Emergence of a novel zoonotic brugian filarial infection during post-validation surveillance for lymphatic filariasis in Sri Lanka.

Abstract

Lymphatic filariasis (LF) affects approximately 120 million people globally and is caused by <i>Wuchereria bancrofti</i>, <i>Brugia malayi</i> and <i>Brugia timori</i>. Sri Lanka was historically endemic for both bancroftian and brugian filariasis, with <i>B. malayi</i> presumed eliminated by the late 1960s. The country achieved validation of LF elimination as a public health problem in 2016. However, sporadic <i>Brugia</i> infections have been detected in microfilaria surveys from the mid-2000s onwards; the sub-periodic periodicity of which is suggestive of a zoonotic origin and warrants further research. Night blood survey (NBS) surveillance was conducted by the Anti-Filariasis Campaign, Ministry of Health, Sri Lanka, from 2019 to 2023. <i>Brugia</i>-positive human samples and archived canine samples were analysed using a next-generation sequencing metabarcoding platform targeting mitochondrial and nuclear loci. Bayesian and neighbour-joining phylogenetic analyses and minimum-spanning network approaches were used to characterise lineage relationships. Among 1,855,165 individuals screened, 52 were identified with <i>Brugia</i>-like microfilariae. Metabarcoding generated 1.2 million high-quality reads with both mitochondrial <i>cox1</i> and ribosomal DNA markers confirming a single <i>Brugia</i> lineage circulating in humans, mainly in children. Sequences of the <i>c</i> <i>ox1</i> gene showed 99.4-100 percent nucleotide identity to the <i>Brugia</i> Sri Lanka (SL) genotype previously detected in dogs in Sri Lanka and Tamil Nadu (India). rDNA sequences showed low similarity to <i>B. malayi</i> or <i>Brugia pahangi</i>, indicating that the parasite represents a distinct <i>Brugia</i> taxon lacking a reference rDNA sequence. The findings provide evidence that human brugian filariasis in Sri Lanka is caused by a previously unrecognised zoonotic <i>Brugia</i> species maintained in dogs. This has important clinical and public health implications given that human infections have occurred in children despite LF being declared eliminated as a public health problem. Crucially, the incorrect classification of circulating filarioid species may lead to inappropriate clinical and programmatic responses. For example, the newly identified canine reservoir of this <i>Brugia</i> genotype means that human-only mass drug administration might not be sufficient to interrupt this species' transmission. These results underscore the need for integrated One Health surveillance to prevent re-establishment of LF and safeguard regional elimination goals. No specific funding was received for the present study. This study was supported by a consulting funding (PRJ_002971).