The Argentine experience with human immune deficiency virus positive patients in the waiting list for liver transplantation: preliminary analysis

Previamente, la seropositividad para el virus de la inmunodeficiencia humana (HIV) era una contraindicación absoluta del trasplante. Sin embargo, reportes de la época posterior al tratamiento antirretroviral altamente activo (HAART) demostraron que los resultados no se diferenciarían de la población HIV negativa. Objetivo. Evaluar la experiencia en Argentina con pacientes HIV positivos incluidos en lista para trasplante hepático. Pacientes y métodos. Se incluyeron 52 pacientes HIV positivos ingresados en lista del 12 de julio de 2005 al 31 de marzo de 2010. Los resultados se compararon con 462 pacientes HIV negativos incluidos en lista durante el mismo período. Los datos se obtuvieron del SINTRA y centros intervinientes. Resultados. La etiología de hepatopatía en el grupo HIV positivo fue: hepatitis C en 40 pacientes, hepatitis B en 3, hepatitis fulminante en 3, alcohol en 2, retrasplante en 2 y otras en 2. El MELD promedio del grupo HIV positivo al ingreso en la lista fue 16,15 (menor de 19 en 40 pacientes, mayor de 19 en 8 y emergencia en 3) y el del grupo HIV negativo fue 16,64 (NS). La evolución en lista de espera para los pacientes HIV positivos y negativos fue respectivamente: muerte en lista 14 pacientes (27%) vs 61 (18,7%) (P < 0,05), trasplante con donante cadavérico 10 (13%) vs 95 (29,4%) (P < 0,01), trasplante con donante vivo 0 (0%) vs 5 (1,1%) (NS), tiempo medio desde el ingreso en lista a la muerte 270,70±298,11 días vs 267,29±266,53 días (NS), tiempo medio en la lista hasta el trasplante 70,26±74,05 vs 261±187,6 días (P < 0,01), MELD medio al fallecimiento 12,54 (13 casos menor de 15, 1 mayor de 19) vs 19,6±9,7 (P < 0,05), y MELD medio al momento del trasplante 24,33 vs 24,1±7,6 (NS). Conclusión. Los resultados del trasplante en pacientes HIV positivos son buenos. Sin embargo, presentan muy alta mortalidad en lista de espera que no correlaciona con su gravedad medida por el score de MELD. Quienes acceden al trasplante lo hacen rápidamente en el contexto de una descompensación, por hepatitis fulminante o por retrasplante.After the introduction of high active antiretroviral therapy (HAART), the human immunodeficiency virus (HIV) was no longer considered a contraindication for transplantation. Yet, liver disease in this population is characterized by an accelerated course that may impact on the waiting list. Objective. To evaluate the experience in Argentina with HIV positive patients listed for liver transplantation. Patients and methods. We analyzed 52 HIV positive patients listed between July 2005 and March 2010 (Group HIV positive). Results were compared with 462 HIV negative patients included during the same period (Group HIV negative). Data were obtained from INCUCAI, the Argentinian procurement organism and from the Transplantation Centers. Results. The etiology of liver disease in the Group HIV positive was hepatitis C 40, HBV 3, fulminant hepatitis 3, alcohol 2, retrasplant 2 and others 2. The mean MELD at the time of listing was 16.15 (lower than 19 in 40 cases, higher than 19 in 8, emergency in 3) in the group HIV positive and 16.64 in the group HIV negative (NS). The outcome in the waiting list for HIV positive and negative patients respectively was: death 14 (27%) vs 61 (18.7%) (P < 0.05), cadaveric donor transplant 10 (13%) vs 95 (29.4%) (P < 0.001), living donor transplant 0 (0%) vs 5 (1.1%) (NS), mean time from listing to death 270.70 298.11 days vs 267.29 266.53 days (NS), mean time from listing to transplant 70.26 74.05 vs 261 187.6 days (P < 0.01), mean MELD at the time of death 12.54 (13 cases lower than 15, 1 higher than 19) vs 19.6 9.7 (P < 0.05), mean MELD at the time of transplantation 24.33 vs 24.1 7.6 (NS). Conclusion. HIV positive patients have high mortality in the waiting list and low access to liver transplantation. MELD score underscores the severity of liver disease in this population when compared to HIV negative patients.Fil: Villamil, Alejandra. Hospital Italiano; ArgentinaFil: Bisignano, Liliana. Incucai; ArgentinaFil: Orozco, Federico. Hospital Italiano de la Plata; ArgentinaFil: Bandi, Juan Carlos. Hospital Italiano de la Plata; ArgentinaFil: Barcán, Laura. Hospital Italiano de la Plata; ArgentinaFil: McCormack, Lucas. Hospital Alemán; ArgentinaFil: Gondolesi, Gabriel Eduardo. Fundación Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Santibañes, Eduardo. Hospital Italiano de la Plata; ArgentinaFil: Gadano, Adrián. Hospital Italiano de la Plata; Argentin

