Seroprevalencia de anticuerpos IgG antirubéola y anticitomegalovirus en mujeres entre 16 y 40 años residentes en Tunja, Colombia / Seroprevalence of anti-rubella and anti-cytomegalovirus IgG antibodies in women aged between 16 and 40 years, living in Tunja, Colombia

RESUMEN Objetivo Determinar la seroprevalencia de anticuerpos IgG anti-rubéola y anti-citomegalovirus en un grupo de mujeres entre 16 y 40 años, residentes en Tunja. Métodos Investigación descriptiva de corte transversal, en la cual se incluyeron mujeres de 16 a 40 años, por medio de un muestreo no probabilístico por conveniencia. Las variables sociodemográficas fueron registradas mediante encuesta. Se empleó ensayo inmunoenzimático para la determinación cuantitativa de anticuerpos IgG frente a rubéola y citomegalovirus en suero. La estadística aplicada al estudio se llevó a cabo por medio del programa estadístico SPSS versión 21. Resultados El estudio incluyó un total de 154 mujeres en edad fértil, estableciéndose una seropositividad para IgG anti-rubéola de 96,1% (n=148) (IC 95% 93,0 - 99,1) y anti-citomegalovirus de 90,9% (n=140) (IC 95% 86,3 - 95,4). Conclusión Una de cada diez mujeres en estudio está en riesgo de adquirir una infección primaria por citomegalovirus y una de cada 30 por rubéola. El control prenatal por medio de determinaciones serológicas frente a citomegalovirus y rubéola durante el embarazo es primordial en estos casos.(AU)

ABSTRACT Objective To determine the seroprevalence of anti-rubella and anti-cytomegalovirus IgG antibodies in a group of women aged between 16 and 40 years, residents of Tunja. Methods Descriptive, cross-sectional research in women aged between 16 and 40 years included by means of non- probability sampling for convenience. Sociodemographic variables were recorded by applying a survey. An enzyme immunoassay was used for the quantitative determination of rubella and cytomegalovirus IgG antibodies in serum. The statistical analysis was carried out using the statistical program SPSS version 21. Results The study included 154 women of childbearing age, establishing seropositivity for anti-rubella IgG of 96.1% (n=148) (95%CI: 86.3 - 95.4) Conclusion One in ten women included in the study is at risk of primary cytomegalo-virus infection and one in 30 of rubella infection. Prenatal care using serological determinations of cytomegalovirus and rubella during pregnancy is essential in these cases.(AU)

Cutaneous involvement by cytomegalovirus in a renal transplant recipient as an indicator of severe systemic infection

Abstract Cytomegalovirus is an opportunistic virus that commonly affects immunosuppressed patients. Cutaneous involvement by this virus is rare and occurs in significantly immunocompromised hosts, with a poor prognosis. Skin ulcers may represent the first sign of systemic infection by cytomegalovirus in these patients. Herein, a case of a systemic infection by Cytomegalovirus presenting as genital and oral ulcers in a kidney-transplant recipient is reported.

Modulación de la apoptosis por cytomegalovirus en la perspectiva del sistema nervioso central / Modulation of apoptosis by cytomegalovirus, from the perspective of the central nervous system

Apoptosis is one of the most effective mechanisms against the spread of pathogens such as viruses. However, viruses have developed measures to counter the protective role of apoptosis in infected cells. Cytomegalovirus (CMV) represents the major cause of congenital infection worldwide triggering important damage in the developing central nervous system (CNS). Several mechanisms of apoptosis prevention during CMV infection have been described, among them, viral proteins and RNAs are capable of prevent apoptosis by the intrinsic and extrinsic pathways as well as the one mediated by stress in the endoplasmic reticulum. Nevertheless, the CMV pro-apoptotic effect remains enigmatic and it has been suggested as a bystander effect in non-infected cells. This review summarizes the mechanisms by which CMV modulates the signaling pathways involved in apoptosis. It also includes a brief description of the permissiveness of the CNS to CMV infection and the generated cell death after infection, which may relate to the observed damage during a congenital infection.

La apoptosis representa uno de los mecanismos de defensa más eficaces frente a la propagación de patógenos como lo son los virus. No obstante, éstos han desarrollado medidas para contrarrestar el papel protector de la apoptosis en las células infectadas. Citomegalovirus (CMV) es considerado la principal causa de infecciones congénitas a nivel mundial, afectando de forma importante el sistema nervioso central (SNC) en desarrollo. Diversos mecanismos de prevención de apoptosis durante la infección por CMV han sido descritos, entre los cuales, se encuentran proteínas y ARNs virales capaces de evitar la apoptosis por las vías intrínseca, extrínseca y la mediada por estrés del retículo endoplásmico. Sin embargo, aún representa un enigma el efecto pro-apoptótico de CMV que se sugiere actúe como un efecto espectador sobre las células no infectadas. En el presente trabajo se ofrece una revisión de los mecanismos mediante los cuales CMV modula las vías de señalización involucradas en la apoptosis. Asimismo se incluye una breve descripción de la permisividad del SNC a la infección por CMV y sobre la muerte celular generada tras la infección, que pueden relacionarse con el daño observado durante una infección congénita.

