Neuromelioidosis outbreak in Tamil Nadu, India: an investigation of transmission with genomic insights.

Abstract

In May 2023, we investigated a cluster of neuromelioidosis notified from Tamil Nadu state in southern India to describe case characteristics and identify the infection source. We searched for probable cases presenting with fever and brainstem syndrome, supported by radiological findings suggestive of neuromelioidosis. Cases were confirmed by isolation of <i>Burkholderia pseudomallei</i> from tissue, blood, or cerebrospinal fluid (CSF), or by PCR. The cases were described by time (epidemic curve), place (spot map), and person (clinical characteristics). Infection sources and virulence markers were identified by genome sequencing of the clinical and environmental isolates. Whole genome sequencing data were analysed to investigate the expression of <i>Burkholderia mallei</i>-like <i>bimA</i> _<i>Bm</i> gene, and a phylogenetic tree was constructed to study sequence similarity to the global isolates. We identified 21 probable cases between July 2022 and April 2023 (median age = 33 years; 11 females; five confirmed) across four districts in Northern Tamil Nadu. Seventeen cases were from a single district and 10 reported prior dental treatment at a clinic. Cases with dental exposure had higher fatality (8/10 vs. 1/11) and shorter time to death (median 17 days vs. 1 death at day 56) than sporadic cases. The <i>bimA</i> _<i>Bm</i> gene, which is associated with neurotropism, was identified in all three clonal isolates (two from the cases and one from the environmental isolate from the in-use saline bottle). Whole genome sequencing identified the ST1553 strain as being associated with the current outbreak. Genetic analysis of 209 isolates available in the public database with metadata revealed that ST1553, the strain responsible for the outbreak, clustered with isolates from India and Australia that expressed the <i>B. mallei-like bimA</i> _<i>Bm</i> <i>allele</i>. We confirmed a large cluster of neuromelioidosis from South India, likely representing sporadic cases from environmental sources and cases linked to an iatrogenic source at a dental clinic. Rapid and high case fatality among dental cases supports the direct trans-neural spread of <i>B. pseudomallei</i> to the brainstem following inoculation via contaminated saline. Expression of <i>B. mallei-like bimA</i> _<i>Bm</i> <i>allele may have contributed to the increased neurological manifestations of melioidosis.</i> None.