Tuberculosis in Northern Manitoba

Gary Podolsky MD

Objectives:

•  To describe the medical importance of Tuberculosis in Manitoba and Globally

•  Describe to methods of prevention, diagnosis and treatment of Tb

•  Describe future prospects in Tb management

Tuberculosis (Tb) is a severe bacterial infection of the lungs and other organs.

One in three people in the world are infected with Tb and it kills three million people each year. TB is considered the most common cause of death from a single infectious organism, Mycobacterium tuberculosis.

Canadians have a long history of suffering from TB. In the 19 th century, one fifth of Canadians were infected with this disease and large numbers died. In the beginning of the 20 th century, the mortality rate among Aboriginal people of Saskatchewan and Alberta reached as high as 9,000 per 100,000

Improvements in socioeconomic conditions, public health services, drug therapy and medical surveillance in Canada markedly reduced the mortality rate [0.4 per 100,000 by 1987] and overall incidence rates (5.9 per 100,000 by 1998).

TUBERCULOSIS IN NORTHERN CANADA

Tb usually follows a pattern - where there is poverty, poor nutrition another co morbid conditions causing chronic health concerns there is tuberculosis. Northern Manitoba follows a similar demographic and cluster cases of tuberculosis occur in Aboriginal settlements making the Canadian North a high risk for Tb. On the other hand Tb can also occur in affluent areas of developed Southern Manitoba like Winnipeg so there is no 'low risk' population. Another recognized source is emigrants to Canada.

Those with occupational exposure to or those with first-degree relatives of tuberculosis patients are also at extreme risk.

Contagiousness is related to the length of exposure to and infectivity of the contact person. Infection is contracted by droplet nuclei from coughing. The bacteria are then ingested by alveolar macrophages in the lungs causing the primary infection. This then spreads through the blood (hematogenously) and becomes a latent Tb infection.   

Latent Tb by definition has no symptoms and is diagnosed with the Tuberculin skin test.

( Mantoux test ) where tuberculin protein is injected intradermally on the forearm to see if that person has been sensitized to tuberculin in the past (either with a prior exposure to the disease or vaccination with BCG). Immunodiagnosis techniques may be used in the future. Treatment of latent Tb can involve months of therapy with anti-tuberculosis drugs.

Active Tb disease will develop in 10% of these latent infections (usually this occurs within 2 yrs in 80% of those who do develop disease). The lungs are most commonly infected (about 50%). On x-ray cavitations, caseation and fibrosis can be seen. Only pulmonary Tb is infectious to others. A direct stain for acid-fast bacilli diagnoses active Tb and this is confirmed by culture. Chest X-rays will show lung infection. Two of the worst types of Tb infection occur more in children under 5 yrs and are miliary (generalized infection) and Tb meningitis.

GENERAL RISK FACTORS FOR TUBERCULOSIS:

Tb is poverty related. As soon as living conditions improve the Tb incidence goes down. In Northern Communities overcrowding and substance abuse also contribute to Tb propagation.

HIV and AIDS can accelerate the symptoms of Tb.

HIV increases the progression of Tb from 10% of latent infections towards active per life to 10% per year of those affected.

With the rise of HIV, Tb has risen and is expected to rise further. There is an under appreciated risk to the traveller of Tb infection but little exists data to prove this.

There are reports of Tb outbreaks among airplane passengers who had sat next to heavily infected individuals who were actively coughing during long flights.

There are outbreaks of Tb among air travelers although this is felt to be very low. The risk aboard an aircraft is felt to be similar to that of waiting inside a doctor's office. Air quality aboard planes is not the issue but proximity to an infected neighbour who is coughing.

TUBERCULOSIS IN NORTHERN MANITOBA

Certain groups in Canada are at higher risk for acquiring TB, such as:

•  Aboriginal population (defined as status and non-status)

•  Indian

•  Metis

•  Inuit, and Innu

•  Foreign-born individuals from countries with high prevalence rates of TB

•  The homeless

•  HIV-infected population

TB IN ABORIGINAL COMMUNITIES

In 1998, the incidence rate among non-Aboriginal Canadians was 1.5 per 100,000; in contrast, the status Indian, total Aboriginal and foreign-born population had incidence rates of 35.4, 22.5 and 21.4 per 100,000 respectively. The proportion of TB cases reported in Canada from foreign-born emigrants has increased, from 35% in 1980 to 64% in 1998.

