INTRODUCTION:

The family paramyxovirdae genera Hendra virus includes the Nipah Virus (Niv), which has a wide spectrum of hosts¹. A developing zoonotic disease caused by the Nipah virus (NiV) is transferred to individuals through touch with illmammals or defective food. It might transfer by one human to human during direct contact with ill individual. The Nipah virus has flying foxes (Pteropus species) as its natural hosts².

NiV may cause fever inflammation in brain and serious respiratory sickness in person, and in certain outbreaks, its case-fatality rate (CFR) can exceed 100%³. The first NiV outbreak in Malaysia was amplified by pigs, and the NiV reservoir in nature has been shown to be pteropid fruit bats⁴. In contrast, a range of different mammalian species may contract the NiV virus⁵. In West Malaysia's state of Perak, where pig farming was a prominent industry, the first cases reportedly surfaced in late September 1998. Cases remained in this region up to the beginning in march 1999. The second cluster occurred at Sikamat, a small town in the autonomous state of Negri Sembilan, between November 1998 and February 1999⁶. A NiV epidemic was first detected in India in West Bengal, in 2001 (there were 66 probable cases and 45 fatalities); later, in 2007, reports of the outbreak were made in District Nadia, and surrounding areas of Bangladesh. Five fatalities and five likely cases. Because there hasn't been any evidence of an intermediary animal host, bat-to-person and person-to-personspread have been hypothesised^7-8. An epidemic of encephalities among malasian pig breeders in 1999 lead to initial identification of the paramayxoviridae family member nipah virus RNA virus⁹. Case mortality rate for recent NiV encephalitis epidemics were high in Bangladesh, Malasiya¹⁰. NiV may last for days in situation such as sticky fruit pulp¹¹. In Bangladesh, human to human spreading was the cause of a number of Nipah outbreaks. The most conclusive evidence of Nipah virus transmission came from human to humanin Faridpur incident2004¹². There are now no authorised vaccinations instead basic care is available. WHO designated, the wide geographic distribution of NiV host reservoir, the possibility of zoonotic and human transmission, in addition to diseases li2mitation in terms of prevention and treatment^13-15.

Nipah virus is a member of: -

Virus	Nipah virus
Genera	Henipavirus
Family	Paramyxoviridae

Discovery of Nipah virus:

Virologists at the University of Malaya identified a virus in the patient’sbrain fluidwho had inflammation of brain at starting of march 1999. A virus from the Paramyxoviridae family was identified from studies of the virus utilising electron microscopy (EM). The initial isolate, which was given the name Nipah virus, was based on a lethal human case from the neighbourhood of Sungai Nipah in Negeri Sembilan¹⁶. It causes acute illness in individuals which is identified by destruction in CNS. NiV normally takes 4 to 14 days to incubate^17,18.

Classification Of Nipah Virus: -

The second is a symbiotic relationship between the two. The tightly connected HeV virus which was discovered during an investigation into the 1995 deadly illness, endemic in mares and individulas in Australia, serves as the prototypical virus for the genus. Another analysis of the NiV genomic sequences categorization revealed that HeV and Nipah Virus are novel paramyxoviruses that must be placed in a new genus since they didn’t match witheither of the family's prevailing genera. The international council for viral taxonomy authorised the formation of the distinct genera Henipavirus in 2002¹⁹.

Replication of Niv:

In order to comprehend the impact of nipah virus replication in the numerous host cell was investigated in order to better understand the pathobiology of nipah virus infectious disease and the probability that the variations in the sign and severity of NiV infection between individuals and pigs were brought due to the different role of the various cells to assist with nipah virus replication. In both pig and human lung fibroblasts, excellent NiV replication rates were observed^20,21. According to the results of multiplication in human lung fibroblast cells, Nipah virus may be able to reproduce practically everywhere at the point of arrival. From there, it can infect neighbouring cells either by producing contagious viral particles or by using the cell-to-cell transmission mechanism^22,23. The most common ways that people become infected are through breathing nebulized NiV or by coming into intimate exposure to the body fluids and infected pigs’ secretions²⁴. The NiV virus also may move to the brain across the blood-brain barrier by transmigrating through infected monocytes²¹. The most likely method of contamination of the neurons is cell-to-cell spreading, it may be the reason for the enormous syncytial cell-based foci-like wounds that were observed in certain infected brainregions²⁵.

Structure of Nipah Virus

Sign and Symptoms:

Infected people usually display flu-like signs, including a high body temperature, headache, myalgia, sore throat, and weakness. a decline in stability and spatial awareness, unusual fatigue, altered consciousness, and neurological symptoms, which can occasionally include vomiting and nausea²⁶. Atypical pneumonia and other respiratory issues, such as acute respiratory distress, can also occur in certain patients with the NiV²⁷. Those who are severely harmed may experience renal failure, septicaemia, and gastrointestinal bleeding²⁸. Critical cases of seizures and inflammation of brain leads to unconsciousness within 24 to 48hours²⁶.

