Loss of T-Cell Multifunctionality and TCR-Vβ Repertoire Against Epstein-Barr Virus Is Associated With Worse Prognosis and Clinical Parameters in HIV+ Patients

Epstein-Barr virus (EBV) is an oncogenic virus associated with the development of aggressive and poor-prognosis B-cell lymphomas in patients infected with human immunodeficiency virus (HIV+ patients). The most important risk factors for these malignancies include immune dysfunction, chronic immune activation, and loss of T-cell receptor (TCR) repertoire. The combination of all these factors can favor the reactivation of EBV, malignant cell transformation, and clinical progression toward B-cell lymphomas. The overarching aim of this study was to evaluate the frequency, phenotype, functionality, and distribution of TCR clonotypes for EBV-specific T-cell subpopulations in HIV+ patients at different clinical stages and for HIV+ patients with B-cell lymphoma, as well as to establish their association with clinical variables of prognostic value. Factors were studied in 56 HIV+ patients at different clinical stages and in six HIV+ subjects with diagnosed B-cell lymphoma. We found a significant decrease in all subpopulations of EBV-specific CD4+ T cells from HIV+ patients at stage 3 and with B-cell lymphoma. EBV-specific effector CD8+ T cells, particularly effector memory cells, were also reduced in HIV+ patients with B-cell lymphoma. Interestingly, these cells were unable to produce IFN-γ and lacked multifunctionality in HIV+ patients. The TCR-Vβ repertoire, which is key for protection against EBV in healthy individuals, was less diverse in HIV+ patients due to a lower frequency of TCR-Vβ2+, Vβ4+, Vβ7.1+, Vβ9+, Vβ13.6+, Vβ14+, Vβ17+, Vβ22+ CD4+, Vβ14+, and Vβ17+ CD8+ T cells. HIV+ patients with positive plasma EBV loads (EBV+HIV+) had a noteworthy decrease in the levels of both TNF-α+ and multifunctional TNF-α+/IL-2+ and TNF-α+/IFN-γ+ CD8+ T cells. Altogether, our findings demonstrate that HIV+ patients have significant alterations in the immune response to EBV (poor-quality immunity) that can favor viral reactivation, escalating the risk for developing EBV-associated B-cell lymphomas

Toxicidad hematológica asociada al tratamiento con sulfonamidas y pirimetamina en pacientes VIH positivos y toxoplasmosis cerebral en un hospital de tercer nivel en Colombia

Objective. To determine the frequency of hematologic adverse effects associated with treatment for cerebral toxoplasmosis in HIV / AIDS patients. Design: Retrospective case series. Location: University Hospital Hernando Moncaleano Perdomo (HMP), Neiva, Colombia. Population. Patients with cerebral toxoplasmosis and HIV / AIDS treated at the infection service unit between 2006 and 2009. Población. Pacientes con toxoplasmosis cerebral y VIH/SIDA atendidos en el servicio de infectología entre 2006-2009. Results. 51 patients were evaluated during the study period. 40 (78%) were men. The average age was 33 years. 25 patients had cerebral toxoplasmosis as the first marker of HIV infection. 60.7% of cases had hematologic toxicity. 42% of patients had anemia before treatment. The peak onset of bone marrow toxicity was the sixth day of the start of treatment schedule. The anti-toxoplasma scheme that was most commonly associated with myelotoxicity was the combination of pyrimethamine/sulfadoxine, trimethoprim-sulfamethoxazole and clindamycin in 48% of cases. Objetivo. Determinar la frecuencia efectos adversos hematológicos asociados al tratamiento para toxoplasmosis cerebral en pacientes VIH/SIDA. Diseño. Serie de casos retrospectiva. Lugar. Hospital Universitario Hernando Moncaleano Perdomo (HMP), Neiva- Colombia. Población. Pacientes con toxoplasmosis cerebral y VIH/SIDA atendidos en el servicio de Infectología entre 2006-2009. Resultados. 51 pacientes fueron evaluados durante el periodo de estudio. 40 (78%) fueron hombres. El promedio de edad fue 33 años. 25 pacientes presentaban toxoplasmosis cerebral como primer marcador de Infección VIH. El 60,7% de los casos presentaron toxicidad hematológica. 42% de los pacientes presentaron anemia previa al tratamiento. El pico de aparición de toxicidad medular fue al sexto día de inicio del esquema de tratamiento. El esquema antitoxoplasma que más comúnmente fue asociado a mielotoxicidad fue la combinación de pirimetamina/sulfadoxina, trimetoprimsulfametoxazol y clindamicina en 48% de los casos

In Vitro Neutralisation of Rotavirus Infection by Two Broadly Specific Recombinant Monovalent Llama-Derived Antibody Fragments

