BCG Infection due to MPT64-Negative Strain: A Diagnostic Challenge
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
Authors: Suresh, Parasmal; Biswas, Lalitha; Prasad, Vinitha; Kumar, Anil; Sivadas, Suchitra; Khan, Sadia; Biswas, Raja
MPT64 is a 24-kDa immunogenic protein that is widely used as a diagnostic marker for the differentiation of Mycobacterium tuberculosis complex (MTBC) from nontuberculous Mycobacterium (NTM). Unlike Mycobacterium bovis, Bacillus Calmette-Guerin(BCG) vaccine strains with RD2 deletion do not secrete MPT64. Culture isolates from infections due to these strains may be falsely identified as nontuberculous Mycobacterium in the absence of clinical correlation. Here, we present one case each of BCG adenitis and osteitis, both of which were considered as MPT64 card-negative Mycobacterium spp. (i.e., NTM) and were later identified as M. bovis BCG Danish 1331 strain. The first case was a 4-month-old female infant admitted with swollen lymph nodes in the left supraclavicular and the left axillary region of 1 month duration. The second case was of a 1-year-and-5-month-old male child who presented with a limp on the left leg and soft tissue swelling of 1 month duration on the anterolateral aspect of the left knee joint. In both cases, BCG vaccine was administered at birth on the left deltoid region and had healed without any complication. Clinical samples in both cases were positive by Xpert tuberculosis/RIF for MTBC, and cultures grew acid-fast bacilli which were negative by MPT64 assay. The clinical implication of infections due to M. bovis BCG is immense as they are inherently resistant to pyrazinamide, and the presence of disseminated BCG infection in young children is a hallmark of serious immune deficiency which needs to be ruled out.
1-(1-Arylethylpiperidin-4-yl)thymine Analogs as Antimycobacterial TMPK Inhibitors
Authors: Jian, Yanlin; Hulpia, Fabian; D. P. Risseeuw, Martijn; Forbes, He Eun; Caljon, Guy; Munier-Lehmann, Helene; I. M. Boshoff, Helena; Van Calenbergh, Serge
A series ofMycobacterium tuberculosisTMPK (MtbTMPK) inhibitors based on a reported compound3were synthesized and evaluated for their capacity to inhibitMtbTMPK catalytic activity and the growth of a virulentM. tuberculosisstrain (H37Rv). Modifications of the scaffold of3failed to afford substantial improvements inMtbTMPK inhibitory activity and antimycobacterial activity. Optimization of the substitution pattern of the D ring of3resulted in compound21jwith improvedMtbTMPK inhibitory potency (three-fold) and H37Rv growth inhibitory activity (two-fold). Moving the 3-chloro substituent of21jto thepara-position afforded isomer21h, which, despite a 10-fold increase in IC50-value, displayed promising whole cell activity (minimum inhibitory concentration (MIC) = 12.5 mu M).