Nipah Virus: A Medical Threat

 

Mr. Avinash B. Thalkari1*, Mr. Pawan N. Karwa2, Vivek. M. Thorat1, Sakshi K. Jadhav2

1Vasant Pharmacy College, Kaij, Maharashtra.

2Gurukrupa Institute of Pharmacy (DEGREE), Near Chatrapatthi Sugar Factory, NH- 222 Gadi Road, Majalgaon-431131, Maharashtra.

*Corresponding Author E-mail: karwapawan99@gmail.com

 

 

ABSTRACT:

As we know that a now of viruses are speeding in the surroundings due to the interactions of unwanted particle with our body. Nipah virus is one of the existing virus infection which is leading to the various caused yearly disease outbreaks with tremendous cases of the facility ratio seen in Bangladesh our neighboring nation. Nipah virus leads to the encephalitis as well as systemic vasculitis, also sometimes in the combination various respiratory diseases. Pteropus species fruit bats act as the natural species of Nipah virus and here the zoonotic transmission can occur directly or via an intermediate host; human-to-human can occur regularly. In this review we have a main site of interaction point related to the the current state of knowledge on the pathogenesis and transmission of Nipah virus, focusing on its signs and symptoms and also the basic primary treatment to inhibit it.

 

KEYWORDS: Virus, infection, symptom’s, pathogenesis, treatment.

 

 


1.    INTRODUCTION:

Nipah Virus is a disease listed in the World Organization for Animal Health (OIE)Nipah Virus or simply NiV is an fatal infectious disease which was first to be seen in the domestic pigs in Malaysia and Singapore in the 1998 and 1999. There are particular evidences of the Nipahinfection seen among several species of domestic animals which includes dogs, cats, goats, and horses as well the Sheeps. However, since in initial timeline it has primarily the humans in different regions of the world. Respiratory and occasional nervous signs are seen in thepigs. The organism which causes Nipah Virus encephalitis is an RNA virus belonging to the family Paramyxoviridae, with the genus Henipavirus, and is closely related to Hendry virus(1).

 

Human Nipah virus (NiV) infection, is as well as a drastic abnormal disease. In India, during 2001 and 2007 two such cases were to be reported in the humans belonging to the West Bengal which is the neighboring to the Bangladesh. Large fruit bats of Pteropusgenus are the main natural reservoir towards the NiV. In Bangladesh, NiV was first identified in the outbreak of encephalitis in 2001. This was due to the genetic diversity of the various viral strains.In that period it was important to develop various safety guidelines for the surveillance, diagnosis, case management, prevention and control of Nipah virus encephalitis so that human cases can be detected with a ease and later the human-to-human transmission chain can be exhibited to some extent.(2) The Nilesh is a name which is originated from the Sungai Nipah, a village situated in the Malaysian Peninsula where the pig farmers became ill with encephalitis.(3) Nipah Virus Infection (NiV) was also be seen in the importance in the South-East Asia Region.(4) Now accordingly more than 60% of the recently identified infectious agents which have been affecting the rural as well as the urban people over the few decades decadeshavearised due to the pathogens which have existing by the animal source or the animal products. Of these zoonotic infections, 70% originate from wildlife. Bats have been identified as the major destrocturfor the zoonotic viruses which includines the Ebola, Marburg, SARS and also the Melaka viruses. The Nipah Virus (NiV) represents another new emerging zoonosis, one of the most important bat-borne pathogens discovered in recent decades. Similarly, at the beginning in pigs there was a bit confusion with Classical swine fever .(5)

 

