RESUMEN
PURPOSE: This study was conducted to investigate the efficacy of routine screening for high-frequency hearing loss (HFHL) including 3000, 6000, and 8000 Hz frequencies with conventional test frequencies (1000, 2000, and 4000 Hz) in adults and children in a university outreach program. METHOD: Screening outcomes were examined in 2 cohorts of adults (Cohort 1, N = 315, M = 66.2 years; Cohort 2, N = 67, M = 68.3 years) and children (Cohort 1, N = 177, M = 6.5 years; Cohort 2, N = 57, M = 6.9 years) with a high-frequency screen protocol (1000-8000 Hz at 25 dB HL for adults and 20 dB HL for children) using supra-aural headphones. A rescreen was conducted in Cohort 2 with a modified protocol using insert earphones and monitored ambient noise levels. RESULTS: Average total test time significantly increased (p < .0001) and nearly doubled with inclusion of 3000-, 6000-, and 8000-Hz frequencies, adding approximately 1 min. Rescreen referral rates decreased by approximately 2%-16% at 1000-8000 Hz (approximately 13%-16% at 6000 and 8000 Hz) using the modified protocol in adults and children, supporting false-positive responses using supra-aural headphones. CONCLUSION: Screening for HFHL should include insert earphones in order to prevent potential errors, particularly at 6000 and 8000 Hz.
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Pérdida Auditiva de Alta Frecuencia/diagnóstico , Pruebas Auditivas/métodos , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Pruebas Auditivas/instrumentación , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Intensive chemotherapy in children with cancer results in long-term impairment of humoral immunity. Whereas most studies to date focused on children with acute lymphoblastic leukemia (ALL), little data have been published on patients suffering from Hodgkin disease or from solid tumors. We therefore analyzed the loss of protective immunity (defined as immunity at the time of diagnosis and lack of immunity after completion of therapy) against vaccine-preventable diseases in children treated for various malignancies. METHODS: Children and adolescents <21 years of age at diagnosis and treated between 2001 and 2010 for various malignancies in the Department of Pediatric Hematology and Oncology, University of Frankfurt, were included in the retrospective chart review. Antibody levels against measles, mumps, rubella and varicella-zoster-virus (VZV) were routinely assessed at the time of diagnosis and within 12 months after completion of therapy. RESULTS: The study population consisted of 195 children (122 male); 80 patients had ALL, 15 acute myelogenous leukemia (AML), 18 non-Hodgkin lymphoma (NHL), 22 Hodgkin disease, and 60 various solid tumors. Overall, 27%, 47%, 19%, and 17% of the patients lost their humoral immunity against measles, mumps, rubella, and VZV, respectively. The risk of losing protective antibody titers depended on age with a higher risk in younger children. The loss of protective humoral immunity occurred significantly more often in patients with ALL compared to patients with any other underlying malignant disease (hematological malignancies such AML and NHL, Hodgkin disease or solid tumors). CONCLUSIONS: Our data demonstrate that a significant number of children lose pre-existing humoral immunity against measles, mumps, rubella, and VZV after completion of chemotherapy. This loss occurs more often in children with ALL than in children with AML, solid tumors and Hodgkin disease. Our results underline the need for post-chemotherapy revaccination of childhood cancer survivors.
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Anticuerpos Antivirales/sangre , Antineoplásicos/efectos adversos , Inmunidad Humoral , Neoplasias/inmunología , Adolescente , Antineoplásicos/uso terapéutico , Varicela/inmunología , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Sarampión/inmunología , Paperas/inmunología , Neoplasias/tratamiento farmacológico , Estudios Retrospectivos , Rubéola (Sarampión Alemán)/inmunología , Adulto JovenRESUMEN
The sensitivity of the VecTest antigen-capture and RT-PCR assays were compared to brain tissue culture in Vero cells for the detection of WNV in a sample of dead birds collected in East Texas and southern Louisiana during the summer of 2003. Cell culture was used as the gold standard, because it yielded the most positives. Direct culture of brain tissue and the WNV antigen-capture assay, done on oropharyngeal swabs, gave statistically comparable results (46% and 40% positive, respectively). In contrast, RT-PCR done on brain homogenates was significantly less sensitive than direct tissue culture (33% compared to 46%, respectively). Results indicated that RT-PCR may not be consistently the most sensitive assay for detection of WNV in dead bird brain tissue and that the VecTest antigen-capture assay has a number of advantages over the other two detection techniques for routine surveillance activities.
