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Scovia Nalugo Mbalinda,1,* Mark Kaddumukasa,2,* Josephine Nambi Najjuma,3,* Doreen R Birungi,2,* Martin Ntambi Kaddumukasa,1,4,* Jennifer B Levin,5,* Carolyn Harmon Still,6,* Christopher J Burant,7,* Avani C Modi,8,* Elly T Katabira,2,* Martha Sajatovic5,* 1Department of Nursing, College of Health Sciences, Makerere University, Kampala, Uganda; 2Department of Medicine, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda; 3Department of Nursing, Mbarara University of Science and Technology, Mbarara, Uganda; 4Department of Medicine, Mulago Hospital, Kampala, Uganda; 5Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center & Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA; 6Louis Stokes VA Medical Center, Geriatric Research Education, and Clinical Center, Cleveland, OH, 44106, USA; 7Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, 44106, USA; 8Cincinnati Children, S Hospital Medical Center, Cincinnati, Ohio, USA*These authors contributed equally to this workCorrespondence: Scovia Nalugo Mbalinda, Email snmbalinda@gmail.comBackground: People of all ages are affected by epilepsy, a prevalent chronic brain illness that is primarily found in underdeveloped nations. It is very necessary to implement epilepsy self-management techniques to support individuals with epilepsy in order to impact outcomes related to epilepsy. The purpose of this 2-site randomised controlled experiment is to investigate this further, based on encouraging preliminary evidence.Methods: A total of 188 adult people with epilepsy (PWE) attending the neurology clinics at Mulago and Mbarara hospitals and consent to participate in the study will be recruited. They will be randomised into intervention versus enhanced treatment control (eTAU) study groups. The intervention group will receive 12-week “intensive” educational sessions and a 12-week remotely accessed telephone follow-up stage. The controls will continue in their usual care supplemented by written materials on epilepsy in their preferred language and tailored to the reading level of most patients at the clinic. SMART-U consists of 2 main components: a 12-week “intensive” group format stage and a 12-week remotely accessed telephone follow-up stage. SMART-U will be assessed for acceptability, fidelity, and efficacy compared to eTAU. The primary study outcome is the mean change in cumulative past 24-week seizure frequency (24 weeks prior to the study baseline compared to the 24-week follow-up). Seizure frequency will be via self-report with corroboration by family/support system informants whenever possible. Participants will self-report the seizure frequency (numeric count) that they experienced between baseline and 13 weeks and again between 13 and 24 weeks, and the mean change from baseline to 24 weeks in QOL.Discussion: The curriculum-guided Self-Management intervention for Reducing The epilepsy burden among Ugandans (SMART-U) program is anticipated to reduce the epilepsy burden seizure frequency and improve other health outcomes, including depression, functional status and health resource use.Trial Registration Number (TRN): NCT06139198.Date of registration: November142023.Keywords: self-management, epilepsy, targeted management, intervention

Scovia Nalugo Mbalinda,1 Mark Kaddumukasa,2 Josephine Nambi Najjuma,3 Martin Kaddumukasa,1,4 Jane Nakibuuka,1,4 Christopher J Burant,5 Shirley Moore,6 Carol Blixen,7 Elly T Katabira,1 Martha Sajatovic7 1Department of Nursing, School of Health Sciences, College of Health Sciences, Makerere University, Kampala, Uganda; 2Department of Medicine, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda; 3Department of Nursing, Mbarara University of Science and Technology, Mbarara, Uganda; 4Department of Medicine, Mulago Hospital, Kampala, Uganda; 5Louis Stokes VA Medical Center, Geriatric Research Education, and Clinical Center, Cleveland, OH, 44106, USA; 6Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, 44106, USA; 7Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center & Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USACorrespondence: Scovia Nalugo Mbalinda, Department of Nursing, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda, Tel +256782212151, Email snmbalinda@gmail.comPurpose: Evidence supporting secondary stroke in sub-Saharan Africa is scarce. This study describes the incidence of stroke recurrence and associated risk factors in sub-Saharan Africa.Methods and Materials: Scientific databases were systematically searched from January 2000 to December 2022 for population-based observational studies, case-control or cohort studies of recurrent stroke involving adults aged 18 years and above in sub-Saharan Africa (SSA). We assessed the quality of the eligible studies using the Critical Appraisal Skills Program (CASP) checklist for observational studies.Results: Six studies met the inclusion criteria and were included in this study. Stroke recurrence rates in SSA ranged from 9.4% to 25%. Majority of the studies were conducted from Western Africa and showed that stroke recurrence rates are high within sub-Saharan Africa ranging from 2% to 25%. The known stroke risk factors such as hypertension, chronic alcohol consumption, etc., remained the leading causes of stroke recurrence. The studies reported a higher mortality rate ranging from 20.5 − 23% among those with recurrent strokes compared to primary strokes.Conclusion: This systematic review is an update and summary of the available literature on stroke recurrence within sub-Saharan Africa. Further studies are warranted to assess the outcomes and burden of stroke recurrence in SSA.Keywords: stroke recurrence, sub-Saharan Africa, risk factors, secondary prevention, cardiovascular disease

Martin Kaddumukasa,1 Alyssa M Edwards,2 Josephine Nambi Najjuma,3 Scovia Nalugo Mbalinda,4 Jane Nakibuuka,1 Christopher J Burant,5 Shirley M Moore,6 Carol Blixen,2 Elly T Katabira,1 Martha Sajatovic,2 Mark Kaddumukasa1 1Department of Internal Medicine, College of Health Sciences, Makerere University, Kampala, Uganda; 2Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH, USA; 3Department of Nursing, Mbarara University of Science and Technology, Mbarara, Uganda; 4Department of Nursing, College of Health Sciences, Makerere University, Kampala, Uganda; 5Louis Stokes VA Medical Center, Geriatric Research Education, and Clinical Center, Cleveland, OH, USA; 6Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, USACorrespondence: Martin Kaddumukasa, Email kaddumart@gmail.comAbstract: The study set out to perform a systematic literature review of evidence-based interventions that target the reduction of secondary stroke risk in Africa. The review analyzed longitudinal intervention studies conducted in Sub-Saharan Africa, focusing on adult participants who had suffered a prior stroke. It encompassed publications and peer-reviewed papers sourced from reputable databases, including PubMed, Ovid, Cochrane, and Web of Science. Three randomized clinical trial (RCT) studies were included with sample sizes ranging from 16 to 400 participants, mean age ranged between 50 and 66 years, with 64.5% male participants. All studies applied multidisciplinary team interventions of enhanced patient follow-up involving care givers, nurse educators, physicians, and social workers. Interventions ranged from comprehensive patient education, tracking of medication adherence and enforcing healthy lifestyle behaviors (regular exercise, regular BP checks, and dietary changes). We found a decrease in Systolic Blood Pressure over time in 2 of 3 treatment groups, an improvement in medical adherence in all treatment groups, and a decrease in cholesterol levels in 1 treatment group. Evidence-based interventions involving multidisciplinary teams and comprehensive patient education were found to demonstrate promising results in reducing secondary stroke risk in Africa, leading to significant improvements in medical adherence and reductions in systolic blood pressure in the majority of treatment groups. However, more research is required to confirm the influence of these interventions on cholesterol levels and to establish their lasting advantages in preventing strokes among African communities.Keywords: secondary stroke risk, risk interventions, Sub-Saharan Africa

