BACKGROUND:Severe anaemia is a major cause of hospital admission and mortality in children living in sub-Saharan Africa, but data on its association with invasive bacterial infection are sparse. We aimed to characterise severe anaemia and its association with invasive bacterial infection in Kenyan children. METHODS:In this retrospective observational study, we systematically collected admission data for children aged 1 month to 14 years admitted to Kilifi County Hospital, Kenya, between Aug 1, 1998, and July 31, 2024. We excluded children with missing haemoglobin data. We examined prevalence, trends, and factors associated with severe anaemia and very severe anaemia, and the association between severe or moderate anaemia and odds of bacteraemia. Anaemia severity was defined using WHO age-specific thresholds. FINDINGS:Of the 84 348 admissions, representing 64 499 unique children (28 232 [43·8%] females and 36 265 [56·2%] males), included in our analysis, 16 715 (19·8%) admissions had severe anaemia. Severe anaemia was associated with multiple, co-occurring risk factors, including sickle cell disease, malaria, HIV, and malnutrition. As malaria transmission declined (2004-09), the age distribution of severe anaemia shifted towards older children; cases in children aged 5-14 years increased from 16·4% during the high-transmission era (1998-2003) to 44·7% during the low-transmission era (2010-24). Compared with mild or no anaemia, severe anaemia was associated with higher odds of in-hospital mortality (adjusted odds ratio 2·1 [95% CI 1·9-2·3]) and bacteraemia (2·7 [2·5-3·0]), particularly with non-typhoidal Salmonella (6·1 [4·6-8·1]), Escherichia coli (5·7 [4·2-7·7]), Haemophilus influenzae (4·3 [3·0-6·4]), Streptococcus pneumoniae (3·5 [2·9-4·2]), and Klebsiella pneumoniae (2·4 [1·4-4·0]). Moderate anaemia was also associated with increased odds of bacteraemia and mortality. INTERPRETATION:Severe anaemia in hospitalised Kenyan children is multifactorial, increasingly affects older children, and is strongly associated with pathogen-specific bacteraemia and increased mortality. These findings support prompt evaluation for bacteraemia and closer clinical management in severely anaemic children to improve survival. FUNDING:Wellcome and the Science for Africa Foundation to the DELTAS Africa programme.

BACKGROUND:Respiratory syncytial virus (RSV) is the leading cause of hospital admission for lower respiratory infection in infants worldwide, with more than 95% of deaths occurring in low-income and middle-income countries. Predictors of adverse outcomes following RSV hospitalisation remain poorly defined. We aimed to identify clinical and anthropometric predictors of mortality among infants admitted with RSV pneumonia and to assess changes in mortality over a 25-year surveillance period. METHODS:In this retrospective cohort study, we analysed 25 years of paediatric surveillance at Kilifi County Hospital, Kilifi, Kenya, spanning 25 successive RSV seasons. Neonates (aged <28 days) and post-neonatal infants (aged 28 days to 12 months) admitted with WHO-defined pneumonia were tested for RSV and demographic, anthropometric, and clinical data were recorded at admission. The primary outcome was in-hospital death among infants admitted with RSV pneumonia. Predictors of mortality were identified using random-forest and multivariable logistic regression, and temporal trends in mortality and anthropometric status were examined. FINDINGS:Of 75 482 admissions of infants to Kilifi County Hospital between Jan 1, 2001, and July 13, 2025, 19 299 (25·6%) met WHO pneumonia criteria and 2745 (22·7%) had RSV. Of these infants, 2390 (87·1%) were post-neonatal, of whom 58 (2·4%) died in hospital with 44 (76%) deaths within 7 days of admission. Mortality was independently associated with congenital heart disease (odds ratio 3·51 [95% CI 1·37-8·97]), severe undernutrition (per 1-unit reduction in weight-for-age Z score: 1·59 [1·28-1·99]), and hypoxaemia (per 1% decrease in peripheral oxygen saturation: 1·05 [1·03-1·08]). 38 (70·4%) of 54 infants with RSV who died in hospital had a mid-upper arm circumference below the severe acute malnutrition threshold of 11·5 cm. There was no evidence of a sustained decline in RSV-associated in-hospital mortality or improvement in anthropometric status over the 25-year study period. INTERPRETATION:RSV mortality in Kenyan infants remains high and has not declined over 25 years. Severe undernutrition and congenital heart disease identify infants with RSV who are at the highest risk of in-hospital death. These findings highlight the role of chronic anthropometric deficits in RSV outcomes and support targeted nutritional interventions to reduce mortality. FUNDING:Bill & Melinda Gates Foundation and Wellcome.

