Chronic kidney disease in patients admitted to the medical ward of Mbarara Regional Referral Hospital in southwestern Uganda: Prevalence and associated factors

Background: In tropical Africa, although chronic kidney disease (CKD) is common, there are few data about its’ prevalence among patients admitted to a general medical ward. Aim: We proposed to determine the prevalence of CKD among patients admitted to a general medical ward in Uganda. Methods: We conducted a cross sectional study consecutively enrolling adults admitted to the medical ward of Mbarara Regional Referral Hospital over three months. We collected socio-demographic and clinical data including presenting symptoms, history of diabetes, hypertension, and use of nephrotoxic medication. Consenting patients provided spot morning urine specimen for measurement of urine albumin and we also drew patients’ blood for measurement of markers of renal function, complete blood count, hepatitis B surface antigen, and HIV. We also performed renal sonography for all included patients. We defined CKD as a glomerular filtration rate (eGFR) less than 60ml/min/1.73m².We used logistic regression to assess for factors associated with CKD. Results: Of the 372 patients enrolled, 57 (15.3%) had CKD. Body swelling (OR=2.79, 95% CI 1.53-5.07; p=0.001), active urine sediment (OR=3.13, 95% CI 1.64-6.41; p=0.016), microalbuminuria (OR=1.92, 95% CI 1.07-3.43; p=0.028), history of hypertension (OR=3.65, 95% CI 1.69-7.90; p=0.001), and high blood pressure (OR=3.34, 95% CI 1.33-8.40; p=0.010) were independently associated with CKD. Conclusion: Chronic kidney disease is common with hypertension as the etiology and associated with body swelling, active urine sediment and microalbuminuria among patients admitted to a general medical ward in southwestern Uganda. Screening for CKD of patients at risk should be prioritized in general medical wards.Key words: Chronic kidney disease, epidemiology, nephrotoxicity, poor resource setting, Ugand

Résection trans urétrale de la prostate : première expérience à Bukavu, RD Congo: Transurethral resection of the prostate: pilot experience in Bukavu, DR Congo

Context and objective. Despite its large use as alternative to open surgical adenomectomy, transurethral resection of the prostate (TURP) is still poorly performed in many African countries. The purpose of this study was to describe a pilotTURP experience in Bukavu. Methods.This retrospective study included 159 patients (average age: 68 ± 8.5 years) with benign prostatic hypertrophy (BPH), treated at three medical centres in Bukavu between February 2014 andFebruary 2017. Socio-demographic, clinical, and ultrasound data were recorded, and comorbidities and complications reported. Each patient was questionned about treatment received before surgery. Results. The average prostatic volume was 53.2 ± 22 grams. All patients were severelysymptomatic (mean International Prostate Symptoms Score (IPSS) 26.8 ± 5.8) and severely bored (mean quality of life score (QOL) 6.2 ± 0.8).Hypertension (42%) and type 2 diabetes (41%) were the most common comorbidities. The most frequent complications of BPH were urinary tractinfection (44%) and urinary retention (40%). Prior to hospital admission, 60% of patients used traditional medicine. Conclusion.This study has revealed a late reference of patients to the hospital, when the illness is already in advanced stage with complications. There is a need of implementing educational measures targeting early detection and reference of patients with BPH in this area. Résumé Contexte et objectif. Bien que la résection trans urétrale de la prostate (RTUP) se soit imposée comme alternative à l’adénomectomie chirurgicale classique à ciel ouvert, sa pratique reste exceptionnelle dans quelques contrées africaines. L’objectif de la présente étude était de décrire la première expérience de la RTUP à Bukavu. Méthodes. La présente étude documentaire a porté sur 159 patients avec hypertrophie bénigne de la prostate (HBP), opérés dans 3 centres médicaux de Bukavu entre février 2014 et février 2017. Les paramètres d’intérêts comprenaient les données sociodémographiques, cliniques, échographiques les comorbidités, les complications et l’attitude thérapeutique avant l’intervention. Résultats. Leur âge moyen était de 68±8,5 ans. Le volume prostatique moyen était de 53,2 ± 22 grammes. Tous les patients étaient sévèrement symptomatiques (score international des symptômes prostatiques (IPSS) moyen de 26,8 ± 5,8) et fortement ennuyés (score de la qualité de vie (QOL) moyen de 6,2 ± 0,8). L’hypertension artérielle (42%) et le diabète sucré de type 2 (41 %) étaient les comorbidités les plus fréquentes. Les complications de l’HBP les plus fréquentes étaient l’infection urinaire (44 %) et la rétention urinaire (40%). Avant l’admission à l’hôpital, 60% des patients ont eu recours à la médecine traditionnelle. Conclusion. L’avènement de la RTUP à Bukavu a permis de déceler que la majorité des patients avec HBP consultent très tardivement au stade de sevérité symptomatique et des complications. Une campagne d’éducation, information et communication de la population sur le dépistage précoce de l’HBP est à envisager

