Orientia tsutsugamushi genotypes associated with severe scrub typhus in South India

Orientia tsutsugamushi is an obligate intracellular bacterium with a complex genome, causing mite-borne scrub typhus in many parts of Asia.

We determined O. tsutsugamushi genotypes in chigger mites, small mammal hosts and human fever cases to explore genotype-specific virulence. We enrolled scrub typhus patients from two hospitals in Tamil Nadu, India.

Chigger mites were collected from small mammals trapped in 25 rural villages located within the catchment areas of the hospitals. Samples underwent screening for Orientia with real-time PCR followed by nested PCR of the partial tsa56 gene and Sanger sequencing.

Phylogenetic trees were used to group sequences into clades, labelled according to the nearest reference genotypes. We determined 138 tsa56 sequences from 1165 blood samples from human fever cases, 63 sequences from 762 chigger pools, and 58 sequences from 874 small mammals.

Sequences were grouped into nine genotypes. The two most common genotypes in chiggers and small mammals were never found in human scrub typhus cases, while genotypes common in humans were rare in chiggers.

There was a positive relationship between the human-to-chigger genotype prevalence ratio and the genotype-specific proportions of human infections that were severe (r= 0.87, p= 0.011). Two genotypes, labelled Kato-Vellore and TA763-Vellore, caused 72% of infections involving shock and all five observed deaths.

The genotype-specific risk of shock was closely associated with the prevalence of eschar skin lesions (r= 0.84, p= 0.017).

O. tsutsugamushi genotypes differed strongly between chiggers and human fever patients and showed marked variation in clinical severity.