Rotavirus (RV) is a major cause of diarrhoeal disease and mortality in African children. The impact of RV vaccination on child health has been limited by low vaccine effectiveness in resource-constrained settings. We urgently need better vaccines to control RV disease, delivery of which will require an improved understanding of RV biology. We hypothesised that the genetics of RV disease and immunity are likely to be mutually informative of RV biology. We performed genome-wide association studies of infection-induced and vaccine-derived RV immunity, hospitalised RV gastroenteritis (RVGE) risk and all-cause diarrhoeal disease risk in > 3,000 Ugandan, Kenyan and Zambian children. In doing so, we expand on the role of human blood group antigen secretion in RV infection and immunity, resolving complex interactions between secretor status, ABO blood group, Lewis antigen and viral genotype. We further identify a separate, novel locus at chromosome 2q12, rs59241810:T, associated with increased anti-RV IgA responses and lower risk of RVGE and all-cause diarrhoea with dehydration. Variation at rs59241810 regulates monocyte LIMS1 expression, thereby impacting IFNγ-induced hepatocyte growth factor (HGF) secretion, suggesting a role for monocyte-derived HGF in the generation of anti-RV IgA responses. Our data reveal the complex interplay between immunity, disease, pathogen variation and host genetics in RV infections, and identify LIMS1/HGF signalling as a target to design more effective anti-RV vaccines.

Few longitudinal studies have examined the long-term health impact of changing malaria prevention and treatment strategies in Africa. This study analyses 35 years of clinical surveillance among paediatric malaria admissions in Kilifi, Kenya. Children aged 1 month to 14 years who were residents of rural Kilifi Health and Demographic Surveillance System and admitted to Kilifi County Hospital between January 1990 and December 2024 were included. Community malaria exposure was estimated using infection prevalence among children admitted for trauma, elective surgery, bites and neoplasms. Malaria admissions were defined as hospitalisations with a positive blood slide and a primary or co-morbid malaria diagnosis. Severe malaria phenotypes including severe anaemia, cerebral malaria, hyper-parasitaemia and in-hospital mortality were also examined. Binomial and Poisson regression models assessed temporal differences, using 1990–1996 as the reference period. Community malaria prevalence declined from 35

Burkitt’s lymphoma (BL) is a type of non-Hodgkin lymphoma that may account for more than 40

Background Burkitt’s lymphoma (BL) is a type of non-Hodgkin lymphoma that may account for more than 40% of childhood malignancies in tropical Africa. The endemic version is common in equatorial Africa, where a BL belt has been mapped. The role of P. falciparum malaria infection in BL has been postulated but not substantiated. The decrease in P. falciparum malaria infection offers an opportunity to examine this association. Methods In this study, we utilized data collected over three decades (1990–2020) and examined the trends in annual admission incidence rates of Burkitt’s lymphoma among pediatric admissions (0–14 years) in relation to the reduction in malaria admissions. Findings: Ninety-five patients with Burkitt’s lymphoma were identified, of whom 72 (75.8%) were male. During the first epoch (1990–1999) and second decade, 29 cases and 62 cases were diagnosed, resulting in 10-year cumulative incidence rates of 93.1 cases and 130.3 cases per 100,000, respectively. In the third decade, 2010–2019, there were only 4 cases (cumulative incidence of 10.2 cases per 100,000). With one-way ANOVA, the F statistic for within- and between-group comparisons was significant (p < 0.0001), indicating that the decline across the three epochs was statistically significant. Similarly, the median parasite density decreased from 13,966.5 (interquartile range (IQR) 123,910) in the first epoch to 7,224 (IQR 107,634) in the third epoch (Kruskal‒Wallis chi-square test, 12.3; P = 0.0021). One-way ANOVA for within- and between-group comparisons was equally significant (p < 0.001). The correlation coefficient between endemic BL and P. falciparum malaria infection was 0.53, indicating a strong positive correlation (P = 0.0024), implying that as P. falciparum malaria infection decreased, the endemic BL incidence rate decreased. Interpretation: There has been a significant reduction in the annual incidence rates of Burkitt’s lymphoma in the coastal region of Kenya. It is plausible that this decrease can be explained by an equally sustained and significant decline in the number of falciparum malaria infections.

