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LETTER TO EDITOR
Year : 2020  |  Volume : 14  |  Issue : 3  |  Page : 269-271

Screening for dengue virus in endemic areas prior to transplantation: Indian perspective


Department of Nephrology and Renal Transplantation, Virinchi Hospitals and Max Superspeciality Medical Centre, Hyderabad, Telangana, India

Date of Submission02-Apr-2020
Date of Acceptance05-Aug-2020
Date of Web Publication30-Sep-2020

Correspondence Address:
Dr. Praveen Kumar Etta
Department of Nephrology and Renal Transplantation, Virinchi Hospitals and Max Superspeciality Medical Centre, Hyderabad, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_25_20

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How to cite this article:
Etta PK. Screening for dengue virus in endemic areas prior to transplantation: Indian perspective. Indian J Transplant 2020;14:269-71

How to cite this URL:
Etta PK. Screening for dengue virus in endemic areas prior to transplantation: Indian perspective. Indian J Transplant [serial online] 2020 [cited 2020 Oct 31];14:269-71. Available from: https://www.ijtonline.in/text.asp?2020/14/3/269/296885



Sir,

Dengue is a mosquito-borne viral disease. Nonvectoral transmission from asymptomatic live and deceased donors to transplant recipients has been reported.[1],[2] Dengue could also present as subclinical infection in the recipient at the time of transplantation, which can become symptomatic later. This is problematic, particularly in endemic countries such as India. Recently, we have diagnosed dengue fever in a prospective kidney donor just 2 days before her scheduled donor nephrectomy. She had fever, headache, and body pains associated with mild leukopenia and thrombocytopenia. We have treated her with supportive measures and have performed her surgery after 4 weeks of recovery from illness. Posttransplant period was uneventful, and recipient had immediate graft function. There was no evidence of donor-derived infection in the recipient. Retrospectively, we have analyzed the literature regarding the role of routine screening for dengue in donors and recipients at the time of transplantation in endemic areas, and the ideal interval to take up for transplant surgery for both donor and recipient if they found positive for dengue. The literature is scarce, but few centers in endemic areas have adopted a protocol of routine screening, especially during the outbreaks of dengue.[2] Is it imperative to screen both donors and recipients for dengue virus (DENV) before organ transplantation in India.

Dengue is caused by four antigenically distinct DENV serotypes 1, 2, 3, and 4. Each serotype can cause the full spectrum of disease from a subclinical infection to a mild self-limiting disease, the dengue fever and a severe disease that may be fatal, the dengue hemorrhagic fever/dengue shock syndrome. All the four serotypes of DENV have circulated in India at different times, but generally one serotype dominates a given outbreak.[3] A large proportion of the adults in India have been exposed to dengue as reflected by a high prevalence of dengue seropositivity (≈57%). Infection with one serotype produces life-long immunity to that serotype alone. The secondary infection with another serotype may lead to more severe disease. The presence of pre-exisiting antidengue antibodies increases viremia titers by a phenomenon known as antibody-dependent enhancement of infection. The risk of severe disease from secondary infection increases if someone previously exposed to serotype DENV-1 contracts serotype DENV-2 or DENV-3, or if someone previously exposed to DENV-3 acquires DENV-2. In recent years, co-circulation of all four DENV serotypes in single outbreak was reported from the several parts of India.[4],[5],[6] Hence, secondary and concurrent infections with multiple DENV serotypes are commonly encountered in India, with their life-threatening risk. The secondary infection can also result due to the transplantation of the dengue-infected allograft to a recipient who had exposed to dengue in the past. If the transplant recipients get dengue accidentally due to undiagnosed pretransplant infection in either donor or recipient, it can be fulminant and life threatening in the early posttransplant period.[7] Being a dengue-endemic region, this can happen more frequently in India, and these patients are likely exposed to multiple serotypes of the DENV.[8] The incubation period of dengue is 4–6 days (range 3–14 days). The ratio of asymptomatic to symptomatic dengue infections may range from 2:1 to 10:1. In hyperendemic regions, it was estimated that for every one symptomatic case, there can be 67 cases that are asymptomatic (but can still be viremic).[3] The infected persons could transmit virus as early as or even earlier than 2 days before symptoms develop. The presence of asymptomatic carriers and the ability to transmit virus for a short period before the onset of symptoms may enable accidental occurrence of infection following transplantation.

Due to the risk of transmission from asymptomatic blood donors, the American Association of Blood Banks and the Centers for Disease Control and Prevention have recommended the screening of blood products for dengue in endemic countries. In few endemic countries, blood donors who have been infected with DENV are deferred for periods of up to 6 months (Singapore and Hong Kong). In nonendemic countries, the deferral period is as short as 2 weeks (UK) and 4 weeks (United States, Australia, and New Zealand). In 2017, guidelines for blood donor selection and blood donor referral by the National Blood Transfusion Council, India, have been approved. The blood donors in India who had a history of dengue are deferred for 6 months following full recovery; and for those who have visited, donation is deferred for 4 weeks following return from dengue endemic area if no febrile illness is noted.[9] However, none of the transplant guidelines have recommended dengue screening prior to transplantation and a specific deferral period before taking up for transplant surgery if the donor or recipient found positive for dengue.

