What Should Be Done? Russia Is Facing a Possible Pandemic

Fighting IILD… To no effect…

As the influenza and influenza-like diseases (IILD) affect humans more often than other diseases, both patients and doctors share an illusion that these illnesses can be successfully prevented or treated. It is supported by hundreds of products present on the market that are positioned as preventive or treating medicines. But how great is their effect?

For example, how effective is vaccination against IILD, which is supposed to be the most effective? It turns out that in the years when there is no mass disease incidence, vaccination practically does not decrease the chance of catching a cold. For adults this chance decreases by less than 10 %, that is, by a value that can hardly be detected by modern methods. The reason is simple: in these years the diseases are caused by different pathogens, and that is why the vaccine against only a couple of them does not work in most cases. For an obvious reason the predominant pathogens of the season are discovered too late…

Sometimes other data can be found: morbidity decrease as a result of vaccination by 50 or even 80 %. These figures, strange as it may seem, are true; however, they are obtained when not all infected people but only those who had a definite type of influenza are taken into account. For example, let us consider that among each 100 of IILD-patients ten people, on average, have influenza of a definite type. In the case of 50 % vaccination only five of them will fall ill; however, this makes up only 5% in 100 patients. Figures of this kind are of interest not to the patients, but to the scientists, for they make it possible to predict the effect of vaccination at the time of an epidemic.

It is worth noting that for people living in retirement homes the vaccination effectiveness is somewhat higher, up to 25 %, for the pathogens are more homogenous there. It is also important that at vaccination the number of complications decreases. This will be discussed later. However, on the whole we have to disappoint those working people who are attracted by the chance if not to get sick in winter then at least to quickly get better due to vaccination: IILDs of vaccinated people are shorter by an infinitesimal value — on average by 0.4 of the day.

The situation with the medicines for chemotherapy of influenza is no better. The best known and widespread remedies — adamantanes (rimantadine, amantadine) help in the case of A-type influenza, which includes more than 90 % of circulating viruses (read more about the influenza viruses’ classification in “Science First Hand”, issue 3(9), 2006). The new medicines, including zanamivir and oseltamivir containing so called NI — neuraminidase (the surface protein of the virus) inhibitors, are effective in the case of influenza of A and B types. But how much do they help? If one begins to take the medicines within the first forty-eight hours after the first symptoms the symptomatic period is just one day shorter. Side effects are such that every third patient stops the treatment.

The trouble is that even these few and ineffective specific remedies lose their effectiveness very quickly. In 2003–2004 about 10 % of all known strains of the A type viruses were resistant to adamantanes. The data of an investigation in 2005–2006 show such resistance in nine out of ten strains circulating in the USA! The situation with the NI-medicines is slightly better: in the USA the resistance to them is rare, and they are about a hundred times more expensive. In January 2006, it was recommended there to stop using adamantanes and to use NIs only in special cases.

As for the Russian market, there are a lot of medicines to treat influenza, such as arbidol, aflubin, gripferon, imunofan, etc. As they are, as a rule, allowed without special “blind” randomized controlled tests (RCT), their effectiveness is unknown. Symptomatic folk remedies, such as hot drinks with honey, raspberry jam, and herbal teas can really lessen the edema of mucous membranes and temporarily make the patient feel better. However, they cannot be classified as drugs of specific treatment in the true sense. We know about some of such remedies, for example, about the thick chicken broth described in the Old Testament, as much as our forefathers: no scientific research of their effectiveness has been conducted.

37 years without a pandemic

Despite the fact that the recovery from IILDs usually takes place without any treatment, a part of patients get complications. They include, first of all, pneumonia, not necessarily serious but, considering a great number of the patients, the deathly toll is large (the share of the perished from the number of the ill is 0.04 %). This is not many when forecasting the outcome of an individual case, but it is impressive on the world scale. As about 20 % of the planet population (about 1.2 billion) is affected by IILDs every year, more than 500 thousand people in the world die of complications annually!

Even more people die in influenza epidemics. Studies of the bodies, frozen in permafrost areas, of those who died from “Spanish influenza” in 1918, show reliably that the epidemic was caused by one of the viral strains of A type influenza. That epidemic took the lives of more than 20 million people at the assumed lethality of 2–3 %. If such an epidemic happens again, about 70 million people will die, and many will fall ill within a very short time of about a few months. As the medical staff is in close contact with the ill, they will be affected in the worst way. The public health system will be not only overstrained but also weakened.

Modern variants of the bird flu virus are transmitted to humans at close contacts with infected birds, causing the serious disease.
So far the virus cannot be transmitted from human to human. It is unknown whether this ability will appear or whether the future pandemic will be caused by another virus. We can only suppose that sooner or later this has to happen

How justified are these forecasts? It is well known that the time intervals between the influenza pandemics in the 20th century were from 10 to 42 years. The last one is already lasting 37 years. It witnessed the birth of two generations. That is why, even if a new pandemic virus will be quite like the previous one, the most part of the world population will still be highly susceptible to it.

