Cytomegalovirus reactivation in patients diagnosed with severe COVID-19: A point prevalence study in a general hospital / Reactivación de citomegalovirus en pacientes diagnosticados de COVID-19 grave: Un estudio de prevalencia en un hospital general

Purpose: To determine the prevalence of CMV reactivation in a population admitted for severe COVID-19 to a general hospital. Methods: Point prevalence study in all hospitalized patients with severe COVID-19 (admitted either to general wards or ICU). Determination of the presence of CMV DNA in circulating blood. COVID-19 was confirmed in patients with compatible clinical manifestations, usually with pneumonia and a positive nasopharyngeal PCR test. Results: We included 140 hospitalized patients with COVID-19 who consented to participate. A total of 16 patients (11.42%), had circulating CMV-DNA in peripheral blood at the time of the study. Patients with positive CMV viral load were mainly ICU patients (11/37 -29,7%) and only 5/103 cases (4,85%) were hospitalized into general wards. The accumulated doses of corticosteroids (prednisone equivalents) in the study day were (median and IQR) 987.50 mg (396.87-2,454.68) and 187.50 mg (75.00-818.12) respectively in CMV positive and negative patients (p < 0.001). A significant proportion of CMV positive patients were discovered because of the study and were clinically unsuspected by their physicians. The coinfected COVID-CMV positive population had a higher risk of accumulated secondary nosocomially-acquired infections and a worse prognosis. Conclusion: CMV reactivation should be systematically searched in patients in COVID-19 cases admitted to the ICU. (AU)

Objetivo: Determinar la prevalencia de reactivación del CMV en una población ingresada por COVID-19 grave en un hospital general. Métodos: Estudio de prevalencia en todos los pacientes hospitalizados con COVID-19 (ingresados en salas generales o UCI). Determinación de la presencia de ADN de CMV en sangre. COVID-19 fue confirmado en pacientes con manifestaciones clínicas compatibles, generalmente con neumonía y una prueba de PCR nasofaríngea positiva. Resultados: Se incluyeron 140 pacientes hospitalizados con COVID-19 que firmaron el consentimiento. Un total de 16 pacientes (11,42%), tenían ADN-CMV circulante en sangre periférica en el momento del estudio. Los pacientes con carga viral CMV positiva eran principalmente pacientes de UCI 11/37 (29,7%) y solo 5/103 casos (4,85%) fueron hospitalizados en salas generaleres. Las dosis acumuladas de corticoides (equivalentes de prednisona), en el día del estudio fueron (mediana y RIQ) 987,50 mg (396,87-2.454,68) y 187,50 mg (75,00-818,12) respectivamente en pacientes con CMV positivo y negativo (p< 0,001). Una proporción significativa de pacientes con CMV positivos fueron descubiertos debido al estudio y fueron clínicamente insospechados por sus médicos. La población coinfectada con COVID-CMV positivo tuvo un mayor riesgo de infecciones nosocomiales secundarias acumuladas y un peor pronóstico. Conclusión: La reactivación de CMV debe buscarse sistemáticamente en pacientes con COVID-19 ingresados en la UCI. (AU)

Intrapartum and Postpartum Reactivation of Hepatitis B in Pregnant Patients: a multicentre study / Reactivación intraparto y posparto de la hepatitis B en pacientes embarazadas: un estudio multicéntrico

Introduction: Changes in the immune system during pregnancy have been associated with reactivation of the hepatitis B virus in women chronic hepatitis B infection not receiving antiviral therapy. The aim of this study is to examine the development of intrapartum and postpartum hepatitis B reactivation in pregnant patients not being treated for chronic hepatitis B.Material and Methods: Pregnant women diagnosed with chronic hepatitis B and not receiving treatment between 2017 and 2022 in five centres in the east and southeast Turkey included in this study. In order to evaluate biochemical and viral reactivation from intrapartum and postpartum periods, patients with data for at least two periods were included in the study.Results: Evaluations were made on 171 pregnant women diagnosed with chronic hepatitis B. Reactivation occurred in 43 (25.2%) patients, in the postpartum period in 14 (32.35%) and in the intrapartum period in 29 (67.44%). Reactivation occurred most often in the 3rd trimester (n: 13, 30.2%). A significant increase was observed in the alanine aminotransferase levels of the patients with reactivation in the first trimester compared to 6 months prepartum and in the second trimester compared to the first trimester (p=0.038, p=0.039, respectively). The prepartum HBV DNA level (cut-off point =192 IU/ml) of patients with HBeAg negativity was found to have diagnostic power for reactivation of 0.684 (95% CI: 0.575-0.792, p=0.002) with 65.9% sensitivity and 68.6% specificity. Viral reactivation was observed in the first trimester in one patient and hepatitis B surface antibody was seen in the postpartum period.Conclusions: Asymptomatic viral reactivation occurred at the high rate of 25.1% in this series. To be able to identify reactivation as early as possible, pregnant patients should be followed up closely in the intrapartum and postpartum periods. (AU)

