Avian Flu Diary: PLoS NTDS: Prioritizing Surveillance of Nipah Virus in India

Credit: Current Opinion in Virology 2019,34:79–89

#14,155

While long known to carry rabies, over the past 25 years bats have gained new respect for hosting - and occasionally transmitting - dozens of viruses capable of infecting humans. EcoHealth Alliance published a letter in Nature (Host and viral traits predict zoonotic spillover from mammals) in 2017 providing the first comprehensive analysis of viruses known to infect mammals.

From their website summary:

The study shows that bats carry a significantly higher proportion of viruses able to infect people than any other group of mammals; and it identifies the species and geographic regions on the planet with the highest number of yet-to-be discovered, or ‘missing’, viruses likely to infect people. This work provides a new way to predict where and how we should work to identify and pre-empt the next potential viral pandemic before it emerges.

Indeed, there is evidence that Many Human Viruses May Have Jumped from Bats, including mumps and measles, and that zoonotic viruses such as Ebola, Marburg, SARS, MERS-CoV, and Nipah all originated in bats.

Aside from rabies - which kills nearly 60,000 each year around the world - the two bat diseases of greatest concern are MERS-CoV and Nipah, as both have shown limited human-to-human transmission.

The Nipah virus - normally carried by fruit bats common to S.E. Asia - was only first identified 20 years ago after an outbreak in Malaysia, which spread from bat to pigs - and then from pigs to humans - eventually infecting at least 265 people, killing 105 (see Lessons from the Nipah virus outbreak in Malaysia).

The WHO Nipah Summary reads:

Key facts

Nipah virus infection in humans causes a range of clinical presentations, from asymptomatic infection (subclinical) to acute respiratory infection and fatal encephalitis.

The case fatality rate is estimated at 40% to 75%. This rate can vary by outbreak depending on local capabilities for epidemiological surveillance and clinical management.

Nipah virus can be transmitted to humans from animals (such as bats or pigs), or contaminated foods and can also be transmitted directly from human-to-human.

Fruit bats of the Pteropodidae family are the natural host of Nipah virus.

There is no treatment or vaccine available for either people or animals. The primary treatment for humans is supportive care.

The 2018 annual review of the WHO R&D Blueprint list of priority diseases indicates that there is an urgent need for accelerated research and development for the Nipah virus.

While most of the Nipah action has been centered in Bangladesh for the past 20 years, last summer, in Nipah Transmission In Kerala Outbreak, we looked at the apparently robust household and nosocomial transmission of the Nipah virus in Southern India.

Thiat outbreak was fortunately stopped at 19 cases, and declared over on July 1st, 2018, but a fresh case was reported earlier this month in the same region (see India: MOH Confirms Nipah Case In Kerala) sparking new concerns.

While old world fruit bats (Pteropodidae) have been pegged as the natural host for Nipah (and for its less well known Australian cousin Hendra), that family encompasses scores of species, and other types of bats may also be carriers.

We also know that in addition to bats and humans - other mammals have been infected in the wild (horses, pigs, and dogs) - and many others have been experimentally infected in the lab (including guinea pigs, hamsters, ferrets, squirrel monkeys, and African green monkeys).

For an excellent, and fairly recent review of Nipah and Hendra, I can heartily recommend the JCM mini-review Nipah Virus Infection by Brenda S. P. Ang, Tchoyoson C. C. Lim, Linfa Wang.

Today, however, we have a study - published this week in PLoS Neglected Tropical Diseases - that uses machine learning to try to narrow down the field of bat species with the potential to host Nipah virus in India.

You'll find a some excerpts from a press release from the Cary Institute of Ecosystem Studies, followed by excerpts from and a link to the full open-access study.

Model predicts bat species with the potential to spread deadly Nipah virus in India

Findings can help guide surveillance and prevent deadly outbreaks

Cary Institute of Ecosystem Studies

(EXCERPT)

India is home to an estimated 113 bat species. Just 31 of these species have been sampled for Nipah virus, with 11 found to have antibodies that signal host potential. Plowright notes, “Given the role bats play in transmitting viruses infectious to people, investment in understanding these animals has been low. The last comprehensive and systematic taxonomic study on the bats in India was conducted more than a century ago.”

Machine leaning, a form of artificial intelligence, was used to flag bat species with the potential to harbor Nipah. Han explains, “By looking at the traits of bat species known to carry Nipah globally, our model was able to make predictions about additional bat species residing in India with the potential to carry the virus and transmit it to people. These bats are currently not on the public health radar and are worthy of additional study.”

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Prioritizing surveillance of Nipah virus in India

Raina K. Plowright, Daniel J. Becker, Daniel E. Crowley, Alex D. Washburne, Tao Huang, P. O. Nameer, Emily S. Gurley, Barbara A. Han

Published: June 27, 2019
https://doi.org/10.1371/journal.pntd.0007393

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.

(SNIP)

In addition to sampling bat reservoir hosts, sampling plans should consider that henipaviruses could be maintained in domestic recipient hosts. These hosts, with closer and more frequent contact with humans, can become bridge hosts for human infections [36].

For example, Nipah virus was repeatedly introduced into intensive commercial pig populations in Malaysia. These repeated introductions of Nipah virus into pig farms allowed accumulation of herd immunity and the conditions for long term persistence and regional spread that facilitated transmission to humans [10].

To narrow potential spillover pathways to humans in India, studies should consider susceptible domestic animal species with husbandry that facilitates virus persistence (e.g., intensive commercial farming systems with high turnover of animals).

Projecting the risk of Nipah virus outbreaks in humans requires identification of the reservoir hosts and the dynamics of Nipah virus within those hosts. Our predictions inform initial sampling that can be followed by a sequence of studies that investigate the bat species highlighted here. The machine learning approaches presented here can be the first step in a research pipeline to eventually understand the mechanisms underpinning epidemiologically important cross-species contacts.

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The past couple of decades have been an excellent time to be a Chiropterist, as the number of bat borne disease threats continue to mount. A few (non-Nipah) examples include: