SOUTHEAST ASIAN J TROP MED PUBLIC HEALTH
136 Vol 35 No. 1 March 2004
Correspondence: Dr Mee Sun Tsai, Division of Chest Medicine, Kaohsiung Medical University Hospital, 100 Shih Chuan First Road, Kaohsiung, 807 Taiwan, ROC. Tel: 7-3121101-6013 or 7-3208251; Fax: 886-7-3208251
E-mail: mesuts@cc.kmu.edu.tw
INTRODUCTION
The incidence of pulmonary tuberculosis has increased recently, although there were only about four thousand seven hundred cases of HIV ( Hu-man Immunodeficiency Virus ) infection reported in Taiwan in the past 20 years. Studies were done on 217 cases of patients with present and/or pre-vious pulmonary tuberculosis who had visited the Chest Division of Internal Medicine, Kaohsiung Medical University Hospital from 1999 to 2002. We tried to present the data of the current clinical status of pulmonary tuberculosis in this area and the recurrence rate of the infection, as well as to analyze antituberculosis drug resistance and the
A SUBSET OF CLINICAL STATUS OF PULMONARY
TUBERCULOSIS IN SOUTHERN TAIWAN
Mee Sun Tsai, Inn Wen Chong, Jhi Jhu Hwang, Tung Heng Wang and Ming Shyan Huang Division of Chest Medicine, Department of Internal Medicine, Kaohsiung Medical University
Hospital, Kaohsiung, Taiwan, Republic of China
Abstract. The aims of this study were to present the clinical status of pulmonary tuberculosis in
Southern Taiwan and to analyze the reasons for failure of antituberculosis treatment in order to achieve a higher rate of success after treatment. Two hundred and senventeen adult patients, aged 15 to 90 years old who presented to the Chest Division, Kaohsiung Medical University Hospital from 1999 to 2002 with a diagnosis of Pulmonary Tuberculosis, were retrospectively studied. We compared the rate of recurrence of pulmonary tuberculosis by dividing the cases into 2 groups: those who com-pleted treatment and those who did not. We also determined the age distributions for when initial diagnosis of pulmonary tuberculosis was made among these 217 cases. In 90 culture proven cases, antituberculosis drug susceptibility was tested to determine the rate of drug resistance. We also as-sessed the reasons for failure of treatment. Age distribution analysis showed that initial infection began at a young age, was widely spread, and occurred regardless of age. There were 116 cases that completed antituberculosis treatment and 101 cases that did not. Of the 116 cases, only 16 relapsed, whereas 79 of the 101 cases relapsed. In cases where completely treated patients relapsed, the period before recurrence was indefinite. Most of the cases of incompletely treated patients relapsed earlier. In the 90 culture proven cases in which antituberculosis drug susceptibility was tested, 39 patients showed resistance to at least one drug, 9 patients were resistant to only one drug, 9 patients were resistant to two drugs and 21 patients were resistant to more than 3 drugs. The common reasons for failure of treatments were: 1) poor patient compliance to medication: 50 cases, 2) multiple drug resistance: 30 cases, 3) delayed treatment: 19 cases. Some cases included a combination of the above.
reasons for failure of treatment in order to achieve a higher rate of treatment success.
MATERIALS AND METHODS We retrospectively studied 217 cases of adult patients with present and/or previous pulmonary tuberculosis who had visited the Chest Division of Internal Medicine, Kaohsiung Medical Uni-versity Hospital from 1999 to 2002. All of the cases were studied retrospectively. Pulmonary tuberculosis was diagnosed based on the follow-ing methods (Bates, 1979; Thomas, 1986; Weg, 1988; Catanzaro et al, 2000; Harries et al, 2001): (1) sputum, transbronchial washing or brushing fluid, or pleural effusion smear and/or culture was positive for tuberculosis bacilli. On the condition in which smear without culture was performed, the clinical course was consistent with pulmonary tuberculosis; (2) transbronchial or pleural biopsy revealed typical Langerhans giant cell granuloma
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with positive tuberculosis bacilli by acid-fast stain or culture; (3) clinical course, including clinical presentation, chest radiographs and empirical treatment, was consistent with pulmonary tuber-culosis. The series of chest radiographs were re-viewed by two national board certified radiolo-gists and one national board certified pulmonary specialist; (4) patient’s past medical history con-firmed pulmonary tuberculosis which had been treated with antituberculosis medication and had been regularly followed at the clinic.
