FLU, I CHOOSE YOU: EVOLUTION OF INFLUENZA VIRUS AND ITS CONSEQUENCES

The state budgetary professional education institution of the

Healthcare Department of Moscow

«Medical college № 6»

FLU, I CHOOSE YOU: EVOLUTION OF INFLUENZA VIRUS AND ITS CONSEQUENCES

Koltcova Natalia Alekseevna

4th year student, specialisation 31.02.03 Laboratory diagnosis

academic advisor – Afromeeva Tatyana Aleksandrovna, english teacher of SBPEIHDM «MC № 1»

2019

What are the most dangerous infectious diseases? Plague, cholera, HIV are beyond doubt. But not many people without medical education would include flu into this list. And at the same time, most scientists and doctors agree that flu is currently one of the most dangerous infections and deserves maximum attention.

World Health Organization (WHO) gives us such numbers as about 3 to 5 million cases of severe illness, and about 290 000 to 650 000 respiratory deaths each year caused by flu [8]. What exactly makes this virus so dangerous and why can't we curb it even though vaccination campaigns are regularly conducted? This, as well as the evolution and history of the virus, will be considered in this review.

The first question that should be clarified is that influenza differs from other respiratory viral infections in a number of symptoms [4], often causes complications in high-risk groups, and can cause not only annual epidemics, but also pandemics. The thing that should be in every mind is that not every cold is a flu.

There are three types of influenza virus that can cause illness in humans: A, B, C. Type C virus is a mild one for humans, but types A and B are not so simple. Influenza A viruses are divided into subtypes depending on the combination of proteins hemagglutinin and neuraminidase and causes the greatest difficulties, influenza B viruses are not divided into subtypes, but have several lineages. Both can cause seasonal epidemics. However, flu is anthropozoonotic disease, and also circulates among birds, livestock and other animals. Virus is especially dangerous when it comes to the human population from outside, and people do not have an immunological memory for this type. In this case, most successful strains of the virus can cause very severe disease. Over the past hundred years, humanity has been through such pandemics four times.

The worst flu pandemic took over the planet in 1918-1919 and claimed, according to various estimates, from 50 to 100 million lives, more than First world war that had just ended for that time. Some communities were destroyed completely. There was no way to detect the pathogen, no antimicrobial drugs to treat bacterial complications then. However, complications usually did not even appear, and the disease killed its victim in the first days. It was also surprising that under attack were mostly young healthy people of 20-30 years. Doctors, making an autopsy, observed only a “decomposed wet foamy mass” instead of lungs, in fact, the patient choked on his own blood [2]. “Spanish flu”, as it was called, remained a mystery for the scientists for a very long time, until finally it was solved in 21st century by sequencing viral RNA from the lungs of the woman, buried in permafrost.  The causative agent was influenza A virus subtype H1N1. The same serotype caused the 2009 pandemic, that was called “Swine flu”. In 2009, the fatal victims were from 100 to 400 thousand people.

Two other pandemics, the 1957 Asian flu and the 1968 Hong Kong flu, were caused by the H2N2 and H3N2 serotypes, respectively, and had between 1 and 4 million deaths each. [8]

What is the reason for such success of the virus? The answer is quite simple – it is its variability. The two proteins used for serotyping type A influenza, hemagglutinin (promotes the attachment of a viral particle to the cell) and neuraminidase (facilitates the release of newly formed viral particles from the cell surface) have 18 and 10 currently defined types. Only 3 and 2 of them are currently circulating in the human population, respectively. However, nothing gives us a guarantee that the virus will not pass to a person from an animal population. This situation did happen already in the recent past, when in 1997 in Hong Kong a dangerous number of cases of infection with bird flu H5N1 were recorded [2]. To prevent the spread of infection and possible mutation of the virus, when it could be transmitted from person to person, about 1.2 million poultry were destroyed in Hong Kong, and all subsequent imported birds were subjected to strict control. In the case of the formation of a successful hybrid of the bird virus with the human virus, a new pandemic could not be avoided. And such opportunity exists always.

This possibility is given to the virus by a phenomenon called antigenic shift. Segmented RNA genes of the influenza virus, when it enters the cell simultaneously with another strain, tend to mix segments, which can lead to the emergence of a new virus with radically altered pathogenic and antigenic properties [1]. Such viruses have the potential to become pandemic.

