Chapter 11 of the Canadian Tuberculosis Standards: Tuberculosis contact investigation and outbreak management

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Authors and affiliations

Elizabeth Rea; Tuberculosis Program, Toronto Public Health, Toronto, Ontario, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

Jessika Huard; Direction régionale de santé publique, Centre intégré universitaire de santé et de services sociaux du Centre-sud-de-l'Île-de-Montréal, Montréal, Québec, Canada; Nunavik Regional Board of Health and Social Services, Public Health, Kuujjuaq, Québec, Canada

Robyn Lee; Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Nunavik Regional Board of Health and Social Services, Public Health, Kuujjuaq, Québec, Canada

Key points

1. Introduction

Contact investigation and clinical follow-up of those who are infected or have active disease is an essential component of TB programs in Canada, and of the WHO framework for TB elimination in low-burden countries.Footnote 1Footnote 2Footnote 3 Several studies have found contact investigation incorporating treatment of the identified active cases and contacts with LTBI to be cost-effectiveFootnote 4; in modeling studies, household contact investigation LTBI treatment follow-up may contribute as much as 18-27% to a decline in active TB incidence over 5-15 years, compared to no contact investigation and follow-up.Footnote 5Footnote 6

Reporting of active TB disease is required in all Canadian jurisdictions; in part, this is to ensure that contact investigation can be carried out quickly, in an organized, collaborative manner. TB programs in North America typically find a median of 4 (average of 6) close contacts for each TB case.Footnote 7Footnote 8 The majority of Canadian-born children with TB disease have a known close TB exposure, highlighting the importance of contact investigation, especially in the household.Footnote 9

Contact investigation demands considerable time, expertise and coordination. It is best carried out by public health/TB program authorities in collaboration with treating clinicians and other providers. Anxiety, stigma and lack of knowledge about TB among those exposed may be major issues. Provision of clear, credible and consistent information about TB and the clinical follow-up plan is essential.

1.1. Glossary of terms

See Appendix A: Glossary.

2. Objectives of contact investigation

Contact investigation has three main objectives. In order of priority these are:

  1. Identify and initiate treatment for secondary cases of active TB disease. Typically, 1-2% of close contacts are found to have active disease at the time of contact investigation; the proportion is about 3.3% for smear-positive pulmonary patients.Footnote 7Footnote 10 Early identification and treatment reduces the morbidity and mortality risk of TB disease for these individuals and rapidly reduces the risk of further transmission to others. This objective is particularly critical for contacts who are vulnerable to rapid progression if infected, such as children less than 5 years of age or those with significant immune suppression.Footnote 9Footnote 11
  2. Identify and treat the infectious source patient if the index patient is less than 5 years old. TB disease in a young child (whether pulmonary or extra-pulmonary) is a sentinel event. The younger the child, the more likely this reflects recent transmission, usually from an undiagnosed adolescent or adult in the household, or other caregiver close to the child (see Chapter 9: Pediatric tuberculosis).Footnote 9Footnote 12Footnote 13 Source-case investigation (also known as "reverse contact investigation") should be carried out when TB disease is diagnosed in any child less than 5 years old.Footnote 14Footnote 15 Source investigation should also be done when a cluster of tuberculin skin tests (TST) conversions is identified in an institutional setting with no known source patient, and may be considered for patients with pleural TB if TB program resources allow.Footnote 16 However, source investigations usually give very low yield; even for patients less than 5 years old a source case is identified in less than half of investigations.Footnote 12 Source-case investigation is not advised for individuals of any age with LTBI identified on a routine screening.
  3. Identify contacts with LTBI in order to offer preventive treatment. Without treatment, about 5% of newly infected contacts will develop active disease within two years of exposure. Thus, a well-functioning contact investigation and follow-up program can reduce morbidity and mortality among infected contacts, and over time can contribute substantially to TB elimination.

3. Principles of contact investigation

3.1. Prioritize the work

This is the most important principle. Contact investigation should be prioritized according to the infectiousness of the source case and the extent of exposure and immunologic vulnerability of those exposed. This will allow the TB program to put the most effort into those contacts at most risk.

3.2. Rapidly initiate contact investigation

When notification of a new TB diagnosis is received, the public health authority should ensure that all medical investigations to confirm the diagnosis and determine the degree of infectiousness are under way, and the patient is in home isolation or hospital airborne isolation. Once pulmonary/laryngeal TB is confirmed (by GeneXpert or other nucleic acid amplification test, by positive smear in regions with little non-tuberculosis mycobacterium infection or by positive culture), or if the clinical suspicion is sufficiently strong to begin TB treatment pending laboratory confirmation, then investigation of household and other high-priority contacts should begin promptly, especially for any children less than 5 years old and immunocompromised individuals (see Chapter 2: Transmission and pathogenesis of tuberculosis and Chapter 3: Diagnosis of tuberculosis disease and drug-resistant tuberculosis). Investigation of contacts beyond the high-priority group (see below) should always await laboratory confirmation of the diagnosis.

Good practice statement:

3.3. Assess the risk of transmission

The transmission risk assessment focuses on how infectious the patient is, over what time period, and the duration, proximity and characteristics of the space where exposure occurred. Factors associated with TB transmission are reviewed in detail in Chapter 2: Transmission and pathogenesis of tuberculosis.

