Impact and benefit-cost ratio of a program for the management of latent tuberculosis infection among refugees in a region of Canada.

INTRODUCTION: The identification and treatment of latent tuberculosis infection (LTBI) among immigrants from high-incidence regions who move to low-incidence countries is generally considered an ineffective strategy because only ≈14% of them comply with the multiple steps of the 'cascade of care' and complete treatment. In the Estrie region of Canada, a refugee clinic was opened in 2009. One of its goals is LTBI management. METHODS: Key components of this intervention included: close collaboration with community organizations, integration within a comprehensive package of medical care for the whole family, timely delivery following arrival, shorter treatment through preferential use of rifampin, and risk-based selection of patients to be treated. Between 2009-2020, 5131 refugees were evaluated. To determine the efficacy and benefit-cost ratio of this intervention, records of refugees seen in 2010-14 (n = 1906) and 2018-19 (n = 1638) were reviewed. Cases of tuberculosis (TB) among our foreign-born population occurring before (1997-2008) and after (2009-2020) setting up the clinic were identified. All costs associated with TB or LTBI were measured. RESULTS: Out of 441 patients offered LTBI treatment, 374 (85%) were compliant. Adding other losses, overall compliance was 69%. To prevent one case of TB, 95.1 individuals had to be screened and 11.9 treated, at a cost of $16,056. After discounting, each case of TB averted represented $32,631, for a benefit-cost ratio of 2.03. Among nationals of the 20 countries where refugees came from, incidence of TB decreased from 68.2 (1997-2008) to 26.3 per 100,000 person-years (2009-2020). Incidence among foreign-born persons from all other countries not targeted by the intervention did not change. CONCLUSIONS: Among refugees settling in our region, 69% completed the LTBI cascade of care, leading to a 61% reduction in TB incidence. This intervention was cost-beneficial. Current defeatism towards LTBI management among immigrants and refugees is misguided. Compliance can be enhanced through simple measures.

In the footsteps of Albert Calmette: an ecological study of TB, leprosy and potential exposure to wild-type Mycobacterium bovis.

BACKGROUND: One hundred years ago, Albert Calmette developed an avirulent strain of Mycobacterium bovis, but there is no evidence that his BCG strain was more immunogenic than wild-type M. bovis. Geographic variations in BCG efficacy remain ill-understood. We hypothesized that exposure to M. bovis through unpasteurized milk might protect against Mycobacterium tuberculosis and Mycobacterium leprae. METHODS: After excluding high-income countries (with universal milk pasteurization) and microstates, an ecological study comprising 113 countries was conducted. National data were obtained from United Nations agencies and international organizations about milk production per capita (1980-1999) as a proxy for exposure to wild-type M. bovis, TB (2000-2019) and leprosy (2005-2019) incidence, HIV prevalence (2000-2019), human development index (2010), global hunger index (2010), neonatal BCG coverage (1980-1999), urbanization (2000) and temperature (1990-2020). Multiple linear regression analyses were performed using log-transformed variables. RESULTS: For TB, the association differed by region. An inverse association with milk production was seen in regions outside, but not within, sub-Saharan Africa, after adjustment for confounders. The incidence of leprosy was inversely associated with milk production when combining all countries, but the association was stronger in sub-Saharan Africa. CONCLUSIONS: Exposure to wild-type M. bovis through unpasteurized milk may provide cross-protection against M. tuberculosis and M. leprae and contribute to geographic disparities in BCG efficacy. This needs to be confirmed by individual-level studies.

JC Virus Granule Cell Neuronopathy as AIDS-Presenting Illness.

JC virus is the etiological agent of progressive multifocal leukoencephalopathy, a white matter demyelinating disease that mostly affects immunocompromised patients. JC virus can also infect neurons and meningeal cells and cause encephalitis, meningitis and granule cell neuronopathy. We report a patient with JC virus granule cell neuronopathy, without concomitant progressive multifocal leukoencephalopathy, presenting as inaugural acquired immune deficiency syndrome-related illness. This patient's human immunodeficiency virus infection remained undiagnosed for several months after neurological symptoms onset. We review JC virus pathophysiology, clinical manifestations, treatment and prognosis, and emphasize the importance of considering human immunodeficiency virus infection and related opportunistic infections in the differential diagnosis of new-onset isolated cerebellar disease.

Case Series: Report of the First Two Human Indigenous Cases of Cryptococcus gattii Infection in Eastern Canada.

