Search

Judith Owokuhaisa,1 Catherine N Abaasa,2 Rose Muhindo,3 Pius Musinguzi,4 Godfrey Zari Rukundo5 1Faculty of Medicine, Department of Physiotherapy, Mbarara University of Science and Technology, Mbarara, Uganda; 2Faculty of Medicine, Department of Medical Laboratory Sciences, Mbarara University of Science and Technology, Mbarara, Uganda; 3Faculty of Medicine, Department of Internal Medicine, Mbarara University of Science and Technology, Mbarara, Uganda; 4Faculty of Medicine, Department of Nursing, Mbarara University of Science and Technology, Mbarara, Uganda; 5Faculty of Medicine, Department of Psychiatry, Mbarara University of Science and Technology, Mbarara, UgandaCorrespondence: Judith Owokuhaisa, Email jowokuhaisa@must.ac.ugBackground: Screening for kidney disease (KD) among high-risk patients (patients with hypertension or diabetes) allows early diagnosis, intervention and delayed progression of the disease. In low- and middle-income countries (LMIC), KD screening is still sub-optimal. This study explored the healthcare providers’ perceived barriers and facilitators to KD screening among older adults with hypertension and diabetes in Mbarara southwestern Uganda.Methods: This was a descriptive qualitative study among healthcare providers caring for older adults with diabetes mellitus and hypertension at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda. In-depth interviews were conducted using a semi-structured interview guide. Interviews were audio-recorded, transcribed verbatim, and thematically analyzed to develop themes of barriers and facilitators.Results: We conducted 30 in-depth interviews among healthcare providers. Barriers to screening for kidney disease included patient related factors according to healthcare providers (financial hardships, poor health seeking behavior, limited knowledge and awareness), healthcare factors (work overload, ineffective patient healthcare provider communication) and system/policy related factors (lack of laboratory supplies, lack of guidelines and poor medical record keeping and documentation). With respect to facilitators, we found formation of peer support groups, effective team, and continuous medical education (CME).Conclusion: Healthcare providers encounter substantial but modifiable barriers in screening older adults for KD. The identification of barriers and facilitators in timely KD detection gives us an outlook of the problem in Uganda and leads for proposals of action. Interventions that address these barriers and promote facilitators may improve the healthcare provider’s effectiveness and capacity to care including screening for patients at risk of KD.Keywords: healthcare providers, barriers, facilitators, screening, kidney disease, hypertension, diabetes, older, adults

Andrew Mutekanga,1,&ast; Edwin Nuwagira,1,&ast; Elias Kumbakumba,2 Victoria Nyaiteera,3 Stephen Asiimwe,4 Medal Gasumuni,5 Nelson Wandera,5 Robert Natumanya,5 Denis Akena,5 Siraje Senoga,1 Joseph Kyobe Kiwanuka,6 George Kateregga,6 Emmanuel Munyarugero,6 Fardous Charles Abeya,1 Paul Stephen Obwoya,1 Stephen Ttendo,6 Rose Muhindo1,&ast; 1Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda; 2Department of Pediatrics and Child Health, Mbarara University of Science and Technology, Mbarara, Uganda; 3Department of ENT, Mbarara University of Science and Technology, Mbarara, Uganda; 4Global Health Collaborative, Massachusetts General Hospital, Boston, MA, USA; 5Department of Medicine, Mbarara Regional Referral Hospital, Mbarara, Uganda; 6Department of Anesthesiology and Critical Care, Mbarara University of Science and Technology, Mbarara, Uganda&ast;These authors contributed equally to this workCorrespondence: Rose Muhindo, Mbarara University of Science and Technology, P.O. Box 1410, Mbarara, Uganda, Tel +256772406337, Email rosie@must.ac.ugBackground: COVID-19 has created a burden on the healthcare system globally. Severe COVID-19 is linked with high hospital mortality. Data regarding 30-day in-hospital mortality and its factors has not been explored in southwestern Uganda.Methods: We carried out a retrospective, single-center cohort study, and included all in-patients with laboratory-confirmed, radiological, or clinical severe COVID-19 admitted between April 2020 and September 2021 at Mbarara Regional Referral Hospital (MRRH). Demographic, laboratory, treatment, and clinical outcome data were extracted from patients’ files. These data were described comparing survivors and non-survivors. We used logistic regression to explore the factors associated with 30-day in-hospital mortality.Results: Of the 283 patients with severe COVID-19 admitted at MRRH COVID-19 unit, 58.1% were male. The mean age ± standard deviation (SD) was 61± 17.4 years; there were no differences in mean age between survivors and non-survivors (59 ± 17.2 versus 64.4 ± 17.3, respectively, p=0.24) The median length of hospital stay was 7 (IQR 3– 10) days (non-survivors had a shorter median length of stay 5 (IQR 2– 9) days compared to the survivors; 8 (IQR 5– 11) days, p< 0.001. The most frequent comorbidities were hypertension (30.5%) and diabetes mellitus (30%). The overall 30-day in-hospital mortality was 134 of 279 (48%) mortality rate of 47,350× 105 with a standard error of 2.99%. The factors associated with 30-day in-hospital mortality were age: 65 years and above (aOR, 3.88; 95% CI, 1.24– 11.70; P =0.020) a neutrophil to lymphocyte ratio above 5 (aOR, 4.83; 95% CI, 1.53– 15.28; P =0.007) and oxygen requirement ≥ 15L/min (aOR, 15.80; 95% CI, 5.17– 48.25; P < 0.001).Conclusion: We found a high 30-day in-hospital mortality among patients with severe forms of COVID-19. The identified factors could help clinicians to identify patients with poor prognosis at an early stage of admission.Keywords: severe, COVID-19, 30-day in hospital mortality

Nsheka Bonny Patrick,1 Tadele Mekuriya Yadesa,1,2 Rose Muhindo,3 Stephen Lutoti4 1Department of Pharmacy, Mbarara University of Science and Technology, Mbarara, Uganda; 2World Bank, ACE II, Pharmacy Biotechnology and Traditional Medicine Center (PHARMBIOTRAC), Mbarara University of Science and Technology, Mbarara, Uganda; 3Department of Internal Medicine, Mbarara University of Science and Technology, Mbarara, Uganda; 4Department of Pharmacy, Makerere University, Kampala, UgandaCorrespondence: Tadele Mekuriya YadesaDepartment of Pharmacy, Mbarara University of Science and Technology, PO Box 1410, Mbarara, UgandaEmail maatiikoo4@gmail.comBackground: Glycemic control is associated with long-term complications in type 2 diabetes management. However, updated reports on glycemic control that are crucial to reducing diabetes mellitus complications remain scarce.Objective: The objective of this study is to evaluate glycemic control and contributing factors among type 2 diabetes mellhitus patients attending the outpatient diabetic clinic at Mbarara Regional Referral Hospital.Methods: A cross-sectional study was conducted at Mbarara Regional Referral Hospital outpatient diabetes clinic between July and October 2020. Participants were subjected to a questionnaire-based interview and glycosylated hemoglobin (HbA1C) was determined as a marker of glycemic control among participants. The collected data was entered into and analyzed by Stata version 13. The odds ratio was used to determine the strength of association between variables. The cut-off value for all statistical significance tests was set at p< 0.05 with CI of 95%.Results: A total of 223 participants were interviewed, and the majority (188, 84.3%) had poor glycemic control (HbA1C ≥ 7%). Importantly, 81.7% (49/60) and 90.0% (99/110) of those who did not adhere to diet and physical exercise recommendations respectively, had poor glycemic control. Multivariate logistic regression revealed that poor glycemic control was more prevalent among participants aged 25– 60 years (AOR=4.48, 95%CI: 1.56– 14.50, p-value=0.009) and those aged above 60 years (AOR=4.28, 95%CI: 1.18– 15.58, p-value= 0.03) compared to the youth, 18– 24 years of age.Conclusion: The prevalence of poor glycemic control among type 2 diabetes patients in this study is high and patient’s age was identified to be an independent risk factor. We recommend any intervention by the hospital that promotes diabetes education and optimizes lifestyle and medication adherence; ultimately to achieve good glycemic control especially for adult patients.Keywords: type 2 diabetes mellitus, poor glycemic control, glycosylated hemoglobin A1C