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Enfermedades de las Aves/diagnóstico , Inmunoensayo/veterinaria , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Fiebre del Nilo Occidental/veterinaria , Virus del Nilo Occidental/aislamiento & purificación , Animales , Antígenos Virales/análisis , Enfermedades de las Aves/virología , Encéfalo/virología , Chlorocebus aethiops , Inmunoensayo/métodos , Vigilancia de la Población , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Sensibilidad y Especificidad , Células Vero , Fiebre del Nilo Occidental/diagnóstico , Virus del Nilo Occidental/genética , Virus del Nilo Occidental/inmunologíaRESUMEN
To initiate invasion of the mosquito midgut, Plasmodium ookinetes secrete chitinases that are necessary to cross the chitin-containing peritrophic matrix en route to invading the epithelial cell surface. To investigate chitinases as potential immunological targets of blocking malaria parasite transmission to mosquitoes, a monoclonal antibody (MAb) was identified that neutralized the enzymatic activity of the sole chitinase of Plasmodium falciparum, PfCHT1, identified to date. This MAb, designated 1C3, previously shown to react with an apical structure of P. falciparum ookinetes, also reacts with a discrete apical structure of P. gallinaceum ookinetes. In membrane feeding assays, MAb 1C3 markedly inhibited P. gallinaceum oocyst development in mosquito midguts. MAb 1C3 affinity isolated an approximately 210-kDa antigen which, under reducing conditions, became a 35-kDa antigen. This isolated 35-kDa protein cross-reacted with an antiserum raised against a synthetic peptide derived from the P. gallinaceum chitinase active site, PgCHT1, even though MAb 1C3 did not recognize native or recombinant PgCHT1 on Western blot. Therefore, this affinity-purified 35-kDa antigen appears similar to a previously identified protein, PgCHT2, a putative second chitinase of P. gallinaceum. Epitope mapping indicated MAb 1C3 recognized a region of PfCHT1 that diverges from a homologous amino acid sequence conserved within sequenced chitinases of P. berghei, P. yoelii, and P. gallinaceum (PgCHT1). A synthetic peptide derived from the mapped 1C3 epitope may be useful as a component of a subunit transmission-blocking vaccine.
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Anticuerpos Antiprotozoarios/inmunología , Quitinasas/inmunología , Proteínas Fúngicas , Malaria/transmisión , Plasmodium falciparum/inmunología , Plasmodium gallinaceum/inmunología , Aedes/parasitología , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales/inmunología , Reacciones Cruzadas , Mapeo Epitopo , Epítopos , Datos de Secuencia Molecular , Plasmodium falciparum/enzimología , Plasmodium gallinaceum/enzimología , Homología de Secuencia de AminoácidoRESUMEN
The development of transmission-blocking vaccines is one approach to malaria control. To identify novel Plasmodium zygote- and ookinete-secreted proteins as targets of blocking malaria transmission, monoclonal antibodies (MAbs) were produced against parasite-secreted proteins found in Plasmodium gallinaceum ookinete culture supernatants. Four MAbs-1A6, 2A5, 2B5, and 4B6-were identified that bound to P. gallinaceum zygotes and ookinetes in diverse patterns in terms of spatial localization on parasites, time course of antigen expression, and Western immunoblot patterns. MAbs 2A5 and 4B6 recognized more than one protein band as detected by Western immunoblot of P. gallinaceum ookinete supernatants. Beginning at 0 h postfertilization, MAb 2A5 recognized a diverse set of antigens; at 10 h postfertilization, MAb 4B6 recognized several antigens as well. MAb 1A6 recognized a single approximately 17-kDa protein, and 2B5 recognized a single approximately 32-kDa protein at 15 h postfertilization. In membrane feeding assays to assess the effect of these MAbs on P. gallinaceum infectivity for Aedes aegypti mosquitoes, the addition of MAbs 1A6 and 2B5 to infectious blood meals significantly inhibited oocyst development in the mosquito midgut. In contrast, MAb 2A5 seemed to enhance infectivity. These results demonstrate that Plasmodium ookinetes secrete proteins (in addition to previously characterized chitinases) that may be targets for blocking malaria transmission. Future investigation of ookinete-secreted neutralization-sensitive molecules should provide valuable insight into mechanisms by which ookinetes exit the blood meal, penetrate and transverse the peritrophic matrix, and invade the mosquito midgut epithelium.