The Zika Crisis

mosquitoIn 2015, the Zika virus outbreak began in the northeast region of Brazil. According to the World Health Organization, there has been 3174 suspected cases of microcephaly in Brazil since January 2, 2016, including 38 deaths (1). The northeastern region of Brazil continues to be the area most affected, with the highest number of suspected cases. On April 13, 2016, the US Centers for Disease Control and Prevention (CDC) published a paper in The New England Journal of Medicine which concluded that there is a direct causal relationship between prenatal exposure to Zika virus and the outcome of microcephaly and brain abnormalities in the exposed infants (2). While the common symptoms of Zika infection are fever, rash, joint pain, and conjunctivitis lasting from several days to a week after exposure from an infected mosquito’s bite, a recent study recounts two cases of patients who had contracted the Zika virus and later succumbed to acute disseminated encephalitis (ADEM) (3).  This is a condition in which the immune system attacks the body, producing swelling in the brain and spinal cord and damaging the myelin which serves to protectively encase nerve fibers. The same study also describes four patients who had Zika and then developed Guillain-Barré syndrome, a condition where the immune system attacks the body’s peripheral myelin.

Zika virus is quickly spread through the bite of the female Aedes aegypti mosquito, a mosquito that is usually associated with warmer climates. This species of mosquito bites during the day. The Pan American Health Organization (PAHO) sent out a warning of the first confirmed Zika virus infection in Brazil on May 2015, and on February 2016, the World Health Organization (WHO) declared Zika virus a public health emergency of international concern (PHEIC). The PAHO lists the following areas where local transmission of Zika virus is active (4): Aruba, Barbados, Belize, Bonaire, Brazil, Colombia, Costa Rica, Cuba, Curacao, Dominica, Dominican Republic, Ecuador, El Salvador, French Guiana, Guadeloupe, Guatemala, Guyana, Haiti, Hondruas, Jamaica, Martinique, Mexico, Nicaragua, Panama, Paraguay, Peurto Rico, Saint Vincent and the Grenadines, Saint Lucia, Saint Martin, Sint Maarten, Suriname, Trinidad and Tobago, US Virgin Islands, and Venezuela. Locally transmitted cases of Zika have been reported in the Commonwealth of Puerto Rico, the US Virgin Islands, and American Samoa. There is potential for Zika virus to continue to spread to other countries due to the expanding range of the Aedes aegypti mosquito. A population of this species not carrying Zika was found in Capitol Hill, Washington, DC. Genetic analysis revealed that this particular mosquito population survived five winters in the area (5). Although theAedes aegypti is the species most responsible for spreading the Zika virus, other mosquito species in the Aedes genus can also transmit it to humans. Once the virus enters the bloodstream of a human through the bite of a female mosquito (the male mosquitoes do not bite), another female mosquito can acquire Zika by feeding upon the same host, which can then go on to infect another human. In an area with many Aedes mosquitoes, the process will repeat itself exponentially, leading to widespread viral transmission. A possible solution can be to use genetically modified mosquitoes that are male which reproduce with local female mosquitoes to yield offspring which do not live past the pupae stage. Oxitec (6), a British biotechnology company, developed such a mosquito which has already been released and tested successfully in the Cayman Islands in 2010, leading to a drastic 80 percent reduction in population of Aedes aegypti. Release of the same strain of GMO mosquitoes in the suburb of Juazeiro, Brazil in 2011 resulted in a 81-95 percent reduction of Aedes aegypti in the test region. It is also possible to breed mosquitoes to be genetically resistant to diseases such as dengue, malaria, yellow fever and Zika. Gamma radiation is being used in Brazil to sterilize male mosquitoes. Moscamed, a non-profit organization based in Brazil, took to breeding 12 million male mosquitoes per week, sterilizing them with the cobalt-60 irradiator, and then releasing them into select high-risk areas (7). The released sterile males mosquitoes then meet wild female mosquitoes, but no offspring can be produced. As there is no vaccine available right now, the current method of battling Zika virus is to reduce the population of Aedes mosquitoes.

It has been found that the Zika virus can also be transmitted sexually from an infected human male to his sexual partners via vaginal or anal sex (8), and that the virus can remain for a longer duration in semen than in blood. As of now, it is not known whether a woman can sexually spread Zika virus, or if it can be transmitted through saliva or vaginal fluids. Couples who are pregnant, or men who have travelled to areas affected by Zika are advised by the CDC to abstain from sex or use condoms.

The Zika virus is in the Flavivirus genus of viruses, which also include the West Nile virus, dengue virus, tick-borne encephalitis virus, and yellow fever virus. As a flavivirus, the Zika virus is enveloped, has a capsid of icosahedral symmetry, and contains a single-stranded positive-sense RNA genome. The Zika genome is about 10.8 kilobase pairs long. The positive-sense RNA is significant because once the virus enters the host cell, this RNA viral genome can be directly translated into a viral polypeptide, which is then cleaved into structural proteins and proteins to aid in the replication process. The envelope (E) glycoprotein protruding from the membrane of the virus is used for attachment and entrance into human cells.  For the development of a potential vaccine for Zika virus, a segment of the E glycoprotein unique to the Zika virus can be used in the vaccine to mount an antibody-mediated immune response, possibly conferring immunity from future attacks of the virus.

