Recently, Machado et al.1 reported on two patients infected with Zika virus (ZIKV) after HSCT in Brazil. The symptoms included fever, headache, exanthema, myalgia, and arthralgia. In comparison to cases of infections with dengue or chikungunya viruses, the course of the disease was mild, and no complications have occurred. To date, an additional four probable cases of ZIKV transmission through blood transfusion have been reported.2, 3, 4
With several recent outbreaks of ZIKV infection in various parts of the world, followed by an increased incidence of neurological consequences, such as microcephaly and other congenital neurological syndromes after vertical transmission from an infected mother to her foetus during pregnancy, and Guillain–Barre syndromes, this emerging infectious threat has also focused the attention of transplant physicians.5, 6
The transmission of ZIKV through cells, tissues, and organs remains unknown. Up to 15 May 2017, no ZIKV infection was reported in the EBMT Registry. Nevertheless, in this awareness letter we present the basic information about ZIKV to transplant community.
ZIKV disease is caused by an RNA virus belonging to Flaviviridae family, which is transmitted to humans mainly by Aedes aegypti mosquitoes as the vector. The virus can also be transmitted by sexual contact, via blood transfusion and possibly by other tissues or organs donated by infectious donors.7, 8 So far, 0.5–2.8% of blood donations were tested positive for ZIKV-RNA in areas at risk, such as French Polynesia, Puerto Rico, and Martinique,9, 10, 11, 12 while in USA, ZIKV was found in 14/358,786 (0.004%) blood donations.13
ZIKV infection is typically a mild disease in the general population, and 80% of cases are asymptomatic. The other cases are characterised by a self-limiting febrile illness lasting 4–7 days, accompanied by rash, arthralgia, myalgia and non-purulent conjunctivitis. ZIKV infection can be confirmed by direct detection of ZIKV-RNA or specific viral antigens in clinical samples, while virus-specific antibodies can usually be detected from day 4 or 5 of illness. Cross-reaction in case of infection or vaccination with other flaviviruses may occur. Up to now, no latency of ZIKV has been observed.
Guidelines on safety of substances of human origin were published recently by European Center for Disease Prevention and Control (ECDC).14 In order to diagnose ZIKV infection, three groups of criteria were established: laboratory (for confirmed or probable case), clinical and epidemiological (Table 1). The level of diagnosis of ZIKV infection is classified as: confirmed case (if a person meets the laboratory criteria for a confirmed case); probable case (when a person meets the laboratory criteria for a probable case); and possible case (in a person meeting the clinical criteria and the epidemiological criteria). To date, there is no specific antiviral treatment available and no vaccine to prevent ZIKV infections.
ECDC categorised areas of epidemiological profile of vector-borne ZIKV transmission (Table 2). It reflects only to areas of risk of autochthonous, vector-borne case of ZIKV infection. For substances of human origin, the safety measures should be triggered when an area is classified as category 1 of ZIKV transmission, continued if the area evolves into the category 2, and discontinued when and area becomes category 3. In non-affected areas and areas of transmission categories 3 and 4, safety measures are applied only to travellers returning from areas of transmission categories 1 and 2. Measures to decrease the risk of donor-derived infection are based on exclusion of donors with increased risk of being infected, and laboratory screening of donations/donors.
The general guideline is that blood, tissues and cells should not be imported from areas of transmission categories 1 and 2. In special circumstances or for life-saving procedures, blood, tissues and cells may be imported from affected areas if tested negative for the presence of ZIKV. Depending on the risk posed by ZIKV infection to the safety of blood and blood components in affected areas of transmission categories 1 and 2, the national blood establishment can either temporarily suspend or continue blood donations. In non-affected areas and areas of transmission categories 3 and 4, deferral of the donor for 28 days is recommended if donor: (i) was diagnosed with ZIKV infection (28 days after cessation of symptoms); (ii) has just returned from an affected area; (iii) had sexual contacts with a male who has been diagnosed with ZIKV infection or travelled or lived in a ZIKV-affected area during the 3 months prior to the sexual contact.
If cord blood or placental tissues donation is planned, pregnant women with a diagnosis of ZIKV infection are not eligible, while pregnant women returning from an affected area of transmission categories 1 and 2 may donate cord blood or placental tissues if tested negative for ZIKV-RNA. Donation of cord blood and placental tissues should be suspended in affected areas of transmission categories 1 and 2 and reinstated 9 months after the end of the outbreak has been declared.
For bone marrow (BM) and peripheral blood hematopoietic stem cells (PBSCT), the risk of ZIKV transmission is the same as via blood transfusion, however if no other donor is found, transplant centre may have to accept a higher risk for transmission of the pathogen through BM/PBSCT or perform laboratory testing of the donor beyond the standard tests for blood donors.
In areas of transmission categories 1 and 2, due to the high proportion of asymptomatic cases of ZIKV infection, deferral policies might be ineffective in areas of transmission categories 1 and 2, so the transplantation should be performed providing that BM/PBSC donors tested negative for ZIKV-RNA. In non-affected areas and areas of transmission categories 3 and 4, the donation of BM/PBSC should be postponed for 28 days for donors diagnosed with ZIKV infection after cessation of symptoms, asymptomatic donors after returning from an affected area, and donors who had sexual contacts with men who have been diagnosed with ZIKV infection or who travelled or lived in a ZIKV-affected area during the last 6 months before the sexual contact. If donation cannot be postponed, donors at risk should be screened for ZIKV-RNA and accepted if they tested negative.
The biovigilance system should include also post-donation information both from donors and recipients. Living donors of organs, tissues and cells should be encouraged to inform the tissue establishment or procurement centre if they develop symptoms compatible with ZIKV infection within 28 days after donation. Upon this information the centre should investigate the case, and information should be supplied to all involved parties. When a recipient of tissue or cells is diagnosed with ZIKV infection, the transplant centre should investigate the incident and inform the tissue establishment or procurement centre. Findings of possible, probable or confirmed donor-derived infections should be reported to the relevant authority as serious adverse reactions and to the national biovigilance system.
In conclusion, clinicians dealing with substances of human origin need to be vigilant and aware of the risk of donor-derived ZIKV transmission through transfusion and transplantation. Measures to prevent ZIKV transmission through blood or hematopoietic cells should be taken in both affected and non-affected areas. The general strategy for areas of transmission categories 1 and 2 is that blood, tissues, and cells should not be imported or BM/PBSC donors should be tested for ZIKV-RNA, while in areas of transmission categories 3 and 4 as well as in non-affected areas, donation of BM/PBSC from donors at risk should be postponed for 28 days or BM/PBSC donors should be tested for ZIKV-RNA.
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The authors declare no conflict of interest.
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Styczynski, J., Hoek, J., Knelange, N. et al. No report on Zika virus infection in EBMT registry: Infectious Diseases Working Party statement. Bone Marrow Transplant 52, 1345–1346 (2017). https://doi.org/10.1038/bmt.2017.145
Current Infectious Disease Reports (2018)