Antigenemia y reacción de polimerasa en cadena en tiempo real en el diagnóstico de enfermedad por citomegalovirus en adultos con virus de inmunodeficiencia adquirida / Antigenemia and real time polymerase chain reaction for diagnosis of cytomegal ovirus disease in HIV infected adults

Background: Cytomegalovirus (CMV) infection is frequent in HIV adults. It is unknown usefulness of quantitative methods for diagnosing the CMV disease in Chilean patients. Aim: To determine the performance of antigenemia and real time polymerase chain reaction (rtPCR) in the diagnosis of CMV disease in Chilean HIV adults. Method: Detection of CMV by viral isolation (AVR), antigenemia and quantitative rtPCR in HIV adults. Results: The 102 adults with suspected CMV disease had lower LTCD4 count and higher HIV viral load than 77 patients without suspicion (p < 0.05). Antigenemia and PCR were positive in 47 (46.1%) and 37 (36.3%) adults with clinical suspicion and in 2 (2.6%) and 4 (5.2%) of 77 without suspicion. The sensitivity, specificity, positive and negative predictive value of antigenemia and RPCtr were 92%, 80%, 72% and 95% and 72%, 95%, 92% and 80%, respectively. The cutoff values were ≥ lcell (+) and ≥ 5.5 log10 copies/2 x 10(6) cells. CMV was isolated in 6/179 patients (3.4%), all symptomatic. Conclusión: Positivity of antigenemia and rtPCR are similar for diagnosing CMV disease in Chilean HIV adults. AVR is inappropriate as a gold standard for its low performance.

Introducción: La infección por citomegalovirus (CMV) es frecuente en adultos con virus de inmunodeficiencia humana (VIH). No se ha establecido la utilidad de los métodos cuantitativos para diagnosticar enfermedad por CMV en pacientes chilenos. Objetivo: Determinar la positividad de antigenemia y reacción de polimerasa en cadena en tiempo real (RPC-TR) en el diagnóstico de enfermedad por CMV en adultos chilenos con infección por VIH. Metodología: Se detectó CMV mediante aislamiento viral rápido (AVR), antigenemia y reacción de polimerasa en cadena en tiempo real (RPC-TR) cuantitativa en adultos infectados por VIH, con y sin sospecha de enfermedad por CMV. Resultados: El recuento de LT CD4 fue menor y mayor la carga de VIH en 102 sintomáticos respecto a 77 asintomáticos (p < 0,05). La antigenemia y la RPC-TR fueron positivas en 46 y 36% de los enfermos y en 3 y 5% de los asintomáticos respectivamente. La sensibilidad, especificidad, valor predictor positivo y negativo de la antigenemia y la RPC-TR fueron 92%, 80%, 72% y 95% y 72%, 95%, 92% y 80%, respectivamente. Los valores de corte fueron ≥ 1 núcleo (+) y ≥ 5,5 log10 copias/2 x 10(6) céls. Se aisló CMV en 3,4%, todos los sintomáticos. Conclusión: La antigenemia y la RPC-TR tienen una positividad similar para diagnosticar enfermedad por CMV en adultos chilenos con infección por VIH. El AVR es inapropiado como referencia por su baja positividad.

Cutaneous cytomegalovirus infection in a child with hyper IgE and specific defects in antibody response to protein vaccines

Cytomegalovirus (CMV) infection is a common opportunistic systemic infection in immunocompromised patients, but skin involvement is rare. Herein, we report a 10 year-old girl from consanguineous parents who was referred to our center because of disseminated maculopapular rash. She had history of upper and lower respiratory tract infections. In immunological studies, increased serum IgE level and decreased responses to tetanus and diphtheria were detected. Polymerase chain reaction (PCR) examination of bronchoalveolar lavage and serum sample revealed the presence of CMV. Early diagnosis of cutaneous CMV and appropriate treatment are the key actions in management of patients with underlying immunodeficiencies to avoid further complications.

Comparison of the performance of polymerase chain reaction and pp65 antigenemia for the detection of human cytomegalovirus in immunosuppressed patients / Comparação de métodos para detecção de infecção por citomegalovírus em pacientes imunossuprimidos

INTRODUCTION: Human cytomegalovirus (HCMV) is often reactive in latently infected immunosuppressed patients. Accordingly, HCMV remains one of the most common infections following solid organ and hemopoietic stem cell transplantations, resulting in significant morbidity, graft loss and occasional mortality. The early diagnosis of HCMV disease is important in immunosuppressed patients, since in these individuals, preemptive treatment is useful. The objective of this study was to compare the performance of the in-house qualitative polymerase chain reaction (PCR) and pp65 antigenemia to HCMV infection in immunosuppressed patients in the Hospital de Clínicas of Porto Alegre (HCPA). METHODS: A total of 216 blood samples collected between August 2006 and January 2007 were investigated. RESULTS: Among the samples analyzed, 81 (37.5 percent) were HCMV-positive by PCR, while 48 (22.2 percent) were positive for antigenemia. Considering antigenemia as the gold standard, sensitivity, specificity, positive predictive values and negative predictive values for PCR were 87.5 percent, 76.8 percent, 51.8 percent and 95.5 percent respectively. CONCLUSIONS: These results demonstrated that qualitative PCR has high sensitivity and negative predictive value (NPV). Consequently PCR is especially indicated for the initial diagnosis of HCMV infection. In the case of preemptive treatment strategy, identification of patients at high-risk for HCMV disease is fundamental and PCR can be useful tool.

