‘Independent Nipah Spillovers Are A Better Outcome Than An Outbreak’

NiV infection is a zoonotic illness that is transmitted to people from animals--an event termed as a ‘spillover’. The state of Kerala has reported 10 spillovers of Nipah virus since 2018, of which four occurred just this year.

It can also be transmitted through contaminated food or directly from person to person. Fruit bats of the Pteropodidae family are the natural hosts of NiV. It was first recognised in Malaysia in 1999, and presently does not have licensed treatment or drugs.

Nipah potentially puts 2 billion people across the world at risk of infection, according to Coalition for Epidemic Preparedness Innovations (CEPI), among the world’s largest funders of Nipah virus research. Two vaccines against Nipah virus are set to enter human clinical trials in Bangladesh next year.

Given the deadly nature of the virus, which has a case fatality rate of 40% to 75%, not all laboratories can test for Nipah. The European Centre for Disease Prevention and Control designates different levels of safety required to handle specimen: the diagnostic RT-PCR and serology on inactivated samples can be done under biosafety level 2 (BSL-2) conditions; the virus inactivation has to be done at BSL-3; and virus propagation, isolation, quantification and neutralisation require BSL-4 facilities--which have the highest biosafety level requirements.

In 2023, Kerala established a One Health Centre for Nipah Research and Resilience in Kozhikode’s Government Medical College. Anish T.S., an expert in infectious diseases epidemiology and nodal officer of the research centre said, “...independent spillovers are a better outcome than an outbreak”. An outbreak would mean one person can infect multiple people, which would be alarming and require an investigation into the number of infections from one person, he explained.

“There have been around 36 cases [overall] in Kerala. Nearly 60% of them acquired it from hospitals and not from a primary source like bats,” said Anish. “So if the cases have to be reduced, the intervention has to be in hospitals, which includes wearing a mask to avoid an infection.”

Anish is a member of the Kerala State Medical Board of Nipah and member of Collaborative Open Research Consortium of WHO for Paramyxo viruses. He served as the epidemiologist and convenor to Kerala’s Expert Group for COVID 19 and as a public health consultant to the state’s disaster management authority on health-related disasters.

In an interview, he talks about the concerns with NiV, challenges in ascertaining the source and reasons for repeated Nipah outbreaks, and the health systems response in the state.

Edited excerpts:

The One Health Centre for Nipah Research was setup in 2023. There have been outbreaks since then. How has work proceeded in terms of meeting its objectives?

Presently, the One Health Centre is a small unit. The unit began during the 2023 outbreak. This is the fifth outbreak but it was only fully functional by 2024. We support the existing [health] systems with respect to Nipah. Broadly Kerala is prone to many infections including high threat pathogens like Nipah which can cause a high proportion of mortality.

In some cases the virus can mutate and lead to large outbreaks or a pandemic. Nipah can be categorized as one such disease. Another one is highly pathogenic avian influenza (commonly known as Bird Flu) which is a global concern. In the case of Avian influenza, although it was restricted to birds initially there was spillover to animals, especially cattle. India reported its first human infection [in 2021]. Like Covid, avian influenza is a fast mutating virus due to which it could be the next pandemic. The third, in Kerala, is the Kyasanur forest disease which is a viral BSL-4 disease transmitted by ticks. It is present in two districts--Wayanad and Malappuram--although not as fatal as Nipah.

Due to these concerns, the institute was setup in Kozhikode in 2023 which is close to the Western Ghats. It has the potential to develop into an institute which can study the epidemiology and behaviors of high threat infections. Presently, as a small unit, we support outbreak management. We mainly focus on the inter-epidemic period to build resilience to help people take precautions, create guidelines, and coordinate with district administration to identify high risk zones. So our work is done mainly between outbreaks. At the time of an outbreak [like Nipah], we have guidelines to handle the issue

How many people are involved at the centre?

