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 Table of Contents  
Year : 2017  |  Volume : 1  |  Issue : 2  |  Page : 85-93

Tuberculosis Serology is Useful in Rural Areas

Director of Research Parabolic Biologicals, 1320 Beauvechain, Belgium

Date of Web Publication23-Nov-2017

Correspondence Address:
Roland Maes
Parabolic Biologicals, Rue De L' Écluse 2, 1320 Beauvechain
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bbrj.bbrj_82_17

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The fight on tuberculosis initiated after World War II with the imposition of the Bacillus Calmette–Guérin (BCG) vaccine by the WHO in 1950, and the discovery of the drug streptomycin, which was rapidly followed by a recommended 4 drug regimen (isoniazid, ethambutol, rifampicin, pyrazinamide, and streptomycin being reserved to resistant cases). The diagnostic that justified a treatment was based on the microscopic examination of bacterial presence in sputum, that is, the bacilloscopy, and on culture in vitro of the pathogen, which is more expensive and much more demanding on time. During the following 7 decennia, this approach remained unchanged: no new vaccines were developed despite the documented observed ineffectiveness of the BCG, and the 4 drug regimen (plus streptomycin) admitted additional drugs only from 2012 on. The ineffectiveness of the original 4 + 1-drug cocktail, that became obvious in France in 1994, is traced in part to the immunodepressing effect of some of them. The use of only four drugs also favors defensive mutations by the pathogen. The late addition of more antibiotics to the regular regimen applied to multidrug-resistant-cases may be useful on the immediate term but side effects are crimpling and evidently, measures in addition to “more drugs” must be taken to control the disease. A diagnostic based exclusively on antigen detection remained the norm during nearly 7 decennia. This detection benefited from technologically improved methods (e.g., the interferon test and the numerous nucleic acid amplification tests). The latest of these is the GeneXpert/RIF test. This newly devised antigen test is a quantitative improvement on previous tests detecting the presence of the antigen. However, due to its centralized system of analysis and inaccuracy, it is not suited for rural areas, and it does not favor communication between mycobacteriologist, immunologist, and clinician. In this review article, the concentration is on those rare publications that highlighted the problem posed by various diagnostic tests and their application.

Keywords: Antibodies, Bacillus Calmette–Guérin vaccine, GeneXpert/RIF test, serology, tuberculosis

How to cite this article:
Maes R. Tuberculosis Serology is Useful in Rural Areas. Biomed Biotechnol Res J 2017;1:85-93

How to cite this URL:
Maes R. Tuberculosis Serology is Useful in Rural Areas. Biomed Biotechnol Res J [serial online] 2017 [cited 2022 May 27];1:85-93. Available from: https://www.bmbtrj.org/text.asp?2017/1/2/85/219113

  Introduction Top

Tuberculosis (TB) fight in 2017 reminds of a terminal patient lurching from one experimental treatment to the next in hopes that something changes the fate of a fight racing toward doom. The article “Can the Triumphant March of TB be Stopped?”[1] evaluated in 2016 the various means currently applied to manage the global fight against TB. It concluded that the prescribed policy has shattered the lives of hundreds of thousands and induced huge expenditures, in vain, during decades. We badly need policymakers who can face the unstable, risky reality they have created. It is an extremely sad reality, which can, however, be improved, forthwith, with treatments, diagnosis, and prognosis methods readily available but until today neglected. These are presented in the book “Is tuberculosis our new challenge.”[2]

The Xpert/RIF diagnostic instrument as the preferential diagnostic test is a huge possibility of diagnostics being advised disproportionate to the need. The instrument costs US $ 17,000 or more, the cartridges cost US $60.0 and a 3-year warranty may cost as much as US $18,500–$20,950 for the GX XVI 16. This instrument is oversensitive, much too expensive, detects one type of drug-resistant strain only and is hardly suited for the working environment in rural areas of countries in development. Its accuracy is also questioned: three publications pointed out that between one-third and two-thirds of extrapulmonary TB culture-positive cases escape detection by this test.