INTRODUÇÃO: O citomegalovírus humano (HCMV), causador de infecção latente, reativa com frequência em pacientes imunossuprimidos. Portanto, o HCMV permanece uma das infecções mais comuns após transplantes de órgãos sólidos e de células hematopoiéticas resultando em significativa morbidade, perda do enxerto e ocasional mortalidade. Assim, o diagnóstico precoce para uma terapia preventiva é de grande importância. Este estudo visa comparar o desempenho dos métodos PCR qualitativo in-house e antigenemia pp65 para o diagnóstico de infecção por CMV em pacientes imunossuprimidos do Hospital de Clínicas de Porto Alegre. MÉTODOS: O estudo foi realizado em 216 amostras de sangue total (EDTA) coletadas de 85 pacientes, entre agosto de 2006 e janeiro de 2007. RESULTADOS: Dentre as 216 amostras analisadas, 81 (37,5 por cento) amostras apresentaram resultados positivos na PCR, enquanto 48 (22,2 por cento) apresentaram resultados positivos na antigenemia. A sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo para a PCR, considerando antigenemia como padrão foram 87,5 por cento, 76,8 por cento, 51,8 por cento e 95,5 por cento, respectivamente. CONCLUSÕES: Estes resultados demonstraram que a PCR tem alta sensibilidade e valor preditivo negativo. Consequentemente PCR é especialmente indicada para o diagnóstico inicial de infecção por HCMV. No caso da estratégia de terapia preventiva, a identificação de pacientes com alto risco para a doença por HCMV é fundamental e a PCR pode ser uma ferramenta útil.

Comparación de las técnicas de reacción de polimerasa en cadena en tiempo real y antigenemia para la detección de citomegalovirus en sangre de niños sometidos a trasplantes / Comparison of real-time polymerase chain reaction and antigenemia assay to detect cytomegalovirus in pediatric transplants

Background: Cytomegalovirus (CMV) infections are an important cause of morbidity and mortality in transplant recipient. To date, the antigenemia assay is the most used technique for diagnostic and management of CM V infections. However, quantification of CMV viral load by real time polymerase chain reaction (RT-PCR) has becoming the method of choice to detect CMV in a rapid, sensitive and specific manner. Objective: To compare antigenemia and RT-PCR assays in the detection of CMV in blood sample from solid organ and bone marrow transplant (BMT) in children attended at the Dr. Luis Calvo Mackenna Hospital. Methods: In a prospective study, we detect the presence of CMV in blood sample by RT-PCR and antigenemia assays. Results: We analyzed 219 blood samples from 68 children subjected to kidney, liver and BMT. Out of 219 samples analyzed, 147 were negative and 33 were positive for CMV by both techniques. Thirty-seven samples were positive only by RT-PCR and 2 by antigenemia. Considering the antigenemia as a reference, RT-PCR shows 94 percent, 80 percent, 34 percent and 99 percent sensitivity, specificity, positive and negative predictive values, respectively. The kappa coefficient between both techniques was 0.528. Conclusion: Quantitative determination of CMV viral load by RT-PCR is a sensitive technique with excellent negative predictive valué compared to antigenemia. Our results support the use of RT-PCR as a technique that might facilítate the diagnostic and treatment of active CMV infection in pediatric transplants.

Antecedentes: Las infecciones por citomegalovirus (CMV) corresponden a una importante causa de morbilidad y mortalidad en pacientes sometidos a trasplantes. Hasta la fecha, la detección de CMV en células infectadas en sangre periférica mediante la técnica de inmunofluorescencia (antigenemia) es la más utilizada para el diagnóstico y monitorización de la infección por este agente. Sin embargo, en el último tiempo la cuantificación de la carga de ácido nucleico (ADN) de CMV en sangre mediante la técnica de reacción de polimerasa en cadena en tiempo real (RPC-TR) ha permitido la detección de CMV de forma más rápida, sensible y específica. Objetivos: Comparar las técnicas de antigenemia y RPC-TR para la detección de CMV en sangre en niños sometidos a trasplante de órganos sólidos y trasplante de precursores hematopoyéticos (TPH) en el Hospital Dr. Luis Calvo Mackenna. Metodología: En un estudio prospectivo de seguimiento preventivo de reactivación se detectó la presencia de CMV en muestras de sangre utilizando las técnicas de RPC-TR y antigenemia. Resultados: Se analizaron 219 muestras de sangre, correspondiente a 68 niños sometidos a trasplante de hígado, riñon y TPH. De las muestras analizadas, 147 fueron negativas y 33 positivas para CMV utilizando ambas técnicas. Treinta y siete muestras resultaron ser positivas sólo por RPC-TR y dos sólo por antigenemia. Tomando en cuenta la antigenemia como referencia, la RPC-TR mostró una sensibilidad, especificidad, valor predictor positivo y negativo de 94 por ciento, 80 por ciento, 34 por ciento y 99 por ciento, respectivamente. El índice de concordancia entre ambas técnicas tuvo un valor de kappa = 0,528. Conclusión: La determinación cuantitativa de ADN de CMV por RPC-TR es una técnica sensible, con un gran valor predictor negativo comparada con la antigenemia. Los resultados obtenidos en este trabajo apoyan el uso de RPC-TR para el diagnóstico y tratamiento oportuno de las infecciones activas por CMV en niños sometidos a trasplantes.

