{"title":"印度泰米尔纳德邦的类神经瘤病暴发：一项具有基因组见解的传播调查","authors":"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 , Manoj Murhekar","doi":"10.1016/j.lansea.2025.100602","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>We searched for probable cases presenting with fever and brainstem syndrome, supported by radiological findings suggestive of neuromelioidosis. Cases were confirmed by isolation of <em>Burkholderia pseudomallei</em> 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 <em>Burkholderia mallei</em>-like <em>bimA</em><sub><em>Bm</em></sub> gene, and a phylogenetic tree was constructed to study sequence similarity to the global isolates.</div></div><div><h3>Findings</h3><div>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 <em>bimA</em><sub><em>Bm</em></sub> 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 <em>B. mallei-like bimA</em><sub><em>Bm</em></sub> <em>allele</em>.</div></div><div><h3>Interpretation</h3><div>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 <em>B. pseudomallei</em> to the brainstem following inoculation via contaminated saline. Expression of <em>B. mallei-like bimA</em><sub><em>Bm</em></sub> <em>allele may have contributed to the increased neurological manifestations of melioidosis.</em></div></div><div><h3>Funding</h3><div>None.</div></div>","PeriodicalId":75136,"journal":{"name":"The Lancet regional health. Southeast Asia","volume":"37 ","pages":"Article 100602"},"PeriodicalIF":6.2000,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Neuromelioidosis outbreak in Tamil Nadu, India: an investigation of transmission with genomic insights\",\"authors\":\"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 , Manoj Murhekar\",\"doi\":\"10.1016/j.lansea.2025.100602\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>We searched for probable cases presenting with fever and brainstem syndrome, supported by radiological findings suggestive of neuromelioidosis. Cases were confirmed by isolation of <em>Burkholderia pseudomallei</em> 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 <em>Burkholderia mallei</em>-like <em>bimA</em><sub><em>Bm</em></sub> gene, and a phylogenetic tree was constructed to study sequence similarity to the global isolates.</div></div><div><h3>Findings</h3><div>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 <em>bimA</em><sub><em>Bm</em></sub> 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 <em>B. mallei-like bimA</em><sub><em>Bm</em></sub> <em>allele</em>.</div></div><div><h3>Interpretation</h3><div>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. 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引用次数: 0
摘要
2023年5月，我们调查了印度南部泰米尔纳德邦报告的一起类神经瘤病聚集性病例，以描述病例特征并确定感染源。方法我们寻找可能出现发热和脑干综合征的病例，并有影像学表现提示类神经瘤病。病例通过从组织、血液或脑脊液（CSF）中分离出假霍尔德氏菌或通过PCR证实。病例按时间（流行曲线）、地点（点状图）和人（临床特征）进行描述。对临床分离株和环境分离株进行基因组测序，鉴定感染源和毒力标记。利用全基因组测序数据分析马雷样伯克霍尔德菌bimABm基因的表达情况，并构建系统发育树研究其序列与全球分离株的相似性。研究结果：我们在2022年7月至2023年4月期间确定了21例可能病例(中位年龄= 33岁；11个女性;在泰米尔纳德邦北部的四个地区发现了5例确诊病例。17例来自一个地区，10例报告曾在诊所接受牙科治疗。与散发性病例相比，牙齿暴露病例死亡率更高（8/10 vs 1/11），死亡时间更短（中位17天vs 1例56天死亡）。在所有三个克隆分离株（两个来自病例，一个来自使用中的生理盐水瓶的环境分离株）中均鉴定出与嗜神经性相关的bimABm基因。全基因组测序确定ST1553菌株与当前疫情有关。对具有元数据的公共数据库中的209株分离株进行遗传分析显示，导致此次暴发的菌株ST1553与来自印度和澳大利亚的表达马利芽孢杆菌样bimABm等位基因的分离株聚集在一起。我们证实了来自南印度的一大群类神经瘤病，可能是环境源的散发病例和牙科诊所的医源性病例。在牙科病例中，快速和高病死率支持假芽孢杆菌通过污染的生理盐水接种后直接跨神经传播到脑干。马利梭菌样双abm等位基因的表达可能与类鼻疽病的神经学表现增加有关。
Neuromelioidosis outbreak in Tamil Nadu, India: an investigation of transmission with genomic insights
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.
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