Multisystem Zoonoses

Zoonoses

multisystem infections in humans caused by animals

What type of virus is Arenavirus?

ssRNA virus

Arenaviruses

viruses carried by various species of rodent that is shed in rodent excreta (urine/feces) that is severe (sometimes lethal) with extensive hemorrhaging and multi organ involvement

How are humans infected with Arenaviruses?

Direct contact with infected rodent

Inhalation of infectious excreta

Working/recreation in areas where rodents exist

What type of cells are infected by Arenavirus?

macrophages (induce cytokine and interferon release and promote cell and vascular damage)

What is the incubation period of arenavirus?

\~10-14 days

Lymphocytic choriomeningitis (LCM) virus (type of arenavirus) originates in what animal?

mouse and hamster

Lassa fever virus (type of arenavirus) originates in what animal?

African bush rat

What is the treatment option for arenavirus?

Ribavirin

What is the incubation period of lassa fever?

5-10 days

What are the clinical features of lassa fever?

Pharyngitis, diarrhea and nausea

Hemorrhage, capillary damage, hemoconcentration and collapse

Hemoconcentration

an increase in the concentration of cellular elements in the blood, resulting from loss of plasma

What is the presentation of LCM virus?

Febrile illness with flu-like myalgia

What can be seen in LCM virus infections?

Perivascular mononuclear infiltrates in the neurons

Hemorrhagic fever with renal syndrome is caused by which viruses?

Hantaan virus and the Seoul viruses

What are the clinical manifestations of hemorrhagic fever with renal syndrome?

Febrile illness

Hypotension, hemorrhage and renal syndrome

Hemorrhagic fever with renal syndrome was prevalent in american soldiers that were deployed where?

deployed to Korea

How is hemorrhagic fever with renal syndrome diagnosed?

Diagnosed by molecular and serological methods

What type of virus is the ebola virus?

filovirus, ssRNA virus

What does ebola virus cause?

Hemorrhagic fever

Extensive tissue necrosis in liver, spleen lymph nodes, and lungs

Nausea, vomiting, and diarrhea

Disseminated intravascular coagulation

What are the different ebola viruses?

Zaire virus, Sudan virus, Tai Forest virus, Bundibugyo virus

Reston virus (doesn’t cause disease in humans)

What animal serves as a reservoir for ebola virus?

fruit bats

Ebola virus replicates in what cell types?

macrophages, monocytes, and DCs

Infection of ebola virus in endothelial cells causes what?

cytolysis, vascular injury, leakage

How is ebola virus transmitted?

enters through mucous membranes or abraded skin (contaminated syringes/needles, burial preparations, sexual contact, direct contact w/ blood/body fluids w/ infected)

NOT aerosol transmission

Survivors of ebola virus develop what?

develop arthralgia, uveitis, and hearing loss

Viral RNA from ebola virus can be detected in what bodily fluids?

detected in semen, breast milk, eye fluid, and CSF in the absence of viremia

How do you detect viral RNA from ebola virus?

RT-PCR

What are treatment options for ebola virus?

IV rehydration, electrolyte re-balance

Antiviral agents brincidofovir and favipravir

Experimental treatments w/ convalescent plasma, monoclonal antibodies

Crimean-Congo Hemorrhagic Fever is caused by what type of virus?

negative sense, ssRNA virus

Crimean-Congo Hemorrhagic Fever is transmitted by what?

by ixodid ticks

Crimean-Congo Hemorrhagic Fever is transmitted by what?

transmitted by contact with infected animals (hares, cattle, goats, seabirds) or person to person by exposure to infected body fluids

What does Crimean-Congo Hemorrhagic Fever cause?

severe hemorrhagic fever, shock, and disseminated intravascular coagulation

The mortality rate for Crimean-Congo Hemorrhagic Fever is up to 80%. What treatment is available to decrease the mortality rate?

