Late diagnosis, delayed presentation and late presentation among persons enrolled in a clinical HIV cohort in Ontario, Canada (1999-2013).

OBJECTIVES: Timely HIV diagnosis and presentation to medical care are important for treatment and prevention. Our objective was to measure late diagnosis, delayed presentation and late presentation among individuals in the Ontario HIV Treatment Network Cohort Study (OCS) who were newly diagnosed in Ontario. METHODS: The OCS is a multi-site clinical cohort study of people living with HIV in Ontario, Canada. We measured prevalence of late diagnosis [CD4 count < 350 cells/µL or an AIDS-defining condition (ADC) within 3 months of HIV diagnosis], delayed presentation (≥ 3 months from HIV diagnosis to presentation to care), and late presentation (CD4 count < 350 cells/µL or ADC within 3 months of presentation). We identified characteristics associated with these outcomes and explored their overlap. RESULTS: A total of 1819 OCS participants were newly diagnosed in Ontario from 1999 to 2013. Late diagnosis (53.0%) and presentation (54.0%) were common, and a quarter (23.1%) of participants were delayed presenters. In multivariable models, the participants of delayed presentation decreased over calendar time, but that of late diagnosis/presentation did not. Late diagnosis contributed to the majority (> 87%) of late presentation, and the prevalence of delayed presentation was similar among those diagnosed late versus early (13.4 versus 13.4%, respectively; P = 0.99). Characteristics associated with higher odds of late diagnosis/presentation in multivariable analyses included older age at diagnosis/presentation; African, Caribbean and Black race/ethnicity; Indigenous race/ethnicity; female sex; and being a male who did not report sex with men. There were lower odds of late diagnosis/presentation among participants who had ever injected drugs. In contrast, delayed presentation risk factors included younger age at diagnosis and having ever injected drugs. CONCLUSIONS: Late presentation is common in Ontario, as it is in other high-income countries. Our findings suggest that efforts to reduce late presentation should focus on facilitating earlier diagnosis for the populations identified in this analysis.

Interferon-gamma release assays piloted as a latent tuberculous infection screening tool in Canadian federal inmates.

BACKGROUND: Interferon-gamma release assays (IGRAs) may be useful in diagnosing latent tuberculous infection (LTBI) in inmates; however, published experience in these settings is limited. OBJECTIVE: To identify variables associated with IGRA positivity among Canadian federal inmates with positive tuberculin skin test (TST) results. DESIGN: On intake, TST-positive (≥10 mm) inmates were offered an IGRA (QuantiFERON(®)-TB Gold), and demographic and historical data were collected. IGRA-positive and -negative inmates were compared using the χ(2) test and multivariable logistic regression; the final model's goodness of fit was assessed using Hosmer-Lemeshow test and area under the receiver operating characteristic curve (AUC). RESULTS: Of 96 TST-positive inmates, 31 (32.3%) were IGRA-positive. Variables associated with positive IGRA were age >45 years (11/20 vs. 20/75, P = 0.016) and previous LTBI treatment (9/20 vs. 13/55, P = 0.032) in univariate analysis, and being from a country with a moderate or high estimated tuberculosis (TB) incidence (OR 3.5, 95%CI 1.3-9.4, P = 0.013) and absence of bacille Calmette-Guérin (BCG) vaccination (OR 3.3, 95%CI 1.2-9.0, P = 0.017) in multivariable analysis. The data fit the model well, classifying the group better than chance alone (AUC 0.67, P = 0.007). CONCLUSION: High discordance with TST, particularly among BCG-vaccinated inmates and those from low TB incidence countries, suggest that IGRA may be useful in Canadian federal penitentiary screening programmes.

Local epidemic history as a predictor of tuberculosis incidence in Saskatchewan Aboriginal communities.

BACKGROUND: Average tuberculosis (TB) incidence rates are high in Canadian Aboriginal communities, but there is significant variability within this group. OBJECTIVE: To determine whether local history of post-contact TB epidemics is predictive of contemporary epidemiology among Aboriginal communities in Saskatchewan, Canada. METHODS: TB incidence, age-specific morbidity patterns and rates of clustering of TB genotypes from 1986 to 2004 were compared between two groups of communities: Group 1, in which post-contact epidemics of TB were established around 1870, and Group 2, in which they were delayed until after 1920. Concomitant effects of socio-economic and geographic variables were explored with multivariate models. RESULTS: Group 2 communities were characterized by higher annual incidence of TB (median 431 per 100,000 population vs. 38/100,000). In multivariate models that included socio-economic and geographic variables, historical grouping remained a significant independent predictor of community incidence of TB. Clustering of TB genotypes was associated with Group 2 (OR 8.7, 95%CI 3.3-22.7) and age 10-34 years (OR 2.5, 95%CI 1.1-5.7). CONCLUSIONS: TB transmission dynamics can vary significantly as a function of a population's historical experience with TB. Populations at different stages along the epidemic trajectory may be amenable to different types of interventions.

Patterns of tuberculosis risk over time among recent immigrants to Ontario, Canada.

