Research Projects

Scrub typhus (ST) is a zoonotic illness caused by the bacterium Orientia tsutsugamushi and is transmitted to humans through the larval stage, known as chiggers, of mites belonging to the Leptotrombidium genus. The genus Orientia is classified under the order Rickettsiales and the family Rickettsiaceae. The disease is endemic to the “tsutsugamushi triangle,” which spans southeastern Asia to the Pacific, but recent reports indicate its emergence in regions beyond this geographic range. The World Health Organization identifies scrub typhus as a significantly underdiagnosed and underreported illness globally, frequently necessitating hospitalization. Globally, scrub typhus threatens 1 billion people annually, with approximately 1 million cases reported. Clinical manifestations of ST range from acute undifferentiated febrile illness (AUFI) to severe conditions like multiorgan failure. Mortality rates highlight the seriousness of the disease, with untreated cases showing a fatality rate of 6.0%, while timely treatment reduces mortality to 1.4%. Severe complications, including central nervous system involvement (13.6%), multiorgan dysfunction (24.1%), and adverse outcomes during pregnancy, emphasize its public health impact. In India, scrub typhus is recognized as the most prevalent reemerging rickettsial infection. However, much of the reported data come from tertiary care centers and geographically limited studies, leaving a significant gap in understanding its prevalence, especially in rural areas. The disease’s ecology is complex, involving Leptotrombidium deliense mites and small mammal reservoirs, with circulating serotypes such as Gilliam, Karp, and TA678 identified during monsoon and post-monsoon seasons. The intricate interplay between environmental, microbial, and host factors poses challenges to effective disease control. Current treatments for scrub typhus are constrained by limited antibiotic options and the emergence of strains resistant to available antibiotics. Additionally, there are mixed reports regarding the susceptibility and resistance profiles of O. tsutsugamushi, further complicating treatment strategies. Understanding the bacterium’s mechanisms of immune evasion, biphasic metabolic adaptations between intracellular and extracellular stages, and pathogenicity is essential. However, these aspects remain poorly characterized. This study aims to address these challenges by investigating potential new antibiotics and exploring the repurposing of existing drugs to treat scrub typhus effectively. A combined approach will be employed to elucidate the molecular, cellular, and host–pathogen interactions, along with the genomic diversity of O. tsutsugamushi. Identifying novel drug targets is the key objective of this research. The findings from this study are expected to provide crucial insights into the treatment of scrub typhus, offering opportunities to develop targeted therapeutic strategies and mitigate the disease burden globally.