Elevada seroprevalencia de citomegalovirus, virus herpes simplex tipo 1 y virus Epstein Barr en adultos con virus de la inmunodeficiencia humana / High seroprevalence of cytomegalovirus, herpes simplex type 1 virus and Epstein Barr virus infection among human immunodefciency virus-infected adults

Background: Cytomegalovirus (CMV), herpes simplex type 1 (HSV-1) and Epstein Barr virus (EBV) are latent persistent infections. Their reactivation may cause illnesses and death in human immunodefciency virus-infected (HIV) people. World wide seroprevalence of these viruses is over 50 percent. In Chile, information is not available. Aim: To determine the seroprevalence of CMV, HSV-1 and EBV in Chilean HIV-infected adults. Patients and Methods: A total of 400 HIV- infected adults aged 17 to 67 years (340 males) were studied during 2005 and 2006. CMV, HSV-1 and EBV serum antibodies were measured by enzyme-linked immunoabsorbent assay. Results: The mean lapse from the diagnosis of HIV and serum testing was 67 months and 69.5 percent patients received antiretroviral therapy. Sixty seven percent of the sample were men who had sex with men (MSM). The seroprevalence for CMV, HSV-1 and EBV were 98.5, 92.2 and 99.7 percent, respectively. No patient had negative antibodies for all three viruses. Male patients that were negative for HSV-1 had a lower frequency of MSM than the rest of males (26 percent vs 62 percent, p < 0.01). Conclusions: There is a high prevalence of positive antibodies against CMV, HSV-1 and EBV in Chilean adults infected with HIV. Specifc diagnostic tests and antiviral therapy should be available for these patients.

Neonatal cytomegalovirus infection: diagnostic modalities available for early disease detection.

CMV is a ubiquitous virus. In India, there is high seroendemicity with almost 99% adults showing IgG antibodies. Infection or re-activation becomes important in immunocompromised host (Transplant recipients, Cancer therapy patients and patients with HIV/AIDS). Neonates form a distinctive high risk population for congenital CMV infection and suffer disastrous sequlae of the same. Neonatal infections may be congenital in nature or may be acquired after birth during first month of life via infected breast milk or due to exposure to high risk blood products. The risk for transmission of the virus to the fetus is higher in primary infected mothers than in mothers with reactivated disease. Primary CMV infections are reported in 1-4% of seronegative women during pregnancy and the risk for viral transmission to fetus is 30-40%. Reactivation of a CMV infection during pregnancy is reported in 10-30% of seropositive women and the risk of transmitting the virus is about 1-3%. The adverse outcome of congenital neonatal CMV infection includes- microcephaly (70%), intellectual impairment (60%), sensineural hearing loss (35%), choriorenitis (22%), hepatosplenomegaly (70%), jaundice (68%), thrombocytopenia (65%), low birth weight (65%), pneumonitis (2-5%) and congenital heart disease (<5%). About 5-10% of congenitally infected asymptomatic infants will have neurological problems later in life the most common of which is unilateral or bilateral sensory neural hearing loss. All immunocompromised hosts, including pre-term neonates, mount weak antibody responses (IgM), making serological detection of CMV infection in them, fallacious. Thus, it is imperative to use antigen detection methods such as quantitative PCR or PP65 Antigenaemia assays to detect CMV infection in immunocompromised host. Sakhuja et al and Minz et al have demonstrated that PP65 Antigenaemia assay is very good for diagnosing CMV disease in renal transplant recipients. The present review tends to highlight the role of newer diagnostic modalities in early CMV infection detection in neonatal population.

[Significance of CMV-seropositivity in the alterations of CD4[+] T- cell subsets and expression of their phenotyping markers in B-cell chronic lymphocytic leukemia]

B-cell chronic lymphocytic leukemia [B-CLL] is a B-cell malignancy which has been associated with a variety of abnormalities in non-malignant T cells. Viral antigens are able to produce profound alterations in T-cell and cytomegalovirus [CMV] has been involved in T-cell abnormalities in healthy elderly individuals. Therefore, the relationship between these changes and CMV was studied in CLL patients. This was a cross sectional study and included 79 B-CLL patients [41 CMV seropositive and 38 CMV seronegative]. The cell counting was done by Coulter cell counter. The T-cell subgroups and cell phenotype were studied by monoclonal antibodies and flow cytometry. The secretion of cytokine was detected by intracellular cytokine staining post stimulation and short time culture. CD8[+] and CD4[+]CD8[dim] T cell subgroups were significantly more in CMV[+] patients than CMV negatives [P<0.01]. IFN-gamma producing T cells were significantly more in CMV [+] patients, whereas IL-2 producing T cells were more in CMV[-] patients [P<0.05 and P<0.01, respectively]. A prominent decrease was seen in the expression of CD27, CD28, CD45RA and CCR7 in CMV[+] patients, whereas CD45RO and CD57 showed significant rise [P<0.05 and P<0.001, respectively]. CMV seropositivity causes broad alterations in T-cells and expression of terminally differentiated phenotype in B-CLL patients. Therefore, such profile in B-CLL is highly related to CMV seropositivity