Rotavirus is the main cause of viral gastroenteritis in young children. Therefore, the development of inexpensive antiviral products for the prevention and/or treatment of rotavirus disease remains a priority. Previously we have shown that a recombinant monovalent antibody fragment (referred to as Anti-Rotavirus Proteins or ARP1) derived from a heavy chain antibody of a llama immunised with rotavirus was able to neutralise rotavirus infection in a mouse model system. In the present work we investigated the specificity and neutralising activity of two llama antibody fragments, ARP1 and ARP3, against 13 cell culture adapted rotavirus strains of diverse genotypes. In addition, immunocapture electron microscopy (IEM) was performed to determine binding of ARP1 to clinical isolates and cell culture adapted strains. ARP1 and ARP3 were able to neutralise a broad variety of rotavirus serotypes/genotypes in vitro, and in addition, IEM showed specific binding to a variety of cell adapted strains as well as strains from clinical specimens. These results indicated that these molecules could potentially be used as immunoprophylactic and/or immunotherapeutic products for the prevention and/or treatment of infection of a broad range of clinically relevant rotavirus strains

Multicenter study in Colombia: Impact of a multidimensional International Nosocomial Infection Control Consortium (INICC) approach on central line–associated bloodstream infection rates

Background: The objective of this study was to analyze the impact of a multidimensional infection control approach and the use of the International Nosocomial Infection Control Consortium (INICC) Surveillance Online System on central line–associated bloodstream infection (CLABSI) rates from June 2003-April 2010. Methods: We conducted a prospective, before-after surveillance study of 2,564 patients hospitalized in 4 adult intensive care units (ICUs) and 424 patients in 2 pediatric ICUs of 4 hospitals in 2 cities of Colombia. During baseline, we performed outcome surveillance of CLABSI applying the Centers for Disease Control and Prevention's National Healthcare Safety Network definitions. During intervention, we implemented the INICC multidimensional approach and the ISOS, which included a bundle of infection prevention practice interventions, education, outcome surveillance, process surveillance, feedback on CLABSI rates and consequences, and performance feedback of process surveillance. Bivariate and multivariate regression analyses were performed using a logistic regression model to estimate the effect of the intervention on the CLABSI rate. Results: The baseline rate of 12.9 CLABSIs per 1,000 central line (CL) days, with 3,032 CL days and 39 CLABSIs, was reduced to 3.5 CLABSIs per 1,000 CL days, with 3,686 CL days and 13 CLABSIs, accounting for a 73% CLABSI rate reduction (relative risk, 0.27; 95% confidence interval, 0.14-0.52; P=.002). Conclusions: Implementing the INICC multidimensional infection control approach for CLABSI prevention was associated with a significant reduction in the CLABSI rate of ICUs of Colombia.Fil: Álvarez Moreno, Carlos A.. Universidad Nacional de Colombia; ColombiaFil: Valderrama Beltrán, Sandra L.. Pontificia Universidad Javeriana; ColombiaFil: Rosenthal, Víctor D.. International Nosocomial Infection Control Consortium; ArgentinaFil: Mojica Carreño, Beatriz E.. Clínica Nueva; ColombiaFil: Valderrama Márquez, Ismael A.. Hospital El Tunal Ese; ColombiaFil: Matta Cortés, Lorena. Universidad Libre; ColombiaFil: Gualtero Trujillo, Sandra M.. Pontificia Universidad Javeriana; ColombiaFil: Rodríguez Peña, Jazmín. Pontificia Universidad Javeriana; ColombiaFil: Linares Miranda, Claudia J.. Pontificia Universidad Javeriana; ColombiaFil: Gonzalez Rubio, Ángela P.. Pontificia Universidad Javeriana; ColombiaFil: Vega Galvis, María C.. Pontificia Universidad Javeriana; ColombiaFil: Riaño Forero, Iván. Pontificia Universidad Javeriana; ColombiaFil: Ariza Ayala, Beatriz E.. Pontificia Universidad Javeriana; ColombiaFil: García Laverde, Germán. Clínica Nueva; ColombiaFil: Susmann, Otto. Clínica Nueva; ColombiaFil: Mancera Páez, Oscar. Hospital El Tunal Ese; ColombiaFil: Olarte, Narda. Hospital El Tunal Ese; ColombiaFil: Rendón Campo, Luis F.. Universidad Libre; ColombiaFil: Astudillo, Yamileth. Universidad Libre; ColombiaFil: Trullo Escobar, María del Socorro. Universidad Libre; ColombiaFil: Orellano, Pablo Wenceslao. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Tecnológica Nacional; Argentina. International Nosocomial Infection Control Consortium; Argentin