Dispersal of Mycobacterium tuberculosis via the Canadian fur trade.

Patterns of gene flow can have marked effects on the evolution of populations. To better understand the migration dynamics of Mycobacterium tuberculosis, we studied genetic data from European M. tuberculosis lineages currently circulating in Aboriginal and French Canadian communities. A single M. tuberculosis lineage, characterized by the DS6(Quebec) genomic deletion, is at highest frequency among Aboriginal populations in Ontario, Saskatchewan, and Alberta; this bacterial lineage is also dominant among tuberculosis (TB) cases in French Canadians resident in Quebec. Substantial contact between these human populations is limited to a specific historical era (1710-1870), during which individuals from these populations met to barter furs. Statistical analyses of extant M. tuberculosis minisatellite data are consistent with Quebec as a source population for M. tuberculosis gene flow into Aboriginal populations during the fur trade era. Historical and genetic analyses suggest that tiny M. tuberculosis populations persisted for ∼100 y among indigenous populations and subsequently expanded in the late 19th century after environmental changes favoring the pathogen. Our study suggests that spread of TB can occur by two asynchronous processes: (i) dispersal of M. tuberculosis by minimal numbers of human migrants, during which small pathogen populations are sustained by ongoing migration and slow disease dynamics, and (ii) expansion of the M. tuberculosis population facilitated by shifts in host ecology. If generalizable, these migration dynamics can help explain the low DNA sequence diversity observed among isolates of M. tuberculosis and the difficulties in global elimination of tuberculosis, as small, widely dispersed pathogen populations are difficult both to detect and to eradicate.

Transmission of Mycobacterium tuberculosis Beijing Strains, Alberta, Canada, 1991-2007.

Beijing strains are speculated to have a selective advantage over other Mycobacterium tuberculosis strains because of increased transmissibility and virulence. In Alberta, a province of Canada that receives a large number of immigrants, we conducted a population-based study to determine whether Beijing strains were associated with increased transmission leading to disease compared with non-Beijing strains. Beijing strains accounted for 258 (19%) of 1,379 pulmonary tuberculosis cases in 1991-2007; overall, 21% of Beijing cases and 37% of non-Beijing cases were associated with transmission clusters. Beijing index cases had significantly fewer secondary cases within 2 years than did non-Beijing cases, but this difference disappeared after adjustment for demographic characteristics, infectiousness, and M. tuberculosis lineage. In a province that has effective tuberculosis control, transmission of Beijing strains posed no more of a public health threat than did non-Beijing strains.

Who's talking? Communication between health providers and HIV-infected adults related to herbal medicine for AIDS treatment in western Uganda.

Communication between patients and physicians about herbal medicine is valuable, enabling physicians to address issues of potential herb-drug interactions and ensuring appropriate medical care. As seemingly harmless herbal remedies may have detrimental interactions with various HIV antiretroviral drugs, the importance of communication is intensified, but often stifled around the use of herbal medicine in the treatment of HIV/AIDS. In western Uganda, 137 HIV-infected adults attending conventional HIV/AIDS treatment programmes (67 of whom were receiving antiretroviral therapy) shared their experiences and perceptions about traditional herbal medicine and related patient-physician communication issues through interviews and focus group discussions. Although close to 64% of respondents reported using herbal medicine after being diagnosed with HIV, only 16% of these respondents had informed their conventional medical practitioners about using these herbs. Furthermore, only 13% of antiretroviral therapy recipients had inquired about concurrent herb-antiretroviral drug use with their HIV/AIDS treatment providers, largely because they perceived a low acceptance and support for herbal medicine by conventional medical practitioners. Importantly however, almost 68% of HIV-infected adults indicated they would be willing to discuss herbal medicine use if directly asked by a conventional medical practitioner, and the overwhelming majority (91%) said they were amenable to following physician advice about herbal medicine. As such, improved patient-physician communication about herbal medicine is needed, and we recommend that herbal medicine histories be completed when patient histories are taken. Also, HIV/AIDS treatment programmes should be encouraged to develop specific patient-physician communication standards and best practice guidelines to ensure that patients can make informed decisions about herb and pharmaceutical drug co-therapy based on known risks, particularly in the case of AIDS patients receiving antiretroviral therapy. Communication about herbal medicine usage should be viewed as a timely and cost-effective component of antiretroviral therapy programmes, one which may contribute to the overall success of AIDS treatment in Africa.

Towards the elimination of paediatric tuberculosis in high-income, immigrant-receiving countries: a 25-year conventional and molecular epidemiological case study.