2.     Aetiology:

TheNipah virus is closely related to Hendra virus (HeV) and Cedarvirus.(6,7) Among Paramyxoviruses, henipaviruses are characterized bya wider host range and a larger genome(6), when compared tothe other members of the family, such as measles virus and caninedistemper virus, showing generally a narrow host range and geneticallystable with an almost uniform genome size shared by all members ofParamyxovirinae.Nipah is an envelope, negative-sense, single-stranded RNA virus,with a genome sequence size of about 18,000 nucleotides. NiVgenomeorganization comprises six major genes present in all Paramyxovirus: RNA polymerase and nucleocapsid genes (N, P and L); envelopemembrane protein genes (F and G); and matrix protein (M). Theattachment (G) glycoprotein which binds the viral receptor, and thefusion (F) glycoprotein which drives virus-host cell membrane fusion, are the two membrane-anchored envelope glycoproteins responsiblefor host cell infection by NiV(8). Visions are pleomorphic, ranging insize from 40 to 600 nm in diameter(9) As other animal Paramyxovirus, the virus is inactivated by 60°Cfor 60 minutes. It is behaves between the pH 4.0 and 10.0. It survives forlong periods in favorable conditions, for days in fruit bat urineand contaminated fruit juice. It is susceptible
to disinfectants. Lipid solvents, such as alcohol and ether, andsodium hypochlorite solutions were used e
ectively in outbreaks fordisinfection (10)

 

3.     Epidemiology:

According to the latest updates so far, NiV has infected about 477 people and killed nearly about 252 since 1998. The distribution of NiV outbreaks in Bangladesh and India during 2001 to 2008 is shown in Figure 1. The various Outbreaks of Nipah in south Asian have a strong seasonal pattern and a possesss a limited geographical range. The fatality rate of NiV ranges from 40-70% although it has been as high as 100% in some outbreaks. The boundaries and name shown on this map do not imply any expression or any opinion what so ever on the part of World Health Organization concerning the legal status of any country, territory, city or area of its authorities or concerning the delimitation of its frontiers or boundries.

 

Figure 1: Chronological distribution of outbreak of Nipah virus infection in South Asia, 2001-2008(11)

 

4.     Species Susceptible to NiV:

As we know that the Humans, pigs, bats, dogs, cats, goats and horses are the most sensible towards the NiV infection(12,13). NiV infection has been reported also in sheep in the few researches,(14), but the observation could not be further confirmed and remainscontroversial(15,16) Clinical disease can be observed in experimentalconditions in ferret (Mustelaputoriusfuro) (17) guinea pig (Caviaporcellus)(18) squirrel monkey (Saimirisciureus)(19), African green monkey (Chlorocebusaethiops)(20,21) hamster (Cricetinae)(22) and in suckling mouse (Musmusculus), or deleted for the type I interferonreceptor (IFNAR)(23,24)

 

5.     Signs and symptoms:

The primary symptoms seen with theNipah virus begins with fever and headache followed by inflammation of the brain also called the encephalitis, drowsiness and disorientation are also characterized by mental illness and the confusion state. A few cases have been suffering from the respiratory symptoms in the early period. These signs and symptoms can progress to a critical state i.e, comma within 24 to 48 hours. About 40% of hospitalized cases have died also is serious fact. Serious nervous disease with Nipah virus encephalitis has been shown to cause long term illness in some patients that survive, including persistent convulsions and personality changes. Symptoms usually appear five to 14 days after exposure to the virus.(25) The incubation period seen between the four days to 2 weeks, but may be extended up to 45 - 60 days. In the human the infection ranges from ancommon changes an family become to fatal to be treated. Infected people initially develop influenza-like symptoms of high fever, headache, myalgia, sore throat and weakness. This gets followed by impairment in spatial perception and stability, feeling abnormally sleepy, altered consciousness, and neurological signs, sometimes accompanied by nausea and vomiting, that indicate acute encephalitis septicaemia, gastrointestinal bleeding, and renal impairment(5)

 

The following symptoms are commonly observed:

1.     Fever

2.     Altered mental status

3.     Severe weakness

4.     Headache

5.     Respiratory distress

6.     Cough

7.     Vomiting

8.     Muscle pain

9.     Convulsion

10. Diarrhea

 

Neurological signs:

1.     Oculoparesis

2.     Pupillary abnormality

3.     Facial weakness

4.     Bulbar weakness

5.     Limb weakness

6.     Reduced deep tendon reflexes

7.     Plantar-absent/extensor

 

General signs seen:

·       Reduced GCS score

·       Raised temperature

·       Increased respiratory rate (Adult: ≥25/min; children of ≥ 12 months: ≥ 40/min)