Background: Preeclampsia is the second leading cause of maternal death in Uganda. WHO recommends using magnesium sulphate (MgSO4) to prevent and treat preeclampsia with severe features (PEC) and eclampsia. MgSO4 is used to prevent eclampsia and treat women who experience an eclamptic convulsion to avoid severe maternal/infant illnesses and death. We set out to assess MgSO4 administration patterns in women with PEC or eclampsia and the immediate newborn outcomes of neonates., Methods: This was an analytical observational cohort study at Kawempe National Referral Hospital in Uganda. Two hundred ten pregnant mothers with PEC or eclampsia were recruited in the study after receiving the loading dose of MgSO4 and then followed through labour and delivery to observe MgSO4 administration patterns and immediate newborn outcomes using Apgar and Thompson scores. SPSS version 23 was used to analyse data, and both bivariate and multivariate logistic regressions were used to determine factors associated with the low Apgar score at five minutes., Results: Overall, majority of the patients received more than one dose with 33.3% received a sixth dose of MgSO4. The majority, 84.8%, of the mothers delivered live babies, 31.0% babies had complications, and were admitted to the neonatal intensive care unit (NICU). NICU admissions were mostly due to respiratory distress21.4%, preterm delivery21.0%, and 5.5% died within seven days. Majority 93.3% of the newborns had an Apgar score of seven and above at five minutes, of the newborns who were Thompson scored, 70.4% scored between 1 to 10 which is mild HIE. Initiation of MgSO4 treatment within one hour from prescription (AOR = 0.49, CI: 0.01-1.94), 4-hourly timing of the first maintenance dose (AOR = 0.22, CI: 0.06-0.79) and having complete doses of MgSO4 treatment (AOR = 0.89, CI: 0.03-3.05) decreased the likelihood of having low Apgar scores at five minutes., Conclusions: Timely administration of the first maintenance dose of MgSO4 decreases the likelihood of low Apgar score at 5 min and NICU admission in newborns, and most NICU admissions were due to respiratory distress and preterm delivery., Competing Interests: Declarations Ethics approval and consent to participate Ethical review and approval were obtained from the Research Ethics Committee (REC) of the School of Health Sciences, College of Health Sciences at Makerere University under REC number MAKSHSREC-2022–330. Administrative clearance and permission to collect data were obtained from the management of Kawempe National Referral hospital. All participants gave written informed consent to participate voluntarily in the study prior to data collection and were informed that there would be no consequences if they withdraw from the study at any given point of the study if they wished not to continue. Participants who could not read or write were asked to provide informed verbal consent after the script was read to them by the research assistant in order to assist in the comprehension of the research and informed verbal consent process, and these participants signed the written consent form by putting a thumb print. Information collected from the respondents was held with confidentiality through the use of anonymous questionnaires which were filed and kept under lock and key throughout the whole data collection and analysis process. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Stroke outcomes among young adults in Uganda are unclear. This study therefore determined the clinical characteristics and 30-day outcome among young adults with an acute stroke. In a prospective observational cohort study, 61 young adults with confirmed stroke were followed up for 30 days. Socio-demographic and clinical characteristics were collected using a study questionnaire. Kaplan-Meier curves, and modified Poisson regression were performed for factors associated with the 30-day mortality outcome. A third of the screened stroke survivors, (61/195) were young adults aged between 18 and 50 years. About two-thirds were male. More than half were diagnosed with ischaemic strokes while 42.6% had a haemorrhagic stroke. Nearly half (29/61) were known hypertensives, 43% (26/61) had a history of alcohol consumption with 95% classified as dependent on CAGE assessment. Ten percent had a prior smoking history while 29% of the female gender had a prior history of oral contraception use. Twenty-three percent (14/61) of the young stroke patients died within 30 days of stroke onset (95% CI: 0.01, 0. 901). A history of smoking (adjusted prevalence ratio: aPR;5. 094, 95% CI: 3.712, 6. 990) and stroke severity National Institutes of Health Stroke score (NIHSS) >16; Prevalence ratio (PR) -3. 301, 95%CI: 1. 395, 7. 808) and not drinking alcohol (aPR (adjusted prevalence ratio) -7. 247, 95% CI: 4. 491, 11.696) were associated with 30- day mortality. A third of all stroke survivors were young adults. About 23. 3% died within 30 days of stroke onset. Stroke severity and a history of smoking were associated with mortality. Identifying high risk patients and early outpatient follow up may help reduce the 30-day mortality in our settings., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2023 Nampogo 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: Greater blood pressure variability has detrimental effects on clinical outcome after a stroke; its effects are controversial and have not been evaluated in Sub-Saharan Africa (SSA)., Methods: We conducted a prospective study of patients with CT head confirmed ischemic and hemorrhagic strokes admitted to a tertiary hospital within 7 days of onset of unilateral neurological deficits. Blood pressure variability indices, standard deviation (SD) and coefficient of variation (CV) of systolic and diastolic blood pressure between day 0 and day 7, were calculated with a subsequent modified Rankin Scale (mRS) score on day 14 post-stroke. Linear regression was performed to determine the exponential coefficients of mortality at 14 days post- stroke., Results: Out of 120 patients, 51.7% were female, 52.5% had ischemic stroke and the overall median age was 65 (IQR 54-80) years. Twenty (16.7%) patients died within a median survival time of 7 days, while 32 (26.7%) died by day 14 post-stroke. Patients with hemorrhagic stroke had an overall SDSBP of 16.44 mmHg while those with ischemic stroke had an overall SDSBP of 14.05 mmHg. In patients with ischemic stroke, SDSBP had adjusted coefficients of 1, p  = 0.004 with C·I: 1.01-1.04 and NIHSS had adjusted coefficients of 1, p  = 0.019 with C·I: 1.00-1.03 while in patients with hemorrhagic stroke, SDSBP had adjusted coefficients of 1, p  = 0.045 with C·I: 1.00-1.04 and NIHSS had adjusted coefficients of 1, p  ≤0.001 with C·I: 1.01-1.03., Conclusion: Exponential increase in Blood Pressure Variability (BPV) and stroke severity scale were independently associated with early mortality among all stroke patients in our study. We recommend future studies to evaluate whether controlling BPV among patients with stroke in Sub-Saharan Africa can reduce mortality., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors. Published by Elsevier B.V.)

