NTMs exposure have been long postulated to have a mediating effect on protective efficacy of BCG vaccine in TB endemic countries like India.how can we identify such exposure? Are there any ways to treat such infections. Since NTMs eliminate BCG, does they have role in protection for TB in non vaccinated individuals.
There is no perfect way to identify environmental exposure to NTMs. Individuals with significant exposure will have a reaction to PPD derived from NTMs (the so-called "Battey Antigen" or similar products) They will also respond, slightly more weakly, to PPD from M. tuberculosis. But there are so many NTMs and almost none of them are characterised, so the degree of reactivity will vary unpredictably from place to place and will be affected by what PPD or antigen is used. For example, we tested antibody reactivity to a heat shock protein from M. leprae in 4 different populations from different regions (New Zealand, Nepal, Samoa and Sweden). In the first three of them, less than 1% of the general population reacted, though almost all leprosy patients tested did. But in the Swedish population well over half of the population reacted. Since leprosy has long been eradicated in this population, the most likley answer was that an environmental mycobacteria in that region produced a cross-reacting antigen. That was proved, when the bacteria - a Mycobacterium W-type - was eventually isolated.
In animal experiments, sensitising with environmental mycobacteria gives some very weak protection vs MTB - but much less than BCG. Sensitised animals however can still kill BCG effectively.
What seems to be happening is that common environmental mycobacteria can induce a weak degree of crossreactive immunity against tuberculous mycobacteria. This weak immunity is enough to rapidly eliminate BCG, which is highly attenuated and easily killed, even by weak immune responses. But it is not enough to eliminate MTB, which is highly virulent, and has effective mechanisms to avoid or reduce the host's immune response.
" Unexpected high responses to tuberculin skin-test in farmed red deer: Implications for tuberculosis control" provides an empirical example of the problems associated with TB diagnostic in animals as a result of cross-reactivity of NTM and other related bacteria.
This paper may give you some clues of how these kind of problems has been addressed in wild animals.
See these links may be useful for you.
1) How to avoid the impact of environmental mycobacteria ...
www.sciencedirect.com/science/.../S22125531140001...
Traduire cette page de O Parkash - 2014 - Cité 3 fois - Autres articles
Epidemiological and experimental studies have pointed out that, prior exposure to prevailing environmental mycobacteria could be responsible for the poor ...
2) Consequence of prior exposure to environmental ...
www.ncbi.nlm.nih.gov/pubmed/18329343 Traduire cette page
de M Thom - 2008 - Cité 21 fois - Autres articles 7 mars 2008 - Consequence of prior exposure to environmental mycobacteria on BCG vaccination and diagnosis of tuberculosis infection. Thom M(1) ...
3) The influence of previous exposure to environmental ...
www.ncbi.nlm.nih.gov › ... › PubMed Central (PMC) Traduire cette page
de RE Weir - 2006 - Cité 71 fois - Autres articles 12 sept. 2006 - The influence of previous exposure to environmental mycobacteria on the interferon-gamma response to bacille Calmette–Guérin vaccination ...
An estimated Abbas Ali Husain
How to avoid the impact of environmental mycobacteria in human health, it is a question that since the last century we have been doing in Mexico.
For a long time there was better control through environmental sanitation, better control of chronic debilitating diseases and better nutrition for children.
Most cases of primary infection lung (TBP), tuberculosis have been detected in young people and adults by contact or near patients with active pulmonary tuberculosis, most of them relatives.
Other cases of tuberculosis, the less, M. bovis infection (ingestion of unpasteurized milk and derivatives thereof) and M. avis. (Poultry farms)
In the decade of the 80s and 90s of last century, with health policies and program of universal vaccination in children, the picture was better because many deaths of neonates and infants were avoided with the application of BCG , because many cases of tuberculous meningitis and disseminated tuberculosis in those children were avoided. So far this vaccination program in Mexico is maintained.
The population of adolescents and young adults who are infected with tuberculosis had stabilized until the emergence in our country for many cases with HIV / AIDS, drug-resistant TB cases.
As is generally known, protection against TB, which is achieved by vaccination with BCG varies widely; approximately 50% and 80-90% for TBP in tuberculous meningitis and disseminated tuberculosis.
