Zika Virus in the Americas: An Obscure Arbovirus Comes Calling

The explosive spread of Zika virus (ZIKV) in the Americas, which follows closely on the chikungunya virus (CHIKV) pandemic that began in 2013, once again underscores the challenges posed by emerging arthropod-borne viruses (arboviruses) in a time of rapid globalization.¹ The Zika virus, which was first isolated in 1947 from a sentinel monkey in the Zika forest of Uganda, is a flavivirus that is related to dengue virus (DENV), yellow fever virus, West Nile virus, and Japanese encephalitis virus. Like DENV, yellow fever virus, and CHIKV (an alphavirus), ZIKV is transmitted by the bite of an infected female mosquito, most notably Aedes aegypti, an invasive, anthropophilic species that is well adapted to urban environments.¹

Until recently, ZIKV was confined to Africa and southeast Asia, where it caused only sporadic infections in humans. This changed in 2007 when ZIKV caused an epidemic in the Yap Islands in the Federated States of Micronesia.^1,2 Although nearly three-fourths of the Yap population was infected, there were no ZIKV-associated hospitalizations or deaths. The next ZIKV epidemic occurred in French Polynesia during 2013 through 2014.^1,2 An estimated 11% of the population was infected. Approximately 80% of the infections were asymptomatic. The majority of those who had clinical symptoms of ZIKV infection presented with mild disease that was characterized by low-grade fever, a maculopapular eruption spreading from the face to the trunk and extremities, arthralgia, and conjunctivitis. However, 41 patients who had serologically confirmed ZIKV infection developed Guillain-Barré syndrome (GBS), an autoimmune condition that results in acute or subacute flaccid paralysis. Although GBS had been observed previously in patients who were infected with other arboviruses (eg, DENV and CHIKV), this was the first time that GBS was associated with ZIKV infection.²

Since 2014, ZIKV has caused multiple outbreaks in several South Pacific islands including Chile’s Easter Island. In early 2015, the health departments of several states in northeast Brazil reported clusters of patients who presented with a maculopapular eruption with or without fever and with or without headache, joint swelling, and muscle pain.^1,2 In May 2015, Brazil’s Ministry of Health announced that ZIKV was circulating in the country. Reports emerged in late 2015 of a sharp increase (ie, approximately 20-fold) in the number of infants born with microcephaly in the ZIKV-affected areas of Brazil. This observation raised international alarm because microcephaly, a condition in which the brain is underdeveloped, had not previously been associated with flavivirus infection. Although studies are ongoing, accumulating clinical and epidemiological data suggest a causal role for ZIKV in the development of microcephaly in the infants who were infected in utero.^1,2

The Zika virus has continued to spread via viremic travelers to multiple countries throughout Latin America and the Caribbean. Infection of A aegypti mosquito populations has resulted in autochthonous transmission of ZIKV, which is fueled by an abundance of the vector coupled with large numbers of susceptible humans who live in densely populated, urban centers with poor sanitary conditions. On February 1, 2016, the World Health Organization declared that the rapid spread of ZIKV in the Americas and the increasing reports of cases of congenital malformations and neurological complications in ZIKV-affected areas constitute a “public health emergency of international concern.”³ The World Health Organization called for a coordinated effort to improve surveillance of ZIKV infection and its complications, to accelerate the development of vaccines and diagnostic tests, and to intensify mosquito control efforts.

Because ZIKV infection can cause a variable clinical syndrome ranging from no symptoms to symptoms that are similar to those of DENV and CHIKV infection, surveillance based on clinical criteria can be misleading.^1,2 A nucleic acid amplification assay, the reverse transcriptase–polymerase chain reaction, can differentiate ZIKV from other flaviviruses and CHIKV, but this assay has low sensitivity with serum samples because the period of viremia is short (ie, 1-5 days after the onset of symptoms). Although serologic analysis is typically the mainstay of viral surveillance, the interpretation of available diagnostic tests for ZIKV can pose problems due to the presence of cross-reactive antibodies to other flaviviruses, particularly DENV, that develop following infection or vaccination.^1,2 Because of the need for better diagnostic tests, Chembio Diagnostics and Bio-Manguinhos/Fiocruz (Oswaldo Cruz Foundation, Brazil) have partnered to produce a rapid, point-of-care (POC) assay to specifically detect IgM and IgG antibodies to ZIKV and a multiplex POC assay to simultaneously detect antibodies to ZIKV, DENV, and CHIKV.⁴ The multiplex POC assay could be of particular utility in areas where these arboviruses cocirculate.

At present, vaccines to prevent ZIKV infection and antiviral agents to treat infection are not available.^1,2 Thus, control efforts must focus on the mosquito vector and on education of the public, particularly pregnant women and those of reproductive age, to avoid mosquito bites and to use safe sexual practices to prevent ZIKV infection. Resistance of mosquitoes to insecticides and the logistics of identifying and eliminating mosquito breeding sites in large urban centers present challenges to mosquito control. Novel approaches such as the release of genetically modified mosquitoes to reduce local populations of A aegypti are being explored and could decrease the transmission of ZIKV and perhaps some other arboviruses.^2,5 However, the possibility that additional mosquito species, such as Aedes albopictus, could act as vectors for ZIKV warrants additional consideration for the design of vector control strategies.^1,6

Zika virus disease and ZIKV congenital infection are now nationally notifiable conditions in the United States. Clinicians are encouraged to report suspected ZIKV cases to their state or local health department to facilitate diagnosis and to mitigate autochthonous transmission. Travel-associated cases of ZIKV have been documented in the United States, but as of April 6, 2016, autochthonous transmission has only been reported for the US territories of Puerto Rico, the US Virgin Islands, and American Samoa.⁷ Although relatively rare, sexual transmission of ZIKV (ie, from an infected male to female partner) has been described in the United States and some other countries.⁸

According to the Centers for Disease Control and Prevention, the risk of a widespread ZIKV outbreak in the United States remains minimal. Nonetheless, Bogoch et al⁹ estimated that more than 192 million individuals reside in areas of the United States that are conducive to seasonal transmission of ZIKV and nearly 23 million individuals reside in areas that are conducive to year-round transmission. Fortunately, the “built environment” that is present in much of the United States affords substantial protection against mosquitoes. However, some areas of the US-Mexico border region from Texas to California are predicted to be at high risk for autochthonous transmission of ZIKV.¹⁰ This is because of the potential for the introduction of ZIKV due to the influx of travelers from ZIKV-affected regions, the high percentage of low-income residents who live and/or work in conditions that allow frequent exposure to mosquitoes, and the climate, which can sustain the A aegypti vector virtually year-round. Until a vaccine becomes available, effective mosquito control, education of health care professionals and the public, and enhanced surveillance to detect and monitor early infection and to ensure safety of the blood supply will be key to mitigating the impact of ZIKV on the health of the US population. Hopefully, what we learn while confronting ZIKV will be of benefit when the next obscure arbovirus comes calling.

Corresponding Author: Lola V. Stamm, PhD, University of North Carolina at Chapel Hill, Gillings School of Global Public Health, Department of Epidemiology, Program in Infectious Diseases, 3302 Hooker Research Center, S Columbia St, Chapel Hill, NC 27599-7435 (lstamm@email.unc.edu).

Published Online: May 11, 2016. doi:10.1001/jamadermatol.2016.1499.

Conflict of Interest Disclosures: None reported.