Tuberculosis- Rob Striker,
• “Captain of all these men of death”-
attributed to Osler
The student should be able to:
• State the magnitude of the global tuberculosis problem in
terms of disease morbidity and mortality (#s) &
• Define the terms MDR and XDR TB and discuss their
impact on global health.
• Discuss BCG immunization as a control measure.
• Discuss the relationship between HIV infection &
• Distinguish between exposed, infected and diseased from
• Explain the significance of latent TB in the elderly.
• Recognized for >3000 years
• Chronic bacterial infection causing high
disease morbidity and mortality world-wide
• Airborne disease that is transmitted only
after prolonged exposure to someone with
• TB usually infects the lungs but can be
present in any organ, can be an STD, and
Aerosols generated by coughing,
sneezing and talking dry to form
droplet nuclei. Those (1-5um)
containing 1-3 bacilli are inhaled
• DISEASE STATUS -
– ~ 2 billion people infected world-wide
– ~ 9 million world-wide develop active
tuberculosis annually; ~2 million die
– ~ 10 million new cases in 2005; 1 billion new
cases in 2020.
– Emergence of drug resistant Mycobacterium
• 98% of cases in developing countries with an
increase of ~3% annually, 10% in African
• 80% of cases seen in 22 countries; about half in 5
countries: India, China, Indonesia Nigeria and
• Not confined to developing countries: 70%
increase in former USSR between 1990 and 1995
with MDR-TB ~40% of these cases.
TUBERCULOSIS IN THE USA
• In 19th century killed more than any other disease
• Improvements in nutrition, pollution/, housing,
sanitation in first half of 20th century cut cases to
• Further decline in case rates due to effective
antibiotic therapies in the 40s & 50s with lowest
rates in mid-1980s
• Resurgence peaked in 1992
• Between 10-15 million have latent TB; ~10% will
develop active disease during lifetime. Elderly
with reactivation tuberculosis a threat to infants
and young children.
• 18,371 active cases in 1998.
• In some sectors of US society TB rates now
surpass those in world’s poorest countries.
• TB transmission occurs in the impoverished,
malnourished, drug & alcohol addicted,
overcrowded or in poor health suffering from
chronic diseases and malignancies
• Minorities disproportionately affected.
• Societal issues
– poverty, overcrowding, immigration (how are the poor
• Political issues
– war, resettlement, immigration
• Health issues
– malnutrition, drug abuse, HIV infection,
• Economic issues
– drug costs, health care
THE PROBLEM OF DRUG
• Emergence of drug resistance some 50 years ago.
• Mutation frequencies range from 1 in 105 to 1 in 108
• Primary drug resistance to single drug occurs in
previously untreated cases ~9%.
• Secondary drug resistance occurs in patient who fails to
complete course of treatment and relapses.
• These selected strains also have spontaneous mutations
to other drugs-produce MDR-TB in new hosts.
• MDR-TB difficult and expensive to treat.
• XDR-TB even worse with higher mortality.
CDC & WHO SURVEY OF
DRUG RESISTANT M.TB
• 17,690 TB isolates examined during 2000-2004
• 20% MDR
• 2% XDR
SIGNIFICANCE OF XDR TB
“ XDR TB has emerged as a threat to public
health and TB control, raising concerns of a
future epidemic of virtually untreatable
( MMWR, March 24, 2006)
CAUSES OF DRUG
• Inadequate dosage or treatment with too
• Lack of compliance
– Patients fail to take medication consistently for
6-12 months necessary for cure.
– Patients feel better after 3 or 4 weeks
– Drugs have unpleasant side effects (how many
pills can u take a day?)
– Addicts sell TB drugs to buy narcotics
• Commitment to fight TB at national and
– Control measures…immunization
Diagnosis and surveillance of
• Tuberculin test (Purified Protein Derivitive PPD)
• Chest x ray
• Patient history
• Clinical signs and symptoms
• QuantiFERON-TB Gold
• Invasive procedures
A positive tuberculin test
How is a PPD used?
• To identify newly infected contacts
• To identify potentially infectious spreaders
before putting them in a shared
• To identify potentially infectable people
• How long do immune responses last?
Two steps needed to rule out
latent infection in person you
plan on testing annually
• The first PPD/ Ag can be enough to awaken
the immune response but not enough to get
a positive test
• IF you test again u might accidentally think
• Can NOT boost to a + test if never first saw
tuberculosis or close relative
• Identification of infected individuals.
• Isolation of active disease (incarceration).
• Treating infected individuals with drugs in
combination (DOTS-directly observed therapy
• Identification of MDR TB & XDR TB cases
followed by proper treatment.
• Patient education.
• Current vaccine, bacile Calmette Guerin (BCG), is
a live attenuated vaccine aimed at protecting naïve
• 100 million BCG vaccinations given to children
– will prevent 30,000 cases of tuberculosis meningitis
during first 5 years of life & 11,000 cases of miliary
• BCG immunization does not protect adults against
• WORLD WIDE
– HIV/AIDS epidemic
– Politics–the will to do something about problem
– Political unrest/war
– Lack of public health infrastructure
– Lack of health care services
– Unscrupulous drug manufactures
– HIV/AIDS epidemic
– Civil rights
– Lack of health services
– Lack of isolation facilities
• MMWR, March 24, 2006
• Multidrug and extensively drug-
resistantTB(M/XDR-TB) 2010: WHO GLOBAL
REPORTON SURVEILANCE AND RESPONSE
• P.M. Small and M. Pai. 2010. Tuberculosis
Diagnosis-Time for a Game Change. NEJM.
• M. C. Raviglione and I. Smith. 2007. XDR
Tuberculosis-Implications for Global Public
Health. NEJM. 356:7
• Mountains Beyond Mountains by Tracy Kidder–
the story of Paul Farmer a doc who is making a