Fruit bats, also called flying foxes, are the animal reservoir for NiV in nature. Nipah virus is also known to cause illness in pigs and people. Infection with NiV is associated with encephalitis swelling of the brain and can cause mild to severe illness and even death. Outbreaks occur almost annually in parts of Asia, primarily Bangladesh and India.
Nipah virus infection can be prevented by avoiding exposure to sick pigs and bats in areas where the virus is present, and not drinking raw date palm sap which can be contaminated by an infected bat.
Nipah rarely infects people, but when it does, it can make them very, very sick. It causes encephalitis, a brain inflammation that is often fatal and that can cause long-term disabilities in survivors. In some outbreaks, it has also caused severe respiratory infections, according to the World Health Organization.
Each outbreak is different. In some of the earlier outbreaks, Nipah virus infection killed 40 percent of people. It can also remain in the body for months and even years, according to the Centers for Disease Control and Prevention. Nipah virus is carried by fruit bats. Instead, the problem comes when people and livestock share fruit with bats. Nipah was first identified in Malaysia in Many farmers also grew mango trees near the pig pens. Bats would drop pieces of mango into the pens, and the pigs would grab them.
This is vital to determine the spectrum of NiV strains circulating in India and South Asia, know if there are more-virulent forms of the virus, and to make generalisable predictions on when bats experience outbreaks, Epstein said.
He added that even if NiV outbreak among fruit bats in India may follow a similar cyclic pattern, the periodicity may be different. Commenting on the study, virologist Upasana Ray, who was unrelated to the research team, said the findings highlight the importance of surveillance of animal pathogens to predict their odds of spilling over to humans.
Such ELISAs are valuable diagnostic methods for seromonitoring of swine population and probably livestock and wildlife animals. A unique primer set targeting the N gene has been reported. Advancements in the field of diagnosis of emerging zoonotic pathogens following an integrated One Health approach need to be explored optimally Bird and Mazet Vaccination of humans is an integral part of preventing infection due to NiV.
Prevention also includes vaccination of livestock especially pigs and probably horses in endemic areas Broder et al. Of note, outbreaks cannot be prevented amongst the livestock population in areas where contamination of date palm sap acts as major contributor to the spread of NiV infection. However, if vaccination of livestock is made cheap it may prove to be successful in certain regions. Extensive research involving preclinical studies in a number of animals and nonhuman primates have identified multiple vaccine candidates, including vectored and subunit vaccines, offering protective immunity Satterfield et al.
Among vectored vaccines, one employing vesicular stomatitis virus has shown protection inferrets, African green monkeys, as well as hamsters Mire et al.
Despite these developments, funding for human clinical trials of candidate vaccines remains a problem for academic community. The pharmaceutical companies are hesitant to invest in research on development of vaccines for diseases like Nipah, which are rare occurrences, despite the high fatality.
A collaborative effort has been undertaken by both government and pharmaceutical companies, known as the Coalition for Epidemic Preparedness Innovations CEPI. It was formed in January for developing safe, efficacious and affordable vaccines against diseases associated with pandemic potential, like Nipah Satterfield CEPI aims to develop two new experimental vaccines within five years, in the first phase of the clinical trial.
It is anticipated that field efficacy studies of such vaccines could be done during massive outbreaks Satterfield DNA vaccines, virus-like particles, virus vectors live and recombinant , and other advanced vaccines have been developed as strategies of immunization against both HeV and NiV Walpita et al.
A recombinant measles virus rMV vaccine that expresses envelope glycoprotein of NiV has been found to be promisingfor use in man Yoneda A replication-competent, recombinant VSV-vectored vaccine encoding NiV glycoprotein was reported to show high efficiency in a hamster model. A single intramuscular dose of the vaccine conferred protective immunity in African green monkeys one month after vaccination Prescott et al.
Healthcare workers and family contacts attending Nipah cases should be considered for Nipah vaccination, in order to limit human-to-human transmission and curb outbreaks DeBuysscher et al. A very strong virus-specific immune response is generated through vaccination which inhibits the virus replication and shedding. Such vaccine could provide protection from NiV in disease outbreaks. Attenuated live vaccines as well as subunit G recombinant platforms have also been tested Satterfield et al.
The immunogenicity of the NiV-VLP vaccine was high because the VLPs possess the native characteristics of the virus including the size, morphology and surface composition Jegerlehner et al. A recent work reported a novel strategy of adding a cholesterol group to the C-terminal heptad repeat HRC of the F protein that facilitated membrane targeting and fusion of the peptide.
Enhanced penetration of the central nervous system and significant increase in antiviral effects were observed with these peptides Porotto et al. Golden Syrian hamsters immunized with these VLPs developed high titres of neutralizing antibody in serum, and showed complete protection upon viral challenge Walpita et al.
