JOINT MOH/ NCID GUIDANCE ON NIPAH VIRUS INFECTION FOR HEALTHCARE PROFESSIONALS
DISEASE BACKGROUND AND OUTBREAK CHARACTERISTICS
1. The Nipah Virus (NiV) is an RNA virus that belongs to the genus Henipavirus of the Paramyxovirus family. Its natural reservoir hosts are fruit bats (Pteropus spp.) and possibly other species of bats. Pigs may serve as intermediate amplifying hosts for outbreaks in humans. Animal-to-human transmission may occur by: (i) direct contact with infected animals, such as bats and pigs, or their body fluids or excretions; and (ii) consumption of raw date palm sap or fruits contaminated by saliva or urine of infected bats. Limited human-to-human transmission of NiV among family, caregivers, community contacts, and healthcare providers of infected NiV patients through close contact with their secretions and excretions has been documented.
2. NiV was first identified in an outbreak of acute encephalitis among pig farmers in Malaysia in 1998-1999, which saw 265 cases of acute encephalitis (brain infection), accounting for 105 deaths. As part of this outbreak, Singapore saw 11 cases in March 1999, with one fatality. A high incidence of cases during the Malaysia-Singapore outbreak presented with encephalitis or had neurological symptoms, with no occurrence of human-to-human transmission. In subsequent outbreaks in Bangdalesh and India, a higher incidence of respiratory involvement were reported with limited human-to-human transmission.
3. NiV infection can cause severe neurological symptoms and/or encephalitis and pneurmonia. It is a highly fatal illness, with a case fatality ratio (CFR) estimated between 40 to 75% in past outbreaks depending on local capabilities for epidemiological surveillance and clinical management (CFR ~ 40% for outbreaks in Malaysia and Singapore; CFR >70% for outbreaks in Bangladesh). At present, there are no licensed vaccines or therapeutics available for the prevention and treatment of NiV infection.
4. On 12 September 2023, the Kerala State Health Department of India confirmed an outbreak of NiV in Kozhikode district, Kerala State. As of 29 September, six laboratory-confirmed human cases of NiV infection, including two deaths (CFR: 33%), were reported in this outbreak. Public health measures including closure of public institutions, quarantine, contact tracing, strengthening surveillance and infection control activities at health facilities, and risk communications to the community had been imposed to mitigate the spread of NiV infection in Kerala. At the time of publication, most public health measures have been lifted, although the public was advised to exercise caution till 26 October, which marks the 42nd day after the last reported case on 15 September. The source of the outbreak remains under investigation. More information on the outbreak in Kerala can be found at https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON490.
SIGNS AND SYMPTOMS
5. The incubation period of the NiV in humans is between 4 to 45 days, with >90% of symptoms developing between 4 and 14 days after exposure. Asymptomatic and mild infections have been reported, but only a minority of infected persons (<10%) were found to be truly asymptomatic. Human-to-human transmission has been reported. Duration of infectious period is unknown, but it likely begins during the incubation period and continues until the patient stops shedding the virus.
6. As the signs and symptoms for NiV are non-specific, doctors should be alert to any traveller from NiV-affected regions with these presentations. In addition, doctors should always ask for travel history in patients presenting with signs and symptoms of encephalitis or respiratory distress, as they can be the result of many severe travel-related illnesses.
7. Doctors should suspect NiV infection in patients who present with:
AND
- Within the last 14 days prior to onset of symptoms,
- Travel from NiV affected countries or regions (currently Kerala, India) with an ongoing NiV outbreak; OR
- Exposure to bats or bat-contaminated food or pigs; OR
- Exposure to a confirmed NiV case; OR
- Consumed sap or other products from palm trees
8. NiV infection is a notifiable disease under the Infectious Diseases Act (IDA). Any patient suspected of being infected with NiV infection should be reported to MOH immediately via the Surveillance Duty Officer, followed by submission of the MD131 Notification of Infectious Diseases Form through the Communicable Diseases Live & Enhanced Surveillance (CDLENS) system.
DIAGNOSIS
9. Diagnosis in acute infection is primarily by detection of NiV by PCR in blood samples. The samples can be sent to the National Public Health Laboratory (NPHL) for diagnosis of acute NiV infection. Where in doubt, the laboratory should contact NPHL for further assistance.