Three years ago the humankind was already alarmed when cases of atypical pneumonia coming from Indochina were registered. It was determined that the disease called “severe acute respiratory syndrome” — SARS — was caused by a virus and is serious, with lethality of about 10 %. However, some time later, owing to certain measures to limit travels and isolate contacts, the spread of SARS was stopped. Some doctors deny the clinical reality of this severe disease considering it a mere result of progress in laboratory diagnostics. Indeed, the etiological structure of pneumonia is varied, and it often takes a serious course. For example, only in the USA about 200 thousand people are hospitalized with various post-influenza complications every year, and 36 thousand of the patients die of them, mainly of pneumonia.

The SARS attack made it evident for the humankind that it is not ready for a new influenza pandemic, and in a sense it is as unprotected as in 1918. Certainly, now there is a system to study the viruses, and tissue samples are delivered to laboratories of America and Europe every day. Computer systems keep track of the results of analyses, making them known to all specialists included in the world within several minutes. When a new virus appears, vaccine producers immediately start developing an appropriate vaccine. The optimistic picture is spoiled by just one thing: the system is not fast enough in comparison with a possible epidemic spread rate. It takes from 8 to 12 days to identify the virus after the first patients have been registered. In this time the virus can spread so widely that it may be impossible to stop it. And the mutant pandemic virus strain may appear not only in one place or from that “bird flu” strain (H5N1) that attracts everybody’s attention today.

Unfortunately, flu vaccines are created only by few large producers: more than 95 % of the plants are located in five countries. That is why the system is vulnerable. Besides, in the existing conditions the vaccine will appear not earlier than in half a year, and its quantity will be catastrophically insufficient even for the vaccination of the population of the producing countries themselves.

Strategic preparation

Thus, in half a year the virus might get a grip on the world and take its heavy toll. The world economy will suffer, the finances will move to safe zones; poor countries will suffer most from the virus, and their problems will be aggravated… Closing the borders will severely affect the economy of all countries, not excepting Russia. A sacramental question arises: What has to be done? The governments of many countries began strategic preparation for a possible pandemic of serious influenza, which is seen by many as a natural continuation of today’s epidemic of bird infection.

Before the outbreak of the most recent epidemic, the International Veterinarian Organization did not recommend to vaccinate poultry against influenza, for this was considered to speed up the virus mutation. Now there is only a warning to those countries that conduct or plan vaccination. As the infection of humans from birds leads to serious consequences, and the extermination of the great poultry livestock and limitations on its transportation and sale bring about great losses, some countries risked vaccination in hope that if the virus transmission in poultry is stopped, it will disappear in the wild nature by itself. Of all possible outcomes only one is evident, that is, tremendous expenditures on the vaccination. Besides, the effectiveness of the vaccination has so far been proved only for chickens; for other birds either there is no vaccine or it is ineffective.

The world needs Russia in the preparation for a pandemic as much as Russia needs the world. No single country or organization has enough resources to successfully withstand the threat

Naturally, the situation of excitement stirs swindlers to activity: suspicious vaccines are sold not only in Russian villages — in the USA more than a thousand of employees of a big company was vaccinated against “bird flu” with… distilled water! Uncontrollable fear might lead to something even worse than that. While coordinating specialized organizations, UNO developed a strategy for early detection of the infection, efficient communication of information, and containment of the infection spread until a needed quantity of the vaccine is produced.

The vaccine producers are urgently developing a new technology, “faster” than the usual one, and are going to submit it for approval in the USA and Europe. Large European and American producers joined their efforts in an association, which includes many small companies, with which governments begin active collaboration. Unfortunately, this does not apply to the Russian government or to Russian producers who, neither quantitavely nor qualitatively, meet the country’s demand even in usual conditions (recall the “Russian influenza” epidemic caused by our nfluenza vaccine not so long ago). This causes serious alarm, for the lives of millions of Russians will depend on the adequate vaccine supply. The solution to the problem of vaccination against influenza within the framework of strategic preparation to a pandemic should not be left to the market; nor should it be limited by providing small grants to support the producers.

There is no doubt that efforts to fully localize a new infection within a limited territory will fail. All organizations engaged in the strategic preparation for a pandemic in recent years believe that the infection spread can only be slowed down by isolating the patients at home. To minimize the death rate it is planned to isolate the infected together with their families. It is supposed that all of them will get antiviral medicaments by mail and take them for prophylaxis. For this, strategic stocks of the necessary medicines are being created, and a tactics of their long storage with packing as needed is being developed.

