Tuberculosis and Other Mycobacterial Infections

A specter is haunting the world-the specter of the dual pandemic of multi-drug-resistant (MDR) tuberculosis (TB) and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) infection. The epidemic of drug addiction and the associated growth of crime and imprisonment in some countries further enhance the threat of the deadly combination of TB + HIV. Michael Iseman and Lee Reichman labeled this situation as the “Time Bomb.” We called it the new white plague, as a reminder of the “Great White Plague” of the 19th century, an epidemic of tuberculosis that killed 25% of Europeans, even without the burden of HIV and drug resistance.

For many years, TB was the most neglected health problem in the world. The situation started to change in the last decade. In 1993, the World Health Organization (WHO) declared TB a global emergency, and launched in 1994-95 the “Framework for Effective TB Control,” which is currently known as “DOTS (directly observed therapy, short-course),” or “WHO TB Strategy.” In 1993, the World Bank endorsed investment in TB control, calling the antimicrobial therapy of TB “one of the most cost-effective of all interventions.” The problem attracted the interest of the media, and external financial support from the United States and other countries for TB control around the world began to increase dramatically. There is not enough space in this introduction to include the list of current international and national organizations involved in sponsoring the fight against TB.

Is this attention enough to allow us to be optimistic? What else should be done to stop TB?

One of the obstacles in proper implementation of TB control programs is that many governments and local authorities, whose involvement is most essential for such programs, have insufficient understanding of the problem's magnitude. Therefore, their education, as well as education of the public about tuberculosis (and other mycobacterial infections), remains the key element of any national program. The starting point is education of the educators-the medical professionals involved in such programs. A substantial number of monographs and other publications in this area have provided constantly updated information in the field, including the issues of operational research, administration, and scientific progress.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18]

The goal of this issue of Seminars is to present short reviews on some of the most important issues on tuberculosis and other mycobacterial infections. One of the previous issues of Seminars (1997, Volume 18, Number 5) was also dedicated to tuberculosis. The current issue addresses some new topics that were not addressed in the 1997 issue; namely, leprosy, infections caused by nontuberculous mycobacteria, molecular epidemiology of tuberculosis, latent tuberculosis infection, and tuberculosis in children. Due to the limitation of space, some of the topics of the 1997 edition, such as alcoholism and tuberculosis, and the interpretation of laboratory reports, are not addressed at this time. Unfortunately, for the same reason, we could not include some other important topics in this issue, such as the role of radiology in diagnosis, the role of the laboratory in prevention of drug-resistant tuberculosis epidemics, the role of surgery, and case management of patients with MDR-TB. I am most grateful to all the contributors for their dedication, their excellent reviews, and their valuable time.

As for the publication of 1997, I have again invited representatives of the most authoritative organizations-WHO and the Centers for Disease Control and Prevention (CDC)-and some of the most prominent leading experts in the field to participate in this issue of Seminars. Therefore, it is most likely that the articles of this publication contain the predominantly accepted views and standards. I hope that these authoritative views will not prevent readers from critical and creative analyses of the presented facts and recommendations, especially when it comes to unavoidable controversies in the articles on some of the issues. After all, even Gautama Buddha has said, “Do not believe in anything merely on the authority of your teachers and elders.”

Among the issues that may, at first glance, appear to be controversial, are recommendations for detection, diagnosis, and management of tuberculosis patients worldwide, and policies in industrialized countries. On the one hand, modern epidemiological studies conducted in the United States clearly proved that pulmonary tuberculosis patients with negative sputum smear results (∼50% of all culture-positive patients) represent a significant source of infection, even when detected and treated. It is not known, however, the role these patients play as a source of infection when they are undetected and untreated, but one could assume the worst. On the other hand, WHO recommendations on the DOTS strategy focus only on patients with positive smear results. This is because the WHO initiative is mainly targeting countries with limited resources, and relying on smear examination as the main diagnostic tool as a part of the initial introduction of the DOTS program. The reader will notice that when resources allow, the expanded DOTS strategy takes into account the inclusion of other diagnostic means such as radiology, culture isolation, and drug-susceptibility testing, and eventually, the DOTS-plus strategy, when needed. It is important to stress that patients with smear-negative (culture-positive) pulmonary tuberculosis are no longer labeled as “noninfectious,” though there are no doubts that patients with positive smear results are more infectious (not just “infectious,” as stated in some previous publications) and still represent the major source of infection.

