Nipah virus (NiV) is a Para- myxovirus that has recently been responsible for outbreaks in India. In 2018, it caused an outbreak in Kozhikode that resulted in 17 deaths. This year, it has again resurfaced in Kerala. The index case was identified in the Department of Neurology at Aster Medcity, Kochi, Kerala. Due to early detection, isolation and containment measures initiated by all of the involved departments, there were no further cases identified. A number of close family members, close contacts and nursing personnel were placed under observation or isolation in the nearby Cochin Medical College, Nipah isolation ward. Repeated sampling of suspected cases did not disclose any further infections and the infection was contained at ‘Patient Zero’. In this article, we discuss the clinical presentation of the index case.
A 23 year old man presented to the emergency department with a high grade fever of 8 days duration. After visiting multiple hospitals, he had been referred to us. He was from Thodupuzha [Idukki district], 60 kilometers from Kochi. He had visited Trissur, from where he came back home after 2 days with fever.
On day 8, in the ED, he was febrile, delirious and had tremors of his limbs as well as spontaneous myoclonus and dysarthria. His mother denied any history of similar illness among his friends, any significant past medical history or recreational drug abuse. He underwent an MRI brain scan, which showed numerous similar sized small infarcts scattered in the subcortex and cerebellum as well as the pontoesencephalon. These lesions were visible only on the diffusion weighted MRI (DWMRI) images and did not enhance with contrast. The initial differential diagnosis was that of multiple septic emboli. An urgent Echo cardiogram was performed at the bedside and did not dis- close any valvular lesions indicative of infective endocarditis.
Blood cultures were sent and common endemic infections such as leptospirosis, scrub typhus, dengue and malaria were ruled out. A chest x-ray was also normal. The patient was started on injections of Ceftriaxone and Vancomycin at meningitic doses and transferred to the ward. The next morning, as he was still delirious, a lumbar puncture was performed and a cerebrospinal fluid (CSF) sample was sent for an encephalitic test panel (including DNA and RNA viruses). The patient was started on Acyclovir injections at 10mg/kg Q8H. CSF testing showed around 50 cells, predominantly lymphocytic, with normal sugar and protein levels. The encephalitic panel was positive for Nipah virus the next evening.
The patient was noted to have dysautonomic features such as tachycardia, volatile blood pressures and unexplained tachypnea. He was immediately transferred to the medial ICU and isolation precautions were initiated. The next morning, he was started on 2g solid dose Ribavirin, followed by 1.2g on days 2-10. The CSF, blood, urine and throat swabs were further tested with Real- time PCR, nested RT-PCR and anti-Nipah human IgM and IgG antibodies via the enzyme-linked immunosorbent assay (ELISA). By day 10, further dysautonomia in the form of urinary retention developed, and an indwelling Foley’s catheter was placed. The urine and CSF were positive for Nipah Viral RNA, IgM and IgG antibodies on day 8.
The patient was noted to be persistently delirious (hyperactive delirium) and was agitated. He was intermittently sedated with fentanyl. By the end of the second week, the indwelling catheter could be removed and he was gradually ambulated. As NiV urine PCR remained positive on day 16, he remained in isolation. By day 20 all samples tested negative and he was transferred out of isolation. All indwelling catheters and lines were re- moved. A new MRI did not show any new lesions. However the patient remained febrile and had persistent tachycardia. Repeated blood and urine cultures, CRP, ProCalcitonin, Chest xray and blood counts were normal. After all sources of infection had been ruled out, the possibility of a central fever with dysautonomia was considered. He was started on symptomatic treatment with Naproxen for fever and Ivabradine for tachycardia, both of which improved. His arterial blood gases remained normal throughout his clinical course and he did not require any venti- latory support.
As the first reported patient, our patient was the index case of Nipah virus in 2019 in Kerala. The infection was contained at
Aster Medcity. NiV has been well known to cause outbreaks in vari- ous south east Asian countries, starting with Malaysia in Septem- ber 1998, followed by Singapore in 1999. Subsequent outbreaks have occurred every year in Bangladesh from 2001 onwards. In 2001, NiV was detected in India (West Bengal, 2001 & 2007). In May 2018, a NiV outbreak was noted in north Kerala (Kozhikode). The infection was traced to fruit bats and coincided with the bat breeding season which runs from December to May.
A number of methods can be used to diagnose NiV infection. These include serum neutraliza- tion tests such as ELISA, viral PCR, viral isolation or immunohistochemistry on biopsy specimens. These tests are run at a number of Virology laboratories including The National Institute of Virology (NIV), Pune, NIV Alleppey and the Manipal institute of Virology. However, we could also obtain a prompt and rapid turn-around time from XCyton Diagnostics in Bengaluru. The turn-around time of 36 hours enabled us to immediately diagnose NiV and rapidly initiate isolation measures.
Of the 10 cases reported from Kozhikode, 7 of them developed encephalitis. 2 patients survived and 1 died of ARDS. Even among the cases of encephalitis, mor- tality was predominantly due to acute respiratory distress syndrome (ARDS). However, in all mortalities, the duration from on- set to death was quite rapid, and there was no time to complete adequate neuroimaging. Most of these patients also had dysauto- nomia (tachycardia and fluctuating blood pressures). In view of the severity of the encephalitis, a neurogenic pulmonary edema is also a possibility, however this could not be proven in any of the cases and ARDS was considered more likely. Myocarditis was also considered in some of the patients. As NiV primarily causes a small vessel vasculitis, this could explain the small infarct-like lesions in the brain on the MRI. The two survivors had a milder form of the disease and could also complete a course of oral Ribavirin for up to 14 days. None of the patients received NiV monoclonal antibody therapy. The survivors also did not suffer any sequalae of NiV infection.
In common with our patient, most of the NiV encephalitis patients had fever, altered sensorium and dysautonomic features. The dysautonomia probably oc- curred due to brainstem involvement. The rapid progression, high mortality rate and brainstem involvement further underscores the similarity of Niv to ‘Rabies’ which is albeit uncommonly also acquired from bats.