Using Minimally Invasive Tissue Sampling and Determination of Cause of Death to Establish Etiologies of Community Respiratory Deaths Among Zambian Infants and Children

In low-to-middle-income countries, acute lower respiratory infection (ALRI) remains the leading infectious cause of death among infants and children under 5 years old. Case-control studies based on upper respiratory sampling have informed current understandings of ALRI etiologies; in contrast, minimally invasive tissue sampling (MITS) offers a method of directly interrogating lower respiratory tract pathogens to establish etiologic distributions. This study performed in the postmortem setting used MITS and a Determination of Cause of Death (DeCoDe) panel to elucidate the causes of fatal pneumonia in the community in Lusaka, Zambia. For deceased infants and children under age 5 years whose next-of-kin provided consent, a verbal autopsy was obtained and 6 lung tissue biopsies from each case were sent for histopathology and multiplex polymerase chain reaction testing. Subsequently, a multi-disciplinary DeCoDe panel met to review each case, determine if the child died of respiratory causes, construct a causal chain of diagnoses directly leading to the death, and determine if the death was preventable (i.e., if an identifiable intervention would have averted the death). Among 106 deaths, 49 were adjudicated as respiratory deaths, with etiologic causes including Klebsiella pneumoniae (13), Streptococcus pneumoniae (5), and Pneumocystis jirovecii (4), among others. Of note, for 21 respiratory deaths, a causative pathogen could not be identified despite clinical and histopathologic evidence of ALRI. A large majority of all deaths were considered preventable (90/106 or 85%). This study demonstrates the impact of certain respiratory pathogens through direct in situ tissue sampling with supportive pathologic data and presents a useful method of studying the etiologic distribution of fatal ALRIs in settings where many deaths occur in the community.