Identifying modifiable risk factors for mortality in children aged 1-59 months admitted with WHO-defined severe pneumonia: a single-centre observational cohort study from rural Malawi.

OBJECTIVE: Although HIV infection, severe malnutrition and hypoxaemia are associated with high mortality in children with WHO-defined severe pneumonia in sub-Saharan Africa, many do not have these conditions and yet mortality remains elevated compared with high-resource settings. Further stratifying mortality risk for children without these conditions could permit more strategic resource utilisation and improved outcomes. We therefore evaluated associations between mortality and clinical characteristics not currently recognised by the WHO as high risk among children in Malawi with severe pneumonia but without HIV (including exposure), severe malnutrition and hypoxaemia. METHODS: Between May 2016 and March 2018, we conducted a prospective observational study alongside a randomised controlled trial (CPAP IMPACT) at Salima District Hospital in Malawi. Children aged 1-59 months hospitalised with WHO-defined severe pneumonia without severe malnutrition, HIV and hypoxaemia were enrolled. Study staff assessed children at admission and ascertained hospital outcomes. We compared group characteristics using Student's t-test, rank-sum test, χ2 test or Fisher's exact test as appropriate. RESULTS: Among 884 participants, grunting (10/112 (8.9%) vs 11/771 (1.4%)), stridor (2/14 (14.2%) vs 19/870 (2.1%)), haemoglobin <50 g/L (3/27 (11.1%) vs 18/857 (2.1%)) and malaria (11/204 (5.3%) vs 10/673 (1.4%)) were associated with mortality compared with children without these characteristics. Children who survived had a 22 g/L higher mean haemoglobin and 0.7 cm higher mean mid-upper arm circumference (MUAC) than those who died. CONCLUSION: In this single-centre study, our analysis identifies potentially modifiable risk factors for mortality among hospitalised Malawian children with severe pneumonia: specific signs of respiratory distress (grunting, stridor), haemoglobin <50 g/L and malaria infection. Significant differences in mean haemoglobin and MUAC were observed between those who survived and those who died. These factors could further stratify mortality risk among hospitalised Malawian children with severe pneumonia lacking recognised high-risk conditions.

Bubble continuous positive airway pressure for children with high-risk conditions and severe pneumonia in Malawi: an open label, randomised, controlled trial.

BACKGROUND: Pneumonia is the leading cause of death among children globally. Most pneumonia deaths in low-income and middle-income countries (LMICs) occur among children with HIV infection or exposure, severe malnutrition, or hypoxaemia despite antibiotics and oxygen. Non-invasive bubble continuous positive airway pressure (bCPAP) is considered a safe ventilation modality that might improve child pneumonia survival. bCPAP outcomes for high-risk African children with severe pneumonia are unknown. Since most child pneumonia hospitalisations in Africa occur in non-tertiary district hospitals without daily physician oversight, we aimed to examine whether bCPAP improves severe pneumonia mortality in such settings. METHODS: This open-label, randomised, controlled trial was done in the general paediatric ward of Salima District Hospital, Malawi. We enrolled children aged 1-59 months old with WHO-defined severe pneumonia and either HIV infection or exposure, severe malnutrition, or an oxygen saturation of less than 90%. Children were randomly assigned 1:1 to low-flow nasal cannula oxygen or nasal bCPAP. Non-physicians administered care; the primary outcome was hospital survival. Primary analyses were by intention-to-treat and interim and adverse events analyses per protocol. This trial is registered with ClinicalTrials.gov, number NCT02484183, and is closed. FINDINGS: We screened 1712 children for eligibility between June 23, 2015, and March 21, 2018. The data safety and monitoring board stopped the trial for futility after 644 of the intended 900 participants were enrolled. 323 children were randomly assigned to oxygen and 321 to bCPAP. 35 (11%) of 323 children who received oxygen died in hospital, as did 53 (17%) of 321 who received bCPAP (relative risk 1·52; 95% CI 1·02-2·27; p=0·036). 13 oxygen and 17 bCPAP patients lacked hospital outcomes and were considered lost to follow-up. Suspected adverse events related to treatment occurred in 11 (3%) of 321 children receiving bCPAP and 1 (<1%) of 323 children receiving oxygen. Four bCPAP and one oxygen group deaths were classified as probable aspiration episodes, one bCPAP death as probable pneumothorax, and six non-death bCPAP events included skin breakdown around the nares. INTERPRETATION: bCPAP treatment in a paediatric ward without daily physician supervision did not reduce hospital mortality among high-risk Malawian children with severe pneumonia, compared with oxygen. The use of bCPAP within certain patient populations and non-intensive care settings might carry risk that was not previously recognised. bCPAP in LMICs needs further evaluation before wider implementation for child pneumonia care. FUNDING: Bill & Melinda Gates Foundation, International AIDS Society, Health Empowering Humanity.