The magazine "Vaccines" has just published a work by researchers from the University of Bari and the Puglia Region, where they report, updating them, the main results of the famous "report" of the Apulian Epidemiological Observatory of 2018 on the measles-mumps-rubella vaccine- chickenpox (MPRV), which was already given considerable emphasis by the mass media. The precise quotation is as follows: Stefanizzi, P., et al. (2019). Adverse Events Following Measles-Mumps-Rubella-Varicella Vaccination and the Case of Seizures: A Post Marketing Active Surveillance in Puglia Italian Region, 2017-2018. Vaccines (Basel) 7, 7040140.
First of all, we must congratulate the authors for the simple fact of having developed the research and published the work. These days, even having real numbers is a luxury. Research resoundingly confirms that MPRV vaccination causes many adverse effects. However, as the work is presented and the "reassuring" conclusions of the summary leave many questions open and raise concerns.
Children (second year of life) were enrolled on a voluntary basis, adverse event surveillance diaries were used, and their parents were also interviewed 25 days after vaccination, or even after a further month if there were still symptoms of adverse reactions. 2540 children were enrolled; 2149/2540 (84,6%) completed post-vaccination follow-up. Among these 2149 cases, 992 adverse events were recorded following the vaccine, with a reporting rate of 46,2 × 100 doses. 883/992 (89,0%) events were not serious, while 109/992 (11,0%) were serious. For serious events, the causality assessment was performed using the algorithm proposed by the WHO: 82/109 causal associations consistent with MPRV immunization were detected (reporting rate: 3,8 × 100). The authors report that most of the 82 serious events had resolved within 25 days of vaccination, while a group of 12 children had longer lasting consequences, which however resolved within the following month.
In the table I have listed the main numbers of the Apulian research, with reference only to the SERIOUS adverse reactions and certainly caused by the vaccine. In the right column I have reported my extrapolation to the Italian population of an annual cohort of 400,000 children, a purely indicative and approximate calculation, because it is not said that the Apulian sample is representative for all of Italy. Furthermore, as the authors rightly point out, it is evident that a sample of 2000 subjects cannot be considered valid to report any rare or very rare adverse events.
The serious vaccine-related adverse reactions were 3,8 per 100 doses, i.e. 3.800 per 100.000 doses. If we think that AIFA in its 2018 vaccine report reported 12,7 serious reactions per 100.000 doses, we must conclude that someone is wrong. And big.
What leaves more perplexing is that the authors conclude, in the summary (which in most cases is read by those who do not have the time or competence to read the whole text): “Since no emerging signs were detected, our program data active surveillance confirmed the safety profile of the MPRV vaccine. "3.800 serious reactions per 100.000 doses instead of 12,7 out of 100.000 previously known is not an" emerging signal "?
There is something unconvincing in this conclusion. First of all, a careful eye can find a certain degree of pre-judgment, or at least a contradiction. Indeed, it is stated that the research was done to study the risk of adverse events and safety control standards. Yet, already in the introduction, the authors "anticipate" the result by claiming that "there is a low tolerance for potential risks of adverse events, even if vaccines are held to higher control standards than other medical products [1–5] . ”This claim is questionable, because the same research shows that it is not true (controls are based on inefficient reporting systems) and furthermore it is well known that a pharmacokinetic test is not required for the registration and marketing of vaccines, so it is not known where the injected product ends up or how much remains in the body.
In support of their claim, the Apulian authors cite five bibliographical entries, but no credible one is found. In fact, the cited bibliography refers to the control systems of the adverse reactions, those that should be studied with this research, but does not demonstrate at all the control standard of the product itself. Among those cited, there is only one work that directly supports this concept (their bibliography No. 3): “The evaluation of the safety of vaccines is exhaustive and continuous; starting from the non-clinical evaluation of their individual components in terms of purity, stability and sterility, continuing throughout the clinical development phase and the entire duration of the use of the vaccine; including the post-approval phase ". Signed: Alberta Di Pasquale, GSK Vaccines, Wavre, Belgium. How to ask the innkeeper if the wine is good. But the curious thing is that the work of the Apulian researchers shows that what Di Pasquale supports is NOT TRUE: the surveillance systems of adverse reactions, so far based almost exclusively on spontaneous reporting, are seriously inefficient.