To achieve the acceptance of such an expensive instrument on an exclusive basis, meaning therewith the dispatch of serology, a meta-analysis of publications on TB-serodiagnostic[3] banned TB-serology despite the errors committed in the execution of this meta-analysis and notwithstanding the usefulness of the serodiagnosis, which cannot possibly be assimilated to an antigen-detection test.[4] The authors of this meta-analysis had no idea of the function of antibodies against the TB pathogen when they analyzed with statistics the accuracy of serological data.

  The Tuberculosis Disease Top

Close to a quarter of today's global population has a latent TB infection – around 1.7 billion people. Nearly 100 million children carry a latent TB infection.[5] The current pool of 1.7 billion latent infections alone would prevent the number of those with TB from reaching the global targets set by the World Health Organization for 2035. Many of these people live in rural areas, and this reality alone justifies the application of a simple prognostic method as TB-serology, in these areas.

Most infected human beings in developed countries eliminate TB spontaneously, without external help. The analysis of the IgG, IgA, and IgM antibody classes present in the serum of blood donors, in Nice (France), is given here [Figure 1]. If the IgG and IgA antibodies are present in reduced amounts, the IgM antibodies are detectable in a number of donors, betraying fleeting incipient infections that will be disposed of quietly without symptoms. The number of infections detected by IgM antibodies is very great and conforms with the claim that unapparent infections occur very frequently. The monitoring of IgM antibodies in high-burden countries appears therefore of little informative value [Figure 1].
Figure 1: The analysis of the IgG, IgA, and IgM antibody classes present in the serum of blood donors, in Nice (France)

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Asymptomatic disease and unapparent infections detected by IgG and IgA positivity occur mostly in those people whose immune defenses suddenly face a massive TB overload (e.g., physicians, nurses, relatives of sputum-positive cases, and cashiers in supermarkets)[6] and in those people whose immune system is either naturally weak (genetic defect) or else impaired (stress, starvation, malnutrition, IV drug abusers, and other diseases). TB is an immunological disease.[7] Dr B. R. Chatterjee of the Leprosy Mission of Purulia, in West Bengal, underlined the importance of the immunological aspect of TB and leprosy as early as 1990.[8] Knowledge of the immune status of the patient is obtainable by serological measurements, which give valuable prognostic and diagnostic clues.

Dr. Fadda and coworkers analyzed the production of IgG antibodies by four patients from the beginning of a specific chemotreatment [Figure 2].[9]
Figure 2: IgG production by four patients after the start of treatment

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“C” means a positive culture, which is still today determinant for clinicians to initiate treatment. One patient was devoid of antibodies at entry and failed to produce significant amounts of IgG antibody during treatment, but the treatment eliminated the pathogen (negative cultures on the 2nd month of treatment). The second patient had a low level of antibodies at the start of the treatment, and the treatment, successful since the pathogen was eliminated from the 4th month of treatment on, only timidly amplified their production. The third patient is most interesting. Prof. Fadda disclosed to me that the heavy load of the pathogen in cultures after 2 months of treatment, and the obvious incapacity of the treatment to improve the physical condition of the patient, made him change the regimen, with a spectacular rise in antibodies production and elimination of the pathogen. The fourth patient had a good level of antibodies at entry and these increased during the successful treatment [Figure 2].

In the case “one” above, only IgG antibody production was followed, and the patient was without IgG antibodies throughout, yet the chemotherapy eliminated the pathogen. The next two figures [Figure 3] and [Figure 4], obtained by me, consist in the follow-up of three antibodies' classes produced during the specific treatment of a single patient. The first figure shows that the abrogation of antibodies of the IgG type may not be accompanied by an abrogation of other antibodies' classes: this figure shows IgG (◼), IgM (*), and IgA (▴) production during treatment of one patient during 12.5 months. Only IgM antibodies were detectable at a good level, at entry.
Figure 3: Follow-up of three classes of antibodies produced during a patient's specific treatment

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Figure 4: Follow-up with three classes of antibodies in the first treatment and treatment after relapse

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The treatment immediately spurred the synthesis of IgA and IgM antibodies but not of IgG antibodies [Figure 3].

