TB and other Mycobacteria

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TB and other Mycobacteria

• Marcel A. Behr
• marcel.behr_at_mcgill.ca www.molepi.mcgill.ca

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Toronto Star Dec. 3, 2000. Man may have spread
TB in S. Ontario HAMILTON -
Public health officials say a Caribbean man who
may have infected dozens of people in southern
Ontario with a deadly strain of drug-resistant
tuberculosis was contagious when he went through
health testing to get into Canada. Hamilton
health officials believe the man, whose name
hasn't been released, lived undetected in the
Hamilton-Wentworth region for a year with one of
the worst types of TB that doesn't respond to one
or all of the medications that cure the disease.
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Toronto Star Dec. 28, 2000
TB carrier sues Canada for admitting him
HAMILTON - An immigrant with a deadly
strain of drug-resistant tuberculosis who was
exposed to more than 1,000 Ontario residents
while ill is suing the federal government for
allowing him to enter Canada in the first
place. Gaspare Benjamin, a 37-year-old singer
from the Dominican Republic, was mistakenly
cleared to come to Canada in December 1999 with
the infectious disease.
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Le Devoir, April 23, 2002
Trois cas de tuberculose active à l'UdeM
Le Devoir, Isabelle Paré, le mardi 23 avril
2002 Les tests réalisés la semaine dernière à
l'Institut thoracique de Montréal
(ITM) révèlent que trois des 52
étudiants et professeurs de
l'Université de Montréal qui ont été exposés à la
tuberculose sur le campus ont développé la
forme active de la maladie.
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Mycobacteria overview

• Introduction and Definitions
• Epidemiology of Mycobacterioses
• TB Pathogenesis and clinical presentation
• TB Diagnosis
• TB Treatment
• TB Prevention
• Conclusions

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Mycobacteria Background

• most Mycobacteria non-pathogenic
• soil water organisms, more each year
• Mycobacterium tuberculosis tuberculosis (TB)
• also M. bovis, M. africanum
• M. leprae is the agent of leprosy
• Mycobacterium avium avian TB
• also causes disease in AIDS
• M. avium paratuberculosis paraTB or Johnes
  disease of ruminants

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Mycobacteria Properties

• Most slow growing bacteria
• Doubling time about one day
• c.f. E coli 30 min.
• Gram-positive, but dont gram stain
• Mycolic acid cell wall
• acid fast staining
• Acid-fast bacilli positive synonym for
  Mycobacteria is here , R/O TB

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AFB smear
AFB (shown in red) are tubercle bacilli
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Definitions

• Tuberculosis (TB) is the diseased state
• actively replicating bacteria
• contagious, culture positive
• Tuberculous infection is the carrier state
• clinically latent
• non-infectious, tuberculin positive
• Mycobacteria classified as M. tuberculosis or M.
  other than TB (MOTT)

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TB Epidemiology

• Occasionally from animals (e.g. milk)
• With pasteurization, most TB now due to human -
  human transmission
• transmitted in respiratory aerosols
• 1/3 worlds population carry M. tuberculosis not
  infectious
• 8 million cases / year contagious
• 3 million deaths / year

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Tuberculosis Global epidemiology
1.7 billion people
8.4 million cases, 1.9 million deaths each year
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Reported TB Cases US, 1953-98
100,000
70,000
Change in case definition

50,000
Cases (Log Scale)

30,000
20,000
10,000
53
60
70
80
90
98
Year
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Factors Contributing to Increase in TB
Morbidity 1985-1992

• Deterioration of the TB public health
  infrastructure
• HIV/AIDS epidemic
• Immigration from countries where TB is common
• Transmission of TB in congregate settings

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Factors Contributing to Decrease in TB Morbidity
Since 1993

• Increased efforts to strengthen TB control
• programs that
• Promptly identify persons with TB
• Initiate appropriate treatment
• Ensure completion of therapy
• NOTE Immigration still happens and HIV has not
  gone away

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Reported Cases of TB by Country of Birth -
United States, 1986-1998
40
35
30
25
Foreign-born
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Recent Cases per 100,000 population
15
10
All Cases
5
U.S.-born
0
86
98
87
88
89
90
91
92
93
94
95
96
97
Year
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Pathogenesis of Mycobacterial infections

• Best studied for M. tuberculosis
• Initial insult likely function of
• which Mycobacterium
• dose
• site of infection (gut / lungs)
• immune status of host
• age
• constitutive immunity (host genetics)
• acquired immunity (naïve vs. primed, HIV,
  nutrition, etc.)

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Outcomes after Mycobacterial exposure

• Exposure, no infection
• ? frequency
• perhaps bacteria dead/killed at contact
• Exposure, infection, never disease
• 10x more common than disease for TB
• likely even more common with MOTT
• Exposure, infection, disease, /- death
• variable latent period

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Tuberculosis Transmission and Natural History
Infection
Initial containment 95
Early Progression - 5
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Tuberculosis Transmission and Natural History
Self-Cure 90
Infection
Initial containment 95
Early Progression - 5
Late Progression - 5
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TB Pathogenesis

• 10 of infected persons with normal immune
• systems develop TB at some point in life
• HIV strongest risk factor for development of TB
  if
• infected
• Risk of developing TB 7 to 10 each year
• Certain medical conditions / drugs increase risk
  that TB infection will progress to TB disease