Immunoinformatic advances have been utilized for developing peptide-based NiV vaccine by prediction and modeling of T-cell epitopes of NiV antigenic proteins. Specific epitopes, viz. Such predicted peptides can potentially stimulate T-cell-mediated immunity and could have utility in developing epitope-based vaccines to counter NiV. Such approach identified B-cell epitope sequences in phosphoprotein to , polymerase enzyme gene to and nucleocapsid protein to These studies are oriented for the validation of potential vaccine candidate protein portions from Nipah virus which could then spearhead towards the development of fruitful subunit vaccines Ravichandran et al.
The development of animal models of NiV disease is another priority, in order to evaluate the preventive and therapeutic approaches. This will help in employing successful immunization strategies both active as well as passive by targeting the envelope glycoprotein of the virus Broder et al.
An overview on different vaccine strategies available for Nipah virus NiV is presented in Table 1 and few important vaccine platforms are depicted in Figure 5. Vaccine platforms for NiV.
Recombinant measles virus rMV vaccine that expresses envelope glycoprotein of NiV has been found to be effective vaccine candidate. A recombinant vaccine based on vesicular stomatitis virus replication-competent has been developed in recent years encoding a glycoprotein of NiV.
Outbreaks of NiV invoke costly emergency responses around the world. NiV poses a greater threat in regions associated with risk factors and with poor indicators of development Tekola et al. With climate change and human encroachment into flying fox habitats, it is likely that outbreaks will occur in new locations Satterfield Strategies other than vaccination also play crucial roles in prevention and control of human NiV infection and would prove to be more economical.
Prevention of infection in livestock could be an efficacious strategy in regions where theyserve as intermediate hosts. It involves keeping fruit as well as bat roosting trees away from the livestock farms and grazing lands susceptible to virus contamination. In certain countries, like Malaysia, such effort is already proven to be highly effective Satterfield The control is much tougher in regions where contaminated date palm sap is the primary source of NiV. In such regions, human behavioral changes, viz.
In Bangladesh, date palm sap is usually harvested overnight. The nocturnal activities of bats such as drinking from, defecating or urinating in the date palm sap collection jars have become evident through infrared cameras. Measures to prevent the access of bat to the sap stream of the date palm tree as well as shaved surface can minimize the risk of human exposure to NiV in such settings Khan et al.
Creating public awareness about avoidance of consumption of raw sap and preventing contamination of the sap collection potswere the essential approaches to prevent the disease in Bangladesh during — Nahar et al. When the genomes of Squirrel monkey, Cynomolgus macaques and African green monkey are analyzed it sheds light on protection against the infection caused by NiV with the aid of immune factors of man. Cynomolgus macaques do not develop signs of NiV infection while Squirrel monkeys and African green monkeys develop symptomatic infection.
NiV is endemic in Southeast Asia where co-evolution of the virus has taken place likely with other Henipaviruses apart from NiV. Squirrel monkeys are found in central as well as south America while African green monkeys inhabit Africa. Full genome sequencing along with annotation of such species of primates is possible due to the availability of improved DNA sequencing technology.
This can yield insights on the host genetics conferring susceptibility of certain primate species to NiV infection and might inform on therapeutic and preventive targets in humans Satterfield The National Centre for Disease Control NCDC reported that implementation of infection control and precaution at both household and hospital levels helps to limit the NiV disease outbreak.
Sporadic nature of NiV outbreaks, lack of information of exact correlates of protective immunity, lack of interest among private pharmaceutical companies, and inadequate availability of BSL4 laboratory facilities to test the vaccines or therapeutics against NiV in preclinical models pose challenges to NiV vaccine development.
Development of diagnostics suitable for field conditions, immunotherapeutic approaches, vaccines and antiviral drugs are urgent priorities for long-term measures aimed at prevention and control of NiV disease. Utmost care should be taken in order to avoid direct contact with the persons infected by NiV.
Personal protection devices, viz. In nations having no past history of Nipah viral outbreak, anticipatory preparedness for rural as well as urban outbreaks of the disease will ultimately help in prevention and control of potential outbreaks Donaldson and Lucey Control measures adopted during the NiV outbreaks in Malaysia have shown the involvement of multidisciplinary, multi-ministerial teams in a close collaborative and cooperative manner with various agencies at international level Chua Such approach needs to be adopted in case of the unpredictable disease outbreaks and deadly epidemics for controlling the spread of the virus Kumar and Anoop Kumar With recent outbreaks of emerging and re-emerging pathogens posing challenges to humanity, a rapid detection and characterization of infectious agents is being emphasized worldwide as well as laboratories are getting prepared for performing more advanced and sophisticated research to counter disease outbreaks owing to lethal pathogens flaring up in the 21 st Century.
