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Table of Contents
REVIEW ARTICLE
Year : 2022  |  Volume : 16  |  Issue : 5  |  Page : 53-56

Endemic viral disease - Expert group opinion for solid organ transplant recipients in South Asia – Dengue, chikungunya, Zika, rabies, Japanese encephalitis, and Nipah virus


1 Adjunct Prof Infectious Diseases - Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
2 Consultant Infectious Diseases and Tropical Medicine, Apollo Hospitals, Chennai, Tamil Nadu, India
3 Fellow Infectious Diseases, Apollo Hospitals, Chennai, Tamil Nadu, India
4 Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
5 Consultant Nephrology, Teaching Hospital, Candy, Srilanka
6 Department of Nephrology and Renal Transplant Medicine, Medanta Kidney and Urology Institute, Medanta Medicity, Gurugram, Haryana, India

Date of Submission03-Dec-2021
Date of Acceptance28-Feb-2022
Date of Web Publication18-Oct-2022

Correspondence Address:
Dr. Venktasubramanian Ramsubramanian
Apollo Hospitals, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_127_21

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  Abstract 


South Asia is endemic to many virus infections such as arboviruses such as dengue virus, chikungunya virus, Zika virus, Japanese encephalitis (JE) virus, and rabies virus. Arbovirus infections present as fever, rash, arthralgia, myalgia, etc., Although transmission of these viruses has rarely been reported in organ transplants, in the endemic season, there is a possibility as the donor might be in an incubation period. Donor deferral for at least 30 days is advised in any donor with confirmed or suspected cases of arboviral infection. Rabies and JE can cause encephalitis and remain undiagnosed many times, so donors with unknown etiology of encephalitis should be excluded from donation. Nipah virus is an emerging virus, which is reported mainly from Bangladesh, Siliguri, and Kerala in India, however, no case of donor-derived infection has been reported yet.

Keywords: Dengue, Japanese encephalitis, rabies, South Asia, transplant, Zika virus


How to cite this article:
Ramsubramanian V, Guruprasad S, Prabha P K, Sridharan S, Kohli HS, Wazil A W, Bansal SB. Endemic viral disease - Expert group opinion for solid organ transplant recipients in South Asia – Dengue, chikungunya, Zika, rabies, Japanese encephalitis, and Nipah virus. Indian J Transplant 2022;16, Suppl S1:53-6

How to cite this URL:
Ramsubramanian V, Guruprasad S, Prabha P K, Sridharan S, Kohli HS, Wazil A W, Bansal SB. Endemic viral disease - Expert group opinion for solid organ transplant recipients in South Asia – Dengue, chikungunya, Zika, rabies, Japanese encephalitis, and Nipah virus. Indian J Transplant [serial online] 2022 [cited 2022 Dec 9];16, Suppl S1:53-6. Available from: https://www.ijtonline.in/text.asp?2022/16/5/53/358659




  Introduction Top


Viral infections are a challenge in diagnosis and treatment. Quite often, these infections are subclinical and evade detection. Sometimes, the infections are transient and mild in the immunocompetent. Moreover, the symptoms of a lot of them, especially the arboviral infections, are similar, making diagnosis frustrating. Infections in the donor or recipient may theoretically compromise outcomes. This article outlines the approach to endemic viral infections in solid organ transplantation in South Asia.


  Arboviral Diseases Top


Background

Chikungunya virus, dengue virus, and Zika virus (ZIKV) are arboviruses transmitted by urban Aedes species, predominantly Aedes aegypti and Aedes albopictus. South Asian countries are endemic regions for dengue and chikungunya.[1] Zika is also an emerging arboviral disease in this part of the world.[2] Donors living in this region are likely to transmit the disease to recipients. Few cases of donor-derived dengue have already been reported.[3]

Epidemiology

Dengue fever (DF) has been endemic in many countries in the world and including South Asian countries.[4] DF has been reported from almost all states in India. The seroprevalence of 38% has been reported in a recent meta-analysis from India.[5] The outbreaks of chikungunya have been reported from India from 1963 onward, however, there has been a recent surge in chikungunya infection in India and other countries in South Asia (SA) from 2005 onward.[6] India has been the epicenter of CHKV infection, and almost all states have been affected by it. The outbreaks of the ZIKV have been reported from the Indian states of Kerala, Rajasthan, and recently in Uttar Pradesh (UP).[7]