Furthermore, informative is the monitoring of the antibodies production in a patient whose treatment was positive, yet relapsed: the next figure follows a patient for IgG (◼), IgM (*), and IgA (▴) antibodies during the first treatment and treatment after relapse [Figure 4]. No antibody of any class was detected at the beginning of the first treatment, but all three increased significantly as soon as treatment started and declined to base level with recovery. Normally, an immunized organism retains a memory of the infection so that, on relapse, he does not anymore produce IgM antibodies in large amounts but immediately answers the renewed invasion with a huge production of IgG antibodies. However, and most surprisingly, no sign of immunological booster effect could be observed on either IgG or IgA antibodies' production during the secondary infection, which were produced at the same level as the one observed during the first treatment, as if the patient was without immunological memory. Presumably, the drugs used to eradicate the bug also eradicated the memory cells [Figure 4].

  The Chemotherapy Top

The above-presented graphs of specific treatment show that, at entry, the majority of the patients have low levels of antibodies, indicative of an immune suppression induced by the pathogen. In most cases, the specific treatment allows a resumption of antibody production. However, the nature of the drugs used influences the immune status of the patient in different ways and do play a role in the outcome of treatment.

Streptomycin and rifampicin kill not only TB but also harm the cells involved in the immune defense system. Inclusion of these cytocidal drugs in treatment has consistently been shown to be beneficial, with treatment failure occurring in 5% to 10% of cases but rises sometimes to 44%. This low number (5% to 10%) represents a therapeutic success but also a failure, accentuated by the 44% failure rate sometimes observed. The four drugs were administered during decennia at their maximal tolerated concentration. These drugs may very well weaken the immune system of the patient to a point where his immune mechanisms become unable to dispose of the resident live intracellular mycobacteria subsisting after completion of the therapy or its early abandon due to intolerance. In the best of cases, 5% of the treated patients will relapse. In the worst case, up to 44% of the patients may relapse and turn resistant to one drug and 30% resistant to both isoniazid and rifampicin.[10]

In December 2012, the US Food and Drug Administration approved bedaquiline (i.e., Sirturo®) for the treatment of pulmonary drug-resistant TB. The drug is claimed to inhibit specifically mycobacterial adenosine 5'-triphosphate synthase, an enzyme essential for the generation of energy in Mycobacterium tuberculosis. The drug is known to elicit mycobacterial drug-resistance and associates with a disquieting number of dangerous side-effects. These are waved away in view of the urgency of the problem.[11] Another recommended drug is ciprofloxacin. This broad-spectrum antibiotic functions by inhibiting three enzymes necessary to separate bacterial DNA strands, thereby inhibiting cell division. As a result of its widespread use to treat minor infections readily treatable with older, less broad-spectrum antibiotics, many bacteria have developed resistance to this drug in recent years, leaving it significantly less effective than it would have been otherwise. Delamanid is recommended for extensively drug-resistant-TB treatment.[12] An examination of the data given in [Table 1] of this communication #12 reveals that 17 patients were treated with Delamanid for 6 months in addition to the regular regimen. The failure of the treatment at 24 months amounted to 35%, which is not good. The WHO has added in 2016, clofazimine to its list, in what is known as “The Bangladesh Regime” developed at the Tropical Institute of Antwerp (Belgium). It is said to reduce the time of treatment from about 2 years down to 9 months and represents a considerable progress.
Table 1: Frequency of antimycobacterial IgG antibodies in patients suffering from various illnesses

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These additional drugs, given in addition to the regular 4-drug regimen, are an extension of the current approach that consists summarily in “find the bug and stamp it out!” but the impact of these drugs on the immune system of individual patients is not considered as it should (see Fadda's successful regimen change) and immunotherapeutic approaches addressing the needs of individual patients, which are novel and constructive means to meet the multidrug-resistant (MDR)-TB rising peril, are still neglected.

The conclusion to be drawn is that TB antibodies' production in patients is personalized, associated in the immense majority of the cases to an immunodepression inflicted by the pathogen and sometimes also by the drugs, affecting in a different way all three classes of antibodies.

  The Bacillus Calmette–guérin Vaccine Top

TB serology is also useful to monitor Bacillus Calmette–Guérin (BCG) vaccinated infants. I give here the results of two investigations concerning its application.

The first study, performed in Ankara,[13] followed during 3 years infants monitored for the production of IgG and IgM antibodies against purified protein derivative (PPD), that is tuberculin, or A60 [Figure 5]. This superb study showed that, at birth, a considerable number of children had received passively from their mothers IgG antibodies against antigen 60 (A60), which is a factor of protection,[14] but few children had antibodies against PPD. In Ankara, the possibility of latent TB infections in about 50% of the mothers, who would have IgG antibodies, is by no means an irrational hypothesis. IgM antibodies against A60 and PPD, which do not cross the placental barrier, were of course absent at birth. At birth, about half of the babies were thus passively protected by maternal IgG antibodies, which disappeared from the circulation 4 months after birth, despite the inoculation of the BCG vaccine. Fifteen months after vaccination, all the children, without any exception, began the production of large amounts of IgM antibodies against PPD. These IgM antibodies are indicative of a recent infection and were presumably directed against the nonpeptide moiety of the tuberculin. Fewer children produced in the meantime IgM antibodies against the factor of protection (A60) [Figure 5].
Figure 5: Infants monitored during 3 years for the production of IgG and IgM antibodies against purified protein derivative and antigen 60

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An additional study, to my knowledge not published by the authors, was done in Paris (France) at the Hôpital Necker-Enfants Malades. At Necker-Enfants Malades, non-BCG vaccinated infants <2 years old were compared to BCG-vaccinated infants less than and older than 5 years for IgG antibodies' production against A60 [Figure 6].
Figure 6: Non-Bacillus Calmette–Guérin vaccinated infants were compared to Bacillus Calmette–Guérin-vaccinated infants for IgG antibodies' production against A60

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IgG antibodies are not detected in the non-vaccinated group, as is expected, but antibodies in the two vaccinated groups are also absent, with respectively only two very weakly positive cases and one case barely emerging above the cutoff line. These borderline-positive 3 cases may be traced to increased exposure of the children to contacts outside the home (i.e., nursery, kindergarten, and relatives). The absence of IgG antibodies against A60 during the 5 years that followed the BCG-vaccination is remarkable since A60 is the dominant antigen in the experimental infections [Figure 6].[14]

These two studies on the production of antibodies by vaccinated children and infants confirm what had been signaled as early as 1927: the BCG does not elicit the abundant production of protecting antibodies. References[1],[2] expose that it sometimes promotes TB and leprosy infections.

  The Value of the Xpert/RIF Diagnostic Tool Top

Prof. Pai attributed on August 1, 2013,[15] the surge of TB in India not to the ban of serology recently applied in India but to the use by the Indian private sector of substitute mediocre diagnostic tests as the interferon test, and he advocated the use of the Xpert/RIF instrument for the diagnostic of TB. In the name of ethics,[16] the extension of the use of the Xpert/RIF instrument to the Private Sector was promoted at a subsidized price:

“These prices are approximately <50% the private market prices before Initiative for Promoting Affordable and Quality TB Tests was launched, and the prices are comparable to the banned TB enzyme-linked immunosorbent assay (ELISA) test for three antibodies. Thus, for the money, patients were paying for inaccurate tests, they can now get WHO-endorsed, high-quality tests.”[17]

The Hindu newspaper article stated further: “The price for cartridges is internationally set at $9.98 per cartridge. No matter who is buying it (in any country).”

