Utility and Challenges of a Multi-pathogen Diagnostic Platform for Characterizing Public Health Threats of Severe Acute Respiratory Infections in Six Countries

BACKGROUND: Pneumonia causes significant morbidity and mortality worldwide. Comprehensive etiology studies of pneumonia in adults are limited; however, new diagnostics enable simultaneous detection of multiple pathogens in respiratory specimens. Characterizing the public health threat of severe acute respiratory infection (SARI) may enhance global health security. We studied potential etiologies of SARI among adults in six countries over a 12-month period using multi-pathogen diagnostics. METHODS: We enrolled SARI cases (acute onset of fever and cough, requiring hospitalization, in an adult) from Global Disease Detection sites in Bangladesh, China, Egypt, Guatemala, Kenya, and Thailand and healthy frequency-matched controls (2 controls: 5 cases) by time (onset), age group (18–49, 50–64, 65+ years), and catchment area. Demographics, clinical data, and nasopharyngeal and oropharyngeal specimens were collected from cases and controls. Specimens were tested for 16 viruses and 14 bacteria using Taqman(®) Array Card, which uses real-time reverse transcriptase polymerase chain reaction. RESULTS: We enrolled 2,388 cases and 1,135 controls from Oct 2013 through Oct 2015. Age distribution (Figure) and seasonality varied by site: enrollment peaked in summer months in Bangladesh, Thailand, and China, and in winter months in Egypt, but was stable throughout the year in Guatemala and Kenya. Case fatality rate across all study locations was 2.3% (range 0–7.0%). One or more pathogens was detected in 76% of cases and in 67% of controls; ≥2 pathogens were detected in 42% of cases and 37% of controls. Pathogens more commonly detected among cases than controls included influenza A (OR 13.3, CI 7.0–25.2; 12.8% of cases vs. 1.1% of controls), influenza B (OR: 27.0, CI 8.6–84.8; 8.1% vs. 0.3%), and respiratory syncytial virus (RSV) (OR: 9.4, CI 3.4–25.8; 4.0% vs. 0.4%). CONCLUSION: In this SARI study, frequent detection of multiple pathogens in the oro- and nasopharynx of both cases and controls made etiology attribution difficult. Influenza and RSV, however, were likely to be causes of SARI. Because upper respiratory tract specimens may not accurately reflect disease in the lung, better specimens are needed to determine pneumonia etiology, particularly for bacteria. DISCLOSURES: All authors: No reported disclosures.