Unusual clinical spectra of childhood severe malaria during malaria epidemic in eastern Uganda: a prospective study.

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.

Impact of early continuous positive airway pressure in the delivery room (DR-CPAP) on neonates < 1500 g in a low-resource setting: a protocol for a pilot feasibility and acceptability randomized controlled trial.

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 .