Seven-year retrospective study understanding the latent TB infection treatment cascade of care among adults in a low incidence country.

BACKGROUND: Prevention of TB is paramount to achieving elimination targets as recommended by the World Health Organization's action framework for low incidence countries striving to eliminate TB. Although the rates of TB in Canada are low, understanding the latent TB infection (LTBI) cascade is paramount to identifying gaps in care and treatment barriers, thereby increasing the effectiveness of preventive strategies. The purpose of this study was to examine the LTBI cascade of care and identify barriers to treatment completion in adults referred from primary care to a regional tertiary care TB clinic in Ottawa, Canada. METHODS: Electronic medical records between January 2010 and December 2016 were reviewed retrospectively and an LTBI cascade of care was constructed from The Ottawa Hospital TB clinic and surrounding primary care clinics. A cohort of 2207 patients with untreated LTBI was used to ascertain the associations between demographic and clinical factors for both treatment non-initiation and non-completion using log-binomial univariable and multivariable regression models. RESULTS: Of 2207 patients with untreated LTBI who were seen in the clinic during the study period, 1771 (80.2%) were offered treatment, 1203 (67.9% of those offered) started treatment, and 795 (66.1% of those started) completed treatment. In multivariable analysis, non-initiation of treatment was associated with older age (adjusted risk ratio [aRR] 1.06 per 5-year increase, 95% CI: 1.03-1.08) and female gender (aRR 1.28, 95% CI: 1.11-1.47). Non completion of treatment was associated with referral from the TB Clinic back to the primary care team following initial consult (aRR 1.62, 95% CI: 1.35-1.94) and treatment with the standard of 9 months of Isoniazid (9H) compared to 4 months of Rifampin (4R) (aRR 1.45, 95% CI:1.20-1.74). CONCLUSIONS: LTBI treatment completion was significantly decreased among patients who were referred back to primary care from the TB clinic. The 4R regimen resulted in more people completing LTBI treatment compared to 9H in keeping with a recently published RCT. Improved education, communication, and collaboration between tertiary care TB clinics and primary care teams may improve treatment completion rates and address the TB burden in low incidence communities in Canada.

A case of relapsed Mycobacterium chelonae pulmonary infection presenting with severe weight loss and treated with a combination of antibiotic therapy and percutaneous feeding.

Mycobacterium chelonae is a type of nontuberculous mycobacteria most commonly associated with skin and soft tissue infections. We present a case of recurrent M. chelonae pulmonary infection presenting with severe weight loss. After recurrence, sputum cultures remained positive for 2 years despite appropriate antibiotics. Cultures only became negative after the addition of intravenous imipenem and jejunostomy feeds. The rarity of M. chelonae pulmonary infection means that optimal treatment regimens have not yet been fully established but a regimen of clarithromycin plus an additional antibiotic has been recommended1. The prognosis of such infections also remains unclear but lower rates of macrolide resistance suggest that the prognosis may be better than the closely related species M. abscessus. Although its benefit has not been proven, nutrition supplementation, including percutaneous enteral feeding, can be considered for refractory NTM infection in underweight patients.

The implementation of rifapentine and isoniazid (3HP) in two remote Arctic communities with a predominantly Inuit population, the Taima TB 3HP study.

Background: The incidence of TB among Inuit is the highest in Canada. A significantly shorter latent TB infection (LTBI) treatment with rifapentine and isoniazid once weekly for 12 weeks (3HP) is now available in limited settings in Canada.Methods: A prospective open-label 2-year observational postmarketing study was conducted introducing 3HP for the first time in Canada in Iqaluit followed by a program rollout in Qikiqtarjuaq, Nunavut.Results: A total of 247 people were offered 3HP, 102 in the Iqaluit postmarketing study and 145 in the Qikiqtarjuaq program roll out. Although statistical significance was not reached, more people who started treatment completed treatment in the 3HP group (Iqaluit, 60/73 (82.2%) and Qikiqtarjuaq, 89/115 (77.4%)) than in the historical control 9INHgroup (306/420 = 72.9%) (p = 0.2). Most of the adverse events in 3HP treated patients were associated with mild discomfort but no disruption of normal daily activity. Not drinking alcohol was associated with increased 3HP completion (OR 13.33, 95% CI, 2.27-78.20) as was not taking concomitant medications (OR 7.19, 95% CI, 1.47-35.30).Conclusions: The present study supports the feasibility and safety profile of 3HP for the treatment of LTBI in Nunavut.

