Systematic Review, Meta-analysis, and Cost-effectiveness of Treatment of Latent Tuberculosis to Reduce Progression to Multidrug-Resistant Tuberculosis

Abstract

Background Evidence-based recommendations for treating persons having presumed latent tuberculosis (LTBI) after contact to infectious multidrug-resistant (MDR) tuberculosis (TB) are lacking because published data consist of small observational studies. Tuberculosis incidence in persons treated for latent MDR -TB infection is unknown. Methods We conducted a systematic review of studies published 1 January 1994–31 December 2014 to analyze TB incidence, treatment completion and discontinuation, and cost-effectiveness. We considered contacts with LTBI effectively treated if they were on ≥1 medication to which their MDR-TB strain was likely susceptible. We selected studies that compared treatment vs nontreatment outcomes and performed a meta-analysis to estimate the relative risk of TB incidence and its 95% confidence interval. Results We abstracted data from 21 articles that met inclusion criteria. Six articles presented outcomes for contacts who were treated compared with those not treated for MDR-LTBI; 10 presented outcomes only for treated contacts, and 5 presented outcomes only for untreated contacts. The estimated MDR-TB incidence reduction was 90% (9%–99%) using data from 5 comparison studies. We also found high treatment discontinuation rates due to adverse effects in persons taking pyrazinamide-containing regimens. Cost-effectiveness was greatest using a fluoroquinolone/ethambutol combination regimen. Conclusions Few studies met inclusion criteria, therefore results should be cautiously interpreted. We found a reduced risk of TB incidence with treatment for MDR-LTBI, suggesting effectiveness in prevention of progression to MDR-TB, and confirmed cost-effectiveness. However, we found that pyrazinamide-containing MDR-LTBI regimens often resulted in treatment discontinuation due to adverse effects.

Incidence and Prevalence of Tuberculosis in Iran and Neighboring Countries

“…Nine million people are contracted with tuberculosis annually that three million of them are not diagnosed for quality-assured tuberculosis treatment that two of three million from untreated population die each year [14,31]. In some case delay in diagnosis is because of latent form of tuberculosis [32]. If the therapy for tuberculosis is not adequate resulted to drug-resistant strain of M. tuberculosis.…”

“…Drug-resistant tuberculosis is another concern caused irregular or inadequate therapy [1,32]. The resistance to at least two most potent first-line drugs for tuberculosis treatment (including Isoniazid and Rifampin) known as multidrug-resistant tuberculosis (MDR-TB).…”

The burden of multidrug-resistant tuberculosis in children

“…Children in the households of MDR-TB patients who have TB infection are at high risk of developing MDR-TB disease in the future. Although clinical trials are ongoing, observational data strongly suggest the effectiveness of preventive therapy in reducing the risk of progression of MDR-TB 17 . Alternatively, periodic evaluation of child contacts for 2 years can ensure that if they develop TB disease, they are diagnosed early and treated promptly with an effective regimen 18 .…”

Tuberculosis Screening and Treatment in Solid Organ Transplantation

“…Levofloxacin and moxifloxacin are active against MTB and have been attractive candidate drugs for LTBI treatment in liver-transplant candidates or recipients given lower rates of hepatotoxicity than isoniazid and significantly fewer DDIs than rifampin. Fluoroquinolone-based regimens have been used for LTBI treatment among contacts with multi-drug resistant TB, though evidence for efficacy is sparse relative to the standard LTBI treatment regimens [42,43]. A promising multicenter study comparing levofloxacin versus isoniazid in liver-transplant candidates and recipients was stopped early due to a high incidence of sometimes-severe tenosynovitis though a small case series also reported infrequent ADRs with a fluoroquinolone-based regimen [44,45].…”