Blood group O is associated with protection against severe malaria and reduced size and stability of P. falciparum-host red blood cell (RBC) rosettes compared to non-O blood groups. Whether the non-O blood groups encoded by the specific ABO genotypes AO, BO, AA, BB and AB differ in their associations with severe malaria and rosetting is unknown. The A and B antigens are host RBC receptors for rosetting, hence we hypothesized that the higher levels of A and/or B antigen on RBCs from AA, BB and AB genotypes compared to AO/BO genotypes could lead to larger rosettes, increased microvascular obstruction and higher risk of malaria pathology. We used a case-control study of Kenyan children and in vitro adhesion assays to test the hypothesis that "double dose" non-O genotypes (AA, BB, AB) are associated with increased risk of severe malaria and larger rosettes than "single dose" heterozygotes (AO, BO). In the case-control study, compared to OO, the double dose genotypes consistently had higher odds ratios (OR) for severe malaria than single dose genotypes, with AB (OR 1.93) and AO (OR 1.27) showing most marked difference (p = 0.02, Wald test). In vitro experiments with blood group A-preferring P. falciparum parasites showed that significantly larger rosettes were formed with AA and AB host RBCs compared to OO, whereas AO and BO genotypes rosettes were indistinguishable from OO. Overall, the data show that ABO genotype influences P. falciparum rosetting and support the hypothesis that double dose non-O genotypes confer a greater risk of severe malaria than AO/BO heterozygosity.

Background Understanding the age patterns of disease is necessary to target interventions to maximise cost-effective impact. New malaria chemoprevention and vaccine initiatives target young children attending routine immunisation services. Here we explore the relationships between age and severity of malaria hospitalisation versus malaria transmission intensity. Methods Clinical data from 21 surveillance hospitals in East Africa were reviewed. Malaria admissions aged 1 month to 14 years from discrete administrative areas since 2006 were identified. Each site-time period was matched to a model estimated community-based age-corrected parasite prevalence to provide predictions of prevalence in childhood ( Pf PR 2–10 ). Admission with all-cause malaria, severe malaria anaemia (SMA), respiratory distress (RD) and cerebral malaria (CM) were analysed as means and predicted probabilities from Bayesian generalised mixed models. Results 52,684 malaria admissions aged 1 month to 14 years were described at 21 hospitals from 49 site-time locations where Pf PR 2–10 varied from < 1 to 48.7%. Twelve site-time periods were described as low transmission ( Pf PR 2–10 < 5%), five low-moderate transmission ( Pf PR 2–10 5–9%), 20 moderate transmission ( Pf PR 2–10 10–29%) and 12 high transmission ( Pf PR 2–10 ≥ 30%). The majority of malaria admissions were below 5 years of age (69–85%) and rare among children aged 10–14 years (0.7–5.4%) across all transmission settings. The mean age of all-cause malaria hospitalisation was 49.5 months (95% CI 45.1, 55.4) under low transmission compared with 34.1 months (95% CI 30.4, 38.3) at high transmission, with similar trends for each severe malaria phenotype. CM presented among older children at a mean of 48.7 months compared with 39.0 months and 33.7 months for SMA and RD, respectively. In moderate and high transmission settings, 34% and 42% of the children were aged between 2 and 23 months and so within the age range targeted by chemoprevention or vaccines. Conclusions Targeting chemoprevention or vaccination programmes to areas where community-based parasite prevalence is ≥10% is likely to match the age ranges covered by interventions (e.g. intermittent presumptive treatment in infancy to children aged 2–23 months and current vaccine age eligibility and duration of efficacy) and the age ranges of highest disease burden.