The Infectious Diseases Institute (IDI), established in 2001, was the first autonomous institution of Makerere University set up as an example of what self-governing institutes can do in transforming the academic environment to become a rapidly progressive University addressing the needs of society This paper describes the success factors and lessons learned in development of sustainable centers of excellence to prepare academic institutions to respond appropriately to current and future challenges to global health. Key success factors included a) strong collaboration by local and international experts to combat the HIV pandemic, along with b) seed funding from Pfizer Inc., c) longstanding collaboration with Accordia Global Health Foundation to create and sustain institutional strengthening programs, d) development of a critical mass of multi-disciplinary research leaders and managers of the center, and e) a series of strong directors who built strong governance structures to execute the vision of the institute, with subsequent transition to local leadership., Conclusion: Twenty years of sustained investment in infrastructure, human capital, leadership, and collaborations present Makerere University and the sub-Saharan Africa region with an agile center of excellence with preparedness to meet the current and future challenges to global health., (© 2022 Nakanjako D et al.)

Introduction: Stroke burden is rapidly increasing globally. Modifiable risk factors offer an opportunity to intervene, and targeting hypertension is a key actionable target for stroke risk reduction in sub-Saharan Africa. This 3-site planned randomized controlled trial builds on promising preliminary data., Methods: A total of 246 Ugandan adults will be recruited randomized to experimental intervention vs. enhanced treatment control. Intervention participants will receive six weekly group-format stroke risk reduction self-management training sessions, and the controls will receive information on cardiovascular risk. The primary study outcome is systolic B.P. measured at baseline, 13-week, 24 weeks (6 months). Secondary outcomes include other biological and behavioral stroke risk factors., Discussion: The curriculum-guided self-management TargetEd MAnageMent Intervention (TEAM) program is anticipated to reduce the stroke burden in Uganda., Trial Registration: ClinicalTrials.gov identifier: NCT04685408, registered on 28 December 2020., Competing Interests: The authors have declared that no competing interests exist.

Background: Controlled prescription drug use disorders are a growing global health challenge in Sub-Saharan Africa. Effective supply chain regulations on dispensing and stock control are important for controlling this epidemic. Since compliance with these regulations in resource-limited countries is poor, there is need to understand its predictors in order to reduce the risk of prescription drug use disorders., Methods: A mixed-methods study utilizing a structured questionnaire and a simulated client guide was undertaken in Kampala and Mbale towns in Uganda. The questionnaire recorded self-reported dispensing and verified stock control practices and their covariates from 101 private pharmacies. The guide recorded actual dispensing practices from 27 pharmacies. Snowball sampling was done to enrich the sample with pharmacies that stock opioids. The mean compliance with good dispensing and stock control practices was calculated. Multivariate logistic regression analyses were applied to identify predictors of compliance., Results: The mean compliance with dispensing and stock control requirements was 82.9% and 23%, respectively. Twenty percent and 40% of the pharmacies dispensed pethidine without a prescription and with invalid prescriptions, respectively. Having a pharmacist on duty (OR = 5.17; p = 0.02), prior in-service training on narcotics regulations (OR = 3.51; p = 0.04), and previous narcotics audits by the regulator (OR = 5.11; p = 0.01) were independent predictors of compliance with stock control requirements. Pharmacies with a previous history of poor compliance with dispensing requirements were less likely to demonstrate good compliance (OR = 0.21; p = 0.01)., Conclusions: There is suboptimal compliance to controlled prescription drug regulations among Uganda's pharmacies. A previous history of poor compliance to dispensing requirements predicted low compliance in subsequent assessments. Training and regulatory audits increased compliance in stock control but not dispensing. Expansion of training and audits to more pharmacies and/or incentives for compliance are necessary.

Objective: Activated (CD38HLA-DR) PD-1 CD4 T cells are strongly associated with virus replication and disease progression in untreated HIV-1 infection, and viral persistence in individuals on ART. Few studies have examined cell-associated viral load (CAVL) in different activated CD4 T-cell populations to measure relative contributions to viral reservoirs., Design: Longitudinal assessment of HIV-1 chronically infected Ugandans initiating ART, to investigate activated CD4 T-cell populations and their contribution to viral reservoirs., Methods: We followed 32 HIV-1 chronically infected individuals from Kampala, Uganda, and determined their CD4 T-cell counts and viral load at baseline, 6, and 12 months after the initiation of ART. T-cell populations were sorted based on activation profiles and gag DNA was measured to determine CAVL within these populations. Soluble factors associated with inflammation were measured in plasma using a multiplexed platform., Results: Concomitant with viral load decline and CD4 T-cell count rebound, the activated PD-1 CD4 T-cell population contracted upon initiation of ART. Baseline levels of activated PD-1 CD4 T cells correlated with plasma levels of IP-10 and TNFRII. Interestingly, a higher baseline level of activated PD-1 CD4 T cells was associated with poorer CD4 T-cell recovery after 12 months of ART. This population contributed significantly to the cell-associated HIV DNA load at baseline, whereas their contribution declined on ART, indicating high turnover., Conclusion: Activated PD-1 CD4 T cells are predictors of poor immunologic recovery on ART and may represent a short-lived component of HIV-1 reservoirs.

Background: Optimal adherence to oral pre-exposure prophylaxis (PrEP) for HIV prevention involves aligning consistent PrEP use with periods of risk to achieve prevention-effective adherence. Prevention-effective adherence is predicated on individuals discontinuing PrEP during periods without expected risk. For stable, serodiscordant couples, antiretroviral therapy (ART) adherence by the HIV-positive partner markedly decreases HIV transmission risk, potentially obviating the need for continued PrEP use; yet little is known about actual lived experiences of discontinuing PrEP., Methods: In-depth qualitative interviews were conducted with HIV-uninfected PrEP users in serodiscordant couples taking part in the Partners Demonstration Project at IDI-Kasangati, Kampala, Uganda. Open-ended interviews elicited information on the partnered relationship; understandings of PrEP; prevention strategies; and experiences of PrEP discontinuation. An inductive, thematic, content-analytic approach was used to analyze study data., Results: Uninfected partners experienced PrEP as a valued resource for preventing HIV acquisition. Despite ongoing ART use by HIV-positive partners for a period of time consistent with viral suppression, discontinuation of PrEP was experienced as a loss of protection and a corresponding increase in risk of HIV acquisition. Uninfected partners responded with strategies aimed at offsetting this subjective sense of increased risk, specifically: (1) changing sexual practices; (2) prioritizing fidelity in the relationship; (3) increasing reliance on condoms; and (4) seeking evidence of partners' ART adherence., Conclusions: These experiences highlight the challenges PrEP users in serodiscordant couples face in discontinuing PrEP for prevention-effective adherence. Flexible interventions that support individuals during this transition may increase comfort with discontinuing PrEP when alternative prevention strategies provide protection, such as a partner's consistent adherence to ART.

