L9 MHD: Zoonoses

Question 1

Brucella

1. What 4 animals serve as a reservoir of Brucella?
2. How do humans become infected with the disease?

Answer 1

1. Goats, cattle, pigs, dogs
2. Humans infected by contact with animals (slaughterhouse, veterinarians, farmers, lab techs) or by ingesting contaminated milk or dairy
   * Especially unpasteurized goat cheese*

Question 2

Category A bioterrorism agents are high-priority agents that pose a risk to national security (easily disseminated, result in high mortality rates, cause panic). Name 3 Category A bioagents.

Answer 2

1. Bacillus Anthracis (anthrax)
2. Yersinia Pestis (bubonic plague)
3. Francisella Tularensis (Tularemia)

Question 3

Category B bioterrorism agents are the 2nd highest priority agents that are moderately easy to disseminate, result in moderate morbidity rates/low mortality rates, and require specific enhancements of CDC’s diagnostic capacity. Name 3 category B agents.

Answer 3

1. Brucella Species (Brucellosis)
2. Food safety threats (Salmonella species/E.Coli O157:H7, Shigella)
3. Burkholderia Pseudomallei (Melioidosis)

Question 4

Emerging infectious diseases such as Nipah virus and hantavirus are examples of what category bioterrorism agent?

Answer 4

Category C

-3rd highest priority that includes pathogens that could be engineered for mass dissemination in the future because of availability, ease of production, and potential for high morbidity/mortality rates.

Question 5

What animal do the following Brucella species originate from?

• Brucella Melitensis
• Brucella Suis
• Brucella Abortus
• Brucella Canis

Answer 5

-B. melitensis: Goats, Sheep, Camels (most virulent!)
-B. suis: Pigs
B. abortus: Cattle
B. canis: Dogs (least common)

Question 6

Describe the pathogenesis of Brucella

Answer 6

1. Organisms penetrate skin/mucosal membranes
2. Phagocytosized by macrophages/monocytes
   * *facultative intracellular organisms**
3. Carried to spleen, liver, bone marrow, lymph nodes, and kidneys
4. Organisms multiply in macrophages in RE system
5. Host reaction is the formation of small granulomas

Question 7

How does a humoral antibody affect the outcome of a Brucella infection? Cell-mediated immunity?

Answer 7

Brucella= intracellular organism of the reticuloendothelial system

• Humoral Ab does NOT affect outcome, T-Cell immunity determines recovery
• Organisms are able to survive intracellularly because they inhibit polymorphonuclear leukocyte degranulation
• Predilection for erythritol rich tissues in animals
• *placenta in animals- results in spontaneous abortions**

Question 8

Brucella Clinical Manifestations

1. How long until symptoms appear?
2. What are the initial symptoms?
3. What is the key clinical feature of the disease?
4. What organs are enlarged?

Answer 8

1. Symptoms appear 2-8 wks after exposure
2. Initial: non-specific symptoms (people feel like they have the flu): malaise, chills, sweats, fatigue, weakness, myalgias
3. Key clinical feature: UNDULANT FEVER- a fever that is intermittent/cyclical. Organisms sequestered in granulomas in tissue/BM. Release of organisms into circulation causes reappearance of fever! TEST
4. Splenomegaly, lymphandenopathy, hepatomegaly

Question 9

What are the signs of advanced disease with a brucella infection?

Answer 9

1. GI symptoms (70%)
2. Osteolytic lesions/joint effusions (20-60%)
3. Respiratory symptoms (25%)
   * *Less common: CNS (meningitis/meningoencephalaitis), CV manifestations (endocarditis with septic embolization), GU tract (orchitis, renal granulomas), ocular
4. Chronic infections (patients can be chronically ill for over 12 months)

Question 10

1. What is the preferred way to diagnose Brucella?

2. Serological tests look for what?

Answer 10

1. Preferred method of Dx: Blood cultures with extended incubation time
   * *Brucella is slow growing**
   - Bone marrow is the preferred site (best yield but most invasive), culture can also be taken from blood, liver, or lymph nodes
2. Serology tests: presumptive diagnosis
   - Looking for titers of Ab against Brucella or elevated febrile agglutinin titer
   - Four fold rise in titer indicative of disease
   - Single titer of >1:80
   - Antibody titer >1:160 (seen in 5-10% of the population living in endemic areas)