Clinical features

Arbovirus infections present with acute febrile illness; a patient may also have rash, myalgia, arthralgia, and conjunctival injection. Acute arthritis, shorter duration of fever, rash, myalgia/arthralgia, and conjunctivitis are more prominent in chikungunya fever, while abdominal pain, leukopenia, neutropenia, and thrombocytopenia are more prominent in DF.[1]

Diagnosis

Serological diagnosis of dengue, chikungunya, and Zika can be made using immunoglobulin M (IgM) antibodies. A positive antigen test is diagnostic for dengue and chikungunya but is present only in the first 5 days of illness. IgM antibodies take 5–7 days to develop and remain in circulation for almost 4–8 weeks.[5],[6] Nucleic acid amplification tests (nucleic acid testing/polymerase chain reaction) may be utilized for early diagnosis if available for these infections [Table 1].
Table 1: Arboviral infections, transmission, and diagnosis

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Donor screening

Routine screening of these infections is not recommended, however, as disease transmission is periodic/seasonal, donor screening for dengue (NS1Ag) should be done during periods of high transmission in endemic regions. If a donor is confirmed to have any of these arboviral infections, then donor deferral for 30 days is recommended for dengue and chikungunya and 120 days for Zika.[2]

Donor acceptance criteria

Donor deferral should be done if any potential donor has suffered from a febrile illness suggestive of these arboviral infections, especially within the previous 30 days. Organs from deceased donors with signs and symptoms suggestive of recent arbovirus infection (<30 days) should be discarded.

Management

There is no specific therapy for these viruses. Adequate hydration and supportive care are the only available options. Organ transplant recipients may take longer to recover and may be slow to defervesce due to underlying immunosuppressed state.

Recipients who travel to an endemic region

Unfortunately, to date, no vaccine is standardized for these infections. Dengue vaccine (Dengvaxia) has not been approved in India till now and it being a live attenuated vaccine is not studied in immunosuppressed patients.[8] Travelers should reduce skin exposure to mosquito bites with barrier methods, such as insect repellents and long-sleeved or permethrin-treated clothing.


  Japanese Encephalitis Top


Background

Japanese encephalitis virus (JEV) is a flavivirus related to dengue, yellow fever, and West Nile viruses, and is spread by mosquitoes.[9] Cases start in June and the peak season is September. Transmission is mostly through mosquito bites; however, donor-derived infection is possible.[10] Till date, no case has been reported of JEV, which has been donor derived.

Epidemiology

JEV is the main cause of viral encephalitis in many countries of Asia, including India, with an estimated 68,000 clinical cases every year.[9] The most commonly affected state in India is UP, particularly eastern UP, which accounts for roughly 75% of cases all over India in recent estimates.[11]

Clinical features

JEV presents like any other encephalitis causing virus, and patients may have neck stiffness, disorientation, coma, seizures, and spastic paralysis. It should be suspected in any patient presenting with short history of febrile illness and altered mental status. Although symptomatic Japanese encephalitis (JE) is rare, the case-fatality rate among those with encephalitis can be as high as 30%.[9] Permanent neurologic or psychiatric sequelae can occur in 30%–50% of those with encephalitis. Clinically, it is difficult to differentiate JE from other cases of encephalitis/encephalopathy

Diagnosis

The ideal method for laboratory confirmation is by testing cerebrospinal fluid (CSF) or serum for JEV-specific IgM antibody.[12]

Donor screening and acceptance criteria

Routine screening of donors for JEV is not recommended, but organ harvesting from a person suffering from encephalitis, particularly for which treatment does not exist, is contraindicated.[10]

Management

There is no specific therapy for JE, and treatment is mainly supportive. Patients are not infectious but should avoid further mosquito bites. A number of antiviral agents have been investigated, including Interferon (IFN)-alfa-2a and diethyldithiocarbamate (a low molecular weight dithiol). However, none of these have convincingly been shown to improve the outcome of JE.[9]

Recipients who travel to an endemic region

The prevention of JE is based largely on two interventions: mosquito control and by immunization. To reduce the risk for JE, all travelers to JE endemic areas should take precautions to avoid mosquito bites. Personal preventive measures include the use of mosquito repellents, long-sleeved clothes, coils, and vaporizers. Travelers spending extensive time in JE endemic areas are recommended to get vaccinated before travel.

