HTLV-1 infection in solid organ transplant donors and recipients in Spain.

BACKGROUND: HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. METHODS: All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. RESULTS: A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. CONCLUSION: The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy.

Rapid subacute myelopathy following kidney transplantation from HTLV-1 donors: role of immunosuppresors and failure of antiretrovirals.

Two kidney transplant recipients from a single donor became infected with HTLV-1 (human T-lymphotropic virus type 1) in Spain. One developed myelopathy 8 months following surgery despite early prescription of antiretroviral therapy. The allograft was removed from the second recipient at month 8 due to rejection and immunosuppressors discontinued. To date, 3 years later, this patient remains infected but asymptomatic. HTLV-1 infection was recognized retrospectively in the donor, a native Spaniard who had sex partners from endemic regions. Our findings call for a reappraisal of screening policies on donor-recipient organ transplantation. Based on the high risk of disease development and the large flux of persons from HTLV-1 endemic regions, pre-transplant HTLV-1 testing should be mandatory in Spain.

Human T-lymphotropic virus type 1 infection and disease in Spain.

: Human T-lymphotropic virus type 1 (HTLV-1) infection is a neglected disease despite roughly 15 million people are chronically infected worldwide. Lifelong less than 10% of carriers develop life-threatening diseases, mostly a subacute myelopathy known as tropical spastic paraparesis (TSP) and a lymphoproliferative disorder named adult T-cell leukemia (ATL). HTLV-1 is efficiently transmitted perinatally (breastfeeding), sexually (more from men to women) and parenterally (transfusions, injection drug user (IDU), and transplants). To date there is neither prophylactic vaccine nor effective antiviral therapy. A total of 327 cases of HTLV-1 infection had been reported at the HTLV-1 Spanish registry until December 2016, of whom 34 had been diagnosed with TSP and 25 with ATL. Overall 62% were Latin American immigrants and 13% were persons of African origin. The incidence of HTLV-1 in Spain has remained stable for nearly a decade with 20-25 new cases yearly. Of the 21 newly diagnosed HTLV-1 cases during year 2016, one was a native Spaniard pregnant woman, and four presented with symptomatic disease, including three with ATL and one with TSP. Underdiagnosis of HTLV-1 in Spain must be high (iceberg model), which may account for the disproportionate high rate of symptomatic cases (almost 20%) and the late recognition of preventable HTLV-1 transmissions in special populations, such as newborns and transplant recipients. Our current estimate is of 10 000 persons living with HTLV-1 infection in Spain. Given the large flux of immigrants and visitors from HTLV-1 endemic regions to Spain, the expansion of HTLV-1 screening policies is warranted. At this time, it seems worth recommending HTLV testing to all donor/recipient organ transplants and pregnant women regardless place of birth. Although current leukoreduction procedures largely prevent HTLV-1 transmission by blood transfusions, HTLV testing of all first-time donors should be cost-effective contributing to unveil asymptomatic unaware HTLV-1 carriers.

Using NS5B Sequencing for Hepatitis C Virus Genotyping Reveals Discordances with Commercial Platforms.

We aimed to evaluate the correct assignment of HCV genotypes by three commercial methods-Trugene HCV genotyping kit (Siemens), VERSANT HCV Genotype 2.0 assay (Siemens), and Real-Time HCV genotype II (Abbott)-compared to NS5B sequencing. We studied 327 clinical samples that carried representative HCV genotypes of the most frequent geno/subtypes in Spain. After commercial genotyping, the sequencing of a 367 bp fragment in the NS5B gene was used to assign genotypes. Major discrepancies were defined, e.g. differences in the assigned genotype by one of the three methods and NS5B sequencing, including misclassification of subtypes 1a and 1b. Minor discrepancies were considered when differences at subtype levels, other than 1a and 1b, were observed. The overall discordance with the reference method was 34% for Trugene and 15% for VERSANT HCV2.0. The Abbott assay correctly identified all 1a and 1b subtypes, but did not subtype all the 2, 3, 4 and 5 (34%) genotypes. Major discordances were found in 16% of cases for Trugene HCV, and the majority were 1b- to 1a-related discordances; major discordances were found for VERSANT HCV 2.0 in 6% of cases, which were all but one 1b to 1a cases. These results indicated that the Trugene assay especially, and to a lesser extent, Versant HCV 2.0, can fail to differentiate HCV subtypes 1a and 1b, and lead to critical errors in clinical practice for correctly using directly acting antiviral agents.

