25 Unculturable Bacteria: Spirochetes and Rickettsia Flashcards
What are the 3 genera of spirochetes that cause human illnesses?
Treponema (syphilis)
Leptospira (leptospirosis)
Borrelia (relapsing fever and lyme disease)
T/F- Spirochetes are long slender rods that are related to gram negatives (LPS-like); they have endoflagella under a sheath (axial fibril-like flagella)
True
Treponemes species are defined by disease. Name 4 examples along with the diseases they cause.
T. pallidum-syphilis
T. pertenue-yaws
T. carateum-pinta
T. endemicum-bejel
T/F- normal flora do not contain treponemes
False. Normal flora may contain non-pathogenic treponemes
T/F- Treponemes have been kept alive in conditions with reduced oxygen, however, genomics predicts they are aerobes, but they have never been cultured on lab media
True
What facilitates dissemination of treponemes in the body?
readily attach to endothelial cells and pass through blood vessel walls
Treponema pallidum is responsible for disease?
Syphilis
-60% probability of transmission if sex with infected parter
-46x more common in gay men than straight men
-more common in men than women
-rates increasing in past several years
-Primary/Secondary disease are most infectious stages
Non-sexual transmission: congenital syphilis (400 cases/yr in U.S.) and Bejel/Siti are disease of children
T/F- syphilis does not change risk of transmitting or acquiring HIV
False, it increases risk:
- Indirect: a portal for HIV entry through lesions and attracting HIV target cells to lesions
- Direct: possibly upregulates HIV replication
Describe the natural course of a hard chancre in primary syphilis
- organism penetrates skin/mucous membrane and develops lesion and initial inoculation site
- organism replicates at this lesion and then spreads through blood stream (regional lymphadenopathy common). CD4 t cells and macrophages predominate.
- Chancre resolves without treatment while bacteria seeds other parts of body
When does secondary syphilis develop and what are the common manifestations?
- develops 6-8 weeks after resolution of primary lesion (CD8 response)
- maculopapular rash on flank, shoulder, arm, chest, back, hands, soles of feet, malaise, headache, generalized lyphadenopathy (lymphadenopathy resolves in 2 months)
What are some less common manifestations of secondary syphilis?
fever, anorexia, mucous patches, condylomata lata (infectious), alopecia, meningitis, myalgia, ocular complaints, hepatic, pulmonary or neuro involvement
What’s latent syphilis?
period of disappearance of secondary manifestations until therapeutic cure occurs OR until tertiary symptoms develop. Divided into early and late phases.
Important details of early latent phase (first year of latency)?
Many patients experience recurrence of secondary symptoms and remain INFECTIOUS to sexual partners
Important details of Late latent phase (>1 year of latency)?
Patients are not considered infectious and even without treatment 72% of T. palladium infected pts with remain symptom free forever. 28% progress to tertiary syphilis.
What is tertiary syphilis?
- few viable bacteria remain
- hypersensitivity to bacterial antigens causes GUMMA lesions
- cardio: aortic aneurysm, valvular insufficiency, coronary artery ostial stenosis
- Neuro: CN palsy, personality changes, delusions
- Outcome is death for tertiary syphilis
What are GUMMA lesions?
- small rubber granuloma infiltrates of monocytes
- any organ
- non-infectious
What is the underlying systemic pathophysiology of syphilis?
- lesions at all stages show vasculopathic changes (enderarteritis and periarteritis)
- dense local infiltrates (macrophages, lymphocytes, plasma cells, PMNs, histiocytes
- granulomata often present and assume necrotizing nature
Outcomes of congenital syphilis?
-Hutchinson’s teeth, Saddle nose, Saber shins, fulminant disseminated infections, lesions of skin and bone, deafness
T/F- syphilis bacteria can cross the placenta to infect the fetus
True
T/F- untreated syphilis in pregnancy can result in spontaneous abortion, still birth, premature delivery, or perinatal death
True
T/F- T. pallidum can be grown in culture
False. Cannot be grown in culture (makes no amino acids)
T/F- T. pallidum outer membrane does not contain LPS and contains very few proteins
True, this allows it to evade the immune system
T/F- binding between T. pallidum outer membrane proteins and host cell glycoproteins (fibronectin, laminin) occurs
True
T/F- Treponema is an intracellular pathogen that elicits weak stimulation of the innate, humoral, and cell-mediated defenses that eradicates the bacteria
False
- extracellular pathogen
- elicits STRONG immune response but it does NOT eradicate the bacteria. Lipoproteins play a crucial role in stimulating the innate mechanism during all stages.