Another ability - antigenic drift - is the constant appearance of mutations in the virus genome due to errors in the operation of RNA polymerase. Thus, the virus exists in the form of a quasispecies. Current species are determined by passing through the evolutionary “bottleneck” [1]. However, our immunity no longer has weapons against the new strain.

It is because of this ability that there is no single cure for the annual influenza epidemic, the virus is changing too fast, and humanity has to manage to make new vaccines for each new season based on many observations, calculations and predictions.

Vaccination is the main way to prevent flu at the moment, although it is not perfect. Vaccines are mainly indicated for children, the elderly, pregnant women and people with weakened immune system. It is important to vaccinate not only these high-risk groups, but also healthy adults, as this helps to reduce the spread of the disease during annual epidemic. At the moment, vaccination is carried out for the most part by local vaccines, among which the most common are: Sovigripp, Grippol plus, Grippol and Ultrix. [6] Each of them has its weak points, however, we can observe a clear negative correlation between the number of vaccinated and sick people (see Fig.1).

However, vaccine production is a complex and long process, which is also complicated by the constant mutation of the virus, and scientists all over the world monitor the prevailing strains and make forecasts based on which the decision on the composition of the vaccine for the next epidemic season is made. That is why the vaccine needs to be renewed every year. In case of a pandemic strain, there is also hope for its early detection and making a suitable vaccine.

Figure 1. The dynamics of the morbidity of influenza and the number of vaccinated against influenza in the period 1996-2018 in Russia.

What should be done if flu eventually has been caught? Speaking about antiviral drugs, we can divide them into two groups: drugs of the adamantane group (Amantadine, Rimantadine), to which flu has developed resistance at some point, and at the moment their use is considered inappropriate; and neuraminidase inhibitors (Oseltamivir, Zanamivir), which effectiveness is also disputable [8]. Neuraminidase inhibitors are prescribed only in severe cases. No other drugs affect the influenza virus and are only symptomatic.

To summarize the information received, there are several ways that humanity can affect the morbidity of influenza:

1. Predict. In this field the work of many people - scientists, doctors, veterinarians - should be globally united. Thanks to global monitoring, it is possible to prevent a potential pandemic at the root, as well as develop effective vaccines against annual epidemics.

2. Prevent. Global vaccination coverage, as well as basic personal hygiene allows to reduce morbidity to a minimum.

3. Treat. Antiviral drugs against flu are currently not as effective as antibiotics for bacterial infections, so there should not be high hopes for them. However, the development of new drugs that can treat the flu more effectively is needed.

In order for each of these steps to be real, basic competence in these matters is necessary for all the people, and the important role of every medic is to provide correct and useful information about flu, so that there could be less sad outcomes in that field of medicine in our society.

Bibliography:

1. Cordingley, Michael G. Viruses: Agents of evolutionary invention. – Harvard University Press, 2017.
2. Kolata, G. Flu. The story of the great influenza pandemic of 1918 and the search for the virus that caused it. – Brockman, Inc., 1999.
3. Lennette’s laboratoty diagnosis of viral infections/ Edited by Keith R. Jerome. – Informa Healthcare USA, Inc., 2010.
4. Levinson, W. Review of Medical Microbiology and Immunology. -  13th edition. – McGraw-Hill Education, 2014.
5. Chugunov, A. Racing with virus: epidemiology and ecology of influenza virus. [Electronic resource] / A. Chugunov // Biomolecula. – 2011. – Access mode: https://biomolecula.ru/articles/gonki-s-virusom-epidemiologiia-i-ekologiia-virusa-grippa
6. Remish, A. A lot is not always good: "Ultrix", "Grippol", "Sovigripp" — what to choose? [Electronic resource] / A. Remish // Biomolecula. – 2019. – Access mode: https://biomolecula.ru/articles/mnogo-ne-znachit-khorosho-ultriks-grippol-sovigripp-chto-vybrat#source-5
7. Shah, Sonia Pandemic. Tracking contagions, from cholera to ebola and beyond. - Sarah Crichton Books, 2016.
8. Influenza [Electronic resource] / World Health Organization. – Access mode: https://www.who.int/influenza/en/