RESUMEN
X-linked agammaglobulinemia (XLA) has been associated with a broad range of infections, but enteroviral disease represents one of the most damaging infections. The risk of enteroviral infection in XLA is lower now than in the setting of intramuscular immunoglobulin or in patients without immunoglobulin replacement, but the rate of infection has not declined significantly in the era of intravenous immunoglobulin replacement. Enteroviruses can cause inflammation of nearly every organ, but in XLA, infections often manifest as dermatomyositis or chronic meningoencephalitis. Difficulty and delay in recognizing symptoms and lack of specific therapy contribute to the poor outcomes. Furthermore, cerebrospinal fluid detection of enteroviruses is not very sensitive. Reluctance to perform brain biopsies can lead to significant delays. The other feature compromising outcomes is the lack of specific therapy. High-dose peripheral and intraventricular immunoglobulin have been used, but failure is still common. New antienteroviral drugs are in development and show promise for immunodeficient patients with life-threatening infections with enterovirus.
Asunto(s)
Agammaglobulinemia , Infecciones por Enterovirus , Enfermedades Genéticas Ligadas al Cromosoma X , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/tratamiento farmacológico , Agammaglobulinemia/epidemiología , Agammaglobulinemia/virología , Antivirales/uso terapéutico , Encéfalo/diagnóstico por imagen , Encéfalo/virología , Preescolar , Enterovirus/genética , Enterovirus/aislamiento & purificación , Infecciones por Enterovirus/diagnóstico , Infecciones por Enterovirus/tratamiento farmacológico , Infecciones por Enterovirus/epidemiología , Infecciones por Enterovirus/virología , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/tratamiento farmacológico , Enfermedades Genéticas Ligadas al Cromosoma X/epidemiología , Enfermedades Genéticas Ligadas al Cromosoma X/virología , Humanos , Imagen por Resonancia Magnética , Masculino , Éteres Fenílicos/uso terapéuticoRESUMEN
Oligonucleotide microarrays have been applied to microbial surveillance and discovery where highly multiplexed assays are required to address a wide range of genetic targets. Although printing density continues to increase, the design of comprehensive microbial probe sets remains a daunting challenge, particularly in virology where rapid sequence evolution and database expansion confound static solutions. Here, we present a strategy for probe design based on protein sequences that is responsive to the unique problems posed in virus detection and discovery. The method uses the Protein Families database (Pfam) and motif finding algorithms to identify oligonucleotide probes in conserved amino acid regions and untranslated sequences. In silico testing using an experimentally derived thermodynamic model indicated near complete coverage of the viral sequence database.