Lecture 25 - Tuberculosis

Actinobacteria
Actinobacteria is a new phylum that was developed because DNA evidence suggested that they belonged together. They all had a high guanine and cytosine ratio, and were consistent with Gram-positive bacteria, but are really Gram-nonreactive.

Bacteria that fall into this category are mycobacterium and corynebacterium.

Tuberculosis
"Having tuberculosis" refers to a clinical infection of Mycobacterium tuberculosis, which means that a patient is showing symptoms. The following is the etiology (genus and specific epithet) of TB-causing bacteria.

Mycobacterium tuberculosis
Mycobacteriumm is considered a tubercule bacillus, and is the main cause of clinical tuberculosis. The main host for this specific organism is humans.

Mycobacterium bovis
Main host is cows, can be found in milk.

MOTT
Mycobacteria other than tubercule bacillus, or NTM (Non-tuberculous mycobacterium) MOTTs include Mycobacterium kansasii and Mycobacterium avium, also known as Mycobacterium intracellular, is the common strain in AIDS patients. To treat for MOTTs one may require surgery in addition to antibacterial treatments.

Description
The organism is Gram-nonreactive, but is consistent with Gram-positive bacteria. The main test is the acid-fact stain, which stains pink in the presence of mycobacteria. The culture for mycobacteria is the Lowenstein-Jensen media, which contains potato flour, eggs, and malachite green, which inhibits other Gram-positive bacteria over 2-4 weeks to grow, but more pathogenic strains can take even longer to grow. They look waxy.

Morbidity
Morbidity is occurrence and is reported in the Morbidity and Mortality Weekly Report (MMWR).

In the U.S., 13k individuals are diagnosed with a clinical (active) case of TB. 15M people have latent TB in the U.S. About 1/3 of the world's population is a carrier for TB.

Mortality
Before the 1900s, it accounted for 20-30% of the deaths. It has gone down to 2k per year in the US, and 2M per year worldwide.

Transmission
Transferred by droplet infection in microaerosols. 1-3 bacilli per droplet, and only 10 is needed for the ID50.

Predisposing factors
Advanced age, poor diet (alcoholism/being poor), and prolonged stress.

Demonstration of Virulence
Humans are easily infected but can stay resistant to the bacteria. Only 5% get active infection. White blood cells can't phagocytose mycobacterium because the bacteria is too wavy. The body makes tubercules to contain the bacteria instead. When the tubercule grows from a 1-3mm size a larger tubercule, it is considered cavitary and a risk factor. A cavitary tubercule is what is seen on X-rays, and could break open and spread.

Primary tuberculosis is when the infection stays in the lungs. 90% of the time, infections in the U.S. stay primary.

Secondary (extrapulmonary, miliary (skin), osseous (bones), which only occurs in about 5% of the cases.) tuberculosis can occur when TB spreads outside of the lungs.

Incubation Period
6 months on average.

Symptoms
Pleurisy - vague chest pains

Periodic Fever

Fatigue

Coughing (Blood)

Weight Loss (used to be called consumption)

Diagnosis
Sputum smear is less sensitive than the culture method, and is only used for active cases of TB

When you go to the doctor with symptoms, they will do an x-ray, smear, and culture.

1st risk factor is positive smear and/or culture. 2nd risk factor is having cavitary tubercules (shown by X-rays).

Skin tests use protein extracts as antigens to test for the presence of antibodies in the host.

Mantoux test is the skin test for TB, which uses PPD (purified protein derivative), 0.0001mg in 0.1mL of water. An induration (hardening) of 5mm+ is positive for an AIDS patient, 10mm+ is a positive reading for non-whites, and 15mm+ is positive for normal people. The Mentoux test only tests for antibodies to TB, so if you have gotten a vaccine for TB, it will show a false positive.

Tuberculin anergy - when all your body's antibodies are focused on the actual infection that it doesn't attack the Mantoux test.

Old tuberculin (OT) is only used by vets.

Interferon gamma release assay (INGRAs) tests for 2 antigens that are on Myco. tuberculosis, an almost nothing else, including bovis and avium. It is a more specific test than the Mantoux method

Treatment
Usually use more than one drug, over 6 to 24 months. INH can be used as a single drug in AIDS patients, usually for 9 months, to treat latent cases of TB. INH can also be used as a chemoprophylaxis agent (prophylactic) for older people or people at high risk. Directly observed therapy improves cure rates because it ensures that they take their drugs.

Empiric initial treatment: Isoniazid, rifampin, pyrazinamide (permeates macrophages), which all come in the drug Rifater, and ethambutol.

If susceptible to all drugs, stop giving ethambutol, but keep giving rifater until you've given it for 2 months. Then give Rifamate (INH, Rifampin) for 4 months (if patient has 1 risk factor) or 7 months (if patient has 2 risk factors).

If resistant to INH, treat patient with Rifampin, Pyrazinamide, and either Ethambutol or Streptomycin for 6-9 months.

If MDR or XDR, treat with 4-7 susceptible drugs for 18-24 months. Monthly smears and cultures are obtained to make sure no drug resistance develops. Treats for 12-18 more months after smears and cultures are negative. Cure rate for XDR TB is only 50-60%, and if the organism does not respond to treatment after 3-4 months then surgery happens.

Retreatment - 7% of the time treatment will need to be re-administered to a patient, but only about 7% of the cases are due to resistance developing. The other cases are due to patient noncompliance, which goes to prove that directly observed therapy is important.

Prevention
In order to prevent the spread of TB, one can quarantine people with the disease, educate people about the seriousness of the disease, or give INH as a prophylactic for 6-12 months (if negative for Mantoux). BCG (Bacillus Calmette Guerin) is a live vaccine of Mycobacterium bovis which only lasts 5-15 years and is only 80% effective in children and 20-50% effective in adults.