Question 11

Describe Brucella’s morphology

1. What does a gram stain show?
2. Fast or slow growing?
3. Preferred growth media?

Answer 11

1. Poorly staining, small coccobaciliary gram negative rod (looks like grains of sand)- VERY TINY
2. Slow growing
3. Requires enriched media (chocolate agar with cysteine crystals) to grow and prolonged incubation

Question 12

1. What is the best way to treat Brucellosis?

2. How long must the disease be treated?

Answer 12

1. Oral tetracyclines along with ahminoglycosides (gentamicin/streptomycin)
   * *treatment involves agents that penetrate and have activity within phagocytic cells!**
2. Because of the chronic nature of some infections (brucella getting into the bone marrow- periodically gets released), disease must be treated for a prolonged time

Question 13

Relapses occur in 10% of Brucella patients.

What are 2 ways of controlling the disease? Is a vaccine available?

Answer 13

1. Controlled by immunizing livestock
2. Tell patients to avoid unpasteurized milk and dairy products

No human vaccine available.

Question 14

Meat factory workers, veterinarians, farmers, and travelers who consumed dairy in Mexico are at risk of what disease?

Answer 14

Brucella

Question 15

The following: 
“ Glandular Fever”
“Rabbit Fever”
“Tick Fever”
“Deer Fly Fever”
“Ohara Disease”
 are all names for what zoonotic agent?

Answer 15

Tularemia

Question 16

1. How does a pt get a Tularemia infection?
2. What is the causative agent?
3. In what 3 states is tularemia most prevalent?

Answer 16

1. Disease is caused by handling infected rabbits (animal contact) or by deer fly/tick bites, contact with cat who caught an infected rabbit, consumption of contaminated meat/water, inhalation of infectious aerosol in lab or while dealing with the infected animal
2. Causative agent = Francisella Tularensis
3. Most patients are men (hunters) who live in Arkansas, Oklahoma, and Missouri

Question 17

Describe the pathogenesis of Tularemia

-How many pathogens needed to cause infection?

Answer 17

1. Organisms enter through breaks in skin or mucous membranes
   * *Ulcer may develop at entry site**
2. Disseminate via bloodstream to regional lymph nodes
3. Host response is granuloma formation (like Brucella)

Tularemia is very virulent! Only a limited number of pathogens needed to cause an infection!

Question 18

1. What contributes to Tularemia’s virulence?

2. Is humoral or cellular immunity required for recovery?

Answer 18

1. Bacterial capsule- antiphagocytic
2. Cellular immunity required for recovery- tularemia is a facultative intracellular organism
   * *Humeral antibody response remains elevated for years**

Question 19

What are the 6 forms of Tularemia? How is each contracted? What is the most common? Which has the highest mortality?

Answer 19

1. Ulceroglandular Infection
   - Most common form
   - Papule at site of entry- necrotic and ulcerates
   - Regional lymph nodes swell
   - Rabbit associated cases involve fingers/hands; tick associated cases involve lesions on trunk/perineum/legs/heads & neck
2. Oculoglangular
   - Conjunctival inoculation via fingers- unilateral painful conjunctivitis
3. Typhoidal Infection- GI tract
   - After ingestion of large # of organisms
   - Fever, prostration, weight loss
   - HIGHEST MORTALITY
4. Pneumonic Infection
   - Inhalation of low counts of organisms
   - Pneumonic/systemic illness
5. Glandular form: adenopathy- swollen neck
6. Oropharyngeal form
   - Ingestion of infected meat/water
   - Fever/throat pain with exudative pharyngitis or tonsillitis
   - Pharyngeal ulcers and pseudomembranes
   - Cervial, pre-parotid, and retropharyngeal lymphandenopathy

Question 20

What are 4 ways Tularemia can be diagnosed/identified?

