Nipah virus infection is a serious disease that can spread from animals to humans. It is caused by the Nipah virus (NiV), which belongs to the Henipavirus group of viruses in the Paramyxoviridae family. The virus is naturally carried by fruit bats, especially those of the genus Pteropus. In humans, the illness can range from showing no symptoms at all, to mild flu-like sickness, to severe breathing problems and dangerous brain inflammation (encephalitis), which can be fatal.
People can catch the virus in several ways: through contact with infected animals such as pigs, touching surfaces or food contaminated by bat secretions, drinking raw date palm sap that bats have licked or urinated on, or through close contact with infected people. Person-to-person spread has been confirmed, particularly in outbreaks in Bangladesh and India, which has raised concerns about its potential to cause larger epidemics.
The virus was first discovered in 1998 during an outbreak among pig farmers in Malaysia, which also spread to Singapore through pig exports. Since then, small outbreaks have occurred almost every year in South and Southeast Asia, with most cases reported in Bangladesh and India. Death rates from the infection are high, usually between 40% and 75%, making it one of the deadliest known emerging diseases.
The first signs of Nipah virus infection are similar to influenza, with symptoms such as fever, headache, muscle pain, and dizziness. In severe cases, the disease can quickly worsen, leading to swelling of the brain (encephalitis), seizures, coma, and failure of multiple organs.
Currently, there are no approved vaccines or specific medicines to treat Nipah virus. Care is supportive, meaning doctors can only manage symptoms and complications. Prevention mainly involves avoiding contact with bats and pigs, not drinking raw date palm sap or eating fruit that may have been contaminated, and following strict infection-control practices during outbreaks.
History of Nipah Virus
The Nipah virus was first identified during an outbreak in Malaysia between 1998 and 1999. The outbreak primarily affected pig farmers and abattoir workers, who were infected through close contact with pigs carrying the virus. More than 250 human cases were reported, with over 100 deaths, and millions of pigs were culled to control the spread. The disease was first mistaken for Japanese encephalitis due to similar neurological symptoms, but further investigation identified a novel virus, later named Nipah virus after Sungai Nipah, a village in Malaysia where early cases were detected. The outbreak also extended to Singapore through imported pigs, resulting in several human infections.
Following the Malaysian outbreak, sporadic cases and outbreaks have been reported almost every year, primarily in South and Southeast Asia. Bangladesh confirmed its first outbreak in 2001, and since then has experienced repeated episodes, often linked to the consumption of raw date palm sap contaminated by fruit bat secretions. India has also reported several outbreaks, notably in West Bengal in 2001 and 2007, and in Kerala in 2018, 2019, 2021, and 2023, with high fatality rates.
Over time, the epidemiology of Nipah virus infection has shifted. While the initial Malaysian outbreak was driven by pig-to-human transmission, later outbreaks in Bangladesh and India have shown clear evidence of direct bat-to-human transmission and human-to-human spread. These findings have heightened global concern about the virus’s potential to cause larger epidemics.
Since the 1999 discovery, research has focused on understanding how the virus spreads, improving laboratory diagnosis, and investigating vaccines and antiviral treatments. Nipah virus is now considered a priority pathogen by the World Health Organization (WHO) due to its high case-fatality rate, lack of specific treatment, and potential to cause widespread outbreaks.
Causes and Transmission
Nipah virus infection occurs primarily through contact with certain animals or exposure to bodily fluids from infected individuals. The virus has specific animal hosts and spreads in defined ways between animals and humans, as well as between humans.
Primary Animal Reservoirs
Fruit bats, particularly those of the genus Pteropus (commonly known as flying foxes), are recognized as the natural reservoirs of Nipah virus. These bats can harbor the virus without showing signs of illness, enabling its persistence within bat populations across large geographical ranges. Viral shedding occurs through bat saliva, urine, feces, and birthing fluids.
Human exposure often results from contact with food or surfaces contaminated by these secretions. In parts of South Asia, consumption of raw date palm sap contaminated by bats is a well-documented route of transmission. Bats may lick the sap as it drips from trees or urinate in collection pots, introducing the virus into the food supply.
