Hypoxaemia is a common complication of pneumonia and a major risk factor for death, but less is known about hypoxaemia in other common conditions. We evaluated the epidemiology of hypoxaemia and oxygen use in hospitalised neonates and children in Nigeria. We conducted a prospective cohort study among neonates and children (<15 years of age) admitted to 12 secondary-level hospitals in southwest Nigeria (November 2015-November 2017) using data extracted from clinical records (documented during routine care). We report summary statistics on hypoxaemia prevalence, oxygen use, and clinical predictors of hypoxaemia. We used generalised linear mixed-models to calculate relative odds of death (hypoxaemia vs not). Participating hospitals admitted 23,926 neonates and children during the study period. Pooled hypoxaemia prevalence was 22.2% (95%CI 21.2-23.2) for neonates and 10.2% (9.7-10.8) for children. Hypoxaemia was common among children with acute lower respiratory infection (28.0%), asthma (20.4%), meningitis/encephalitis (17.4%), malnutrition (16.3%), acute febrile encephalopathy (15.4%), sepsis (8.7%) and malaria (8.5%), and neonates with neonatal encephalopathy (33.4%), prematurity (26.6%), and sepsis (21.0%). Hypoxaemia increased the adjusted odds of death 6-fold in neonates and 7-fold in children. Clinical signs predicted hypoxaemia poorly, and their predictive ability varied across ages and conditions. Hypoxaemic children received oxygen for a median of 2-3 days, consuming ∼3500 L of oxygen per admission. Hypoxaemia is common in respiratory and non-respiratory acute childhood illness and increases the risk of death substantially. Given the limitations of clinical signs, pulse oximetry is an essential tool for detecting hypoxaemia, and should be part of the routine assessment of all hospitalised neonates and children.

The indirect effects of pneumococcal conjugate vaccines (PCVs) are mediated through reductions in carriage of vaccine serotypes. Data on PCVs in Asia and the Pacific are scarce. Fiji introduced the ten-valent PCV (PCV10) in 2012, with a schedule consisting of three priming doses at 6, 10, and 14 weeks of age and no booster dose (3 + 0 schedule) without catch-up. We investigated the effects of PCV10 introduction using cross-sectional nasopharyngeal carriage surveys. We did four annual carriage surveys (one pre-PCV10 and three post-PCV10) in the greater Suva area in Fiji, during 2012-15, of 5-8-week-old infants, 12-23-month-old children, 2-6-year-old children, and their caregivers (total of 8109 participants). Eligible participants were of appropriate age, had axillary temperature lower than 37°C, and had lived in the community for at least 3 consecutive months. We used purposive quota sampling to ensure a proper representation of the Fiji population. Pneumococci were detected by real-time quantitative PCR, and molecular serotyping was done with microarray. 3 years after PCV10 introduction, vaccine-serotype carriage prevalence declined, with adjusted prevalences (2015 vs 2012) of 0·56 (95% CI 0·34-0·93) in 5-8-week-old infants, 0·34 (0·23-0·49) in 12-23-month-olds, 0·47 (0·34-0·66) in 2-6-year-olds, and 0·43 (0·13-1·42) in caregivers. Reductions in PCV10 serotype carriage were evident in both main ethnic groups in Fiji; however, carriage of non-PCV10 serotypes increased in Indigenous Fijian infants and children. Density of PCV10 serotypes and non-PCV10 serotypes was lower in PCV10-vaccinated children aged 12-23 months than in PCV10-unvaccinated children of the same age group (PCV10 serotypes -0·56 [95% CI -0·98 to -0·15], p=0·0077; non-PCV10 serotypes -0·29 [-0·57 to -0·02], p=0·0334). Direct and indirect effects on pneumococcal carriage post-PCV10 are likely to result in reductions in pneumococcal disease, including in infants too young to be vaccinated. Serotype replacement in carriage in Fijian children, particularly Indigenous children, warrants further monitoring. Observed changes in pneumococcal density might be temporal rather than vaccine related. Department of Foreign Affairs and Trade of the Australian Government through the Fiji Health Sector Support Program; Victorian Government's Operational Infrastructure Support Program; Bill & Melinda Gates Foundation.

