The Zika Virus and Microcephaly

Zika virus is an arthropod-borne flavivirus discovered in Africa in 1947. When infected by the virus, most persons are asymptomatic or demonstrate generally mild, self-limited illness characterized by fever, rash, arthralgia, and conjunctivitis. The first widespread outbreak of the Zika virus was recognized on Yap Island, Federated States of Micronesia, in 2007, followed by outbreaks in Southeast Asia and the Western Pacific, including a large outbreak in French Polynesia in 2013-14.

Since the identification of the Zika virus infection in Brazil in May, 2015, the virus has spread rapidly throughout the Americas, and as of February 2016, thirty-one countries and territories had reported cases.

A bite of the Aedes aegypti mosquito is the main route of exposure, but sexual, maternal-fetal, and intrapartum transmission have all been documented. To date, all cases reported in the continental United States have been travel-associated, whereas in the U.S. territories (American Samoa, Puerto Rico, and U.S. Virgin Islands), the vast majority of cases have been locally acquired vector-borne.

Although infection with the Zika virus generally leads to mild disease, its emergence in the Americas has coincided with a marked increase in babies being born with microcephaly, a neurological disorder present at birth and defined as head circumference at least 2 SD smaller than the mean for sex, age, and ethnicity and with head circumference at least 3 SD smaller being deemed severe. Congenital microcephaly is a condition associated with a reduction in brain volume and is often caused by genetic or environmental factors that affect fetal brain development.

Prenatal viral infections, such as rubella and cytomegalovirus, hypertensive disorders, and maternal alcohol have also been associated with the condition. Cases have been reported after intrauterine infection with West Nile virus (also a flavivirus) and Chikungunya virus. Given the widespread nature of the Zika virus epidemic in the Americas, the temporally associated increase in microcephaly cases in Brazil, and the retrospective findings of a cluster of microcephaly and neurologic disorders associated with the Zika virus in French Polynesia, the WHO declared Zika virus a Public Health Emergency of International Concern on February 1, 2016.

In order to reduce the risk of microcephaly, recommendations included avoidance of travel to affected countries by pregnant and childbearing aged women, use of condoms with partners returning from affected countries, and pregnancy delay.

In order to better quantify the risk of microcephaly associated with the Zika virus infection, a retrospective study based on data from the completed Zika virus outbreak in French Polynesia in 2013-14 was reported in The Lancet by Simon Cauchemez, PhD, and colleagues from the Institut Pasteur.

Based on four datasets providing information on all cases of microcephaly, weekly number of consultations for suspected Zika infection, seroprevalence for Zika virus antibodies, and the number of births during the outbreak, the researchers developed a mathematical and statistical model to illustrate the association between the Zika virus and microcephaly and demonstrated the risk for microcephaly to be greatest during the first trimester of pregnancy.

According to the analysis, it is estimated that the risk for microcephaly for mothers with the Zika virus infection during the first trimester is about 1%. Although the risk appears low compared to other intrauterine viral infections (e.g., rubella, cytomegalovirus), the incidence of the Zika virus infection is very high during outbreaks (eg, 66% in French Polynesia and 73% in the island of Yap). Therefore, despite the relatively low fetal risk, infection with the Zika virus is an extremely important public health matter.