Does microscopy help diagnose syphilis?
- Gram stain will not work
- can use phase contrast, dark field, or fluorescent microscopy
Are there screening assays for syphilis?
- -screening assays for non-treponemal antibodies detect IgG and IgM against cardiolipin (most sensitive in secondary and latent infection-100% vs 80% in primary and tertiary)
- rapid plasmid reagin test (RPR)
- venereal disease research laboratory test (VDRL) best for neurosyphilis
What confirmatory tests can be used for syphilis?
- Indirect Fluorescent Antibody (fluorescent treponemal antibody ‘FTA’)
- Treponema pallidum particle agglutination test (TP-PA)
How do you treat syphilis?
- treat at all stages of disease with parenteral penicillin injections
- no resistance to penicillin
- later stage=longer therapy needed
- if allergic to penicillin use ceftriaxone or doxycycline
- can be reinfected after treatment
T/F condoms always prevent syphilis infection
False. condom use is not necessarily helpful to prevent transmission of T. pallidum unless the infected area is completely covered and potential exposure site is protected
T/F- there is a vaccine for syphilis
False
What organism causes “relapsing fever” and lyme disease?
Borrelia
Compare epidemic relapsing fever and endemic relapsing fever
- epidemic: caused by B. recurrentis, body louse borne, humans are reservoirs
- endemic: caused by many Borrelia sp., small mammal reservoirs, transmitted by soft-shelled tick vector
What species of Borrelia causes lyme disease in the U.S.? What is it’s vector and reservoir?
B. burgdorferi
reservoir: farm animals, rodents, pets
vector: Ixodes scapularis (deer tick)
Important details of relapsing fevers
- associated with ospC gene
- organisms with one ospC gene are cleared but organisms expressing another take over
- diagnosed by presence of organisms in peripheral blood smear
T/F- lyme disease is the most common vector borne disease in the U.S. with peak transmission in late spring (juvenile ticks) and summer (adult ticks) and 10% of B. burgdorferi infections are asymptomatic
true
Describe time course of Lyme disease
- early localized phase: bull’s eye rash (erythema migrans) 1-2 weeks after bite with flu like symptoms (20% have no EM and only show fever, headache, malaise)
- Late disseminated: if untreated, 60% will progress to this phase, joint swelling/arthritis (high risk in HLA-DR4 pts), neuroborreliosis=>chronic polyneuropathy, encephalopathy, insomnia, malaise, mental changes. Debilitating but rarely fatal.
Describe virulence of lyme diseas
- unusual small, linear 950 kb chromosome with 12+ plasmids
- genome encodes 150 lipoproteins (stimulate innate defense via TLR-2 and CD14 on macrophages
- OspA, B, C, etc. plasma encoded lipoproteins in an LPS-free outer membrane help adapt and survive in host + stimulate autoimmune response in some, =>T cell response to Osp causes them to recognize synovial and neuronal proteins
How is Lyme disease diagnosed?
- clinical features
- serologic tests (ELISA, IFA are sensitive, western blot is specific) can be used if enough time has passed, but cannot differentiate active from past infection
How is lyme disease treated?
- doxycycline for non-pregnat patients >9 yrs old
- duration depends on stage of disease (localized skin infection:14 days), early disseminated disease (21 days), lyme associated arthritis (30-60 days), late or severe disease with cardiac/neuro involvement use IV antibiotics for 4 weeks
T/F- treatment of lyme disease is not required if the tick is unengorged or attached less than two days
True
T/F- there is no vaccine for lyme disease and getting it once does not confer immunity against future infections
True
T/F- leptospira causes zoonoses
true
What are common hosts of leptospira?
dogs, rats, livestock, sea lions, opossums etc. Commonly infect renal tubules in reservoirs leading to prolonged shedding in urine=>gets into lakes, contracted while swimming or during floods. humans are incidental hosts.
T/F- Leptospira spreads human to human
No documented person to person spread
What is the mechanism of infection of leptospira?
Thin, highly motile leptospires penetrate intact mucous membranes or conjunctiva or enter skin through small cuts or abrasions then spreads through blood to all tissues (and CSF) especially the liver
How does leptospirosis present in patients?
- most show no or mild symptoms and do not seek medical care
- some experience flu like symptoms, myalgia, abdominal pain, conjunctival suffusion, skin rash, aseptic meningitis (up to 25% of cases)
- 5-10% will have icteric leptospirosis (Weil’s disease) which is the most severe form
What is Weil’s disease?
