OPINION

Anatomy of an outbreak

“The Kerala government’s extraordinary response is no solace for Mohammed Salih’s family who have lost four members in three weeks to the Nipah virus.” The relatives of V. Moosa, Salih’s father, offer prayers at his burial in Kozhikode. (Below) Virologist Govindakarnavar Arunkumar, head of the Manipal Centre for Virus Research, with his team at the Kozhikode Medical college.SPECIAL ARRANGEMENT/ S. Ramesh KurupPhoto: S. Ramesh Kuru

“The Kerala government’s extraordinary response is no solace for Mohammed Salih’s family who have lost four members in three weeks to the Nipah virus.” The relatives of V. Moosa, Salih’s father, offer prayers at his burial in Kozhikode. (Below) Virologist Govindakarnavar Arunkumar, head of the Manipal Centre for Virus Research, with his team at the Kozhikode Medical college.SPECIAL ARRANGEMENT/ S. Ramesh KurupPhoto: S. Ramesh Kuru  

The way Kerala has handled the Nipah virus outbreak holds crucial lessons for the rest of India.Priyanka Pullareports on how a deadly virus is being tackled byan alert administration

At around 2 a.m. on May 17 morning, a grievously sick Mohammed Salih, a 28-year-old architect from Kerala’s Perambra town, was rushed by his family to Kozhikode’s Baby Memorial Hospital. Salih was vomiting, had a high fever, and was in a mentally agitated state. The doctor on call, critical care physician A.S. Anoop Kumar, knew these symptoms meant encephalitis, an inflammation of brain tissue that kills hundreds in India every year. Kumar tried to stabilise Salih, but by around 9 a.m., when the hospital’s neurologists came to examine him, it was obvious that something was very wrong.

Even though Salih was receiving top-end care, his condition was worsening rapidly. He had some very peculiar symptoms, recalls Chellenton Jayakrishnan, one of the neurologists who treated him. His heart was racing at over 180 beats per minute and his blood pressure had shot up. His limbs were limp, displaying no reflexes. These symptoms were unlike any encephalitis cases that the team had ever seen. Jayakrishnan and his colleagues ruled out, one by one, dozens of common causes of encephalitis. Salih couldn’t have Japanese encephalitis. The mosquito-borne infection typically doesn’t affect more than one person in a household, and his younger brother, Sabith, had died about 12 days ago after showing similar symptoms. His father and aunt, too, had contracted the infection.

Rabies, another possible cause of encephalitis, was ruled out too. “If the family had been exposed through a common pet, they would have fallen sick at the same time,” says Jayakrishnan. Salih had fallen sick days after Sabith did. So, was this a case of poisoning? The team ruled this out, too. Toxins could trigger encephalitis-like symptoms but were usually not accompanied by fever.

The neurologists knew by then that they were looking at an exotic virus, possibly never seen in Kerala before. Anoop Kumar decided to call for help. He turned to virologist Govindakarnavar Arunkumar at Karnataka’s Manipal Centre for Virus Research (MCVR), about 300 km from Kozhikode. Salih’s samples were dispatched to MCVR.

Forty-seven-year-old Arunkumar has investigated several mystery outbreaks of encephalitis in the past. In 2015, his team found a recurrent epidemic in Uttar Pradesh’s Gorakhpur to be Scrub Typhus, a diagnosis that was later confirmed by other researchers. A year later, he joined hands with virologist T. Jacob John to uncover the etiology of an encephalitis-like syndrome in Odisha’s Malkangiri district. For four years now, Arunkumar has been heading a surveillance project which tests patients with fever in 10 States for over 40 pathogens. As part of this project, MCVR upgraded one of its labs to Biosafety Level 3 two years ago, so they could work with highly lethal pathogens like the Kyasanur Forest Disease virus. This upgrade gave Arunkumar the chance to expand his testing repertoire. And the pathogen he was eyeing was the deadly Nipah virus.