Diagnosis:

As a result of NiV infection's signs being similar to those of other febrile infections, early detection is crucial for preventing an epidemic and enabling proper patient management. The laboratory testing for NiV includes the following procedures: viral isolation, neutralisation testing, IgG/IgM/antigen ELISA, immunofluorescence assay, nucleic acid amplification testing (NAAT, e.g., PCR and sequencing), and histopathology^29-31.

Bats To Humans’ Transmission:

Epidemiological research in Bangladesh has identified three possible ways that the NiV virus might spread from bats - human. Consuming raw date palm juice is the way that is most frequently mentioned. From Dec. -March, date palm sap is predominantly gathered in west central Bangladesh.Overnight, sap flows from a tap inserted into the tree trunk into a visible clay container. Bats [P. giganteus] come upon date palm sap plants, according to studies utilising thermal sensors, and they consume the sap while it's being harvested³². Nipah virus can endure on sugar-rich environments like fruit pulps for many days³³. The NiV Bats can spread a virus to people in Bangladesh via domesticated animals as a secondary means of transmission. Fruit bats frequently discharge saliva that is packed with fruit. Animals raised in Bangladesh for food go foraging. Domestic animals are occasionally sap from a date palm has been has been polluted with bat faeces and is hazardous for use by people. Domesticated animals may get the virus from humans and other animals after contracting it from domesticated animals³⁴. Finally, certain people could come into direct touch with bat fluids that are NiV-infected³⁵.

Human To Human Transmission:

Exposure to the bodily fluids of infected individuals appears to be a viable route for human-to-human transmission, despite the fact that it is not prevalent. As respiratory distress symptoms were more prevalent in Bangladesh later, they were seen in outbreak of Malaysian, there is proof that NiV may be spread from human to human^36,37. Research suggested that close exposure to the respiratory discharge of critically sick patients cause human-human transmission. NiV can linger on surfaces, increasing the possibility of NiV transfer by fomite^37-41. The transmission of NiV from person to person seems to be particularly dependent on respiratory secretions. NiV RNA is easily detected in people who have the infection in saliva^42,43. In Bangladesh, it is customary for family members to be in close physical touch while a member is ill. More hands-on treatment is anticipated the more serious the illness. About all of the hands-on treatment for Nipah patients was given by family and friends, who lacked any professional training in medicine or infection control⁴⁴. As seen the behaviours like laying the sick person's head on the family member's lap, trying to give them drinks with a spoon or glass in between coughing, and loving, there was an unexpectedly strong demand for intimate physical touch in the moments before death⁴⁵. All those who spread Nipah perished, indicating that the danger of transmission is increased by late stages of sickness, most likely with high virus titters⁴⁶. There were two major outbreaks in India: one in 2002 in West Bengal, which resulted in 66 probable cases and 46 fatalities, and another in 2008 in Nadia, which resulted in six cases with a 100% fatality rate. Anywhere in Bangladesh's Nipah belt, these diseases first appeared. In April 2018, Kerala, a southern state, a geographical area distinct from previously affected places, declared a NiV epidemic in the Kozhikode and Malappuram districts. The practise of consuming date palm sap is uncommon in this area. There would be 18fatalities and 19 confirmed cases as of June 1st, 2018. All patients were in the age group that is economically productive, and there was no variation in their gender^47,48.

Nipah Virus Disease Causing Pathway:

Linkage of Coronavirus and The Nipah Virus:

According to rumours from specialists, NiV is most likely to be COVID-19's successor as the next pandemic agent. Nonetheless, COVID-19 safety measures have assisted in reducing the spread of the NiV in places like Kerala. NiV infection shares many of the same symptoms as COVID-19 since it is a respiratory illness. Nevertheless, NiV infection does not frequently cause loss of taste or smell, which has been reported as a defining sign of COVID-19 infection. Similar to Nipah virus, some people who catch it experience no symptoms. According to the WHO, NiV has a significant mortality rate (41-46%), moving far more deadly as corona virus, whose death rate varies from 0.2% to 20% with relation to disease site. In comparison to corona virus, where diseased people are more contagious before signs show, Nipah virus patients have the most possibility of infection in diagnostic periods. Despite the increasedrate of death ofNipah virus, COVID-19 is more infectious⁴⁹.

