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Abstract 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).

Abstract Background Postnatal growth failure (PGF), a multifactorial condition is common in preterm infants and infants born weighing

Abstract Background Preterm birth is the leading cause of childhood mortality, and respiratory distress syndrome is the predominant cause of these deaths. Early continuous positive airway pressure is effective in high-resource settings, reducing the rate of continuous positive airway pressure failure, and the need for mechanical ventilation and surfactant. However, most deaths in preterm infants occur in low-resource settings without access to mechanical ventilation or surfactant. We hypothesize that in such settings, early continuous positive airway pressure will reduce the rate of failure and therefore preterm mortality. Methods This is a mixed methods feasibility and acceptability, single-center pilot randomized control trial of early continuous positive airway pressure among infants with birthweight 800–1500 g. There are two parallel arms: (i) application of continuous positive airway pressure; with optional oxygen when indicated; applied in the delivery room within 15 min of birth; transitioning to bubble continuous positive airway pressure after admission to the neonatal unit if Downes Score ≥ 4 (intervention), (ii) supplementary oxygen at delivery when indicated; transitioning to bubble continuous positive airways pressure after admission to the neonatal unit if Downes Score ≥ 4 (control). A two-stage consent process (verbal consent during labor, followed by full written consent within 24 h of birth) and a low-cost third-party allocation process for randomization will be piloted. We will use focus group discussions and key informant interviews to explore the acceptability of the intervention, two-stage consent process, and trial design. We will interview healthcare workers, mothers, and caregivers of preterm infants. Feasibility will be assessed by the proportion of infants randomized within 15 min of delivery; the proportion of infants in the intervention arm receiving CPAP within 15 min of delivery; and the proportion of infants with primary and secondary outcomes measured successfully. Discussion This pilot trial will enhance our understanding of methods and techniques that can enable emergency neonatal research to be carried out effectively, affordably, and acceptably in low-resource settings. This mixed-methods approach will allow a comprehensive exploration of parental and healthcare worker perceptions, experiences, and acceptance of the intervention and trial design. Trial registration The study is registered on the Pan African Clinical Trials Registry (PACTR) PACTR202208462613789. Registered 08 August 2022. https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=23888 .

Abstract Background Pneumonia remains the leading cause of mortality among children under 5 years. Poor nutritional status increases pneumonia mortality. Nutritional status assessed by anthropometry alone does not provide information on which body composition element predicts survival. Body composition proxy measures including arm-fat-area (AFA), arm-muscle-area (AMA), and arm-muscle-circumference (AMC) could be useful predictors. Objective To compare the ability of fat and muscle mass indices to predict 6-month survival among children with severe pneumonia. Methods This prospective cohort study was nested in the COAST-Nutrition trial (ISRCTN10829073, 06/06/2018) conducted between June 2020 and October 2022 in Uganda and Kenya. We included children aged 6–59 months hospitalized for severe pneumonia with hypoxemia. Children with severe malnutrition, known chronic lung or cardiac diseases were excluded. Anthropometry and clinical status were assessed at enrolment and at follow-up to day 180. We examined Receiver Operator Characteristic (ROC) curves of fat and muscle mass indices with 6-month survival as the outcome, and compared the areas under the curve (AUCs) using chi-square tests. Cox survival analysis models assessed time-to-mortality. Results We included 369 participants. The median age was 15-months (IQR 9, 26), and 59.4% (219/369) of participants were male. The baseline measurements were: median MUAC 15.0 cm (IQR 14.0,16.0); arm-fat-area 5.6cm2 (IQR 4.7, 6.8); arm-muscle-area 11.4cm2 (IQR 10.0, 12.7); and arm-muscle-circumference 12.2 cm (IQR 11.5, 12.9). Sixteen (4.3%) participants died and 4 (1.1%) were lost-to-follow-up. The AUC for Arm-Fat-Area was not significantly higher than that for Arm-Muscle-Area and Arm-Muscle-Circumference [AUC 0.77 (95%CI 0.64–0.90) vs. 0.61 (95%CI 0.48–0.74), p = 0.09 and 0.63 (95%CI 0.51–0.75), p = 0.16 respectively], but was not statistically different from MUAC (AUC 0.73 (95%CI 0.62–0.85), p = 0.47). Increase in Arm-Fat-Area and Arm-Muscle-Circumference significantly improved survival [aHR 0.40 (95%CI 0.24–0.64), p =

Abstract Background Malaria is the leading cause of hospitalizations and death in Uganda, particularly in children under the age of five. Studies have shown that adherence to the World Health Organization (WHO) guidelines for the management of severe malaria reduces mortality in hospitalized children. This study aimed to determine the impact of targeted interventions on adherence to the WHO severe malaria treatment guidelines in children at a Ugandan hospital as part of a quality improvement initiative. Methods Interventions included workflow changes, such as obtaining patient blood samples for diagnostic testing by the admitting healthcare provider as well as utilizing patient caregivers to assist nursing staff in timing medications. An additional intervention was the use of an admission checklist sticker. The post-intervention sample was compared to the baseline assessment. The primary outcome was the proportion of patients receiving care consistent with all aspects of the WHO guidelines. Secondary outcomes included the proportion of patients receiving malaria diagnostic testing, those receiving at least 3 doses of artesunate, the timely administration of artesunate, and adherence to other guideline components. Statistical analyses were conducted using GraphPad PRISM 9.0. Comparisons between groups were analysed using Chi-square or Fisher’s exact test for categorical variables and Mann–Whitney test for continuous variables. Results The post-intervention group included 230 patients with a median age of 5 years [4–8], and 58% of patients were male. Adherence to all aspects of the WHO guidelines was achieved in 10% of patients in the post-intervention group compared to 3% of patients in the baseline (P = 0.007). Appropriate malaria diagnostic testing was performed in 85% of patients post-intervention compared to 66% of patients in the baseline (P

