- Email: [email protected]
The Zika epidemics and transplantation
Author’s Accepted Manuscript The Zika Epidemics and Transplantation Fernanda P. Silveira, Silvia V. Campos
http://www.jhltonline.org
PII: DOI: Reference:
S1053-2498(16)30058-4 http://dx.doi.org/10.1016/j.healun.2016.03.010 HEALUN6231
To appear in: Journal of Heart and Lung Transplantation Accepted date: 26 Cite this article as: Fernanda P. Silveira and Silvia V. Campos, The Zika Epidemics and Transplantation, Journal of Heart and Lung Transplantation, http://dx.doi.org/10.1016/j.healun.2016.03.010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
The Zika Epidemics and Transplantation
Fernanda P. Silveira1 and Silvia V. Campos2 1 Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA, USA 2
Pulmonary Division, Lung Transplant Group, Heart Institute (InCor),
University of São Paulo, São Paulo, Brazil
Corresponding author: Fernanda P. Silveira, MD 3601 Fifth Avenue, Suite 3A Pittsburgh, PA, USA, 15237 Phone: (412) 648-6601 Fax: (412) 648-6399 Email: [email protected]
Abstract: In the last few months an epidemic of Zika virus (ZIKV) has affected several countries and it continues to spread rapidly. This virus was initially thought to cause only a mild febrile illness; however, the current epidemic has shown that it is associated with serious complications. Increasing reports are linking ZIKV to devastating conditions such as microcephaly in newborns and important neurological syndromes. Although ZIKV infection has not yet been reported in transplant recipients, it is likely that it will be reported soon, due to the number of transplants performed in affected areas and to global travel. In this manuscript we discuss the impact of ZIKV in transplantation, and propose recommendations to prevent donor-derived infections.
The end of 2015 and the beginning of 2016 were marked by public health concerns surrounding the epidemic of Zika virus (ZIKV) in several parts of the globe, leading the World Health Organization (WHO) to declare a Public Health Emergency of International Concern on February 1, 2016. The full scope of implications of this epidemic to organ transplant recipients and candidates is not yet known; however, it is expected that these patients will be affected. There is a possibility that clinical manifestations in these patients may be different, due to immunosuppression and end organ dysfunction. Another area of concern is transmission through organ donation. Therefore, it is imperative that the transplant community be prepared to deal with this threat. In this article, we discuss the implications of the ZIKV epidemics to organ transplantation. ZIKV is an RNA virus of the Flaviviridae family, genus Flavivirus. It is transmitted by the Aedes mosquitoes, which also transmit dengue, yellow fever and chikungunya. ZIKV was first isolated in 1947 from a rhesus monkey in Zika Forest, Uganda and until it caused an epidemic on Yap Island in Micronesia in 2007 (1), in Gabon in 2010 (2) and in the French Polynesia in 2013 (3) it was largely ignored. Since those outbreaks, it has been known that this virus had the potential to spread to countries where the vector is present; however, ZIKV had not been regarded as a major threat since infection is asymptomatic in up to 80% of individuals and disease thought to manifest as mild febrile illness, with associated rash, arthralgia, and conjunctivitis. ZIKV arrived in Brazil, a populous country infested with both Aedes aegypti and A. albopictus, in 2015. For the first time, a large non-susceptible population exposed to an abundance of the mosquito vector was exposed to the virus and we became aware of serious complications potentially associated with ZIKV. In December 2015, the Brazilian government reported a significant increase in the number of cases of microcephaly in newborns. More recently, an increase in the number of cases of Guillain-Barré syndrome (GBS) has been observed in affected regions. In a short period of time evidence linking ZIKV to these two devastating conditions as well as other adverse pregnancy outcomes has become available, including newer data from the French Polynesia epidemic (4-8). Meanwhile, documented reports of sexual and blood transmission have intensified apprehension about infection spread (9-11). As of February 29th 2016, thirty six countries and territories, primarily in the Americas but also in Oceania/Pacific Islands and Africa, were found to have active ZIKV
transmission (11). As of March 2nd 2016, 153 cases of travel-associated ZIKV disease were reported in the U.S. (11). Due to the epidemics and its potential for morbidity, the Center for Disease Control and Prevention (CDC) released a travel advisory discouraging pregnant women from traveling to countries with ZIKV transmission. It also recommends that men who reside in or have traveled to an area of active ZIKV transmission who have a pregnant partner abstain from sexual activity or use condoms during sex (12). The Federal Drug Administration (FDA) issued guidance to defer blood donation for 28 days following return from countries with ZIKV outbreaks (13). WHO issued similar interim guidance, which in addition included recommendation for donor deferral for no less than 28 days after resolution of symptoms in case of donors with confirmed ZIKV infection and donors with a clinical history consistent with ZIKV