The Tuberculosis Prevention and Control Unit of Health Canada implemented guidelines recommended by the World Health Organization in 1997 Despite adoption of these guidelines, incidence rates of TB are still high in certain geographic and demographic zones. This makes the elimination of the disease by recommended time periods put forth by Health Canada, an increasingly difficult goal to meet.

Most (75%) of TB patients in Canada live in three provinces: Ontario, Quebec and British Columbia. Furthermore, 90% of all TB cases in the country attributed to the foreign-born population reside in these provinces.

In Manitoba however, the make up of TB patients is distinctly different. The majority of TB cases are among Canadian-born, with the highest incidence among treaty Aboriginals (48.4 per 100,000 overall, with rates as high as 496.3 per 100,000 in select communities.)

All diagnosed cases of tuberculosis in Manitoba are registered in the Manitoba Central Tuberculosis Registry (MCTR) at the Health Sciences Center (HSC) in Winnipeg. Case finding in Manitoba is done by clinical diagnosis of symptomatic patients and by contact tracing. Administered treatment is drug therapy of a combination of first line antituberculosis drugs: rifampin, isoniazid, pyrazinamide, ethambutol, and/or streptomycin. Direct observed therapy (DOT) verifies a completed course of treatment. Ninety-five percent of patients under DOT complete treatment in Manitoba

Tuberculosis Trends in Manitoba( January 1st 1992 and December 31st 1999)

There were 855 reported cases of tuberculosis in Manitoba. Most were born in Canada (70.6%) and almost half of the total patients were with treaty status (44.4%). Non-treaty CB individuals contributed 26.2% of total cases and FB population contributed 29.4% (figure 3 ).

The age distribution of TB cases varies between the three population subgroups. For the treaty status subgroup, the incidence in the oldest (65+) age group was 17.3 times that in the youngest (0-14) age group, whereas this ratio was 10.9 for the non-treaty population, and only 1.3 for the foreign-born population

The TB incidence rate per 100,000 person-years for Manitoban communities ranged from 19.9 to 496.3 per community. Almost all of these cases were in registered treaty individuals. The remaining 15.1% of total patients live in urban areas other than Winnipeg and rural areas other than reserves. Individuals living in urban places other than Winnipeg or rural areas other than reserves experienced a rate of only 4.1 per 100,000 person-year.

The overall Winnipeg incidence rate (9.7 per 100,000 person-years) was comparable to the overall Manitoba's rate (9.2 per 100,000 person-years).

Significant independent risk factors for Tb include :

•  Gender Males are twice as likely to develop clustered TB than females

•  Age

•  Geographic residence

•  Ethnic origin. Treaty status patients are at four times higher risk of developing clustered TB than those without treaty status

•  Residence on a reserve have a five times higher risk of having clustered TB than those living in Winnipeg

TB TRENDS IN MANITOBA

The 1940s marked the beginning of a sharp decline in TB incidence rates in Canada. Unfortunately, the last 10 years have shown a levelling off of total incidence rates at approximately 7 per 100,000, with no decline.

Manitoba shares these same national trends but although rates have declined for every subpopulation, comparative rates among treaty individuals in Manitoba (48.4 per 100,000) are still more than ten times than those of the non-treaty subgroup (3.3 per 100,000).

EMIGRATION TB COMPARED WITH ENDEMIC TB

The overall majority of TB cases in Canada are attributed to immigration, the population distribution of tuberculosis in Manitoba is distinctly different than in the other provinces. While foreign-born cases represent 81% of Ontario TB patients, 48% of Quebec TB patients and 60% of TB patients in British Columbia, in contrast, they represent only 29% of the total TB cases in Manitoba between 1992 and 1999.

TB in Manitoba can be examined in two distinct, parallel categories. These categories are Canadian TB, where the source of the strains and the patients is Canadian, and foreign TB, where both the patients and strains are from outside Canada.

The treaty subgroup, with 44.4% of all tuberculosis cases in Manitoba, comprises the largest group of cases, despite the fact that they represent only 8.9% of Manitoba's population. This figure is probably an underestimated. Certain northern First Nation communities have TB incidence rates that are markedly elevated (up to 496.3 per 100 000 person-years). Winnipeg and nine Aboriginal reserves of northern Manitoba appear to be the two reservoirs that maintain the bulk of clustered TB cases. Patients on reserves were found to be more than six times as likely to have clustered TB compared to patients in Winnipeg.