- severe form of infection by leptospira
- jaundice, acute renal failure, pulmonary and cardiac symptoms, and ocular manifestations all may occur
- rapid progression, fatality of 5-15%
What are Leptospira’s virulence factors?
- “LPS like” molecule in outer membrane (lower endotoxin activity than LPS)
- can attach to epithelial cells
- lipoproteins in outer membrane play a role (similar to other Spirochetes)
How is Leptospira treated?
penicillin G
Doxycycline
Are animal vaccinations available against leptospira?
yes, this is used for prevention
How is leptospirosis diagnosed?
- Serologic test called microscopic agglutination test (MAT)
- won’t gram stain, darkfield unreliable
- Culture is very slow
T/F- Rickettsia is an obligate intracellular parasite
True
What are the 5 “more or less” unrelated bacterial genera that cause somewhat similar “Rickettsial” diseases. What type of pathogens are they?
Rickettsia, Ehrlichia, Coxiella, Orientia, Anaplasma.
- All obligate intracellular pathogens
- All small gram negative coccobacilli/short rods
Why are the Rickettsial diseases obligate intracellular pathogens?
Need host to metabolize sugars and synthesize all their nucleotides, lipids, and amino acids
How do Rickettsial diseases manifest clinically?
acute phase: fever, headache, myalgias, nausea, vomiting, cough, thrombocytopenia, elevated liver enzymes, normal to low WBC counts
later phase: manifestations vary greatly
How are Rickettsial infections transmitted?
most via arthropod vectors (ticks, mites, fleas, lice) exception is Q fever (due to C. burnetii) which is transmitted via ingestion of milk or aerosols of partition (birth) material from sheep, dogs, other animals.
-Some via inhalation
T/F- some rickettsial diseases cause rashes which may be macular, maculopapular, or vesicular in MOST of those infected
True, although Q fever rash is rare
T/F- some rickettsial diseases cause pneumonitis (pneumonia without pus) because they don’t elicit a massive PMN response
True
T/F- because rickettsial diseases are intracellular, they cannot cause meningoencephalitis or toxic shock syndrome
False, they can cause both of these
What is rickettsial pox caused by and how is it spread?
- R. akari
- spread by mites
- in cities
- papule where bitten->wchar->systemic spread (fever, rash)
T/F- epidemic (louse-borne) typhus is caused by R. prowazecki which is a human body louse
True
T/F- endemic (murine) typhus is caused by R. typhi which is a rat flea and spread from rodents
True
Scrub typhus is caused by Orienta tsutsugamushi and which is associated with chiggers and mites. What symptoms does this cause in humans?
Headache, fever, rash
What organism causes Q fever? How is it spread and what are the symptoms?
- caused by Coxiella burnetii
- spread through unpasteurized milk or aerosol of dried placenta of farm animals
- can be asymptomatic or flu-like with pneumonia, hepatitis, endocarditis
How does Coxiella burnetii, which causes Q fever, replicate?
in phagolysosomes (needs acidic environment)
What are the 2 phases of Q fever?
This organism undergoes genetic variation of the cell wall LPS resulting in two phases:
Phase I: infectious, no antibody response
Phase II: acute disease, antibody response
What organism is human monocytotropic ehrlichiosis (HME) caused by and what is it’s vector?
- caused by E. chaffeensis
- Lone Star Tick (generally infects leukocytes, particularly monocytes)
How does E. chaffeensis (the cause of HME) reproduce?
within membrane-bound vacuoles in the cytoplasm
What is the micro colony of replicating E. chaffeensis called? If you see this can it be used to diagnose HME?
morulae, yes (but only seen in a minority of cases)
Are rashes in HME patients more common in kids or adults?
30% of adults, 60% of kids
What organism causes Rocky Mountain spotted fever? What is the vector?
R. rickettsia
-vector: wood tick and american dog tick
How do female ticks infected with Rocky mountain spotted fever pass on bacteria?
trans-ovariallly (an infected blood meal is not necessarily required)
What is the cause of spots in rocky mountain spotted fever?
rickettsial infections:
- increase vascular permeability (disrupt adherents junctions)
- cause oxidative stress (but no toxins)
- release of procoagulant factors, activates coagulation cascade
- spots start peripherally, move centrally
How is rocky mountain spotted fever diagnosed?
- diagnosis is diffult in acute stage since 97% of people won’t have characteristic spots yet
- 7-10 days after onset, diagnosis can be confirmed with serologic test
How is rocky mountain spotted fever treated?
- MUST provide empiric treatment before disease is confirmed
- doxycycline is antibiotic of choice for both children and non-pregnant adults
