Journal Mobile Options
Table of Contents
Vol. 45, Suppl. 2, 1999
Issue release date: July 1999
Chemotherapy 1999;45(suppl 2):26–33

Directly Observed Therapy, Short-Course: The Best Way to Prevent Multidrug- Resistant Tuberculosis

Yew W.W.
Tuberculosis and Chest Unit, Grantham Hospital, Hong Kong, China

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Adherence to therapy in patients with tuberculosis (TB) is a major determinant of their outcomes. Unfortunately, there are no currently known predictors of adherence, given that this phenomenon represents a complex, task-specific behavior. Notwithstanding criticisms from civil liberty advocates, directly observed therapy (DOT), facilitated by education, holistic care, enablers and incentives, is still the best strategy to ensure patient adherence to treatment. To enhance delivery of DOT, short-course chemotherapy (SCC) must be strongly advocated. Monitoring of patient progress, dependable drug supply, and adequate programme funding are other important elements of the entire strategy. Indeed, since the global resurgence of TB and associated rampant drug resistance in the 1990s, directly observed therapy, short-course (DOTS) has now become the WHO strategy for effective TB control. Data obtained so far in different continents worldwide have underscored the unrivalled efficacy of DOTS in ensuring treatment success and preventing development of acquired drug resistance. The recent WHO/International Union against Tuberculosis and Lung Disease (IUATLD) global project on anti-TB drug resistance surveillance has also revealed that countries in which >33–90% of the population has access to the WHO DOTS strategy have, as a group, lower levels of drug resistance: primary multidrug-resistant (MDR) (1.4%; median) and acquired MDR index (0.6; median). The use of SCC was also inversely associated with the prevalence of combined resistance to any drug. Countries with MDR rates >2% reported using SCC in a median of 70% of their patients, compared with 100% in countries with MDR rates <2% (WHO/TB/97.229). Despite greater initial cost, DOTS is a more cost-effective strategy than self-administered therapy because it decreases the re-treatment costs associated with therapy failure and acquired drug resistance. Finally, in addition to harnessing the complementary roles of a national tuberculosis programme and community participation, DOTS might be further enhanced by the use of newly developed drugs with a long duration of action or more potent bactericidal and sterilizing activities.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Goble M, Iseman MD, Madsen LA, Waite D, Ackerson L, Horsburgh CR: Treatment of 171 patients with pulmonary tuberculosis resistant to isoniazid and rifampin. N Engl J Med 1993;328:527–532.
  2. Telzak EE, Sepkowitz K, Alpert P, Mannheimer S, Medard F, El-Sadr W, Blum S, Gagliardi A, Salomon N, Turett G: Multidrug-resistant tuberculosis in patients without HIV infection. N Eng J Med 1995;333:907–911.
  3. Park MM, Davis AL, Schluger NW, Cohen H, Rom WN: Outcome of MDR-TB patients, 1983–1993: Prolonged survival with appropriate therapy. Am J Respir Crit Care Med 1996;153:317–324.
  4. Chaulet P, Raviglione M, Bustreo F: Epidemiology, control and treatment of multidrug- resistant tuberculosis. Drugs 1996;52(suppl 2):103–108.
  5. Crofton J, Chaulet P, Maher D: Guidelines for the management of drug-resistant tuberculosis. WHO/TB/96.210 (Rev 1). Geneva, World Health Organization, 1997.
  6. Antituberculosis drug resistance in the world: The WHO/IUATLD global project on antituberculosis drug resistance surveillance. WHO/TB/97.229. Geneva, World Health Organization, 1997.
  7. Lambregts-van-Weezenbeek CSB, Veen J: Control of drug-resistant tuberculosis. Tuber Lung Dis 1995;76:455–459.
  8. Fujiwara PI, Sherman LF: Multidrug-resistant tuberculosis: Many paths, same truth. Int J Tuberc Lung Dis 1997;1:297–298.
  9. Chaulet P: Compliance with anti-tuberculosis chemotherapy in developing countries. Tubercle 1987;68(suppl):S19–S24.
  10. Chaulet P: Compliance with chemotherapy for tuberculosis: Responsibilities of the Health Ministry and of Physicians. Bull Int Union Tuberc 1990;66(suppl):S33–S35.
  11. Sumartojo E: When tuberculosis treatment fails: A social behavioral account of patient adherence. Am Rev Respir Dis 1993;147:1311–1320.
  12. Burman WJ, Cohn DL, Rietmeijer CA, Judson FN, Sbarbaro JA, Reves RR: Noncompliance with directly observed therapy for tuberculosis: Epidemiology and effect on the outcome of treatment. Chest 1997;111:1168–1173.
  13. Advisory Council for the Elimination of Tuberculosis: Initial therapy of tuberculosis in the era of multidrug resistance: Recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR 1993;42:RR/7.
  14. Bayer R, Wilkinson D: Directly observed therapy for tuberculosis: History of an idea. Lancet 1995;345:1545–1548.
  15. Efferen LS: In pursuit of tuberculosis control: Civil liberty vs public health. Chest 1997;112:5–6.
  16. Fox W: Self-administration of medicaments: A review of published work and a study of the problems. Bull Int Union Tuberc 1962;32:307–331.
  17. Sbarbaro JA: All patients should receive directly observed therapy in tuberculosis. Am Rev Respir Dis 1988;138:1075–1076.