disease (14). So far, no cases of ZIKV have been reported in transplant recipients and the risk of development of severe disease due to ZIKV in these patients is unknown. However, due to the rapid spread of the virus in Brazil, where almost 8,000 solid organ transplants are performed yearly (15), cases of ZIKV disease in organ transplant recipients will likely be described soon. Since the degree and frequency of serious illness by ZIKV in transplant recipients is presently unknown, we call for adopting a cautious approach. Until more is learned about ZIKV in transplantation, patients on the transplant waitlist and organ transplant recipients should avoid unnecessary travel to areas with ZIKV transmission. If travel can’t be avoided or if they live in areas of ZIKV transmission, they should employ protective measures to avoid mosquito bites, such as insect repellents, wearing white long-sleeved shirts and long pants, and mosquito nets. ZIKV has been identified in semen and there have been cases of sexual transmission from affected men. However, there has been no evidence of sexual transmission from infected women. Therefore, we recommend that these patients abstain from sexual activity or use condoms during sex with a man who lives or has been to an area of ZIKV transmission (table 1). Women who are transplant recipients and live in areas of ZIKV transmission should carefully consider their pregnancy plans. In addition to the risks of pregnancy itself in a transplant recipient, there is also the risk of microcephaly and other birth defects if infected with ZIKV during pregnancy. These women should be informed of these risks and encouraged to delay pregnancy until more is known.
Transplant recipients and their physicians should familiarize themselves with the main clinical signs and complications of ZIKV infection, including neurological syndromes such as GBS. Specific instructions to seek specialized medical care if they become ill should be given to patients. The patients who should be tested for ZIKV infection must have both a compatible clinical presentation and epidemiological history. The clinical presentations include: a) fever, maculopapular rash, conjunctivitis, myalgia/arthralgia, retro-orbital pain; b) GBS, encephalitis, encephalomyelitis or any other unexplained neurological syndrome. The epidemiological history should include either: travel to or living in an area of ZIKV transmission; unprotected sex with a man who lives or has been to an area of ZIKV transmission; recent receipt of blood transfusion; or recent transplant. Diagnosis can be made by PCR of blood within the first 5 days after onset of symptoms and/or urine if within the first 14 days after onset of symptoms. Since there is an overlap between the symptoms of ZIKV infection and those caused by dengue and chikungunya, these other infections should be considered in the differential diagnosis, as well as cytomegalovirus infection. If ZIKV infection is confirmed, reduction in immunosuppression should be considered as a way to potentially avoid severe symptoms. The potential of donor transmission of ZIKV brings its own specific challenges, especially given the fact that currently there is not a donor antibody screening test for ZIKV. Recently, the United Network for Organ Sharing (UNOS) published a guidance statement on ZIKV, encouraging organ procurement organizations and transplant centers to focus on recent travel history and epidemiologic risk factors, as well as recent donor symptoms, and consider that the risk of donor derived infection should be balanced with the benefits of transplantation in each potential recipient (16). We propose detailed strategies to decrease the risk of donor-derived ZIKV infection (table 1). The evaluation of deceased donors should, whenever possible, include both a detailed travel and sexual history. The main factors in decision-making are whether the donor has been to a ZIKV-affected area or had sex with a man who has been to a ZIKV-affected area; the type of donor (deceased vs. living); and history of compatible symptoms (Table 1). There are limited data on the length of time the virus persists in tissues. Out of an abundance of caution, organs should not be accepted for transplantation during the first
6 months after resolution of symptoms in the donor. Transplantation from a living donor may need to be postponed. Since up to 80% of infections can be asymptomatic and adequate serology for ZIKV is still in development, it is challenging to make recommendations for asymptomatic living donors residing in ZIKV-affected areas. We feel that excluding these donors would cause more harm than benefit, due to its impact on the donor pool. In order to minimize the risk of infection, potential living donors should be counseled on the measures to avoid mosquito bites and only practice protected sex until donation. We recommend that transplant centers discuss with recipients that there is an unknown risk of ZIKV transmission in this setting. Recipients of such donors should be monitored carefully in the first post-transplant months. At this point, there are many unknowns about the effects of ZIKV on transplantation. The transplant community must be tuned in to new developments as they arise, and be prepared to work together, particularly with colleagues in the areas that the most affected by this new threat.
