Zika: The Expanding and Deepening Threat

Marc Gozlan, MD

Disclosures

November 14, 2016

August 2016

Early August 2016. On August 3, 2016, the National Institutes of Health announced that they had launched a clinical trial of a Zika virus investigational DNA vaccine intended to prevent the infection. Initial safety and immunogenicity data from this phase 1 trial in 80 healthy adults are expected by January 2017.

On August 4, 2016, California reported that two babies had been born with Zika-related microcephaly. Meanwhile, on August 9, Texas reported its first fatal Zika-linked microcephaly case, and Florida said that the total number of locally transmitted Zika cases in Miami stood at 21.

On August 10, 2016, a Brazilian study[90] provided details of an association between congenital Zika virus infection and arthrogryposis. This condition had already been described a few months earlier in two studies of newborns with congenital Zika virus infection,[13,30] but not in detail. In a series of seven children, arthrogryposis was found in the arms and legs of six children (86%) and the legs of one child (14%). The authors suggested two possible mechanisms: tropism of Zika virus for the neurons or neural progenitor cells, with involvement of peripheral motor neurons and central motor neurons, or embryonic vascular disorders.[90]

As of August 10, 2016, there were 6587 Zika cases in US territories—an increase of 1039 cases from the previous week. The United States had 1962 cases, 137 more in just 1 week. The CDC reported 15 live-born infants with birth defects and six pregnancy losses with birth defects and laboratory evidence of Zika virus infection.[91]

Meanwhile, 66 countries and territories had reported evidence of mosquito-borne Zika virus transmission since 2015, including 52 with a first reported outbreak from 2015 onward.[91] On August 12, 2016, a public health emergency in response to the Zika outbreak was declared in Puerto Rico (Figure 7).

Figure 7. Global spread of Zika virus, 2013-2016.[93] Courtesy of the World Health Organization.

In other research developments, an article showed that Zika virus can infect adult murine neural progenitor cells in mice, leading to cell death and reduced proliferation.[92] Even though it was yet to be determined whether the death of these adult neural progenitor cell populations has any long-term effects in the rodents, this study raised the question of what the repercussions would be on neurogenesis in infected human adults. These mouse experiments suggested that Zika virus neuropathology may not be limited to developing fetuses.[92]

Mid- to late August 2016. At the same time, on August 17, 2016, a report from Brazil, published online in the New England Journal of Medicine[93] described two cases of likely Zika virus transmission by blood transfusion from one infected person who donated platelets by apheresis while asymptomatic. Although neither patient was found to be positive for Zika virus on PCR assay or reported symptoms associated with Zika virus infection, this was evidence for Zika virus transmission by means of blood transfusion.

The potential for transmission in transfused donated blood components is obviously a concern, owing to the detection of Zika viremia in healthy blood donors. Indeed, in March 2016, Brazilian health officials had confirmed the first two cases of transmission of Zika virus through blood transfusions, and in June 2016, testing in Puerto Rico showed evidence of Zika virus in 1.1% of blood donations.[79]

On August 11, 2016, Italian researchers report the Zika virus RNA detection in semen 188 days (6 months) after the onset of symptoms[94]

On August 26, 2016, a CDC early report, posted online,[95] documented a second case of sexually transmitted Zika virus from an asymptomatic man, returning from an Zika-endemic area (the Dominican Republic), to his nontraveling female partner. The couple had condomless sex on two occasions, the second including fellatio, 10 days and 14 days after the man's return. Two days after the episodes of condomless vaginal intercourse and 6 days after the second sexual encounter, the woman developed symptoms of Zika virus infection.[95]

It appeared that knowledge about the maximum delay for possible sexual transmission from the time of infection owing to long persistence of the virus in semen, as well as knowledge of possible transmission from asymptomatic infected individuals, were of great interest for public health in terms of establishing control measures.

In other key developments about sexual transmission of Zika virus, US researchers published findings on the viral replication and disease consequences after vaginal infection of pregnant mice with Zika virus.[96] They reported that Zika virus replicates within the genital mucosa and persists in the vaginal mucosa (up to 4-5 days). Moreover, this study showed that vaginal Zika virus infection of pregnant mice leads to fetal brain infection.

These results highlighted the vaginal tract as a highly susceptible site for Zika virus replication and were consistent with the report of sexual transmission from an infected female.[84] So far, said the authors, it is not known whether sexual transmission of Zika virus poses a different risk for birth defects than mosquito-borne transmission in pregnant women. However, these experimental results in mice hinted at negative consequences on fetal development after vaginal Zika virus exposure during early pregnancy.[96]

In other developments, a phase 1 clinical trial of a candidate Zika DNA vaccine was launched by Inovio Pharmaceuticals in Puerto Rico.

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