Rickettsia, Zoonotic Bact, Lect 31 Exam 3

Front 1

Define zoonotic disease

Back 1

Zoonotic diseases are caused by organisms that are transmitted from animals to humans. Some are transmitted directly from the animal reservoir and others are transmitted via vectors, e.g. fleas, mosquitoes, or ticks. Although we will focus on bacterial zoonotic diseases in this lecture, you should also be aware that there are viral, fungal, and parasitic zoonoses, as well. The major bacterial diseases transmitted by ticks in the United States are Lyme disease, Rocky Mountain Spotted Fever (RMSF), ehrlichiosis, relapsing fever, and tularemia.

Front 2

Rickettsia
1) important properties

Back 2

1. Very short rods (coccobacilli).
2. Structure similar to Gram-negative rods; have a loosely adherent slime layer.
3. Stain poorly with Gram stain.
4. Obligate intracellular parasites.

Front 3

Rickettsia transmission and epidemiology

Back 3

1. Maintained in the environment in arthropods (the reservoir) and transmitted to humans
by arthropod bites (zoonoses), except for R. prowazekii which causes epidemic typhus
and occurs only in humans (transmitted via lice).

2. Incidence of disease based on geography:
a. Distribution of arthropod vector.
b. Risk of exposure.

Front 4

Describe Rocky Mountain Spotted Fever

Back 4

a. Caused by Rickettsia rickettsii.

b. Characterized by acute onset of nonspecific symptoms: high fever and chills, severe
headache, myalgia, prostration.

c. 2 to 6 days later, a rash may appear—usually on hands and feet first, then
moving inward (centripetally) to the trunk. Rash starts as macules, progresses
to petechiae.

d. CNS involvement can also involve delirium and coma.

e. In severe cases, disseminated intravascular coagulation (DIC), edema, and
circulatory collapse can occur. Can be fatal, if untreated, within 8 days after onset of
symptoms.

f. Diagnosis must be made clinically and treatment started immediately—lab tests are
based on serology and they take too long.

g. Occurs most frequently along U.S. east coast in VA, NC, GA where the dog tick
(Dermancentor variabilis) is found.
i. Tick is both a reservoir and vector of R. rickettsii. Ticks acquire lifelong infection
via transovarian route.
ii. Humans are accidental hosts (not reservoirs)—there is no

Front 5

Epidemic typhus.
1) What is it caused by?
2) How is it transmitted?
3) What are the clinical symptoms?

Back 5

1) caused by Rickettsia prowzekii
2)
ii. Not commonly found in the U.S. Is associated with poverty and wars; currently
occurs in developing countries in Africa and South America.

iii. Transmitted person-to-person by lice (vector), humans are the primary reservoir.
3) iv. The louse ingests the organism when it bites a bacteremic patient. The organism
replicates in the gut epithelium of the louse and is excreted in the feces when it
bites the next person. Autoinoculation occurs when the bite is scratched.

v. The louse eventually dies within 2 to 3 weeks so it’s not a great reservoir. There is no louse-to-louse transmission, so human infection is an obligatory stage in the bacterium’s life cycle.
3) vi. Characterized by sudden onset of chills, fever, headache, other flu-like
symptoms ~1 to 3 weeks after louse bites host.

vii. 5 to 9 days after onset of symptoms, maculopapular rash develops on trunk and
spreads peripherally (centrifugally). Rash becomes petechial and spre

Front 6

What is the treatment for rickettsia

Back 6

1. Tetracyclines (e.g. doxycycline)
2. Chloramphenicol is 2nd choice.

Front 7

Describe prevention of rickettsial diseases

Back 7

1. Based on avoidance or protection from exposure to arthropod vectors or animal reservoirs (protective clothing, repellents).

2. For RMSF, inspection of skin for ticks after possible exposure is critical. Tick must remain attached for several hours to transmit disease. No vaccine for RMSF.

3. For typhus, good personal hygiene and delousing.

Front 8

What are the important properties of borrelia?

Back 8

a. Irregular, loosely coiled spirochetes that are motile.

b. Visualized by darkfield microscopy and Giemsa and silver stains.

Front 9

Describe the transmission and epidemiology of borrelia.

Back 9

a. Multiple Borrelia species can cause Lyme disease, including: B. burgdorferi
B. garinii, B. azfelii—these last 2 species are more common in Europe.

b. Transmitted by ticks, primarily Ixodes scapularis in northeastern and north central
U.S.; this tick can also transmit Anaplasma phagocytophilum and Babesia microti.
Small mammals are the reservoir (white-footed mouse); large mammals (deer) are
required for tick life cycle, but are not significant reservoir.
There is no human-to-human spread.

c. Highest incidence of disease is in late spring and summer, coincident with highest
feeding activity of nymphs.

d. Inspection of skin for ticks, which are the size of a poppy seed, is critical for prevention of disease since tick must feed for 24 - 48 to transmit infectious dose.

e. Occurs worldwide. In U.S., occurs primarily in the Northeast.

f. Lyme disease is the most common vector-borne disease in the U.S.

