Diagnosis

The decision by a ministry of health to initiate or expand TB infection testing requires preparedness of medical services. Many of the people who may be eligible for TPT will need to be able to access this important intervention. This means that referral pathways and health services must be planned or reorganized to ensure that all individuals among target populations are tested promptly and linked to appropriate treatment based on the test results. This is best accomplished by adopting a patient-centred approach that considers the individual’s needs and perspectives.

To date, the criteria for a positive TBST have been established by the manufacturers. These criteria are based on clinical data in relatively small numbers of patients. In addition, all of the studies to date evaluating accuracy of these tests have used cross-sectional designs. Data from prospective observational or experimental studies may result in modification of these criteria in the future.

Table 3.2. Criteria for a positive TBST

The active ingredient in C-TST (formerly known as the ESAT6-CFP10 test, Anhui Zhifei Longcom, China) is an ESAT-6–CFP-10 fusion recombinant protein expressed in genetically modified E. coli. Each test dose of 0.1 mL contains 5 U of recombinant M. tuberculosis fusion protein, and auxiliary ingredients – disodium hydrogen phosphate, potassium dihydrogen phosphate, sodium chloride, phenol and polysorbate 80 (41).

Fig. 3.3. C-TST vials

Diaskintest (Generium, Russian Federation) is a recombinant protein produced by genetically modified culture of Escherichia coli BL21 (DE3)/pCFP-ESAT, diluted with sterile isotonic phosphate buffer solution, with a preservative (phenol). One dose (0.1 mL) of the product contains 0.2 μg of CFP-10–ESAT-6 recombinant protein, and excipients – disodium phosphate dihydrate, sodium chloride, potassium dihydrogen phosphate, polysorbate 80, phenol and water for injection (40).

Fig. 3.2. Diaskintest package and vial

Cy-Tb (formerly known as the C-Tb test, Serum Institute of India) contains a 1:1 ratio of two recombinant proteins of ESAT-6 and CFP-10 was previously produced by genetically modified Lactobacillus lactis, by Statens Serum Institute (Denmark). One single test dose of 0.1 mL contains 0.05 μg of rdESAT-6 and 0.05 μg of rCFP-10.

Fig. 3.1. Vial of Cy-Tb

The sensitivity of TST based on different size criteria of induration was established among people who had been treated for and had recovered from microbiologically confirmed TB (34). Of these, 98% had a reaction of 5 mm or more to TST, 90% had a reaction of 10 mm or more but only 60% had a reaction of 15 mm or more. On the other hand, reactions to TST due to BCG or nontuberculous mycobacteria are usually smaller than TST reactions due to true infection with M. tuberculosis (11, 12).

The original tuberculin material used by Mantoux in his first studies of tuberculin reactions was a highly heterogeneous mix of substances from killed M. tuberculosis(9). This so-called old tuberculin was replaced in 1941 by a standardized preparation of PPD from M. tuberculosis. A single standard lot of this material was produced by Florence Seibert, termed “PPDS” (32); since then, all newly produced tuberculin material has been produced using the same methods and tested against this standard, measuring induration in sensitized guinea pigs.

To avoid barriers or delays created by TB infection testing, and to minimize associated losses in the TB infection care cascade, an integrated person-centred care model is preferred for TB infection diagnosis and treatment. Here, “integrated” means carrying out screening for TB disease and testing for TB infection in parallel, and “person-centred care” means coordination of multiple care activities during the same visits.