Emerging Infectious Diseases
Nipah virus encephalitis is a neurological and respiratory zoonotic disease caused by the Nipah virus (NiV). Along with Hendra virus (HeV), which causes respiratory illness in horses and humans, NiV belongs to the genus Henipavirus. Fruit bats belonging to the Pteropus genus are the natural hosts of both NiV and HeV, and have a broad geographic range. Transmission to humans can occur through contact with infected bats, food contaminated by bat secretions, as well as contact with infected intermediate hosts (e.g. pigs and horses) and other NiV/HeV-infected humans. Symptoms include fever, headache, drowsiness, disorientation, altered consciousness; severe cases may progress to encephalitis, seizures and coma.
The first recorded NiV outbreak occurred in 1998 among pig farmers in Malaysia and Singapore, leading to 265 cases and 105 deaths (40% case fatality ratio). Since the first outbreak, there have been more than 20 human outbreaks of NiV infection in Bangladesh and India, with at least 346 cases and 260 deaths overall. The most recent outbreak occurred in May 2018, in Kerala, India, with 18 confirmed cases and 16 deaths (89% case fatality ratio). In 1994 in Australia, HeV spilled over from bats to horses and later to humans; since then there have been at least seven human cases and four deaths. There is also serological evidence of NiV cross-neutralizing antibodies in both bat and human populations in sub-Saharan Africa. Despite no recorded henipaviral outbreaks in humans, this evidence suggests that spill-over events have indeed occurred in sub-Saharan Africa and increased surveillance efforts are warranted.
During the 2018 Indian outbreak, there was only a single episode of animal-to-human spill-over; the driver of the epidemic was human-to-human transmission, with the index case transmitting the disease in 19 out of the 22 cases. In such situations, timely detection and prompt utilisation of PEP are vital for outbreak control.
In the absence of an approved drug, Nipah virus case management relies on supportive care and off-label use of ribavirin, an anti-viral. Nipah infection often involves the central nervous system; therefore, an ideal therapeutic agent should be capable of crossing the blood-brain barrier. Additionally, new drugs are needed for post-exposure prophylaxis. A few small-molecule and biological approaches have been explored; however, the evidence generation involving antivirals such as remdesivir and favipiravir so far is limited to early-stage research using animal models.
The WHO draft Nipah virus vaccine Target Product Profile recommends that an ideal vaccine should have a reactive use-case profile – rapid protection, single dose, high efficacy, thermostability and provision of protection against both strains of Nipah. The current vaccine pipeline is made up of mostly pre-clinical candidates, with only two candidates entering clinical trials. Almost all candidates are monovalent – utilising either the Bangladesh or Malaysia strain.
Even in the absence of an effective vaccine, timely and accurate detection can help in deploying effective non-pharmaceutical countermeasures, such as Malaysia’s targeting of animal-to-human spill-over. Developing an appropriate diagnostic test is challenging due to poorly understood disease kinetics (in cerebrospinal fluid, saliva and other fluids), cross-reactivity with different strains especially in animals, and high rates of false-negative results from IgM serology-based tests. Consequently, there are currently no accurate point-of-care molecular tests or RDTs available, with specialised laboratories required to handle the isolation of Nipah virus in suspected samples.
A monoclonal antibody, m102.4, remains the only novel therapeutic to undergo human trials. Molbio Diagnostics received approval from the Indian regulators for a molecular test based on its TruNat platform to detect NIV has developed. In 2022, PHV02, a recombinant vesicular stomatitis virus based vaccine, became only the second candidate to enter clinical trials.