Search

Objective: To compare the prognostic value of mid-upper arm circumference (MUAC), weight-for-height Z -score (WHZ) and weight-for-age Z -score (WAZ) for predicting death over periods of 1, 3 and 6 months follow-up in children. Design: Pooled analysis of twelve prospective studies examining survival after anthropometric assessment. Sensitivity and false-positive ratios to predict death within 1, 3 and 6 months were compared for three individual anthropometric indices and their combinations. Setting: Community-based, prospective studies from twelve countries in Africa and Asia. Participants: Children aged 6–59 months living in the study areas. Results: For all anthropometric indices, the receiver operating characteristic curves were higher for shorter than for longer durations of follow-up. Sensitivity was higher for death with 1-month follow-up compared with 6 months by 49 % (95 % CI (30, 69)) for MUAC < 115 mm (P < 0·001), 48 % (95 % CI (9·4, 87)) for WHZ < -3 (P < 0·01) and 28 % (95 % CI (7·6, 42)) for WAZ < -3 (P < 0·005). This was accompanied by an increase in false positives of only 3 % or less. For all durations of follow-up, WAZ < -3 identified more children who died and were not identified by WHZ < -3 or by MUAC < 115 mm, 120 mm or 125 mm, but the use of WAZ < -3 led to an increased false-positive ratio up to 16·4 % (95 % CI (12·0, 20·9)) compared with 3·5 % (95 % CI (0·4, 6·5)) for MUAC < 115 mm alone. Conclusions: Frequent anthropometric measurements significantly improve the identification of malnourished children with a high risk of death without markedly increasing false positives. Combining two indices increases sensitivity but also increases false positives among children meeting case definitions. [ABSTRACT FROM AUTHOR]

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency state in humans. The clinical phenotype is variable and includes asymptomatic individuals, episodic hemolysis induced by oxidative stress, and chronic hemolysis. G6PD deficiency is common in malaria-endemic regions, an observation hypothesized to be due to balancing selection at the G6PD locus driven by malaria. G6PD deficiency increases risk of severe malarial anemia, a key determinant of invasive bacterial disease in malaria-endemic settings. The pneumococcus is a leading cause of invasive bacterial infection and death in African children. The effect of G6PD deficiency on risk of pneumococcal disease is undefined. We hypothesized that G6PD deficiency increases pneumococcal disease risk and that this effect is dependent upon malaria.Methods: We performed a genetic case-control study of pneumococcal bacteremia in Kenyan children stratified across a period of falling malaria transmission between 1998 and 2010.Results: Four hundred twenty-nine Kenyan children with pneumococcal bacteremia and 2677 control children were included in the study. Among control children, G6PD deficiency, secondary to the rs1050828 G>A mutation, was common, with 11.2% (n = 301 of 2677) being hemi- or homozygotes and 33.3% (n = 442 of 1329) of girls being heterozygotes. We found that G6PD deficiency increased the risk of pneumococcal bacteremia, but only during a period of high malaria transmission (P = 0.014; OR 2.33, 95% CI 1.19-4.57). We estimate that the population attributable fraction of G6PD deficiency on risk of pneumococcal bacteremia in areas under high malaria transmission is 0.129.Conclusions: Our data demonstrate that G6PD deficiency increases risk of pneumococcal bacteremia in a manner dependent on malaria. At the population level, the impact of G6PD deficiency on invasive pneumococcal disease risk in malaria-endemic regions is substantial. Our study highlights the infection-associated morbidity and mortality conferred by G6PD deficiency in malaria-endemic settings and adds to our understanding of the potential indirect health benefits of improved malaria control. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency (ID) is a major public health burden in African children and accurate prevalence estimates are important for effective nutritional interventions. However, ID may be incorrectly estimated in Africa because most measures of iron status are altered by inflammation and infections such as malaria. Through the current study, we have assessed different approaches to the prediction of iron status and estimated the burden of ID in African children.Methods: We assayed iron and inflammatory biomarkers in 4853 children aged 0-8 years from Kenya, Uganda, Burkina Faso, South Africa, and The Gambia. We described iron status and its relationship with age, sex, inflammation, and malaria parasitemia. We defined ID using the WHO guideline (ferritin < 12 μg/L or < 30 μg/L in the presence of inflammation in children < 5 years old or < 15 μg/L in children ≥ 5 years old). We compared this with a recently proposed gold standard, which uses regression-correction for ferritin levels based on the relationship between ferritin levels, inflammatory markers, and malaria. We further investigated the utility of other iron biomarkers in predicting ID using the inflammation and malaria regression-corrected estimate as a gold standard.Results: The prevalence of ID was highest at 1 year of age and in male infants. Inflammation and malaria parasitemia were associated with all iron biomarkers, although transferrin saturation was least affected. Overall prevalence of WHO-defined ID was 34% compared to 52% using the inflammation and malaria regression-corrected estimate. This unidentified burden of ID increased with age and was highest in countries with high prevalence of inflammation and malaria, where up to a quarter of iron-deficient children were misclassified as iron replete. Transferrin saturation < 11% most closely predicted the prevalence of ID according to the regression-correction gold standard.Conclusions: The prevalence of ID is underestimated in African children when defined using the WHO guidelines, especially in malaria-endemic populations, and the use of transferrin saturation may provide a more accurate approach. Further research is needed to identify the most accurate measures for determining the prevalence of ID in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background: Mortality in paediatric emergency care units in Africa often occurs within the first 24 h of admission and remains high. Alongside effective triage systems, a practical clinical bedside risk score to identify those at greatest risk could contribute to reducing mortality. Methods: Data collected during the Fluid As Expansive Supportive Therapy (FEAST) trial, a multi-centre trial involving 3,170 severely ill African children, were analysed to identify clinical and laboratory prognostic factors for mortality. Multivariable Cox regression was used to build a model in this derivation dataset based on clinical parameters that could be quickly and easily assessed at the bedside. A score developed from the model coefficients was externally validated in two admissions datasets from Kilifi District Hospital, Kenya, and compared to published risk scores using Area Under the Receiver Operating Curve (AUROC) and Hosmer-Lemeshow tests. The Net Reclassification Index (NRI) was used to identify additional laboratory prognostic factors. Results: A risk score using 8 clinical variables (temperature, heart rate, capillary refill time, conscious level, severe pallor, respiratory distress, lung crepitations, and weak pulse volume) was developed. The score ranged from 0-10 and had an AUROC of 0.82 (95 % CI, 0.77-0.87) in the FEAST trial derivation set. In the independent validation datasets, the score had an AUROC of 0.77 (95 % CI, 0.72-0.82) amongst admissions to a paediatric high dependency ward and 0.86 (95 % CI, 0.82-0.89) amongst general paediatric admissions. This discriminative ability was similar to, or better than other risk scores in the validation datasets. NRI identified lactate, blood urea nitrogen, and pH to be important prognostic laboratory variables that could add information to the clinical score. Conclusions: Eight clinical prognostic factors that could be rapidly assessed by healthcare staff for triage were combined to create the FEAST Paediatric Emergency Triage (PET) score and externally validated. The score discriminated those at highest risk of fatal outcome at the point of hospital admission and compared well to other published risk scores. Further laboratory tests were also identified as prognostic factors which could be added if resources were available or as indices of severity for comparison between centres in future research studies. [ABSTRACT FROM AUTHOR]