Answer 20

1. Culture- best way to diagnose, but is very dangerous due to its high infectivity
   * *Culture from blood, pleural fluids, lymph nodes, wounds, conjunctival swabs, tissue**
   * *notify lab if you suspect Tularemia- they’ll take special precautions to protect themselves**
2. Immunofluorescent Stain of smears- rapid Dx
3. Serological Dx- acute and convalescent agglutinin antibody titers (PAIRED TITER)
4. PCR

Question 21

Characteristics of Francisella Tularensis:

1. Gram __________, looks like what on a gram stain?
2. Growth requirements?
3. Strict aerobe or anaerobe?
4. Does Tularensis require a long or short incubation time?

Answer 21

1. Small Gram Negative coccobacilli, looks like Brucella on the gram stain (small grains of sand)
2. Does not grow on routine media-it requires cysteine supplemented media & sulfhydryl compounds for growth
   * Chocolate agar can be used*
3. Strict aerobe
4. Requires a long incubation time- could be up to 3 weeks!

Question 22

1. What antibiotics are used to treat Tularemia?
2. How could disease be avoided?
3. Is there a vaccine available?

Answer 22

1. Streptomycin, Gentamycin, Tetracycline, or Choramphenicol can be used to treat
2. Prevent by removing tick promptly and avoid contact with dead animals (stop picking up roadkill off the side of the road, Solo)
3. Live attenuated vaccine available

Question 23

Pasteurella Spp. Characteristics

1. Gram stain?
2. Motility?
3. Are they facultative intracellular organisms like the other zoonoses?
4. Oxidase test?
5. Catalase test?
6. Fermenation?
7. What antibiotic are they treated with and why is this unusual?

Answer 23

1. Gram-negative bacilli
2. Non-motile
3. NOT facultative intracellular organisms
4. OXIDASE POSITIVE TEST
5. Catalase positive
6. Fermentative
7. Treated with Penicillin- this is unusual because they are gram negative! TEST

Question 24

1. Pasteurella Multocida is caused by what animal?
2. What occurs at wound site?
3. What could occur following deep wound puncture?
4. Is this infection serious?

Answer 24

1. CATS
   Most human infections are wound infections/cellulitis following cat bites
2. Pain, swelling, and serosanguinous drainage at wound site
3. Septic arthritis and osteomyelitis may occur following deep puncture wound
4. Serious infection! Wide excision debridement may occur in compromised hosts (diabetics)

Question 25

Pasteurella multocida lab findings: 1. Gram stain? 2. Aerobic or anaerobic? 3. Grows on what kind of media? What kind of media does it not grow on? 4. What do colonies look like and what odor do they give? 5. Oxidase test? 6. Penicillin resistant or susceptible?

Answer 25

1. Small bipolar gram negative rods 2. Facultative anaerobe 3. Grows on blood and chocolate but NOT MacConkey agar **TEST** This is atypical because usually MacConkey agar is selective for gram negative rods 4. Large buttery colonies with moth ball odor 5. Oxidase positive 6. Penicillin-susceptible **Culture lesion site and collect blood for culture**

Question 26

Plague: The Disease 1. Reserviors? 2. Vector of Transmission?

Answer 26

1. Wild rodents, city rats, squirrels and prairies dogs in the SW U.S. 2. Flea bites, contact with infected animal tissue and inhaled aerosolized organisms- human to human transmission that occurs during epidemics

Question 27

Plague: Disease of Antiquity- Major Plague Pandemics - First Pandemic? - Second Pandemic? - Third Pandemic?

Answer 27

First Pandemic - The Justinian Plague: (A.D. 541-544) named after Roman emperor 6th century. 100+ million deaths. Began in Egypt, spread through Middle East and Mediterranean Europe. Second Pandemic - 1st epidemic (A.D. 1347-1351) known as the Black Death, killed 17-28 million Europeans, 30-40% of that population. **Encompassed all the "known world"** Third Pandemic - started in 1855 in Yunnan, a Southwestern province of China Local epidemics subsequently took place all over the world until the 1950’s when the pandemic ended

Question 28

Plague in the US 1. How did plague reach the United States? What year? 2. Reluctance of California health officials to admit that plague existed in Chinatown resulted in initiation of _________ infection? 3. Where in the US was the plague most prevalent?