Paediatric tuberculosis among the foreign-born: utility of the Canadian TB immigration medical surveillance programme.

BACKGROUND: There are few data on the utility of screening paediatric immigrants for tuberculosis (TB) in low TB burden countries. OBJECTIVE: To evaluate the utility of the Canadian immigration medical examination and TB Medical Surveillance (TBMS) for detecting paediatric TB disease. DESIGN: A 10-year population-based retrospective cohort study of foreign-born children (ages 0-10 years) and adolescents (ages 11-17 years) immigrating to Ontario, Canada, using linked immigration and public health databases. RESULTS: Among 232 169 individuals (median follow-up of 5.7 years), active TB was diagnosed at or after immigration in 125 cases (20 children and 105 adolescents), at an overall rate of 54/100 000 (14/100 000 children, 116/100 000 adolescents). All cases originated from 34 countries. Active TB was diagnosed in 0/419 children and 10/418 adolescents referred for medical surveillance, representing only 8.0% of all cases. TBMS referrals were correlated with a previous diagnosis of TB (κ = 0.8) and were driven by country of origin (e.g., hazard ratio 31.2 for the Philippines). Rates of pre-immigration TB diagnosis varied considerably among high TB burden countries. CONCLUSIONS: The current Canadian system detects little TB disease, and reveals very different rates of pre-immigration paediatric TB diagnosis in different high TB burden countries. These data provide a basis for improving TB screening strategies for immigrants to low TB burden countries.

A shorter treatment regimen for latent tuberculosis infection holds promise for at-risk Canadians.

Despite recent success in reducing its incidence, tuberculosis remains a considerable challenge in Canada, particularly among foreign-born and Indigenous populations. A key component of the strategy for controlling the disease is the treatment of latent tuberculosis infection. The standard treatment consists of isoniazid (INH) daily for nine months. In recent years, shorter regimens have been developed in the hope of increasing rates of treatment acceptance and completion. Of these, the shortest and most recently developed is a combination of INH and rifapentine taken once weekly for 12 doses (3HP), typically using directly observed therapy (DOT). This regimen has been approved by the Food and Drug Administration in the United States but is not yet authorized in Canada. Based on a rapidly expanding number of observational studies and randomized controlled trials, 12 weeks of 3HP appears to have similar efficacy to nine months of INH, a favourable adverse event profile and potentially improved rates of treatment completion. Although rates of treatment acceptance, the role of self-administered therapy and the regimen's cost-effectiveness within the Canadian context remain uncertain, 3HP is a promising alternative to existing treatments for LTBI.

Primary care pearls to help eliminate tuberculosis in Canada.

Although Canada has a low incidence of tuberculosis (TB), certain populations, including the foreign-born and Canadian-born Indigenous peoples, continue to be disproportionately represented among reported cases. The overall incidence rates of active TB in Canada have not significantly changed in the past decade and work still needs to be done to reach TB elimination goals set by the World Health Organization (WHO). In trying to achieve TB elimination in Canada, primary care clinicians, with the support of public health professionals and TB experts, can help by focusing on 1) targeted screening and treatment of latent TB infection (LTBI) and 2) timely diagnosis and referral of active TB disease. The following article focuses on some key primary care considerations to keep in mind in day-to-day patient care. To help conduct targeted screening and treatment for LTBI, several key populations, including immigrants from high TB burden countries, Indigenous peoples and several other at-risk groups, are outlined. Reactivation of LTBI plays a significant role in TB burden and is likely an area of major potential impact in achieving TB elimination. Advancement in LTBI treatment, including short course therapy, is also described. In addition, to help make a timely diagnosis of active TB, several key risk factors, including several co-morbidities which increase the risk of developing TB disease, can be considered. Being front-line in patient care, keeping in mind some of these key pearls may aid primary care providers to have potential impact on eliminating TB in Canada.

A retrospective review of cancer treatments and outcomes among Inuit referred from Nunavut, Canada.

