Chapter 13: Canadian Tuberculosis Standards 7th Edition: 2014 – Tuberculosis surveillance and screening in selected high-risk populations
- Table of Contents
- Chapter 1. Epidemiology of Tuberculosis in Canada
- Chapter 2. Pathogenesis and Transmission of Tuberculosis
- Chapter 3. Diagnosis of Active Tuberculosis and Drug Resistance
- Chapter 4. Diagnosis of Latent Tuberculosis Infection
- Chapter 5. Treatment of Tuberculosis Disease
- Chapter 6. Treatment of Latent Tuberculosis Infection
- Chapter 7. Nonrespiratory Tuberculosis
- Chapter 8. Drug-resistant Tuberculosis
- Chapter 9. Pediatric Tuberculosis
- Chapter 10. Tuberculosis and Human Immunodeficiency Virus
- Chapter 11. Nontuberculous Mycobacteria
- Chapter 12. Contact Follow-up and Outbreak Management in Tuberculosis Control
- Chapter 13. Tuberculosis Surveillance and Screening in Selected High-risk Populations
- Chapter 14. Tuberculosis Prevention and Care in First Nations, Inuit and Métis Peoples
- Chapter 15. Prevention and Control of Tuberculosis Transmission in Health Care and Other Settings
- Chapter 16. Bacille Calmette-Guérin (BCG) Vaccination in Canada
Chapter 13 - Tuberculosis surveillance and screening in selected high-risk populations
Chris Greenaway, MD, MSc
Kamran Khan, MD, MPH, FRCPC
Kevin Schwartzman, MD, MPH
Table of Contents
- Key Messages/Points
- Screening - Definitions, Tools and Goals
- Targeting Groups for Screening
- Screening Immigrants for Tuberculosis Infection and Disease
- Screening of People with Medical or Behavioral Risks for TB Infection and Disease
- Conclusions and Recommendations
- Screening for and treatment of latent tuberculosis infection (LTBI) should only be undertaken if the local TB control program already effectively manages active TB cases and their contacts.
- The selection of people for targeted LTBI screening and treatment is based on their risk of prior TB exposure and their risk of reactivation, balanced against the likelihood of safe completion of treatment, including the risk of hepatotoxicity, which increases with age.
- Groups discussed in this chapter that may warrant targeted screening are the foreign-born, people with non-HIV immune suppression and other medical or behavioural risk factors for TB, and long-term visitors to countries with higher TB incidence.
- Other groups that may be considered for targeted LTBI screening are discussed in other chapters and include TB contacts, people with HIV infection, Canadian-born Aboriginal Peoples, children, and employees and users of health care and correctional facilities.
- Most foreign-born groups undergo a mandatory medical examination prior to arrival in Canada, which includes chest radiography to detect active TB. Those found to have active TB must be treated prior to arrival to ensure that they are no longer infectious. Citizenship and Immigration Canada (CIC) requires that individuals with previously treated TB and those with abnormal chest radiographs but without active TB detected in this program undergo TB surveillance after arrival.
- Only a small proportion of all cases of active TB diagnosed in the foreign-born after arrival in Canada are detected during the immigration post-landing surveillance program. This underscores the need for additional screening programs for subgroups of the foreign-born at increased risk of TB reactivation.
- To improve uptake of LTBI screening and treatment in the foreign-born population, investment in TB education programs for patients and providers should be considered together with delivery of care in a culturally sensitive manner with good access to interpreters.
- To improve the likelihood of safe completion of LTBI treatment in vulnerable groups, such as injection drug users and the homeless, it is suggested that patients be assessed to determine coexisting viral hepatitis in order to decrease the possibility of hepatotoxic effects of LTBI treatment. Those at highest risk of reactivation should be considered for special measures to enhance adherence, such as directly observed LTBI treatment and/or incentives and enablers.
The last three decades have seen marked shifts in the epidemiology of TB in Canada. Active disease is increasingly concentrated in specific population subgroups, notably the foreign-born, Aboriginal Peoples and people with medical, social and/or behavioural risk factors, such as HIV infection, homelessness and injection drug use (refer to Chapter 1, Epidemiology of Tuberculosis in Canada).
While it is recommended that the first priorities in TB control remain the timely detection and treatment of active TB followed by suitable management of contacts at risk, the concentration of TB in specific groups makes it relevant to consider targeted screening. Targeted screening interventions systematically seek to diagnose and treat active TB or LTBI among those at increased risk of infection and/or progression to active disease. In this chapter, the focus is on TB surveillance and screening of immigrants and refugees; people with non-HIV immune suppression and other medical, social or behavioural risk factors for TB; and long-term visitors to higher-incidence countries. Screening and management of active TB and LTBI among TB contacts, people with HIV infection, Aboriginal Peoples, children, and employees and users of health care and correctional facilities are discussed in other chapters.
Surveillance refers to an ongoing process of (a) systematic collection of pertinent, high-quality data; (b) orderly consolidation and evaluation of these data; and (c) prompt dissemination of the results to those who need to know, particularly those who are in a position to take actionReference 1.
Generally, the objectives of a surveillance program are to guide health interventions, estimate trends, identify groups at high risk, monitor changes in patterns of transmission, evaluate prevention strategies and suggest hypotheses for further research.
