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 Table of Contents  
REVIEW ARTICLE
Year : 2017  |  Volume : 20  |  Issue : 1  |  Page : 10-15

Zika virus: Docile or deadly?


Department of Infectious Diseases, Shifa College of Medicine, Islamabad, Pakistan

Date of Web Publication11-Jan-2017

Correspondence Address:
Haider Ghazanfar
Shifa College of Medicine, Pitrus Bukhari Road, H-8/4, Islamabad
Pakistan
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DOI: 10.4103/1119-0388.198098

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  Abstract 

Zika virus (ZIKV) has been declared a global public health emergency by the World Health Organization (WHO). The WHO has estimated that 4 million people can be infected by ZIKV by the end of 2016 if proper preventive measures are not taken. Our search results had yielded a total of 373 articles, of which 40 articles were included for perusal. In this review, we highlight the pathogenesis of ZIKV, different modes of transmission of ZIKV, and issues related to the diagnosis of ZIKV. Serological tests have shown strong cross-reactivity of immunoglobulin M against other flaviviruses. We have also highlighted possible preventive steps that can be deployed to prevent the epidemic from getting out of hands. The article also highlights the implication of the forthcoming Summer Olympic Games in Brazil on the spread of ZIKV. With the development of its vaccine still in embryonic stages, proper preventive strategies are the need of the hour.

Keywords: Epidemiology, Flaviviridae, vector-borne infections, zika virus


How to cite this article:
Ghazanfar H, Irfan A, Assad S. Zika virus: Docile or deadly?. Trop J Med Res 2017;20:10-5

How to cite this URL:
Ghazanfar H, Irfan A, Assad S. Zika virus: Docile or deadly?. Trop J Med Res [serial online] 2017 [cited 2017 Oct 21];20:10-5. Available from: http://www.tjmrjournal.org/text.asp?2017/20/1/10/198098


  Introduction Top


Zika virus (ZIKV) has been declared a global public health emergency by the World Health Organization (WHO). It was first identified in Uganda in 1947 in rhesus monkeys and was first identified in humans in 1952.[1] Since then, several ZIKV human isolates have been obtained from Africa and Southeast Asia including Pakistan.[2],[3] The current outbreak of this virus was first recognized in Northeastern Brazil in early 2015.[4],[5] According to the Brazilian Ministry of Health, between 440,000 and 1,300,000 cases of ZIKV infections may have occurred in 2015 in the Brazilian states.[6] By January 2015, locally transmitted cases have been reported in 20 other countries in the Americas by the Pan American Health Organization.[7] The WHO has estimated that 4 million people can be infected by the ZIKV by the end of 2016 if proper preventive measures are not taken. Global distribution of ZIKV is shown in [Figure 1].
Figure 1: Current global distribution of Zika virus

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  Methods Top


We did a narrative clinical review on epidemiology, transmission, clinical manifestation, diagnosis, and prevention of ZIKV. Online articles were searched on PubMed, EMBASE, COCHRANE Library, and Google Scholar from January 2016 to April 2016. This review was conducted to answer the following question: What is ZIKV virus, how is ZIKV transmitted, how to diagnose ZIKV virus, how to treat ZIKV virus, how to control ZIKV virus and current controversy regarding ZIKV virus? Keywords used to search articles were "ZIKV," "ZIKAV," "Zika virus," "morbidity," and "mortality." Articles were reviewed from January 2016 to February 2016. Search results had yielded a total of 373 articles, of which 40 articles were included for perusal. Full-text primary peer-reviewed articles in English published from 1964 to 2016 were considered for review. "Primary Research" was defined as studies where the authors reported their own data. Articles published in other languages or not addressing the above-mentioned questions were not included in the study.