Disclaimer: The authors do not have a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript.
Acknowledgments: The authors thank Frederico G. S. Toledo for his critical review of the manuscript and insightful editorial comments.
Reference 1.
Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, et al. Zika
virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med. 2009 Jun 11;360(24):2536-43. 2.
Grard G, Caron M, Mombo IM, Nkoghe D, Mboui Ondo S, Jiolle D, et al. Zika virus in
Gabon (Central Africa)--2007: a new threat from Aedes albopictus? PLoS Negl Trop Dis. 2014 Feb;8(2):e2681. 3.
Ioos S, Mallet HP, Leparc Goffart I, Gauthier V, Cardoso T, Herida M. Current Zika
virus epidemiology and recent epidemics. Med Mal Infect. 2014 Jul;44(7):302-7. 4.
Schuler-Faccini L, Ribeiro EM, Feitosa IM, Horovitz DD, Cavalcanti DP, Pessoa A, et
al. Possible Association Between Zika Virus Infection and Microcephaly - Brazil, 2015. MMWR Morb Mortal Wkly Rep. 2016;65(3):59-62. 5.
Mlakar J, Korva M, Tul N, Popovic M, Poljsak-Prijatelj M, Mraz J, et al. Zika Virus
Associated with Microcephaly. N Engl J Med. 2016 Feb 10. 6.
Brasil P, Pereira JP, Jr., Raja Gabaglia C, Damasceno L, Wakimoto M, Ribeiro
Nogueira RM, et al. Zika Virus Infection in Pregnant Women in Rio de Janeiro - Preliminary Report. N Engl J Med. 2016 Mar 4. 7.
Calvet G, Aguiar RS, Melo AS, Sampaio SA, de Filippis I, Fabri A, et al. Detection and
sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study. Lancet Infect Dis. 2016 Feb 17. 8.
Cao-Lormeau VM, Blake A, Mons S, Lastere S, Roche C, Vanhomwegen J, et al.
Guillain-Barre Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet. 2016 Feb 29. 9.
Musso D, Baud D. Zika virus: time to move from case reports to case control. Lancet
Infect Dis. 2016 Feb 17. 10.
Foy BD, Kobylinski KC, Chilson Foy JL, Blitvich BJ, Travassos da Rosa A, Haddow
AD, et al. Probable non-vector-borne transmission of Zika virus, Colorado, USA. Emerg Infect Dis. 2011 May;17(5):880-2.
11.
CDC. Zika virus. 2016 [cited 2016 March 7]; Available from:
http://www.cdc.gov/zika/transmission. 12.
Oster AM, Brooks JT, Stryker JE, Kachur RE, Mead P, Pesik NT, et al. Interim
Guidelines for Prevention of Sexual Transmission of Zika Virus - United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65(5):120-1. 13.
US Federal Drug Administration. 2016 [cited 2016 February 22]; Available from:
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm486359.htm. 14.
