RESUMEN
Pre-emptive antiviral treatment efficiently prevents occurrence of cytomegalovirus (CMV) disease in allogeneic stem cell transplant recipients. However, successive treatment courses can be necessary. The current study was aimed at determining factors that could influence the response to antiviral treatment, in particular the donor CMV serostatus. A total of 147 consecutive CMV-seropositive recipients (R+) were included and prospectively monitored for 6 months after transplantation. Reactivation of CMV occurred in 111 patients, 61 of 78 with a CMV-positive donor (D+) and in 50 of 69 with a CMV-negative donor (D-) (p 0.45). Baseline viral loads and initial viral doubling times did not differ between D+/R+ and D-/R+. Fifteen D+/R+ and four D-/R+ had self-resolving CMV infections. A total of 92 patients received antiviral treatment and 81 (88%) had a significant decrease in CMV load under therapy. Repeated CMV episodes were observed in 67% of those and were significantly more frequent in D-/R+ than in D+/R+ (p <0001). Half-life of CMV under treatment was significantly longer in D-/R+ than in D+/R+. Treatment failure observed in eight recipients was associated with low leucocyte count at reactivation onset, and was significantly more frequent in D-/R+ (six patients) than in D+/R+ (two patients) (p <0.0001). CMV strains resistant to antivirals were found in two D-/R+. Donor CMV serostatus influenced neither CMV reactivation occurrence nor the kinetics of CMV DNA load in the early phase of CMV replication but had a significant impact on response to antiviral therapy. Virological drug-resistance remained rare.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/virología , Citomegalovirus/fisiología , Trasplante de Células Madre Hematopoyéticas , Donantes de Tejidos , Receptores de Trasplantes , Activación Viral , Adolescente , Adulto , Anciano , Niño , ADN Viral , Farmacorresistencia Viral , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
PURPOSE: Human herpesvirus 6 (HHV6) is an emerging cause of interstitial pneumonia in immunocompromised hosts. However, the clinical significance of a positive PCR test for HHV6 in respiratory samples from patients with hematological malignancies remains unclear. METHODS: We retrospectively studied the features and outcomes of 29 critically ill hematology patients with acute respiratory failure and lung pulmonary infiltrates visible on a chest radiograph, who tested positive for a qualitative PCR for HHV6 in bronchoalveolar lavage fluid. RESULTS: Of the 29 patients, 18 (62%) were stem cell transplant recipients and 11 (38%) had received chemotherapy. All patients had a fever. Clinical manifestations consistent with extra-pulmonary HHV6 disease were noted in 17 (59%) patients. One or more co-pathogens were found in 25 (86%) patients. The four remaining patients diagnosed with HHV6 pneumonia and subsequently recovered with foscarnet therapy. Antiviral therapy was also given to seven patients with co-infections, of whom two ultimately died. CONCLUSIONS: In most cases, HHV6 recovered from BAL fluid is a co-pathogen whose clinical relevance remains undetermined. However, in some cases, HHV6 is the only pathogen, along with disseminated systemic viral disease, and the patient is likely to benefit from foscarnet therapy.
Asunto(s)
Líquido del Lavado Bronquioalveolar/virología , Herpesvirus Humano 6/aislamiento & purificación , Herpesvirus Humano 6/patogenicidad , Síndrome de Dificultad Respiratoria/virología , Adulto , Trasplante de Médula Ósea/patología , Broncoscopía/métodos , Femenino , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/virología , Hematología , Herpesvirus Humano 6/crecimiento & desarrollo , Humanos , Huésped Inmunocomprometido , Unidades de Cuidados Intensivos , Leucocitos Mononucleares/virología , Masculino , Persona de Mediana Edad , Neumonía/virología , Reacción en Cadena de la Polimerasa , Síndrome de Dificultad Respiratoria/complicaciones , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Human herpesviruses 6 (HHV-6), 7 (HHV-7) and 8 (HHV-8) are lymphotropic herpesviruses that may cause opportunistic diseases in immunosuppressed patients such as transplant or AIDS patients. The new commercial CMV HHV-6, 7, 8 R-gene kit (Argene, Varilhes, France) for the simultaneous quantitation of HHV-6 and qualitative detection of HHV-7 and HHV-8 was evaluated using whole blood samples (respectively, n=175, 100 and 161) and using different extraction and real-time PCR platforms in two Centers A and B. In comparison with HHV-6 in-house real-time PCR the commercial kit showed agreements of 96% (n=75) and 85% (n=100) in A and B, respectively, with significant Spearman's correlation between both techniques (in A: r=0.97 [p<0.001]; in B: r=0.70 [p<0.001]). The Bland-Altman test results and prospective monitoring of patients confirmed the accuracy of these HHV-6 real-time PCR techniques. The agreement between the in-house HHV-7 PCR and commercial kit was of 86% (n=100). In comparison with in-house HHV-8 real-time PCRs, the commercial kit showed agreements of 100% (n=61) and 93.7% (n=96) in A and B, respectively. These results demonstrate that the new commercial CMV HHV-6, 7, 8 R-gene kit was an efficient and reliable tool for the diagnosis of herpesvirus 6, 7, 8 infections.