·       Increased heart rate (Adult: ≥100/min; children of ≥ 12 months: ≥ 140/min)

·       Crepitation’s in lung

·       Hypertension/Hypotension (2)

 

7.     Transmission:

bats, also known as ‘flying foxes,’ belonging to the genus Pteropusare natural reservoir hosts of the Nipah and Hendra viruses. The virus is mostly seen in the urine of the bat following bat feces, saliva, and birthing fluids. Perhaps as a result of deforestation programs, the Malaysian pig farms where the disease first originated had fruit trees which attracted the bats from the tropical forest, thus exposing domestic pigs to bat urine and feces. It is thought that these excretions and secretions initiated the infection in pigs which was then followed by a rapid spread through intensively reared pigs. The reason behind the transmission between farmers is may be due to fomites or also arise due to the stiking of virus on clothing, equipment, boots, vehicles, etc. Which are their primary needs.

 

In Human cases of Nipah virus infection in Bangladesh were first recognized in 2001, where the 13 people acquired Nipah virus encephalitis, nine of whom died. Nipah virus disease outbreaks and/or sporadic cases of Nipah virus infection have been detected in Bangladesh almost every year since then. Transmission in Malaysia and Singapore was seen through the pigs as intermediate, and amplifying host and nosocomial transmission was the main source of Nipah virus infections in India. However, Nipah virus infections in Bangladesh are either the result of food-borne transmission, most likely through the consumption of raw date palm sap contaminated with Nipah virus by fruit bats during collection, or of human-to-human transmission, which has been shown to account for 50% of cases during some outbreaks. (Figure 1) Infected bats shed virus in their excretiory and as wellin the secretions including the saliva, urine, semen and excreta but they are symptomless carriers. The NiV is highly contagious among pigs, can spread by coughing. Direct contact with infected pigs also and was to identified as the primary mode of transmission in humans when it was first recognized in a large outbreak in Malaysia in 1999.In the outbreak of 1998- 1999 the infected people were about Ninety percent and in them were either the pig farmers or had contact with pigs.

 

8.     Nipahdisease spread in humans:

Clinical diseaseNipah virus infected patients generally present with fever and altered mental status; neurological signs ofdisease progress over time, leading to coma and ultimately death. Although neurological diseaseis the main complication with Nipah virus infection, respiratory disease also occurs to varying degrees: duringthe 1998–1999 outbreak in Malaysia and Singapore,25% of cases presented with respiratory disease, compared with 69% of cases in Bangladesh . In someof the patients from Bangladesh radiographic findingswere consistent with acute respiratory distress. Thecase: fatality ratio in Nipah virus infected people is high: 40% during the outbreak in Malaysia and Singapore; in Bangladesh and India the overall case: fatality ratiois70%, but may be 100% in individual outbreaks. In the nipah virus disease survivors, long-term neurologicaldeficiencies are seen frequently. Moreover, late-onsetor relapse encephalitis has been observed; in one casethis late-onset encephalitis occurred 11 years after theinitialNipah virus infection. Histopathological findings All available data on histopathological changes inhumans infected with Nipah virus were obtained in asingle study, performed during the Nipah virus outbreak in Malaysia and Singapore. The main site ofinfection in Nipah virus patients was the endothelium. Systemic vasculitis was observed in almost all patients, mainly involving blood vessels in the CNS, but bloodvessels in lungs, heart and kidneys were also affected. Perivascular cuffing, thrombosis, necrosis and endothelial cell syncytia were also observed. In the CNS, neurons were clearly infected with Nipahvirus, as indicated by immunohistochemistry. In the lungs, fbrinoid necrosis was noted in alveoli adjacent to smallvessels with vasculitis, and alveolar hemorrhage andpulmonary edema were observed frequently. In thespleens of many cases, acute necrotizing lesions intheperiarteriolar sheaths and lymphoid depletion wereobserved. In the kidneys of one-third of patients, focalglomerular fibroid necrosis was seen.(26)

 

(27)

 

