RESUMEN
BACKGROUND: Death in patients with chikungunya is rare and has been associated with encephalitis, hemorrhage, and septic shock. We describe clinical, histologic, and immunohistochemical findings in individuals who died following chikungunya virus (CHIKV) infection. METHODS: We identified individuals who died in Puerto Rico during 2014 following an acute illness and had CHIKV RNA detected by reverse transcriptase-polymerase chain reaction in a pre- or postmortem blood or tissue specimen. We performed histopathology and immunohistochemistry (IHC) for CHIKV antigen on tissue specimens and collected medical data via record review and family interviews. RESULTS: Thirty CHIKV-infected fatal cases were identified (0.8/100 000 population). The median age was 61 years (range: 6 days-86 years), and 19 (63%) were male. Death occurred a median of 4 days (range: 1-29) after illness onset. Nearly all (93%) had at least 1 comorbidity, most frequently hypertension, diabetes, or obesity. Nine had severe comorbidities (eg, chronic heart or kidney disease, sickle cell anemia) or coinfection (eg, leptospirosis). Among 24 fatal cases with tissue specimens, 11 (46%) were positive by IHC. CHIKV antigen was most frequently detected in mesenchymal tissues and mononuclear cells including tissue macrophages, blood mononuclear cells, splenic follicular dendritic cells, and Kupffer cells. Common histopathologic findings were intra-alveolar hemorrhage and edema in the lung, chronic or acute tenosynovitis, and increased immunoblasts in the spleen. CHIKV infection likely caused fatal septic shock in 2 patients. CONCLUSIONS: Evaluation of tissue specimens provided insights into the pathogenesis of CHIKV, which may rarely result in septic shock and other severe manifestations.
Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Diabetes Mellitus , Fiebre Chikungunya/complicaciones , Fiebre Chikungunya/epidemiología , Comorbilidad , Humanos , Masculino , Persona de Mediana Edad , Puerto RicoRESUMEN
Protothecosis is a rare disease caused by environmental algae of the genus Prototheca. These are saprophytic, non-photosynthetic, aerobic, colorless algae that belong to the Chlorellaceae family. Seven different species have been described. Prototheca zopfii genotype 2 and P. wickerhamii are most commonly involved in pathogenic infections in humans and animals. The objective of this work is to describe, for the first time, a case of protothecosis caused by P. zopfii genotype 1 in a dog. The dog, a 4-year-old mix bred male, was presented to a veterinary clinic in Montevideo, Uruguay, with multiple skin nodules, one of which was excised by surgical biopsy. The sample was examined histologically and processed by PCR, DNA sequencing, and restriction fragments length polymorphisms for the detection and genotyping of P. zopfii. In addition, transmission electron microscopy and scanning electron microscopy were performed. Histology showed severe ulcerative granulomatous dermatitis and panniculitis with myriads of pleomorphic algae. Algal cells were 4-17 µm in size, with an amphophilic, 2-4-µm-thick wall frequently surrounded by a clear halo, contained flocculant material and a deeply basophilic nucleus, and internal septae with daughter cells (endospores) consistent with endosporulation. Ultrastructurally, algal cells/endospores at different stages of development were found within parasitophorous vacuoles in macrophages. Prototheca zopfii genotype 1 was identified by molecular testing, confirming the etiologic diagnosis of protothecosis.
