The Absence of Evidence for Nipah in Fruit Bats Is Not Evidence of Absence

This is because it is difficult to find a bat that is infected.

There has been much speculation over the source of the Nipah virus that triggered an outbreak in Kozhikode, Kerala. Last week, the state animal husbandry department captured and tested insectivorous bats (Megaderma spasma) from a well in the compound belonging to a family whose members were the virus’s first victims – and found no virus in them.

News reports have pointed out that the virus’s reservoir is different: fruit bats of the species Pteropus medius (formerly Pteropus giganteus). A fresh effort is underway to capture and test fruit bats – but the delay could mean that the virus may not be found in them at all. Should this happen, it still wouldn’t mean that bats were not the source of the virus.

This is because it is difficult to find a bat that is infected.

Bats “may only be infectious for a week or two, and then they clear the virus and they’re no longer infectious,” said Jonathan Epstein, a veterinarian and epidemiologist at EcoHealth Alliance, New York, who has, for over a decade, studied Nipah outbreaks and the bats that cause them, in Malaysia, India and Bangladesh. “That’s why these outbreaks are relatively rare events, given the fact that these bats are so abundant and so common but very few of them are ever actually shedding virus at a given time.”

Epstein and others had conducted an experimental study of Pteropus bats in 2011 and found that the time window in which the bats are capable of passing on the infection to other animals or humans is quite small. In fact, the virus can’t be found in experimentally infected bats after a few weeks. The few bats in an infected population that could be shedding the virus may be doing so in low quantities and for a short duration.

“Finding that bats don’t have Nipah virus at the time of sampling certainly doesn’t mean that it didn’t come from those bats, particularly P. medius,” Epstein said. “The overwhelming abundance of evidence really shows that this bat is the reservoir for Nipah virus on the subcontinent in Bangladesh and in India.”

The National Centre for Disease Control, which is involved in investigating the Kerala outbreak, is aware of this, too.

Pulling at the bats thread

In Bangladesh, Nipah virus infections arise from consuming date palm sap contaminated by bat urine or saliva. On the other hand, the outbreak in Malaysia in 1998 was traced to pigs that ate fruits infected by bats; the pigs had then passed the infection on to humans. Domesticated animals sampled in the area of the Kerala outbreak have so far not been found to carry the virus.

It is possible that the virus may have arrived in Kerala in infected fruits, some of which the first victim might have consumed. But it’s more likely that the virus has always been silently circulating in the wild.

Pteropus bats are known to be the reservoir species for the Nipah and the closely related Hendra viruses, collectively called henipaviruses. And evidence of a henipavirus infection has been found in Pteropus bats in a wide region, from Australia to Madagascar. This, along with the fact that infected bats do not show any overt signs of illness, suggests that these bats have co-evolved with henipaviruses.

In India, fruit bats have been tested for the Nipah virus. A 2012 study by researchers from the National Institute of Virology, Pune, and the US Centres for Disease Control and Prevention had found the virus in only one of 140 bats tested in Maharashtra and West Bengal. The other 139 bats were not found to have even the antibodies necessary to fight the virus. (The paper noted the need for a systematic survey to understand the Nipah virus’s distribution.)

A 2008 paper had found that 20 of 41 bats tested in Haryana had antibodies to the Nipah virus. Apart from the difference in location, this disparity in the proportion of bats with antibodies to the virus is not surprising, according to Epstein.

“In Pteropid bats and P. medius in particular, we find that there are different proportions of bats in any given colony exposed to the Nipah virus when we look,” he said. This proportion is always changing, and what such surveys reveal will only be a snapshot.

In Kerala, the state department of animal husbandry has been criticised for having sampled insectivorous bats first. The bats had been captured from a well reportedly cleaned by the first victims of the virus before they had fallen ill. But this choice – seemingly done in a bid to allay public anxiety – and the negative result has now sowed confusion, with news reports claiming wrongly that bats have been proven to not be the source of the infection.

Mohammad Sabith, the virus’s first victim (although he wasn’t tested for it) died on May 5. Since then, fruit bats in the area that may have been the source of the virus could have cleared the virus from their bodies.

“Depending on when bats are sampled, it really does make a difference as to whether we will or won’t detect the virus,” said Epstein. This delay, together with the fact that only a small number of bats in any given colony are infectious to begin with, means that it’s possible the virus won’t be found from fruit bats in the area.