  What is Zika Virus? Top


ZIKV is a mosquito-borne disease which belongs to the genre Flavivirus.[1] It is a nonsegmented, single-stranded, positive-sense RNA genome molecule which is 10,794 bases long.[8] The virion is approximately 40 nm in diameter with surface projections that are approximately 5-10 nm. It contains a nucleocapsid surrounded by a host member-derived lipid bilayer that contains envelope proteins E and M. African and Asian lineages are the two main lineages of ZIKV.[7],[8] The pathogenesis of the virus starts with an infection of the dendritic cell near the site of inoculation, followed by spread to lymph nodes and bloodstreams. The virion after gaining access to the bloodstream attaches itself to the host cell membrane via the envelope protein. The virus membrane fuses with the endosomal membrane, and the single-stranded RNA (ssRNA) genome of the virus is released into the cytoplasm. It is translated into a polyprotein which is cleaved to form structural and nonstructural protein. Replication takes place in endoplasmic reticulum resulting in double-stranded RNA genome which is further transcribed, resulting in additional ssRNA. The new virions are then transported to the Golgi apparatus and eventually excreted into the intracellular space. ZIKV antigens have also been found in infected cell nuclei hinting some replication of ZIKV may occur in the nuclei.


  How is Zika Virus Transmitted? Top


Aedes mosquitoes are the known vectors for ZIKV.[1] Aedes aegypti is also the primary vector of dengue virus (DENV), chikungunya virus (CHIKV), and yellow fever virus. This mosquito is most commonly found in the urban setting. It usually bites during the morning and late afternoon hours. The incubation time for ZIKV in mosquito vectors has been found to be approximately 10 days. The vertebrate hosts of the ZIKV are primarily the monkeys and humans. ZIKV has also been known to spread through intrauterine transmission, intrapartum, blood transfusion, and sexual transmission.[6],[9] ZIKV nonvector-borne sexual transmission was first observed in a study done in the United States of America.[10] Although the ZIKV has been detected in breast milk, the spread through breastfeeding has not been documented.[9] The chances of transmission from an infected person to an uninfected person are highest during the first week of ZIKV infection. Due to increased global travel, the global prevalence of A. aegypti has markedly increased.[11] This might contribute to the rapid spread of ZIKV.


  What are the clinical symptoms of Zika Virus Disease? Top


About 80% of the patients infected by the ZIKV are asymptomatic.[12] Symptomatic patients usually experience low-grade fever, maculopapular rash, headache, stomach ache, dizziness, anorexia, arthralgia, and nonpurulent conjunctivitis. These symptoms usually are mild and self-resolve over a 1-week course. According to information from the previous outbreaks, fatalities due to ZIKV are rare. As these symptoms are similar to the dengue and CHIKV, it has been recommended that the patients with suspected ZIKV infections should be evaluated and evaluated for possible DENV or CHIKV.

In the current outbreak, there has been increasing evidence about the association of ZIKV and microcephaly in newborns.[13] There has been an average 20-fold increase in the incidence of microcephaly in Brazil. The case definition of microcephaly used is "head circumference at the birth of 33 cm or below (newborns after 37-43 weeks of gestation)." ZIKV has been found to be positive in newborns affected with microcephaly.[14] There is still a need for more evidence to confirm this association. The full spectrum of outcomes associated with ZIKV-infected pregnancy is unknown, and there is a need for further studies on it. Although pregnant women can be infected with the ZIKV in any trimester,[15] the first trimester has been thought to be the most dangerous time period. It is not known how the virus enters the placenta and damages the brain of the fetus. There is no evidence of whether the pregnant women are more susceptible to ZIKV or experience a more severe spectrum of diseases.