9.     Pathogenesis:

All pathologic findings of NiV infection in human that have been identified so far are based on Malaysian studies. The pathologic findings in the brain of Nipah encephalitis cases showed evidence of necrotizing vacuities. There was widespread central nervous system (CNS) involvement due to severe vasculitis of mainly small blood vessels, which resulted in endothelial damage. Eosinophilic cytoplasmic and nuclear viral inclusions were detected in many neurons adjacent to vasculitic vessels, a finding which is present in infections caused by other paramyxoviruses. The main pathology appeared to be widespread ischemia and infarction caused by vasculitis-induced thrombosis, although direct neuronal invasion may also play a major role in the pathogenesis of the encephalitis. Alveolar hemorrhage, pulmonary edema and aspiration pneumonia were often encountered in the lungs . These may lead to pneumonia and acute respiratory distress syndrome (ARDS) ultimately. It was found that the Nipah virus was classified internationally amongthe one of the biosecurity level (BSL) pathogen. NiV has a number of important attributes that makes it a potential to be agents of bioterrorism.(2)

 

(28)

 

10. Treatment:

Now there is no proper remedy to treat the Nipah infection. However, the national health care providers possess the supportive medications (i.e., rest, fluid intake) in order to control the symptom’s. Now by implementation the use of the antiviral drug, ribavirin, can help to reduce the of the duration of fever and the severity of disease. However, how well this treatment cures the disease or improves survival is still under the curtains. (25)

 

11. General Management:

·       Isolation

·       Barrier nursing

·       Hand washing with soap & water before and after handling/visiting patients

·       Resuscitation

·       Care of unconscious patent

·       O2 inhalation

·       Nutritional support

·       Maintain fluid and electrolyte

·       Fluid restriction

·       Maintain intake output chart

·       Bronchodilators may be given through large spacers(2)

 

A WHO Aide–memoire on Standard Precautions kit is available

 

at: http://www.who.int/csr/resources/publications/ standardprecautions/en/

 

index.html A vaccine is being developed. A recombinant sub-unit vaccine formulation protects against lethal Nipah virus challenge in cats.21 ALVAC Canarypox vectored Nipah F and G vaccine appears to be a promising vaccine for swine and has potential as a vaccine for humans.(4)

 

12. CONCLUSION:

After studying all the pathophysiology of a disease which has been harming all the living organisms it can be concluded that proper precautions should be taken regarding the nipah virus in order to have control over it. As it is rightly said that precautions is better than cure so all the necessary precaution’s should be taken in order to avoid it. Doctor should be consulted on a regular basis. If we think any problem in body maintaining. fruits and vegetables should be washed before eating or cooking. Special care should be taken of small kids.

 

13. REFERENCES:

1.      O.I.E Terrestrial Animal Health code:www.oie.int/en/ international-standard-setting/terrestrial-code/access-online.

2.      National Guideline for Management, Prevention and Control of Nipah Virus Infection including Encephalitis Directorate General of Health Services Ministry of Health & Family Welfare Government of the People’s Republic of Bangladesh Technical support: World Health Organization, Bangladesh Country Office.1ST edition: December 2011, page no 5-7.

3.      National Center for Emerging and Zoonotic Infectious DiseasesDivision of High-Consequence Pathogens and Pathology (DHCPP).

4.      Information on Nipah virus identification in countries of the Asia-Pacific Region received from WHO Collaborating Centre for Viral Zoonoses, Division of Neurovirology, Chulalongkorn University, Bangkok, Thailand.

5.      Giangaspero M (2013) Nipah Virus. Trop Med Surg 1: 129. doi:10.4172/ 2329-9088.1000129Nip

6.      Eaton BT, Mackenzie JS, Wang LF (2007) Henipaviruses. In: Knipe DM, Griffn DE, Lamb RA, Straus SE, Howley PM et al., editors. Fields Virology.Philadelphia: Lippincott Williams & Wilkins. pp. 1587-1600.

7.      Marsh GA, de Jong C, Barr JA, Tachedjian M, Smith C, et al. (2012) Cedar virus: a novel Henipavirus isolated from Australian bats. PLoSPathog 8: e1002836.

