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

Richard Chawana; Vicky Baillie; Alane Izu; Fatima Solomon; Quique Bassat; Dianna M Blau; Robert F Breiman; Martin Hale; Eric R Houpt; Sanjay G Lala; Roosecelis B Martines; Azwifarwi Mathunjwa; Susan Nzenze; Jayani Pathirana; Karen L Petersen; Pratima L Raghunathan; Jana M Ritter; Jeannette Wadula; Sherif R Zaki; Shabir A Madhi

doi:10.1093/cid/ciz550

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

Clin Infect Dis. 2019 Oct 9;69(Suppl 4):S361-S373. doi: 10.1093/cid/ciz550.

Authors

Richard Chawana^{1

2}, Vicky Baillie^{1

2}, Alane Izu^{1

2}, Fatima Solomon^{1

2}, Quique Bassat^{3

4

5

6

7}, Dianna M Blau⁸, Robert F Breiman⁹, Martin Hale¹⁰, Eric R Houpt¹¹, Sanjay G Lala^{12

13}, Roosecelis B Martines¹⁴, Azwifarwi Mathunjwa^{1

2}, Susan Nzenze^{1

2}, Jayani Pathirana^{1

2}, Karen L Petersen¹², Pratima L Raghunathan⁸, Jana M Ritter¹⁴, Jeannette Wadula¹⁵, Sherif R Zaki¹⁴, Shabir A Madhi^{1

2}

Affiliations

¹ Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa.
² Department of Science and Technology/National Research Foundation, Vaccine Preventable Diseases, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa.
³ ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
⁴ Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique.
⁵ Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.
⁶ Pediatric Infectious Diseases Unit, Pediatrics Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
⁷ Consorcio de Investigacion Biomedica en Red de Epidemiologia y Salud, Spain.
⁸ Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
⁹ Emory Global Health Institute, Emory University, Atlanta, Georgia, USA.
¹⁰ National Health Laboratory Service, Department of Anatomical Pathology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
¹¹ Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, USA.
¹² Department of Paediatrics, and University of the Witwatersrand, Johannesburg, South Africa.
¹³ Perinatal HIV Research Unit, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand, Johannesburg, South Africa.
¹⁴ Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
¹⁵ National Health Laboratory Service, Department of Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

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.

Keywords: South Africa; child mortality; diarrhea; minimally invasive tissue sampling; pneumonia.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Autopsy / methods
Cause of Death
Child
Child, Preschool
Diagnosis
Epidemiologic Studies
Female
Humans
Infant
Infant, Newborn
Male
Pilot Projects
Prospective Studies
South Africa
Specimen Handling / methods*