Introducción: Los cambios en el sistema inmunológico durante el embarazo se han asociado con la reactivación del virus de la hepatitis B en mujeres con infección crónica por hepatitis B que no reciben terapia antiviral. El objetivo de este estudio es examinar el desarrollo de la reactivación de la hepatitis B intraparto y posparto en pacientes embarazadas que no reciben tratamiento para la hepatitis B crónica.Material y Métodos: Mujeres embarazadas diagnosticadas de hepatitis B crónica y que no recibieron tratamiento entre 2017 y 2022 en cinco centros del este y sureste de Turquía incluidos en este estudio. Para evaluar la reactivación bioquímica y viral de los períodos intraparto y posparto, se incluyeron en el estudio pacientes con datos de al menos dos períodos.Resultados: Se evaluaron 171 gestantes con diagnóstico de hepatitis B crónica. La reactivación ocurrió en 43 (25,2%) pacientes, en el puerperio en 14 (32,35%) y en el intraparto en 29 (67,44%). La reactivación ocurrió con mayor frecuencia en el tercer trimestre (n: 13, 30,2%). Se observó un aumento significativo en los niveles de alanina aminotransferasa de las pacientes con reactivación en el primer trimestre en comparación con los 6 meses preparto y en el segundo trimestre en comparación con el primer trimestre (p = 0,038, p = 0,039, respectivamente). Se encontró que el nivel de ADN del VHB antes del parto (punto de corte = 192 UI/ml) de pacientes con HBeAg negativo tenía un poder diagnóstico para la reactivación de 0,684 (IC del 95 %: 0,575-0,792, p = 0,002) con una sensibilidad del 65,9 % y una sensibilidad del 68,6 %. % especificidad. Se observó reactivación viral en el primer trimestre en una paciente y se observaron anticuerpos de superficie contra la hepatitis B en el período posparto.Conclusiones: La reactivación viral asintomática ocurrió en la alta tasa de 25,1% en esta serie. ... (AU)

Trasplante cardíaco en miocardiopatía chagásica: 23 años de experiencia en un centro de referencia / Heart Transplantation in Chagas Cardiomyopathy: 23-Year Follow-Up in a Referral Center

RESUMEN Introducción: La enfermedad de Chagas afecta aproximadamente a 6 millones de personas en América Latina. El 25 a 35% evoluciona hacia la Miocardiopatía Chagásica (MCh). Una opción terapéutica en sus estadios avanzados es el trasplante cardíaco (TxC). Objetivos: Comparar la supervivencia de pacientes con TxC por MCh frente a otras etiologías. Analizar la incidencia de la reactivación (Ra) de enfermedad de Chagas y su impacto en la supervivencia en este subgrupo de pacientes. Material y métodos: Se evaluaron retrospectivamente pacientes con TxC entre agosto 1998 y marzo 2021. Se analizó la supervivencia mediante curvas de Kaplan-Meier y log rank test. El diagnóstico de Ra se realizó mediante métodos moleculares, prueba de Strout en sangre periférica, tejido miocárdico y/o cutáneo. Resultados: De 606 pacientes con TxC, 39 (6,4%) presentaban MCh. Seguimiento medio 4,4 años (Rango Intercuartilo 1,2-8,6). Edad subgrupo MCh 51 años (RIC 45-60). Hombres 28 (72%). Se documentó Ra en el 38,5% de los pacientes. Supervivencia a 1, 5 y 10 años en TxC por MCh con Ra versus no Ra: 85%, 76% y 61% versus 72%, 55% y 44% (p = 0,3). Supervivencia a 1, 5 y 10 años en TxC por MCh versus TxC por otras causas: 79%, 65% y 50% versus 79%, 62% y 47% (p = 0,5). Conclusión: En nuestra serie no se encontró diferencia estadísticamente significativa en la supervivencia de los pacientes trasplantados cardíacos por MCh en comparación con aquellos trasplantados por otras causas; así como tampoco entre los pacientes que reactivaron la enfermedad de Chagas y los que no lo hicieron.

ABSTRACT Background: Chagas disease affects about 6 million people in Latin America, and 25 to 35% progress to Chagas cardiomyopathy (ChCM). Heart transplantation (HTx) is a therapeutic option in advanced stages. Objectives: The aim of this study is to compare survival of patients with HTx due to ChCM versus those transplanted for other etiologies and to analyze the incidence of Chagas disease reactivation (Ra) and its impact on survival in this group of patients. Methods: Patients undergoing HTx between August 1998 and March 2021 were retrospectively evaluated. Survival was analyzed using Kaplan-Meier curves and the log-rank test. The diagnosis of Ra was performed by molecular methods, Strout's test in peripheral blood, myocardial tissue or skin tissue. Results: Of 606 patients with Htx, 39(6,4%) presented ChCM. Median follow up was 4.4 years (interquartile range 1.2-8.6). Median age of the subgroup with ChCM was 51 years (IQR 45-60) and 28 were men (72%). Reactivation was documented in 38.5% of the patients. Survival at 1, 5 and 10 years in HTx recipients due to ChCM and Ra versus no Ra was 85%, 76% and 61% versus 72%, 55% and 44%, respectively (p = 0.3). Survival at 1, 5 and 10 years in HTx recipients due to ChCM versus HTx for other causes was 79%, 65% and 50% versus 79%, 62% and 47%, respectively (p = 0.5). Conclusion: In our series we did not find statistically significant differences in survival of heart transplant recipients due to ChCM versus those transplanted due to other reasons. Survival in patients with Chagas disease reactivation and those without reactivation was also similar.