Risks of adverse perinatal and maternal outcomes among women with hypertensive disorders of pregnancy in southwestern Uganda.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) are a leading cause of global perinatal (fetal and neonatal) and maternal morbidity and mortality. We sought to describe HDP and determine the magnitude and risk factors for adverse perinatal and maternal outcomes among women with HDP in southwestern Uganda. METHODS: We prospectively enrolled pregnant women admitted for delivery and diagnosed with HDP at a tertiary referral hospital in southwestern Uganda from January 2019 to November 2019, excluding women with pre-existing hypertension. The participants were observed and adverse perinatal and maternal outcomes were documented. We used multivariable logistic regression models to determine independent risk factors associated with adverse perinatal and maternal outcomes. RESULTS: A total of 103 pregnant women with a new-onset HDP were enrolled. Almost all women, 93.2% (n = 96) had either pre-eclampsia with severe features or eclampsia. The majority, 58% (n = 60) of the participants had an adverse perinatal outcome (36.9% admitted to the neonatal intensive care unit (ICU), 20.3% stillbirths, and 1.1% neonatal deaths). Fewer participants, 19.4% (n = 20) had an adverse maternal outcome HELLP syndrome (7.8%), ICU admission (3%), and postpartum hemorrhage (3%). In adjusted analyses, gestational age of < 34 weeks at delivery and birth weight <2.5kg were independent risk factors for adverse perinatal outcomes while referral from another health facility and eclampsia were independent risk factors for adverse maternal outcomes. CONCLUSION: Among women with HDP at our institution, majority had preeclampsia with severe symptoms or eclampsia and an unacceptably high rate of adverse perinatal and maternal outcomes; over a fifth of the mothers experiencing stillbirth. This calls for improved antenatal surveillance of women with HDP and in particular improved neonatal and maternal critical care expertise at delivering facilities. Earlier detection and referral, as well as improvement in initial management at lower level health units and on arrival at the referral site is imperative

Case Report: Birth Outcome and Neurodevelopment in Placental Malaria Discordant Twins.

Maternal infection during pregnancy can have lasting effects on neurodevelopment, but the impact of malaria in pregnancy on child neurodevelopment is unknown. We present a case of a 24-year-old gravida three woman enrolled at 14 weeks 6 days of gestation in a clinical trial evaluating malaria prevention strategies in pregnancy. She had two blood samples test positive for Plasmodium falciparum using loop-mediated isothermal amplification before 20 weeks of gestation. At 31 weeks 4 days of gestation, the woman presented with preterm premature rupture of membranes, and the twins were delivered by cesarean section. Twin A was 1,920 g and Twin B was 1,320 g. Both placentas tested negative for malaria by microscopy, but the placenta of Twin B had evidence of past malaria by histology. The twins' development was assessed using the Bayley Scales of Infant and Toddler Development-Third Edition. At 1 year chronologic age, Twin B had lower scores across all domains (composite scores: cognitive, Twin A [100], Twin B [70]; motor, Twin A [88], Twin B [73]; language, Twin A [109], Twin B [86]). This effect persisted at 2 years chronologic age (composite scores: cognitive, Twin A [80], Twin B [60]; motor, Twin A [76], Twin B [67]; language, Twin A [77], Twin B [59]). Infant health was similar over the first 2 years of life. We report differences in neurodevelopmental outcomes in placental malaria-discordant dizygotic twins. Additional research is needed to evaluate the impact of placental malaria on neurodevelopmental complications. Trial registration number: ClinicalTrials.gov number, NCT02163447. Registered: June 2014, https://clinicaltrials.gov/ct2/show/NCT02163447

Pharmacokinetics and pharmacodynamics of azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a protocol for a Phase II randomised controlled trial [version 1; peer review: awaiting peer review]

Background: African children with severe malaria are susceptible to Gram-negative bacterial co-infection, largely non-typhoidal Salmonellae, leading to a substantially higher rates of in-hospital and post-discharge mortality than those without bacteraemia. Current evidence for treating co-infection is lacking, and there is no consensus on the dosage or length of treatment required. We therefore aimed to establish the appropriate dose of oral dispersible azithromycin as an antimicrobial treatment for children with severe malaria and to investigate whether antibiotics can be targeted to those at greatest risk of bacterial co-infection using clinical criteria alone or in combination with rapid diagnostic biomarker tests. Methods: A Phase I/II open-label trial comparing three doses of azithromycin: 10, 15 and 20 mg/kg spanning the lowest to highest mg/kg doses previously demonstrated to be equally effective as parenteral treatment for other salmonellae infection. Children with the highest risk of bacterial infection will receive five days of azithromycin and followed for 90 days. We will generate relevant pharmacokinetic data by sparse sampling during dosing intervals. We will use population pharmacokinetic modelling to determine the optimal azithromycin dose in severe malaria and investigate azithromycin exposure to change in C-reactive protein, a putative marker of sepsis at 72 hours, and microbiological cure (seven-day), alone and as a composite with seven-day survival. We will also evaluate whether a combination of clinical, point-of-care diagnostic tests, and/or biomarkers can accurately identify the sub-group of severe malaria with culture-proven bacteraemia by comparison with a control cohort of children hospitalized with severe malaria at low risk of bacterial co-infection. Discussion: We plan to study azithromycin because of its favourable microbiological spectrum, its inherent antimalarial and immunomodulatory properties and dosing and safety profile. This study will generate new data to inform the design and sample size for definitive Phase III trial evaluation

