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Table of Contents
REVIEW STRATEGY
Year : 2022  |  Volume : 1  |  Issue : 1  |  Page : 7-13

Bacille Calmette – Guérin vaccination: Experience from the past and its perspective further


Department of Research, Parabolic Biologicals, 1320 Beauvechain, Belgium

Date of Submission30-Oct-2021
Date of Decision22-Jan-2022
Date of Acceptance16-Feb-2022
Date of Web Publication23-Mar-2022

Correspondence Address:
Roland Maes
Parabolic Biologicals, Rue de l' Ecluse, 2, 1320 Beauvechain
Belgium
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpdtsm.jpdtsm_1_21

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  Abstract 


Today, tuberculosis (TB) kills one person in 14 s in India and one in 12 s, worldwide (that comes to approximate 4000 people per day). The majority of cases are invisible because they are either confined in sanatoria and/or do not encumber regular hospitalization, in contrast to SARS-CoV-2 (COVID-19) pandemic. The COVID-19 pandemy has put in glaring light the fragility of the elders, the minorities, and the exposure of the healthcare agents that was similar to Mycobacterium tuberculosis infection. The mayhem of coronavirus might be repeated itself with the foreseen rise of TB, that would affect the healthcare system resemble much of what occurred during the last 3 years (2019-till date). We must keep in mind that currently TB is neglected and that it might expand again, due to the COVID-19 pandemic. In this review, the past and further perspective of Bacille Calmette–Guérin (BCG) vaccination is described. In addition, the tuberculin skin-testing which has a complex and long story was reviewed. Furthermore, the effect and side-effect of BCG vaccination compared and discussed.

Keywords: Bacille Calmette–Guérin, pandemic, tuberculosis, vaccine


How to cite this article:
Maes R. Bacille Calmette – Guérin vaccination: Experience from the past and its perspective further. J Prev Diagn Treat Strategies Med 2022;1:7-13

How to cite this URL:
Maes R. Bacille Calmette – Guérin vaccination: Experience from the past and its perspective further. J Prev Diagn Treat Strategies Med [serial online] 2022 [cited 2022 Dec 8];1:7-13. Available from: http://www.jpdtsm.com/text.asp?2022/1/1/7/340547




  Introduction Top


Koch et al. in Berlin used the Ziehl–Neelsen stain in 1882 to observe under the microscope the presence of the tubercle bacillus in sputum (this is referred to as “bacilloscopy” and commonly said “smear-positive” or “smear-negative”)[1],[2],[3] [Figure 1]. Bacilloscopy became a standard diagnostic and remained so until today.[3] Koch announced an additional standard diagnostic and a treatment, based on a TB extract named “Old Tuberculin.”[1],[2] The second standard diagnostic, -the skin test (which is still abundantly used today)-, was the intradermal inoculation of a small quantity of tuberculin. Three days later, a swelling appears at the site of inoculation if the subject had been previously infected with tuberculosis (TB). Using old tuberculin as a cure, Koch made a fortune before conceding that the old tuberculin awakened dormant TB. The competition for a vaccine remained open.[1],[2]
Figure 1: The tubercle bacillus

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  The Bacille Calmette–Guérin Vaccine Top


The Friedmann vaccine based on M. cheloni was used previously with satisfaction and without side effects but Bacille Calmette–Guérin (BCG) is the only vaccine available today and has been used for more than 90 years. However, its efficacy remains controversial.[4] BCG stands for BCG, the names of the two investigators who developed the BCG vaccine (Albert Calmette and Camille Guérin) at the Pasteur Institute of Lille in 1900.[4],[5] Although no universal BCG vaccination policy exists throughout the world; some countries only recommend its use and others have implemented immunization programs.[4] In 1921, Calmette decided that the time was ripe for a trial of the vaccine in man. The first human administration of BCG was by Benjamin Weill-Halle (1875-1958) assisted by Raymond Turpin (1895-1988) at the Charité Hospital, Paris a few hours after giving birth to a healthy infant.[4],[6]

Early evidence of inefficacy and infectiousness of Bacille Calmette–Guérin

Calmette observed that children had developed a mild extra-pulmonary tuberculous infection after drinking milk contaminated with Mycobacterium bovis, appeared protected against more serious forms of pulmonary TB.[1] This observation prompted him to attenuate a strain of M. bovis during 13 years by repeat subculture in vitro (meaning growth of the bacterium in a liquid substrate on glass instead of in animals [in vivo]).[1] The attenuated live bacillus so obtained limited, in guinea pigs, the dissemination of inhaled TB bacilli toward the liver as well as their secondary dissemination toward the lung. However, this live vaccine infected various organs for several months and provoked a general lymphatic disease that Calmette and his collaborator Guerin claimed to heal spontaneously within 3 weeks.[1],[5] The vaccine lent no protection at all to monkeys at risk: All vaccinated monkeys contracted TB on exposure.[1],[7]

Calmette refused to take this crucial observation into account although this was an indication that BCG could favor TB infections.[7],[8] The apparently positive results obtained with guinea pigs prompted Calmette to vaccinate newborns in 1926. The proof of the efficacy of the vaccine in newborns was, according to Calmette, the skin allergy, which he assumed the BCG elicited, and he held that a successful vaccination generated an allergy betrayed by a positive tuberculin skin test.[1]

Lignières showed in 1927 and 1928 that the BCG was neither completely attenuated nor efficacious.[8] In England, the statistician Greenwood observed in 1928 that the results obtained by Calmette to prove the efficacy and harmlessness of this vaccine were flawed because the vaccinated children were kept in a protected environment under tight medical supervision by nurses who fed them well and cared for them whereas the unvaccinated children used as controls were children living in the slums of France.[8],[9] Greenwood was right: The general infantile mortality, in the protected environment where the vaccinated children were confined, was 17% in 1922 and had dropped to 5.1% in 1926, at the moment they were vaccinated, indicating that the reduction in mortality in the protected environment started well before the vaccination took place.[8],[9]

The pediatrician Ferru went through the whole of the BCG problem, starting in 1926 with the vaccination of children by Calmette and the opposition to it by Lignières in 1927, and wrote the following chapters:[1],[7],[8]

  • Chapter 2: The rude controversy Calmette–Lignières
  • Chapter 5: The arrogant rejection of the critics
  • Chapter 6: The silent contestation
  • Chapter 7: The international pseudo-congress of Paris
  • Chapter 8: The inordinate practice of the vaccination
  • Chapter 9: Massive and monopolized propaganda
  • Chapter 10: Denatured information
  • Chapter 11: Oppressive dogmatism
  • Chapter 12: The masquerade of retaliation
  • Chapter 13: Back to facts.


Finally, he concludes and warned that TB will return with a vengeance.

France had imposed the BCG as sole vaccine against TB in 1950, with the active support and participation of the World Health Organization (WHO)[8] [Figure 2].
Figure 2: Posters and poststamp extolling the merits of the Bacille Calmette-Guérin (BCG) vaccine. Contrary to what is claimed, to vanquish TB is far from being a play but is a war, and we are losing it despite the BCG, which does not protect. (a) French Ministry of Health educational poster supporting BCG vaccination, (b) poster edited by the French Ministry of Health in 1964. The caption reads: To vanquish TB in only a play, thanks to the BCG. Image courtesy of J. P. Zellweger. (c) Stamp of the National Tuberculosis Defense Committee

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Based on the book written by Ferru,Fougerousse a junior deputy of the mayor of Ostwald, a neighborhood of Strasbourg (France), held in December 1977 a modest conference to his constituency, in which he dared express doubt about the value of the BCG vaccine against TB.[10]

On February 2, 1978, the local newspaper “the Last News of the Alsace” (Les Dernières Nouvelles d'Alsace” [DNA]). wrote about TB: “The (French) experts are honest, competent, and knowledgeable; they are there, to tell the truth without dogmatism or occultation. They found that the number of (TB) cases among the French vaccinees was <2 per million whereas it amounted to 15 per 100.000 among not-vaccinated. Moreover, the vaccine is particularly efficacious in infants, against tuberculous meningitis.”[10]

However, the regression of the tuberculous endemy grinded to a halt in France 10 years later, in 1987.[8] Grosset mentioned 10,000 new cases in 1994 in France and concluded that the fight against TB was a total failure.[11] Janet Cornwall replied tartly in 1997 that the reason of the failure was the greed and ineptness of the TB-actors, among which Grosset played a predominant role.[8]

That same year, Frimodt-Moller et al. published (1978) in the Bulletin of the International Union against TB[12],[13],[14],[15],[16],[17],[18],[19],[20] that the BCG was not safe, i.e., was iatrogenic.[8],[21] This warning, and all those that had been given since 1927 and which were pouring in later, was given no heed.[8]

How could this vaccine have been used for so long despite the evidence of its malfunctioning, given in 1927? Because TB regressed in the West after World War II. This improvement was traced to the policy of vaccination with the BCG, to visual detection of the presence of the TB pathogen in the lungs and stamping the bug out with 4 drugs: Isoniazid in 1952, pyrazinamide in 1954, ethambutol in 1962, and rifampicin in 1963, (plus streptomycin in 1944, for the resistant cases) given during 6–9 months, which was claimed necessary and sufficient to eliminate TB.[3] All the public health agents in charge of TB in France and by the WHO thought it would soon be eradicated.

Tuberculin allergy based on tuberculosis vaccination (1928-1948)

Calmette observed in 1928 that only 28% of the vaccinated children held in a protected environment reacted on an intradermal tuberculin injection.[1],[22] This was half the frequency of reactors observed at the same time among vaccinated children kept in an open environment, which amounted to 60%.[1],[22]

How explain these results, when the expectation was that the BCG would induce a positive skin test at 100%?

Calmette did not comment on the poor reactivity of 28% where he had expected 100%, and attributed the twofold increase in reactivity among the exposed vaccinees at risk (60%) to an unapparent TB infection.[1],[22] He was right in this, but he did not consider the possibility that BCG does not or only rarely provoke a delayed-type hypersensitivity (DTH) reaction betrayed by a skin test,-as he should have concluded from these results-, and did not explain the scarce 28% reactors observed among vaccinees held in confinement.[1],[22]

Were these 28% reactions due to the vaccine-as he assumed-or were they also indicative of asymptomatic TB infections? Could it be that the vaccine protected poorly or, worse, was iatrogenic and induced per se TB infections that were, in this case, unapparent?

The conclusion should have been that the positive skin test observed after a BCG vaccination was due to a TB infection induced by the BCG, similar to the reactivation of dormant TB observed by Koch after vaccination with Old Tuberculin. Such a conclusion implied concordance with the German, which the hyper-chauvinist Calmette could not conceive, and also the ubiquitous presence of the TB pathogen, even in secluded areas, without any evidential proof, and this conclusion was not envisioned.

The first Congress of BCG held the June 18, 1948, at the Pasteur Institute deviously claimed unanimously (with one abstention by Ferru) that BCG provokes within a short time a neat and lasting allergy induced by tuberculin with a skin test[8],[23] (The observation of Calmette, i.e., only 28% of the vaccinees showed a positive skin test, was superbly ignored). This allergy is a DTH because the allergy becomes apparent with a delay of 3 days after the challenge, and was taken as proof that the vaccine had been efficacious and protective.[8],[24] A second vaccination was recommended if the first one had not elicited a positive tuberculin reaction. This was a sure way to induce a TB infection, unapparent or symptomatic, as I will show infra.[8]

Vaccination campaigns (1950-2020)

France imposed in 1950 by law the BCG vaccination of all infants and young tuberculin-negative adults of the country and throughout the French Empire.[8] Recalcitrant parents faced 2 years of prison, and Dr. Alain Dumas was punished with a month' suspension of professional activity in 1999, because he had prescribed the Friedmann vaccine.[1],[25]

The vaccination campaign started in Djibouti and Madagascar.[1],[26] G. Comstock, a US Health Service expert who followed TB clinical trials, reported in 1995 that nothing was done to verify the efficacy of the vaccine, which was immediately reported nefarious by the local Public Health officers, who observed excess TB cases among the vaccinees.[8] The WHO organized the vaccination in Libya.[8] The Netherlands and the USA refused the BCG on a routine basis, a measure that in no way favored the endemy above that observed in covered countries.[10] The consequence of the mass vaccination (13.874.000 subjects) with a deficient vaccine was a rampant spread of TB and leprosy throughout the world.

Leprosy

The promotion of leprosy by BCG was published in 1960 and again twice in the nineties.[8],[27] In addition, Bagshawe et al. observed in 1989 in New Guinea, a TB-free zone, a 9-fold excess of leprosy cases which affected only vaccinees <5 years old, during the first 5 years following the BCG vaccination.[26],[28] These repeat warnings were all ignored, the Indian newspaper of January 29, 2017, announced an alarming recrudescence of leprosy in India: “Why India needs to step up its fight: In 2015, the country accounted for 60% of new cases of leprosy globally.”[8],[28]

Pulmonary tuberculosis

India

The WHO and UNICEF provided support for a BCG vaccine Production Center at Guindy, Madras/Chennai, in 1948.[8],[21] Vaccination was extended to schools in almost all states of India in 1949. A year later, P. V. Benjamin reported that TB infection was so widespread that no part of the country was free from it. Frimodt-Moller et al. vaccinated Indian villagers also in 1950, and published in 1978 an excess of 90% TB cases among the vaccinees.[8],[21] To salvage the BCG, a committee appointed jointly by the Indian Council Medical Research and the WHO acknowledged that the BCG is powerless against lung TB but that it provides substantial protection against childhood forms of TB such as tubercular meningitis; it recommended to give the vaccine before the end of the 1st year after birth.[8] The WHO and the US Health Service organized the vaccination of 260,000 Indians in 1970 (the Chingleput trial), controlled by Comstock. S. P. Tripathy reported in 1986 that this vaccination resulted after a year in a 100% excess of symptomatic TB among the vaccinees.[8],[29] Four years after vaccination, the excess in symptomatic cases was 150%.[8],[29]

Hong Kong

Wong and Oppenheimer started a vaccination campaign of infants in 1954.[30] They claimed a reduction of infant TB mortality rate from 100% to 0% within 16 years, a result that commands admiration and adhesion.[30] Hidden was the fact that infant TB mortality rate in this British colony had already decreased by 40% within the 2 years that preceded the vaccination campaign.[8],[30]

Iran

Majdzadeh et al. reported in 1996 that the adjusted effectiveness of BCG vaccination of adults in the protection of pulmonary TB was − 0.37, with a 95% interval of confidence (IC) stretching from − 1.66 to + 0.31, indicating that the BCG favors transmission.[8],[31]

Brazil

Sousa, Ph. Lagrange and H. David et al, and the American Barry Bloom, member of the US National Academy of Sciences, published in 1997 in the Proceedings of the National Academy of Sciences, US (PNAS USA) that the epidemic of TB occurring after the vaccination of the Yanomamo Amazonian tribe with BCG in 1994 was due to its immunological naivety.[8],[32]

The “immunological naivety” explanation is a myth. It propped up in Sweden, the Netherlands, and the United Kingdom during the coronavirus pandemy of 2020 and is a narrative that was initially created to not deal with genocide. R. Dunba-Ortiz exposes in An Indigenous peoples' history of the United States (ISBN: 978-080705783-4; 2015) that the Native Americans would not have been so vulnerable to diseases if white settlers had not strived to wipe them out.[33] Their food sources were taken from them, their trade routes were cut off and many were enslaved. It is this unrelenting physical and psychological assault that depressed native peoples' immune systems and rendered them vulnerable, not immunological naivety.[33]

Were the Yanomami immunologically naïve?

The PNAS publication reports that the first case of TB among the Yanomami was observed 29 years previously, in 1965, with more cases appearing in the 1970s.[8],[34] The population was vaccinated in 1994 because TB cases were uncovered among its members. The population was exposed to TB before the vaccination took place and the TB patients present in its midst did not cause an epidemic.[8],[34] The result of the vaccination was that 82% of the vaccinated population contracted TB. A presumed immunological naivety had nothing to do with this epidemic. The epidemiological proof that the origin of the epidemic was the vaccine is indisputable. The PNAS publishes without referees controlling the soundness of the conclusions drawn, and B. Bloom et al. could publish whatever he wanted.[8],[34] The authors indulged in deception. The BCG vaccination of the Brazilian indigenous population proceeded recklessly further, with some villages showing an average incidence in the period 1991-2002 that was 2500 per 100,000, almost 50 times higher than the regional average, with about half the cases diagnosed in children <15 years old.[8],[34]

Tuberculous meningitis (1978-1999)

As said, the newspaper DNA had proclaimed in 1978 the beneficial activity of BCG against tuberculous meningitis. It reaffirmed it on July 14, 1993.[10]

The proof of infectiousness of BCG for meninges had been given by Lignières in 1928 and was given again in France by Tardieu et al. in 1988, who prudently published their observation in English.[1],[35] It was callously negated by Grosset and Schwoebel in 1991, who published in French, but confirmed in Iran in 1999 by Bagghaie, et al.[8],[36] In this Iranian study of 100 children suffering from meningitis, only 10% responded to a tuberculin test (90% were thus immune-depressed) and only 22% were meninges-smear positive, which is the percentage defined as usual and normal for bacilloscopy by Miörner et al. in 1994.[8],[37]

Of the 30 children with a history of vaccination, 9/30 died (30%) versus 20/70 (28.6%) among the nonvaccinated children. These percentages of mortality are very close.[8],[38] The authors noted that the symptoms among the vaccinated surviving children were milder. This is in line with the affirmation published in the German Allgemeine Zeitung of September 29, 1982, that the BCG is not efficacious against meningitis and, at most, attenuates the symptoms.[8] (I remind here the affirmation in the Journal DNA February 2, 1978: “The [French] experts are honest, competent and knowledgeable; they are there to tell the truth without dogmatism or occultation. And the vaccine is particularly efficacious in infants, against tuberculous meningitis.” This is also currently claimed in Wikipedia).

