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Zika: what caused it? We will know when the work is done.

On February 1, 2016, the World Health Organization declared a public health emergency of international concern as a result of the possible link between Zika virus (ZIKV) infection during pregnancy and microcephaly. This outbreak is reported in the Caribbean and Latin America. Zika virus is a RNA flavivirus (Aedes aegypti and Aedes albopictus) related to West Nile, dengue, Japanese encephalitis viruses, and yellow fever and is transmitted by mosquitoes. Other routes of infection for ZIKV, including rare sexually transmitted cases, have been reported.

The virus was first isolated in a rhesus macaque caged in the Zika forest of Uganda in 1947 and described in humans in 1952. It was largely limited to equatorial areas of Africa and Asia until appearing on the island of Yap in Micronesia in 2007, and sparking an outbreak in French Polynesia in 2013-14. The population of Yap Island is only 7,391. The outbreak was a relatively mild disease characterized by rash, arthralgia, and conjunctivitis. The attack rate among residents was about 5.8 per 100 residents. The median age of infected patients was 34 years; patients ranged in age from newborns to 76 years (Duffy et al., 2009). There were no deaths or hospitalizations; no associated microcephaly reported.

In late spring 2015 Brazil began reporting an increased incidence of infants born with microcephaly coincident with an outbreak of the French Polynesian strain of ZIKV. In May 2015, the Pan American Health Organization (PAHO) issued an alert regarding the first confirmed ZIKV infection in Brazil. This outbreak has rapidly spread to over 24 countries and territories in the Americas, including Puerto Rico and the U. S. Virgin Islands with imported cases in travelers in several US states.

There are currently travel alert warnings issued to countries where the outbreak is occurring--something that was delayed nine months with the outbreak of Ebola. No such alerts were seen in the first carefully studied ZIKV outbreak, which was on Yap Island in Micronesia in 2007 with its fewer than 12,000 residents. The current outbreak is the first in which scientists have seen the virus invade a large continent where no one is immune and is spreading explosively. Why is this outbreak associated with microcephaly?

The history of the virus and its discovery according to WHO (World Health Organization): its historical home, since discovery in 1947, has been in a narrow equatorial belt stretching across Africa and into equatorial Asia. For decades, the disease, transmitted by the Aedes genus of mosquito affected mainly monkeys. In humans, ZIKV occasionally caused a mild disease of low concern.

In 2007, ZIKV expanded its geographical range to cause the first documented outbreak in the Pacific islands, in the Federated States of Micronesia.

From 2013-2014, four additional Pacific island nations documented large ZIKV outbreaks. In French Polynesia, the outbreak was associated with neurological complications at a time when the virus was co-circulating with dengue. That was a unique feature, but difficult to interpret--but was not described as microcephaly (WHO, 2016).

The striking deformity of microcephaly has been at the center of the viral epidemic. Babies born with microcephaly have been reported among infants born to pregnant women infected with ZIKV. Microcephaly most often occurs because the brain fails to grow at a normal rate. Skull growth is determined by brain growth. Brain growth takes place while in the womb and during infancy. It has no clear prognosis, no treatment and no cure. The diagnosis comes halfway through pregnancy, if at all.

The most likely causes of microcephaly include infections, genetic disorders, and severe malnutrition (Kinsman and Johnston, 2011). The genetic conditions are:

* Cornelia de Lange Syndrome

* Cri du chat Syndrome

* Down syndrome

* Rubinstein-Taybi Syndrome

* Seckel Syndrome

* Smith-Lemli-Opitz Syndrome

* Trisomy 18

* Trisomy 21

Some indirect causes are:

* Uncontrolled phenylketonuria (PKU) in the mother

* Methylmercury poisoning

* Congenital rubella

* Congenital toxoplasmosis

* Congenital cytomegalovirus (CMV)

* Use of certain drugs during pregnancy, especially alcohol and phenytoin

There are many uncertainties about this virus, including whether it is directly responsible for the misshapen skulls of babies born to infected mothers--and there should be uncertainty. For example, there are four types of dengue virus, and the severity of infection can range from mild aches and pains all the way to an Ebola-like hemorrhagic death. For years, scientists tried to pinpoint which strain caused which symptoms, but it is now known that the worst outcomes arise when an individual is infected sequentially with different strains, triggering his immune system into a massive overreaction. With this, and other complicated examples of mosquito-carried viral diseases in mind, the WHO is very cautiously referring to an "association" between microcephaly and the Zika virus--not yet cause and effect. ZIKV has already gone from being an epidemic to an endemic disease in Brazil, meaning the virus may now be a permanent feature of the nation's ecology and that of the western hemisphere. It is likely that ZIKV will return in seasonal cycles, as have other mosquito-carried viruses such as yellow fever, West Nile virus, chikungunya, and dengue; each of which have made permanent homes in ecologies ranging from the Amazon rainforest to posh Caribbean resorts to Andean villages to Mexico City.

