Relapse, re-infection and mixed infections in tuberculosis disease

Abstract

Tuberculosis (TB) disease can be characterized by genotypic and phenotypic complexity in Mycobacterium tuberculosis bacilli within a single patient. This microbiological heterogeneity has become an area of intense study due its perceived importance in drug tolerance, drug resistance and as a surrogate measure of transmission rates. This review presents a descriptive analysis of research describing the prevalence of mixed-strain TB infections in geographically distinct locations. Despite significant variation in disease burden and a rampant human immunodeficiency virus (HIV)-TB co-epidemic, there was no difference in the prevalence range of mixed infections reported in African countries when compared to the rest of the world. The occurrence of recurrent TB was associated with a higher prevalence of mixed-strain infections, but this difference was not reported as statistically significant. These interpretations were limited by differences in the design and overall size of the studies assessed. Factors such as sputum quality, culture media, number of repeated culture steps, molecular typing methods and HIV-infection status can affect the detection of mixed-strain infection. It is recommended that future clinical studies should focus on settings with varying TB burdens, with a common sample processing protocol to gain further insight into these phenomena and develop novel transmission blocking strategies.

Recurrent tuberculosis among HIV-coinfected patients: a case series from KwaZulu-Natal

“…Distinguishing between relapse and reinfection requires comparing the homology of M. tuberculosis strains isolated during the first and recurrent TB episodes using molecular-based DNA fingerprinting techniques. 7 , 8 …”

Small Animal Model of Post-chemotherapy Tuberculosis Relapse in the Setting of HIV Co-infection

“…TB recurrence due to relapse, reinfection, or reactivation of a latent Mtb infection continues to be a critical obstacle in the control and eradication of tuberculosis. HIV infection is an important contributing factor for: the current incidence of TB treatment failure or post-therapy relapse (Pulido et al, 1997;Crampin et al, 2010;Narayanan et al, 2010;Unis et al, 2014;Gadoev et al, 2017); the probability of death as a result of recurrent TB (Alvaro-Meca et al, 2014); and the development of Mtb drug resistance following relapse (Yoshiyama et al, 2004;McIvor et al, 2017). The challenges to investigations in human subjects and lack of experimental models has resulted in a poor understanding of the mechanisms for relapse TB in those with HIV.…”

“…Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection is the leading cause of infectious disease-related mortality, with the World Health Organization estimating 10 million cases of TB and 1.45 million deaths in 2018 (WHO, 2019). Completion of combination drug therapy leads to clinical cure in most subjects, however, a spectrum of incomplete cures that range from latent infection to active TB occur frequently (Dooley et al, 2011;Rockwood et al, 2016;McIvor et al, 2017) and play an important role in the global TB burden (Chao and Rubin, 2010;Mirsaeidi and Sadikot, 2018). In those with bacteriological evidence of cure following drug therapy, recurrent TB can occur due to endogenous reactivation (relapse) or re-infection.…”

Considerations for biomarker-targeted intervention strategies for tuberculosis disease prevention

“…A CORTIS with repeated longitudinal COR measurements could provide insight into these issues [29] . Future trials might also assess the performance of the COR to detect post-treatment recurrence, which ranges from 2 to 10% in hyperendemic communities [30] , [31] , [32] , [33] , or as a correlate of treatment response [10] , [34] , [35] . Future implementation studies could also be designed to estimate cost savings or adverse event reduction by comparing cost/adverse events of the biomarker-based test-and-treat strategy with those of alternative strategies.…”