Search

Background: Malaria and anaemia contribute substantially to child morbidity and mortality. In this study, we sought to jointly model the residual spatial variation in the likelihood of these two correlated diseases, while controlling for individual-level, household-level and environmental characteristics., Methods: A child-level shared component model was utilised to partition shared and disease-specific district-level spatial effects., Results: The results indicated that the spatial variation in the likelihood of malaria was more prominent compared to that of anaemia, for both the shared and specific spatial components. In addition, approximately 30% of the districts were associated with an increased likelihood of anaemia but a decreased likelihood of malaria. This suggests that there are other drivers of anaemia in children in these districts, which warrants further investigation., Conclusions: The maps of the shared and disease-specific spatial patterns provide a tool to allow for more targeted action in malaria and anaemia control and prevention, as well as for the targeted allocation of limited district health system resources., (© 2022. The Author(s).)

Background: In resource-limited settings, acute respiratory infections continue to be the leading cause of death in young children. We conducted postmortem investigations in children <5 years hospitalized with a clinical diagnosis of respiratory disease at Kenya's largest referral hospital., Methods: We collected respiratory and other tissues postmortem to examine pathologic processes using histology, molecular and immunohistochemistry assays. Nasopharyngeal, trachea, bronchi and lung specimens were tested using 21-target respiratory pathogen real-time reverse transcription polymerase chain reaction assays deployed on Taqman Array Cards. Expert panels reviewed all findings to determine causes of death and associated pathogens., Results: From 2014 to 2015, we investigated 64 pediatric deaths (median age 7 months). Pneumonia was determined as cause of death in 70% (42/52) of cases where death was associated with an infectious disease process. The main etiologies of pneumonia deaths were respiratory syncytial virus (RSV) (n = 7, 19%), Pneumocystis jirovecii (n = 7, 19%), influenza A (n = 5, 14%) and Streptococcus pneumoniae (n = 5, 14%)-10% of cases had multi-pathogen involvement. Among the other 10 deaths associated with a nonpneumonia infectious process, 4 did not have an etiology assigned, the others were associated with miliary tuberculosis (2), cerebral thrombosis due to HIV (1), Enterobacteriaceae (1), rotavirus (1), and 1 case of respiratory infection with severe hypokalemia associated with RSV., Conclusions: In spite of well-established vaccination programs in Kenya, some deaths were still vaccine preventable. Accelerated development of RSV monoclonal antibodies and vaccines, introduction of seasonal influenza vaccination, and maintenance or improved uptake of existing vaccines can contribute to further reductions in childhood mortality., Competing Interests: Since completion of this work, S.S.C. has joined Sanofi Pasteur, France and M.-A.W. has joined the Institute of Tropical Medicine in Antwerp, Belgium. The other authors have no conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Anaemia and malaria are the leading causes of sub-Saharan African childhood morbidity and mortality. This study aimed to explore the complex relationship between anaemia and malaria in young children across the districts or counties of four contiguous sub-Saharan African countries, namely Kenya, Malawi, Tanzania and Uganda, while accounting for the effects of socio-economic, demographic and environmental factors. Geospatial maps were constructed to visualise the relationship between the two responses across the districts of the countries., Methods: A joint bivariate copula regression model was used, which estimates the correlation between the two responses conditional on the linear, non-linear and spatial effects of the explanatory variables considered. The copula framework allows the dependency structure between the responses to be isolated from their marginal distributions. The association between the two responses was set to vary according to the district of residence across the four countries., Results: The study revealed a positive association between anaemia and malaria throughout the districts, the strength of which varied across the districts of the four countries. Due to this heterogeneous association between anaemia and malaria, we further considered the joint probability of each combination of outcome of anaemia and malaria to further reveal more about the relationship between the responses. A considerable number of districts had a high joint probability of a child being anaemic but not having malaria. This might suggest the existence of other significant drivers of childhood anaemia in these districts., Conclusions: This study presents an alternative technique to joint modelling of anaemia and malaria in young children which assists in understanding more about their relationship compared to techniques of multivariate modelling. The approach used in this study can aid in visualising the relationship through mapping of their correlation and joint probabilities. These maps produced can then help policy makers target the correct set of interventions, or prevent the use of incorrect interventions, particularly for childhood anaemia, the causes of which are multiple and complex.