We compared the rate of recurrence of pul-monary tuberculosis by dividing the cases into 2 groups: those who completed treatment and those who did not. A complete course of treatment con-sisted of one of the following (MacGregor, 1988; Barnes and Barrows, 1993; American Thoracic Society, 1994; US Department of Health and Human Services Public Health Service, 1994a; Society of Internal Medicine of Taiwan, 1995; Ormerod, 2001): (1) ethambutol and isoniazid for at least 18 months or ethambutol, isoniazid and pyrazinamide for at least 9 months; (2) ethambu-tol and rifampin for at least 12 months or etham-butol, rifampin and pyrazinamide for at least 6 months; (3) isoniazid and rifampin (or plus etham-butol) for 9 months; or (4) isoniazid, rifampin, ethambutol and pyrazinamide for 6 months. In-completely treated cases included poor patient compliance to medication, delayed treatment sec-ondary to misdiagnosis, as well as some cases with irregular medication. In the culture proven 90 cases, we routinely performed drug suscepti-bility tests with isoniazid, ethambutol, pyrazina-mide, rifampin, streptomycin, kanamycin and cycloserine to asses the patients’ drug resistance. We also determined the age distribution for when initial diagnosis of pulmonary tuberculosis was made among these 217 cases. We also assessed the reasons for failure of treatment.
RESULTS
Age distribution analysis showed that ini-tial infection began at a young age, was widely spread, and occurred regardless of age-with a pre-dominance of cases among older individuals (Fig 1). There were 116 cases that completed antitu-berculosis treatment and 101 cases that did not.
Of the 116 cases, only 16 relapsed, whereas 79 of the 101 incompletely treated cases relapsed. The recurrence rate of incompletely treated patients (78.2%) was much higher than that of completly treated patients (13.8%) (Table 1). In cases where completely treated patients relapsed, the period before recurrence was indefinite (Fig 2). How-ever, some cases were only followed up for a short period of time. Most of the cases of incompletely treated patients relapsed earlier (Fig 3.) The non-recurrent cases in the incompletely treated group were only followed for one to ten years. In the 90 culture proven cases in which antituberculo-sis drug susceptibility was tested, 39 patients (43%) showed resistance to at least one drug, 9 patients (10%) were resistant to only one drug, including 7 with primary resistance, 9 patients (10%) were resistant to two drugs, including 4 with primary resistance, and 21 patients (23%) were resistant to more than 3 drugs, including 6 with primary resistance. The common reasons for failure of treatments were: 1) poor patient compliance to medication: 50 cases; 2) multiple drug resistance: 30 cases; 3) delayed treatment: 19 cases. Some cases included a combination of the above.
DISCUSSION
In Kaohsiung, Bacille Calmette-Guerin
(BCG) Vaccination(Menzies and Vissandjee,
1992) is routinely and widely performed for pro-phylaxis of tuberculosis in infant and children. Purified Protein Derivative (PPD) Skin Test is not popular for predicting infection in this area. Age
Table 1
Comparison of complete and incomplete antituberculosis treatment.
Classified Complete Incomplete antituberculosis antituberculosis antituberculosis treatment treatment treatment
Total cases (N) 116 101
Non-recurrent cases (N) 100 22 Recurrent cases (N) 16 79 Recurrence rate (%) 13.8 78.2
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distribution analysis showed that initial infection began at a young age, was widely spread, and oc-curred regardless of age. Because there were only about four thousand seven hundred cases of HIV infection in the past 20 years, the incidence of pulmonary tuberculosis brought on by HIV in-fection was not as high as that of other countries. Although the incidence of pulmonary tuberculo-sis is disproportional to tuberculous prophylaxis (US Department of Health and Human Services
Public Health Service, 1990),preventive
treat-ment with BCG vaccination and/or antitu-berculosis drugs such as isoniazid or rifampin is strongly needed in this area. BCG vaccination has been routinely used as prophylaxis, but few people have had antituberculosis drug prophylaxis with a positive PPD skin test. The recurrence rate of incompletely treated patients (78.2%) was much higher than that of completed treated patients (13.8%). Even though the completely treated group had a lower rate of recurrence, it was still a disappointingly high ratio. It was difficult to distinguish between relapse and reinfection for those recurrent pulmonary tuberculosis cases. Relapse might take a short period of time to recur after treatment. Because there may be the same opportunity for reinfection, the incomplete treatment group could have a higher relapse rate and the complete treat-ment group a higher reinfectioun rate.
The completely treated patients had an unpredictable time of recurrence, which varied from the time of just finished anti-tuberculosis medication to more than 20 years (Fig 2). Most of the non-recurrent cases of incompletely treated patients were only followed for a short period of time or for less than 10 years (Fig 3). If the non-recurrent cases were followed for longer periods of time, they might have a higher recurrence rate in the incompletely treated group. In the 90 culture proven cases where antituberculosis drug susceptibility was tested, 30 cases (33%) were resistant to at least two drugs and 21 of 30 cases (23%) resistant to more than 3 drugs, a high re-sistance rate. In order to achieve a higher
Fig 1–Age distribution of 217 cases of pulmonary tuberculo-sis. 60 50 40 30 20 10 0 TB cases Age (years) 15 20 30 40 50 60 70 80 90 5 21 26 40 42 50 28 5 20 15 10 5 0 Cases 0 5 10 15 20 25 30 Years 25 20 15 10 5 0 Cases 0 5 10 15 20 25 30 Years
Fig 2–Clinical courses of complete antituberculous treatment (recurrent cases vs non-recurrent cases); non-recurrent pulmonary tuberculous cases; recurrent and/or persistant pulmonary tuberculous cases.