3.3.1. Infectiousness of the index patient

The single greatest factor determining the extent of initial contact investigation is the degree of infectiousness of the index patient.Footnote 17 With limited exceptions, only adolescents and adults with pulmonary and laryngeal TB are infectious and require contact investigation (see also Chapter 2: Transmission and pathogenesis of tuberculosis and Chapter 9: Pediatric tuberculosis).Footnote 14Footnote 18 Pleural TB should be assumed to include pulmonary involvement until ruled out by sputum results. Sputum-smear status is the most reliable indicator of infectiousness; the "worst" (i.e., most positive) result is used to evaluate infectiousness.Footnote 19Footnote 20 Infectiousness for both drug-resistant TBFootnote 10 and patients co-infected with human immunodeficiency virus (HIV) should be evaluated by the usual criteria.

Figure 1. Timelines for contact investigation
Figure 1
Figure 1: Text description

This flow chart describes the timelines for contact investigation.

  • Notification of TB disease should occur within 48 hours of diagnosis. The treating physician and laboratory should notify that a person has been newly diagnosed with TB disease to the appropriate public health authority within 48 hours of diagnosis.
  • Investigation should occur in the next 24 hours. Once notification of a new TB diagnosis is received, within 24 hours, the public health authority should initiate interaction with the patient and/or health care provider to ensure adequate airborne isolation, provide basic TB information and any urgent support, identify the household contacts, and direct any who are ill to immediate assessment.
  • Contact tracing interview should occur in the next 1-3 days. The initial contact tracing interview should be done within 3 days for the full set of contacts and to promptly identify high priority contacts. A home visit should be considered.
  • Begin screening for high priority contacts in the next 1-7 days. Clinical assessment of high-priority contacts should begin within 7 calendar days of being identified as contacts.
  • Complete screening of high priority contacts in the next 30 days. Initial clinical assessment of high-priority contacts should be completed within 4 weeks of identification.

3.3.2. Likely period of infectiousness

There is no clear epidemiologic evidence on when infectiousness begins. Pulmonary TB is generally considered to become infectious at the onset of cough (or worsening of a baseline cough), and this should be the priority timeframe for contact investigation. If no cough or other respiratory symptoms are reported, the onset of other symptoms attributable to TB may be used to estimate the onset of infectiousness. In practice, it is often difficult to know with certainty when symptoms began.

The US Centers for Disease Control and PreventionFootnote 14 recommends, based on expert opinion, that patients with smear-positive or symptomatic disease should be considered to have been infectious for three months before onset of respiratory symptoms or the first positive finding consistent with TB, whichever is longer. Asymptomatic, non-cavitary TB with a negative smear should be considered infectious four weeks before the first positive finding consistent with TB.

For contact investigation, the period of infectiousness effectively ends when the index patient is placed in isolation from others (this may be before or after diagnosis; at home with no contacts, or on admission to formal airborne isolation in hospital) or is no longer infectious due to TB treatment, whichever comes first. See also Appendix B: De-isolation review and recommendations.

3.3.3. Degree of exposure to the index patient: duration, proximity

Household members are consistently at highest risk of becoming infected, even from index patients with smear-negative disease, as they have very close contact over extended periods.Footnote 10Footnote 11Footnote 20Footnote 21Footnote 22Footnote 23Footnote 24 Beyond this group, there are so many variables in TB transmission that it is difficult to quantify the exact duration of exposure that constitutes a significant risk, and each case should be evaluated on its specific characteristics.Footnote 20Footnote 22Footnote 23Footnote 25Footnote 26 In theory, there is no amount of exposure to infectious TB that is absolutely without risk; in practice, almost all transmission occurs with close, prolonged or repeated contact over days or months.

It is not social closeness to the person with TB, but rather, the amount of time in a shared airspace that is the critical issue. For example, IT personnel may report working very closely with team members but spend little time together in shared air space if the work is mainly done electronically; someone who has minimal interaction with the TB patient but works in the neighboring cubicle is at much higher risk. Among household members, those who share a bedroom with the TB patient are at higher risk, independent of other exposure factors.Footnote 20

For context, 2 large North American studies (each with more than 3,000 contacts) identified 120-250 cumulative hours of exposure as a reasonable threshold for contact investigation.Footnote 20Footnote 25 Another study found that contacts who had LTBI had a mean of 321 cumulative hours of close exposure to the index patient, compared with 211 hours for uninfected contacts.Footnote 23 In school settings, it is generally only students who share classes with an infectious person who are at risk; consistent with the closeness of interactions, schoolchildren are more likely to become infected by a fellow student with TB than by a teacher with TB.Footnote 27Footnote 28Footnote 29Footnote 30Footnote 31 Two Scandinavian studies documented minimal risk of transmission to children in daycare settings with less than 18-24 hours of cumulative exposure to cavitary, smear-positive adult caregivers.Footnote 32Footnote 33 A transmission study in a Canadian homeless shelter suggested 5 nights (cumulative) in the same room with a cavitary, smear-positive patient as a pragmatic risk threshold for contact investigation.Footnote 34 As an extreme example, in a progressively expanded outbreak investigation among university students exposed to an index patient with laryngeal and cavitary pulmonary TB, the risk of infection per hour of classroom exposure was more than 1% for several shared classes; some contacts converted with as few as 3-4 hours of exposure per week over the infectious period.Footnote 35 Rarely, children less than 5 years old have been infected following extremely short exposure (<30 minutes) in a small space with a highly infectious adult.Footnote 36