COVID-19 monetary transfer in El Salvador: determining factors / Transferência de renda em El Salvador diante da COVID-19: fatores determinantes / Transferencia monetaria en El Salvador ante la COVID-19: factores determinantes

Abstract Given the lack of governmental guidelines, this paper identifies and analyzes the statistical determinants associated with receiving the onetime monetary transfer in El Salvador ($300 dollars) as an economic measure to face the COVID-19 pandemic. A logistic regression was implemented (whether received the transfer or not) based on a probabilistic sample (n=1222) of surveyed people throughout the country. Independent variables were selected drawing upon key characteristics employed internationally in monetary transfers: age, gender, rural area, employment, family income, and education. The text identifies a statistically significant and negative relation between receiving the monetary transfer and two variables: family income and educational level. The need to increase coverage of the program is addressed as well as the importance of considering age, gender, rural areas, and employment as criteria for selecting the beneficiaries in such economic measures.

Resumo Dada a ausência de diretrizes governamentais, o texto apresenta uma análise exploratória e identifica quais são os fatores estatísticos determinantes que explicam a transferência única de renda ($300 dólares) como medida econômica para enfrentar a pandemia gerada pela COVID-19 em El Salvador. Para tal fim, utiliza-se uma análise estatística de regressão logística (receber ou não a ajuda) com base em uma amostra probabilística de respondentes em todo o país (n=1222). Como variáveis independentes emprega-se caraterísticas importantes utilizadas em programas de transferência de renda em todo o mundo: Idade, gênero, zona de procedência, emprego e renda familiar e nível educacional. O presente texto identifica que existe uma relação inversa e estatisticamente significativa entre essa ajuda pública com a renda familiar e o nível educacional. Finalmente, discute-se a necessidade de ampliação do programa econômico e a importância de considerar características como idade, gênero, zona de procedência e emprego nesse tipo de políticas econômicas.

Resumen Ante la falta de lineamientos gubernamentales, el presente texto muestra un análisis exploratorio e identifica cuáles han sido los determinantes estadísticos asociados a la recepción de la transferencia monetaria única ($300 dólares) como medida económica para enfrentar la pandemia de COVID-19 en El Salvador. Para tal efecto, se utiliza un análisis estadístico de regresión logística (recibir la ayuda o no) con base en una muestra probabilística de encuestados en todo el país (n=1222). Como variables independientes se emplean características cruciales utilizadas en programas de transferencias monetarias a nivel internacional: Edad, género, lugar de origen, empleo, ingresos familiares y nivel educacional. El presente texto identifica que existe una relación inversa y estadísticamente significativa entre la asignación de esa ayuda pública, los ingresos familiares y el nivel educacional. Finalmente, se discute la necesidad de ampliación del programa y la importancia de considerar aspectos como edad, género, lugar de origen y empleo en ese tipo de políticas económicas.

Hospitalizaciones por Herpes zoster en niños

El herpes zoster (HZ) en niños es una patología infrecuente. Objetivo: Describir las hospitalizaciones por HZ en niños. Métodos: Prospectivamente se seleccionaron los menores de 12 años hospitalizados con HZ en Pediatría-Infecciosa-HUC, entre el 2000 y 2015. Se recolectaron datos clínico-epidemiológicos, serologías virales y subpoblación de linfocitos. Completado los años de estudio, se evaluó la recurrencia de HZ y la adquisición de condiciones inmunosupresoras. Resultados: De 8 758 niños hospitalizados, 28 fueron seleccionados, ocho presentaron alguna condición inmunosupresora. La edad promedio fue 6,99 años e ingresaron a los 3,92 días de enfermedad. Ninguno tuvo inmunización contra varicela. Consultaron previo al ingreso 12/28 niños con diagnósticos errados 6/12. El antecedente de varicela in útero o antes del año de edad fue más frecuente en los niños sanos (P=0,04). El dermatoma más afectado fue el del trigémino (36 %). La media de hospitalización fue 7,6 días con complicaciones inherentes al virus en 7/28 niños sin diferencias entre sanos e inmucocomprometidos. Los CD4 fueron reportados en 15/28 niños con valores disminuidos en 2/12 inmunocompetentes y 2/3 inmunocomprometidos (P=0,08). Los inmunocomprometidos con CD4 bajos tuvieron un RR=4 de complicarse. Las serologías para el virus de la inmunodeficiencia humana resultaron negativas. No hubo recurrencias HZ ni la adquisición de inmunosupresión en el seguimiento realizado a 9 pacientes. Conclusiones: HZ es una causa rara de hospitalización en pediatría pudiendo afectar inmunocompetentes e inmunocomprometidos, cursando con complicaciones frecuentes con mayor riesgo en niños inmunocomprometidos con CD4 bajos. El antecedente de varicela antes del año de edad fue el factor predisponente detectado.