The expanding range of travel of both humans and mosquitoes have allowed for rapidly widespread transmission of the Zika virus. The head and brain abnormalities caused by prenatal exposure from an infected mother are detrimental, and a direct casual link between the virus and microcephaly/brain defects has been determined by the CDC. For instance, the Zika virus genome was found in the brain of an aborted, infected infant (9) that had microcephaly, and Zika virus antigens were found in the brain of one newborn with microcephaly (10). Autopsies found the presence of Zika virus in the brains of infants with severe microcephaly who died. Pregnant women infected with Zika virus have consistently given birth to infants with microcephaly and other brain abnormalities (11). The CDC further found that women who deliver infants with microcephaly were infected with Zika virus during the first and second trimester of gestation, when the brain starts to form and develop (12). There are two hypotheses directed at explaining how the Zika virus causes birth defects such as microcephaly (13). The first hypothesis posits that the placenta transfers the virus directly from mother to the fetus. The second hypothesis refers to the possible reaction of the placenta in response to Zika, which may contribute to or result in birth defects. Pregnant women are advised not to travel to areas where Zika virus is occurring.

Sierra Delarosa

 

   References

 1) Microcephaly-Brazil. (2016, January 8). Retrieved April 15, 2016, from http://www.who.int/csr/don/8-january-2016-brazil-microcephaly/en/

2) Rasmussen, S. A., M.D., Jamieson, D. J., M.D., Honein, M. A., PhD, & Petersen, L. R., M.D. (n.d.). Zika Virus and Birth Defects — Reviewing the Evidence for Causality. The New England Journal of Medicine. doi:10.1056/NEJMsr1604338

3) American Academy of Neurology. (2016, April 11). Zika virus may now be tied to another brain disease. ScienceDaily. Retrieved April 16, 2016 from www.sciencedaily.com/releases/2016/04/160411082335.htm

4) Countries and territories with autochthonous transmission in the Americas reported in 2015-2016. (n.d.). Retrieved April 15, 2016, fromhttp://www.paho.org/hq/index.php?option=com_content&view=article&id=11603:countries-territories-zika-autochthonous-transmission-americas&catid=8424:contents&Itemid=41696&lang=en

5) Gustin, G. (2016, February 26). Zika Virus Mosquitos Have Been Found…on Capitol Hill. Retrieved April 15, 2016, fromhttp://www.washingtonian.com/2016/02/26/zika-virus-mosquitos-capitol-hill-aedes-aegypti/

6) More on the science: How does oxitec make genetically modified mosquitoes? (n.d.). Retrieved April 15, 2016, fromhttp://www.oxitec.com/oxitec-video/more-on-the-science-how-does-oxitec-make-genetically-modified-mosquitoes/

7) Boadle, A. (2016, February 22). Brazil to fight Zika by sterilizing mosquitoes with gamma rays. Reuters. Retrieved April 15, 2016, from http://www.reuters.com/article/us-health-zika-radiation-idUSKCN0VV2JK

8) Zika and Sexual Transmission. (2016, February 21). Retrieved April 15, 2016, from http://www.cdc.gov/zika/transmission/sexual-transmission.html

9) Mlakar, J., M.D. et al (March 10, 2016). Zika Virus Associated with Microcephaly. The New England Journal of Medicine, 374, 951-958. DOI: 10.1056/NEJMoa1600651

10) Martines RB, Bhatnagar J, Keating MK, et al. Notes from the Field: Evidence of Zika Virus Infection in Brain and Placental Tissues from Two Congenitally Infected Newborns and Two Fetal Losses — Brazil, 2015. MMWR Morb Mortal Wkly Rep 2016;65, 159–160. DOI:http://dx.doi.org/10.15585/mmwr.mm6506e1

11) Rasmussen, S. A., M.D., Jamieson, D. J., M.D., Honein, M. A., PhD, & Petersen, L. R., M.D. (n.d.). Zika Virus and Birth Defects — Reviewing the Evidence for Causality. The New England Journal of Medicine. doi:10.1056/NEJMsr1604338

12) Rasmussen, S. A., M.D., Jamieson, D. J., M.D., Honein, M. A., PhD, & Petersen, L. R., M.D. (n.d.). Zika Virus and Birth Defects — Reviewing the Evidence for Causality. The New England Journal of Medicine. doi:10.1056/NEJMsr1604338

13) Adibi, J. J., ScD. Et al (2016). Teratogenic effects of the Zika virus and the role of the placenta. The Lancet. http://dx.doi.org/10.1016/S0140-6736(16)00650-4

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