BackgroundGlobally, there are an estimated 20.9 million cases of onchocerciasis, with Africa bearing the greatest burden. The World Health Organization (WHO) has targeted the disease for elimination by 2030. As of August 2023, there were 15 foci in 37/48 (76%) districts and one city in Uganda that had reached the elimination phase. However, there is a paucity of data on community involvement in post-elimination surveillance (PES) activities. The communities in the post-elimination phase are expected to maintain surveillance, provide health education, refer cases for treatment, and participate in surveillance. However, it is not clear whether this is being done. In this study, we assessed the feasibility of community involvement in post-elimination surveillance activities in Bududa District, Eastern Uganda, to draw key generalisable lessons for similar settings.MethodsThis was a cross-sectional study employing rigorous mixed methods of data collection. We used a semi-structured questionnaire to collect quantitative data on randomly sampled study participants in two sub-countries in the district. Community involvement in post-elimination surveillance (PES) was our dependent variable, measured using Yes or No questions, and our independent variables were measured on different scales. Computations of proportions and associations were done using Stata 15 software. Conversely, qualitative data were collected via focus group discussions (FGDs) for community participants and key informant interviews (KIIs) for local leaders. For the qualitative component, we had 2 FGDs, each consisting of 8 gender-balanced participants per group and 8 KIIs. Qualitative data analyses were done using a robust thematic framework approach, ensuring the reliability and validity of our findings.ResultsA total of 422 participants with a mean age of 51.4 years (SD = 15.8) participated in the study. Community involvement in post-elimination surveillance was low (14%). Factors associated with involvements were district support [Adjusted odd ratio AOR 14, 95 CI = (2.5, 81.7)], seeing black flies in the environment in a week preceding the survey [AOR 8, 95% CI = (1.5, 42.5)], in one month [AOR 3.8, 95% CI = (1.1, 13.2)], and being a community volunteer in the Ivermectin treatment program [AOR 4.3, 95% CI = (1.03, 17.9)]. Lack of funding, poor motivation, poor program sustainability planning, and a lack of drugs at health facilities were key challenges affecting community involvement in post-elimination surveillance.ConclusionCommunity involvement in onchocerciasis post-elimination surveillance activities in Bududa District in Eastern Uganda was low but could be improved by increased district support, funding, community motivation and sensitisation.

Summary: 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, SpO2 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).

Abstract Background Hydrocephalus is one of the most common neurological disabilities presenting in children. Although there are limited studies on its association with wasting, neurological comorbidities such as dysphagia have been associated with an increased risk of wasting in children. In this study, we aimed to determine the prevalence and factors associated with wasting in children less than five years with hydrocephalus. Methods We conducted a cross-sectional study at various satellite clinics of CURE Children’s Hospital in Uganda between September and November 2021. Children with hydrocephalus were identified at the outpatient departments of the satellite clinics of the Cure Children’s Hospital and these include Mbale, Gulu, Lira, Jinja and Katalemwa. A structured questionnaire was used to collect information on several variables including (1) for the mother: socio-demographic characteristics, partner support, and wealth index (2) for the child: socio-demographic characteristics, clinical symptoms, feeding difficulties and neural comorbidity. Anthropometric measurements were also taken and these included the mid-upper arm circumference. Data were analysed using Stata version 14. We estimated adjusted odds ratios and their corresponding 95% confidence intervals while relying on multivariable logistic regression models. Results The prevalence of wasting among children with hydrocephalus was 23.2% (n = 89/384) (95%CI: 19 − 27.7%). Their mean age was 19.5 months (SD 16.8). Most of the children were below 12 months (47.9%) and were male (57.5%). The factors associated with wasting among children with hydrocephalus included: having; difficulty in chewing and swallowing (AOR = 2.6, (95%CI:1.05–3.94), a poor appetite (AOR = 1.74, (95%CI: 1.31–2.32), difficulty in breathing (AOR = 1.9, (95%CI: 1.18–3.16), chocking on food (AOR = 1.42, (95%CI:1.1–1.9) and attending the Mbale satellite clinic (AOR = 2.1 (95% CI 1.19–3.7). Children under 5 years of age with hydrocephalus that were born to women whose highest level of education was 7 to 10 years of formal schooling (AOR = 0.32, 95%CI: (0.12–0.87) were less likely to be wasted. Conclusions and recommendations The prevalence of wasting among children with hydrocephalus was high. The factors associated with wasting were mainly feeding challenges. We recommend that children with hydrocephalus should be given greater attention regarding their nutrition especially those with various forms of feeding difficulties. The caregivers of children with hydrocephalus should receive counseling on nutrition and on the best modalities to rely on while feeding their children.