Although bats serve as the reservoir, other animals can act as amplifying hosts, facilitating transmission to humans. Pigs were the most significant intermediate hosts during the first major outbreak in Malaysia (1998–1999). Infection spread among pig populations after exposure to bat excretions in orchards adjacent to pig farms. Close contact with infected pigs, particularly in farming and slaughterhouse environments, then allowed transmission to humans.
Experimental studies have shown that several other domestic and wild animals including goats, horses, and cats can become infected. However, pigs remain the primary intermediate host implicated in large-scale human outbreaks.
Human-to-Human Transmission
Human-to-human transmission of Nipah virus has been documented repeatedly, particularly in outbreaks in Bangladesh and India. Transmission occurs mainly through direct contact with bodily fluids such as saliva, blood, urine, and respiratory droplets. Close physical contact with patients during caregiving, including family members and healthcare workers, carries the highest risk.
Nosocomial (hospital-acquired) outbreaks have been reported, where inadequate infection-control measures facilitated spread between patients, staff, and visitors. Unlike bat-to-human or pig-to-human transmission, person-to-person spread has made containment more challenging in densely populated regions.
Transmission is most likely during the symptomatic phase of infection, especially when patients develop respiratory illness or neurological complications. Current evidence suggests that individuals are not contagious during the incubation period before symptoms appear.
Routes of Exposure
Nipah virus reaches humans through three main exposure routes:
- Animal-to-human transmission – occurs via consumption of contaminated food (particularly raw date palm sap) or direct contact with infected pigs or other intermediate hosts. Handling of animal tissues or carcasses increases the risk.
- Environmental exposure – results from contact with objects, surfaces, or food items contaminated by bat secretions. Fallen fruit partially eaten by bats has also been implicated.
- Human-to-human transmission – occurs through close contact with symptomatic patients, especially when proper protective equipment is not used.
Preventing Nipah virus transmission requires minimizing contact with both natural reservoirs and infected individuals. Measures include discouraging consumption of raw date palm sap, covering collection pots to prevent bat contamination, and avoiding fruit that may have been partially eaten by bats.
Farmers and animal handlers are advised to limit contact with sick animals and to use protective gear. In healthcare settings, strict infection-control practices including use of personal protective equipment, isolation of suspected cases, and safe handling of patient waste are critical to preventing secondary outbreaks.
Symptoms and Clinical Presentation
Nipah virus infection presents with specific early signs that rapidly evolve. The disease primarily affects the respiratory and nervous systems, leading to severe complications.
Initial Symptoms
The infection often begins with fever, typically high-grade and sudden in onset. Patients may experience headache, muscle pain, and sore throat.
Other common initial signs include dizziness, vomiting, and fatigue. These symptoms appear within 5 to 14 days of exposure.
Early respiratory issues such as cough and difficulty breathing may also be present but are less common at the onset.
Progression of Disease
Within a few days, symptoms usually worsen, especially involving the central nervous system. Patients may develop confusion and exhibit disorientation.
Drowsiness and lethargy increase, often progressing to coma in severe cases. The respiratory involvement may become more pronounced with acute respiratory distress.
The incubation period can vary, but respiratory failure and neurological decline usually occur within the first two weeks after symptom onset.
Neurological Manifestations
Neurological symptoms dominate as the virus affects the brain. Encephalitis, or brain inflammation, is common and manifests as seizures and impaired consciousness.
Patients can show signs of difficulty speaking, weakness, or paralysis. The extent may range from mild confusion to deep coma.
Long-term neurological impairments may persist in survivors, including memory loss and cognitive dysfunction.
Complications
Severe respiratory illness is a common feature in many outbreaks. Patients may develop acute respiratory distress syndrome (ARDS), a life-threatening condition in which fluid accumulates in the lungs, making breathing difficult and preventing adequate oxygen exchange. In critical cases, this can progress to acute respiratory failure, which often requires mechanical ventilation and intensive care. Respiratory involvement not only worsens outcomes for patients but also increases the risk of human-to-human transmission due to the release of infectious droplets.
Neurological involvement is one of the hallmarks of Nipah virus infection. The virus can cause acute encephalitis, an inflammation of the brain that manifests as seizures, confusion, disorientation, altered consciousness, and, in severe cases, coma. Survivors of encephalitis may experience long-term neurological problems such as personality changes, cognitive impairment, persistent convulsions, or motor dysfunction.