World Health Organization. Maintaining a safe and adequate blood supply during Zika
virus outbreaks2016: Available from: http://www.who.int/csr/resources/publications/zika/Safeblood_supply18Feb2016.pdf?ua=1. 15.
Associação Brasileira de Transplante de Órgãos. Registro Brasileiro de Transplantes.
2015 [cited 2016 March 14]; Available from: http://www.abto.org.br/abtov03/default.aspx?mn=457&c=900&s=0. 16.
United Network for Organ SharingSharing UNfO. Guidance for organ donation and
transplantation professionals regarding the Zika virus. 2016 [cited 2016 February 22]; Available from: https://www.unos.org/guidance-for-organ-donation-and-transplantationprofessionals-regarding-the-zika-virus.
Table 1 - Recommendations for prevention of Zika virus infection in transplant recipients and candidates and prevention of donor-derived infection Recommendation Transplant recipients and candidates Living in area of Zika transmission
Use protective measures to avoid mosquito bites, such as use of insect repellents, use of long-sleeved shirts and pants, use of mosquito nets Abstain from sexual activity or consistently and correctly use condoms during sex with men
Not living in area of Zika transmission
Avoid unnecessary travel to areas with Zika transmission If travel can't be avoided, use protective measures to avoid mosquito bites, such as use of insect repellents, use of long-sleeved shirts and pants, use of mosquito nets Abstain from sexual activity or consistently and correctly use condoms during sex with a man who has been to an area fo Zika transmission for 4 weeks after his return
Deceased donor in areas without Zika transmission Asymptomatic donor with travel to area of Zika transmission in the preceding 4 weeks Asymptomatic donor with history of unprotected sexual activity with men who had been to area of Zika transmission in the preceding 4 weeks Donor with symptoms suggestive of ZIKV infection and with travel to area of Zika transmission in the preceding 6 months Donor with symptoms suggestive of ZIKV infection and with history of unprotected sexual activity with men who had been to area of Zika transmission in the preceding 6 months Deceased donor in areas with Zika transmission Asymptomatic donor
May be considered for organ donation after discussion about risk and benefits of potential donor-derived infection and informed consent May be considered for organ donation after discussion about risk and benefits of potential donor-derived infection and informed consent
Do not utilize donor unless symptoms can be attributed to a condition other than Zika virus and this other condition does not preclude donation
Do not utilize donor unless symptoms can be attributed to a condition other than Zika virus and this other condition does not preclude donation
May be considered for organ donation after discussion about risk and benefits of potential donor-derived infection and informed consent
Donor with symptoms suggestive of ZIKV infection in the preceding 6 months
Do not utilize donor unless symptoms can be attributed to a condition other than Zika virus and this other condition does not preclude donation
Living donor in areas without Zika transmission Asymptomatic living donors with history of travel to area of Zika transmission
Defer donation for 4 weeks after return. If no symptoms develop in 4 weeks, may donate after discussion about risk and benefits of potential donor-derived infection and informed consent
Asymptomatic living donors with history of unprotected sexual activity with men who had been to area of Zika transmission in the preceding 4 weeks
Defer donation for 4 weeks after last unprotected sexual encounter. If no symptoms develop in 4 weeks, may donate after discussion about risk and benefits of potential donor-derived infection and informed consent
Living donors with Zika virus infection
Defer donation for 6 months after onset of symptoms. If recipient's clinical condition does not allow the delay in transplantation, obtain ZIKV PCR 4 weeks after resolution of symptoms and consider donation only if PCR is negative and after discussion of risk and benefits of potential donor-derived infection and informed consent
Living donor in areas with Zika transmission
Living donors with Zika virus infection
Asymptomatic living donors
Defer donation for 6 months after onset of symptoms. If recipient's clinical condition does not allow the delay in transplantation, obtain ZIKV PCR 4 weeks after resolution of symptoms and consider donation only if PCR is negative and after discussion of risk and benefits of potential donor-derived infection and informed consent Discussion about potential risk with recipients. Donors should counseled on measures to avoid infection, such as measures to avoid mosquito bites and consistent and correct use of condons during sex, until donation
http://www.jhltonline.org
PII: DOI: Reference:
S1053-2498(16)30058-4 http://dx.doi.org/10.1016/j.healun.2016.03.010 HEALUN6231
To appear in: Journal of Heart and Lung Transplantation Accepted date: 26 Cite this article as: Fernanda P. Silveira and Silvia V. Campos, The Zika Epidemics and Transplantation, Journal of Heart and Lung Transplantation, http://dx.doi.org/10.1016/j.healun.2016.03.010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
