Microbiology - Greenblatt - Vectored Bacterial Infections of the Blood Flashcards
How do you stain for Borrelia burgdorferi?
Stainable with giemsa, silver stain, IF, visible by standard microscopy
T/F: Asymptomatic clearance of Borrelia burgdorferi is possible.
True
Lyme arthritis is predisposed in what genotypes?
Lyme arthritis predisposed by HLA-DR4 and HLA-DR2 genotypes.
When would you see a high fever in Lyme disease?
Coinfection with Erlichia or Babesiosa
What factor most complicates the development of a Lyme vaccine?
Antibodies raised are not protective against a future infection
T/F: Early Lyme improves rapidly with antibiotics.
True
Treatment of Lyme Disease with Doxycycline can cause what flu-like reaction?
Jarisch-Herxheimer reaction
Successful treatment of any spirochete infection may cause Jarisch-Herxheimer reaction (that and response to treatment may be needed to empirically diagnose Lyme)
What is the pathogen involved in louse-borne relapsing fever?
Pathogen: B. recurrentis
Vector: Pediculus corporis
Reservoir: humans
What is the pathogen involved in tick-borne relapsing fever?
Pathogens: B. hermsii, B. turicatae, B. parkeri, B. duttonii, others
Vectors: soft-bodied ticks Ornithodoros spp
Reservoirs: many mammals and reptiles
What characteristic of spirochete infections is responsible for the relapsing quality or relapsing fever?
Spirochetes access vasculature, disseminate to spleen, bone marrow, liver, lungs, kidneys, CNS
A strong IL10 response and neutralizing antibodies clear sepsis → fever
Spirochetes vary their surface antigens in response to immune selection, when a new pool predominates, disease resumes
Fevered episodes repeat, lower fever and increasingly long breaks between as immune response improves
Which relapsing fever causes complications of pregnancy?
Tick-borne
How would you culture the organisms responsible for relapsing fever?
Peripheral blood smear: spirochetes visible by microscopy with Wright or Giemsa stain if blood taken during febrile period
Can also visualize bacteria w/ IF, darkfield, wet mounts, silver-stained biopsies
Organism can be cultured from blood in special liquid medium, takes 2-6wks
PCR assay available
ELISA is available, better one in the pipeline
What is the treatment for relapsing fever?
Tetracycline, doxycycline, erythromycin, penicillin G used in adults
Erythromycin in children and pregnant/nursing women
IV penicillin or ceftriaxone for meningitis
Louse-borne takes one dose, tick-borne treat for 7-10 days
Jarisch-Herxheimer reaction
How are the “rickettsial” bugs similar to Borrelia?
Arthropod vectors
Mammalian reservoirs
Tetracycline sensitivity
UNLIKE Borrelia: intracellular replication (**must grow in tissue culture) small cocci to short rods
How do most rickettsia infect humans?
By accident (accidental host)
**Exception is epidemic typhus
What are the virulence factors for RMSF?
OmpA&B: adhesion
Type 4 secretion system: entry
Phospholipase A2: escape from endosome
ActA: actin-based cell-cell spread
How does the rash form in RMSF?
Begins on extremities, spreads to trunk;
caused by leakage from damaged blood vessels
What is the treatment for RMSF?
Doxy
Chloramphenicol for pregnant and allergic patients
How does epidemic typhus present?
Abrupt-onset fever, chills
Generalized lymphadenopathy
Abrupt-onset unremitting Headache
Macular, maculopapular, or petechial rash occurs on days 4-7
May begin on the axilla and trunk and spread peripherally. (RMSF rash begins on extremities and spreads centrally)
CNS symptoms (meningoencephalitis) may include dullness, delerium, coma
What is Brill-Zinsser Disease?
Recrudescent Typhus
Mechansims of latency and reactivation are unknown
Less severe than initial course
Risk factors include malnutrition and improper or incomplete antibiotic therapy
May be seen in US among geriatric patients who had typhus during WWII
Human Monocytic Erlychiosis is caused by:
HME is caused by Ehrlichia chaffeensis.
Tiny Gram (-) Obligate intracellular Resemble Rickettsia Replicate in cytoplasm of white cells Form clusters called morulae
Why is erlichiosis dangerous for the elderly or immunocompromised?