A serendipitous diagnosis

The Nipah virus made its first documented appearance in Malaysia in 1998. There, the virus is believed to have jumped from fruit bats of the Pteropus species to domestic pigs paddocked under the trees where such bats roost. From the pigs, the virus travelled to pig breeders, infecting and killing about 105 of them in an outbreak. Nipah next appeared in Bangladesh, triggering nearly 15 outbreaks in the 2000s. The pathogen had a different modus operandi in that country. It mainly infected people who had a taste for raw palm sap, which is frequently contaminated by bat urine and saliva. Once the virus spread to humans, it was transmitted from one person to another through respiratory droplets, a feature that wasn’t seen in Malaysia.

Nipah killed nearly 70% of those it infected in Bangladesh, compared to 40% in Malaysia. During the epidemic years in Bangladesh, the virus also crossed the border to enter West Bengal — twice. The outbreaks occurred in 2001 and 2007 in the districts of Siliguri and Nadia, killing 70 people.

Arunkumar was interested in testing for Nipah for two reasons. First, among the States covered by his surveillance project were Tripura and Assam, both across the border from Bangladesh and potential geographies for Nipah. Second, the virus is thought to be a probable bioterrorism agent. So, in August 2017, the MCVR team was trained by the United States’ Centers for Disease Control and Prevention to test for the Nipah virus. This made the Manipal laboratory only the second facility in India capable of doing so, apart from Pune’s National Institute of Virology (NIV). It was a serendipitous move.

When Arunkumar received Salih’s samples on May 18, he also ruled out common causes of encephalitis such as the Japanese encephalitis virus, the Herpes Simplex virus and Leptospira bacteria. Only one pathogen seemed capable of causing Salih’s symptoms and leading to sickness among several family members at the same time. “It was Nipah,” says Arunkumar.

Meanwhile, doctors at Baby Memorial had also come to the same conclusion. Nipah had crossed Jayakrishnan’s mind on the first day. By the second day, the team had browsed through medical journals and found that Salih’s symptoms closely matched those of the patients affected in the 1998 Malaysian outbreak. Arunkumar ran the samples through a diagnostic test called Real Time Polymerase Chain Reaction (RT-PCR), which detects viral genetic material. Salih, his father V.K. Moosa, and his maternal aunt Mariyam Kandoth all tested positive for Nipah.

As this story went to print, Nipah had claimed the lives of 17 of the 19 people it had infected in Kozhikode, a mortality rate of 89%. The outbreak triggered widespread panic, with families in Perambra deserting their homes en masse. As speculation grew about how the virus was transmitted, N-95 masks appeared all over Kozhikode. When officials announced that the virus could spread through fruits that were half-eaten by bats, people cut down on their fruit purchases.

But without the prompt diagnosis, it could have been worse. In Bangladesh, the first few outbreaks killed dozens in the districts of Meherpur and Naogaon, but were not recognised as Nipah until after they ended. In the 2001 Siliguri outbreak, investigators figured out that it was the Nipah virus that was infecting people only six months later. By then, 60 people had been infected and 45 had died.

India has a poor record of outbreak investigations. About 10,000 people develop encephalitis-like symptoms each year but never get a diagnosis. Some regions, such as Uttar Pradesh’s Gorakhpur and Bihar’s Muzaffarpur, saw thousands of deaths in repeated annual outbreaks before the causes were established. Against this background, the discovery of an exotic pathogen in the very second patient hit by an outbreak, as was the case in Kozhikode, has few precedents.

A brisk State response

Once MCVR had pinpointed the Nipah virus, they had to move quickly. Under the 2005 International Health Regulations, India is obligated to report outbreaks of emerging infectious diseases to the World Health Organisation. The MCVR team had to therefore be doubly sure of its findings. The only way to be so was to ask NIV, Pune, to run Nipah diagnostic tests on a second set of the Perambra family’s samples. As they waited for NIV’s confirmation, Arunkumar told the Baby Memorial doctors that they were dealing with a deadly new virus, and that suspected patients should be isolated immediately. “But we didn’t release the name,” says Arunkumar. Revealing the name publicly would require NIV’s verification, which only came on May 20.

