Treatment for LTBI in contacts of MDR-TB patients, Federated States of Micronesia, 2009–2012

Abstract

SUMMARY SETTING Few studies have shown the operational feasibility, safety, tolerability, or outcomes of multi-drug-resistant latent tuberculous infection (MDR LTBI) treatment. After two simultaneous multidrug-resistant tuberculosis (MDR-TB) outbreaks in Chuuk, Federated States of Micronesia, infected contacts were offered a 12-month fluoroquinolone (FQ) based MDR LTBI treatment regimen. DESIGN Between January 2009 and February 2012, 119 contacts of MDR-TB patients were followed using a prospective observational study design. After MDR-TB disease was excluded, 12 months of daily FQ-based preventive treatment of MDR LTBI was provided by directly observed therapy. RESULTS Among the 119 infected contacts, 15 refused, while 104 began treatment for MDR LTBI. Of the 104 who initiated treatment, 93 (89%) completed treatment, while 4 contacts discontinued due to adverse effects. None of the 104 contacts who undertook MDR LTBI treatment of any duration developed MDR-TB disease; however, 3 of 15 contacts who refused and 15 unidentified contacts developed MDR-TB disease. CONCLUSION Providing treatment for MDR LTBI can be accomplished in a resource-limited setting, and contributed to preventing MDR-TB disease. The Chuuk TB program implemented treatment of MDR LTBI with an 89% completion rate. The MDR LTBI regimens were safe and well tolerated, and no TB cases occurred among persons treated for MDR LTBI.

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…Although no formal guidelines on preventive therapy regimens exist, analysis of many studies 477 suggest efficacy and safety of a fluoroquinolonebased 6-12-month preventive therapy regimen. 478 However, because of the scarce evidence from randomised clinical trials, WHO does not recommend treatment, but advises 2 years of follow up for any person who has been exposed to tuberculosis in the household. Three clinical trials investigating the use of levofloxacin (TB-CHAMP, V-Quin) or delamanid (PHOENIx MDR TB/A5300B) for treatment of child and adult household contacts are underway or will be starting soon (table 13).…”

Tuberculosis Multidrug-resistant Tuberculosis – From Epidemiology to Treatment Design

“…The evidence of the benefit of a preventive treatment for infected contacts is limited, but some studies seem to support a policy of preventive treatment according to the pattern of drug resistance of the index case. 69,70 and clofazimine, is a matter of concern and makes regular monitoring mandatory. 77 Errors in the use of the new drugs may increase the size of the problem in the populations, like the improper use of rifampicine after its introduction, which probably led to the development of MDR-TB.…”

Commentary: A targets framework: Dismantling the invisibility trap for children with drug-resistant tuberculosis

“…86 A consensus exists about best practices to treat DR-TB disease in children, 44 and experience is accumulating in the use of preventive therapy in child MDR-TB contacts. 69,[71][72][73]109 For an exercise to estimate targets, we will use the subset of children exposed at home to MDR-TB. A set of provisional annual targets will be updated every year.…”

“…Preventive therapy regimens for both groups of child contacts could be designed according to expert guidance, based on growing observational evidence of benefit and safety. [68][69][70][71][72][73] If any drug or drug combination can come even close to the spectacular efficacy of isoniazid for treating isoniazidsusceptible latent TB infection in children, 59,113 then it will avert every year large numbers of child cases and deaths due to DR-TB.…”

“…1,66 Although no controlled trials have examined preventive therapy for persons exposed to MDR-TB, 67 experts who have reviewed observational data suggest management of close contacts include preventive therapy regimens for MDR-TB. [68][69][70][71][72][73] Contact investigation has, for half a century, 74 been the best way to find children newly infected with TB and those with early disease. It remains so today.…”