Chapter 4 Travel-Related Infectious Diseases
J. Erin Staples, Stacey W. Martin, Marc Fischer
Zika virus is a single-stranded RNA virus of the Flaviviridae family, genus Flavivirus.
Transmission occurs through the bite of an infected Aedes species mosquito. Intrauterine, perinatal, sexual, laboratory, and possible transfusion-associated transmission have been reported. Zika virus has been detected in human milk, but the risk of transmission through breastfeeding is unknown.
Zika virus was first identified in Uganda in 1947. Before 2007, only sporadic human cases were reported from countries in Africa and Asia. In 2007, the first documented Zika virus disease outbreak was reported in the Federated States of Micronesia. Subsequent outbreaks of Zika virus disease occurred in countries in Southeast Asia and the Western Pacific.
Zika virus was identified for the first time in the Western hemisphere in 2015, with large outbreaks in Brazil. The virus then spread throughout much of the Americas, with 48 countries and territories reporting local transmission. In 2016, large outbreaks occurred in the Caribbean (Puerto Rico and the US Virgin Islands), and limited local transmission was identified in the mainland United States (parts of Florida and Texas). Since then, the number of reported Zika virus disease cases in the Americas has declined in all regions, though there have been occasional increases in reporting from some countries. Current information on Zika virus transmission and travel guidance can be found at wwwnc.cdc.gov/travel/page/zika-travel-information.
Most Zika virus infections are asymptomatic. Symptomatic infections are generally mild. Commonly reported signs and symptoms include fever, maculopapular rash, arthralgia, and nonpurulent conjunctivitis. Other symptoms include myalgia, headache, edema, vomiting, retroorbital pain, and lymphadenopathy. Severe disease requiring hospitalization and deaths are uncommon. However, Guillain-Barré syndrome and rare reports of encephalopathy, meningoencephalitis, myelitis, uveitis, and severe thrombocytopenia have been associated with Zika virus infection.
Vertical transmission of the virus leads to congenital Zika virus infection; sequelae include microcephaly with brain anomalies (and other serious neurologic consequences) and fetal loss. The full range of functional disabilities caused by congenital Zika virus infection is not yet known. Short-term follow-up studies of young children with postnatal Zika virus infections have not identified neurodevelopmental problems; longer-term studies are needed, especially among infants infected during the neonatal period.
Zika virus infection should be considered in patients with acute onset of fever, maculopapular rash, arthralgia, or conjunctivitis who in the two weeks preceding illness onset lived in or traveled to areas with ongoing Zika virus transmission or had sex with someone who lives in or traveled to those areas. However, since Zika and dengue virus infections have similar clinical presentations and global distribution, patients should be evaluated for evidence of these infections based on the most recent epidemiology. As of early 2020, dengue virus outbreaks were occurring in many areas of the world, whereas low to no Zika virus transmission was being reported globally. Zika virus testing guidance is updated as needed to address changes in the global epidemiology of these viruses. While this chapter provides a basic overview of Zika virus diagnostic testing, readers should refer to the CDC website for current Zika virus testing recommendations (www.cdc.gov/zika/hc-providers/testing-guidance.html). In addition to dengue, other considerations in the differential diagnosis for Zika virus disease include chikungunya, malaria, rubella, measles, parvovirus, adenovirus, enterovirus, leptospirosis, rickettsiosis, and group A streptococcal infections.
Nucleic acid amplification testing (NAAT) is used to detect Zika viral ribonucleic acid (RNA) and can be performed on serum, whole blood, urine, cerebrospinal fluid, amniotic fluid, semen, and tissues. However, because Zika virus RNA may be detectable for only a relatively short time, a negative NAAT does not exclude recent Zika virus infection. Serologic testing can detect Zika virus-specific IgM antibodies in serum that typically develop toward the end of the first week of illness and may remain detectable for months to years following infection, making the determination of the timing of infection difficult. False-positive IgM antibody test results also can occur because of nonspecific reactivity or cross-reactivity with other flaviviruses, especially dengue virus. Plaque reduction neutralization testing (PRNT) can be used to discriminate between cross-reacting antibodies in primary flavivirus infections, although neutralizing antibodies might still yield cross-reactive results in people previously infected with or vaccinated against a related flavivirus (secondary flavivirus infection).
Most state health departments and many commercial laboratories perform Zika virus NAAT and IgM testing. Confirmatory neutralizing antibody testing is available at CDC’s Arboviral Diagnostic Reference Laboratory. Health care providers are encouraged to report suspected cases of Zika virus infection to their state or local health departments to facilitate diagnosis and mitigate the risk of local transmission in areas where Aedes species mosquitoes are active. Zika virus disease is a nationally notifiable condition. State health departments should report laboratory-confirmed cases to CDC according to the Council of State and Territorial Epidemiologists case definitions (wwwn.cdc.gov/nndss/conditions/zika/).