Fig 3–Clinical courses of incomplete antituberculous treatment (recurrent cases vs non-recurrent cases); non-recurrent pulmonary tuberculous cases; recurrent and/or persistant pulmonary tuberculous cases
rate of successful treatment, it is suggested that a drug susceptibility test be conducted routinely (American Thoracic Society, 1994; Michael and Iseman 1993).
Poor patient compliance to medication was a very common reason for failure of treatment. This can also induce a drug resistant strains of mycobacterium (Chawla et al, 1992; US Depart-ment of Health and Human Services Public Health
Service, 1994a).The DOT method(Anonymous,
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Department of Health and Human Services Pub-lic Health Service, 1994b) to achieve complete treatment is strongly needed in this area. It is dan-gerous to diagnose post-inflammatory fibrosis as an inactive lesion without antituberculosis treat-ment. Some lesions on chest radiographs might have remained constant for years before becom-ing active. Because of the high incidence and re-currence rates of pulmonary tuberculosis, the fol-lowing is strongly suggested: (1) to lower the in-cidence of pulmonary tuberculosis, aggressive an-tituberculosis treatment is needed for active tu-berculosis patients as well as prophylactic
anti-tuberculosis medication(Barnes and Barrons,
1993; American Thoracic Society, 1994) for pa-tients with a positive PPD skin test and exposure to tuberculosis; (2) to achieve a higher rate of suc-cessful treatment, a drug susceptibility test should be conducted routinely due to the high rates of drug resistance; (3) the Directly Observed Therapy (DOT) method to achieve complete treat-ment is needed in this area due to poor medica-tion compliance.
ACKNOWLEDGEMENTS
I very much appreciate MR Yen Yi Lee and Mrs Yi Shiow Kuo for the patient data collection.
REFERENCES
American Thoracic Society, Medical Section of the American Lung Association. Treatment of tuber-culosis and tubertuber-culosis infection in adults and children. Am J Respir Crit Care Med 1994; 149: 1359-74.
Anonymous. From the CDC and Prevention: a pproaches to improving adherences to antituber-culosis therapy. JAMA 1993; 269: 1096-8. Barnes PF, Barrows SA. Tuberculosis in the 1990s. Ann
Intern Med 1993; 119: 400-10.
Bates JH. Diagnosis of tuberculosis. Chest 1979; 76 (suppl): 757-62.
Catanzaro A, Perry S, Clarridge JE, et al. The role of clinical suspicion in evaluating a new diagnostic
test for active tuberculosis. JAMA 2000; 283: 639-45.
Chawla PK, Klapper PJ, Kamholz SL, et al. Drug re-sistant tuberculosis in an urban population includ-ing patients at risk for human immunodeficiency virus infection. Tuberculosis in the United States.
Am Rev Resp Dis 1992; 146: 280-84.
Harries AD, Hargreaves NJ, Kwanjana JH, et al. Clini-cal diagnosis of smear negative pulmonary tuber-culosis. Int J Tubercul Lung Dis 2001; 5: 1143-7. MacGregor RR. Treatment of mycobacterial diseases of the lungs caused by Mycobacterium tuberculosis. In: Fishman AP, ed. Pulmonary diseases and dis-orders, 2nd ed. Vol 3. McGraw-Hill, 1988: 1869-82.
Menzies R, Bilkis V. Effect of Bacille Calmette-Guerin vaccination on tuberculin reactivity. Am Rev Resp
Dis 1992; 145: 621-5.
Michael D. Iseman. Treatment of multidrug resistant tuberculosis. N Engl J Med 1993; 329: 784-91. Ormerod P. The clinical management of the drug
resis-tant patient. Ann NY Acad Sci 2001; 953: 185-91. Society of Internal Medicine of Taiwan. Treatment regi-mens for pulmonary tuberculosis. Scientific Con-gress and Annual Meeting, 1995: 355-6. Thomas A. Neff bronchoscopy and Bactec for the
di-agnosis of tuberculosis. Am Rev Resp D 1986; 133: 962.
US Department of Health and Human Services Public Health Service. CDC. Atlanta. The use of preven-tive therapy for tuberculous infection in the United States. Recommendations of the Advisory Committee for Elimination of Tuberculosis. Morb
Mortal Wkly Rep 1990; 39 (RR-8): 6-8.
US Department of Health and Human Services Public Health Service. CDC, Division of Tuberculosis Elimination, Atlanta, Georgia. Diagnosis of TB from TB Care Guide Highlights from Core Cur-riculum on Tuberculosis 1994a: 11-8.
US Department of Health and Human Survices Public Health Service. CDC, Division of Tuberculosis Elimination Atlanta, Georgia. Treating tuberculo-sis. A clinical guide, 1994b.
Weg JG. Clinical forms of mycobacterial disease. In: Fishman AP, ed. Pulmonary diseases and disor-ders. 2nd ed. Vol 3. McGraw-Hill, 1988: 1843-63.
