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A reply to the article that brands the serodiagnosis of Tuberculosis

Posted by andamars on 22 Jan 2012 at 10:46 GMT

The WHO pronounced a vigorous rebuttal of the serodiagnosis of tuberculous infections. The verdict was without appeal. Chief among the hurdles facing the use of TB serology is a pervasive attitude that refers to it as “quackery”. However, more than half of the current recommendations of the Infectious Diseases Society of America are based on anecdotal evidence, which is an inherent part of Western medicine.
A comparison was systematically made between microscopy and the serological determination of presence of antibodies to mycobacterial antigens. The two methodologies are totally different and, in addition, the quality of evidence is never questioned for the gold standard itself, although its sensitivity varies from 20% to 80% in pulmonary cases, and of course is 0% in extra-pulmonary cases. Smear-negativity is traced to abacillary cases, extra-pulmonary cases, primary tuberculosis in infants, and also to human errors, explained by lack of electricity, lenses lost or dirty, stains corrupted, sputum contaminated or unsuitable, fatigue of the microscopist. Serological tests can go a long way in the detection of unapparent infections, prognostic and prevention. The immunopathology of TB is a complex phenomenon whose comprehension sheds light on the evolution of the disease.
Conflict of interest is a major reproach risen in the report against the researchers on the ground that kits were donated by manufacturers. It is the least I could have done and this donation took also place for the analysis of the rapid tests by WHO.
To claim repeatedly that the accuracy of investigated tests are even lower than reported because bad results would not have been published is unacceptable : the investigators report their results as they find them, be these findings favourable or not and I mention some references that do so, in the general “Comment” on this article.
The meta analysis emphasizes that no tests were made on infants and children. Six references are noted in the “Comment” on this article, that refer to serodiagnosis in children.
Reference 5 of the report mentions a study that focused on the identification of latent infections. This study reports that 4.7% of skin test positive subjects developed clinical TB within 15 yr of entry into the study. On this basis, it rejected the serodiagnosis for this application. However, a recent evaluation of 20% or more of reactivation risk (as exposed in the “Comment”) reflects more closely the true level of the conversion rate. When correct conclusions are drawn from correctly performed investigations, the Anda-tb test appears not the worst but the best test to detect latent infections.
A myriad of publications exist on all aspects of TB. The first duty of analyses and reviews is to evaluate their worth, the second is to evaluate the validity of the conclusions drawn only from correctly performed studies, and the third is to make correct recommendations based on these correct conclusions. If publications are evaluated properly (see my “Comment” on the article), the following conclusions are drawn:
1. The humoral immune response to TB is just as important as the cellular one, and is subject to depression by the pathogen but the depression acts in a variable way on the different antibodies (IgG, IgM, IgA) elicited in individual patients. A heavy bacterial load may correspond to negative serology, and reverse.
2. One third of humanity is infected by a mycobacterial entity. Most mycobacterial infections are latent and are observed with variable frequency in non –tuberculous patients suffering from diverse diseases, and in healthy contacts. Not all diseases allow a mycobacterial-superposed infection.
3. An immunosuppressive drug may show anti-TB activity in vitro. In patients, the immunosuppression will favour the multiplication of the pathogen.

Competing interests declared: "I developed the anda.TB elisa tests and am the cofounder of Anda
>> Biologicals, Strasbourg."