The use of three antibodies has been discussed supra and never has it been suggested to apply the detection of the three antibody classes at once on a single patient. I will discuss later the claim of “inaccurate tests.” The statement on affordability of the Xpert/RIF instrument is also false. The Treatment Action Group (TAG) observed the contrary in an OPEN LETTER Re: cartridge prices, extended warranties, and business in Russia and the People's Republic of China, sent to the maker of the test, Cepheid, in 2014. To resume this scathing letter in five statements:

  1. We remain disappointed that the price of GeneXpert instruments has not been reduced as requested from the high price of US $17,000 and $17,500
  2. Data presented by the National Health Laboratory Services in South Africa, in March 2013, show module failure rates of 7.94% within 2 years
  3. We are concerned that machines and cartridges are now (n. e. in some countries) subject to extortionate prices
  4. Although the Foundation for Innovative New Diagnostics (n. e. FIND is a daughter company of WHO) website indicates that “the new warranty options have been negotiated by a number of implementers and donors at several stakeholder meetings,” this is not correct
  5. We find it unacceptable that Cepheid should profit from extended warranties in high-burden countries due to high module failure rates and for a technology partly developed by public funds.

This letter mentions high module failure.

On May 2, 2017, Madhukar Pai and Jennifer Furin announced in “Point of view: TB innovations mean little if they cannot save lives DOI: http://dx. doi. org/10.7554/eLife.25956, that as of December 31, 2016, a total of 6,659 GeneXpert instruments (comprising 29,865 modules) and 23,140,350 Xpert MTB/RIF cartridges had been procured in the public sector in 130 of the 145 countries eligible for concessional pricing.[18]

Did this distribution of 23 million cartridges of an expensive and difficult to service diagnostic tool characterized by a high module failure save lives as claimed or, on the contrary, did it help in the spread of the disease?

The positive results of this Cochrane study[18] are disputed by the following three studies conducted by the All India Institute of Medical Sciences, New Delhi, India (AIIMS).[19],[20],[21]

These three publications pointed out that between one-third and two-thirds of extrapulmonary TB culture-positive cases escape detection by this test. This huge number of patients escaping detection allows MDR-patients to wander free on the streets, take airplanes and busses, and contaminate their neighbors with MDR-TB. The reproach could be made that the subjects analyzed by the AIIMS suffered from extrapulmonary TB (EPTB), but this objection is invalid since the WHO approved the test for extrapulmonary cases: GeneXpert is endorsed (i.e., by WHO) for EPTB diagnosis in selected samples, including from the lymph node, cerebrospinal fluid, and tissues.

Two of these incriminating AIIMS publications appeared in 2014 and 2015. They are not mentioned in the TAG (TB Action Group) guide for the use of the Xpert/RIF instrument published in 2017.

  Spread of Multidrug-Resistant Tuberculosis Strains Top

The result of the wide use, especially in South Africa, of this ill-functioning diagnostic tool unadapted to rural areas, was announced on May 9 of this year 2017.[22] This publication provides compelling evidence that drug-resistant TB is expected to increase in some of the world's highest burden countries over the next two decades, and suggests that person-to-person transmission will play an increasingly larger role in the spread of the disease. This includes South Africa, a dedicated user of the GeneXpert/RIF diagnostic test.

A study published in The New England Journal of Medicine confirms this gloomy prospect. The authors observed that most South African victims of a deadly multidrug-resistant strain of TB contracted TB directly from another victim through coughing, spitting, or other close contact. Family contacts were the most dangerous. Other threats included crowded buses and clinic waiting areas. Hospitals were also dangerous. Sixty-one percent of the patients who had spent time in hospitals were linked to another patient in the same hospital. Suspected transmission to co-workers was also found.

This demonstration of the spontaneous spread of multidrug-resistant TB strains from person to person observed in South Africa is alarming because other countries will most likely endure the same calamity.