Tonny Kyagambiddwa,1,&ast; Timothy Mwanje Kintu,1,&ast; Emmanuel Miiro,1,&ast; Franchesca Nabalamba,1 Gloria Suubi Asiimwe,1 Anne Marion Namutebi,2 Fardous C Abeya,3 Boniface A Lumori,3 Isaac Ijuka,4 Rose K Muhindo,1,3 Andrew Mutekanga,1,3 Richard Musinguzi,5 Francis Natuhwera,6 Joseph Ngonzi,1,7 Edwin Nuwagira3,8 1Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda; 2Kabale Regional Referral Hospital, Kabale, Uganda; 3Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda; 4Mayanja Memorial Hospital, Mbarara, Uganda; 5Masaka Regional Referral Hospital, Masaka, Uganda; 6Fort Portal Regional Referral Hospital, Fort Portal, Uganda; 7Department of Obstetrics and Gynecology, Mbarara University of Science and Technology, Mbarara, Uganda; 8Tuberculosis Treatment Unit, Mbarara Regional Referral Hospital, Mbarara, Uganda&ast;These authors contributed equally to this workCorrespondence: Tonny Kyagambiddwa; Edwin Nuwagira, Mbarara University of Science and Technology, Tel +256782980116 ; +256779096887, Email tonnykyagambiddwa97@gmail.com; enuwagira@must.ac.ugBackground: There is scarcity of data regarding young and middle-aged adults hospitalized with severe Corona Virus Disease 2019 (COVID-19) in Africa. In this study, we describe the clinical characteristics and 30-day survival among adults aged 18 to 49 years admitted with severe COVID-19 in Uganda.Methods: We reviewed treatment records of patients admitted with severe COVID-19 across five COVID-19 treatment units (CTU) in Uganda. We included individuals aged 18 to 49 years, who had a positive test or met the clinical criteria for COVID-19. We defined severe COVID-19 as having an oxygen saturation < 94%, lung infiltrates > 50% on imaging and presence of a co-morbidity that required admission in the CTU. Our main outcome was the 30-day survival from the time of admission. We used a Cox proportional hazards model to determine the factors associated with 30-day survival at a 5% level of significance.Results: Of the 246 patient files reviewed, 50.8% (n = 125) were male, the mean ± (standard deviation) age was 39 ± 8 years, majority presented with cough, 85.8% (n = 211) and median C-reactive protein (interquartile range) was 48 (47.5, 178.8) mg/L. The 30-day mortality was 23.9% (59/246). At admission, anemia (hazard ratio (HR): 3.00, 95% confidence interval (CI), 1.32– 6.82; p = 0.009) and altered mental state (GCS < 15) (HR: 6.89, 95% CI: 1.48– 32.08, p = 0.014) were significant predictors of 30-day mortality.Conclusion: There was a high 30-day mortality among young and middle-aged adults with severe COVID-19 in Uganda. Early recognition and targeted management of anemia and altered consciousness are needed to improve clinical outcomes.Keywords: COVID-19, Uganda, mortality, young and middle-aged adults

Background: African children with severe malaria are at increased risk of non-typhoidal salmonellae co-infection. Broad-spectrum antibiotics are recommended by guidelines but the optimal class and dose have not been established. We investigated the optimal dose of oral dispersible azithromycin and whether simple clinical criteria and point-of-care biomarkers could target antibiotics to those at greatest risk of bacterial co-infection., Methods: We conducted a phase I/II trial in Ugandan children with severe malaria comparing a 5-day course of azithromycin: 10, 15 and 20 mg/kg of azithromycin (prescribed by weight bands) spanning the dose-range effective for other salmonellae infection. We generated relevant pharmacokinetic (PK) data by sparse sampling during dosing intervals and investigated associations between azithromycin exposure and potential mechanisms (PK-pharmacodynamics) using change in C-reactive protein (CRP), a putative marker of sepsis, at 72 h (continuous) and microbiological cure (7-day) (binary), alone and as a composite with 7-day and 90-day survival. To assess whether clinical or biomarkers could identify those at risk of sepsis, a non-severe malaria control was concurrently enrolled., Results: Between January 2020 and January 2022, 105 cases were randomised azithromycin doses: 35 to 10 mg/kg, 35 to 15 mg/kg and 35 to 20 mg/kg. Fifty non-severe malaria controls were concurrently enrolled. CRP reduced in all arms by 72 h with a mean reduction of 65.8 mg/L (95% CI 57.1, 74.5) in the 10 mg/kg arm, 64.8 mg/L (95% CI 56.5, 73.1; p = 0.87) in the 20 mg/kg arm and a smaller reduction 51.2 mg/L (95% CI 42.9, 59.5; p = 0.02) in the 15 mg/kg arm. Microbiological cure alone outcome was not analysed as only one pathogen was found among cases. Three events contributed to the composite outcome of 7-day survival and microbiological cure, with no events in the 15 mg/kg arm. The odds ratio comparing 20 vs 10 mg/kg was 0.50 (95% CI 0.04, 5.79); p = 0.58. Due to the low number of pathogens identified, it was not possible to identify better methods for targeting antibiotics including both the cases and controls., Conclusions: We found no evidence for an association between systemic azithromycin exposure and reduction in CRP. Further work is needed to better identify children at highest risk from bacterial co-infection., Trial Registration: ISRCTN49726849 (registered on 27th October 2017)., (© 2024. The Author(s).)

Background: Little is known about outcomes from cancer chemotherapy--associated infections in sub-Saharan Africa. Accordingly, among patients with cancer admitted with postchemotherapy infection in Mbarara, Uganda, we aimed to determine (1) the 30-day case fatality rate, (2) factors associated with mortality rate, and (3) clinical risk score performance., Methods: We enrolled participants aged ≥18 years if they (1) received cancer chemotherapy within the past 30 days, (2) were admitted to the oncology ward, and (3) were prescribed intravenous antibiotics. We used Cox proportional hazards regression to determine predictors of death at 30 days and calculated the area under the receiver operating characteristic curve (AUC) for each clinical risk score., Results: Among 150 participants, 67 (45%) were female, and the median (interquartile range) age was 56 (43-66) years. Esophageal cancer (18%) and pneumonia (42%) were the most common cancer and infection, respectively. Death occurred within 30 days in 63 participants (42%). Quick Sequential Organ Failure Assessment (qSOFA) score ≥2 (adjusted hazard ratio, 2.51 [95% confidence interval, 1.42-4.44]; P = .001), and Universal Vital Assessment (UVA) score >4 (2.13 [.08-4.18, P = .03) were independently associated with death at 30 days. An Eastern Cooperative Oncology Group (ECOG) score ≥3 was similarly independently associated with death at 30 days in the qSOFA and UVA models. The AUCs for qSOFA and UVA scores were 0.70 (95% confidence interval, .63-.79) and 0.72 (.64-.80), respectively., Conclusions: In participants with postchemotherapy infection in Mbarara, Uganda, the case fatality rate was high. ECOG, qSOFA, and UVA scores were associated with death at 30 days., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Sepsis is the leading cause of global death with the highest burden found in sub-Saharan Africa (sSA). The Universal Vital Assessment (UVA) score is a validated resource-appropriate clinical tool to identify hospitalized patients in sSA who are at risk of in-hospital mortality. Whether a decrease in the UVA score over 6 hours of resuscitation from sepsis is associated with improved outcomes is unknown. We aimed to determine (1) the association between 6-hour UVA score and in-hospital mortality, and (2) if a decrease in UVA score from admission to 6 hours was associated with improved in-hospital mortality. We analyzed data from participants with severe sepsis aged ≥14 years enrolled at the Mbarara Regional Referral Hospital in Uganda from October 2014 through May 2015. Among 197 participants, the median (interquartile range) age was 34 (27-47) years, 99 (50%) were female and 116 (59%) were living with HIV. At 6 hours, of the 65 participants in the high-risk group, 28 (43%) died compared to 28 (30%) of 94 in the medium-risk group (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.29,1.08, p = 0.086) and 3 (9%) of 33 in the low-risk group (OR 0.13, 95% CI 0.03, 0.42, p = 0.002). In a univariate analysis of the 85 participants who improved their UVA risk group at 6 hours, 20 (23%) died compared to 39 (36%) of 107 participants who did not improve (OR 0.54, 95% CI 0.27-1.06, p = 0.055). In the multivariable analysis, the UVA score at 6 hours (adjusted OR [aOR] 1.26, 95%CI 1.10-1.45, p<0.001) was associated with in-hospital mortality. When adjusted for age and sex, improvement in the UVA risk group over 6 hours was associated with a non-statistically significant 43% decrease in odds of mortality (aOR 0.57, 95%CI 0.29-1.07, p = 0.08). Targeting a decrease in UVA score over 6 hours from admission may be a useful clinical endpoint for sepsis resuscitation in sSA, but this would need to be proven in a clinical trial., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Null 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.)