Relapsing or late-onset encephalitis has also been documented, in which patients who initially recovered later developed neurological symptoms weeks, months, or even years after infection. This feature distinguishes Nipah virus infection from many other viral encephalitides and complicates long-term prognosis.
In the most severe cases, Nipah virus infection can progress to multi-organ dysfunction syndrome (MODS), where multiple vital organs including the lungs, kidneys, and liver begin to fail simultaneously. This is often accompanied by septic shock, a severe condition caused by overwhelming infection and systemic inflammation.
Secondary bacterial infections are also possible, particularly in patients requiring prolonged hospitalization or mechanical ventilation. These infections can further increase the risk of mortality.
Mortality rates in Nipah virus infection are consistently high. Case-fatality rates vary by outbreak and location, ranging from 40% to more than 70%.
Diagnosis of Nipah Virus Infection
Accurate diagnosis of Nipah virus infection relies on several specialized methods and proper sample collection techniques. Identification must distinguish Nipah virus from other pathogens with similar symptoms to ensure appropriate treatment and containment measures.
Diagnostic Techniques
Laboratory diagnosis of Nipah virus primarily involves molecular tests and serological assays. Reverse transcription polymerase chain reaction (RT-PCR) is the most widely used and reliable diagnostic technique. It identifies viral RNA in clinical specimens, including blood, cerebrospinal fluid (CSF), throat or nasal swabs, and urine. Real-time RT-PCR allows for rapid confirmation during acute infection, particularly in the early symptomatic phase.
Virus isolation using cell culture can confirm diagnosis but is rarely performed outside of research and reference settings. Because Nipah virus is classified as a Biosafety Level 4 (BSL-4) pathogen, virus isolation requires specialized containment laboratories, significantly limiting its availability.
Antibody-based tests such as enzyme-linked immunosorbent assay (ELISA) are used to detect immune responses against the virus. The presence of IgM antibodies indicates recent or active infection, while IgG antibodies signal past infection or exposure. Serology is particularly useful for retrospective diagnosis and for surveillance in outbreak settings, though antibodies may not be detectable during the early phase of illness.
Newer diagnostic approaches, including lateral flow assays and next-generation sequencing (NGS), are under investigation to improve field-level detection and outbreak response.
Sample Collection Methods
Timely and proper sample collection is critical for accurate diagnosis. Blood, CSF, nasopharyngeal swabs, and urine are key specimens used. Samples must be collected during the acute stage, ideally within the first week of symptom onset.
Sterile technique and appropriate cold chain maintenance are essential to preserve viral RNA integrity. Samples should be transported promptly to specialized reference laboratories equipped for high-containment pathogen handling.
During outbreak investigations, additional samples may be collected from animals (e.g., pigs or bats) or environmental sources such as contaminated food or surfaces to trace the origin of infection.
Differential Diagnosis
Because Nipah virus infection presents with non-specific symptoms such as fever, headache, and respiratory distress, it can be mistaken for several other viral diseases. Differential diagnosis is therefore critical.
- Neurological illnesses: Rabies, Japanese encephalitis, and herpes simplex virus encephalitis share overlapping features such as confusion, seizures, and coma.
- Other henipavirus infections: Hendra virus, another closely related henipavirus found in Australia, produces similar neurological and respiratory manifestations.
- Respiratory diseases: Influenza, COVID-19, and severe acute respiratory syndrome (SARS) may resemble early stages of Nipah infection, particularly when respiratory symptoms predominate.
Laboratory testing differentiates Nipah virus by confirming specific viral RNA or antibody presence. Clinical history, exposure risks, and epidemiological context further aid in ruling out other zoonotic and viral encephalitis causes.
Treatment and Management
The management of Nipah virus (NiV) infection is largely supportive, as no licensed antiviral therapy or vaccine currently exists.
Supportive Care
Supportive care forms the basis of treatment for Nipah virus infection. Patients are closely monitored for vital signs, fluid balance, and oxygen levels to prevent complications associated with respiratory and neurological involvement. Hydration and electrolyte replacement are critical, particularly in patients experiencing high fever, vomiting, or reduced oral intake. Nutritional support is emphasized, especially in those with impaired swallowing due to neurological symptoms.