Front 10

Describe pathogensis of borrelia

Back 10

a. Organism spreads from bite site through the skin, then enters the blood stream and
disseminates to heart, joints, CNS.

b. No specific virulence factors have been identified.

Front 11

What are the 3 stages of the progressive disease for borrelia

Back 11

i. Stage 1: erythema migrans: a generally painless, spreading nonpruritic, circular
red rash with a clear center (“bull’s eye”) is commonly seen at the bite site within
one month after tick bite; may or may not be accompanied by flu-like symptoms.
In ~20% of cases no rash seen. Myalgias, fatigue, headache, and arthralgias,
but not arthritis are also common.

ii. Stage 2: Occurs weeks – months later; cardiac and neurologic involvement:
meningoencephalitis, cranial neuropathies (e.g. Bell’s palsy), radiculitis,
peripheral neuropathy, encephalopathy; carditis, including fluctuating degrees of
atrioventricular heart block, sometimes with myocarditis, (usually mild). Followed
by a latent phase lasting weeks – months/years.

iii. Stage 3: Characterized by arthritis of one or few large joints, often the knee;
may also include subtle “Lyme encephalopathy” or polyneuropathy..

Front 12

What's the lab diagnosis of borrelia?

Back 12

a. Clinical manifestations, history of tick bite or exposure, and serologic detection of
IgM or rising IgG titer.

b. Two-step serologic testing recommended by CDC:
i. First step is ELISA or indirect IFA on serum sample for detection of
anti-B. burgdorferi antibodies. If this is positive, perform step 2.

ii. Step 2 is Western blot test on the same serum sample to detect IgM and IgG vs.
specific B. burgdorferi antigens. Must meet specific criteria to be considered
positive.

Front 13

What's the treatment for borrelia?

Back 13

a. Stage 1 and mild symptoms: doxycycline or amoxicillin.

b. Late stage and severe symptoms: ceftriaxone.

Front 14

what's the prevention for borrelia?

Back 14

a. Prevent by avoiding exposure, wear proper clothing, use DEET, perform skin
inspections after potential exposure and remove ticks properly.

b. Prophylactic antibiotics may be given if local area has high percentage of infected
ticks and tick has been attached >48 hours. Monitor for rash, flu-like symptoms for
3 weeks.

c. A recombinant, outer membrane protein vaccine (OspA) was effective in clinical
trials in the U.S. but is currently not available.

Front 15

What are the important properties of brucella?

Back 15

a. Pleomorphic cocci to coccobacillary forms.
b. Gram-negative, but stain irregularly.
c. Obligate intracellular parasites of animals and humans.

Front 16

Brucella transmission and epidemiology

Back 16

a. Transmitted to humans by ingestion of contaminated milk products or by direct
contact with infected tissues.
b. Rare in the U.S.; possible agent of biowarfare.

Front 17

What is the pathogenesis and clinical findings of Brucella?

Back 17

a. Incubation period is 1 to several weeks.
b. Organism disseminates via lymphatic system to bloodstream to various organs.
c. Initial symptoms include malaise, fever, weakness, aches, sweats. Fever rises in
the afternoon and falls at night with accompanying sweats.
d. Lymph nodes enlarge, spleen is palpable; hepatitis and jaundice; osteomyelitis is
the most frequent complication.
e. Symptoms usually subside in weeks/months.
f. Chronic brucellosis may occur with weakness, aches, low-grade fever,
psychoneurotic symptoms (e.g. nervousness).
g. Majority of infections remain latent and asymptomatic.

Front 18

What is the treatment and prevention for Brucella?

Back 18

a. Tetracyclines and others; long-term treatment needed to eradicate.
b. Prevention by avoiding exposure; eradication efforts in cattle; experimental
vaccines.

Front 19

What are the important properties of francisella tularensis (causes tularemia)?

Back 19

a. Small, pleomorphic, pale-staining, Gram-negative coccobacillus.
b. Facultative intracellular organism—replicates in macrophages, but can be found
extracellularly, too.
c. Hard to culture in lab, but very hardy in environment

Front 20

What is the transmission and epidemiology of francisella tularensis?