Pneumococcal carriage is a prerequisite for disease, and underpins herd protection provided by pneumococcal conjugate vaccines (PCVs). There are few data on the impact of PCVs in lower income settings, particularly in Asia. In 2013, the Lao People's Democratic Republic (Lao PDR) introduced 13-valent PCV (PCV13) as a 3 + 0 schedule (doses at 6, 10 and 14 weeks of age) with limited catch-up vaccination. We conducted two cross-sectional carriage surveys (pre- and two years post-PCV) to assess the impact of PCV13 on nasopharyngeal pneumococcal carriage in 5-8 week old infants (n = 1000) and 12-23 month old children (n = 1010). Pneumococci were detected by quantitative real-time PCR, and molecular serotyping was performed using DNA microarray. Post PCV13, there was a 23% relative reduction in PCV13-type carriage in children aged 12-23 months (adjusted prevalence ratio [aPR] 0.77 [0.61-0.96]), and no significant change in non-PCV13 serotype carriage (aPR 1.11 [0.89-1.38]). In infants too young to be vaccinated, there was no significant change in carriage of PCV13 serotypes (aPR 0.74 [0.43-1.27]) or non-PCV13 serotypes (aPR 1.29 [0.85-1.96]), although trends were suggestive of indirect effects. Over 70% of pneumococcal-positive samples contained at least one antimicrobial resistance gene, which were more common in PCV13 serotypes (p < 0.001). In 12-23 month old children, pneumococcal density of both PCV13 serotypes and non-PCV13 serotypes was higher in PCV13-vaccinated compared with undervaccinated children (p = 0.004 and p < 0.001, respectively). This study provides evidence of PCV13 impact on carriage in a population without prior PCV7 utilisation, and provides important data from a lower-middle income setting in Asia. The reductions in PCV13 serotype carriage in vaccine-eligible children are likely to result in reductions in pneumococcal transmission and disease in Lao PDR.

Improving oxygen systems may improve clinical outcomes for hospitalised children with acute lower respiratory infection (ALRI). This paper reports the effects of an improved oxygen system on mortality and clinical practices in 12 general, paediatric, and maternity hospitals in southwest Nigeria. We conducted an unblinded stepped-wedge cluster-randomised trial comparing three study periods: baseline (usual care), pulse oximetry introduction, and stepped introduction of a multifaceted oxygen system. We collected data from clinical records of all admitted neonates (<28 days old) and children (28 days to 14 years old). Primary analysis compared the full oxygen system period to the pulse oximetry period and evaluated odds of death for children, children with ALRI, neonates, and preterm neonates using mixed-effects logistic regression. Secondary analyses included the baseline period (enabling evaluation of pulse oximetry introduction) and evaluated mortality and practice outcomes on additional subgroups. Three hospitals received the oxygen system intervention at 4-month intervals. Primary analysis included 7,716 neonates and 17,143 children admitted during the 2-year stepped crossover period (November 2015 to October 2017). Compared to the pulse oximetry period, the full oxygen system had no association with death for children (adjusted odds ratio [aOR] 1.06; 95% confidence interval [CI] 0.77–1.46; p = 0.721) or children with ALRI (aOR 1.09; 95% CI 0.50–2.41; p = 0.824) and was associated with an increased risk of death for neonates overall (aOR 1.45; 95% CI 1.04–2.00; p = 0.026) but not preterm/low-birth-weight neonates (aOR 1.30; 95% CI 0.76–2.23; p = 0.366). Secondary analyses suggested that the introduction of pulse oximetry improved oxygen practices prior to implementation of the full oxygen system and was associated with lower odds of death for children with ALRI (aOR 0.33; 95% CI 0.12–0.92; p = 0.035) but not for children, preterm neonates, or neonates overall (aOR 0.97, 95% CI 0.60–1.58, p = 0.913; aOR 1.12, 95% CI 0.56–2.26, p = 0.762; aOR 0.90, 95% CI 0.57–1.43, p = 0.651). Limitations of our study are a lower-than-anticipated power to detect change in mortality outcomes (low event rates, low participant numbers, high intracluster correlation) and major contextual changes related to the 2016–2017 Nigerian economic recession that influenced care-seeking and hospital function during the study period, potentially confounding mortality outcomes. We observed no mortality benefit for children and a possible higher risk of neonatal death following the introduction of a multifaceted oxygen system compared to introducing pulse oximetry alone. Where some oxygen is available, pulse oximetry may improve oxygen usage and clinical outcomes for children with ALRI. Australian New Zealand Clinical Trials Registry: ACTRN12617000341325.

