(provided by the applicant): Advances in laboratory diagnostics have greatly enhanced understanding of the infectious etiologies of Acute Febrile Illness (AFI) such as fever of more than a week's duration, including that of Kyasanur Forest Disease (KFD), Leptospirosis, Rickettsial disease such as Scrub Typhus, Dengue and Lyme disease in the Western Ghat region of India. This study aims to characterize the infectious causes of Acute Febrile Illness (AFI) among patients in India, in Sub-District Hospitals in Western Ghat region of India covering Karnataka, Kerala and Tamil Nadu. The study will focus on bacterial, rickettsial and viral causes of AFI. Based on historical patient volumes, it is estimated that approximately 400 patients will be enrolled (i.e., fit the study case definition) over the course of one year between the study sites in the first phase or first year of study. This study plans to roll out in the core area of Shimoga District of Karnataka in the first year to optimize on resources and roll it out to Kerala in secon y ear and Tamil Nadu in the third year. The additions from Kerala and Tamil Nadu would be 200 each. So at the end of 3rd year the intake in the study shall be 800. Patients and/or parents/guardians will be asked to participate at the time of initial presen tation, after determination by the treating clinician that a Blood profile including Complete Blood Count and Blood Culture as well as for those with neurological syndrome lumbar puncture is clinically indicated for patient management. Hospital laboratories routinely perform Gram stain, glucose/protein levels, cell count, and bacterial culture (where media/reagents are available) on cerebrospinal fluid (CSF) obtained via lumbar puncture from patients with AFI. This study would look for pathogens by using ELISA based serological tests and subject the specimen to a battery of other tests to lead to pathogen detection. In our study, clinical samples will be tested for a variety of etiologies associated with AFI such as, Bacterial pathogens (Leptospira, Salmonella, Brucella, Lyme borrelia, S. pneumoniae, H.influenzae, N. meningitidis, Shigella, Campylobacter etc. ), Rickettsial group of organisms (Scrub typhus, Spotted fever group, Ehrlichia, Anaplasma etc.) and Viruses ( KFD, Dengue, Japanese Encephalitis, West Nile Virus, Chikungunya virus, Tick borne Encephalitis virus, Crimean Congo Hemorrhagic Fever virus, Influenza viruses, Respiratory Syncytial Virus, Adenovirus, Coronaviruses, Enteroviruses, Diarrhoeagenic viruses etc.) Polymerase chain reaction (PCR) and serologic analyses of patient blood, CSF, Throat swab and Stool samples will be used to identify additional pathogens known to cause Acute febrile illness. Clinical samples also will be tested for unknown pathogens using PCR- sequence based pathogen discovery techniques.
( 2-3 statements of public health relevance) The Western Ghat Region is home to millions of people at risk for emerging infectious diseases, including acute febrile illnesses such as Kyasanur Forest Disease, dengue, Leptospirosis and rickettsial scrub typhus. Due to their livelihood in agriculture or animal husbandry, the local inhabitants are at higher risk of being exposed to the emerging infectious diseases This project can provide a positive health impact through efficient laboratory testing to diagnose the emerging infectious disease. Through earlier detection, more timely prevention and treatment measures can be offered, ultimately leading to lower morbidity and mortality. Through the data collected and analyzed through this research project, the public health community will have a better understanding of the burden of disease in the Western Ghat Region of Karnataka and Kerala as well as strengthen the public health system to detect and respond to emerging infectious disease threats in a timely manner. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page