Strategies for reducing treatment default in drug-resistant tuberculosis: systematic review and meta-analysis [Review article]

Abstract

B A C K G R O U N D :Scaling up treatment for multidrugr esistant tuberculosis is a global health priority. However, current treatment regimens are long and associated with side effects, and default rates are consequently high. This systematic review aimed to identify strategies for reducing treatment default. M E T H O D S :We conducted a systematic search up to May 2012 to identify studies describing interventions to support patients receiving treatment for multidrugr esistant tuberculosis (MDR-TB). The potential influence of study interventions were explored through subgroup analyses. R E S U LT S : A total of 75 studies provided outcomes for 18 294 patients across 31 countries. Default rates ranged from 0.5% to 56%, with a pooled proportion of 14.8% (95%CI 12.4-17.4). Strategies identified to be associated with lower default rates included the engagement of community health workers as directly observed treatment (DOT) providers, the provision of DOT throughout treatment, smaller cohort sizes and the provision of patient education. C O N C L U S I O N : Current interventions to support adherence and retention are poorly described and based on weak evidence. This review was able to identify a number of promising, inexpensive interventions feasible for implementation and scale-up in MDR-TB programmes. The high default rates reported from many programmes underscore the pressing need to further refine and evaluate simple intervention packages to support patients. K E Y W O R D S : default; retention; MDR-TB THE MULTIDRUG-RESISTANT tuberculosis (MDR-TB) pandemic is rising in prevalence and global importance. There were an estimated 650 000 cases of MDR-TB cases worldwide in 2010, with <5% of all TB patients tested for multidrug resistance. 1 Historically, proportions of MDR-TB among TB cases have been highest in Eastern European countries, although in absolute numbers China and India now contribute 50% of all new MDR-TB cases. 2 Furthermore, in sub-Saharan Africa, the human immunodefi ciency virus (HIV) epidemic and limited resources for comprehensive MDR-TB programmes have aided the spread of MDR-TB and the emergence of extensively drugresistant TB (XDR-TB). 3 MDR-TB, defi ned as Mycobacterium tuberculosis resistant to isoniazid and rifampicin, is more costly and complex to treat than fully susceptible disease, with treatment typically lasting at least 18 months. XDR-TB is defi ned as MDR-TB with additional resistance to a fl uoroquinolone and a second-line injectable agent. 2 Current approaches to treating MDR-TB rely on lengthy treatment durations (typically a minimum of 20 months) using drugs associated with substantial toxicities, often resulting in high default rates. Other reported factors infl uencing treatment default include high costs of treatment for patients in settings where patients must pay, 4 indirect costs such as loss of wages, 5 increased poverty and sex discrimination, 6 dissatisfaction with health care worker attitudes, 7 limited knowledge and negative beliefs and attitudes to treatment, 8 ch...

Reasons for defaulting from drug-resistant tuberculosis treatment in Armenia: a quantitative and qualitative study

“…This is consistent with the fi nding of a recent meta-analysis that showed that patient education was one of the most effective interventions for reducing default in DR-TB. 24 Engaging community health workers as DOT providers in ambulatory treatment was also highlighted as an important intervention. 24 Education could be particularly benefi cial during the out-patient phase of treatment.…”

“…24 Engaging community health workers as DOT providers in ambulatory treatment was also highlighted as an important intervention. 24 Education could be particularly benefi cial during the out-patient phase of treatment. The fi rst months of the out-patient phase were identifi ed as a sensitive period for treatment adherence.…”

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

“…479 However, drug-resistant tuberculosis adherence is challenging for many reasons, including the high pill burden, the frequency of drug-related adverse events, the lengthy duration of treatment, low efficacy of the regimen, and the added common burden of HIV co-infection (panel 1). People with MDR tuberculosis, particularly those with highly resistant strains, are often hospitalised for treatment, which increases costs for the health-care system and the patient, increases the chance of nosocomial transmission of disease, and also loss to follow-up, compared with community-based care.…”

Treatment outcomes for HIV and MDR-TB co-infected adults and children: systematic review and meta-analysis

“…Bibliographies of full-text articles and previous meta-analyses of treatment outcomes among MDR-TB patients were examined for eligible studies. 3,[13][14][15] Authors of relevant studies were contacted for clarification and additional data when necessary.…”