Asunto(s)
Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/patología , Infecciones/veterinaria , Prototheca/aislamiento & purificación , Animales , Biopsia , ADN de Algas/química , ADN de Algas/genética , Enfermedades de los Perros/microbiología , Perros , Genotipo , Histocitoquímica , Infecciones/diagnóstico , Infecciones/microbiología , Infecciones/patología , Masculino , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Prototheca/clasificación , Prototheca/genética , Análisis de Secuencia de ADN , Piel/patología , UruguayRESUMEN
BACKGROUND: Zika virus is an arthropod-borne virus that is a member of the family Flaviviridae transmitted mainly by mosquitoes of the genus Aedes. Although usually asymptomatic, infection can result in a mild and self-limiting illness characterised by fever, rash, arthralgia, and conjunctivitis. An increase in the number of children born with microcephaly was noted in 2015 in regions of Brazil with high transmission of Zika virus. More recently, evidence has been accumulating supporting a link between Zika virus and microcephaly. Here, we describe findings from three fatal cases and two spontaneous abortions associated with Zika virus infection. METHODS: In this case series, formalin-fixed paraffin-embedded tissue samples from five cases, including two newborn babies with microcephaly and severe arthrogryposis who died shortly after birth, one 2-month-old baby, and two placentas from spontaneous abortions, from Brazil were submitted to the Infectious Diseases Pathology Branch at the US Centers for Disease Control and Prevention (Atlanta, GA, USA) between December, 2015, and March, 2016. Specimens were assessed by histopathological examination, immunohistochemical assays using a mouse anti-Zika virus antibody, and RT-PCR assays targeting the NS5 and envelope genes. Amplicons of RT-PCR positive cases were sequenced for characterisation of strains. FINDINGS: Viral antigens were localised to glial cells and neurons and associated with microcalcifications in all three fatal cases with microcephaly. Antigens were also seen in chorionic villi of one of the first trimester placentas. Tissues from all five cases were positive for Zika virus RNA by RT-PCR, and sequence analyses showed highest identities with Zika virus strains isolated from Brazil during 2015. INTERPRETATION: These findings provide strong evidence of a link between Zika virus infection and different congenital central nervous system malformations, including microcephaly as well as arthrogryposis and spontaneous abortions. FUNDING: None.
Asunto(s)
Encéfalo/patología , Encéfalo/virología , Deformidades Congénitas de las Extremidades/virología , Microcefalia/virología , Complicaciones Infecciosas del Embarazo/patología , Complicaciones Infecciosas del Embarazo/virología , Primer Trimestre del Embarazo , Infección por el Virus Zika/congénito , Infección por el Virus Zika/patología , Virus Zika/aislamiento & purificación , Aborto Espontáneo/virología , Adulto , Antígenos Virales/aislamiento & purificación , Autopsia , Brasil , Resultado Fatal , Femenino , Humanos , Inmunohistoquímica/métodos , Lactante , Deformidades Congénitas de las Extremidades/diagnóstico por imagen , Masculino , Microcefalia/patología , Neuroglía/patología , Neuroglía/virología , Placenta/patología , Placenta/virología , Embarazo , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo , ARN Viral/aislamiento & purificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Síndrome , Ultrasonografía Prenatal , Virus Zika/inmunologíaRESUMEN
Zika virus is a mosquito-borne flavivirus that is related to dengue virus and transmitted primarily by Aedes aegypti mosquitoes, with humans acting as the principal amplifying host during outbreaks. Zika virus was first reported in Brazil in May 2015 (1). By February 9, 2016, local transmission of infection had been reported in 26 countries or territories in the Americas.* Infection is usually asymptomatic, and, when symptoms are present, typically results in mild and self-limited illness with symptoms including fever, rash, arthralgia, and conjunctivitis. However, a surge in the number of children born with microcephaly was noted in regions of Brazil with a high prevalence of suspected Zika virus disease cases. More than 4,700 suspected cases of microcephaly were reported from mid-2015 through January 2016, although additional investigations might eventually result in a revised lower number (2). In response, the Brazil Ministry of Health established a task force to further investigate possible connections between the virus and brain anomalies in infants (3).
Asunto(s)
Encéfalo/virología , Placenta/virología , Infección por el Virus Zika/diagnóstico , Virus Zika/aislamiento & purificación , Aborto Espontáneo/virología , Antígenos Virales/aislamiento & purificación , Brasil/epidemiología , Femenino , Humanos , Recién Nacido , Embarazo , ARN Viral/aislamiento & purificación , Virus Zika/inmunología , Infección por el Virus Zika/congénitoRESUMEN
Zika virus is an arthropod-borne virus that is a member of the family Flaviviridae transmitted mainly by mosquitoes of the genus Aedes. Although usually asymptomatic, infection can result in a mild and self-limiting illness characterised by fever, rash, arthralgia, and conjunctivitis. An increase in the number of children born with microcephaly was noted in 2015 in regions of Brazil with high transmission of Zika virus. More recently, evidence has been accumulating supporting a link between Zika virus and microcephaly. Here, we describe findings from three fatal cases and two spontaneous abortions associated with Zika virus infection.