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Zika Virus: An Emerging Infectious Disease

By Carol E Hayes, CNM, MN, MPH

Zika virus disease is a neurotropic virus usually resulting in a mild viral illness, but has been linked to Guillain Barre syndrome (Brasil, P et al.Guillain-Barr้ syndrome associated with Zika virus infection. The Lancet , Volume 387 , Issue 10026, 1482. http://dx.doi.org/10.1016/S0140-6736(16)30058-7 ) and a wide range of adverse pregnancy outcomes. Zika was first identified in macaque in Africa in the 1940’s. It is new the Americas, having recently been introduced in 2014. The Zika virus can be spread by mosquitoes, by sexual contact, and from mother to child while pregnant. The virus is in the same family as West Nile, Dengue, and yellow fever. The virus is transmitted by the Aedes Aegypti and Aedes albopictus mosquitoes, also known as the Asian tiger mosquito. Aedes albopictus is less effective at carrying the virus, but has a broader geographic area. http://www.cdc.gov/zika/vector/range.html This species of mosquito currently circulates in the Southern and Central parts of North America, Central America, the Caribbean, the Northern parts of South America, and parts of Africa and Asia. www.cdc.gov/zika/geo/active-countries.html The Asian tiger mosquito can also transmit Dengue and Chikungunya viruses. There is no evidence that household pets are affected, only humans. If a pregnant woman contracts Zika, her baby is at risk of brain damage (microcephaly) and other neurologic conditions. Zika is the first virus since Rubella linked to birth defects, and it is the first time a vector born pathogen has been linked to congenital anomalies. There is no known treatment. It is a potentially catastrophic and permanent part of our health care landscape.

Transmission of Zika

Transmission from infected mosquito to humans is the main form of transmission. Both species that carry the virus prefer to bite during the day or at dusk and dawn. Transmission has been documented sexually from men to women, women to men, and men to men.

Zika virus infection

Most people infected with Zika virus have few or mild symptoms. The symptoms associated with Zika include maculopapular rash, fever, myalgia, arthralgia, headache, and conjunctivitis, with the itchy rash being very common. Due to the vagueness of symptoms, the differential diagnosis is difficult. Recent travel, or close contact with a person who recently traveled, to Central or South America is currently important to ask any woman who presents with viral symptoms. Recent travel to Africa broadens the differential diagnosis list considerably. Preliminary diagnosis is made by symptoms and travel history. There are many unanswered questions about the infection. What is not known, is how long the virus lives in the blood after symptoms disappear, but the current recommendation is that someone should consider themselves contagious for 4 weeks after infection.

Diagnosis of Zika infection can be made with an RNA test or IgM antibody. The RNA viremia lasts until 5-7 days after symptoms occur. IgM antibodies begin 4-7 days after symptoms, and decline over time. There is a small overlap when both test can be positive.

https://www.cste2.org/docs/Zika_Virus_Disease_and_Congenital_Zika_Virus_Infection_Interim.pdf It is not known how long the virus stays in the body.

There are no commercially available tests. The US Centers for Disease Control and Prevention (CDC) has developed a MAC-Elisa testing kit with significant cross reactivity with other viruses. CDC has also developed Trioplex rRT-PCR that can detect Zika, Chikungunya and Dengue, however false negatives can occur. Coordination for testing is currently occurring between CDC and State and county health department labs when testing is done. http://www.cdc.gov/zika/hc-providers/tools.html The collection, storage and transport of specimens requires clinical staff to follow detailed instructions. The learning curve on this is steep. http://www.cdc.gov/ncezid/dvbd/specimensub/arboviral-shipping.html

Testing of asymptomatic pregnant women should occur for women or their sexual partnetrs that have traveled to Central or South America, the Caribbean, Asia, and Africa; or for those that are symptomatic. Women who test positive should be enrolled in the CDC Zika Pregnancy Registry. http://www.cdc.gov/zika/hc-providers/registry.html

Management in pregnancy

Over the past year, over 3,500 cases of microcephaly with brain calcification have been reported in Brazil, when they normally see a few hundred. (P. Brasil, J.P. Pereira Jr., C. Raja Gabaglia, L. Damasceno, M. Wakimoto, R.M. Ribeiro Nogueira, P. Carvalho de Sequeira, A. Machado Siqueira, L.M. Abreu de Carvalho, D. Cotrim da Cunha, et al.