The epidemiology of tuberculosis (TB) in high-income countries is increasingly dictated by immigration. The influence of this trend on paediatric TB and TB elimination are not well defined. We undertook a 25-year conventional and molecular epidemiologic study of paediatric TB in Alberta, one of four major immigrant-receiving provinces in Canada. All isolates of Mycobacterium tuberculosis were DNA fingerprinted using standard methodology. Between 1990 and 2014, 176 children aged 0-14 years were diagnosed with TB. Foreign-born children or Canadian-born children of foreign-born parents accounted for an increasingly large proportion of total cases during the study period (from 32.1% to 89.5%). Of the 78 culture-positive cases, 35 (44.9%) had a putative source case identified by conventional epidemiology, with 34 (97.1%) having a concordant molecular profile. Of the remaining 43 culture-positive cases, molecular profiling identified spatially and temporally related sources in six cases (14.0%). These six children, along with four other children whose source cases were discovered through reverse-contact tracing, had a high morbidity and mortality. The increasing burden of paediatric TB in both foreign-born children and Canadian-born children of foreign-born parents calls for more timely diagnosis of source cases and more targeted screening for latent TB infection.

Use of traditional herbal medicine by AIDS patients in Kabarole District, western Uganda.

The objective of this cross-sectional study was to assess the use of traditional herbal medicine by AIDS patients in Kabarole District, western Uganda. Using systematic sampling, 137 AIDS patients were selected from outpatient departments of 3 hospitals and interviewed via questionnaire. The questions related to such areas as type and frequency of herbal medicine intake, concomitant herb-pharmaceutical drug use (including herb-antiretroviral drug cotherapy), and the perceived effectiveness of herbal medicine. Overall, 63.5% of AIDS patients had used herbal medicine after HIV diagnosis. Same-day herbal medicine and pharmaceutical drugs use was reported by 32.8% of AIDS patients. Patterns of traditional herbal medicine use were quite similar between those on antiretroviral therapy and those who received supportive therapy only. The primary conclusion is that AIDS outpatients commonly use herbal medicine for the treatment of HIV/AIDS. Pharmacological interactions between antiretroviral drugs and traditional herbal medicines need to be further examined.

Increase in multidrug-resistant tuberculosis (MDR-TB) in Alberta among foreign-born persons: implications for tuberculosis management.

OBJECTIVES: Globally, the prevalence of anti-tuberculosis drug resistance has been increasing. This study sought to identify trends in multidrug-resistant tuberculosis (MDR-TB) among foreign-born persons in Alberta, a major immigrant-receiving province of Canada. METHODS: A retrospective cohort study design was used to investigate the prevalence of MDR-TB in foreign-born culture-positive TB cases between 1982 and 2011. Relevant demographic, clinical and laboratory data were abstracted from the TB Registry, individual medical records and the Provincial Laboratory for Public Health. RESULTS: Of the 2,234 foreign-born culture-positive TB cases in Alberta in 1982-2011, 27 (1.2%) had MDR-TB. Overall, MDR was associated with age <65 years (p=0.025), TB relapse/retreatment, and diagnosis and arrival in the last decade (2002-2011). The prevalence of MDR-TB in 2002-2011 was 2.1%, a significant increase from 0.65% in 1982-1991 (p=0.022) and 0.56% in 1992-2001 (p=0.009). Only immigrants from the Philippines and Vietnam showed a significant increase in the prevalence of MDR-TB between the first two decades and the last. Compared to MDR-TB cases reported in the first two decades, those reported in the last decade were more frequently younger than 35 years of age, new active versus relapse/retreatment cases and diagnosed with non-respiratory versus respiratory TB. In 1992-2011, MDR-TB strains had unique DNA fingerprints. CONCLUSIONS: Recent trends in the prevalence and clinical characteristics of foreign-born MDR-TB cases have important implications for TB case management in Canada. Early diagnosis of MDR-TB, using genotypic drug susceptibility testing, is suggested in foreign-born TB cases at increased risk of being MDR.

Marked disparity in the epidemiology of tuberculosis among Aboriginal peoples on the Canadian prairies: the challenges and opportunities.

BACKGROUND: While it is established that Aboriginal peoples in the prairie provinces of Canada are disproportionately affected by tuberculosis (TB), little is known about the epidemiology of TB either within or across provincial borders. METHODS: Provincial reporting systems for TB, Statistics Canada censuses and population estimates of Registered Indians provided by Aboriginal Affairs and Northern Development Canada were used to estimate the overall (2004 to 2008) and pulmonary (2007 to 2008) TB rates in the prairie provinces. The place of residence at diagnosis of pulmonary TB cases in 2007 to 2008 was also documented. RESULTS: The age- and sex-adjusted incidence of TB in Registered Indians was 52.6 per 100,000 person-years, 38 times higher than in Canadian-born 'others'. Incidence rates in Registered Indians were highest in Manitoba and lowest in Alberta. In Alberta and Saskatchewan, on-reserve rates were more than twice that of off-reserve rates. Rates in the Métis and Registered Indians were similar in Saskatchewan (50.0 and 52.2 per 100,000 person-years, respectively). In 2007 to 2008, approximately 90% of Canadian-born pulmonary TB cases in the prairie provinces were Aboriginal. Outside of one metropolitan area (Winnipeg, Manitoba), most Registered Indian and Métis pulmonary TB cases were concentrated in a relatively small number of communities north of the 53rd parallel. Rates of pulmonary TB in 11 of these communities were >300 per 100,000 person-years. In Manitoba, 49% of off-reserve Registered Indian pulmonary cases were linked to high-incidence reserve communities. INTERPRETATION: The epidemiology of TB among Aboriginal peoples on the Canadian prairies is markedly disparate. Pulmonary TB is highly focal, which is both a concern and an opportunity.