Cytomegalovirus a common cause of intrauterine infection: a case-control study

Congenital cytomegalovirus [CM.V] infection affects nearly 1% of live births in the United States. Ten percent of these infants have symptoms at birth and another 10 to 15% develop hearing loss or developmental problems. The aim of this study was to compare CMV infection [IgM and IgG] rate in infants suspected for intrauterine infection with the control group. A case-control study was performed in the Pediatrics Department of Hazrat Rasool Akram Hospital in Tehran. The study population included 74 suspected cases of intrauterine infection [mean age, 4.7 +/- 3.7 months] and 65 normal healthy controls [mean age, 5.3 +/- 3.1 months]. We compared serum CMV antibodies [IgM, IgG] with ELISA kits. Acute and previous immunity to CMV [IgM and IgG] was found in 41.9% [31/74] and 74% [54/74] of cases, respectively. These figures were 6.2% [4/65] and 95.4% [62/65] in controls, respectively. Acute infection [CMV-IgM.] was more common among cases [p<0.0001], but previous immunity [CMV-IgG] was more prevalent among controls [p<0.00l]. We concluded that CMV is the most common cause of intrauterine infection in infants aged less than 6 months as compared to the healthy ones. We prefer, at least in our country, to consider seropositive [CMV-lgM] infants suspected of intrauterine infection [less than 6 months] as congenital form. To arrest the natural progression of congenital CMV, we recommend prolonged course of oral analogues of ganciclovir for children with symptomatic congenital CMV

Seroprevalence of rubella and cytomegalovirus in nursing students

To detect the prevalence of rubella and cytomegalovirus antibodies in the nursing students. A total of 89 volunteer students in the age range of 18-20 years participated in the study. IgM and IgG antibodies were measured using the Enzyme Linked Fluorescent Assay VIDAS system kit and apparatus. In CMV serology, while anti-CMV IgG was positive in 85.4% and anti-CMV IgM was positive in 9.0% of the patients, the common positivity of anti-CMV IgG and anti-CMV IgM antibodies was determined as 2.2%. In the rubella serology, while rubella IgG positivity was 83.1%, rubella IgM positivity was not detected. It was found that higher rate of the students had experienced rubella and CMV in one period of their life. This is highly important for both their health and the health of the society they provide their services to

Infección y enfermedad por citomegalovirus en niños sometidos a trasplante de órgano sólido: experiencia en un centro de referencia chileno / Cytomegalovirus infection and disease in pediatric solid organ transplarntation: experience in a Chilean multiorganic transplantation center

Cytomegalovirus (CMV) infection and disease in transplant (Tx) recipients may severely complícate the patients outcome. Aim: To determine the incidence, clinical characteristics and risk factors for CMV infection and disease in liver and kidney transplant recipients in a tertiary care children's hospital. Method: A clinical and laboratory evaluation was prospectively performed in 44 and 20 children receiving a renal and liver Tx respectively in the Hospital Luis Calvo Mackenna between 2004 and 2006. Results: At the time of the organ Tx 20.3 percent (13/64) children were seronegative for CMV. Thirty six per cent (23/64) patients were infected with CMV, of whom 32 percent (14/44) received kidney Tx and 9/20 (45 percent) received liver Tx. CMV disease occurred in 52 percent (12/23) of infected patients. CMV disease was characterized by fever (100 percent), anemia (50 percent), leucopenia (16.6 percent) and specific organ involvement (renal graft 60 percent liver graft 57.1 percent, lung 25 percent, intestine 16.6 percent). Variables significantly associated with infection were a CMV seronegative status (p = 0.035) and lower age 5.5 + 3.7 years oíd vs 8.3 + 4.4 years oíd (p = 0.01). Conclusions: Incidence of CMV infection was high in children receiving a solid organ transplant in our institution and near half of infected children developed CMV-associated disease.

La infección y enfermedad por citomegalovirus (CMV) en pacientes sometidos a trasplantes (Tx) es una complicación que condiciona la evolución del injerto y la sobrevida del paciente. Objetivos: Determinar la incidencia de infección y enfermedad por CMV durante los primeros seis meses de efectuados Tx hepático y renal. Caracterizar la enfermedad, e identificar factores de riesgo asociados a infección. Metodología: Análisis prospectivo en 64 pacientes pediátricos sometidos a Tx renal (n: 44) o hepático (n: 20) en el Hospital Luis Calvo Mackenna entre 2004 y 2006. Resultados: Al trasplante, 23,1 por ciento (13/64) eran receptores IgG CMV (-). Cumplieron criterio de infección 36 por cientoo (23/64) de los pacientes, con Tx renal 32 por ciento (14/44) y con Tx hepático 45 por ciento (9/20). Desarrolló enfermedad el 52 por ciento) (12/23) la que se caracterizó porfiebre (100 por cientoo), anemia (50 por cientoo), leucopenia (16,6 por cientoo), disfunción del órgano trasplantado 60 por cientoo en Tx renal, hepático 57, l por cientoo, compromiso pulmonar en 25 por cientoo e intestinal en 16,6 por cientoo del total de pacientes. Variables asociadas a infección fueron: ser receptor IgG CMV (-)pre-Tx (p=0,035) y una menor edad del paciente 5,5 +3,7 vs 8,3 + 4,4 (p= 0,01). Conclusiones: Hay una elevada tasa de infección por CMV en la población de pacientes con Tx renal y hepática en nuestro medio, la mitad de ellos desarrolló enfermedad amenazando la función del injerto.

