What will happen to the flu? Spain pursues a goal that has never been achieved

When during the innocent days of February the covid-19 was dispatched as a simple flu, not only was the pandemic at the doors being downplayed, but also another disease that caused in the 2018-19 season 35,300 hospitalizations, 2,500 ICU admissions and 6,300 deaths, according to the Influenza Surveillance System in Spain. An approximation that points to an unequivocal reality: the coincidence of the peak of the influenza virus with a hypothetical regrowth can be lethal, both due to saturation of available resources and due to the comorbidity between both diseases.

Hence this year preparing for the flu campaign is even more important than ever. “Every year it is important because it prevents diseases, deaths and complications, but this year, with the possibility that the epidemic peak coincides with a second wave, we must try as much as possible to generate the least number of cases and less seriousness ”, he explains. Jose Antonio Navarro Alonso, expert in vaccines of the Spanish Association of Vaccination.

The number in the framework agreement has increased by 6.9%, but the government has made an additional purchase of 5.2 million vaccines

"The authorities are making a great effort to try to increase vaccination," he agrees. Angel Gil, Professor of Preventive Medicine and Public Health at the Rey Juan Carlos University. "In countries of the southern hemisphere such as Australia they have achieved very high coverage and thanks to this they have had almost no admissions for influenza, and that allows the health system to be able to take care of people adequately well." Especially if, as a group of experts in ‘JAMA’ recalled, a “double pandemic“Flu and covid could be a perfect storm of increased income and morbidity.

The government has a plan, which is included in the Early Response Plan in a Pandemic Control Scenario, which involves an extraordinary purchase of flu vaccines. The objective for the next campaign is ambitious, although it is in line with the recommendations of the WHO and the European Commission: reach or exceed vaccination coverage of 75% among those over 65 years of age and among health and social health personnel, and 60% among pregnant women and people at risk.

Ambitious, because current flu coverage figures are far from that number. According to data from the ministry itself, the vaccination rate among those over 65 has rarely exceeded 60%. It has not done so since the 2009-2010 season, when it was at 65.7% due to the reinforcement due to the influenza A outbreak. Last year it was a 54.3%. In the 2018-19 campaign, the average coverage of the Spanish autonomous communities among pregnant women is at a 40.6% and that of health personnel, in 35%.

In other words, it takes an increase of at least 21% among those over 65 and up to 25% in other population groups to reach the goal. Hence the extraordinary purchase that complements those requested by the autonomous communities under the Framework Agreement, which includes all except Andalusia, Catalonia, the Canary Islands and the Basque Country. As Navarro recalls, “it is the first time something like this has been done, that the government acquires on its own vaccines to distribute ”. The acquisition of vaccines is centralized to negotiate prices and establish homogeneous criteria, but once they are obtained, the communities receive and pay for them independently.

The pending subject is those under 65 with other diseases, among which the percentage of vaccinated can remain at 20%

Let's do the math then. The target population in the last year of which there is evidence was 8,790,069 million for those over 65, 2,072,507 from 60 to 64, 244,625 for pregnant women and 497,621 among health personnel. Total, 11,604,822 people. Of all of them, 5,507,565 were vaccinated. If there are 5.2 million additional vaccines, even if the entire target population is not vaccinated (something practically impossible), the increase would be substantial.

However, the account is not so simple, as sources from the pharmaceutical industry recall. Especially since there is a large part of the potentially vulnerable population under 65 years of age that is rarely vaccinated, which should also be tried to reach and whose rate can be around 20% and which is not included in these data. These are patients with heart disease, diabetes or oncological treatment. As Gil recalls, “what happens is that the risk perception of the population is lower, because it seems that the flu is only focused on age, but it can be very serious in other groups. You have to think that the vaccine is destined to eliminate the most serious forms of the flu, that people do not die ”.

Salvador Illa, on August 1. (EFE)

In fact, the Ministry of Health itself recalls in its statistical data that "vaccination coverage against influenza is very low in all groups represented: elderly, health personnel and pregnant women. Even so, the increase in coverage for pregnant women and health personnel is remarkable ”.