Invasive bacterial disease is a major cause of morbidity and mortality in African children. Despite being caused by diverse pathogens, children with sepsis are clinically indistinguishable from one another. In spite of this, most genetic susceptibility loci for invasive infection that have been discovered to date are pathogen specific and are not therefore suggestive of a shared genetic architecture of bacterial sepsis. Here, we utilise probabilistic diagnostic models to identify children with a high probability of invasive bacterial disease among critically unwell Kenyan children with Plasmodium falciparum parasitaemia. We construct a joint dataset including 1445 bacteraemia cases and 1143 severe malaria cases, and population controls, among critically unwell Kenyan children that have previously been genotyped for human genetic variation. Using these data, we perform a cross-trait genome-wide association study of invasive bacterial infection, weighting cases according to their probability of bacterial disease. In doing so, we identify and validate a novel risk locus for invasive infection secondary to multiple bacterial pathogens, that has no apparent effect on malaria risk. The locus identified modifies splicing of BIRC6 in stimulated monocytes, implicating regulation of apoptosis and autophagy in the pathogenesis of sepsis in Kenyan children.

Severe falciparum malaria has substantially affected human evolution. Genetic association studies of patients with clinically defined severe malaria and matched population controls have helped characterise human genetic susceptibility to severe malaria, but phenotypic imprecision compromises discovered associations. In areas of high malaria transmission, the diagnosis of severe malaria in young children and, in particular, the distinction from bacterial sepsis are imprecise. We developed a probabilistic diagnostic model of severe malaria using platelet and white count data. Under this model, we re-analysed clinical and genetic data from 2220 Kenyan children with clinically defined severe malaria and 3940 population controls, adjusting for phenotype mis-labelling. Our model, validated by the distribution of sickle trait, estimated that approximately one-third of cases did not have severe malaria. We propose a data-tilting approach for case-control studies with phenotype mis-labelling and show that this reduces false discovery rates and improves statistical power in genome-wide association studies.

Background: In the 1980s, Streptococcus pneumoniae and Haemophilus influenzae were identified as the principal causes of severe pneumonia in children. We investigated the etiology of severe childhood pneumonia in Kenya after introduction of conjugate vaccines against H. influenzae type b, in 2001, and S. pneumoniae, in 2011. Methods: We conducted a case-control study between August 2011 and November 2013 among residents of the Kilifi Health and Demographic Surveillance System 28 days to 59 months of age. Cases were hospitalized at Kilifi County Hospital with severe or very severe pneumonia according to the 2005 World Health Organization definition. Controls were randomly selected from the community and frequency matched to cases on age and season. We tested nasal and oropharyngeal samples, sputum, pleural fluid, and blood specimens and used the Pneumonia Etiology Research for Child Health Integrated Analysis, combining latent class analysis and Bayesian methods, to attribute etiology. Results: We enrolled 630 and 863 HIV-uninfected cases and controls, respectively. Among the cases, 282 (44%) had abnormal chest radiographs (CXR positive), 33 (5%) died in hospital, and 177 (28%) had diagnoses other than pneumonia at discharge. Among CXR-positive pneumonia cases, viruses and bacteria accounted for 77% (95% CrI: 67%-85%) and 16% (95% CrI: 10%-26%) of pneumonia attribution, respectively. Respiratory syncytial virus, S. pneumoniae and H. influenza, accounted for 37% (95% CrI: 31%-44%), 5% (95% CrI: 3%-9%), and 6% (95% CrI: 2%-11%), respectively. Conclusions: Respiratory syncytial virus was the main cause of CXR-positive pneumonia. The small contribution of H. influenzae type b and pneumococcus to pneumonia may reflect the impact of vaccine introductions in this population.