3.3.4. Characteristics of the space where exposure occurred

The room size and ventilation where exposure occurred (e.g., large cafeterias or lecture halls vs small seminar rooms) may reduce or facilitate transmission: exposure in cramped, ill-ventilated spaces may lead to transmission in much shorter exposure times. Formal ventilation assessment is not generally necessary. However, in hospitals, where ventilation rates can vary greatly, it may be possible to arrange for facility staff to measure air exchanges per hour in the exposure areas. Exposures in areas with lower ventilation can be prioritized, while those with very high ventilation pose much lower risk outside of unprotected aerosolizing procedures (see Chapter 14: Prevention and control of tuberculosis transmission in healthcare settings). Smoking tobacco or other substances with others increases transmission risk, particularly in confined spaces.Footnote 37Footnote 38Footnote 39Footnote 40Footnote 41 TB transmission is rarely thought to occur outdoors, but has been occasionally been documented in groups who smoke together regularly.Footnote 42

Figure 2 illustrates the conjunction of time, proximity and characteristics of the shared air space to assess exposure risk. In this example of exposure in an open-plan office, duration of exposure to the infectious patient was relatively long, but in a large, well-ventilated space. A coworker whose desk is very close nearby has a higher risk of transmission than others sitting far away.

Figure 2. Evaluating exposure risk: time, proximity, characteristics of the shared air space
Figure 2
Figure 2: Text description

The following figure shows the need to consider time, proximity and characteristics of the shared air space to assess exposure risk.

  • More confined space/poor ventilation results in a higher transmission risk
  • Being physically closer results in a higher transmission risk
  • More time in the same air space results in a higher transmission risk

3.4. Contact interview

The interview of an infectious TB patient for contact tracing is one of the most important parts of the investigation. It takes considerable skill and is most successful when done by staff with training/experience in public health interview techniques, including motivational interviewing, and who are familiar with local social patterns.Footnote 43Footnote 44Footnote 45Footnote 46 The initial interview can also lay the foundation for long-term adherence to TB treatment, and should be approached as an integral component of TB care for the patient. Most TB patients in Canada were born in countries with high TB incidence or in First Nations/Inuit communities (see Chapter 1: Epidemiology of tuberculosis in Canada), so language and cultural perceptions about TB, TB stigma and health are very important to support the trust and rapport essential for full disclosure.Footnote 44Footnote 47 Interviews are best carried out in the language the patient is most comfortable with, if necessary through a professional interpreter or an objective third party (not a family member). Face-to-face interviewing, in privacy, is ideal.

Confidentiality of contact investigations should be stressed, but note that legislation may permit or require release of information about the case's diagnosis to specific individuals (including public health authorities). For example, some information may have to be shared in confidence with selected individuals (e.g., a school principal) in order to identify or reach contacts and ensure that they, too, get the medical follow-up they need.

Interviewing is usually best extended over two or more sessions, a week or more apart, as the patient becomes more familiar with public health staff, and the initial stress and anxiety over the diagnosis are resolving. Patients may find it helpful to look at contact lists on their phone, social media, or calendars as a memory aide. Proxy or supplemental interviews with family, close friends, work supervisors, etc. (ideally with patient permission) may be helpful if patients are unable or unwilling to participate. All patients should routinely be asked about the locations where they spend time regularly, as well as names of specific close contacts. Location-based investigation is the basis for social-network approaches discussed below; it is especially critical when highly infectious patients are unable (or unwilling) to name specific contacts in the settings where they spend time.Footnote 48Footnote 49Footnote 50Footnote 51 Location-based screening will inevitably include some nonexposed individuals, but may be the only way to reach contacts at risk in those settings.

All interviews to identify contacts should include the following:

A site visit to assess the home is best practice, even if the initial interview is carried out in hospital, to assess feasibility of home isolation, identification of additional household contacts, identification of any social/practical issues relevant to treatment adherence, and so forth. Site visits to the school or workplace and other exposure locations are also helpful to make contact-investigation decisions (to assess environmental characteristics such as size, layout, use of the space and ventilation; interviews with a direct supervisor can help to identify potential contacts).Footnote 52 Discretion is important, as a site visit may precipitate unnecessary anxiety and/or lead to a breakdown of confidentiality and repercussions for the patient. It is advisable to arrange site visits directly with senior personnel, such as a school principal, division manager or occupational health manager, and emphasize the importance of maintaining confidentiality as much as possible (see Site-based Screening, in the following sections).

4. Organized, systematic contact investigation

4.1 Prioritizing contacts

Recommended priorities for initial contact investigation are outlined below. These are guidelines: it is always important to consider the specific circumstances, work from first principles of TB transmission and re-evaluate according to the results of the investigation as they become available. See Appendix 1 for an example of a structured, risk-based tool to guide initial contact investigation.

Contacts can be prioritized according to high, medium and low priority:

As shown in Figure 3, for index patients who are smear-positive or have cavitary disease, the initial group of contacts to investigate should include both high- and medium-priority contacts. For smear-negative index patients, initial contact investigation should include high-priority contacts only; investigation should be expanded to medium-priority contacts only if there is evidence of transmission among the closer contacts.

Figure 3. Scope of initial contact investigation
Figure 3
Figure 3: Text description

This figure shows the scope of initial contact investigation, with contacts categorized as high, medium or low priority. For smear-positive and/or cavitary TB index patients, the initial contact investigation should include both high- and medium-priority contacts. For smear-negative non-cavitary TB index patients, the initial contact investigation should include high-priority contacts only.