I am the nodal officer. The Kerala Centre for Disease Control and Prevention’s (KCDC) regional office is also situated here. The state project head of KCDC is stationed in Kozhikode affiliated to our institute. We do not have any other staff presently, but we utilise the human resources of the health services and medical education. We have made a few research proposals and seek funding from agencies like WHO and ICMR.

We are also collaborating with other agencies who work under One Health like Institute of Advanced Virology, the government departments of Local Self Government, Animal Husbandry, Environment and Forestry, Kerala State Disaster Management Authority, Kerala Veterinary and Animal Sciences University. We are part of other One Health programmes in various districts.

Nipah outbreaks have been reported since 2018 in Kerala. Kerala had also reported the first case of Covid-19. How have these experiences shaped your own view for the research centre as an institution? What have been the challenges?

There have been around 36 cases in Kerala. Nearly 60% of them acquired it from hospitals and not from a primary source like bats. So if the cases have to be reduced, the intervention has to be in hospitals which includes wearing a mask to avoid an infection. This is very important to reduce the spread of Nipah infections.

If 60% were in hospital infections, another 20% were family clusters. If there are family members showing fever with headache or those with respiratory issues, they must be admitted to hospitals. If the symptoms aggravate, the infection spreads to others. Instead of focusing on bats alone, human behaviour should also be monitored and focused on.

But, these are triggered by a natural infection. Ultimately it would be ideal to prevent spillovers [from animals to humans], but it is difficult to identify the source. Maybe 20-30% of bats are serologically positive, but virological positivity maybe rare. We do not know the context in which a bat is developing an active infection and the context it is transmitted to people. We know that there is 100% similarity between the virus in bats and humans which is genetic proof that bats are reservoirs.

Bats in Kerala harbour specific mutations and it has been around for years. We do not have specific evidence on how virus is transmitted and under what context; through excreta, or intermediaries like other animals etc.

There are some hurdles. For example, research around this requires BSL-4 because it is a high threat pathogen and only National Institute of Virology (NIV), Pune can conduct such research. We won’t get permission to conduct direct research on bats because it may be contaminated with a virus.

[Serology tests are used to look for the presence of antibodies in the blood that show whether a person has been exposed to a virus or other infectious agent. Virological tests the virus and virus agents.]

So, what issues do you face when you can’t conduct research or tests?

NIV is doing a lot of research including serological tests used in animals. For example, a serological test like Enzyme-Linked Immunosorbent Assay (ELISA) [to be made available], a test has to be developed for a specific animal.

Kerala has dedicated centres for conducting virological tests. In Kozhikode Medical College, the government is trying to build a fully functional BSL-3 facility. India has only two BSL-4 facilities; one for human diseases in Pune and another for animal disease in Bhopal. It is unlikely a state institute will have a BSL-4. Given the outbreaks of Nipah, Kozhikode and Manjeri Medical college has operational BSL-3 facilities and so has the Institute of Advanced Virology in Thiruvanthapuram.

The NIV’s field Unit in Alappuzha has a fully functional BSL-3 lab that started functioning recently. In addition to these facilities we are using Truenat tests for Nipah diagnosis--these are point-of-care PCR facilities with not much safety concerns. Truenat could be done in smaller labs also if needed. Compared to other states, I think Kerala has the most diagnostic facilities capable of doing Nipah testing due to which we are able to detect human infections.

Most often we use RT-PCR to diagnose Nipah, which is the gold standard, so the confirmation from an apex lab is just a formality. The control activities will be triggered whenever a positive test result was detected in house. Other states may have to send it to the national labs.

Essentially, the Nipah centre need not establish a virology centre because it is already established in Kerala. Our objective is to create a strategy for community-based research to reduce the number of infections. We try to integrate all the [existing] facilities.

The son of a deceased patient has tested positive, which is a secondary infection in Palakkad. There are multiple primary infections that have been reported, according to media reports. This has not happened in the earlier outbreaks in Kerala. How concerning is this development, given there are no drugs or vaccines that specifically target Nipah?

