Liver and Kidney Recipient Selection of Hepatitis C Virus Viremic Donors: Meeting Consensus Report From the 2019 Controversies in Transplantation.

The development of multiple highly effective and safe direct-acting antivirals to treat hepatitis C virus (HCV) has resulted in greater ease and confidence in managing HCV infection in transplant recipients that in turn has impacted the solid organ transplant community as well. In the United States, the opioid epidemic has increased the number of overdose deaths with a concomitant increase in younger HCV viremic donors after brain death being identified. At the same time, a decrease in HCV viremic transplant candidates has led to a growing interest in exploring the use of HCV viremic liver and kidney donor allografts in HCV-negative recipients. To date, experience with the use of HCV viremic liver and kidney allografts in HCV-negative recipients is limited to a few small prospective research trials, case series, and case reports. There are also limited data on recipient and donor selection for HCV viremic liver and kidney allografts. In response to this rapidly changing landscape in the United States, experts in the field of viral hepatitis and liver and kidney transplantation convened a meeting to review current data on liver and kidney recipient selection and developed consensus opinions related specifically to recipient and donor selection of HCV viremic liver and kidney allografts.

The Brazilian experience of nucleic acid testing to detect human immunodeficiency virus, hepatitis C virus, and hepatitis B virus infections in blood donors.

BACKGROUND: The history of the development and implementation of the Brazilian nucleic acid testing (NAT) platform to detect and discriminate among human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) infections in blood donors is described here. The results for the sensitivity, reproducibility, and NAT yield of the platform since program implementation are provided. STUDY DESIGN AND METHODS: The Brazilian NAT HIV, HCV, and HBV kit was developed and evaluated with regard to analytical sensitivity, specificity, intralot and interlot reproducibility, interfering substances, and genotype and diagnostic sensitivity. Additionally, a sample of identified NAT-yield cases was characterized with regard to viral load. RESULTS: The 95% limits of detection for HIV, HCV, and HBV were 68.02, 102.35, and 9.08 IU/mL, respectively. All replicates were detected with reproducibility assays between the acceptable values. A total of 13,610,536 blood donors was screened from 2010 to 2016, and 63 HIV-yield cases and 28 HCV-yield cases were detected. Among 5,795,424 blood donors screened for HBV from 2014 to 2016, 42 yield cases were found. CONCLUSION: The Brazilian NAT HIV, HCV, and HBV kit is an automated NAT system suitable for routine blood donor screening in a completely traceable process. The analytical sensitivity as well as the diagnostic sensitivity fulfilled all requirements set by the health ministry for blood donor screening. A significant number of transmission cases were prevented by the implementation of this important program.

Disseminated toxoplasmosis in a heart transplant patient despite co-trimoxazole prophylaxis: A case report.

We report the case of a 61 year-old male who underwent heart transplantation eight months before developing a systemic condition with central nervous system, lung, kidney, colonic, cutaneous, and hematologic involvement, found to be secondary to a systemic toxoplasmosis despite co-trimoxazole prophylaxis in a previous-to-transplant seronegative patient receiving a heart from a seropositive donor. A review of prophylactic options in our environment is discussed.

Toxoplasmosis diseminada en un paciente con trasplante de corazón a pesar de la profilaxis con trimetoprim-sulfametoxazol / Disseminated toxoplasmosis in a heart transplant patient despite cotrimoxazole prophylaxis: A case report

Resumen Se reporta el caso de un paciente de sexo masculino, de 61 años de edad, quien ocho meses después de someterse a un trasplante de corazón presentó una enfermedad sistémica con compromiso del sistema nervioso central y del sistema inmunológico, así como de pulmón, riñón, colon y piel, y a quien finalmente se le diagnosticó toxoplasmosis diseminada, a pesar de haber recibido profilaxis con trimetoprim-sulfametoxazol, debido a que el órgano provenía de un donante positivo para toxoplasmosis siendo él un receptor negativo. Se discuten las opciones de profilaxis en nuestro medio.