BACKGROUND: Cancer is a health concern in Inuit populations. Unique cultural, dietary, and genetic factors and geographic isolation influence cancer epidemiology in this group. Inuit-specific data about oncology treatments and survival outcomes in Canadian Inuit referred to urban treatment centres are lacking. METHODS: A retrospective chart review of Inuit patients referred to The Ottawa Hospital Cancer Centre (tohcc) from the Baffin region of Nunavut between 2000 and 2010 was conducted. Nunavut cancer registry data were used to establish the percentage of cancer cases referred and their survival outcomes. RESULTS: Of 307 cancer patients registered among Baffin-region Inuit, 216 [70% (63 men, 153 women)] were referred to tohcc for chemotherapy (ct) and radiation therapy (rt). Mean age in the referred group was 59.3 years (range: 25-89 years), and current smokers constituted half the group (52%). The cancers most commonly leading to referral in men were lung (55%), colorectal (19%), and nasopharyngeal (11%) cancers; in women, they were lung (46%), colorectal (24%), breast (10%), nasopharyngeal (6%), and cervical (5%) cancers. Of the 216 referred patients, 82 (38%) had already undergone surgery, and 18 (8%) received chemoradiation or rt only, all given with curative intent. Among the surgical patients referred, 33 (40%) and 23 (28%) went on to receive adjuvant ct and adjuvant rt respectively. Among 116 patients referred for palliative care, 64 (55%) received ct, 76 (66%) received rt, 43 (37%) received both ct and rt, and 19 (16%) received neither treatment. Median all-stage overall survival was 10 months for patients with lung cancer [95% confidence interval: 6.1 to 13.9 months] and 37 months for patients with colorectal cancer [95% confidence interval: 14.8 to 59.2 months]. CONCLUSIONS: High uptake of palliative and adjuvant ct and rt was observed in the Inuit patients referred to tohcc. Lung cancer was the most common cancer in referred Inuit men and women. The survival rates for Inuit lung cancer patients referred to tohcc were comparable to those in the rest of Canada. Further research is required to understand reasons for non-referral of Canadian Inuit to tohcc.

Sputum induction for tuberculosis diagnosis in an Arctic setting: a cost comparison.

SETTING: Tuberculosis (TB) incidence was 234 per 100 000 in Nunavut, Canada, in 2012. Until recently, some individuals seen in local clinics for presumed TB required costly air evacuation to Southern Canada (Ottawa) for investigation if they were unable to produce sputum spontaneously. OBJECTIVE: To estimate the cost per individual evaluated for TB, associated with the establishment of a sputum induction programme in Iqaluit, Nunavut, Canada. DESIGN: A decision analysis model compared the total cost per individual for two strategies: 1) initial investigation in Iqaluit, with transport to Ottawa for those requiring sputum induction; and 2) sputum induction at the hospital in Iqaluit, with further investigation in Ottawa only if needed. The model simulated diagnostic and treatment paths from the initial clinic visit to completion of TB investigation or treatment (when applicable). RESULTS: The estimated cost per person evaluated for TB with sputum induction in 1) Ottawa vs. 2) Iqaluit was CAD4798 (95% uncertainty range 2923-6650) vs. CAD2479 (1206-4256), respectively. Total costs were influenced by underlying TB prevalence, but local sputum induction consistently yielded cost savings. CONCLUSION: Providing sputum induction in a high-incidence Arctic community such as Iqaluit is projected to generate substantial cost savings in the investigation and management of individuals with presumed TB.

Diagnostic accuracy and clinical role of rapid C-reactive protein testing in HIV-infected individuals with presumed tuberculosis in South Africa.

OBJECTIVE: To determine the accuracy and role of rapid C-reactive protein (CRP) testing in human immunodeficiency virus (HIV) infected individuals with presumed tuberculosis (TB). DESIGN: We enrolled HIV-infected adults (≥18 years)with a cough of ≥2 weeks and negative sputum smears for acid-fast bacilli in KwaZulu-Natal, South Africa. Participants were evaluated for pulmonary TB (PTB) by a nurse with rapid CRP, and independently by a physician by chest radiograph. Rapid CRP test results were compared with laboratory CRP and sputum sent for confirmation of TB. RESULTS: Among 93 participants, 55 (59%) were female, the mean age was 35 years, and the median CD4 count was 177/mm3. Forty-five (54%) participants were diagnosed with PTB. Diagnostic sensitivity and specificity were respectively 95% (95%CI 74­99) and 51%(95%CI 35­66) for rapid CRP >8 mg/l, 87% (95%CI 73­96) and 53% (95%CI 38­68) for nurse assessment, and 69% (95%CI 52­83) and 76% (95%CI 61­87) for physician examination. Combining a negative rapid CRP(≤8 mg/l) with nurse and physician assessments reduced the post-test probability of PTB from 22% to 6% and from 32% to 6%, respectively. CONCLUSION: Rapid CRP testing helped exclude PTB,and may be a valuable test in assisting nurses and physicians in TB-endemic regions.

