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E Hershfield

Publications and source records attributed to E Hershfield.

17 recordsLinked to original sources
PubMed2004

Strain-related virulence of the dominant Mycobacterium tuberculosis strain in the Canadian province of Manitoba.

SETTING: The Canadian province of Manitoba. OBJECTIVE: To confirm the putative hypervirulence observed in Mycobacterium tuberculosis Type1 strain and further characterize the progression and manifestation of pulmonary tuberculosis caused by this strain in comparison to other common clinical isolates from Manitoba. DESIGN: C3H and BALB/c mice were exposed to aerosols either of Type1, Type2, Type5, Type72 or H37Rv strain to study their respective survival profiles. Additionally, bacillary loads and lung histology were examined at 15 days post-exposure. RESULTS: In both mouse models, Type-1 infected mice succumbed to disease significantly earlier than other strains (p < or =0.0002). Differences between average log(10) CFU values between clinical isolates were less than 1log(10) difference. In C3H mice, the amount of granulomatous inflammation was highest in Type1 infected mice but not significantly different than all clinical strains. In contrast, BALB/c mice infected with Type1 induced the lowest amount of granulomatous inflammation compared to other clinical isolates. CONCLUSION: Our results indicate that although mice infected with the Type1 strain died significantly earlier than mice infected with other clinical strains in both C3H and BALB/c mice, the hypervirulence of the Type1 strain is not attributed to the growth rate of the organism, as differences in growth between clinical M. tuberculosis isolates were insignificant.

Animals↗
PubMed2003

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

BACKGROUND: Tuberculosis (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. METHODS: Molecular typing was performed on all isolates available between 1992 to 1997. 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-1beta, IL-10, IL-12, IFN-gamma and TNF-alpha. RESULTS: In 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-1beta, IFN-gamma and TNF-alpha in infected THP-1 cells as compared to H37Ra and H37Rv strains. CONCLUSION: In 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-1beta, IFN-gamma and TNF-alpha is suppressed in Type1 infected culture samples when compared to H37Ra and H37Rv infected cells.

Adult↗
PubMed2003

The molecular epidemiology of tuberculosis in western Canada.

OBJECTIVE: To define the molecular epidemiology of TB in western Canada, and in particular the risk factors for clustering. MEASUREMENTS: We prospectively identified all positive cultures from newly diagnosed cases of TB diagnosed between February 1995 and January 1997 and carried out restriction fragment length polymorphism (RFLP) testing on all isolates. RESULTS: Of 956 cases identified, 944 fulfilled the entry criteria. The mean age was 49.65 years (+/- 22.33), and 508 (53.6%) were males. Three hundred and three (32.1%) subjects were clustered; this varied from 20.2% of the foreign born, 48.4% of Canadian non-Aboriginal and 61.1% of all Aboriginal persons. Younger persons (P = 0.0001), males (P = 0.015), those with pulmonary disease (P < 0.001), living in a shelter in the past year (P < 0.001), drug-susceptible disease (P < 0.036), predisposing factors (P < 0.001), prior contact (P < 0.001), and prior skin test (P < 0.002) were more likely to cluster. Among specific risk factors, HIV infection, injection drug use, alcohol excess, and weight loss were all significant. CONCLUSIONS: In this description of the molecular epidemiology of TB in Western Canada, previous results have been confirmed and extended. These results highlight the importance of identifying specific high risk groups, especially in the context of renewed efforts to target persons for treatment of latent TB infection.

Adult↗
PubMed1999

Tuberculous mycotic aneurysm of the aorta: review of published medical and surgical experience.