Asunto(s)
Sangre/virología , Herpesvirus Humano 6/aislamiento & purificación , Herpesvirus Humano 7/aislamiento & purificación , Herpesvirus Humano 8/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Infecciones por Herpesviridae/diagnóstico , Herpesvirus Humano 6/genética , Herpesvirus Humano 7/genética , Herpesvirus Humano 8/genética , Humanos , Infecciones por Roseolovirus/diagnóstico , Sensibilidad y EspecificidadAsunto(s)
Infecciones por Adenovirus Humanos/tratamiento farmacológico , Antivirales/uso terapéutico , Citosina/análogos & derivados , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfopenia/complicaciones , Organofosfonatos/uso terapéutico , Sobrevivientes , Infecciones por Adenovirus Humanos/complicaciones , Infecciones por Adenovirus Humanos/fisiopatología , Adulto , Cidofovir , Citosina/uso terapéutico , Humanos , Linfopenia/etiología , Linfopenia/virología , Masculino , Factores de Tiempo , Trasplante HomólogoRESUMEN
Automated real-time PCR systems have become the most common method in the quantitation of viral load during cytomegalovirus (CMV) infection in immuno-compromised patients. In order to evaluate a new commercially available CMV real-time PCR assay (CMV R-gene, Argene, France), a pp65 antigenemia assay and four different "in-house" real-time PCR assays were compared to the CMV R-gene for the detection and the quantitation of CMV load in 506 specimens of whole blood from transplant patients in four French hospital laboratories. The CMV R-gene was more sensitive than the pp65 antigenemia: there were 18% antigenemia-negative versus CMV R-gene-positive samples. A significant correlation was found between DNA quantitation by CMV R-gene and the number of positive cells detected by the pp65 antigenemia test (Spearman's rank test, r=0.63, p<0.0001). A CMV DNA load equivalent to 50 pp65-positive cells/200000 polymorphonuclear leukocytes was 5.26log(10)copies/mL of whole blood. When the CMV R-gene kit was compared to the four other "in-house" real-time PCR assays, there were few discordant results (6.7% total for the four laboratories), all detected with a weak positive CMV DNA viral load. Spearman's coefficients showed a good (r=0.82 for laboratory 1, r=0.66 for laboratory 3) to excellent (r=0.99 for laboratory 2, r=0.94 for laboratory 4) correlation between CMV R-gene and the four real-time "in-house" PCR assays. However, the results of CMV DNA viral load generated by CMV R-gene test were constantly higher than those generated by three out of four "in-house" PCR assays. This mean variation in CMV DNA viral load measured by CMV R-gene and "in-house" PCRs was of 0.77log(10), 0.04log(10), 0.77log(10) and 0.97log(10), for laboratories 1, 2, 3 and 4, respectively. We concluded that there was variability between results of different real-time PCR assays for CMV DNA quantitation. This observation emphasized the need of a standardised commercial assay to allow an "inter-laboratory" comparison of results. Our study showed that CMV R-gene is an accurate, efficient, reliable and versatile tool for rapid diagnosis and monitoring of CMV disease in transplantation recipients.