Clinical Indication:

It can be challenging to identify other febrile disorders from NiV infection in its early stages, when it often manifests as febrile encephalitis or pneumonia. Encephalitis with accompanying fatigue and disorientation is one example of a severe condition that can quickly develop to seizures and coma within 48 hours. A dismal prognosis is indicated by the development of encephalitis, which often results in death 6 days or less following the beginning of symptoms⁵⁰. Neurological disorder, including repeated seizures, incapacitating tiredness, and unusual behaviour, affects around 21% of encephalitis survivors⁵¹. There are several neurological conditions present, including localised brainstem involvement, aseptic meningitis and widespread encephalitis⁵².

Epidemiology:

Nipah virus belongs to Paramyxoviridae family, genus Henipavirus, that is similar to homologous to the less harmful Cedar virus and the Hendra virus (HeV)^53-55. Bats with the NiV virus are asymptomatic carriers whose saliva, urine, excreta and semen contain virus⁵⁶. Direct contact with Pteropus saliva or faeces can result in human infection, especially if contaminated food is consumed. Nipah virus outbreak in individuals have a consistent pattern of season throughout the winter and spring, that is most likely corelates with the peteropus breeding season and the palm sap collecting season⁵⁷. While rarely common, exposure to body fluids from infected people seems to be a potential method of person to person spread. There is evidence of Nipah virus disease transmission in different regions since symptoms of breathing difficulties were more common here than they were during the Malaysian outbreak^58,59. Although concrete evidence has been hard to come by, eating fruit that has been eaten by bats has been proposed as a potential transmission path. In Bangladesh, the major transmission pathways that is seen most via consumption of date palm sap and human-human transfer⁶⁰.

Treatment of Nipah Virus:

The main reason that NiV outbreaks are so successful is because of how quickly viruses have a period of asymptomatic incubation and transmit by zoonotic and nosocomial routes. NiV infection is identified by the development of mild fever bouts into severe instances acute cases of brain inflammation with syndrome of respiratory distress, reduced sensory function, confusion⁶¹.

Drugs Used In Nipah Virus:

In Nipah virus treatment Ribavirin was the first antiviral drug which is used. Prior NiV outbreaks in Singapore, two drugs were used: acyclovir and ribavirin^62,63,64. Ribavirin decreased the mortality toll from Malaysian NiV epidemics by 36% during the open label study, following research using animal models were unable to demonstrate its effectiveness⁶⁵. Favipiravir (T-705) is purine analogue that blocks RNA dependent RNA polymerase in laboratory trials that conducted to treat Ebola, and many influenzasantiviral drugs have also shown promise in combating NiV in Syrian hamster animal models^66,67. When NiV epidemic occurred in Singapore in 1999, nine employees of an abattoir were treated with ceftriaxone and another antiviral called acyclovir (Zovirax), and eight of them recovered⁶⁸. There were no results from acyclovir's in vitro tests against NiV. In vitro studies have demonstrated that favipiravir, which goes by the trade name Avigan, and other drugs prevent the replication of the NiV virus⁶⁹. In hamster model research, favipiravir had the strongest antiviral activity against NiV infection⁷⁰. Ritatolimid, an immune system modulator, demonstrated to be influenced in preventing Nipah Virus multiplication or providing security from viral threat is created by rodents producing IFN⁷¹.

Nipah Virus Treatment with Antiviral Medication

Drug	Group of medicines	Year	Mode of action
Ribavirin	Nucleoside analogues	1998	Mainly work by inhibiting the viral polymerase enzyme.
Favipiravir	Purine analogues	2018	RNA dependent RNA-polymerase enzyme uses this molecule as a substrate, and when it recognises as a purine nucleotide, it inhibits its activity and stopping the creation of viral proteins.
Acyclovir	Synthetic nucleoside analogue	1999	The viral DNA polymerase and DNA replication are inhibited by this nucleoside analogue.

Immunization of Animal:

After receiving a subunit inoculation based on a synthetic soluble and oligomeric form of HeV G (sG), animals are completely protected against a high dose Nipah virus infection with no clinical manifestation, evidence of viral multiplication, or pathology. After receiving the immunisation, cats, ferrets, and AGMs produce a sizable quantity of IgG and nAbs that are specific to the NiV virus^72-74. According to the findings of a different study, protection is also provided via a cell-mediated immune response. HeV sG vaccination in pigs did not result in any appreciable amounts of nAb cross reactivity to Nipah virus after exposure⁷⁴. There is a possible contender for an orthologous recombinant Nipah virus sG based on immunisation which offers complete defence against Nipah virus exposure in cats⁷².

Factors Contributing To Outbreak of Nipah Virus:

1. Population growth:The human population is growing and is always influenced by variables including resource availability, climate, trade, and development. Several of the world's most populous regions, including the South East Asia region, have reported NiV prevalence (SEAR)⁷⁶. While making up only 5% of the world's area, the region is home to 26% of all people. While Kerala, a south Indian state, is regarded as one of India's most densely inhabited states, the world's densest metropolitan region is located in Bangladesh⁷⁷.