To define the epidemiology, pathogenesis, pathology, presentation, and management of tuberculous mycotic aneurysm of the aorta (TBAA) in the therapeutic era, we reviewed all of the cases reported in the English language literature from 1945 to the present. To the 39 cases in the published literature, we add two cases of our own. Although it is exceedingly rare, the prevalence of this lesion has remained relatively constant. In 75% of the cases, TBAA appeared to result from erosion of the aortic wall by a contiguous focus; 25% from direct seeding of the aortic intima or of the adventitia or media (via the vasa vasorum). Most of the aneurysms were saccular (90%) and false (88%). The thoracic and abdominal aortas were affected with equal frequency. The mean (+/- SD) age of the patients was 50+/-16 years. Twenty-two were men, and 19 were women. In 63% of the cases, tuberculosis (TB) was diagnosed at presentation. Disseminated TB was present in 46% of the cases. One or more of three clinical scenarios suggested TBAA: persistent pain, major bleeding, and a palpable or radiographically visible para-aortic mass, especially if it is expanding or pulsatile. In turn, each of these findings suggested a complication of TBAA that may be an indication for surgical intervention. Among the patients who were offered both medical and surgical treatment, 20 of 23 (87%) survived. Among those who were offered only one form of treatment or were offered no treatment at all there were no survivors. Both in situ reconstruction with a prosthetic graft, and extra-anatomic bypass appeared to offer excellent results, provided that an effective regimen of antituberculous drugs was delivered postoperatively. We offer our conclusions: (1) symptomatic TBAA is a rare but uniformly fatal lesion if not diagnosed promptly, (2) in the context of active TB, and especially miliary TB, TBAA should be suspected whenever one or more of the three clinical scenarios are present, and (3) combined medical and surgical therapy appears to offer the best chance of a cure.

Adult↗
PubMed1998

Pulmonary tuberculosis treated with directly observed therapy: serial changes in lung structure and function.

OBJECTIVES: (1) To correlate structure (CT) with function in pulmonary tuberculosis (TB), and (2) to describe the evolution of structural and functional abnormalities when pulmonary TB is treated with directly observed therapy. SUBJECTS AND METHODS: Twenty-five patients with drug-susceptible pulmonary TB, 15 cavitary and 10 noncavitary, were studied prospectively. Conventional CT and pulmonary function testing (spirometry, diffusing capacity, and arterial blood gases) were performed at baseline, and after 1 and 6 months of directly observed therapy. RESULTS: All but one patient with noncavitary miliary TB had CT evidence of endobronchial disease, and all patients with cavitary disease had coexistent reduced lung attenuation, the latter presumably a result of gas trapping, hypoxic vasoconstriction, and vascular injury. Functional impairment was minimal and in proportion to the number of diseased segments and cavitary volume. Bronchiectasis was significantly more likely to complicate cavitary than noncavitary disease (64 vs 11%; p<0.05). CONCLUSIONS: CT findings correlate well with function in pulmonary TB. Physiologic data were consistent with the concept that pulmonary TB is an endobronchial disease that causes parallel reductions in ventilation and perfusion. This concurrent involvement of both airways and contiguous pulmonary blood supply offers an explanation for the minimal respiratory limitation experienced by these patients despite often extensive lung disease. Supervised therapy of drug-susceptible disease results in minimal structural and functional residua.

Adult↗
PubMed1997

Pulmonary illness associated with exposure to Mycobacterium-avium complex in hot tub water. Hypersensitivity pneumonitis or infection?

BACKGROUND: Mycobacterium avium complex is common in water. When aerosolized, it is frequently inhaled but rarely causes illness in healthy people. Hypersensitivity pneumonitis to inhaled aerosols has been described; these aerosols are from several sources of water. The pneumonitis forms are collectively known as humidifier lung; the responsible agent in the water remains uncertain. PURPOSE: To report five cases of respiratory illness in healthy subjects using hot tubs contaminated with M avium complex. DESIGN: Descriptive case reports. SETTING: Consultations in two teaching hospitals. PATIENTS: Five healthy people developed respiratory illnesses characterized by bronchitis, fever, and "flu-like" symptoms after using a hot tub. Acute exacerbations of their illness developed within hours of heavy use of the hot tubs. INVESTIGATIONS: A chest radiograph and sputum culture in all, BAL in one, CT scan and lung biopsy in another were performed. Culture of the water of the two hot tubs also was done. RESULTS: Chest radiographs showed interstitial infiltrates or a miliary nodular pattern. Cultures of all sputum samples, the lung biopsy specimens, lung lavage and water samples were positive for M avium complex. The lung biopsy specimen revealed noncaseating granulomas. All patients recovered with no treatment for M avium complex. CONCLUSION: We conclude that the M avium complex in the water was responsible for the pulmonary illnesses. The symptoms and the results of investigations are more suggestive of a hypersensitivity pneumonitis than of an infection, but no serologic proof of an immunologic reaction to the M avium complex or water was obtained.

