Makerere University College of Health Sciences (MakCHS) is a constituent college of Makerere University, Uganda's oldest university. The schools of the college offer undergraduate and postgraduate courses in the biomedical sciences, health sciences, human medicine and public health, covering a broad range of disciplines and specialties.
BACKGROUND:Paediatric acute kidney injury (AKI) is a complication of severe malaria, but its long-term outcomes remain poorly defined in low-income and middle-income countries. We aimed to evaluate the long-term association between paediatric AKI and kidney outcomes and mortality following severe malaria. METHODS:We pooled data from two prospective cohorts of Ugandan children (ie, those aged 6 months-12 years) admitted to hospital with severe malaria between 2008 and 2017. Children with stored admission blood samples available for creatinine measurement were included in the analysis. Surviving participants were enrolled in a follow-up study conducted from 2020 to 2023, when kidney function and survival were assessed, using Cox regression with age as the timescale to model mortality risk. Logistic regression was used to estimate the odds of chronic kidney disease (CKD), defined as two or more consecutive low estimated glomerular filtration rates 90 days or more apart, and long-term major adverse kidney events, defined as CKD or death. Adjusted analyses included the following enrolment characteristics: age, sex, height-for-age Z score, study site, study cohort, severe malaria group (ie, cerebral malaria, severe malarial anaemia, respiratory distress, complicated seizures, or prostration), and HIV status. FINDINGS:At enrolment, the median age was 2·5 years (IQR 1·8-3·5), 622 (57·8%) of 1077 were male and 455 (42·2%) were female, with Kidney Disease: Improving Global Outcomes-defined AKI occurring in 431 (40·0%) children. Over a median of 6·5 years (3·7-8·8), 147 (13·6%) of children died, with nearly half of deaths (71 of 147) occurring after hospital discharge. Adjusted odds of long-term major adverse kidney events were higher among children with AKI (adjusted odds ratio [aOR] 3·14, 95% CI 2·23-4·43), driven by a higher mortality risk (adjusted hazard ratio [aHR] 3·36, 95% CI 2·22-5·10) that remained elevated beyond 2 years after the acute episode (aHR 4·53, 1·80-11·37). AKI survivors had higher odds of chronic kidney disease over follow-up (odds ratio 1·77, 1·07-2·93), although not significant after adjustment (aOR 1·47, 95% CI 0·84-2·56; p=0·18). INTERPRETATION:In this paediatric population, AKI was associated with excess long-term mortality, suggesting AKI is a sentinel event that marks sustained vulnerability to death and highlights limitations of acute-care models in malaria-endemic settings. FUNDING:The US National Institute of Neurological Disorders and Stroke, the Fogarty International Center, the US National Institutes of Allergy and Infectious Diseases, and a Ralph W and Grace M Showalter Young Investigator Award.
Importance:Cerebral malaria and severe malarial anemia are associated with cognitive impairment and decreased academic achievement 1 to 2 years after the initial episode. The extent to which impairment persists into later childhood and adolescence is unknown. Objective:To determine whether severe malaria in children is associated with long-term cognitive impairment or decreased academic achievement. Design, Setting, and Participants:Assessment of Ugandan children enrolled in 2 prior cohort studies of severe malaria; 1247 children completed the prior studies (2008-2018), of whom 958 were traceable (77%), and 939 (75%) enrolled in the present study (2020-2023). Data from 889 individuals younger than 18 years were analyzed. Exposures:Cerebral malaria (n = 184), severe malarial anemia (n = 249), other forms of severe malaria (respiratory distress, complicated seizures, or prostration, n = 239), and unaffected community children (n = 217). Main Outcomes and Measures:Descriptive analysis including age-adjusted z scores of overall cognitive ability, attention, and academic achievement (math, reading). Results:Participants (mean age, 11.1 [SD, 3.4] years; 44.2% female) were tested 4 to 15 years (mean, 8.4 [SD, 2.7] years) after their severe malaria episode. Compared with community children, children with a history of cerebral malaria or severe malarial anemia had lower scores in overall cognition (adjusted mean difference, -0.41 [Bonferroni-corrected 95% CI, -0.74 to -0.09] and -0.31 [95% CI, -0.61 to -0.01], respectively) and math (-0.46 [95% CI, -0.78 to -0.14] and -0.32 [95% CI, -0.61 to -0.03], respectively), while attention and reading scores did not differ significantly. Cognitive and academic scores were not significantly different between children with other forms of severe malaria and community children. In children with cerebral malaria or severe malarial anemia, acute kidney injury, hyperuricemia, and elevated plasma angiopoietin-2 levels at the time of the severe malaria episode were associated with worse z scores in overall cognitive ability (-0.44 [95% CI, -0.80 to -0.08], -0.45 [95% CI, -0.88 to -0.02], and -0.33 [95% CI, -0.63 to -0.03], respectively). In children with cerebral malaria or severe malarial anemia, acute kidney injury was additionally associated with lower z scores in reading (95% CI, -0.42 [95% CI, -0.79 to -0.05]) and math (95% CI, -0.39 [-0.74 to -0.04]). Conclusions and Relevance:Among survivors of a severe childhood malaria episode, cerebral malaria and severe malarial anemia in childhood are associated with cognitive impairment and decreased academic achievement in some metrics 4 to 15 years after the index episode.