But the State health-care machinery did not wait for confirmation. Within hours of Salih’s arrival at Baby Memorial, Kozhikode’s district medical officer, V. Jayashree, had learnt of it. She put together a team of entomologists and visited Salih’s Perambra home on the morning of May 18. They collected mosquito samples and fogged the area, just in case the mosquitoes were the disease vectors.

By the time Arunkumar shared the final results on May 20, State medical associations and government doctors were already on high alert. The State’s Health Minister, K.K. Shylaja, was in the city to oversee the outbreak response. It was easy to move ahead at this point. On May 20 morning, an officer trained in Ebola outbreak protocols instructed the State’s doctors in infection-control measures — isolating patients, using surgical masks and decontaminating surfaces. It was an extraordinarily swift response by any measure. Yet, according to the State’s Director of Health Services, R.L. Saritha, this was routine procedure. “There were two cases of encephalitis. We wanted to prevent the third. This is the usual response in Kerala to all outbreaks,” she says.

Two waves slip through

For all of the Kerala government’s agility in tackling Nipah, the virus proved to be a formidable adversary. When Salih contracted the infection from his younger brother, so did several others. This was the first wave of infection, and Sabith was patient zero — the first to fall sick.

By all accounts, Sabith was a well liked 26-year-old. A plumber by profession, he loved children and animals, says his cousin Jabir. Today, a colony of rabbits sit in a cage in the family’s abandoned Perambra home. They are fed by the neighbours.

Some time on May 3, Sabith grew feverish. His family took him to the Perambra Taluk Hospital, where his condition worsened quickly. On May 5, when he began to lose consciousness, the family shifted him to the Kozhikode Medical College. Later in the night, Sabith died. But during his stay in Perambra Taluk Hospital and the medical college, nurses attended to him, and dozens of neighbours came to look him up.

Such close contact with patient zero led to seven new cases in Perambra Taluk Hospital and 10 in Kozhikode Medical College. Meanwhile, one of the patients infected in the first wave at Perambra went on to get admitted at the Balussery Taluk Hospital on May 17. He infected yet another person, raising the possibility of a second wave of infection at the Balussery hospital. Nipah spreads mainly through respiratory droplets, and sicker patients secrete more virus. It was only in Baby Memorial, which had stricter infection-control protocols, that transmission seems to have stopped.

While State authorities prepare for a second wave of infection, with the Balussery transmission coming to light only on May 31, Arunkumar believes that this wave may not be a large one. For one, infection-control measures were put in place by the 20th, and over 1,400 people who came in contact with the 19 confirmed cases are being closely watched. For another, unlike other viruses like measles in the Paramyxovirus family to which Nipah belongs, Nipah does not spread efficiently and moves only to people within a metre of very sick patients.

This pattern of transmission is typical of how Nipah spread in Bangladesh and West Bengal. In the 2001 Siliguri outbreak, the first wave occurred in the Siliguri District Hospital, where patient zero infected nine others, including five staff members. Two of the patients then joined two other nursing homes, where they spread the illness to 34 others. In contrast to Siliguri, where hospital attendants formed the bulk of the patients, Bangladeshi Nipah cases were mostly related to other patients. A 2009 study in Clinical Infectious Diseases noted that Bangladeshi nurses had less physical contact with patients, as compared to western hospitals. Instead, family members provided hands-on care. Cultural practices like sharing of beds and utensils with patients exacerbated the risk to families, the researchers noted.

In Kerala, the number of confirmed new cases emerging each day has slowed after the first wave from patient zero. But as the Nipah virus can incubate in the body for up to 21 days, health officials cannot take it easy for a while. Only when 42 days, or two incubation periods, pass after the last confirmed case will the State be declared Nipah-free.