Abstract Background Pregnancy and childbirth complications are the leading cause of death among girls aged 15–19 years globally, with low- and middle-income countries (LMICs) accounting for 99% of global maternal deaths of women aged 15–49 years. Despite teenage pregnancies declining in many developing countries in recent years, the COVID-19 period intensified the problem and altered the trend for most countries. We determined the effect of the COVID-19 lockdown on the teenage pregnancy trend in Pakwach district, Uganda, to understand its magnitude in our study population. Methods Using interrupted time series analysis (ITS), sometimes known as quasi-experimental time series analysis. We constructed a time series of the first ANC service utilization records for girls aged 10–19 years in Pakwach district, Uganda, and conducted an interrupted series analysis. We compared the two periods of March 2019 to March 2020 and March 2020 to March 2021. We used Stata 15 to conduct our analysis, performed OLS, and plotted the results. Results The teenage pregnancy trend before the lockdown was decreasing by − 0.203 pregnancies per month, but in the first month after the institution of the lockdown (March 20, 2020), there was an increase in the teenage pregnancy rate of 13.9 pregnancies [95% CI: − 33.6 to 61.5], which corresponds to an increase in the monthly trend in teenage pregnancies (relative to the period before the COVID-19 lockdown trend) of 1.53 girls per month. Conclusion Teenage pregnancies increased during the lockdown. This slight increase depicted the impact of the pandemic on the teenage pregnancy trend associated with the COVID-19 outbreak. The government needs to focus on intervention to reduce this trend and avoid any further increases.

Abstract Background Coronavirus disease 2019 (COVID-19) pandemic affected malaria control activities in sub-Saharan Africa (SSA) resulting in 690,000 excess deaths in the year 2021. The authors hypothesized that COVID-19 affected the World Health Organization (WHO) Test, Treat and Track (T3) strategy that has been implemented in Uganda since 2010. In this study, health worker’s adherence to the T3 strategy during COVID-19 pandemic in Eastern Uganda was studied by assessing their knowledge, skills and practices. Methods A cross-sectional study utilizing mixed quantitative and qualitative data collections methods was conducted at Mbale Regional Referral Hospital in Eastern Uganda between November and December in 2020. Data were captured on demographics, knowledge, skills and practices for both health workers (HWs) and patients. Quantitative data were analysed using STATA 15.0 and reported as descriptive statistics, proportions and statistical associations. Moreover, qualitative data were collected via key informant interviews (KII) among purposively sampled study participants and analysed thematically using NVIVO software. Ethical approval was obtained prior to the study. Results A total of 436 study participants, of whom 103/436 (24%) and 333/436 (76%) were HWs and patients, respectively were studied. Among the HWs with mean age of 34 years (SD = 8.8 years), 81/103 (79%) had good practices, most 63/103 (61%) had good knowledge, and only 11/103 (10.7%) had good skills. Specifically, on the cadres, the laboratory personnel 19/103 (18%) had good knowledge 14/19 (74%) OR: 2.0 (95% CI 0.7–6) and were highly skilled OR: 4.6 (95% CI 1.2—18.1; P

Abstract Background Most data describing severe malaria (SM) in sub-Saharan Africa (SSA) are from research settings outside disease endemic areas. Using routinely collected data from Apac District Hospital, this study aimed at determining the burden and clinical spectrum of severe malaria. Methods This was a retrospective study that reviewed all paediatric admission records for malaria in the 24 months period from Jan 2019 to Dec 2020 at Apac District Hospital. Data on children aged 60 days to 12 years who at admission tested positive for malaria and fulfilled the World Health Organization clinical criteria for surveillance of severe malaria were abstracted using a customized proforma designed to capture variables on social demographic, clinical presentation, treatment, and outcomes. In addition, the tool included laboratory variables for complete blood counts, haemoglobin, and glucose levels. Data were analysed using STATA V15.0. The study had ethical approval from Mbale Regional Referral Hospital REC, Approval No. MRRH-REC 053/2019. Results A total of 5631 admission records were retrieved for this study period. Of these, 3649 (64.8%) were malaria admissions and 3422/3649 were children below 12years, with only 1864 (54.5%) of children having complete data. Of the 1864 children, 745 (40.0%) fulfilled the severe malaria inclusion criteria. Of the 745 children, 51.4% (n = 381) were males. The median age at admission was 31 months (IQR = 17–60). The most common clinical presentations among children with severe malaria were fever 722 (97.3%), cough 478 (64.2%), and difficulty in breathing 122 (17.9%). The median length of hospital stay was 2 (IQR; 2–4) days and 133 (17.9%) had prolonged hospital stay (> 4 days). Factors independently associated with prolonged hospital stay were, presenting with difficulty in breathing, aOR 1.83 (95% CI 1.02–3.27, P = 0.042) and prostration aOR 8.47 (95% CI 1.94–36.99, P = 0.004). A majority of admitted children, 735 (98.7%) survived, while 10 (1.3%) died of SM. Conclusion A high proportion (40.0%) of malaria admissions were due to SM. Prolonged Hospital stay was associated with prostration and difficulty in breathing. Overall mortality was low, 1.3% compared to mortality in the previously reported series. This study was able to use routinely collected data to describe the burden and clinical spectrum of SM. Improvement in the quality of data from such settings would improve disease descriptions for policy, monitoring of epidemics, response to interventions and to inform research.

Abstract 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.

