RESUMEN
Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged recently as a global health threat, causing a pandemic in the Americas. ZIKV infection mostly causes mild disease, but is linked to devastating congenital birth defects and Guillain-Barré syndrome in adults. The high level of cross-reactivity among flaviviruses and their cocirculation has complicated serological approaches to differentially detect ZIKV and dengue virus (DENV) infections, accentuating the urgent need for a specific and sensitive serological test. We previously generated a ZIKV nonstructural protein 1 (NS1)-specific human monoclonal antibody, which we used to develop an NS1-based competition ELISA. Well-characterized samples from RT-PCR-confirmed patients with Zika and individuals exposed to other flavivirus infections or vaccination were used in a comprehensive analysis to determine the sensitivity and specificity of the NS1 blockade-of-binding (BOB) assay, which was established in laboratories in five countries (Nicaragua, Brazil, Italy, United Kingdom, and Switzerland). Of 158 sera/plasma from RT-PCR-confirmed ZIKV infections, 145 (91.8%) yielded greater than 50% inhibition. Of 171 patients with primary or secondary DENV infections, 152 (88.9%) scored negative. When the control group was extended to patients infected by other flaviviruses, other viruses, or healthy donors (n = 540), the specificity was 95.9%. We also analyzed longitudinal samples from DENV-immune and DENV-naive ZIKV infections and found inhibition was achieved within 10 d postonset of illness and maintained over time. Thus, the Zika NS1 BOB assay is sensitive, specific, robust, simple, low-cost, and accessible, and can detect recent and past ZIKV infections for surveillance, seroprevalence studies, and intervention trials.
Asunto(s)
Anticuerpos Antivirales/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Infecciones por Flavivirus/diagnóstico , Proteínas no Estructurales Virales/inmunología , Infección por el Virus Zika/diagnóstico , Virus Zika/inmunología , Adolescente , Anticuerpos Bloqueadores/inmunología , Anticuerpos Monoclonales/inmunología , Niño , Preescolar , Reacciones Cruzadas/inmunología , Dengue/diagnóstico , Dengue/virología , Diagnóstico Diferencial , Infecciones por Flavivirus/virología , Humanos , Estudios Prospectivos , Sensibilidad y Especificidad , Infección por el Virus Zika/virologíaRESUMEN
Abstract: Acute hepatitis E is becoming increasingly recognised in Europe with up to 40% of the population in Southern France being exposed to the virus, which is harboured in pigs. Patients with known liver disease may present with acute hepatitis E and present a diagnostic challenge. For example patients with autoimmune hepatitis (AIH) who are immunosuppressed and contract hepatitis E may be at increased risk of developing chronicity due to concurrent immunosuppression. Importantly, the diagnosis may be missed with the infection misdiagnosed as an autoimmune flare, and immunosuppression increased by the attending physician, thus enhancing the risk of chronicity of infection leading to progressive liver injury in immunocompromised patients. We report a case of acute hepatitis E in a patient with AIH and discuss the features that helped us differentiating it from an autoimmune flare.
Asunto(s)
Humanos , Femenino , Adulto , Enfermedad Aguda , Hepatitis E/diagnóstico , Hepatitis Autoinmune/diagnóstico , Enfermedad Crónica , Valor Predictivo de las Pruebas , Hepatitis E/inmunología , Hepatitis E/virología , Progresión de la Enfermedad , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/tratamiento farmacológico , Diagnóstico Diferencial , Quimioterapia Combinada , Inmunosupresores/uso terapéuticoRESUMEN
Acute hepatitis E is becoming increasingly recognised in Europe with up to 40% of the population in Southern France being exposed to the virus, which is harboured in pigs. Patients with known liver disease may present with acute hepatitis E and present a diagnostic challenge. For example patients with autoimmune hepatitis (AIH) who are immunosuppressed and contract hepatitis E may be at increased risk of developing chronicity due to concurrent immunosuppression. Importantly, the diagnosis may be missed with the infection misdiagnosed as an autoimmune flare, and immunosuppression increased by the attending physician, thus enhancing the risk of chronicity of infection leading to progressive liver injury in immunocompromised patients. We report a case of acute hepatitis E in a patient with AIH and discuss the features that helped us differentiating it from an autoimmune flare.