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Letters to the Editor Indian Pediatrics 2002; 39:404-406 |
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Standardization of Mantoux Test |
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Presently only two tubeculins have been accepted as standard tuberculins by WHO, i.e., PPD-S and PPD RT 23. The Inter-national Standard tuberculins are in custody of the Laboratory of Biological Standards, Staten, Serum Institute, Copenhagen, Denmark(2). In India PPD-RT 23 is manufactured at Guindy Laboratory, Chennai. Some countries like USA use PPD-S (Siebert) of lot 49608. All tuberculins have been standardized for activity in tuberculin units against PPD-S. A standard 5 tuberculin unit (5TU) dose of PPD-S is defined as delayed skin activitiy contained in a 0.1 µg/0.1 ml dose of PPD-S. 1 TU of PPD-RT 23 is equivalent to 5 TU of PPD-S(3). This is for maintaining uniformity and comparability of various test results all over the world. Any pharmaceutical company marketing formulations containing any other type of PPD or in any different strengths from the one mentioned above are best ignored. PPD-RT 23 with Tween 80 of strength 1TU and 2 TU are standardized tuberculins available in India supplied by BCG vaccine Laboratory, Guindy, Chennai. Other tuberculins available in the market are not standardized. Tween 80 is a detergent added to tuberculin to prevent their adsorption on glass or plastic surface. Presently, all tuberculins are manufactured and standardized with Tween 80(4). Hence the old concept of 1TU with tween 80 being equivalent to 5 TU without Tween 80 applies only to old tuberculin (OT) and not to PPD-S or PPD-RT 23. Use of tuberculin strength of 1TU is recommended for standard Mantoux test in India and most tuberculin surveys done in India have been carried out by using 1TU of PPD-RT 23 as per earlier recommendation of WHO. For last 10 years, use of 2TU for surveys has been suggested by WHO but some countries continue to use 1TU for population surveys(5). A recent study from India suggests that since the nonspecific sensitivity (sensitivity due to atypical mycobacterium) is high in our country, 1TU is better in separating infected individuals with disease from infected subjects without disease(6). Therefore, shift to 2 TU is not recommended in our country. For diagnostic purposes we should continue to use 1TU. Tuberculin sensitivity is a delayed type of hypersensitivity reaction in the form of induration at the test site in sensitized host. Histologically the earliest phase of reaction is seen as a perivascular cuffing of mononuclear cells followed by more extensive exudation of mononuclear and polymorphonuclear cells which later migrate to leave only mononuclear cells. When these sensitized T cells come in contact with specific antigens they secrete lymphokines which in turn recruit more lymphocytes at the site of inflammation and give rise to characteristic type IV response(7). Induartion may be due to infection with environmental mycobacteria, BCG induced sensitvity or sensitivity due to infection with Mycobacterium tuberculosis. The size of induration will also vary from region to region due to difference in prevalence of atypical mycobacteria. Induration due to BCG and atypical mycobacteria is less than that due to disease by M. tuberculosis and is usually less than 10 mm(8). While using tuberculin test it should be remembered that in general it detects only presence or absence of infection, i.e., exposure to M. tuberculosis. The amount of induration can suggest active diseased state but is usually not used as a sole diagnostic criteria for tuberculosis. Induration sizes vary from population to population depending on the prevalence of tuberculosis. Cut-offs mentioned in Nelson’s Textbook of Pediatrics are based on CDC criteria for American population which has a very low overall prevalence of tubercular infection as well as disease(9). The predictive value of a positive test in low prevalence population is low because in absence of risk factors a positive result is most likely to be a false positive one. Hence, they have defined lower cut offs for high risk populations and higher for general population. To interpret tuberculin test completely the clinican should clearly understand the epidemiology of tuberculosis in the community and correct indication for tuberculin testing of the individual. In our country with high prevalence of tuberculosis, for practical purposes induration size of tuberculin test can be interpreted as follows: (i) Induration less than 5 mm – no exposure to tubercular bacilli. However, at times trauma due to needle can cause induration up to 4 mm; (ii) Induration between 5-9 mm – this can be due to atypical mycobacteria or BCG vaccination. It may suggest infection in immunocompromised children such as HIV infection or other immunosupression; and (iii) Induation 10 mm or more – an induration of 10 mm or more at 48-72 hours with 1TU PPD-RT 23 in a child with symptoms of tuberculosis should be interpreted as tubercular disease. In high risk situations, i.e., in children with history of contact with smear positive tuberculosis, children living with adults on antitubercular therapy and malnourished children, an induration of 10 mm or more may be an indicator of presence of disease. Greater the amount of induration, more is the likelhood of active disease. Hence the standard recommendation of 10 mm as given in the Revised National Tuberculosis Program (RNTPC) guide-lines(10) is both appropriate and relevant for our country. Situation changes in population suveys where cut off of >15 mm is taken to make the test more specific, e.g., a recent study from National Tuberculosis Center, Bangalore used a cut off of 17 mm with 1TU PPD-RT 23 to identify children with infection with M. tuberculosis in a population survey(6). Such surveys use Mantoux test as the only criteria to find out the prevalence of tubercular disease without the help of risk factors for any other investigation. In such situations the cutoffs vary from region to region depending on the prevalence of atypical mycobacteria and BCG vaccination(11,12). Hence the interpretation of tuberculin test will depend on the situations and factors mentioned above. However, a value of 10 mm or more with 1TU PPD-RT 23 is considered significant in children.
Anju Aggarwal, |
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