Approach Considerations
Zika virus (ZIKV) infection usually is mild and self-limited. There are no specific FDA-approved treatment options or vaccines for treatment and prevention of Zika virus infection. [18]
Medical Care
Supportive care with rest and adequate fluid hydration is advised. Symptoms such as fever and pain can be controlled with acetaminophen and pruritic rash with antihistamines. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with unconfirmed Zika virus infection should be avoided since the use of such drugs in dengue fever is associated with hemorrhagic risk and risk for Reye syndrome in the pediatric population. [35]
The WHO recommends optimal supportive care in patients with Guillain-Barré syndrome, including frequent neurologic examinations, testing of vital signs, and respiratory function monitoring to decrease the likelihood of complications (eg, blood clots, respiratory failure). Patients whose symptoms are escalating rapidly or who are unable to walk should receive intravenous immunoglobulin therapy or therapeutic plasma exchange. [33] Managament of pregnant women with Zika and infants with Congenital Zika syndrome requires specialist consultation and care. Further information is available in the guidelines section.
There are no FDA-approved treatment options for Zika. Multiple antiviral drugs are under investigation for treatment of ZIKV infection. [1, 8, 36] The anti-Zika drugs under investigation target various stages of viral life cycle with direct antiviral activity (nucleoside analogs, polymerase inhibitors, RNA-dependent RNA polymerase inhibitors such as sofosbuvir, galidesivir) or activity against host cell mechanisms (purine or pyrimidine synthesis inhibitors, entry inhibitors). Some of the anti-Zika drugs have shown promising efficacy in in-vivo and in-vitro studies. Few FDA-approved drugs for other non-Zika indications such as interferon (in-vitro antiviral activity), antimalarials like chloroquine and mefloquine (in-vitro anti-Zika activity and safe in all trimesters), anti-helminthics such as ivermectin (antiviral activity), and antibiotics like azithromycin (reduce infectivity) have potential anti-Zika activity but are still under investigation to establish efficacy and safety for use. Overall, there have been multiple challenges associated with development of anti-Zika drugs as these drugs should be able to cross blood-brain barrier and placental barrier in pregnant women and should be safe for consumption during pregnancy. Moreover, any approved anti-Zika drug should be reasonably-priced as the majority of the ZIKV circulation occurs in tropical and sub-tropical countries with limited-resources. [37]
Complications
ZIKV infection during pregnancy can result in congenital Zika syndrome associated with following features:
-
Severe microcephaly
-
Subcortical calcifications
-
Ocular findings: focal pigmentary mottling, chorioretinal atrophy, optic nerve hypoplasia or atrophy
-
Congenital contractures, such as clubfoot or arthrogryposis
-
Hypertonia restricting body movement soon after birth
Consultations
Expert consultation with a maternal-fetal medicine and infectious diseases specialists is advised for management of Zika virus infection during pregnancy.
A multidisciplinary team approach is recommended while caring for infants with congenital Zika syndrome. Consultation with infectious diseases, clinical geneticist, neurology, ophthalmologist, early intervention, and developmental specialists, and family and supportive services is recommended. Other sub-speciality consultation with endocrinology, lactation specialist, nutritionist, gastroenterologist, speech or occupational therapist, orthopedist, physiatrist, physcial therapist, pulmonologist, otolaryngolosit can be considered on a case-by-case basis.
Activity
Patients infected with arboviruses such as Zika virus should be advised to limit activity during symptomatic illness in order to avoid exposure to mosquitoes and potential risk for human-to-arthropod transmission and subsequent local spread of disease. [35]
Prevention
Avoidance of Travel to Areas of Active Zika Virus Transmission
The best method for preventing Zika virus infection is to avoid travel to areas with active Zika virus transmission. Travelers should refer to the CDC site before arranging travel plans for up-to-date information on ZIKV transmission internationally and in US states and territories.
Mosquito Control and Prevention of Mosquito Bites
Residents who live in endemic areas or travelers to endemic areas are advised to avoid mosquito bites. Different strategies to prevent mosquito bites include wearing full-sleeved shirts and long pants, sleeping under a mosquito bed net, using screens on windows and doors, treating clothing and gear with permethrin, or using permethrin-treated clothing and gear. [18]
Environmental Protection Agency (EPA)–registered mosquito-repelling agents such as DEET, picaridin, IR3535, oil of lemon eucalyptus (OLE), 2-undecanone, and para-menthane-diol (PMD) products can be used by all age groups including pregnant and breastfeeding individuals, except for OLE and PMD products, which are contraindicated in those younger than 3 years, for prevention of mosquito bites. Mosquito larval habitats can be controlled by appropriate handling of water-holding containers, including routinely discarding or covering stagnant water or using larvicidal agents. Certain other measures to control mosquitoes, including the use of genetically engineered Aedes aegypti mosquitoes as previously performed to prevent dengue infection by reducing the natural population of mosquitoes, is under investigation.
Caution should be exercised to prevent local transmission of Zika virus from infected patients to uninfected mosquitoes. Mosquito bites should be avoided during initial stages of Zika infection owing to high viremia. This reduces infection of mosquitoes and prevents local spread of viral illness.
Caution should be exercised when traveling overseas to prevent mosquito bites. Travelers preferably should stay in a hotel or lodging with air conditionining or with screens on windows and doors and sleep under a mosquito bed net, preferably permethrin-treated.
