Medical Guidelines

Clinical review

Microbiology and pathogenesis

• The etiologic agent of tuberculosis is Mycobacterium tuberculosis
• Worldwide 8 million new TB infections occur annually
• 1.7 million people die of TB annually
• Globally, TB is the second leading cause of death due to infectious cause (second to HIV)
• Human host is the only known natural reservoir of tuberculin bacteria
• The organism’s ability to cause latent infections allows for high rates of transmission

Natural history

Inhalation of the tubercle bacillus leads to deposition into lung parenchyma.
This proceeds to one of four possible outcomes:

1. acute clearance of the bacterium
2. chronic or latent infection
3. primary or active disease
4. reactivation disease (active disease many years post initial infection)

Transmission

TB transmission occurs person to person via droplet inhalation. Transmissible airborne particles are approximately 1 to 5 microns in diameter. All healthcare practitioners should wear masks when working with suspected TB patients.

In the airways, tuberculosis bacteria are ingested by macrophages. Macrophages, however, cannot arrest multiplication of the individual bacterium. Ultimately the macrophages are destroyed. At this stage immunity develops creating a quiescent state. Infection is often only recognized by reactivity to tuberculin skin testing. In some patients, a Ghon complex, made of infected pulmonary parenchyma and lymph nodes, develops. Primary progression or reactivation may occur here. This is most likely in circumstances of malnutrition or immunosuppression.

Who is contagious?

• People with untreated active pulmonary tuberculosis are contagious. Contagiousness increases in settings of cavitary disease, or when sputum is acid fast bacilli smear (AFB) positive.
• Extrapulmonary tuberculosis is not considered contagious. However, many persons with extrapulmonary disease also have pulmonary disease.

Clinical manifestations

Patients with active pulmonary tuberculosis are often asymptomatic. Constitutional symptoms such as fever, night sweats, weight loss, as well as localized symptoms such as cough may develop. The pulmonary exam is often minimally abnormal. Those who are immunocompromised such as those with HIV infection often present with no classic features. Thus, they are at high risk of transmissibility, dissemination and extrapulmonary infection.

Tuberculosis cough

• often described as initially mild
• usually non productive or productive of scant sputum
• often worse in morning, when accumulated secretions reach highest levels
• cough can progress to productive with yellow/brown sputum (with/without trace blood)
• hemoptysis usually signifies caseous sloughing or endobronchial erosion, usually late in disease
• dyspnea can develop if parenchyma is extensively involved; pleural effusions/pneumothorax may develop

Radiographic abnormalities

The most common abnormality on CXR is hilar adenopathy. Hilar changes can be seen as early as one week after skin test conversion and usually within two months. Within the first three to four months after infection, pleural effusions can develop.

Reactivation TB involves apical posterior segments of upper lung lobes 80–90% of the time. Other common radiographic findings include lesions in the superior segment of the lower lobes as well as anterior segment of the upper lobes.

An anteroposterior X-ray of a patient diagnosed with advanced bilateral pulmonary tuberculosis. Image: CDC

Reactivation tuberculosis

There are multiple terms cited in the literature to describe this stage/type of tuberculosis. These include: chronic TB, post primary TB, adult type progressive TB. 

Reactivation TB results from the reactivation of a previously dormant TB focus which was seeded during the time of primary infection. Reactivation TB represents 90% of adult TB (not including the HIV affected population). The posterior segments of the apical lung zones are often involved. A ‘Simon Focus’ is a small scar in this area, thought to be the original site of spread.

Symptoms of reactivation TB:

• symptoms often begin insidiously
• they are often present for weeks to months before diagnosis
• half to two thirds of patients develop cough, weight loss, fatigue
• one half develop fever, night sweats
• one third develop chest pain and/or dyspnea
• one quarter develop hemoptysis

Laboratory findings:

In most pulmonary TB normal laboratory studies are found. In late disease, hematologic changes include normocytic anemia, leukocytosis and rarely monocytosis. If SIADH (syndrome of inappropriate antidiuretic hormone secretion) develops, hyponatremia may result.

Canadian TB screening & surveillance of immigrants

• The burden of tuberculosis in Canada is costly. Some estimate the direct costs of tuberculosis reach 58 million dollars annually. Tuberculosis treatment is lengthy; tuberculosis patients often require hospitalizations and mortality rates remain high (11%).
• Foreign-born persons account for 65% of Canada’s active tuberculosis.
• Canada’s overall rate of active TB is 5/100 000.
• Foreign-born persons overall have a tuberculosis incidence 20 times higher than non-Aboriginal Canadian-born population.

How are immigrants screened for tuberculosis before arrival to Canada?

Before entry to Canada all persons are screened for active tuberculosis using chest x-ray. If chest x-ray is positive, sputum culture is ordered. These persons include all those > 11 years of age doing one of the following:

1. applying for permanent residency
2. claiming refugee status
3. students and workers staying longer than six months

Those who have active tuberculosis must be adequately treated before entry to Canada. Negative sputum culture results are demonstrated to show this. 

Children less than 11 years of age at time of migration to Canada DO NOT undergo pre-arrival radiographic screening. Thus, this population could benefit from screening once contact has been made with Canadian primary care professionals. In particular, this age population, especially those under 5 years old, are more susceptible to severe or rapidly progressive disease.

Post-Landing Surveillance Program:

Persons applying to enter Canada found to have inactive tuberculosis or previously treated tuberculosis are required to enter Canada’s Post-Landing Surveillance Program. This program requires monitoring within 30 days upon arrival to Canada.