Supportive therapy and ribavirin

Q Fever is caused by what pathogen?

*Coxiella burnetti* (gram-neg)

How is *Coxiella burnetti* transmitted?

through inhalation (lungs) or through consumption of contaminated milk (sheep, cattle, goats - less common)

How long is the incubation period of Q fever?

3 weeks

What are the clinical features of Q fever?

Fever, severe headache, and respiratory symptoms

Atypical pneumoniae

Hepatitis

How is Q fever diagnosed?

PCR

Acute infections of Q fever are treated with what?

oral tetracyclines

Chronic infections of Q fever are treated with what?

Rifampin and doxycycline or TMP-SMX

What pathogen causes anthrax?

*Bacillus anthracis* (gram positive)

How is *Bacillus anthracis* acquired?

from direct contact with infected animals (sheep, goats, cattle, horses) or direct contact with spores

*Bacillus anthracis* spores enter the body where?

via skin and mucus membranes

Where do the spores associated with *Bacillus anthracis* germinate, multiply, and produce toxin?

at the site of entry

*Bacillus anthracis* toxin results in what?

edema and congestion w/ papule formation at the site of entry that ulcerates and forms a black eschar

What 3 toxin protein components are present on a large plasmid for *Bacillus?*

Protective antigen

Edema factor – calmodulin dependent adenylate cyclase

Lethal factor – zinc dependent protease

(PA + EF = edema toxin and PA + LF = lethal toxin)

What toxin protein component of *Bacillus* has the following MOA?

* Capable of cleaving mitogen-activated protein (MAP) kinases
* Leads to cell death

\
A. Edema factor

B. Lethal factor

C. Protective antigen

B. Lethal factor

What toxin protein component of *Bacillus* has the following MOA?

* Increases intracellular cyclic adenosine monophosphate (cAMP) levels
* Results in edema

\
A. Edema factor

B. Lethal factor

C. Protective antigen

A. Edema factor

What is the usual site of entry for cutaneous anthrax?

the skin

Respiratory Anthrax

Inhalation of spores that enter the alveolar macrophages

Growth in the lungs leads to pulmonary edema and mediastinal hemorrhage; Spreads to the blood → leads to mortality

On what type of agar plate can antrhax be cultured on?

good agar

How is cutaneous anthrax treated?

with ciprofloxacin

How is systemic anthrax treated?

with combination antibiotics (Ciprofloxacin or doxycycline + one or more additional antibiotics)

Antitoxin is administered as well

What pathogen causes the plague?

*Yersinia pestis* (gram-neg rods)

What are the reservoirs to the plague?

rodents (rats, squirrels, gerbils, field mice)

How is the plague spread between humans and animals?

by fleas

What virulence factors does *Yersinia pestis* have?

Antiphagocytic capsule

Endotoxin

Proteinaceous toxins

What are clinical features of bubonic plague?

Axilla/groin lymph node tenderness and enlargement to form buboes with hemorrhagic inflammation

Fever

Septicemia, hemorrhagic illness, multisystem involvement

Pneumonic plague results in extensive replication of bacteria in the lung and the development of bronchopneumonia. Because of this, large numbers of bacteria can be found where?

in the sputum

What are common complications associated with the plague?

Disseminated intravascular coagulation

Pneumonia

Meningitis

What is are the mortality rates if the forms of plague are not treated?

Bubonic plague → \~50%

Pneumonic plague → 100%

How is the plague diagnosed?

Recovered in fluid aspirated from lymph nodes & from sputum in pneumonic plague

Giemsa stained or fluorescent antibody

How is the plague treated?

Streptomycin

Doxycycline or ciprofloxacin are also used

Recombinant vaccine is available

What pathogen causes Tularemia and how is it spread?

*Francisella tularensis* and spread by arthropods from infected animals or from contaminated water

*Francisella tularensis* is what type of pathogen?

intracellular pathogen w/ gram-neg rods

Where does *Francisella tularensis* replicate?