Multiplex Real-Time PCR Assay Using TaqMan Probes for the Identification of Trypanosoma cruzi DTUs in Biological and Clinical Samples

Background: Trypanosoma cruzi has been classified into six Discrete Typing Units (DTUs), designated as TcI–TcVI. In order to effectively use this standardized nomenclature, a reproducible genotyping strategy is imperative. Several typing schemes have been developed with variable levels of complexity, selectivity and analytical sensitivity. Most of them can be only applied to cultured stocks. In this context, we aimed to develop a multiplex Real-Time PCR method to identify the six T. cruzi DTUs using TaqMan probes (MTq-PCR).Methods/Principal Findings: The MTq-PCR has been evaluated in 39 cultured stocks and 307 biological samples from vectors, reservoirs and patients from different geographical regions and transmission cycles in comparison with a multi-locus conventional PCR algorithm. The MTq-PCR was inclusive for laboratory stocks and natural isolates and sensitive for direct typing of different biological samples from vectors, reservoirs and patients with acute, congenital infection or Chagas reactivation. The first round SL-IR MTq-PCR detected 1 fg DNA/reaction tube of TcI, TcII and TcIII and 1 pg DNA/reaction tube of TcIV, TcV and TcVI reference strains. The MTq-PCR was able to characterize DTUs in 83% of triatomine and 96% of reservoir samples that had been typed by conventional PCR methods. Regarding clinical samples, 100% of those derived from acute infected patients, 62.5% from congenitally infected children and 50% from patients with clinical reactivation could be genotyped. Sensitivity for direct typing of blood samples from chronic Chagas disease patients (32.8% from asymptomatic and 22.2% from symptomatic patients) and mixed infections was lower than that of the conventional PCR algorithm.Conclusions/Significance: Typing is resolved after a single or a second round of Real-Time PCR, depending on the DTU. This format reduces carryover contamination and is amenable to quantification, automation and kit production.This work received financial support from the Ministry of Science and Technology of Argentina [PICT 2011-0207 to AGS] and the National Scientific and Technical Research Council in Argentina (CONICET) [PIP 112 2011-010-0974 to AGS]. Work related to evaluation of biological samples was partially sponsored by the Pan-American Health Organization (PAHO) [Small Grants Program PAHO-TDR]; the Drugs and Neglected Diseases Initiative (DNDi, Geneva, Switzerland), Wellcome Trust (London, United Kingdom), SANOFI-AVENTIS (Buenos Aires, Argentina) and the National Council for Science and Technology in Mexico (CONACYT) [FONSEC 161405 to JMR]

Chagas' disease and solid organ transplantation

Fil: Lattes, Roberta. Instituto de Nefrología; Argentina.Fil: Altclas, Javier. Sanatorio de la Trinidad Mitre. Enfermedades Infecciosas; Argentina.Fil: Arselán, Sergio. Clínica Privada Velez Sarfield. Sección Enfermedades Infecciosas; Argentina.Fil: Barcán, Laura. Hospital Italiano. Sección Enfermedades Infecciosas; Argentina.Fil: Diez, Mirta. Hospital Universitario de la Fundación Favaloro. Trasplante de corazón; Argentina.Fil: Gadano, Adrian. Hospial Italiano. Trasplante de Hígado; Argentina.Fil: Jacob, Néstor. Hospital Austral. Sección Enfermedades Infecciosas; Argentina.Fil: Maiolo, Elena. Hospital Argerich. Enfermedades Infecciosas; Argentina.Fil: Nagel, Claudia. Hospital Universitario de la Fundación Favaloro. Enfermedades Infecciosas; Argentina.Fil: Riarte, Adelina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Rodriguez, Viviana. Hospital Alemán. Enfermedades Infecciosas; Argentina.Fil: Schiavelli, Ruben. Hospital Argerich. Trasplante de riñón; Argentina.Fil: Schijman, Alejandro G. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular. Laboratorio de Biología Molecular de la Enfermedad de Chagas; Argentina.Fil: Vigliano, Carlos. Hospital Universitario de la Fundación Favaloro. Patología; Argentina.This review summarizes relevant published data on transplant recipients with Chagas' disease and of naïve recipients transplanted with organs from infected donors. Unpublished experience from some of the largest transplant centers in Argentina is also included. The review outlines the guidelines for pretransplant evaluation and for posttransplant management formulated by the Chagas Disease Argentine Collaborative Transplant Consortium