A model to rule out smear-negative tuberculosis among symptomatic HIV patients using C-reactive protein.

SETTING: Improved diagnostic algorithms for sputum smear-negative tuberculosis (SNTB) are needed to address the dramatic increase in SNTB in regions with high human immunodeficiency virus (HIV) prevalence. OBJECTIVE: To determine whether the addition of C-reactive protein (CRP) to a prediction model using simple clinical criteria improves the diagnosis of SNTB among mostly antiretroviral-naïve adult HIV TB suspects in an out-patient setting. DESIGN: A multiple logistic regression model was derived from a database of 228 HIV patients to predict the risk of SNTB using data from a previous prospective study. RESULTS: The derived model demonstrated that male sex, night sweats, fever, low body mass index and anemia increased the probability of having SNTB. CRP improved the accuracy of the model (without CRP, area under the curve [AUC] 0.75, 95%CI 0.68-0.81 vs. model with CRP, AUC 0.81, 95%CI 0.76-0.87, P = 0.0014) to predict SNTB. Using reclassification tables, CRP correctly reclassified 27.9% of the patients (net reclassification improvement, P = 0.0005) into higher or lower risk categories. The strongest effect was seen in the reclassification improvement among patients with no TB, which was 20.6% (P = 0.0023). CONCLUSION: CRP improved the performance of the prediction model in the diagnosis of SNTB in HIV patients, and may play a role in ruling out SNTB in this population. Prospective validation of this model is needed.

A systematic review of the epidemiology, immunopathogenesis, diagnosis, and treatment of pleural TB in HIV-infected patients.

BACKGROUND: High HIV burden countries have experienced a high burden of pleural TB in HIV-infected patients. OBJECTIVE: To review the epidemiology, immunopathogenesis, diagnosis, and treatment of pleural TB in HIV-infected patients. METHODS: A literature search from 1950 to June 2011 in MEDLINE was conducted. RESULTS: Two-hundred and ninety-nine studies were identified, of which 30 met the inclusion criteria. The immunopathogenesis as denoted by cells and cytokine profiles is distinctly different between HIV and HIV-uninfected pleural TB disease. Adenosine deaminase and interferon gamma are good markers of pleural TB disease even in HIV-infected patients. HIV-uninfected TB suspects with pleural effusions commonly have a low yield of TB organisms however the evidence suggests that in dually infected patients smear and cultures have a higher yield. The Gene Xpert MTB/RIF assay has significant potential to improve the diagnosis of pleural TB in HIV-positive patients. CONCLUSIONS: Pleural TB in HIV-infected patients has a different immunopathogenesis than HIV-uninfected pleural TB and these findings in part support the differences noted in this systematic review. Research should focus on developing an interferon gamma-based point of care diagnostic test and expansion of the role of Gene Xpert in the diagnosis of pleural TB.

Effective screening tool to triage recovery rooms for possible tuberculosis patients undergoing bronchoscopy.

SETTING: In 2005, tuberculin skin test conversions were observed following exposure to a patient with active pulmonary tuberculosis (TB) who recovered post-bronchoscopy in an open area at The Ottawa Hospital, Canada. In response, we implemented a screening tool to triage patients to an airborne infection isolation (AII) room pre- and post-bronchoscopy. OBJECTIVE: To evaluate the performance of the screening tool in detecting patients with culture-confirmed TB. DESIGN: All bronchoscopies performed between 1 March 2006 and 31 March 2010 were retrospectively reviewed. RESULTS: Of 1839 patients included (55.3% of bronchoscopies), 210 screened positive, capturing 28 culture-confirmed TB cases. Three patients with positive TB cultures screened negative. The sensitivity of the screening tool was 90.3%; the negative predictive value was 99.8%. A positive screening result was strongly predictive of a positive TB culture. CONCLUSIONS: The screening tool is effective for identifying high-risk patients and triaging them to AII rooms. The pre-bronchoscopy screening tool is simple and inexpensive to implement and has the potential to reduce intra-institutional spread of TB.

Pediatric tuberculosis immigration screening in high-immigration, low-incidence countries.

