What to do with the Zika virus?

Zika virus: an imaginary panic or a real threat?

Natalia Semenko, "Biomolecule"

The phenomenon of the Zika virus can be used in epidemiology textbooks as a vivid example of an underestimated threat. At the beginning of 2016, most infectious disease specialists and epidemiologists were skeptical about the media hype associated with the spread of a new-fangled disease, and argued that the devil is not as terrible as it is painted. The real devil turned out to be much more terrible than the painted one. Moreover, WHO has assigned Zika fever the status of a "global threat", and it doesn't matter how it happened. There is only one question on the agenda – what to do in the current situation?

The appearance of the "zero patient" with microcephaly, who was born in the Brazilian state of Pernambuco to a mother infected with the Zika virus during pregnancy, became the starting point of the epidemic [1]. According to WHO data from September 1, 2016, cases of Zika fever were recorded in 72 countries around the world. The rate of infection spread turned out to be unprecedentedly high, and the transmission pathways and mechanisms are more complex than those of other viruses of a similar nature. The increase in the number of children with congenital defects has actualized the issue of legalizing abortion even in the most conservative countries. In this article we understand why endemic disease has become a global problem, how real it is to get infected and, most importantly, how to live with it.

Zika fever: what kind of beast and where did it come from?

The method of scientific poking and randomness are the main research methods in modern science. The Zika virus was also discovered by chance in the forest of the same name. In 1947, a Flaviviridae family virus with a similar but not identical antigenic structure was isolated in Uganda while monitoring the circulation of the yellow fever virus among rhesus monkeys. It was not studied until 2015, because it was considered a highly endemic disease with low virulence. Only sporadic outbreaks of the disease were observed in Micronesia and Polynesia (Fig. 1). The exceptions were the epidemics on Yap Island (2007) and in French Polynesia (2013). These cases signaled the potential danger of the virus even then, but the world did not hear these "calls" [2].

Figure 1. The history of the spread of the Zika virus. Drawing from the website vox.com .

The Zika virus has a structure typical of the Flaviviridae family: the RNA+ genome (the RNA of the virus in an infected cell plays the role of mRNA), the nucleocapsid and glycoprotein supercapsid, icosahedral type of symmetry (Fig. 2). The basis of the supercapsid is glycoprotein E, which is the main factor of virus adhesion, participates in the unification of the virus envelope with the cell membrane. In addition, the virion includes high-molecular proteins HC1, NS3, NS5 and low-molecular proteins NS2A, NS2B, NS4A and NS4B. Their role is currently poorly understood [3].

Figure 2. Zika virus model (Visual Science Company). Drawing from the website chrdk.ru .

Where and how does the Zika virus spread?

The Zika virus has long been considered a classic example of arbovirus infection. Roughly speaking, groups of viral infections of completely different genetic nature, which are united by only one thing – arthropods as carriers. Specific vectors of the Zika virus are Aedes aegypti mosquitoes (Fig. 3) and Aedes albopictus [2]. The habitat of these species is limited to equatorial and tropical areas. Accordingly, the virus can actively spread only in these regions. It was considered so until recently.

Figure 3. Aedes aegypti is a carrier of the Zika virus. Drawing from the website circleofblue.org .

Due to the rapid spread of Zika fever in Central and South America, confirmation of the transplacental transmission route, as well as the occurrence of non-endemic cases of the disease outside the habitat of the mosquito carriers, scientists began to study in more detail the ways of transmission of the virus. It is clear that whoever is looking for will always find it – this happened as a result of the research. All hypotheses have indirect or small evidence, but they are no less interesting. It is assumed that the virus can be transmitted during blood transfusions, and it has also recently been established that female Aedes mosquitoes can infect their offspring. The possibility of sexual transmission is considered particularly dangerous, because it erases the boundaries of the endemicity of Zika fever and gives this disease a high level of social danger [4].

Why is there so much noise?

In the scientific literature, the clinical picture of fever is called a lite version of dengue fever, not burdened with hemorrhagic syndrome and mortality [5]. However, in order to roughly understand what this means, you still need to find a person who has seen at least once a live patient infected with the dengue fever virus. To put it simply, Zika fever manifests itself in the same way as many other infectious diseases (Fig. 4). It is possible to confirm the diagnosis only in the laboratory.

Figure 4. Clinical picture of Zika fever. Drawing from the website ww.politicswithstyle.com .

It is important to note that laboratory diagnosis of the Zika virus is very difficult and not always accurate. The study by enzyme immunoassay (ELISA) can give false positive results, since the Zika virus contains antigens that cross-react with antibodies of the dengue virus. A more or less reliable method of diagnosis at the moment is polymerase chain reaction (PCR) [6].