SETTING: Canada receives more than 200000 immigrants annually. Immigrants account for 92% of tuberculosis (TB) cases in Toronto, Ontario. Epidemiological profiling of recent immigrants is needed to provide more effective TB programs. DESIGN: A population-based, retrospective cohort study of recent immigrants to Ontario, 1990-1997. We generated adjusted rates, risk ratios (RRs), hazard rates since arrival, and a complementary log-log model to describe TB risk, compare the survival distributions between different sexes, age groups and world regions of birth, and determine predictors of disease. RESULTS: TB in recent immigrants was 23 times (95%CI 20.9-25.5) higher than in Canadian-born, non-aboriginal people. Those aged 16-30 and >65 years experienced the highest rates. Sub-Saharan Africa had the highest rates for both sexes (RR 95.5, 95%CI 84.3-108.2), followed by India and Asia. Hazard rates decreased after arrival, but remained elevated. The highest risk was associated with arrival in 1990 and living in Canada <1 year. CONCLUSION: Risk for TB varied by region of birth, age at landing and time since arrival. Sex was not significant. Persons from sub-Saharan Africa and age >65 years were the highest risk groups. Risk decreased significantly in the first 1-2 years after arrival, after which it plateaued.

Hemopneumothorax in a COPD patient treated with noninvasive positive pressure ventilation: the risk of attendant anticoagulation.

Noninvasive positive pressure ventilation (NIPPV) modalities have been proven to be effective in the setting of exacerbations of chronic obstructive pulmonary disease (COPD). Reported complications include pneumothorax, increased work of breathing, gastric distension and air embolism. This case demonstrates that patients with severe COPD on anticoagulant therapy are potentially at risk for the serious complication of combined lung barotrauma and hemorrhage while on acute NIPPV therapy. This is the first reported case of hemopneumothorax complicating NIPPV therapy.

Expanding the epidemiologic profile: risk factors for active tuberculosis in people immigrating to Ontario.

BACKGROUND: Many people immigrating to Canada come from countries with a high burden of tuberculosis. The aim of this study was to develop a detailed epidemiologic profile of foreign-born people with tuberculosis living in Ontario. METHODS: In this population-based case-control study, cases of tuberculosis diagnosed in 1994-1995 were identified from the database of the Ontario Reportable Disease Information Service and were considered eligible for analysis if a record of landing (receipt of permission to establish residence in Canada) from the period 1986-1995 was found in the Citizenship and Immigration Canada (CIC) database, if the person was at least 11 years of age at the time their visa was issued, and if the person had not been diagnosed with tuberculosis before becoming legally landed in Canada. Control subjects, who met the same criteria as the case subjects but who did not have tuberculosis in 1994-1995, were identified from a CIC database for landed immigrants. RESULTS: A total of 1341 cases of tuberculosis in foreign-born people were reported in Ontario in 1994-1995. A record of landing was found in CIC databases for 1099 of these people, 224 of whom were not legally landed at the time of diagnosis. In total, 602 cases met the inclusion criteria. The 2 strongest determinants of risk among those who had become landed within the preceding 10 years were referral for medical surveillance by immigration officials (odds ratio [OR] 3.8, 95% confidence interval [CI] 2.6-6.0) and world region of origin (Somalia [OR 67.7, 95% CI 31.3-154.9], Vietnam [OR 25.0, 95% CI 12.5-50.0], the Philippines [OR 11.9, 95% CI 6.0-23.3], other sub-Saharan African countries [OR 11.6, 95% CI 5.7-23.2], India [OR 9.7, 95% CI 4.9-18.9], China [OR 6.1, 95% CI 3.1-12.1], other Asian countries [OR 4.7, 95% CI 2.4-9.1], the Middle East [OR 4.1, 95% CI 2.0-8.3], Latin America [OR 1.9, 95% CI 0.9-3.8), and the former socialist countries of Europe [OR 1.8, 95% CI 0.8-3.8]; the reference category was countries with established market economies). Low socioeconomic status was an independent risk factor. INTERPRETATION: The risk of tuberculosis in groups of people migrating to Ontario is highly variable and is influenced by several factors. Successful population-based tuberculosis prevention strategies will need to accommodate this variability.

Outcome of pulmonary tuberculosis treatment in the tertiary care setting--Toronto 1992/93. Tuberculosis Treatment Completion Study Group.