HIV-1 infection expands large populations of late-stage differentiated CD8 T cells that may persist long after viral escape from TCR recognition. In this study, we investigated whether such CD8 T cell populations can perform unconventional innate-like antiviral effector functions. Chronic untreated HIV-1 infection was associated with elevated numbers of CD45RA + CD57 + terminal effector CD8 T cells expressing FcγRIIIA (CD16). The FcγRIIIA + CD8 T cells displayed a distinctive transcriptional profile between conventional CD8 T cells and NK cells, characterized by high levels of IKZF2 and low expression of IL7R This transcriptional profile translated into a distinct NKp80 + IL-7Rα - surface phenotype with high expression of the Helios transcription factor. Interestingly, the FcγRIIIA + CD8 T cells mediated HIV-specific Ab-dependent cellular cytotoxicity (ADCC) activity at levels comparable with NK cells on a per cell basis. The FcγRIIIA + CD8 T cells were highly activated in a manner that correlated positively with expansion of the CD8 T cell compartment and with plasma levels of soluble mediators of antiviral immunity and inflammation such as IP-10, TNF, IL-6, and TNFRII. The frequency of FcγRIIIA + CD8 T cells persisted as patients initiated suppressive antiretroviral therapy, although their activation levels declined. These data indicate that terminally differentiated effector CD8 T cells acquire enhanced innate cell-like characteristics during chronic viral infection and suggest that HIV-specific ADCC is a function CD8 T cells use to target HIV-infected cells. Furthermore, as the FcγRIIIA + CD8 T cells persist in treatment, they contribute significantly to the ADCC-capable effector cell pool in patients on antiretroviral therapy., (Copyright © 2019 The Authors.)

Background: A few reliable national data concerning the etiology of non-traumatic spinal cord injury (SCI) in sub-Sahara Africa exists, mainly because of the limitations of diagnostic imaging. These are both expensive and mostly unavailable in several resource-limited settings. Only a few studies have employed the magnetic resonance imaging (MRI) in documenting non-traumatic SCI and most of these studies are from South Africa. We sought to describe the clinical presentation, MRI radiological patterns, and one-year survival among subjects with non-traumatic SCI in Uganda., Methods: We enrolled a prospective cohort of 103 participants with non-traumatic SCI at Mulago National Referral Hospital Kampala, Uganda in 2013-2015. Participants received standard of care management, with surgical intervention as needed, with one-year follow up. Data were analyzed using Descriptive statistics., Results: In 103 participants with non-traumatic SCI, the median (IQR) age was 37 (18, 85) years and 25% of the participants were HIV-infected. Paraplegia/paraparesis was the most common clinical presentation in 70% (n = 72). Severe disease was present in 82% (n = 85) as per American Spinal Injury Association (ASIA) scale A-C. On MRI, 50% had extradural lesions. However, bone lesions accounted for only 75% of all the extradural lesions. More than 60% of the patients had lesions that could only be diagnosed on MRI. Deaths occurred in 42% (n = 44) of participants, with the highest mortality among those with extradural lesions (60%)., Conclusion: The mortality following non-traumatic spinal cord injuries in Uganda is high. We demonstrated an equal distribution between extradural and intradural lesions, which differs from the historical predominance of extradural lesions. Increased utilization of MRI particularly among young age groups is needed to make a diagnosis.

Introduction: Pre-exposure prophylaxis (PrEP) to prevent HIV infection is being rolled out in Africa. The uptake of PrEP to date has varied across populations and locations. We seek to understand the drivers of demand for PrEP through analysis of qualitative data collected in conjunction with a PrEP demonstration project involving East African HIV serodiscordant couples. Our goal was to inform demand creation by understanding what PrEP means - beyond HIV prevention - for the lives of users., Methods: The Partners Demonstration Project evaluated an integrated strategy of PrEP and antiretroviral therapy (ART) delivery in which time-limited PrEP served as a "bridge" to long-term ART. Uninfected partners in HIV serodiscordant couples were offered PrEP at baseline and encouraged to discontinue once infected partners had taken ART for six months. We conducted 274 open-ended interviews with 93 couples at two Ugandan research sites. Interviews took place one month after enrolment and at later points in the follow-up period. Topics included are as follows: (1) discovery of serodiscordance; (2) decisions to accept/decline PrEP and/or ART; (3) PrEP and ART initiation; (4) experiences of using PrEP and ART; (5) PrEP discontinuation; (6) impact of PrEP and ART on the partnered relationship. Interviews were audio-recorded and transcribed. We used an inductive, content analytic approach to characterize meanings of PrEP stemming from its effectiveness for HIV prevention. Relevant content was represented as descriptive categories., Results: Discovery of HIV serodiscordance resulted in fear of HIV transmission for couples, which led to loss of sexual intimacy in committed relationships, and to abandonment of plans for children. As a result, partners became alienated from each other. PrEP countered the threat to the relationship by reducing fear and reinstating hopes of having children together. Condom use worked against the re-establishment of intimacy and closeness. By increasing couples' sense of protection against HIV infection and raising the prospect of a return to "live sex" (sex without condoms), PrEP was perceived by couples as solving the problem of serodiscordance and preserving committed relationships., Conclusions: The most effective demand creation strategies for PrEP may be those that address the everyday life priorities of potential users in addition to HIV prevention., Clinical Trial Number: NCT02775929., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Introduction: Serodiscordant couples are a priority population for delivery of new HIV prevention interventions in Africa. An integrated strategy of delivering time-limited, oral pre-exposure prophylaxis (PrEP) to uninfected partners in serodiscordant couples as a bridge to long-term antiretroviral treatment (ART) for infected partners has been implemented in East Africa, nearly eliminating new infections. We conducted a qualitative evaluation of the integrated strategy in Uganda, to better understand its success., Methods: Data collection consisted of 274 in-depth interviews with 93 participating couples, and 55 observations of clinical encounters between couples and healthcare providers. An inductive content analytic approach aimed at understanding and interpreting couples' experiences of the integrated strategy was used to examine the data. Analysis sought to characterize: (1) key aspects of services provided; (2) what the services meant to recipients; and (3) how couples managed the integrated strategy. Themes were identified in each domain, and represented as descriptive categories. Categories were grouped inductively into more general propositions based on shared content. Propositions were linked and interpreted to explain "why the integrated strategy worked.", Results: Couples found "couples-focused" services provided through the integrated strategy strengthened partnered relationships threatened by the discovery of serodiscordance. They saw in services hope for "getting help" to stay together, turned joint visits to clinic into opportunities for mutual support, and experienced counselling as bringing them closer together. Couples adopted a "couples orientation" to the integrated strategy, considering the health of partners as they made decisions about initiating ART or accepting PrEP, and devising joint approaches to adherence. A couples orientation to services, grounded in strengthened partnerships, may have translated to greater success in using antiretrovirals to prevent HIV transmission., Conclusions: Various strategies for delivering antiretrovirals for HIV prevention are being evaluated. Understanding how and why these strategies work will improve evaluation processes and strengthen implementation platforms. We highlight the role of service organization in shaping couples' experiences of and responses to ART and PrEP in the context of the integrated strategy. Organizing services to promote positive care experiences will strengthen delivery and contribute to positive outcomes as antiretrovirals for prevention are rolled out., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Introduction: High quality PhD training in sub-Saharan Africa is important to strengthen research evidence to advance development and health. Training a critical mass of independent investigators capable of original scientific research requires strong mentorship, research environments, and international networks. We sought to iteratively improve a PhD training model in Uganda through systems capacity building., Methods: PhD students were selected through a rigorous competitive application and selection process, which included a written proposal and a face-to-face panel interview. The program provided administrative support, paid tuition fees, tools (space, equipment, research money), skills (short research courses on study design, biostatistics, manuscript and grant writing), and infrastructure (finance, grants management support, and lab infrastructure). Guidance to identify local and international mentorship was also provided in addition to two to three group meetings per year where data was presented and progress assessed by the program leaders in addition to available local mentors., Results: Seventeen PhD students were selected, and fifteen will complete training through the MEPI-MESAU program. To date, 60% have completed, including 2 students who started 2 years into the program. So far, 169 publications have been published in the peer-reviewed literature. Our PhD students have supervised and mentored 65 Master's students, which illustrates the cascade effect of PhD training on the academic medical school environment., Conclusions: The systems capacity building approach to PhD training is an efficient and productive training model that allowed strong outputs at lower cost and with relatively few additional mentors to rapidly achieve a critical mass of independent scientists able to conduct original research and mentor others., Competing Interests: The authors have no competing interests to declare., (© 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/.)

