Implications of environmental and pathogen-specific determinants on clinical presentations and disease outcome in melioidosis patients

Background Melioidosis is gaining recognition as an emerging infectious disease with diverse clinical manifestations and high-case fatality rates worldwide. However, the molecular epidemiology of the disease outside the endemic regions such as northeast part of Thailand and northern Australia remains unclear. Methodology/Principal findings Clinical data and B. pseudomallei isolates obtained from 199 culture-confirmed cases of melioidosis diagnosed during 2006-2016 in South India were used to elucidate the host and pathogen specific variable virulence determinants associated with clinical presentations and disease outcome. Further, we determined the temporal variations and the influence of ecological factors on B.pseudomallei Lipopolysaccharide (LPS) genotypes causing infections. Severe forms of the disease were observed amongst 169 (85%) patients. Renal dysfunction and infection due to B.pseudomallei harboring BimA(Bm) variant had significant associations with severe forms of the disease. Diabetes mellitus, septicemic melioidosis and infection due to LPSB genotype were independent risk factors for mortality. LPSB (74%) and LPSA (20.6%) were the prevalent genotypes causing infections. Both genotypes demonstrated temporal variations and had significant correlations with rainfall and humidity. Conclusion/Significance Our study findings suggest that the pathogen specific virulence traits under the influence of ecological factors are the key drivers for geographical variations in the molecular epidemiology of melioidosis. Author summary Amidst the ambiguity of its true incidence, melioidosis is gaining importance as an emerging infection in the Indian subcontinent. Variable virulence genes contributing to varied clinical presentation and the association of LPS genotypes provides key insights regarding the disease dynamics, host and pathogen specific determinants for disease presentations and outcomes among melioidosis patients in India. The study shows the divergence of Indian B.pseudomallei strains in context to LPS genotypes compared to isolates reported worldwide. The association of LPS B with mortality foreshadows the need for understanding the cascade of immune response triggered in the presence of different LPS genotypes.