Many microorganisms studied in veterinary laboratories also have the potential to infect humans Brass et al. Such team should include: medical doctors, veterinarians and agriculturists; officers from public health sectors; vector biologists as well as ecologists and phylogeneticists who can altogether put combined effort for preventing any major outbreak Zumla et al. The role of bats in transmission and spread of the pathogens need to be understood in depth so as to avoid cross-species spill over especially of the deadly virusesat wild and domestic animals as well as human interface.
As an illustration, screening of fecal samples of bats in caves often visited by local residents to gather manure or for hunting in Zimbabwe revealed the significance of virus monitoring and surveillance in bats at sites with high zoonotic diseases transmission ability and to strengthen appropriate prevention and control measures to curtail and check the dissemination of virus to other places Bourgarel et al.
A detailed understanding of the biogeography of the disease is required to comprehend the potential distribution of the NiV disease. Deka and Morshed carried out a study implementing certain means of modelling the risk of regional disease transmission viz. Such approaches help in measuring niche similarity between the ecological features and the Pteropus bats as reservoirs of NiV.
A recent bibliometric study identified a sudden increase in the number of publications referring to the eight pathogens of global concern identified by WHO, viz. Almost two decades after the first report of NiV, a fruitful development in the therapeutical and preventive aspect of this deadly disease is still lacking which adds to the public health threat out of it. According to the reports from the Centers for Disease Control and Prevention CDC , several developing as well as economically deprived countries are at high risk of Nipah outbreak Ramphul et al.
The essence of treatment modalities along with effective therapeutics is understood, once there is an outbreak of an infectious disease. There is a need for administering therapeutics to manage the patients during NiV outbreaks and to prevent the mortality. No specific drug has been yet approved for the treatment of this important disease. Limited work has been done to develop therapeutics against NiV infection. In preclinical studies, monoclonal antibodies have been used for treatment purposes.
Due to the expensive nature of the drugs based on antibodies, identification of broad spectrum antivirals is essential along with focusing on small interfering RNAs siRNAs Satterfield In animal models, the NiV pathogenesis has been understood by shedding light on the crucial nature of phospho-matrix as well as accessory proteins. For the development of novel anti-NiV drugs, such viral proteins, fusion protein and glycoprotein of the virion surface are attractive targets Mathieu et al.
A monoclonal antibody targeting the viral G glycoprotein has been shown beneficial in a ferret model of the NiV disease Bossart et al. A successful outcome of an in vivo study using an investigational therapeutic, i. All the 12 African green monkeys that received m Supportive therapies such as hydration and ventilator support constitute important aspects of clinical management of NiV cases.
Properties like virulence, cell tropism, viral entry into the host cell that includes virus attachment and receptor identification and the process of fusion of membranes of the virus and host cell , etc.
For treating infections caused by Henipaviruses, there were no efficacious therapeutic or prophylactic measures as is evident from the report of Vigant and Lee Even though in case of NiV outbreaks the empirical use of ribavirin has been proven to be beneficial, but its use has got dispute due to its inefficacy in case of infection caused by other Henipaviruses in various animal models Vigant and Lee In animal models, the recent therapeutic approaches against NiV have been validated targeting the early steps in the infection caused by the virus.
These include: use of the virus neutralizing antibodies and blocking the fusion of membrane with peptides binding the fusion protein of the virus Mathieu and Horvat Full protection has been provided by the drug favipiravir T when used for 2 weeks either orally two times a day or through subcutaneous route once a day in Syrian hamsters challenged with Nipah viral lethal dose Dawes et al.
The use of monoclonal antibodies, immunomodulators, convalescent plasma along with intensive supportive care are in vogue for treating severe complications associated with respiratory and nervous system Chattu et al.
Experiments have been conducted to develop concept of prophylactic use of antifusion lipopeptides against the lethal NiV. As far as developing effective lipopeptide inhibitors with convincing biodistribution as well as pharmacokinetic features and efficacious delivery method are concerned results of such experiments are very much crucial Mathieu et al.
Nevertheless, the pathogenesis of the Henipavirus infection including NiV should be understood in a better way for advancing the field of therapy against such kind of viral infection further Mathieu and Horvat Monoclonal antibodies of mouse origin or polyclonal antiserum which is glycoproteins G or F specific are used for passive immunotherapy in hamster modelwhich is found to be protective in nature Guillaume et al.
It is to be noted that when neurological as well as respiratory troubles prevail use of antiviral drug viz. Therapeutic applications of cytokines Dhama et al.
Global adequacy of current and advanced approaches in designing efficient diagnostics, vaccine and drugs as well as their timely availability will give a high strength to counter emerging and re-emerging pathogens as well as alleviate their zoonotic impact and pandemic threats. Over the past two decades, the Nipah viral pathogenesis along with the transmission have been much well understood due to extensive research. This understanding is going to be more advanced in the decade to come. It is important to note in this regard that the practical utility of this understanding will be reflected in the entry of Nipah viral vaccines into clinical trials in humans, and modification of risk factors in order to prevent infection.