Asunto(s)
Infecciones por Citomegalovirus/virología , Citomegalovirus/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Carga Viral/métodos , Francia , Humanos , Sensibilidad y EspecificidadRESUMEN
Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by Chlamydia trachomatis strains belonging to the L1, L2 or L3 genotype. An alert about an outbreak of LGV among MSM in the Netherlands was published in January 2004. The first cases of rectal LGV in France were retrospectively diagnosed in March 2004 and sentinel surveillance for LGV was implemented in April 2004. Most of the participating centres were located in the cities of Paris and Bordeaux. Only confirmed rectal LGV cases were included in the surveillance. Rectal specimens from men that were found to be positive for C trachomatis by PCR were sent to the National Reference Centre for Chlamydia infection for genotyping. Simple epidemiological data provided by clinicians and genotyping results were sent to the Institut de Veille Sanitaire (InVS) where data were anonymously recorded. A total of 328 C. trachomatis rectal strains isolated in men were genotyped by the end of December 2005. Of these, 244 (74%) were LGV strains belonging to the L2 genotype. No L1 or L3 C. trachomatis genotype was found. Diagnosis was made retrospectively for 46 cases. The median age of patients with LGV was 39 years. HIV status was known for 96 patients: 82/96 (85%) were HIV-infected. Most LGV cases were diagnosed in the Paris area (92%). Among the remaining 26% C. trachomatis strains, genotypes Da and G were the most frequent. As with syphilis in recent years, the emergence of LGV in Europe is mainly affecting HIV-infected MSM. The screening and treatment of STIs should be included in the clinical follow-up of all HIV-infected MSM.
Asunto(s)
Linfogranuloma Venéreo/epidemiología , Enfermedades del Recto/epidemiología , Vigilancia de Guardia , Adulto , Chlamydia trachomatis/genética , Chlamydia trachomatis/aislamiento & purificación , Francia/epidemiología , Genotipo , Homosexualidad Masculina , Humanos , Linfogranuloma Venéreo/genética , Masculino , Enfermedades del Recto/genética , Estudios Retrospectivos , Sexo InseguroRESUMEN
Some studies (mostly retrospective) have pointed to an increasing frequency (up to 60%) of herpes simplex virus type 1 (HSV-1) in genital herpes (GH), but they were biased towards severe or atypical cases. We wished to evaluate the frequency of HSV-1 in patients attending our clinic for both first and recurrent episodes of GH. All patients (men and women) with genital lesions compatible with GH were included in a prospective study between May 1999 and April 2002. For all patients a standardized questionnaire, clinical examination, MRC5 culture (Dade Behring), polymerase chain reaction (PCR)-herpes consensus (Argène Biosoft) in case of negative culture and type-specific herpes serology HSV-1 and HSV-2 (Elisa Eurobio) were obtained. Predictive factors associated with HSV-1 and HSV-2 GH were studied by uni- and multivariable analyses. In all, 255 patients had a positive culture (n = 216) or PCR (n = 39). A total of 248 patients had typable herpes (148 men and 100 women). Median age was 33 (27-43); 20% had anal herpes; 48% had clinically recurrent lesions; 21% were HIV +; 20% of men were homosexual; 77% practised oral sex. In all, 36 were HSV-1 (14.5%): more in women, 25/100 (25%), than in men, 11/148 (7.5%) (odds ratio [OR]: 4 [1.8-9.1], P = 0.008). HSV-1 accounted for 23% of cases of first clinical episodes (women: 31.5%; men: 14.7%) (P = 0.02) and 6% of clinically recurrent episodes (women: 15%; men: 1.2%) (OR: 3.8 [1.6-9.1], P = 0.0033). Serological study was done in 239: primary infection was disclosed in 33 (HSV-1: 61%), HSV-2 non-primary first episode in 22 and recurrence in 184 (HSV-1: 8%). In all, 37% of recurrent episodes presented as a first clinical episode. HSV-1 was linked in men with homosexuality (P<0.01) and anilingus (P<0.01), in women with younger age (P<0.01), more sexual intercourses (P<0.0001) and more oral sex (P<0.001). Although HSV-1 is frequent in first clinical (23%) and primary (61%) episodes of GH, recurrent GH remains mostly due to HSV-2 (94%).