Falciparum malaria is an important cause of acute symptomatic seizures in children admitted to hospitals in sub-Saharan Africa, and these seizures are associated with neurological disabilities and epilepsy. However, it is difficult to determine the proportion of seizures attributable to malaria in endemic areas since a significant proportion of asymptomatic children have malaria parasitaemia. We studied children aged 0–13 years who had been admitted with a history of seizures to a rural Kenyan hospital between 2002 and 2008. We examined the changes in the incidence of seizures with the reduction of malaria. Logistic regression was used to model malaria-attributable fractions for seizures (the proportion of seizures caused by malaria) to determine if the observed decrease in acute symptomatic seizures was a measure of seizures that are attributable to malaria. The overall incidence of acute symptomatic seizures over the period was 651/100 000/year (95% confidence interval 632–670) and it was 400/100 000/year (95% confidence interval 385–415) for acute complex symptomatic seizures (convulsive status epilepticus, repetitive or focal) and 163/100 000/year (95% confidence interval 154–173) for febrile seizures. From 2002 to 2008, the incidence of all acute symptomatic seizures decreased by 809/100 000/year (69.2%) with 93.1% of this decrease in malaria-associated seizures. The decrease in the incidence of acute complex symptomatic seizures during the period was 111/100 000/year (57.2%) for convulsive status epilepticus, 440/100 000/year (73.7%) for repetitive seizures and 153/100 000/year (80.5%) for focal seizures. The adjusted malaria-attributable fractions for seizures with parasitaemia were 92.9% (95% confidence interval 90.4–95.1%) for all acute symptomatic seizures, 92.9% (95% confidence interval 89.4–95.5%) for convulsive status epilepticus, 93.6% (95% confidence interval 90.9–95.9%) for repetitive seizures and 91.8% (95% confidence interval 85.6–95.5%) for focal seizures. The adjusted malaria-attributable fractions for seizures in children above 6 months of age decreased with age. The observed decrease in all acute symptomatic seizures (809/100 000/year) was similar to the predicted decline (794/100 000/year) estimated by malaria-attributable fractions at the beginning of the study. In endemic areas, falciparum malaria is the most common cause of seizures and the risk for seizures in malaria decreases with age. The reduction in malaria has decreased the burden of seizures that are attributable to malaria and this could lead to reduced neurological disabilities and epilepsy in the area. [ABSTRACT FROM AUTHOR]

