Lecture 6- TB

Cultural Genocide

".. is the destruction of those structures and practices that allow the group to continue as a group. States that engage in cultural genocide set out to destroy the political and social institutions of the targeted group. Land is seized, and populations are forcibly transferred and their movement is restricted. Languages are banned. Spiritual leaders are persecuted, spiritual practices are forbidden, and objects of spiritual value are confiscated and destroyed. Most significantly , families are disrupted to prevent the transmission of cultural values and identity from one generation to the next."

M. Tuberculosis

- Aerobic, facultative intracellular bacilli, non- motile, non spore forming - Slow growing: basis of chronic nature of infection - delayed diagnosis (30 hrs) - Mycolic acid cell wall - Doesn't stain well with Gram; special staining is needed (Zhiel-Neelsen, aka acid-fast; hence "acid- fast bacilli" (AFB])

At a higher Risk of Getting Infected

- Close contacts with people with infectious TB* - People born in areas where TB is endemic: • Countries • Areas within countries (e.g., Aboriginals in Canada) - Health care professionals - People using inject illicit drugs - Children and the elderly

Miliary TB

- Disseminated-> spread throughout an organ or the body.

Canada: groups at risk of having latent TB

- Immigrants from high TB prevalence countries - Aboriginal population - Recent (<2 years) contact with an active case - Occupational exposure - Travelers to a TB endemic country 50/70

At a higher risk of developing active TB disease

- Immune deficient - Diabetes or silicosis - Recently infected (within the last 2 y) - People with chest x-rays showing previous TB disease - Illicit drug and alcohol abusers

Sustainable Development Goals

-Ensure healthy lives and promote well-being for all at all ages -By 2030, end the epidemic of AIDS, TB, malaria, and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases -By 2035, zero deaths, disease and suffering die to TB

Global Burden of TB

-In 2015, there were an estimated 10.4 million incident TB cases -11% of incident TB cases in 2015 were HIV positive -62% all incident cases were make, and 90% of cases were adults -6 countries accounted for 60% of the global total

6 Countries

-India -Indonesia -China -Nigeria -Pakistan -South Africa

Transmission

-Some people are better spreaders -# of bacteria expelled varies -some patients more effective as aerosolizers - Smear and patients may have >5,000 bacterial/mL -Not everyone gets it -#of of bacteria being expelled into the air - Bacteria in the air volume/space, ventilation - Length of exposure - immune status

WHO Definition

-TB is an infectious disease caused by the bacillus Mycobacterium tuberculosis. -It typically affects the lungs (pulmonary TB) but can also affect other sites (extrapulmonary TB). -The disease is spread when people who are sick with pulmonary TB expel bacteria into the air, for example by coughing. -Overall, a relatively small proportion (5-15%) of the estimated 2-3 billion people infected with M. tuberculosis will develop TB disease during their lifetime. -However, the probability of developing TB disease is much higher among people infected with HIV. -Easy to spread, easy to catch, and hard to get rid of

Treatment

-TB is treatable and (in most cases) curable - Cure the patient - Prevent transmission -Treatment* = 6-9 months -Initial phase: 2 first months - most bacteria are killed -Continuation phase: kill remaining bacteria -Initial treatment - first line of antibiotics -Isoniazid (INH) -Rifampin (RIF) -Pyrazinamide (PZA) and either -Ethambutol (EMB) or streptomycin (SM)

Latent Infection

-no signs -no symptoms

MULTIDRUG RESISTANCE (MRD-TB)

A TB CASE that is resistant to two first-line drugs: isoniazid and rifampicin

Signs and Symptoms

ACTIVE DISEASE (Pulmonary TB) - Productive,prolongedcough (> 2 weeks) - Shortnessofbreath - Chestpain - Hemoptysis - Fever/chills - Appetiteloss/Unexplained weight loss - Nightsweats - Fatigue

Burden of TB

Can be measured in terms of: -incidence -prevalence -mortality

Zoonotic TB

Mycobacterium bovis TB in cattle and people Impact: -livestock productivity -livelihood of poor and marginalized communities -Zoonotic TB (acquired by consuming of unpasteurized dairy products) -In 2015, there were an estimated 149,000 cases of zoonotic TB in the world

EXTENSIVELY DRUG RESISTANCE (XDR-TB)

Resistance to first and second line of drugs, limiting the possibility of cure

Airborne

TB is spread in the air when people with pulmonary TB expel bacteria, • Droplet nuclei, of 1- 5 microns in diameter. • Highly infectious but the majority of people infected may never know: • ~1/3 of the world pop = latent TB 5-10% will develop active TB

Prevalence

The number of cases of TB at a given point in time

Mortality

The number of deaths caused by TB in a given time period, usually 1 year

Incidence

The number of new and relapse cases of TB arising in a given time period, usually 1 year

Pulmonary TB

Usual site of infection or primary focus: runs parenchyma

Extrapulmonary Tb

e.g. pleura, lymph nodes, abdomen, genitourinary tract, skin, joints and bones, meninges

DRUG-RESISTANT TB

the strain of M. tuberculosis is resistant to one first-line drug: isoniazid (INH), rifampin (RMP), pyrazinamide (PZA) and ethambutol (EMB)

Drug-resistant TB in Canada

~90% of strains are susceptible • The major risk factors for DR-TB in Canada are - previous treatment - foreignbirth

Heliotherapy and cod liver oil = Vitamin D

• "Near the beginning of TB treatment in sanatoria, it became known that the sun helped to kill TB bacteria [heliotherapy). • When the Sun's UV rays hit human skin, vitamin D is produced. • Naturally, when cod fish were found to be rich in vitamin D, it followed that their oil was sold as "liquid sunshine"