It is important for providers and public health authorities to understand the distribution of TB in Canadian communities and to detect transmission. Moreover, suitable documentation of the outcomes of screening interventions (e.g. contact investigation, chest radiography for immigrants) allows for quality control assessment and informed decision-making about future policies and their potential targets.
In the context of immigration, the term "medical surveillance" refers to the process whereby immigrants and refugees with inactive TB or previous TB treatment detected in the pre-arrival TB screening program are required by CIC to report to local public health authorities for examination and follow-up.
Screening - Definitions, Tools and Goals
Screening refers to a process that attempts to discover conditions suitable for early preventive or curative intervention. These conditions may not be sufficiently symptomatic to induce patients to seek medical help on their own. Screening may be justified by the prevalence and/or potential severity of the target condition, when its detection permits intervention that improves outcomesReference 2. In the case of active TB, the goal is to reduce unfavourable outcomes and interrupt transmission by instituting prompt and effective treatment. The goal of targeted screening for LTBI is to reduce the likelihood of subsequent progression to active disease among people at increased risk by appropriate initiation, supervision and successful completion of treatment.
Symptom screens and chest radiography are the primary screening tools when the focus is the identification of prevalent, undiagnosed active cases of infectious pulmonary TB (so as to treat and render them noninfectious). Subsequent microbiologic confirmation with sputum smear and culture or other suitable specimens is always recommended (refer to Chapter 6, Treatment of Latent Tuberculosis Infection).
When the focus of screening is the detection of LTBI, either the tuberculin skin test (TST) or the interferon gamma-release assays (IGRAs) may be used. Conditions under which either test is preferred and their interpretation are reviewed in Chapter 4, Diagnosis of Latent Tuberculosis Infection. Positive screening tests for LTBI should be followed by chest radiography to address the possibility of subclinical active TB. Chest radiography also identifies abnormalities that are associated with increased reactivation risk.
- The highest priority in TB control programs is to detect and treat active TB cases and to investigate their contacts.
- Screening and treatment for LTBI should only be undertaken if the TB control program effectively manages active TB cases and their contacts.
- Screening for LTBI is only appropriate when available infrastructure and resources allow the monitoring and support needed to achieve safe and complete treatmentReference 3.
(Strong recommendations, based on moderate to strong evidence)
Targeting Groups for Screening
The choice of which groups should be targeted for LTBI screening and treatment should be based on a number of factors, and the assessment is usually performed in various settings by different professionals, such as public health, occupational health, primary care or subspecialty physicians. The most important factors to take into consideration when selecting people as suitable candidates for LTBI screening and treatment are their risk of prior TB exposure (Table 1) and of reactivation, balanced against the risk of hepatotoxicity (refer to Chapter 6, Treatment of Latent Tuberculosis Infection). The likelihood that individuals will safely complete treatment as prescribed should also be taken into account. Hence, the benefit of screening programs for LTBI will be greatest in those with a higher probability of infection and/or significant risk factors for reactivation, coupled with a low risk of toxicity and a high probability of treatment completion. LTBI treatment may be particularly beneficial in certain subgroups, such as young children and those with severe immunosuppression, for whom there is increased risk of progression to active disease and also a greater risk of severe forms of the disease, such as miliary TB or TB meningitis (refer to Chapter 6).
|Groups at risk||Prevalence
of positive TST
|Setting or group usually responsible
|Close contacts of an active case of pulmonary TB||Variable, higher than source population||Public health, primary care|
|Immigrants from countries with high TB incidence||Public health, primary care|
|Adult (lived >20 years in country with high TB incidence)||53%-61%|
|Injection drug user||Primary care, treatment facilities|
|(TST ≥10 mm)||66%|
|(TST ≥5 mm)||31%|
|Homeless||18% - 51%||Primary care, shelters, public health|
|Aboriginal communitiesReference 1.1||Public health, primary care|
|Health care workersReference 1.1||11%-46%||Occupational health, public health|
|Residents of long-term care facilitiesReference 1.1||6%-25%||Primary care, facility director of care, public health|
|Residents of correctional facilitiesReference 1.1||12%-72%||Inmate health services, public health|
|Travellers to countries with high TB incidence||Variable||Travel medicine, primary care|
|Canadian-born non-Aboriginal children||1-3%||Targeted screening not recommended|
|Canadian-born non-Aboriginal adults, not BCG vaccinated||7%|
|Canadian-born non-Aboriginal adults, BCG vaccinated||65%|
|Canadian-born non-Aboriginal adults, BCG vaccination nonspecified||13%|
Screening Immigrants for Tuberculosis Infection and Disease
Overview of immigration to Canada
Over the course of the last four decades, international migration has increased at an unprecedented rate, the total number of international migrants estimated to be 200 million peopleReference 3. Canada is a leading destination for migrants and receives on average ~250,000 immigrants and refugees annually, who account for almost 20% of the population (2006 CensusReference 5 Reference 6). Over the past 40 years, there has been a major demographic shift in the source countries of new migrants. Before the 1960s, most individuals immigrating to Canada originated from European countries. Since the 1970s, however, most immigrants (>70%) have originated from countries with intermediate or high TB incidence rates in Asia, Africa and Latin AmericaReference 5 Reference 6.
