Tuberculosis and AIDs

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Tuberculosis and AIDs
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• Tuberculosis is more than biology it is a
  statement about society.Keith Wailoo, historian,
  People's Plague, PBS, 1995
• Tuberculosis is a social disease with a medical
  aspect.Sir William Osler

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TB Why Worry About It?

• Leading cause of death at the end of the 19th
  century
• Steady decline in incidence until 1988
• Increase in cases world-wide since then
• WHO declaration of TB as a global emergency in
  1993

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Current Global Trends (2005)

• 2 million people die of TB every year
• 5,000 people every day
• 98 of TB deaths are in the developing world
• TB kills young adults in their most productive
  years

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• TB is the leading cause of death in women
• 1/3 of the worlds population is infected with
  the TB bacillus
• 1 in 10 will develop active TB
• 80 of all TB cases occur in 22 countries
• ½ of these occur in 6 countries

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• 10 highest incidence countries
• India
• China
• Indonesia
• Bangladesh
• Pakistan
• Nigeria
• The Philippines
• Russian Federation

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• Multi-drug resistant TB (MDR-TB) is present in
  virtually all countries surveyed by the WHO
• 425,000 new cases of MDR-TB occur each year
• Highest rates in former USSR China
• In countries with the highest rates of TB/HIV
  co-infection, case fatality rates have risen from
  5 to 20

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• TB is curable
• The most effective way to prevent TB is to treat
  those who have it (WHO)

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Factors Associated with Increase in TB

• Deterioration of public health infrastructure
• HIV epidemic
• Increased emigration from areas of high
  prevalence
• Development of MDR-TB
• Lack of vigilance in high risk areas
• Hospitals
• Prisons
• Personal care homes

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TB Epidemiology in Canada

• Incidence of new and relapsed TB cases has
  generally declined in Canada since 1988
• Manitobas incidence is consistently above the
  national average

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High Risk Populations

• Foreign born
• Canadian born Aboriginal People
• Prisoners
• Seniors

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• Since 1980, the burden of TB has shifted to
  foreign-born Canadians

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Basic Information about TB

• Causative Agent
• Mycobacterium tuberculosis
• Rarely M. bovis
• Non-motile
• Slow growing

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• Obligate
• Cannot grow in the absence of oxygen
• Easily killed
• UV light
• Heat

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• Mode of Transmission
• Person to person
• Coughing
• Sneezing
• Infected droplets suspended in the air
• Pulmonary TB most communicable

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• Pathogenesis
• Not highly contagious
• New infections primarily household contacts of
  index case
• Inhaled droplet settles in upper lobes of lung
• 10 of those who inhale organism develop active TB

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• Primary Stage
• Multiplication of M. tuberculosis
• Little host response
• Non-specific pneumonitis
• Regional lymph node involvement
• Infection appears to subside
• Tuberculin reactivity occurs at this stage

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• Organisms persist within host cells
• Granular formation begins

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• Later Stages
• 1. Dormant infection
• Positive Mantoux only marker
• Most common outcome in healthy individuals
• OR

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• 2. Local spread (pulmonary) with pleural effusion
• Develops over 6 - 12 months
• OR

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• 3. Disseminated (miliary) spread
• Spread via the lymphatic system
• Prefers tissue with
• Low metabolism
• High oxygen tension

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• Most common sites
• Upper lobes of the lungs
• Meninges
• Renal cortex
• Ends of growing bones

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• Immunity
• Tuberculin reactivity (positive Mantoux)
  indicates protection from re-infection
• Principal cause of adult tuberculosis is
  reactivation of a dormant infection

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• Presenting Symptoms
• Respiratory
• Cough
• Expectoration of purulent sputum
• In advanced disease
• Severe compromise of respiratory status
• Cavities evident on chest X-ray

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• Constitutional symptoms
• Fever
• Weight loss
• Anorexia
• Fatigue
• Night sweats
• Pallor
• Anemia

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• Diagnosis
• 1. Mantoux (tuberculin) test
• Intradermal injection of purified protein
  derivative
• Read after 48 - 72 hours
• Positive finding
• 10 mm. or more induration at site of injection

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• Accurate 90 of the time
• Conditions that suppress positive Mantoux
• Age
• Debility
• Acute or fulminate infections
• Immunosuppression

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• 2. Chest X-rays
• Multiple nodules
• Cavity formation
• Contraction with linear shadows loss of volume

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• 3. Microbial specimens
• First AM sputum for culture
• Gastic aspirations
• Smear positive findings are the most infectious
• Cultures take a long time to grow