Background: Infection with Plasmodium falciparum leads to severe malaria and death in approximately 400 000 children each year in sub-Saharan Africa. Blood transfusion might benefit some patients with malaria but could potentially harm others. The aim of this study was to estimate the association between transfusion and death among children admitted to hospital with P falciparum malaria., Methods: In this prospective, multicentre observational study, we analysed admissions to six tertiary care hospitals in The Gambia, Malawi, Gabon, Kenya, and Ghana that participated in the Severe Malaria in African Children network. Patients were enrolled if they were younger than 180 months and had a Giemsa-stained thick blood smear that was positive for P falciparum. Blood transfusion (whole blood at a target volume of 20 mL per kg) was administered at the discretion of the responsible physicians who were aware of local and international transfusion guidelines. The primary endpoint was death associated with transfusion, which was estimated using models adjusted for site and disease severity. We also aimed to identify factors associated with the decision to transfuse. The exploratory objective was to estimate optimal haemoglobin transfusion thresholds using generalised additive models., Findings: Between Dec 19, 2000, and March 8, 2005, 26 106 patients were enrolled in the study, 25 893 of whom had their transfusion status recorded and were included in the primary analysis. 8513 (32·8%) patients received a blood transfusion. Patients were followed-up until discharge from hospital for a median of 2 days (IQR 1-4). 405 (4·8%) of 8513 patients who received a transfusion died compared with 689 (4·0%) of 17 380 patients who did not receive a transfusion. Transfusion was associated with decreased odds of death in site-adjusted analysis (odds ratio [OR] 0·82 [95% CI 0·71-0·94]) and after adjusting for the increased disease severity of patients who received a transfusion (0·50 [0·42-0·60]). Severe anaemia, elevated lactate concentration, respiratory distress, and parasite density were associated with greater odds of receiving a transfusion. Among all study participants, transfusion was associated with improved survival when the admission haemoglobin concentration was up to 77 g/L (95% CI 65-110). Among those with impaired consciousness (Blantyre Coma Score ≤4), transfusion was associated with improved survival at haemoglobin concentrations up to 105 g/L (95% CI 71-115). Among those with hyperlactataemia (blood lactate ≥5·0 mmol/L), transfusion was not significantly associated with harm at any haemoglobin concentration-ie, the OR of death comparing transfused versus not transfused was less than 1 at all haemoglobin concentrations (lower bound of the 95% CI for the haemoglobin concentration at which the OR of death equals 1: 90 g/L; no upper bound)., Interpretation: Our findings suggest that whole blood transfusion was associated with improved survival among children hospitalised with P falciparum malaria. Among those with impaired consciousness or hyperlactataemia, transfusion was associated with improved survival at haemoglobin concentrations above the currently recommended transfusion threshold. These findings highlight the need to do randomised controlled trials to test higher transfusion thresholds among African children with severe malaria complicated by these factors., Funding: US National Institute of Allergy and Infectious Diseases., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The causes of childhood anaemia are multifactorial, interrelated and complex. Such causes vary from country to country, and within a country. Thus, strategies for anaemia control should be tailored to local conditions and take into account the specific etiology and prevalence of anaemia in a given setting and sub-population. In addition, policies and programmes for anaemia control that do not account for the spatial heterogeneity of anaemia in children may result in certain sub-populations being excluded, limiting the effectiveness of the programmes. This study investigated the demographic and socio-economic determinants as well as the spatial variation of anaemia in children aged 6 to 59 months in Kenya, Malawi, Tanzania and Uganda., Methods: The study made use of data collected from nationally representative Malaria Indicator Surveys (MIS) and Demographic and Health Surveys (DHS) conducted in all four countries between 2015 and 2017. During these surveys, all children under the age of five years old in the sampled households were tested for malaria and anaemia. A child's anaemia status was based on the World Health Organization's cut-off points where a child was considered anaemic if their altitude adjusted haemoglobin (Hb) level was less than 11 g/dL. The explanatory variables considered comprised of individual, household and cluster level factors, including the child's malaria status. A multivariable hierarchical Bayesian geoadditive model was used which included a spatial effect for district of child's residence., Results: Prevalence of childhood anaemia ranged from 36.4% to 61.9% across the four countries. Children with a positive malaria result had a significantly higher odds of anaemia [AOR = 4.401; 95% CrI: (3.979, 4.871)]. After adjusting for a child's malaria status and other demographic, socio-economic and environmental factors, the study revealed distinct spatial variation in childhood anaemia within and between Malawi, Uganda and Tanzania. The spatial variation appeared predominantly due to unmeasured district-specific factors that do not transcend boundaries., Conclusions: Anaemia control measures in Malawi, Tanzania and Uganda need to account for internal spatial heterogeneity evident in these countries. Efforts in assessing the local district-specific causes of childhood anaemia within each country should be focused on.