Background: Non-traumatic myelopathy is common in Africa and there are geographic differences in etiology. Clinical management is challenging due to the broad differential diagnosis and the lack of diagnostics. The objective of this systematic review is to determine the most common etiologies of non-traumatic myelopathy in sub-Saharan Africa to inform a regionally appropriate diagnostic algorithm., Methods: We conducted a systemic review searching Medline and Embase databases using the following search terms: "Non traumatic spinal cord injury" or "myelopathy" with limitations to epidemiology or etiologies and Sub-Saharan Africa. We described the frequencies of the different etiologies and proposed a diagnostic algorithm based on the most common diagnoses., Results: We identified 19 studies all performed at tertiary institutions; 15 were retrospective and 13 were published in the era of the HIV epidemic. Compressive bone lesions accounted for more than 48% of the cases; a majority were Pott's disease and metastatic disease. No diagnosis was identified in up to 30% of cases in most studies; in particular, definitive diagnoses of non-compressive lesions were rare and a majority were clinical diagnoses of transverse myelitis and HIV myelopathy. Age and HIV were major determinants of etiology., Conclusion: Compressive myelopathies represent a majority of non-traumatic myelopathies in sub-Saharan Africa, and most were due to Pott's disease. Non-compressive myelopathies have not been well defined and need further research in Africa. We recommend a standardized approach to management of non-traumatic myelopathy focused on identifying treatable conditions with tests widely available in low-resource settings.

Background: No guidelines exist on assessing ventilation through air changes per hour (ACH) using a vaneometer. The objective of the study was to evaluate the position and frequency for measuring air velocity using a vaneometer to assess ventilation with ACH; and to assess influence of ambient temperature and weather on ACH., Methods: Cross-sectional survey in six urban health facilities in Kampala, Uganda. Measurements consisted of taking air velocity on nine separate moments in five positions in each opening of the TB clinic, laboratory, outpatient consultation and outpatient waiting room using a vaneometer. We assessed in addition the ventilation with the "20% rule", and compared this estimation with the ventilation in ACH assessed using the vaneometer., Results: A total of 189 measurements showed no influence on air velocity of the position and moment of the measurement. No significant influence existed of ambient temperature and a small but significant influence of sunny weather. Ventilation was adequate in 17/24 (71%) of all measurements. Using the "20% rule", ventilation was adequate in 50% of rooms assessed. Agreement between both methods existed in 13/23 (56%) of the rooms assessed., Conclusion: Most rooms had adequate ventilation when assessed using a vaneometer for measuring air velocity. A single vaneometer measurement of air velocity is adequate to assess ventilation in this setting. These findings provide practical input for clear guidelines on assessing ventilation using a vaneometer. Assessing ventilation with a vaneometer differs substantially from applying the "20% rule".