Asunto(s)
Instituciones de Atención Ambulatoria , Anticuerpos Antivirales/sangre , Herpes Genital/epidemiología , Herpesvirus Humano 1/aislamiento & purificación , Herpesvirus Humano 2/aislamiento & purificación , Enfermedades de Transmisión Sexual/prevención & control , Adulto , Femenino , Herpes Genital/virología , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/inmunología , Herpesvirus Humano 2/genética , Herpesvirus Humano 2/inmunología , Humanos , Masculino , Paris , Reacción en Cadena de la Polimerasa , Prevalencia , Estudios ProspectivosRESUMEN
Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by Chlamydia trachomatis strains belonging to the L1, L2 or L3 genotype. An alert about an outbreak of LGV among MSM in the Netherlands was published in January 2004. The first cases of rectal LGV in France were retrospectively diagnosed in March 2004 and sentinel surveillance for LGV was implemented in April 2004. Most of the participating centres were located in the cities of Paris and Bordeaux. Only confirmed rectal LGV cases were included in the surveillance. Rectal specimens from men that were found to be positive for C trachomatis by PCR were sent to the National Reference Centre for Chlamydia infection for genotyping. Simple epidemiological data provided by clinicians and genotyping results were sent to the Institut de Veille Sanitaire (InVS) where data were anonymously recorded. A total of 328 C. trachomatis rectal strains isolated in men were genotyped by the end of December 2005. Of these, 244 (74%) were LGV strains belonging to the L2 genotype. No L1 or L3 C. trachomatis genotype was found. Diagnosis was made retrospectively for 46 cases. The median age of patients with LGV was 39 years. HIV status was known for 96 patients: 82/96 (85%) were HIV-infected. Most LGV cases were diagnosed in the Paris area (92%). Among the remaining 26% C. trachomatis strains, genotypes Da and G were the most frequent. As with syphilis in recent years, the emergence of LGV in Europe is mainly affecting HIV-infected MSM. The screening and treatment of STIs should be included in the clinical follow-up of all HIV-infected MSM.
RESUMEN
We recently reported an increased incidence of cirrhosis in hepatitis C virus (HCV)-infected stem cell transplant (SCT) recipients. Here, we describe our experience in the treatment of these patients, which has been, to date, poorly reported in the literature. Among 99 HCV-infected HCT recipients, 36 had HCV-related liver lesions on biopsy requiring therapy. Owing to HCV treatment contraindications, only 61% of patients (22/36) could be treated. In all, 12 patients received more than one course of anti-HCV treatment if they had HCV RNA still detectable after the first course of treatment and no treatment contraindications. Combined therapy (pegylated interferon (IFN): n=9, or standard IFN: n=9, in combination with ribavirin) led to sustained virological response in 4/18 (20%) patients as compared to 2/20 (10%) in patients who received IFN alone. Hematological toxicity was more frequent with combined therapy. While anemia responded to erythropoietin and/or dose modification, thrombocytopenia usually led to treatment interruption (n=3). This study thus highlights the efficacy of combined therapy and emphasizes the fact that the undue safety concerns are not a problem when treating this particular population.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Hepatitis C Crónica/epidemiología , Donadores Vivos , Adolescente , Adulto , Anemia/terapia , Niño , Femenino , Hepatitis C Crónica/transmisión , Prueba de Histocompatibilidad , Humanos , Incidencia , Leucemia/terapia , Pruebas de Función Hepática , Masculino , Trasplante HomólogoRESUMEN
We described a colorimetric method to determine the biochemical phenotype of wild-type and mutated cytomegalovirus (HCMV) DNA polymerases by measuring the incorporation of digoxigenin-labelled nucleotides into the growing DNA chain. Mutations V715M and E756K, which are known to confer foscarnet-resistance, were used as controls. Mutation N495K and a combination of changes K415R and S291P, both observed in foscarnet-resistant isolates, were studied. The mutations were introduced by site-directed mutagenesis into wild-type gene UL54 cloned in an expression vector and then polymerases were synthesised by using a commercially available coupled transcription-translation system. The polymerase activity was measured with and without foscarnet. The activity of polymerases containing the V715M or E756K mutations was inhibited by foscarnet at concentrations 70- and 30-fold higher than that of wild-type polymerase, respectively. Change N495K and combination of K415R and S291P, induced a five- and ten-fold decrease in susceptibility to foscarnet, respectively. The results of this non-radioactive assay were consistent with those obtained with the conventional radioactive assay. Therefore, this novel phenotypic method could be useful for the characterisation of mutations that confer HCMV resistance to foscarnet.