Low levels of viral suppression among refugees and host nationals accessing antiretroviral therapy in a Kenyan refugee camp.

BACKGROUND: Refugees and host nationals who accessed antiretroviral therapy (ART) in a remote refugee camp in Kakuma, Kenya (2011-2013) were compared on outcome measures that included viral suppression and adherence to ART. METHODS: This study used a repeated cross-sectional design (Round One and Round Two). All adults (≥18 years) receiving care from the refugee camp clinic and taking antiretroviral therapy (ART) for ≥30 days were invited to participate. Adherence was measured by self-report and monthly pharmacy refills. Whole blood was measured on dried blood spots. HIV-1 RNA was quantified and treatment failures were submitted for drug resistance testing. A remedial intervention was implemented in response to baseline testing. The primary outcome was viral load <5000 copies/mL. The two study rounds took place in 2011-2013. RESULTS: Among eligible adults, 86% (73/85) of refugees and 84% (86/102) of Kenyan host nationals participated in the Round One survey; 60% (44/73) and 58% (50/86) of Round One participants were recruited for Round Two follow-up viral load testing. In Round One, refugees were older than host nationals (median age 36 years, interquartile range, IQR 31, 41 vs 32 years, IQR 27, 38); the groups had similar time on ART (median 147 weeks, IQR 38, 64 vs 139 weeks, IQR 39, 225). There was weak evidence for a difference between proportions of refugees and host nationals who were virologically suppressed (<5000 copies/mL) after 25 weeks on ART (58% vs 43%, p = 0.10) and no difference in the proportions suppressed at Round Two (74% vs 70%, p = 0.66). Mean adherence within each group in Round One was similar. Refugee status was not associated with viral suppression in multivariable analysis (adjusted odds ratio: 1.69, 95% CI 0.79, 3.57; p = 0.17). Among those not suppressed at either timepoint, 69% (9/13) exhibited resistance mutations. CONCLUSIONS: Virologic outcomes among refugees and host nationals were similar but unacceptably low. Slight improvements were observed after a remedial intervention. Virologic monitoring was important for identifying an underperforming ART program in a remote facility that serves refugees alongside host nationals. This work highlights the importance of careful laboratory monitoring of vulnerable populations accessing ART in remote settings

Pharmacokinetics and pharmacodynamics of azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a protocol for a Phase II randomised controlled trial [version 2; peer review: 1 approved]

Background: African children with severe malaria are susceptible to Gram-negative bacterial co-infection, largely non-typhoidal Salmonellae, leading to a substantially higher rates of in-hospital and post-discharge mortality than those without bacteraemia. Current evidence for treating co-infection is lacking, and there is no consensus on the dosage or length of treatment required. We therefore aimed to establish the appropriate dose of oral dispersible azithromycin as an antimicrobial treatment for children with severe malaria and to investigate whether antibiotics can be targeted to those at greatest risk of bacterial co-infection using clinical criteria alone or in combination with rapid diagnostic biomarker tests. Methods: A Phase I/II open-label trial comparing three doses of azithromycin: 10, 15 and 20 mg/kg spanning the lowest to highest mg/kg doses previously demonstrated to be equally effective as parenteral treatment for other salmonellae infection. Children with the highest risk of bacterial infection will receive five days of azithromycin and followed for 90 days. We will generate relevant pharmacokinetic data by sparse sampling during dosing intervals. We will use population pharmacokinetic modelling to determine the optimal azithromycin dose in severe malaria and investigate azithromycin exposure to change in C-reactive protein, a putative marker of sepsis at 72 hours, and microbiological cure (seven-day), alone and as a composite with seven-day survival. We will also evaluate whether a combination of clinical, point-of-care diagnostic tests, and/or biomarkers can accurately identify the sub-group of severe malaria with culture-proven bacteraemia by comparison with a control cohort of children hospitalized with severe malaria at low risk of bacterial co-infection. Discussion: We plan to study azithromycin because of its favourable microbiological spectrum, its inherent antimalarial and immunomodulatory properties and dosing and safety profile. This study will generate new data to inform the design and sample size for definitive Phase III trial evaluation. Registration: ISRCTN49726849 (27th October 2017)