B3.027 - Chronic Infections Flashcards
What are chronic infections
Infections that are not efficiently cleared by either the innate or adaptive immune response
What are some examples of viruses that cause chronic infection
HIV, CMV, HSV, EBV
What are 6 mechanisms of bacterial persistence
- Antigenic variation of surface antigens
- Colonization of immunoprivileged niches
- Modification of intracellular environment
- Host mimicry
- Resistance to immune effector mechanisms
- Selective gene deactivation
What is a bacterium that displays antigenic variation of surface antigens
Borrelia burgdorferi
What is an example of a bacterium that exhibits colonization of immunoprivileged niches
Salmonella typhi, Mycobacteria leprae
What is type of bacteria exhibit modification of intracellular environment
facultative and obligate intracellular bacteria
What is an example of a bacterium that exhibits host mimicry
Treponema pallidum
What is an example of a bacterium that exhibits resistance to immune effector mechanisms
Borrelia burgdorferi
What causes syphilis
Treponema pallidum
What causes leptospirosis
Leptospira interrogans
What causes relapsing fever
Several borrelia species
What causes Lyme disease
Borrelia burgdorferi
What makes spirochetal flagella unique
Its in the periplasmic space (in between 2 layers of plasma membrane)
What does leptospira have on their cell surface
Lipoproteins and LPS
What does Treponema pallidum have on its cell surface
No major ones and NO LPS (Stealth pathogen)
What does Borellia have on its cell surface
Abundant lipoproteins NO LPS!!!
Clinical presentation of fever, diffuse macular and papular rash of skin including palms and soles, red patches of oral mucosa is indicative of what disease
Syphilis
What causes syphilis
Treponema pallidum
T. Pallidum virulence factors include what
Hyalurinodase fibronectin coat
Few surface proteins
Stealth pathogen
T. Pallidum infection (syphilis) symptoms are caused by what
Immune response to tissue damage
How is T. Pallidum cultured
Rabbit testicles
What is a chancre
Tissue damage at site of pathogen entry in primary syphilis
Painless, heals spontaneously
Describe symptoms of secondary syphilis
- Maculopapular, desquamative rash
- slope is
- Papules and Paquette in groin
- Erythematous mucous patches in mouth
What are symptoms of secondary syphilis
- Maculopapular, desquamatous rash
- Alopecia
- Papules and plaques in groin (condylomata lata)
- Erythematous mucus patches in mouth
What are the 3 types of symtoms seen in tertiary syphilis
Gummatous
Cardiovascular
Neurosyphilis
Where are gummatous lesions seen
Skin, bone, brain
What does cardiovascular syphilis cause
Aortic aneurism
What can neurosyphilis cause
Meningitis
Tables dorsalis - locomotor ataxia
Spinal cord damage with demyelination of dorsal roots
What are symptoms of congenital syphilis
- Stillborn
- Saddleback nose/hutchinsonian teeth
- 2ndary or tertiary syphilis
- Rhinitis
What microscopy methods can you use to diagnose T. Pallidum infection
Darkfield of fresh skin lesions (NOT ORAL)
DFA staining
What serology tests can you run for T. Pallidum
- RPR
2. FTA-ABS
Why cant you rely on RPR alone
Its very sensitive but not specific
Why do you follow RPR with FTA-ABS
Its very specific, to confirm
What does RPR test for
Reagin antibodies against cardiolipin
What is the DOC for syphilis
Penicillin G
What do you use for syphilis in case of a penicillin allergy
Doxycycline, ceftriaxone, tetracycline, azithromycin
What is a Jarisch Herxheimer reaction presentation
Abrupt onset of fever, chills, myalgias, tachycardia, vasodilation with flushing, exacerbated skin rash, mild hypotension
What causes a Jarisch Herxheimer Reaction
Massive release of pro inflammatory cytokines triggered by release of endotoxin like substances from bacteremic organisms
What organisms can cause a Jarisch Herxheimer reaction
T. Pallidum - lipoproteins
Borrelia - Lipoproteins
What is the serotype defining molecule on Leptospira interrogans
LPS
What are asymptomatic hosts of Leptospira interrogans