Background: As pre-exposure prophylaxis (PrEP) becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking PrEP. We investigated whether tenofovir and emtricitabine are excreted into breast milk and then absorbed by the breastfeeding infant in clinically significant concentrations when used as PrEP by lactating women., Methods and Findings: We conducted a prospective short-term, open-label study of daily oral emtricitabine-tenofovir disoproxil fumarate PrEP among 50 HIV-uninfected breastfeeding African mother-infant pairs between 1-24 wk postpartum (ClinicalTrials.gov Identifier: NCT02776748). The primary goal was to quantify the steady-state concentrations of tenofovir and emtricitabine in infant plasma ingested via breastfeeding. PrEP was administered to women through daily directly observed therapy (DOT) for ten consecutive days and then discontinued thereafter. Non-fasting peak and trough samples of maternal plasma and breast milk were obtained at drug concentration steady states on days 7 and 10, and a single infant plasma sample was obtained on day 7. Peak blood and breast milk samples were obtained 1-2 h after the maternal DOT PrEP dose, while maternal trough samples were obtained at the end of the PrEP dosing interval (i.e., 23 to 24 h) after maternal DOT PrEP dose. Tenofovir and emtricitabine concentrations were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays. Of the 50 mother-infant pairs enrolled, 48% were ≤12 wk and 52% were 13-24 wk postpartum, and median maternal age was 25 y (interquartile range [IQR] 22-28). During study follow-up, the median (IQR) daily reported frequency of infant breastfeeding was 15 times (12 to 18) overall, 16 (14 to 19) for the ≤12 weeks, and 14 (12 to 17) for the 13-24 wk infant age groups. Overall, median (IQR) time-averaged peak concentrations in breast milk were 3.2 ng/mL (2.3 to 4.7) for tenofovir and 212.5 ng/mL (140.0 to 405.0) for emtricitabine. Similarly, median (IQR) time-averaged trough concentrations in breast milk were 3.3 ng/mL (2.3 to 4.4) for tenofovir and 183.0 ng/mL (113.0 to 250.0) for emtricitabine, reflecting trough-to-peak breast milk concentration ratios of 1.0 for tenofovir and 0.8 for emtricitabine, respectively. In infant plasma, tenofovir was unquantifiable in 46/49 samples (94%), but emtricitabine was detectable in 47/49 (96%) (median [IQR] concentration: 13.2 ng/mL [9.3 to 16.7]). The estimated equivalent doses an infant would ingest daily from breastfeeding were 0.47 μg/kg (IQR 0.35 to 0.71) for tenofovir and 31.9 μg/kg (IQR 21.0 to 60.8) for emtricitabine, translating into a <0.01% and 0.5% relative dose when compared to the 6 mg/kg dose that is proposed for therapeutic treatment of infant HIV infection and for prevention of infant postnatal HIV infection; a dose that has not shown safety concerns. No serious adverse effects were recorded during study follow-up. The key study limitation was that only a single infant sample was collected to minimize venipunctures for the children. However, maternal daily DOT and specimen collection at drug concentration steady state provided an adequate approach to address the key research question. Importantly, there was minimal variation in breast milk concentrations of tenofovir and emtricitabine (respective median trough-to-peak concentration ratio ~1), demonstrating that infants were exposed to consistent drug dosing via breast milk., Conclusion: In this short-term study of daily directly observed oral PrEP in HIV-uninfected breastfeeding women, the estimated infant doses from breast milk and resultant infant plasma concentrations for tenofovir and emtricitabine were 12,500 and >200-fold lower than the respective proposed infant therapeutic doses, and tenofovir was not detected in 94% of infant plasma samples. These data suggest that PrEP can be safely used during breastfeeding with minimal infant drug exposure., Trial Registration: ClinicalTrials.gov, Identifier: NCT02776748., Competing Interests: I have read the journal's policy, and the authors of this manuscript have the following competing interests: FTC-TDF was donated by Gilead Sciences. CWH reports a prior contract from Gilead Sciences outside the submitted work and a patent pending, both managed by Johns Hopkins. MM has grant funding via the NIH. GJS has research grants from NIH (unrelated), CDC (unrelated), Thrasher Foundation (unrelated), Bill and Melinda Gates Foundation (sponsor), royalties from UpToDate (unrelated), and salary support from the University of Washington. All authors declare no other conflicts of interest.

Background: Hyponatraemia is a common electrolyte disturbance among older patients. We determined the prevalence of and factors associated with hyponatraemia among older patients with predominantly acute decompensated heart failure attending a tertiary hospital in Kampala, Uganda., Objectives: Main study aim: (1) to determine the prevalence of hyponatraemia among patients aged 60 years and above with heart failure attending Mulago National Referral Hospital; (2) to describe the factors associated with hyponatraemia among patients aged 60 years and above with heart failure attending Mulago National Referral Hospital., Setting: The study was conducted in one tertiary hospital located in the northeast of Kampala, Uganda., Participants: 400 adults aged 60 years and above were identified for the study. Of these, 188 were excluded as they did not fulfil the inclusion criteria and one declined to participate, leaving a final study group of 211 older adults aged 60 years and above, with a clinical diagnosis of heart failure using Framingham's criteria., Results: The prevalence of hyponatraemia was 24.2% (51/211). Hyponatraemia was mainly found in patients with mild-to-moderate heart failure, New York Heart Association classes 2 and 3. Of the 51 patients with hyponatraemia, 27 (52.9%) had mild hyponatraemia, while 24 (47.1%) had moderate to severe hyponatraemia of 130-125 mmol/L. History of vomiting (OR=2.94, 95% CI 1.29 to 6.70, p=0.010) and use of loop diuretics (OR=2.71, 95% CI 1.13 to 6.52, p=0.026) were identified as independent factors associated with hyponatraemia among older patients with heart failure., Conclusions: Our study revealed a relatively high prevalence of hyponatraemia among older patients with mild to moderate heart failure. Patients presenting with a history of vomiting from any cause or use of loop diuretics were more likely to have hyponatraemia., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Symptom clusters are gaining importance given HIV/AIDS patients experience multiple, concurrent symptoms. This study aimed to: determine clusters of patients with similar symptom combinations; describe symptom combinations distinguishing the clusters; and evaluate the clusters regarding patient socio-demographic, disease and treatment characteristics, quality of life (QOL) and functional performance. This was a cross-sectional study of 302 adult HIV/AIDS outpatients consecutively recruited at two teaching and referral hospitals in Uganda. Socio-demographic and seven-day period symptom prevalence and distress data were self-reported using the Memorial Symptom Assessment Schedule. QOL was assessed using the Medical Outcome Scale and functional performance using the Karnofsky Performance Scale. Symptom clusters were established using hierarchical cluster analysis with squared Euclidean distances using Ward's clustering methods based on symptom occurrence. Analysis of variance compared clusters on mean QOL and functional performance scores. Patient subgroups were categorised based on symptom occurrence rates. Five symptom occurrence clusters were identified: Cluster 1 (n=107), high-low for sensory discomfort and eating difficulties symptoms; Cluster 2 (n=47), high-low for psycho-gastrointestinal symptoms; Cluster 3 (n=71), high for pain and sensory disturbance symptoms; Cluster 4 (n=35), all high for general HIV/AIDS symptoms; and Cluster 5 (n=48), all low for mood-cognitive symptoms. The all high occurrence cluster was associated with worst functional status, poorest QOL scores and highest symptom-associated distress. Use of antiretroviral therapy was associated with all high symptom occurrence rate (Fisher's exact=4, P<0.001). CD4 count group below 200 was associated with the all high occurrence rate symptom cluster (Fisher's exact=41, P<0.001). Symptom clusters have a differential, affect HIV/AIDS patients' self-reported outcomes, with the subgroup experiencing high-symptom occurrence rates having a higher risk of poorer outcomes. Identification of symptom clusters could provide insights into commonly co-occurring symptoms that should be jointly targeted for management in patients with multiple complaints.

