Zika: The Expanding and Deepening Threat

Marc Gozlan, MD


November 14, 2016

February 5, 2016. The same day that the CDC released updated guidelines, WHO reported in its periodic Zika situation report that a "causal relationship between Zika infection during pregnancy and microcephaly was strongly suspected, though not yet scientifically proven."[6] The total number of countries and territories reporting autochthonous transmission of Zika virus had reached 33, meaning that the geographic distribution of Zika virus had steadily increased since its first detection in Brazil in 2015. Moreover, seven countries reported an increase in the incidence of cases of microcephaly or GBS concomitantly with a Zika virus outbreak.

February 3, 2016. Meanwhile, local health authorities in Brazil reported the first two cases of Zika infection from blood transfusions in Sao Paulo state. The first was in a male liver-transplant recipient who received a blood transfusion in March 2015. The second involved a male gunshot victim who received several transfusions in April 2015. Moreover, a study[7] published in April 2014 showed that in French Polynesia, 3% of samples contained detectable Zika virus RNA during the outbreak, even though the donors were asymptomatic at the time of blood donation from November 21, 2013, to February 17, 2014—indicating the likelihood of transmission by blood transfusion.[8,9,10]

... the geographic distribution of Zika virus had steadily increased since its first detection in Brazil in 2015.

As a safety measure, the US Food and Drug Administration (FDA) issued recommendations for donor screening, donor deferral, and product management to reduce the risk for transfusion-transmitted Zika virus in the United States and its territories.[11] In addition to behavioral- and health-risk questionnaires for blood donors in all areas, the FDA recommended deferrals for donors in unaffected areas who had recently lived in or visited an area with active mosquito-borne transmission of Zika virus.

February 5, 2016. The WHO specified in its Zika situation report that of the 76 reported deaths due to congenital malformations, Zika virus was identified in fetal tissues of five cases, all from northeastern Brazil.[6] This serious situation raised legitimate and understandable concerns among Brazilian women, especially those who were pregnant or considering becoming pregnant. But the WHO emphasized that although the microcephaly cases in Brazil were spatiotemporally associated with the Zika outbreak, more robust investigations and research were needed to better understand this potential link.

At that time, Brazilian health authorities had reported some adverse pregnancy outcomes and congenital central nervous system (CNS) malformations with laboratory confirmation of Zika virus in amniotic fluid, placenta, or fetal tissues.[12,13] The evidence for a causal link between Zika virus infections during pregnancy and congenital CNS malformations was pretty substantial, but the available information was not yet sufficient to scientifically confirm it.

In fact, on February 9, 2016, a report published in MMWR[14] by Brazilian researchers described evidence of a link between Zika virus infection and microcephaly in two congenitally infected newborns and two fetal losses. The authors reported the detection of Zika virus RNA and antigens in brain tissue from infants with microcephaly and in placental tissue from early miscarriages. Histopathologic findings indicated the presence of Zika virus in fetal tissue.[14]

February 16, 2016. The FDA announced the availability of an investigational test to screen blood donations for Zika virus and recommended that areas with active transmission of Zika virus obtain whole blood and blood components from areas without active transmission of Zika virus.[11] As a result of this new guidance, local blood collection in Puerto Rico was suspended. This US territory was identified as an area of active Zika transmission, and health experts expected many thousands of residents to become infected when mosquito season reached its peak the following summer.

No autochthonous Zika virus transmission had yet been reported in the European Union. However, in 2015 and 2016, ministries of health, quoted by the media, reported that several European countries (Austria, Denmark, Finland, France, Germany, Ireland, Italy, Portugal, The Netherlands, Spain, Sweden, United Kingdom) had seen imported cases in persons who had recently traveled to affected countries. In Europe, outside the European Union, Switzerland also reported imported cases.[15]

The European Centre for Disease Prevention and Control (ECDC) said that pregnant women and those who were planning to become pregnant and were intending travel to affected areas should discuss their travel plans and evaluate the risk with their healthcare providers, and consider postponing their travel.


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