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• Treatment
• Long term antimicrobial therapy
• Combination of drugs required for effective Tx
• Use drugs with
• Independent mechanisms of action
• Independent mechanisms of resistance

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• Most common drugs
• Isoniazid INH
• Pyrazinamide PZA
• Rifampin RMP

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• Other drugs
• Para-amino-salicylic acid PAS
• Streptomycin SM
• Ethambutol EMB
• Cycloserine
• Ethionamide
• Kanamycin
• Capreomycin

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• Challenges with Treatment
• 1. Sustaining treatment regimes
• Stigma associated with TB
• Drugs have significant side effects
• Treatment takes several months

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• Making the Tx program meet the clients needs
• Shortened drug regimes
• Clinic hours
• Lifestyle
• Language

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• Enhancing compliance with treatment
• Directly Observed Treatment (DOT)
• Basis for WHO TB eradication program
• Keeping track of progress
• Regular culture sensitivity of sputum
• If drug regime not working, always add 2 more
  drugs

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• 2. Emergence of multi-drug resistant TB (MDR-TB)
• Defined as strains of the TB organism which are
  resistant to at least INH and RMP
• Identified as a major threat to global health

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• MDR-TB makes treatment impossible for those who
  do not have access to more sophisticated and
  expensive anti-TB drugs
• MDR-TB at least 100 times more expensive to treat

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• MDR-TB develops in 2 ways
• 1) direct infection from another individual with
  MDR-TB
• Called Primary MDR-TB

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• 2) Medical mismanagement or erratic client
  compliance
• Called secondary MDR-TB
• Only 50 of MDR-TB can be successfully treated
• Can require Tx. with 9 or more drugs

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• Development of totally resistant strains of TB
  has already occurred
• The spread of these organisms would render TB
  incurable
• WHO states that MDR-TB is a direct consequence of
  lack of political will to deal with TB

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• Highest incidence countries
• China
• Former USSR
• 14 of all new TB cases not responding to
  standard drug treatment

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• Drug resistant-TB incidence in Canada is highest
  amongst foreign born residents
• 90 of drug resistant cases amongst foreign born
  occur in
• Alberta
• BC
• Ontario
• Quebec

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• True patterns of resistance in all populations
  not known
• Not all provinces test routinely for resistance
  to 1st line drugs

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Primary Prevention

• Eradication of active re-activated cases
• Elimination of factors which favour TB
• Poverty
• Crowding
• Malnutrition
• War dislocation of populations

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• Effective control of the HIV/AID epidemic
• Effective global control of TB lost when HIV
  emerged in the late 1980s
• Public education

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• BCG vaccination
• Administered to at-risk populations
• Stimulates cellular immunity
• Reduces incidence of extra-pulmonary TB
• Little effect on epidemiology of TB

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Secondary Prevention

• Epidemiological follow-up of index cases
• Reporting to central authority

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• INH prophylaxis of at-risk groups
• Previously inadequately treated TB
• Presumed inactive TB
• Positive Mantoux text chest x-ray but no
  documented TX
• Mantoux converters
• Household contacts of TB cases

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• Positive Mantoux converters who are
• On prolonged corticosteroids
• On immunosuppressive therapy
• Undergoing gastrectomy
• Immunocompromised
• Screening of health care providers
• Monitoring assessment of residents of long term
  care facilities

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TB AIDS

• AIDS complicates TB control in 2 ways
• 1. Those who already have the TB organism in
  their body are more likely to develop (or re-
  develop) active TB after acquiring AIDS

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• 2. Those with AIDS are more likely to develop
  active TB after being exposed to M. tuberculosis
• TB is still curable in the AIDS patient, but the
  disease process is different in several ways
• The course of the disease is more rapid
• Higher prevalence of extra-pulmonary TB
• Less likely to get cavities in the lungs
• All of these factors make Dx more difficult

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• MDR-TB in the AIDS patient is associated with a
  very high mortality rate
• Death occurs very quickly
• Median survival is a few months

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• The same socio-political-economic factors which
  produced the TB crisis also produced the AIDS
  crisis

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• Prevalence of HIV/TB co-infection in Canada
  uncertain
• HIV status of most individuals diagnosed with TB
  unknown

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• Prevention of HIV/TB Co-Infection requires the
  simultaneous application of all we know about
• Primary/Secondary Prevention of TB
• Primary/Secondary Prevention of MDR-TB
• Primary/Secondary Prevention of AIDS