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Timing of default from tuberculosis treatment: a systematic review

17 Jul 2008

Maria Victoria Valero

Source: Tropical Medicine and International Health (see original article)

Citation: Kruk ME, Schwalbe NR, Aguiar CA (2008). Timing of default from tuberculosis treatment: a systematic review. Trop Med Int Health;13(5)703-712.

Tuberculosis (TB) is one of the most challenging communicable diseases to control effectively. It is predominantly a disease of poverty, with over 80% of cases occurring in Asia or Africa. The continued rise of TB in these regions may be largely attributed to the AIDS pandemic, combined with fragile healthcare delivery systems (1). Another factor is the inadequacy of current treatment regimens. The drugs used are cheap but patients have to take several different drugs every day for many months. This is not easy and so, unsurprisingly, many people default before their treatment is complete (2)

Directly observed therapy (DOT) is recommended by several international organizations, but previous studies of this approach have lacked appropriate comparison groups. Adherence to treatment remains poor; many patients default before their course of drugs is complete (2). A new and extremely worrying threat to TB control is the emergence of strains that cannot be cured by standard established drug regimens. Multidrug resistant (MDR) and extreme drug resistant (XDR) TB emerge in different endemic settings (3). Resistance to at least the two of the major anti-tuberculosis drugs, isoniazid and rifampicin has been termed MDR-TB (1,2). Drug resistant tuberculosis commonly arises through the selection of mutated strains as a result of inadequate chemotherapy. In addition the treatment regimens for MDR-TB are complex, expensive, long-term, associated with high rates of side effects and poor outcome, and high morbidity and mortality (4,5).

The article by Kruk et al. reports a systematic review which aimed to examine the timing of default from TB therapy in low- and middle-income countries. The review also attempted to assess the determinants of default at different points over the treatment course. Medline was searched for peer-reviewed articles published since 1998, using combinations of the terms ‘TB’ and ‘default’ or ‘drop-out’ or ‘compliance’ or ‘adherence’ and ‘therapy’. QUOROM guidelines were followed. Publications written in languages other than English, largely high-income countries and those in which default was not the most important study endpoint were excluded. After applying the inclusion criteria, 15 randomised trials and observational studies were identified. Both directly observed treatment (DOT) and non-DOT programmes were represented.

Eleven of the studies were national DOT TB programmes, following standard international treatment protocols. The three non-DOT studies were from Singapore, India and Pakistan. The results showed that timing of default substantially differed among the studies. By the end of 12 weeks the cumulative default rate in five studies reporting 12-week results ranged between 46.3% and 61.0%. These results suggest that a substantial proportion of patients are dropping out in the later stages of treatment. None of the studies focused on the determinants of default specifically at different durations of treatment in the treatment.

According to the authors, there is limited understanding of the timing of default from TB treatment in the developing world. Future control efforts must seek to reduce treatment duration and remove the risk factors associated with treatment failure, as well as the number of pills and low adherence. In addition the development of new second-line drugs is essential.

As Lin et al. mention, a high level of medication adherence improves clinical outcomes (6). The interplay between clinical outcome and adherence must be a consideration in all patient-provider interactions. It determines the impact of treatment on morbidity and mortality and hence the cost-benefit of the interventions. Clinical interactions, such as clarifying to patients all the treatment steps and the related difficulties and barriers at each visit, are key to successful treatments and, consequently, we cannot forget that a great part of the success in TB control depends on strengthening patient-provider centred actions and interactions.

References

1. Zager E, McNerney R (2008). Multi-drug resistant tuberculosis. BMC Infectious Diseases;8:10 doi:10.1186/1471-2334-8-10. Available from: http://www.biomedcentral.com/1471-2334/8/10 .

2. Jasmer RM et al. Tuberculosis treatment outcomes: Directly observed therapy compared with self-administered therapy. Am J Respir Crit Care Med 2004 Sep 1; 170:561-63. Lawn SD, Wilkinson R (2006). Extensively drug resistant tuberculosis. BMJ;333(7568):559-560.

4. Geoge LJ (2008). Self-determination and compliance in directly observed therapy of tuberculosis treatment in the Kingdom of Lesotho . Soc Work Health Care;46(4):81-99

5. Center for Diseases Control and Prevention (2006). Emergence of Mycobacterium tuberculosis with Extensive Resistance to Second-Line Drugs – Worldwide, 2000-2004. Morb Mortal Wkly Rep;55.

6. Lin EHB, Ciechanowski P (2008). Working with Patients to Enhance Medication Adherence. DOI: 10.2337/diaclin.26.1.17. Clinical Diabetes.26:17-19.

Note: This article is published in a journal which is not open access. To see the full article a subscription to Tropical Medicine and International Health is therefore required. In some developing countries, readers who are based in institutions may be able to access it through the HINARI programme.

2008