performance in comparison to the longer versions. We used STATA 11.2 to analyze the data. The prevalence of a MINI defined depression in this patient sample was 17.4%. The three instruments all performed well, with areas under the curve (AUC) ranging from 0.82 to 0.96. The PHQ-9 showed the best performance characteristics with an AUC of 0.96, a sensitivity of 91.6%, and specificity 81.2%. The extracted versions performed more modestly. All three instruments showed good properties as screening tools; the PHQ-9 has particularly high sensitivity and specificity, and so can be considered useful for screening HIV-positive patients for depression.

Background: Given the high prevalence of depression in primary health care (PHC), the use of screening instruments has been recommended. Both brief and long depression screening instruments have been validated in low and middle income countries (LMIC), including within HIV care settings. However, it remains unknown whether the brief instruments validated in LMIC are as accurate as the long ones., Methods: We conducted a search of PUBMED, the COCHRANE library, AIDSLINE, and PSYCH-Info from their inception up to July 2011, for studies that validated depression screening instruments in LMIC. Data were extracted into tables and analyzed using RevMan 5.0 and STATA 11.2 for the presence of heterogeneity., Results: Nineteen studies met our inclusion criteria. The reported prevalence of depression in LMIC ranged from 11.1 to 53%. The area under curve (AUC) scores of the validated instruments ranged from 0.69-0.99. Brief as well as long screening instruments showed acceptable accuracy (AUC≥0.7). Five of the 19 instruments were validated within HIV settings. There was statistically significant heterogeneity between the studies, and hence a meta-analysis could not be conducted to completion. Heterogeneity chi-squared = 189.23 (d.f. = 18) p<.001., Conclusion: Brief depression screening instruments in both general and HIV-PHC are as accurate as the long ones. Brief scales may have an edge over the longer instruments since they can be administered in a much shorter time. However, because the ultra brief scales do not include the whole spectrum of depression symptoms including suicide, their use should be followed by a detailed diagnostic interview.

Background: Knowledge of tuberculosis has been shown to influence health seeking behaviour; and urban slum dwellers are at a higher risk of acquiring tuberculosis than the general population. The study aim was to assess knowledge of tuberculosis and identify the associated socio-demographic determinants, in order to inform tailored interventions for advocacy, communication and social mobilisation in three urban-slum communities of Uganda., Methods: A cross-sectional survey of 1361 adults between April and October 2011. Data was analyzed by descriptive statistics. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) of potential determinants of tuberculosis (TB) knowledge were estimated by multivariable ordinal logistic regression using Stata 11.2 software., Results: We found low knowledge of TB cause (26.7%); symptoms (46.8%), transmission (54.3%), prevention (34%) and free treatment (35%). Knowledge about TB treatment (69.4) and cure (85.1) was relatively high. Independent determinants of poor knowledge of TB in the multivariable analysis included (aOR, 95% CI) lack of formal education (0.56; 0.38 - 0.83, P = 0.004), unemployment (0.67; 0.49 - 0.90, P = 0.010) and never testing for HIV (0.69; 0.51 - 0.92, P < 0.012). Whilst, older age (1.73; 1.30 - 2.29, P < 0.001) and residing in Lira (2.02; 1.50 - 2.72, P < 0.001) were independent determinants of higher knowledge of TB., Conclusion: This study revealed deficiencies in the public health knowledge about TB symptoms, diagnosis and treatment among urban-slum dwellers in Uganda. Tuberculosis control programmes in similar settings should consider innovative strategies for TB education, advocacy, communication and social mobilisation to reach the youth, unemployed and less-educated; as well as those who have never tested for HIV.