RESUMEN
Respiratory viral infections are major causes of morbidity and mortality in children with SCID and other primary immunodeficiencies who require BMT. Twenty-two of 73 (30%) such children were admitted with respiratory viral infections, of whom 13/22 (59%) died. All viruses were detected in nasopharyngeal aspirate (NPA). Virus was only found in BAL in those with LRTI. Eleven of 22 (50%) had paramyxovirus infections, all with severe viral pneumonitis which worsened post BMT. Five of 11 (45.5%) survived overall. All 11 received aerosolised ribavirin; five of 11 received additional inhaled immunoglobulin and corticosteroid. Three of 5 (60%) survived compared with two of six (33.3%) not thus treated. Three of 22 (13.6%) had adenoviruses; one died of disseminated disease, including pneumonia despite intravenous ribavirin. Eleven patients had rhinovirus detected; nine of 11 (82%) were asymptomatic or coryzal and survived. Two patients with additional severe lung pathologies had LRT rhinovirus and died. All patients received intravenous immunoglobulin. No treatments resulted in viral clearance without successful T cell engraftment. Respiratory viruses, particularly paramyxoviruses and adenoviruses are common, significant pathogens in these patients, significantly worsening outcome of BMT. NPA is an ideal specimen for diagnosis and monitoring of infection. Aggressive treatments may reduce viral replication and damage. Nebulised immunoglobulin and corticosteroid in LRTI may improve respiratory function and outcome.
Asunto(s)
Infecciones por Adenoviridae/epidemiología , Trasplante de Médula Ósea/efectos adversos , Infecciones por Citomegalovirus/epidemiología , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Picornaviridae/epidemiología , Rhinovirus , Inmunodeficiencia Combinada Grave/complicaciones , Infecciones por Adenoviridae/terapia , Niño , Infecciones por Citomegalovirus/terapia , Humanos , Incidencia , Lactante , Infecciones por Paramyxoviridae/terapia , Infecciones por Picornaviridae/terapiaRESUMEN
Respiratory syncytial virus and parainfluenza virus infection carry a poor prognosis in severe combined immunodeficiency (SCID), particularly if the viral load is high. Patients with high viral load develop severe pneumonitis at engraftment which may possibly be modulated by immunotherapy, including high dose nebulised corticosteroids. Further work is required to develop effective treatment for this severe condition.
Asunto(s)
Trasplante de Médula Ósea , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Inmunodeficiencia Combinada Grave/terapia , Antivirales/uso terapéutico , Humanos , Lactante , Infecciones por Paramyxoviridae/tratamiento farmacológico , Infecciones por Paramyxoviridae/virología , Pronóstico , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/virología , Inmunodeficiencia Combinada Grave/virología , Carga ViralRESUMEN
Diagnosis of significant infections by human herpesvirus 6 (HHV6) and 7 (HHV7) in transplant patients has proved difficult because both viruses are ubiquitous and can cause persistent infections in their hosts. The significance of viral DNA detected in peripheral blood leukocytes (PBLs; DNAemia) by PCR is therefore unclear. The interpretation of serological results is complicated by the fact that both primary and secondary infections with other herpesviruses may be associated with a concurrent antibody response to HHV6. Fifty-four renal allograft recipients were studied prospectively and their serological response to HHV6, HHV7 and CMV were compared with the detection of viral DNAemia from the homologous and heterologous viruses. Serum and heparinished blood samples were collected prospectively from 54 renal allograft recipients. DNA was extracted from PBLs and tested for the presence of HHV6, HHV7 and CMV DNA by PCR. Antibodies to HHV6 and HHV7 were measured by an indirect immunofluorescence test and to CMV by an anticomplement immunofluorescence (ACIF) test. CMV IgM antibodies were detected by a commercial enzyme immunoassay. CMV and HHV7 DNAemia were each significantly associated with serological responses to the homologous virus but no such association was found for HHV6 DNAemia. However, patients with consecutively positive DNAemia to any of the viruses (including HHV6) were more likely to have a homologous serological response. Patients who had detectable CMV IgM without a concurrent rise in CMV antibodies were significantly less likely to have CMV DNAemia (odds ratio = 0.16; 95% CI 0.02-0.9). CMV IgM antibodies may be associated with HHV6 or HHV7 DNAemia (odds ratio 2.3; 95% CI 0.5-15). This serological profile may reflect a crossreactive response to HHV6, HHV7 or other herpesviruses. CMV IgM should not be used in isolation for the diagnosis of CMV infection or disease in this group of patients.