Back 20

a. Organism found in U.S. (majority of cases in AK, MS, OK).

b. Endemic in >100 species of wild animals.

c. Transmitted among animals by ticks (transovarial txn in ticks), mites, lice.

d. Humans are “dead-end” hosts (no person-to-person txn) and are exposed via:
i. vector bites, e.g. ticks, biting (e.g. deer, horse) flies, mosquitoes

ii. exposure of skin to infected tissues, e.g. handling sick or dead infected animals,
like rabbits

iii. ingestion of inadequately cooked meat or contaminated water

iv. cat scratches or bites; also a case from pet hamster bite

v. splashing or rubbing infected material in eyes

vi. aerosols, e.g. lab exposures, mowing lawn or cutting brush

Front 21

What is the pathogenesis of francisella tularensis?

Back 21

a. Highly virulent: 10-50 organisms can cause disease.

b. Usually, organism enters skin, forms ulcer at site, enters reticuloendothelial system
and granulomas form; can lead to abscesses.

c. Pathogenesis and virulence factors not well understood; thought to be linked to
organism’s ability to grow in macrophages and induce release of proinflammatory
cytokines that trigger cell death.

Front 22

What are the clinical symptoms of francisella tularensis?

Back 22

Symptoms vary from none to sudden onset of flu-like syndrome (fever, chills,
headache, malaise) after incubation period of 2-10 days, to prolonged onset of low-
grade fever and lymphadenopathy, to septic shock and death; other symptoms vary
with route of entry and organ systems involved.
i. Most cases, associated with bites, present with “ulceroglandular” features with
swollen/painful regional lymph nodes. May see eschar at bite site.

ii. Pneumonic illness can occur if organism transmitted by aerosol, “inhalation
tularemia”; symptoms and radiographic findings similar to other CAP’s, so
diagnosis requires high index of suspicion.

Front 23

What is the lab diagnosis of francisella tualrensis?

Back 23

a. Serology used to confirm, after clinical presentation and history.
b. Difficult and hazardous to culture.

Front 24

What is the treatment and prevention francisella tualrensis?

Back 24

a. Streptomycin
b. Prevention by avoiding exposure; experimental, live, attenuated vaccine available
for those at high risk only

Front 25

Describe the important properties of Yersinia pestis (causes plague).

Back 25

a. Small, Gram-negative rod; exhibits bipolar staining.
b. Protein capsule—important virulence factor.

Front 26

What is transmission and epidemiology of Yersinia pestis?

Back 26

a. Endemic in rodents in Europe, Asia and North America.
b. Sylvatic cycle: Transmitted among wild rodents by fleas.
i. In the U.S., prairie dogs are the main reservoir.
c. Urban cycle (not in U.S.): urban rats are the reservoir; rat fleas are the vector;
occurs under conditions of poor sanitation.
d. Humans are accidental hosts; usually get infected via flea bite; other modes of txn
include: handling of infected animal carcasses, bites/scratches from infected
domestic cats, exposure to aerosols.

Front 27

What is the pathogenesis and clinical symptoms of Yersinia pestis?

Back 27

a. Organisms introduced to host via bite, spread to regional lymph nodes and cause
swelling and pain (buboes—bubonic plague); enter bloodstream and reach high
concentrations; disseminate to various organs and form abscesses.

b. Pneumonic plaque can result from inhalation of contaminated aerosols or septic
emboli that enter the lungs.

c. Endotoxin-related symptoms: high fever, disseminated intravascular coagulation
(DIC) and cutaneous hemorrhages (black death). Septic shock and pneumonia are
life-threatening consequences of infection.

d. ~50% of untreated cases of bubonic plague are fatal; untreated pneumonic plague
is almost always fatal.

e. Y. pestis is one of most virulent organisms known: ID50 is very low; 1 – 10
organisms can cause disease.

Front 28

What is the lab diagnosis of Yersinia pestis?

Back 28

a. Smear and culture of blood or pus from bubo; IF of organism in tissue.
b. Serology.

Front 29

What's the treatment and prevention of Yersinia pestis?

Back 29

a. Streptomycin, promptly!

b. Prevention by avoiding exposure, rodent control; quarantine of patients with plague
and prophylactic tetracycline (or others) for exposed persons; vaccine containing
killed organisms protects against bubonic, but not pneumonic plague (not
commercially available).

Front 30

What are the important properties, transmission + epi, and pathogensis and clinical findings of pasteurella multocida

Back 30

1. Important Properties
a. Small, Gram-negative coccobacilli.
b. Facultative anaerobe

2. Transmission and Epidemiology
a. Organism is a commensal in the oropharynx of animals. Humans get infected from
animal bites, scratches, or contaminated food.

3. Pathogenesis and Clinical Findings
a. Most common clinical disease is localized cellulitis and lymphadenitis following
contact with cat or dog (usually a bite or scratch).