  How to Diagnose Zika Virus Disease? Top


At the moment, there is no commercially available test for ZIKV. The reverse transcription-polymerase chain reaction (RT-PCR) is the test of choice and should be done during the 1st week of illness.[16] The other test including immunoglobulin M (IgM) and neutralizing antibody testing should be performed on specimens collected 4 days after onset of illness. IgM antibodies against ZIKV and other flaviviruses have shown strong cross-reactivity, resulting in false-positive results. According to a study, ZIKV-infected patients can be positive in an IgM assay for DENVs, especially if ZIKV is a secondary Flavivirus infection; however, if the patient has a primary ZKIV infection, then cross-reactivity is minimal.[17] According to another study, urine samples were found to be more helpful in diagnosing ZIKV infection as a higher load of ZIKV RNA was detectable in urine for a longer duration than in serum samples.[18]

Women who have a history of travel to areas with ongoing ZIKV transmitted during pregnancy should be evaluated for ZIKV infection. Testing of asymptomatic women with the absence of fetal microcephaly or intracranial calcifications is not recommended. ZIKV RT-PCR testing can also be performed on amniotic fluid.[9] The sensitivity or specificity of this test is not known. Serial ultrasounds to monitor fetal growth and anatomy are recommended for pregnant women affected with ZIKV. For live birth with evidence of ZIKV infection, testing of frozen placental tissue and cord tissue for ZIKV RNA and histopathology examination of the placenta and umbilical cord is recommended. The mother should also be tested for ZIKV infection if she has not been tested earlier. Ophthalmological evaluation is advised for the newborns with possible ZIKV congenital infection.[19],[20]


  How to treat Zika Virus Disease? Top


There is no specific antiviral treat for ZIKV disease at the moment. Supportive treatments which included rest, fluids, antipyretics, and analgesics are given to the ZIKV-infected patients. It is advised to avoid aspirin and nonsteroidal anti-inflammatory drugs until dengue can be ruled out. This is done to reduce the risk of hemorrhage. The development of a vaccine is in its embryonic stages, and resources can be pooled into research to advance global efforts in the discovery of a vaccine against the disease.


  How to Prevent the Spread of Zika Virus Disease? Top


As there is no specific treatment or vaccine available for ZIKV disease, prevention is essential. The current outbreak in Brazil and other South American countries is exacerbated by the population density. More people living per square kilometer means more people the mosquito can infect. Therefore, it becomes vital to eradicate the ZIKV vector or to prevent it from coming into contact with the population. To avoid contracting the disease, it is essential that contact with the vector is circumvented, and primary prevention of this disease includes using mosquito nets and mosquito repellent creams containing N, N-Diethyl-meta-toluamide, and insecticides may be used to exterminate its vector. It is recommended to cover crib, stroller, and baby carrier with mosquito netting. T-shirts and shorts can be avoided, and long-sleeved shirts with full-length slacks or jeans can be worn in their place. Treating clothing and gear with permethrin is another effective preventive measure. Treated clothing remains protective after multiple washing. As A. aegypti bites mostly during the daytime, it is essential to ensure all of the above protective measures are taken throughout the entire day.[21]

The A. aegypti larvae and eggs are found in standing fresh water. Staying away from standing water and water purification practices will prevent breeding and growth of the mosquito. Water bottles that are unused or have been sitting for lengthy periods of time must be disposed of to avoid the growth of larvae.[22] While watering plants and crops, people can ensure that the water does not stay stagnant for too long.

Awareness of these practices can be spread by public campaigns, pamphlets, media infomercials, and through social media. Doctors and other healthcare professionals should be deployed in ZIKV endemic areas to provide education to volunteers from the population. These volunteers can then pass on the information to the rest of the community in a way which is easier for them to comprehend.

During an outbreak, humans become carriers, and thus, human-to-human transmission is possible. Transmission in this manner may be prevented by isolating patients and preventing sexual intercourse with spouses of the infected. Blood can be screened for the ZIKV before transfusion individuals displaying symptoms. Men who have traveled to affected countries and have not acquired ZIKV symptoms are advised to use condoms for 28 days when they return home, especially if their partner is pregnant. The duration is increased to 6 months if they have acquired ZIKV disease. The Centers for Disease Control has advised against traveling to affected countries for pregnant women and women who are planning to become pregnant.[23] This is in light of the strong association of microcephaly and ZIKV disease. However, ZIKV infection does not pose a risk of birth defects for future pregnancies.[23] Some countries such as Jamaica and El Salvador have advised women not to get pregnant due to the ZIKV epidemic.[24],[25]