The specific circumstances should always be considered (see the Risk Assessment section). For example, a choir group meeting once per week to sing close together indoors may pose significant riskFootnote 53 but a regular outdoor soccer game generally poses little risk.

Expansion of the investigation to low-priority contacts should be only undertaken if there is clear evidence of transmission in the initial investigation, moving in a concentric circle model to the group with next-closest contact (see the section on Expanding Contact Investigation).

4.2. Standard approach to the screening and clinical evaluation of contacts

Clinical assessment, TB screening and follow-up should follow standard practices, and TB programs should have clearly identified clinical referral pathways for contacts (see Chapter 4: Diagnosis of tuberculosis infection and Chapter 9: Pediatric tuberculosis). Participation rates for TB screening may be higher if it is done directly by TB program staff, whether at the home/exposure site, or at a TB clinic.

All identified contacts who have no symptoms of TB disease, and are not already known to have tested positive on a TST or an interferon-gamma release assay (IGRA), should be assessed for LTBI. The results should be interpreted regardless of Bacille Calmette-Guérin (BCG) vaccination status. Similarly, for people whose first-ever TST and/or IGRA is performed because of the contact investigation, a positive result could reflect infection in the past (remotely) rather than by the recent case. Nevertheless, because of the risk associated with recent exposure, for clinical and public health management, the positive result must be interpreted as a recent infection (see also Chapter 4: Diagnosis of tuberculosis infection). If a TST is the screening test for LTBI, high-priority contacts should ideally have both an initial TST immediately and a second TST at least 8 weeks from the last day of exposure, to identify conversion. If LTBI screening is done by IGRA, a single test at 8 weeks after exposure should be done.

In many medium-priority exposure settings, it is most practical to do a single round of screening after 8 weeks from the last exposure. Especially for non-household contacts, participation rates drop significantly between initial and post-8-week screenings as the level of initial anxiety declines, with up to 50% of those whose initial TST is negative lost to follow-up.Footnote 54 Also, as more time elapses before the initial test, it is progressively less likely that conversions will be detectable since many infected contacts may have already converted to a positive TST. Thus, if an initial screening cannot be organized before 4 weeks from the last exposure and loss to follow-up minimized, it is generally more efficient to do a single post-8-week screening. In populations in which many people have prior exposure to TB or BCG vaccination (e.g., immigrants from high-incidence countries), this also avoids false TST "conversion" related to boosting. In the rare situation that low-priority contacts are investigated, we suggest only a single test at least eight weeks from the last day of exposure.

A 2-step TST (two TSTs done a week apart) is not equivalent to an initial and post-8-week TST. Two-step TSTs are not appropriate in contact investigations (see Chapter 4: Diagnosis of tuberculosis infection).

4.3. Contact investigations in special settings

See also Chapter 12: An introductory guide to tuberculosis care serving indigenous peoples and Chapter 14: Prevention and control of tuberculosis transmission in healthcare settings.

4.3.1. Congregate settings and location-based screening

Screening of medium-priority contacts in schools, workplaces, hospitals, correctional facilities, shelters and other congregate settings is generally most efficiently and effectively carried out on site, especially if the number of identified contacts is large. However, it is critical to coordinate with site leadership and be very organized (see Appendix 2 for a recommended approach).

Unless the investigation is conducted in a systematic, risk-based manner, it may result in hundreds of "contacts" with limited or unknowable exposure and often dismal participation rates. There is often pressure to initiate widespread contact investigation from the outset (e.g., to an entire school, including many low-priority contacts). If indiscriminate screening is performed with no accounting of exposure parameters, however, interpretation of results is extremely difficult. Unless the individual has a documented prior TST/IGRA result it is generally impossible to differentiate between a new versus remote infection in the context of a contact investigation. Contacts with minimal exposure may then be mistakenly identified as recently infected and the investigation expanded yet further.

Anxiety may be minimized by limiting the delay between contacting the site and conducting testing, ensuring that key people at the site get the same information at the same time and holding general education sessions about TB and the investigation plan. Communication from all personnel involved in the investigation should be clear, credible and consistent, especially about the actual level of risk involved and the clinical follow-up plan.

4.3.2. People affected by homelessness

Patients with TB who are homeless or underhoused may also suffer from alcoholism, drug addiction or mental illness, as well as other medical co-morbidities.Footnote 55Footnote 56 They often have poor access to health services, resulting in delayed TB diagnosis, worsening of the disease, prolonged infectiousness and thus large numbers of contacts who need to be assessed.Footnote 57Footnote 58Footnote 59 Many homeless shelters and rooming houses (single-room occupancy hotels) are crowded and have poor ventilation, making them high-risk settings for transmission. Where baseline prevalence rates of TST positivity are high, this also means that a large number of contacts will require further assessment and possible LTBI treatment.

Contact information can prove difficult to gather from individuals experiencing homelessness or severe addictions, related to recall, trust and competing priorities; contacts may be difficult to locate and have low participation rates for TB screening. These challenges can be made more manageable by recognizing that such patients are not "business as usual," prioritizing efforts on risk and impact, ensuring person-centered care, collaborating with partners in the homeless/underhoused services sector and allocating adequate resources.Footnote 60 It is generally most productive to try to identify any particularly close friends or longer-term roommates by name, and to focus on location-based investigation for medium-priority contacts.Footnote 61Footnote 62Footnote 63 Homeless individuals may be highly mobile, with many locations exposed. Shelters may have bed logs, which can help to identify roommates; in large shared rooms, prioritize those who spent the most nights with the case and slept closest.Footnote 34Footnote 64 Also questions should be asked regarding time spent at drop-in centers or soup kitchens providing services for the homeless and underhoused (day-use shelters), libraries, bars, "party houses," parks, and so forth. Staff at shelters or social service agencies and close friends or family may be able to identify daily patterns or specific close contacts. If there are gaps in the history during the infectious period, checking for recent hospitalizations or detainment in a correctional facility may identify additional exposures in these settings.

