Treatment of tuberculosis and tuberculosis infection in adults and children. American Thoracic Society and The Centers for Disease Control and Prevention.

Treatment of Tuberculosis. 1. A 6-mo regimen consisting of isoniazid, rifampin, and pyrazinamide given for 2 mo followed by isoniazid and rifampin for 4 mo is the preferred treatment for patients with fully susceptible organisms who adhere to treatment. Ethambutol (or streptomycin in children too young to be monitored for visual acuity) should be included in the initial regimen until the results of drug susceptibility studies are available, unless there is little possibility of drug resistance (i.e., there is less than 4% primary resistance to isoniazid in the community, and the patient has had no previous treatment with antituberculosis medications, is not from a country with a high prevalence of drug resistance, and has no known exposure to a drug-resistant case). This four-drug, 6-mo regimen is effective even when the infecting organism is resistant to INH. This recommendation applies to both HIV-infected and uninfected persons. However, in the presence of HIV infection it is critically important to assess the clinical and bacteriologic response. If there is evidence of a slow or suboptimal response, therapy should be prolonged as judged on a case by case basis. 2. Alternatively, a 9-mo regimen of isoniazid and rifampin is acceptable for persons who cannot or should not take pyrazinamide. Ethambutol (or streptomycin in children too young to be monitored for visual acuity) should also be included until the results of drug susceptibility studies are available, unless there is little possibility of drug resistance (see Section 1 above). If INH resistance is demonstrated, rifampin and ethambutol should be continued for a minimum of 12 mo. 3. Consideration should be given to treating all patients with directly observed therapy (DOT). 4. Multiple-drug-resistant tuberculosis (i.e., resistance to at least isoniazid and rifampin) presents difficult treatment problems. Treatment must be individualized and based on susceptibility studies. In such cases, consultation with an expert in tuberculosis is recommended. 5. Children should be managed in essentially the same ways as adults using appropriately adjusted doses of the drugs. This document addresses specific important differences between the management of adults and children. 6. Extrapulmonary tuberculosis should be managed according to the principles and with the drug regimens outlined for pulmonary tuberculosis, except for children who have miliary tuberculosis, bone/joint tuberculosis, or tuberculous meningitis who should receive a minimum of 12 mo of therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Short-course tuberculosis chemotherapy studies conducted in Poland during the past decade.

During the past decade, six short-course (6-month) chemotherapy regimens were studied in which drugs were given daily and intermittently. Four regimens containing isoniazid, rifampin, and ethambutol caused little toxicity but yielded relapse rates (8-21%) which were unacceptably high. The safety of giving rifampin (450 or 600 mg) twice weekly was confirmed, however, and there was evidence that daily therapy during the 4-month continuation phase was no more effective than twice weekly isoniazid and rifampin. Once weekly therapy during the continuation phase was clearly inadequate. The use of four drugs (isoniazid, rifampin, pyrazinamide, and streptomycin) given daily during the initial 2 months of therapy followed by 4 months of twice weekly isoniazid and rifampin resulted in a nearly 100% cure rate. However, this regimen was not well tolerated by patients. Deleting streptomycin improved the tolerability of the regimen but appears to have slightly increased the frequency of treatment failure and relapse. A suggested model for choosing treatment regimens is presented.

Variations in national health care practices and behaviours and their influence on international research.

Multinational clinical trials are valuable to the understanding of global health problems, but they pose special problems. Our experience with a multinational trial of isoniazid (INH) preventive therapy for tuberculosis revealed marked variation among the seven participating countries in the amount of tuberculosis screening prior to the trial; this variation contributed to the observed differences in the risk of tuberculosis among the countries. The incidence of 'uncooperativeness' and drug side-effects, and the proportion of participants who complied with and completed treatment also varied significantly from country to country. These differences in completion and compliance served to differentially alter the expected risk of tuberculosis among the three regimens being studied. For all factors investigated, variation from country to country was greater than variation from dispensary to dispensary within a country. This suggests that cultural and other national characteristics are more potent determinants of health care practices and behaviours than patient and health care practitioner characteristics.

Epidemic of gynecomastia among illegal Haitian entrants.

Gynecomastia may occur as a normal physiologic development at certain ages or as a result of a variety of pathological conditions. An outbreak of gynecomastia was investigated at two processing centers of the Immigration and Naturalization Service (INS) between December 2, 1981, and May 14, 1982. At the Fort Allen Service Processing Center, Puerto Rico, gynecomastia was initially detected in 77 of 540 Haitian male entrants (14 percent) and in only 6 of 186 male employees of the center (3 percent) who were 18-50 years old; the difference in prevalence was statistically significant. At the Krome North Service Processing Center in Miami, Fla., gynecomastia was initially detected in 52 of 512 Haitian males 18-50 years old (10 percent). Two case-control studies did not demonstrate an association between gynecomastia and a number of factors that might have been related to an exogenous estrogen or to a substance with an estrogenic effect. Estrogen or estrogen-like substances were not found in food, water, or environmental samples. When the populations were rescreened several months later, 76 of the persons with gynecomastia detected in the first screening had had total or partial remission. Persons with remission had arrived earlier--a mean of 21.6 days for those at Fort Allen and 36.7 for those at Krome--than did those with newly detected gynecomastia and those with continuing cases. The difference in arrival dates was significant (P less than .005 for Fort Allen and P less than .001 for Krome). These results, in view of nutritional deprivation in Haiti, suggest that these cases may have been an outbreak of refeeding gynecomastia.