Fear of rapid spread of this epidemic is further increased due to the upcoming Summer Olympic Games in Brazil in August 2016. The Games, which will be held in Rio de Janeiro, which is already well known for its densely situated population, have the potential to further serve as a catalyst to catapult the virus across the world, essentially converting it into a pandemic. The risk of spread can be minimized by taking the necessary precautions, such as making sure water does not stagnate, proper mosquito precautions, and provision of mosquito repellants. Spectators, however, are being advised against coming to the sporting event if they are or have any plan of getting pregnant in the near future because of the high risk of infection.[26],[27] ZIKV stalls can be set up at the multiple venues, including a free checkup for audience members showing symptoms. Pregnant women can use bed nets, appropriate clothing, and mosquito repellents to avoid mosquito bites.[28]


  Current Controversies Top


Based on the findings by Musso et al. who detected the ZIKV particles in samples collected from semen, there is a possibility that the ZIKV is a sexually transmitted disease.[29],[30] If it is true, then testing of ZIKV as a sexually transmitted disease should be also done.[31] In addition, the patients can be coinfected with ZIKV and DENV at the same time, so public health measures while managing an outbreak must be taken accordingly and that ZIKV has been associated with Guillain-Barre syndrome based on suspected immunologic origin.[32],[33],[34] Currently, no vaccine or treatment is available to prevent ZIKV disease. Work on a vaccine is currently underway. Previously, cross-reactivity of human antibodies produced in dengue with those in ZIKV infection has also been described, the implications of which include the possibility of prior infection with dengue conferring a protective effect toward any subsequent exposure to ZIKV.[35] Swanstrom et al. later confirmed the presence of protective cross-reactive antibodies in their study, identifying one epitope of monoclonal antibodies which neutralized the envelope proteins envelope dimer epitope 1 in both dengue and ZIKV.[36] Further promising progress is being made in mice, the search for a vaccine is ongoing, and armed with this information breakthroughs can be made. Research development and preventive efforts should be intensified for ZIKV vaccines to facilitate the surveillance and therapeutics if the connection between microcephaly and ZIKV is confirmed.[37]

The greatest challenge is the immunologic response for ZIKV that arises with serologic cross-reactivity from the "original antigenic sin" phenomenon. This phenomenon highlights the fact that patients who have previously been exposed to a heterologous Flavivirus by natural infection or vaccination, the antibody response to the earlier infecting Flavivirus will be more robust than the response to the present one.[38] Even the plaque reduction neutralization test fails to establish a conclusion in such patients. This is a significant problem in dengue endemic areas where reported population exposure is more than 90% to DENV in the past. There is a possibility that both dengue and ZIKV may be cocirculating in such endemic places.[39]


  Review Applicability to Literature Top


The long-lasting effect of the current ZIKV outbreak in the world is still undecided. Herd immunity, although is reliably adequate to lessen the further transmission, this cannot preclude the call for immediate as well as long-term prevention and control strategies. Whether and where the virus becomes endemic somewhere in the globe is a matter of speculation, but it is of substantial significance for the long-term development and sustainability of countermeasures, such as a ZIKV vaccine.


  Conclusion Top


The ZIKV and DENV belong to the same family; however, the ZIKV has many more catastrophic complications. It has been linked to microcephaly in babies born while their mothers were infected although a causal relationship has not yet been found. We are on the verge of a pandemic owing to the brisk rate of spread of this disease, especially since new modes of transmission, including sexual, blood-blood, and perinatal, have been established. Proper vector precautions, as well as isolation methods, can help fight this rapid spread, including at the Olympic Games later this year, in Brazil. In the meantime, while no treatment or vaccine exists, ongoing efforts to develop a means to cure or prevent ZIKV are showing positive results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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What is Zika Virus?
How is Zika Viru...
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