Eliminating the category II retreatment regimen from national tuberculosis programme guidelines: the Georgian experience
Jennifer Furin a, Medea Gegia b, Carole Mitnick c, Michael Rich d, Sonya Shin e, Mercedes Becerra c, Peter Drobac d, Paul Farmer d, Rocio Hurtado f, J Keith Joseph d, Salmaan Keshavjee e & Iagor Kalandadze b
a. School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, United States of America (USA).
b. National Centre for Tuberculosis and Lung Disease, Tbilisi, Georgia.
c. Harvard Medical School, Boston, USA.
d. Partners In Health, Boston, USA.
e. Brigham and Women's Hospital, Boston, USA.
f. Massachusetts General Hospital, Boston, USA.
Correspondence to Jennifer Furin (e-mail: email@example.com).
(Submitted: 16 June 2011 – Revised version received: 06 September 2011 – Accepted: 21 September 2011 – Published online: 24 November 2011.)
Bulletin of the World Health Organization 2012;90:63-66. doi: 10.2471/BLT.11.092320
Management of patients who have been previously treated for tuberculosis (TB) has been a cause of much debate.1 In 1991, the World Health Organization (WHO) recommended the use of the “category II retreatment regimen” for all patients with a prior history of TB treatment.2,3 The category II regimen added streptomycin to the first-line agents and extended treatment to 8 months. Multiple observational studies have examined outcomes among individuals receiving category II treatment and shown mixed results. Overall success rates are in the 60–80% range,4,5 with notably worse outcomes seen among patients who failed or relapsed after their initial treatment episode.6,7
WHO TB treatment guidelines published in 2010 recommend treatment guided by drug susceptibility testing – using rapid, molecular tests where possible – for all previously treated patients.3 The category II regimen, however, is still recommended for certain patients who return after default or relapse in settings with low risk of multidrug-resistant TB (MDR-TB). There is little documentation concerning implementation of these guidelines and category II remains the standard of care for patients requiring retreatment in most settings in the world. This paper presents the experience of Georgia – a country with a substantial population of previously treated patients and high rates of MDR-TB – in eliminating category II therapy from its National TB Program (NTP) guidelines.
Georgia is a country of 4.4 million people located in the South Caucasus region. The WHO TB case notification rate is 102 per 100 000 population.8 All Georgian TB patients receive culture and drug susceptibility testing as a standard part of diagnosis. In 2009, routine surveillance found MDR-TB in 10.6% of newly diagnosed patients and 32.5% of previously treated cases.9 Programmatic management of drug-resistance TB in Georgia was started in 2006 and in 2009 the country achieved universal access to MDR-TB treatment.
An operational assessment of the utility of category II in Georgia was done in July and August 2010, led by members of the Georgian NTP with a WHO-recruited consultant. The steps taken were: (i) programme review, (ii) consensus building, and (iii) implementation planning (Table 1).
Outcomes of patients treated with category II were assessed in addition to the local epidemiology and programme resources in Georgia. More than 6500 patients received category II therapy between 2007 and 2009 and their outcomes are shown in Table 2.
Georgia has a high burden of TB, particularly drug-resistant TB. Prevalence of HIV in the country is low (< 1%). Culture of the Mycobacterium tuberculosis and drug susceptibility testing is done for all patients diagnosed with TB and Georgia has the resources (human and financial) to continue to do this. It also has a national programme for managing drug-resistant TB. Patients with documented resistance are given treatment regimens based on drug susceptibility test results.
Following this review, the NTP decided to no longer recommend category II treatment in Georgia because of: (i) poor outcomes among patients on category II therapy; (ii) high rates of streptomycin resistance among previously treated patients; (iii) lack of evidence to support category II; and (iv) widespread access to both drug susceptibility testing and treatment for drug-resistant TB. The NTP concluded that patients with documented resistance, including those with mono-resistance, would receive a regimen based on drug susceptibility test results. Those with a history of previous treatment who had pan-susceptible disease would receive HREZ (first-line drugs).
Consensus building was initiated and led by the Georgian NTP; as such, there was strong political will. It held a series of meetings with TB care providers to review and discuss the decision openly. Most of the NTP staff in Georgia are actively involved in TB patient care, and ongoing provider relationships allowed for rapid consensus building. The NTP also used an evidence-based analysis to support its decision. There were some concerns that previously treated patients with pan-susceptible disease still needed a “stronger” regimen but, upon further review, there was little evidence to support this claim. There was little resistance to this policy change so, once internal consensus was reached, the NTP applied for regulatory changes and category II was removed from recommendations for TB treatment.
Following the elimination of category II treatment, the programme has committed time and resources to expanding access to rapid, molecular-based drug susceptibility testing. Georgia will also continue its commitment to universal management of all forms of drug-resistant TB and monitor resistance and patient outcomes. Operational research on the discontinuation of category II treatment – including cost implications and provider and patient experiences – will be carried out as funding permits.
The experience from Georgia is an important example of how category II treatment can be successfully removed from NTP guidelines in settings where it is of limited utility. Georgia used an operational assessment of its national data to reach consensus on the use of category II within its specific context. There was little resistance to policy change in the country because the review was initiated and led by the NTP. Although it may not be possible to generalize this experience to all settings, the review was done retrospectively and outcome data are pending, the Georgian experience may serve as a roadmap for other countries.
The operational assessment concluded that there were no patients in Georgia for whom category II treatment was appropriate. Patients with a history of previous treatment who have pan-susceptible disease are now treated with first-line drugs. Patients with mono- or poly-resistance are treated with appropriate regimens. Patients with MDR-TB are treated with second-line therapy.
Georgia is a unique setting but other countries with different profiles may be able to use this model to determine whether they should use category II. Each country will need to do its own programme review of category II outcomes. They can then use these data to prioritize whether they will continue to use category II or invest in improved diagnostics and drug-resistant TB treatment or both. This paper presents an important example of putting WHO recommendations into action. It is hoped the experience from Georgia can inspire other TB programmes to assess the utility of category II regimens – and other programmatic TB recommendations – in their settings (Box 1).
Box 1. Summary of main lessons learnt
- The National Tuberculosis Program initiated and led the policy decision and worked closely with health-care providers to build consensus.
- Evidence-based analysis was used to support the decision.
- Time and resources were committed to expand access to rapid, molecular-based drug susceptibility testing and management of drug-resistance.
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