In Mexico the diagnosis of tuberculosis is made in form with specific clinical symptoms (respiratory), PPD skin test positive, smear and bacillus culture and imaging studies (x-ray), in some cases even by ELISA and immunological tests RIA
I think the solution is sought in my country and others around the world, it is to obtain a more potent BCG vaccine, achieved through genetic engineering (recombinant DNA) using antigens derived from the structure or secretion mycobacteria, including the 38 kDa antigen, 30/32 kDa, 40 kDa etc ..
Cheers
Sincerely
Dr. Jose Luis Garcia Vigil
Thanks to distinguished persons for sharing their views.
NTMs exposure has been one of main reasons for BCG failure. However I believe modification in BCG genome may not solve the issue, as even today DNA based vaccine for TB have been a failure and have been in trials for a very long time. It has been also two decades. Identifcation of such exposure in mothers is essential, as they may pass Ab's against NTMs to children, which also may block beneficial effect of BCG vacination
Agree that so far not found a better vaccine against infection with M. tuberculosis BCG.
While a vaccine that has at least similarly immunogenic potency and safety can not be discovered, you will have to continue using BCG.
To date there is research (Phase I) in Switzerland, a vaccine derived from attenuated live M. tuberculosis bacilli. 36 were vaccinated volunteers with no prior exposure to M. tuberculosis, which at 210 days post-vaccination developed very strong immune response and no serious adverse reactions (adverse reactions similar to BCG). Phase II investigation in humans will take place in South Africa. This stage will last two years and the new vaccine will be used in newborns.
A summary of these results on page spread (Web) from eMedicine (www.medcenter.com) article "Francois Spertini et al Safeti of human Immunisation with a live-attenuated vaccine Mycobacterium tuberculosis. A randomized double blind controlled Phase I trial. Lancet Respiratory Medicine 2015 "
Cheers
Dr. Jose Luis Garcia Vigil
There are two important things to remember about BCG vaccination.
The first is that the dose of live vaccine that you give is not significantly protective by itself. A similar dose of killed BCG - which contains the same amount of antigen as a live dose - is useless. BCG needs to replicate and expand to generate an immune response that can give significant protection. If for example, you give a normal protective dose of BCG and then treat with antibiotics a few days later to kill it, you block the development of immunity. So prior sensitisation to mycobacteria blocks BCG replication and thus you get no benefit from the vaccine.
The second thing is that BCG generates a CMI response that wanes after time. By 8 years post vaccination, the level of protection falls to about 15-20% and by 15 years post vaccination, there is essentially no immunity to MTB observable. This is not unusual - we have lots of vaccines, such as pertussis, or even smallpox, that show a similar profile.
These two factors, just by themselves, explain virtually all the variation in efficacy reported from clinical trials. They also explain why neonatal vaccintion with BCG, although it has been very successful in reducing the high mortality from TB in early life, has had virtually no effect on adult TB rates.
This has important implications for vaccine design. The first is that a stronger immune response after vaccination is not necessarily better. What we need is longer-lasting immunity. If that is not possible, then we need a vaccine that can boost immunity in adolescents and adults, who in many cases will be already sensitised to mycobacterial antigens
It is true that we need a vaccine that immunizes against M. tuberculosis for longer. It is also better immunized with vaccines with dead bacilli with live attenuated bacilli (the risk of adverse reactions in long-term monitoring, "F-IV drug research" is greater).
As additional data, most adolescents, youth and adults of Mexico (approximately 80%) have already been in contact with M. tuberculosis.
Cheers
BCG vaccination in the Newborn (RN) and infants is highly effective. In countries with high risk of infection and likely exposure to environmental mycobacteria (Mexico case) it is indicated the use of the vaccine from birth without having to perform tuberculin skin test.
They are exempt from vaccination premature RN and HIV positive mothers. Also at high risk of local complications or systemic spread of M. tuberculosis, children with congenital or acquired disease (Di George, Bruton disease, HIV + cases, corticosteroid use, leukemias, kwashiorkor type malnutrition) immunodeficiency.
Although the child is exposed to environmental mycobacteria if BCG immunization is indicated and if the characteristic scar at the site of the application is developed.
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