Asunto(s)
Citomegalovirus/inmunología , ADN Viral/sangre , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/virología , Herpesvirus Humano 6/inmunología , Herpesvirus Humano 7/inmunología , Trasplante de Riñón/efectos adversos , Reacción en Cadena de la Polimerasa/métodos , Adolescente , Adulto , Anciano , Anticuerpos Antivirales/sangre , Niño , Preescolar , Citomegalovirus/genética , Femenino , Infecciones por Herpesviridae/sangre , Herpesvirus Humano 6/genética , Herpesvirus Humano 7/genética , Humanos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Trasplante HomólogoRESUMEN
Fifty-six renal allograft recipients were studied prospectively for 3 months or longer after transplant. The polymerase chain reaction (PCR) was used to screen peripheral blood leucocyte (PBL) specimens for CMV, human herpesvirus 6 (HHV6) and human herpesvirus 7 (HHV7) DNA (DNAemia) in 67 healthy controls and in serial (fortnightly) PBL specimens from the 56 allograft recipients. None of the healthy controls had detectable CMV DNAemia, although HHV6 and HHV7 DNAemia was found in 7% and 9% of individuals respectively. In contrast, DNAemia due to CMV, HHV6 and HHV7 was found in 50%, 36% and 39% of patients respectively, at some time during the post-transplant period. Of the 28 patients who had CMV DNAemia, eight developed "CMV disease". The risk of progression to "CMV disease" was increased in patients with concurrent DNAemia to all three viruses (relative risk 3.7; 95% CI 1.3-10.5). The relative risk of "CMV disease" for patients with concurrent CMV and HHV7 was also increased (RR = 3.5; 95% CI = 1.1-11.6), while the association between CMV and HHV6 was inconclusive (RR = v2.1; 95% CI = 0.7-6.6). The first 26 patients recruited to the study also had serial serum samples tested for antibody responses to the three viruses. "CMV disease" was associated with rising antibody titres to HHV7 (Fisher's exact test, P = 0.02), and weakly so with HHV6 (P = 0.07). It is concluded that in patients with CMV DNAemia, concurrent infection/reactivation HHV7 (and possibly HHV6) is associated with an increased risk of progression to "CMV disease".
Asunto(s)
Anticuerpos Antivirales/sangre , Infecciones por Citomegalovirus/virología , Citomegalovirus/aislamiento & purificación , ADN Viral/análisis , Infecciones por Herpesviridae/virología , Herpesvirus Humano 7/aislamiento & purificación , Trasplante de Riñón/efectos adversos , Adolescente , Adulto , Anciano , Niño , Preescolar , Citomegalovirus/genética , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/inmunología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/inmunología , Herpesvirus Humano 6/genética , Herpesvirus Humano 6/inmunología , Herpesvirus Humano 6/aislamiento & purificación , Herpesvirus Humano 7/genética , Herpesvirus Humano 7/inmunología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Trasplante HomólogoRESUMEN
The age-related prevalence of antibodies to herpesviruses was compared in England and Hong Kong. Altogether 327 sera from England and 266 sera from Hong Kong were tested for antibodies to herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV-6). Herpesvirus infections were common in both countries but generally were acquired earlier and were more prevalent in Hong Kong. Over 90% of children in Hong Kong were infected with VZV, EBV, and HHV-6 by 8 years of age. HSV and CMV were the least prevalent childhood infections in both countries, although, 30-40% of babies in Hong Kong became infected during the first year of life. CMV infections were rare throughout childhood in the English cohort. Overcrowding and early attendance at kindergarten may aid more efficient and earlier transmission of herpesvirus in Hong Kong. The high prevalence of CMV in particular may have implications for the management of young pregnant women and organ transplant recipients in Hong Kong.
Asunto(s)
Anticuerpos Antivirales/sangre , Herpesviridae/inmunología , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Citomegalovirus/inmunología , Inglaterra/epidemiología , Herpesvirus Humano 3/inmunología , Herpesvirus Humano 4/inmunología , Herpesvirus Humano 6/inmunología , Hong Kong/epidemiología , Humanos , Lactante , Recién Nacido , Simplexvirus/inmunologíaRESUMEN
In order to optimize viral antigen production, the growth characteristics of human herpesvirus-6 (HHV-6) (strain AJ) were studied in two cell lines: HSB-2 and JJHAN. The cells were infected with different multiplicities of infection (moi) and viral growth was monitored by appearance of cytopathic effect (CPE), total and viable cell count, immunofluorescence test, immunoblotting, and electron microscopy. Although > or = 70% of JJHAN cells showed CPE when infected at high moi, only 5% of the cells contained viral antigens when tested with immunofluorescence. In contrast the percentage of cells showing fluorescence in HSB-2 cells reached > or = 30% when infected at > or = 1:50. More than 10 polypeptides of molecular weight ranging between 31-140 kD appeared in the HSB-2 cultures by immunoblotting while only 3 polypeptides were detected in the JJHAN cultures at high moi. Different stages of virus maturation were seen in the HSB-2 cells by electron microscopy but the replication of the virus in JJHAN cells appeared to be restricted. For the purpose of antigen production the optimal conditions for the AJ strain of HHV-6 were found to be culturing in HSB-2 cells at a concentration of 1:25-1:50 infected to uninfected cells and harvesting after 7 days.