Asunto(s)
Antivirales/farmacología , Citomegalovirus/efectos de los fármacos , Citomegalovirus/enzimología , ADN Polimerasa Dirigida por ADN/metabolismo , Foscarnet/farmacología , Células Cultivadas , ADN Polimerasa Dirigida por ADN/efectos de los fármacos , Embrión de Mamíferos , Fibroblastos , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
We describe 6 patients who were coinfected with human immunodeficiency virus (HIV) type 1 and wild-type hepatitis B virus (HBV), in whom complete and sustained antiviral activity against wild-type HBV strains was attained during 96 weeks of combination therapy with lamivudine and tenofovir. The use of combination therapy with lamivudine and tenofovir for the treatment of HBV infection is very promising in the treatment of HIV/HBV coinfection.
Asunto(s)
Adenina/análogos & derivados , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Hepatitis B/tratamiento farmacológico , Lamivudine/uso terapéutico , Organofosfonatos/uso terapéutico , Adenina/uso terapéutico , Adulto , Quimioterapia Combinada , Femenino , Infecciones por VIH/complicaciones , Hepatitis B/complicaciones , Humanos , Masculino , Persona de Mediana Edad , TenofovirRESUMEN
Whether valaciclovir (VCV) prophylaxis could be responsible for ganciclovir (GCV)-resistance of Human cytomegalovirus (HCMV) in transplantation has never been documented. A multicentric retrospective pilot study was undertaken to detect GCV-resistance through mutations within the UL97 gene in renal transplant recipients who experienced active HCMV infection and received valacyclovir prophylaxis. Twenty-three patients who experienced HCMV antigenaemia or DNAemia during or at the end of prophylaxis were included. UL97 genotyping was carried out on peripheral blood samples, using a nested in-house PCR, which amplified the full-length UL97 gene. One patient has a resistance-related mutation (M460I); the major risk factor for emergence of resistance in this patient was the presence of early and persistent antigenaemia. GCV-resistance during VCV-prophylaxis was rare after renal transplantation. However, special attention must be paid to patients developing early active HCMV infection under prophylaxis.
Asunto(s)
Aciclovir/análogos & derivados , Antivirales/farmacología , Infecciones por Citomegalovirus/tratamiento farmacológico , Citomegalovirus/efectos de los fármacos , Ganciclovir/farmacología , Trasplante de Riñón/efectos adversos , Valina/análogos & derivados , Aciclovir/uso terapéutico , Sustitución de Aminoácidos , Antivirales/uso terapéutico , Quimioprevención , Citomegalovirus/genética , Infecciones por Citomegalovirus/virología , Farmacorresistencia Viral/genética , Femenino , Ganciclovir/uso terapéutico , Humanos , Persona de Mediana Edad , Fosfoproteínas/sangre , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Proyectos Piloto , Estudios Retrospectivos , Valaciclovir , Valina/uso terapéutico , Proteínas de la Matriz Viral/sangreRESUMEN
Herpes simplex virus (HSV) infections are very common in the general population and among immunocompromised patients. Acyclovir (ACV) is an effective treatment which is widely used. We deemed it essential to conduct a wide and coordinated survey of the emergence of ACV-resistant HSV strains. We have formed a network of 15 virology laboratories which have isolated and identified, between May 1999 and April 2002, HSV type 1 (HSV-1) and HSV-2 strains among hospitalized subjects. The sensitivity of each isolate to ACV was evaluated by a colorimetric test (C. Danve, F. Morfin, D. Thouvenot, and M. Aymard, J. Virol. Methods 105:207-217, 2002). During this study, 3900 isolated strains among 3357 patients were collected; 55% of the patients were immunocompetent. Only six immunocompetent patients excreted ACV-resistant HSV strains (0.32%), including one female patient not treated with ACV who was infected primary by an ACV-resistant strain. Among the 54 immunocompromised patients from whom ACV-resistant HSV strains were isolated (3.5%), the bone marrow transplantation patients showed the highest prevalence of resistance (10.9%), whereas among patients infected by human immunodeficiency virus, the prevalence was 4.2%. In 38% of the cases, the patients who excreted the ACV-resistant strains were treated with foscarnet (PFA), and 61% of them developed resistance to PFA. The collection of a large number of isolates enabled an evaluation of the prevalence of resistance of HSV strains to antiviral drugs to be made. This prevalence has remained stable over the last 10 years, as much among immunocompetent patients as among immunocompromised patients.
