Preventive therapy with isoniazid. Cost-effectiveness of different durations of therapy.

Daily administration of isoniazid for one year to persons infected with Mycobacterium tuberculosis is effective in considerably reducing the risk of disease. From a practical viewpoint, this approach to prevention is less than ideal because it results in considerable costs as health care providers monitor for possible hepatotoxic effects and because it is difficult to maintain compliance for 12 months. The efficacy and toxicity of isoniazid preventive therapy regimens of 12, 24, and 52 weeks' duration were recently assessed in a study conducted in Eastern Europe. We used data from this study to conduct a cost-effectiveness analysis of the three alternative regimens. The results indicate that over a wide range of assumptions, a regimen of 24 weeks' duration is more cost-effective than either the 12- or 52-week regimen. Using base case estimates, the cost per case prevented for the 24-week regimen was $7,112, compared with $16,024 for the 52-week regimen. Among a cohort of 1,000 persons treated, each additional case prevented by the 52-week regimen would cost $80,807. Thus, a shorter course of isoniazid preventive therapy is relatively cost-effective compared with current policy.

Drug resistance among previously treated tuberculosis patients, a brief report.

The choice of an appropriate chemotherapeutic regimen for the treatment of tuberculosis is more difficult if the patient has been treated for tuberculosis in the past. This study was undertaken to determine drug-resistance rates among patients previously treated with isoniazid (INH), streptomycin (SM), and/or paraaminosalicylic acid (PAS). The study population consisted of 4,017 patients for whom the length and type of previous therapy was known. Forty-one per cent of these patients were found to be excreting organisms resistant to 1 or more of the following 3 drugs: INH, SM, and PAS. Resistance to INH was encountered most (36.8%), followed by resistance to SM (19.2%), and resistance to PAS (17.2%). Resistance rates were considerably higher among the 1,168 patients who had previously received monotherapy (60%) than among those who had never received single-drug therapy (33%). In general, the percentage of patients excreting resistant organisms increased with increasing duration of the previous therapy. The implications of these findings for the design of retreatment regimens are discussed.

Isoniazid-related hepatitis: a U.S. Public Health Service cooperative surveillance study.

After an outbreak of hepatitis in Washington, D.C. in 1970 among a group of persons taking isoniazid to prevent tuberculosis, an isoniazid surveillance study was conducted among 13,838 persons in 21 participating health departments. Age appeared to be the predominant factor influencing the risk of developing isoniazid-related hepatitis, i.e., increasing age was associated with an increasing risk. Drinking alcohol, especially on a daily basis, also seemed to enhance the risk of hepatitis among persons concurrently taking isoniazid. In general, case rates among males and females of the same race, and rates among different races, were not markedly different; however, there were striking differences in the case rates among males of different races. The incidence of hepatitis varied greatly among the 21 cities, but was not unique to any geographic region, nor was it related to a specific manufacturer of isoniazid. The onset, in most cases, occurred within the first few months of treatment. Eight fatalities were reported by the 21 participating health departments, 7 occurring in one city. Black females accounted for 5 of the 8 deaths. This information provides a basis for weighing the benefits of isoniazid in preventing tuberculosis against the risk of its causing hepatitis. Close monitoring for overt signs or symptoms of hepatitis among persons receiving isoniazid preventive therapy is indicated, especially for persons greater than or equal to 35 years of age and those who drink alcoholic beverages on a daily basis.

Efficacy of BCG vaccination in prevention of cancer: an update.

From 1949 to 1951, a controlled trial of BCG vaccinations was conducted in Puerto Rico. The 191,827 children, 1-18 years of age, initially enrolled in the study were skin-tested with tuberculin to determine their eligibility for vaccination. A total of 82,269 children were classified as reactors and not vaccinated. Of the 109, 558 nonreactors, 31,586 refused vaccination, 50,634 were vaccinated with BCG, and 27,338 were left unvaccinated as controls. We ascertained the incidence of cancer over an average follow-up period of 23.3 years in the latter two groups using the Puerto Rico Central Cancer Registry. By the end of December 1973, a total of 77 cancers had been diagnosed among the controls and 150 among the vaccinees. The overall incidence of cancer among the two groups was similar. Although a number of differences existed between the vaccinee group and the controls in regard to the incidence of cancer at various "sites", none of these differences was statistically significant. However, when cases of lymphosarcoma and Hodgkin's disease were combined for analysis, a statistically significant excess of cases occurred among the vaccinees. We concluded that BCG vaccination had no protective effect on the subsequent development of cancer in this population. The slight excess of cases of lymphosarcoma and Hodgkin's disease among the vaccinees raised the possibility that BCG may have had an adverse effect.

A continuing survey of primary drug resistance in tuberculosis, 1961 to 1968. A U.S. Public Health Service cooperative study.

From 1961 through 1968 the incidence of primary drug resistance was monitored among patients admitted to 22 participating hospitals. The patients were believed to have newly diagnosed, previously untreated, bacteriologically proved pulmonary tuberculosis. During the study period the level of primary resistance to isoniazid, streptomycin, and para-aminosalicylic acid remained very low; there was no indication that primary resistance to these drugs was increasing. Investigation of patient histories revealed that a significant proportion of persons initially believed to have been previously untreated actually had received prior chemotherapy. Resistance rates to both isoniazid and streptomycin were significantly higher among younger patients than among older patients. No relationship was found between race or sex and primary resistance rates. The low incidence of drug resistance found in this survey suggests that disease caused by virulent resistant organisms occurs infrequently.