Objectives: We compared minimally invasive tissue sampling (MITS) with conventional autopsy (CA) in detection of respiratory pathology/pathogens among Kenyan children younger than 5 years who were hospitalized with respiratory disease and died during hospitalization., Methods: Pulmonary MITS guided by anatomic landmarks was followed by CA. Lung tissues were triaged for histology and molecular testing using TaqMan Array Cards (TACs). MITS and CA results were compared for adequacy and concordance., Results: Adequate pulmonary tissue was obtained by MITS from 54 (84%) of 64 respiratory deaths. Comparing MITS to CA, full histologic diagnostic concordance was present in 23 (36%) cases and partial concordance in 19 (30%), an overall 66% concordance rate. Pathogen detection using TACs had full concordance in 27 (42%) and partial concordance in 24 (38%) cases investigated, an overall 80% concordance rate., Conclusions: MITS is a viable alternative to CA in respiratory deaths in resource-limited settings, especially if combined with ancillary tests to optimize diagnostic accuracy., (© American Society for Clinical Pathology, 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Hyperlactataemia is often associated with a poor outcome in severe malaria in African children. To unravel the complex pathophysiology of this condition the relationship between plasma lactate levels, parasite density, pro- and anti-inflammatory cytokines, and haemozoin-containing leucocytes was studied in children with severe falciparum malarial anaemia., Methods: Twenty-six children with a primary diagnosis of severe malarial anaemia with any asexual Plasmodium falciparum parasite density and Hb < 5 g/dL were studied and the association of plasma lactate levels and haemozoin-containing leucocytes, parasite density, pro- and anti-inflammatory cytokines was measured. The same associations were measured in non-severe malaria controls (N = 60)., Results: Parasite density was associated with lactate levels on admission (r = 0.56, P < 0.005). Moreover, haemozoin-containing neutrophils and IL-12 were strongly associated with plasma lactate levels, independently of parasite density (r = 0.60, P = 0.003 and r = -0.46, P = 0.02, respectively). These associations were not found in controls with uncomplicated malarial anaemia., Conclusion: These data suggest that blood stage parasites, haemozoin and low levels of IL-12 may be associated with the development of hyperlactataemia in severe malarial anaemia.

Background: Malaria resistance by the sickle cell trait (genotype HbAS) has served as the prime example of genetic selection for over half a century. Nevertheless, the mechanism of this resistance remains the subject of considerable debate. While it probably involves innate factors such as the reduced ability of Plasmodium falciparum parasites to grow and multiply in HbAS erythrocytes, recent observations suggest that it might also involve the accelerated acquisition of malaria-specific immunity., Methods and Findings: We studied the age-specific protection afforded by HbAS against clinical malaria in children living on the coast of Kenya. We found that protection increased with age from only 20% in the first 2 y of life to a maximum of 56% by the age of 10 y, returning thereafter to 30% in participants greater than 10 y old., Conclusions: Our observations suggest that malaria protection by HbAS involves the enhancement of not only innate but also of acquired immunity to the parasite. A better understanding of the underlying mechanisms might yield important insights into both these processes.

Interleukin-12 (IL-12) is an important regulatory cytokine in infection and immunity. Administration of IL-12 may reduce complications of severe malaria in rodents. Polymorphisms in IL12B, the gene encoding the IL-12 p40 subunit, influence the secretion of IL-12 and susceptibility to Type 1 diabetes. We therefore investigated whether IL12B polymorphisms may affect the outcome of severe malaria. Homozygosity for a polymorphism in the IL12B promoter was associated with increased mortality in Tanzanian children having cerebral malaria but not in Kenyan children with severe malaria. Furthermore, homozygotes for the IL12B promotor polymorphism had decreased production of nitric oxide, which is in part regulated by IL-12 activity. These studies suggest that IL12B polymorphisms, via regulation of IL-12 production, may influence the outcome of malaria infection in at least one African population.