The usefulness of dengue screening before transplant in preventing perioperative transmission of dengue was studied recently from North India.[10] The prospective renal transplant recipient and live donor pairs were screened for dengue infection using nonstructural protein 1 (NS1) antigen and IgM antibody testing within 1 week before transplant. There were 44 donor recipient pairs screened, out of which screening was positive in eight pairs. All the patients with positive dengue screening underwent renal transplant surgery 6 weeks following negative NS1 antigen. After a mean waiting period of 6 weeks, NS1 was negative in all pairs while IgM antibody was persisting in two donors and one recipient. Only one of these patients had dengue infection during the early posttransplant period. However, out of 36 pairs with negative dengue screening two had dengue in early posttransplant period. The authors have concluded that dengue screening is effective in reducing its perioperative transmission and associated morbidity, and transplantation can be done after 6 weeks of negative NS1 antigen test.

Laboratory diagnosis of dengue can be performed by isolation of virus, serological tests, dengue antigen, and molecular detection tests. The dengue NS1 antigen-capture ELISA is useful for the detection of dengue early in the disease. The specificity of NS1 assay is very high (98%–100%), and thus is useful for early detection of infection within first 5 days. Compared with primary infections, the NS1 assay has lower sensitivity for secondary infections (DENV IgG positive) where preexisting NS1 antibodies in the serum could inhibit the detection of NS1 antigen. Hence, NS1 assay should be interpreted with caution in dengue hyperendemic regions such as India where secondary infection is prevalent. The NS1 assay also seemed to be less sensitive when used in patients within the 1st day from illness onset. There might be no significant difference in sensitivity of the NS1 assay for different DENV serotypes; however, few studies have found that the sensitivity of the NS1 assay was lower for DENV-2 and -4 infections. A possible explanation for this finding is that a clinically overt DENV-2 infection is more likely to occur in the context of secondary infection than primary infection, and hence, the associated reduction in sensitivity of the NS1 assay. False-positive NS1 is very rare, except for possible cross-reactivity with other flaviviruses and possibly, cytomegalovirus. IgM dengue antibodies appear by 3–5 days, peaks in 2 weeks, and declines within 2–3 months. The IgM antibody capture ELISA is especially useful in the diagnosis of recent infection. Reverse transcriptase-PCR is very sensitive and specific for the detection of viral RNA within the first 7 days after the symptoms appear. A prototype dengue RNA transcription-mediated amplification assay is also available. In areas where dengue is endemic, the ability to run low cost and high-performance tests, such as the NS1 antigen test ± IgM serology during outbreaks, could allow the detection of asymptomatic carriers of the virus in organ donors and recipients. It may be noted that screening of only blood samples may still present the risk of missing transmissible virus present in the kidneys (or other organs like liver) but no longer present in the blood.

In view of these findings, screening of organ donors and recipients for dengue in endemic regions may be considered and at our center, we have implemented a protocol of routine pretransplant screening with NS1 antigen (± IgM serology) detection in all live donors and recipients 2–3 days prior to elective renal transplantation during outbreaks of dengue; for deceased donors, screening is decided on case to case basis. Donor-derived infections pose an avoidable source of morbidity and mortality for the transplant recipient. Although few centers have adopted a similar protocol, more studies are required to recommend routine pretransplant screening for DENV in endemic regions; to establish its sensitivity, cost-effectiveness and feasibility; and to suggest the time interval to take up for transplant surgery if the donor or recipient is found positive for dengue.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Cedano JA, Mora BL, Parra-Lara LG, Manzano-Nuñez R, Rosso F. A scoping review of transmission of dengue virus from donors to recipients after solid organ transplantation. Trans R Soc Trop Med Hyg 2019;113:431-6.  Back to cited text no. 1
    
2.
Rosso F, Pineda JC, Sanz AM, Cedano JA, Caicedo LA. Transmission of dengue virus from deceased donors to solid organ transplant recipients: Case report and literature review. Braz J Infect Dis 2018;22:63-9.  Back to cited text no. 2
    
3.
Chakravarti A, Arora R, Luxemburger C. Fifty years of dengue in India. Trans R Soc Trop Med Hyg 2012;106:273-82.  Back to cited text no. 3
    
4.
Vaddadi K, Gandikota C, Jain PK, Prasad VSV, Venkataramana M. Co-circulation and co-infections of all dengue virus serotypes in Hyderabad, India 2014. Epidemiol Infect 2017;145:2563-74.  Back to cited text no. 4
    
5.
Mishra B, Turuk J, Sahu SJ, Khajuria A, Kumar S, Dey A, et al. Co-circulation of all four dengue virus serotypes:First report from Odisha. Indian J Med Microbiol 2017;35:293-5.  Back to cited text no. 5
[PUBMED]  [Full text]  
6.
Shrivastava S, Tiraki D, Diwan A, Lalwani SK, Modak M, Mishra AC, et al. Co-circulation of all the four dengue virus serotypes and detection of a novel clade of DENV-4 (genotype I) virus in Pune, India during 2016 season. PLoS One 2018;13:e0192672.  Back to cited text no. 6
    
7.
Rosso F, Sanz AM, Parra-Lara LG, Moncada PA, Vélez JD, Caicedo LA. Dengue virus infection in solid organ transplant recipients: A case series and literature review. Am J Trop Med Hyg 2019;101:1226-31.  Back to cited text no. 7
    
8.
Mutheneni SR, Morse AP, Caminade C, Upadhyayula SM. Dengue burden in India: Recent trends and importance of climatic parameters. Emerg Microbes Infect 2017;6:e70.  Back to cited text no. 8
    
9.
Available from: http://naco.gov.in/national-blood-transfusion-council-nbtc-0. [Last accessed on 2020 Apr 01].  Back to cited text no. 9
    
10.
Kallepalli V, Sharma A, Kenwar DB, Singh S, Kohli HS, Singh MP, et al. Impact of dengue screening prior to renal transplant: A single center experience. Transplantation 2019;103 (11S):S26.  Back to cited text no. 10
    




 

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