Asunto(s)
Aciclovir/farmacología , Antivirales/farmacología , Simplexvirus/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Animales , Trasplante de Médula Ósea , Chlorocebus aethiops , Farmacorresistencia Viral , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trasplante de Órganos , Células VeroRESUMEN
BACKGROUND: The hypothetical responsibility of sperm donation in cytomegalovirus (CMV) transmission to recipients and precautions to prevent this transmission are widely discussed. The aim of this French CECOS Federation study was to evaluate both the reality and the importance of the CMV risk due to donor sperm and the relevance of measures used to screen it. METHODS: We conducted a prospective multicentric study. CMV was detected by rapid and conventional cultures and by PCR in the frozen sperm of donors who met the normal criteria required of semen donors, irrespective of their CMV serological status. RESULTS: 635 samples from 231 donors (39.4% IgG(+)) were obtained and tested by culture; 551 samples from 197 donors were also tested by PCR. From those samples, 0.78% were culture(+), 1.57% culture(+) and/or PCR(+); 3.3% of seropositive donors and 0.72% of initially seronegative donors were culture(+), but in the latter seroconversion occurred during the quarantine period; of the 197 PCR-tested donors, 3.5% (6.2/1.7) were PCR(+), 3.3% (5.3/1.45) culture(+) and/or PCR(+). PCR(+) samples can be culture(-) and vice versa. The most strongly positive sample corresponded to an initially seronegative donor. CONCLUSION: The best strategy to prevent potential CMV risk is to test donors for CMV IgG and IgM antibody at the outset and after a 6 month period of quarantine and to reject initially IgM seropositive donors or donors who seroconvert during the quarantine period.
Asunto(s)
Criopreservación , Infecciones por Citomegalovirus/transmisión , Semen/virología , Donantes de Tejidos , Anticuerpos Antivirales/análisis , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/prevención & control , Femenino , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Masculino , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Cuarentena , Medición de Riesgo , Pruebas Serológicas/métodos , Factores de TiempoRESUMEN
Reported here is the case of a patient who spontaneously recovered from hemophagocytic syndrome associated with acute B19 infection and concomitant Epstein-Barr virus reactivation. The previously healthy 37-year-old-man was hospitalized after 10 days of high fever, arthralgia and arthritis and was determined to have hemophagocytic syndrome. Immunoglobulin (Ig) M antibodies to Epstein-Barr virus (EBV) capsid antigen, early antigen and parvovirus B19 (B19) were found. B19 DNA and low-level EBV DNA were detected in bone marrow, serum and peripheral blood mononuclear cells. The patient recovered spontaneously without any treatment. Two months later anti-B19 IgG antibodies were detected, while at 9-month follow-up, anti-B19 IgM antibodies were no longer detectable and B19 DNA had disappeared from serum. To the best of our knowledge, this is the first report of spontaneous resolution of hemophagocytic syndrome associated with acute B19 infection and concomitant EBV reactivation in an otherwise healthy adult.
Asunto(s)
Infecciones por Virus de Epstein-Barr/diagnóstico , Histiocitosis de Células no Langerhans/diagnóstico , Infecciones por Parvoviridae/diagnóstico , Parvovirus B19 Humano/aislamiento & purificación , Enfermedad Aguda , Adulto , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/inmunología , Estudios de Seguimiento , Histiocitosis de Células no Langerhans/complicaciones , Histiocitosis de Células no Langerhans/inmunología , Humanos , Inmunocompetencia , Masculino , Infecciones por Parvoviridae/complicaciones , Infecciones por Parvoviridae/inmunología , Remisión EspontáneaAsunto(s)
Aciclovir/análogos & derivados , Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/prevención & control , Terapia de Inmunosupresión/métodos , Trasplante de Riñón/inmunología , Valina/análogos & derivados , Valina/uso terapéutico , Antígenos Virales/sangre , Infecciones por Citomegalovirus/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Profármacos/uso terapéutico , ValaciclovirRESUMEN
To evaluate the long-term immune reconstitution after allogeneic haematopoietic stem cell transplantation (SCT), we prospectively screened standard immune parameters in a series of 105 patients, at a median time of 15 months after SCT. Analysing lymphoid phenotypes, in vitro immune functions and immunoglobulin levels, we found that, more than 1 year post SCT, cellular and humoral immunity was still altered in a significant number of patients. CD4+ T cells were < 200/microl in one third of patients, and the CD4/CD8 ratio was still reversed in 78% of patients. Almost all patients showed positive T-cell responses against mitogens, but antigen-specific proliferation assays identified 20% to 80% of non-responders. B-cell counts were reconstituted in 61% of the patients, but levels of total immunoglobulins were still low in 59%. In multivariate analyses, human leucocyte antigen (HLA) disparity between donor and recipient and chronic graft-versus-host disease were the leading causes affecting immune reconstitution. Interestingly, cytomegalovirus (CMV) infections were strongly associated with normal CD8+ T-cell counts. Studying the impact of impaired immune reconstitution on the rate of infections occurring in the 6 years following screening, we identified three parameters (low B-cell count, inverted CD4/CD8 ratio, and negative response to tetanus toxin) as significant risk factors for developing such late infections.