Methods for Detecting Mycobacterial Mixed Strain Infections-A Systematic Review

Abstract

Mixed strain infection (MSI) refers to the concurrent infection of a susceptible host with multiple strains of a single pathogenic species. Known to occur in humans and animals, MSIs deserve special consideration when studying transmission dynamics, evolution, and treatment of mycobacterial diseases, notably tuberculosis in humans and paratuberculosis (or Johne's disease) in ruminants. Therefore, a systematic review was conducted to examine how MSIs are defined in the literature, how widespread the phenomenon is across the host species spectrum, and to document common methods used to detect such infections. Our search strategy identified 121 articles reporting MSIs in both humans and animals, the majority (78.5%) of which involved members of the Mycobacterium tuberculosis complex, while only a few (21.5%) examined non-tuberculous mycobacteria (NTM). In addition, MSIs exist across various host species, but most reports focused on humans due to the extensive amount of work done on tuberculosis. We reviewed the strain typing methods that allowed for MSI detection and found a few that were commonly employed but were associated with specific challenges. Our review notes the need for standardization, as some highly discriminatory methods are not adapted to distinguish between microevolution of one strain and concurrent infection with multiple strains. Further research is also warranted to examine the prevalence of NTM MSIs in both humans and animals. In addition, it is envisioned that the accurate identification and a better understanding of the distribution of MSIs in the future will lead to important information on the epidemiology and pathophysiology of mycobacterial diseases.

Keywords: Mycobacterium; complex; detection; infections; methods; mixed strain; non-tuberculous; tuberculosis.

Figure 1

Schematic of different infection events involving pathogens from the same genus. The green circle represents a permissive host whereas the dark blue rectangle and purple oval indicate different species of pathogens belonging to the same genus. The rectangles of different colors indicate distinct strains derived from the same species, where blue indicates microevolution and red, mixed strain infection.

Figure 2

Flow diagram of search strategy. Modified preferred reporting items for systematic reviews and meta-analyses (PRISMA) results for search on mycobacterial MSI detection. Details are provided in material and methods section and Supplementary Table 1.