Elderly or immunocompromised patients are at increased risk for
severe ehrlichiosis; may develop meningitis or disseminated intravascular coagulation
T/F: Most cases of erlichiosis resolve on their own and are asymptomatic.
True
Is chloramphenicol effective at treating HME?
No; use doxy
same with Anaplasmosis
Anaplasma and Erlichiosis both grow what in cells?
Morulae
T/F: Serology can confirm exposure to Lyme but not the disease itself.
True
How do you diagnose relapsing fever?
Diagnose relapsing fever by peripheral blood smear; spirochetes are usually visible during febrile periods
Obligate intracellular parasites and can only be grown:
Obligate intracellular parasites and can only be grown in vitro in tissue culture (like viruses).
The Ricksettsiae require what assay to visualize?
All of the rickettsiae are difficult to stain chemically and require microimmunofluorescent assay to visualize (blood and/or biopsy).
Is it okay to treat children with doxy for the rickettsiae?
Because of the gravity of these illnesses, small children may be treated with tetracyclines but pregnant women are not. Alternate treatments for pregnant and allergic patients are chloramphenicol (Rickettsia) or fluoroquinolones (Ehrlichia, Anaplasma).
What is the major difference between borrelia and rickettsia?
Borrelia are spirochetes, rickettsia range from small cocci to short rods
Borrelia exhibit extracellular replication, rickettsia exhibit intracellular replication via binary fission (obligate intracellular parasites - can’t reproduce outside a host cell)
What are common features of borrelia and rickettsia?
Arthropod vectors (ticks or lice) except Q fever
Mammalian reservoirs
Tetracycline sensitivity
True or false? A typhus infection can lead to typhoid fever.
False. Typhus is a rickettsia, typhoid fever is caused by a salmonella
How do you detect borrelia?
giemsa, silver stain, IF, visible by standard microscopy
Why do humans get infected with rickettsia?
accidental transmission - usual life cycle is back and forth from mice to ticks
**endemic typhus is the exception
Which rickettsia infection is associated with a characteristic rash?
Rocky mountain spotted fever -
Where in the body does rocky mountain spotted fever reproduce?
What virulence factors aid in its pathogenesis?
invades and multiples in vascular endothelial cells
OmpA&B: adhesion
Type 4 secretion system: entry
Phospholipase A2: escape from endosome
ActA: actin-based cell-cell spread
What causes the rash in rocky mountain spotted fever? *Hint – it helps to remember the site of reproduction
Rash is caused by leaking from damaged blood vessels
Where (geographically) is rocky mountain fever most commonly seen? What is the vector?
East Coast
dog tick
Pt. exibits clinical signs of Headache, Fever, Myalgia. Vasculitis then appears leading to a widely disseminated rash, which begins on extremities, spreads to trunk. If left untreated symptoms could progress to delerium, coma, DIC, edema, circulatory collapse (18% untreated mortality). What is the Dx? What is the organism’s name and relevant features for identification? Vector? What is the alternative to the preferred treatment for patients who are allergic or pregnant?
Rocky mountain spotted fever.
Rickettsia rickettsi
Gram (-) very short rod
Vector - Dermacentor variabilis (dog tick)
Tx - Doxy for adults and kids, Chloramphenicol for pregnant mothers or people with allergies to doxycycline.
Describes clinical presentation of rocky mountain spotted fever.
What is a rickettsial tick borne infection that begins with a eschar (dark scab of dead skin)?
Mediterranean spotted fever - otherwise similar to rocky mountain spotted fever but less severe
severe cases arise if: older age, alcoholism, or glucose-6-phosphatase dehydrogenase deficiency
Same treatment (doxy for adults/kids, chloramphenicol for pregnant mothers or if allergic to doxy)
What is unique about Endemic Typhus from all other Rickettsia?
What is the vector?
humans are normal host and reserviour
body louse, sometimes head or pubic lice
If humans are the host and reseviour for endemic typhus, how does the rickettsia spread?
louse vector must feed on infected host then feed on uninfected host (infected person –> louse –> uninfected person)
Louse vector will develop infection! Endemic typhus rickettsia (R. prowazekii) will multiply in infected louse allimentary tract, cause an obstruction, and kill the louse
What are the virulence factors for R. prowazekii? What disease does this cause? What cell type does it target? What symptom does it cause by targeting this cell type?