  The Value of a Blood Test Top

In mammals, and human beings are mammals, the cellular immunity and the humoral immunity are intertwined. The humoral immunity plays as an essential part in the fight against an infectious disease as does the cellular immunity.

The Anda TB serological test is a blood test for the detection of antibodies against TB and other mycobacteria. It had been in use during 25 years in India when it was banned[3],[23],[24] in association with the implementation of the Revised National TB Control Program (RNTCP), which was meant to eradicate TB. The result of this implementation of the RNTCP in India was that the control program lost all control on the spread of TB and the surge of multidrug-resistant TB in India. A disaster whose amplitude is unprecedented in the history of Public Health was heralded on February 11, 2013, by the British Medical Journal: “Tuberculosis looks set to defy concerted efforts to treat it successfully with powerful drugs, turning the clock back to the 1930s.” The Wall Street Journal confirmed this triumphant march of TB forward by the announcement on February 16 that India's emergency strategy to defeat the disease encourages its spread: “Global TB fight hits a wall. India's new strategy actually makes disease more drug-resistant, doctors say.” I have pointed out, however, that the “new strategy” was by no means new but simply an amplification of the means applied during the previous 6 decennia.[1],[2]

As early as 1999, S. Goodman published in Ann. Intern. Med, 130:995–1004: “Toward Evidence-Based Medical Statistics: The P value Fallacy,” warning that a policy based on the P value is erroneous. The authors of the meta-analysis and the WHO experts who validated it disregarded this warning and endorsed false conclusions by banning blood tests that had been used with success during the previous 25 years in India by the private sector. The American Statistical Association warned that the statistics used to propose a policy of serology exclusion[3],[23],[24] did not allow such a policy decision: “The society's members had become increasingly concerned that the P value was being misapplied in ways that cast doubt on statistics generally. In its statement, the American Society of Anesthesiologists advises researchers to avoid drawing scientific conclusions or making policy decisions based on P values alone.”[25] A publication[26] and the newspaper “The Hindu”[27] claimed the serology to be unreliable but also to be basely expensive in India, with the proposal to replace it with the GeneXpert/RIF diagnostic test.

This shameful “Hindu” editorial appeared in June 26, 2012. No change in policy was noted thereafter and the “Guide to Tuberculosis Diagnostic Tools” edited by the TAG in 2017 states:

  On Page 20 of the Guide Top

All currently available blood-based, or serological (also called serodiagnostic), tests for the detection of pulmonary TB and EPTB are not WHO-recommended for use. In fact, the WHO issued a negative recommendation (meaning “do not use this test” for serological TB tests). The reason leading to the lack of endorsement of the blood-based tests for active TB is that such tests have low sensitivity (high false-negative results) and low specificity (high false-positive results). Activists advised the banning of such tests for use in India, particularly in the private sector, and such efforts successfully led to India banning the tests.

The reproach made in this guide of high false-positive results had been studied by Mandler in 1991, who evaluated the presence of IgG antibodies against A60 in 940 healthy Italians.[28] He discovered that only 4% of the general population in this low-TB incidence country has low but significant levels of anti-A60 antibodies. This admirable study did away with the claim of unspecific positive responses but pointed out to a small residual number of positive cases in a supposedly healthy population.

The results are assembled in a solid line, with only 4% of the values above this baseline [Figure 7]. These 4% were restricted to two groups of persons, HIV-seropositive groups, and drug addicts, both of which are high-exposure groups. This Italian study published in 1991 was preceded with a study done in France, published in 1989.[29] The results of this in-depth study of supposedly “false-positive” cases is given here [Table 1].
Figure 7: Seroanalysis of IgG antibodies against antigen 60, in 940 healthy adult Italians

