Rapid Development of Subacute Myelopathy in Three Organ Transplant Recipients after Transmission of Human T-Cell Lymphotropic Virus Type I from a Single Donor.

Abstract

Rapid Development of Subacute Myelopathy in Three Organ Transplant Recipients after Transmission of Human T-Cell Lymphotropic Virus Type I from a Single Donor. Transplantation 2003; 75: 102. H.K. Osman, C. Toro, B. Rodés, E. Poveda, V. Soriano Human T-Cell Lymphotropic Virus Type 1: Is it Time to Screen Organ Donors and Recipients? Human T-cell lymphotropic virus type 1 (HTLV-1) was isolated in 1980 from patients with adult T-cell leukemia/lymphoma (ATL), a distinct T-cell lymphoid malignancy first described in Japan in 1977. Subsequent seroepidemiologic and molecular studies confirmed the virus to be the putative causative agent of ATL and the neurologic condition termed HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The virus has also been associated with other inflammatory and immune-mediated conditions including uveitis, polymyositis, alveolitis, arthritis, thyroiditis, and Sjögren’s syndrome, although, excluding uveitis, a clear causative relationship has not been established with any of these conditions (1). HTLV-1 infection is endemic in southern Japan, the Caribbean, parts of Africa, the Pacific Melanesian islands, and Papua New Guinea and is found among immigrants from these regions residing in Europe and the United States. The virus is transmitted through sexual intercourse, from mother to child vertically and by breastfeeding, by sharing intravenous needles, and by blood transfusion. The risk of virus infection varies with the mode of transmission. Breastfeeding for more than 6 months carries a risk of transmission of 20%, whereas children breastfed for 3 months or less have only 5% risk of transmission. The precise impact of sexual transmission is difficult to define, but it is noted that transmission is more effective from infected males to females than the reverse. Blood transfusion carries the highest risk: The probability of seroconversion in recipients of contaminated blood is 13% to 60%. The virus is cell associated, and packed red cells, whole blood, and platelets (but not frozen fresh plasma) are considered the source of virus transmission. However, most HTLV-1 infections are attributable to transmission through sexual contact or from mother to child through prolonged breastfeeding. In endemic areas, measures to reduce the rate of infection include screening of blood donors, antenatal screening, and recommendation of artificial feeding for infected mothers. In this issue of Transplantation, Carlos Toro and colleagues report the transmission of HTLV-1 from a single donor to three organ (two kidneys and one liver) transplant recipients who subsequently developed TSP. All three patients presented with subacute myelopathy within 2 years posttransplant and were HTLV-1 seropositive. Retrospective analysis of a stored serum sample from the donor confirmed his seropositivity for HTLV-1. Detailed molecular studies on HTLV-1 sequences amplified from two of the recipients indicated a common source of infection. Both patients demonstrated a high viral load and were infected with a viral subtype associated with increased risk for TSP. The evidence of infection in these three recipients by the donor was convincing, although it wasn’t clear from the report whether all three recipients were HTLV-1 seronegative before the transplant or whether they received blood products during or after the transplant. There have been two previous reports of possible HTLV-1 transmission by solid organ donations (2,3). The first report described a child who received a kidney from her infected mother and seroconverted to HTLV-1 83 days posttransplant (2). Although the child was breastfed for 1 year, she was still seronegative when she received the kidney at 2 years of age, and there was no possibility of infection through blood transfusion because all blood products were screened for HTLV-1. The child demonstrated neither neurologic nor hematologic evidence of HTLV-1 related disease 4 years after the transplant. The second report described a kidney transplant recipient who presented with TSP 4 years after his operation (3). The patient was seronegative pretransplant, did not receive any blood products before, during, or after the transplant, and denied any risky sexual behavior. These reports raise the question of whether organ donors in nonendemic areas should be screened for HTLV-1. Seroprevalence of HTLV-1 among low-risk populations in the United States and Europe is generally less than 1% compared with 3% to 6% in the Caribbean region and 30% in southern Japan. The prevalence among blood donors is 0.017% in the United States, 0.004% in France, and 0.002% in Sweden and The Netherlands. The prevalence is 0.005% in the United Kingdom, but higher rates of infection were detected among donors of Afro-Caribbean origin (0.084%). However, the rate of infection among pregnant women attending antenatal clinics in the United Kingdom is higher, ranging from 0.17% (in mothers born in endemic areas) to 0.012% (in mothers born in nonendemic areas and not of Afro-Caribbean origin) (4). The higher prevalence among pregnant women could be explained by the facts that a higher proportion of blood donors in the United Kingdom have no Afro-Caribbean connections and that blood donors are screened to exclude high-risk groups. Each year, approximately 800 organ donors are recruited in the United Kingdom. Assuming a seroprevalence between 0.005% and 0.17% in the general population, it is expected that at least one donor will be HTLV-1 seropositive. With multiorgan donations, this will represent a risk of infection to a minimum of three recipients. By using blood transfusion as an analogy, the probability of infection in recipients of contaminated blood is between 13% and 60%. The lower probability reflects the current practice of improved separation methods and efficient removal of white blood cells (where the virus is normally found), a practice that cannot be applied in organ donations. The lifetime risk among HTLV-1 carriers of developing ATL or TSP is estimated to be 5% and 2.5%, respectively, and the incubation period ranges from 10 to 30 years. However, the risk of developing TSP is increased if infection is acquired through blood transfusion. There is evidence to indicate that disease acquired from blood transfusion can occur after a shorter incubation period, and that immunosuppressed individuals are at increased risk of developing disease than healthy carriers of the virus. The increased risk of infection and disease is believed to be caused by the high viral load in blood. The risk of HTLV-1 infection and disease through organ donations is expected to be equivalent or even higher than blood donation, because organ transplant recipients are usually immunosuppressed (some more than others), and infected organs also carry a high viral load. The burden of diseases associated with HTLV-1 is significant because there is no effective treatment for TSP or ATL, which have a high mortality rate. Results from several therapeutic trials with antivirals have shown limited clinical benefit for patients (5). What about solid organ recipients? There is evidence to indicate that carriers of HTLV-1 who receive transplants and immunosuppressive treatment are at increased risk of developing ATL and TSP (6). The exact prevalence of HTLV-1 among the transplant population is unknown. In 2001, there were 2,700 solid organ transplantations performed in the United Kingdom, and there were 5,500 patients on the waiting list. These figures are expected to rise each year. Given a seroprevalence rate between 0.005% and 0.17%, it is expected that approximately two recipients will be carriers of the virus. The screening of such a population would allow the prevalence of HTLV-1 carriage among potential recipients to be assessed and the true association between such carriage and the development of HTLV-1 associated diseases after transplantation to be determined. Would screening of donors lead to unnecessary rejection of organs? There are some concerns that serologic tests for HTLV-1 have a high incidence of false positive results, and that confirmatory assays usually take a long time to perform. However, the currently available assays have a level of sensitivity and specificity equivalent to the assays in use for hepatitis B and C and human immunodeficiency virus screening. Positive results, as in all the other currently performed donor-screening tests, will enable the transplant surgeon to make an informed decision about the suitability of the organ. The decision should be based on a proper risk assessment of the donor and the risk of significant disease or death to the recipient if the transplant were not performed. In September 2002, after a long period of debate, the blood transfusion service in the United Kingdom began screening all of their donors for evidence of HTLV-1 infection. I believe it is also the right time for organ transplant donors and recipients to be screened for the virus. In the United Kingdom, there should be a consistent policy to ensure that donated blood and organs are safe.