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

Angel Miraclin Thirugnanakumar; Prabu Rajkumar; Karthik Gunasekaran; Pavithra Mannam; Manickam Ponnaiah; Girish Kumar Chethrapilly Purushothaman; Aravind Velmurugan; Ayyan Raj Neeravi; Jobin John Jacob; Solomon D. Cruz; Bhagteshwar Singh; Prabhakar Appaswamy Thirumal; Anitha Jasper; Malu Mohan; Devika Shanmugasundaram; Ananth Abraham; Senthil Thangarajan; Tony Panicker; Bijesh Nair; Aravintharaj Selvakumar; Ranjith K. Moorthy; Baylis Vivek Joseph; Krishna Prabhu; Devarajulu Reddy Sirasanambati; Shalini Nair; Murali Umapathy; Kishore Pitchamuthu; Balusamy Murugesan; Sowmya Sathyendra; Samuel George Hansdak; Hema Paul; Rajesh Isaiah; Kundavaram Paul P Abhilash; Aditya V. Nair; Vivek Mathew; Ajith Sivadasan; Maya Mary Thomas; Sanjith Aaron; John Antony Jude Prakash; Geeta Chacko; Priscilla Rupali; Tom Solomon; Somasundaram Anavarathan; Selvavinayagam Thirumalaichiry Sivaprakasam; Balaji Veeraraghavan; Manoj Murhekar

doi:10.1016/j.lansea.2025.100602

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

Angel Miraclin Thirugnanakumar, Prabu Rajkumar, Karthik Gunasekaran, Pavithra Mannam, Manickam Ponnaiah, Girish Kumar Chethrapilly Purushothaman, Aravind Velmurugan, Ayyan Raj Neeravi, Jobin John Jacob, Solomon D. Cruz, Bhagteshwar Singh, Prabhakar Appaswamy Thirumal, Anitha Jasper, Malu Mohan, Devika Shanmugasundaram, Ananth Abraham, Senthil Thangarajan, Tony Panicker, Bijesh Nair, Aravintharaj SelvakumarRanjith K. Moorthy, Baylis Vivek Joseph, Krishna Prabhu, Devarajulu Reddy Sirasanambati, Shalini Nair, Murali Umapathy, Kishore Pitchamuthu, Balusamy Murugesan, Sowmya Sathyendra, Samuel George Hansdak, Hema Paul, Rajesh Isaiah, Kundavaram Paul P Abhilash, Aditya V. Nair, Vivek Mathew, Ajith Sivadasan, Maya Mary Thomas, Sanjith Aaron, John Antony Jude Prakash, Geeta Chacko, Priscilla Rupali, Tom Solomon, Somasundaram Anavarathan, Selvavinayagam Thirumalaichiry Sivaprakasam, Balaji Veeraraghavan, Manoj Murhekar

Clinical Sciences

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

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 bimABm 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 bimABm 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 bimABmallele.

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 bimABmallele may have contributed to the increased neurological manifestations of melioidosis.

Original language	English
Article number	100602
Journal	The Lancet Regional Health - Southeast Asia
Volume	37
DOIs	https://doi.org/10.1016/j.lansea.2025.100602
Publication status	Published - 21 May 2025

Keywords

Burkholderia mallei–like bimA gene
Burkholderia pseudomallei
Dental procedures
Neuro virulence
Neuromelioidosis
Outbreak
South India

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.lansea.2025.100602

PIIS2772368225000733 (1)Final published version, 1.87 MBLicence: CC BY-NC-ND

Cite this

Miraclin Thirugnanakumar, A., Rajkumar, P., Gunasekaran, K., Mannam, P., Ponnaiah, M., Chethrapilly Purushothaman, G. K., Velmurugan, A., Raj Neeravi, A., Jacob, J. J., Cruz, S. D., Singh, B., Appaswamy Thirumal, P., Jasper, A., Mohan, M., Shanmugasundaram, D., Abraham, A., Thangarajan, S., Panicker, T., Nair, B., ... Murhekar, M. (2025). Neuromelioidosis outbreak in Tamil Nadu, India: an investigation of transmission with genomic insights. The Lancet Regional Health - Southeast Asia, 37, Article 100602. https://doi.org/10.1016/j.lansea.2025.100602

@article{5aa3dbd0597942d3a56d9990ab08dcce,

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

abstract = "BackgroundIn 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.MethodsWe 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 bimABm gene, and a phylogenetic tree was constructed to study sequence similarity to the global isolates.FindingsWe 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 bimABm 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 bimABmallele.InterpretationWe 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 bimABmallele may have contributed to the increased neurological manifestations of melioidosis.",

keywords = "Burkholderia mallei–like bimA gene, Burkholderia pseudomallei, Dental procedures, Neuro virulence, Neuromelioidosis, Outbreak, South India",

author = "\{Miraclin Thirugnanakumar\}, Angel and Prabu Rajkumar and Karthik Gunasekaran and Pavithra Mannam and Manickam Ponnaiah and \{Chethrapilly Purushothaman\}, \{Girish Kumar\} and Aravind Velmurugan and \{Raj Neeravi\}, Ayyan and Jacob, \{Jobin John\} and Cruz, \{Solomon D.\} and Bhagteshwar Singh and \{Appaswamy Thirumal\}, Prabhakar and Anitha Jasper and Malu Mohan and Devika Shanmugasundaram and Ananth Abraham and Senthil Thangarajan and Tony Panicker and Bijesh Nair and Aravintharaj Selvakumar and Moorthy, \{Ranjith K.\} and Joseph, \{Baylis Vivek\} and Krishna Prabhu and \{Reddy Sirasanambati\}, Devarajulu and Shalini Nair and Murali Umapathy and Kishore Pitchamuthu and Balusamy Murugesan and Sowmya Sathyendra and Hansdak, \{Samuel George\} and Hema Paul and Rajesh Isaiah and \{Paul P Abhilash\}, Kundavaram and Nair, \{Aditya V.\} and Vivek Mathew and Ajith Sivadasan and Thomas, \{Maya Mary\} and Sanjith Aaron and \{Jude Prakash\}, \{John Antony\} and Geeta Chacko and Priscilla Rupali and Tom Solomon and Somasundaram Anavarathan and \{Thirumalaichiry Sivaprakasam\}, Selvavinayagam and Balaji Veeraraghavan and Manoj Murhekar",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s)",