Abstract We report the case of a 61 year-old male who underwent heart transplantation eight months before developing a systemic condition with central nervous system, lung, kidney, colonic, cutaneous, and hematologic involvement, found to be secondary to a systemic toxoplasmosis despite co-trimoxazole prophylaxis in a previous-to-transplant seronegative patient receiving a heart from a seropositive donor. A review of prophylactic options in our environment is discussed.

Risk factors for hepatitis C virus infection in the Colombian Caribbean coast: A case-control study.

INTRODUCTION: An estimated 6.8-8.9 million people are infected with hepatitis C virus in Latin America, of which less than 1% receives antiviral treatment. Studies so far in Colombia have attempted to determine the prevalence of the disease in some risk groups, thus preventing the identification of other factors potentially involved in the spread of the infection. OBJECTIVES: To identify traditional and non-traditional risk factors for chronic hepatitis C in the Colombian Caribbean coast. MATERIALS AND METHODS: This was a case-control study (1:3) matched by health care provider and age (± 10 years) conducted at the primary care level of gastroenterology and hepatology outpatient services. All patients with a positive ELISA underwent a confirmatory viral load test. A multivariate logistic regression analysis identified the independent predictors of infection. RESULTS: Blood transfusion (OR=159.2; 95% CI: 35.4-715; p<0.001) and history of hospitalization before 1994 (OR=4.7; 95% CI: 1.3-17.1; p=0.018) were identified as the only two independent predictors of infection. CONCLUSION: It is necessary to check the reproducibility of these results and to conduct cost-effectiveness studies before recommending their use in the design of new screening strategies.

Factores de riesgo para la infección por el virus de la hepatitis C en la Costa Caribe colombiana: un estudio de casos y controles / Risk factors for hepatitis C virus infection in the Colombian Caribbean coast: A case-control study

Resumen Introducción. Se estima que, aproximadamente, 6,8 a 8,9 millones de personas están infectadas por el virus de la hepatitis C en Latinoamérica, de las cuales menos del 1 % llega a recibir tratamiento antiviral. En los estudios llevados a cabo hasta ahora en Colombia, se ha propuesto determinar la prevalencia de la enfermedad en algunos grupos de riesgo, y no se ha hecho el análisis de otros factores potencialmente implicados en el contagio. Objetivos. Determinar los factores de riesgo tradicionalmente analizados y otros no estudiados antes para la hepatitis C crónica en la Costa Caribe colombiana. Materiales y métodos. Se hizo un estudio de casos y controles (1:3) emparejados por empresa promotora de salud y edad (± 10 años), en el primer nivel de atención de hepatología y gastroenterología. A todos los pacientes positivos en la prueba ELISA se les hizo una prueba confirmatoria de carga viral. En el análisis de regresión logística multivariable se determinaron los factores predictores independientes de infección. Resultados. La transfusión sanguínea (odds ratio, OR=159,2; IC95% 35,4-715; p<0,001) y el antecedente de hospitalización antes de 1994 (OR=4,7; IC95% 1,3-17,1; p=0,018) se determinaron como los dos únicos factores independientes predictores de infección. Conclusión. Es necesario comprobar la reproducibilidad de estos resultados y hacer estudios de costo-efectividad antes de recomendar su utilización en el diseño de nuevas estrategias de cribado.

Abstract Introduction: An estimated 6.8-8.9 million people are infected with hepatitis C virus in Latin America, of which less than 1% receives antiviral treatment. Studies so far in Colombia have attempted to determine the prevalence of the disease in some risk groups, thus preventing the identification of other factors potentially involved in the spread of the infection. Objectives: To identify traditional and non-traditional risk factors for chronic hepatitis C in the Colombian Caribbean coast. Materials and methods: This was a case-control study (1:3) matched by health care provider and age (± 10 years) conducted at the primary care level of gastroenterology and hepatology outpatient services. All patients with a positive ELISA underwent a confirmatory viral load test. A multivariate logistic regression analysis identified the independent predictors of infection. Results: Blood transfusion (OR=159.2; 95% CI: 35.4-715; p<0.001) and history of hospitalization before 1994 (OR=4.7; 95% CI: 1.3-17.1; p=0.018) were identified as the only two independent predictors of infection. Conclusion: It is necessary to check the reproducibility of these results and to conduct cost-effectiveness studies before recommending their use in the design of new screening strategies.