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The diseases may be subdivided in three groups: the group where the frequency of seropositivity against antigen 60 is very high, the group devoid of A60 seropositivity, and the group with variable frequency. The positive cases detected among nontuberculous patients are thus not false but true because not distributed at random. A French “Work-Physician,” Dr. Wirrmann, had the curiosity to verify the IgG-seropositivity of the employees of a supermarket in Strasbourg (France). He discovered that 50% of healthy employees in contact with the general population (i.e., the cashiers) and therefore at higher risk of exposure, had low IgG anti-TB titers, whereas those people employed in administrative tasks and shielded from public contact had none.[6]

This statement of excess false positives is further disproved by the very recent study performed on humoral TB-IgG antibodies by the AIIMS, whose outcome was published in 2017.[30] The publication is available on Internet. Search the site nature.com scientific reports and search for evaluation of 5 novel protein markers.

The results obtained by the All India Institute are identical to those obtained by A60 used in the Anda-TB blood test. I include the [Figure 3] of Singh et al. publication and a similar study done by Zou et al. with the Anda-TB blood test in China,[31] which allows you to compare the respective results.

  The Indian and the Chinese Evaluations of Tuberculosis-Serology Top

[Figure 8] is [Figure 3] of the Singh et al. publication. Only IgG antibodies were analyzed with 7 different antigens. Under, you have the results of IgG (left) and IgA (right) serology obtained with Anda-TB, based on A60. In both studies, you observe some positive cases among controls and negative cases among TB-patients. These are not false but true positive and negative cases as I have shown supra.
Figure 8: Scatter plots of ELISA results using our novel recombinant antigens and the reference antigens [Figure 8]. Recombinant antigens assayed are rSS1, rSS2, rSS3, rSS4, rSS5, Esat-6, and 38 kDa Ag). The serum samples used were from of healthy controls, diseased controls, TB patient (PTB, EPTB, and HIV-TB), and MDR-TB. The scatter plot indicates the antibody level per subject analyzed. A dotted horizontal line is included to show the cutoff value for individual antigen

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This close similarity in results (IgG antibodies analyzed by Singh et al. and IgG and IgA antibodies analyzed by Zou et al.) indicate that the objection of poor specificity ((high number of false-positive results) to justify the rejection of the Anda-TB serological test[3],[23],[24] was invalid since none are observable in the control groups of both tests [Figure 9].
Figure 9: Seroanalysis of antibodies IgG and IgA

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The test developed by the AIIMS is the result of years of industrious research and functions perfectly well. The test developed by the AIIM is a significant addition to our diagnostic tools, especially to detect extrapulmonary TB, latent infections prone to convert, as well as a prognostic tool for the detection of chronically anergic patients whose depressed immune defenses can be stimulated by immunoenhancers as the Mycobacterium vaccae immunotherapy,[32] which works well when applied with a good intelligence of immunology[2] or the food supplement based on uleine, developed by Parabolic biologicals.[33]

  Leprosy Top

Leprosy is a mycobacterium as is TB and is, like TB, a disease known since millennia. It is a dishonorable disease, a disease that must be hidden and that receives little attention. Yet, everywhere around the world, it is on the rise. The newspaper “The Hindu” published on January 29, 2017: “Why India needs to step up its fight against leprosy”.

The newspaper says

“In 2015, the country accounted for 60% of new cases of leprosy globally. The number of new cases indicates the degree of continued transmission of infection. Global statistics show that 199,992 (94%) of new cases were reported from 14 countries reporting more than 1000 new cases each. Only 6% of new cases were reported from the rest of the world. While the mode of transmission of leprosy is not known, the most widely held belief is that the disease was transmitted by contact between those with leprosy and healthy persons. More recently, the possibility of transmission by the respiratory route is gaining ground.”

However, one mode of transmission of leprosy is known since 1960. The surge of leprosy cases recently denoted in India affects principally children. In the book entitled “Is tuberculosis our new challenge?”[2] I list (pages 69–70) 4 publications that denounce the promotion of leprosy by the BCG vaccine: the first was published in 1960,[34] the 3 others in 1989,[35] 1991,[36] and 1994.[37] The warning was thus given well in advance.