Development of a Clinical Score to Stratify the Risk for Carbapenem-Resistant Enterobacterales Bacteremia in Patients with Cancer and Hematopoietic Stem Cell Transplantation

Identifying the risk factors for carbapenem-resistant Enterobacterales (CRE) bacteremia in cancer and hematopoietic stem cell transplantation (HSCT) patients would allow earlier initiation of an appropriate empirical antibiotic treatment. This is a prospective multicenter observational study in patients from 12 centers in Argentina, who presented with cancer or hematopoietic stem-cell transplant and developed Enterobacterales bacteremia. A multiple logistic regression model identified risk factors for CRE bacteremia, and a score was developed according to the regression coefficient. This was validated by the bootstrap resampling technique. Four hundred and forty-three patients with Enterobacterales bacteremia were included: 59 with CRE and 384 with carbapenem-susceptible Enterobacterales (CSE). The risk factors that were identified and the points assigned to each of them were: ≥10 days of hospitalization until bacteremia: OR 4.03, 95% CI 1.88–8.66 (2 points); previous antibiotics > 7 days: OR 4.65, 95% CI 2.29–9.46 (2 points); current colonization with KPC-carbapenemase-producing Enterobacterales: 33.08, 95% CI 11.74–93.25 (5 points). With a cut-off of 7 points, a sensitivity of 35.59%, specificity of 98.43%, PPV of 77.7%, and NPV of 90.9% were obtained. The overall performance of the score was satisfactory (AUROC of 0.85, 95% CI 0.80–0.91). Finally, the post-test probability of CRE occurrence in patients with none of the risk factors was 1.9%, which would virtually rule out the presence of CRE bacteremia

Development of a Clinical Score to Stratify the Risk for Carbapenem-Resistant Enterobacterales Bacteremia in Patients with Cancer and Hematopoietic Stem Cell Transplantation