Adolescent↗
PubMed1997

Disseminated tuberculosis with and without a miliary pattern on chest radiograph: a clinical-pathologic-radiologic correlation.

SETTING: Province of Manitoba, Canada. OBJECTIVE: To describe the characteristics of disseminated tuberculosis (TBD) with and without a miliary pattern on chest radiograph, to determine the mortality, and to identify the demographic and clinical features associated with survival. DESIGN: A retrospective case review. RESULTS: Of 2013 cases of active tuberculosis reported to the Provincial Tuberculosis Registry between January 1979 and December 1993, 56 had disseminated disease. The odds of developing TBD were significantly higher in females. Compared to those with a miliary pattern (n = 42), those without a miliary pattern on chest radiograph (n = 14) were significantly more likely to have a risk factor for tuberculosis (86% vs 52%, P < 0.05) and to die (86% vs 21%, P < 0.001). The diagnosis of TBD was significantly more likely to be made at postmortem in non-miliary compared to miliary patients (43% vs 5%, P < 0.05). Amongst patients with a miliary pattern, the presence of one or more risk factors for tuberculosis was associated with a significantly higher mortality (P < 0.05). Meningitis was very uncommon and did not determine the outcome. CONCLUSION: Disseminated tuberculosis patients without a miliary pattern on chest radiograph have an extremely high mortality rate; those with a miliary pattern may also succumb, especially if co-morbid with a condition known to increase the risk of tuberculosis.

Adult↗
PubMed1993

Antituberculous drug resistance in Manitoba from 1980 to 1989.

OBJECTIVES: To estimate the magnitude of antituberculous drug resistance and identify the risk factors for its development in tuberculosis patients in Manitoba over a 10-year period. As well, to examine the clinical course of the patients whose initial or subsequent isolates of Mycobacterium tuberculosis were resistant to one or more drugs. DESIGN: Comparison of drug-resistant and non-drug-resistant cases of tuberculosis. SETTING: Manitoba. PATIENTS: All people with tuberculosis reported to the Central Tuberculosis Registry of Manitoba between Jan. 1, 1980, and Dec. 31, 1989. MAIN OUTCOME MEASURES: Of 1478 cases of active tuberculosis 1086 were culture positive, and drug susceptibility testing was performed in these cases. The clinical course, including outcome of treatment, of all drug-resistant cases was described. RESULTS: Of 1086 culture-positive cases of tuberculosis 77 (7.1%) were drug resistant. Odds ratios suggested that the risk of drug resistance was significantly higher among the immigrants than among the other Canadians. Compared with the other Canadians the risk of drug resistance was 9.9 times greater among the immigrants in whom tuberculosis developed within the first year after arrival in Canada and 5.4 times greater among the immigrants in whom it developed 2 to 5 years after arrival in Canada. Of the 71 patients with drug-resistant disease whose type of resistance was known 62% had never taken antituberculous drugs before and 38% had. Most (91%) of the 77 cases of drug-resistant disease were resistant to first-line drugs, especially isoniazid and streptomycin. Thirty-two (42%) of the 77 cases were resistant to two or more first-line drugs. Of patients with drug-resistant disease a subgroup of 10 had disease that became resistant to several drugs over the 10-year period. The outcome of treatment in these individuals was poor, and they presented a particular public health problem. CONCLUSION: Resistance to one or more first-line antituberculous drugs continues to complicate the treatment of tuberculosis and may facilitate the spread of the disease.