Background: Acute seizures are common among children admitted to hospitals in resource poor countries. However, there is little data on the burden, causes and outcome of neonatal seizures in sub-Saharan Africa. We determined the minimum incidence, aetiology and immediate outcome of seizures among neonates admitted to a rural district hospital in Kenya. Methods: From 1st January 2003 to 31st December 2007, we assessed for seizures all neonates (age 0-28 days) admitted to the Kilifi District Hospital, who were resident in a defined, regularly enumerated study area. The population denominator, the number of live births in the community on 1 July 2005 (the study midpoint) was modelled from the census data. Results: Seizures were reported in 142/1572 (9.0%) of neonatal admissions. The incidence was 39.5 [95% confidence interval (CI) 26.4-56.7] per 1000 live-births and incidence increased with birth weight. The main diagnoses in neonates with seizures were sepsis in 85 (60%), neonatal encephalopathy in 30 (21%) and meningitis in 21 (15%), but only neonatal encephalopathy and bacterial meningitis were independently associated with seizures. Neonates with seizures had a longer hospitalization [median period 7 days - interquartile range (IQR) 4 to 10] -compared to 5 days [IQR 3 to 8] for those without seizures, P = 0.02). Overall, there was no difference in inpatient case fatality between neonates with and without seizures but, when this outcome was stratified by birth weight, it was significantly higher in neonates ≥ 2.5 kg compared to low birth weight neonates [odds ratio 1.59 (95%CI 1.02 to 2.46), P = 0.037]. Up to 13% of the surviving newborn with seizures had neurological abnormalities at discharge. Conclusion: There is a high incidence of neonatal seizures in this area of Kenya and the most important causes are neonatal encephalopathy and meningitis. The high incidence of neonatal seizures may be a reflection of the quality of the perinatal and postnatal care available to the neonates. [ABSTRACT FROM AUTHOR]

Background: There is an increasing recognition that children remain at elevated risk of death following discharge from health facilities in resource-poor settings. Diarrhea has previously been highlighted as a risk factor for post-discharge mortality.Methods: A retrospective cohort study was conducted to estimate the incidence and demographic, clinical, and biochemical features associated with inpatient and 1-year post-discharge mortality amongst children aged 2-59 months admitted with diarrhea from 2007 to 2015 at Kilifi County Hospital and who were residents of Kilifi Health and Demographic Surveillance System (KHDSS). Log-binomial regression was used to identify risk factors for inpatient mortality. Time at risk was from the date of discharge to the date of death, out-migration, or 365 days later. Post-discharge mortality rate was computed per 1000 child-years of observation, and Cox proportion regression used to identify risk factors for mortality.Results: Two thousand six hundred twenty-six child KHDSS residents were admitted with diarrhea, median age 13 (IQR 8-21) months, of which 415 (16%) were severely malnourished and 130 (5.0%) had a positive HIV test. One hundred twenty-one (4.6%) died in the hospital, and of 2505 children discharged alive, 49 (2.1%) died after discharge: 21.4 (95% CI 16.1-28.3) deaths per 1000 child-years. Admission with signs of both diarrhea and severe pneumonia or severe pneumonia alone had a higher risk of both inpatient and post-discharge mortality than admission for diarrhea alone. There was no significant difference in inpatient and post-discharge mortality between children admitted with diarrhea alone and those with other diagnoses excluding severe pneumonia. HIV, low mid-upper arm circumference (MUAC), and bacteremia were associated with both inpatient and post-discharge mortality. Signs of circulatory impairment, sepsis, and abnormal electrolytes were associated with inpatient but not post-discharge mortality. Prior admission and lower chest wall indrawing were associated with post-discharge mortality but not inpatient mortality. Age, stuntedness, and persistent or bloody diarrhea were not associated with mortality before or after discharge.Conclusions: Our results accentuate the need for research to improve the uptake and outcomes of services for malnutrition and HIV as well as to elucidate causal pathways and test interventions to mitigate these risks. [ABSTRACT FROM AUTHOR]

