Zika Virus: A Potentially New Old Threat?

The recent recognition of birth defects like microcephaly and intracranial calcifications in some offspring of women infected during pregnancy with the mosquito-borne flavivirus Zika virus has prompted recommendations and guidelines for managing pregnant women and their infants from the CDC, World Health Organization (WHO), and the European Centre for Disease Prevention and Control. ^1-3 This relationship may yet prove circumstantial but should be taken seriously.

For me, one of the strongest attractions of infectious diseases as a specialty is the steady emergence or re-emergence of interesting and challenging infectious agents. Zika, the most recent in a very long list of such agents, was first discovered in 1947 (almost 70 years ago!) in the Zika Forest of Uganda near Lake Victoria, and it has only very recently been recognized as a potentially important human pathogen in the Western Hemisphere.⁴

Zika is another mosquito-borne single-stranded RNA flavivirus, like yellow fever, dengue, St. Louis encephalitis virus, West Nile, and Japanese encephalitis virus.  

The full extent of Zika infections in any country is incompletely known because of the limited availability of testing reagents in areas of apparent endemicity in Central and South America. However, dramatically increased numbers of infants with microcephaly and/or intracranial calcifications in Brazil, Ecuador, and elsewhere have coincided with sharp increases in Zika infections. 

Apparently about 80% of human Zika virus infections are asymptomatic; symptomatic individuals have non-specific features like fever, maculopapular rash, arthralgias and non-purulent conjunctivitis lasting up to 7 days,¹ making accurate clinical diagnoses very difficult. Preliminary Brazilian data suggest a possible causal relationship with Zika in one-third to one-quarter of affected infants .

Known vectors of Zika, Aedes aegypti and possibly Ae. albopictus , are found throughout much of the Western Hemisphere, and Zika transmission thus mirrors dengue and chikungunya.  

Officials with the WHO have, as of Feb. 1, declared Zika a “global health emergency,” and have predicted a likely spread of Zika virus to all Western Hemisphere countries except Canada and Chile. They have recommended travel restrictions during pregnancy. For a completely updated list of affected countries/regions, clinicians can visit: http://www.cdc.gov/zika/geo/index.html.

Although Zika cases have been identified in the United States, including in Florida and Illinois, to date it has only been noted in travelers from known endemic areas, especially Brazil.¹ As with dengue and chikungunya, that Ae. aegypti  and Ae. albopictus are in the United States raises concern about autochthonous transmission here.

The CDC and some state health departments perform Zika testing (RT-PCR, IgM ELISA, and a highly specific plaque reduction test), but no commercial tests are available. The CDC Interim Guidelines provide very detailed guidance to practitioners regarding which infants should be tested: 1) those with microcephaly or intracranial calcifications whose mothers traveled to or lived in an area with Zika transmission during pregnancy, and 2) those with or without microcephaly or intracranial calcifications whose mothers have a travel history and positive or inconclusive Zika testing results.¹

Prevention of Zika infection in pregnancy relies upon the usual mosquito control measures (wearing long sleeves and pants, using repellents, especially DEET, avoiding areas with known Zika transmission, using screened windows and doors, and air conditioning). Some high-risk countries have recently urged women to avoid pregnancy for the next 2 years (El Salvador)⁵ or delaying pregnancy for the next 2 years (Colombia and Ecuador).

Future control measures for Zika and other Ae. aegypti-transmitted infections may result from current innovative studies.⁶ The United Kingdom-based firm Oxitec has developed genetically-modified male Ae. aegypti that cannot produce viable offspring. Females mating with bioengineered males lay eggs that hatch, but the larvae cannot survive to maturity. In early studies in Brazil, an 82% to 90% reduction in wild Ae. aegypti populations was achieved in field trials. This technology could greatly reduce dengue and chikungunya as well as Zika infections if larger trials show similar efficacy.

References

1. Staples J, Dziuban E, Fischer M et al. Interim Guidelines for the Evaluation and Testing of Infants with Possible Congenital Zika Virus Infection — United States, 2016.Morb Mortal Wkly Rep. 2016;65(3):1-5. doi:10.15585/mmwr.mm6503e3er.
2. European Centre for Disease Prevention and Control. Rapid Risk Assessment: Zika Virus Epidemic in the Americas: Potential Association with Microcephaly and Guillain-Barre Syndrome. Stockholm, Sweden; http://ecdc.europa.eu/en/publications/Publications/zika-virus-americas-association-with-microcephaly-rapid-risk-assessment.pdf
3. Zika Virus Infection-Brazil and Colombia. WHO website. http://www.who.int/csr/don/21-october-2015-zika/en. October 25, 2015. Accessed January 29, 2016. 
4. Haddow AD, Schuh AJ, Yasuda CY, et al: Genetic Characteristics of Zika Virus Strains. PLoS Negl Trop Dis. 2012;6(2):e1477.
5. Ahmed A. El Salvador’s Advice on Zika Virus: ‘Don’t Have Babies’. New York Times. January 25, 2016. http://www.nytimes.com/2016/01/26/world/americas/el-salvadors-advice-on-zika-dont-have-babies.html. Accessed January 29, 2016.
6. Enserink M. An Obscure Mosquito-Borne Disease Goes Global. Science. 2015;350(6264):1012-1013.