The two main administrative classifications of migrants arriving in Canada are 1) permanent residents who come to Canada to resettle and 2) temporary residents who are visiting, studying or working in Canada but who maintain their own nationality. Permanent and temporary residents are further classified into several subgroups (refer to Table 2). In addition, Canada receives more than 35 million international visitors per year Reference 8. Most groups apply for permission to come to Canada while still living in their countries of origin, an important exception is refugee claimants who apply for status after arrival in CanadaReference 6.
|Annual number of migrants Table 1 - Footnote A|
|Economic class (business and economic migrants)||187,000|
|Family class (family reunification)||60,000|
|Humanitarian class (refugees resettled from abroad
or selected in Canada from refugee claimant population)
(those arriving in Canada and claiming to be a refugee)
|Irregular migrants (no official migration status)Table 1 - Footnote B||~200,000|
Epidemiology and predictors of TB among the foreign-born in Canada
Canada is a low-incidence country and had an overall TB disease rate of 4.6 per 100,000 population in 2010Reference 9. The majority of the 1,577 reported cases (66%) occurred in the foreign-born population, which has an overall 13-fold greater incidence of TB than the non-Aboriginal Canadian-born population (13.3 vs. 1.0 cases/100,000 population), although rates are as high as 500 times greater in certain subgroups of immigrantsReference 9 Reference 10. The strongest predictors of active TB development in immigrant populations are the global region of origin, immigration category (refugees at 2-fold increased risk compared with other immigrants), the presence of underlying medical comorbidities, the time since arrival in Canada and recent travel to countries with a high TB incidenceReference 10 Reference 17. (also, refer to Chapter 1, Epidemiology of Tuberculosis in Canada). Refugees and foreign-born children from high-incidence countries are particularly important subgroups to consider for targeted screening, for the reasons listed below.
Refugee populations have consistently been reported to have an approximately 2-fold increased risk of active TB compared with the immigrant population, at least within the first year after arrivalReference 18-21. This may be due to a higher prevalence of LTBI in the refugee population and crowded conditions that increase the likelihood of recent exposure to TBReference 22.
Foreign-born children less than 11 years of age from high-incidence countries do not undergo pre-arrival radiographic screening for TB (refer to the Operations Directorate, Health Branch Immigration Medical Examination InstructionsReference 23. For this and several other reasons children may particularly benefit from LTBI screening and treatment. In children less than 5 years of age there is higher likelihood of severe or rapidly progressive disease, such as miliary TB or TB meningitisReference 24 Reference 25. Furthermore, TB in young children is more often paucibacillary or extrapulmonary and therefore more difficult to diagnoseReference 24 Reference 25. Finally, children with LTBI have many years of life in which active TB may develop and a relatively low risk of hepatotoxicity (refer to Chapter 9, Pediatric Tuberculosis).
Immigration TB screening requirements for the foreign-born
Pre-entry tuberculosis screening
CIC requires all individuals applying for permanent residency and certain individuals applying for temporary residency to undergo an immigration medical examination (IME) before arrival, which includes a chest radiograph for applicants ≥11 years of age (refer to Table 3) (refer to Citizenship and Immigration Canada, Overseas Processing (OP)Reference 26. The objective of this program is to detect prevalent active TB in migrants prior to arrival in Canada so as to ensure that they are treated and are no longer infectious on arrival. This screening program does not aim to detect or treat LTBI. Once the IME has been completed it is valid for a period of 12 monthsReference 27. Most visitors do not require this examination. CIC's determination of which temporary residents or visitors require an IME is based on their place of origin (a 3-year average incidence rate of all cases of TB of ≥30/100,000 population), the duration of the visit (longer than 6 months) and occupation (workers in close contact with others). For most migrants the IME is performed before departure from the country of origin by a designated medical professional, and the cost is borne by the applicant. The exceptions to this are convention refugees for whom the examination is provided free and refugee claimants, who claim refugee status after arrival in Canada and undergo an IME shortly after arrival.
Note: In 2009 the World Health Organization changed its method of reporting the global burden of TB and began reporting annual incidence of ALL TB cases per 100,000 rather than annual incidence of smear-positive TB. To reflect this change, the definition of high TB incidence countries/territories has changed from 15 per 100,000 smear-positive TB cases to 30 per 100,000 for all forms of active TB cases (3-year average)Reference 11. The 3-year moving average is used to adjust for unstable rates in some jurisdictions. Furthermore, estimated rates adjusted for under-reporting of cases are used for some countries, rather than the country's reported incidence rate. To view current international incidence rates, refer to the Public health Agency of Canada, Tuberculosis Prevention and Control.
Chest x-rays are examined for evidence of active or inactive TB disease by a local radiologist. CIC, in consultation with Canadian TB specialists, grades chest x-rays according to an 18-factor ascending scale of findings characteristic of active TB disease or inactive TB infectionReference 27. Individuals with certain abnormalities on their chest x-ray must submit three consecutive sputum samples for smear and culture. Those unable to submit sputum will be required to repeat the chest radiography 6 months after the initial one to establish stability. Those found to have active TB must complete a course of treatment consistent with Canadian standards. Before being given permission to enter Canada by CIC, they must submit proof of successful treatment completion, three negative sputum smears and cultures, and stable and/or improving chest x-rays taken over a minimum period of 3 months. In 2011 active TB was identified during 0.09% of 500,992 immigration medical assessments (Dr. Sylvain Bertrand, Citizenship and Immigration Canada, personal communication).