The first reported case of Coronavirus Disease 2019 (COVID-19) in Rwanda occurred on March 14 2020. By the end of July 2024, a total of 133,518 individuals had tested positive for the infection, resulting in 1,468 deaths and 132,039 had fully recovered. The success of COVID-19 elimination in Rwanda hinges on the public's level of acceptance of the COVID-19 vaccination. Although COVID-19 is no longer a pandemic anymore, the World Health Organisation recommends countries vaccinate their populations to protect them from COVID-19 and its variants. Globally, COVID-19 has affected 704,753,890 people, caused 7,010,681 deaths and 675,619,811 have recovered. This study aimed to assess the acceptability of COVID-19 vaccines among adults aged 18 years and above in Rwanda. A cross-sectional study was conducted from January to March 2022 to determine the associations between COVID-19 vaccine acceptance (VA) with respondents' characteristics, using logistic regression analysis. This study enrolled 2,126 respondents with a mean age of 31 years, the majority of whom were females (82.2%), 51.4% had completed primary education, and 78.7% were married. Most respondents recognized the importance of COVID-19 vaccination for both personal health and community well-being. The study found a high rate of COVID-19 vaccine acceptance, with 91.6% of respondents expressing VA and an overall VA rate of 98.2%. Having a relationship with the child(ren) was the only characteristic associated with COVID-19 vaccine acceptance (p; 3.2 × 10 - 3 , OR; 2.9, 95% C.I; 1.4-5.9). In conclusion, the study found a high rate of COVID-19 vaccine acceptance among adults in Rwanda, with COVID-19 associated with having a relationship with the child(ren). The study recommends the need for mass educational campaigns and awareness-raising efforts to understand of COVID-19 vaccines., (© 2024. The Author(s).)

Children hospitalised with severe malnutrition have high mortality and readmission rates post-discharge. Current milk-based formulations target restoring ponderal growth but not the modification of gut barrier integrity or microbiome which increases the risk of gram-negative sepsis and poor outcomes. We propose that legume-based feeds rich in fermentable carbohydrates will promote better gut health and improve overall outcomes. We conducted an open-label phase II trial at Mbale and Soroti Regional Referral Hospitals, Uganda, involving 160 children aged 6 months to 5 years with severe malnutrition (mid-upper arm circumference (MUAC) < 11·5 cm and/or nutritional oedema). Children were randomised to a lactose-free, chickpea-enriched legume paste feed (LF) ( n 80) v . WHO standard F75/F100 feeds ( n 80). Co-primary outcomes were change in MUAC and mortality to day 90. Secondary outcomes included weight gain (> 5 g/kg/d), de novo development of diarrhoea, time to diarrhoea and oedema resolution. Day 90 MUAC increase was marginally lower in LF v . WHO arm (1·1 cm (interquartile range (IQR) 1·1) v . 1·4 cm (IQR 1·40), P = 0·09); day 90 mortality was similar (11/80 (13·8 %) v . 12/80 (15 %), respectively, OR 0·91 (95 % CI 0·40, 2·07), P = 0·83). There were no differences in any of the other secondary outcomes. Owing to initial poor palatability of the LF, ten children switched to WHO feeds. Per-protocol analysis indicated a trend to lower day 90 mortality and readmission rates in the LF (6/60 (10 %) and 2/60(3 %)) v . WHO feeds (12/71(17·5 %) and 4/71(6 %)). Further refinement of LF and clinical trials are warranted, given the poor outcomes in children with severe malnutrition.

Background: Severe pneumonia in African children results in poor long-term outcomes (deaths/readmissions) with undernutrition as a key risk factor. We hypothesised additional energy/protein-rich Ready-to-Use Therapeutic Foods (RUTF) would meet additional nutritional requirements and improve outcomes., Methods: COAST-Nutrition was an open-label Phase 2 randomised controlled trial in children (aged 6 months-12 years) hospitalised with severe pneumonia (and hypoxaemia, SpO 2 <92%) in Mbale, Soroti, Jinja, Masaka Regional Referral Hospitals, Uganda and Kilifi County Hospital, Kenya (ISRCTN10829073 (registered 6th June 2018) PACTR202106635355751 (registered 2nd June 2021)). Children were randomised (ratio 1:1) to enhanced nutritional supplementation with RUTF (plus usual diet) for 56 days vs usual diet (control). The primary outcome was change in mid-upper arm circumference (MUAC) at 90 days as a composite with mortality. Secondary outcomes include anthropometric status, mortality, and readmissions at Days 28, 90 and 180., Findings: Between 12 August 2018 and 22 April 2022, 846 eligible children were randomised, 424 to RUTF and 422 to usual diet, and followed for 180-days [12 (1%) lost-to-follow-up]. RUTF supplement was initiated in 417/419 (>99%). By Day 90, there was no significant difference in the composite endpoint (probabilistic index 0.49, 95% CI 0.45-0.53, p = 0.74). Respective 90-day mortality (13/420 3.1% vs 14/421 3.3%) and MUAC increment (0.54 (SD 0.85) vs 0.55 (SD 0.81)) were similar between arms. There was no difference in any anthropometric secondary endpoints to Day 28, 90 or 180 except skinfold thickness at Day 28 and Day 90 was greater in the RUTF arm. Serious adverse events were higher in the RUTF arm (n = 164 vs 108), mainly due to hospital readmission for acute illness (54/387 (14%) vs 37/375 (10%)., Interpretation: Our study suggested that nutritional supplementation with RUTF did not improve outcomes to 180 days in children with severe pneumonia., Funding: This trial is part of the EDCTP2 programme (grant number RIA-2016S-1636-COAST-Nutrition) supported by the European Union, and UK Joint Global Health Trials scheme: Medical Research Council, Department for International Development, Wellcome Trust (grant number MR/L004364/1, UK)., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Author(s).)

In many countries in Africa, there is a 'paradoxical surplus' of under and unemployed nurses, midwives, doctors and pharmacists which exists amidst a shortage of staff within the formal health system. By 2030, the World Health Organisation Africa Region may find itself with a shortage of 6.1 million health workers alongside 700,000 un- or underemployed health staff. The emphasis in policy debates about human resources for health at most national and global levels is on staff shortage and the need to train more health workers. In contrast, these 'surplus' health workers are both understudied and underacknowledged. Little time is given over to understand the economic, political and social factors that have driven their emergence; the ways in which they seek to make a living; the governance challenges that they raise; nor potential interventions that could be implemented to improve employment rates and leverage their expertise. This short communication reflects on current research findings and calls for improved quantitative and qualitative research to support policy engagement at national, regional and global levels., (© 2024 The Authors. The International Journal of Health Planning and Management published by John Wiley & Sons Ltd.)

Background: Kidney dysfunction is a common, progressive condition that is increasingly becoming a global public health issue. Because the kidneys are the major route for drug excretion, impaired renal function can change the pharmacokinetics and pharmacodynamics of drugs that are renally excreted. Additionally, patients with kidney dysfunction often have co-morbidities and the associated use of multiple medications which increases the risk of drug-related problem (DRP) occurrence. This study aimed to determine the prevalence, types, and factors associated with DRPs in patients with kidney dysfunction., Method: We conducted a prospective observational study over 3 months among hospitalized patients diagnosed with acute kidney injury or chronic kidney disease who were hospitalized in the medical ward, and patients attending the renal outpatient clinic at Mbarara Regional Referral Hospital. A total of 183 participants were enrolled through the use of a consecutive sampling technique. DRPs were classified according to the PCNE classification version 9.1. Data analysis was carried out using SPSS version 25., Results: A total of 174 patients with kidney dysfunction were included in the study with a mean ± SD age of 50.34 ± 18.13 years. A total of 219 DRPs were incurred by 138 (79.3%) study participants. The most common DRPs were 'Untreated symptoms or indication' (35.6%) followed by 'adverse event (possibly) occurring' (28.3%), and 'effect of drug treatment not optimal' (23.3%). Antimicrobials were the most involved drugs in suboptimal drug treatment (31.3%) and unnecessary drug treatment (32.1%). The study showed that length of hospital stay ≥ 5 days (AOR = 6.39, 95% CI: 1.75-23.27; p-value = 0.005) significantly increased the risk of DRP occurrence., Conclusion: The current results, in agreement with previous literature, showed a high burden of DRPs among patients with kidney dysfunction. Antimicrobials were the most involved drugs in suboptimal as well as in unnecessary drug treatment. Longer hospital stay significantly increased the risk of DRPs. The high prevalence of DRPs in patients with kidney dysfunction and the potential impact on antimicrobial resistance underscores the importance of regular medication reviews and close monitoring of patients with renal dysfunction., (© 2023. The Author(s).)