Duration of Dengue Viremia in Blood Donors and Relationships Between Donor Viremia, Infection Incidence and Clinical Case Reports During a Large Epidemic.

BACKGROUND: Dengue viruses (DENV-1-4) pose a transfusion-transmission risk. This study estimated the dengue RNA detection period in asymptomatic blood donors and relationships between donor viremia and dengue incidence during a large epidemic. METHODS: Donor samples from the 2012 dengue transmission season in Rio de Janeiro, Brazil, were tested for DENV RNA by a transcription-mediated amplification (TMA) assay, with DENV types and viral loads determined by polymerase chain reaction. Samples collected during the first and last weeks of enrollment were tested for DENV immunoglobulin (Ig) G and IgM to estimate incidence during the study period, which was analyzed relative to nucleic acid amplification technology (NAT) yield to estimate the duration of NAT-detectable viremia and compared with reported clinical dengue cases in Rio. RESULTS: Samples from 16 241 donations were tested; 87 (0.54%) were confirmed as DENV-4 RNA positive. Dengue IgM-positive/IgG-positive reactivity increased from 2.8% to 8.8%, indicating a 6.2% incidence (95% confidence interval [CI], 3.2%-9.1%) during the study period. Based on these data, we estimated a 9.1-day period (95% CI, 4.4-13.9 days) of RNA detectable with TMA. With 100 475 reported cases of clinical dengue, 1 RNA-positive donation was identified per 800 DENV cases. CONCLUSIONS: These parameters allow projections of dengue incidence from donor NAT yield data and vice versa, and suggest that viremic donations will be rare relative to clinical disease cases.

Transmission of endemic St Louis encephalitis virus strains by local Culex quinquefasciatus populations in Cordoba, Argentina.

BACKGROUND: St Louis encephalitis virus (SLEV) is a re-emerging human pathogen widely distributed in the American continent. Although it is not fully understood, the SLEV transmission network may involve Culex quinquefasciatus mosquitoes as vectors and Columbidae species as hosts. METHODS: To calculate infection rates, we inoculated Cx. quinquefasciatus mosquitoes from Córdoba, Argentina by feeding them on viremic chicks. RESULTS: We observed differences in infection rate among the viral strains, the highest rate (78/87 mosquitoes, 90.8%) being seen in strain 78V-6507. After re-feeding on susceptible chicks, mosquitoes were able to transmit the virus. CONCLUSION: Our findings suggest that Cx. quinquefasciatus populations are susceptible to and able to transmit different SLEV strains.

Fetal infections and antibody profiles in pigs naturally infected with porcine circovirus type 2 (PCV2).

The aim of this study was to describe early infections with porcine circovirus type 2 (PCV2) in naturally infected piglets and the piglets' serologic profiles. A total of 20 sows (15 PCV2-vaccinated and 5 unvaccinated) and 100 newborn piglets were studied. Colostrum and serum of the sows and serum of the presuckling piglets were obtained on the day of parturition. Milk samples were collected on day 20 postpartum. Blood samples were taken and the piglets weighed on days 1, 20, 42, 63, and 84 postpartum. Colostrum and milk were evaluated for infectious PCV2 and for PCV2 total antibody (TA), neutralizing antibody (NA), and IgA. Serum samples were evaluated for PCV2 TA, NA, IgA, IgM, and DNA. The sows had high levels of TA and NA in serum and colostrum; however, 11 and 5, respectively, of the 20 colostrum and milk samples contained infectious PCV2. In the serum, PCV2 DNA and IgM were detected in 17 and 5, respectively, of the 20 sows. Nine piglets were born with PCV2 antibodies, which indicates in utero transmission of PCV2 after the period of immunocompetence (> 70 d of gestation). On day 1 postpartum, PCV2 DNA was detected in 29 of the 100 serum samples from the piglets. There was no difference between the weights of viremic and nonviremic piglets throughout the study. In conclusion, even on farms with sows that have high PCV2 antibody titers, vertical transmission of PCV2 may occur, resulting in piglet infection.