Vaccine

Four main types of JE vaccines are currently in use: inactivated mouse brain-derived vaccines, inactivated Vero cell-derived vaccines, live attenuated vaccines, and live recombinant (chimeric) vaccines. The JENVAC is an inactivated Vero cell-derived vaccine, made indigenously, from an Indian strain of the JEV. It is both safe and highly effective against all known strains of JEV. The seroconversion rates are close to 90% in the immunocompetent.[13]


  Rabies Top


Background

Rabies virus (family Rhabdoviridae, genus Lyssavirus) is an enveloped, negative, single-stranded RNA virus. After the virus is inoculated into humans, through the saliva or bites or scratches from an infected animal, it is taken up through peripheral nerves. Then, through retrograde transport, the virus infects the central nervous system and causes encephalitis; this process may take weeks to months.[14] The disease still remains largely fatal. More than 95% of disease is caused by dog bites due to the large population of stray dogs in India.[15] Transmission of rabies through organ transplant has been reported in the form of clusters, where organs procured from a single donor lead to transmission to many recipients.[16],[17]

Epidemiology

India is the most affected country with rabies in the world. Approximately 35% of all deaths due to rabies occur in India. Various studies have shown that roughly 10,000–20,000 deaths occur annually in India due to rabies.[15]

Clinical features

The disease can be acquired through bite of an infected animal and rarely through organ transplant. Rabies is categorized into two types based on clinical symptoms, the manic (encephalitis) type and paralytic rabies (the former is more common). Any patient who comes with a history of altered mental status and history of an animal bite should be evaluated for rabies.[14] As such, donor-derived rabies is uncommon, so testing for rabies in a case of encephalitis should be done after common causes have been ruled out.[17]

Diagnosis

The demonstration of antibodies in the serum or in CSF in the absence of a history of vaccination for rabies is an indirect evidence of rabies infection. Interpretation of test results may be difficult since the host immune response may vary among individuals. The negative serological tests do not rule out rabies. Serological testing is not useful for antemortem diagnosis because of late seroconversion and the high mortality rate but may be of value in the diagnosis of paralytic rabies, where the survival is relatively longer.[18] Demonstration of virus antigen through fluorescent antibody test in brain biopsy specimens (which are largely obtained postmortem) is the gold standard.[18]

Donor screening and donor acceptance criteria

Routine screening of donors is not recommended. As the disease is mostly fatal and the incubation period ranges from a few days to a few years, it is advised not to procure organs from a donor with unspecified encephalitis.[10]

Management

There is no specific antiviral agent effective against rabies. Treatment remains restricted to supportive care. However, postexposure prophylaxis (PEP) is very effective. PEP consists of rabies vaccine and either anti-rabies immunoglobulin or more recently introduced monoclonal antibody. Postvaccination antibody levels should be checked in these patients to document that they have mounted adequate immunity. As per the WHO Expert Rabies Committee, a neutralizing antibody level of ≥0.5 international units/mL of serum suggests a positive protective antibody response to vaccination.[19]

Recipients who travel to an endemic region

There is no clear recommendation of preexposure prophylaxis for patients with organ transplant. However, a transplant traveling to a highly endemic area for rabies or a recipient who works with animals may be given vaccination for rabies (refer to section on Vaccines).


  Nipah Virus Top


Nipah virus belongs to the Paramyxoviridae family and is naturally harbored by pteropid fruit bats (flying foxes). They are zoonotic pathogens with a wide host range. Nipah is a cause of outbreaks of viral encephalitis initially identified in Malaysia but subsequently reported from Bangladesh, Siliguri, and recently from Kerala in India.[20],[21] To date, no donor-derived case has been reported of Nipah, so routine screening of donors for Nipah is not recommended. Any harvesting from a deceased donor who may have had encephalitis is discouraged.


  Conclusion Top


In conclusion, endemic viral infections are not uncommon in South Asia and diagnosis and therapy may be challenging. Data is scarce on the recommendations of approach to solid organ transplantation for donors and recipients with endemic viral infections including arboviral and rabies. Outcomes may be severely compromised in a few infections like rabies. A careful approach is warranted to ensure patient safety.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Gubler DJ. Human arbovirus infections worldwide. Ann N Y Acad Sci 2001;951:13-24.  Back to cited text no. 1
    
2.
Bhardwaj S, Gokhale MD, Mourya DT. Zika virus: Current concerns in India. Indian J Med Res 2017;146:572-5.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Gupta RK, Gupta G, Chorasiya VK, Bag P, Shandil R, Bhatia V, et al. Dengue virus transmission from living donor to recipient in liver transplantation: A case report. J Clin Exp Hepatol 2016;6:59-61.  Back to cited text no. 3
    
