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

Abstract

Background: 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.

Methods: We searched for probable cases presenting with fever and brainstem syndrome, supported by radiological findings suggestive of neuromelioidosis. Cases were confirmed by isolation of Burkholderia pseudomallei 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 Burkholderia mallei-like bimA _Bm gene, and a phylogenetic tree was constructed to study sequence similarity to the global isolates.

Findings: 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 bimA _Bm 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 B. mallei-like bimA _Bm allele.

Interpretation: 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 B. pseudomallei to the brainstem following inoculation via contaminated saline. Expression of B. mallei-like bimA _Bm allele may have contributed to the increased neurological manifestations of melioidosis.

Funding: None.

Keywords: Burkholderia mallei–like bimABm gene; Burkholderia pseudomallei; Dental procedures; Neuro virulence; Neuromelioidosis; Outbreak; South India.

Fig. 1

Distribution of neuromelioidosis cases by residence in Tamil Nadu, India, 2022–2023. Indian subcontinent (top-left). Southern state of Tamil Nadu (Bottom-left). Five districts in Northern Tamil Nadu showing the distribution of neuromelioidosis cases (right). Dental clinic. Residence of cases. Residence of index case.

Fig. 2

a—Distribution of neuromelioidosis cases by month of symptom onset and type of exposure in Tamil Nadu, India, June 2022–April 2023. Sporadic. Dental. Died. Index case. b—Time intervals between exposure, symptom onset and outcome of neuromelioidosis cases by type of exposure in Tamil Nadu, India, June 2022–June 2023. Date of exposure to dental procedures. Date of symptom onset. Date of outcome (died). Date of outcome (alive). Interval between exposure and symptom onset. Interval between symptom onset and outcome. B. pseudomallei isolated from a brain sample. B. pseudomallei isolated from an environmental sample in the dental clinic.

Fig. 3

(a–d): MRI T2 weighted coronal imaging showing ‘tunnel-sign’, involvement of white matter tracts causing cerebritis, (e–h): MRI showing typical progression along the corticospinal tracts, with involvement of posterior limb of internal capsule and ascent along the fibres, causing cerebritis.

Fig. 4

Phylogenetic analysis of Burkholderia pseudomallei genomes, highlighting outbreak isolates within a global context. (a) A core SNP-based maximum likelihood phylogeny of B. pseudomallei genomes (n = 227), rooted on the MSHR5619 isolate. (b) A detailed view of the Indian B. pseudomallei genome cluster, depicting virulence profiles and host factors. Isolates belonging to ST1553 are shaded in lavender. Key metadata, including location, Bayesian Analysis of Population Structure (BAPS-Level 1), source of isolate, and host disease, are represented as coloured strips. The presence of BimA_Bm is shown in a heatmap. Colour codes for variables are provided in the inset legend. Branches are marked with symbols: red for outbreak isolates, green for contextual isolates, and yellow for surveillance isolates from the study site. The scale bar indicates substitutions per site. The phylogenetic tree was visualized and annotated using iTOL (https://itol.embl.de/).