Dengue viremia in blood donors identified by RNA and detection of dengue transfusion transmission during the 2007 dengue outbreak in Puerto Rico.

BACKGROUND: In 2007, a total of 10,508 suspected dengue cases were reported in Puerto Rico. Blood donations were tested for dengue virus (DENV) RNA and recipients of RNA-positive donations traced to assess transfusion transmission. STUDY DESIGN AND METHODS: Blood donation samples from 2007 were maintained in a repository and tested individually for DENV RNA by transcription-mediated amplification (TMA); a subset was further tested by an enhanced TMA (eTMA) assay. TMA-reactive samples were considered confirmed if TMA (including eTMA) was repeat reactive (RR). All TMA-RR samples were tested by quantitative, DENV type-specific reverse transcriptase-polymerase chain reaction (RT-PCR) and for anti-DENV immunoglobulin (Ig)M by enzyme-linked immunosorbent assay. Samples positive by RT-PCR were further tested for infectivity in mosquito cell culture. Patients receiving components from TMA-RR donations were followed. RESULTS: Of 15,350 donation samples tested, 29 were TMA-RR for a prevalence of 1 per 529 (0.19%). DENV Types 1, 2, and 3 with viral titers of 10(5) to 10(9) copies/mL were detected by RT-PCR in 12 samples of which all were infectious in mosquito culture. Six TMA-RR samples were IgM positive. Three of the 29 recipients receiving TMA-RR donations were tested. One recipient in Puerto Rico transfused with red blood cells containing 10(8) copies/mL DENV-2 became febrile 3 days posttransfusion and developed dengue hemorrhagic fever. The recipient was DENV-2 RNA positive by RT-PCR; both the donor and the recipient viruses had identical envelope sequences. CONCLUSIONS: High rates of viremia were detected in blood donors in Puerto Rico coupled with the first documented transfusion transmission of severe dengue disease, suggesting that further research on interventions is needed.

Estimated prevalence of dengue viremia in Puerto Rican blood donations, 1995 through 2010.

BACKGROUND: Dengue virus (DENV) nucleic acid amplification testing of blood donations during epidemics in endemic locations, including Puerto Rico, has suggested possible sizable transfusion transmission risk. Estimates of the long-term prevalence of DENV viremic donations will help evaluate the potential magnitude of this risk in Puerto Rico. STUDY DESIGN AND METHODS: Estimates of the prevalence of DENV viremia in the Puerto Rican population at large from 1995 through 2010 were derived from dengue case reports and their onset dates obtained from islandwide surveillance, estimates of case underreporting, and extant data on the duration of DENV viremia and the unapparent-to-apparent dengue infection ratio. Under the assumptions that viremia prevalence in blood donors was similar to that of the population at large and that symptomatic persons do not donate, statistical resampling methods were used to estimate the prevalence of dengue viremia in blood donations. RESULTS: Over the 16-year period, the maximum and mean daily prevalences of dengue viremia (per 10,000) in blood donations in Puerto Rico were estimated at 45.0 (95% confidence interval [CI], 36.5-55.4) and 7.0 (95% CI, 3.9-10.1), respectively. Prevalence varied considerably by season and year. CONCLUSION: These data suggest a substantial prevalence of DENV viremia in Puerto Rican blood donations, particularly during outbreaks.

[Evaluation of the potential organ and tissue donor within the pandemic of influenza H1N1]. / Valoración del potencial donante de órganos y tejidos en el seno de la pandemia por gripe A H1N1.

The pandemic strain of H1N1 supposes a challenge to the health care system in general and for Intensive Care Units (ICU) in particular. Therefore, it will undoubtedly have repercussions on the organ and tissue donation process. In a possible scenario of bed shortage in the ICU and difficulties in maintaining the surgical activity at a normal pace, a significant effort must be made to assure the maintenance of normal transplant activity, which should not be considered as an elective surgical procedure. Another problem related with the impact of the pandemic on the organ donation process is the possibility that a donor with influenza virus could transmit the disease to recipients. This work aims to clarify this issue, reviewing existing data on the potential transmission of influenza viruses with transplanted organs or tissue, the recommendations published in other countries and those developed in Spain by an ad hoc work group that is made up by representatives from the National Transplant Organization, the Ministry of Health and Social Policy, Regional Offices of Transplant Coordination, and various scientific societies, including SEMICYUC.

