Gentamicin concentration and acute kidney injury in term neonates treated for neonatal sepsis with gentamicin and ampicillin-cloxacillin combination.

Gentamicin is widely used to treat neonatal infections caused by both Gram-negative and Gram-positive bacteria, and the WHO recommends its use while monitoring serum creatinine and gentamicin concentrations to avoid drug-induced nephrotoxicity and ototoxicity. Yet in some resource-limited settings, the drug is used without monitoring. A population pharmacokinetics study involving term neonates with neonatal infection admitted to a neonatal unit. Participants were started on intravenous gentamicin 5 mg/kg once a day in combination with ampicilin-cloxacillin. Blood samples for serum gentamicin concentration were taken at 0.25, 0.5, 1, 2, 3, 5, 6, 8, 10, 12, 14, 16, 18, 20, 23, and 24 hours after the initial dose, each participant contributing two samples to the 24 hour sampling schedule. An additional sample for trough concentration was taken from each participant just before the third gentamicin dose while serum creatinine concentration was measured before and after treatment. Twenty-four participants were enrolled into the study and included in the final analysis. Mean (SD) peak and trough serum gentamicin concentrations were 16.66 (0.64) µg/mL and 3.28 (0.70) µg/mL, respectively. Gentamicin clearance (CL) was 0.40 mL min-1 kg-1 and volume of distribution (VD) was 0.31 L kg-1. Mean (SD) serum creatinine level after treatment was 209.7 (70.4) µmol/L compared to 103.3 (23.6) µmol/L before treatment [mean difference (106.4 ± 67.1; 95% confidence interval (CI): 78.1; 134.7 µmol/L; t (23) = 7.77; P < 0.001]. All participants fulfilled the Kidney Disease Improving Global Outcomes (KDIGO) criteria for acute kidney injury after treatment. Treatment of neonatal infection with antimicrobial regimen containing gentamicin, without renal function and gentamicin concentration monitoring, carries a significant risk for drug-induced acute kidney injury.

Hypertension and immune activation in antiretroviral therapy naïve people living with human immunodeficiency virus.

BACKGROUND: The pathogenesis of hypertension (HTN) in people living with HIV/AIDS (PLHIV) is complex and remains not fully understood. Chronic immune activation (IA) is postulated to be one of the culprits. This notion is derived from studies in HIV-uninfected populations and/or animals while data on HTN and how it relates to IA in PLHIV remains scarce. We determined the relationship between HTN and IA among antiretroviral therapy (ART) naïve PLHIV. METHODS: We analysed baseline data of 365 out of 430 clinical trial participants whose main aim was to investigate the effect of low-dose aspirin on HIV disease progression in PLHIV starting ART. Soluble CD14 (sCD14), T cells co-expressing CD38 and HLA-DR, and PD-1 were the IA and exhaustion markers, respectively studied and were analysed by flow cytometry. Mann-Whitney U-test was used for comparison of the markers by HTN status. A robust Poisson regression model was used to determine the predictors for HTN. RESULTS: A quarter of the 365 were hypertensive (25.3%, 95% CI 20.9-29.8%), and, had higher median (IQR) body mass index (kg/m2) (23.4 (19.6, 28.0) versus 21.9 (19.3, 25.1)) and lower median (IQR) estimated glomerular filtration rate (mL/min/1.73m2) (101.2 (79.4, 126.9) versus 113.6 (92.7, 138.8)) than normotensive participants (p < 0.05). Participants with HTN had higher median frequencies of all markers of IA and exhaustion but lower sCD14 (p > 0.05). None of these markers significantly predicted the occurrence of HTN. CONCLUSION: Studied markers of IA and exhaustion were higher in PLHIV with HTN than those without but were unpredictive of HTN. Larger multicentre studies with a wider range of markers are needed to confirm the role of IA in HIV-associated HTN.

Hypertension and traditional risk factors for cardiovascular diseases among treatment naïve HIV- infected adults initiating antiretroviral therapy in Urban Tanzania.