Applicants identified as having inactive pulmonary TB are permitted to enter Canada but are placed under medical surveillance and referred to provincial/territorial public health authorities to report for post-landing surveillance (refer below) within 30 days of arrival.
Inactive pulmonary TB is defined as follows:
- a history of treated active TB and/or
- an abnormal chest x-ray suggestive of TB and
- two chest x-rays taken at an interval of 3 months apart with stable appearance and three negative sputum smears and cultures or
- two chest x-rays taken at an interval of 6 months apart with stable appearance.
|Entrants to Canada||Criteria|
|Foreign nationals applying for permanent residency (immigrants and refugees selected abroad)||Mandatory for all.|
|Foreign nationals claiming refugee status in Canada||Mandatory for all.|
|Foreign nationals applying for temporary residency (including students, workers and visitors)||Those who will stay in Canada for more than 6 months and who have spent 6 or more consecutive months in a country/territory with high TB incidence, as designated by the Public Health Agency of Canada, during the 1 year immediately preceding the date of seeking entry (application) to Canada.|
|Foreign nationals applying for temporary residency and seeking to work in certain occupations||Mandatory for all who are seeking to work in an occupation in which the protection of public health is essential regardless of length of stay and country of origin AND for agricultural workers from a country/territory with high TB incidence, as designated by the Public Health Agency of Canada. The occupational list is available at the Citizenship and Immigration Canada, Medical exam requirements for temporary residents (visitors, students and workers)|
|Seriously ill foreign nationals||May be requested to undergo an immigration medical examination if an Immigration Canada or Canada Border Services Agency officer has reasonable grounds to believe that the person is medically inadmissible to Canada, regardless of anticipated length of stay in Canada and country of origin.|
(On-line) ccdr canada communicable disease report
CIC's Medical Surveillance Program is designed to refer applicants found in the course of their IME to have previously treated TB or inactive pulmonary TB to the Canadian provincial or territorial public health authorities as soon as possible upon their arrival in Canada. Approximately 2% of those who undergo pre-arrival chest radiographic TB screening are targeted for medical surveillance (Dr. Sylvain Bertrand, Citizenship and Immigration Canada, personal communication). Immigrants requiring medical surveillance receive a Medical Surveillance Undertaking Form (IMM 0535B) and an information handout with instructions on how to contact provincial/ territorial public health authorities upon arrival in Canada. They must report to, or be contacted by, a public health authority within 30 days of entry. For complex inactive pulmonary TB cases, evaluation and follow-up should begin within 7 days (refer to Citizenship and Immigration Canada, Operational Bulletin 340).
This is a passive surveillance system, and the implementation varies among the different provinces and territories, some having a centralized process and others having a decentralized system. Provincial/territorial public health authorities report to the CIC Medical Surveillance Program as to whether the immigrant has been compliant with the requirement for medical surveillance. Compliance is defined as keeping the first appointment with the clinician or being assessed by a specialist designated by public health. Compliance with surveillance varies by province/territory, averaging ~70% (Dr. Sylvain Bertrand, CIC, personal communication). Participation in the Medical Surveillance Program is a formal "condition of landing." While there is currently no enforcement of participation, CIC will not process any further immigration applications from an immigrant under the Medical Surveillance Program (e.g. to extend a visa or apply to become a citizen) until they have met the program requirement.
Immigrants are responsible for their own health care funding until eligible for provincial/territorial health care insurance, which in some jurisdictions may not be until 90 days after arrival. For those under medical surveillance, this may mean a delay of examination, radiography, other necessary procedures and treatment for LTBI for at least 3 months. Temporary health care for refugees and refugee claimants may be covered by the Interim Federal Health Program, a health care coverage program managed by CIC. This will provide coverage for the IME when done in Canada, screening for and treatment of active TB, if detected, as well as screening for and treatment of LTBI in all groups eligible for the Public Health and Public Safety package. Information on the Interim Federal Health Program is available at Citizenship and Immigration Canada, Interim Federal Health Program: Summary of Benefits.
Timely compliance with the requirement for medical surveillance has been shown to improve in the following circumstanceReference 28:
- Advising the immigrant of the need for medical surveillance before travel to Canada or at the port of arrival;
- Providing documents requesting medical surveillance in the language of the immigrant (if not fluent in English or French);
- Provincial/territorial health insurance coverage for medical surveillance immediately upon arrival in Canada with no waiting period;
- Pre-screening of individuals by public health staff prior to clinician assessment in order to identify those with symptoms and signs of active TB or those at high risk of rapid progression of LTBI to active disease;
- Centralized clinics for assessment, when feasible, allowing staff to become more experienced and efficient;
- Extended clinic hours; and
- Readily available and culturally sensitive interpretation services.
