Mycobacteriosis

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Mycobacteriosis
Joseph Horvath, M.D. USC Division of Infectious
Diseases

• Clinical correlations 7
• Med Micro 2008

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Mycobacteria

• Tuberculosis
• Leprosy (Hansen Disease)
• BCG hypersensitivity and infection
• MOTT
• AIDS related disseminated MAC
• Immune reconstitution disease

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Mycobacteria

• All species resist decloration, i.e. acid fast
• All cause granulomatous inflammation
• All are more common and/or more severe with cell
  mediated immune dysfunction
• Can cause delayed diagnosis if not specifically
  sought
• Only TB spread person to person

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Dx of Mycobacteria

• Smear- acid fast stains (Kinyoun, auromine)
  rare false positives
• Culture all species other than M.tb and M.
  leprae must be correlated clinically
• PCR currently only for interpretation
  respiratory secretion smear () and PCR ()
  means TB, smear () but PCR (-) means MOTT, smear
  (-) but PCR () means TB
• Histology granulomatous inflammation narrows
  differential greatly even if stains (-) for AFB

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Mycobacterium leprae

• Unique infection able to manifest full spectrum
  from nearly unopposed to intense granulomatous
  immune response
• Temperate climates worldwide
• La.,Ark.,Tx.,Miss.in USA
• Not grown in vitro
• Respiratory tract entry, seeks cooler areas
• Infects schwan cells causing neuropathy

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Histology of Leprosy
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Acid-Fast Stain M. leprae
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MOTT

• Over 100 species, most of little, no or unknown
  virulence
• Similar to TB in histology and staining, trained
  technicians can distinguish
• All can be normal flora except M.kansasii
• None person to person
• Diagnosis requires more than simply recovering
  from non-sterile specimen

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MOTT Classification

• Growth-rate /morphologic system obsolete
• Clinically useful to classify by host, organ
  system (pulmonary vs. lymphatic, cutaneous,
  disseminated)
• Treatment varies greatly with species

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MOTT Risk Factors

• Structural lung disease (MAC, kansasii,)
• Trauma/surgical (M.marinum, rapid growers)
• Cellular immune defect (rapid growers, MAC)
• Gamma interferon/IL-12 defect
• AIDS (MAC, rapid growers, genevensa, hemophilum)
• Recurrent aspiration, achalasia (MAC, rapid
  growers)
• Fish tank (M.marinum)
• Reptiles ( M chelonei)
• Children Scrofula (M. scrufula, MAC)
• Hot-Tubs Hypersensitivity pneumonitis (MAC)

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MAC

• M. avium complex includes M. intracellulare,
  other clinically insignificant ones
• By far main MOTT in AIDS
• 4 types in relatively competent hosts
• 1) fibrocavitary COPD, etc.
• 2) fibronodular older women,
• collagen
  defect
• 3) cystic fibrosis
• 4) hypersensitivity (hot tub)
  pneumonitis

Presumed by assoc. with mitral valve prolapse,
scoliosis,joint hypermobility,pectus excavatum
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Fibronodular MAC with bronchiectasis
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Rx of MOTT

• Very little correlation or predictive data from
  susceptibilty testing except for
• M.kansasii - rifampin
• MAC clarithromycin
• M.chelonei, fortuitum, abscessus
  formal
• mics
• None susceptible to PZA
• Most susceptible to clarithro, amikacin imipenem,
  quinolones except M. abscessus
• Duration varies usually at least 1- 11/2 year
  after sputum smears turn negative

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Dx. Of M.tb

• PPD very limited role in dx of active disease
  due to high rate of false (-) and true - but
  unrelated phenonenon
• Can help in CNS disease, pericarditis
• Definition of () PPD depends on circumstances
  (size, prior tests, host etc.)
• Prior BCG must assume positive skin test could
  be due to subsequent TB infection
• Interferon based assays M.tb specific immune
  response to TB proteins, identifies PPD reaction
  as TB rather than MOTT, more sensitive than PPD
  for screening, less for active disease

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Rx. of TB

• Standard regimen for all unless
• -Suspected resistance ( foreign born,
  failed
• prior Rx)
• -Pregnancy, coexistent liver disease,
  drug
• interaction concerns, intolerance
• Direct observed Rx when possible
• Some strains not treatable

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Clinical Cases Mycobacteria

• 1 77 y/o with new nodules on screening CT 5
  years after remission of NSCLC
• 2 77 y/o with worsening lesions while on
  prednisone for recent ITP
• 3 55 y/o with fever and cough for 3 weeks
• 4 70 y/o with chronic dyspnea

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TB Miliary, Extra-Pulmonary Disease

• Non specific symptoms may dominate miliary or
  disseminated TB
• Psoas abscess, with or without vertebral
  osteomyelitis, CNS disease relatively common
• May occur with or without active pulmonary disease

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TABLE 4 Characteristics of patients with
nontuberculous mycobacteria pulmonary
infections
MAC M.xenopi
M. kansasii RGM/non-CF
Subjects n
125 66
34 16 Underlying
conditions Pre-existing pulmonary disease
89 (71.2) 28 (42.4) 7 (20.6)
8 (50) Previous M. tuberculosis
35 (28) 17 (25.8)
9 (26.5) 3 (18.7)
Immunosupression/transplantation 34 (27.7)
17 (25.8) 5 (14.7) 1 (6.2)
None/anorexia
14 (11.2) 18 (27.3) 15
(44.1) 4 (25) Radiographic
abnormalities Infiltrates
46 (36.8) 1 (31.8)
12 (35.3) 8 (50) Nodules
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(22.4) 21 (31.8) 10 (29.4)
3 (18.7) Cavitation
13 (10.4) 11 (16.7)
13 (38.2) 1 (6.2) Nonspecific
4 (35.2)
19 (28.8) 4 (11.7) 7
(43.7) No symptoms
35 (28) 22 (33.3) 10 (29.4)
0 (0) Data are presented as n,
mean (range) or n (), unless otherwise stated.
MAC Mycobacterium avium-intracellulare complex
M. xenopi Mycobacterium xenopi M. Adapted from
Dailloux et.al. Eur.Respir.J.,2006281211