tuberculosis fai hassan & rashida brown. what is tb? a lung infection mostly caused by m....
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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