Recent Conversion of Tuberculin Skin Test
 
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Ira Shah
Consultant in Pediatric Infectious Diseases and Pediatric Hepatology, Nanavati Hospital and Incharge Pediatric HIV, TB and Liver Clinics, B J Wadia Hospital for Children, Mumbai, India.

Address for Correspondence: Dr Ira Shah, 1, B Saguna, 271, B St Francis Road, Vile Parle {W}, Mumbai 400056.


Clinical Problem :
A 5 year old girl weighing 14kgs was referred in view of positive Tuberculin skin test {TST} {15mm by 2 TU} in November 2015. She had been tested as she had fever for 3 days but was currently asymptomatic. Chest X ray was normal and there was no contact with a patient having tuberculosis {TB}. Her TST in August 2015 was negative. She was advised Quantiferon TB Gold test that was negative.


Question :
What is the cause of her positive TST now_?

Expert Opinion :
This is recent conversion of TST. Mantoux conversion is the development of new or enhanced hypersensitivity due to infection with tuberculous or non-tuberculous mycobacteria, including BCG vaccination. Mantoux conversion is defined as a change {within a two-year period} of Mantoux reactivity which meets either of the following criteria:
• A change from a negative to a positive reaction
• An increase of = 10 mm
Conversion has been associated with an annual incidence of TB disease of 4 percent in adolescents or 6 percent in contacts of smear-positive cases. {1}
Quantiferon TB Gold assay is an interferon-gamma {IFN-_?} release assay {IGRA} based on the fact that T-cells sensitized with tuberculous antigens produce IFN-_? when they are re-exposed to mycobacterial antigens. IGRAs assess response to M. tuberculosis proteins by measuring IFN-_?. The antigens used are not present in BCG and non-tuberculous mycobacteria and this test help to determine false positive mantoux results that may come due to these infection. The QuantiFERON-TB Gold {QFT-G, Cellestis, Australia} and the newer version QuantiFERON-TB Gold In-Tube {QFT-GIT, Cellestis, Australia} are whole-blood based enzyme-web addressed immunosorbent assays {ELISA} measuring the amount of IFN- _? produced in response to specific M. tuberculosis antigens {QFT-G: early secretory antigen target-6 {ESAT-6} and culture filtrate protein 10 {CFP-10}, QFT-GIT: ESAT-6, CFP-10, TB7.7}. However, ESAT-6 and CFP-10 antigens are present in M. kansasii, M. szulgai, and M. marinum, and sensitization to these organisms might contribute to the release of IFN-_? in response to these antigens and cause false-positive IGRA results. {2}
Thus, a positive TST and a negative QFT-GIT is suggestive of infection due to non-tuberculous mycobacteria {NTM} in this child. It is unlikely to be due to BCG vaccination as in India, BCG is given at birth and there is no recent BCG given in this child. NTMs also known as atypical mycobacteria or mycobacteria other than Mycobacterium tuberculosis {MOTT} usually cause infections in immunocompromised humans. NTM are ubiquitous organisms and can be isolated from soil, house dust, water, food and animals. Transmission is by inhalation, ingestion or direct contact with a contaminated environmental source. Exposure to NTM may cause a positive TST but may not lead to disease. Since the child is currently asymptomatic, this NTM infection does not require any treatment.

References
1. Menzies D. Interpretation of repeated tuberculin tests. Boosting, conversion, and reversion. Am J Respir Crit Care Med. 1999`159:15–21.
2. Mazurek GH, Jereb J, Vernon A, LoBue P, Goldberg S, Castro K, Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, CDC . Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infection - United states .June 25, 2010 , 59{RR05}`1-25 Available at. ww.cdc ,gov, mmwr. Accessed June 26, 2010.


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