BACKGROUND: Cardiovascular diseases (CVDs) have become an important cause of ill health and death among people living with HIV and/or AIDS (PLHIV) in the antiretroviral therapy (ART) era. There is scarce data on the burden of hypertension (HTN) and risk factors for CVDs among PLHIV in developing countries, including Tanzania during the ART era. OBJECTIVE(S): To determine the prevalence of HTN and risk factors for CVDs among ART naïve PLHIV initiating ART. METHODS: We analysed baseline data of 430 clinical trial participants on the effect of low-dose aspirin on HIV disease progression among HIV-infected individuals initiating ART. HTN was the outcome CVD. Traditional risk factors for CVDs studied were age, alcohol consumption, cigarette smoking, individual and family history of CVDs, diabetes mellitus (DM), obesity/overweight, and dyslipidaemia. A generalized linear model (robust Poisson regression) was used to determine the predictors for HTN. RESULTS: The median (IQR) age was 37 (28, 45) years. Females were the majority contributing 64.9% of all participants. The prevalence of HTN was 24.8%. The most prevalent risk factors for CVDs were dyslipidaemia (88.3%), alcohol consumption (49.3%), and overweight or obesity (29.1%). Being overweight or obese predicted the occurrence of HTN, aPR 1.60 (95% CI 1.16-2.21) while WHO HIV clinical stage 3 was protective against HTN, aPR 0.42(95% CI 0.18-0.97). CONCLUSION: The prevalence of HTN and traditional risk factors for CVDs in the treatment naïve PLHIV initiating ART are significant. Identifying these risk factors and managing them at the time of ART initiation may lower future CVDs among PLHIV.

Mentorship of young researchers in resource-limited settings: experiences of the mentees from selected health sciences Universities in Tanzania.

INTRODUCTION: Mentorship is an essential component of research capacity building for young researchers in the health sciences. The mentorship environment in resource-limited settings is gradually improving. This article describes mentees' experiences in a mentorship program for junior academicians amid the COVID-19 pandemic in Tanzania. METHODS: This is a survey study that examined the experiences of mentees who participated in a mentorship program developed as part of the Transforming Health Education in Tanzania (THET) project. The THET project was funded by the US National Institutes of Health (NIH) under a consortium of three partnering academic institutions in Tanzania and two collaborating US-based institutions. Senior faculty members of respective academic institutions were designated as mentors of junior faculty. Quarterly reports submitted by mentees for the first four years of the mentorship program from 2018 to 2022 were used as data sources. RESULTS: The mentorship program included a total of 12 mentees equally selected from each of the three health training institutions in Tanzania. The majority (7/12) of the mentees in the program were males. All mentees had a master's degree, and the majorities (8/12) were members of Schools/Faculties of Medicine. Most mentors (9/10) were from Tanzania's three partnering health training institutions. All mentors had an academic rank of senior lecturer or professor. Despite the onset of the COVID-19 pandemic, the regular weekly meetings between mentors and mentees were not affected. By the fourth year of the mentorship program, more than three-quarters of mentees had published research related to the mentorship program in a peer-reviewed journal, over half had enrolled in Ph.D. studies, and half had applied for and won competitive grant awards. Almost all mentees reported being satisfied with the mentorship program and their achievements. CONCLUSION: The mentorship program enhanced the skills and experiences of the mentees as evidenced by the quality of their research outputs and their dissemination of research findings. The mentorship program encouraged mentees to further their education and enhanced other skills such as grant writing. These results support the initiation of similar mentorship programs in other institutions to expand their capacity in biomedical, social, and clinical research, especially in resource-limited settings, such as Sub-Saharan Africa.

Molecular surveillance of chloroquine-resistant Plasmodium falciparum in sub-Saharan African countries after withdrawal of chloroquine for treatment of uncomplicated malaria: A systematic review.