Homeless contacts may have significant challenges following through on TB screening, medical evaluation and treatment for LTBI.Footnote 65 TB programs should prioritize active case finding in order to curtail additional transmission in this high-risk group, and include LTBI screening if the program will be able to support counseling, follow-up and treatment for infected individuals. Non-judgmental and supportive TB staff, screening activities with the explicit goal of reducing barriers to participation and judicious use of incentives and enablers can help increase participation rates.Footnote 66Footnote 67 It may be possible to find "missing" contacts through confidential alert lists at key service providers so that if these individuals arrive, public health/TB program staff can connect with them for follow-up, though it is essential that partner agencies do not stigmatize these individuals.

Screening on-site at the exposure location and/or in a single session will usually have more success than arrangements involving extra visits or travel (e.g., sputum collection or a portable chest x-ray machine at a shelter-based screening clinic; a one-stop-shop approach at a hospital TB clinic).Footnote 67Footnote 68Footnote 69Footnote 70Footnote 71 Similarly, IGRA may be preferable to TST for LTBI assessment if blood collection can be done on site. Both tests require individuals to be located twice if the goal is initiation of LTBI treatment, but the timeline for the second visit is not so constrained for IGRA as it is for reading a TST. Active participation and encouragement from trusted staff at the shelter or day program during screening clinics is especially helpful. Persistence and flexibility are critical; someone who is not willing to participate on one day may be willing another time.

4.3.3. Contacts during air travel and other transport

The risk of TB transmission during commercial airplane travel is low, and the value of actively screening airplane contacts is limited.Footnote 72 Nevertheless, the WHO has published guidelines outlining the procedures for notifying contacts exposed on international flights with a total duration of ≥8 hours within the previous three months.Footnote 73 Notification of people with TB who report a history of air travel while infectious should be made to the Public Health Agency of Canada (PHAC) through the provincial/territorial TB program. The reporting form can be found at the Government of Canada’s Tuberculosis for public health professionals webpage.

The few published reports of contact tracing after exposure to TB on buses and trains indicate that transmission is possible on repeated daily exposure to the infectious individual, or on long-distance/multi-day trips.Footnote 74 Such events appear rare, and usually involve highly infectious patients and specific environmental circumstances (e.g., daily school bus travel on a crowded, long-duration route in winter, with closed windows and recirculated air).Footnote 75 Taxi rides for local travel have not been associated with transmission.Footnote 76 There is no evidence to support contact tracing related to local public transportation, particularly given the logistic hurdles and considerable inefficiency of contact tracing in these circumstances.Footnote 77

4.3.4. Contact during residence or travel in a high-TB-incidence country

This is covered in Chapter 13: Tuberculosis surveillance and tuberculosis infection testing and treatment in migrants.

4.4. Expanding contact investigation

Contact investigation is iterative; the results of each contact investigation should be reviewed by the public health TB program as they become available, to guide decisions about expansion and/or additional outreach interventions. Recent transmission is considered to have occurred if a secondary case of active TB is identified in any contact, there are clear TST conversions among contacts, the prevalence rate of TST ≥10 mm among contacts is significantly higher than expected (for example, 60% among contacts when the expected prevalence rate is 40%) or a child contact less than 5 years is infected (without another probable source). See Appendix 3 for a table of LTBI prevalence in various Canadian population groups. A fundamental challenge is that transmission can be very difficult to evaluate when the background rate of positive TST results is unknown or high. This is often the case in Canada, where the majority of patients with TB — and many of their close contacts — are foreign-born, originally from high-TB-incidence countries; it is also the case in Indigenous communities with high rates of TB. Thus, Canadian-born contacts with no high-risk travel, particularly children, may have the clearest results for assessing transmission as they are less likely to have prior TB exposure (see Chapter 4: Diagnosis of tuberculosis infection).

When there is evidence of transmission, the investigation should first address any remaining unassessed high-priority contacts, and investigate medium-priority contacts if this has not already been done. Genotyping/whole genome sequencing to compare index and secondary cases should be requested, but further contact tracing should not be delayed pending results. Expansion to low-priority contacts with the next-most level of exposure or who are young children/immunocompromised, in a concentric circle manner, should only be considered if recent transmission is found in medium-priority contacts.

