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.

Whole Genome Sequencing Links Mycobacterium bovis From Cattle, Cheese and Humans in Baja California, Mexico

“…This could be indicative of multiple introductions of bTB into the diaries and highlights the lack of control in the movement of animals in the region. Previous studies in M. tuberculosis have also found mixed infections in humans more frequently in high-TB burden regions ( 61 ). Though a well-studied occurrence in humans, information on identification of mixed M. bovis infections in cattle through WGS is scarce; thus, the results shown here may be useful for future comparisons.…”

Presence of Human Pathogens of the Borrelia burgdorferi sensu lato Complex Shifts the Sequence Read Abundances of Tick Microbiomes in Two German Locations

“…In contrast to Ca. Neoehrlichia, Mycobacterium are widely distributed in various environments such as soil, water, human and animal hosts [ 56 ]. The majority of tick-borne microbiome analyses based on 16S rRNA gene surveys have frequently reported worldwide members of the genus Mycobacterium [ 18 , 57 , 58 ].…”

Who infects whom?—Reconstructing infection chains of Mycobacterium avium ssp. paratuberculosis in an endemically infected dairy herd by use of genomic data

“…This approach was applied to several pathogens, including tuberculosis in humans for which the most commonly employed cut-off is based on the finding that epidemiologically linked patients were genomically linked by �5 SNPs, with an upper bound of 12 SNPs between any two linked isolates [36]. Thresholds for discriminating mixed infections from within-host evolution still lack standardization [37]. Even when this analysis was largely insensitive to the mutation rate, it needs to be kept in mind that rates of evolution (and as a result also distance thresholds) may differ across lineages of the same species [22].…”