Identifying the risk factors for carbapenem-resistant Enterobacterales (CRE) bacteremia in cancer and hematopoietic stem cell transplantation (HSCT) patients would allow earlier initiation of an appropriate empirical antibiotic treatment. This is a prospective multicenter observational study in patients from 12 centers in Argentina, who presented with cancer or hematopoietic stem-cell transplant and developed Enterobacterales bacteremia. A multiple logistic regression model identified risk factors for CRE bacteremia, and a score was developed according to the regression coefficient. This was validated by the bootstrap resampling technique. Four hundred and forty-three patients with Enterobacterales bacteremia were included: 59 with CRE and 384 with carbapenem-susceptible Enterobacterales (CSE). The risk factors that were identified and the points assigned to each of them were: ≥10 days of hospitalization until bacteremia: OR 4.03, 95% CI 1.88–8.66 (2 points); previous antibiotics > 7 days: OR 4.65, 95% CI 2.29–9.46 (2 points); current colonization with KPC-carbapenemase-producing Enterobacterales: 33.08, 95% CI 11.74–93.25 (5 points). With a cut-off of 7 points, a sensitivity of 35.59%, specificity of 98.43%, PPV of 77.7%, and NPV of 90.9% were obtained. The overall performance of the score was satisfactory (AUROC of 0.85, 95% CI 0.80–0.91). Finally, the post-test probability of CRE occurrence in patients with none of the risk factors was 1.9%, which would virtually rule out the presence of CRE bacteremia.Fil: Herrera, Fabián. Centro de Educación Medica E Invest.clinicas; ArgentinaFil: Torres, Diego. Centro de Educación Medica E Invest.clinicas; ArgentinaFil: Laborde, Ana. Fundación Para Combatir la Leucemia; ArgentinaFil: Berruezo, Lorena. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos "prof. Dr. Rodolfo Rossi".; ArgentinaFil: Jordán, Rosana. Hospital Británico de Buenos Aires; ArgentinaFil: Roccia Rossi, Inés. Hospital International General Acute Gral San Martin; ArgentinaFil: Valledor, Alejandra. Hospital Italiano; ArgentinaFil: Costantini, Patricia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Dictar, Miguel. Instituto Alexander Fleming; ArgentinaFil: Nenna, Andrea. Fundacion Marie Curie;Fil: Pereyra, María Laura. Universidad Austral; ArgentinaFil: Lambert, Sandra. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Benso, José. Hospital Italiano; ArgentinaFil: Poletta, Fernando Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Gonzalez Ibañez, María Luz. Fundación Para Combatir la Leucemia; ArgentinaFil: Baldoni, Nadia. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos "prof. Dr. Rodolfo Rossi".; ArgentinaFil: Eusebio, María José. Hospital Británico de Buenos Aires; ArgentinaFil: Lovano, Fiorella. Hospital International General Acute Gral San Martin; ArgentinaFil: Barcán, Laura. Hospital Italiano; ArgentinaFil: Luck, Martín. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Racioppi, Agustina. Instituto Alexander Fleming; ArgentinaFil: Tula, Lucas Fernando. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Pasterán, Fernando. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Corso, Alejandra. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Rapoport, Melina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Nicola, Federico. Centro de Educación Medica E Invest.clinicas; ArgentinaFil: García Damiano, María Cristina. Fundación Para Combatir la Leucemia; ArgentinaFil: Carbone, Ruth. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos "prof. Dr. Rodolfo Rossi".; ArgentinaFil: Monge, Renata. Hospital Británico de Buenos Aires; ArgentinaFil: Reynaldi, Mariana. Hospital International General Acute Gral San Martin; ArgentinaFil: Greco, Graciela. Hospital Italiano; ArgentinaFil: Bronzi, Marcelo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Valle, Sandra. Instituto Alexander Fleming; ArgentinaFil: Chaves, María Laura. Fundacion Marie Curie;Fil: Vilches, Viviana. Universidad Austral; ArgentinaFil: Blanco, Miriam Edith. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Carena, Alberto Ángel. Centro de Educación Medica E Invest.clinicas; Argentin

Sequences and concentrations of primers and probes used in the multiplex real-time PCR assays.

<p>^a[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref044" target="_blank">44</a>]; ^b[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref045" target="_blank">45</a>]; SL-IR, spliced leader intergenic region; 18S, 18S-ribosomal ADN; COII, cytochrome oxidase II; 24Sα, 24Sα-ribosomal ADN; MTq, multiplex Real-Time PCR; BHQ, Black Hole Quencher. The + in front of the nucleotide indicates an LNA (Locked Nucleic Acid) monomer substitution.</p><p>Sequences and concentrations of primers and probes used in the multiplex real-time PCR assays.</p

<i>T</i>. <i>cruzi</i>, <i>T</i>. <i>rangeli</i> and <i>Leishmania</i> spp. isolates used to evaluate the analytical performance of the multiplex real-time PCR genotyping assays.

<p>References: ^a[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref006" target="_blank">6</a>]; ^b[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref026" target="_blank">26</a>]; ^c[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref027" target="_blank">27</a>]; ^d[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref028" target="_blank">28</a>]; ^e[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref029" target="_blank">29</a>]; ^f[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref030" target="_blank">30</a>]; ^g[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref031" target="_blank">31</a>]; ^h[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref032" target="_blank">32</a>]; ⁱ[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref033" target="_blank">33</a>] ^j[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref034" target="_blank">34</a>]; ^k[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref022" target="_blank">22</a>]; ^l[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref023" target="_blank">23</a>]; ^m[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref035" target="_blank">35</a>]; ⁿ[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref036" target="_blank">36</a>]; ^o[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref037" target="_blank">37</a>]; ^p[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref038" target="_blank">38</a>]; ^q[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref039" target="_blank">39</a>]; ^r[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref040" target="_blank">40</a>]; ^s[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003765#pntd.0003765.ref041" target="_blank">41</a>]. DTU, Discrete Typing Unit; nd, no data.</p><p><i>T</i>. <i>cruzi</i>, <i>T</i>. <i>rangeli</i> and <i>Leishmania</i> spp. isolates used to evaluate the analytical performance of the multiplex real-time PCR genotyping assays.</p