The probability of finding infected individuals among less-exposed contacts, and the likelihood that this group of contacts will follow up on screening and LTBI treatment recommendations, should also be considered in any decision to expand from the initial set of contacts.Footnote 7Footnote 11Footnote 20Footnote 25 Contact participation rates tend to be lower in less-close contacts, contacts of less-infectious patients and in adults compared with children.Footnote 78Footnote 79 For some TB patients, it may not be possible to identify a feasible group of next-most-exposed contacts. Individuals with only transient or occasional exposure (e.g., attending the same school or workplace but not in the same classroom or area of the workplace; customers at a store with a staff case) rarely warrant investigation in the absence of a declared outbreak.Footnote 80

5. Classical TB genotyping, whole genome sequencing and social network analysis: Additional tools for detecting transmission and outbreaks

The following techniques are key programmatic tools for outbreak detection and response, along with standard field epidemiology data.Footnote 81Footnote 82

Mycobacterial interspersed repetitive units: Variable Number Tandem Repeats (MIRU-VNTR) involves counting the number of repeats in up to 24 sites in the Mycobacterium tuberculosis (M. tuberculosis) genome and using this information to generate a signature pattern. If the MIRU-VNTR patterns of isolates from two persons are different, this usually means there was no transmission, while if the patterns are the same, this may support recent transmission between them, that can then be refuted or confirmed by the epidemiologic investigation. This technique can also be used to help determine whether recurrent TB is a relapse or new infection, and to investigate potential specimen mix-ups in the lab.

Whole genome sequencing: Whole genome sequencing (WGS) provides information on nearly 100% of the M. tuberculosis genome. Single base-pair changes, called single nucleotide polymorphisms (SNPs), in one patient's M. tuberculosis genome can be compared to another's to help rule out transmission, by applying a specific threshold of similarity as measured in SNPs. In Canada, WGS for TB was first applied to an outbreak in British Columbia more than a decade ago.Footnote 50 WGS identified two separate transmission clusters, whereas only one was identified with MIRU-VNTR. WGS has since been applied in a variety of settings, including to investigate transmission among persons experiencing homelessness in TorontoFootnote 83 and in Northern Canada.Footnote 84Footnote 85Footnote 86Footnote 87

At present, MIRU-VNTR offers some advantages when compared to WGS: MIRU is already performed as part of public health surveillance in Canada; provincial and national laboratories have extensive experience with this method; turnaround times are relatively short (2-4 weeks); and most public health teams have experience in interpreting the results. In regions with high M. tuberculosis genetic diversity due to immigration and importation of global M. tuberculosis lineages, such as major Canadian urban centers, MIRU-VNTR may be sufficient for surveillance of transmission or discrimination of relapse versus reinfection based on the high probability of seeing different M. tuberculosis lineages. However, in many Northern communities, the genetic diversity of M. tuberculosis is extremely low, and all isolates have the same or very similar MIRU-VNTR pattern simply because the relevant strain has been circulating in this population for decades. Hence, MIRU-VNTR is not useful for discriminating recent transmission from reactivation or relapse from reinfection in these settings; WGS is needed.Footnote 84Footnote 87Footnote 88 For evaluating TB transmission, WGS can substantially reduce the amount of false clusteringFootnote 89 and is demonstrably more consistent with epidemiologic data.Footnote 90 WGS has also been shown to provide higher resolution for discriminating relapse from reinfection.Footnote 91Footnote 92Footnote 93 However, it is important to emphasize that epidemiological confirmation is always necessary in the interpretation of results of either MIRU-VNTR or WGS.

Isolates from all patients in an outbreak share the same MIRU-VNTR pattern. However, with WGS, (particularly for outbreaks with long duration), individual SNPs that accumulate over time in each patient's bacteria can be used to understand transmission within the outbreak. This can better identify source casesFootnote 94 and super spreading events,Footnote 84Footnote 86 and help discriminate different chains or sub-groups of transmission.Footnote 84Footnote 86Footnote 87 Linkage with corresponding clinical and epidemiological data can then be used to identify associated risk factors and inform targeted interventions. In program evaluation, WGS can be useful in estimating the proportion of cases due to recent transmission versus reactivation; the proportion of recurrences due to relapse versus reinfection; or the impact of community-wide interventions on transmission.Footnote 84Footnote 92Footnote 93Footnote 95Footnote 131

Given these advantages, WGS is now recognized as the gold standard for identifying TB transmission and discrimination of relapse/reinfection. In recent years, a number of jurisdictions have transitioned to routine WGS for their TB surveillance programs, including the UK,Footnote 96 USA,Footnote 97 NetherlandsFootnote 98 and the state of Victoria in Australia (Dr. Gonçalves da Silva, personal communication). However, WGS has not yet been widely adopted by TB diagnostic laboratories in Canada because of concerns about cost compared to MIRU-VNTR, need for bioinformatics infrastructure and lengthy turnaround times. Importantly, costs of WGS can be offset by eliminating redundant molecular diagnostic tests. For example, New York StateFootnote 99 estimated an incremental cost for WGS of only US$60 per isolate in 2017.Footnote 99 In the past 2 years, substantial laboratory and bioinformatics analytic capacity has also been developed for genomics of SARS-Cov-2. Given this and the availability of published M. tuberculosis-specific bioinformatics pipelines,Footnote 100 this infrastructure seems within reach. Finally, the turn-around time for WGS-based reporting for resistance was as little as 15 days from early culture positivity in New York StateFootnote 99 and Australia.Footnote 101 A UK-based study found no difference in time to results with MIRU or WGS but estimated that WGS results could have been available 21 days earlier than MIRU results if done under more realistic conditions.Footnote 100

Hence, we suggest consideration be given to transitioning from classical genotyping methods to WGS for routine surveillance of transmission and for outbreak investigations. This transition would provide most immediate advantages in settings with limited M. tuberculosis strain diversity (i.e., Northern Canada), and could then be applied more widely as costs decrease.