Background: Single low-dose primaquine (SLDPQ) effectively blocks the transmission of Plasmodium falciparum malaria, but anxiety remains regarding its haemolytic potential in patients with glucose-6-phopshate dehydrogenase (G6PD) deficiency. We, therefore, examined the independent effects of several factors on haemoglobin (Hb) dynamics in falciparum-infected children with a particular interest in SLDPQ and G6PD status., Methods: This randomised, double-blind, placebo-controlled, safety trial was conducted in Congolese and Ugandan children aged 6 months-11 years with acute uncomplicated P. falciparum and day (D) 0 Hbs ≥ 6 g/dL who were treated with age-dosed SLDPQ/placebo and weight-dosed artemether lumefantrine (AL) or dihydroartemisinin piperaquine (DHAPP). Genotyping defined G6PD (G6PD c.202T allele), haemoglobin S (HbS), and α-thalassaemia status. Multivariable linear and logistic regression assessed factor independence for continuous Hb parameters and Hb recovery (D42 Hb > D0 Hb), respectively., Results: One thousand one hundred thirty-seven children, whose median age was 5 years, were randomised to receive: AL + SLDPQ (n = 286), AL + placebo (286), DHAPP + SLDPQ (283), and DHAPP + placebo (282). By G6PD status, 284 were G6PD deficient (239 hemizygous males, 45 homozygous females), 119 were heterozygous females, 418 and 299 were normal males and females, respectively, and 17 were of unknown status. The mean D0 Hb was 10.6 (SD 1.6) g/dL and was lower in younger children with longer illnesses, lower mid-upper arm circumferences, splenomegaly, and α-thalassaemia trait, who were either G6PDd or heterozygous females. The initial fractional fall in Hb was greater in younger children with higher D0 Hbs and D0 parasitaemias and longer illnesses but less in sickle cell trait. Older G6PDd children with lower starting Hbs and greater factional falls were more likely to achieve Hb recovery, whilst lower D42 Hb concentrations were associated with younger G6PD normal children with lower fractional falls, sickle cell disease, α-thalassaemia silent carrier and trait, and late treatment failures. Ten blood transfusions were given in the first week (5 SLDPQ, 5 placebo)., Conclusions: In these falciparum-infected African children, posttreatment Hb changes were unaffected by SLDPQ, and G6PDd patients had favourable posttreatment Hb changes and a higher probability of Hb recovery. These reassuring findings support SLDPQ deployment without G6PD screening in Africa., Trial Registration: The trial is registered at ISRCTN 11594437., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: There are no pharmacokinetic data of single low dose primaquine (SLDPQ) as transmission blocking in African children with acute Plasmodium falciparum and glucose-6-phosphate dehydrogenase deficiency (G6PDd)., Methods: Primaquine pharmacokinetics of age-dosed SLDPQ (shown previously to be gametocytocidal with similar tolerability as placebo) were characterised in falciparum-infected Ugandan and Congolese children aged 6 months to 11 years, treated on admission with standard 3-day dihydroartemisinin-piperaquine or artemether-lumefantrine plus SLDPQ: 6 m-<1 y: 1.25 mg, 1-5 y: 2.5 mg, 6-9 y: 5 mg, 10-11 y: 7.5 mg. LC-MS/MS-measured plasma primaquine and carboxyprimaquine (baseline, 1, 1.5, 2, 4, 8, 12, 24 h) were analysed by noncompartmental analysis. Multivariable linear regression modelled associations between covariates, including cytochrome-P450 2D6 metaboliser status, and outcomes., Findings: 258 children (median age 5 [interquartile range (IQR) 3-7]) were sampled; 8 (3.1%) with early vomiting were excluded. Primaquine doses of 0.10-0.40 (median 0.21, IQR 0.16-0.25) mg base/kg resulted in primaquine maximum plasma concentrations (Cmax) of 2.3-447 (median 103.0, IQR 72.1-140.0) ng/mL between 1.0 and 8.0 (median 2) hours (T max ) and median areas under the drug concentration curves (AUC 0-last ) 730.2 (6 m-<1 y, n = 12), 582.8 (1-5 y, n = 126), 871.1 (6-9 y, n = 80), and 931.0 (10-11 y, n = 32) ng∗h/mL. Median elimination half-live (T½) was 4.7 (IQR 3.8-5.6) hours. Primaquine clearance/kg peaked at 18 months, plateauing at 4 y. Increasing CYP2D6 metaboliser activity score [poor (3/250), intermediate (52/250), normal (150/250), ultrarapid (5/250), indeterminate (40/250)] and baseline haemoglobin were significantly associated with a lower primaquine AUC 0-last ,which increased with increasing mg/kg dose and age but was independent of the artemisinin treatment used., Interpretation: Age-dosed SLDPQ resulted in variable primaquine exposure that depended on bodyweight-adjusted dose, age, baseline haemoglobin and CYP2D6 metaboliser status, but not on dihydroartemisinin-piperaquine or artemether-lumefantrine. These data support age-dosed SLDPQ for transmission blocking in sub-Saharan Africa., Funding: This work was cofunded by the UK Medical Research Council, Wellcome Trust, and UK Aid through the Global Health Trials (grant reference MR/P006973/1). The funders had no role in the study design, execution, and analysis and decisions regarding publication., Competing Interests: Declaration of interests All authors declare that they have no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Acute kidney injury (AKI) has in the past been considered a rare complication of malaria in children living in high-transmission settings. More recently, however, a growing number of paediatric case series of AKI in severe malaria studies in African children have been published (Artesunate vs Quinine in the Treatment of Severe P. falciparum Malaria in African children and Fluids Expansion as Supportive Therapy trials). The Paracetamol for Acute Renal Injury in Severe Malaria Trial (PARIST) therefore, aims to assess feasibility, safety and determine the effective dose of paracetamol, which attenuates nephrotoxicity of haemoproteins, red-cell free haemoglobin and myoglobin in children with haemoglobinuric severe malaria., Methods: PARIST is a phase I/II unblinded randomised controlled trial of 40 children aged >6 months and <12 years admitted with confirmed haemoglobinuric severe malaria (blackwater fever), a positive blood smear for P. falciparum malaria and either serum creatinine (Cr) increase by ≥0.3 mg/dL within 48 hours or to ≥1.5 times baseline and elevated blood urea nitrogen (BUN) >20 mg/dL. Children will be randomly allocated on a 1:1 basis to paracetamol intervention dose arm (20 mg/kg orally 6-hourly for 48 hours) or to a control arm to receive standard of care for temperature control (ie, tepid sponging for 30 min if fever persists give rescue treatment). Primary outcome is renal recovery at 48 hours as indicated by stoppage of progression and decrease of Cr level below baseline, BUN (<20 mg/dL). Data analysis will be on the intention-to-treat principle and a per-protocol basis.Results from this phase I/II clinical trial will provide preliminary effectiveness data of this highly potential treatment for AKI in paediatric malaria (in particular for haemoglobinuric severe malaria) for a larger phase III trial., Ethics and Dissemination: Ethical and regulatory approvals have been granted by the Mbale Hospital Institutional Ethics Review Committee (MRRH-REC OUT 002/2019), Uganda National Council of Science and Technology (UNCST-HS965ES) and the National drug Authority (NDA-CTC 0166/2021). We will be disseminating results through journals, conferences and policy briefs to policy makers and primary care providers., Trial Registration Number: ISRCTN84974248., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In sub-Saharan Africa (SSA), malaria remains a public health problem despite recent reports of declining incidence. Severe malaria is a multiorgan disease with wide-ranging clinical spectra and outcomes that have been reported to vary by age, geographical location, transmission intensity over time. There are reports of recent malaria epidemics or resurgences, but few data, if any, focus on the clinical spectrum of severe malaria during epidemics. This describes the clinical spectrum and outcomes of childhood severe malaria during the disease epidemic in Eastern Uganda., Methods: This prospective cohort study from October 1, 2021, to September 7, 2022, was nested within the 'Malaria Epidemiological, Pathophysiological and Intervention studies in Highly Endemic Eastern Uganda' (TMA2016SF-1514-MEPIE Study) at Mbale Regional Referral Hospital, Uganda. Children aged 60 days to 12 years who at admission tested positive for malaria and fulfilled the clinical WHO criteria for surveillance of severe malaria were enrolled on the study. Follow-up was performed until day 28. Data were collected using a customized proforma on social demographic characteristics, clinical presentation, treatment, and outcomes. Laboratory analyses included complete blood counts, malaria RDT (SD BIOLINE Malaria Ag P.f/Pan, Ref. 05FK60-40-1) and blood slide, lactate, glucose, blood gases and electrolytes. In addition, urinalysis using dipsticks (Multistix ® 10 SG, SIEMENS, Ref.2300) at the bedside was done. Data were analysed using STATA V15.0. The study had prior ethical approval., Results: A total of 300 participants were recruited. The median age was 4.6 years, mean of 57.2 months and IQR of 44.5 months. Many children, 164/300 (54.7%) were under 5 years, and 171/300 (57.0%) were males. The common clinical features were prostration 236/300 (78.7%), jaundice in 205/300 (68.3%), severe malarial anaemia in 158/300 (52.7%), black water fever 158/300 (52.7%) and multiple convulsions 51/300 (17.0%), impaired consciousness 50/300(16.0%), acidosis 41/300(13.7%), respiratory distress 26/300(6.7%) and coma in 18/300(6.0%). Prolonged hospitalization was found in 56/251 (22.3%) and was associated with acidosis, P = 0.041. The overall mortality was 19/300 (6.3%). Day 28 follow-up was achieved in 247/300 (82.3%)., Conclusion: During the malaria epidemic in Eastern Uganda, severe malaria affected much older children and the spectrum had more of prostration, jaundice severe malarial anaemia, black water fever and multiple convulsions with less of earlier reported respiratory distress and cerebral malaria., (© 2023. The Author(s).)