Herpes zoster (HZ) in children is an uncommon condition. Objective: To describe children's herpes zoster hospitalization. Methods: children under 12 years of age hospitalized with HZ in Pediatrics-Infectious-HUC between 2000 and 2015 were selected. Clinical and epidemiological data, viral serology and lymphocyte subpopulation were collected. After completing the years of study, viral recurrence and the acquisition of immunosuppressive conditions were evaluated. Results: Of 8 758 hospitalized children, 28 were selected, eight with immunosuppressive status. The mean age was 6.99 years and they were hospitalized at 3.92 days from the onset of the illness. Twelve patients were consulted prior to their admittance and 6 were misdiagnosed. The history of varicella in utero or before the first year was more frequent in healthy children (P=0.04). The most affected dermatome was the trigeminal (36 %). An average hospitalization duration was 7.6 days with complications inherent to virus in 7/28 children with no difference between healthy and immunocompromised ones. None was immunized against varicella. CD4 was reported in fifteen children with low count in 2/12 immunocompetent and 2/3 immunocompromised (P=0.08). Immunocompromised patients with complicated HZ and low CD4 had a RR = 4.1. Serologies for the human immunodeficiency virus came out negative. There were no HZ recurrences nor the acquisition of immunosuppression in the follow-up of nine patients. Conclusions: HZ is a rare cause of hospitalization that may affect immunocompetent children well as immunocompromised ones and frequently presents complications with a greater risk to the immunocompromised group with low CD4. The antecedent of varicella before the first year of age was the predisposing factor detected.

Reactivation of hepatitis B associated with immunosuppressants and chemotherapy. Natural history, risk factors and recommendations for prevention. / Reactivación de la hepatitis B asociada a agentes inmunodepresores y a quimioterapia. Historia natural, factores de riesgo y recomendaciones para prevenirla.

Although the risk of reactivation of hepatitis B in patients treated with immunosuppressants has been known for years and, if there are recommendations, data from some surveys indicate that the study of the serological profile of HBV infection before starting immunosuppressive treatment is not universal practice. Taking into account the serious consequences that the reactivation of the infection with HBV may entail, we believe that it is necessary to disclose the importance of this problem among the health professionals who prescribe these treatments as well as the recommendations to be followed. In fact, in recent years, the use of chemotherapy and potent immunosuppressants in patients with neoplastic processes and in non-neoplastic pathology of various specialties has been increasingly frequent, increasing the population of patients at risk of reactivation of HBV.

Serología del virus de la hepatitis B: para múltiples escenarios, múltiples exámenes / Serology of hepatitis B virus: multiple scenarios and multiple exams

Resumen El virus de la hepatitis B (VHB) tiene un gran impacto mundial. No obstante la disponibilidad de la vacuna, 2000 millones de personas se han infectado agudamente y, de ellos, 240 millones persisten crónicamente infectados. La infección tiene diferentes formas de presentación tales como infección aguda, infección crónica, infección oculta y reactivación cuando hay inmunosupresión. Así mismo, hay marcadores muy sensibles como el anticore, cuya positividad puede tener diversos significados. El recientemente descrito antígeno relacionado con el antígeno core es un marcador emergente que podría reemplazar al ácido desoxirribonucleico (ADN) viral. En la presente revisión se discuten los exámenes de laboratorio necesarios para el diagnóstico de los diferentes escenarios de la infección.

Abstract Hepatitis B virus (HBV) has an enormous global impact. Despite the availability of a vaccine, two billion people have been acutely infected. Of these, 240 million remain chronically infected. The infection has different forms of presentation including acute infections, chronic infections, hidden infections, and reactivation when there is immunosuppression. Similarly, there are very sensitive markers such as anti-core, but a positive test can have different meanings. This recently described antigen which is related to the core antigen is an emerging marker that could replace viral DNA. In this review we discuss the laboratory tests necessary for diagnosing the various scenarios of the infection.

Uterine Involution in Hosltein cows in the province of Carchi, Ecuador / Involución uterina en vacas Holstein en la provincia El Carchi, Ecuador

Abstract Objective. To evaluate the uterine involution in Holstein cow, under the conditions of production of the bovine dairy cattle in the province El Carchi, Ecuador. Materials and Methods. Sixty cows were selected and the time for uterine involution was determined by the recto-vaginal examination, ultrasonography and the clinical score of the regression of the uterus. The statistical parameters for each variable were determined. The effect of parity and body condition (CC) on complete uterine involution was evaluated by multifactorial ANOVA and the LSD test to compare means. Results. The clinical involution of the uterus, without taking into account the clinical score occurred at 29.86±7.71 days but considering this notation was at 42 ± 0.39 days. The uterine involution took place earlier (p<0.05) in cows with BCS ≥ 3.5 at birth than in those with BCS <3.5. In second calving cows it was at 25.17±1.32 days and it was extended (p<0.05) for the third and fourth calving. The occurrence of the dominant follicle and ovulation occur at 16.63 ± 3.83 and 27.76±7.71 days, respectively. Conclusions. The clinical involution of the uterus occurred in less time when the recto-vaginal examination was considered, compared when it was evaluated taking into account the clinical score. The uterine involution process is influenced by parity and body condition at calving.