Rescue of synthetic salmonid rhabdovirus minigenomes.

Synthetic T7-driven cDNA minigenomes containing the bacterial chloramphenicol acetyltransferase gene as a reporter were derived from the genome of two salmonid novirhabdoviruses, infectious haematopoietic necrosis virus (IHNV) and viral haemorrhagic septicaemia virus (VHSV). We showed that an exogenous IHNV RNA minigenome transfected into fish cells could be rescued following IHNV infection as it was replicated, encapsidated and transcribed. When cells were infected with a recombinant vaccinia virus expressing T7 RNA polymerase (vTF7-3), transfected with the plasmid carrying the IHNV minigenome (genomic- and antigenomic-sense) and superinfected with IHNV, rescue of the minigenome was more efficient. Heterologous VHSV/IHNV rescue experiments failed. Finally, when the IHNV N, P and L proteins were expressed from cDNAs in cells, the minigenome was also successfully rescued, indicating that the nucleocapsid proteins were biologically functional. These data represent the first example of rescue experiments for non-mammalian rhabdoviruses replicating at a low temperature.

Rebrote de parotiditis en la era vacunal. Factores implicados en un brote en Navarra, 2006–2007 / Resurgence of mumps in the vaccine era. Factors involved in an outbreak in Navarre, Spain, 2006–2007

Fundamento y objetivo: Se analiza un brote de parotiditis ocurrido en Navarra entre agosto de 2006 y diciembre de 2007, con amplia afectación de vacunados. Pacientes y método: Los casos de parotiditis notificados se completaron mediante búsqueda en las historias de atención primaria, de urgencias, de hospitales y en los informes de laboratorio. Se analizan los factores que pudieron incidir en la aparición de casos según la cohorte de nacimiento. Resultados: Se detectaron 2.866 casos de parotiditis (tasa de ataque de 4,7 por 1.000), con el 61% en varones y la máxima incidencia a los 19 años (intervalo intercuartil de 16-25 años). El 14% de los casos se confirmó por laboratorio: 59 por aislamiento viral, 14 por reacción en cadena de la polimerasa y 333 por presencia de inmunoglobulina M específica en suero. En 7 casos se identificó el genotipo G1. El 21% de los casos había nacido antes de 1980 (cohortes prevacunales). El 0,2% todavía no tenía la edad de vacunación (15 meses). Entre las cohortes nacidas entre 1980 y 2000 (con oportunidad de vacunación), el 94,5% de los casos había recibido alguna dosis y el 88,3% había recibido 2 dosis. El 31% de los casos ocurrió en cohortes vacunadas en la primera dosis (1995–1997) o en la segunda (1986–1988) con la cepa Rubini. Además, hubo constancia de 772 casos que tenían 2 dosis con la cepa Jeryl Lynn. Conclusiones: Este extenso brote se explica por la concurrencia de varios factores. La vacuna actual ha reducido considerablemente la incidencia de parotiditis, pero no parece capaz de eliminar totalmente la circulación del virus (AU)

Background and objetive: We analysed a mumps outbreak that occurred in Navarre between August 2006 and December 2007, in which vaccinated persons were widely affected. Patients and methods: Reports of mumps cases were completed by searching primary, emergency and hospital records and laboratory reports. Factors that could affect the occurrence of cases were analysed by birth cohort. Results: A total of 2866 mumps cases were detected (attack rate 4.7/1000), with 61% of cases in men and a peak incidence at age 19 (inter-quartile range 16–25 years). 14% of cases were confirmed by laboratory: 59 by virus isolation, 14 by PCR and 333 by IgM. The G1 genotype was identified in 7 cases. 21% of cases had been born before 1980 (pre-vaccine cohorts), and 0.2% had not yet reached the vaccination age (15 months). In the cohorts born between 1980 and 2000 (with the opportunity for vaccination), 94.5% of cases had received at least one dose and 88.3%, two doses. 31% of cases occurred in cohorts vaccinated with a first (1995–1997) or second (1986–1988) dose of the Rubini strain. There was also a record of 772 cases who had received two doses of the Jeryl Lynn strain. Conclusions: His widespread outbreak is explained by the concurrence of various factors. The current vaccine has substantially reduced the incidence of mumps, but appears unable to totally eliminate virus circulation (AU)