Earl Hershfield

Epidemiology and Clinical Spectrum of Blastomycosis Diagnosed at Manitoba Hospitals

Blastomyces dermatitidis is a dimorphic fungus endemic to Canada and the United States. Few reports regarding blastomycosis in Canada have been published. We retrospectively reviewed the medical charts of 143 patients with confirmed cases of blastomycosis diagnosed in hospitals in Manitoba, Canada, from 1988 through 1999. The annual incidence rate of blastomycosis in Manitoba was 0.62 cases per 100,000 population, compared with 7.11 cases per 100,000 population in the Kenora, Ontario district. The average age of patients was 38.0 years, and males accounted for 65.0% of cases. An increased incidence of blastomycosis was observed in the Aboriginal subpopulation. Organ systems involved were as follows: respiratory system (93.0% of cases), skin (21.0%), bone (13.3%), genitourinary tract (1.4%), and the central nervous system (1.4%); 6.3% of patients died, and death was associated with a short clinical course. This study provides a summary of the current status of blastomycosis in this area of endemicity in Canada.

The impact of HIV on the usefulness of sputum smears for the diagnosis of tuberculosis.

In a developing country, 289 patients were examined for active pulmonary mycobacterial disease (sputum smear and culture) and HIV infection (serology) to compare the sensitivity and positive predictive value of sputum smears for diagnosing pulmonary tuberculosis in patients with and without antibodies to HIV. Seventy-nine percent of HIV-seronegative vs 66% of HIV-seropositive patients with positive cultures for Mycobacterium tuberculosis were smear positive (P less than .05), and a positive sputum smear predicted the presence of M. tuberculosis in 90% of HIV seronegative vs 80% of HIV seropositive patients (P less than .05). In our opinion, HIV did not significantly compromise the diagnostic utility of the sputum smear.

Tuberculous pericarditis: Long-term outcome in patients who received medical therapy alone☆

A conservative approach to operative intervention in the treatment of active tuberculous pericarditis was adopted and only 4 of 16 consecutive patients underwent pericardiectomy, all within 2 months of diagnosis. One patient died of constrictive pericarditis despite pericardiectomy, and one died of acute bronchopneumonia after 8 months of otherwise successful medical management. All 14 long-term survivors were reevaluated to exclude chronic constrictive pericarditis and other potential sequelae of tuberculous pericarditis. Reevaluation included physical examination, chest radiograph, electrocardiogram, M-mode and two-dimensional echocardiogram, computed tomography (CT) scan, and in patients less than or equal to 75 years of age, incremental cycle exercise to maximum oxygen consumption. None were found to have chronic constrictive pericarditis or convincing evidence of other recognized complications of tuberculous pericarditis. Our results suggest that when pericardiectomy is not required for the relief of cardiac compression during the acute phase of tuberculous pericarditis and patients are treated with medical therapy alone, an excellent long-term outcome may be anticipated.

Conventional and molecular epidemiology of Tuberculosis in Manitoba

BackgroundTo describe the demographic and geographic distribution of tuberculosis (TB) in Manitoba, thus determining risk factors associated with clustering and higher incidence rates in distinct subpopulations.MethodsData from the Manitoba TB Registry was compiled to generate a database on 855 patients with tuberculosis and their contacts from 1992–1999. Recovered isolates of M. tuberculosis were typed by IS6110 restriction fragment length polymorphisms. Bivariate and multivariate logistic regression models were used to identify risk factors involved in clustering.ResultsA trend to clustering was observed among the Canadian-born treaty Aboriginal subgroup in contrast to the foreign-born. The dominant type, designated fingerprint type 1, accounts for 25.8% of total cases and 75.3% of treaty Aboriginal cases. Among type 1 patients residing in urban areas, 98.9% lived in Winnipeg. In rural areas, 92.8% lived on Aboriginal reserves. Statistical models revealed that significant risk factors for acquiring clustered tuberculosis are gender, age, ethnic origin and residence. Those at increased risk are: males (p < 0.05); those under age 65 (p < 0.01 for each age subgroup); treaty Aboriginals (p < 0.001), and those living on reserve land (p < 0.001).ConclusionMolecular typing of isolates in conjunction with contact tracing data supports the notion of the largest ongoing transmission of a single strain of TB within the treaty-status population of Canada recorded to date. This data demonstrates the necessity of continued surveillance of countries with low prevalence of the disease in order to determine and target high-risk populations for concentrated prevention and control measures.