Background: WHO recommends gametocytocidal, single low-dose primaquine for blocking the transmission of Plasmodium falciparum; however, safety concerns have hampered the implementation of this strategy in sub-Saharan Africa. We aimed to investigate the safety of age-dosed, single low-dose primaquine in children from Uganda and the Democratic Republic of the Congo., Methods: We conducted this randomised, double-blind, placebo-controlled, non-inferiority trial at the Mbale Regional Referral Hospital, Mbale, Uganda, and the Kinshasa Mahidol Oxford Research Unit, Kinshasa, Democratic Republic of the Congo. Children aged between 6 months and 11 years with acute uncomplicated P falciparum infection and haemoglobin concentrations of at least 6 g/dL were enrolled. Patients were excluded if they had a comorbid illness requiring inpatient treatment, were taking haemolysing drugs for glucose-6-phosphate dehydrogenase (G6PD) deficiency, were allergic to the study drugs, or were enrolled in another clinical trial. G6PD status was defined by genotyping for the G6PD c.202T allele, the cause of the G6PD-deficient A- variant. Participants were randomly assigned (1:1) to receive single low-dose primaquine combined with either artemether-lumefantrine or dihydroartemisinin-piperaquine, dosed by bodyweight. Randomisation was stratified by age and G6PD status. The primary endpoint was the development of profound (haemoglobin <4 g/dL) or severe (haemoglobin <5 g/dL) anaemia with severity features, within 21 days of treatment. Analysis was by intention to treat. The sample size assumed an incidence of 1·5% in the placebo group and a 3% non-inferiority margin. The trial is registered at ISRCTN, 11594437, and is closed to new participants., Findings: Participants were recruited at the Mbale Regional Referral Hospital between Dec 18, 2017, and Oct 7, 2019, and at the Kinshasa Mahidol Oxford Research Unit between July 17, 2017, and Oct 5, 2019. 4620 patients were assessed for eligibility. 3483 participants were excluded, most owing to negative rapid diagnostic test or negative malaria slide (n=2982). 1137 children with a median age of 5 years were enrolled and randomly assigned (286 to the artemether-lumefantrine plus single low-dose primaquine group, 286 to the artemether-lumefantrine plus placebo group, 283 to the dihydroartemisinin-piperaquine plus single low-dose primaquine group, and 282 to the dihydroartemisinin-piperaquine plus placebo group). Genotyping of G6PD identified 239 G6PD-c.202T hemizygous males and 45 G6PD-c.202T homozygous females (defining the G6PD-deficient group), 119 heterozygous females, 418 G6PD-c.202C normal males and 299 G6PD-c.202C normal females (defining the non-G6PD-deficient group), and 17 children of unknown status. 67 patients were lost to follow-up and four patients withdrew during the study-these numbers were similar between groups. No participants developed profound anaemia and three developed severe anaemia: from the G6PD-deficient group, none (0%) of 133 patients who received placebo and one (0·66%) of 151 patients who received primaquine (difference -0·66%, 95% CI -1·96 to 0·63; p=0·35); and from the non-G6PD-deficient group, one (0·23%) of 430 patients who received placebo and one (0·25%) of 407 patients who received primaquine (-0·014%, -0·68 to 0·65; p=0·97)., Interpretation: Gametocytocidal, age-dosed, single low-dose primaquine was well tolerated in children from Uganda and the Democratic Republic of the Congo who were infected with P falciparum, and the safety profile of this treatment was similar to that of the placebo. These data support the wider implementation of single low-dose primaquine in Africa., Funding: UK Government Department for International Development, UK Medical Research Council, UK National Institute for Health Research, and the Wellcome Trust Joint Global Health Trials Scheme., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The World Health Organization has promoted "test and treat" guidelines for malaria since 2010, recommending all suspected malaria cases be confirmed with a parasitological test, typically a rapid diagnostic test (RDT), prior to treatment with antimalarial medications. However, many fevers at private drug shops in Uganda continue to be treated presumptively as malaria without diagnostic testing., Methods: The purpose of this study was to document private sector malaria case management in rural Uganda through a cross-sectional survey of drug shop clients in Bugoye sub-county. Drug shop vendors ( n = 46) recorded information about sales interactions with clients reporting fever or requesting antimalarials and collected capillary blood samples from clients who purchased medications without an RDT. We estimated the proportion of clients who purchased an RDT, adhered to the RDT result, and received antimalarials without having laboratory-confirmed malaria., Results: Most drug shops were unlicensed (96%) and sold RDTs (98%). Of 934 clients with suspected malaria who visited study drug shops during the data collection period, only 25% bought an RDT. Since some clients reported previous RDTs from the public sector, 40% of clients were aware of their malaria status at the drug shop. Among those with negative tests, 36% still purchased antimalarials. Sixty-five percent of clients who purchased an antimalarial without an RDT subsequently tested negative., Conclusions: Despite national guidelines, drug shop clients who purchase antimalarials from drug shops in Bugoye are often not tested to confirm a malaria diagnosis prior to treatment. Most clients treated presumptively with antimalarials did not have malaria. Interventions are needed to improve malaria case management and rational drug use in the private sector., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shelus, Mumbere, Mulogo, Barrington, Baguma, Muhindo, Herrington, Emch, Maman and Boyce.)

Objective: The study aim was to evaluate the prevalence and predictors of hypertension among an urban adult population in Mbarara city, Western Uganda., Methods: We evaluated blood pressure measurements, social demographic and clinical parameters of adults living in Mbarara city, Uganda. These parameters were extracted from medical records of adults who participated in the Uganda World Kidney Day 2020 health screening activities. A total of 302 adults were evaluated for hypertension using the American College of Cardiology/American Heart Association 2017 (blood pressure threshold 130/80 mmHg) and International Society of Hypertension 2020 guidelines (threshold 140/90 mmHg)., Results: The mean age of the participants was 42.5 years (standard deviation: 15.1) and majority were male 195/302 (64.6%). Using American College of Cardiology/American Heart Association 2017 guidelines, 156/302 (51.7%) adults were newly diagnosed with hypertension compared to 68/302 (22.5%) newly diagnosed with hypertension using International Society of Hypertension 2020 guidelines. Only 23/302 (7.6%) were on treatment. Based on American College of Cardiology/American Heart Association 2017 guidelines, age ≥40 years and overweight/obesity were statistically significant predictors of hypertension (p < 0.05 for all) at multivariate analysis. Using the International Society of Hypertension 2020 guidelines, age ≥40 years predicted hypertension., Discussion: The prevalence of hypertension is high among this urban adult population irrespective of the guidelines used, highlighting the need for hypertension prevention interventions.

Background: Hypertension is a key contributor to the global epidemic of cardiovascular disease and is responsible for more deaths worldwide than any other cardiovascular risk factor. Hypertensive disorders of pregnancy, of which preeclampsia and eclampsia are the most common forms, have been shown to be a female-specific risk factor for chronic hypertension., Objective: This study aimed to determine the proportion and risk factors for persistent hypertension at 3 months after delivery among women with hypertensive disorders of pregnancy in Southwestern Uganda., Study Design: This was a prospective cohort study of pregnant women with hypertensive disorders of pregnancy admitted for delivery at Mbarara Regional Referral Hospital in Southwestern Uganda from January 2019 to December 2019; however, women with chronic hypertension were excluded from the study. The participants were followed up for 3 months after delivery. Participants with a systolic blood pressure of ≥140 mm Hg or a diastolic blood pressure of ≥90 mm Hg or receiving antihypertension therapy at 3 months after delivery were considered to have persistent hypertension. Multivariable logistic regression was used to determine independent risk factors associated with persistent hypertension., Results: A total of 111 participants with hypertensive disorders of pregnancy diagnosed at hospital admission were enrolled with a follow-up rate of 49% (54/111) at 3 months after delivery. Of these women, 21 of 54 (39%) had persistent hypertension 3 months after delivery. In the adjusted analyses, an elevated serum creatinine level (>106.08 µmol/L [≤1.2 mg/dL]) at admission for delivery was the only independent risk factor for persistent hypertension at 3 months after delivery (adjusted relative risk, 1.93; 95% confidence interval, 1.08-3.46; P =.03), controlling for age, gravidity, and eclampsia., Conclusion: Approximately 4 of 10 women presenting with hypertensive disorders of pregnancy at our institution remained hypertensive 3 months after delivery. Innovative strategies are needed to identify these women and provide long-term care to optimize blood pressure control and reduce future cardiovascular disease after hypertensive disorders of pregnancy., (© 2023 The Authors.)