Background: Malnutrition and malaria are both significant causes of morbidity and mortality in African children. However, the extent of their spatial comorbidity remains unexplored and an understanding of their spatial correlation structure would inform improvement of integrated interventions. We aimed to determine the spatial correlation between both wasting and low mid upper arm circumference (MUAC) and falciparum malaria among Somalian children aged 6–59 months. Methods: Data were from 49 227 children living in 888 villages between 2007 to 2010. We developed a Bayesian geostatistical shared component model in order to determine the common spatial distributions of wasting and falciparum malaria; and low-MUAC and falciparum malaria at 1 × 1 km spatial resolution. Results: The empirical correlations with malaria were 0.16 and 0.23 for wasting and low-MUAC respectively. Shared spatial residual effects were statistically significant for both wasting and low-MUAC. The posterior spatial relative risk was highest for low-MUAC and malaria (range: 0.19 to 5.40) and relatively lower between wasting and malaria (range: 0.11 to 3.55). Hotspots for both wasting and low-MUAC with malaria occurred in the South Central region in Somalia. Conclusions: The findings demonstrate a relationship between nutritional status and falciparum malaria parasitaemia, and support the use of the relatively simpler MUAC measurement in surveys. Shared spatial distribution and distinct hotspots present opportunities for targeted seasonal chemoprophylaxis and other forms of malaria prevention integrated within nutrition programmes. [ABSTRACT FROM AUTHOR]

Background: There are few epidemiologic data on invasive bacterial infections among children in sub-Saharan Africa. We studied every acute pediatric admission to a rural district hospital in Kenya to examine the prevalence, incidence, types, and outcome of community-acquired bacteremia. Methods: Between August 1998 and July 2002, we cultured blood on admission from 19,339 inpatients and calculated the incidence of bacteremia on the basis of the population served by the hospital. Results: Of a total of 1783 infants who were under 60 days old, 228 had bacteremia (12.8 percent), as did 866 of 14,787 children who were 60 or more days of age (5.9 percent). Among infants who were under 60 days old, Escherichia coli and group B streptococci predominated among a broad range of isolates (14 percent and 11 percent, respectively). Among infants who were 60 or more days of age, Streptococcus pneumoniae, nontyphoidal salmonella species, Haemophilus influenzae, and E. coli accounted for more than 70 percent of isolates. The minimal annual incidence of community-acquired bacteremia was estimated at 1457 cases per 100,000 children among infants under a year old, 1080 among children under 2 years, and 505 among children under 5 years. Of all in-hospital deaths, 26 percent were in children with community-acquired bacteremia. Of 308 deaths in children with bacteremia, 103 (33.4 percent) occurred on the day of admission and 217 (70.5 percent) within two days. Conclusions: Community-acquired bacteremia is a major cause of death among children at a rural sub-Saharan district hospital, a finding that highlights the need for prevention and for overcoming the political and financial barriers to widespread use of existing vaccines for bacterial diseases. N Engl J Med 2005;352:39-47. [ABSTRACT FROM AUTHOR]

This article focuses on treatment of severely malnourished HIV-infected children in Africa. The article explains that the high amount of malnourished HIV-infected children has increased the need for facility-based treatment, while children not infected can receive home-based therapy with therapeutic foods. The article includes treatment tactics for infected and uninfected children, mortality rates, and differences in recovery and treatment for both HIV-infected and non-infected children with severe malnutrition.

Severe anaemia often secondary to malaria is a major contributor to child mortality in sub-Saharan Africa. We have confirmed that use of simple clinical and laboratory criteria can identify those children likely to benefit most from treatment. We have also shown that the speed of response may be critical. The quality and capacity of blood transfusion services could therefore have a major, direct effect on inpatient child mortality. [ABSTRACT FROM AUTHOR]