Many Infected, not so many ill

• A relatively small proportion of people with Mycobacterium tuberculosis infection will develop TB disease • TB is slightly more reported among men than women • TB affects mostly adults in the economically productive age groups - 2/3 of cases occur among people aged 15-59 yr probability of developing TB is much higher for HIV+

BCG vaccination

• BCG is the only vaccine currently in use against TB - Is alive attenuated vaccine derived from Mycobacterium bovis • The original strain was developed at the Pasteur Institute in Paris in 1921 - Strains further development through repeated sub- culturing in many labs around the world • These newer strains may differ, one from another, antigenic ally • The protective effect of BCG: - Vaccinated against unvaccinated children is estimated at 74%: 64% for meningitis, and up to 78% for disseminated disease • In Canada, BCG has been limited to the First Nations and Inuit populations, in which it has been part of a TB elimination strategy - In 1947, the federal government began to vaccinate "the Indian children of British Columbia" with the bacillus Calmette-Guérin (BCG). - In 1972, there were still an annual tuberculin test, BCG vaccination, and an x-ray program being undertaken at student residences in Saskatchewan

TB marginalization

• By 1909, the school application form for all residential schools instructed physicians who were inspecting potential students not to admit any "child suffering from scrofula [a term used to describe some forms of TB] or any form of tubercular disease."

TB in Residential Schools

• Canada's residential schools and residences for Aboriginal children operated for approximately 130 years • For most of that period, they were funded by Indian Affairs and operated under contract by a number of leading religious denominations. - "It is clear that residential schools were a key component of a Canadian government policy of cultural genocide."

Canadian TB cases and incidence rate 1990-2010

• Declining in the last 20 yrs (in number and the incidence rate • In 1990, the rate was 7.0 per 100,000 population • In 2010 was 4.6 per 100,000 population (1,577 cases reported for 2010).

HISTORY of TB

• In 1546 (?) Girolamo Fracastoro was the first to propose, in his work De contagione, that "phthisis" was transmitted by an invisible virus • In 1720, Benjamin Marten wrote that TB as caused by some type of animacula • 1800s: Consumption, white plague, thought hereditary... sanatoria were built • In 1869, Jean Antoine Villemin demonstrated that the disease was contagious • 1882: Koch discovered etiologic agent • 1943: First anti-TB drug: Streptomycin (Discover by grad student Albert Schatz) • Mid-1980s: TB started increasing • HIV/AIDS • 1993: WHO declared TB a global emergency • 2000: Millennium Development Goals (#6) • 2015: The Sustainable Development Goals (Goal 3: Ensure healthy lives and promote well-being for all at all ages)

Drug-resistant TB globally

• MDR-TB: almost 60% in India, China & the Russian Federation • Extensively drug-resistant TB (XDR-TB): identified in 84 countries; the average proportion of MDR-TB cases with XDR- TB is 9.0%

Ethology

• Mainly caused by Mycobacterium tuberculosis "M. tuberculosis complex" - M. tuberculosis - the major human pathogen - M. bovis - causes TB in animals and humans - M. africanum - M. microti - M. canetti • Also: some non-tuberculous mycobacteria - infrequent, but M. avium can cause TB in HIV patients

Factors contributing to the TB crisis in the residential schools

• TB etiology was unknown until 1882 when Robert demonstrated the existence of tuberculosis bacteria • In the late 19th and early 20th centuries, tuberculosis was the dominant cause of death in Europe and North America • Poor nutrition & housing, and overwork were interlinked; death and death rates were highest among the poor and the institutionalized • TB decline started even before scientists had determined that the disease was communicable - isolation of tubercular patients in sanatoria - improved sanitation - Better nutrition • The first effective TB antibiotic, streptomycin, was developed by Selman Waksman and colleagues in 1944, it did not become widely available until 1948.

Disproportionate TB burden in First Nations people

• Throughout the 1930s, the First Nations death rate from tuberculosis never fell below 600 deaths per 100,000 - But for the overalll Canadian population fell from 79.8 per 100,000 in 1930 to 53.6 per 100,000 in 1939 • In western Canada, the differences in the health conditions of First Nations people and the rest of the population could be measured by the tuberculosis death rates: - In 1934, First Nations people made up 2.2% of the Manitoba population, but accounted for 31% of the tuberculosis deaths - In Saskatchewan, the comparable figures were 1.6% of population and 27% of deaths - In Alberta, they were 2.1% and 34%, respectively - In British Columbia, they were 3.7% and 35%, respectively • There would be no significant improvement in the First Nations tuberculosis death rate until after the Second World War • In 1943, the First Nations tuberculosis death rate was 662.6 per 100,000; by 1957, it was 42.0 per 100,000.183 • By 1960, tuberculosis had been dislodged from its position as the primary cause of death among First Nations people, falling to eighth position. • An Inuit tuberculosis crisis was identified in the 1950s. The Inuit tuberculosis death rate hit 569 per 100,000 in 1952; it fell to 84 per 100,000 in 1960.185

Vitamin D

• Vitamin D sufficiency: beyond bone health • Immunoregulatory properties to fight of infectious diseases including TB - VitaminD acts as a signalling molecule controlling innate immune responses leading to the production of antimicrobial peptides involved in intracellular mycobacteria killing - The only natural sources of vitamin D in the Canadian food supply are fatty fish and egg yolks. - Health Canada's daily recommended intakes (RDAs) for vitamin D, updated in 2011....600 IU for people 1-70,

Why does drug resistance occur?

• When the treatment regimen is inadequate to begin with • When there is intermittent or erratic ingestion of the prescribed anti-TB drugs • When the patient is malabsorbing one or more of the drugs in the treatment regimen • In special TB presentations where drug cannot reach bacteria easily