Objective To describe chest radiograph findings among children hospitalized with clinically diagnosed severe pneumonia and hypoxaemia at three tertiary facilities in Uganda. Methods The study involved clinical and radiograph data on a random sample of 375 children aged 28 days to 12 years enrolled in the Children's Oxygen Administration Strategies Trial in 2017. Children were hospitalized with a history of respiratory illness and respiratory distress complicated by hypoxaemia, defined as a peripheral oxygen saturation (Sp[O.sub.2]) < 92%. Radiologists blinded to clinical findings interpreted chest radiographs using standardized World Health Organization method for paediatric chest radiograph reporting. We report clinical and chest radiograph findings using descriptive statistics. Findings Overall, 45.9% (172/375) of children had radiological pneumonia, 36.3% (136/375) had a normal chest radiograph and 32.8% (123/375) had other radiograph abnormalities, with or without pneumonia. In addition, 28.3% (106/375) had a cardiovascular abnormality, including 14.9% (56/375) with both pneumonia and another abnormality. There was no significant difference in the prevalence of radiological pneumonia or of cardiovascular abnormalities or in 28-day mortality between children with severe hypoxaemia (Sp[O.sub.2]: < 80%) and those with mild hypoxaemia (Sp[O.sub.2]: 80 to < 92%). Conclusion Cardiovascular abnormalities were relatively common among children hospitalized with severe pneumonia in Uganda. The standard clinical criteria used to identify pneumonia among children in resource-poor settings were sensitive but lacked specificity. Chest radiographs should be performed routinely for all children with clinical signs of severe pneumonia because it provides useful information on both cardiovascular and respiratory systems. Objectif Decrire les resultats des radiographies thoraciques effectuees sur des enfants hospitalises chez qui une pneumonie aigue et une hypoxemie ont ete diagnostiquees dans trois etablissements tertiaires en Ouganda. Methodes Letude repose sur des donnees cliniques et radiographiques relatives a un echantillon aleatoire de 375 enfants ages de 28 jours a 12 ans, recrutes pour l'essai Children's Oxygen Administration Strategies Trial en 2017. Les enfants hospitalises presentaient des antecedents de maladie et de detresse respiratoires aggravees par une hypoxemie, qui se definit comme une saturation en oxygene peripherique (Sp[O.sub.2]) < 92%. Sans etre informes des resultats cliniques, des radiologues ont interprete les radiographies thoraciques a l'aide de la methode standardisee de l'Organisation mondiale de la Sante en matiere d'etablissement de rapports de radiographie thoracique en pediatrie. Enfin, nous avons consigne les resultats cliniques et radiographiques par le biais de statistiques descriptives. Resultats Au total, 45,9% (172/375) des enfants souffraient de pneumonie radiologique, 36,3% (136/375) presentaient une radiographie thoracique normale et 32,8% (123/375) affichaient d'autres anomalies radiographiques, avec ou sans pneumonie. En outre, 28,3% (106/375) avaient developpe une anomalie cardiovasculaire; parmi eux, 14,9% (56/375) etaient atteints a la fois d'une pneumonie et d'une autre anomalie. Aucune difference notable n'a ete constatee en termes de prevalence pour la pneumonie radiologique, les anomalies cardiovasculaires ou encore la mortalite a 28 jours entre les enfants avec une grave hypoxemie (Sp[O.sub.2]: < 80%) et ceux avec une legere hypoxemie (Sp[O.sub.2]: 80 a < 92%). Conclusion Les anomalies cardiovasculaires se sont revelees relativement frequentes parmi les enfants hospitalises pour une pneumonie severe en Ouganda. Les criteres cliniques standard employes pour identifier une pneumonie chez les enfants issus de milieux ou les ressources sont limitees etaient pertinents mais manquaient de precision. Des radiographies thoraciques devraient systematiquement etre realisees sur tous les enfants presentant des signes cliniques de pneumonie severe car elles fournissent des informations utiles sur les systemes cardiovasculaire et respiratoire. Objetivo Describir los diagnosticos mediante radiografia de torax en ninos hospitalizados con hipoxemia y neumonia grave diagnosticada clinicamente en tres centros de atencion especializada de Uganda. Metodos El estudio incluyo datos clinicos y radiograficos de una muestra aleatoria de 375 ninos de entre 28 dias y 12 anos incluidos en el ensayo Children's Oxygen Administration Strategies Trial (Ensayo de estrategias de administracion de oxigeno en ninos) en 2017. Los ninos fueron hospitalizados con antecedentes de enfermedad respiratoria y dificultad respiratoria complicada por hipoxemia, definida como una saturacion periferica de oxigeno (Sp[O.sub.2]) Resultados En total, el 45,9 % (172/375) de los ninos tenian neumonia por radiografia, el 36,3 % (136/375) tenian un torax normal por radiografia y el 32,8 % (123/375) tenian otras anomalias por radiografia, con o sin neumonia. Ademas, el 28,3 % (106/375) tenia una anomalia cardiovascular, incluido el 14,9 % (56/375) con neumonia y otra anomalia. No hubo diferencias significativas en la prevalencia de neumonia por radiografia o de anomalias cardiovasculares ni en la mortalidad a los 28 dias entre los ninos con hipoxemia grave (Sp[O.sub.2]: Conclusion Las anomalias cardiovasculares fueron relativamente frecuentes entre los ninos hospitalizados por neumonia grave en Uganda. Los criterios clinicos estandar utilizados para identificar la neumonia entre los ninos que viven en lugares con pocos recursos eran fiables, pero carecian de especificidad. La radiografia de torax se deberia realizar de forma rutinaria en todos los ninos con signos clinicos de neumonia grave, ya que proporciona informacion util sobre los aparatos cardiovascular y respiratorio., Introduction Pneumonia is a leading cause of morbidity and mortality in children globally, accounting for around one million fatalities each year, with the largest burden in low- and middle-income countries. [...]

Abstract 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.