The Zika Epidemics and Transplantation
Fernanda P. Silveira1 and Silvia V. Campos2 1 Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA, USA 2
Pulmonary Division, Lung Transplant Group, Heart Institute (InCor),
University of São Paulo, São Paulo, Brazil
Corresponding author: Fernanda P. Silveira, MD 3601 Fifth Avenue, Suite 3A Pittsburgh, PA, USA, 15237 Phone: (412) 648-6601 Fax: (412) 648-6399 Email: [email protected]
Abstract: In the last few months an epidemic of Zika virus (ZIKV) has affected several countries and it continues to spread rapidly. This virus was initially thought to cause only a mild febrile illness; however, the current epidemic has shown that it is associated with serious complications. Increasing reports are linking ZIKV to devastating conditions such as microcephaly in newborns and important neurological syndromes. Although ZIKV infection has not yet been reported in transplant recipients, it is likely that it will be reported soon, due to the number of transplants performed in affected areas and to global travel. In this manuscript we discuss the impact of ZIKV in transplantation, and propose recommendations to prevent donor-derived infections.
The end of 2015 and the beginning of 2016 were marked by public health concerns surrounding the epidemic of Zika virus (ZIKV) in several parts of the globe, leading the World Health Organization (WHO) to declare a Public Health Emergency of International Concern on February 1, 2016. The full scope of implications of this epidemic to organ transplant recipients and candidates is not yet known; however, it is expected that these patients will be affected. There is a possibility that clinical manifestations in these patients may be different, due to immunosuppression and end organ dysfunction. Another area of concern is transmission through organ donation. Therefore, it is imperative that the transplant community be prepared to deal with this threat. In this article, we discuss the implications of the ZIKV epidemics to organ transplantation. ZIKV is an RNA virus of the Flaviviridae family, genus Flavivirus. It is transmitted by the Aedes mosquitoes, which also transmit dengue, yellow fever and chikungunya. ZIKV was first isolated in 1947 from a rhesus monkey in Zika Forest, Uganda and until it caused an epidemic on Yap Island in Micronesia in 2007 (1), in Gabon in 2010 (2) and in the French Polynesia in 2013 (3) it was largely ignored. Since those outbreaks, it has been known that this virus had the potential to spread to countries where the vector is present; however, ZIKV had not been regarded as a major threat since infection is asymptomatic in up to 80% of individuals and disease thought to manifest as mild febrile illness, with associated rash, arthralgia, and conjunctivitis. ZIKV arrived in Brazil, a populous country infested with both Aedes aegypti and A. albopictus, in 2015. For the first time, a large non-susceptible population exposed to an abundance of the mosquito vector was exposed to the virus and we became aware of serious complications potentially associated with ZIKV. In December 2015, the Brazilian government reported a significant increase in the number of cases of microcephaly in newborns. More recently, an increase in the number of cases of Guillain-Barré syndrome (GBS) has been observed in affected regions. In a short period of time evidence linking ZIKV to these two devastating conditions as well as other adverse pregnancy outcomes has become available, including newer data from the French Polynesia epidemic (4-8). Meanwhile, documented reports of sexual and blood transmission have intensified apprehension about infection spread (9-11). As of February 29th 2016, thirty six countries and territories, primarily in the Americas but also in Oceania/Pacific Islands and Africa, were found to have active ZIKV
transmission (11). As of March 2nd 2016, 153 cases of travel-associated ZIKV disease were reported in the U.S. (11). Due to the epidemics and its potential for morbidity, the Center for Disease Control and Prevention (CDC) released a travel advisory discouraging pregnant women from traveling to countries with ZIKV transmission. It also recommends that men who reside in or have traveled to an area of active ZIKV transmission who have a pregnant partner abstain from sexual activity or use condoms during sex (12). The Federal Drug Administration (FDA) issued guidance to defer blood donation for 28 days following return from countries with ZIKV outbreaks (13). WHO issued similar interim guidance, which in addition included recommendation for donor deferral for no less than 28 days after resolution of symptoms in case of donors with confirmed ZIKV infection and donors with a clinical history consistent with ZIKV disease (14). So far, no cases of ZIKV have been reported in transplant recipients and the risk of development of severe disease due to ZIKV in these patients is unknown. However, due to the rapid spread of the virus in Brazil, where almost 