BACKGROUND: A wide spread of chloroquine resistance prompted its discontinued use for treatment of uncomplicated malaria in several African countries. However, disappearances of chloroquine-resistant parasites have been reported in areas with restricted use of chloroquine. This review reports the current prevalence of chloroquine-resistant Plasmodium falciparum using Pfcrt K76T and Pfmdr1 N86Y genotypes. METHODS: A PROSPERO registered systematic review searched evidence from PubMed/MEDLINE, Science Direct and Google Scholar. The search included studies on chloroquine-resistant/ susceptible P. falciparum in humans between January 1st, 2000 and May 15th, 2020. The search was conducted on 15th of May, 2020. RESULTS: Out of 519 searched records, 15 studies qualified for final analysis with 8040 samples genotyped for Pfcrt K76T. Of 8040, 43.6% (837/1572; 95%CI: -0.9 to 88.1%) carried resistant genotypes versus 23.0% (1477/6468; 95%CI: 15.7-30.2%) while for 4698 samples analyzed for Pfmdr1 N86Y, 52.4% (592/1090; 95%CI: 42.3-62.5%) had resistant genotypes versus 25.9% (1314/3608; 95%CI: 5.8-46.0%), before and after chloroquine withdrawal, respectively. The median time since chloroquine withdrawal to data collection was 7.0 (interquartile range: 4.5-13.5) years. Low prevalence of resistant genotypes (Pfcrt K76T) was reported in Zambia (0%) in 2013, Malawi (0.1%) in 2009, Tanzania (0.2%) in 2018 and Madagascar (0.3%) in 2007 with significant variations in the included studies. CONCLUSIONS: Chloroquine-resistant P. falciparum continues to disappear in countries with withdrawal of chloroquine. Areas with significant susceptible parasites, reintroduction of chloroquine can be considered, preferably in combination with other safe and affordable antimalarials.

Effect of aspirin on HIV disease progression among HIV-infected individuals initiating antiretroviral therapy: study protocol for a randomised controlled trial.

INTRODUCTION: An increase in cardiovascular disease (CVD) among people living with HIV infection is linked to platelet and immune activation, a phenomenon unabolished by antiretroviral (ARV) drugs alone. In small studies, aspirin (acetylsalicylic acid [ASA]) has been shown to control immune activation, increase CD4+ count, halt HIV disease progression and reduce HIV viral load (HVL). We present a protocol for a larger ongoing randomised placebo controlled trial on the effect of an addition of ASA to ARV drugs on HIV disease progression. METHODS AND ANALYSIS: A single-centre phase IIA double-blind, parallel-group randomised controlled trial intends to recruit 454 consenting ARV drug-naïve, HIV-infected adults initiating ART. Participants are randomised in blocks of 10 in a 1:1 ratio to receive, in addition to ARV drugs, 75 mg ASA or placebo for 6 months. The primary outcome is the proportion of participants attaining HVL of <50 copies/mL by 8, 12 and 24 weeks. Secondary outcomes include proportions of participants with HVL of >1000 copies/mL at week 24, attaining a >30% rise of CD4 count from baseline value at week 12, experiencing adverse events, with normal levels of biomarkers of platelet and immune activation at weeks 12 and 24 and rates of morbidity and all-cause mortality. Intention-to-treat analysis will be done for all study outcomes. ETHICS AND DISSEMINATION: Ethical approval has been obtained from institutional and national ethics review committees. Findings will be submitted to peer-reviewed journals and presented in scientific conferences. TRIAL REGISTRATION NUMBER: PACTR202003522049711.

How do community advisory boards fulfil their ethical role in HIV clinical trials? A protocol for a systematic review of qualitative evidence.

INTRODUCTION: Community advisory boards (CABs) continue to gain wide use and acceptance in global health research including in HIV clinical trials. They provide means through which community concerns regarding the trial can be considered by the research team, and provide an important platform of communication between the researchers and the community about study goals. Therefore, this systematic review protocol will guide the review of qualitative evidence on the ethical roles of CABs in HIV clinical trials based on the three fundamental ethical principles: respect for the person, beneficence and justice. METHODS AND ANALYSIS: This systematic review of qualitative evidence will involve searching four medical databases: PubMed, ScienceDirect, CINAHL and Cochrane Library. Additionally, other relevant evidence will be obtained through hand searching and grey literature. Searches will be limited to studies published in the English language from 1989 (the year that CABs were first established in HIV clinical trials) to 2019. Articles searched will be screened by two independent authors based on inclusion and exclusion criteria. Included articles will be appraised for quality using the Critical Appraisal Skills Programme checklist and followed by qualitative data extraction. Findings will be analysed based on the meta-aggregative approach with the aid of EPPI-Reviewer 4 web-based software. ETHICS AND DISSEMINATION: Ethical approval does not apply to this review. Data will be disseminated through scientific conferences and peer-reviewed journals to inform policies and stake-holders about the ethical role of CABs. PROSPERO REGISTRATION NUMBER: CRD42019133787.