BACKGROUND: Tuberculosis (TB) screening in migrant children, including immigrants, refugees and asylum seekers, is an ongoing challenge in low TB incidence countries. Many children from high TB incidence countries harbor latent TB infection (LTBI), and some have active TB disease at the point of immigration into host nations. Young children who harbor LTBI have a high risk of progression to TB disease and are at a higher risk than adults of developing disseminated severe forms of TB with significant morbidity and mortality. Many countries have developed immigration TB screening programs to suit the needs of adults, but have not focused much attention on migrant children. OBJECTIVE: To compare the TB immigration medical examination requirements in children in selected countries with high immigration and low TB incidence rates. DESIGN: Descriptive study of TB immigration screening programs for systematically selected countries. RESULTS: Of 18 eligible countries, 16 responded to the written survey and telephone interview. CONCLUSION: No two countries had the same approach to TB screening among migrant children. The optimal evidenced-based manner in which to screen migrant children requires further research.

Tuberculosis retreatment category predicts resistance in hospitalized retreatment patients in a high HIV prevalence area.

SETTING: Rates of multidrug-resistant tuberculosis (MDR-TB) are currently as high as 7.7% in retreatment cases in KwaZulu-Natal, South Africa. MDR-TB prevalence is known to be high in patients categorized as treatment failures. Recent reports have questioned the effectiveness of the World Health Organization (WHO) Category II regimen in retreatment TB cases. OBJECTIVE: To determine whether treatment category predicts susceptibility patterns and outcomes in a hospitalized population of retreatment TB cases. DESIGN: Retrospective cohort of 197 pulmonary retreatment cases. RESULTS: Retreatment cases treated with the standard retreatment regimen had a high in-hospital mortality (19.8%), or poor outcome (26.4%) and a high rate of MDR-TB (16.2%). The 'treatment failure' category predicted resistance, with 57.1% of patients exhibiting any resistance compared to other treatment categories (P = 0.02); 53.8% of patients with any resistance experienced poor outcomes, compared to 16.6% of pan-susceptible cases (P = 0.02). There was a trend towards poor outcome in the treatment failure category (42.9%, P = 0.13). CONCLUSION: The retreatment category 'treatment failure' is associated with a high prevalence of resistance in an area of high human immunodeficiency virus (HIV) prevalence. The 'treatment failure' category should be used to identify patients who may benefit from alternative regimens using directed, intensified therapy or second-line agents instead of the current standard retreatment regimen.

"Crack lung and heart" presenting after chemotherapy in a 65-year-old man with non-Hodgkin lymphoma.

Crack cocaine can cause a variety of pulmonary and cardiac complications. Pulmonary findings in a 65- year-old man with non-Hodgkin lymphoma who presented with shortness of breath not resolving with antibiotics are presented here. The usual manifestation of "crack lung" in an unusual clinical circumstance underlines the importance of a clinical history in such cases. The finding of "crack lung" preceded the diagnosis of probable "crack heart." No other similar published case reports could be identified in the literature.

A systematic review of the psychological risk factors associated with near fatal asthma or fatal asthma.

Psychological factors such as anxiety, depressive disorders and/or personality disorders may predispose patients with asthma to near fatal asthma (NFA) or fatal asthma (FA). NFA is defined by an asthma exacerbation resulting in respiratory arrest requiring mechanical ventilation or a pCO(2) >or=45 mm Hg. Most studies have used the case-control study design. Several studies analyzing the effects of psychological factors on the risk of NFA or FA have shown conflicting results. We reviewed all of the literature found by the systematic search done of psychological factors on the risk NFA or FA. A MEDLINE search identified 423 articles between 1960 and March 2006. Seven case-controlled studies were identified following strict applications of the inclusion and exclusion criteria. Due to the significant heterogeneity in the measurement of the psychological factors, a summary statistic was not calculated. The trial characteristics were tabulated and qualitative trends were observed to explain the heterogeneity in the results of the studies. Recommendations on future studies in the field are outlined in detail. Following a systematic assessment of all published studies, we cannot conclude that psychological factors increase the risk of NFA and FA.

Blastomycosis in a young African man presenting with a pleural effusion.

Blastomyces dermatitidis is a dimorphic fungus endemic to north-western Ontario, Manitoba and some parts of the United States. The fungus is also endemic to parts of Africa. Pulmonary and extrapulmonary findings of a 24-year-old African man who presented with weight loss, dry cough and chronic pneumonia not resolving with antibiotic treatment are presented. The unusual occurrence of pulmonary blastomycosis associated with skin lesions and a moderate pleural effusion is reported.