Mycobacterium tuberculosistransmission from patients with drug-resistant compared to drug-susceptible TB: a systematic review and meta-analysis

Abstract

The extent to which drug-resistant (DR) Mycobacterium tuberculosis strains cause infection and progression to tuberculosis (TB) disease in comparison to drug-susceptible (DS) strains is unknown. Studies in guinea pigs and in vitro experiments have suggested a reduced fitness of organisms that harbour mutations that confer drug resistance [1,2]; it was therefore believed that transmitted drug resistance was a rare event. However, more recent work using molecular typing has shown transmission events occurring in the context of DR-TB [3]. Understanding the risk of transmission, infection and progression to disease in the context of DR-TB is important to guide control measures and help predict the evolution and magnitude of the multidrug-resistant (MDR)-TB epidemic. Hence, we performed a systematic review and meta-analysis to assess whether M. tuberculosis transmission and progression to TB disease (risk/rate of M. tuberculosis infection in all contacts, risk/rate of TB disease in all contacts and risk/rate of TB disease in infected contacts) differ between DR-and DS-TB.The M. tuberculosis infection was the outcome in five studies [5,[7][8][9][10]. The pooled relative risk of M. tuberculosis infection defined by positive TST using a fixed or random effects model was 1.24 (95% CI 1.08-1.42 fixed, 95% CI 0.98-1.44 random) comparing contacts of index cases with MDR-TB and DS-TB. Heterogeneity was high with an I 2 of 75%.@ERSpublications No evidence that drug-resistant TB results in fewer infections or cases in contacts than drugsusceptible TB http://ow.ly/dgez30f87dr Cite this article as: Kodama C, Lange B, Olaru ID, et al. Mycobacterium tuberculosis transmission from patients with drug-resistant compared to drug-susceptible TB: a systematic review and meta-analysis. Eur Respir J 2017; 50: 1701044 [https://doi.

Transmission of drug-resistant tuberculosis in HIV-endemic settings

“…However, in-vitro competition assays have shown fitness differences between strains with and without resistance, albeit in highly artificial in-vitro experiments. 75 Studies into rates of infection or progression to disease in contacts of multidrug-resistant tuberculosis relative to drug-susceptible tuberculosis have yielded variable results, as described previously, 25 and molecular epidemiology studies defining transmission in terms of clustering of strains suggest lower fitness for resistant strains. 76…”

“…Contact investigation studies are another approach to measuring the relative infectiousness of drug-resistant tuberculosis cases. A recent meta-analysis, 25 assessing whether M tuberculosis transmission and progression to tuberculosis disease differ between drug-resistant and drug-susceptible tuberculosis, found a greater likelihood of M tuberculosis infection in contacts of drug-resistant tuberculosis index patients compared with drug- susceptible tuberculosis index cases, but no difference in risk of tuberculosis disease. This increase in the number of infected contacts of drug-resistant index cases could be due to prolonged duration of infectiousness in drug-resistant tuberculosis as a result of diagnostic delays.…”

“…Interventions in tuberculosis infection control include administrative controls, environmental controls, and the use of personal protective equipment. With little evidence for biological differences in transmission potential, 25 environmental controls and the use of personal protective equipment should have similar effects on the transmission of drug-susceptible and drug-resistant tuberculosis. However, administrative controls that aim to interrupt transmission by facilitating early initiation of effective treatment 126 rely on the ability of health systems to promptly detect drug resistance.…”

Bedaquiline- versus injectable-containing drug-resistant tuberculosis regimens: a cost-effectiveness analysis

“…The current analysis does not explore the economic impact of TB transmission dynamics. Each untreated or failing patient continues to transmit the disease and expands the reservoir of potential future XDR-TB cases [59,60]. An assessment of the economic impact of stemming transmission of DR-TB should be undertaken to provide a broader understanding of the cost-effectiveness discussion in the public health context.…”

An e-registry for household contacts exposed to multidrug resistant TB in Mongolia

“…Meta analyses of MDRTB contact tracing studies have shown that 41.3–61.3% of household contacts have latent TB infection, and that 3.4–6.5% develop active disease [ 13 – 15 ]. Despite significant heterogeneity in the studies included in these systematic reviews they have consistently identified a substantial yield of secondary tuberculosis cases among household and close contacts.…”