During the initial assessment of these individuals, active TB should be ruled out with special attention to symptoms or signs of active TB. If these are present chest radiography and sputum smears and cultures should be performed as deemed appropriateReference 29. For those found not to have active TB, testing for LTBI (TST or IGRA), unless previously known to be positive, should be performed and those identified as having LTBI should be considered for treatment as outlined in Chapter 6, Treatment of Latent Tuberculosis Infection. Those who have completed an adequate and well-documented course of LTBI treatment can be discharged. The need for and duration of follow-up for those not completing LTBI treatment is unclear. In general, such people should be advised of the potential risk of reactivation and told to return for evaluation if symptoms arise (also, refer to Chapter 6). People who are discharged from follow-up should be advised to seek medical attention promptly if symptoms develop that are suggestive of TB and to tell their health care provider about their history of medical surveillance for TB as a result of their IMEReference 29.
Post-arrival domestic LTBI screening
There are no routine post-arrival domestic LTBI screening programs for immigrants in Canada. There are, however, published primary care guidelines and several screening programs managed by different organizations, for example, school-based screening, immigrant and refugee clinics, services for migrant workers and targeted screening of certain high-risk migrantsReference 30-45. Undocumented migrants are difficult to access and remain a challenge, as they are not systematically screened in any of the existing programs.
Effectiveness of TB screening programs for immigrants
Active and inactive TB
Recent estimates of the yield of active TB and inactive TB found in pre-immigration chest radiography screening in migrants to Canada was found to be 0.05% and ~2% respectivelyReference 46. In a recent systematic review and meta-analysis 1.3% of migrants assessed in the post-landing surveillance program in Canada were found to have active TBReference 47. Only 67% of those targeted for this surveillance actually completed the screening process, thus highlighting the importance of improving the functioning of these programReference 47. Furthermore, only 2%-15% of all cases of active TB in the foreign-born population in Canada and the United States are detected during required immigration screening programs (post-landing surveillance, refugee claimants or people applying to change immigration status)Reference 48-51. The majority of TB in the foreign-born occurs outside of pre-immigration screening as a result of reactivation of LTBI. Although TB rates among the foreign-born are highest in the first 5 years after arrival (refer to Chapter 1, Epidemiology of Tuberculosis in Canada), the risk of TB is higher than that of the non-Aboriginal Canadian-born population throughout their lifetimeReference 13 Reference 45 Reference 52. The Canadian Thoracic Society believes this highlights the importance of additional screening programs to control TB in the immigrant population.
Latent TB infection
Detecting (for example, with TSTs or IGRAs) and treating LTBI in the immigrant population after arrival is an attractive alternative to chest radiography screening programs. Unfortunately, LTBI screening programs for immigrants perform poorly. In a systematic review and meta-analysis of studies of LTBI screening and treatment in immigrants after arrival in low TB incidence countries (Canada, United States, Spain, Italy and Australia), only 32% of TST-positive immigrants completed LTBI treatmentReference 53. This suboptimal performance was due to losses and dropouts at all steps of the process: 69.0% completed screening, and 77.0% of those with a diagnosis of LTBI were offered treatment; of these, 83.0% started treatment, of whom 71.0% completed treatmentReference 53. Similarly, LTBI screening and treatment in the post-landing surveillance program in Canada and the United States resulted in only 26% of people with a positive TST completing LTBI treatmentReference 47.
Challenges and barriers to the uptake of LTBI screening and treatment in immigrants
Implementing widespread, comprehensive LTBI screening and treatment programs in migrants is challenging for many reasons, the most important of which is the extremely large pool of migrants at risk who are not easily accessible through present health care programs. The potential pool of migrants at risk of reactivation of LTBI to active disease is enormous, given that there are ~6 million migrants living in Canada, ~200,000 new permanent residents and 1.2 million visitors arriving from countries with high TB incidence each year, of whom ~50% have LTBIReference 4 Reference 7 Reference 8. In addition there are 350,000-400,000 new temporary residents, including foreign workers, foreign students, refugee claimants and those in humanitarian groups, arriving each year in CanadaReference 6. A recent US study highlights the importance of the potential large pool of unscreened people with LTBI at risk of TB reactivation: only 41% of cases of active TB diagnosed within 1 year of arrival occurred in those who had been screened in the pre-landing screening program. The majority of cases occurred in unscreened people, i.e. temporary workers and exchange students (37%), business travellers and tourists (16%) and non-immigrant visitors from Canada and Mexico (7%)Reference 54. In Canada some temporary workers are screened, but most of these other groups are not (Table 3).
Exposure in countries with high TB incidence may also be an important risk factor in immigrants who have been living in Canada for more than 2 years and return home for prolonged periods. Several studies have estimated that 20%-50% of active TB cases in the foreign-born population are due to recent return travel to their countries of originReference 15-17. Accessing this population is a challenge, as only a minority (20%-30%) seek pre-travel advice, and there are no programs to routinely re-evaluate returning travelersReference 55-57. Furthermore, people at increased risk of LTBI reactivation who have medical and/or behavioural risk factors are not easily identified, current diagnostic tools do not permit identification of those at higher risk, and the length of LTBI treatment regimens deters completion (refer to Chapter 4, Diagnosis of Latent Tuberculosis Infection).