Is it possible to reach the proposed figures for this year? "The year 40% was requested among health workers and it is almost reached, but we are still far from 60%. We are going little by little and I believe that we will not arrive, but as far as possible we will have to vaccinate everyone we can ”, the professor values. "Among those over 65 we already had higher figures from previous seasons, so I think it is possible." Navarro recalls that "we have always fallen short of those objectives." It would therefore be a historic milestone.

Another factor must be taken into account, and it is that, most likely, the flu will have a lower incidence than other years because the precautions being taken Due to the coronavirus epidemic, such as hygiene or the use of masks, will also impact the transmission of influenza. This is what has happened in Australia, where the number of cases during the southern winter has decreased significantly. Although this is a statistic that should be taken with care, the Australian government health department pointed out that the levels of impact of the flu have been reduced since mid-March. Something that extends to other countries in the southern hemisphere such as Chile or New Zealand.

Running since February

One of the reasonable doubts that may arise in the current situation is whether, by having focused our efforts on the covid vaccine, we will not have left the flu aside. There should be no problem: the formula for this year's campaign was created since February, when the coronavirus was still in its early stages.

Some Eastern European countries may be having trouble getting the amount requested

“The vaccines from the northern hemisphere that are used in the flu season from October to March beginsn to be made in January and February”Recalls Navarro. “That comes from several laboratories in the world that study the genome of the viruses that circulate, and from that it arises what is believed to be the virus that will circulate in eight and nine months. There is a lag, so in February the process begins so that in September it is distributed throughout the northern hemisphere ”. Navarro dismisses fears of shortages: despite interest in the covid, no flu vaccine production plant will be closed. Rather to the contrary, it will be tried increase demand to deal with the offer.

In this case, the WHO published the composition on February 28 this year with the recommendation of the compositions of the trivalent and quadrivalent vaccines. Among the trivalents, those produced from embryonated and live attenuated eggs must have strains similar to A / Guangdong-Maonan / SWL1536 / 2019 (H1N1) pdm09, A / Hong Kong / 2671/2019 (H3N2) and B / Washington / 02 / 2019 (B / Victoria lineage). Those produced by cell cultures, A / Hawaii / 70/2019 (H1N1) pdm09, A / Hong Kong / 45/2019 (H3N2) and B / Washington / 02/2019 (B / Victoria lineage). And, in tetravalents, in addition, a strain equivalent to B / Phuket / 3073/2013.

Workers of a Chinese pharmaceutical company work with chicken embryos infected with the H1N1 virus in 2009. (EFE)

The city names refer to the laboratories of the surveillance network that identify the circulating virus samples, by finding new strains that differ from the current ones. The vaccine manufacturing process occurs throughout the spring with limited capacity in mind, so by this time of year, it should already be about to complete the manufacture of the first lots. That is one of the difficulties that the Ministry refers to: that “when the covid-19 pandemic began, the flu vaccine purchase processes and the Framework Agreement were already underway and it was difficult to modify the number of doses ”.

There is the crux of the matter this year. In a foreseeable increase in demand that could give rise to a hypothetical competition between them in which Spain would start with a certain advantage as part of the European Union. “To prevent double circulation from worsening, all the countries in the western area have considered trying to increase coverage, but a cdare is to try and another to get it, because we have never reached the goal for people over 65 years old ”, adds Navarro. However, he considers that there should not be a problem as the laboratories have put the batteries early to meet the demand. Only some Eastern European countries, some industry sources suggest, could be having trouble getting the quantity on offer.

"The volumes for the northern hemisphere season will be delivered gradually from the end of this summer until the end of 2020."

One of the thorny issues in this regard is that Spain does not have laboratories capable of producing vaccines, while other countries such as Germany, France or the United Kingdom do have that capacity. At most, our country carries out ‘fill & finish’ processes. Around 80% of vaccines are produced in Europe and distributed throughout the world. In the case of Sanofi, one of the companies that produce the influenza vaccine that is ordered in Spain, most of the production takes place in Europe and the US, "Centers that have the technology and experience necessary to be able to manufacture more than 200 million doses in such a short time," as he explains Ignacio Sáez-Torres, responsible for Sanofi Pasteur Iberia. About 70% of the production time is spent on quality testing.