Social network analysis is an extension of traditional field epidemiology; it systematically examines the social relationships between cases and contacts to identify settings and behaviors that characterize transmission events, and can be used to visualize or quantify the strength of these connections. Social network analysis has been used extensively in TB outbreaks, most often together with genotyping/WGS; computer software programs for formal social network analysis are available.Footnote 48Footnote 50Footnote 102Footnote 103Footnote 104

6. Management of a TB outbreak

TB outbreaks generally last for several years; as a result, response and control are major undertakings.Footnote 105Footnote 106Footnote 107Footnote 108Footnote 109 TB outbreaks take place in settings where 1) widespread transmission is possible, and 2) the exposed population is vulnerable to rapid development of secondary cases. Social determinants of health underlie most outbreaks: inadequate housing (overcrowding, inadequate ventilation) and limited access to healthcare (resulting in delayed diagnosis and prolonged infectiousness) promote transmission to large numbers of contacts. Among these contacts, young children are especially at risk for progression to TB disease, but other individual risk factors — smoking, poorly controlled diabetes, malnutrition, etc.— are often associated with poverty. Thus, outbreaks are more likely to occur in already-challenged settings, such as among homeless or other marginalized populations and in remote Inuit or First Nations communities.Footnote 50Footnote 84Footnote 109 TB outbreaks are also well-documented in congregate settings, including hospitals and long term care homes, correctional facilities, and shelters.Footnote 110Footnote 111Footnote 112

Good practice statement:

6.1. Definition

An outbreak is the occurrence of more cases than expected over a given time period, with ongoing transmission. Outbreaks may be suspected due to clustering of cases by location, time, behavioral factors or strain genotype.Footnote 113Footnote 114 Note that cases may increase without ongoing transmission, for example due to changes in migration patterns.

The following is a working definition of outbreaks,Footnote 14 intended to help identify and contain rapidly evolving clusters:

Most situations that have been recognized as TB outbreaks involve chains of many more than 2 secondary cases, or one previously unrecognized link to a secondary case, and extend over several years. A slower cluster of linked cases that spans several years may still require heightened TB program response for an identifiable population group yet not be an "outbreak" by the aforementioned definition.

By definition, once an outbreak is declared, additional cases are usually restricted to those who have the outbreak strain, as confirmed by genotyping/WGS of TB isolates. Note that additional unrelated cases may also be diagnosed within the same population during the outbreak period.

While there is no standard for declaring a TB outbreak over, we suggest a functional timeline of 2 years past the last case, consistent with the highest risk period for close contacts to develop active TB.Footnote 115

6.2. Goals

The goals of the investigation and management of an outbreak of TB are as follows:

6.3. Managing an outbreak

TB outbreak response involves ongoing assessment for transmission patterns via detailed social network interviews and genotyping/WGS; managing multiple, often overlapping, contact investigations; and active case finding and outreach with the at-risk population.Footnote 67Footnote 116Footnote 117 At the same time, caseloads for TB patients and for medical follow-up and LTBI treatment of contacts are increased during outbreaks. See Appendix 4 for a more detailed discussion of the recommended components of outbreak response and community-wide screening.

6.3.1. Organization and resources

Assistance from beyond the TB program is usually necessary. Outbreak response within the public health/TB program is often most efficiently organized using an Incident Management System-type structure, with well-defined roles for all those involved. An outbreak coordinating group, chaired by key individuals from the public health/TB program, and including clinical TB experts, hospitals, laboratory and the affected community, is strongly advised.

Good practice statement:

6.3.2. Community outreach and education

TB outbreaks are anxiety-provoking and may be stigmatizing. Often, they take place in a context of limited or inaccurate information about TB and sometimes, negative cultural/historical associations. All these can prolong the outbreak, as lack of recognition of the significance of their symptoms or fear of receiving a diagnosis of TB among individuals can lead to delay in seeking medical care. It is crucial to begin outreach to the affected community and coordinated media communications as early as possible, with information about TB and the outbreak response.Footnote 118

6.3.3. Community-wide screening

In small remote communities, or sometimes in closed settings/well-defined sub-populations, screening the entire affected community may be a useful strategy to consider when local TB resources are not able to manage multiple overlapping cases and contact investigations in an escalating outbreak. It may also be more efficient if a large proportion of the community has already been identified as contacts. This approach has been used recently in Nunavut and Nunavik, and more loosely in urban homeless populations.

6.3.4. Evaluating the outbreak response and identifying fundamental causes

Ongoing evaluation of process and outcomes will help to refine the outbreak response and ensure adequate resources. Both outbreak response and final policy recommendations should address the specific challenges in social determinants of health and/or behavioral risks that fueled the outbreak. In facility-based outbreaks a systematic assessment of conditions (including ventilation) and infection-control policies and practices may also identify concrete areas for improvement (see also Chapter 14: Prevention and control of tuberculosis transmission in healthcare settings). Individual cases can be treated and cured, but it is difficult to contain outbreaks or reduce endemically high rates of TB without addressing the fundamental causes.Footnote 1Footnote 108

Supplemental material

Toronto Public Health contact and screening parameters tool (PDF).

Acknowledgments

We acknowledge and are grateful for the contributions provided by: Rehannah Khan RN, Lauranne Larose RN, Stéphanie Michaud RN, Valerie Messier MD, Carolyn Pim MD, and Paul Rivest MD.

Disclosure Statement

The Canadian Thoracic Society (CTS) TB Standards editors and authors declared potential conflicts of interest at the time of appointment and these were updated throughout the process in accordance with the CTS Conflict of Interest Disclosure Policy. Individual member conflict of interest statements are posted on the CTS website.