Fever and pain are generally managed with acetaminophen (paracetamol), while nonsteroidal anti-inflammatory drugs (NSAIDs) are typically avoided because of the potential risk of bleeding. Neurological status is regularly assessed, as encephalitis is a common and severe complication. Early identification of altered mental status, seizures, or loss of consciousness allows for prompt escalation of care.
Antiviral Therapies
No antiviral drugs have been formally approved for the treatment of Nipah virus infection. The antiviral agent ribavirin has been used experimentally in several outbreaks, but clinical evidence for its effectiveness remains inconclusive. Other compounds, such as favipiravir, have shown activity against Nipah virus in laboratory models, but their role in human treatment has not yet been established.
Research is ongoing into monoclonal antibodies that specifically target Nipah virus glycoproteins. The investigational monoclonal antibody m102.4 has shown promise in animal studies and has been administered to a limited number of humans under compassionate use protocols, though it remains in the experimental stage. Broad-spectrum antiviral agents and novel therapeutics are also under study, but their availability is currently restricted to clinical trials.
Preventive or prophylactic use of antivirals is not recommended due to insufficient data on efficacy and safety.
Critical Care Management
Patients with severe Nipah virus infection often require admission to intensive care units. Respiratory complications such as acute respiratory distress syndrome (ARDS) or respiratory failure may necessitate mechanical ventilation and supplemental oxygen therapy. Cardiovascular instability, including septic shock, is managed with intravenous fluids and vasopressor agents to maintain blood pressure.
Neurological complications such as seizures are treated with anticonvulsant medications under specialist supervision. In cases of encephalitis, careful management of intracranial pressure and neurological function is essential. Multi-organ failure may occur in advanced stages, requiring coordinated organ support and multidisciplinary care.
Isolation protocols must be strictly followed to prevent nosocomial transmission. Multidisciplinary teams coordinate care to manage complications and organ support effectively.
Prevention and Control Strategies
Effective prevention and control of Nipah virus infection require specific actions at the individual level, and healthcare settings.
Individual Protective Measures
- Food Safety Practices – Avoid consuming raw date palm sap, as fruit bats may contaminate it with saliva, urine, or feces; boiling or pasteurizing sap inactivates the virus; wash fruits with safe water before eating and consume only well-cooked food.
- Avoidance of Animal Contact – Avoid direct contact with pigs and other potential hosts in outbreak-prone areas; during the 1998–1999 Malaysian outbreak pigs were amplifying hosts; individuals working with livestock should use PPE such as gloves, boots, and protective clothing.
- Precautions in Human-to-Human Transmission – Human-to-human transmission has occurred in Bangladesh and India; caregivers and healthcare workers should wear gloves, masks, gowns, and eye protection; frequent handwashing with soap or alcohol-based sanitizers is essential.
- Travel-Related Precautions – Travelers to outbreak regions should monitor health advisories, avoid unnecessary visits to healthcare facilities, practice good hygiene, and minimize contact with individuals showing respiratory or neurological symptoms.
- Additional Preventive Behaviors – Although mosquitoes are not vectors of Nipah virus, mosquito nets and repellents can help prevent secondary infections; public health campaigns stress education and behavior change, especially regarding raw sap consumption in rural communities.
Healthcare Facility Protocols
Healthcare settings must enforce strict infection control protocols, including isolating suspected and confirmed Nipah virus patients in negative-pressure rooms where possible. Staff should consistently use personal protective equipment (PPE).
Routine screening of admitted patients for symptoms compatible with Nipah infection helps early identification. Procedures generating aerosols require additional precautions to prevent airborne transmission.
Training healthcare workers on patient handling, safe waste disposal, and sterilization reduces nosocomial infections. Facilities should maintain clear communication channels with public health authorities for timely reporting and guidance.