The Kerala government’s extraordinary response is, unfortunately, no solace for Salih’s family. Within a span of three weeks, they have lost four members. In the verandah of a neat two-storied house in Perambra, Salih’s uncle, Haji Moidu, sits staring ahead. His family and friends have gathered around him to mourn the loss of his wife Mariyam, brother Moosa, and nephews. Soon after Salih’s death, his aunt and father also succumbed to Nipah.

But even before the family could come to terms with the deaths, several media outlets had published false information about the victims. A local daily wrote that Sabith had travelled to Malaysia, acquiring the Nipah virus there. The family is furious. “They have attempted to isolate us,” they say, showing Sabith’s passport. The only foreign nation Sabith visited was the United Arab Emirates, in search for a job.

Trapping the suspects

The question of how Sabith contracted the virus remains a mystery, given that the only other Indian outbreaks have happened in West Bengal. But the strongest suspects now are Kozhikode’s large fruit bat populations. The species were found to be carriers of the Nipah virus in both Malaysia and Bangladesh.

This is also why two teams of researchers from NIV are currently camping in Kozhikode to collect samples from fruit bats. It’s going to be an uphill task. For one, experiments have shown that the Nipah virus circulates within bats for brief periods of time, during which the likelihood of transmission to humans, or a “spillover” event, increases. In a 2011 study published in the American Journal of Tropical Hygiene and Medicine , virologists experimentally infected fruit bats from Malaysia and Australia with the Nipah virus, and the closely related Hendra virus. When they tried to isolate the pathogen from the bats only a few days later, they were unable to do so in most cases.

“It’s very challenging to find the virus in bats, even when you are looking in a known reservoir, and that’s because of the nature of the infection,” says Jonathan Epstein, an epidemiologist with the U.S.-based EcoHealth Alliance and an author of the study. According to Epstein, the Nipah infection doesn’t last for very long in bats. “Unless your timing is good, and you are collecting samples close to when the first case was exposed, your chances diminish,” he explains.

Sabith fell sick on May 3, and it is possible that the virus is undetectable in Perambra’s fruit bats now. However, the mammals may still be carrying antibodies to the Nipah virus, which remain for longer. But it isn’t clear if NIV will test for antibodies, in addition to the viral genes. In an email to The Hindu , NIV director D.T. Mourya said the group’s front line test would be RT-PCR, which only detects viral genes. Unless the NIV researchers are able to find a large number of bats, they may not have enough blood and urine samples to look for antibodies.

To make matters more difficult, trapping bats is a tough job. The Indian flying fox can weigh over a kilogram, with a wingspan of up to five feet. The team’s strategy will be to raise large nets on 60-feet high poles, so that bats unseeingly fly into them. Meanwhile, the district animal husbandry department will collect bat droppings and urine from the ground. This, too, is becoming harder as monsoon hits Kerala. “Collecting bat droppings is not easy when it is raining. The quantity of urine is only 0.5 ml per animal,” says A.C. Mohandas, the district animal husbandry officer at Kozhikode. Without enough samples, we may never know how Nipah travelled to Kerala.

Even if fruit bats are eventually found to be the source of Nipah, it may not be easy to establish how Sabith came in contact with them. Early interviews with his family had revealed that he and his brother had supervised the cleaning of a bat-infested well near his house. However, when animal husbandry officials checked the well, they were only able to collect a single bat from an insectivorous species. This sample turned out negative for Nipah. Another explanation could be that Sabith unwittingly ate a fruit contaminated with bat saliva. If this was the route of exposure, it’s doubtful it will be confirmed. But exposure through bitten fruits is not unlikely.

At Sabith’s Perambra home, three neighbours, all undergraduate students, stop by to chat. They had known Sabith’s family and were shocked by the swiftness with which his family succumbed. The conversation drifts to how Sabith may have contracted the virus. One of them says, “We used to consume half-eaten guavas and mangoes all the time. We would just remove the bitten part and eat the rest. Nothing ever happened to us.” I ask them if they continue to do so. “No,” he says. “We are too scared now.”

With inputs from Jayanth A.S.

The Hindu obtained the consent of Mohammed Sabith’s immediate family to use their real names

Recommended for you