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BCG Infection due to MPT64 – Negative Strain: A Diagnostic Challenge

Publication Type : Journal Article

Source : American Journal of Tropical Medicine Hygiene, Volume 103: Issue 3, 2020

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Campus : Kochi

School : School of Medicine

Department : Microbiology

Year : 2020

Abstract : Live attenuated BCG vaccine was introduced to the world in 1921.1 In countries like India, with a high burden of tuberculosis (TB), the WHO recommends BCG vaccination of all children at birth to prevent tuberculous meningitis and disseminated TB in young children and infants.1 Among the various BCG strains, Glaxo 1077, Pasteur 1173, Danish 1331, and Tokyo 172 account for almost 90% of the vaccines worldwide.1,2 Whereas Pasteur 1173 and Danish 1331 are considered as strong strains (higher vaccine efficacy), Glaxo 1077 and Tokyo 172 are weak strains (lower vaccine efficacy).1,2 The genealogy of BCG vaccine strains based on historical data shows that BCG strains differ in the presence of mpb64 gene and the number of copies of IS6110 gene.3,4 The ancestral BCG strain obtained before 1925 had two copies of IS6110 and mpb64 genes, but subsequently loss of one IS6110 happened in 1925–1926 followed by loss of mpb64 gene around 1927–1931.3,4 The mpb64 gene is present in BCG-Japan, BCG-Sweden, BCG-Moreau, BCG-Birkhaug, and BCG-Russia, whereas it is absent in BCG-Danish, BCG-Pasteur, BCG-Glaxo, BCG-Tice, and BCG-Connaught. Complications due to BCG vaccination are influenced by BCG strain, dose, age, technique of immunization, and the underlying immune status of the vaccines.2,3 The incidence of severe complications ranges from 2 to 1,000 per million vaccinations and is most often seen in patients with primary immunodeficiency disorders such as chronic granulomatous disease, severe combined immunodeficiency, type 1 cytokine axis defect, DiGeorge syndrome, and HIV infection.1,3 Severe complications may require chemotherapy with antiTB drugs, which get complicated by the inherent resistance to pyrazinamide in all Mycobacterium bovis strains.1,5 Because of inherent resistance to pyrazinamide, the CDC recommends a triple-drug regimen consisting of rifampicin, isoniazid, and ethambutol with treatment duration being extended to 9 months for treatment of disease due to M. bovis.6 Disseminated BCG infection in young children could be an indication of serious immune deficiency, which needs to be investigated and ruled out. Therefore, differentiation of M. bovis BCG from Mycobacterium tuberculosis as well as from nontuberculous mycobacteria (NTM) is crucial for appropriate treatment. Assays for MPT64 protein have been recommended by the Foundation for Innovative New Diagnostics for rapid identification of the M. tuberculosis complex using the BACTEC MGIT 960 liquid culture system [Becton Dickinson Diagnostics, Sparks, MD].7 The assays are routinely performed all over the world, both in developed and developing countries, as suggested by two meta-analyses on their performance in accurately identifying the M. tuberculosis complex in liquid culture.8,9 We report two cases of BCG infection due to M. bovis BCG strains which were MPT64 negative.

Cite this Research Publication : Parasmal Suresh, Lalitha Biswas, Vinitha Prasad, Anil Kumar, Suchitra Sivadas, Sadia Khan, and Raja Biswas "BCG Infection due to MPT64-Negative Strain: A Diagnostic Challenge", American Journal of Tropical Medicine Hygiene, 2020

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