Screening for latent TB

The following text was retrieved from this 2010 document:

PHAC has an exhaustive table of countries and their smear positive TB rate (scroll down). Or, use the map below.

What screening tests are available in Canada?

The two tests available in Canada to diagnose latent tuberculosis infection are the tuberculin skin test and interferon gamma release assays. The sensitivities for these tests are estimated to be 70–90%. Specificities for both tests are >95%.

Tuberculin skin test versus IGRA

The most recent Canadian guidelines recommend using tuberculin skin testing as the initial and primary screening tool for both adults and children. IGRA (Interferon-Gamma Release Assay) is a whole blood test recommended as a sequential tool for those who have tested positive by tuberculin skin test, but are in low risk categories. Thus, IGRA is recommended to rescreen those who have high likelihood of false positive results from tuberculin skin test.

(Note: IGRA is not available in all parts of BC. Please contact the BC Center for Disease Control for up to date local information).

Advantages of IGRA testing is that as opposed to skin testing which requires follow up, blood testing is completed in one visit only. Also, previous BCG vaccination does not cause cross reactivity.

How does the BCG vaccine affect TB screening?

• Those vaccinated with the BCG (Bacillus Calmette-Guérin) vaccine are at risk for false positive tuberculin skin test results due to cross reactivity
• The current WHO recommendation is for all children living in high tuberculosis zones to be vaccinated. Thus, many Canadian refugees may have received BCG vaccination while in their home country
• The likelihood of false-positive skin tests caused by cross reactivity is inversely proportional to the time since BCG vaccination. Age at time of vaccination also plays a role.
• For example: In the first 10 years after vaccination, 42% of those vaccinated after age two will have positive tuberculin skin tests. Those vaccinated while a neonate will have a lesser chance of resulting positive on tuberculin skin test. For those who were vaccinated less than 10 years ago, 21% will result positive, if vaccinated after age two. 1-2% will result positive if vaccinated as neonate, less than 10 years ago

If tuberculin skin testing is positive, what are the next steps?

When a tuberculin skin test is performed and resulted positive, all persons should undergo CXR to rule out active TB. Thorough history should be taken, with a focus on symptoms of:

• cough
• weight loss
• fever
• night sweats
• hemoptysis

Practitioners should also send three samples of sputum (and/or specimens from other sites) for smear and culture.

Many family physicians refer TST positive patients to one of BC’s TB clinics. Therapy can then be managed by experienced practitioners. Contact the BCCDC for advice in the setting of positive TST. 

Treatment

Treatment of active tuberculosis:

Due to increasing concerns of resistance, patients with suspected or confirmed active TB are usually treated with multi drug therapy. Regimens usually include four first line medications such as isoniazid, rifampin, pyrazinamide, and ethambutol. Quadrupal therapy is usually maintained for two months. This is followed by de-escalation of therapy with isoniazid and rifampin continued for seven months. Total treatment time is nine months.

Treatment of latent tuberculosis infection: what are the risks and benefits?

A nine-month course of Isoniazid is the standard of care for treating latent tuberculosis infection in Canada. It has been shown to decrease the likelihood of active tuberculosis in people with latent tuberculosis infection. The overall efficacy of isoniazid treatment is 62% - 93% after 12 months depending on treatment compliance. In those who take >80% of treatment doses, efficacy increases to >90%.

The most significant risk associated with isoniazid therapy is hepatotoxicity. This most often manifests as a transient and asymptomatic increase in liver function tests. Rarely, symptomatic hepatitis can develop. This condition is usually reversible with isoniazid cessation. Very rarely (>0.01%) fulminant hepatitis and liver failure occurs. This can lead to death.

Some subgroups carry increased risk of hepatotoxicity. These include those with pre-existing liver disease, alcoholism, usage of other hepatotoxic medications/drugs. All patients on isoniazid treatment should have monthly blood work for monitoring. All immigrant and refugee populations should be informed of isoniazid’s risk profile. Clear descriptions of possible symptoms and side effects should be explained, with interpreters if necessary.

BC Tuberculosis Control Clinics

Information Retrieved from BCCDC

New Westminster - TB Control Clinic

Diagnosis, treatment and follow up of patients with active tuberculosis (TB) disease or latent TB infection. TB medication for patients with active TB disease or latent TB infection. Resources and multilingual education materials about TB and related issues. Skin tests and chest x-rays when indicated.

Please note: Skin tests are performed by appointment only. There is a fee of $40.00 for tuberculin skin testing. Payment may be made in cash, exact amount only or by cheque. No credit or debit cards are accepted.

Vancouver - Downtown Outreach TB Clinic

TB and related outreach services.

Vancouver - TB Control Clinic

Diagnosis, treatment and follow up of patients with active tuberculosis (TB) disease or latent TB infection. TB medication for patients with active TB disease or latent TB infection. Resources and multilingual education materials about TB and related issues. Skin tests and chest x-rays when indicated.

Please note: Skin tests are performed by appointment only. There is a fee of $40.00 for tuberculin skin testing. Payment may be made by Mastercard, Visa, cash (exact amount only) or debit card.

Victoria - TB Clinic (Vancouver Island Health Authority)

Diagnosis, treatment and follow up of patients with active tuberculosis (TB) disease or latent TB infection. Resources and multilingual education materials about TB and related issues. Skin tests and chest x-rays when indicated.

Translated patient handouts

BC Lung Association

Minnesota Department of Health

References

Tuberculosis: Evidence Review for Newly Arriving Immigrants and Refugees

British Columbia Center for Disease Control