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 (27 th October 2017)., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Olupot-Olupot P et al.)

The World Health Organization recommends all suspected malaria cases be confirmed with a parasitological test, typically a rapid diagnostic test (RDT), prior to treatment. Despite recommendations, many fevers presenting at private drug shops are treated presumptively as malaria without diagnostic testing. The purpose of this qualitative study was to describe community perceptions of RDTs and explore ways to improve malaria case management at drug shops in Bugoye, western Uganda. A total of 63 in-depth interviews were conducted between September and December 2021 with 24 drug shop clients, 19 drug shop vendors, 12 community health workers, and 8 health and community officials. Data was analyzed using thematic content analysis and narrative techniques. While drug shop clients valued RDTs, the cost of the test limited their use. Further, mistrust in negative results and fear about treatment options for conditions other than malaria led to nonadherence to negative RDTs. Improvement with antimalarials after a negative RDT, or no RDT at all, was seen as proof an individual had malaria, reinforcing the acceptability of liberal antimalarial use. Drug shop vendors were knowledgeable about malaria case management but financially conflicted between recommending best practices and losing business. While clients viewed drug shop vendors as trusted health professionals, health officials distrusted them as business owners focused on maximizing profits. Study results suggest public-private partnerships that recognize the essential role of drug shops, better incorporate them into the healthcare system, and leverage the high levels of community trust in vendors, could provide greater opportunities for oversight and training to improve private-sector malaria case management. Interventions that address financial barriers to RDT use, emphasize the financial benefits of malaria testing, increase vendor knowledge about illnesses confused with malaria, and improve the quality of vendor-client counseling could increase RDT uptake and improve adherence to RDT results., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Shelus 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: Despite being a priority population for COVID-19 vaccination, limited data are available regarding acceptability of COVID-19 vaccines among people living with HIV (PLWH) in Sub-Saharan Africa. We described COVID-19 vaccine acceptability and factors associated with vaccine acceptability among PLWH in Uganda., Methods: This was a cross-sectional study conducted among PLWH, aged ≥18 years, enrolled participants who were seeking HIV care from six purposely selected accredited ART clinics in Kampala. We obtained data on vaccine acceptability defined as willingness to accept any of the available COVID-19 vaccines using interviewer-administered questionnaires. In addition, we assessed vaccination status, complacency regarding COVID-19 disease, vaccine confidence, and vaccine convenience. Factors associated with COVID-19 vaccine acceptability were evaluated using modified Poisson regression with robust standard errors., Results: We enrolled 767 participants of whom 485 (63%) were women. The median age was 33 years [interquartile range (IQR) 28-40] for women and 40 years [IQR], (34-47) for men. Of the respondents 534 (69.6%,95% confidence interval [CI]: 66.3%-72.8%) reported receiving at least one vaccine dose, with women significantly more likely than men to have been vaccinated (73% vs. 63%; p = 0.003). Among the unvaccinated 169 (72.7%, 95% CI: 66.6%-78.0%) were willing to accept vaccination, had greater vaccine confidence (85.9% had strong belief that the vaccines were effective; 81.9% that they were beneficial and 71% safe for PLWH; 90.5% had trust in health care professionals or 77.4% top government officials), and believed that it would be easy to obtain a vaccine if one decided to be vaccinated (83.6%). Vaccine acceptability was positively associated with greater vaccine confidence (adjusted prevalence ratio [aPR] 1.44; 95% CI: 1.08-1.90), and positive perception that it would be easy to obtain a vaccine (aPR 1.57; 95% CI: 1.26-1.96)., Conclusion: vaccine acceptance was high among this cohort of PLWH, and was positively associated with greater vaccine confidence, and perceived easiness (convince) to obtained the vaccine. Building vaccine confidence and making vaccines easily accessible should be a priority for vaccination programs targeting PLWH., Competing Interests: The author(s) declare that they have no competing interests., (Copyright: © 2022 Muhindo 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 and Objectives: Adequate supplies of donor blood remain a major challenge in sub-Saharan Africa. This is exacerbated by a lack of confirmatory testing for transfusion-transmitted infections by blood transfusion services (BTS), leading to significant blood disposal owing to putatively high seroprevalence rates amongst Ugandan blood donors. We aimed to ascertain the false discovery rate of the Architect anti-hepatitis C virus (HCV) screening assay and categorize screen-reactive samples into three groups: presumed false positive, active and past infection, and develop an algorithm for confirmatory testing., Materials and Methods: A total of 470 screen-reactive HCV blood donations were retested using the Architect anti-HCV assay, an alternative antibody test (SD Biosensor) and a core antigen (cAg) test. signal-to cut-off (S/CO) ratios and pre-analytical factors (centrifugation speed, haemolysis check, time between collection and testing) were recorded. Based on the S/CO ratio evaluation, we propose a testing algorithm to guide supplemental tests., Results: The false discovery rate of the Architect anti-HCV assay was 0.84 as 395/470 (84%) screen-reactive samples had no evidence of HCV infection (SD Biosensor and cAg negative) (presumed false positive), 38/470 (8.1%) were antigenaemic, and 32/470 (6.8%) had evidence of past infection. The median S/CO ratios of the presumed false-positive and active infection samples were 1.8 and 17.3, respectively. The positive predictive value of HCV positivity in samples with ratios above 12 was 91.8%. On retesting, 104/470 (22.1%) samples became negative., Conclusion: The Architect anti-HCV assay has a very high false discovery rate in Ugandan BTSs, leading to excessive blood disposal. Pre-analytical factors likely contribute to this. An introduction of confirmatory testing using an algorithm based on S/CO ratio evaluation could limit unnecessary blood wastage and donor deferral., (© 2022 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Background: The presence of acute kidney injury (AKI) in pre-eclampsia complicates treatment including; increasing length of hospital stay and a need to access services like dialysis which are largely expensive in resource-limited settings. We aimed to determine incidence and predictors of acute kidney injury among women with severe pre-eclampsia at Mbarara Regional Referral Hospital in southwestern Uganda., Methods: We carried out a hospital-based prospective cohort study from 16 November  2018 to 18 April 2019, among pregnant women with severe pre-eclampsia followed up in the hospital. We enrolled 70 mothers with severe pre-eclampsia and eclampsia; we excluded patients with a history of chronic kidney disease, chronic hypertension, and gestational hypertension. Data on socio-demographics, laboratory parameters, health system, obstetric and medical factors were collected. Baseline serum creatinine, complete blood count, and CD4 T-cell count were all done at admission (0-hour). A second serum creatinine was done at 48-hours to determine the presence of AKI and AKI was defined as a relative change of serum creatinine value at least 1.5 times the baseline (i.e., at admission) within 48 h. The proportion of women diagnosed with acute kidney injury among the total number of women with severe pre-eclampsia was reported as incidence proportion. Univariate and multivariate logistic regression was used to establish the association between acute kidney injury and severe pre-eclampsia., Results: Incidence of acute kidney injury was high (42.86%) among women with severe pre-eclampsia. Antenatal care attendance was protective with an odds ratio of 0.14 (0.03, 0.73), p-value 0.020 at bivariate analysis but had no statistical significance at multivariate analysis. Eclampsia was an independent risk factor for acute kidney injury. (aOR 5.89 (1.51, 38.88), p-value 0.014., Conclusion: The incidence of acute kidney injury in patients with severe pre-eclampsia is high. Eclampsia is an independent risk factor of acute kidney injury. The findings of this study highlight the urgent need for more research and better perinatal care for these women., (© 2022. The Author(s).)