We have conducted analysis using mobile phone tower data, CCTV footage and interviews and almost certain that these are multiple primary infections. It is unlikely that they knew common persons through which an infection was transmitted. With Nipah, an infected person will be very ill due to which it is unlikely that they will be outside in the community.

Secondly, the second patient, in Palakkad, was mostly confined to her home during the incubation period. The patient's home is prone to a spillover because there is a huge bat roost.

I think the bat roost near the patient’s house was the biggest I had seen--a colony rather than a roost, located in a rubber plantation. Based on trees and branches, there are an estimated 10,000 bats. Due to the size of the colony, many bats may be infected simultaneously and they may be traveling to different locations. An average weight of a flying fox bat is around 600-700 grams and eats around half a kilo of fruits and food. This will require 5,000 kg of food which will require bats to raid a larger area. This may be leading to a spread of infection to others.

While there are tiny possibilities of spread, we are almost certain that the infections are independent spillovers.

I feel that three independent spillovers are a better outcome than an outbreak. If there is an outbreak it means that one person can infect multiple people, which will require an investigation into the number of infections from one person. That would be alarming.

The other issue is, why are we seeing three independent cases which have not happened earlier. A Nipah spillover is [thought to be] rare. If there are three rare events, then it means it is not rare. Is it becoming common or is it the strength of surveillance? If it is the latter, it could be dispersed over time. But in this case, it is unlikely.

Would you say that it is this same bat colony that is a possible source for infections in other locations in the district?

While it is difficult to say, there is a high likelihood due to the aerial distance of the colony to the patient’s home is around 7 km. Furthermore, there are other smaller roosts which can get infected. Once a proportion of bats are infected, it will create a herd immunity among them and the infection stops in that area. But some other roost [that] may not have immunity gets infected. This is why Nipah is elusive.

How do you understand the scale of infection and immunity in a bat roost or colony?

There have been studies in Bangladesh, but those in Kerala are far fewer. Studies in Bangladesh have shown that when a bat roost is infected, the seroprevalence (percentage of bats showing antibodies against Nipah virus) will be low. As infection sets in, seroprevalence will be high. In Kerala, NIV conducted a serial survey of bats in February-September 2023. It showed that in February, it was lower compared to September. During this period bats are getting infected, following which immunity builds. It is a cycle, which could be a reason why spillovers are happening around this period.

The hypothesis is that if the roost is immune, there is a low chance of a spillover because there is no active viral transmission among bats. But the immunity may be limited to a few years and the older ones may be immune due to multiple Nipah infections [at different times]. With younger uninfected bats, again the immunity [of the roost] will reduce.

There can also be a geospatial pattern where the infection moves in a specific direction due to existing immunity in specific locations. This may be the case in Kerala where the case has been reported in the northern parts and moving south [in the subsequent years]. But these are theories or hypotheses, which can help take precautions [against an outbreak].

How is the contact tracing protocol different in case of Nipah compared to say Covid, given that there are more cases being reported?

Nipah contact tracing is easier compared to other diseases. Nipah does not transmit in the pre-symptomatic phase, but only after a patient develops a symptom at the advanced stages (fifth or sixth day where there is maximum transmission). While the last phase is important [to curb transmission], due to high case fatality we are cautious in the initial phase also.

There is no need for quarantine or contact tracing before a person develops symptoms. So it is easier to put resources into tracing people after a patient develops symptoms. In isolation, the person may be intubated and in ICU which does not require contact tracing as they are not exposed.

In most cases, the incubation period is 14 days. But in one case in Kerala, the patient’s symptoms showed on day 12, but it was detected by the [health] system on day 17. So according to our protocol, we keep a person in observation for 21 days. We test only if there are symptoms.

When you are strategising a community health- or community-led response, who are you typically targeting? In Kerala, accredited social health activists (ASHAs) who are the crucial link for community health are protesting for wages/entitlements. What role do the ASHAs play in this case and how does the public health system overall, including doctors, respond to recurrent outbreaks as serious as Nipah?