A promising direction in laboratory diagnostics is the use of nanotechnology. A striking example is the spectroscopy method using silver nanoparticles that amplify the signal. The technique is based on SERS – raman scattering of light. Thanks to this type of diagnosis, trace virus particles in biological material can be detected in less than 1 minute, as well as strains of reproducing viruses can be identified, revealing even the smallest spectral differences in the structure of proteins [7].

Atomic force microscopy (AFM) is another method that can be used to study rather than diagnose the Zika virus and not only it. The essence of the study is that the virion is "felt" with the help of scanning probes, subsequently mapping its surface (Fig. 5) [8].

Figure 5. Operation diagram of the atomic force microscope. Drawing from the website physics4thecool.com .

But back to the clinic. After 2-12 days from the moment of penetration into the dendritic skin cells (the target of the virus), after overcoming the lymph nodes, viremia develops as the last barrier. Simultaneously with viremia, fever, macular-papular rashes, muscle pain and conjunctivitis appear. Recovery occurs in 100% of cases 7 days after the first symptoms appear. "What's the catch?" – you ask and you will be right. The main problem is the development of prenatal pathology and possible complications [5].

The occurrence of prenatal pathology, namely microcephaly in newborns (Fig. 6) infected with the Zika virus in utero, has become the main cause of excitement in scientific circles and the media. The diagnosis of microcephaly is a verdict that puts an end to the possibility of living a normal physical and social life. This defect is completely beyond correction, but is diagnosed in the early stages, when abortion is still possible. And here there is already a bioethical conflict [9], social issues. It becomes quite difficult. Actually, more on that later. At the moment, it is important to understand the degree of danger of the virus itself. The fact that the Zika virus was the cause of microcephaly is almost undeniable. Its particles were found both in the amniotic fluid of fetuses with microcephaly, and directly in the brain during the study of cases that ended fatally [10]. The statistics are frightening: since the beginning of the Zika virus epidemic and by the end of 2015, the number of microcephalic children in Brazil was 1,248. For comparison, in 2014, only 59 cases of this defect were observed in the same region. According to the level of danger for pregnant women, the Zika virus is on the same level as rubella, but in this case there is no vaccine or other reliable way to protect yourself. And that's why it's scary.

Figure 6. Comparison of the head size of a child with microcephaly syndrome
with a physiological norm. Drawing from the website ilive.com.ua .

As for complications in adults, this is the case when it is rare, but aptly. Guillain-Barre syndrome is manifested by neurological disorders that have the pathogenesis of sluggish paralysis. Patients have muscle weakness, facial nerve paralysis and bulbar paralysis. The latter causes the death of 5% of patients. Another 20% become disabled due to pathology, which scares even more. There is no direct evidence of a link between Guillain-Barre syndrome and Zika virus infection yet, but the fact that WHO is talking about it seems to hint [11].

So many letters, but what to do?

It all depends on whether you are "already" or "still". If you have already, in the sense, become infected, then there is no etiotropic treatment at the moment, as for most viral infections. In general, antiviral drugs are such an interesting topic that it would be worth devoting a separate article to, but this is not about that now. Treatment of Zika fever in patients is carried out symptomatically and ends with convalescence. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used... Important detail: before prescribing NSAIDs, it is mandatory to conduct differential laboratory diagnostics (ELISA, PCR) in order to exclude dengue fever (Fig. 7). The use of NSAIDs in any fevers with hemorrhagic syndrome is categorically contraindicated, since these drugs inhibit cyclooxygenase type 1, which leads to disruption of the blood clotting process and can provoke deterioration of the patient's condition [12].

Figure 7. Laboratory diagnostics is mandatory 
at the diagnosis of "Zika fever". Drawing from the website bbc.com .

If we talk about prevention, there is no specific prevention. Several pharmaceutical corporations announced the development of the vaccine in 2015, including Sanofi, Inovio, Hawaii Biotech, GSK. The medical community had high hopes for the development of the Sanofi regional division in Hawaii, since earlier it was this concern that created and tested a vaccine against dengue fever [13]. Also recently, American scientists announced the creation and successful animal testing of an innovative DNA vaccine against the Zika virus. The drug is created using genetic engineering. A certain sequence of nucleotides encoding virus antigens is embedded in the vaccine vector (it can be either a weakened virus or a bacterial plasmid). When entering the cells of the body, the nucleotide sequence is replicated and "forces" the cell to synthesize the necessary immunogenic, but not pathogenic proteins. The immune system reacts with the synthesis of antibodies – there is a stable humoral immunity. The Zika virus vaccine has been tested on laboratory animals. It stimulates the stable production of IgM and IgG in mice and primates, resistance to infection correlates with the viral neutralizing activity of the blood serum of experimental animals [14]. It is quite possible that in the near future the drug can count on clinical trials.