Improving outcomes beyond survival for high-risk newborns in resource-limited settings is an emerging challenge. Global estimates demonstrate the scale of this challenge and significant gaps in morbidity outcome data in high mortality contexts. A systematic review was conducted to document the prevalence of neurodevelopmental impairment in high-risk newborns who were followed up into childhood in low- and middle-income countries. High-risk newborns were defined as low, very or extremely low birthweight, preterm infants or those surviving birth asphyxia or serious infections. Electronic databases were searched and articles screened for eligibility. Included articles were appraised according to STROBE criteria. Narrative review was performed and median prevalence of key neurodevelopmental outcomes was calculated where data quality allowed. 6959 articles were identified with sixty included in final review. At follow-up in early childhood, median estimated prevalence (inter-quartile range) of overall neurodevelopmental impairment, cognitive impairment and cerebral palsy were: for survivors of prematurity/very low birthweight 21.4% (11.6-30.8), 16.3% (6.3-29.6) and 11.2% (5.9-16.1), respectively, and for survivors of birth asphyxia 34.6% (25.4-51.5), 11.3% (7.7-11.8) and 22.8% (15.7-31.4), respectively. Only three studies reporting outcomes following newborn serious bacterial infections were identified. There was limited reporting of important outcomes such as vision and hearing impairment. Major challenges with standardised reporting of key exposure and developmental outcome variables and lack of control data were identified. Understanding the limitations of the available data on neurodevelopmental outcome in newborns in resource-limited settings provides clear direction for research and efforts to improve long-term outcome in high-risk newborns in these settings.

Pneumococcal disease is a major contributor to global childhood morbidity and mortality and is more common in low- and middle-income countries (LMICs) than in high-income countries. Pneumococcal carriage is a prerequisite for pneumococcal disease. Pneumococcal conjugate vaccine reduces vaccine-type carriage and disease. However, pneumococcal carriage and disease persist, and it is important to identify other potentially modifiable factors associated with pneumococcal carriage and determine if risk factors differ between low, middle, and high-income countries. This information may help inform pneumococcal disease prevention programs. This systematic literature review describes factors associated with pneumococcal carriage stratified by country income status and summarises pneumococcal carriage rates for included studies. We undertook a systematic search of English-language pneumococcal nasopharyngeal carriage studies up to 30^thJune 2021. Peer-reviewed studies reporting factors associated with overall pneumococcal nasopharyngeal carriage in healthy, community-based study populations were eligible for inclusion. Two researchers independently reviewed studies to determine eligibility. Results are presented as narrative summaries. This review is registered with PROSPERO, CRD42020186914. Eighty-two studies were included, and 46 (56%) were conducted in LMICs. There was heterogeneity in the factors assessed in each study. Factors positively associated with pneumococcal carriage in all income classification were young age, ethnicity, symptoms of respiratory tract infection, childcare attendance, living with young children, poverty, exposure to smoke, season, and co-colonisation with other pathogens. Breastfeeding and antibiotic use were protective against carriage in all income classifications. Median (interquartile range) pneumococcal carriage rates differed by income classification, ranging from 51% (19.3–70.2%), 38.5% (19.3–51.6%), 31.5% (19.0–51.0%), 28.5% (16.8–35.4%), (P= 0.005) in low-, lower-middle, upper-middle, and high-income classifications, respectively. Our findings suggest that where measured, factors associated with pneumococcal nasopharyngeal carriage are similar across income classifications, despite the highest pneumococcal carriage rates being in low-income classifications. Reducing viral transmission through vaccination and public health interventions to address social determinants of health would play an important role.