Malaria and invasive non-typhoidal Salmonella (NTS) are life-threatening infections that often co-exist in African children. The iron-regulatory hormone hepcidin is highly upregulated during malaria and controls the availability of iron, a critical nutrient for bacterial growth. We investigated the relationship between Plasmodium falciparum malaria and NTS bacteremia in all pediatric admissions aged <5 years between August 1998 and October 2019 (n=75,034). We then assayed hepcidin and measures of iron status in five groups: (1) children with concomitant severe malarial anemia (SMA) and NTS (SMA+NTS, n=16); and in matched children with (2) SMA (n=33); (3) NTS (n=33); (4) cerebral malaria (CM, n=34); and (5) community-based children. SMA and severe anemia without malaria were associated with a 2-fold or more increased risk of NTS bacteremia, while other malaria phenotypes were not associated with increased NTS risk. Children with SMA had lower hepcidin/ferritin ratios (0.10; interquartile range [IQR]: 0.03-0.19) than those with CM (0.24; IQR: 0.14-0.69; P=0.006) or asymptomatic malaria (0.19; IQR: 0.09-0.46; P=0.01) indicating suppressed hepcidin levels. Children with SMA+NTS had lower hepcidin levels (9.3 ng/mL; IQR: 4.7-49.8) and hepcidin/ferritin ratios (0.03; IQR: 0.01-0.22) than those with NTS alone (105.8 ng/mL; IQR: 17.3-233.3; P=0.02 and 0.31; IQR: 0.06-0.66; P=0.007, respectively). Since hepcidin degrades ferroportin on the Salmonella-containing vacuole, we hypothesize that reduced hepcidin in children with SMA might contribute to NTS growth by modulating iron availability for bacterial growth. Further studies are needed to understand how the hepcidin-ferroportin axis might mediate susceptibility to NTS in severely anemic children.

This is a replication dataset for the manuscript: "Malaria infection and severe disease risks in Africa." These data were obtained from 13 hospitals in East Africa that had a continuous paediatric ward surveillance established for the purposes of monitoring acute febrile illness aetiology, disease burden epidemiology or research settings for improvements in hospital case-management. Each site used malaria diagnostics on all febrile presentations, an electronic medical record form that recorded standardised features of severe malaria and documented residential addresses on all admissions. The data includes the signs and symptoms of the three common paediatric severe malaria phenotypes (severe malaria anaemia, respiratory distress and cerebral malaria) including alternative definitions of these severe pathologies.

Abstract Background Most previous studies support a direct link between total parasite load and the clinical severity of Plasmodium falciparum malaria infections. Methods We estimated P. falciparum parasite loads in 3 groups of children with malaria infections of differing severity: (1) children with World Health Organization–defined severe malaria (n = 1544), (2) children admitted with malaria but without features of severity (n = 200), and (3) children in the community with asymptomatic parasitemia (n = 33). Results Peripheral parasitemias were highest in those with uncomplicated malaria (geometric mean [GM] parasite count, 111 064/μL; 95% confidence interval, CI, 86 798–141 819/μL), almost 3 times higher than in those with severe malaria (39 588/μL; 34 990–44 791/μL) and >100 times higher than in those with asymptomatic malaria (1092/μL; 523–2280/μL). However, the GM P. falciparum histidine-rich protein 2 (PfHRP2) values (95% CI) increased with severity, being 7 (4–12) ng/mL in asymptomatic malaria, 843 (655–1084) ng/mL in uncomplicated malaria, and 1369 (1244–1506) ng/mL in severe malaria. PfHRP2 concentrations were markedly lower in the subgroup of patients with severe malaria and concomitant invasive bacterial infections of blood or cerebrospinal fluid (GM concentration, 312 ng/mL; 95% CI, 175–557 ng/mL; P < .001) than in those without such infections (1439 ng/mL; 1307–1584; P < .001). Conclusions The clinical severity of malaria infections related strongly to the total burden of P. falciparum parasites. A quantitative test for plasma concentrations of PfHRP2 could be useful in identifying children at the greatest clinical risk and identifying critically ill children in whom malaria is not the primary cause.

