M. tuberculosis molecular variation in CNS infection: evidence for strain-dependent neurovirulence.

OBJECTIVE: To determine the molecular diversity among Mycobacterium tuberculosis isolates associated with central nervous system tuberculosis (CNS TB) in a defined cohort of HIV uninfected patients. DESIGN/METHODS: A retrospective analysis was performed of clinical and laboratory data for all patients with CNS TB diagnosed in Manitoba, Canada, between 1979 and 1996. Restriction fragment-length polymorphisms (RFLP) of archival isolates of M. tuberculosis from CNS TB patients were determined and interpreted against the frequency of different isolates from all TB patients in the years 1992 to 1996. RESULTS: Among 2,334 patients with active TB, CNS TB was diagnosed in 42 (1.8%); meningitis with or without tuberculoma in 76%; and tuberculoma alone in 24%. CNS TB patients were significantly more likely to be young (<40 years old), female, and of Aboriginal origin. Morbidity (fixed/recurrent CNS deficit) rate was 29% and mortality rate was 26%. An adverse outcome, either morbidity or mortality, was significantly more common in those with meningitis. RFLP analysis of isolates (n=19) from CNS TB patients revealed 13 distinct restriction patterns with a predominance of the type 1 pattern (n=6). The frequency of type 1 restriction pattern was significantly greater in patients with CNS TB compared to all TB patients in Manitoba. CONCLUSIONS: CNS TB continues to have a high morbidity and mortality despite modern methods of detection and treatment. Although several strains of M. tuberculosis cause CNS TB, the current study suggests that the occurrence of CNS TB may be strain-dependent.

Two-step tuberculin testing in staff and residents of a nursing home.

This study examined the prevalence and determinants of tuberculin reactors and the booster response in 272 (97%) residents and 218 (69%) staff of an urban nursing home where a case of miliary TB was being investigated. Many subjects were foreign born (56%), and 15% had a history of BCG vaccination (34% of staff). Testing was done with 5 TU PPD-S (Connaught). Those with < 10 mm induration at 48 h were retested at 1 wk. Test sizes > 9 mm were classified positive (reactors). A questionnaire was given to collect information on risk factors for a positive test. Results showed that 28% (36% staff and 22% of residents) of subjects were reactors at the initial test, 6% at the booster test (staff and residents), and 32% at either test (40% staff and 26% residents). BCG (OR 4.8) and foreign birth (OR 1.7) were significantly associated with total reactors. The association with foreign birth was inversely related to the time since immigration. Only BCG was associated with a positive booster test (OR 6.7). Of positive tuberculin reactions in individuals with a history of BCG, 72% were attributed to the vaccine. We concluded that (1) staff as well as residents should be two-step tested when retesting is anticipated; (2) the prevalence of tuberculin reactors is highly related to the prevalence of BCG vaccinees and foreign birth; and (3) chemoprophylaxis is probably not indicated for isolated tuberculin reactors with a history of BCG.

A statistical chronicle of tuberculosis in Canada: Part II. Risk today and control.

This report marks over 50 years of publication by Statistics Canada of annual reports on Tuberculosis Statistics. These years have witnessed what has been described as a conquest of tuberculosis in Canada. To quote George Jasper Wherrett in the Miracle of the Empty Beds: One hundred years ago the word consumption (as tuberculosis was then called) struck horror in human hearts. Today, in the western world, it barely evokes any emotion save a too easy surprise that it still exists. This statistical chronicle of tuberculosis in Canada is divided into two parts. Part I: From the Era of Sanatorium Treatment to the Present pulls together data from yellowed-with-age reports on tuberculosis and vital statistics, historical accounts, and modern computer files, to document the changes in tuberculosis incidence and mortality over past decades to the present. Part II: Risk Today and Control takes a closer look at those most vulnerable to contracting tuberculosis. It also looks at the future, the need for maintaining and, indeed, strengthening vigilance, and the work yet to be done to eradicate tuberculosis in Canada. The fight against tuberculosis is far from over.

A statistical chronicle of tuberculosis in Canada: Part I. From the era of sanatorium treatment to the present.