No specific antiviral treatment is available for Zika virus disease. Treatment is generally supportive and can include rest, fluids, and use of analgesics and antipyretics. Because aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) can increase the risk of hemorrhage in patients with dengue, avoid use of these medications until dengue can be ruled out. People infected with Zika, dengue, or chikungunya virus should be protected from further mosquito exposure during the first week of illness to decrease the possibility of local transmission. Carefully evaluate pregnant women with laboratory evidence of Zika virus infection; closely manage these cases for possible adverse pregnancy outcomes. Guidance for the diagnosis, evaluation, and management of infants with possible congenital Zika virus infections is available at www.cdc.gov/pregnancy/zika/testing-follow-up/evaluation-testing.html.
No vaccine or preventive drug is available. However, several candidate vaccines are in various stages of development. All travelers to areas with Zika virus transmission should take steps to avoid mosquito bites to prevent the risk of Zika virus and other vectorborne infections (see Chapter 3, Mosquitoes, Ticks & Other Arthropods). Persons with possible Zika virus exposure who want to reduce their risk for sexual transmission of Zika virus to an uninfected partner should use condoms or abstain from sex. Blood donations in the United States are now routinely screened for Zika virus RNA to reduce the risk of transfusion-associated transmission.
Pregnant women should avoid travel to any area with risk of Zika virus transmission. Pregnant women who travel to one of these areas should talk to their health care provider before traveling and strictly follow steps to avoid mosquito bites or sexual transmission during travel. There is no restriction on the use of insect repellents by pregnant women if used in accordance with the instructions on the product label. Male partners of pregnant women who travel to areas with risk of Zika virus transmission should abstain from sex or use condoms for the duration of the pregnancy to avoid sexual transmission to their pregnant partners. Women and their partners who are trying to become—or who are interested in becoming—pregnant should take steps to protect themselves from Zika virus infection. Mothers are encouraged to breastfeed infants even after possible Zika virus exposure, as available evidence indicates the benefits of breastfeeding outweigh the theoretical risks associated with Zika virus infection transmission through breast milk.
CDC website: www.cdc.gov/zika
- Adebanjo T, Godfred-Cato S, Viens L, Fischer M, Staples JE, Kuhnert-Tallman W, et al. Update: interim guidance for the diagnosis, evaluation, and management of infants with possible congenital Zika virus infection—United States, October 2017. MMWR Morb Mortal Wkly Rep. 2017;66(41):1089–99.
- Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med. 2009 Jun 11; 360(24):2536–43.
- Gregory CJ, Oduyebo T, Brault AC, Brooks JT, Chung KW, Hills S, et al. Modes of transmission of Zika virus. J Infect Dis. 2017;216(10):S875–83.
- Hall V, Walker WL, Lindsey NP, Lehman JA, Kolsin J, Landry K, et al. Update: noncongenital Zika virus disease cases—50 U.S. states and the District of Columbia, 2016. MMWR Morb Mortal Wkly Rep. 2018;67(9):265–9.
- Hills SL, Fischer M, Petersen LR. Epidemiology of Zika virus infection. J Infect Disease. 2017;216(10):S868–74.
- Krow-Lucal ER, de Andrade MR, Abath Cananéa JN, Staples JE, Coelho GE. Association and birth prevalence of microcephaly attributable to Zika virus infection among infants in Paraíba, Brazil, in 2015–16: a case-control study. Lancet Child Adol Health. 2018;2(3)205–13.
- McArthur MA. Zika virus: Recent advances towards the development of vaccines and therapeutics. Viruses. 2017;9(6):143.
- Oduyebo T, Polen KD, Walke HT, Reagan-Steiner S, Lathrop E, Rabe IB, et al. Update: interim guidance for health care providers caring for pregnant women with possible Zika virus exposure—United States (including U.S. territories), July 2017. MMWR Morb Mortal Wkly Rep. 2017;66(29):781–93.
- Petersen LR, Jamieson DJ, Powers AM, Honein MA. Zika Virus. N Engl J Med. 2016 Apr 21; 374(16):1552–63.
- Reynolds, MR, Jones AM, Petersen EE, Lee EH, Rice ME, Bingham A, et al. Vital signs: update on Zika virus–associated birth defects and evaluation of all U.S. infants with congenital Zika virus exposure—U.S. Zika Pregnancy Registry, 2016. MMWR Morb Mortal Wkly Rep. 2017;66(13):366–73.