Zika: The Expanding and Deepening Threat

Marc Gozlan, MD

Disclosures

November 14, 2016

April 2016

April 6-7, 2016. On April 7, 2016, microcephaly or CNS malformation cases had been detected in 21 out of 27 states in Brazil, the reported increase being concentrated in the northeast region.[49]

Zika virus appeared to predominantly affect neural tissues. A subsequent paper on neuroimaging in 23 infants whose mothers had symptoms (low-grade fever and cutaneous rash) that were compatible with Zika virus infection during the first or second trimester of pregnancy was published online on April 6, 2016, in the New England Journal of Medicine.[50]

The Brazilian authors reported severe brain damage in all cases. Indeed, head CT images showed that intracranial calcifications, ventriculomegaly, and abnormal hypodensity of the white matter were seen in all the infants. The CT findings in this case series reinforced the link between the neurotropic Zika virus and the disruption of brain development observed in these infants.[50]

... intracranial calcifications, ventriculomegaly, and abnormal hypodensity of the white matter were seen in all the infants."

Meanwhile, another team, working in the same city of Recife in Pernambuco, published detailed findings from brain imaging (CT and MRI) in the British Medical Journal[51] from a case series of the first 23 cases of congenital infection and microcephaly presumably associated with the Zika virus in the current Brazilian epidemic. Again, severe cerebral damage was found on imaging in most of the children.

By now, 33 countries and territories in the Americas reported mosquito-borne transmission.[48] Colombia reported 58,790 suspected cases of infections with Zika virus.[48] Furthermore, Cape Verde, off the coast of West Africa, identified 206 confirmed cases of Zika virus and reported two microcephaly cases in the context of the Zika virus outbreak.[48] This was the first time that the Zika virus was responsible for outbreaks linked to neurologic disorders and microcephaly was detected in Africa. It now appeared that Cape Verde received more than 7000 travelers from Zika virus-affected countries in 2015, including direct flights from northeastern Brazil.[52] (Figure 5).

Figure 5. Cumulative number of countries, territories and areas reporting Zika virus transmission in years, 2007-2014, and monthly from January 1, 2015 to April 6, 2016.[52] Courtesy of the World Health Organization.

April 8, 2016. Ecuador notified WHO of a large die-off of howler monkeys in Pacoche Forest Reserve. Among 39 monkeys that were found dead in early February 2016, two samples were found positive for Zika virus by RT-PCR. This was the first detection of Zika virus infection in nonhuman primates reported in Ecuador and the first in the Americas, suggesting a new transmission cycle that could allow the virus to persist.

On April 20, 2016, Zika virus was detected by Brazilian researchers in a capuchin monkey.[53] This virus had 100% similarity to other Zika virus circulating in humans in South America. This was the first report on Zika virus detection among neotropical primates, which indicated the possibility that they could act as reservoirs.

Meanwhile, on April 13, 2016, the CDC issued a report, published online in the New England Journal of Medicine,[54] confirming the causal link between Zika virus infection during pregnancy and microcephaly in light of multiple epidemiologic studies and isolation of Zika virus in fetal brain tissue and amniotic fluid. On the basis of a review of the available evidence and using two sets of criteria (the Shepard criteria for proof of teratogenicity in humans and the Bradford-Hill criteria for causality), this article concluded that[54]:

[S]ufficient evidence has accumulated to infer a causal relationship between prenatal Zika virus infection and microcephaly and other severe brain anomalies. Also supportive of a causal relationship is the absence of an alternative explanation; despite the extensive consideration of possible causes, researchers have been unable to identify alternative hypotheses that could explain the increase in cases of microcephaly that were observed first in Brazil and then retrospectively in French Polynesia, and now in preliminary reports that are being investigated in Colombia.

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