Missing link: Animal models to study whether Zika causes birth defects

Becker, Rachel

doi:10.1038/nm0316-225

Cited by 15 publications

(12 citation statements)

References 19 publications

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“…In Pernambuco, a single reference hospital neurological unit held 131 cases with suspected ZIKV involvement (5) . The virus was later detected in seven of these cases through PCR and virus isolation, confirming the association between ZIKV infection and neurological disorders, as suggested in French Polynesian studies (2) (6) .…”

Section: Introductionmentioning

confidence: 99%

Zika in Pernambuco: rewriting the first outbreak

Brito

Oliveira

et al. 2016

Rev. Soc. Bras. Med. Trop.

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Introduction: A Zika virus epidemic was registered in 2015 in Northeast Brazil. In the State of Pernambuco, thousands of classical cases transpired, and in the following months, neurological disturbances in adults and microcephaly in newborns emerged as complications. After the peak of the epidemic, the official system reported only four cases of Zika virus but over 100,000 cases of dengue virus. The vigilance system was unable to retrospectively estimate cases or to issue an alert to officially notified cases with possible inconsistence concerning specific arbovirosis diagnoses. Methods: To evaluate the frequency of different arbovirosis diagnoses based on clinical-epidemiologic criteria, from January to April 2015, we conducted a hospitalbased cross-sectional study retrospectively analyzing suspected cases of arbovirosis. Results: Of 1,046 total suspected cases of arbovirus, 895 (86%) were classified as probable Zika virus cases, and 151 (14%) as probable dengue virus cases. The most frequent manifestations in probable Zika virus cases were exanthema (100%), pruritus (50.7%), fever (20.4%) and arthralgia (27.7%). Conclusions: In contrast to the official data, during the peak months of the arbovirosis epidemic of 2015, most cases were compatible with Zika virus infections. Hospital-based studies, although retrospective and based on secondary data from clinical files, might provide a better estimate of the number of cases relative to currently available data, if derived from several urgent care units of representative areas of a city or state.This would partially retrospectively correct some inconsistences regarding official notifications.

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Section: Introductionmentioning

confidence: 99%

Zika in Pernambuco: rewriting the first outbreak

Brito

Oliveira

et al. 2016

Rev. Soc. Bras. Med. Trop.

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“…Thirty-nine cases of GBS were reported after the outbreak, but ZIKV was not isolated from these patients (5) (7) . In the Northeast of Brazil, from April 2015 an increase in the number of neurological cases was noticed (12) . Confirmation of the association took place in the State of Pernambuco, where positive results for ZIKV were obtained by RT-PCR and viral isolation from 7 serum samples and 1 amniotic fluid sample.…”

Section: Neurological Involvementmentioning

confidence: 99%

“…Of these 7 cases, 4 presented with GBS, 2 with acute disseminated encephalomyelitis, and one with meningoencephalitis. A further 70 neurological cases are under investigation, aiming to clarify details of the outbreak (12) (38) . Seven other Latin countries reported an increase in the number of GBS cases (19) .…”

Section: Neurological Involvementmentioning

confidence: 99%

“…There were 58 cases in a single month, far exceeding the total number of cases registered in previous years (5 in 2011, 9 in 2012, 10 in 2013, and 12 in 2014). Primary and secondary causes were suggested, but the initial investigation of these cases made the physician raise the hypothesis of ZIKV (10) (11) (12) , based on the following clinical and epidemiological evidence: a) many cases appeared in a short time, occurring simultaneously in different cities and states, characteristic of a disease with a high attack rate and rapid dissemination, a phenomenon associated with diseases transmitted by arthropods; b) in addition to microcephaly, imaging tests showed some common findings: Periventricular and cortical micro-calcifications, hypoplasia cerebellar and, in some cases,lissencephaly, compatible with congenital infections which were later described in detail (47) ; c) diseases associated with TORCH (toxoplasmosis, rubella, cytomegalovirus, syphilis, human immunodeficiency virus, parvovirus B19), because of their modes of transmission, are not associated with major outbreaks; d) prenatal and perinatal research revealed negative test results for TORCH infections; e) most (70%) mothers reported a clinical presentation compatible with ZIKV infection in their first trimester of pregnancy, which took place during a period in which there was a ZIKV outbreak in the region; f) ZIKV has a greater neurotropism than other arboviruses; g) other arboviral infections endemic and epidemic in the region, such as dengue or Chikungunya, are not associated with congenital malformations Moreover, Chikungunya had not been detected in many Northeast states in the beginning of the year.…”

Section: Microcephaly: From Suspicion To Confirmation Of the Associationmentioning

confidence: 99%

“…In the second quarter of that year, the association between ZIKV infection and neurological symptoms/signs in adults was confirmed. Moreover, in October 2015, a novel hypothesis was suggested, that ZIKV infection and neonatal microcephaly are associated, based on clinical and epidemiological observation and investigation (10) (11) (12) .…”

Section: Introductionmentioning

confidence: 99%

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One year after the Zika virus outbreak in Brazil: from hypotheses to evidence

Brito

Cordeiro

2016

Rev. Soc. Bras. Med. Trop.

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In the second quarter of 2015, the association between Zika virus infection and neurological symptoms was confirmed in adults. Moreover, in October 2015 a novel suspicion was raised based on clinical and epidemiological observations: that an association between Zika virus infection and neonatal microcephaly may exist. A year after the first reports on Zika virus in Brazil, many hypotheses and much evidence on the patterns of involvement of the disease and its complications have been produced, both in this country and others; other hypotheses still need to be clarified. This review is a synthesis of a new chapter in the history of medicine; it outlines the main results produced.

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Animal Models for Dengue and Zika Vaccine Development

Santos

Fink

2018

Advances in Experimental Medicine and Biology

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The current status of animal models in the study of dengue and Zika are covered in this review. Mouse models deficient in IFN signaling are used to overcome the natural resistance of mice to non-encephalitic flaviviruses. Conditional IFNAR mice and non-human primates (NHP) are useful immuno-competent models. Sterile immunity after dengue vaccination is not observed in NHPs. Placental and fetal development in NHPs is similar to humans, facilitating studies on infection-mediated fetal impairment.

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Missing link: Animal models to study whether Zika causes birth defects

Cited by 15 publications

References 19 publications

Zika in Pernambuco: rewriting the first outbreak

Zika in Pernambuco: rewriting the first outbreak

One year after the Zika virus outbreak in Brazil: from hypotheses to evidence

Animal Models for Dengue and Zika Vaccine Development

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