Answer 28

1. Y. pestis probably entered the U.S. through the port of San Francisco by boat * *After plague hit Hong Kong it spread rapidly- hit San Fran in 1900** 2. Sylavatic infection (organism enters rodent population) 3. Through sylvatic infection (primarily in the ground squirrel), the infection eventually covered much of the western U.S. (13 States) with the majority of cases occurring in Arizona, California, Colorado, New Mexico, Oregon

Question 29

Plague in the US -From 1947-1996, 390 cases in US resulting in 60 (15.4%) deaths Of the following, which had the most cases? Which caused the most deaths? -Pneumonic -Septicemic -Unclassified -Bubonic

Answer 29

Bubonic: 327 (84%) cases, 44 (14%) deaths Septicemic: 49 (13%) cases, 11 (22%) deaths Pneumonic: 7 (2%) cases, 4 (57%) deaths Unclassified: 7 and 1 death - Bubonic = most cases - Pneumonic most fatal

Question 30

Yersinia pestis - Epidemiology 1. Causative agent of what? 2. What are the two epidemic forms? 3. What domestic animal is a carrier of yersinia pestis?

Answer 30

1. Causative agent of the plague 2. Urban plague- maintained in rat population- spread to humans by fleas - Sylvatic Plague- endemic in western USA- carried by prairie dogs, mice, rabbits and rats. Found in forest areas. 3. Domestic cats permitted to roam freely in areas where plague occurs in rodents are at increased risk for infection- increase peridomestic transmission to humans * *Since 1977 cats have been identified as the source of 15 human plague infections**

Question 31

Key Identifying Features of Yersinia Pestis 1. Member of what group? 2. Oxidase test? 3. Motility? 4. Gram stain? 5. Slow or fast growing colonies? 6. Colony appearance? 7. Growth media? 8. Growth temperature?

Answer 31

1. Member of enterobacteriaceae 2. Oxidase negative 3. Non-Motile 4. Small, coccobacillary on gram stain, bipolar staining- "safety pins" 5. Slow growing on ordinary media 6. After 48 hours, fried egg or beaten copper appearance when viewed under the microscope; small pinpoint colonies on MacConkey 7. Growth media: MacConkey 8. Faster growth at 28C than 37C

Question 32

Describe the pathogenesis of the plague.

Answer 32

1. Organisms multiply in the flea's gut 2. Flea bites human or another rodent 3. Organisms move from bite site to lymph nodes 4. Organisms multiply in lymph nodes, necrosis and swelling-->causes a Bubo 5. Organisms spread to blood, lungs, liver, and spleen

Question 33

Pathogenesis of the Plague 1. What type of organism? 2. Multiplies freely where? 3. What are black buboes? 4. Where does systemic infection spread? 5. What is pneumonic disease characterized by? 6. Terminal cyanosis is known as what?

Answer 33

1. Facultative intracellular organisms (can survive in macrophages) 2. Resists killing, multiplies in mononuclear phagocytes & freely in the extracellular environment 3. Black buboes= enlarged tender lymph nodes with hemorrhagic necrosis 4. Systemic infection spreads to liver, lung, spleen 5. Pneumonic disease characterized by necrotizing hemorrhagic pneumonia 6. Terminal cyanosis = Black Death

Question 34

BUBONIC PLAGUE 1. What are the clinical symptoms of the plague? 2. How long after bite does a bubo show up? 3. What percent of patients have positive blood cultures? 4. What is the mortality rate if untreated?

Answer 34

1. Sudden onset of fever, chills, weakness, and headache. Within hours notice intense pain in anatomic region with buboes, become prostrate and lethargic. 2. Fever and painful bubo 2-7 days after bite 3. 80% have positive blood cultures 4. 75% mortality if untreated

Question 35

SEPTICEMIC PLAGUE 1. Direct infection of what? 2. Symptoms? 3. What causes the name "Black Death?" 4. What percent of patients become septic with + blood cultures? 5. Why are fatality rates high with septicemic plague?

Answer 35

1. Direct infection of bloodstream by flea bite, or spread of microorganism from Lymph node to blood 2. High fever, delirium, seizures in children, septic shock, DIC (disseminated intravascular coagulation) 3. Black hemorrhagic splotches gave rise to the name “Black Death” 4. 100% of pts. become septic with + blood cultures 5. Fatality rate high due to delay in Dx and Tx

Question 36

PNEUMONIC PLAGUE 1. What two ways can the plague reach the lungs? 2. What are initial symptoms? 3. What does sputum usually contain? 4. What quickly follows initial symptoms?