Background: Symptom distress is poorly described in persons living with HIV, with limited attention paid to physical and psychological symptom prevalence to inform optimal clinical care., Objectives: The study objective was to measure seven-day-period prevalence of symptoms among HIV-infected adult outpatients and determine if self-reported symptom burden is associated with antiretroviral therapy (ART), CD4 T-cell count, and clinical disease stage., Methods: Adult patients were consecutively recruited from HIV outpatient clinics at two referral and teaching hospitals in Uganda. Of 343 patients approached, 302 (88%) participated. Patients described symptoms during the previous week using the Memorial Symptom Assessment Scale Short Form, and level of physical functionality using the Karnofsky Performance Status (KPS) tool on the interview day., Results: A high symptom burden was reported, with the most prevalent being worry (94%), feeling sad (92%), hunger (82%), feeling nervous (75%), and feeling drowsy/tired (62%). Patients with KPS scores of <70 reported more symptoms (23 versus 10; F=289.68, P<0.001) and higher symptom distress (P<0.04 for all analyses). Neither ART nor CD4 T-cell count were associated with symptom burden. WHO clinical stage 4 was associated with psychological symptom burden (OR 2.94, P=0.011, CI 1.281-6.735). Men were more likely to experience higher symptom burden., Conclusion: In the ART era, ambulatory HIV/AIDS patients continue to experience a high physical and psychological symptom burden. For those with advanced disease, psychological symptoms are particularly important. It is important to be observant of gender differences in patterns of symptom distress in HIV outpatient care settings. The high prevalence of hunger warrants attention as it may compromise ART initiation and adherence to ART.

Background: Highly active antiretroviral therapy (HAART) has been associated with liver toxicity. The role of monitoring for liver toxicity has not been well studied in resource-limited settings (RLS)., Objectives: To determine the background prevalence and incidence of liver injury and describe the associated signs and symptoms of acute hepatitis after initiating HAART; and to determine the role of liver enzyme tests in monitoring hepatotoxicity., Methods: In this prospective study, in Mulago Hospital AIDS Clinics, we consecutively enrolled adult patients initiated on one of three first line HAART regimens [Stavudine (d4T)-Lamivudine (3TC) and nevirapine (NVP); Zidovudine (AZT)-3TC and Efavirenz (EFV) or d4T-3TC-EFV]. We monitored ALT (alanine aminotransferase) and clinical evidence of acute hepatitis at baseline, 2(nd), 6(th), 10(th) and 14(th) week of therapy., Results: Two hundred and forty HIV-positive HAART- naïve patients were enrolled in the study. The baseline prevalence of transaminitis was 1.7% with an incidence of 4.2% at 14 weeks. Grade 3-4 hepatotoxicity was documented in 1.3%. Jaundice was seen in grade 2-4 ALT elevations. Being on concurrent HAART and antituberculous drugs was associated with grade 2-4 toxicity compared to those who were only on HAART [OR; 16.0 (95% CI; 2.4-104.2)]., Conclusions: Incidence of severe hepatotoxicity within three months of first-line antiretroviral therapy was low, suggesting that routine measurement of transaminases may not be necessary in all patients initiating HAART in RLS. Routine measurement may be important in following patients on HAART and concurrent TB treatment as well as those with jaundice to avoid missing hepatotoxicity.

Although more than 25 million people in sub-Saharan Africa have human immunodeficiency virus (HIV) infection, little is known regarding their cancer risk. We investigated cancer risk among persons with HIV/AIDS in Uganda using record-linkage. We linked records of 12,607 HIV-infected persons attending The AIDS Support Organization (TASO) in Kyadondo County from October 1988 through December 2002 to the Kampala Cancer Registry. We calculated standardized incidence ratios (SIRs) to identify increased cancer risks in the early (4-27 months after TASO registration), late (28-60 months), or combined (4-60 months) incidence periods. We identified 378 cancers (181 prevalent, 197 incident) among TASO participants. Of incident cancers, 137 (70%) were AIDS-defining cancers. Risk was increased in the early-incident period, compared to the general population, for the AIDS-defining cancers: Kaposi sarcoma (SIR 6.4, 95%CI 4.8-8.4), non-Hodgkin lymphoma (6.7, 1.8-17), and cervical carcinoma (2.4, 1.1-4.4). These three cancers were also increased in the combined periods. Risks of five non-AIDS-defining cancers were increased in the combined periods: Hodgkin lymphoma (5.7, 1.2-17) and cancers of the conjunctiva (SIR 4.0; 1.5-8.7), kidney (16, 1.8-58), thyroid (5.7, 1.1-16), and uterus (5.5, 1.5-14). Cancers of the breast, nasopharynx, and lung were increased either in the early or late incident periods only. Among 407 children, seven cancers were observed, of which five were Kaposi sarcoma. The application of a record-linkage design in Africa broadens the repertoire of epidemiological tools for studying HIV-infected populations. We confirm the increased risks of AIDS-defining cancers and report increased risks of a few non-AIDS-defining cancers.

Our objective was to determine the level of adherence and reasons for non-adherence to antiretroviral therapy (ART) among HIV-positive (HIV+) people on ART in a resource-limited setting. Patients receiving ART were recruited into the cross-sectional study from three treatment centres in Kampala, Uganda. The number of missed doses over the last three days was assessed by structured patient interviews and dichotomized at +/-95% adherence. Reasons for non-adherence were assessed with both structured patient interviews and unstructured qualitative interviews. Independent predictors of non-adherence were assessed with multivariate logistic regression. In all, 304 HIV-infected persons on ART were enrolled into the study. Factors associated with non-adherence were marital status (odds ratio (OR) = 2.93, 95% confidence interval (CI) 1.32-6.50) and low monthly income <50 US$ [OR = 2.77, 95% CI 1.64-4.67]. We concluded that levels of self-reported adherence in patients receiving ART in Kampala are comparable to levels in resource-rich settings with inability to purchase and secure a stable supply as a major barrier to adherence.