The relationship between community prevalence of Plasmodium falciparum and the burden of severe, life-threatening disease remains poorly defined. To examine the three most common severe malaria phenotypes from catchment populations across East Africa, we assembled a dataset of 6506 hospital admissions for malaria in children aged 3 months to 9 years from 2006 to 2020. Admissions were paired with data from community parasite infection surveys. A Bayesian procedure was used to calibrate uncertainties in exposure (parasite prevalence) and outcomes (severe malaria phenotypes). Each 25% increase in prevalence conferred a doubling of severe malaria admission rates. Severe malaria remains a burden predominantly among young children (3 to 59 months) across a wide range of community prevalence typical of East Africa. This study offers a quantitative framework for linking malaria parasite prevalence and severe disease outcomes in children.

Abstract Background Malaria transmission has recently fallen in many parts of Africa, but systematic descriptions of infection and disease across all age groups are rare. Here, an epidemiological investigation of parasite prevalence, the incidence of fevers associated with infection, severe hospitalized disease and mortality among children older than 6 months and adults on the Kenyan coast is presented. Methods A prospective fever surveillance was undertaken at 6 out-patients (OPD) health-facilities between March 2018 and February 2019. Four community-based, cross sectional surveys of fever history and infection prevalence were completed among randomly selected homestead members from the same communities. Paediatric and adult malaria at Kilifi county hospital was obtained for the 12 months period. Rapid Diagnostic Tests (CareStart™ RDT) to detect HRP2-specific to Plasmodium falciparum was used in the community and the OPD, and microscopy in the hospital. Crude and age-specific incidence rates were computed using Poisson regression. Results Parasite prevalence gradually increased from childhood, reaching 12% by 9 years of age then declining through adolescence into adulthood. The incidence rate of RDT positivity in the OPD followed a similar trend to that of infection prevalence in the community. The incidence of hospitalized malaria from the same community was concentrated among children aged 6 months to 4 years (i.e. 64% and 70% of all hospitalized and severe malaria during the 12 months of surveillance, respectively). Only 3.7% (12/316) of deaths were directly attributable to malaria. Malaria mortality was highest among children aged 6 months–4 years at 0.57 per 1000 person-years (95% CI 0.2, 1.2). Severe malaria and death from malaria was negligible above 15 years of age. Conclusion Under conditions of low transmission intensity, immunity to disease and the fatal consequences of infection appear to continue to be acquired in childhood and faster than anti-parasitic immunity. There was no evidence of an emerging significant burden of severe malaria or malaria mortality among adults. This is contrary to current modelled approaches to disease burden estimation in Africa and has important implications for the targeting of infection prevention strategies based on chemoprevention or vector control.

Few previous studies have reported the effects of glucose-6-phosphate dehydrogenase (G6PD)-deficiency on child health in Africa. We conducted a case-control study in which cases (n 5 6829) were children admitted, for any reason, to Kilifi County Hospital, Kenya, while controls (n 5 10 179) were recruited from the surrounding community. Cases were subclassified based on their clinical and laboratory findings at admission. We calculated the prevalence of specific diseases by G6PD c.202 genotype, the only significant cause of G6PD-deficiency in this area, then estimated the association between genotype and admission with specific conditions using logistic regression. Among neonates, the prevalence of jaundice was higher in both G6PD c.202T heterozygotes (40/88; 45.5%; P=.004) and homo/hemizygotes (81/134; 60.5%; P<.0001) than in wild-type homozygotes (157/526; 29.9%). Median bilirubin levels also increased across the groups, being highest (239 mmol/L; interquartile range 96-390 mmol/L) in G6PD c.202T homo/hemizygotes. No differences were seen in admission hemoglobin concentrations or the prevalence of anemia or severe anemia by G6PD c.202 genotype. On case control analysis, G6PD heterozygosity was negatively associated with all-cause hospital admission (odds ratio 0.81; 95% confidence interval 0.73-0.90; P<.0001) and, specifically, admission with either pneumonia or Plasmodium falciparum parasitemia; while, conversely, it was positively associated with Gram-positive bacteremia. G6PD c.202T homo/heterozygosity was positively associated with neonatal jaundice, severe pneumonia, the receipt of a transfusion, and in-patient death. Our study supports the conclusion that G6PD c.202T is a balanced polymorphism in which a selective advantage afforded to heterozygous females against malaria is counterbalanced by increased risks of neonatal jaundice, invasive bacterial infections, and anemia.