BackgroundTuberculosis (TB) is the leading cause of death among infectious agents globally. An estimated 10 million people are newly diagnosed and 1.5 million die of the disease annually. Uganda is among the 30 high TB-burdenedd countries, with Karamoja having a significant contribution of the disease incidence in the country. Control of the disease in Karamoja is complex because a majority of the at-risk population remain mobile; partly because of the nomadic lifestyle. This study, therefore, aimed at describing the factors associated with drug-susceptible TB treatment success rate (TSR) in the Karamoja region.MethodsThis was a retrospective study on case notes of all individuals diagnosed with and treated for drug-susceptible TB at St. Kizito Hospital Matany, Napak district, Karamoja from 1st Jan 2020 to 31st December 2021. Data were abstracted using a customised data abstraction tool. Data analyses were done using Stata statistical software, version 15.0. Chi-square test was conducted to compare treatment success rates between years 2020 and 2021, while Modified Poisson regression analysis was performed at multivariable level to determine the factors associated with treatment success.ResultsWe studied records of 1234 participants whose median age was 31 (IQR: 13-49) years. Children below 15 years of age accounted for 26.2% (n = 323). The overall treatment success rate for the study period was 79.3%(95%CI; 77.0%-81.5%), with a statistically significant variation in 2020 and 2021, 75.4% (422/560) vs 82.4% (557/674) respectively, (P = 0.002). The commonest reported treatment outcome was treatment completion at 52%(n = 647) and death was at 10.4% (n = 129). Older age, undernutrition (Red MUAC), and HIV-positive status were significantly associated with lower treatment success: aPR = 0.87(95%CI; 0.80-0.94), aPR = 0.91 (95%CI; 0.85-0.98) and aPR = 0.88 (95%CI; 0.78-0.98); respectively. Patients who were enrolled in 2021 had a high prevalence of treatment success compared to those enrolled in 2020, aPR = 1.09 (95%CI; 1.03-1.16).ConclusionTB TSR in Matany Hospital was suboptimal. Older age, poor nutrition, and being HIV-positive were negative predictors of treatment success. We propose integrating nutrition and HIV care into TB programming to improve treatment success.

Background Children hospitalised with severe acute malnutrition (SAM) are frequently complicated (>50%) by diarrhoea ( ≥3 watery stools/day) which is accompanied by poor outcomes. Rehydration guidelines for SAM are exceptionally conservative and controversial, based upon expert opinion. The guidelines only permit use of intravenous fluids for cases with advanced shock and exclusive use of low sodium intravenous and oral rehydration solutions (ORS) for fear of fluid and/or sodium overload. Children managed in accordance to these guidelines have a very high mortality. The proposed GASTROSAM trial will reappraise current recommendations with mortality as the primary outcome. We hypothesize that liberal rehydration strategies for both intravenous and oral rehydration in SAM children with diarrhoea may reduce adverse outcomes. Methods An open Phase II trial, with a partial factorial design, enrolling children in Uganda, Kenya, Nigeria and Niger aged 6 months to 12 years with SAM hospitalised with gastroenteritis (>3 loose stools/day) and signs of moderate and severe dehydration. In Stratum A (severe dehydration) children will be randomised (1:1:2) to WHO plan C (100mls/kg Ringers Lactate (RL) with intravenous rehydration (IV) given over 3-6 hours according to age including boluses for shock), slow rehydration (100 mls/kg RL over 8 hours (no boluses)) or WHO SAM rehydration regime (ORS only (boluses for shock (standard of care)). Stratum B incorporates all children with moderate dehydration and severe dehydration post-intravenous rehydration and compares (1:1 ratio) standard WHO ORS given for non-SAM (experimental) versus WHO SAM-recommended low-sodium ReSoMal. The primary outcome for intravenous rehydration is mortality to 96 hours and for oral rehydration a change in sodium levels at 24 hours post-randomisation. Secondary outcomes include measures assessing safety (evidence of pulmonary oedema or heart failure); change in sodium from post-iv levels for those in Stratum A; perturbations of electrolyte abnormalities (severe hyponatraemia

Abstract Background Infections are one of the leading causes of death in the neonatal period. This trial aims to evaluate if the provision of alcohol-based hand rub (ABHR) to pregnant women for postnatal household use prevents severe infections (including sepsis, diarrhoea, pneumonia, or death) among infants during the first three postnatal months. Methods Through a cluster-randomised trial in eastern Uganda, 72 clusters are randomised in a 2-arm design with rural villages as units of randomisation. We estimate to include a total of 5932 pregnant women at 34 weeks of gestation. All women and infants in the study are receiving standard antenatal and postnatal care. Women in the intervention group additionally receive six litres of ABHR and training on its use. Research midwives conduct follow-up visits at participants’ homes on days 1, 7, 28, 42, and 90 after birth and telephone calls on days 14, 48, and 60 to assess the mother and infant for study outcomes. Primary analyses will be by intention to treat. Discussion This study will provide evidence on the effectiveness of a locally available and low-cost intervention in preventing neonatal sepsis and early infant infections. If ABHR is found effective, it could be implemented by adding it to birthing kits. Trial registration Pan African Clinical Trial Registry, PACTR202004705649428. Registered 1 April 2020, https://pactr.samrc.ac.za/ .

