Profile of lung pathology at autopsy in children under the age of five years dying from Severe Acute Respiratory Infections (SARI) at Kenyatta National Hospital

Abstract

Background: Respiratory diseases alone cause an estimated 20% of deaths in children under the age of five attributed to mainly by severe acute respiratory infections, a cause of death that is treatable. Therefore these deaths are, in large part, preventable. The challenge is to know the cause of death, and the co-factors contributing to the death, in the preventable cases. The gold standard of obtaining accurate information on the cause of death is a post-mortem examination. Objective: To determine the leading causes of fatal respiratory disease and describe the pathological features in the lungs at autopsy among Kenyan children less than five years who died in KNH. Design: Hospital based prospective descriptive study. Setting: Kenyatta National Hospital Paediatric wards and Farewell home, University of Nairobi histopathology laboratory and KEMRI-CDC laboratories. Study population: Decedent children aged 1 to 59 months meeting the SARI case definition of acute respiratory infection and required hospitalization at the time of hospital admission. Methodology: After death, informed written consent was obtained from next of kin and clinical autopsy conducted using a standardized procedure to collect tissue and fluid samples. Fresh lung tissue was obtained using sterile techniques by both minimally invasive autopsy procedure and open lung biopsy during autopsy. The lung biopsies obtained were prepared for histopathology evaluation and molecular diagnostic tests using PCR technology. Results: A total of 33 (51.6%) males and 31 (48.4%) females underwent autopsy. The median age (IQR) was 9.5 months (4 – 13.5) with 91.6% of the children aged less than 24 months. 43 (67.2%) children were malnourished with 28 (43.75%) of them being severely malnourished. 12 (18.75%) children had congenital anomalies and trauma was evident in 7 (10.9%) children five of them having head injuries. At histopathology, acute pyogenic pneumonia was the most observed lung disease pattern at 39.3% followed by interstitial pneumonia at 29.9% mainly due to viral infections and Pneumocystis jirovecii pneumonia. Diffuse alveolar damage (DAD) was seen in 21.5% as a result of acute lung injury and aspiration pneumonia identified in four cases (0.4%), whereas chronic granulomatous inflammation due to Mycobacterium tuberculosis was observed in two cases (0.2%) Klebsiella pneumonia, Streptococcus pneumoniae and Escherichia coli were the most common bacterial isolates; others included Staphylococcus aureus, Haemophilus influenza and Enterobacteriaceae. The commonest viral pathogens identified were RSV and CMV at 14.1% and 12.5% respectively. Fungal infections were evident in 20.3% of the cases with PCP seen in 7 (10.9%) children who had features of immunosuppression. Other fungal agents identified included candida species affecting 4 (6.25%) children and aspergillus species in 2 (3.1%) children. 40 cases were reviewed to compare minimally invasive core needle lung biopsies versus open lung biopsies at autopsy there was concordance on major diagnostic finding at 65% (26 cases), however 14 cases (35%) were discordant. (p = 0.017) Conclusion: Acute pyogenic pneumonia was the commonest cause of SARI deaths in children, significantly due to Klebsiella pneumoniae, Streptococcus pneumoniae and Escherichia coli infections. There was higher than expected opportunistic infections due to PCP and CMV as important causes of SARI deaths. Malnutrition and congenital malformations mainly CHD are major risk factors associated with SARI deaths with a significant number of children having life threatening physical trauma. There was positive concordance of major histopathologic findings with minimally invasive tissue samples (MITS) and full autopsy samples.