BACKGROUND: Completion of treatment of active cases of tuberculosis (TB) is the most important priority of TB control programs. This study was carried out to assess treatment completion for active cases of pulmonary TB in Toronto. METHODS: Consecutive cases of culture-proven pulmonary TB were obtained from the microbiology laboratories of 5 university-affiliated tertiary care centres in Toronto in 1992/93. A standard data-collection tool was used to abstract information from inpatient and outpatient charts. For patients who were transferred to other treatment centres or lost to follow-up, the local health unit was contacted for information about treatment completion. If incomplete information was obtained from these sources, data from the provincial Reportable Disease Information System were also reviewed. The main outcome analysed was treatment outcome, with cases classified as completed (record of treatment completion noted), transferred (patient transferred to another centre but no treatment results available), defaulted (record of defaulting in patient chart but no record of treatment completion elsewhere, or patient still receiving treatment more than 15 months after diagnosis) or dead (patient died before treatment completion). RESULTS: Of the 145 patients 84 (58%) completed treatment, 25 (17%) died, 22 (15%) defaulted and 14 (10%) were transferred. The corresponding values for the 22 patients with HIV coinfection were 6 (27%), 5 (23%), 8 (36%) and 3 (14%). Independent predictors of failure to complete treatment were injection drug use (adjusted odds ratio [OR] 5.7, 95% confidence interval [CI] 1.5 to 22.0), HIV infection (adjusted OR 4.6, 95% CI 1.4 to 14.7) and adverse drug reaction (adjusted OR 2.9, 95% CI 1.1 to 7.9). Independent predictors of death included age more than 50 years (adjusted OR 16.7, 95% CI 2.6 to 105.1), HIV infection (adjusted OR 16.1, 95% CI 3.9 to 66.4), immunosuppressive therapy (adjusted OR 8.0, 95% CI 1.9 to 34.4) and infection with a multidrug-resistant organism (adjusted OR 30.7, 95% CI 1.5 to 623.0). INTERPRETATION: Treatment completion rates in tertiary care hospitals in Toronto in 1992/93 were below the rate recommended by the World Health Organization. Careful surveillance of treatment completion is necessary for the management of TB in metropolitan centres in Canada.

Evaluation of Roche Amplicor PCR assay for Mycobacterium tuberculosis.

The Roche Amplicor Mycobacterium tuberculosis PCR test (RMtb-PCR) was compared with mycobacterial culture, with the BACTEC 460 system and inoculation on Lowenstein-Jensen media. Results were interpreted with an adjusted "gold standard" incorporating clinical diagnosis. A total of 1,480 clinical specimens from 1,155 patients, including tissues and fluids, as well as 141 specimens which demonstrated a positive growth index on the BACTEC 460 system were assessed. The sensitivity, specificity, and positive and negative predictive values of RMtb-PCR compared with the adjusted gold standard for clinical specimens were 79, 99, 93, and 98%, respectively. In smear-positive specimens, the sensitivity of RMtb-PCR was 98% versus 53% for smear-negative specimens. When RMtb-PCR was performed two times per week, PCR results were available an average of 21 days before the culture results. For specimens demonstrating a positive growth index on the BACTEC 460 system, RMtb-PCR had a sensitivity and specificity of 98 and 100%, respectively. This study demonstrates the value of a commercial nucleic acid amplification kit for rapid diagnosis of M. tuberculosis, particularly in smear-positive specimens or BACTEC culture-positive specimens.

Relative roles of prostaglandins and leukotrienes in canine hypoxic pulmonary vasoconstriction.

We indirectly examined the role of prostaglandins and leukotrienes in modulation of hypoxic pulmonary vasoconstriction. We used a cyclo-oxygenase inhibitor (indomethacin) and a lipoxygenase inhibitor (diethylcarbamazine) in an in-situ canine lung lobe preparation. We measured total resistance in two control groups ventilated with either 35% O2 or 3% O2 (groups CC and HC respectively). Two additional groups treated with indomethacin (groups CI and HI), and two groups treated with the combination of indomethacin and diethylcarbamazine (groups CID and HID), were also ventilated with either 35% O2 or 3% O2 respectively. Total resistance was significantly greater in hypoxic groups compared with their respective control oxygen groups. Total resistance was greatest in group HI (0.288 +/- 0.103 cm H2O.ml-1 min-1), intermediate in group HID (0.153 +/- 0.016 cm H2O.ml-1 min-1) and lowest in group HC (0.066 +/- 0.017 cm H2O.ml-1 min-1). We concluded that cyclo-oxygenase blockade augments hypoxic pulmonary vasoconstriction by decreasing production of a vasodilating prostaglandin. Hypoxia also increases production of a vasoconstricting leukotriene in the presence of cyclo-oxygenase blockade with indomethacin.

The outcome of chemoprophylaxis on tuberculosis prevention in the Canadian Plains Indian.

A 1986 audit of self-administered anti-tuberculous prophylaxis (SAP) revealed a compliance rate of 25% at six weeks, 8% at 16 weeks, and 5% at 52 weeks. A short affordable program of daily observed prophylaxis (DOP) and education was developed to improve the compliance rate. The sustaining influence of a six week intervention on one year of prophylaxis was determined. Forty-two of 114 (37%) eligible patients began chemoprophylaxis and were randomly assigned to two groups - 21 in Group 1 with DOP and education, and 21 in Group 2 with SAP and education. After six weeks, Group 1 compliance was greater than 1986 compliance (p less than 0.001) and greater than Group 2 compliance (p less than 0.05), and Group 2 compliance was greater than 1986 compliance (p less than 0.01). At 16 weeks, 10 weeks after DOP and education were discontinued, the compliance of the three groups was not different. Since 63% of persons who represent potential future tuberculosis were lost in the evaluation process before starting preventive treatment, and 5% of those who began preventive treatment completed treatment, only 2% of potential future tuberculosis was prevented. DOP and education significantly improved compliance but the improvements were not sustained after DOP and education were discontinued.