AbstractBackgroundNeonatal jaundice (NNJ) is common in sub‐Saharan Africa (SSA), and it is associated with sepsis. Despite the high incidence, little has been documented about developmental impairments associated with NNJ in SSA. In particular, it is not clear if sepsis is associated with greater impairment following NNJ.MethodsWe followed up 169 participants aged 12 months (57 cases and 112 controls) within the Kilifi Health Demographic Surveillance System. The diagnosis of NNJ was based on clinical laboratory measurement of total serum bilirubin on admission, whereas the developmental outcomes were assessed using the Developmental Milestones Checklist and Kilifi Development Inventory.ResultsThere were significant differences between the cases and controls in all developmental domains. Cases scored lower in language functioning (mean [M] = 6.5, standard deviation [SD] = 4.3 vs. M = 8.9, SD = 4.6; p < .001); psychomotor functioning (Mdn = 23, interquartile range [IQR] = 17–34 vs. Mdn = 31.0, IQR = 22.0–44.0; Mann–Whitney U = 4,122, p = .002); and socio‐emotional functioning ([Mdn = 30.0, IQR = 27.0–33.0 vs. Mdn = 34.0, IQR = 30.0–37.0], Mann–Whitney U = 4,289, p < .001). There was no evidence of association between sepsis and psychomotor (rpb = −.2, p = .214), language (rpb = −.1, p = .510), and socio‐emotional functioning (rpb = .0, p = .916). Significant and medium to large portions of the variance (34–64%) in the developmental outcomes among children who survived NNJ were associated with home birth, low maternal education, and feeding problems during the first days of life.ConclusionsNNJ is associated with developmental impairments in the early childhood years; however, NNJ associated with sepsis does not lead to more severe impairment. Prenatal and postnatal care services are needed to reduce the negative impact of NNJ for children from low resourced settings.

Many parts of Africa have witnessed reductions in Plasmodium falciparum transmission over the last 15 years. Since immunity to malaria is acquired more rapidly at higher transmission, the slower acquisition of immunity at lower transmission may partially offset the benefits of reductions in transmission. We examined the clinical spectrum of disease and predictors of mortality after sustained changes in transmission intensity, using data collected from 1989 to 2016. We conducted a temporal observational analysis of 18,000 children, aged 14 days to 14 years old, who were admitted to Kilifi County Hospital, Kenya, from 1989 to 2016 with malaria. We describe the trends over time of the clinical and laboratory criteria for severe malaria and associated risk of mortality. During the time periods 1989–2003, 2004–2008, and 2009–2016, Kilifi County Hospital admitted averages of 657, 310, and 174 cases of severe malaria per year including averages of 48, 14, and 12 malaria-associated deaths per year, respectively. The median ages in years of children admitted with cerebral malaria, severe anaemia, and malaria-associated mortality were 3.0 (95% confidence interval (CI) 2.2–3.9), 1.1 (95% CI 0.9–1.4), and 1.1 (95% CI 0.3–2.2) in the year 1989, rising to 4.9 (95% CI 3.9–5.9), 3.8 (95% CI 2.5–7.1), and 5 (95% CI 3.3–6.3) in the year 2016. The ratio of children with cerebral malaria to severe anaemia rose from 1:2 before 2004 to 3:2 after 2009. Hyperparasitaemia was a risk factor for death after 2009 but not in earlier time periods. Despite the evidence of slower acquisition of immunity, continued reductions in the numbers of cases of severe malaria resulted in lower overall mortality. Our temporal data are limited to a single site, albeit potentially applicable to a secular trend present in many parts of Africa.