year = "2025",

month = may,

day = "21",

doi = "10.1016/j.lansea.2025.100602",

language = "English",

volume = "37",

journal = "The Lancet Regional Health - Southeast Asia",

issn = "2772-3682",

publisher = "Elsevier Ltd",

}

Miraclin Thirugnanakumar, A, Rajkumar, P, Gunasekaran, K, Mannam, P, Ponnaiah, M, Chethrapilly Purushothaman, GK, Velmurugan, A, Raj Neeravi, A, Jacob, JJ, Cruz, SD, Singh, B, Appaswamy Thirumal, P, Jasper, A, Mohan, M, Shanmugasundaram, D, Abraham, A, Thangarajan, S, Panicker, T, Nair, B, Selvakumar, A, Moorthy, RK, Joseph, BV, Prabhu, K, Reddy Sirasanambati, D, Nair, S, Umapathy, M, Pitchamuthu, K, Murugesan, B, Sathyendra, S, Hansdak, SG, Paul, H, Isaiah, R, Paul P Abhilash, K, Nair, AV, Mathew, V, Sivadasan, A, Thomas, MM, Aaron, S, Jude Prakash, JA, Chacko, G, Rupali, P, Solomon, T, Anavarathan, S, Thirumalaichiry Sivaprakasam, S, Veeraraghavan, B & Murhekar, M 2025, 'Neuromelioidosis outbreak in Tamil Nadu, India: an investigation of transmission with genomic insights', The Lancet Regional Health - Southeast Asia, vol. 37, 100602. https://doi.org/10.1016/j.lansea.2025.100602

TY - JOUR

T1 - Neuromelioidosis outbreak in Tamil Nadu, India

T2 - an investigation of transmission with genomic insights

AU - Miraclin Thirugnanakumar, Angel

AU - Rajkumar, Prabu

AU - Gunasekaran, Karthik

AU - Mannam, Pavithra

AU - Ponnaiah, Manickam

AU - Chethrapilly Purushothaman, Girish Kumar

AU - Velmurugan, Aravind

AU - Raj Neeravi, Ayyan

AU - Jacob, Jobin John

AU - Cruz, Solomon D.

AU - Singh, Bhagteshwar

AU - Appaswamy Thirumal, Prabhakar

AU - Jasper, Anitha

AU - Mohan, Malu

AU - Shanmugasundaram, Devika

AU - Abraham, Ananth

AU - Thangarajan, Senthil

AU - Panicker, Tony

AU - Nair, Bijesh

AU - Selvakumar, Aravintharaj

AU - Moorthy, Ranjith K.

AU - Joseph, Baylis Vivek

AU - Prabhu, Krishna

AU - Reddy Sirasanambati, Devarajulu

AU - Nair, Shalini

AU - Umapathy, Murali

AU - Pitchamuthu, Kishore

AU - Murugesan, Balusamy

AU - Sathyendra, Sowmya

AU - Hansdak, Samuel George

AU - Paul, Hema

AU - Isaiah, Rajesh

AU - Paul P Abhilash, Kundavaram

AU - Nair, Aditya V.

AU - Mathew, Vivek

AU - Sivadasan, Ajith

AU - Thomas, Maya Mary

AU - Aaron, Sanjith

AU - Jude Prakash, John Antony

AU - Chacko, Geeta

AU - Rupali, Priscilla

AU - Solomon, Tom

AU - Anavarathan, Somasundaram

AU - Thirumalaichiry Sivaprakasam, Selvavinayagam

AU - Veeraraghavan, Balaji

AU - Murhekar, Manoj

PY - 2025/5/21

Y1 - 2025/5/21

N2 - BackgroundIn 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.MethodsWe 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 bimABm gene, and a phylogenetic tree was constructed to study sequence similarity to the global isolates.FindingsWe 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 bimABm 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 bimABmallele.InterpretationWe 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 bimABmallele may have contributed to the increased neurological manifestations of melioidosis.

AB - BackgroundIn 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.MethodsWe 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 bimABm gene, and a phylogenetic tree was constructed to study sequence similarity to the global isolates.FindingsWe 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 bimABm 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 bimABmallele.InterpretationWe 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 bimABmallele may have contributed to the increased neurological manifestations of melioidosis.

KW - Burkholderia mallei–like bimA gene

KW - Burkholderia pseudomallei

KW - Dental procedures

KW - Neuro virulence

KW - Neuromelioidosis

KW - Outbreak

KW - South India

U2 - 10.1016/j.lansea.2025.100602

DO - 10.1016/j.lansea.2025.100602

M3 - Article

AN - SCOPUS:105005520675

SN - 2772-3682

VL - 37

JO - The Lancet Regional Health - Southeast Asia

JF - The Lancet Regional Health - Southeast Asia

M1 - 100602

ER -

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

Abstract

Keywords

UN SDGs

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