Impairment of cytomegalovirus-specific cellular immune response as a risk factor for cytomegalovirus disease in transplant recipients: [review]

Human cytomegalovirus (CMV) infection is common in most people but nearly asymptomatic in immunocompetent individuals. After primary infection the virus persists throughout life in a latent form in a variety of tissues, particularly in precursor cells of the monocytic lineage. CMV reinfection and occurrence of disease are associated with immunosuppressive conditions. Solid organ and bone marrow transplant patients are at high risk for CMV disease as they undergo immunosuppression. Antiviral treatment is effective in controlling viremia, but 10-15 percent of infected patients can experience CMV disease by the time the drug is withdrawn. In addition, long-term antiviral treatment leads to bone marrow ablation and renal toxicity. Furthermore, control of chronic CMV infection in transplant recipients appears to be dependent on the proper recovery of cellular immunity. Recent advances in the characterization of T-cell functions and identification of distinct functional signatures of T-cell viral responses have opened new perspectives for monitoring transplant individuals at risk of developing CMV disease.

Impact of cytomegalovirus and grafts versus host disease on the dynamics of CD57+CD28-CD8+ T cells after bone marrow transplant

OBJECTIVES: The present study aimed to evaluate the dynamics of CD28 and CD57 expression in CD8+ T lymphocytes during cytomegalovirus viremia in bone marrow transplant recipients. METHODS: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients. To evaluate the expression of CD57 and CD28 on CD8+ T lymphocytes, flow cytometry analysis was performed on blood samples for four months after bone marrow transplant, together with cytomegalovirus antigenemia assays. RESULTS: Compared to cytomegalovirus-seronegative healthy subjects, seropositive healthy subjects demonstrated a higher percentage of CD57+ and a lower percentage of CD28+ cells (p<0.05). A linear regression model demonstrated a continuous decrease in CD28+ expression and a continuous increase in CD57+ expression after bone marrow transplant. The occurrence of cytomegalovirus antigenemia was associated with a steep drop in the percentage of CD28+ cells (5.94 percent, p<0.01) and an increase in CD57+ lymphocytes (5.60 percent, p<0.01). This cytomegalovirus-dependent effect was for the most part concentrated in the allogeneic bone marrow transplant patients. The development of acute graft versus host disease, which occurred at an earlier time than antigenemia (day 26 vs. day 56 post- bone marrow transplant), also had an impact on the CD57+ subset, triggering an increase of 4.9 percent in CD57+ lymphocytes (p<0.05). CONCLUSION: We found continuous relative changes in the CD28+ and CD57+ subsets during the first 120 days post- bone marrow transplant, as part of immune system reconstitution and maturation. A clear correlation was observed between the expansion of the CD57+CD28-CD8+ T lymphocyte subpopulation and the occurrence of graft versus host disease and cytomegalovirus viremia.

Despistaje de infección por citomegalovirus en niños VIH positivos mediante PCR: relación con serología y evolución clínica / PCR screening for cytomegalovirus infection in HIV-positive children: relationship between serology and clinical evolution

En pacientes VIH positivos es fundamental diagnósticar infección por CMV. La relación entre serología, detección viral y evolución clínica no está plenamente establecida. Detectar la presencia de CMV por PCR en sangre periférica en pacientes pediátricos, sin síntomas de infección, VIH positivos; relacionar estos resultados con la serología y la evolución clínica durante un año de seguimiento. Criterios de inclusión: Niños menores de 12 años, ambos sexos, infección diagnosticada por VIH, recibiendo terapia antirretroviral altamente efectiva (TARAE), consentimiento informado por escrito, firmado. La serología anti CMV se realizó mediante el método ELISA, la semicuantificación de CMV en sangre periférica, mediante PCR, y el inmunofenotipaje por citometría de flujo. Aquellos niños con carga viral inicial detectable para CMV fueron evaluados un año después (valoración cualitativa y oftalmológica). Correlación de Pearson, t Student. Se estudiaron 23 niños, 17 menores de 6 años; 21 de ellos (82.6 por ciento): lgG CMV +. Dos pacientes (8.7 por ciento): lgM CMV+ y promedio de carga viral: 11920 VID, dos IgM-IgG+, promedio de carga de 23129 VID; el resto negativos; todos con linfocitos CD4+ por encima del 25 por ciento. 50 por ciento de los niños con carga viral negativa para CMV, con contajes de CD4+ inferiores al 25 por ciento. El análisis de correlación de Pearson no mostró correlación entre la carga viral del VIH y los valores de VID para CMV (R²=0.13). Linfocitos CD8+: 32,3 ± 6,8 por ciento en los pacientes con carga para CMV, estadísticamente inferior al promedio del grupo sin cargas virales CMV: 49,1 ± 8,8. (t Student= 3,508; g.l: 17. P<0,003). Ningún niño presentó evidencia de enfermedad órgano específica (EOE), incluyendo retinitis. Independientemente de la presencia o no de IgM positiva para CMV, 4 pacientes tuvieron carga viral detectable. No hay correlación entre las cargas virales de ambos virus. Ningún niño con carga viral detectable para CMV...