In November 2017, the EPA registered a novel biopesticide (ZAP Males) in an attempt to control populations of Aedes albopictus (Asian tiger mosquitoes). In this approach, male mosquitoes of this species are infected with a strain of Wolbachia pipientis that prevents healthy offspring when the infected males mate with Aedes albopictus females. This has been approved in twenty US states, including California, Connecticut, Delaware, Illinois, Indiana, Kentucky, Massachusetts, Maine, Maryland, Missouri, New Hampshire, New Jersey, Nevada, New York, Ohio, Pennsylvania, Rhode Island, Tennessee, Vermont, Florida, Hawaii, Texas, and West Virginia, as well as the District of Columbia. [38] Similarly, an experimental use permit for field testing and release of Wolbachia-infected Ae aegypti male mosquitoes was issued by the EPA in Florida, Texas, and California. The results of these field studies are not available yet.
Preventing Other Modes of Zika Virus Transmission
Until recently, the mosquito was the only known vector for Zika virus transmission. As the infection spreads, new possible routes of transmission facilitating human-to-human spread of the virus without an intermediate vector have been discovered. The CDC has issued interim guidelines advising sexual abstinence or regular use of condoms to prevent the spread of Zika virus to sexual partners, especially during pregnancy. [39]
On July 6, 2018, the FDA issued guidance to all blood centers in all states and US territories to screen donated whole blood and blood components with blood screening nucleic acid test approved by FDA. An FDA-approved pathogen-reduction device can considered to be used for plasma and apheresis platelet donations. [40]
The CDC advises that women with Zika (symptomatic or asymptomatic) or travel to an area with Zika outbreak should wait at least 2 months from symptom onset or a positive test date or return before attempting to conceive and should use condoms or abstain from sex. In case of travel by a male partner or both partners, at least a 3-month wait time is advised. [41]
A travel alert has been issued for pregnant women in any trimester to avoid or postpone travel to areas with ongoing Zika outbreak. [35] Travel to areas with current or past transmission but no ongoing outbreak should be discussed with healthcare provider to asses risk. Appropriate precautions to prevent mosquito bites should be taken when traveling to all other areas with presence of Aedes mosquitoes.
Zika Virus Vaccine Development
No vaccine is approved and available for the prevention of Zika virus infection.
Multiple pre-clinical and clinical trials are ongoing across the world to develop a vaccine against ZIKV. [42] Various vaccine candidates are under development such as DNA and RNA-based vaccines, inactivated whole virus and live attenuated vaccines, viral vector and protein antigen vaccines. Few clinical trials have progressed to phase 1 or 2. A summary of all vaccines currently under investigation is listed in table 1.
Table 1. Zika virus vaccines currently in development (Open Table in a new window)
| Type | Name and Sponsor | Antigen | Phase |
|---|---|---|---|
|
|
Pre-membrane and Envelope |
I |
|
|
Whole virion |
I |
|
|
Pre-membrane and Envelope |
I & II (VRC only) |
|
|
Pre-membrane and Envelope |
I |
Abbreviations: NIAID: National Institute of Allergy and Infectious Diseases, WRAIR: Walter Reed Army Institute of Research, BIDMC: Beth Israel Deacones Medical Center, VRC: Vaccine Research Center
Long-Term Monitoring
Evidence suggests that Zika infection prior to pregnancy would not pose a risk for birth defects to a future pregnancy. Based on previous studies, a person with a history of Zika virus infection is protected from a future Zika infection.
-
Rash in a patient with Zika virus infection. Courtesy of Carolina O Barbosa, MD, and Antonio C Bandeira, MD, Salvador, Brazil.
-
Rash in a patient with Zika virus infection. Courtesy of Carolina O Barbosa, MD, and Antonio C Bandeira, MD, Salvador, Brazil.
-
Rash in a patient with Zika virus infection. Courtesy of Carolina O Barbosa, MD, and Antonio C Bandeira, MD, Salvador, Brazil.
-
Rash in a patient with Zika virus infection. Courtesy of Carolina O Barbosa, MD, and Antonio C Bandeira, MD, Salvador, Brazil.
-
Laboratory-confirmed symptomatic Zika virus disease cases reported to ArboNET by states and territories - United States, 2017. Courtesy of the Centers for Disease Control and Prevention (CDC).
-
World map of areas with color-coded risk for Zika based on current or previously reported Zika cases, as of November 4, 2019. Courtesy of the Centers for Disease Control and Prevention (CDC).
-
Diagnostic testing to interpret infection from Dengue and Zika virus. Courtesy of the Centers for Disease Control and Prevention (CDC).
-
Dengue and Zika virus diagnostic testing interpretation in nonpregnant and pregnant patients. Courtesy of the Centers for Disease Control and Prevention (CDC).
-
Testing algorithm for pregnant women with a clinically compatible illness and risk for Zika and Dengue virus. Courtesy of the Centers for Disease Control and Prevention (CDC).
-
Dengue and Zika virus testing recommendations for nonpregnant persons with a clinically compatible illness and risk for infection with both viruses. Courtesy of the Centers for Disease Control and Prevention (CDC).
-
Interpretation of results of laboratory testing of infant’s blood, urine, and/or cerebrospinal fluid for evidence of congenital Zika virus infection. Courtesy of the Centers for Disease Control and Prevention (CDC).
-
Recommendations for the evaluation of infants with possible congenital Zika virus infection based on infant clinical findings, maternal testing results, and infant testing results - United States, October 2017. Courtesy of the Centers for Disease Control and Prevention (CDC).
-
Consultations for infants with clinical findings consistent with congenital Zika syndrome - United States, October 2017. Courtesy of the Centers for Disease Control and Prevention (CDC).
Tables
| Type | Name and Sponsor | Antigen | Phase |
|---|---|---|---|
|
|
Pre-membrane and Envelope |
I |
|
|
Whole virion |
I |
|
|
Pre-membrane and Envelope |
I & II (VRC only) |
|
|
Pre-membrane and Envelope |
I |
