IDCM Issue 4: Quick Facts about Zika Virus

Post Date: 
2016-04-22
Author: 
Natasha Chida, MD, MSPH
 
 
What is the Zika virus?
   
The Zika virus (ZIKV) is a flavivirus that was first identified in 1947 in Uganda. Historically it circulated predominantly in wild primates, and the first human case was reported in 1952.1 Prior to the current epidemic, outbreaks had been reported in tropical Africa, Southeast Asia, and the Pacific Islands. 
 
ZIKV is transmitted by Aedes mosquitos (predominantly Aedes aegypti), which are endemic across the Americas. Aedes aegypti is found in southern US states, and Aedes albopictus is found in eastern and southern US states.2 In laboratory tests, Aedes albopictus has been found to transmit the virus; however, whether it will become a significant ZIKV vector remains unknown.3
 
 
Where is ZIKV currently circulating?
   
The current epidemic began in Brazil in spring 2015.4 Since then the virus has spread rapidly. Local ZIKV transmission has been reported in more than 40 countries, including in the following regions/countries: the Caribbean, Central America, the Pacific Islands, South America, Cape Verde, and Mexico.2 While no local transmission of the virus has been reported in the continental US, transmission has been reported in Puerto Rico, the US Virgin Islands, and American Samoa.
 
Brazil remains the country with the highest number of cases and highest number of related fetal and infant abnormalities. In a recent study, 88 pregnant women with a clinical syndrome consistent with ZIKV were tested in Brazil; of those, 72 tested positive for ZIKV. Of the 72, 42 underwent prenatal ultrasonography, and fetal abnormalities were observed in 12 (29%). No fetal abnormalities were observed among the 16 women who tested negative for ZIKV.5 Of note, the first ZIKV-linked case of birth defects has now been reported in Colombia.6
 
 
How is ZIKV spread?
   
ZIKV RNA and/or antigen has been identified in:
 
  • Blood: Present up to 1 week, although in one report viremia duration was 11 days.
  • Semen: Present for at least 2 weeks.
  • Amniotic fluid
  • Placenta
  • Urine
  • Products of conception
  • Fetal brain tissue.2,7
 
A recent study also isolated infectious ZIKV particles in breast milk, although there have been no reports of infants developing ZIKV disease due to breastfeeding.8
 
Three patterns of spread have been identified: bites by infected mosquitos, transplacental, and sexual. In Brazil, reports of transmission through blood transfusion are currently being investigated.2 Due to the potential for sexual transmission, it is recommended that pregnant women use condoms during vaginal, anal, and oral sex, or abstain from sexual activity altogether.
 
 
Is there a relationship between ZIKV infection during pregnancy and fetal or congenital birth defects?
   
Since the beginning of the current epidemic a correlational relationship had been described between fetal and infant microcephaly and ZIKV, but a definitive relationship was not proven. However, a group of investigators from the US Centers for Disease Control and Prevention (CDC) recently concluded that enough evidence has accumulated to infer that ZIKV is a cause of microcephaly and other fetal brain defects.4 The investigators used Shepard’s criteria, a group of 7 criteria that identify teratogens, to establish the link.9 ZIKV is now the first flavivirus to be identified as a teratogen.1 We also now know this is not the first time microcephaly cases increased following a ZIKV outbreak. A recent retrospective evaluation of an outbreak that occurred in Polynesia between 2013-2014 found increased incidence of microcephaly cases (as well as increased rate of Guillain-Barre syndrome).4
 
At this time, it is not known how ZIKV leads to fetal brain abnormalities. However, in one study, the virus was found to infect human embryonic cortical neural progenitor cells, which then produced infectious ZIKV particles. The virus also led to increased cell death and dysregulated the cell cycle and transcription.10
 
 
How can ZIKV be diagnosed?
   
A PCR test can be used on serum in the first week of symptoms, although this test has not been validated. After that, antibody tests can be used, although these tests can return false-positive results for ZIKV in the presence of other flaviviruses. A negative IgM test 2–12 weeks after known exposure suggests a recent ZIKV infection did not occur. In the US, samples can be sent for testing through local and state health departments to the CDC (https://www.cdc.gov/ncezid/dvbd/specimensub/arboviral-shipping.html). Results take at least 3 weeks to return.  
 
