Exogenous Reinfection with Multidrug-Resistant Mycobacterium by murplelake78

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									Exogenous Reinfection with
   Multidrug-Resistant
Mycobacterium tuberculosis
in Patients with Advanced
       HIV Infection


        Celeste Nadal
            Purpose
Determine the epidemiological
 connections between cases of
 multidrug-resistant tuberculosis (MDRT)


            Rationale
Prevention of future MDRT outbreaks
             Outline
 Background
  Mycobacterium tuberculosis
  Tuberculosis disease
  HIV and Tuberculosis
 Methods
 Results
 Conclusions
Mycobacterium tuberculosis


              Characteristics
                Obligate aerobe
                Rod shaped
                Acid fast
                Mycolic acid cell wall
Tuberculosis Disease (TB)
 Sites of infection




 Mode of infection
   Airborne
              Pulmonary TB
Internal symptoms
   Development of tubercles
   Consumption
   Sputum


External symptoms
  Minor cough
  Mild fever
  Fatigue
  Weight loss
  Coughing up blood
  Chest pain
        TB and HIV
Increased susceptibility in
 immunosuppressed individuals

Infection in HIV positive individuals
  113 times more likely
  7 to 10% risk PER YEAR
 Multidrug-Resistant
Tuberculosis Infection
Primary drug resistance
  Infection with multidrug-resistant TB

Acquired drug resistance
  Development of resistance during therapy
  Possibly due to inadequate treatment
       Research Protocol
Trace M. tuberculosis transmission

  Isolation and culture of bacterial sample
  Evaluation of medical records
    Follow-up studies
  Radiometric broth method
  Restriction-fragment-length polymorphisms
   analysis
  Radiometric Broth Method
Determine susceptibility to
  Isoniazid (0.1-0.2 mg/ml)
  Rifampin (2 mg/ml)
  Streptomycin (6.0 mg/ml)
  Ethambutol (7.5 mg/ml)
  Pyrazinamide (100 mg/ml)- testing began later in study

Tests for critical concentration
  The level of a drug which distinguishes the strain from a
   strain that has never been in contact with the drug
  1% colony growth in presence of antibiotic
 Restriction-Fragment-Length-
Polymorphisms (RFLPs) Analysis
  Form of DNA fingerprinting
    Extract genomic DNA
    Restriction enzyme digestion
      PvuII
    Southern blot
      Gel electrophoresis
      Transfer to nylon membrane
      Hybridized with labeled probes
   RFLP Patterns of Patients with
Persistently Drug-Susceptible Isolates
   RFLP Patterns of Patients with
Increasingly Drug-Resistant Isolates
  RFLP Patterns Indicating Exogenous
Reinfection with New Multidrug-Resistant
         Strain in HIV+ Patients
Clinical Course of Four Patients with
    AIDS and Multidrug-Resistant
            Tuberculosis
                          Triangles
                            Out-patient
                             visits
                          Circle
                            Negative TB
                             culures
                          Boxes
                            Positive TB
                             cultures

                          PCP
                            Pneumonia
       Conclusion
RFLP Analysis
  Confirmed acquired drug resistance
  Demonstrated Third mechanism of
   developing Multidrug-resistant
   tuberculosis infection
    Exogenous reinfection
Follow-up
  Lack of acquired immunity to MTB in
   HIV pos patients are more likely to
   become reinfected with MDR-TB
        Prevention
Routine skin testing for tuberculosis

Prompt and consistent treatment

Decrease open tuberculosis units

								
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