This report marks over 50 years of publication by Statistics Canada of annual reports on tuberculosis statistics. These years have witnessed what has been described as a conquest of tuberculosis in Canada. To quote George Jasper Wherrett in The Miracle of the Empty Beds: One hundred years ago the word consumption (as tuberculosis was then called) struck horror in human hearts. Today, in the western world, it barely evokes any emotion save a too easy surprise that it still exists. This statistical chronicle of tuberculosis in Canada is divided into two parts. Part I: From the Era of Sanatorium Treatment to the Present pulls together data from yellowed-with-age reports on tuberculosis and vital statistics, historical accounts and modern computer files, to document the changes in tuberculosis incidence and mortality over past decades to the present. Part II: Risk Today and Control takes a closer look at those most vulnerable to contracting tuberculosis. It also looks at the future, the need for maintaining and, indeed, strengthening vigilance, and the work yet to be done to eradicate tuberculosis in Canada. The fight against tuberculosis is far from over.

Tuberculosis surveillance in immigrants to Manitoba.

Despite a decrease in the incidence of tuberculosis in Canada over the last decade, the proportion of cases in people not born in Canada has increased. To determine the prevalence of active tuberculosis at the first surveillance clinic visit and the incidence of the disease over a 2-year to 6-year follow-up period, we reviewed the records of all 523 immigrants admitted to Manitoba between 1981 and 1985 who were placed under surveillance. Of the 523, 429 (82%) were seen at least once in the clinic. Among the 429, active tuberculosis was diagnosed at the first visit in 12 (3%) and during the follow-up period in 7 (2%). The relative risk of tuberculosis was 4.5 times higher for immigrants under surveillance than for those not under surveillance. Of the 483 immigrants who were to be seen in Winnipeg 232 (48%) were noncompliant: 94 were not seen at any time, and 138 did not attend for the full follow-up period. Active disease was not reported to have developed in any of the noncompliant subjects. Noncompliers were significantly older than compliers (p less than 0.005), and variations in compliance were noted according to region of origin. Further attempts to improve compliance with surveillance without resorting to punitive measures are indicated.

Tuberculosis status and social adaptation of Indochinese refugees.

The relationship between tuberculosis and social adaptation of Indochinese refugees in Manitoba, Canada, is examined in 43 randomly selected refugees treated for active and inactive tuberculosis (cases) and their matched controls. Tuberculosis status did not significantly affect adaptation as measured by selected scales and indicators. Significant predictors of better personal well-being included a low number of family members outside the household in Manitoba, non-use of traditional medicine, female gender, and high individual income. Tuberculosis status was not a significant predictor.

Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease.

The effects of broad-spectrum antibiotic and placebo therapy in patients with chronic obstructive pulmonary disease in exacerbation were compared in a randomized, double-blinded, crossover trial. Exacerbations were defined in terms of increased dyspnea, sputum production, and sputum purulence. Exacerbations were followed at 3-day intervals by home visits, and those that resolved in 21 days were designated treatment successes. Treatment failures included exacerbations in which symptoms did not resolve but no intervention was necessary, and those in which the patient's condition deteriorated so that intervention was necessary. Over 3.5 years in 173 patients, 362 exacerbations were treated, 180 with placebo and 182 with antibiotic. The success rate with placebo was 55% and with antibiotic 68%. The rate of failure with deterioration was 19% with placebo and 10% with antibiotic. There was a significant benefit associated with antibiotic. Peak flow recovered more rapidly with antibiotic treatment than with placebo. Side effects were uncommon and did not differ between antibiotic and placebo.

A case-control study to evaluate the effectiveness of mass neonatal BCG vaccination among Canadian Indians.

This paper reports a case-control study to assess the protective effect of BCG (bacille Calmette-Guérin) vaccination among Indian infants in Manitoba, Canada. A record of past BCG vaccination was found in 49 per cent of the tuberculosis cases, compared to 77 per cent of the controls, yielding a relative risk of 0.30. Stratified analysis, controlling for age, increased the relative risk to 0.39 (95% confidence interval 0.22 - 0.69). The preventive fraction was 44 per cent. Non-differential misclassification of exposure status could have occurred; if this was adjusted for, the relative risk would be reduced. If only bacteriologically confirmed cases were analyzed, the age-adjusted relative risk was 0.27. The protective effect of BCG vaccination in the newborn among Manitoba Indians is therefore at least 60 per cent. The implications for health policy in this population are further discussed.