Symptoms alone cannot guide all evaluations, as the majority of people are asymptomatic or have mild symptoms (including rash, fever, joint pain, headache, and conjunctivitis).11 For every symptomatic case there are an estimated 4 asymptomatic ones; mothers of children with microcephaly may be asymptomatic.3 CDC therefore recommends the testing of serum for evidence of ZIKV infection in the following2:
 
  • Persons who have had possible sexual exposure to ZIKV and develop signs or symptoms consistent with ZIKV disease.
  • Pregnant woman with possible sexual exposure to ZIKV if either she OR her male partner developed symptoms consistent with ZIKV disease.
  • Pregnant women who had possible exposure to ZIKV who do not reside in an area with active transmission. 
  • Pregnant women residing in an endemic area with symptoms consistent with ZIKV and pregnant women who are asymptomatic at the initiation of prenatal care. 
 
 
What are the recommendations for persons attempting conception?
   
Routine testing is not currently recommended for asymptomatic women or men who are attempting conception who have possible exposure to ZIKV, because the performance of current available diagnostics in asymptomatic persons is unknown. For women and men attempting conception and living in areas with active transmission, CDC recommends individual discussions with healthcare providers.2 CDC also recommends women with ZIKV disease wait at least 8 weeks from symptom onset before attempting conception, and for men with ZIKV disease to wait at least 6 months from symptom onset before attempting conception.2 This is because it is unknown how long the virus stays in semen.  
 
For women and men not living in areas with active transmission who have had possible exposure to the virus but no clinical illness consistent with ZIKV disease, CDC recommends waiting at least 8 weeks after exposure to attempt conception.2 Possible exposure to ZIKV includes travel to or residence in an area of active ZIKV transmission, or unprotected sex with a man who traveled to/resided in an area of active transmission.2

 

Bottom Line: Our understanding of ZIKV continues to develop, but we have much more to learn. Public health strategies to combat the epidemic and care for those affected by the virus will need to evolve as our understanding of the virus increases.

 
References
 
  1. Fauci AS, Morens DM. Zika Virus in the Americas--Yet Another Arbovirus Threat. N Engl J Med. 2016; 374(7):601-4. PMID: 26761185.
  2. US Centers for Disease Control and Prevention Website. https://www.cdc.gov/ZIKV/. Accessed 4/18/2016.
  3. Dyer O. Zika virus spreads across Americas as concerns mount over birth defects. BMJ. 2015;351:h6983. PMID: 26698165.
  4. Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR.  Zika Virus and Birth Defects - Reviewing the Evidence for Causality. N Engl J Med. 2016 [Epub ahead of print]. PMID: 27074377.
  5. Brasil P, Pereira JP Jr, Raja Gabaglia C, et al. Zika virus infection in pregnant women in Rio de Janeiro — preliminary report. N Engl J Med. 2016 [Epub ahead of print]. PMID: 26943629.
  6. Butler D. First Zika-linked birth defects detected in Colombia. Nature. 2016;531(7593):153. PMID: 26961637.
  7. Mlakar J, Korva M, Tul N et al. Zika Virus Associated with Microcephaly. N Engl J Med. 2016;374(10):951-8. PMID: 26862926.
  8. Dupont-Rouzeyrol M, Biron A, O'Connor O. Infectious Zika viral particles in breastmilk. Lancet. 2016;387(10023):1051. PMID: 26944028.
  9. Shepard TH. "Proof" of human teratogenicity. Teratology. 1994;50:97-98. PMID: 7801306. 
  10. Tang H, Hammack C, Ogden SC. Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth. Cell Stem Cell. 2016. pii: S1934-5909(16)00106-5. PMID: 26952870.
  11. Armstrong P, Hennessey M, Adams M. MMWR Morb Mortal Wkly Rep. 2016;65(11):286-9. PMID: 27023833.
 

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The Johns Hopkins Center for Clinical Global Health Education is a clinical research, education, and leadership development center in the Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine. We conduct clinical research, and we train, support, and empower healthcare providers and researchers working in resource-limited communities who share our commitment to improve health outcomes.