Resumen Objetivo. Evaluar la involución uterina en vacas Holstein, en las condiciones de producción de la ganadería bovina lechera en la provincia El Carchi, Ecuador. Materiales y métodos. Se seleccionaron 60 vacas y se determinó el tiempo para la involución uterina mediante la exploración recto-vaginal, ultrasonografía y la puntuación clínica de la regresión del útero. Se determinaron los estadígrafos descriptivos de cada variable. Se evaluó el efecto de la paridad y la condición corporal (CC) sobre la completa involución uterina mediante un ANOVA multifactorial y la prueba LSD para comparar las medias. Resultados. La involución del útero, sin tomar en cuenta la puntuación clínica ocurrió a los 29.86 ± 7.71 días pero considerando esta notación fue a los 42±0.39 días. La involución uterina ocurrió más temprano (p<0.05) en las vacas con CC al parto ≥ que 3.5 que en las que la tenían < de 3.5. En las vacas de segundo parto fue a los 25.17 ± 1.32 días y se prolongó (p<0.05) en el tercero y cuarto parto. La aparición del folículo dominante y la ovulación ocurrieron a los 16.63±3.83 y 27.76±7.71 días, respectivamente. Conclusiones. La involución clínica del útero considerando el examen recto-vaginal ocurrió en menor tiempo que cuando se evaluó considerando la puntuación clínica. El proceso de involución uterina está iinfluenciado por la paridad y la CC al parto.

Reactivation of Hepatitis B virus in kidney transplant recipients with previous clinically resolved infection: A single-center experience.

BACKGROUND: Hepatitis B virus (HBV) reactivation in kidney transplant recipients (KTR) involves important morbidity and mortality. Despite being more common in patients who are HBsAg-positive, it may occur in patients with clinically resolved infection (HBsAg-negative and anti-HBc-positive), in whom the presence of the protective anti-HB antibody is thought to decrease the risk of reactivation. Data regarding reactivation rates in this population are scarce. OBJECTIVE: To retrospectively evaluate the risk of HBV reactivation in KTR with previously resolved infection. MATERIAL AND METHODS: Retrospective cohort study including patients who underwent a kidney transplant between January 1994 and December 2014 with resolved HBV infection at the time of transplantation (anti-HBc seropositivity without detectable HBsAg, with or without anti-HB-positive antibodies and normal liver enzymes). RESULTS: Out of 966 patients, 95 patients with evidence of resolved HBV infection were analyzed, of which 86 had a titer of anti-HBs >10mIU/ml. Mean follow-up time was 93 months; 12 patients had lost anti-HBs. Two patients showed evidence of reactivation. Risk factors associated with loss of anti-HBs were elderly age (>60) and occurrence of acute graft rejection (p<0.05). CONCLUSION: The risk of HBV reactivation in KTR with previously resolved infection is not negligible at 2%. Elderly age and acute rejection were associated with loss of anti-HBs, and these patients may benefit from closer monitoring of HBV DNA levels. Routine serology and/or HBV viral load monitoring in HBsAg-negative, anti-HBc-positive patients is recommended and should be emphasized in these patients.

Enfermedad de Chagas en el sistema nervioso central en paciente con infección por VIH: dificultades diagnósticas y terapéuticas / Chagas disease in the central nervous system in patient infected with HIV: diagnostic and therapeutic difficulties

Chagas disease (ChD), caused by the protozoan Trypanosoma cruzi, is an endemic anthropozoonosis in Latin America, linked to deficients socio-economic and cultural aspects and is considered one of the neglected tropical diseases. We report a fatal case of Chagas disease reactivation with central nervous system involvement in a patient with HIV infection, whose diagnosis was confirmed by positive PCR (polymerase chain reaction) test of blood, with treatment response efficiency with benznidazol and management and etiologic treatment was difficult due to limited number of antitrypanosomal drugs and the occurrence of frequent and serious adverse effects.

La enfermedad de Chagas, causada por el protozoo Trypanosoma cruzi, es una antropo-zoonosis endémica en Latinoamérica, vinculada con aspectos socio-económico-culturales deficitarios y considerada una de las enfermedades desatendidas. Presentamos un caso fatal de una reactivación de la enfermedad de Chagas con afectación del sistema nervioso central en un paciente con infección por VIH. El diagnóstico se confirmó por reacción de polimerasa en cadena (RPC) positiva en sangre. Tuvo una buena respuesta al tratamiento con benznidazol. Las dificultades en el manejo del tratamiento etiológico se debieron al número limitado de medicamentos antitripanosomiásicos y la aparición de efectos adversos graves.