Finally, LTBI screening programs for immigrants and refugees encounter many barriers at the level of the patient, provider and infrastructure/institution. Patient-level barriers include the stigma of TB and its association with HIV, linguistic barriers and difficulties coming to appointments because of inconvenient clinic locations or limited clinic hoursReference 42 Reference 58-60. Provider barriers to offering screening to migrants are related to inadequate knowledge of which migrants should be screened or how they should be followed upReference 61-63. Poor adherence to treatment for LTBI is associated with barriers similar to those for LTBI screening. They include linguistic barriers, cultural taboos and stigmatization, low education level, perceived low risk of progression from LTBI to active disease, belief that positive results from TSTs are due to BCG (Bacille Calmette-Guérin), reluctance to undergo venipuncture, and economic factors (costs of travel, lack of insurance, delays in obtaining insurance, missed days at work)Reference 58-60 Reference 64-66. Until these issues can be addressed, LTBI screening and treatment in Canada after arrival should be focused on migrants at increased risk of active TB.
Strategies to optimize LTBI screening and treatment in the foreign-born
Control of TB in low-incidence settings will need novel strategies to more effectively access all foreign-born groups at risk of LTBI. Improving cultural and linguistic infrastructure may increase the uptake of screening and treatment in the immigrant populationReference 42 Reference 67-69. Several studies show that having a cultural case manager or that matching migrants to a health care provider with similar language or cultural background increased the probability of LTBI treatment completionReference 42 Reference 64 Reference 67. Educating health care providers in identifying migrants at risk is also an important strategy. In a study in which primary care providers were educated about how and whom to screen for TB, the proportion of patients screened for LTBI increased, and the proportion identified with active TB also increaseReference 61.
Some of the barriers to delivering LTBI treatment may be best addressed by providing it in an integrated primary care setting where a trusting relationship has been established and where several health issues are being managed at the same time. Clinics with longer hours after the usual work day may help people who have difficulties getting time off work to come to clinic visits. Similarly, engaging migrants will require effort on several levels, including care that is tailored to their linguistic and cultural backgrounds, and better pre-travel counselling in the primary care settingReference 55-57. Engaging immigrant community resource agencies may be effectiveReference 70. In addition to programmatic improvements, the development of new diagnostic tests that can identify the 10% of people with LTBI whose disease will ultimately reactivate, and shorter LTBI treatment courses would be ideal. Given the magnitude of human migration, the long-term solution will ultimately depend on investment in global TB control to decrease the TB morbidity and exposure in source countrieReference 71.
Screening of People with Medical or Behavioural Risks for TB Infection and Disease
Medical Risk Factors that Increase TB Reactivation
There are several medical conditions and therapies that increase the risk of TB reactivation (refer to Chapter 6, Treatment of Latent Tuberculosis Infection). Subgroups with an increased prevalence of LTBI (Table 1) who also have medical conditions that increase the risk of LTBI reactivation should be targeted for screening and treatmentReference 52. Diabetes is a particularly important medical risk factor, as it is more common in certain immigrant groups and the Aboriginal population, and is associated with a 2-3.6 fold increased risk of active TB developmentReference 72. Diabetes affects more than 2 million Canadians and has an overall prevalence of 6%, increasing with age up to a prevalence of 20% in the 75-79 age groupReference 73. Immigrants from South Asia have a 3-4 fold higher risk of having diabetes as compared with the Canadian-born population, and immigrants from Latin America, the Caribbean and sub-Saharan Africa have about a 2 fold increased riskReference 74 Reference 75. End-stage renal disease is another important medical risk factor, as it is a common complication of diabetes. Patients receiving hemodialysis are at substantially elevated risk of active TB, with cited relative risks ranging from 10-25 times the background incidenceReference 76.
There are no systematic evaluations of screening for and treatment of LTBI among people with medical risk factors for active TB, other than HIV. A recent cost-effectiveness analysis suggested that, at a group level, screening and treatment of individuals with these conditions would have little public health impact and would confer limited gains in quality-adjusted survivalReference 77. This analysis, however, was based on relative risks of reactivation of 2 or less for most of these conditions.
Recommendations for LTBI screening in the foreign- born
and those with underlying medical conditions
For the following recommendations refer to Table 1 for a list of those with an increased prevalence of TST positivity and Table 1 in Chapter 6, Treatment of Latent Tuberculosis Infection, for the conditions that increase the risk of TB reactivation. The recommendations are summarized in Table 4.
- Routine screening of people with a low prevalence of LTBI and medical risk factors with a low relative risk for LTBI reactivation (i.e. a relative risk of <2.0 compared with a healthy individual without known risk factors for reactivation) is not recommended.
(Conditional recommendation, based on moderate evidence)
- Foreign-born children up to age 20 should be offered LTBI screening and treatment as soon as possible after arrival.
(Conditional recommendation, based on moderate evidence)
- Refugees from countries with high TB incidence should be offered LTBI screening and treatment up until age 50 years, because refugee status is associated with a slightly increased risk of TB reactivation.
(Conditional recommendation, based on weak evidence)
- Population groups with increased prevalence of LTBI (such as the foreign-born from countries with high TB incidence) and with conditions presenting a slightly increased risk of reactivation (i.e. refugee status) should be offered LTBI screening and treatment up until age 50 years.