One workaround is to sample a larger number of bats at a time. However, only three insectivorous bat samples from the well were tested, according to Scroll. The National Institute of High Security Animal Diseases in Bhopal, which is testing the samples, has now asked for 50 fruit bat samples. Further, the test results of samples displayed in the news report show that they were tested for viral genetic material, not antibodies. Arun Zachariah, of the Kerala Veterinary and Animal Sciences University, Wayanad, confirmed this. He had been involved in capturing the bats and collecting blood, urine, saliva and faecal samples. If deliberate, it’s unclear why this choice of test was made.

Antibodies are easier to detect, and if Nipah antibodies are found in bats in the area, it would be evidence that the virus has indeed been circulating among them. (Bats are known to lose antibodies too, Epstein said, though the period over which this happens is unknown.)

Differences between various outbreaks

Analysis of Nipah outbreaks in Bangladesh between 2001 and 2007 suggests that there have been more than 20 instances of bat-to-human transmissions of the virus. In Malaysia in 1998, it seems there had been a single transmission from bat to pig, which was responsible for an epidemic that killed 105 people and led to the mass culling of pigs.

Animals – cattle and goats apart from pigs – in the vicinity of affected areas in Bangladesh were found to have antibodies to a virus similar to Nipah, and many humans infected in these outbreaks had had contact with sick animals. After the outbreak in Siliguri, West Bengal, by contrast, domestic animals were not tested to see if they could have been intermediate hosts – nor were bats.

Half the patients in the numerous outbreaks in Bangladesh had been infected by other people. The human-to-human transmission during the 2001 outbreak in Siliguri was also high, about 75%. The ratio was similarly high in the Kerala outbreak as well, with the first confirmed patient, Mohammad Salih, suspected to have acquired it from his brother Sabith; the latter died on May 5.

All known cases since then have either been family members of Salih, people who had had contact with him or those who had shared a hospital ward with others who had acquired the infection from Salih. Thus far, the virus has claimed 14 lives, with three more infected people in intensive care.

A more disastrous outbreak may have been averted partly because not all patients appeared to transmit the virus. In the 1998 outbreak in Malaysia, no confirmed case of human-to-human transmission was recorded, while in Bangladesh only 7% of patients had infected others.

There is another difference: the Malaysia strain of the virus caused neurological symptoms – below normal or absent reflexes, involuntary contractions of muscles, difficulty in eye movement – in humans. The Bangladesh and West Bengal strains (similar to each other) appeared to cause more severe respiratory symptoms in addition to neurological ones. Further, patients who had difficulty breathing had been found to be more likely to infect others.

Known unknowns

That not all Nipah-infected patients transmit the virus appears to be the case in the present outbreak in Kerala as well, according to observations made by G. Arunkumar of the Manipal Centre for Virus Research, Manipal. He noted that only patients in the disease’s acute stage appeared to infect others.

Why this is so is unknown. “I think one of the things we’re still working to learn in the scientific community,” said Epstein, “is how the genetics of the virus translates into the clinical outcomes for patients in terms of how easily it spreads from person to person and how severe the disease is.”

There remain other mysteries about the virus and its ecology. “Disease emergence,” one paper noted, “is fundamentally an ecological process – the challenge is to identify the underlying drivers, and counter them.”

We don’t yet know what these drivers are. What are the mechanisms by which the virus is kept in circulation among bats? What are the particular factors that must occur together for the virus to “spill over” from bats to other animals or humans? To add to the mystery: an individual bat that has cleared the infection may experience recrudescence – the virus may have been present all along, untraceably, and may reappear later and circulate in the otherwise healthy bat once again.

Regardless of whether bats in Kerala are found to carry the virus, culling them – which some news reports suggest might be underway – is not a solution.

“These bats, P. medius, are incredibly important ecologically in terms of pollination and seed dispersal,” Epstein said. “In every case where there’s a Nipah virus outbreak, the transmission from bats to humans is accidental – usually contamination of some type of food resource, whether it’s date palm sap or fruit. And so this is really an opportunity for people to understand that we do share habitat and food with many different types of wildlife. But the answer is not to try to exterminate bats or to get rid of them.”

Nithyanand Rao is a freelance science writer.