Prospective evaluation of household contacts of persons with hantavirus cardiopulmonary syndrome in chile.

BACKGROUND: Andes virus (ANDV) infection, which has a case fatality rate of 37% in Chile, often occurs in household clusters and may be transmitted from person to person. METHODS: To determine the incidence and risk factors for additional household cases, we conducted a prospective study among recent household contacts of persons with hantavirus cardiopulmonary syndrome (HCPS) in Chile, including testing of serum for anti-hantavirus antibodies and blood cells for ANDV RNA by reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: We enrolled 76 index case patients and 476 household contacts, of whom 16 (3.4%) developed HCPS; 32.6% of 92 cases occurred in household clusters. The risk of HCPS was 17.6% among sex partners of index case patients, versus 1.2% among other household contacts (P<.001). Person-to-person transmission was definite in 3, probable in 9, and possible in 2 of the 16 additional household case patients. We detected ANDV RNA by RT-PCR in peripheral blood cells 5-15 days before the onset of symptoms or the appearance of anti-hantavirus antibodies. CONCLUSIONS: In recent household contacts of persons with HCPS in Chile, the risk of HCPS was greatest among sex partners. Among the household contacts who developed HCPS, viremia preceded the onset of symptoms and the appearance of anti-hantavirus antibodies by up to 2 weeks.

Venezuelan equine encephalitis virus transmission and effect on pathogenesis.

Quantifying the dose of an arbovirus transmitted by mosquitoes is essential for designing pathogenesis studies simulating natural infection of vertebrates. Titration of saliva collected in vitro from infected mosquitoes may not accurately estimate titers transmitted during blood feeding, and infection by needle injection may affect vertebrate pathogenesis. We compared the amount of Venezuelan equine encephalitis virus collected from the saliva of Aedes taeniorhynchus to the amount injected into a mouse during blood feeding. Less virus was transmitted by mosquitoes in vivo (geometric mean 11 PFU) than was found for comparable times of salivation in vitro (mean saliva titer 74 PFU). We also observed slightly lower early and late viremia titers in mice that were needle injected with 8 PFU, which represents the low end of the in vivo transmission range. No differences in survival were detected, regardless of the dose or infection route.

Identification of hepatitis C virus RNA in peritoneal dialysis fluid of patients with viremia.

BACKGROUND: The potential risk for transmission of hepatitis C virus (HCV) by peritoneal dialysis (PD) has been studied previously, with conflicting results. METHODS: To assess whether HCV crosses the peritoneal membrane, the following determinations were performed in 16 patients (7 males, 9 females; mean age 41.8 years; mean time on PD 14 +/- 15 months) undergoing PD: serum anti-HCV using second-generation enzyme-linked immunosorbent assay (ELISA), serum and PD fluid HCV RNA by nested polymerase chain reaction, HCV genotyping by restriction fragment length polymorphism, and serum HCV load by branched DNA assay. RESULTS: Anti-HCV was positive in 10 patients. Serum HCV RNA was positive in 7 anti-HCV-positive patients and negative in all anti-HCV-negative patients. Fluid HCV RNA was detected in 5 (71.4%) patients testing positive for serum HCV RNA and in none testing negative for serum HCV RNA. Serum HCV genotype was 1a in 3 patients and 1b in 4; PD fluid HCV genotype was 1a in 1 patient and 1b in 4. Genotypes in serum and fluid were concordant when both were positive. Serum viral load ranged from nondetectable by the quantitative method to 5.1 MEq genome/mL in patients with fluid infection, and 1.05 MEq and 29 MEq genome/mL in the remaining 2 patients without detectable HCV in PD fLuid. CONCLUSIONS: HCV crosses the peritoneal membrane and may be detected in the dialysate of PD patients with proven viremia. Although our study population was small for firm conclusions to be drawn, this passage does not seem to depend upon the serum viral load. Our data support the notion that PD fluid needs careful handling and local disinfection to prevent possible spreading of viruses, in the institutional and the domestic environments.