Nevertheless, the claim that the BCG protects against meningitis continues to be asserted repeatedly in France with effrontery, and the Pasteur Institute continues to advise BCG vaccination in France in 2018, even if no more obligatory since 2007.[3]

The tuberculin proof of the iatrogenic activity of Bacille Calmette–Guérin (1999-up to date)

The skin allergy induced by a BCG inoculation was found in 1999 in Saudi Arabia to be of the order of 7.8%, 5 years after vaccination.[8],[39] An Italian study conducted in Turin by Bugiani et al. confirmed this, also in 1999, and attributed the skin induration not to BCG but a tuberculous infection.[8],[39] These observations came in support of G. Comstock, who had followed the Chingleput trial.[29] He remarked in 1994 that vaccinees responded either not at all or else with an induration similar to the one obtained with TB patients.[29] He also had observed that the positive response was obtained mainly among vaccinees who had been former TB patients. This observation reminds of the Old Tuberculin, whose use as a vaccine by Koch lead to a reactivation of dormant TB.[8],[29]

These proofs that the reactivity to tuberculin following a BCG vaccination was not due to the vaccine but to TB were corroborated by a Swedish study analyzing the sensitivity to tuberculin of vaccinated and unvaccinated children, published in 1992.[40]

Sweden had wisely discontinued the BCG vaccination as early as 1975. This allowed Larsson et al. to conduct a comparative study of the sensitivity to tuberculin of vaccinated and nonvaccinated children.[8],[40] Three percent of the nonvaccinated controls were tuberculin-reactive, which was proof of a latent TB infection, and 49% of the vaccinated children were positive.[8],[40] Larsson et al. attributed this huge number not to a latent TB infection induced by the vaccine, as he should have, but to a sensitization directly due to the BCG, as claimed by the Pasteur Institute and the WHO.[40] The children in Sweden spend the long dark winter months at home, caring for pet animals (birds and fishes).[8] The Swedish investigators controlled the skin reactivity of their subjects not only with tuberculin but also with avianin and scrofulascein, which would indicate infections with M. avium and Mycobacterium scrofulasceum, mycobacteria that infect birds and fishes.[8] They found that 58% of the vaccinated children reacted to scrofulacein and 67% to avianin, while the frequencies found with these two sensitins in nonvaccinated children were only 25% for scrofulacein and 32% for avianin.[26],[36],[41] Larsson et al. concluded correctly that BCG favored infections by atypical mycobacteria but refused to extend this conclusion to TB because it challenged the paradigm under which he worked, namely that BCG induces a skin reactivity. Tony Jenkins, the referee who examined a manuscript on the subject, which traced the skin reactivity after BCG-vaccination to TB, rejected it on the ground that most mycobacteriologists attributed the skin reactivity to sensitization with the BCG. Whatever evidence to prove a case, there will always be a genius way of explaining it away.

Reported Side effects of Bacille Calmette–Guérin-vaccine from 1928 to 1993

Linières observed in 1928 that one of two BCG-vaccinated sisters died from a BCG infection. This was of no significance to the French experts who all affirmed loud and repeatedly whenever a suspicion arose, that the BCG was innocuous (I expose this frenetic denegation of the reality of the situation at length in “La France malade de sa médecine,” ed. de Paris, 2005).[10],[42]

Dahlstroehm and I. Sjögren warned of the frequent occurrence of side-effects of BCG vaccinations in 1977.[8],[43] The innocuousness of the vaccine was affirmed by Lotte et al. in 1988.[8],[44] However Romanus et al. published in 1993 that the adverse reactions in healthy and immunocompromised children under 6 years of age vaccinated with the Danish BCG vaccine, were ten times more frequent than was previously reported.[8],[45]


  Conclusion Top


I proceeded to a critical examination of the data published, to demonstrate that the BCG vaccine was not very effective because of the genetic changes of BCG, genetic changes of TB, and genetics changes of population which might be cause of the reduction in the efficacy of BCG. Therefore, I recommend to the mycobacteriologist To revise the strategy of BCG vaccination from this available information.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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