Introduction: Total Lymphocyte Count (TLC) has been found to be an inexpensive and useful marker for staging disease, predicting progression to AIDS and death and monitoring response to ART. However, the correlation between TLC and CD4 has not been consistent. Access to HAART is expanding in Kampala, Uganda, yet there are no published data evaluating the utility of TLC as inexpensive surrogate marker of CD4 cell count to help guide therapeutic decisions., Objective: To evaluate clinical illnesses and total lymphocyte count (TLC) as surrogate markers of the CD4 cell count in HIV infected persons being considered for ART., Methods: A total of 131 patients were enrolled and evaluated by clinical assessment, TLC and CD4 count. Clinical illnesses and TLC dichotomized at various cut-point values were used to determine the sensitivity, specificity, and positive and negative predictive values (PPV and NPV) for the diagnosis of CD4 count <200 cells/mm 3 among 100 participants fulfilling criteria for WHO clinical stage 2 and 3., Results: A strong correlation was observed between TLC and CD4 (r = 0.73, p<0.0001). For all clinical syndromes, except pulmonary tuberculosis, the positive predictive values (PPV) for a CD4 count <200 cells/mm 3 were high (>80%) but the negative predictive values (NPV) were low. Using the WHO recommended TLC cut-off of 1200 cells/mm 3 to diagnose a CD4 less than 200 cells/mm 3 , the PPV was 100%, and the NPV was 32%., Conclusion: Our data showed a good correlation between TLC and CD4 cell count. However, the WHO recommended TLC cut-off of 1200 did not identify the majority of WHO stage 2 and 3 patients with CD4 counts less than 200 cells/mm 3 . A more rational use of TLC counts is to treat all patients with WHO stage 2 and 3 who have a TLC <1200 and to limit CD4 counts to patients who are symptomatic but have TLC of >1200.

A 30-year old black woman presented with gradual onset of weakness of the legs associated with burning sensation in the feet for two months. She had been using two hydroquinone based skin bleaching creams (MGC by M. G. C. International, MEKAKO by Anglo Fabrics BOLTON Ltd) for about four years. Her BP was 80/40 mm Hg supine with un-recordable diastolic pressure on standing. She had decreased power (Grade 3/5), loss of deep tendon reflexes and impairment of deep sensation in the lower limbs. A complete blood count, urinalysis, serum electrolytes, serum creatinine and uric acid were all normal. Oral GTT, VDRL and brucella tests were negative. Chest and abdominal radiographs did not show any abnormalities. A diagnosis of peripheral neuropathy with autonomic neuropathy possibly due to hydroquinone toxicity was made and she was advised to stop using hydroquinone based skin bleaching creams. Four months later she was asymptomatic, her BP was 120/80 mmHg supine and standing, and neurological examination was normal. The case raises the question of whether hydroquinone based skin bleaching creams could be a cause of peripheral neuropathy and underscores the need for research on hydroquinone based skin bleaching creams and neuropathy particularly in black women involved in the sale and/or use of skin bleaching creams.

Chloroquine-resistant falciparum malaria is a serious problem in much of sub-Saharan Africa. However, it is desirable to continue to use chloroquine as first-line therapy for uncomplicated malaria where it remains clinically effective. To identify predictors of chloroquine treatment failure, a 14-day clinical study of chloroquine resistance in patients with uncomplicated falciparum malaria was performed in Kampala, Uganda. Among the 258 patients (88% follow-up), 47% were clinical failures (early or late treatment failure) and 70% had parasitological resistance (RI-RIII). Using multivariate analysis, an age less than five (odds ratio [OR] = 3.4, 95% CI = 1.8-6.3) and a presenting temperature over 38.0 degreesC (OR = 2.0, 95% CI = 1.1-3.7) were independent predictors of treatment failure. In addition, patients who last took chloroquine 3 to 14 days prior to study entry were significantly more likely to be treatment failures compared to patients with very recent (less than 3 days) or no recent chloroquine use. In areas with significant chloroquine resistance, easily identifiable predictors of chloroquine treatment failure might be used to stratify patients into those for whom chloroquine use is acceptable and those for whom alternative treatment should be used.

Diarrhea is the most common gastrointestinal symptom in human immunodeficiency virus (HIV) infection. It affects up to 90% of patients, becoming more frequent and severe as the immune system deteriorates. It often is associated with significant morbidity and mortality particularly in the developing countries. Gastrointestinal infections, some of which are attributable to inadequate sanitation and poor hygiene are the predominant cause of diarrhea, although multiple medications, including traditional herbs, also may be causes. The basic principles of management include detection of treatable causes, relief of symptoms, prevention of malnutrition, and psychosocial support. In up to 60% of cases, no cause can be identified, partly because of inadequate investigative facilities. Symptomatic treatment is the mainstay of management particularly when no cause can be identified. Unfortunately this can be extremely difficult when the patient is severely immune-suppressed. There is poor response to motility control drugs, such as loperamide, and others, such as octreotide, are too expensive. Fluid replacement should be started early to prevent excessive dehydration. This should be combined with nutritional support to prevent malnutrition. Psychosocial support, including counselling, for both the patient and the caring relatives, is required to alleviate anxiety, particularly when the diarrhea becomes intractable.

Background: Interferon alfa (IFN-alpha) exhibits dose related in vitro activity against human immunodeficiency virus (HIV), with complete inhibition of HIV replication at IFN-alpha concentrations > or = 256 IU/ml. In mid-1990, Kenyan investigators reported that oral administration of an extremely low dose (150 IU/day) of natural human (nHu) IFN-alpha resulted in complete alleviation of AIDS related complex and AIDS symptoms and resolution of opportunistic infections without additional treatment. Moreover, loss of HIV antibody seropositivity was reported in approximately 10% of treated patients. Subsequent small studies failed to substantiate these spectacular claims, but controversy on the efficacy of this treatment persisted., Methods: We studied 559 adult Ugandan patients with WHO stage 2-4 HIV infection and a Karnofsky performance score of more than 50, who had not received any drugs with antiretroviral activity in the previous 3 months. The patients were randomly assigned in a double blind fashion either to 150 IU oral nHuIFN-alpha/day or placebo. The duration of treatment was extended from 28 weeks to 60 weeks 9 months after enrollment had started. At that time 112 subjects had already received 28 weeks of treatment and been discontinued from the study., Results: Both study groups were comparable with respect to all baseline characteristics studied, except that the nHuIFN-alpha group had slightly lower absolute CD4+ lymphocyte counts (median 60.7 x 10(6)/l) than the placebo group (median 85.3 x 10(6)/l) (p = 0.033). Therefore, all analyses were adjusted for CD4+ lymphocyte counts at entry. In both treatment groups there was relentless progression of HIV disease. Subjects treated with nHuIFN-alpha and placebo had similar mortality, disease progression rates, decline of CD4+ lymphocyte counts and Karnofsky performance scores, and prevalence of symptoms. No patient reverted to HIV-1 seronegative antibody status. Serious adverse events were not seen. Quality control of the study medication documented that the active drug indeed contained IFN-alpha activity., Conclusions: The current large, randomised, double blind, placebo controlled study did not show any benefit from oral treatment with 150 IU nHuIFN-alpha/day in a population of African patients with symptomatic HIV infection.