Modelling the natural history of HIV infection in individuals and its epidemiological implications.

The variation of viraemia in the natural course of HIV infection is expected to have major influence on the probability of transmission and, consequently, on the epidemiology of HIV/AIDS. In this paper we propose a model which takes into account the time evolution of HIV viraemia (measured as HIV-RNA copies per ml of blood) in an infected individual and its impact on the threshold for the establishment of an endemic level, and mainly on the relative contribution of each of the clinical phases of the infection to the total transmission of HIV per infected individual. We consider that an infected individual passes through three phases of viraemia. The first phase, which lasts for 6-7 weeks, is characterized by very high viraemia. In the second phase, which lasts about 10 years, the viraemia is much lower, increasing again in the last phase, which lasts up to two years, and ends in full-blown AIDS. We show that the relative contribution of each phase to the total transmission of HIV is very sensitive to the model we assume for the dependence of the transmissibility of HIV on the viral load. For instance, if we assume that transmissibility is proportional to the decimal logarithm of viraemia, then the second phase predominates always. Due to the epidemiological importance of this fact, it is clear that further improvement on virological research to better understand the dependence of HIV transmissibility on the viral concentration in biological fluids is necessary.

Human T-cell leukaemia/lymphoma virus risk may be enhanced in some selected donor populations.

BACKGROUND AND OBJECTIVES: Certain patient ethnic groups may require blood components from donors under-represented in the UK donor population. Selective recruitment of Afro-Caribbean donors is therefore necessary but was considered to pose an increased risk of human T-cell leukaemia/lymphoma virus (HTLV) infection. To assess this a seroprevalence study of HTLV was undertaken in Afro-Caribbean and Caucasian donors. MATERIALS AND METHODS: Sera from 1100 Afro-Caribbean and 1100 Caucasian donors were tested for antibody to HTLV. Reactive samples were confirmed for specificity using an algorithm comprising two additional assays and polymerase chain reaction (PCR) where possible. RESULTS: Six Afro-Caribbean donors (0.55%) were considered to be infected with HTLV I. CONCLUSION: Donor selection in this case caused a significantly elevated prevalence of HTLV infection and serves as a warning of the need for care in the design of policies for selective donor recruitment.

Papel del rhodnius prolixus en la transmisión del virus de la encefalitis equina venezolana / The role of rhodnius prolixus in the transmission of venezuelan equine encephalomyelitis virus

Se investigó el papel del Rhodnius prolixus (chipos) como agente transmisor del virus de la Encefalitis Equina Venezolana (EEV), mediante ensayos con alimentación en pollos en fase virémica y con mezcla sangre-virus, y posterior realimentación sobre ratones recién nacidos. Igualmente se averiguó aspectos relacionados con la persistencia del virus en la especie citada de triatoma, así como la infecciosidad del agente para pollos de corta edad. Los resultados mostraron que no hubo transmisión directa del virus desde los chipos a los ratones en prueba, indicando un nulo papel del Rhodnius prolixus en el ciclo epidemiológico de la EEV. Se comprobó la persistencia del virus en los chipos hasta diez días después de la comida infectada y una viremia de breve duración y bajo título en los pollos

Transmission of Venezuelan equine encephalomyelitis virus by Aedes sollicitans and Aedes taeniorhynchus (Diptera: Culicidae).

Experimental studies compared the vector competence of Aedes sollicitans (Skuse) and Ae. taeniorhynchus (Wiedemann) collected on Assateague Island, Va., for an epizootic strain (Trinidad donkey) of Venezuelan equine encephalomyelitis (VEE) virus. Infection rates were significantly higher in Ae. sollicitans (101/107, 94%) than in Ae. taeniorhynchus (103/175, 59%), even though both species fed concurrently on the same infected hamsters. Similarly, dissemination and transmission rates were significantly higher in the Ae. sollicitans population tested. Although both Ae. taeniorhynchus and Ae. sollicitans are natural vectors of VEE virus, the latter species should be considered a more efficient vector of VEE epizootic strains, based on its greater susceptibility to infection and higher transmission rates.