Summary: 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–

Abstract Background Malaria is one of the most common causes of hospital admission and death in children under the age of five. The World Health Organization (WHO) has issued guidelines for the identification and treatment of severe malaria. Evidence has shown that adherence to standardized malaria treatment protocols improves outcomes. As a baseline assessment in preparation for a malaria treatment quality improvement project, this study aimed to determine adherence to the WHO severe malaria treatment guidelines in children at a Ugandan Regional Referral Hospital. Methods A retrospective review was performed on a convenience sample of children discharged between June 2021 and March 2022 from the Mbale Regional Referral Hospital Paediatrics Ward with a diagnosis of severe malaria. Data were collected using a standardized case report form. Demographics, presenting symptoms, laboratory results, treatments, length of stay, and mortality were extracted. Comparison of treatments received to items recommended in the WHO guidelines was undertaken to determine adherence. Results 147 patients were included. The median age was 5 years (IQR 2–7 years), and 55% were male. The most common features of severe malaria were haemoglobinuria (49%), haemoglobin

Abstract Background A rapid increase in community transmission of COVID-19 across the country overwhelmed Uganda’s health care system. In response, the Ministry of Health adopted the home-based care strategy for COVID-19 patients with mild-to-moderate disease. We determined the characteristics, treatment outcomes and experiences of COVID-19 patients under home-based care during the second wave in Kapelebyong district, in eastern Uganda. Methods We conducted a sequential explanatory mixed-methods study. We first collected quantitative data using an interviewer-administered questionnaire to determine characteristics and treatment outcomes of COVID-19 patients under home-based care. Cured at home was coded as 1 (considered a good outcome) while being admitted to a health facility and/or dying were coded as 0 (considered poor outcomes). Thereafter, we conducted 11 in-depth interviews to explore the experiences of COVID-19 patients under home-based care. Multivariable logistic regression was used to assess factors associated with poor treatment outcomes using Stata v.15.0. Thematic content analysis was used to explore lived experiences of COVID-19 patients under home-based care using NVivo 12.0.0 Results A total of 303 study participants were included. The mean age ± standard deviation of participants was 32.2 years ± 19.9. Majority of the participants [96.0% (289/303)] cured at home, 3.3% (10/303) were admitted to a health facility and 0.7% (2/303) died. Patients above 60 years of age had 17.4 times the odds of having poor treatment outcomes compared to those below 60 years of age (adjusted odds ratio (AOR): 17.4; 95% CI: 2.2–137.6). Patients who spent more than one month under home-based care had 15.3 times the odds of having poor treatment outcomes compared to those that spent less than one month (AOR: 15.3; 95% CI: 1.6–145.7). From the qualitative interviews, participants identified stigma, fear, anxiety, rejection, not being followed up by health workers and economic loss as negative experiences encountered during home-based care. Positive lived experiences included closeness to friends and family, more freedom, and easy access to food. Conclusion Home-based care of COVID-19 was operational in eastern Uganda. Older age (> 60 years) and prolonged illness (> 1 months) were associated with poor treatment outcomes. Social support was an impetus for home-based care.

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 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 (

Background: COVID-19 vaccination is the latest preventive intervention strategy in an attempt to control the global pandemic. Its efficacy has come under scrutiny because of break through infections among the vaccinated and need for booster doses. Besides, although health workers were prioritized for COVID-19 vaccine in most countries, anecdotal evidence points to high levels of reluctance to take the vaccine among health workers. We assessed COVID-19 vaccine hesitancy among health workers in Dokolo district, northern Uganda. Methods: This was a mixed-method, cross-sectional descriptive study. A customised self-administered data collection tool was used to collect quantitative data on characteristics, vaccination status and factors for or rejection of vaccine uptake. We conducted multivariable logistic regression to assess the association between selected exposures and vaccine hesitancy using Stata version 15. Conversely, qualitative data were collected using key informant interviews (KIIs) among 15 participants that were purposively selected. Data were analysed using thematic content analysis with the help of NVivo 12.0. Results: Of the 346 health workers enrolled, (13.3% [46/346]) were vaccine hesitant. Factors associated with vaccine hesitancy included fear of side effects (Adjusted Odds Ratio [AOR]: 2.55; 95% Confidence Interval [95%CI]: 1.00, 6.49) and health workers’ lack of trust in the information provided by health authorities (AOR: 6.74; 95% CI: 2.43, 18.72). Similar factors were associated with vaccine hesitancy when we used the vaccine hesitancy score. Fear of side effects, distrust in vaccine stakeholders, and lack of trust in the vaccine were barriers to COVID-19 vaccination among health workers. Conclusion: A small proportion of health workers were found to be hesitant to take the COVID-19 vaccine in this study. The paucity of COVID-19 vaccine safety information, which eroded the health workers’ trust in the information they received on the vaccine, was responsible for health workers hesitancy to take up the vaccine in Uganda.

Objectives: To estimate the prevalence of cytomegalovirus (CMV) infections among newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus in Uganda. Design and Methods: Three populations—newborn-mother pairs, neonates with sepsis, and infants (≤3 months) with nonpostinfectious (NPIH) or postinfectious (PIH) hydrocephalus—were evaluated for CMV infection at 3 medical centers in Uganda. Quantitative PCR (qPCR) was used to characterize the prevalence of CMV. Results: The overall CMV prevalence in 2498 samples across all groups was 9%. In newborn-mother pairs, there was a 3% prevalence of cord blood CMV positivity and 33% prevalence of maternal vaginal shedding. In neonates with clinical sepsis, there was a 2% CMV prevalence. Maternal HIV seropositivity (adjusted odds ratio [aOR] 25.20; 95% confidence interval [CI] 4.43–134.26; p = 0.0001), residence in eastern Uganda (aOR 11.06; 95% CI 2.30–76.18; p = 0.003), maternal age

