Prioritizing surveillance of Nipah virus in India

Abstract

The 2018 outbreak of Nipah virus in Kerala, India, highlights the need for global surveillance of henipaviruses in bats, which are the reservoir hosts for this and other viruses. Nipah virus, an emerging paramyxovirus in the genus Henipavirus, causes severe disease and stuttering chains of transmission in humans and is considered a potential pandemic threat. In May 2018, an outbreak of Nipah virus began in Kerala, > 1800 km from the sites of previous outbreaks in eastern India in 2001 and 2007. Twenty-three people were infected and 21 people died (16 deaths and 18 cases were laboratory confirmed). Initial surveillance focused on insectivorous bats (Megaderma spasma), whereas follow-up surveys within Kerala found evidence of Nipah virus in fruit bats (Pteropus medius). P. medius is the confirmed host in Bangladesh and is now a confirmed host in India. However, other bat species may also serve as reservoir hosts of henipaviruses. To inform surveillance of Nipah virus in bats, we reviewed and analyzed the published records of Nipah virus surveillance globally. We applied a trait-based machine learning approach to a subset of species that occur in Asia, Australia, and Oceana. In addition to seven species in Kerala that were previously identified as Nipah virus seropositive, we identified at least four bat species that, on the basis of trait similarity with known Nipah virus-seropositive species, have a relatively high likelihood of exposure to Nipah or Nipah-like viruses in India. These machine-learning approaches provide the first step in the sequence of studies required to assess the risk of Nipah virus spillover in India. Nipah virus surveillance not only within Kerala but also elsewhere in India would benefit from a research pipeline that included surveys of known and predicted reservoirs for serological evidence of past infection with Nipah virus (or cross reacting henipaviruses). Serosurveys should then be followed by longitudinal spatial and temporal studies to detect shedding and isolate virus from species with evidence of infection. Ecological studies will then be required to understand the dynamics governing prevalence and shedding in bats and the contacts that could pose a risk to public health.

Fig 1. Global map of Nipah virus sampling effort and detections.

The country-level distribution of whether bats have been sampled for Nipah virus and whether positive detections have occurred using PCR or serology (noting that serological detection likely includes cross-reactions with Nipah-like viruses). Light blue shading shows regions of India where bats have been found positive for Nipah virus (states of Haryana, Maharashtra, West Bengal); studies did not report exact sampling coordinates [40, 41]. Shapefiles were obtained from the maps and mapdata packages in R. The right panels show the number of sampling events and the percentage of positive detections by PCR or serology in each country.

Fig 2. Phylogeny of Indian bats and Nipah virus detections.

Serological detections of Nipah virus are scattered across the bat phylogeny, although sampling coverage across the phylogeny is low (see also Table 1). Note that serological assays for Nipah virus likely cross-react with Nipah-like henipaviruses.

Fig 3. Predicted probability of top 20 Indian bat species being Nipah virus positive.

Nipah virus has been detected in Pteropus medius, but other bat species have either known exposure (serological reactivity to Nipah virus) or predicted exposure based on our analysis of Nipah virus surveys. Red indicates having evidence of Nipah virus exposure or infection (by serology or PCR) and blue indicates no previous evidence of Nipah virus exposure.

Fig 4. Range of predicted bat species.

Geographic ranges of bat species that are in the 90^th percentile of similarity (based on generalized boosted regression) with other bat species that are positive for Nipah virus from Asia, Australia, and Oceana (based on PCR or serology). The terrestrial mammal range shapefile was downloaded from the IUCN website (http://www.iucnredlist.org/technical-documents/spatial-data) and the figure was created with ArcGIS.