Funding

The 8th edition Canadian Tuberculosis Standards are jointly funded by the CTS and the Public Health Agency of Canada, edited by the CTS and published by the CTS in collaboration with the Association of Medical Microbiology and Infectious Disease (AMMI) Canada. However, it is important to note that the clinical recommendations in the Standards are those of the CTS. The CTS TB Standards editors and authors are accountable to the CTS Respiratory Guidelines Committee (CRGC) and the CTS Board of Directors.

The CTS receives unrestricted grants which are combined into a central operating account to facilitate the knowledge translation activities of the CTS Assemblies and its guideline and standards panels. No corporate funders played any role in the collection, review, analysis or interpretation of the scientific literature or in any decisions regarding the recommendations presented in this document.

Appendix 1. Example of a structured, risk-based tool for initial contact investigation

Please see the online supplemental material for an example of a structured, risk-based tool for initial contact investigation.

This Toronto Public Health tool was developed in a southern urban Canadian setting; it may not be suitable for all contexts. For more information, contact targettb@toronto.ca.

If adapted, please acknowledge Toronto Public Health.

Appendix 2. Recommended approach for site-based screening

Appendix 3. Expected range of LTBI prevalence in various Canadian populations

Population Prevalence of LTBI (%) Type of test Publication year
Close contacts born in Canada/USFootnote 20 31.0 TST
(≥5 mm)
2020
Close contacts born outside Canada/USFootnote 20 75.6 TST
(≥5 mm)
2020
First Nations schoolchildren on reserve, routine school screening (at low risk of TB exposure)Footnote 119

BCG in infancy 5.7
no BCG 0.2

TST
(≥10 mm)
2011
Kindergarten children, routine school screening, Iqaluit, NunavutFootnote 120 11.4 TST
(≥10 mm)
2019
Government-assisted refugeesFootnote 121 36.0 TST
(≥10 mm)
2016
Refugees, medium-incidence origin (about 20/100,000)Footnote 122 9.0 IGRA 2018
Migrant children, school-based screeningFootnote 123 22.8 TST
(≥10 mm)
2010
Refugees, very high-incidence origin (>300/100,000)Footnote 124 51.0 IGRA 2016
Federal inmatesFootnote 125 17.6 TST
(≥10 mm)
2008
Dialysis patients, routine screeningFootnote 126 11.5 IGRA 2020
Hematologic cancer patients, routine screeningFootnote 127 8.2 TST
(≥10 mm)
2020

Abbreviations:
LTBI, latent tuberculosis infection; TST, tuberculin skin tests; BCG, Bacille Calmette-Guerin; IGRA interferon-gamma release assay

Appendix 4. Components of outbreak response and community-wide screening

The components recommended for TB outbreak response are similar to those for site-based screening in congregate settings, but much expanded in scope and duration:

Community-wide screening seeks to rapidly reduce prevalent infectious TB via active case-finding in an entire population, and usually also to identify and treat the pool of recent contacts with LTBI. It can also help reduce individual stigma, which can be a real stumbling block for contact investigation and follow-up in smaller communities. As an outbreak-response strategy, it is only practical in small, well-defined populations such as remote northern communities, closed settings or more loosely in homeless outbreaks. It is usually done as a single high-intensity event over 6-8 weeks as a "catch-up" effort, particularly in situations where it is difficult to rapidly assess individual level of contact in a close-knit community, or a majority of the community has already been identified as contacts. It has also been used in repeated lower-intensity cycles (e.g., annually) as part of a TB elimination strategy in com- munities with ongoing high TB rates or repeated outbreaks. This approach needs fewer outside staff and smaller working space, but for a longer commitment.Footnote 129Footnote 130 A recent study using Nunavik data found both single and repeated community-wide screening strategies to be cost-effective in high-incidence remote communities with frequent outbreaks.Footnote 131

Community-wide screening takes considerable planning and resources beyond usual program operations; the decision to proceed should be made only after consideration of the broad local health and community context. TB programs should first consider the healthcare capacity and effectiveness of the current outbreak response. Local staff turnover and lack of TB expertise may be a contributing factor and are common challenges in remote communities; it may be sufficient to supplement the local health care team with additional TB-specific nurses, epidemiologic support, among others, for an extended period to manage the increased TB case/contact needs. If this is neither feasible nor sufficient, then community-wide screening may be a realistic strategy.

Community-wide screening should not be undertaken without consultation with and agreement of community leaders, and all components of the healthcare system (local health center, referral hospital, regional health authority, etc.). It is essential to ensure that resources are adequate to balance TB and LTBI care needs resulting from the community-wide screening with other healthcare needs in the community; a community-wide screening almost always means pulling TB resources from elsewhere in the system and diverting local healthcare resources from other conditions, some of which may also be in crisis (e.g., mental health, addictions, other outbreaks).

In addition to the general outbreak response components recommended above, community-wide screening in remote communities requires consideration of additional logistics:

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Georgia Department of Health. Guidelines for Preventing and Controlling Tuberculosis in Atlanta Homeless Housing Facilities. 2016. https://dph.georgia.gov/sites/dph.georgia.gov/files/TB%20guidelines_5.26.16_EK_FINAL_v2.pdf. Accessed August 27, 2021.

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San Francisco Department of Public Health. San Francisco Shelter Client TB Screening Guidelines. Accessed August 20 2021. https://www.sfcdcp.org/tb-control/tuberculosis-information-for-medical-providers/shelter-client-screening-guidelines/.

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