Abstract Background Virtual global health partnership initiatives (VGHPIs) evolved rapidly during the COVID-19 pandemic to ensure partnership continuity. However the current landscape for VGHPI use and preference is unknown. This study aimed to increase understanding of GH partners’ perspectives on VGHPIs. Methods From 15 October to 30 November 2020, An online, international survey was conducted using snowball sampling to document pandemic-related changes in partnership activities, preferences for VGHPIs, and perceived acceptability and barriers. The survey underwent iterative development within a diverse author group, representing academic and clinical institutions, and the non-profit sector. Participants from their professional global health networks were invited, including focal points for global health partnerships while excluding trainees and respondents from the European Economic Area. Analysis stratified responses by country income classification and partnership type. Authors used descriptive statistics to characterize responses, defining statistical significance as α = 0.05. Results A total of 128 respondents described 219 partnerships. 152/219 (69%) partnerships were transnational, 157/219 (72%) were of > 5 years duration, and 127/219 (60%) included bidirectional site visits. High-income country (HIC) partners sent significantly more learners to low- to middle-income country (LMIC) partner sites (p

BackgroundEvidence suggests use of herbal and conventional medicines in the treatment of Sickle Cell Disease (SCD). We examined factors associated with caregivers' use of combined herbal and conventional medicine to treat children with SCD.MethodsA cross-sectional study was conducted at Jinja Regional Referral Hospital between January and March 2022. Caregivers of children with SCD aged 1 to 18 years attending the Sickle Cell Clinic were interviewed using structured questionnaires. We collected data on caregivers' socio-demographic characteristics, perceptions of and intentions to use either or both therapies, self-reported use of either or both therapies and community and health-related factors. A multivariable logistic regression model was computed to assess the factors independently associated with caregivers' use of combined therapy, using Stata version 15.0.Results372 caregivers were interviewed. On average, respondents were aged 34.3 years (Standard Deviation [SD]: ±9.8 years). 37% (n = 138) of the caregivers reported the use of both herbal and conventional medicine, 58.3% (n = 217) reported use of only conventional medicine, while 4.6% (n = 17) reported use of herbal medicine only. Higher odds of using combination therapy were found in caregivers aged 60+ years (adjusted odds ratio [AOR] = 11.8; 95% CI: 1.2, 115.2), those with lower secondary education (AOR = 6.2; 95% CI: 1.5, 26.0), those who believed in the safety of herbal medicine (AOR = 3.3; 95% CI: 1.5, 7.6) and those who thought that use of both therapies were safe (AOR = 7.7; 95% CI: 3.5, 17.0).ConclusionMore than one-third of the caregivers reported use of combined herbal and conventional medicine, most of whom were older (>60%) and had lower secondary education. There is need for targeted health promotion to educate caregivers about the dangers of using both herbal and conventional medicines in treating children with SCD.

Background: Globally, prematurity is the leading cause of death in neonates and therefore a major contributor to the under 5-year mortality. The study assesses the prevalence and risk factors associated with preterm birth at a Regional Referral Hospital in Eastern Uganda. Methods: This was a descriptive cross-sectional study conducted at a Regional Referral Hospital in Eastern Uganda. A questionnaire was used to capture data on maternal socio-demographic features, and obstetrical causes of preterm birth. Additional information was got from maternal medical records. In total, 350 mother-baby pairs were studied. Bivariate and multivariate logistic regression models were fitted so as to establish the factors associated with preterm birth. A p-value

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).

Abstract The composition of the maternal vaginal microbiome influences the duration of pregnancy, onset of labor, and even neonatal outcomes. Maternal microbiome research in sub-Saharan Africa has focused on non-pregnant and postpartum composition of the vaginal microbiome. Here we aimed to illustrate the relationship between the vaginal microbiome of 99 laboring Ugandan women and intrapartum fever using routine microbiology and 16S ribosomal RNA gene sequencing from two hypervariable regions (V1–V2 and V3–V4). To describe the vaginal microbes associated with vaginal microbial communities, we pursued two approaches: hierarchical clustering methods and a novel Grades of Membership (GoM) modeling approach for vaginal microbiome characterization. Leveraging GoM models, we created a basis composed of a preassigned number of microbial topics whose linear combination optimally represents each patient yielding more comprehensive associations and characterization between maternal clinical features and the microbial communities. Using a random forest model, we showed that by including microbial topic models we improved upon clinical variables to predict maternal fever. Overall, we found a higher prevalence of Granulicatella, Streptococcus, Fusobacterium, Anaerococcus, Sneathia, Clostridium, Gemella, Mobiluncus, and Veillonella genera in febrile mothers, and higher prevalence of Lactobacillus genera (in particular L. crispatus and L. jensenii), Acinobacter, Aerococcus, and Prevotella species in afebrile mothers. By including clinical variables with microbial topics in this model, we observed young maternal age, fever reported earlier in the pregnancy, longer labor duration, and microbial communities with reduced Lactobacillus diversity were associated with intrapartum fever. These results better defined relationships between the presence or absence of intrapartum fever, demographics, peripartum course, and vaginal microbial topics, and expanded our understanding of the impact of the microbiome on maternal and potentially neonatal outcome risk.