Further, such understanding will be great aid in developing techniques along with therapeutics for treatment of infected subjects for reduction of morbidity as well as mortality. Prevention of such zoonotic disease in agricultural and healthcare workers should be a priority. Scientists have presented from platform like Global Outbreak Alert and Response Network GOARN especially after the outbreaks in Bangladesh and India and marked the necessity of development of network communicating between veterinary and medical services concerning this disease.
By involving the multiple sectors and with multidisciplinary approach, precise and concrete preventive strategies can be planned and implemented. There is requirement of coordination between institutes as well as at the international level among virologists from both medical and veterinary fields as well as ecologists for understanding to the fullest the period and mechanism involved in excretion of the virus by the bats.
At the same time, the common people should be educated about food hygiene as well as hygiene at personal level. Inspection of all the imported livestock at the time of arrival and also before travel at the point of origin is essential. Proper isolation, quarantine and disinfection protocol including infrastructure facilities and trained personnel with protective clothing should be in place to respond quickly upon identification of any new case.
There should be maintenance of proper hygiene at maximum level for slaughtering such livestock. For preventing future NiV outbreaks, a continuous surveillance in the area of human health, animal health, and reservoir hosts should be carried out to determine the prevalence and to predict risk of virus transmission in human and swine populations.
Successful accelerated development of preventive vaccines and therapeutic antibodies or antivirals are need of the hour to control the spread and treat the infected patients during an outbreak.
Collaborative efforts such as CEPI and biotech companies will accelerate the vaccine or therapeutic development for NiV. All authors declare that there exist no commercial or financial relationships that could in any way lead to a potential conflict of interest.
National Center for Biotechnology Information , U. Journal List Vet Q v. Vet Q. Published online Apr Mourya k. Shyma K. Devendra T. Author information Article notes Copyright and License information Disclaimer. K Nagar. K Nagar, West Tripura , India. This article has been cited by other articles in PMC.
Abstract Nipah Nee-pa viral disease is a zoonotic infection caused by Nipah virus NiV , a paramyxovirus belonging to the genus Henipavirus of the family Paramyxoviridae. Keywords: Nipah virus NiV , bats, diagnosis, encephalitis, epidemiology, pathology, prevention, control, vaccines, therapeutics, zoonosis. Nipah virus Nipah virus NiV is a paramyxovirus Henipavirus genus, Paramyxovirinae subfamily, Paramyxoviridae family, order Mononegavirales , an emerging virus that can cause severe respiratory illness and deadly encephalitis in humans.
Open in a separate window. Figure 1. Transmission of the Nipah virus Bats serve as reservoir hosts for several high risk pathogens, including Nipah, rabies and Marbug viruses. Figure 2. Epidemiology and disease outbreaks In , NiV disease was recognized for the first time in Malaysia in persons who were in contact with swine population. Figure 3. Molecular epidemiology For comparison of the open reading frame sequence of the NiV with those from other members of the Paramyxovirinae subfamily, phylogenetic analysis had been used widely and by such approach the closest relation between NiV and Henipavirus has been proven Chua et al.
The disease 8. Pathogenesis In the initial stage of illness in man, detection of NiV can be done in epithelial cells of the bronchiole Chua et al. Figure 4. Clinical signs and symptoms Highly pathogenic NiV causes symptomatic infections in pigs and humans.
In humans The virus is responsible for causing severe and rapidly progressing illness in humans with the respiratory system as well as the central nervous system CNS mainly getting affected Hossain et al. In animals In pigs, the disease is also known as porcine respiratory and encephalitis syndrome PRES , barking pig syndrome BPS in peninsular Malaysia or one-mile cough.
Postmortem findings Magnetic resonance imaging MRI studies in human patients have revealed that the cortex, pons as well as temporal lobes of brain get involved. Public health significance and zoonotic aspects NiV is the most recently emerging zoonotic and highly deadly virus having pandemic threat. Laboratory diagnosis Confirmation of the human as well as animal NiV infections can be done by isolation of the virus along with performing serological tests and tests to amplify viral nucleic acids.
Vaccines Vaccination of humans is an integral part of preventing infection due to NiV. Figure 5. Table 1. Different vaccine strategies available for Nipah virus NiV. Prevention and control measures Outbreaks of NiV invoke costly emergency responses around the world. Therapeutics and treatment modalities The essence of treatment modalities along with effective therapeutics is understood, once there is an outbreak of an infectious disease.
Conclusion and future directions Over the past two decades, the Nipah viral pathogenesis along with the transmission have been much well understood due to extensive research. Disclosure statement All authors declare that there exist no commercial or financial relationships that could in any way lead to a potential conflict of interest.
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