Tuberculosis in household contacts of multidrug-resistant tuberculosis patients

Grandjean, Louis; Crossa, Aldo; Gilman, Robert H.; Herrera, Cesar; Bonilla, César; Jave, Oswaldo; Cabrera, José Luis; Martin, Laura J.; Escombe, A. Roderick; Moore, David

doi:10.5588/ijtld.11.0030

Cited by 42 publications

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“…Overall, TB, either incident or prevalent, is found in 4.1% of the MDR-TB contacts, which is higher than the corresponding prevalence rates of 1.9% and 1.7% reported among household contacts of drug-susceptible TB in the same locality [8,22], but lower than the reported rates of 5% in another MDR-TB contact study in 2011 [23] and 4.5% in one meta-analysis [24]. While smear positivity and cavitary disease were shown to be significant predictors of TB among contacts exposed to predominantly drug-susceptible TB in our previous study [22], this study found a significant association between an XDR-TB index patient and the occurrence of both prevalent and secondary cases among contacts exposed to MDR-TB.…”

Section: Discussionmentioning

confidence: 39%

“…Among the 704 household contacts included in the final analysis, 12 (1.7%) prevalent cases were found: three XDR-TB cases associated with three XDR-TB index cases; one XDR-TB, four MDR-TB, three drug-susceptible TB and one culture negative TB case associated with seven MDR-TB index cases. The median number of contacts per index case was three (range [1][2][3][4][5][6][7][8]. RFLP analysis among 11 index-prevalent contact pairs showed 100% concordance in three pairs with XDR-TB, 100% concordance in one MDR-TB index case pairing with one contact with XDR-TB, 50% concordance in four non-XDR MDR-TB pairs, and no concordance in three MDR-TB index cases pairing with three contacts with drug-susceptible TB.…”

Section: Methodsmentioning

confidence: 99%

“…MDR-TB and XDR-TB reportedly require prolonged treatment, with a high risk of treatment failure [1,2]. Slow bacteriological conversion and treatment failure may increase the risk of transmission within the community, as suggested by reports of secondary TB transmission within the household [3,4]. However, few studies have systematically evaluated the magnitude of such transmission risks within a defined geographical area, such as a metropolitan city.…”

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confidence: 99%

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Transmission of multidrug-resistant and extensively drug-resistant tuberculosis in a metropolitan city

Leung

Leung²,

Kam³

et al. 2012

Eur Respir J

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Multidrug-resistant (MDR)-tuberculosis (TB) and extensively drug resistant (XDR)-TB reportedly lead to increased household transmission. This is a retrospective cohort study of active TB occurring among household contacts exposed to MDR-TB.Of 704 contacts in 246 households, initial screening identified 12 (1.7%) TB cases (prevalent cases) and 17 (2.4%) contacts that subsequently developed active TB (secondary cases) after a median (range) duration of 17 (5-62.5) months. Eight prevalent cases and three secondary cases had MDR-TB. TB incidence rates per 100 000 person-years were 254.9 overall and 45.0 for MDR-TB. XDR-TB in the index MDR-TB patient significantly increased the odds of identifying a prevalent TB case to 4.8 (95% CI 1.02-22.5), and the hazard of finding a secondary TB case to 4.7 (95% CI 1.7-13.5). Molecular fingerprinting confirmed household transmission of MDR-TB. Of 20 retrievable isolates from 27 XDR-TB index cases, restriction fragment length polymorphism analysis showed clustering among 13 (65%), with 11 (55%) due to recent transmission by n-1 method and an identifiable household source in only three (27.2%) of the 11 cases.XDR-TB relative to MDR-TB significantly increases household transmission of TB, probably reflecting prolonged/higher infectivity, and indicating a need for prolonged household surveillance. XDR-TB may largely transmit outside of the household settings.

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Section: Discussionmentioning

confidence: 39%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Transmission of multidrug-resistant and extensively drug-resistant tuberculosis in a metropolitan city

Leung

Leung²,

Kam³

et al. 2012

Eur Respir J

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“…The model initially sampled 700 household sizes from the distribution of household sizes in the trial [1]. 213 of these had an initial MDR-TB case, 487 an initial DS-TB case.…”

Section: Detailed Overview Of Simulationmentioning

confidence: 99%

“…Mycobacterium tuberculosis (Mtb) is a highly prevalent bacterium, thought to infect just under a quarter of the world's population (1). Treatment of tuberculosis (TB) disease is not simple and drug-susceptible tuberculosis (DS-TB) requires a multiple drug regimen taken for at least 6 months (2).…”

Section: Introductionmentioning

confidence: 99%

The relative fitness of drug resistantMycobacterium tuberculosis: a modelling study of household transmission in Peru