In HIV-positive patients the diagnosis of CMV infection is essential. The relationship between serology, viral detection and clinical evolution has not been fully established. To detect the presence of CMV in peripheral blood by PCR testing in HIV positive pediatric patients with no infection symptoms, and to relate the results with serology and clinical evolution during a year follow up. Inclusion criteria: Children under twelve years of age, both genders, with a diagnosis of HIV infection, and receiving HAART therapy, written consent signed by parents. Anti CMV serology was performed by ELISA, semi-quantification of CMV in peripheral blood by PCR and immunophenotyping by flow-cytometry. Children with detectable initial viral load for CMV were submitted to aqualitative and ophtalmologic assessment one year later. Statistics: Pearson’s Correlation, Student’s t. 23 children, both genders, 17 under 6 years of age; 21 (82.6%): IgG CMV+. Two patients (8.7%): IgM CMV+ and viral load. 11920 IDV, two with IgM- IgG+, viral load average: 23129 IDV. The rest of the children were negative, all with lymphocytes CD4+ above 25%. 50% of the children had a negative viral load for CMV with CD4+ counts under 25%. There was no correlation between the HIV viral load and IDV values for CMV (r2=0.13). Lymphocytes CD8+32.3+ 6.8% in patients with viral load for CMV.This is statistically lower than the average for the group without viral loads CMV: 49.1 + 8.8 (Student’s t= 3.508; g.l: 17. p<0.003). No child showed evidence of specific organ disease (SOD), including retinitis. Regardless of serology for IgM, 4 patients had detectable viral loads. There was no correlation between the viral loads of the two viruses. No child with detectable viral load for CMV developed a specific organ disease, probably due to a highly efficient antiretroviral treatment. Viral load quantification for CMV in HIV + patients is recommended, regardless of specific IgM result.

The incidence of cytomegalovirus infection in lung transplant recipients under universal prophylaxis with intravenous ganciclovir

The best strategy for control of cytomegalovirus (CMV) infection in lung transplant patients is still not determined. The aim of this study was to document the incidence of CMV infection in a cohort of lung transplant recipients under universal prophylaxis with intravenous ganciclovir. All patients received immunosuppressive regimens consisting of cyclosporine, azathioprine, and prednisone. Regardless of CMV serostatus, intravenous ganciclovir was prescribed for every patient in the first 3 months post-transplantation. CMV infection was defined as the detection of CMV pp65 in leukocytes. Eighty-two lung transplant patients were included over a 5-year period. The incidence of CMV infection in the first year post-transplantation was 68.3 percent, occurring after a median length of 114 days (range, 26-343 days). This study revealed a high incidence of CMV infection in the first year following lung transplantation despite prolonged universal ganciclovir prophylaxis.

Autopsy-proven causes of death in lungs of patients immunocompromised by secondary interstitial pneumonia

PURPOSE: To present the more frequent associations found in autopsies of immunocompromised patients who developed secondary interstitial pneumonia as well as the risk of death (odds ratio) in having specific secondary interstitial pneumonia according to the cause of immunocompromise. METHOD: From January 1994 to March 2004, 17,000 autopsies were performed at Hospital das Clínicas, São Paulo University Medical School. After examining the pathology report review, we selected 558 of these autopsies (3.28 percent) from patients aged 15 years or more with primary underlying diseases who developed radiologically diffuse infiltrates of the lung during their hospital course and died after secondary interstitial pneumonia (bronchopneumonia, lobar pneumonia, interstitial pneumonia, diffuse alveolar damage, pulmonary recurrence of underlying disease, drug-induced lung disease, cardiogenic pulmonary edema, or pulmonary embolism). Histology slides were reviewed by experienced pathologists to confirm or not the presence of secondary interstitial pneumonia. Statistical analysis included the Fisher exact test to verify any association between histopathology and the cause of immunocompromise; a logistic regression was used to predict the risk of death for specific histological findings for each of the independent variables in the model. RESULTS: Secondary interstitial pneumonia was histologically represented by diffuse interstitial pneumonitis ranging from mild nonspecific findings (n = 213) to a pattern of diffuse alveolar damage (n = 273). The principal causes of immunocompromise in patients with diffuse alveolar damage were sepsis (136 cases), neoplasia (113 cases), diabetes mellitus (37 cases), and transplantation (48 cases). A high risk of death by pulmonary edema was found for patients with carcinoma of colon. Similarly, in patients with lung cancer or cachexia, A high risk of death by bronchopneumonia (OR = 3.6; OR = 2.6, respectively) was found. Pulmonary...