Primary tuberculosis infection in patients treated with tumor necrosis factor-alpha antagonists and a negative initial screening.

INTRODUCTION: Despite screening for latent tuberculosis (TB), new cases of TB infection are detected in patients treated with anti-TNF-α and negative initial screening, some of them after long treatment, which points more to a new infection. OBJECTIVES: To describe the cases that have presumably developed a primary tuberculous infection during treatment with anti-TNF-α drugs. METHODS: Retrospective audit (1999-2012). Inclusion criteria were: a) anti-TNF-α treatment; b) initial latent TB screening negative; c) TB diagnosed during anti-TNF-α treatment; d) suspected primary TB infection (diagnosis after at least 12 months on anti-TNF-α). Clinical, epidemiological, therapeutic and outcome variables were reviewed. RESULTS: Two cases of primary TB infection were found out of of 771 anti-TNF-α treated patients (0.2%). One woman aged 41 suffered TB pneumonia after 35 months of treatment with adalimumab, and a male aged 37 who developed disseminated TB after 107 months of treatment with infliximab. CONCLUSIONS: Although uncommon, during TNF antagonist therapy, TB risk persists despite negative initial screening, so clinicians should be aware of TB during the entire treatment.

Evasión de la respuesta inmune por virus herpes simplex / Immune evasion by herpes simplex viruses

Herpes simplex viruses and humans have co-existed for tens of thousands of years. This long relationship has translated into the evolution and selection of viral determinants to evade the host immune response and reciprocally the evolution and selection of host immune components for limiting virus infection and damage. Currently there are no vaccines available to avoid infection with these viruses or therapies to cure them. Herpes simplex viruses are neurotropic and reside latently in neurons at the trigeminal and dorsal root ganglia, occasionally reactivating. Most viral recurrences are subclinical and thus, unnoticed. Here, we discuss the initial steps of infection by herpes simplex viruses and the molecular mechanisms they have developed to evade innate and adaptive immunity. A better understanding of the molecular mechanisms evolved by these viruses to evade host immunity should help us envision novel vaccine strategies and therapies that limit infection and dissemination.

Los virus herpes simplex y humanos co-existen desde decenas de miles de años. Esta prolongada relación se ha traducido en la evolución y selección de determinantes virales para evadir la respuesta inmune y recíprocamente la evolución y selección de componentes inmunes del hospedero para limitar la infección viral y el daño que producen. Actualmente no existen vacunas para evitar la infección de estos virus o terapias que la curen. Los virus herpes simplex son neurotrópicos y permanecen latentes en neuronas de ganglios trigémino y dorsales, reactivándose esporádicamente. La mayoría de las recurrencias por virus herpes simplex son sub-clínicas y por tanto pasan inadvertidas. Aquí discutimos los pasos iniciales de la infección porvirus herpes simplex y los mecanismos moleculares que estos virus han desarrollado para evadir la respuesta inmune innata y adaptativa. Una mejor comprensión de los mecanismos moleculares evolucionados por estos virus para evadir la respuesta inmune del hospedero deberían ayudarnos visualizar nuevas estrategias para desarrollar vacunas y terapias que limiten su infección y diseminación.

[Hepatitis B virus reactivation in rituximab-treated patients: incidence and risk factors]. / Reactivación del virus de la hepatitis B en pacientes tratados con rituximab: incidencia y factores de riesgo.

Hepatitis B virus (HBV) reactivation after chemotherapy regimens is a well-known complication. The incidence and risk factors for HBV reactivation remain to be elucidated. We aimed to determine the incidence and risk factors for HBV reactivation in patients receiving rituximab, and the potential role of the cumulative rituximab dose in HBV reactivation. We retrospectively reviewed 320 patients receiving rituximab in our hospital. Of these, 42 (13.12%) had serological markers of hepatitis B. During follow-up, 21% (9/42) had HBV reactivation. Risk factors for reactivation were HBsAg positivity (p < 0.05), isolated anti-HBc positivity (p < 0.05), marginal zone lymphoma, and Mantle cell lymphoma (p < 0.05). The median rituximab dose tended to be higher in patients with reactivation (p = 0.06).

Miocarditis aguda y meningoencefalitis por Trypanosoma cruzi en un paciente seropositivo al VIH / Acute miocarditis and meningoencephalitis caused by Trypanosoma cruzi in an HIV-seropositive patient

La enfermedad de Chagas, endémica en Argentina, transcurre en dos fases: aguda y crónica. En los pacientes seropositivos al VIH, el Trypanosoma cruzi afecta a aquellos con inmunodeficiencia severa, se localiza principalmente en el sistema nervioso central y menos frecuentemente en el miocardio. La distinción entre miocarditis aguda y reactivación de la infección crónica, no es sencilla. El bajo recuento de linfocitos T CD4+ es un factor predictivo positivo de reactivación. En los enfermos con inmunodeficiencia avanzada, los resultados negativos de las pruebas serológicas no excluyen el diagnóstico de enfermedad de Chagas, que se confirma por la aplicación de métodos directos en sangre o líquido cefalorraquídeo. Se presenta el caso de un paciente infectado por el VIH, adquirido por transmisión vertical, con inmunodeficiencia severa, miocarditis aguda y compromiso del SNC. La parasitemia y parasitorraquia positivas para T. cruzi, establecieron la asociación de estos síntomas con la enfermedad de Chagas(AU)