Adolescent↗
PubMed1991

Impact of human immunodeficiency virus type 1 on tuberculosis in rural Haiti.

We conducted a case-control study to determine the relative and attributable risk of HIV seropositivity for bacillary-positive (smear and/or culture) pulmonary tuberculosis in Haiti. There were 274 patients with tuberculosis and an equal number of control subjects. Antibodies to HIV were present in 67 (24%) patients and eight (3%) control subjects. Odds ratios suggested that the risk of pulmonary tuberculosis was 15.7 times as great (95% confidence interval, 4.8 to 5.0; p less than 0.05) in patients 20 to 39 yr of age who were HIV-seropositive than in HIV-seronegative patients. In contrast, the relative risk in those 40 to 59 yr of age was elevated (3.0 times), though not significantly (lower 95% confidence interval, 0.8). In the 20- to 39-yr age group, 31% of tuberculosis was attributable to HIV infection (95% confidence interval between 23 and 39%). HIV-seropositive and HIV-seronegative patients did not differ with respect to sputum smear positivity. HIV-seronegative patients were twice as likely to be infected with resistant organisms, though this was not significant. We conclude that HIV infection is a major risk factor for pulmonary tuberculosis in young adult residents of Haiti. This, together with the fact that similar proportions of HIV-seropositive and HIV-seronegative patients were potentially infectious, suggests that without vigorous counteraction tuberculosis will become a greater problem for Haiti.

Acquired Immunodeficiency Syndrome↗
PubMed1991

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.

Adolescent↗
PubMed1990

Antituberculous drug resistance in central Haiti.

To determine the prevalence of antituberculous drug resistance in Haiti, we conducted a 1-yr survey in a central district. From a bacillary positive (smear and/or culture positive) case rate of 80/100,000, there were 282 patients from whom Mycobacterium tuberculosis was cultured. Each isolate was packaged and delivered to Canada where speciation and drug susceptibility testing were performed. Reported resistances are those using the proportions method (Laboratory Center for Disease Control, Ottawa, Canada). Resistance to one or more drugs was found in 22% of isolates. Age was the most important predictor of resistance in Haiti; resistance rates for age groups less than 14, 14 to 29, 30 to 44, greater than or equal to 45 were 8, 19, 22, and 31%, respectively. In patients not known to have received antituberculous drugs in the past, resistances were isoniazid (19%), streptomycin (5%), ethambutol (2%), ethionamide (2%), rifampin (1%). We conclude that antituberculous drug resistance is prevalent in Haiti, especially in older age groups, and that in persons with no known antituberculous drug use in the past, resistance to isoniazid is significant.

Adolescent↗
PubMed1989

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.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Drug resistance study of Mycobacterium tuberculosis in Canada, February 1, 1993 to January 31, 1994.

OBJECTIVE: To estimate the prevalence of resistance of Mycobacterium tuberculosis to first-line antituberculosis drugs in Canada. METHODS: M. tuberculosis isolates from one third of all culture-positive tuberculosis (TB) cases diagnosed between February 1, 1993 to January 31, 1994 in Canada were collected prospectively. Proportion of drug-resistant isolates and the factors related to drug resistance were measured. RESULTS: Of 458 study cases, 40 (8.7%) had resistance to at least one first-line antituberculosis drug, of which 5.9% had mono-resistance, 0.7% had multidrug-resistance(MDR-TB)--i.e., resistance to at least isoniazid and rifampin--and 2.2% had other patterns. The overall prevalence of resistance among the foreign-born cases was 10.6% with the highest level among those who resided in Canada for less than four years (15.5%). CONCLUSIONS: Canada has a relatively low prevalence of antituberculosis drug resistance and a very low prevalence of MDR-TB. Some new immigrants to Canada may be at higher risk for drug resistance and their initial treatment needs to be tailored accordingly.

Adolescent↗