Six-months isoniazid-rifampin therapy for pulmonary tuberculosis. Report of a United States Public Health Service Cooperative Trial.

In a multicenter trial of 2 regimens for treatment of pulmonary tuberculosis, all patients received 300 mg of isoniazid (INH) and 600 mg of rifampin (RIF) daily for 6 months (the Initial Phase). During the next 9 months (the Maintenance Phase) patients received either daily INH (300 mg) and ethambutol (EMB) (15 mg per kg body weight) or matching placebos. Of the 672 patients who met the admission criteria, only 309 (46%) completed the Initial and Maintenance Phases. Approximately 20% of the patients failed to keep their appointments. Adverse drug reaction, most commonly hepatotoxicity, accounted for the withdrawal of 37 patients (5.5%). No visual toxicity caused by EMB was observed. During the Maintenance Phase, 3 patients who were taking INH and EMB, and 16 who were taking placebos, developed relapses, i.e., 2 or more positive cultures. The significant difference in relapse rate between regimens (Fisher's exact test, p less than 0.001) demonstrates the inadequacy of INH-RIF given alone for only 6 months.

Evaluation of tuberculosis control programs: some national trends.

Increasing numbers of tuberculosis control programs compile information about the number, location, bacteriologic status, and chemotherapy status of tuberculosis patients within their jurisdiction. Reports from these programs show that during the 1970s the prevalence of patients requiring supervision decreased three times faster than the incidence of tuberculosis; this decline occurred because low relapse rates among patients who had received adequate therapy allowed the recommended duration of follow-up after completion of therapy to diminish from lifetime to none. The prevalence of patients hospitalized for tuberculosis decreased four times faster than the incidence of tuberculosis because the duration of hospitalization decreased from many months to a few weeks and because a small proportion of patients were hospitalized. Future declines in these two program aspects are expected to be much smaller and should parallel the decline in morbidity more closely. Other measures of program performance have shown a less favorable trend and suggest an impeded flow of information to the health department from other persons or agencies involved in the care of tuberculosis.

Recent trends in tuberculosis in children.

From 1976 through 1981, the incidence of tuberculosis in the United States among children 0 through 14 years of age failed to decline. The incidence had declined at a rate of about 9% per year from 1962 through 1975. The failure was observed for both sexes and for white children and children of "other" races. Data confined to 1980 and 1981 suggested that Hispanic children with tuberculosis may have accounted for the stability of the tuberculosis case rate among white children. Tuberculosis among Indochinese refugee children accounted for the stability of the case rate among children of other races.

Tuberculosis among Indochinese refugees in the United States.

Surveys of state tuberculosis control programs revealed that of the 262,602 Indochinese refugees who entered the United States in 1979 and 1980, approximately 1.5% either had tuberculosis at the time of entry or developed it by the end of 1980; another 18% were placed on preventive therapy. The refugees comprised 5.3% of the nationally counted cases during the two-year period. Age- and sex-specific incidence rates among Indochinese refugees were 30 to 200 times higher than those for other persons in the United States. For refugees who arrived in 1979, the incidence of tuberculosis during 1980 (231 per 100,000) was only one third the incidence during 1979 (719 per 100,000). For refugees who entered the United States in 1980, the incidence during 1980 was 480 per 100,000. Bacteriologic confirmation of the diagnosis was reported for only 26% of refugees, compared with 79% of other patients with tuberculosis in the United States, suggesting overdiagnosis of tuberculosis among refugees. However, age-specific rates of bacteriologically positive tuberculosis were still 14 to 70 times higher for refugees than for the United States as a whole.

Foreign-born persons with tuberculosis in the United States.

Two recent surveys of selected states and cities suggest that foreign-born persons account for approximately 15 per cent of the new cases of tuberculosis reported annually in the areas surveyed. In both surveys the largest number of foreign-born persons came from the Western Hemisphere, the next largest from Asia. The largest number of foreign-born persons with tuberculosis are in the 15-29 year age group, presumably because most entering aliens are in this age group. Among persons with tuberculosis, a larger per cent of foreign-born patients have extrapulmonary disease than do native-born patients. About 50 per cent of the foreign-born persons with tuberculosis entered the United States within the five years prior to onset of disease. Within the United States, significant inter-area variation exists in the proportion of persons with tuberculosis who are foreign-born and in countries of origin of these persons.

Transmission of multiple drug-resistant tuberculosis: report of a school and community outbreak.

An outbreak of tuberculosis in 1976 was caused by mycobacteria resistant to isoniazid (INH), streptomycin (SM), and para-aminosalicylic acid (PAS). High rates of infection associated with exposure to the index case suggested that transmission of resistant organisms had occurred, and the subsequent appearance of bacteriologically proven INH-SM-PAS-resistant tuberculosis in four school contacts of the index case confirmed this fact. Retrospective investigation revealed that the school outbreak was part of an ongoing community outbreak dating back at least to 1964. Through the use of case histories, drug-susceptibility patterns, and phage typing, 15 documented and seven presumed INH-SM-PAS-resistant, epidemiologically linked cases were found; two of these persons died of tuberculosis. Six additional cases with INH-SM-PAS resistance that could not be epidemiologically linked to the outbreak were also identified. The potential of drug-resistant strains for causing disease in humans should not underestimated.