Chagas disease, endemic in Argentina, goes through two stages: acute and chronic. In VIH seropositive patients, Trypanosomacruzi affects those with severe immunodeficiency; it is mainly located in the central nervous system and less frequently in the myocardium. Distinction between acute myocarditis and chronic infection reactivation is not simple. Low T CD4+ lymphocyte count is a positive predictive factor of reactivation. In patients with advanced immunodeficiency, negative results of serological tests do not exclude diagnosis of Chagas disease which may bre confirmed through the application of direct methods in blood and cerebrospinal fluid. The case of a VIH infected patient who got the disease through vertical transmission with severe immunodeficiency, acute myocarditis and central nervous system damage. Positive parasitemia and parasitorrachya for T. cruzi established the association between these symptoms and Chagas disease(AU)

[Biochemical, serological and virologic follow-up in patients with chronic untreated hepatitis B virus infection: inactive carrier, chronic HBeAg-negative and immune-tolerant hepatitis]. / Seguimiento bioquímico, serológico y virológico en pacientes con infección crónica por el virus de la hepatitis B no tratados: portador inactivo, hepatitis crónica HBeAg negativo e inmunotolerante.

Biochemical, serological and virologic follow-up is necessary for patients with chronic untreated HBV infection while the infection persists. For patients who are inactive carriers, follow-up helps detect reactivation or loss of HBsAg. After the loss of HBsAg, follow-up is not recommended unless the patient requires immunosuppressive therapy. For patients with chronic HBeAg-negative hepatitis with normal ALT levels and a viral load between 2000 and 20,000 IU/mL, follow-up is required to assess the progression of the disease. For patients who are immune-tolerant, follow-up helps assess the spontaneous seroconversion of HBeAg.

[Treatment hepatitis B reactivation in the transplant]. / Tratamiento de la reactivación del virus de la hepatitis B en el trasplante.

The indication for liver transplantation for those with hepatitis B virus (HBV) infection represents some 5%-10%, with a declining trend, due in large measure to the efficacy of antiviral drugs. Similarly, the use of nucleoside/nucleotide analogues, with or without specific gamma globulin, has helped prevent HBV infection recurrence. The posttransplantation recurrence of HBV infection can be defined as the reappearance of circulating HBsAg and HBV DNA detectable in 2 measurements. Treatment is based on the use of nucleoside/nucleotide analogues, as with patients who have not been transplanted, and is based on the same principles. Profound immunosuppression of patients with liver transplants causes the HBV DNA levels to be very high and requires rapid and effective viral replication suppression. Entecavir and tenofovir are the first-line treatments. Tenofovir is effective for treatment-naïve patients and those with lamivudine-resistance. Entecavir is highly effective for treatment-naïve patients but should be restricted in cases of prior treatment with lamivudine.

Inactive fibrotic lesions versus pulmonary tuberculosis with negative bacteriology.

This article analyzes the concept of inactive fibrotic lesions of presumed tuberculous origin (old healed tuberculosis), defined by radiological characteristics and a positive tuberculin skin test (TST), and we examine the evidence-based foundation for the indication of treatment of latent tuberculosis infection in these cases. We explore the risk of reactivation in older and recent literature, and the problems raised by the differential diagnosis with active tuberculosis with negative bacteriology. We also analyze data on the prevalence of fibrotic lesions in the recent literature. We examine the possible role of Interferon Gamma Release Assays (IGRAs) versus TST and other molecular antigen detection techniques in sputum that can aid in establishing the diagnosis and we discuss the current indications for chemoprophylaxis and the different options available. We propose diagnostic guidelines and therapeutic algorithms based on risk stratification by age and other factors in the management of radiological lesions that raise a differential diagnosis between fibrotic lesions and active pulmonary tuberculosis with negative bacteriology.

Reactivación de Citomegalovirus en crisis de enfermedad inflamatoria intestinal: un análisis retrospectivo / Cytomegalovirus reactivation in inflammatory bowel disease: a retrospective analysis

