Kinetics of viral RNA, immunoglobulin-M & G antibodies in Kyasanur forest disease

BACKGROUND & OBJECTIVES: Kyasanur forest disease (KFD) is an infectious disease discovered in Karnataka State of India in 1957; since then, the State has been known to be enzootic for KFD. In the last few years, its presence was observed in the adjoining five States of the Western Ghats of India. The present study was conducted to understand the kinetics of viral RNA, immunoglobulin M (IgM) and IgG antibody in KFD-infected humans for developing a diagnostic algorithm for KFD. METHODS: A prospective follow up study was performed among KFD patients in Sindhudurg district of Maharashtra State, India. A total of 1046 suspected patients were tested, and 72 KFD patients were enrolled and followed for 17 months (January 2016 to May 2017). Serum samples of KFD patients were screened for viral RNA, and IgM and IgG antibodies. RESULTS: KFD viral positivity was observed from 1(st) to 18(th) post-onset day (POD). Positivity of anti-KFD virus (KFDV) IgM antibodies was detected from 4(th) till 122(nd) POD and anti-KFDV IgG antibodies detected from 5(th) till 474(th) POD. A prediction probability was determined from statistical analysis using the generalized additive model in R-software to support the laboratory findings regarding viral kinetics. INTERPRETATION & CONCLUSIONS: This study demonstrated the presence of KFD viral RNA till 18(th) POD, IgM antibodies till 122(nd) POD and IgG till the last sample collected. Based on our study an algorithm was recommended for accurate laboratory diagnosis of KFDV infection. A sample collected between 1 and 3 POD can be tested using KFDV real-time reverse transcriptase polymerase chain reaction (RT-PCR); between 4 and 24 POD, the combination of real-time RT-PCR and anti-KFDV IgM enzyme-linked immunosorbent assay (ELISA) tests can be used; between POD 25 and 132, anti-KFDV IgM and IgG ELISA are recommended.