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TB and other Mycobacteria

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Chest Radiograph. Abnormalities often seen in apical. or posterior segments ... Persons with fibrotic changes on chest radiograph consistent with old healed TB ... – PowerPoint PPT presentation

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Title: TB and other Mycobacteria


1
TB and other Mycobacteria
  • Marcel A. Behr
  • marcel.behr_at_mcgill.ca www.molepi.mcgill.ca

2
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.
3
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.
4
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.
5
Mycobacteria overview
  • Introduction and Definitions
  • Epidemiology of Mycobacterioses
  • TB Pathogenesis and clinical presentation
  • TB Diagnosis
  • TB Treatment
  • TB Prevention
  • Conclusions

6
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

7
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

8
AFB smear
AFB (shown in red) are tubercle bacilli
9
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)

10
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

11
(No Transcript)
12
Tuberculosis Global epidemiology
1.7 billion people
8.4 million cases, 1.9 million deaths each year
13
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
14
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

15
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

16
Reported Cases of TB by Country of Birth -
United States, 1986-1998
40
35
30
25
Foreign-born
20
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
17
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.)

18
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

19
Tuberculosis Transmission and Natural History
Infection
Initial containment 95
Early Progression - 5
20
Tuberculosis Transmission and Natural History
Self-Cure 90
Infection
Initial containment 95
Early Progression - 5
Late Progression - 5
21
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

22
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

23
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.
24
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

25
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

26
Cultures
Colonies of M. tuberculosis growing on media
  • Use to confirm diagnosis of TB
  • Results in 2-3 weeks

27
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

28
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

29
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

30
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

31
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

32
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

33
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

34
Reading the Tuberculin Skin Test
  • Read reaction 48-72 hours
  • after injection
  • Measure only induration
  • Record reaction in millimeters

35
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

36
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

37
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
38
Inability of the PPD in distinguishing active TB
from inactive infection
TB contacts
Active TB
Inactive TB infection
39
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

40
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

41
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

42
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
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