Zika Virus Infection in Pregnant Women in Rio de Janeiro - Preliminary Report.

N. Engl. J. Med. (2016) http://dx.doi.org/10.1056/NEJMoa1602412) Congenital Zika virus was confirmed when viral Zika RNA and antigen were found in products of conception, placental tissue, amniotic fluid, and fetal brain tissue. Zika virus infects the placenta and target fetal neural cells resulting in fetal growth restriction, fetal demise, and lack fetal brain development (microcephaly). (Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR. Zika Virus and Birth Defects - Reviewing the Evidence for Causality. N Engl J Med. 2016 Apr 13 http://www.nejm.org/doi/full/10.1056/NEJMsr1604338 ) (CDC. Increase in Reported Prevalence of Microcephaly in Infants Born to Women Living in Areas with Confirmed Zika Virus Transmission During the First Trimester of Pregnancy — Brazil, 2015. MMWR March 11, 2016 / 65(9);242–247. http://www.cdc.gov/mmwr/volumes/65/wr/mm6509e2.htm?s_cid=mm6509e2_w)

(Miller, JN, Cao, B, Govero, J, etal. Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise. Cell. Volume 165, Issue 5, 19 May 2016, Pages 1081–1091. doi:10.1016/j.cell.2016.05.008)

The virus is unlikely to affect future pregnancies. After infected, the individual is likely protected in future, similar to Cytomegalo Virus. There is no known treatment. Supportive therapy and fever management are all we have for treatment. For those women exposed to or infected with Zika during pregnancy, the CDC has created a Zika Pregnancy Registry. http://www.cdc.gov/zika/hc-providers/registry.html


Diagnosing Microcephaly in exposed infants

Infants exposed to Zika prenatally can have a range of insults, including eye abnormalities, hearing impairment, seizures, swallowing impairment, hypertonicity and posturing, contractures, including club foot and curving of the joints, severe irritability, developmental delay, growth abnormalities, including intrauterine growth restriction and

disproportionate growth (head size alone affected). (Karwowski MP, Nelson JM, Staples JE, et al. Zika Virus Disease: A CDC Update for Pediatric Health Care Providers. Pediatrics. 2016;137(5):e20160621 http://pediatrics.aappublications.org/content/137/5/e20160621.long) It appears, like other teratogens, that infection in the first trimester causes severe problems. We have limited data on the insult from infection in the second and third trimester. There is no data yet on insults to children infected in infancy or early childhood. The neurotropic nature of the virus causes fetal brain tissue injury called Fetal Brain Disruption Sequence. This includes a decrease of total brain tissue, absent or poorly formed brain structures, with resulting microcephaly, and is associated with calcium deposits in the brain indicating brain damage.

The definition of Zika-Related Congenital Microcephaly is

Live Births

  • Head circumference (HC) at birth <3rd percentile for gestational age and sex, OR
  • If HC at birth is not available, HC <3rd percentile for age and sex within the first 6 weeks of life, adjusted for gestational age if preter Stillbirths and Elective Terminations
  • HC at delivery <3rd percentile for gestational age and sex

Preventing the disease

Aedes Aegypti mosquitoes mostly bite during the day, prefer man made breeding areas, lives indoors as well as outdoors, are hard to control, and have widespread resistance to insecticide. The Aedes Aegypti lays its egg in the water as well as at edge of water; the eggs can sit dormant for months, and then hatch when the water comes back. Aedes Aegypti prefers to breed in small man made containers, and can breed in a table spoon of water. Local reservoirs include plants such as Magnolia tree leaves, Holly bush leaves, and English ivy. Manmade containers include gutters, bird baths, plant saucers, garbage cans, pet bowls, pool covers, and old tires. Areas of the rural south, with limited garbage pick up, and local dumping of garbage, has been shown to increase Aedes Aegypti populations.

http://blogs.cdc.gov/publichealthmatters/2016/03/zikaandwater/

A four pronged approach to reduce populations includes: kill it inside, kill it outside, larvae control and personal protection against being bitten.