A population-based cohort study of Mycobacterium tuberculosis Beijing strains: an emerging public health threat in an immigrant-receiving country?

INTRODUCTION: Mycobacterium tuberculosis Beijing strains are frequently associated with tuberculosis outbreaks and drug resistance. However, contradictory evidence and limited study generalizability make it difficult to foresee if the emergence of Beijing strains in high-income immigrant-receiving countries poses an increased public health threat. The purpose of this study was to determine if Beijing strains are associated with high risk disease presentations relative to other strains within Canada. METHODS: This was a retrospective population-based study of culture-confirmed active TB cases in a major immigrant-receiving province of Canada in 1991 through 2007. Of 1,852 eligible cases, 1,826 (99%) were successfully genotyped. Demographic, clinical, and mycobacteriologic surveillance data were combined with molecular diagnostic data. The main outcome measures were site of disease, lung cavitation, sputum smear positivity, bacillary load, and first-line antituberculosis drug resistance. RESULTS: A total of 350 (19%) patients had Beijing strains; 298 (85%) of these were born in the Western Pacific. Compared to non-Beijing strains, Beijing strains were significantly more likely to be associated with polyresistance (aOR 1.8; 95% CI 1.0-3.3; p = 0.046) and multidrug-resistance (aOR 3.4; 1.0-11.3; p = 0.049). Conversely, Beijing strains were no more likely than non-Beijing strains to be associated with respiratory disease (aOR 1.3; 1.0-1.8; p = 0.053), high bacillary load (aOR 1.2; 0.6-2.7), lung cavitation (aOR 1.0; 0.7-1.5), immediately life-threatening forms of tuberculosis (aOR 0.8; 0.5-1.6), and monoresistance (aOR 0.9; 0.6-1.3). In subgroup analyses, Beijing strains only had a significant association with multidrug-resistant tuberculosis (aOR 6.1; 1.2-30.4), and an association of borderline significance with polyresistant tuberculosis (aOR 1.8; 1.0-3.5; p = 0.062), among individuals born in the Western Pacific. CONCLUSION: Other than an increased risk of polyresistant or multidrug-resistant tuberculosis, Beijing strains appear to pose no more of a public health threat than non-Beijing strains within a high-income immigrant-receiving country.

The tuberculin skin test is unreliable in school children BCG-vaccinated in infancy and at low risk of tuberculosis infection.

BACKGROUND: The tuberculin skin test (TST) is often used to screen for latent tuberculosis infection (LTBI) in school children, many of whom were bacille Calmette-Guérin (BCG)-vaccinated in infancy. The reliability of the TST in such children is unknown. METHODS: TSTs performed in low-risk BCG-vaccinated and -nonvaccinated grade 1 and grade 6 First Nations (North American Indian) school children in the province of Alberta, Canada, were evaluated retrospectively. To further assess the specificity of the TST, BCG-vaccinated children with a positive TST (≥10 mm of induration) and no treatment of LTBI were administered a QuantiFERON-TB Gold In-Tube test (QFT-GIT, Cellestis International). RESULTS: A total of 3996 children, 2063 (51.6%) BCG-vaccinated and 1933 (48.4%) BCG-nonvaccinated, were screened for LTBI. Vaccinated children were more likely than nonvaccinated children to be TST positive (5.7% vs. 0.2%, P < 0.001). Vaccinated children with a positive TST were more likely to have a recent past TST as compared with those with a negative TST (6.8% versus 2.8%, P = 0.01). Among 65 BCG-vaccinated TST-positive children who underwent a QFT-GIT, only 5 (7.7%; 95% CI: 2.5%, 17.0%) were QFT-GIT positive. A TST of ≥15 mm was more likely to be associated with a positive QFT-GIT than a TST of 10 to 14 mm, 16.0% (95% CI: 4.5%, 36.1%) versus 2.5% (95% CI: 0.1%, 13.2%), P = 0.047. CONCLUSION: The TST is unreliable in school children, BCG-vaccinated in infancy, and who are at low risk of infection. The QFT-GIT is a useful confirmatory test for LTBI in BCG-vaccinated TST-positive school children.