Potential of Minimally Invasive Tissue Sampling for Attributing Specific Causes of Childhood Deaths in South Africa: A Pilot, Epidemiological Study

Abstract

Background Current estimates for causes of childhood deaths are mainly premised on modeling of vital registration and limited verbal autopsy data and generally only characterize the underlying cause of death (CoD). We investigated the potential of minimally invasive tissue sampling (MITS) for ascertaining the underlying and immediate CoD in children 1 month to 14 years of age. Methods MITS included postmortem tissue biopsies of brain, liver, and lung for histopathology examination; microbial culture of blood, cerebrospinal fluid (CSF), liver, and lung samples; and molecular microbial testing on blood, CSF, lung, and rectal swabs. Each case was individually adjudicated for underlying, antecedent, and immediate CoD by an international multidisciplinary team of medical experts and coded using the International Classification of Diseases, Tenth Revision (ICD-10). Results An underlying CoD was determined for 99% of 127 cases, leading causes being congenital malformations (18.9%), complications of prematurity (14.2%), human immunodeficiency virus/AIDS (12.6%), diarrheal disease (8.7%), acute respiratory infections (7.9%), injuries (7.9%), and malignancies (7.1%). The main immediate CoD was pneumonia, sepsis, and diarrhea in 33.9%, 19.7%, and 10.2% of cases, respectively. Infection-related deaths were either an underlying or immediate CoD in 78.0% of cases. Community-acquired pneumonia deaths (n = 32) were attributed to respiratory syncytial virus (21.9%), Pneumocystis jirovecii (18.8%), cytomegalovirus (15.6%), Klebsiella pneumoniae (15.6%), and Streptococcus pneumoniae (12.5%). Seventy-one percent of 24 sepsis deaths were hospital-acquired, mainly due to Acinetobacter baumannii (47.1%) and K. pneumoniae (35.3%). Sixty-two percent of cases were malnourished. Conclusions MITS, coupled with antemortem clinical information, provides detailed insight into causes of childhood deaths that could be informative for prioritization of strategies aimed at reducing under-5 mortality.

The evolution of minimally invasive tissue sampling in postmortem examination: a narrative review

“…The year 2019 saw a sharp rise in the quantity of MITS publications, including a study of children dying of respiratory illness in Kenya and a study of stillbirths and neonates in Ethiopia [34,35]. A large proportion of the 2019 increase in MITS publications is attributable to the October 2019 release of 13 articles describing MITS from the experience of the Child Health and Mortality Prevention Surveillance (CHAMPS) Network [2,15,33,36,37,[54][55][56][57][58][59][60][61][62]. With promising results from the relatively few validation studies completed, the CHAMPS Network rapidly endorsed the use of MITS and is poised to both build on earlier validation studies and also improve on a number of aspects of MITS such as reducing the time and expense associated with performing MITS.…”

“…Based on the sample sizes and ages identified in the 28 primary studies using MITS in postmortem examination there have been roughly 40% more MITS carried out in LMICs than in HICs. There have been nearly twice as many MITS in adults as in stillbirths, neonates, and children combined; however, in LMICs, the majority of MITS conducted have been in children, neonates, and stillbirths ( Figure 3) [10,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][35][36][37][38][39][40][41][42]64].…”

National Neonatal Sepsis Task Force launch: Supporting infection prevention and surveillance, outbreak investigation and antimicrobial stewardship in neonatal units in South Africa

“…Many infection-related preterm deaths are possibly 'mislabelled' as prematurity related, owing to a lack of accurate diagnostics. [4,7] Death notification forms, the basis of burden of disease and mortality studies, often indicate only the underlying cause rather than the immediate cause of death, resulting in underestimation of infectionrelated deaths in preterm infants. Current SA neonatal mortality data [1] do not account for deaths in extremely-low-birthweight babies (<1 000 g) and babies who remain hospitalised in a neonatal unit beyond 28 days of life.…”

Diagnosis and management of community-acquired pneumonia in children: South African Thoracic Society guidelines

“…[44,66,67] In the Child Health and Mortality Prevention Surveillance (CHAMPS) Program, a study designed to establish the infectious aetiology of fatal illness in children dying in hospital, K. pneumoniae was identified in 16% of community-acquired pneumonia deaths, and the most common organism isolated in death from hospital-acquired infection in Soweto. [68] Non-fermenting Gramnegatives, such as Moraxella catarrhalis or Pseudomonas aeruginosa are increasingly recognised as contributors to bacterial pneumonia in children (evidence level II).…”