On May 17th, 2018 at 2 am, a 28-year-old male presented to the Emergency Department at Baby Memorial Hospital Kozhikode (BMH) in Calicut, a city in the state of Kerala, South India. He had vomiting, high fever and mental agitation. He was unstable and so was transferred to the closed multidisciplinary unit of the hospital. Shortly after admission, the patient developed myocarditis and severe circulatory failure.
Dr Anoop Kumar is the Chief of Critical Care Medicine at Baby Memorial Hospital and was working early that morning. After discussing differential diagnoses with his team and sending samples to the Manipal Centre of Virology, a diagnosis of Nipah was confirmed. Unfortunately, within 24 hours, the patient succumbed to the disease.
The Nipah virus, a newly emerging zoonosis, was first identified during an outbreak in Malaysia in 1998 when pig farmers and people in close contact with pigs were being hospitalised for encephalitis and respiratory illnesses. Over 300 patients were reported with over 100 deaths. Consequently, more than a million pigs were culled, causing a substantial economic loss for Malaysia. Although in this outbreak in Malaysia pigs were the intermediate host of the Nipah Virus, fruit bats are the natural reservoir of the virus. Recently, the Indian Council for Medical Research confirmed that the fruit bat was the cause behind the outbreak in Kerala.
The Kerala outbreak had a mortality rate of 89%, with 17 fatalities out of the 19 infected patients. Fortunately, the outbreak was contained in a matter of weeks and a potentially dangerous pandemic was halted. How did the doctors know they were dealing with something unusual? How were they able to contain such a deadly virus so quickly? To find out more, we interviewed Dr Anoop Kumar.
A young man without any known illnesses was treated in a primary care centre for two days with fever and vomiting. He developed an altered sensorium and was consequently referred to our centre on May 17th, 2018. On arrival at the Emergency Department, he was restless and confused. Given his symptoms, we had a working diagnosis of a Central Nervous System (CNS) infection. After having a CT brain scan, he was admitted to the closed multidisciplinary intensive care unit (ICU).
On admission to the ICU, he was delirious, confused, hypertensive, tachycardic, and tachypnoeic. His CT scan revealed moderate cerebral oedema without any parenchymal lesions. His blood tests revealed normal blood gases, normal hepatic, renal and coagulation parameters with normal blood counts except for mild thrombocytopenia.
He was electively ventilated. His initial bedside ultrasound evaluation was normal with normal left ventricular contractility. He was started on empirical treatment for probable CNS infection and on anti-brain oedema measures.
Samples were sent for toxicology analysis and to the Manipal Centre of Virology Research (MCVR) after discussing with the Director Dr Arun Kumar.
On the morning of May 18th, 2018, a detailed discussion was held with a team of experts on the differential diagnosis. Various differential diagnoses that were discussed included toxicological agents, rabies and an unusual encephalitis. My colleague, Dr Jaya Krishnan suggested the possibility of Nipah around the same time we heard back from the Manipal Centre of Virology Research. It was confirmed that the aetiological agent which caused his illness was Nipah virus. Unfortunately, the patient died that day. The autopsy confirmed the diagnosis.
Even after initial stabilisation, he continued to have severe tachycardia and hypertension requiring intravenous hypotensive drugs. He also had severe sweating - more than regular febrile patients. Within a few hours, he became hypotensive requiring vasopressor therapy. Serial ultrasound examination revealed severe global left ventricular systolic dysfunction favouring the diagnosis of myocarditis. His cardiac markers also suggested myocarditis.
It was also revealed that other family members had experienced similar symptoms and one family member had died.
The abnormal clinical features exhibited by these cluster of patients along with the death of the initial patient two weeks before alerted the critical care team that it could be an unusual viral syndrome.
Along with routine investigations, samples were sent for detailed toxicological analysis (after the initial rapid toxicology screen was negative). Urine, CSF, blood and throat swabs were collected from all patients and samples were sent to the Virology Institute in triple layer packing after informing the Institute of the detailed clinical picture.
The mainstay of treatment is supportive care. There is no approved treatment available for Nipah virus infection. The use of high dose ribavirin showed some reduction in mortality in the Malaysia outbreak. However, recent animal studies show no clear benefits for administering the drug for Nipah infections. Favipiravir and monoclonal antibodies have efficacy in animal models in neutralising the Nipah virus. They are expected to be approved for human use in the future.
Unfortunately, there is a high mortality with persistent neurological sequelae. There is a chance of delayed recurrence as well.
Initially, as the diagnosis was probable encephalitis, and so only routine ICU infection control measures were adopted. The next day we had a clinical suspicion of Nipah so contact precautions were taken including isolation in a negative pressure chamber. As we were not sure of the diagnosis at that point, Personal Protective Equipment (PPE) kits were not used. Once we got laboratory confirmation on the evening of the second day, we instituted strict contact isolation, patients were treated in negative pressure isolation rooms, we used PPE kits and modified linen, and cleaning and dietary policies were adopted. Infection control measures in the ICU were heightened and training sessions were started on infection control, and donning and doffing of PPE (adopted from Ebola and MERS-CoV CDC policies).
Patients were treated in our unit and we did not refer. It was decided to establish Calicut Medical College Hospital as the sole treatment centre for Nipah patients - all subsequent patients were taken there.
We initially reported to the Integrated Disease Surveillance Program (IDSP) - once we noticed a clustering of patients with unusual symptoms. For the rest of the outbreak, active surveillance programmes were initiated for contact tracing by the National Institute of Epidemiology.
Patients and the community wanted to know about the infectivity, mode of transmission, treatment options and contact management.
No. Our textbooks did not mention anything about Nipah.
In our area, we mainly see dengue fever, leptospirosis, scrub typhus, viral hepatitis, and enteric fever. Rarely, we see Japanese encephalitis, TB meningitis or herpes encephalitis.
Due to the high mortality (initially 100%) with a high person-to-person transmission, there was a sense of panic among the public.
We were not at all prepared for such a highly infectious disease. We also didn't have experience in dealing with such outbreaks in the past. Still, our state government and health authorities (with support from the public) allowed us to contain the spread of disease.
Definitely. Kerala state has one of the highest literacy rates, highest health awareness and best health parameters in India. Public cooperation and the natural inclination of the people to help made a big difference.
As mentioned, the local government has designated the Medical College Hospital’s isolation units for any new patients. We are actively evaluating all patients with encephalitis for Nipah and taking contact precautions until we receive a negative report for Nipah.
I would have taken adequate contact precautions from the first day. I would have also wanted to inform the lab and forensic department (during the autopsy) about the necessary precautions when dealing with such a pathogen.
The outbreak was reported on May 19th and the last patient reported was on May 30th.
Because this was an unusual presentation, we took a detailed history, maintained close observation and conducted a thorough clinical examination. We also had multidisciplinary bedside discussions early on which helped us with the diagnosis. Various strategies were implemented which made the quick containment possible. A special task force was set up which comprised of government officials, healthcare directors, doctors from public and private sectors, State Animal Husbandry, police and intelligence, and staff from the National Centre for Disease Control (NCDC), National Institute of Epidemiology (NIE), and the Indian Council of Medical Research (ICMR). Review meetings were held every day along with media briefings.
We were given guidelines for case identification, contact tracing, treatment-supportive care, infection control measures, and food control. Mortuary policies which established safe burial practices were formulated. We followed strict Ebola protocols from day one. We also followed strict contact tracing by field health workers. Close to 2000 contacts were traced and screened.
In addition to having good public-private partnerships, we had good cooperation among the public in Calicut.
Thank you Dr Kumar for sharing your experiences and we thank the relatives of the patient for their consent to share these details.
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