CLINICAL MANAGEMENT
10. The initial clinical manifestations of NiV infection are non-specific and are similar to other diseases such as viral encephalitis, bacterial meningoencephalitis and pneumonia. It is important to evaluate and manage (as applicable) suspect cases for more common causes of encephalitis (including Japanese encephalitis virus and rickettsial infections) or acute respiratory distress according to local guidelines until the diagnosis of NiV infection is confirmed.
11. Patients with NiV infection generally present with fever, headache, dizziness and vomiting. Central nervous system (CNS) involvement occurs in the vast majority of symptomatic cases. A broad spectrum of neurological presentations has been reported, including aseptic meningitis, focal brainstem involvement, and diffuse encephalitis. Seizures and myoclonic jerks may occur in 20% of patients, while cerebellar signs are reportedly common. The disease is rapidly progressive for a majority of patients, with clinical deterioration leading to brainstem dysfunction and coma in 5-7 days. In survivors, relapsing and late-onset encephalitis (up to 11 years in the longest known case) are distinguishing features, occurring in up to 20% of cases. MRI brain in patients with CNS involvement typically demonstrates multiple small, discrete, hyper-intense lesions in the cerebral cortex, subcortical and deep white matter. Disseminated multifocal and confluent lesions in both cortex and white matter were also observed. CSF is abnormal in the majority of patients, showing lymphocytic pleocytosis and elevated protein.
12. Respiratory involvement occurs in up to 69% of cases, with the majority presenting with cough and dyspnoea. Chest X-ray changes of pneumonia and acute respiratory distress have been described.
13. Clinical management is supportive, and the respective specialists (neurologists, respiratory physicians, infectious diseases physicians, etc.) can be consulted according to clinical needs. Ribavirin has been used to treat NiV infections, but there are no rigorous studies on its actual efficacy. There are monoclonal antibody therapies that are currently under development and evaluation for treatment of NiV infections, and one monoclonal antibody from Australia, m102.4, has completed phase 1 clinical trials and has been used on a compassionate use basis. In addition, the antiviral treatment remdesivir has been effective in nonhuman primates when given as post-exposure prophylaxis, and may be complementary to immunotherapeutic treatments, although human data are lacking . Late remdesivir treatment (3 days post infection) has been reported to partially protect African green monkeys from lethal Nipah virus infection.The drug ribavirin was used to treat a small number of patients in the initial Malaysian NiV outbreak, but its efficacy in people is unclear. Confirmed cases can be transferred to NCID for further management at the discretion of the primary physician/hospital.
INFECTION PREVENTION AND CONTROL
14. Patients who are under investigation or confirmed to have NiV infection should ideally be isolated in an airborne infection isolation room (AIIR) and be placed on strict contact, droplet and airborne precautions – healthcare staff directly involved in patient care should don PPE1 comprising gowns, gloves, N95 masks and eye protection (face shield/ eye goggles) when attending to these patients. Risk to healthcare staff can be mitigated with good infection prevention and control practices. Visitors should not be allowed.
15. All waste generated during the care of NiV suspect and confirmed patients should be handled as biohazard waste, according to institutional policy.
16. Linen and laundry from suspects and confirmed cases should be managed as infectious linen and laundry. Institutions may consider the use of disposable linen.
17. Rooms occupied by suspect or confirmed cases of NiV should be terminally cleaned with bleach-based disinfectants after discharge. Enhancement of terminal cleaning with either UV-C disinfection system or hydrogen peroxide vaporization is recommended.
18. On the management of deceased bodies of suspect or confirmed cases of NiV, the handling of the body should be kept a minimum . The ward/hospital staff should ensure the following:
- All orifices must be plugged in with 10,000 ppm sodium hypochlorite.
- The body is double-bagged in sealed and leak-proof heavy-duty plastic cadaveric body bags, before the body is taken out of the isolation room.
- The surface of each body bag is wiped down with a suitable disinfectant (e.g. bleach), sealed and affixed with a ‘biohazard’ label.
- The body should not be sprayed, washed or embalmed.
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1: Personal protective equipment (PPE) posture will be reviewed from time to time as more data about the outbreak is available.