There are around 27,000 ASHAs in Kerala. Only around 500 ASHAs are on strike. While a few are protesting, many ASHAs are working. In 2018, we did not have an exposure to Nipah. At that time, it was reported by private hospitals. Since then, the cases have been reported by the health system.

In 2023 and 2024, the initial outbreak was picked up by ASHAs. They are supposed to do home-based surveys [to report health issues]. One of the important issues they have to report is Acute Encephalitis Syndrome (AES). An ASHA, in 2024, reported a patient who had died due to AES in a private hospital. When the District Surveillance Officer was informed, the deceased patient's blood samples were taken from a private hospital where he had died. The patient was initially thought to have died due to dengue during the tests. This shows that it is difficult to identify Nipah because the majority of the cases will be a single case. In India, less than 5% of the AES receive a diagnosis. In Kerala, it is as high as 60%.

Why do you say that the diagnosis is better in Kerala when it comes to AES?

If it is Nipah, a person develops fever on day 1, and may die by day 5 if an antiviral treatment is not available, unless the [health] system is able to pick it. Many people die in hospitals and we do not know the reason. Ultimately, it is the efficiency of the system to diagnose cases.

So, even if at a community level we can identify and report, Nipah cannot be confirmed without a lab diagnosis. Nipah is a rare reason for AES. Unless the health system is able to specifically identify Nipah, the reason for AES cannot be identified.

Even if Pteropus bats [fruit bats or flying fox] are found everywhere and virus is observed in them in different parts of India, why is Kerala reporting human cases of Nipah? It may be due to strong surveillance mechanisms.

You said that there is a short time, in the case of Nipah, for symptoms to become serious or fatal. As of July 15, there were 675 in the contact list. According to DHS Nipah guidelines, sample collection should be done only after admission into an isolation facility, and ensuring that the staff member doing the collection is following proper infection control practices. How does the health services ensure that tests to specifically identify Nipah are done if people report fever?

Usually people in [home] isolation are not tested because 90% of Nipah cases will not transmit. So there is no point in testing so many people without evidence. If a person develops symptoms, even a fever, we do a Nipah PCR test. If it is positive, the person has to be admitted to a hospital isolation facility. Otherwise a person is quarantined for 21 days at home.

Suppose there are more positive cases, which is not the case in Malappuram and Palakkad, it means the index patent was infectious. In that context, we can decide that before release everyone must be tested. Usually it is not the practice to test a person after isolation unless there is super-spreading.

In 2023, the contacts of the patient who was infected first were tested for Nipah using the RT-PCR test. The Truenat test is only for screening and the test result is available quickly. If a person is in isolation, the validity of the test is more important than the urgency.

How do you manage the community’s response to Nipah containment, considering it is an infection that has high fatality? Even during Covid, there was contact-tracing and containment zones, but people were not happy with restrictions placed on them. Who has the primary responsibility in ensuring information on Nipah or other serious pathogens trickles down to communities?

There are challenges. Primary high risk contacts or those who are in contact with the patient without protection at the symptomatic time have to be identified and quarantined. This is challenging and one part [of the health response]. It is unplanned and people find it difficult. We have a [public] responsibility in the case of Nipah which is a high risk infection.

An infection is an opportunity for the virus to mutate and be exposed to human immunomechanisms. When this gets transmitted, the natural bat virus is not getting transmitted, but a modified one. In another person, their immunity will try to suppress the virus which creates an evolutionary pressure [on the virus]. There will be a natural selection of virus strains which can evade immunity of a person. So, this can create a virus which has a pandemic potential. It becomes very important to identify infection in the beginning.

The primary responsibility for us would be to ensure that the infection does not go beyond someone infected, to curb more infections. In such cases like Nipah, the power of the district administration is invoked.

We welcome feedback. Please write to respond@indiaspend.org. We reserve the right to edit responses for language and grammar.