This is but one example of a controversy, understanding of which requires thoughtful perception of the materials presented in this issue of Seminars, not just learning the facts and statements but also attempting their critical analysis. There is no doubt that thinking is the most difficult job in the world, which brings us to a dilemma in perception of various documents issued by authoritative organizations.

In many countries, recommendations on therapy or protocols for diagnosis (even laboratory procedures) are mandated, leaving no room for any challenges or creative thinking. For example, in Russia such documents are issued as decrees by the Ministry of Health (prikaz) and are to be adhered to without question. A lot of time is spent on refining these mandatory documents, including involvement of some international experts. Unfortunately, as some of the leading Russian experts have stated, these decrees are often already outdated by the time they are issued.

In the United States, any such documents; for example, statements by the CDC, ATS (American Thoracic Society), ASM (American Society for Microbiology), or NCCLS (National Committee on Clinical Laboratory Standards), constitute recommendations only, and are not mandated. Even the approval of any medication or laboratory diagnostic tool by the Food and Drug Administration (FDA) is mandatory for the manufacturer only but does not necessarily apply to the user. Nevertheless, there is a tendency among some medical professionals, and especially among medical administrators, to perceive these recommendations as mandatory: such an approach is easier because it does not require any critical analysis or thinking.

I hope that the articles published in this issue of Seminars will serve not only as a source of information but also as a stimulus for a creative approach to the presented facts and recommendations. “The aim of education should be to teach us how to think, rather than what to think-rather to improve our minds, so as to enable us to think for ourselves, than to load the memory with thoughts of other men” (Bill Beattie).

REFERENCES

• 1 Kubica GB, Wayne LG The Mycobacteria: A Sourcebook. Vols 1, 2. New York; Marcel Dekker 1984
• 2 Ratledge C, Stanford J, Grange J The Biology of the Mycobacteria. Vols 1-3. New York; Academic 1982-1989
• 3 Heifets LB Drug Susceptibility in the Chemotherapy of Mycobacterial Infections. Boca Raton; CRC 1991
• 4 Bloom BR Tuberculosis (Pathogenesis, Protection, and Control). Washington, DC; ASM 1994
• 5 Friedman LN Tuberculosis (Current Concepts and Treatment). Boca Raton; CRC 1994
• 6 Porter JDH, McAdams KPWJ Tuberculosis: Back to the Future. New York; John Wiley & Sons 1994
• 7 Heifets LB Clinical mycobacteriology. Clin Lab Med. 1996 16(3)
• 8 Iseman MD, Huitt GA Tuberculosis. Clin Chest Med 1997 18(1)
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• 10 Gangadharam PRJ, Jenkins PA Mycobacteria. Vols 1, 2. New York; Chapman and Hall-International Thomson Publishing (Thomson Science) 1998
• 11 Porter JDH, Grange JM Tuberculosis (an Interdisciplinary Perspective). London; Imperial College Press 1999
• 12 Portaels F, Rigouts L, Bastian I Tuberculosis, the Real Millennium Bug: Proceedings of the International Colloquium. Antwerp: Prince Leopold Institute of Tropical Medicine 1999
• 13 Harward Medical School Open Society Institute .The Global Impact of Multi-Drug Resistant Tuberculosis. Boston; Harvard Medical School 1999
• 14 Reichman LB, Hershfield ES Tuberculosis: A Comprehensive International Approach. New York; Marcel Dekker 2000
• 15 Iseman M D. A Clinician Guide to Tuberculosis. Philadelphia; Lippincott Williams & Wilkins 2000
• 16 Rieder H L. Interventions for Tuberculosis Control and Elimination. Paris; International Union Against Tuberculosis and Lung Disease 2002
• 17 Catanzaro A, Daley CL Lung Disease Due to Nontuberculous Mycobacterial Infections. Clin Chest Med 2002 23(3)
• 18 Brennan PJ Proceedings from the 4th world congress on tuberculosis. Tuberculosis 2002 83(special issue)(1-3)