Zika: The Expanding and Deepening Threat

Marc Gozlan, MD

Disclosures

November 14, 2016

At the same time, after consideration of the available scientific evidence, the FDA issued a revised guidance recommending universal testing of individual units of donated whole blood and blood components for Zika virus in all states and US territories.[97]

On August 31, 2016, a new analysis[98] based on data from seven countries (Bahia State, Brazil; Colombia; the Dominican Republic; El Salvador; Honduras; Suriname; and Venezuela) found a strong link between Zika infection and GBS. It showed that changes in the reported incidence of Zika virus disease during 2015 and early 2016 were closely associated with changes in the incidence of GBS. Indeed, when the incidence of Zika disease increased, so did the incidence of GBS. Moreover, in the six countries that reported decreases in the incidence of Zika disease, the incidence of GBS also declined. Because Zika virus and dengue virus co-circulate in these regions, the researchers explored, but did not find, a link between dengue infection and the incidence of GBS.[98]

Although women had a 75% higher incidence rate of Zika disease than men, especially those aged between 20 and 49 years, the incidence of GBS was 28% higher among men than among women. The researchers found an increase in the incidence of GBS that was 2.0 times higher than baseline in El Salvador and 9.8 times higher in Venezuela.[98] This imposes a substantial burden on populations and health services in this region of Latin and Central America.

September 2016

Early September 2016. On September 2, 2016, in an advance online article in Nature Medicine,[99] US researchers reported for the first time the development of fetal brain lesions after subcutaneous Zika virus inoculation in a pregnant pigtail macaque at 119 days of gestation, which corresponded to about 28 weeks of human pregnancy. Using ultrasound, MRI, detection of Zika virus RNA in the fetus, and histopathology, they noted arrested fetal brain growth and viral neuroinvasion—findings consistent with the congenital Zika syndrome seen in humans.[99] In particular, the authors noted that the marked lag in fetal biparietal diameter growth observed on ultrasound reflects the arrest of white-matter expansion detected by MRI, adding that a similar arrest in biparietal diameter has been reported in human pregnancy with presumed Zika virus infection in the third trimester.[99]

On September 6, 2016, WHO updated its recommendationspublished precisely 3 months earlier (on June 7)[78] on the prevention of sexual transmission of Zika virus, because it appeared that sexual transmission of Zika virus was possible and more common than previously assumed. On the basis of new epidemiologic data, WHO recommended that the length of time that asymptomatic males returning from areas with active Zika virus transmission should follow safer-sex practices be extended from 8 weeks to 6 months—the same duration that was recommended for symptomatic males.[79] The same day, signs of congenital brain injury due to Zika virus acquired in the third pregnancy trimester were reported for the first time by Brazilian researchers.[100]

... signs of congenital brain injury due to Zika virus acquired in the third pregnancy trimester were reported for the first time.

On September 7, 2016, WHO published an update of the evidence for a causal link to congenital brain abnormalities and GBS.[101] The panel of experts concluded that the most likely explanation for available evidence from outbreaks of Zika virus infection and clusters of microcephaly was Zika virus infection during pregnancy, and also that Zika virus infection was a trigger of GBS. The expert panel recognized that Zika virus alone may not be sufficient to cause either congenital brain abnormalities or GBS. It was not known whether these effects depended on as yet uncharacterized cofactors being present. Nor was it known whether dengue virus played a part; dengue virus is carried by the same species of mosquito and has circulated in many countries during the same period.[101]

On September 15, 2016, less than 2 weeks after the report of a study describing the consequences on fetal brain of inoculation of Zika virus in a pregnant macaque, Brazilian researchers reported the preliminary results of the first study to examine the association between microcephaly and in utero Zika virus infection in cases and controls at the time of birth.[102]

Mid- to late September 2016. This ongoing prospective case/control study aims to include 200 cases and 400 controls. It is taking place in Recife, Pernambuco State—the hotspot of the microcephaly epidemic in Brazil. The results show that 80% of mothers (24 of 30 cases) of neonates with microcephaly had Zika virus infection, compared with 64% (39 of 61) of mothers of controls. Thus, this study—the first to estimate the seroprevalence of Zika virus infection in pregnant women in an epidemic area in Brazil—indicates a high frequency of Zika virus infection also among mothers of live neonates without microcephaly, brain abnormalities, or major birth defects.

This high level of seroprevalence reflects the rapid spread of Zika virus in this region. Among the neonates with microcephaly, 41% (13 of 32 cases) had Zika virus infection confirmed by RT-PCR on serum samples, compared with none of the 62 controls tested.[102] These preliminary results reinforce once again the association between microcephaly and Zika virus infection during pregnancy, although the authors note that their ongoing study may identify possible cofactors. As of September 17, 2016, Brazil had confirmed 1949 cases of microcephaly linked to Zika virus, mostly concentrated in the country's northeast region, with another 3030 cases under investigation.

WHO declared that 71 countries and territories have reported evidence of mosquito-borne Zika virus transmission since 2015.

On September 29, 2016, WHO declared that 71 countries and territories have reported evidence of mosquito-borne Zika virus transmission since 2015.[103] In total, 21 countries or territories have reported microcephaly and other CNS malformations potentially associated with Zika virus infection or suggestive of congenital Zika virus infection. Four of these 21 countries have reported microcephalic babies born to mothers in countries with no endemic Zika virus transmission but who reported recent travel history to Zika-affected countries. Moreover, 18 countries and territories have reported an increased incidence of GBS or cases of GBS associated with Zika virus.[103]

On September 30, 2016, once again the CDC expanded its recommendation for men potentially exposed to Zika virus when a couple is trying to conceive,[104] in line with new scientific evidence and recently updated WHO guidance.[79] For men, the amount of time to use a condom or not have sex was increased to at least 6 months after the last possible exposure.

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