Week 6: Tuberculosis

I.              Organism

a.    Mycobacterium Tuberculosis (MTB)

b.    Named after tuber like lesions (granulomas)

c.    Also called consumption, pthisis (I am wasting)

d.    Grows slowly, generation time of 12-24

e.    Needs acid fast stain - pink

II.            Transmission

a.    Respiratory droplet nuclei

b.    Waxy coat of bacteria keeps it from drying out for hours

c.    Inhalation

d.    Probability of transmission depends on:

                                              i.     Infectiousness of index

                                            ii.     Environment of exposure

                                          iii.     Duration of exposure

e.    Infection chances increase with close contact with smear positive patient

f.      About 15 people infected from an open case each year

III.         Pathogenesis

a.    Last bronchiole = terminal bronchiole

b.    Double layered membrane = pleura

c.    Steps:

                                              i.     Inhaled bacteria reach alveoli

                                            ii.     Ingested by macrophages

                                          iii.     Multiply and spread through the bloodstream

d.    Chance of disease progression

                                              i.     10% per life

                                            ii.     10% per year for HIV positive

e.    Once progressed, without treatment:

                                              i.     50% pulmonary TB patients die

                                            ii.     25% self cured

                                          iii.     25% remain chronically ill

f.      Stages of Disease

                                              i.     Primary infection

1.    Forms Primary Complex

2.    Occurs in children

                                            ii.     Latent Infection – LTBI

                                          iii.     Post primary infection

1.    Reactivation or reinfection

2.    Occurs in adults

                                           iv.     Common disease sites

1.    Lungs

a.    Granulomas

b.    Cavitation

c.    Necrosis

d.    Fibrosis

2.    Pleura

3.    Central Nervous System –CNS

4.    Lymphatic System

5.    Genitourinary Sites

6.    Bones and Joints

7.    Disseminated

                                             v.     HIV does not increase infection risk, increases disease progression

                                           vi.     Immunity

1.    Pathogen presents persistent chronic antigenic stimulus

2.    Cells can fight back and then lyse, spreading infection

                                         vii.     Symptoms

1.    Cough three+ weeks

2.    Sputum

3.    Weight loss

IV.         Diagnosis

a.    Clinical diagnosis

                                              i.     Exam

                                            ii.     Tuberculin (Mantoux) testing, slightly different antigens

                                          iii.     Chest x ray

b.    Lab Diagnosis

                                              i.     Sputum smear – pink

                                            ii.     Culture and sensitivity testing

                                          iii.     PCR testing

c.    Delayed Hypersensitivity Testing (PPD) Purified Protein Derivative

                                              i.     Intradermal inoculation

                                            ii.     Measure swelling after 72 hours

V.           Treatment

a.    First Line Drugs

                                              i.     Isoniazid (INH)

                                            ii.     Rifampicin (RF)

b.    Second Line Drugs

c.    MDR –TB (Multidrug resistant) ALWAYS resistant to the primary first line drugs

VI.         Control

a.    1/3 World population has TB

b.    Global Emergency 1993

c.    9 million people a year infected

d.    Biggest killer of AIDS patients

e.    DOTS Directly Observed Therapy Short Course

                                              i.     Developed in India, medicine taking witnessed due to long treatment

f.      Doing better in USA until HIV/AIDS

g.    Only 50% cases reported

h.    No 100% diagnostic tool

i.      Resurgence:

                                              i.     HIV

                                            ii.     Immigration (60% U.S. cases)

                                          iii.     High risk environments

                                           iv.     No TB infrastructure