What are three human diseases caused by atypical bacteria?
1. Chronic pulmonary disease-Mycobacterium TB
2. Borrelia Burgdorferi (lyme disease): vector born
3. Helicbacter pylori (peptic ulcer)
What do atypical bacteria have in common?
-Human pathogens only
-Cause chronic infections that can go unnoticed
- Important to diagnose quickly
-Curable with antibiotics if caught early
What is mycobacterium tuberculosis?
-Nonmotile, aerobic bacillus has a very lipid rich cell wall.
-They are not stained by normal grain stain but by acid-fast stain (acid-fast bacilli)
-Chronic pulmonary disease
What are the virulence factors of M. Tuberculosis?
-Cell wall lipids withstand phagocytic killing and cause necrosis of tissue
-Able to stay alive in macrophages, intracellular growth
- Lipoarabinomanna (LAM) can induce inflammation
-Surface proteins are very immunogenic-Induce CMIR (Cell-meidated immune response)
-Highly infectious (5-200 organisms can start the disease).
What is the cell wall structure of M. Tuberculosis?
-PG layer is bound to arabinogalactose-mycolic acid
-Cell wall is overlaid with lipids such cord factor, sulfatides, wax D, and surface proteins.
-Has a plasma membrane, PG layer, arabinogalactan, mannose-capped lipoarabinomannan, plasma-associated and cell wall associated protein, mycolic acid, glycolipid surface molecules
What are the disease caused by M Tuberculosis?
-Granulomatous infection of the lung (TB)
Effectiveness of bacterial elimination is in part related to the size of infection
Localized collections of activated macrophages (granulomas) prevent further spread of the bacteria
-Macrophages can penetrate into small granulomas (less than 3 mm) and kill all the organisms contained in them. Larger necrotic/caseous granulomas become encapsulated with fibrin that effectively protects bacteria from macrophage killing
-Bacteria can remain dormant or reactivate later, when immunologic response wanes it.
-Pulmonary disease called Wasting disease (malaise, weight loss, bloody sputum)
What are granulomas?
-Lesions in the lung.
-Form when an intracellular pathogen or its constituents cannot be totally eliminated.
-infected macrophages are gathered in the center of the lesion surrounded by T cells
What is extra-pulmonary disease?
aka Military TB
-Hematogenous spread to multiple organs
-Caused by M. Tuberculosis
What is the epidemiology of TB?
-Highly infectious (5-200 to start disease)
-Worldwide, 1/3 of population is infected with TB
-Fewer than 15,000 new cases in US in 2003 (mostly AIDS patients)
-Populations at risk: immunocompromised, HIV, drug/alcohol, homeless, exposed to disease
-Humans are the only natural reservoir, person to person spread by infectious aerosols.
How do you diagnosis TB?
-Skin test, Mantoux test
-Reactivity of intradermal injection of mycobacterial antigen PPD
-PPD is purified-protein derivative of cell wall
-Reaction is measured in 48 hours
- Induration of more than 15 mm is considered a positive skin test
What is the TB immunization?
-Live attenuated Mycobacterium bovis: Bacillus of Calmette Guerin (BCG)
-Not for immunocompromised patients
-Recipients become skin test positive for TB
What does a >5 mm of induration in a TB test?
-HIV positive, patients receiving immunosuppressive therapy, recent contacts of patients with TB, patients with abnormal chest radiographs with prior TB
What does a >10 mm of induration in a TB test?
-Recent immigrants from high-prevalence countries, injection drug users, residents of high risk setting, elderly, patients with AIDS, homeless, health care/prison workers, high risk: chronic renal failure, diabetes, weight loss, children younger than 4 years or exposed to adults at high risk
What does a >15 mm of induration in a TB test?
-Persons at low risk for tuberculosis
What is a mycobacterium bovis?
-Used for TB immunization
-A cattle pathogen
-Cause disease in zoo keepers/cattle farmers
-Can cause pulmonary disease by consumption of contaminated milk but is destroyed by milk pasteurization.
Other than a TB, what other ways can you diagnosis M. TB?
-Microscopy and culture are sensitive and specific
What is the prevention of M. TB?
-Multiple drug regimens and prolonged treatment are required to prevent development of drug resistant strains
-Control of disease through active surveillance, prophylactic and therapeutic intervention, and careful case monitoring
-Some countries, TB vaccine
What is vector-born disease Lyme Borelliosis?
-Genus borrelia are gram negative bacilli
-Spirochetes helps to penetrate tissue/cells
-Cause of lyme disease
-Borrelia burgdorfei: agent of lyme disease, leading cause of vector born disease in US
- Transmitted by hard-shelled (Ixodes) ticks that live on rodents, deer, domestic pets, more recently recognized in 49 states.
What are the virulence factors of Borrelia burgdorferi?
-bacteria can escape from blood and penetrate tissues (similar to PMN)
-Outer surface protein (OSP) is very immunogenic and triggers inflammatory responses within tissues and causes damage right at the site
What is the first stage of lyme disease?
Early manifestation stage:
-Easy to treat
-Incubation period of 3-30 days
-A rash at the site of tick bite, erythema migrans (migrates out, bullseye), occurs in 80% of cases
-Systemic symptoms of fatigue, headache, fever, chills, muscle pain, lymphadenopahty
-Resolves in 4 weeks due to humoral immunity
What is the second stage of lyme disease?
-Occurs in 80% of patients, hard to treat
-Occurs when bacteria escape from blood to tissues and survive there but stimulate immune system which causes the damage (protein induces inflammation)
-Occurs within few weeks to 2 years following onset of disease
-Late stage has two phases
What are the two phases of the late stage of lyme disease?
-10-15% of patients and can last for days to months