The impact of childhood malnutrition on mortality from pneumonia: a systematic review and network meta-analysis.

INTRODUCTION: Childhood malnutrition is widespread in low-income and middle-income countries (LMICs) and increases the frequency and severity of infections such as pneumonia. We aimed to identify studies investigating pneumonia deaths in malnourished children and estimate mortality risk by malnutrition severity. METHODS: We conducted a systematic review of MEDLINE, EMBASE and Global Health databases to identify relevant studies. We used a network meta-analysis to derive ORs of death from pneumonia for moderately and severely underweight children using low weight-for-age, the most reported measure of malnutrition. We compared meta-estimates of studies conducted before and after 2000 to assess changes in mortality risk over time. We estimated the prevalence of underweight hospitalised children from hospital-based cohort studies and calculated the population attributable fraction of in-hospital pneumonia deaths from being underweight using our results. RESULTS: Our network meta-analysis included 33 544 underweight children from 23 studies. The estimated OR of death from pneumonia was 2.0 (95% CI 1.6 to 2.6) and 4.6 (95% CI 3.7 to 5.9) for children moderately and severely underweight, respectively. The OR of death from pneumonia for those severely underweight was 5.3 (95% CI 3.9 to 7.4) pre-2000 and remained high post-2000 at 4.1 (95% CI 3.0 to 6.0). Prevalence of underweight children hospitalised with pneumonia varied (median 40.2%, range 19.6-66.3) but was high across many LMIC settings. We estimated a median 18.3% (range 10.8-34.6) and 40.9% (range 14.7-69.9) of in-hospital pneumonia deaths were attributable to being moderately and severely underweight, respectively. CONCLUSIONS: The risk of death from childhood pneumonia dramatically increases with malnutrition severity. This risk has remained high in recent years with an estimated over half of in-hospital pneumonia deaths attributable to child malnutrition. Prevention and treatment of all child malnutrition must be prioritised to maintain progress on reducing pneumonia deaths.

Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination.

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.