Abstract Background Severe anaemia (haemoglobin

Background: β-thalassemia is rare in sub-Saharan Africa and to our knowledge there has been no case of homozygous β-thalassemia major reported from this region. In a recent cohort study, we identified four β-thalassemia mutations among 83 heterozygous carriers in Kilifi, Kenya. One of the mutations identified was a rare β-globin gene initiation codon mutation (ATG➝ACG) (rs33941849). Here we present a patient with β-thalassemia major resulting from this mutation, only the second homozygous patient to have been reported. Methods: The female patient presented to Kilifi County Hospital aged two years with a one week left sided abdominal swelling. Clinical, hematological and genetic information were collected at admission and follow-up. Results: Admission bloods revealed marked anemia, with a hemoglobin (Hb) value of 6.6 g/dL and a low mean corpuscular volume of 64 fL. High performance liquid chromatography (HPLC) revealed the absence of HbA0 and elevated levels of HbF, suggesting a diagnosis of β-thalassemia major. Sequencing revealed that the child was homozygous for the rs33941849 initiation codon mutation. Conclusions: We hope that this study will create awareness regarding the presence of β-thalassemia as a potential public health problem in the East Africa region and will prompt the development of local guidelines regarding the diagnosis and management of this condition.

Introduction Blackwater fever (BWF), a complication of malaria, has in the past been considered as a rare complication of malaria in children living in high transmission settings. More recently, however, a growing number of paediatric clusters of BWF cases have been reported predominantly in sub-Saharan Africa (SSA). The aim of this study is to map evidence on BWF among children in SSA from 1 January 1960 to 31 December 2021.Methods and analysis This review will be guided by Arksey and O’ Malley’s methodological framework for scoping reviews with methodological refinements by Levac et al and will comply with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews’ guidelines. Five electronic databases (MEDLINE via PubMed, Embase, the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and PsycINFO) will be systematically searched using predefined keywords. In addition, reference lists of included articles will be searched. Our multidisciplinary team has formulated search strategies and two reviewers will independently complete study eligibility screening, final selection and data extraction. A third reviewer will adjudicate the final decision on disputed articles. Bibliographic data and abstract content will be collected and analysed using a data-charting tool developed iteratively by the research team.Ethics and dissemination This scoping review being a secondary analysis does not require ethics approval. We anticipate results of this review will broaden understanding of paediatric BWF in SSA and identify its research gaps in SSA. We will be disseminating results through journals and conferences targeting primary care providers.

Purpose The life-saving role of oxygen therapy in African children with severe pneumonia is not yet established. Methods The open-label fractional-factorial COAST trial randomised eligible Ugandan and Kenyan children aged > 28 days with severe pneumonia and severe hypoxaemia stratum (SpO.sub.2 3 h receipt of oxygen were excluded. The primary endpoint was 48 h mortality; secondary endpoints included mortality or neurocognitive sequelae at 28 days. Results The trial was stopped early after enrolling 1852/4200 children, including 388 in the severe hypoxaemia stratum (median 7 months; median SpO.sub.2 75%) randomised to HFNT (n = 194) or LFO (n = 194) and 1454 in the hypoxaemia stratum (median 9 months; median SpO.sub.2 88%) randomised to HFNT (n = 363) vs LFO (n = 364) vs permissive hypoxaemia (n = 727). Per-protocol 15% of patients in the permissive hypoxaemia group received oxygen (when SpO.sub.2 < 80%). In the severe hypoxaemia stratum, 48-h mortality was 9.3% for HFNT vs. 13.4% for LFO groups. In the hypoxaemia stratum, 48-h mortality was 1.1% for HFNT vs. 2.5% LFO and 1.4% for permissive hypoxaemia. In the hypoxaemia stratum, adjusted odds ratio for 48-h mortality in liberal vs permissive comparison was 1.16 (0.49-2.74; p = 0.73); HFNT vs LFO comparison was 0.60 (0.33-1.06; p = 0.08). Strata-specific 28 day mortality rates were, respectively: 18.6, 23.4 and 3.3, 4.1, 3.9%. Neurocognitive sequelae were rare. Conclusions Respiratory support with HFNT showing potential benefit should prompt further trials., Author(s): K. Maitland [sup.1] [sup.4], S. Kiguli [sup.2], P. Olupot-Olupot [sup.3], M. Hamaluba [sup.4], K. Thomas [sup.5], F. Alaroker [sup.6], R. O. Opoka [sup.2] [sup.7], A. Tagoola [sup.7], V. Bandika [...]

Abstract Background Few recent descriptions of severe childhood malaria have been published from high-transmission regions. In the current study, the clinical epidemiology of severe malaria in Mbale, Eastern Uganda, is described, where the entomological inoculation rate exceeds 100 infective bites per year. Methods A prospective descriptive study was conducted to determine the prevalence, clinical spectrum and outcome of severe Plasmodium falciparum malaria at Mbale Regional Referral Hospital in Eastern Uganda. All children aged 2 months–12 years who presented on Mondays to Fridays between 8.00 am and 5.00 pm from 5th May 2011 until 30th April 2012 were screened for parasitaemia. Clinical and laboratory data were then collected from all P. falciparum positive children with features of WHO-defined severe malaria by use of a standardized proforma. Results A total of 10 208 children were screened of which 6582 (64%) had a positive blood film. Of these children, 662 (10%) had clinical features of severe malaria and were consented for the current study. Respiratory distress was the most common severity feature (554; 83.7%), while 365/585 (62.4%) had hyperparasitaemia, 177/662 (26.7%) had clinical jaundice, 169 (25.5%) had severe anaemia, 134/660 (20.2%) had hyperlactataemia (lactate ≥ 5 mmol/L), 93 (14.0%) had passed dark red or black urine, 52 (7.9%) had impaired consciousness and 49/662 (7.4%) had hypoxaemia (oxygen saturations