2. Socio-Economic Scenario: The population, economy, and level of poverty all contribute to a country's strengths. The bulk of the SEAR's member states are either developing or underdeveloped. The lives of inhabitants in these countries are tormented by pandemics, diseases, and natural catastrophes. Although being a significant source of revenue for farmers, pigs and pig sties are to blame for the NiV pandemic in Malaysia⁷⁸.

3. Deforestation and Climate Change: The growth of grazing and agriculture, industrialisation, and urbanisation are all thought to be contributing to the alarming pace of deforestation in the SEA area. The spread of Ebola in Africa and human contact with Ebola-infected bats have both been connected to deforestation ⁷⁹. Due to greater interaction with NiV-infected bats, deforestation is believed might be the main factor behind the Malaysian Nipah virus epidemic in 1997-1998, much as the Ebola outbreak ⁸⁰. The El Nino-caused drought was followed by the Malaysian NiV epidemic⁸¹.

4. Intervention to Reservoir Habitats: The primary cause of the decline in bat habitats is deforestation. Fructivorous and nectarivorous Pteropus bats are reported to live in tropical woods all over the world. They aid in the dispersal of native and commercially significant crops and plants. Besides from replenishing the genetic variety in forest regions that had been manipulated, they serve as the only pollinators on several marine islands. Tourism, deforestation, and fruit collecting all significantly contribute to habitat loss⁸².

Nipah Virus Prevention: Main goal of preventative efforts have been to stop date palm sap from becoming contaminated, raise public knowledge of the risks associated with date palm sap consumption, and preventing the spread of the disease by person to person. It has been discovered that covering the date palm trees' sap-producing regions efficiently prevents interaction with bats⁸³. While an epidemic is active, the WHO gives advice staying away from pigs and bats along with avoiding eating fruits that have been bitten by bats or consuming toddy, juice, or raw date palm sap. Gloves should be used while operating ill mammals or their parts in addition to operation of culling and killing, to lower the danger of animal-to-human transmission. Implementing infection control procedures including patient isolation, wearing personal protective equipment, and practising basic hand hygiene are all part of preventing the spread of diseases from one person to another. Connections identified by contact tracing are examined, followed by monitoring, till the outcomes are unfavourable. Around patients, hospital surfaces have been discovered to be NiV-contaminated⁸⁴. In preclinical research using rodents or nonhumanapes’ model, a variety of applicants for vaccine have demonstrated full protection against the NiV illness⁸⁵.

In Different Regions, Nipah Virus Mortality and Morbidity:

Year and Month	Countries	Total Deaths	Total Cases	No. of fatality
September 1998- April 1999	Malaysia	267	107	41%
March 1999	Singapore	13	3	11%
All years	Malaysia – Singapore	277	108	41%
January – February 2001	Siliguri (India)	68	47	70%
April – May 2001	Meherpur (Bangladesh)	15	11	71%
January 2003	Naogaon (Bangladesh)	14	10	70%
January - 2004	Rajbari (Bangladesh)	33	25	76%
April – 2004	Faridpur (Bangladesh)	38	28	77%
January – march 2005	Tangill (Bangladesh)	13	14	95%
January – February 2007	Thakur gaon (Bangladesh)	9	6	45%
March 2007	Pabna (Bangladesh)	9	7	65%
April 2007	Bangladesh	4	3	35%
April 2007	India	5	2	36%
February 2008	Bangladesh	7	9	100%
April 2008	Bangladesh	8	9	100%
January 2009	Bangladesh	4	2	3%
February – march 2010	Faridpur, Rajbari, Gopalganj (Bangladesh)	19	15	88.50%
January – February 2011	Dinajpur, rangpur (Bangladesh)	46	42	93%
February 2012	Natore, Rajbari and Gopalganj (Bangladesh)	15	12	83%
All years	Bangladesh and India	282	213	77%
March – May 2014	Philippines	19	10	55%
February 2015	Nilphamari, faridpur (Bangladesh)	10	7	68%
May 2018	Malappuram (India)	20	18	90%
June 2019	India	2	1	1%

CONCLUSION:

In the past 20 years, reports of the zoonotic virus NiV have been made in a number of nations, with Kerala, India, providing the most previous reports. It possesses mechanisms to inhibit the host's antiviral response and is linked to significant morbidity and death in both people and animals. Implementing public readiness and awareness is essential for managing and successfully containing NiV epidemics. This study provides an overview of our current knowledge of the clinical indications, epidemiology, preventative reactions brought on by NiV infection, and host responses to therapeutic and candidate vaccines.

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Received on 23.05.2023 Modified on 23.08.2023

Res. J. Pharmacology and Pharmacodynamics.2023;15(4):223-230.

DOI: 10.52711/2321-5836.2023.00039