For next season, as it appears in the BOE, the four batches of vaccines of the Framework Agreement have been awarded to Seqirus and Sanofi for 24 million euros. A number of around 4.7 million vaccines, 6.9% more than the previous season, to which must be added the additional 5.2 managed through the emergency procedure outside the Framework Agreement, which includes 13 communities. Other, Catalonia, Andalusia, the Basque Country and the Canary Islands, make the purchase on their own, which raises the number by another three million. In total we could reach about 14 million.

The big question is: is there productive capacity if all countries increase their demand in the same way? As you remember from the industry, it is more about extend production times and extend the campaign. That is, do not put more pans to fry more eggs, but clean the pan and re-fry more eggs that would not have been fried in other years. The limit would be, in any case, at the beginning of vaccine production for the southern hemisphere.

"I can say that we have managed to increase the production of doses of influenza vaccines compared to 2019, which was already more than the production of 2018, and that means the largest number of flu doses we have ever produced. This year, if everything goes as we expect, we will be able to deliver more than 200 million doses of flu vaccines around the world, ”adds Sáez-Torres. "The total volumes for the northern hemisphere season, which is Spain, will be delivered gradually from the end of this summer until the end of 2020."

One of the reinforcements that Sanofi has carried out is the influenza vaccine with high antigenic load, "Especially indicated to protect those over 65 against the flu and its complications", one of the great hopes for the future. As Gil recalls, “in Spain a commitment has been made to the vaccine with a high antigenic load that will be used to vaccinate in nursing homes, and which can significantly improve their quality of life. The range has been greatly expanded in the coming years to have more effective vaccines ”.

When and where?

The other big question is when the vaccination campaign should begin for next year. According to the Ministry, the ideal would be to carry it out "as soon as be possible in the month of October ”. However, the possibility of advancing the campaign even at the end of August has been raised, at which time the vaccines will begin to be distributed to the respective communities. In general, it is usually in October when the vaccines arrive at the centers and the campaign begins around the 20th of that same month.

"If we want to reach 75%, something that is already being done in countries like France is to have the support of pharmacy offices"

Own Fernando Simon he admitted the possibility that advancing the campaign would be "interesting." The advantages, in this case, would be to reduce the impact of influenza at an early stage, as well as the possible confusion between cases of influenza and coronavirus and to expand coverage. "We would have less problems when it comes to differentiating them and when it comes to treating patients ”, Simón acknowledged.

Most experts, however, agree when it comes to remembering that overtaking can be dangerous in the long run, since it is possible that if vaccinations are too early, these do not cover the entire winter period. "Among the older population, the antibodies generated by the vaccine decay in four or five months," recalls Navarro. For this reason, the campaign usually begins in the month of October. "If the vaccination is carried out in September and the virus does not begin to circulate until February, it is possible that those antibodies fall to unprotective levels."

Photo: EFE.

The ideal would be a balance between maximizing coverage and protection. For example, advancing the campaign a bit, between one and two weeks, to have more time for vaccination without losing the protection period. Because, as Navarro adds, "you have to have the mentality that not everyone has to get vaccinated in the first week, but rather extend the term." Which brings us to another question: will there be enough hands to give so many vaccines?

As Gil recalls, the vaccination points have increased in recent years, and they are no longer only health centers or hospitals, but also companies, nursing homes or universities like the ones where he works, which receive the doses from their communities. "If we want to achieve 75% vaccination, an important help that is being done in other countries is to have the support of pharmacy offices," he adds. "Although here it is still a bit conflictive, to vaccinate in the pharmacy offices, they could supply them with all the pertinent controls." According to data from the Federation of Pharmaceutical Trade Unions of France, almost 2,200,000 French people were vaccinated in pharmacies in the 2018-19 campaign. But that is another story.