8,000 solid organ transplants are performed yearly (15), cases of ZIKV disease in organ transplant recipients will likely be described soon. Since the degree and frequency of serious illness by ZIKV in transplant recipients is presently unknown, we call for adopting a cautious approach. Until more is learned about ZIKV in transplantation, patients on the transplant waitlist and organ transplant recipients should avoid unnecessary travel to areas with ZIKV transmission. If travel can’t be avoided or if they live in areas of ZIKV transmission, they should employ protective measures to avoid mosquito bites, such as insect repellents, wearing white long-sleeved shirts and long pants, and mosquito nets. ZIKV has been identified in semen and there have been cases of sexual transmission from affected men. However, there has been no evidence of sexual transmission from infected women. Therefore, we recommend that these patients abstain from sexual activity or use condoms during sex with a man who lives or has been to an area of ZIKV transmission (table 1). Women who are transplant recipients and live in areas of ZIKV transmission should carefully consider their pregnancy plans. In addition to the risks of pregnancy itself in a transplant recipient, there is also the risk of microcephaly and other birth defects if infected with ZIKV during pregnancy. These women should be informed of these risks and encouraged to delay pregnancy until more is known.
Transplant recipients and their physicians should familiarize themselves with the main clinical signs and complications of ZIKV infection, including neurological syndromes such as GBS. Specific instructions to seek specialized medical care if they become ill should be given to patients. The patients who should be tested for ZIKV infection must have both a compatible clinical presentation and epidemiological history. The clinical presentations include: a) fever, maculopapular rash, conjunctivitis, myalgia/arthralgia, retro-orbital pain; b) GBS, encephalitis, encephalomyelitis or any other unexplained neurological syndrome. The epidemiological history should include either: travel to or living in an area of ZIKV transmission; unprotected sex with a man who lives or has been to an area of ZIKV transmission; recent receipt of blood transfusion; or recent transplant. Diagnosis can be made by PCR of blood within the first 5 days after onset of symptoms and/or urine if within the first 14 days after onset of symptoms. Since there is an overlap between the symptoms of ZIKV infection and those caused by dengue and chikungunya, these other infections should be considered in the differential diagnosis, as well as cytomegalovirus infection. If ZIKV infection is confirmed, reduction in immunosuppression should be considered as a way to potentially avoid severe symptoms. The potential of donor transmission of ZIKV brings its own specific challenges, especially given the fact that currently there is not a donor antibody screening test for ZIKV. Recently, the United Network for Organ Sharing (UNOS) published a guidance statement on ZIKV, encouraging organ procurement organizations and transplant centers to focus on recent travel history and epidemiologic risk factors, as well as recent donor symptoms, and consider that the risk of donor derived infection should be balanced with the benefits of transplantation in each potential recipient (16). We propose detailed strategies to decrease the risk of donor-derived ZIKV infection (table 1). The evaluation of deceased donors should, whenever possible, include both a detailed travel and sexual history. The main factors in decision-making are whether the donor has been to a ZIKV-affected area or had sex with a man who has been to a ZIKV-affected area; the type of donor (deceased vs. living); and history of compatible symptoms (Table 1). There are limited data on the length of time the virus persists in tissues. Out of an abundance of caution, organs should not be accepted for transplantation during the first
6 months after resolution of symptoms in the donor. Transplantation from a living donor may need to be postponed. Since up to 80% of infections can be asymptomatic and adequate serology for ZIKV is still in development, it is challenging to make recommendations for asymptomatic living donors residing in ZIKV-affected areas. We feel that excluding these donors would cause more harm than benefit, due to its impact on the donor pool. In order to minimize the risk of infection, potential living donors should be counseled on the measures to avoid mosquito bites and only practice protected sex until donation. We recommend that transplant centers discuss with recipients that there is an unknown risk of ZIKV transmission in this setting. Recipients of such donors should be monitored carefully in the first post-transplant months. At this point, there are many unknowns about the effects of ZIKV on transplantation. The transplant community must be tuned in to new developments as they arise, and be prepared to work together, particularly with colleagues in the areas that the most affected by this new threat.