the WHO is very cautiously referring to an "association" between microcephaly and the Zika virus--not yet cause and effect

So, what happened when the explosive disease hit the Brazilian country? What is the guidance, given the virus is like some we have known but yet much remains unknown? Why could there be an association with microcephaly? If ZIKV does cause microcephaly, it seems to be an extremely rare complication given the long history of the viruses' existence and causes of outbreaks as shown above.

In Brazil, researchers say they are seeing a disproportionate number of microcephalic infants with what appear to be severe deformities, many with four striking malformations at once: a large degree of brain tissue loss; unusually smooth, wrinkleless brains; many calcium deposits; and smaller cerebellums, which play a role in motor control, according to Dr. Albert I. Ko, an infectious-diseases specialist at Yale School of Public Health who is helping Brazilian health officials (Stein, 2016). However, Brazil has had outbreaks of this virus before without such association. Do the answers come within the first wave of epidemiological discovery or later? Did the answer come within the first wave of discovery of Human-immunodeficiency Virus? What about initially when thousands of people were getting sick and dying from the 'Broad Street pump'?

In 2014 the government added the chemical pyriproxyfen to water supplies. The aim was to lessen the mosquito population in Brazil. Soon after, birth defects in newborns began. Neighboring Colombia is also battling ZIKV where approximately 3000 pregnant Colombian women have been infected. But in that country there is no microcephaly outbreak. Pyriproxyfen has not been used on Colombia mosquitoes (Salerno, 2015).

Strategies for prevention and control of ZIKV disease included what is best known to do for any mosquito population carrying disease: promoting the use of insect repellent and interventions to reduce the abundance of potential mosquito vectors. It was so with West Nile Virus and it has been the case with the same Aedes species, carrying ZIKV, which can breed in the smallest pools of water and usually bite during the day.

Epidemiological principles include detection/surveillance, investigation, analytic study, evaluation, linkages, and policy development. The goals are to: track progress of a disease to determine cause and spread; mitigate/eliminate the source; educate the public; and establish prevention measures. The principles will not change despite what organism may be organizing with each moment to attack. As with any mosquito infestation, spraying is the first expected action; and was done in all outbreaks. Often the containment policy must come quicker than the definitive result of an epidemiological study.


Duffy, M., Chen, T., Hancock, W. T., Powers, A. M, Kool. J. L. Lanciotti, R. S., ... Mayes, E. B. (2009). Zika virus outbreak on Yap Island, Federated States of Micronesia. Presented at: The 56th Annual Meeting of the American Society of Tropical Medicine and Hygiene; Nov. 4-8, 2007, Philadelphia and New England Journal of Medicine, 360(24), 2536-2543. doi: 10.1056/ NEJMoa0805715.

Kinsman, S. L., Johnston, M. V. (2011). Congenital anomalies of the central nervous system. In Kliegman, R. M., Stanton, B. F., St. Geme, J. W. III, Schor, N. F., Behrman, R. E., eds. Nelson Textbook of Pediatrics, 19th ed. Philadelphia, PA: Saunders Elsevier.

Salerno, A. (2015). Pesticide, Not Zika, Is Causing Birth Defects, Scientists Charge. The Institute for National Healing. Retrieved on February 25, 2016, from charge/

Stein, R. (2016). Zika Virus: Big Zika Virus Outbreak Unlikely in The U.S., Officials Say. Nashville Public Radio. Retrieved February 28, 2016, from say

World Health Organization. (2016). Zika Virus. Retrieved on February 25, 2016, from zika/en/

by Stephanie B.C. Bailey, MD MSHSA

Dr. Bailey is Interim Dean of the College of Health Sciences, Tennessee State University in Nashville. She served as the Chief for Public Health Practice at CDCprior to coming to TSU and the Director of Health for Metropolitan Nashville/Davidson County, Tennessee, prior to CDC. She is a lifetime champion for community health excellence.
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Title Annotation:Guest Editor
Author:Bailey, Stephanie B.C.
Publication:International Journal of Childbirth Education
Article Type:Editorial
Geographic Code:3BRAZ
Date:Apr 1, 2016
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