We are also perplexed when we read sentences that minimize 3,8% of serious reactions, knowing that a reaction is classified as serious where it has determined: death or danger of life, serious or permanent disability, congenital anomalies / deficit of the newborn, hospitalization o prolonged hospitalization, another clinically relevant condition.
Some of the authors' comments on their results also leave something to be desired, such as in this passage: “The percentage of non-serious adverse events was higher than the Italian estimate indicated for 2017 in the latest AIFA report (88,7% vs. 80,0 , 2013% in the AIFA ratio) and higher than the Puglia passive surveillance figure in the 2017-88,7 period (75,4% vs. 2018%): this result seems to indicate that the underestimation of the passive surveillance of adverse events mainly concerned non-serious adverse events "(and here they cite the 220.127.116.11 Puglia Observatory report). But this speech (with that vague "mainly") lets the reader believe that passive surveillance of serious events is efficient, which is totally false, based on the same report of the Observatory of the Puglia Region previously published: in Table 49,69 . in fact, it was read that the reporting rate of SERIOUS adverse events with active surveillance was 100 per 0,12 doses, while with passive surveillance it was 100 per 414 doses. The difference between active and passive, if mathematics is not an opinion, was XNUMX times!
Given the numbers in the table, how can one not ask the questions: "But is the number of serious adverse events for natural diseases or vaccination greater?", Or "Adding all the cases of measles, mumps, rubella and chicken pox, are we sure that the total suffering of children for these diseases exceeds that due to the MPRV vaccines (also taking into account that the vaccine must be done twice and maybe more)? "or" Why, pending such safety uncertainties, the MPRV vaccine is been made mandatory? "
Experts of medicine and public hygiene (Donzelli, A. & Demicheli, V. (2018) Epidemiol. Prev. 42, 65-70) claim that "chickenpox is relatively mild in children aged between 1 and 9 years, while the the risk of worse consequences is progressive with age and very high in the elderly. Yet there is a real danger that the strategy of vaccinating all children "by carpet" will gradually increase the age of the cases, which has already happened with the measles and mumps: Some side effects of the vaccine are not trivial and the duration of protection is still uncertain, as is the cost-effectiveness of mass vaccination and its long-term effects, with reference to the reactivation of the virus and the incidence shingles in the general population, which may have increased in the long term. "
These experts suggest that a different rational choice could be to offer selective vaccination only to teenagers with a negative history of chickenpox. In practice, young children whose parents do not intend to take the risks of adverse effects could be assumed to take on the "risk" of the disease, with a double advantage: on an individual level, those who contracted "natural" disease would remain immune throughout their lives. (avoiding to take it in old age) and at a social level the maintenance of a certain "circulation" of the virus would allow to keep active also the immunization obtained with the vaccine, for the benefit of the vaccinated.
I repeat that the most questionable thing in my opinion is the fact that the Apulian authors write in the summary that "our data from the active surveillance program confirmed the safety profile of the MMRV vaccine". What does all this mean in real terms? Who said that? Is this the opinion of those who produce the vaccines, of those who inject them, of the parents, or of those who have been vaccinated? It would be very important for future research to pay more attention to this type of problem, connected to the relationship between citizens-users-financiers and the healthcare system. From researchers I would have expected a calculation of the benefit / risk ratio.
Finally, I agree with the conclusion of the text (which is not read in the summary): "surveillance programs must be periodically implemented with active surveillance in order to improve the overall performance of the pharmacovigilance system and validate data and signals emerging from spontaneous reporting activities ". We hope that the Apulian and Italian health authorities will start serious programs of this type also on the other vaccines, to the whole interest of the population and above all of our children.