(Conditional recommendation, based on weak evidence)
- Population groups with increased prevalence of LTBI and with conditions that pose a moderate risk of reactivation (i.e. diabetes) should be offered LTBI screening and treatment up until age 65 years.
(Conditional recommendation, based on weak evidence)
- Everyone with conditions associated with a high risk of LTBI reactivation should be considered for screening (refer to Table 4).
(Conditional recommendation, based on moderate evidence)
- Providing LTBI screening and care to the immigrant population in a culturally sensitive manner with good access to interpreters should be considered.
(Conditional recommendation, based on weak evidence)
|Group at risk||Group to be screened||Age limit for screening|
For categories 1-3, conditional recommendation, based on moderate to weak evidence
1. Close contacts of an active case of pulmonary TB
|As soon as possible after diagnosis of the index case (refer to chapter 12)||Any age|
2. Immigrants from countries with high TB incidence
|Fibronodular changes on chest x-ray (usually in the context of Post-Landing Surveillance)||Any age|
|All children and adolescents as soon as possible after arrival||Up to age 20 years|
|Immigrants and refugees with underlying medical comorbidities with the following risk of TB reactivation: Table 4 - Footnote A
3. Medical comorbidities Table 4 - Footnote A
|All individuals regardless of prior TB exposure should be considered for screening if they have certain medical comorbidities that increase risk of TB reactivation (refer to Table 1 in Chapter 6 for categorization of risk)
4. Injection drug user OR the homeless
|In the presence of underlying medical comorbidities with the following risk of TB reactivation Table 4 - Footnote A
Travellers to countries with high TB incidence Table 4 - Footnote C
|≥1 month of travel with very high risk contact, particularly direct patient contact in a hospital or indoor setting, but possibly including work in prisons, homeless shelters, refugee camps or inner city slums.||Up to 50 years if single post-travel TST|
≥3 months of travel to TB incidence country >400/100,000 population Table 4 - Footnote G
≥6 months of travel to TB incidence country 200-399/100,000 population
≥12 months of travel to TB incidence country 100-199/100,000 population
Any age if documented TST conversion
|Refer to Chapter 10|
|Refer to Chapter 14|
Health care workers
|Refer to Chapter 15|
Residents of long-term care facilities
|Refer to Chapter 15|
Residents of correctional facilities
|Refer to Chapter 15|
The incidence rate of active TB in homeless populations is markedly higher than in their non-homeless counterparts. Despite the challenges in accurately quantifying the number of homeless people, one study estimated the incidence rate of active TB in Toronto's homeless population to be 71 cases per 100,00Reference 79. Homeless people are also frequently envisioned as Canadian-born individuals; however, recent studies have identified a growing proportion of foreign-born homeless people with active TBReference 80. Given the elevated risk of TB drug resistance in many foreign-born populations, this study highlights the risk of drug-resistant disease emerging and propagating within urban shelter systems; hence, adequate infection control measures, including environmental controls in these institutions are recommended (also, refer to Chapter 15, Prevention and Control of Tuberculosis Transmission in Health Care and Other Settings).
The prevalence of LTBI in homeless populations is also markedly elevated relative to non-homeless populations and has been reported as ranging between 18% and 51Reference 81. Many homeless people are at increased risk of active TB not only because of repeated TB exposures but also because of the high frequency of medical comorbidities that can compromise their immunitReference 82. Among homeless people with active TB, the frequency of HIV coinfection has been reported to range from 5% to 60%Reference 80Reference 83-85;. While LTBI therapy offers the potential to significantly reduce the risk of active TB in homeless people, it is complicated by challenges with adherence to therapy and adverse drug reactions. LTBI treatment completion rates in homeless populations have been reported to be as low as 19%. However, the use of incentives and enablers, and directly observed (preventive) therapy have been used effectively to increase the likelihood of successful treatment completion up to 44%Reference 86.
Alcohol and/or substance abuse can complicate the treatment of LTBI, not only by affecting adherence to therapy but also by increasing the risk of adverse drug reactions. Concurrent alcohol abuse during LTBI therapy, particularly with isoniazid, markedly increases the risk of hepatotoxicity (up to 4 fold with daily alcohol intakeReference 87. While LTBI treatment with rifampin is much shorter in duration than isoniazid and is associated with a lower risk of hepatotoxicityReference 88, it is important that health care providers carefully assess and exclude active TB before considering its use. This is because the development of rifampin resistance (if individuals are inadvertently treated for LTBI with rifampin when they have subclinical, undetected active TB) would have very serious short-term clinical implications for patients, and could have lasting public health repercussions to those accessing or providing services within the shelter systemReference 89. Given the potential risk of hepatotoxity due to high rates of associated alcohol use and low rates of treatment completion, efforts to offer LTBI screening and treatment should be reserved for those with a moderate or high risk of TB reactivation.
- The homeless should be offered LTBI screening and treatment up to age 65 if they have an underlying medical condition that confers moderate risk of reactivation or at any age if there is a medical condition that confers a high risk of reactivation.