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Clinical Manifestations of TB

• General
• fever, weight loss, weakness, consumption
• Organ specific
• pneumonia cough, sputum /- blood
• scrofula swollen lymph nodes
• meningitis headache, obtundation
• miliary TB no obvious source
• genitourinary sterile pyuria

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Chest Radiograph
Abnormalities often seen in apical or posterior
segments of upper lobe or superior segments of
lower lobe May have unusual appearance in
HIV-positive persons Cannot confirm diagnosis
of TB
Arrow points to cavity in patient's right upper
lobe.
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Evaluation for TB

• Medical history
• Physical examination
• Mantoux tuberculin skin test
• for latent infection, not for active TB (see
  below)
• Chest radiograph
• Bacteriologic or histologic exam
• microscopy
• culture
• DNA based detection

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Specimen Collection

• 3 sputum specimens for smear examination and
  culture
• Persons unable to cough up sputum
• induce sputum
• bronchoscopy
• gastric aspiration
• Follow infection control precautions during
  specimen collection

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Cultures
Colonies of M. tuberculosis growing on media

• Use to confirm diagnosis of TB
• Results in 2-3 weeks

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Basic Principles of Treatment

• Provide safest, most effective Rx in shortest
  time
• Multiple drugs to which the organisms susceptible
• mutation rate about 10-7
• patient with TB may have 1010 organisms
• Never add single drug to failing regimen
• Ensure adherence to therapy

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Directly Observed Therapy (DOT)

• Health care worker watches patient swallow each
• dose of medication
• Consider DOT for all patients
• DOT should be used with all intermittent regimens
• DOT can lead to reductions in relapse and
  acquired
• drug resistance
• Use DOT with other measures to promote adherence

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Treatment of TB

• Initiate four drugs
• Isoniazid (INH)
• Rifampin (RIF)
• Pyrazinamide (PZA)
• Ethambutol (EMB) or streptomycin (SM)
• Adjust regimen when drug susceptibility results
  known
• Total treatment usually 8 weeks of 4 drugs 16
  weeks of 2 drugs 24 weeks total

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Prioritizing TB Control

• Identify and treat active TB, to reduce number of
  contagious persons
• Identify contacts of cases, to test for recent
  infection and provide chemoprophylaxis
• Identify people with latent infection as
  potential candidates for chemoRx
• ? role of BCG vaccination

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Groups That Should Be Tested for LTBI

• Persons at higher risk for exposure to TB
• Close contacts of a person known or suspected
• to have TB
• Residents and employees of high-risk
• congregate settings
• Health care workers (HCWs) who serve high-
• risk clients
• Foreign-born persons from areas where TB is
• common

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Groups That Should Be Tested for LTBI (Cont.)

• Persons at higher risk for TB disease once
  infected
• Persons with HIV infection
• Persons recently infected with M. tuberculosis
• Persons with certain medical conditions
• Persons with a history of inadequately treated TB

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Administering Tuberculin Skin Test

• Inject intradermally 0.1 ml of 5
• TU PPD tuberculin
• Produce wheal 6 mm to 10 mm
• in diameter
• Do not recap, bend, or break
• needles, or remove needles from syringes
• Follow universal precautions for infection control

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Reading the Tuberculin Skin Test

• Read reaction 48-72 hours
• after injection
• Measure only induration
• Record reaction in millimeters

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Classifying the Tuberculin Reaction

• gt 5 mm is classified as positive in
• HIV-positive persons
• Recent contacts of TB case
• Persons with fibrotic changes on chest radiograph
  consistent with old healed TB
• Patients with organ transplants and other
• immunosuppressed patients

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Classifying the Tuberculin Reaction (cont.)

• gt 10 mm is classified as positive in others
• e.g. medical students
• gt 15 mm is cut-off for in CDC guidelines
  because South-East U.S. has environmental
  Mycobacteria which can cause weak positive PPD
• N.B. Targeted skin testing programs should only
  be conducted among high-risk groups and where
  you plan to act on results

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Factors that affect the PPD Reaction
Type of Reaction Possible Cause False-positi
ve Nontuberculous mycobacteria
BCG vaccination
Anergy False-negative Recent TB
infection
Very young age (lt 6 months old)
Live-virus vaccination
Overwhelming TB
disease
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Inability of the PPD in distinguishing active TB
from inactive infection
TB contacts
Active TB
Inactive TB infection
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Anergy

• Cannot R/O Dx based on negative skin test result
• Consider anergy in persons with no reaction if
• HIV infected or immunosuppressive therapy.
• Overwhelming TB disease
• Severe or febrile illness
• Viral infections and live-virus vaccinations
• Anergy testing no longer routinely recommended

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Treatment of LTBI with Isoniazid (INH)

• 9-month regimen considered optimal
• Children should receive 9 months of therapy
• Can be given twice-weekly if directly observed

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Preventive Vaccination

• Most countries in world give BCG at birth
• Efficacy against pediatric TB 80
• Efficacy against pulmonary TB unknown
• probably little protection
• BCG therefore likely saves lives
• BCG may have no impact on ongoing epidemic

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TB - Concluding Remarks

• TB epidemic old, but not going away
• TB continues to be barometer of social conditions
• social disease AND infectious disease
• Tools needed to combat TB
• better Dx
• better Rx
• better prevention
• new vaccine