Disclaimer: The authors do not have a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript.
Acknowledgments: The authors thank Frederico G. S. Toledo for his critical review of the manuscript and insightful editorial comments.
Reference 1.
Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, et al. Zika
virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med. 2009 Jun 11;360(24):2536-43. 2.
Grard G, Caron M, Mombo IM, Nkoghe D, Mboui Ondo S, Jiolle D, et al. Zika virus in
Gabon (Central Africa)--2007: a new threat from Aedes albopictus? PLoS Negl Trop Dis. 2014 Feb;8(2):e2681. 3.
Ioos S, Mallet HP, Leparc Goffart I, Gauthier V, Cardoso T, Herida M. Current Zika
virus epidemiology and recent epidemics. Med Mal Infect. 2014 Jul;44(7):302-7. 4.
Schuler-Faccini L, Ribeiro EM, Feitosa IM, Horovitz DD, Cavalcanti DP, Pessoa A, et
al. Possible Association Between Zika Virus Infection and Microcephaly - Brazil, 2015. MMWR Morb Mortal Wkly Rep. 2016;65(3):59-62. 5.
Mlakar J, Korva M, Tul N, Popovic M, Poljsak-Prijatelj M, Mraz J, et al. Zika Virus
Associated with Microcephaly. N Engl J Med. 2016 Feb 10. 6.
Brasil P, Pereira JP, Jr., Raja Gabaglia C, Damasceno L, Wakimoto M, Ribeiro
Nogueira RM, et al. Zika Virus Infection in Pregnant Women in Rio de Janeiro - Preliminary Report. N Engl J Med. 2016 Mar 4. 7.
Calvet G, Aguiar RS, Melo AS, Sampaio SA, de Filippis I, Fabri A, et al. Detection and
sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study. Lancet Infect Dis. 2016 Feb 17. 8.
Cao-Lormeau VM, Blake A, Mons S, Lastere S, Roche C, Vanhomwegen J, et al.
Guillain-Barre Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet. 2016 Feb 29. 9.
Musso D, Baud D. Zika virus: time to move from case reports to case control. Lancet
Infect Dis. 2016 Feb 17. 10.
Foy BD, Kobylinski KC, Chilson Foy JL, Blitvich BJ, Travassos da Rosa A, Haddow
AD, et al. Probable non-vector-borne transmission of Zika virus, Colorado, USA. Emerg Infect Dis. 2011 May;17(5):880-2.
11.
CDC. Zika virus. 2016 [cited 2016 March 7]; Available from:
http://www.cdc.gov/zika/transmission. 12.
Oster AM, Brooks JT, Stryker JE, Kachur RE, Mead P, Pesik NT, et al. Interim
Guidelines for Prevention of Sexual Transmission of Zika Virus - United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65(5):120-1. 13.
US Federal Drug Administration. 2016 [cited 2016 February 22]; Available from:
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm486359.htm. 14.
World Health Organization. Maintaining a safe and adequate blood supply during Zika
virus outbreaks2016: Available from: http://www.who.int/csr/resources/publications/zika/Safeblood_supply18Feb2016.pdf?ua=1. 15.
