Elsevier

The Lancet

Volume 365, Issue 9456, 22 January 2005, Pages 318-326
The Lancet

Articles
Clinical outcome of individualised treatment of multidrug-resistant tuberculosis in Latvia: a retrospective cohort study

https://doi.org/10.1016/S0140-6736(05)17786-1Get rights and content

Summary

Background

Latvia has one of the highest rates of multidrug-resistant tuberculosis (MDRTB). Our aim was to assess treatment outcomes for the first full cohort of MDRTB patients treated under Latvia's DOTS-Plus strategy following WHO guidelines.

Methods

We retrospectively reviewed all civilian patients who began treatment with individualised treatment regimens for pulmonary MDRTB in Latvia between Jan 1, and Dec 31, 2000. We applied treatment outcome definitions for MDRTB, developed by an international expert consensus group, and assessed treatment effectiveness and risk factors associated with poor outcome.

Findings

Of the 204 patients assessed, 55 (27%) had been newly diagnosed with MDRTB, and 149 (73%) had earlier been treated with first-line or second-line drugs for this disease. Assessment of treatment outcomes showed that 135 (66%) patients were cured or completed therapy, 14 (7%) died, 26 (13%) defaulted, and treatment failed in 29 (14%). Of the 178 adherent patients, 135 (76%) achieved cure or treatment completion. In a multivariate Cox proportional-hazards model of these patients, independent predictors of poor outcome (death and treatment failure) included having previously received treatment for MDRTB (hazard ratio 5·7, 95% CI 1·9–16·6), the use of five or fewer drugs for 3 months or more (3·2, 1·1–9·6), resistance to ofloxacin (2·6, 1·2–5·4), and body-mass index less than 18·5 at start of treatment (2·3, 1·1–4·9).

Interpretation

The DOTS-Plus strategy of identifying and treating patients with MDRTB can be effectively implemented on a nationwide scale in a setting of limited resources.

Introduction

Since the Global Anti-tuberculosis Drug Resistance Surveillance Project, organised by WHO, and the International Union Against Tuberculosis and Lung Disease (IUATLD) began, Latvia has consistently had one of the highest proportions of multidrug-resistant tuberculosis (MDRTB) or tuberculosis caused by strains of Mycobacterium tuberculosis resistant to at least isoniazid and rifampicin.1, 2, 3 In 1996 in Latvia, MDRTB was reported in 14% of patients newly diagnosed with tuberculosis but without a history of treatment for this disease, and in 54% of those with a history of such treatment.2 In response to rapidly rising rates of tuberculosis, the Latvian national tuberculosis programme began implementation of the WHO-recommended DOTS (directly observed therapy short course) strategy in 1996. This strategy consists of government commitment; passive case detection by smear microscopy; administration of directly observed treatment of all tuberculosis patients with the standardised 6-month short-course chemotherapy regimen of isoniazid, rifampicin, pyrazinamide, and ethambutol;4 a regular supply of high quality anti-tuberculosis drugs; and standardised recording and reporting. However, the short-course chemotherapy regimen of the DOTS strategy is ineffective in MDRTB;5 cure rates have generally been less than 60%.6, 7 With such low cure rates, many patients with MDRTB remain infectious for long periods and continue to spread infection in the community. Therefore, in addition to the DOTS strategy, special treatment strategies for MDRTB are essential in settings where rates of MDRTB are high.8

To address this need, WHO has worked with many international partners to develop the DOTS-Plus strategy for MDRTB, designed to operate within an existing and well functioning DOTS programme.4, 9, 10, 11 This strategy offers two general approaches to treatment on the basis of existing programme capabilities: (1) standardised treatment in which all patients with MDRTB receive the same treatment regimen derived from predominant patterns of resistance in the community; or (2) individualised treatment in which patients with MDRTB receive comprehensive drug susceptibility testing, and treatment regimens are tailored accordingly. The Green Light Committee was formed to help to improve access to second-line drugs for MDRTB for programmes that could show a well functioning DOTS programme.12 In 2000, Latvia committed full funding to treat all MDRTB patients, and by 2001 it received Green Light Committee approval.

After implementing the DOTS strategy and documenting high rates of MDRTB in 1996, the Latvian national tuberculosis programme began implementing the DOTS-Plus strategy in 1998 using an individualised treatment approach.13 By 2000, full treatment for all patients with MDRTB was available and was provided through a combination of hospital based and ambulatory based treatment with limited external support. Our aim was to assess MDRTB management under routine programme conditions and treatment effectiveness and risk factors associated with poor treatment outcomes.

Section snippets

Patients

The national tuberculosis programme registered all patients newly diagnosed with tuberculosis and those being retreated, including prisoners, in the national tuberculosis registry. All patients had sputum specimens submitted for M tuberculosis culture and drug susceptibility testing at time of diagnosis. An isolate of M tuberculosis was regarded as MDRTB if it showed in-vitro resistance to at least isoniazid and rifampicin. All laboratory results for M tuberculosis culture and drug

Results

During 2000, 211 patients were registered as having MDRTB. 46 of these patients died and four defaulted before starting treatment. 15 began treatment during the following year. Thus 146 patients with MDRTB, diagnosed in 2000, started treatment in 2000. Furthermore, 28 patients with MDRTB who were diagnosed in 1999 also started treatment in 2000 and were thus included in the 2000 treatment cohort under assessment. An additional 30 patients who had relapsed or defaulted after previous treatment

Discussion

We have shown that two-thirds of patients with MDRTB, who started treatment in 2000, achieved a positive outcome and, under national programme conditions, three-quarters of patients who adhered to MDRTB treatment achieved a successful outcome. The high overall treatment efficacy is encouraging, especially in the context of programme conditions and widespread drug resistance.

Our Cox proportional-hazards analysis identified critical predictors of poor treatment outcomes that could enable the

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