I observed, in studying the publication cited as reference 35, published in the WHO Bulletin, that it reports “a 9-fold excess of leprosy cases which affected only vaccines <5 years old in New Guinea, a TB free-zone, during the first 5 years following BCG vaccination.” A nine-fold excess should have brought an interdiction of vaccination with the BCG vaccine but did not. The BCG vaccination of newborns and infants promotes leprosy.

Leprosy is incurable. To bring some relief to the patients, one may envision an immune-therapy based on a food supplement that boosts the production of Nitric Oxide.[33]

  Conclusion Top

TB is a poor pathogen: about one quart of humanity is infected by TB, but only a fraction of this population shows, at some time, symptoms. The number of TB cases increases and decreases worldwide not according to vaccination campaigns but according to hygiene and well-being. The world is presently in a phase of economic, social, and moral degradation and TB surges again.

The Western management of the TB problem has chosen to ignore the reality of the global situation, and the urgency of solutions sensibly adapted to its needs. The importance of poverty as the crucial factor that will determine success or failure was recognized as early as 1999[38] and remains so in 2017. Addressing poverty is likely to be the most crucial factor of the Global Health Plan to Stop TB 2016-2020 as a significant public health problem.[39] A. Barton declared on October 26, 2016, at the 47th Union World Conference on Lung Health, Liverpool, England:

Even “free” TB treatment can come with catastrophic costs. Even before the costs of getting diagnosed, picked up in some high-TB incidence countries by patients themselves, and even before treatment brings its own costs, the financial toll of TB has already begun. Those costs include medical expenses incurred on the way to the screening and testing that finally leads to answers, related, but nonmedical expenses that include transportation, and lost work hours during all of that those alone can make up about half the costs of being sick with TB, with more to follow as treatment, hospitalization (where patient may have to supply their own food and linens) side-effects, stigma, and debilitation bring more costs. And those in turn bring higher risks of treatment failure, recurring disease, and new infections for other household members.”

The Indian Minister of Health should have the courage first to recognize the frailty of the WHO experts and ignore their advice. He should allow the newly developed Indian blood-test for TB diagnosis and prognosis and staunchly resist the expensive interferon test presently recommended by the WHO for prognostic purposes of latent cases. A blood test is much cheaper and easier to perform than an interferon test, an ELISA reader is an instrument that is ubiquitous, and the capacity of blood tests to detect latent infections has been abundantly proven.[6],[29],[30],[40],[41] He also should divert the money squandered on poorly performing and expensive GeneXpert and interferon tests, to the relief of this poverty by making available drinking water, pipe water and sewage disposal, birth control if culturally admitted, a life freed of stress and misery, which is not equal to poverty, and a balanced food diet, with a food supplement able to booster immune responses, to those so badly in need of these to combat the disease.


We would like to thank Prof. Dr. Bhaskar C. Harinath for his suggestions and comments.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Maes R. Can the triumphant March of TB be stopped. A critical appraisal of the currently applied policy of eradication. Clin Microbiol 2016;5:1-7.  Back to cited text no. 1
Maes R. Is Tuberculosis Our New Challenge? LAP Lambert Academic Publishing: Trademark of OmniScriptum GmbH & Co. KG; 2016. ISBN 978-3-330-01065-9.  Back to cited text no. 2
Steingart KR, Flores LL, Dendukuri N, Schiller I, Laal S, Ramsay A, et al. Commercial serological tests for the diagnosis of active pulmonary and extrapulmonary tuberculosis: An updated systematic review and meta-analysis. PLoS Med 2011;8:e1001062.  Back to cited text no. 3
Maes R. Clinical usefulness of serological measurements obtained by antigen 60 in mycobacterial infections: Development of a new concept. Klin Wochenschr 1991;69:696-709.  Back to cited text no. 4
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]

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