Risk factors for reactivation of tuberculosis in Manitoba.

Although rates of reported cases of active tuberculosis have been declining in Manitoba and throughout Canada over the past two decades, the percentage of active cases due to reactivated tuberculosis has remained relatively constant. From 1976 to 1981, 113 cases of reactivated tuberculosis were listed in the Manitoba tuberculosis registry. We found that 36 cases did not meet our criteria for reactivation, primarily because there was no 6-month period of inactivity; another 5 cases could not be verified. In more than half of the remaining 72 the initial episode had occurred before 1960. We also randomly selected from the registry as controls 118 age- and sex-matched cases of nonreactivated tuberculosis. We found that registered Indian status was significantly associated with risk of reactivation, especially when the initial disease had been extensive. Awareness of high-risk groups, earlier diagnosis and adequate treatment are needed to prevent reactivated tuberculosis.

Standard therapy for tuberculosis 1985.

PIP: Numerous clinical trials of chemotherapy for tuberculosis conducted throughout the world over the past 4 decades have established 2 basic principles of treatment: effective treatment requires the initial concomitant administration of at least 2 drugs to which the patient's organisms are susceptible; and cure of tuberculosis requires that treatment continue beyond the time of sputum conversion and amelioration of symptoms. The treatment of tuberculosis was revolutionized in the late 1960s with the introduction of rifampin. Shorter regimens of 6-9 months in duration became possible. Scores of trials of short-course chemotherapy have been conducted, and more are planned. The goals of the new treatment regimens are to achieve effective sterilization of the tuberculous lesion in the shortest time possible. A table lists drugs now in use in the US and Canada and gives the usual doses, common side effects, and important interactions among drugs. Chemotherapeutic regimens acceptable for use in the US and Canada are well-defined combinations of drugs which must be regularly administered in the recommended dosages and rhythm for a specific time period. Regimens should be highly effective, i.e., a relapse rate of less than 5%, and have a low risk of toxic effects. Regimens also should be acceptable to patients and applicable on a community-wide basis. The regimens recommended meet these criteria and are backed by well-conducted clinical trails. A 9-month regimen consisting of isoniazid and rifampin throughout, usually supplemented in the initial phase by ethambutol, streptomycin, or pyrazinamide, is a well-tolerated regimen which will cure virtually all patients with susceptible organisms. The initial daily phase may last 2-8 weeks; the continuation phase may be administered daily or twice weekly. These regimens have an overall bacteriologic relapse rate of between zero and 4%. When 4 drugs -- isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin -- are given under close during supervision during the initial 2 months of daily or "induction" therapy, followed by an additional 4 months of isoniazid and rifampin, the results have been excellent. Where primary resistance to isoniazid or streptomycin is suspected, the patient should be placed on 1 of the following 3 regimens: isoniazid, rifampin, and ethambutol; isoniazid, rifampin, pyrazinamide, and streptomycin; or isoniazid, rifampin, pyrazinamide, and ethambutol. Short-course chemotherapy for extrapulmonary tuberculosis and chemotherapy of tuberculosis in children are reviewed along with several conditions which affect therapy -- tuberculosis during pregnancy, renal and hepatic disease, cancer and other conditions associated with immunosuppression, and drug interaction.^ieng

Lymphadenitis as a late complication of BCG vaccination.

Lymphadenitis is a relatively common complication following intradermal BCG vaccination, and usually occurs 6 to 9 months after injection. However, lymphadenitis following BCG given by the scarification method is rare. We report a case of BCG lymphadenitis occurring 11 and 18 years after vaccination by the scarification method.

Chronic obstructive pulmonary disease following idiopathic pulmonary fibrosis.

The rapid development of irreversible airflow obstruction in two nonsmoking women who recovered from acute idiopathic pulmonary fibrosis is discussed. Pulmonary fibrosis was diagnosed clinically and by lung biopsy. Recovery both clinically and radiologically was complete. Several pulmonary function studies in both patients showed a typical restrictive pattern (reduced lung volumes and carbon dioxide diffusing capacity, normal FEV1/FVC ratio). Within one year both patients exhibited an obstructive pattern of dysfunction (hyperinflation, gas trapping, reduced airflow measurements). These patients illustrated irreversible airway obstruction following recovery from the restrictive stage of pulmonary fibrosis.