8.      Lamb RA, Parks GD (2007) Paramyxoviridae: The viruses and their replication. In: Knipe DM, Griffn DE, Lamb RA, Straus SE, Howley PM et al., editors. Fields Virology. Philadelphia: Lippincott Williams & Wilkins. pp. 1449-1496.

9.      Hyatt AD, Zaki SR, Goldsmith CS, Wise TG, Hengstberger SG (2001) Ultrastructure of Hendra virus and Nipah virus within cultured cells and host animals. Microbes Infect 3: 297-306.

10.   World Organisation for Animal Health (Offce International des Épizooties: OIE) (2009) Nipah (virus encephalitis). Technical Disease Cards, OIE, Paris.

11.   WWW.WHO.in

12.   Lam SK, Chua KB (2002) Nipah virus encephalitis outbreak in Malaysia. ClinInfect Dis 34 Suppl 2: S48-51.

13.   Luby SP, Gurley ES, Hossain MJ (2012) Transmission of human infection withNipah virus. In: Institute of Medicine (US). Improving Food Safety through a One Health Approach: Workshop Summary. Washington (DC): National Academies Press (US), A11.

14.   Uppal PK (2000) Emergence of Nipah virus in Malaysia. Ann N Y Acad Sci916: 354-357.

15.   Cobey S (2005) Nipah virus. The Henipavirus ecology collaborative research group.

16.   Center for Food Security and Public Health (2007) Nipah Virus Infection.

17.   Bossart KN, Zhu Z, Middleton D, Klippel J, Crameri G, et al. (2009) A Neutralizing Human Monoclonal Antibody Protects against Lethal Disease in a New Ferret Model of Acute Nipah Virus Infection. PLoSPathog 5: e1000642.

18.   Torres-Velez FJ, Shieh WJ, Rollin PE, Morken T, Brown C, et al. (2008) Histopathologic and immunohistochemical characterization of Nipah virus infection in the guinea pig. Vet Pathol 45: 576-585.

19.   Marianneau P, Guillaume V, Wong T, Badmanathan M, Looi RY, et al. (2010) Experimental infection of squirrel monkeys with nipah virus. Emerg Infect Dis 16: 507-510.

20.   Geisbert TW, Daddario-DiCaprio KM, Hickey AC, Smith MA, Chan YP, et al. (2010) Development of an acute and highly pathogenic nonhuman primate model of Nipah virus infection. PLoS One 5: e10690.

21.   Rockx B, Bossart KN, Feldmann F, Geisbert JB, Hickey AC, et al. (2010) A novel model of lethal Hendra virus infection in African green monkeys and the effectiveness of ribavirin treatment. J Virol 84: 9831 9839.

22.   de Wit E, Bushmaker T, Scott D, Feldmann H, Munster VJ (2011) Nipah virus transmission in a hamster model. PLoSNegl Trop Dis 5: e1432.

23.   Dhondt KP, Mathieu C, Chalons M, Reynaud JM, Vallve A, et al. (2013) Type I interferon signaling protects mice from lethal henipavirus infection. J Infect Dis 207: 142-151.

24.   Wang X, Ge J, Hu S, Wang Q, Wen Z, et al. (2006) Effcacy of DNA immunization with F and G protein genes of Nipah virus. Ann N Y AcadSci 1081: 243-245.

25.   World Health Organization. (2014).www.who.int/csr/disease/ nipah/en/..www.cdc.gov/vhf/nipah/.

26.   Animal models of disease shed light on Nipah virus pathogenesis and transmission Emmie de Wit and Vincent J Munster Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, RockyMountain Laboratories, Hamilton, MT, USAJournal of Pathology J Pathol2015; 235: 196–205 Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/path.4444, 14 September 2014 page no 197-199.

27.   https://doi.org/10.1016/j.coviro.2016.12.003

28.   https://www.researchgate.net/publication/11005512

 

 

Received on 27.03.2020         Modified on 12.04.2020

Accepted on 28.04.2020       ©A&V Publications All right reserved

Res.  J. Pharmacology and Pharmacodynamics.2020; 12(2): 83-87.

DOI: 10.5958/2321-5836.2020.00016.6