Does DOTS work in populations with drug-resistant tuberculosis?

Summary

Background

Directly observed therapy (DOTS) is the main strategy for prevention and control of tuberculosis worldwide. However, its effect on tuberculosis transmission in populations with moderate rates of drug-resistant disease is not known.

Methods

This population-based prospective study in southern Mexico between March, 1995, and February, 2000, was based on passive case finding and detection of acid-fast bacilli in sputum samples to diagnose pulmonary tuberculosis. We also used cultures, drug-susceptibility testing, bacterial genotyping, and monitoring of treatment outcomes.

Findings

We enrolled 436 patients; the HIV seroprevalence rate was 2%. We used three indicators to monitor continuing tuberculosis transmission: the incidence rate of pulmonary tuberculosis, which decreased by 54·4% between 1995 and 2000, from 42·1 to 19·2 per 10⁵ population (p=0·00048); the percentage of clustered pulmonary tuberculosis cases, which decreased by 62·6% from 22% to 8% (p=0·02); and the rate of primary drug resistance, which decreased by 84·0% from 9·4 to 1·5 per 10⁵ population (p=0·004). Rates of multidrug-resistant (MDR) tuberculosis also decreased (p<0·0001). The case-fatality ratio was 12% for MDR tuberculosis (five of 41), 7% for strains resistant to at least one drug after exclusion of MDR (four of 55), and 3% for pansusceptible strains (nine of 272). There were 13 treatment failures (11%) in 1995 and one (2%) in 2000 (p=0·012).

Interpretation

Even in settings with moderate rates of MDR tuberculosis, DOTS can rapidly reduce the transmission and incidence of both drug-susceptible and drug-resistant tuberculosis. However, further interventions, such as drug-susceptibility testing and standardised or individualised treatment regimens, are needed to reduce mortality rates for MDR tuberculosis.

Introduction

Coincident with expanded efforts to strengthen tuberculosis prevention and control programmes worldwide, there is growing concern about currently reported and potential future rates of multidrug-resistant (MDR) tuberculosis.1, 2 Although there is consensus about the desirability of optimum treatment for all patients with tuberculosis, including those who have resistant organisms, there are few data to guide policy on how best to control and prevent the disease in areas where drug resistance is prevalent. WHO and the International Union Against Tuberculosis and Lung Disease have adopted DOTS (directly observed therapy, short course) as the main strategy for programmatic tuberculosis control. DOTS consists of five main elements: political commitment; case detection by sputum microscopy; directly observed therapy of a standard short-course regimen; uninterrupted supply of all essential drugs; and a standard recording and reporting system that allows assessment of treatment results and overall programme performance. DOTS does not include specific therapy for patients with drug-resistant tuberculosis, but a surge in drug-resistant tuberculosis in several parts of the world requires effective implementation of the DOTS strategy to prevent the occurrence of new MDR tuberculosis cases and to reduce transmission of Mycobacterium tuberculosis.³

Since 1995, we have carried out a population-based molecular epidemiological study of tuberculosis in a health jurisdiction in southern Mexico. Although a national tuberculosis control programme was implemented in Mexico before 1996, a programme review by the WHO Global Tuberculosis Programme identified inadequate technical policies and management deficiencies.⁴ The main problems were excessive emphasis on case detection to the detriment of case holding, policy differences between the Ministry of Health and social security services, and inadequate information systems to monitor essential programme activities such as use of antituberculosis drugs and treatment outcomes. To bring the programme in line with the WHO-recommended DOTS strategy, changes were initiated in 1996 in pilot areas including the Orizaba Health Jurisdiction, to be gradually extended nationwide.⁵ There were major improvements to the five elements of the WHO DOTS strategy for tuberculosis control in Mexico, including sustained government commitment to tuberculosis control by modification and standardisation of the guidelines for the national tuberculosis control programme, standardisation of programme procedures nationwide, and training of health-care workers to implement the DOTS programme. The programme standardised diagnosis on the basis of quality-assured sputum-smear microscopy for passive case finding, mainly among symptomatic patients presenting to health services and by use of trained laboratory workers and quality-control procedures. Standard short-course chemotherapy with direct observation of treatment, by physicians and community health-care workers trained in proper case management, was provided to all cases. In addition, the information and referral systems were improved to ensure adequate, uninterrupted supplies of quality-assured drugs. A standard, computerised nominal registry of patients, shared by local, state, and national authorities, and a system for programme monitoring were established to assess the treatment outcomes of all tuberculosis patients.⁶

Surveillance studies in three states by the Mexican Ministry of Health identified moderate prevalence rates of drug-resistant tuberculosis.¹ The pilot DOTS programme in Orizaba provided an opportunity to assess the epidemiological effect of DOTS in a region where 20·7% of new cases were resistant to at least one antituberculosis drug and 3·3% were MDR tuberculosis.⁷ We prospectively measured the incidence rate of pulmonary tuberculosis, the amount of tuberculosis transmission demonstrable with molecular epidemiological techniques, and the rate of primary resistance to at least one first-line drug over a 5 year period.