Sixty percent of Manitoba's entire population lives in Winnipeg and there is considerable mobility between Winnipeg and the reserve communities. Types of contact relationships are important factors in explaining the spread of TB

ELIMINATION OF TB IN MANITOBA

Elimination of TB has been defined as less than 1 case per 100,000 people per year. By this standard, recent transmission to Canadian-born non-treaty status individuals has been nearly eliminated, reaching incidence rates of only 3.3 per 100,000.

Complete elimination of TB in Manitoba has been targeted for 2010, with 5% reduction in incidence per year as a goal Targeting and intensifying control measures in the immigrant and treaty status Aboriginal subpopulations are a priority for tuberculosis elimination in Manitoba

Figure 4 Sanatorium at Ninnete

HEALTH CARE WORKERS AND TB

Health Care professionals (Nurses, Doctors, and Paramedics) are also felt to be at risk for Tb, since they are exposed to many sick people, including those institutionalized for chronic illness. Single exposures may not be high risk but accumulated encounters increase the chance of infection.

At present all new health care professionals are required to have a two-step Mantoux test performed and documented followed by annual one step Mantoux tests (depending on their institution).

TUBERCULOSIS IN TRAVELERS TO DEVELOPING COUNTRIES

Risk to travelers of Tb exposure can be expressed from the rate of Mantoux skin test conversions from negative to positive indicating that exposure has occurred. A Peace Corps study showed 15 per 1000 travelers' skin test conversions. In another study, health care volunteers had a conversion rate 7.9 while tourists had a rate of 3.5. Expatriates and long term tourists have a risk of Tb that becomes similar to the host country (1-3 %).

TB CONTROL FOCUSES ON:

1. Avoiding exposure.
2. BCG vaccination.
3. Identifying and treating latent Tb infections.

AVOIDING TUBERCULOSIS EXPOSURE

This is an important point but sometimes under stressed. Healthcare workers, Travelers, and relatives of those with tuberculosis should be knowledgeable about the signs and symptoms of tuberculosis. Avoiding unnecessary contact with high-risk contacts through education.

BCG VACCINE :

The BCG (Bacille Calmette-Guerin) vaccine is a live attenuated vaccine of Mycobacterium Bovis (cow tuberculosis), which protects against disease but not infection. It will induce Tb sensitivity but not infection.

Studies compare different effectiveness and opinions vary from country to country from 0-80%. In better-designed studies, it appears to have a more proven benefit. Closer to the equator studies have shown less protection.

BCG does protect against the miliary and meningeal Tb infections. Duration is thought to be about 10-15 yrs. Although used in the past with high- risk populations (native children and military personnel), it is not presently given routinely in Manitoba except for some high-risk situations up north. In some countries where it is given, it is administered at least 6 wks before travel. Contraindications to its use are: immune suppression, any HIV infection regardless of their CD4 counts, and a positive Mantoux test. Complications include having an abscess formation at the inoculum site.

Precautions- Care must be given when selecting candidates for the BCG vaccine. Individuals with suggestion of immunocompromization should not receive the BCG. One child died of disseminated BCG infection in Manitoba after receiving the BCG. It was later determined that this infant had a congenital immunosuppression.

The BCG vaccine protects against disease but not against the infection. Studies conclude 0-80% protection. Closer to the equator there is less protection. Protection cannot be predicted, (0-80%). BCG protects against miliary (widespread disseminated), and meningeal Tb. Although BCG is used in certain parts it is not given in Manitoba. High- risk aboriginal children may receive BCG.

Future Tuberculosis vaccines are being researched. The most promising candidates are those using "Naked DNA" technology, which is still far from being available.

Case history A Pediatrician colleague reated that one of her Aboriginal infants died from disseminated BCG infection from the vaccine because of an unknown hereditary immune deficiency. This highlights that BCG is not without risks, particularly in HIV positive mothers.

IDENTIFICATION OF TB EXPOSURE:

The Mantoux skin test or Tuberculin Sensitivity Test (TST)

The Mantoux test consists of injecting 0.1 ml of purified tuberculin protein intradermally. An experienced doctor or nurse, 48hrs-72hr later must read the injection site. This protein is not infectious and there is no risk of acquiring Tb from this test. The immune system will recognize the tuberculin protein if that person has been sensitized (either be exposure to Tb or with the BCG vaccine) and mount an immune response at the injection site (which becomes red and indurated).