Cytomegalovirus (CMV) is considered an agent involved in reactivation of inflammatory bowel disease (IBD). In our country there are no studies or guidelines to standardize CMV search in that setting. Objective: To describe the prevalence of CMV infection in hospitalized patients with IBD. Methods: Retrospective analysis of patients hospitalized due to IBD crisis from June 2007 to June 2009 at a university health center. Electronic cards, laboratory data, and endoscopic study were reviewed. CMV reactivation was diagnosed by means of antigenemia assay, and/or histopathology. Results: 88 IBD crises were identified (74 patients), in 52 a CMV study was requested (47 with antigenemia assay). Mean age was 38.5 years-old, 54 percent female, ulcerative colitis 67.3 percent, Crohn disease 32.7 percent. IBD crisis were classified as follows; severe 57.7 percent, moderate or mild 42.3 percent. The CMV diagnosis test was positive in 5 cases (9.6 percent), all of them were severe crisis (16.6 percent in severe crisis versus 0 percent in moderate/mild crisis, p = 0.055). In the group of steroid resistant disease the CMV antigenemia was positive in 66.6 percent versus 2.17 percent of non-steroid resistant patients (p = 0.0002). Test to detect CMV performed after the third day of hospitalization were positive in 36.36 percent versus those performed earlier, which were positive in 2.43 percent (p = 0.004). Conclusion: High prevalence of CMV infection in cases of severe IBD crisis was detected, specifically in a subgroup of steroid-resistant patients and three days after hospital admission. These findings suggest the importance to search CMV in this subgroup of patients.

Introducción: El citomegalovirus (CMV) puede participar en la reactivación de la enfermedad inflamatoria intestinal (EII). En nuestro medio no se ha estudiado el rol de CMV en pacientes hospitalizados por crisis de EII. Objetivo: Estimar la prevalencia de la reactivación de CMV en crisis de EII que requirieron hospitalización. Métodos: Análisis retrospectivo de pacientes hospitalizados en un centro de salud universitario por EII entre junio de 2007 y junio de 2009. Se revisaron registros clínicos electrónicos, laboratorio y estudio endoscópico. La reactivación de CMV se diagnosticó mediante antigenemia y/o histología. Resultados: Se identificaron 88 crisis de EII (74 pacientes), en 52 se solicitó estudio de CMV (47 con antigenemia). 67,3 por ciento fueron colitis ulcerosa; 32,7 por ciento enfermedad de Crohn. Edad promedio 38,5 años, 54 por ciento sexo femenino. La exacerbación fue catalogada como grave en 57,7 por ciento de los casos, moderada o leve en 42,3 por ciento. Se detectó reactivación de CMV en 5 pacientes (9,6 por ciento), los que se caracterizaron por presentar crisis grave (16,6 por ciento en crisis grave versus 0 por ciento en crisis leve/moderada, p = 0,055), refractariedad a corticoides (66,6 por ciento en corticorrefractarios versus 2,17 por ciento en sensibles a corticoides, p = 0,0002) y hospitalización mayor de 3 días (36,36 por ciento en hospitalización > 3 días versus 2,43 por ciento en estudio temprano, p = 0,004). Conclusión: En pacientes hospitalizados por crisis de EII es frecuente detectar evidencia de reactivación de CMV, la que se concentra en las crisis graves, corticorrefractarias y con hospitalización mayor de 3 días. Estos datos sugieren que la búsqueda de CMV debiera ser dirigida a este subgrupo de pacientes.

Mecanismos de evasión y persistencia de Mycobacterium tuberculosis durante el estado de latencia y posibles estrategias para el control de la infección latente / Mechanisms of evasion and persistence of Mycobacterium tuberculosis during the latencystate and potential strategies to control latent infection

Mycobacterium tuberculosis, el agente causal de la tuberculosis, infecta aproximadamente alrededor de 54 millones de personas en todo el mundo cada año y constituye una de las principales causas de muerte entre las enfermedades infecciosas. La mayoría de los individuos infectados con M tuberculosis desarrollan una infección latente, etapa en la que este microorganismo sobrevive dentro del hospedero, evadiendo los mecanismos de defensa del sistema inmune del portador. La terapia actual de la tuberculosis comprende la administración de cuatro antimicrobianos durante seis meses. No obstante, M tuberculosis es capaz de sobrevivir después de varios meses de tratamiento con esa terapéutica antimicrobiana combinada. Existen evidencias de que el bacilo tuberculoso, durante la fase estacionaria de crecimiento, incrementa su tolerancia a los ambientes de estrés. El costo de los fßrmacos empleados para el tratamiento y el incremento de cepas de M tuberculosis multidrogorresistentes constituyen uno de los motivos principales para desarrollar una nueva vacuna contra la tuberculosis. Sin embargo, su erradicación està afectada por la capacidad que posee el bacilo tuberculoso de sobrevivir en estado de latencia durante décadas, en las condiciones de hipoxia y causar infecciones recurrentes(AU)

Mycobacterium tuberculosis, the causative agent of tuberculosis, infects approximately 54 million people around the world each year and is a leading cause of death among infectious diseases. Most individuals infected with M tuberculosis develop a latent infection stage at which this organism survives within the host, evading the defense mechanisms of the host immune system. Current TB therapy involves administration of four antibiotics for six months. However, M tuberculosis is able to survive after several months of treatment with this antimicrobial combination therapy. There is evidence that the TB bacilli during the stationary phase of growth, increases tolerance to stress environments. The cost of drugs used for treatment and the increase of M tuberculosis multidrug resistant strains, is one of the main reasons for developing a new vaccine against tuberculosis. However, the elimination of the disease has been prevented by the ability of the bacillus to both survive in latency for decades, under conditions of hypoxia and to cause recurrent infections(AU)