Clonal Complexity in Mycobacterium tuberculosis Can Hamper Diagnostic Procedures

Abstract

Clonal complexity is increasingly accepted in Mycobacterium tuberculosis infection, including mixed infections by Ն2 strains, which usually occur in settings with a high burden of tuberculosis and/or a high risk of overexposure to infected patients. Mixed infections can hamper diagnostic procedures; obtaining an accurate antibiogram is difficult when the susceptibility patterns of the strains differ. Here, we show how mixed infections can also prove challenging for other diagnostic procedures, even outside settings where mixed infections are traditionally expected. We show how an unnoticed mixed infection in an HIV-positive patient diagnosed in Madrid, Spain, with differences in the representativeness of the coinfecting strains in different sputum samples, markedly complicated the resolution of a laboratory crosscontamination false positivity alert.KEYWORDS tuberculosis, clonal complexity, mixed infection, diagnostic procedures C lonally complex infections are increasingly accepted in Mycobacterium tuberculosis infection. Mixed infection (i.e., the simultaneous infection by Ն2 different M. tuberculosis strains) is one of the most widely studied types of clonally complex infections (1-4). Mixed tuberculosis (TB) infection requires either simultaneous coinfection by a number of strains or, more likely, overexposure of an infected patient whose initial infection has not resolved to another patient infected by a different strain.Mixed infections are more likely in prisons, shelters, substandard overcrowded housing, and in other high-burden settings, where the possibility of overexposure is higher (2, 3, 5). The fact that mixed infections are not considered outside these contexts can hamper diagnostic procedures; for example, an unnoticed mixed infection can affect the result of antibiotic susceptibility testing. Rates of resistance are higher in regions where mixed infections are more frequent and in countries hosting immigrants from these regions; therefore, it is not uncommon for mixed infections to involve strains with different susceptibility patterns (6-8). However, although clonally complex infections are now beginning to be taken into account in the above-mentioned settings and for specific diagnostic procedures, equivalent efforts have not been made outside these contexts. Similarly, no efforts have been made to evaluate the impact of mixed infections on diagnostic procedures other than antibiotic susceptibility testing.We show how an unnoticed mixed M. tuberculosis infection in a case diagnosed in Madrid, Spain considerably hampered management of a laboratory cross-contamination alert.(The results of this study were partially presented at the 2015 ESM Meeting, Riga, Latvia.)

A Mycobacterium tuberculosis Beijing strain persists at high rates and extends its geographic boundaries 20 years after importation

“…Similar ASO-PCRs have been applied to prospectively determine the presence of an MDR M . tuberculosis strain in Equatorial Guinea 13 and in retrospective collections and to identify potential secondary cases caused by two XDR Beijing strains imported from Russia to Spain 14 .…”