(Conditional recommendation, based on weak evidence)
- Homeless people with medical conditions associated with a high risk of reactivation should be considered for special measures to enhance adherence, such as directly observed LTBI treatment and/or incentives and enablers.
(Conditional recommendation, based on weak evidence)
Injection Drug Users
Injection drug use is associated with a heightened prevalence of LTBIReference 90-92. and with blood-borne pathogens. In particular, chronic hepatitis C infection has been identified with high frequency in studies of injection drug users (IDUs), prevalence rates exceeding 60%Reference 93 Reference 94. Chronic infection with hepatitis B is also frequent among IDUsReference 84, and although concurrent infection with hepatitis B, C and/or HIV is less common, these viral infections in combination can accelerate the course of liver disease and consequently present heightened risks of hepatotoxicity to those receiving LTBI treatment. Despite the increased risk of drug toxicity, many studies have shown that LTBI treatment can be safely administered to IDUs provided that their liver function tests and clinical status are carefully and regularly monitoredReference 95-97. While asymptomatic, low-grade elevations in liver function tests are not uncommon in individuals with viral hepatitis, a significant proportion of these people are still able to safely complete LTBI therapy. People with LTBI who have experienced complications with isoniazid or have a high baseline risk of hepatotoxicity could be considered for treatment with rifampin once the presence of active TB has been carefully excluded.
The benefits of LTBI therapy can be substantial, particularly for IDUs with HIV infection or other forms of immunosuppression. However, treatment adherence among currently active IDUs may be suboptimal and consequently can decrease the overall effectiveness of treatment. A systematic review of LTBI therapy among IDUs in Canada and the United States revealed that treatment completion rates ranged between 39% and 70%Reference 98. As with other vulnerable populations, incentives and enablers and/or directly observed therapy for LTBI can increase the likelihood of successful treatment completionReference 98. Two US-based studies modeling the health and economic effects of programs dedicated to LTBI treatment in IDUs have shown that such programs can be cost-effectiveReference 99 Reference 100. Given the potential risk of hepatotoxity due to a high rate of associated alcohol use and/or coinfection with viral hepatitis, and low rate of treatment completion, efforts to identify and offer LTBI screening and treatment should be reserved for those with a moderate or high risk of TB reactivation.
- Current or past intravenous drug users should be offered LTBI screening and treatment up to age 65 if they have an underlying medical condition associated with moderate risk of reactivation, and should be offered screening at any age if they have a medical condition associated with a high risk of reactivation.
(Conditional recommendation, based on weak evidence)
- Those at highest risk of reactivation should be considered for special measures to enhance adherence, such as directly observed LTBI treatment and/or incentives and enablers.
(Conditional recommendation, based on weak evidence)
Travellers to countries with higher TB incidence are at risk of acquiring infection during travel. The risk increases with longer duration of travel and higher TB incidence in the destination country, and is also affected by the type of travel and the work done (if any) in these countries. Long-term travellers to countries with higher TB incidence have a similar risk of acquiring infection during their visit as the local populationReference 101. Risk is particularly elevated for travellers who work in health carReference 101. Similarly, immigrants who return to their home countries to visit friends and relatives are at risk of exposure to TB infection and development of disease. Two U.K. studies in immigrants from the Indian subcontinent estimated that ~20% of cases of TB in the U.K. were due to recent travel to their countries of originReference 16 Reference 17. More recently, 56% of TB cases in the Moroccan immigrant population in the Netherlands were associated with recent travel to MoroccReference 15.
The Committee to Advise on Tropical Medicine and Travel (CATMAT) has published guidelines on risk assessment and prevention of TB in travellers, including screening for and treatment of LTBI in travellers who make prolonged or high-risk tripsReference 78. These are summarized in Table 4 but have been modified to reflect the change in the definition of a high TB incidence country, from 15/100,000 smear-positive cases to 30/100,000 population of ALL TB cases. Refer to the Public Health Agency of Canada, Canada Communicable Disease Report for additional information. For most travellers judged to require screening for LTBI, a single post-trip TST or IGRA (refer to Chapter 4) should be sufficientReference 102. For individuals who are expected to undergo serial or repeated testing (e.g. health care workers), a pre-travel two-step TST is recommended (and IGRA is NOT recommended, refer to Chapter 4). Pre-travel testing is also recommended for people in whom the distinction between conversion and longstanding infection is particularly important, e.g. those at increased risk of treatment toxicity because of older age, alcohol consumption or liver disease. Conditional recommendation, based on weak evidence
Conclusions and Recommendations
The selection of people as suitable candidates for targeted LTBI screening and treatment is based on consideration of their risk of prior TB exposure and of reactivation, balanced against their risk of hepatotoxic effects and the likelihood of safe completion of treatment. To improve uptake of LTBI screening in immigrants, investment in TB education programs for patients and providers and in infrastructure is suggested, as well as programs that can be offered in a culturally sensitive manner with good access to interpreters. In the homeless population and injection drug users, patients with LTBI should be assessed for hepatitis comorbidities that may increase hepatotoxicity; incentives, enablers and directly observed therapy should be considered to achieve LTBI treatment completion for those who have immunosuppressive illness or are HIV positive. For a summary of specific recommendations for each group refer to Table 4.
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