Rodents
Dogs
Farm animals
Where does leptospira persist in its hosts
Renal tubules, shed in urine
Describe the life cycle of leptospira in a human
- Infection via intact mucosa or broken skin
- Septicemia
- Damage of small blood vessel endothelium
- Exit
What can damage of small blood vessel endothelium cause in a human
Meningitis
Nephritis
Hepatitis
Hemorrhage
What are some occupational exposures to leptospira
Miners, vets, farmers, butchers
When do cases of leptospira peak
Warmer moths (recreational exposure)
How do you diagnose leptospira
Gold standard is agglutination test
Can you culture Leptospira
Yes but its slow
Blood/urine - + during first 10 days
Urine - after 1 week will be +
What microscopy method can be used to diagnose leptospira
DFA
What is the drug of choice for Leptospira
Penicillin IV
What other than penicillin can be used for Leptospira
Doxycycline preventitively
Amoxicillin
Ampicillin
What are two causes of relapsing fever
Tick Bourne and louse Bourne
Which type of relapsing fever causes epidemics
Louse Bourne
Which type of relapsing fever is endemic
Tick Bourne
What is TBRF caused by
Borrelia sp
What is RBRF caused by
B. Recurrent is
What causes TBRF ID
1
How types of ticks are fast feeders
Ornithopods, usually <20 min at night
RF borrelia are present where on the tick and how does it get to the human
Salivary glands and quickly transmitted with saliva upon feeding
How is LBRF transmitted
Crushing of louse
What causes relapses of fever from borrelia
Antigenic variation and serotype switching
Recombination fo silent genes into single expression site
Each serotype of borrelia is defined by what
Expression of a different single immunodominant surface lipoprotein
How do you diagnose borrelia causing relapsing fever
Blood smear (sn 70%) CDC will do a western blot but there is cross reactivity with other spirochetes so false positives can happen
What drug is used for TBRF
Doxycycline
What drug is used for LBRF
Tetracycline
After giving dose why do you keep patient for 12 hours
Looking out for Jarisch Herxheimer
How is Lyme disease transmitted
Lxodes ticks
What are symptoms of Lyme disease
Facial palsy
Circular rash
What is the most common vector borne disease in US
Lyme
How long do ixode ticks feed for
Several days
What is the window of time you can pull a tick off for and not get disease
48 hours
Why does it take so long for ixode ticks to transmit spirochetes
They are in the midgut and have to get to the salivary glands
What are the symptoms of Lyme disease
Erythema migrants (bulls eye rash) Diffuse symptoms are malaise, fatigue, headache, fever, chills, MSK pain, lymphadenopathy
What is diagnostic for Lyme disease as far as the EM
Over 2 inches in diameter or 5 cm
What is nueroborreliosis
Neurological symptoms of disseminate Lyme disease
- meningitis
- Bell’s palsy
- Encephalitis
- Radiculopathy
- Cranial neuritis
What are the cardiac symptoms of disseminated Lyme disease
Pericarditis
Myocarditis
AV nodal block
What are symptoms of late disseminated Lyme disease
Encephalopathy
Acrodermatitits chronicum atrophicans
Oligoaricular arthritis (usually unilateral)
What virulence factor does B. Burgdorferi have to help with its colonization and survival
OspA - binds to tick midgut receptor and protects other bacterial proteins from tick Proteases
What B. Burgdorferi virulence factors help it with persistence
Osp C Adhesins Broad complement resistance Factor H Antigenic variation
What does Osp Cdo
Binds immunomodulary tick saliva protein and blocks phagocytosis by macrophages and binds complement C4b
What are CRASPs
Block MAC, complement regulator aquiring surface proteins
What causes Lyme arthritis
Lipoproteins cause constant inflammatory stimulus to join causing edema associated with neutrophil infiltration
What is the genetic link to refractory arthritis caused by antibiotics
HLA.DRB1
How does the OspA vaccine work
Recombinant lipidated Osp A blocks transmission, tick up takes antibodies killing spirochetes with OspA