Background: Rectovaginal group B Streptococcus (GBS) colonisation in pregnant individuals at the time of labour is a major risk factor for invasive GBS disease by age 7 days (early-onset disease). We aimed to investigate the prevalence of rectovaginal GBS colonisation at the time of labour among pregnant women and vertical transmission to their newborns across selected low-income and middle-income African and south Asian countries., Methods: This prospective, observational study was undertaken at 11 maternity and obstetric care facilities based in Ethiopia, Kenya, Mozambique, Nigeria, Mali, South Africa, Bangladesh, India, and Bhutan. HIV-negative pregnant women aged 18-45 years who were in the early stages of labour and at least 37 weeks' gestation were eligible for inclusion. Lower vaginal and rectal swabs and urine were collected from the women, and swabs of the umbilicus, outer ear, axillary fold, rectum, and throat were obtained from their newborns, for GBS culture. Standardised sampling and culture using direct plating and selective media broth for detection of GBS colonisation was undertaken at the sites. Serotyping of GBS isolates was done in South Africa. The primary outcome was the prevalence of rectovaginal GBS among pregnant women, analysed in participants with available data. This study is registered with the South African National Clinical Trials Register, number DOH-27-0418-4989., Findings: 6922 pregnant women were enrolled from Jan 10, 2016, to Dec 11, 2018, of whom 6514 (94·1%; 759-892 per country) were included in the analysis; data from Bhutan were not included in the study due to issues with specimen collection and processing. Overall, the prevalence of maternal GBS colonisation was 24·1% (95% CI 23·1-25·2; 1572 of 6514); it was highest in Mali (41·1% [37·7-44·6]; 314 of 764) and lowest in Ethiopia (11·6% [9·5-14·1]; 88 of 759). The overall rate of vertical transmission of GBS from women with rectovaginal GBS colonisation was 72·3% (70·0-74·4; 1132 of 1566); it was highest in Mozambique (79·2% [73·3-84·2]; 168 of 212) and lowest in Bangladesh (55·8%, 47·5-63·8; 77 of 138). The five most common GBS colonising serotypes were Ia (37·3% [34·9-39·7]; 586 of 1572), V (28·5% [26·3-30·8]; 448 of 1572), III (25·1% [23·0-27·3]; 394 of 1572), II (9·2% [7·8-10·7]; 144 of 1572), and Ib (6·5% [5·4-7·8]; 102 of 1572). There was geographical variability in serotype proportion distribution; serotype VII was the third most common serotype in India (8·6% [5·3-13·7]; 15 of 174) and serotype VI was mainly identified in Bangladesh (5·8% [3·0-11·0]; eight of 138) and India (5·7% [3·2-10·3]; ten of 174)., Interpretation: Our study reported a high prevalence of GBS colonisation in most settings, with some geographical variability even within African countries. Our findings suggest that serotypes not included in current multivalent capsular-polysaccharide GBS vaccines prevail in some regions, so vaccine efficacy and post-licensure effectiveness studies should assess the effect of vaccination on maternal GBS colonisation given the potential for replacement by non-vaccine serotypes., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests SAM declares grant funding to his institution for research on GBS, separate from this study, from Pfizer, GlaxoSmithKline, and Minervax. GK declares grant funding to his institution for research on GBS from the Bill & Melinda Gates Foundation and PATH. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The understanding of the epidemiology of severe malaria in African children remains incomplete across the spectrum of Plasmodium falciparum transmission intensities through which communities might expect to transition, as intervention coverage expands., Methods: Paediatric admission data were assembled from 13 hospitals serving 17 communities between 1990 and 2007. Estimates of Plasmodium falciparum transmission intensity in these communities were assembled to be spatially and temporally congruent to the clinical admission data. The analysis focused on the relationships between community derived parasite prevalence and the age and clinical presentation of paediatric malaria in children aged 0-9 years admitted to hospital., Results: As transmission intensity declined a greater proportion of malaria admissions were in older children. There was a strong linear relationship between increasing transmission intensity and the proportion of paediatric malaria admissions that were infants (R2 = 0.73, p < 0.001). Cerebral malaria was reported among 4% and severe malaria anaemia among 17% of all malaria admissions. At higher transmission intensity cerebral malaria was a less common presentation compared to lower transmission sites. There was no obvious relationship between the proportions of children with severe malaria anaemia and transmission intensity., Conclusion: As the intensity of malaria transmission declines in Africa through the scaling up of insecticide-treated nets and other vector control measures a focus of disease prevention among very young children becomes less appropriate. The understanding of the relationship between parasite exposure and patterns of disease risk should be used to adapt malaria control strategies in different epidemiological settings.

Severe malaria is clinically similar to other severe febrile illnesses. However, in endemic areas, parasitological confirmation of parasitemia is often unavailable or unreliable. False-positive malaria microscopy is common. The most important consequence of treating only for malaria when no parasitemia exists is failure to address other life-threatening conditions. Invasive bacterial infections are detected in up to one third of children with clinical features of severe malaria but a slide with results negative for malaria. Even among genuinely parasitized children, severe illness is not always due to malaria in endemic areas. We believe that routine use of parenteral antibiotics among children with a slide that indicates malaria and life-threatening disease is warranted because invasive bacterial infections are likely to be under-ascertained and are associated with increased mortality. Published data on co-morbidity with HIV infection and malnutrition are reviewed. A structured approach to assessment and care is essential, and is largely independent of underlying etiology.