Replicates in macrophages, neutrophils, epithelial and endothelial cells

What is a virulence factor associated with *Francisella tularensis?*

Antiphagocytic, polysaccharide rich capsule

What pathogen is a tier 1 agent that is very dangerous?

*Francisella tularensis*

What is the pathogenesis of *Francisella tularensis?*

Inhibits phagosome-lysosome fusion, secretes proteins that facilitate escape, and replicates in cytosol

The antiphagocytic, polysaccharide rich capsule present on *F. tularensis* protects the pathogen from what?

protects against complement-mediated killing

What type of T cells stimulate IFNγ for better intracellular killing in *F. tularensis* infection?

TH1-CD4 T cells

What are the clinical features of Tularemia?

Skin ulcer

Granulomatous nodules around reticuloendothelial cells

Rash formation

How are infected tissues with Tularemia examined?

by fluorescent antibody staining

What is the drug of choice for Tularemia?

Streptomycin (Doxycycline & gentamicin are options)

Vaccine (live attenuated bacterial) available for pts w/ occupation risk

*Pasteurella multocida*

Gram negative; Small, facultatively anerobic, fermentative coccobaccili

*Pasteurella multocida* grows well on what type of agar?

blood agar (does NOT grow well on MacConkey agar)

What virulence factor is present on *Pasteurella multocida?*

polysaccharide capsule

What are clinical features of *Pasteurella multocida?*

Localized cellulitis or lymphadenitis

Chronic respiratory disease

Systemic infections (immunocompromised)

How is *Pasteurella multocida* transmitted to humans?

through animal scratch or bite

How is *Pasteurella multocida* treated?

with amoxicillin/clavulanate

What pathogen causes Leptospirosis?

*Leptospira interrogans* (Spirochete)

How is Leptospirosis transmitted to humans?

by ingestion of/exposure to contaminated food or water

What community of people are at risk for infection by Leptospirosis?

Miners, farmers, sewage workers, and water sport people

What does leptospirosis infection cause?

chronic kidney function

What is the incubation period of leptospirosis?

1-2 weeks

What is the main clinical sign of leptospirosis?

damage to endothelia of blood vessels

Weil’s disease

Severe form of leptospirosis with hemorrhagic complication that results in kidney and liver failure

Multiplication of leptospirosis can cause what?

Hepatitis

Jaundice

Hemorrhage in the liver

Uremia and bacteriuria in the kidney

Aseptic meningitis

Conjunctival or scleral hemorrhage

How is leptospirosis diagnosed?

Through serology (bacteria isolated from blood, CSF, & urine)

What have been successful antibiotics in treating leptospirosis?

Penicillin and doxycycline

What antibiotic can be used to prevent leptospirosis disease in individuals exposed?

doxycycline

What causes Brucellosis?

*Brucella* species

Human brucellosis (aka undulant fever or malta fever) is common in what population of individuals?

farmers, veterinarians, and slaughterhouse workers

*Brucella* species

Gram negative – very small intracellular bacterium that infects the Reticuloendothelial cells

Where do *Brucella* species survive and live for prolonged periods of time?

in the Reticuloendothelial cells

*Brucella* species typically cause what to happen in animals?

causes spontaneous abortion and infertility

How many bacteria result in an infectious does of *Brucella melitensis?*

\
A. 5 bacteria

B. 10 bacteria

C. 25 bacteria

D. 50 bacteria

E. 100 bacteria

B. 10 bacteria

How many bacteria result in an infectious does of *Brucella suis?*

\
A. 5 bacteria

B. 10 bacteria

C. 25 bacteria

D. 50 bacteria

E. 100 bacteria

D. 50 bacteria

What type of *Brucella* affects cows?

\
A. *Brucella abortus*

B. *Brucella canis*

C. *Brucella melitensis*

D. *Brucella suis*

A. *Brucella abortus*