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia/inmunología , Leucemia/terapia , Adolescente , Adulto , Azatioprina/uso terapéutico , Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Ciclosporina/uso terapéutico , Infecciones por Citomegalovirus/inmunología , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Glucocorticoides/uso terapéutico , Enfermedad Injerto contra Huésped/inmunología , Humanos , Inmunosupresores/uso terapéutico , Células Asesinas Naturales/inmunología , Activación de Linfocitos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Factores de Riesgo , Toxina Tetánica/administración & dosificación , Trasplante HomólogoRESUMEN
OBJECTIVE: To determine whether the humoral anti-chlamydia antibody response might be related to the ineffective bacterial elimination seen in patients with Chlamydia trachomatis reactive arthritis, particularly in men, who have a higher prevalence of the disease than women. METHODS: The number and specificity of the antibody responses to 27 different C trachomatis antigens were determined by western blots in serum samples from patients with C trachomatis urogenital infection, with and without reactive arthritis, with a special regard to the sex of the patients. RESULTS: Patients with reactive arthritis had antibodies to significantly fewer chlamydia antigens than those with urethritis only. Antibodies from men recognised significantly fewer antigens than antibodies from women. The IgA class antibodies were slightly more relevant than those of the IgG class for differentiation of patients with reactive arthritis from those with uncomplicated genitourinary infection. CONCLUSIONS: In patients with acute C trachomatis infection the development of reactive arthritis may be related, particularly in men, to a deficient humoral response, to antigens which perhaps play a part in the clearance of the bacteria. Men who cannot generate antibodies to a large number of antigens may be less able to contain the local infection, allowing a wide systemic dissemination of the organisms to the joints.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Artritis Reactiva/inmunología , Infecciones por Chlamydia/inmunología , Chlamydia trachomatis/inmunología , Enfermedades de Transmisión Sexual/inmunología , Adolescente , Adulto , Especificidad de Anticuerpos , Antígenos Bacterianos/inmunología , Infecciones por Chlamydia/transmisión , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Factores SexualesRESUMEN
To improve the reliability of the serodiagnosis of Chlamydia trachomatis infections, an immunoblot analysis, a microimmunofluorescence titration, and different immunoassays using synthetic peptides derived from species-specific epitopes in variable domain IV of the major outer membrane protein or recombinant antigens (heat shock protein 70 [hsp70], hsp60, hsp10, polypeptide encoded by open reading frame 3 of the plasmid [pgp3], macrophage infectivity potentiator, and a fragment of the total lipopolysaccharide) were evaluated. Because cross-reactions between chlamydial species have been reported, the microimmunofluorescence tests were also performed with Chlamydia pneumoniae and Chlamydia psittaci used as antigens, and C. pneumoniae-specific antibodies were also determined by immunoassays. Since the presence of antimicrobial antibodies must be interpreted in light of their prevalence in the general population, responses obtained with serum samples from patients with well-defined infection (i.e., with positive urethral or endocervical C. trachomatis DNA amplification) were compared to those obtained with samples from healthy blood donors. The best sensitivity (86%) with a specificity of 81% was obtained for immunoblotting results, when the number of individuals with > or =10 immunoglobulin G (IgG) and/or > or =2 IgM responses to the different C. trachomatis antigens was considered. A 13-kDa antigen was recognized by most of the samples (86% for IgG) from patients with acute urogenital infection but rarely (3%) by those from healthy blood donors (P < 0.0001). The sensitivity and specificity results obtained for serum antibodies to peptides or recombinant antigens were slightly lower than those results obtained for the number of responses to whole C. trachomatis antigens, which were 76 and 77%, respectively, when IgG responses to both recombinant hsp60 and pgp3 were considered.