Answer 36

1. Plague bacillus reaches lungs by hematogenous spread (bloodstream) or by inhalation of infectious aerosol from plague pt. with cough. – pt sneezes and coughs- spreads like TB/cold/flu 2. Initially: headache, malaise, fever vomiting, prostration and confusion; pts. develop cough, chest pain, hemoptysis. 3. Sputum usually purulent and contains plague bacillus (Patient highly infectious) 4. Quickly followed by sepsis and death unless therapy initiated within one day following onset of symptoms

Question 37

Plague should be suspected in febrile pts. who have been exposed to rodents or other mammals in known epidemic areas of the world. 1. What part of the US is susceptible to the plague? 2. Yersinia pests is identified as a potential bioterrorism agent- what category is it?

Answer 37

1. US- Southwest is more likely to have the plague- include in differential diagnosis * *PATIENT FROM COLORADO/ARIZONA/NEW MEXICO **TEST** 2. Yersinia pestis is Identified as a potential bioterrorism agent CATEGORY A *TEST*

Question 38

1. What is the best way to diagnose the plague? | 2. What are typical lab findings?

Answer 38

1. Bacteriologic Dx. can be made with a smear and culture of a bubo aspirate, blood, or sputum sample. Must notify lab of possible Y. pestis! 2. Laboratory Findings -WBC count of 10,000 to 20,000 cells/mm3 -Platelet counts may be normal or low with DIC (disseminated intravascular coagulation- platelets are being consumed so # might fall)

Question 39

1. What is the best treatment for yersinia pestis? 2. Can you use penicillin? 3. Should you do susceptibility testing? 4. How can you avoid the plague? 5. Chemoprophylaxis with what abx? 6. Is a vaccine available?

Answer 39

1. Streptomycin: alternatives include gentamicin, chloramphenicol, and tetracyclines. 2. Penicillin's and cephalosporin's are not effective in treating plague 3. Susceptibility testing is not recommended 4. Avoid contact with dead rodents and rat and flea control measures should be taken to avoid plague 5. Chemoprophylaxis with tetracycline 6. Vaccine available for high risk patients

Question 40

A 6 Y.O. boy arrives with his mother in ER complaining of pain in right arm where a cat had bit him the previous day. PASTEURELLA- main organism seen from cats. The next morning the boy awoke crying and complaining of pain in his hand. Temp 39 C. Skin over the wound is erythematous. Material from the wound is submitted for culture and Gram stain. The laboratory reports growth of gram-negative coccobacilli. The organisms were faculatatively anaerobic but failed to grow on MacConkey agar. Which organisms is most likely responsible for this infection? A) Capnocytophaga (human bites) B) Eikenella (human bites) C) Escherichia (gram negative facultative anaerobe) D) Fusobacterium (gram neg. facultative anaerobe) E) Pasteurella

Answer 40

Pasteurella

Question 41

Which arthropod is the most important vector of tuleremia? a) House fly b) Flea c) Lice d) Tsetse fly e) Tick

Answer 41

Tick- primarily from infected rabbits

Question 42

``` During a military conflict in Somalia, several soldiers develop a febrile illness characterized by abrupt onset of fever with rigors, severe headaches, myalgias, arthralgias, lethargy, photophobia, and coughing. Conjunctival suffusion and a petechial rash develop 4 days into the illness and then fade after 1 to 2 days at the time symptoms wane. Splenomegally and hepatomegaly are also observed. After 1 week, the symptoms recur. Blood cultures are collected during febrile phase and are positive after extended (7 days) incubation with small, faint staining gram-negative coccobacill. What is the likely etiologic agent for this disease? A) Brucella melitensis B) Escherichia coli C) Francisella tularensis D) Haemophilus influenzae E) Pasteurella multocida ```

Answer 42

Brucella melitensis *** UNDULATING FEVER*** -says that the illness fades & then comes back!

Question 43

Amino glycosides can be used to treat all but which? 1. Tularemia 2. Brucella 3. Pasterella 4. Yersinia Pestis

Answer 43

ALL except PASTEURELLA --> penicillin!