Background: Malaria epidemics are a well-described phenomenon after extreme precipitation and flooding. Yet, few studies have examined mitigation measures to prevent post-flood malaria epidemics., Methods: We evaluated a malaria chemoprevention program implemented in response to severe flooding in western Uganda. Children aged ≤12 years from 1 village were eligible to receive 3 monthly rounds of dihydroartemisinin-piperaquine (DP). Two neighboring villages served as controls. Malaria cases were defined as individuals with a positive rapid diagnostic test result as recorded in health center registers. We performed a difference-in-differences analysis to estimate changes in the incidence and test positivity of malaria between intervention and control villages., Results: A total of 554 children received at least 1 round of chemoprevention, with 75% participating in at least 2 rounds. Compared with control villages, we estimated a 53.4% reduction (adjusted rate ratio [aRR], 0.47; 95% confidence interval [CI]: .34-.62; P < .01) in malaria incidence and a 30% decrease in the test positivity rate (aRR, 0.70; 95% CI: .50-.97; P = .03) in the intervention village in the 6 months post-intervention. The impact was greatest among children who received the intervention, but decreased incidence was also observed in older children and adults (aRR, 0.57; 95% CI: .38-.84; P < .01)., Conclusions: Three rounds of chemoprevention with DP delivered under pragmatic conditions reduced the incidence of malaria after severe flooding in western Uganda. These findings provide a proof-of-concept for the use of malaria chemoprevention to reduce excess disease burden associated with severe flooding., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: Fluid bolus resuscitation in African children is harmful. Little research has evaluated physiologic effects of maintenance-only fluid strategy., Design: We describe the efficacy of fluid-conservative resuscitation of septic shock using case-fatality, hemodynamic, and myocardial function endpoints., Setting: Pediatric wards of Mbale Regional Referral Hospital, Uganda, and Kilifi County Hospital, Kenya, conducted between October 2013 and July 2015. Data were analysed from August 2016 to July 2019., Patients: Children (≥ 60 d to ≤ 12 yr) with severe febrile illness and clinical signs of impaired perfusion., Interventions: IV maintenance fluid (4 mL/kg/hr) unless children had World Health Organization (WHO) defined shock (≥ 3 signs) where they received two fluid boluses (20 mL/kg) and transfusion if shock persisted. Clinical, electrocardiographic, echocardiographic, and laboratory data were collected at presentation, during resuscitation and on day 28. Outcome measures were 48-hour mortality, normalization of hemodynamics, and cardiac biomarkers., Measurement and Main Results: Thirty children (70% males) were recruited, six had WHO shock, all of whom died (6/6) versus three of 24 deaths in the non-WHO shock. Median fluid volume received by survivors and nonsurvivors were similar (13 [interquartile range (IQR), 9-32] vs 30 mL/kg [28-61 mL/kg], z = 1.62, p = 0.23). By 24 hours, we observed increases in median (IQR) stroke volume index (39 mL/m 2 [32-42 mL/m 2 ] to 47 mL/m 2 [41-49 mL/m 2 ]) and a measure of systolic function: fractional shortening from 30 (27-33) to 34 (31-38) from baseline including children managed with no-bolus. Children with WHO shock had a higher mean level of cardiac troponin ( t = 3.58; 95% CI, 1.24-1.43; p = 0.02) and alpha-atrial natriuretic peptide ( t = 16.5; 95% CI, 2.80-67.5; p < 0.01) at admission compared with non-WHO shock. Elevated troponin (> 0.1 μg/mL) and hyperlactatemia (> 4 mmol/L) were putative makers predicting outcome., Conclusions: Maintenance-only fluid therapy normalized clinical and myocardial perturbations in shock without compromising cardiac or hemodynamic function whereas fluid-bolus management of WHO shock resulted in high fatality. Troponin and lactate biomarkers of cardiac dysfunction could be promising outcome predictors in pediatric septic shock in resource-limited settings., Competing Interests: Drs. Obonyo, Olupot-Olupot, and Uyoga are funded and supported through the Wellcome Trust and the Department for International Development funded DELTAS Africa Initiative (DEL-15-003). Dr. Obonyo received funding from Imperial College London (Institutional Strategic Support Funds [105603/Z/14/Z]) and Wellcome Trust Imperial College Centre for Global Health Research [100693/Z/12/Z]) and the Initiative to Develop African Research Leaders/Kenya Medical Research Institute-Wellcome Trust Research Programme. Dr. Chebet received funding from Mbale Clinical Research Institute. Drs. Olupot-Olupot, Nteziyaremye, Muhindo, and Maitland received support for article research from Research Councils UK. Drs. Nteziyaremye, Chebet, Muhindo, and Maitland received support for article research from Wellcome Trust/Charity Open Access Fund. Dr. Maitland received funding from Wellcome East African Overseas Programme Award from the Wellcome Trust (203077/Z/16/Z). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Progress against malaria has stalled and may even be slipping backwards in high-burden countries. This is due to a range of factors including insecticide resistance and mosquito feeding behaviours that limit contact with widely-employed interventions including long-lasting insecticidal nets and indoor-residual spraying. Thus, further innovations in malaria control are urgently needed., Methods: The pilot was a randomized, placebo-controlled pilot study of permethrin-treated baby wraps-known locally as lesus-in children 6-18 months of age at a single site in rural western Uganda. Fifty mother-infant pairs were assigned to permethrin-treated or untreated lesus in a 1:1 allocation. Participants and clinical staff were blinded to group assignments through use of sham treatment and re-treatment of lesus. Participants attended scheduled clinic visits every 2 weeks for a total 12 weeks. The primary outcome of interest was the safety of the intervention, assessed as changes in the frequency of use, rates of discontinuation, and incidence of adverse events, such as skin rash. Secondary outcomes included acceptability and feasibility of the intervention as measured through participant satisfaction and completion of study activities, respectively., Results: Overall, rates of retention and participation were relatively high with 86.0% (43 of 50) of participants completing all scheduled visits, including 18 (75.0%) and 25 (96.2%) in the intervention and control arms respectively. By the conclusion of the 12-week follow-up period, one adverse event (0.35 events per 100 person-weeks, one-sided 95% CI 0.0-1.65) was reported. Satisfaction with the lesu was high in both groups. In each study arm, there were five incident RDT positive results, but the only PCR-positive results were observed in the control group (n = 2)., Conclusions: Permethrin-treated baby wraps were well-tolerated and broadly acceptable. Adverse events were infrequent and mild. These findings support future trials seeking to determine the efficacy of treated wraps to prevent P. falciparum malaria infection in young children as a complementary tool to existing household-based interventions., Trial Registration: ClinicalTrials.gov Identifier: NCT04102592, Registered 25 September 2019. Available at: https://clinicaltrials.gov/ct2/show/NCT04102592., (© 2022. The Author(s).)

The clinical epidemiology of adults admitted with reduced level of consciousness (LOC) in sub-Saharan Africa (SSA) and the impact of HIV infection on the risk of mortality in this population is unknown. We secondarily analyzed data from a cohort study that enrolled 359 consecutive adults with reduced LOC presenting to Mbarara Regional Hospital in Uganda with the aim of comparing the prognostic utility of the Full Outline of Unresponsiveness (FOUR) score to the Glasgow Coma Scale (GCS) Score. For this analysis, we included 336 individuals with known HIV serostatus, obtaining clinical, laboratory, and follow-up data. We recorded investigations and treatments deemed critical by clinicians for patient care but were unavailable. We computed mortality rates and used logistic regression to determine predictors of 30-day mortality. The median GCS was 10. Persons living with HIV infection (PLWH) accounted for 97 of 336 (29%) of the cohort. The 30-day mortality rate in the total cohort was 148 of 329 (45%), and this was significantly higher in PLWH (57% versus 40%, adjusted odds ratio [aOR] 2.39: 95% confidence interval [CI]: 1.31-4.35, P = 0.0046). Other predictors of mortality were presence of any unmet clinical need (aOR 1.72; 95% CIL 1.04-2.84, P = 0.0346), anemia (aOR 1.68; 95% CI: 1.01-2.81, P = 0.047), and admission FOUR score < 12 [aOR 4.26; 95% CI: 2.36-7.7, P < 0.0001). Presentation with reduced LOC in Uganda is associated with high mortality rates, with worse outcomes in PLWH. Improvement of existing acute care services is likely to improve outcomes.

Pediatric acute respiratory illness (ARI) is one of the most common reasons for evaluation at peripheral health centers in sub-Saharan Africa and is frequently managed based on clinical syndrome alone. Although most ARI episodes are likely caused by self-limited viral infections, the majority are treated with antibiotics. This overuse contributes to the development of antimicrobial resistance. To evaluate the preliminary feasibility and potential impact of adding pathogen-specific and clinical biomarker diagnostic testing to existing clinical management algorithms, we conducted a prospective, observational cohort study of 225 children presenting with malaria-negative, febrile ARI to the outpatient department of a semi-urban peripheral health facility in southwestern Uganda from October 2019 to January 2020. In addition to routine clinical evaluation, we performed influenza and Streptococcus pneumoniae antigen testing and measured levels of C-reactive protein, procalcitonin, and lactate in the clinic's laboratory, and conducted a follow-up assessment by phone 7 days later. Almost one-fifth of participants (40/225) tested positive for influenza. Clinical biomarker measurements were low with C-reactive protein of >40 mg/L in only 11% (13/222) of participants and procalcitonin >0.25 ng/mL in only 13% (16/125). All but two children received antibiotic treatment; only 3% (7/225) were admitted. At follow-up, 59% (118/201) of caregivers reported at least one persistent symptom, but fever had resolved for all children. Positive influenza testing was associated with persistent symptoms. In summary, we demonstrate that simple, rapid pathogen-specific testing and biomarker measurement are possible in resource-limited settings and could improve syndromic management and, in turn, antibiotic stewardship. IMPORTANCE Globally, respiratory illness is one of the most common reasons that children seek care. It is often treated inappropriately with antibiotics, which can drive the development of antibiotic resistance. In resource-rich settings, testing for specific pathogens or measurement of clinical biomarkers, such as procalcitonin and C-reactive protein, is often employed to help determine which children should receive antibiotics. However, there are limited data on the use of these tests in resource-constrained, outpatient contexts in sub-Saharan Africa. We enrolled children with respiratory illness presenting to a clinic in southwestern Uganda and performed testing for influenza, Streptococcus pneumoniae, C-reactive protein, and procalcitonin on-site. Almost all children received antibiotics. We demonstrate that employing clinical algorithms that include influenza and clinical biomarker testing could significantly decrease antibiotic prescriptions. Our study therefore provides preliminary data to support the feasibility and potential utility of diagnostics to improve management of respiratory illness in resource-constrained settings.