The skin is measured for induration (hardness and swelling) around the site and not erythema (redness alone). That is why it is important for skin tests to be read by an experienced nurse or doctor as individuals (including doctors and nurses themselves) may misread this test by confusing simple bruising with a positive test or mistaking a positive induration for a normal interpretation.

Local guidelines for interpretation should be followed, as tuberculin doses are not universally standardized.

In Manitoba 10mm of induration is felt to be a positive test. Sensitivity of this test may be affected by insulin dependant diabetes and pregnancy although these people should still be tested if indicated.

There may also exist a booster effect from having a recent Mantoux test if given recently.

Doing a two-step Mantoux test can detect this. This test checks to see if a boosting effect occurs from the first injection of tuberculin rather than because of true exposure to Tuberculosis.

The Mantoux test is done once and then again 1-3 weeks later to see if a boosting effect takes place. If a boosting effect does take place then this should be documented and factored in when reading future Mantoux tests since it is now known that this individual has a boosting effect with regards to tuberculin sensitivity. Still a chest x-ray is also performed on all individuals with a positive first or second step Mantoux.

Individuals who had been vaccinated with the BCG vaccine may have a positive Mantoux although if vaccinated in their first year of life they may be Mantoux negative. If a BCG has been done in the past it is recommended to do the 2 step Mantoux. Individuals with weakened immune response may show anergy or the inability to mount an immune response against the Mantoux test and will be false negative.

The Mantoux test has several limitations:

False positives from other forms of Mycobacteria in the environment may lead to overdiagnosis.

False negatives happen when the individual is anergic- that is unable to mount an effective immune response against the tuberculin protein. Conditions such as malnutrition, diabetes, HIV (which is much more common in tuberculosis), and pregnancy.

Although less commonly performed, an anergy screen can be done when anergy is suspected.

The individual may be tested with several antigens at well-labeled sites that may include- ragweed, cryptosporidium, normal saline and tuberculin. A normal individual may respond positively with ragweed. An individual who develops a wheal from plain normal saline may just simply only sensitive and this should be considered in interpreting mantouxs since these individuals are sensitive to all injections.

Quantaferon

This is new test that measures the amount of interferon that correlates with tuberculosis infections. It is hopeful that this will prove to be a quantitative objective test which will improve the diagnosis of tuberculosis. By speeding up new diagnoses this will hopefully have a positive impact on the incidence of tuberculosis in communities. At present quantaferon has been accepted as a validated test by many countries but not Manitoba Health.

TREATMENT OF POSITIVE CONVERSIONS (NEW LATENT INFECTIONS)

WHEN TO TREAT?

All new suspected conversions should be referred to a local Tuberculosis Treatment Program for further assessment and follow-up. For infected individuals, drugs will need to be taken for months and patients need to be followed.

TUBERCULOSIS CONCLUSION:

1. Health Care professionals, Relatives of people with tuberculosis and long- term travelers have an elevated risk for contracting Tb.
2. BCG may be recommended for high- risk travelers (although not in Canada). It still has limited uses up in Northern communities.
3. Serology may replace skin tests in future, which could make in detection much easier.
4. Newer vaccines are unlikely to come out in the very near future.
5. At present the best way to control Tb is to promptly treat new cases and have people who are in high-risk situations.

TUBERCULOSIS LINKS

Fanning EA: Globalization of tuberculosis. CMAJ 1998, 158:611-612.

Raviglione MC, Snider DE, Kochi A: Global epidemiology of tuberculosis: morbidity and mortality of a worldwide epidemic.JAMA 1995, 273:220-226.

Long R, ed: Canadian Tuberculosis Standards.Canadian Lung Association and Health Canada5 Edition 2000

Long R, Njoo H, Hershfield E: Tuberculosis: 3. Epidemiology of the disease in Canada.

CMAJ 1993, 160:1185-1190.

Blackwood KS, Al-AzemA, Elliott , LJ, Hershfield , ES Kabani M Conventional and molecular epidemiology of Tuberculosis in Manitoba BMC Infectious Diseases 2003

Print :, Yellow Book 2001, and The CDC Pink Book 2000 .

CDC http://www.cdc.gov/nchstp/tb/faqs/qa.htm

tuberculosis.net http://www.tuberculosis.net/

who http://www.who.int/gtb/

Stop TB http://www.who.int/gtb/

Nature http://www.nature.com/nm/special_focus/tb/