We report the two first cases of human C. gattii meningoencephalitis acquired on the Canadian east coast, from the province of Quebec. Unlike C. neoformans, C. gattii is not known to have an established ecological niche on the North American east coast. C. gattii has recently been responsible for major outbreaks in British Columbia, Canada, and in the American pacific northwest. However, no human cases acquired in other Canadian provinces have been reported to our knowledge. The source of acquisition remains unclear for both patients but since neither had traveled outside of the province of Quebec, we discuss the possibilities of environmental and animal-associated acquisition, as well as the possible established endemicity in new areas. These cases add to the growing reported human and animal cases in areas previously not thought to be endemic for C. gattii.

Fluoroquinolones and risk for methicillin-resistant Staphylococcus aureus, Canada.

Receipt of fluoroquinolones was the predominant risk factor for Clostridium difficile-associated disease (CDAD) during an epidemic in Quebec, Canada. To determine the role of antimicrobial drugs in facilitating healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection and to compare this role with their effects on methicillin-susceptible S. aureus infection and CDAD, we conducted a retrospective cohort study of patients in a Quebec hospital. For 7371 episodes of care, data were collected on risk factors, including receipt of antimicrobial drugs. Crude and adjusted hazard ratios (AHR) were calculated by Cox regression. Of 150 episodes of MRSA colonization and 23 of MRSA infection, fluoroquinolones were the only antimicrobials that increased risk for colonization (AHR 2.57, 95% confidence interval [CI] 1.84-3.60) and infection (AHR 2.49, 95% CI 1.02-6.07). Effect of antimicrobial drugs on MRSA colonization and infection was similar to effect on CDAD and should be considered when selecting antimicrobial drugs to treat common infections.

An observational study comparing 2-hour 75-g oral glucose tolerance with fasting plasma glucose in pregnant women: both poorly predictive of birth weight.

BACKGROUND: The definition and treatment of glucose intolerance during pregnancy are matters of intense controversy. Our goal was to examine the value of the 75-g oral glucose tolerance test (OGTT) in terms of its ability to predict birth weight percentile in a group of women with singleton pregnancies who received minimal treatment for their glucose intolerance. METHODS: We reviewed the results of OGTTs performed between 24 and 28 weeks' gestation in a group of 300 consecutive high-risk women (mean age 29.5 years [95% confidence interval, CI, 28.9-30.1]; parity 1.5 [95% CI 1.4-1.7]) whose plasma glucose level 1 hour after a randomly administered 50-g glucose load was 8.0 mmol/L or above. These data were compared with results for a randomly selected control group of 300 women whose plasma glucose level 1 hour after a 50-g glucose load was less than 8.0 mmol/L (mean age 28.0 years [95% CI 27.4-28.6]; parity 1.5 [95% CI 1.3-1.6]). RESULTS: For 76 (25.3%) of the 300 high-risk women, the plasma glucose level 2 hours after a 75-g glucose load (confirmatory OGTT) was 7.8 mmol/L or more, but only 6 of these were treated with insulin, which emphasizes the low level of intervention in this group. Thirty (10.0%) of the neonates in this group were large for gestational age (LGA; adjusted weight at or above the 90th percentile). This proportion did not significantly differ from the proportion for the control group (25 or 8.3%). After exclusion of the 6 insulin-treated women, simple correlations between birth weight percentile and fasting or 2-hour plasma glucose levels were very weak (r = 0.23 and 0.16 respectively; p < 0.01). The correlation between birth weight percentile and fasting or 2-hour plasma glucose persisted in a multiple regression analysis that included the following maternal variables: age, prepregnancy weight, weight gain during pregnancy, parity and smoking. In the multivariate models, the standardized coefficients for fasting and 2-hour plasma glucose levels were low (r = 0.19 [p < 0.001] and r = 0.13 [p = 0.02] respectively). These multivariate models could not explain more than 22% of the total variability in birth weight percentile. INTERPRETATION: In this population of pregnant, untreated diabetic women, plasma glucose levels (either fasting or after various glucose loads) were independently but poorly correlated with birth weight; no more than 3% to 5% of birth weight variability could be explained by changes in glucose tolerance. Fasting plasma glucose was consistently but marginally better than the plasma glucose level 2 hours after 75-g glucose load for predicting LGA neonates. We conclude that neonatal macrosomia is influenced by variables that are largely independent of plasma glucose concentrations.