METHODS: During autopsy of individuals that died in 2014 following an acute febrile illness, tissue specimens were collected from major organs and tested for evidence of infection with CHIKV and dengue virus (DENV) by IHC and RT-PCR. Pre- and post-mortem blood specimens collected through passive and enhanced surveillance, respectively, were tested for evidence of infection with CHIKV and DENV by RT-PCR. Data from medical records, autopsy findings, family interviews, and diagnostic test results were compiled.
RESULTS: In total, 30 laboratory-positive CHIKV-associated fatal cases were identified (0.9 per 100,000 population), of which 7 (23%) had been reported via passive surveillance. All cases were positive for CHIKV infection and negative for DENV infection by RT-PCR in blood and/or tissue specimens. Median age was 61 years (range: 6 days–85 years), and 19 (63%) were male. Median day of death post-illness onset was 6 (range: 1–21). Ten (33%) individuals died at home, and 6 (20%) had not sought medical care. Nearly all (93%) individuals had ≥1 co-morbidity, most frequently hypertension (53%), diabetes (50%), and obesity (47%). Three cases had only one recognized co-morbidity: diabetes, hypertension, or asthma. Nine case-patients had severe co-morbidities (e.g., chronic liver or kidney disease, sickle cell anemia) and/or co-infections (e.g., leptospirosis, nosocomial) that may have predisposed them to fatal outcome. Of 24 cases with available tissue specimens, 11 (46%) were positive by IHC. CHIKV antigen was detected in multiple organs, predominantly in mesenchymal tissues and cells of the mononuclear phagocytic system. Common histopathologic findings in tissue from IHC-positive cases included intraalveolar hemorrhage and edema.
CONCLUSIONS: Evaluation of autopsy tissue provides evidence on the pathologic consequences of CHIKV infection that cannot be gained by blood-based diagnostic testing. Because of the inherent difficulty in determining the contribution of CHIKV infection to fatal outcome, such cases should be reported to public health authorities as “CHIKV-associated fatal cases”. Improved surveillance and additional research are needed to better understand the burden and role of CHIKV infection in fatal cases.