Associação Brasileira de Transplante de Órgãos. Registro Brasileiro de Transplantes.
2015 [cited 2016 March 14]; Available from: http://www.abto.org.br/abtov03/default.aspx?mn=457&c=900&s=0. 16.
United Network for Organ SharingSharing UNfO. Guidance for organ donation and
transplantation professionals regarding the Zika virus. 2016 [cited 2016 February 22]; Available from: https://www.unos.org/guidance-for-organ-donation-and-transplantationprofessionals-regarding-the-zika-virus.
Table 1 - Recommendations for prevention of Zika virus infection in transplant recipients and candidates and prevention of donor-derived infection Recommendation Transplant recipients and candidates Living in area of Zika transmission
Use protective measures to avoid mosquito bites, such as use of insect repellents, use of long-sleeved shirts and pants, use of mosquito nets Abstain from sexual activity or consistently and correctly use condoms during sex with men
Not living in area of Zika transmission
Avoid unnecessary travel to areas with Zika transmission If travel can't be avoided, use protective measures to avoid mosquito bites, such as use of insect repellents, use of long-sleeved shirts and pants, use of mosquito nets Abstain from sexual activity or consistently and correctly use condoms during sex with a man who has been to an area fo Zika transmission for 4 weeks after his return
Deceased donor in areas without Zika transmission Asymptomatic donor with travel to area of Zika transmission in the preceding 4 weeks Asymptomatic donor with history of unprotected sexual activity with men who had been to area of Zika transmission in the preceding 4 weeks Donor with symptoms suggestive of ZIKV infection and with travel to area of Zika transmission in the preceding 6 months Donor with symptoms suggestive of ZIKV infection and with history of unprotected sexual activity with men who had been to area of Zika transmission in the preceding 6 months Deceased donor in areas with Zika transmission Asymptomatic donor
May be considered for organ donation after discussion about risk and benefits of potential donor-derived infection and informed consent May be considered for organ donation after discussion about risk and benefits of potential donor-derived infection and informed consent
Do not utilize donor unless symptoms can be attributed to a condition other than Zika virus and this other condition does not preclude donation
Do not utilize donor unless symptoms can be attributed to a condition other than Zika virus and this other condition does not preclude donation
May be considered for organ donation after discussion about risk and benefits of potential donor-derived infection and informed consent
Donor with symptoms suggestive of ZIKV infection in the preceding 6 months
Do not utilize donor unless symptoms can be attributed to a condition other than Zika virus and this other condition does not preclude donation
Living donor in areas without Zika transmission Asymptomatic living donors with history of travel to area of Zika transmission
Defer donation for 4 weeks after return. If no symptoms develop in 4 weeks, may donate after discussion about risk and benefits of potential donor-derived infection and informed consent
Asymptomatic living donors with history of unprotected sexual activity with men who had been to area of Zika transmission in the preceding 4 weeks
Defer donation for 4 weeks after last unprotected sexual encounter. If no symptoms develop in 4 weeks, may donate after discussion about risk and benefits of potential donor-derived infection and informed consent
Living donors with Zika virus infection
Defer donation for 6 months after onset of symptoms. If recipient's clinical condition does not allow the delay in transplantation, obtain ZIKV PCR 4 weeks after resolution of symptoms and consider donation only if PCR is negative and after discussion of risk and benefits of potential donor-derived infection and informed consent
Living donor in areas with Zika transmission
Living donors with Zika virus infection
Asymptomatic living donors
Defer donation for 6 months after onset of symptoms. If recipient's clinical condition does not allow the delay in transplantation, obtain ZIKV PCR 4 weeks after resolution of symptoms and consider donation only if PCR is negative and after discussion of risk and benefits of potential donor-derived infection and informed consent Discussion about potential risk with recipients. Donors should counseled on measures to avoid infection, such as measures to avoid mosquito bites and consistent and correct use of condons during sex, until donation