BACKGROUND:Tongue swabs are a promising alternative specimen for tuberculosis (TB) diagnosis. Although test specificity exceeds 98%, sensitivity is lower than sputum-based molecular testing. We investigated whether the use of tongue swabs could increase sample availability, resulting in similar diagnostic yield. METHODS:In this cross-sectional study (July 2024-January 2025), we screened consecutive people with presumptive TB at health centers in the Philippines, Vietnam, Uganda, and Zambia. Participants were asked to provide tongue swabs and referred for routine sputum collection. Tongue swabs were tested in research laboratories using the MiniDock MTB Test (Guangzhou Pluslife Biotech Co., Ltd., China); sputum was tested using WHO-recommended molecular testing per national guidelines. We compared diagnostic yield, defined as proportion of positive test results among all participants, between tongue swab- and sputum-based molecular testing with a prespecified 3.0% non-inferiority margin. RESULTS:Of 1639 participants, 851 (51.9%) were female, 415 (25.3%) were diagnosed with HIV, and 132 (8.1%) were children <5 years. All provided tongue swabs, but only 1389 (84.7%) produced sputum. Diagnostic yield was 3.8% (63/1639) for tongue swabs and 4.1% (68/1639) for sputum-based (68/1639, 4.1%) molecular testing. The difference (0.3%, 95% CI -0.6 to +1.2) was within the prespecified non-inferiority margin. Results were consistent across countries and key subgroups (age, sex, and HIV status). CONCLUSIONS:Tongue swab-based molecular testing with MiniDock MTB achieved non-inferior diagnostic yield compared with sputum-based molecular testing. These findings support scale-up of swab-based platforms as a cost-efficient alternative, particularly where sputum collection is challenging or smear microscopy remains the primary diagnostic method.
Pre-eclampsia, a significant contributor to maternal and newborn mortality and morbidity, is a common pregnancy-specific hypertensive disorder that affects multiple systems, including the renal system. The consequences of pre-eclampsia on the survivors’ kidneys may result in abnormal renal function post-delivery, ultimately leading to the onset of chronic kidney disease. Despite pre-eclampsia being very common in women of African ancestry, there are hardly any studies that have investigated its long-term consequences in women of sub-Saharan Africa. This study aimed to establish the incidence and factors associated with abnormal renal function three months after delivery among pre-eclampsia survivors in a peri-urban Ugandan setting. Between November 2018 and June 2019, we recruited a prospective cohort of 116 women who experienced pre-eclampsia. Clinical and laboratory information were gathered at both delivery and three months postpartum. The incidence of abnormal renal function among pre-eclampsia survivors was assessed based on those with an estimated glomerular filtration rate < 90 ml/min/1.73 m², determined using the CKD-EPI equation. Multivariate modified Poisson regression with robust standard errors was conducted to identify factors associated with abnormal renal function. A high incidence of abnormal renal function, amounting to 16.7