Clinical and epidemiological characteristics of probable cases of congenital Zika syndrome and dengue antibody levels, Tuxtla Gutierrez, Chiapas, Mexico

Introduction: We previously found that the occurrence of congenital Zika syndrome was under-reported in Mexico. It was postulated that high dengue virus antibody levels found at the population-level in endemic countries might have contributed to the occurrence of the regional pandemic of Zika disease. A case series of suspected cases of congenital Zika syndrome in a maternity hospital in Tuxtla Gutierrez, Chiapas, Mexico was assembled to assess why they were not reported and to explore the hypothesis of dengue virus antibody-dependent enhancement of Zika disease. Methods: We used a quantitative approach to describe clinical and imaging records and used data from interviews of a total of 13 suspected cases of congenital Zika syndrome. We also quantitated dengue 1 and 2 antibodies using an 80% plaque reduction neutralization test of sera specimens obtained from the mothers of these 13 cases and compared them to those of a group of mothers who delivered normal newborns in the same hospital. Results: Only one of the suspected cases was laboratory-confirmed because appropriate specimens were not collected from the newborns as required by the case definition. We found 1) microcephaly, 2) hypoplasia/hypogeneses, thinning or absence of brain structures, 3) multiple birth defects, 4) calcifications, and cysts, 5) meningocele/encephalocele, and 6) hydrocephalus in 100 %, 76.9 %, 38.5 %, 38.5 %, 30.8 %, and 23.1 %, respectively of the case series. The cases clustered geographically, and 77 % occurred between May 2016 to March 2017 and recalled or were told by a doctor they had Zika fever. There was a four-fold increased risk of congenital Zika syndrome among those with dengue 1 antibody as compared to those with dengue 2 antibodies (odds ratio = 3.6; 95 % confidence interval: 0.7, 20.5), reaching only borderline statistical significance. Conclusions: We found in the largest maternal facility of the capital of the State of Chiapas, in Mexico, that only 7.7 % of suspected cases were confirmed, and that the rather complex requirement of cerebrospinal fluid specimens or serological specimens of newborns for suspected cases of congenital Zika syndrome used during the pandemic resulted in low sensitivity of the surveillance system. The finding of higher levels of dengue 1 than dengue 2 antibodies in cases than the referent population, requires further evaluation and may suggest a role for dengue antibody-dependent response in Zika disease.

Introducción: Previamente los autores habían encontrado evidencia de sub-notificación de la ocurrencia del síndrome congénito por Zika en México. Se ha postulado que niveles elevados de anticuerpos contra los virus del dengue a nivel poblacional en los países endémicos hubiese contribuido a la ocurrencia de la pandemia regional de enfermedad por Zika. Ensamblamos una serie de casos sospechosos de síndrome congénito por Zika en un hospital de maternidad en Tuxtla Gutiérrez, Chiapas, México, para evaluar por qué no fueron notificados y explorar la hipótesis de enfermedad por Zika incrementada por anticuerpos anti-dengue. Métodos: Utilizamos un enfoque cuantitativo para describir 13 casos sospechosos de síndrome congénito por revisamos registros clínicos e imágenes, entrevistas. También cuantificamos los niveles de anticuerpos para los virus dengue 1 y 2 en suero de las madres de los casos comparados con los de mujeres que tuvieron recién nacidos normales en el mismo hospital. Resultados: Solamente uno de los 12 casos sospechosos fue confirmado por laboratorio, porque en los demás no se recolectaron especímenes adecuados de los neonatos como lo requería la definición de casos. Encontramos 1) microcefalia, 2) hipoplasia y adelgazamiento de las estructuras cerebrales, 3) malformaciones múltiples, 4) calcificaciones o quistes, 5) meningocele/encefalocele, y 6) hidrocefalia en: 100 %, 76.9 %, 38.5 %, 38.5 %, 30.8 %, y 23.1 %, en ese orden entre los casos sospechosos. Los casos se aglutinaron geográficamente y 77 % ocurrieron entre Mayo del 2016 y Marzo del 2017, y sus madres recordaban que tuvieron o que un profesional de la salud les dijo que tuvieron fiebre por Zika. Encontramos un incremento de casi 4 veces en el riesgo de síndrome congénito por Zika para aquellos con altos niveles de anticuerpos anti-dengue 1 comparado con anticuerpos anti-dengue 2 (cociente de suertes = 3.6; intervalo de confianza del 95 %: 0.7, 20.5), alcanzando solamente una significancia estadística limítrofe. Conclusiones: Encontramos en el establecimiento de atención a la maternidad más grande en la capital de Chiapas, México, que solamente 7.7 % de los casos sospechosos de síndrome congénito por Zika fueron confirmados y que los relativamente complejos requerimientos de la definición de casos de muestras serológicas o de líquido cefalorraquídeo resultó en una baja sensibilidad del sistema de vigilancia. El hallazgo de niveles más altos de anticuerpos a dengue 1 que dengue 2 requiere más evaluación y pudiera sugerir un papel de la respuesta dependiente de anticuerpos al dengue en Zika.

Arthropod-Borne viral Diseases in Peru

Arthropode-Borne viral diseases have been a significant cause of morbidity and mortality for several decades in Peru. Epidemics and epizootics of Venezuelan equine encephalitis (VEE), subtype IAB virus occurred among humans and equine at intermittent intervals from 1925 through 1973 along the Pacific coastal plains, extending southward from the most northern Departament of Tumbes to the Departament of Ica. While the VEE IAB virus has not been detected since 1973, several isolates of VEE ID and an isolate VEE IIIC were obtained during 1971 and 1975 from mosquitoes and/or sentinel hamster in Quistococha, northeastern Amazon region. In 1994, the first human cases, associated with VEE virus ID were diagnosed among Peruvian soldiers near Pantoja, northern Amazon region, and during 1995, primarily among students and military personnel in Iquitos, northastern Amazon region. As early as 1913 , a disease resembling yellow fever was recognized in the Amazon region Peru. Outbreaks of this disease have continued to occur, apparently at annual interval, with the most recent and the largest sylvan outbreak ever recorded in Peru being documented during 1995 along the eastern foothills of the Andes Mountains. In 1990, dengue (DEN) 1 and DEN4 were first isolated in Peru during an outbreak of DEN fever among residents of the city of Iquitos, northeastern Amazon basin region. Seroepidemiological and case surveillance studies conducted 1992 through 1995 documented that DEN 1 continued to cause cases of DEN fever in Iquitos, and in 1995, an outbreak was associated with the introduction of DEN 2 into the community. Outbreaks of DEN fever, associated with DEN 1 occurred during 1994 and 1995 in the northern coastal cities of Tumbes and Piura, and in Pucallpa, Amazon basin region. In 1995, the first isolations of DEN 2 were obtained from febriles cases in Tumbes, Piura and Pucallpa. Although 2 serotypes of DEN were associated with human infection, none of the cases presented with hemorragic manifestations. The first isolations of Oropouche (ORO) fever virus were obtained during 1992 from febrile patients in Iquitos. The virus was isolated during 1994 from febrile cases and serological results revealed that ORO was the cause of an outbreak in the southeastern Amazon region. A single isolate of ORO virus was obtained during 1995 from a febrile patient in Iquitos