Background: Periodic testing of female sex workers (FSW) for sexually transmitted infections (STIs) is a core component of global and national responses to achieve population-level STI elimination. We conducted a qualitative study to explore barriers and facilitators of regular syphilis and HIV testing among FSW in Uganda., Methods: Within a quasi-experimental study among 436 FSW to assess the effect of peer education and text message reminders on uptake of regular STI and HIV testing among FSW, we conducted 48 qualitative interviews in four cities in Uganda from August-December 2018. We purposively selected FSW who tested for syphilis and HIV every 3-6 months; 12 FSW were interviewed in each city. Sex worker interviews explored: 1) reasons for periodic syphilis and HIV testing; 2) barriers and facilitators of testing; 3) experiences of testing; and 4) challenges faced while seeking testing services. Data were analyzed using thematic content analysis., Results: Thematic analysis revealed individual- and health system-level barriers and facilitators of testing. For syphilis, barriers were a) interpersonal stigma, low perceived severity of syphilis and testing misconceptions (individual); and b) judgmental provider attitudes, paucity of facilities offering syphilis testing, stockouts of test kits and high cost (health system). Facilitators were c) desire to remain healthy, get married and have children, knowing the benefits of early treatment, influence of male partners/clients and normative testing behaviors (individual); and d) sex worker clinics offering dual syphilis/HIV testing (health system). For HIV, barriers included: a) internalized stigma (individual); and b) unfavorable clinic hours, stigma, discrimination, and unfriendly provider (health system). Facilitators were a) motivations to stay healthy and attract clients, habitual testing, self-efficacy, doubts about accuracy of negative test results, and use of post-exposure prophylaxis (individual); and d) availability of testing facilities (health system). Syphilis and HIV had similar testing barriers and facilitators., Conclusions: HIV programs are likely to be important entry points for syphilis testing among FSW. Multi-level interventions to address testing barriers should consider focusing on these service delivery points. Extending the dual syphilis and HIV testing approach to FSW may improve testing uptake for both infections at public health facilities and decrease population-level incidence., (© 2021. The Author(s).)

Background: Long-lasting insecticidal nets (LLINs) remain a cornerstone of malaria control, but strategies to sustain universal coverage and high rates of use are not well-defined. A more complete understanding of context-specific factors, including transmission intensity and access to health facilities, may inform sub-district distribution approaches and tailored messaging campaigns., Methods: A cross-sectional survey of 2190 households was conducted in a single sub-county of western Uganda that experiences highly variable malaria transmission intensity. The survey was carried out approximately 3 years after the most recent mass distribution campaign. At each household, study staff documented reported LLIN use and source among children 2 to 10 years of age and performed a malaria rapid diagnostic test. Elevation and distance to the nearest health facility was estimated for each household. Associations between parasite prevalence and LLIN use were estimated from log binomial regression models with elevation and distance to clinic being the primary variables of interest., Results: Overall, 6.8% (148 of 2170) of children age 2-10 years of age had a positive RDT result, yielding a weighted estimate of 5.8% (95% confidence interval [CI] 5.4-6.2%). There was substantial variability in the positivity rates among villages, with the highest elevation villages having lower prevalence than lowest-elevation villages (p < .001). Only 64.7% (95% CI 64.0-65.5%) of children were reported to have slept under a LLIN the previous night. Compared to those living < 1 km from a health centre, households at ≥ 2 km were less likely to report the child sleeping under a LLIN (RR 0.86, 95% CI 0.83-0.89, p < .001). Households located farther from a health centre received a higher proportion of LLINs from government distributions compared to households living closer to health centres., Conclusions: LLIN use and sourcing was correlated with household elevation and estimated distance to the nearest health facility. The findings suggest that current facility-based distribution strategies are limited in their reach. More frequent mass distribution campaigns and complementary approaches are likely required to maintain universal LLIN coverage and high rates of use among children in rural Uganda.

We enrolled 250 febrile children in western Uganda to compare the results of malaria rapid diagnostic tests (RDTs) when using capillary vs venous blood. Participants were tested with 4 different RDT types. Polymerase chain reaction testing was performed as the reference standard. Sensitivity and specificity were broadly similar across RDT types and sampling method. Agreement between sample type was high, ranging from 0.95 to 0.99. When following the manufacturer's recommended interpretation, only 5 tests would have resulted in a different clinical diagnosis. These results demonstrate that malaria RDTs perform similarly when using capillary or venous blood in febrile children with Plasmodium falciparum malaria., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Acute kidney injury (AKI) is a frequently encountered clinical condition in critically ill patients and is associated with increased morbidity and mortality. In our resource-limited setting (RLS), the most common cause of AKI is sepsis and volume depletion. Sepsis alone, accounts for up to 62 % of the AKI cases in HIV-positive patients., Objective: The major goal of this study was to determine the incidence and risk predictors of AKI among HIV-infected patients admitted with sepsis at a tertiary hospital in Uganda., Methods: In a prospective cohort study, we enrolled adult patients presenting with sepsis at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda between March and July 2020. Sepsis was determined using the qSOFA criteria. Patients presenting with CKD or AKI were excluded. Sociodemographic characteristics, physical examination findings, and baseline laboratory values were recorded in a data collection tool. The serum creatinine and urea were done at admission (0-hour) and at the 48-hour mark to determine the presence of AKI. We performed crude and multivariable binomial regression to establish the factors that predicted developing AKI in the first 48 h of admission. Variables with a p < 0.01 in the adjusted analysis were considered as significant predictors of AKI., Results: Out of 384 patients screened, 73 (19 %) met our inclusion criteria. Their median age was 38 (IQR 29-46) years and 44 (60.3 %) were male. The median CD4 T-cell count was 67 (IQR 35-200) cells, median MUAC was 23 (IQR 21-27) cm and 54 (74.0 %) participants were on a regimen containing Tenofovir Disoproxil Fumarate (TDF). The incidence of AKI in 48 h was 19.2 % and in the adjusted analysis, thrombocytopenia (Platelet count < 150) (adjusted risk ratio 8.21: 95 % CI: 2.0-33.8, p = 0.004) was an independent predictor of AKI., Conclusions: There is a high incidence of AKI among HIV-positive patients admitted with sepsis in Uganda. Thrombocytopenia at admission may be a significant risk factor for developing AKI. The association of thrombocytopenia in sepsis and AKI needs to be investigated.

Background: Measles outbreaks are prevalent throughout sub-Saharan Africa despite the preventive measures like vaccination that target under five-year-old children and health systems strengthening efforts like prioritizing the supply chain for supplies. Measles immunization coverage for Kasese district and Bugoye HC III in 2018 was 72 and 69%, respectively. This coverage has been very low and always marked red in the Red categorization (below the national target/poor performing) on the national league table indicators. The aim of this study was to assess the scope of the 2018-2019 measles outbreak and the associated risk factors among children aged 0-60 months in Bugoye sub-county, Kasese district, western Uganda., Methods: We conducted a retrospective unmatched case-control study among children aged 0-60 months with measles (cases) who had either a clinical presentation or a laboratory confirmation (IgM positivity) presenting at Bugoye Health Centre III (BHC) or in the surrounding communities between December 2018 and October 2019.. Caregivers of the controls (whose children did not have measles) were selected at the time of data collection in July 2020. A modified CDC case investigation form was used in data collection. Quantitative data was collected and analyzed using Microsoft excel and STATA version 13. The children's immunization cards and health registers at BHC were reviewed to ascertain the immunization status of the children before the outbreak., Results: An extended measles outbreak occurred in Bugoye, Uganda occured between December 2018 and October 2019. All 34 facility-based measles cases were documented to have had maculopapular rash, conjunctivitis, and cough. Also, the majority had fever (97%), coryza (94.1%), lymphadenopathy (76.5%), arthralgias (73.5%) and Koplik Spots (91.2%) as documented in the clinical registers. Similar symptoms were reported among 36 community-based cases. Getting infected even after immunized, low measles vaccination coverage were identified as the principal risk factors for this outbreak., Conclusion: Measles is still a significant problem. This study showed that this outbreak was associated with under-vaccination. Implementing a second routine dose of measles-rubella vaccine would not only increase the number of children with at least one dose but also boost the immunity of those who had the first dose.