Many countries are actively cooperating with a special organization of producers of antivirus medicines. As there is no hope that, when the need arises, there will be enough time to produce the needed quantity without any help, the producers license the production of medicines and create production chains that increase the process efficiency on the international level. Unfortunately, Russia does not take part in this important business, although WHO disseminated all necessary information about the plan of preparation to an influenza pandemic translated into Russian.

How many ALV devices are there in Russia?

It is said that the Russian government is getting ready to buy antivirus medicines. Meanwhile, there is practically no proper production in our country: domestic producers offer Chinese rimantadine and other ineffective medicines of the kind packed in our plants. However, even if the government offers tenders for the purchase of NI-preparations, which are more effective against influenza, it will not be a way out of the situation. The point is that even though NI-preparations shorten the symptomatic period and reduce the number of complications, they do not decrease the patients’ infectiousness. Moreover, for cases of H5N1 strain influenza in Asia high resistance to NI was registered. Nobody knows how high will be the resistance of the future pandemic virus.

In the pandemic containment strategy, all possible actions are considered. Some countries prepare for the use of face masks by the population and medical staff: not those well-known ineffective gauze bandages, but special N95 masks, whose effectiveness in protecting against the respiratory infection is supposed to be high on the basis of laboratory tests. European countries store billions of such masks for the medical staff and population for the case of a possible pandemic. There are such masks on the Russian market, but the majority of doctors, nurses, and druggists have never seen them.

Additional special isolated beds provided with artificial lung ventilation (ALV) facilities are being created. In Singapore alone, 1400 of such beds have already been prepared for this purpose. And what do you think, how many of ALVs are there in our hospitals besides those used daily for anaesthesia and intensive therapy? Meanwhile, the absence of reserve ALVs means that 5–10 % of those patients who will be hospitalized with serious influenza during a possible pandemic will die.

The preparation for a pandemic requires strategic planning of the work of medical services. Thus, as a result of a recent study conducted in the USA it was determined that in case of a pandemic threat about a half of public health workers will not work. And not only because hospitals are places where the chance to become infected is the highest, but also because pre-schools and schools will be closed. If we assume that the hospital staff will catch the infection and even die more often than others, we should get ready for a real organizational catastrophe in the public health service. We need not only detailed plans but also real full-scale training with the participation of medical workers, to achieve better interaction between all structures at the municipal, regional, and national levels.

Unfortunately, to this day the main emphasis in Russia is given to the prevention of bird flu spread, but these necessary actions cannot replace the preparation for a pandemic that may be caused by another mutated virus. However, there were no Russian representatives at the meeting of world experts in Geneva in April 2006. The meeting was devoted to the prospects of using the production facilities specializing in animal vaccines to produce a human vaccine. Russian representatives did not attend all other meetings on the preparation for a pandemic.

In March 2006, the Russian government discussed the issue “About the participation of the Russian Federation in the efforts of the world community aimed at controlling influenza, including bird influenza”. Vice-prime minister D. Medvedev was appointed head of the governmental committee on bird flu control. This gave hope that the government would begin a strategic preparation of the country and, first of all, of its public health service, for a possible pandemic, including every medical worker, governor, and mayor.

However, several months have passed, but the situation in Russia has not changed. Though now, as never before, it is evident that a couple of antiplague suits will not protect the staff of the clinics and their patients. A state program providing the participation of all people is what we need. We cannot expect miracles. While the majority leader in the US Congress called the preparation for an influenza pandemic the “Manhattan Project of the 21st century” (similarly to the project on the creation of the first atomic bomb, in which unprecedented intellectual, material, and industrial resources were involved), our country, figuratively speaking, is once again planning to “mobilize cartages and carrier pigeons from the population” (that is how it was before the World War II!). It seems that we failed to learn the lesson of history…

References

1. Jefferson T., Smith S., Demicheli V., Harnden A., Rivetti A., Di PC. Assessment of the efficacy and effectiveness of influenza vaccines in healthy children: systematic review. Lancet 2005; 365(9461):773–780.

2. Jefferson T., Rivetti D., Rivetti A., Rudin M., Di PC, Demicheli V. Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review. Lancet 2005; 366(9492):1165–1174.

3. Jefferson T., Smith S., Demicheli V., Harnden A., Rivetti A. Safety of influenza vaccines in children. Lancet 2005; 366(9488):803–804.

4. Jefferson T., Demicheli V., Rivetti D., Jones M., Di PC, Rivetti A. Antivirals for influenza in healthy adults: systematic review. Lancet 2006; 367(9507):303–313.

5. Bright R. A., Shay D. K., Shu B., Cox N. J., Klimov A. I. Adamantane resistance among influenza A viruses isolated early during the 2005–2006 influenza season in the United States. JAMA 2006; 295(8):891–894.