INtegration of DEPression Treatment into HIV Care in Uganda (INDEPTH-Uganda): study protocol for a randomized controlled trial

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

Clinical Differences between Younger and Older Adults with HIV/AIDS Starting Antiretroviral Therapy in Uganda and Zimbabwe: A Secondary Analysis of the DART Trial

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. Methods: 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

Sub-Saharan Africa preparedness and response to the COVID-19 pandemic : A perspective of early career African scientists

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

Clinical differences between younger and older adults with HIV/AIDS starting antiretroviral therapy in Uganda and Zimbabwe: a secondary analysis of the DART trial

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

A comparision of the yield of three tuberculosis screening modalities among people living with HIV: a retrospective quasi-experiemental study

Abstract 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

Comparing the accuracy of brief versus long depression screening instruments which have been validated in low and middle income countries: a systematic review

Abstract 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 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.</p

Efficacy of antimalarial herbal medicines used by communities in malaria affected regions globally: a protocol for systematic review and evidence and gap map

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, IC50; Ring Stage Assay, RSA0–3 hou; Trophozoite Survival Assay, TSA50.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

Persistence of chloroquine resistance alleles in malaria endemic countries: a systematic review of burden and risk factors

Abstract 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 I2-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 (IC50  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