Vaccine Research and Development
Research into vaccines against Nipah virus (NiV) has been a global health priority since the virus was first identified in 1998. Nipah virus poses a serious public health threat due to its ability to cause severe encephalitis and respiratory disease, its high case fatality rate, and the potential for human-to-human transmission during outbreaks. Despite the urgency, no licensed vaccine currently exists, and research remains in preclinical and early clinical phases. The sporadic nature of Nipah outbreaks, combined with their geographic concentration in South and Southeast Asia, complicates vaccine development. Conducting large-scale efficacy trials is difficult because outbreaks are unpredictable, short in duration, and often limited to rural or resource-constrained areas. Furthermore, the virus requires Biosafety Level-4 (BSL-4) containment, limiting laboratory research capacity. A vaccine candidate must not only demonstrate robust protective immunity but also be safe for use in populations at high risk, including healthcare workers, farmers, and individuals in endemic regions.
Several vaccine platforms are under investigation, including vector-based vaccines, subunit vaccines, and mRNA vaccines.
- Vector-Based Vaccines: Viral vector approaches, such as those using adenoviruses, measles virus backbones, or vesicular stomatitis virus (VSV), deliver NiV glycoprotein genes to stimulate an immune response. Experimental vaccines based on these vectors have demonstrated strong antibody and T-cell responses in animal models, including non-human primates.
- Subunit Vaccines: Subunit formulations focus primarily on the viral glycoprotein (G protein), which mediates attachment to host cells. Recombinant soluble G protein vaccines have induced neutralizing antibodies and conferred protection in ferret and hamster models. These vaccines are considered safer because they do not involve live virus, but they often require adjuvants to enhance immune responses.
- mRNA Vaccines: Following the success of mRNA vaccine technology against COVID-19, research has expanded to apply similar methods to Nipah virus. mRNA vaccines encoding viral proteins aim to stimulate rapid and durable immune responses. Preclinical studies are ongoing, and early results suggest that this platform could accelerate vaccine readiness for emerging infectious diseases like NiV.
- DNA Vaccines: DNA-based candidates have also been tested in animal models, showing potential to elicit neutralizing antibodies and cell-mediated responses, though their clinical utility remains under evaluation.
Animal studies have provided encouraging data, with several candidates protecting non-human primates from lethal NiV challenge.
| Vaccine Type | Development Status | Key Features |
| Vector-based | Preclinical/Phase 1 trials | Uses harmless viruses to deliver NiV proteins |
| Subunit | Preclinical | Contains purified viral proteins to stimulate immune response |
| mRNA | Experimental | Utilizes genetic instructions to produce viral proteins in the body |
Challenges persist in translating animal model success to humans. The rarity and unpredictability of Nipah outbreaks complicate large-scale human trials.
The Coalition for Epidemic Preparedness Innovations (CEPI) is actively funding Nipah vaccine projects. Their goal includes accelerating research through partnerships and preparedness for potential outbreaks.
Nipah Virus Outbreaks
Nipah virus outbreaks have occurred sporadically since its discovery, often linked to contact with infected animals or contaminated food.
The first identified Nipah virus outbreak occurred in Malaysia and Singapore in 1998-1999. It infected over 260 people, causing 105 deaths. The outbreak was primarily associated with pig farms, where pigs acted as amplifying hosts after exposure to fruit bats of the genus Pteropus. Human cases largely involved pig farmers and abattoir workers who had close occupational contact with infected animals. The outbreak had major economic consequences, leading to the culling of over one million pigs to halt transmission.
In 2001, outbreaks in Bangladesh emerged, involving direct human-to-human transmission and consumption of date palm sap contaminated by fruit bats. These outbreaks demonstrated a higher fatality rate, often exceeding 70%.
India experienced outbreaks in 2001 and 2018. The 2018 Kerala outbreak resulted in 17 cases with 17 fatalities, highlighting the virus’s lethal potential and challenges in containment.
Lessons Learned
Key lessons include the importance of identifying animal reservoirs early to prevent zoonotic spillover. The Malaysia outbreak underscored risks in pig farming, prompting changes in livestock management.
Human-to-human transmission in Bangladesh and India revealed the need for infection control in healthcare settings. Better protective measures and public awareness campaigns have since been prioritized.
The role of traditional foods like date palm sap as transmission vehicles led to targeted interventions in affected regions. Surveillance systems have been strengthened for rapid outbreak detection.