The easiest way to provide non-specific prevention is for tourists: well, you don't go to the regions of the epidemic in a pregnant state! In all other cases, it is not necessary to cancel trips, but it is better to observe precautions. They include the use of repellents, mosquito nets, protected sexual contacts. The authorities of countries with the presence of an epidemic or the risk of its occurrence should carry out preventive disinfection and destruction of the offspring of Aedes mosquitoes (Fig. 8).

Figure 8. The destruction of vector mosquitoes is necessary to prevent
the spread of the Zika virus. Drawing from the website realgreen.com .

How does the Zika virus epidemic affect the world?

The spread of Zika fever around the globe has caused a significant resonance in society precisely due to the teratogenic effect of the virus. The fact is that the most serious epidemic situation in connection with this disease has developed in the countries of Africa, Central and South America. Very often these are countries with a sharply patriarchal culture (especially African ones), where not only abortions are not allowed, but the tradition of female circumcision is still popular there (Nigeria, Cameroon, Congo, etc.) [15]! In Latin America, first of all, in Brazil, the situation is not much better: the possibility of artificially terminating a pregnancy is just a rare exception that confirms the rule. Because of the fear of congenital pathology in a child, women in these countries very often go for an illegal abortion, which is fraught with death. This state of affairs cannot but worry society, therefore, in many Latin American countries, for the first time in many years, the issue of legalizing abortion was raised (Fig. 9). However, at the moment no decision was followed even in Brazil, where the resonance was particularly high [16].

Figure 9. Demonstration in support of women's right to free abortion.
Drawing from the website spain.org.ru .

In addition, the epidemic of Zika fever for some time threatened the 2016 Olympic Games in Rio de Janeiro. Several teams even refused to participate in the competition because of the danger of infection. However, now that the Games have already ended, we can safely say that the Zika virus has not affected the Olympics in any way.

In conclusion

It is difficult to say how strong the spread of the Zika virus will be, whether it will remain a pandemic status, which is attributed to the disease by part of the scientific community. In many ways, everything depends on whether the sexual pathway of transmission of infection is confirmed, whether the pathogen adapts to new vectors, in particular, to other representatives of the genus Aedes. Perhaps an effective and safe vaccine will be created later – then the danger of the disease will be completely leveled. In the meantime, it remains to relax, follow the news and not panic ahead of time.

Literature

1. Zika virus: the history of its spread. (2016). BBC Russian Service;
2. Hayes E.B. (2009). Zika virus outside Africa. Emerg. Infect. Dis. 15, 1347–1350;
3. Chambers T.J., Hahn C.S., Galler R., Rice C.M. (1990). Flavivirus genome organization, expression, and replication. Annu. Rev. Microbiol. 44, 649–688;
4. Foy B.D., Kobylinski K.C., Chilson Foy J.L., Blitvich B.J., Travassos da Rosa A., Haddow A.D. et al. (2011). Probable non-vector-borne transmission of Zika virus, Colorado, USA. Emerg. Infect. Dis. 17, 880–882;
5. Heang V., Yasuda C.Y., Sovann L., Haddow A.D., Travassos da Rosa A.P., Tesh R.B., Kasper M.R. (2012). Zika virus infection, Cambodia, 2010. Emerg. Infect. Dis. 18, 349–351;
6. Shan C., Xie X., Barrett A.D., Garcia-Blanco M.A., Tesh R.B., Vasconcelos P.F. et al. (2016). Zika virus: diagnosis, therapeutics, and vaccine. ACS Infect. Dis. 2, 170–172;
7. Mustafin I.G. (2011). Nanotechnology in the diagnosis of infectious diseases. Healthy Nation. 3, 25–27;
8. Lozovskaya E. (2004). Atomic force microscopy. Science and life;
9. biomolecule: "Studies on bioethics";
10. Vogel G. (2015). Fast-spreading virus may cause severe birth defects. Science News;
11. A disease caused by the Zika virus. (2016). WHO Newsletter;
12. Pregnancy management in the context of Zika virus infection. (2016). WHO website;
13. Zika Virus For Health Care Providers: Clinical Evaluation & Disease. (2016). CDC Website;
14. Dowd K.A., Ko S.-Y., Morabito K.M., Yang E.S., Pelc R.S., DeMaso C.R. et al. (2016). Rapid development of a DNA vaccine for Zika virus. Science. doi: 10.1126/science.aai9137;
15. Klintsevich M. (2016). Female circumcision – why it is done and what are the consequences. Moscow Medicine;
16. Carneiro J. (2014). Why are Brazilian politicians silent about abortion? BBC Russian Service.

Portal "Eternal youth" http://vechnayamolodost.ru  05.10.2016