INSIDE: Make sure every window has a tight fitting screen. Run the water in every sink or shower weekly to flush water in the trap. Check drip pans for dehumidifiers, refrigerators, heat boilers and AC units. Standing water should be drained or larvicide should be added.

OUTSIDE: Weekly tip and toss any container with water. If you own rain barrels, or water cisterns, use the environmentally friendly bacteria Bacillus thuringiensis v. israelensis.(Bti) It is a unique toxicity, mostly to mosquitoos and black flies, causing death to larvae after ingestion. Bti is not effective on mosquito pupae or adults. Bti does not harm birds or mammals, but may reduce biodiversity if used extensively in wetlands (http://www.doh.wa.gov/CommunityandEnvironment/Pests/Mosquitoes/Bti ) . It can be purchased in granular, bits or discs. If you have a septic tank, make sure the tank vent is sealed. Check the storm water drainage in the neighborhood. If you see standing water call the local city or county to come and control the mosquitoes. http://www.cdc.gov/dengue/resources/factSheets/SepticTankFactSheetEnglishNCEZID.pdf

PERSONAL PROTECTION: Use EPA registered repellent at all times when outdoors. Wear long sleeves and slacks when feasible. Use condoms with each session of intercourse to prevent sexual transmission. http://www.cdc.gov/Features/stopmosquitoes/index.html


RESOURCES

ACOG

ACOG Zika page

http://www.acog.org/About-ACOG/ACOG-Departments/Zika-Virus

Practice Advisory: Updated Interim Guidance for Care of Obstetric Patients And Women Of Reproductive Age During a Zika Virus Outbreak. Updated June 23, 2106

http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Interim-Guidance-for-Care-of-Obstetric-Patients-During-a-Zika-Virus-Outbreak

CDC

Zika home page

http://www.cdc.gov/zika/index.html

http://www.cdc.gov/zika/hc-providers/pregnant-woman.html

Questions and Answers for Healthcare Providers Caring for Pregnant Women and Women of Reproductive Age with Possible Zika Virus Exposure

http://www.cdc.gov/zika/hc-providers/qa-pregnant-women.html

Interim Guidance for Health Care Providers Caring for Pregnant Women with Possible Zika Virus Exposure - United States, July 2016(MMWR, Jul. 25, 2016)

Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure — United States, 2016. MMWR. April 1, 2016 / 65(12);315–322

http://www.cdc.gov/mmwr/volumes/65/wr/mm6512e2.htm?s_cid=mm6512e2_w

Preventing Transmission of Zika Virus in Labor and Delivery Settings Through Implementation of Standard Precautions — United States, 2016. MMWR, March 25, 2016 / 65(11);290–292 http://www.cdc.gov/mmwr/volumes/65/wr/mm6511e3.htm?s_cid=mm6511e3_w

Update: OngoingZikaVirus Transmission — Puerto Rico, November 1, 2015–July 7, 2016
Laura Adams, DVM; Melissa Bello-Pagan, MS; Matthew Lozier, PhD; et al.
MMWRMorb Mortal Wkly Rep 2016;65(Early Release)

Information for pregnant women about Zika

http://www.cdc.gov/zika/pregnancy/index.html

WHO

Facts about Zika virus

http://www.who.int/mediacentre/factsheets/zika/en/

Zika Questions and answers

http://www.who.int/features/qa/zika/en/


 



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