The epidemiology, symptoms, diagnosis and management of Nipah virus infections.
Nipah virus infection is caused by the paramyxovirus Nipah virus (genus Henipavirus). Nipah virus is related to, but distinct from, Hendra virus. The natural animal reservoir of Nipah virus is bats, particularly fruit bats of the Pteropus genus. Nipah virus infections in humans were reported for the first time in 1998, following identification of the virus during an outbreak of acute encephalitis in Nipah, Malaysia, with cases also seen in Singapore.
Outbreaks have occurred subsequently in parts of North East India and almost annually since 2001 in specific districts in Bangladesh. Cases of henipavirus infection have also occurred in the Philippines, believed to have been caused by Nipah virus or a Nipah-like virus.
In May 2018 an outbreak was reported in Southern India for the first time, in Kozhikode district of Kerala (see map). Local fruit bats tested positive for the virus. The outbreak was short lived, with 18 confirmed cases.
Nipah virus has been isolated from the urine of bats in Malaysia, and antibodies against Nipah virus have been detected in 23 species of bat across Asia, and also in bats in Ghana and Madagascar. However, human outbreaks of Nipah virus infection have not been identified outside South and South East Asia, and most outbreaks have occurred in rural or semi-rural locations.
The 1998 Malaysian outbreak occurred following a spill-over event, whereby Nipah virus from bats spread to pigs, with subsequent transmission occurring between pigs, followed by transmission to humans exposed to the infected urine and/or respiratory secretions of infected pigs. Other outbreaks have been associated with consumption or collection of foodstuffs, such as raw or partially fermented date palm sap, which were contaminated with bat saliva and/or excreta containing Nipah virus.
Human-to-human transmission also occurs, although the relative contribution of this mode of transmission has varied considerably between outbreaks. Close and direct, unprotected contact with infected patients, especially those with respiratory symptoms, has been implicated as a transmission risk. Person-to-person transmission was responsible for most of the cases in the Kerala outbreak in May/June 2018.
Both human-to-human and horse-to-human transmission (slaughtering horses or consuming infected horse meat) were identified in the Philippines outbreak in 2014. There is evidence that Nipah virus can infect other animals, including dogs, cats, goats and sheep.
The most important complication of Nipah virus infection is encephalitis, which is associated with a high mortality rate; however, the full spectrum of clinical illness is not completely understood. The incubation period is thought usually to be 4 to 14 days, although a period as long as 45 days has been reported.
Typically patients present with a sudden onset, non-specific flu-like or febrile illness, sometimes with gastrointestinal symptoms. Pneumonia and other respiratory manifestations have also been described as a feature, but their onset appears to be variable. These are typically in addition to other signs and symptoms and vary in frequency according to the outbreak (29% in Malaysia; 75% in Bangladesh).
In many of the patients in reported series, symptoms and signs of encephalitis and/or meningitis developed after 3 to 14 days of initial illness. Cerebrospinal fluid abnormalities are similar to those seen in other acute viral CNS infections. Magnetic resonance imaging of the brain may reveal multiple small subcortical and deep white matter lesions, without surrounding oedema, but these abnormalities may be seen in other acute CNS infections.
Rapid progression to critical illness is said to occur in approximately 60% patients. Mortality has also varied between outbreaks but is high overall (40 to 75%). Neurological sequelae may occur in survivors, including relapsing encephalitis with delayed reactivation of latent virus infection.
Nipah virus is classed as an airborne high consequence infectious disease (HCID) in England and clinical assessment should be performed by specialist hospital staff, with adherence to strict infection prevention and control precautions (see below) to prevent secondary transmission.
There are currently no agreed case criteria for Nipah virus infection. Consider Nipah virus infection in a patient with a relevant travel or exposure history who presents with a compatible illness, with the onset of illness within 14 days following a potential exposure. Nipah virus infection is a rare disease and other travel associated and common infections should also be considered in the differential diagnosis.
Any suspected cases in England should be discussed with local infection specialists and with the Imported Fever Service (IFS) (24 hour telephone service: 0844 778 8990). The IFS can advise on whether laboratory testing is indicated. The IFS is also available to clinicians in Scotland, Wales and Northern Ireland.
Any suspected cases should be notified immediately to the nearest PHE Health Protection Team.
In the UK, the Rare and Imported Pathogens Laboratory (RIPL) at PHE Porton Down is the designated diagnostic laboratory. The mainstay of Nipah virus detection at RIPL is RT-PCR. Serology for Nipah antibodies is not available.
Any suspected case should be discussed with local infection specialists and with the IFS, as above. The IFS can advise on whether laboratory testing is indicated, and if so, will provide advice about the samples types required. IFS will also advise on sample collection precautions and transport requirements.
There is no proven, specific treatment for Nipah virus infection, and there is no preventative vaccine; treatment is supportive.
Clinical management of confirmed cases in England should be provided by specialist infectious diseases and critical care teams that are capable of safely managing patients with high consequence infectious diseases.
Patients have received ribavirin in previous outbreaks, but it was not possible to determine a beneficial effect of treatment. Ribavirin was ineffective in small animal models, as was chloroquine. Several experimental therapies are in pre-clinical development or phase 1 clinical trials, including monoclonal antibodies, fusion inhibitors, and novel antivirals.
Nipah virus is one of the pathogens in the WHO R&D Blueprint list of epidemic threats requiring urgent research and development action, including animal and human vaccine development. Further information on experimental therapies and vaccine development is available from WHO.
Infection prevention and control
Prevention of transmission of infection by airborne and contact routes is required. Studies have shown contamination of surfaces in hospitals during outbreaks, suggesting that there may be a risk of fomite-mediated transmission. Since Nipah virus infection is an airborne HCID, strict infection prevention and control (IPC) measures are required when caring for both suspected and confirmed patients. Appropriate respiratory isolation is essential for suspected and confirmed cases.
Hospital clinicians are advised to follow the same IPC measures used for suspected and confirmed cases of Middle East respiratory syndrome (MERS); this guidance is available on the PHE website.
Clinical laboratories should be informed in advance of samples submitted from suspected or confirmed diagnosis of Nipah virus infection, so that they can perform local risk assessments, minimise risk to laboratory workers and, where appropriate, safely perform laboratory tests that are essential to clinical care. Nipah virus is an ACDP/SAPO Hazard Group 4 pathogen.
Advice for travellers to endemic areas
Those travelling to endemic areas, particularly areas with active outbreaks, should avoid contact with bats and their environments, and sick animals. Consumption of raw or partially fermented date palm sap should be avoided. Wash fruit with clean water and avoid any fruit that has been partially eaten by animals or that may be contaminated (for example windfall fruit).
For information about current outbreaks and travel advice, see NaTHNaC
UK risk assessment
Nipah virus does not occur in the UK. Globally, Nipah virus infection has never been reported in a traveller.
The risk of a case from an outbreak area being imported into the UK is very low if standard precautions are undertaken. The main risk activities for Nipah virus infection are associated with local practices (for example collection and consumption of raw or fermented date sap) that are generally not undertaken by tourists.
The risk for other travellers, such as those visiting friends and relatives or doing local volunteer work, maybe higher dependent on activities undertaken.