TUBERCULOSIS

Fai Hassan & Rashida Brown

What is TB?

A lung infection

Mostly caused by M. tuberculosis

Generation time 15-20 hrs

Genetically diverse

Aerobic, Gram-positive

No outer cell membrane

High lipid content in cell wall

Infects alveolar macrophages

Immune response is very complicated

Stages of Infection

Picture of M. tuberculosis

TB: Not so humble beginnings Index case: The mystery of the 500 000 year old

mummy

3000 BCE – 100 CE:

Independent international epidemics

Treatments varied from urine to blood, and from

living in the mountains to living underground

Middle ages – 1850s

Death toll rises to 25%

•Franz Kafka•George Orwell•Most of the Brontë family•Louis Braille

Famous Victims of TB

19th & 20th Centuries

1993TB is worldwide epidemic

1980s

Vaccination campaign

1967

Rifampicin becomes part of treatment

1952

Isoniazid is discovered

1944

Streptomycin is discovered1906

BCG vaccine is discovered

1882

Robert Koch discovers M. tuberculosis

1854

First sanatorium is opened

The Vaccination Campaigns of TB

Started in the 1940s

WHO was under a lot of criticism for the campaign

Vaccination campaign of the 1980s

Why? Because of MDR-TB & HIV

Vaccination rejuvenated in 2006

Why? Because of XDR-TB

Also because of the South African outbreak

(discussed later)

Vaccination Campaign: New Hope

Standard Vaccine: BCG

Safety concern with HIV+ patients

Potential solution for HIV+ patients: M. viccae

Vaccines currently in development:

MVA85A

rBCG30

72F fusion protein

ESAT6-Ag85b fusion protein

What about TB in Canada?

What about TB in Canada?

New Smear Positive Cases in Canada 1990-2007

Global TB Incidence Comparison

Diagnosis

Skin Test

Test exposure to TB

PPD is injected just under skin of the inner forearm

AFB Smear and culture

Acid-fast bacillus

 Positive cultures identify the mycobacterium and

drug resistance

Diagnosis

Chest X-Ray

Gold Test

Whole-blood test to diagnose LTBI and

tuberculosis TB disease

Chest X-ray of Patient with TB

Treatment Protocol

DOTS

Directly Observed Treatment, Short-course

Most efficient and cost-effective method of treating TB

Integrated Strategy

Appropriate diagnosis of TB

Registration of each patient detected

Standardized multi-drug

Individual patient outcome evaluation

DOTS costs only US $3 - $7 for every healthy year of life gained

Fact

TB Medication

The most common anti-TB medicines are:

Isoniazid

Rifampicin

Pyrazinamide

Ethambutol

Minimum of 3 drugs over a 6-month period

Isoniazid, Rifampicin and Pyrazinamide for 2 months

Followed by Isoniazid and Rifampicin for a further 4

months

Drug Resistance

The improper use of antibiotics in chemotherapy

of drug-susceptible TB patients

Administration of improper treatment regimens by

health-care workers

Failure to ensure that patients complete the whole

course of treatment

Treatment requires extensive chemotherapy for

up to two years

Drug Resistant TB

Multidrug-resistant TB (MDR-TB)

Does not respond to first-line drugs

Bacillus resistant to at least Isoniazid and Rifampicin

Present in all countries

Extensively drug-resistant TB (XDR-TB)

Does not respond to second-line drugs

Extremely difficult to treat

Cases have been confirmed in more than 50 countries

MDR-TB

MDR-TB

Geographic Distribution of XDR-TB

Current Issues

Rapid spread due to increased air travel and immigration

Immense socioeconomic burden Growing at-risk populations Instances of limited access to diagnosis

and treatment

Poverty

Majority of TB-related deaths are in the developing

world

There were 9.27 million new TB cases in 2007

80% were in 22 countries

13 of the 15 countries with the highest estimated TB

incidence rates are in Africa

Half of all new cases are in six Asian countries

Bangladesh, China, India, Indonesia, Pakistan and the

Philippines

Gapminder

Number of Infectious TB Cases Reported vs. Poverty (% living below nationally defined poverty line)

Gapminder graph

TB Distribution in 2006

Poverty distribution in 2006

TB/HIV Co-infection

Major cause of death among people living with HIV/AIDS

Compromised immune systems

A total of 1.77 million people died from TB in 2008,

456 000 of those people were living with HIV

9.4 million new cases in 2008, 1.4 million are HIV-related

Most of these cases in Sub-Saharan Africa

Collaborative TB/HIV programming is needed

HIV prevalence in incident TB cases (%), By Country, Total, 2007

TB Vaccination of HIV+ Individuals

New TB vaccine specifically designed for HIV-positive

people

Pre-clinical trials with guinea pigs

Safer and more potent than the current TB vaccine

Current BCG vaccine can cause serious long-term

complications if HIV weakens the immune system

New method to limit replication of the vaccine in the body

Enough to stimulate the immune system to produce T cells, but

not enough to overwhelm the immune system

Gender

Higher TB mortality in men than among women

TB is a leading infectious cause of death among women

Affects women mainly in their economically and

reproductively active years

Tremendous social impact

Annually, 750 000 women die of TB

Over 3 million contract the disease

Accounts for about 17 million DALYs

Prisons

The level of TB, and MDR-TB in prisons

significantly higher than that of the civilian

population 

Due to:

Late diagnosis, inadequate treatment, overcrowding,

poor ventilation and repeated transfers

HIV infection and other pathology more common in

prisons (e.g. malnutrition, substance abuse)

Smokers

Smoking increases the risk of TB disease

by more than two-and-a-half times

More than 20% of global TB incidence

may be attributable to smoking

Correlation between Smoking and TB

Current Research

LXR proteins in the mouse immune response to airway infection

New target for therapeutics

Molecules that activate LXRs provided protection from both a

new infection and established infections

Using gene chips to look at how TB bacteria behave in different

environments

Slowly growing bacteria are non-responsive to treatment with

isoniazid

Reason why it takes six months to treat pulmonary TB

successfully

Halve the prevalence of infectious TB as well as TB-attributable mortality, and begin to reduce incidence.

2015 Millennium Development Goal

Millennium Development Goal Stop TB Strategy:

Pursue high-quality DOTS expansion

Address TB/HIV, MDR-TB, and at-risk groups

Contribute to health system strengthening

Engage all care providers

Empower people with TB through partnership

Promote research