OBJETIVO: Apresentar as associações mais freqüentes encontradas em autópsias de pacientes imunossuprimidos que desenvolveram pneumonia intersticial secundária bem como o risco de óbito (Odds Ratio) de desenvolver PIS associada à causa da imunossupressão. MÉTODO: De janeiro de 1994 a março de 2004, 17000 autópsias foram realizadas no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. A partir da revisão dos laudos patológicos foram selecionados 558 destas autópsias (3,28 por cento) de pacientes com 15 anos de idade ou mais, com alguma doença de base que desenvolveu um infiltrado pulmonar radiologicamente difuso durante o curso da hospitalização e que depois foi para óbito com pneumonia intersticial secundária (broncopneumonia, pneumonia lobar, pneumonia intersticial, dano alveolar difuso, doença pulmonar recorrente, doença pulmonar induzida por drogas, edema pulmonar cardiogênico e embolismo pulmonar). As lâminas histológicas foram revisadas por patologistas experientes para confirmar ou não a presença de pneumonia intersticial secundária. A análise estatística incluiu o "Teste exato de Fisher" para verificar associação entre a histolopatologia e causa de imunocomprometimento; e regressão logística para predizer o risco de óbito por achados histológicos específicos para cada variável independente do modelo. RESULTADOS: A pneumonia intersticial secundária foi representada histológicamente por pneumonite intersticial difusa variando de características não especificas leves (n=213) ao padrão histológico de dano alveolar difuso (n=273). A principal causa de imunossupressão nos pacientes com dano alveolar difuso foi sepse (136 casos), neoplasia (113 casos), diabetes melito (37 casos) e transplantados (37 casos). O maior risco de morte por edema pulmonar foi encontrado nos pacientes com carcinoma de cólon. Da mesma forma, nos pacientes com câncer pulmonar ou cachexia ocorreu um alto risco de morte (OR=3.6; OR=2.6, respectivamente)...

Infeccion por citomegalovirus con compromiso hepatico en adultos inmunocompetentes / Cytomegalovirus infection with hepatic involvement in immunocompetent adults

Evaluamos retrospectivamente a 73 adultos inmunocompetentes que consultaron entre marzo de 1999 y marzo de 2004 a un centro infectológico ambulatorio por fiebre y astenia, con elevación discreta de las transaminasas y serología compatible con infección reciente por citomegalovirus (CMV). Excluimos a pacientes con antecedentes de transfusiones, adicciones e inmunodeficiencias, así como aquellos con alteraciones hepáticas preexistentes o con serología compatible con infección aguda por hepatitis A, B, C (VHA, VHB, VHC) o virus Epstein Barr (VEB). El diagnóstico de infección reciente por citomegalovirus se efectuó mediante la detección de IgM específica (ELISA de captura), seroconversión o aumento cuádruple del título de IgG específica, en presencia de un cuadro clínico compatible. Los síntomas más frecuentes fueron: fiebre (85%) y astenia (83%), cefalea (25%), esplenomegalia (20%), adenomegalia (22%), faringitis (25%), mialgia (25%) y hepatomegalia (19 %). Se encontró elevación discreta de transaminasas y linfomonocitosis en todos los pacientes (73/73). La elevación promedio de GPT fue de 6 veces y la de GOT fue de 3.5 veces su valor límite. Las características clínicas que diferencian la infección por CMV de la infección por VEB son la menor frecuencia de poliadenopatías y faringitis en la primera. El diagnóstico diferencial de la infección por CMV con compromise hepático con las hepatitis A y B agudas se basa en la ausencia de ictericia, la menor elevación de las transaminasas, la linfomonocitosis intensa y la presencia de IgM específica que caracterizan a la infección por CMV. En conclusión, ante un paciente joven, previamente sano, con fiebre, astenia intensa, linfomonocitosis y elevación discreta de transaminasas, es importante investigar infección por citomegalovirus.

We retrospectivelyevaluated 73 immunocompetent adult patients assisted at our Infectious Diseases Clinic betweenMarch 1999 and March 2004 who presented fever and asthenia, mild to moderate increase of transaminasesand serological findings compatible with recent cytomegalovirus infection. We excluded patients with a history oftransfusions, drug abuse, immunodeficiencies, preexistent hepatic impairment or serological findings compatible with acute hepatitis A, B and C (HAV, HBV, HCV) and Epstein Barr virus (EBV). The laboratory diagnosis ofrecent cytomegalovirus infection was made by especific IgM detection (ELISA) or a significant increase of specific IgG. The most frequent symptoms were fever (85%) and asthenia (83%), followed by cephalea (25%), splenomegaly (20%), adenomegalies (22%), pharyngitis (25%), myalgias (25%) and hepatomegaly (19%). All the patients showed moderate increase of transaminases and lymphomonocytosis (73/73). In average, ALT wasincreased by 6 fold and AST by 3.5 fold. The clinical characteristics that differentiate CMV infection from Epstein-Barr infection are the lesser frequency of adenomegalies and pharyngitis in the former. The differential diagnosisof CMV infection with hepatic involvement from acute hepatitis A and B, is based on the absence of jaundice,the lower elevation of transaminases, the intense lymphomonocytosis and the presence of specific IgMagainst CMV that are characteristic of CMV infection. In conclusion, in previously healthy young adults with fever, intense asthenia, lymphomonocytosis and moderate increase in transaminases levels, cytomegalovirus infectionshould be investigated.