Endemic typhus - R. prowazekii multiples in vascular endothelial cells using same adherence virulence factor as R. rickettsii (rocky mountain spotted fever) – outer membrane proteins A&B (OmpA&B)
Causes vasculitis
How does the infected vector inoculate an uninfected host with R. prowazekii?
defecation (of the gram negative short rod in the louse feces) - requires some form of abrasion to enter host through skin
Pt. presents with abrupt-onset fever, chills
Generalized lymphadenopathy, and abrupt-onset of unremitting Headache. 4-7 days later a macular, maculopapular, or petechial rash occurs, beginning on the axilla and trunk and spread peripherally. Occasionally associated with nonproductive cough, deafness. If left untreated Pt. may progress to CNS symptoms (meningoencephalitis), dullness, delerium, coma. At ~ 2 weeks untreated, there is 20-60% mortality from vascular collapse or pneumonia.
What is the Dx? What organism is responsible? How was it transmitted?
description is clinical symptoms of Endemic Typhus caused by infection of vascular endothelium by R. prowazekii. Transmission is through lice/louse shit that gets into cut or scrape. Petechial rash is due to blood leakage from vascular endothelial damage.
Associated with lack of personal hygene and cold weather.
What is Brill-Zinsser Disease? What are risk factors?
Recrudescent Typhus (typhus that has undergone latency and reactivation)
malnutrition and improper or incomplete antibiotic therapy for previous typhus infection (e.g. elderly or those who got typhus in WWII)
What differentiates endemic typhus from the other rickettsial spotted fevers?
lice not tick vector of transmission
humans are host and reservoir
recurrences occur in recrudescent form
What is maurine typhus? Vector?
Flea (not louse) borne version of endemic typhus that is accidentally transferred to humans - milder form of disease
What is scrub typhus?
Humans are accidental host to the Leptotrombidium akamushi (chigger) vector and O. tsutsugamushi bacterium
Milder than endemic typhus
60% Eschar forms at bite site
Regional lymph node and pulmonary involvement (cough) more common
How is typhus diagnosed? Treated?
Take blood sample prior to antibiotic therapy, then give antibiotics (Doxycycline or chloramphenicol). Positive response to antibiotics + indirect immunofluorescence assay is confirmation of Typhus
For doxy resistance use Azithromycin and rifampicin
What causes human monocytic ehrlichiosis?
Ehrlichia chaffeensis
What dissease does Ehrlichia chaffeensis cause?
human monocytic ehrlichiosis
What dissease is caused by Anaplasma phagocytophilum
Human granulocytic ehrlichiosis aka human granulocytic anaplasmosis
What is the vector for Ehrlichia chaffeensis? What dissease does it cause?
ixodes scapularis (deer/black legged tick) - human monocytic ehrlichiosis
What is the bacteriology of the organism that causes human monocytic ehrlichiosis?
Ehrlichia chaffeensis
Tiny Gram (-) Obligate intracellular Resemble Rickettsia Replicate in cytoplasm of white cells Form clusters called morulae
What are the typical symptoms of Human monocytic ehrlichiosis? How long after exposure do they present? Who are the most likely to be affected? What are the most severe symptoms?
What two other tick bite co-infections should be ruled out?
Infection often asymptomatic; most cases resolve without diagnosis
Symptoms may appear a week after bite: Severe headache, myalgias, fever, shaking chills, GI symptoms
Elderly or immunocompromised patients are at increased risk for severe ehrlichiosis; may develop meningitis or disseminated intravascular coagulation
Co-infections of two tick-borne pathogens transmitted by the same vector do happen (rule out babesiosis and Lyme disease)
Why is infection with Anaplasma phagocytophilum
called Human granulocytic anaplasmosis
Because it infects and grows inside neurotrophils (type of granulocyte)
What is the bacteriology of anaplasma?
Small, Gram(-)
Obligate intracellular
Reside in early endosome of white blood cells (specifically granulocytes)
Grow into morulae - solid clusters of cells
Ehrlichia, anaplasma, and C. pneumoniae only organisms known to grow within neutrophils
3) Your patient presents in the summer with a round rash. Because he enjoys hiking and
you practice in a Lyme-endemic area, you decide to treat him for a possible B.
burgdorferi infection. He has no drug allergies. Which course of treatment would be
most appropriate?
a. 20 days amoxicillin
b. 20 days doxycycline
c. 7 days doxycycline
d. 6 months doxycycline
b