4.
Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature 2013;496:504-7.  Back to cited text no. 4
    
5.
Ganeshkumar P, Murhekar MV, Poornima V, Saravanakumar V, Sukumaran K, Anandaselvasankar A, et al. Dengue infection in India: A systematic review and meta-analysis. PLoS Negl Trop Dis 2018;12:e0006618.  Back to cited text no. 5
    
6.
Translational Research Consortia (TRC) for Chikungunya Virus in India. Current status of Chikungunya in India. Front Microbiol 2021;12:695173.  Back to cited text no. 6
    
7.
Malhotra B, Gupta V, Sharma P, Singh R, Sharma H, Vyas M, et al. Clinico-epidemiological and genomic profile of first Zika virus outbreak in India at Jaipur city of Rajasthan state. J Infect Public Health 2020;13:1920-6.  Back to cited text no. 7
    
8.
da Costa VG, Marques-Silva AC, Floriano VG, Moreli ML. Safety, immunogenicity and efficacy of a recombinant tetravalent dengue vaccine: A meta-analysis of randomized trials. Vaccine 2014;32:4885-92.  Back to cited text no. 8
    
9.
Kulkarni R, Sapkal GN, Kaushal H, Mourya DT. Japanese encephalitis: A brief review on Indian perspectives. Open Virol J 2018;12:121-30.  Back to cited text no. 9
    
10.
Basavaraju SV, Kuehnert MJ, Zaki SR, Sejvar JJ. Encephalitis caused by pathogens transmitted through organ transplants, United States, 2002-2013. Emerg Infect Dis 2014;20:1443-51.  Back to cited text no. 10
    
11.
Kumari R, Joshi PL. A review of Japanese encephalitis in Uttar Pradesh, India. WHO South East Asia J Public Health 2012;1:374-95.  Back to cited text no. 11
    
12.
Kakkar M, Dhole TN, Rogawski ET, Chaturvedi S. Public health laboratory surveillance and diagnosis of Japanese encephalitis: Time to revisit. Indian Pediatr 2016;53:33-5.  Back to cited text no. 12
    
13.
Singh A, Mitra M, Sampath G, Venugopal P, Rao JV, Krishnamurthy B, et al. A Japanese encephalitis vaccine from India induces durable and cross-protective immunity against temporally and spatially wide-ranging global field strains. J Infect Dis 2015;212:715-25.  Back to cited text no. 13
    
14.
Dietzschold B, Schnell M, Koprowski H. Pathogenesis of rabies. Curr Top Microbiol Immunol 2005;292:45-56.  Back to cited text no. 14
    
15.
Radhakrishnan S, Vanak AT, Nouvellet P, Donnelly CA. Rabies as a public health concern in India – A historical perspective. Trop Med Infect Dis 2020;5:162.  Back to cited text no. 15
    
16.
Gode GR, Bhide NK. Two rabies deaths after corneal grafts from one donor. Lancet 1988;2:791.  Back to cited text no. 16
    
17.
Zhang J, Lin J, Tian Y, Ma L, Sun W, Zhang L, et al. Transmission of rabies through solid organ transplantation: A notable problem in China. BMC Infect Dis 2018;18:273.  Back to cited text no. 17
    
18.
Mani RS, Madhusudana SN. Laboratory diagnosis of human rabies: Recent advances. ScientificWorldJournal 2013;2013:569712.  Back to cited text no. 18
    
19.
“WHO Expert Consultation on Rabies. Second Report,” World Health Organization Technical Report Series 982; 2013.  Back to cited text no. 19
    
20.
Luby SP, Hossain MJ, Gurley ES, Ahmed BN, Banu S, Khan SU, et al. Recurrent zoonotic transmission of Nipah virus into humans, Bangladesh, 2001-2007. Emerg Infect Dis 2009;15:1229-35.  Back to cited text no. 20
    
21.
Ajith Kumar AK, Anoop Kumar AS. Deadly Nipah outbreak in Kerala: Lessons learned for the future. Indian J Crit Care Med 2018;22:475-6.  Back to cited text no. 21
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Abstract
Introduction
Arboviral Diseases
Japanese Encepha...
Rabies
Nipah Virus
Conclusion
References
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