Identification of a predominant isolate of Mycobacterium tuberculosis using molecular and clinical epidemiology tools and in vitro cytokine responses

BackgroundTuberculosis (TB) surveillance programs in Canada have established that TB in Canada is becoming a disease of geographically and demographically distinct groups. In 1995, treaty status aboriginals from the province of Manitoba accounted for 46% of the disease burden of this sub-group in Canada. The TB incidence rates are dramatically high in certain reserves of Manitoba and are equivalent to rates in African countries. The objective of our study was to identify prevalent isolates of Mycobacterium tuberculosis in the patient population of Manitoba using molecular epidemiology tools, studying the patient demographics associated with the prevalent strain and studying the in vitro cytokine profiles post-infection with the predominant strain.MethodsMolecular typing was performed on all isolates available between 1992 to1997. A clinical database was generated using patient information from Manitoba. THP-1 cells were infected using strains of M. tuberculosis and cytokine profiles were determined using immunoassays for cytokines IL-1β, IL-10, IL-12, IFN-γ and TNF-α.ResultsIn Manitoba, 24% of the disease burden is due to a particular M. tuberculosis strain (Type1). The strain is common in patients of aboriginal decent and is responsible for at least 87% of these cases. Cytokine assays indicate that the Type1 strain induces comparatively lower titers of IL-1β, IFN-γ and TNF-α in infected THP-1 cells as compared to H37Ra and H37Rv strains.ConclusionIn Manitoba, Type1 strain is predominant in TB patients. The majority of the cases infected with this particular strain are newly active with a high incidence of respiratory disease, positive chest radiographs and pulmonary cavities. In vitro secretion of IL-1β, IFN-γ and TNF-α is suppressed in Type1 infected culture samples when compared to H37Ra and H37Rv infected cells.

Tuberculous Lymphadenitis in Manitoba: Incidence, Clinical Characteristics and Treatment

BACKGROUND Tuberculous lymphadenitis (TBL) is an important form of extrapulmonary tuberculosis (TB). Recent studies have shown an increase in TBL in Canada. OBJECTIVES To determine the incidence of TBL in Manitoba and to identify the characteristics associated with its presentation, diagnosis and treatment METHODS Population data from the Manitoba Health Population Registry, the First Nations and Inuit Health Branch of Health Canada, and Statistics Canada were used to calculate incidence. Case characteristics and outcomes were determined by a systematic, retrospective review of all cases between January 1, 1990 and December 31, 2000. RESULTS One-hundred forty seven cases of TBL were identified during the study period; 77% confirmed by culture; 68% women. TBL was found in Canadian-born/nonstatus Aboriginal (12%), status Aboriginal (29%) and foreign-born (59%) populations. Incidence of TBL was 1.17 per 100,000 person years (95% CI 0.98 to 1.36). The highest incidence was in status Aboriginals over 65 years (16.85 per 100,000 person years; 95% CI 3.37 to 30.33). TBL is seen most often in Western Pacific women. The most common presentation was a single, enlarged cervical node (80%). No atypical mycobacterium was found. Drug resistance occurred in 13% of cases and only in the foreign-born. Cure rates (81%) were influenced by comorbidity and burden of TB disease. Relapse occurred in 8.1 per 1000 person years of follow-up (95% CI 1.7 to 23.7). CONCLUSIONS Respiratory physicians, who manage the majority of TB disease in Canada, need to remain aware that TB is an important and treatable cause of enlarged lymph nodes.

Tuberculosis status and social adaptation of Indochinese refugees.

The relationship between tuberculosis and social adaptation of Indochinese refugees in Manitoba 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.

The Lack of Association Between Bacille Calmette-Guerin Vaccination and Clustering of Aboriginals with Tuberculosis in Western Canada

BACKGROUND Tuberculosis (TB) remains a major health problem for Aboriginal people in Canada, with high rates of clustering of active TB cases. Bacille Calmette-Guerin (BCG) vaccination has been used as a preventive measure against TB in this high-risk population. OBJECTIVES The study was designed to determine if BCG vaccination in Aboriginal people influenced recent TB transmission through an analysis of the clustering of TB cases. METHODS A retrospective analysis of all culture-positive Mycobacterium tuberculosis cases in Aboriginal people in western Canada (1995 to 1997) was performed. Isolates were analyzed using standard methodology for restriction fragment length polymorphism and spoligotyping. RESULTS Of 256 culture-positive Aboriginal TB cases, BCG status was confirmed in 216 (84%) cases; 34% had been vaccinated with BCG, 57% were male and 56% were living on-reserve. Patients who had been vaccinated with BCG were younger than unvaccinated individuals (mean age 32.4+/-1.65 years versus 45.0+/-1.8 years, P<0.0001). Clustering was found in 62% of cases: 59% of non-BCG vaccinated cases were clustered versus 68% of those vaccinated with BCG (P=0.16). Younger patients (younger than 60 years of age) were more likely to be clustered in the univariate analysis (P<0.01). When age, sex, province, and HIV and reserve status were controlled for, BCG vaccination was not associated with clustering (OR 1.3, 95% CI 0.7 to 2.6). CONCLUSIONS BCG vaccinated Aboriginal people were no less likely to have active TB from recently transmitted disease. BCG vaccination appears to have limited value in preventing clustering of TB cases within this high-risk community.