Knight

Zimic²,

Funk

et al. 2017

Preprint

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The relative fitness of drug resistant versus susceptible bacteria in an environment dictates resistance prevalence. Estimates for the relative fitness of resistant Mycobacterium tuberculosis (Mtb) strains are highly heterogeneous, many are derived from in-vitro experiments and few studies have estimated relative fitness in the field. Measuring fitness in the field allows us to determine how the environment (including factors such as host genetics, TB treatment regimen etc.) influences the ability for bacteria to survive, be transmitted and cause secondary cases of disease.We designed a household structured, stochastic mathematical model to estimate the fitness costs associated with multi-drug resistance (MDR) carriage in Mtb strains in Lima, Peru over a 3-year period. By fitting the model to data from a large prospective cohort study of TB disease in household contacts we estimated the fitness, relative to susceptible strains with a fitness of 1, of MDR-Mtb strains to be 0.33 (95% credible interval: 0.17-0.54) or 0.39 (0.26-0.58), if only transmission or progression to disease, respectively, was affected by MDR. The relative fitness of MDR-Mtb increased to 0.57 (0.43-0.73) when the fitness cost was modelled to influence both transmission and progression to disease equally.We found the average relative fitness of MDR-Mtb circulating within households in Lima, Peru between 2010-2013 to be significantly lower than susceptible-Mtb circulating at the same time and location. If these fitness levels do not change, then existing TB control programmes are likely to keep MDR-TB prevalence at the current levels in Lima, Peru. Significance StatementThe relative fitness of drug resistant strains is a key determinant of resistance prevalence. We used a new quantitative framework to directly estimate the average relative fitness cost of multi-drug resistant (MDR-) Mycobacterium tuberculosis (Mtb) strains from a household study in Lima, Peru. This showed that the relative fitness of MDR-Mtb was substantially lower than that of drug-susceptible Mtb strains circulating at the same time and location, suggesting that with current control methods MDR-TB diseases levels may be held stable in Lima, Peru.

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Preventive Therapy for Multidrug Resistant Latent Tuberculosis Infection: An Ethical Imperative with Ethical Barriers to Implementation?

Nguyen

Fox

Mason

et al. 2020

Public Health Ethics Analysis

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Multidrug resistant tuberculosis (MDR-TB) has a substantial impact on individuals and communities globally, including lengthy, expensive and burdensome therapy with high rates of treatment failure and death. Strategies to prevent disease are well established for those who acquire latent tuberculosis infection (LTBI) after exposure to drug susceptible TB (DS-TB). However, there has been limited research or programmatic experience regarding the prevention of MDR-TB. Accordingly, while global recommendations strongly emphasize the need to deliver LTBI therapy after TB exposure, most programs do not do so where MDR LTBI is identified. The paucity of prospective randomized trial evidence for the effectiveness of MDR LTBI therapy, and concerns regarding its adverse effects, have been used to justify a reluctance to scale up programmatic interventions to prevent MDR-TB, or to participate in research evaluating such strategies. However, such a response fails to adequately balance potential risks of therapy with the substantial harms associated with inaction. Furthermore, the cost of inaction falls disproportionately on the most vulnerable members of society, including children. Delays in implementing proven preventive strategies may also mask hidden programmatic concerns, particularly regarding the financial cost and other burdens of treating drug resistant infection. Reticence to engage with preventative therapy for MDR-TB, even in the absence of high-level evidence, may run counter to the best interests of individuals who have been exposed to MDR-TB. This chapter will explore ethical tensions raised by expanding access to preventative therapies for MDR-TB, and consider how ethically optimal responses to this adverse condition may be evaluated. An ethical perspective on evidentiary burden will be addressed, emphasizing how MDR LTBI research may both offer, and be shaped by, paradigmatic insights into human research ethics more generally. Emerging research and illustrations from the authors programmatic engagement in Vietnam are offered as case examples, because social and community expectations and norms may challenge, or support, implementation of therapy for drug-resistant infection. Such circumstances prompt consideration of the broader questions of social impact, such as the potential for widespread preventive therapy to accelerate the development of antimicrobial resistance.

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Tuberculosis in household contacts of multidrug-resistant tuberculosis patients

Abstract: The high percentage of diseased household contacts highlights an opportunity for household-level interventions to prevent transmission, whether or not these cases were all attributable to the index case.

Cited by 42 publications

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Transmission of multidrug-resistant and extensively drug-resistant tuberculosis in a metropolitan city

Transmission of multidrug-resistant and extensively drug-resistant tuberculosis in a metropolitan city

The relative fitness of drug resistantMycobacterium tuberculosis: a modelling study of household transmission in Peru

Preventive Therapy for Multidrug Resistant Latent Tuberculosis Infection: An Ethical Imperative with Ethical Barriers to Implementation?

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