A sobering 99% of deaths in children under five occur in low- and middle-income countries, say concerned researchers, who found that 82% of these deaths – many from malnutrition and HIV – could be prevented, and that minimally invasive biopsies could also help determine causes and provide critical data.
The study, from the international CHAMPS network and which used the minimally invasive autopsy technique developed by the Barcelona Institute for Global Health (ISGlobal), found an infectious agent in 87% of cases and identified malnutrition as the most common underlying cause of death.
“If we want to prevent these deaths, we need to know the causes, but the problem is we lack reliable data,” said Quique Bassat, ICREA (Catalan Institution for Research and Advanced Studies) researcher at ISGlobal, an institution supported by the “la Caixa” Foundation.
Clinical data and family or caregiver testimonies (verbal autopsies) are often used to determine the causes in low-resource areas, but they are not detailed enough.
In addition, it is important to distinguish between underlying causes (i.e. those that start the chain of events leading to death) and the immediate cause of death.
“This distinction is critical because death can result from the interaction between different conditions,” said Bassat, who is part of the ISGlobal team that has developed and validated a minimally invasive technique to obtain biopsies from different organs to determine causes of death through histopathological and microbiological analysis.
This post-mortem minimally invasive tissue sampling (MITS) technique was adopted by CHAMPS, an international child mortality surveillance network launched in 2016.
In this study, a CHAMPS team led by Bassat investigated the causes of child deaths in seven countries in sub-Saharan Africa and South East Asia (South Africa, Mozambique, Sierra Leone, Kenya, Mali, Ethiopia and Bangladesh), distinguishing between underlying, intermediate and immediate causes.
The analysis included 636 deaths in children aged one month to five years that occurred in the community or in the hospital between 2016 and 2020. A MITS was performed in all cases, and clinical and verbal autopsy information was collected.
Malnutrition the main trigger
The most common underlying causes of death were: malnutrition (16.5%), HIV (11.9%), malaria (11.2%), congenital defects (10.1%), respiratory infections (8.4%) and diarrhoea (7.2%).
An infectious agent was found in 87% of cases (the most frequent was Klebsiella pneumoniae, a bacterium mainly associated with hospital infections, followed by the malaria parasite P. falciparum and Streptococcus pneumoniae, a pneumonia-causing bacterium).
“Only 25% of deaths were due to a single cause; all the others were due to a complex interaction of factors,” said Bassat.
The study concluded that 82% of the deaths could have been prevented, opening up many opportunities to design targeted interventions with high impact.
The team said that minimally invasive autopsies also allow for the analysis of deaths that occur in the community (at home), providing valuable information on how to prevent deaths that escape the health system.
Study details
Causes of death among infants and children in the Child Health 1 and Mortality Prevention Surveillance (CHAMPS) Network
Published in JAMA Network Open on 26 July 2023
Quique Bassat, Dianna Blau, Shabir Madhi, et al.
Key Points
Question Can the investigation of causes of childhood death in high-mortality settings be improved by the use of post-mortem minimally invasive tissue sampling?
Findings This cross-sectional study presents data on 632 post-neonatal deaths (age 1-59 months) from 7 sub-Saharan and Asian high-mortality sites adequately characterised through histopathologic analysis, microbiological diagnostics, clinical data, and verbal autopsies. Malnutrition, HIV, malaria, congenital birth defects, lower respiratory tract infections, and diarrhoeal diseases were the most common underlying causes of childhood deaths, an infection was present in the causal chain in 86.9% of the cases, and 82.3% of deaths were deemed potentially preventable by the expert panels evaluating them.
Meaning The results of this study demonstrate the potential of the minimally invasive tissue sampling tool to reliably investigate causes of child deaths and highlight the significant role of infections in high-child-mortality settings, providing concrete opportunities for action to enhance child survival.
Abstract
Importance
The number of deaths of children younger than 5 years has been steadily decreasing worldwide, from more than 17 million annual deaths in the 1970s to an estimated 5.3 million in 2019 (with 2.8 million deaths occurring in those aged 1-59 months [53% of all deaths in children aged <5 years]). More detailed characterisation of childhood deaths could inform interventions to improve child survival.
Objective
To describe causes of post-neonatal child deaths across 7 mortality surveillance sentinel sites in Africa and Asia.
Design, Setting, and Participants
The Child Health and Mortality Prevention Surveillance (CHAMPS) Network conducts childhood mortality surveillance in sub-Saharan Africa and South Asia using innovative post-mortem minimally invasive tissue sampling (MITS). In this cross-sectional study, MITS was conducted in deceased children aged 1 to 59 months at 7 sites in sub-Saharan Africa and South Asia from December 3, 2016, to December 3, 2020. Data analysis was conducted between October and November 2021.
Main Outcomes and Measures
The expert panel attributed underlying, intermediate, and immediate conditions in the chain of events leading to death, based on histopathologic analysis, microbiological diagnostics, clinical data, and verbal autopsies.
Results
In this study, MITS was performed in 632 deceased children (mean [SD] age at death, 1.3 [0.3] years; 342 [54.1%] male). The 6 most common underlying causes of death were malnutrition (104 [16.5%]), HIV (75 [11.9%]), malaria (71 [11.2%]), congenital birth defects (64 [10.1%]), lower respiratory tract infections (LRTIs; 53 [8.4%]), and diarrhoeal diseases (46 [7.2%]). When considering immediate causes only, sepsis (191 [36.7%]) and LRTI (129 [24.8%]) were the 2 dominant causes. An infection was present in the causal chain in 549 of 632 deaths (86.9%); pathogens most frequently contributing to infectious deaths included Klebsiella pneumoniae (155 of 549 infectious deaths [28.2%]; 127 [81.9%] considered nosocomial), Plasmodium falciparum (122 of 549 [22.2%]), and Streptococcus pneumoniae (109 of 549 [19.9%]). Other organisms, such as cytomegalovirus (57 [10.4%]) and Acinetobacter baumannii (39 [7.1%]; 35 of 39 [89.7%] considered nosocomial), also played important roles. For the top underlying causes of death, the median number of conditions in the chain of events leading to death was 3 for malnutrition, 3 for HIV, 1 for malaria, 3 for congenital birth defects, and 1 for LRTI. Expert panels considered 494 of 632 deaths (78.2%) preventable and 26 of 632 deaths (4.1%) preventable under certain conditions.
Conclusions and Relevance
In this cross-sectional study investigating causes of child mortality in the CHAMPS Network, results indicate that, in these high-mortality settings, infectious diseases continue to cause most deaths in infants and children, often in conjunction with malnutrition. These results also highlight opportunities for action to prevent deaths and reveal common interaction of various causes in the path toward death.
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