    External Resources

  18. Moulding T: New responsibilities for health departments and public health nurses in tuberculosis – Keeping the outpatient on therapy. Am J Public Health 1966;56:416–427.
  19. Nardell EA: Beyond four drugs: Public health policy and the treatment of the individual patient with tuberculosis. Am Rev Respir Dis 1993;148:2–5.
  20. Kritski AL, Rodrigues de Jesus LS, Andrade MK, Werneck-Barroso E, Monteiro S, Vieira MA, Haffner A, Riley LW: Retreatment tuberculosis cases: Factors associated with drug resistance and adverse outcomes. Chest 1997;111:1162–1167.
  21. Annas GJ: Control of tuberculosis – The law and the public’s health. N Engl J Med 1993;328:585–588.
  22. Fox W: Whither short-course chemotherapy? Br J Dis Chest 1981;75:331–357.
  23. Global Tuberculosis Programme: Global tuberculosis control. WHO/GTB/97.225. Geneva, World Health Organization, 1997.
  24. Kochi A: Is DOTS the health breakthrough of the 1990s? World Health Forum. Geneva, World Health Organization. 1997;18:225–247.
  25. Sbarbaro JA: Compliance: Inducements and enforcements. Chest 1979;76(suppl):S750–S756.
  26. Grange JM: DOTS and beyond: Towards a holistic approach to the conquest of tuberculosis. Int J Tuberc Lung Dis 1997;1:293–296.
  27. Volmink J, Garner P: Systematic review of randomized controlled trials of strategies to promote adherence to tuberculosis treatment. BMJ 1997;315:1403–1406.
  28. Hong Kong Chest Service/British Medical Research Council: Five-year follow-up of a controlled trial of five 6-month regimens of chemotherapy for pulmonary tuberculosis. Am Rev Respir Dis 1987;136:1339–1342.

    External Resources

  29. Singapore Tuberculosis Service/British Medical Research Council: Five-year follow-up of a clinical trial of three 6-month regimens of chemotherapy given intermittently in the continuation phase in the treatment of pulmonary tuberculosis. Am Rev Respir Dis 1988;137:1147–1150.

    External Resources

  30. Weis SE, Slocum PC, Blais FX, King B, Nunn M, Matney GB, Gomez E, Foresman BH: The effect of directly observed therapy on the rates of drug resistance and relapse in tuberculosis. N Engl J Med 1994;330:1179–1184.
  31. Fujiwara PI, Cook SV, Rutherford CM, Crawford JT, Glickman SE, Kreiswirth BN, Sachdev PS, Sukhminder S, Osahan SS, Ebrahimzadeh A, Frieden TR: A continuing survey of drug-resistant tuberculosis, New York City, April 1994. Arch Intern Med 1997;157:531–536.
  32. Chaulk CP, Moore-Rice K, Rizzo R, Chaisson RE: Eleven years of community-based directly observed therapy for tuberculosis. JAMA 1995;274:945–951.
  33. Floyd K, Wilkinson D, Gilks C: Comparison of cost effectiveness of directly observed treatment (DOT) and conventionally delivered treatment for tuberculosis: Experience from rural South Africa. BMJ 1997;315:1407–1411.
  34. Moore RD, Chaulk CP, Griffiths R, Cavalcante S, Chaisson RE: Cost-effectiveness of directly observed versus self-administered therapy for tuberculosis. Am J Respir Crit Care Med 1996;154:1013–1019.

    External Resources

  35. Moulding T, Dutt AK, Reichman LB: Fixed-dose combinations of antituberculous medications to prevent drug resistance. Ann Intern Med 1995;122:951–954.
  36. Mitchison DA: How drug resistance emerges as a result of poor compliance during short course chemotherapy for tuberculosis. Int J Tuberc Lung Dis 1998;2:10–15.
  37. Burman WJ, Dalton CB, Cohn DL, Butler JRG, Reves RR: A cost–effectiveness analysis of dierctly observed therapy vs self-administered therapy for treatment of tuberculosis. Chest 1997;112:63–70.
  38. Fujiwara PI, Larkin C, Frieden TR: Directly observed therapy in New York City: History, implementation, results and challenges. Clin Chest Med 1997;18:135–148.
  39. Iseman MD, Cohn DL, Sbarbaro JA: Directly observed treatment of tuberculosis: We can’t afford not to try it. N Engl J Med 1993;328:576–578.
  40. Tam CM, Chan SL, Lam CW, Leung CC, Kam KM, Morris JS, Mitchison DA: Rifapentine and isoniazid in the continuation phase of treating pulmonary tuberculosis. Am J Respir Crit Care Med 1998;157:1726–1733.
  41. Nolan CM: Beyond directly observed therapy for tuberculosis. Chest 1997;111:1151–1152.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50