ZOONOSES

I. Encounter - What all of these diseases have in common is the animal reservoir. Humans are usually an accidental, dead end host. There are a couple of exceptions, and one related disease (typhus) has only a human host with an arthropod vector. Most are not transmissible between humans. With the exceptions of Lyme disease, Rocky Mountain Spotted Fever and Ehrlichiosis, these are extremely rare in the United States

II. Entry - Many are through the bite of an arthropod vector, some from an animal bite; some from inhalation of contaminated materials or animal droppings, some from ingestion of food.

III.Spread - All of these infections spread beyond the initial site of inoculation and become systemic to varying degrees.

IV. Multiplication - many are fastidious and require special media, the rickettsia require tissue culture.

V.Evade defenses - Since most of these infections spread, phagocytes and complement must be dealt with. Most are intracellular pathogens, and many are intracellular pathogens of phagocytes

VI. Damage - inflammation, intracellular cytotoxicity, few have overt exotoxins.

VII.Spread to new hosts - see. I. - humans are usually a dead-end host.

Borrelia bergdorferi A. gram-negative spirochete B. Disease - Lyme disease (Lyme borreliosis) - thousands of cases per year C. Diagnosis - clinical presentation and serology D. Encounter/entry - deer tick bite; nymphal stage (very small) more likely than adult; mice are immediate reservoir, but deer are essential for tick life cycle E. spread - yes - through skin and body

F. Damage - 1. Stage one: 3 - 30 days after bite - Bull's eye rash - erythema chronicum migrans, painless; flu-like symptoms - fever, chills, myalgia, fatigue, headache; secondary skin lesions possible; arthralgia; endothelial infection

2. Stage 2: weeks to months later - cardiac and neurologic involvement

3. Latent stage

4. Third stage - arthritis of large joints; also chronic progressive neurological disease; immune response to persistent bacterial antigens?5. Autoimmunity ?

G. Spread to new human hosts – no

H. Vaccine - a new vaccine has just been licensed by the FDA

LEPTOSPIRA. 1. Microbiology: spirochete, detected by dark field 2. Disease: biphasic illness:

a. First phase: bacteremic; 1 week i. Nonspecific: abrupt fever, headache, conjunctival suffusion, GI complaints, myalgia, rash ii. bloodstream organs (liver, kidney) jaundice, hemorrhage, renal failure iii. Resolution of fever - humoral response (immune phase).

b. Second phase: immune phase occurs ~2 days after the first phase; 1-4 weeks; aseptic meningitis, conjunctivitis, diffuse lymphadenopathy, hepatosplenomegaly.c. Weil’s syndrome (icteric leptospirosis): after first phase; triad: hemorrhage, jaundice/hepatitis, renal failure. Creatinine phosphokinas (CPK) extremely high due to myositis.

3. Diagnosis: a. Culture CSF, blood, urine – low yield b. Dark field microscopy – (+) only during early infection. c. Serology: ELISA

4. Encounter/entry: a. Ingestion or contact with contaminated urine from infected

domestic animals (dogs, sheep, cattle, goat, sheep) or rats. b. Broken skin and mucous membrane. c. Occupational hazard for farmers, veterinarians, hunters.

5. Spread to human host: No

6. Damage: a. Toxin - displaces long-chain fatty acids from host

endothelial cells -> breakdown of blood vessel wall spirochete dissemination.

b. Thermolabile hemolysin.

RICKETTSIACEAE.A. General characteristics:

1. Gram-negative coccobacilli (Giemsa stain best) 2. 4 genera in this class:

a. Rickettsiab. Bartonella c. Coxiella (does NOT cause skin rash)d. Ehrlichia

3. Unique characteristics:a. All transmitted by arthropods except:

i. Bartonella – direct contact ii. Coxiella – aerosol inhalation

b. Obligate intracellular parasite of i. Endothelial cells: Rickettsia ii. Leukocytes: other genera.

4. All are susceptible to doxycycline or tetracycline.

Rickettsia rickettsii.a. Disease - Rocky Mountain spotted fever (mainly in eastern

US), only about 100 cases per year in U.S.

b. Clinical manifestation i. Acute onset of fever, headache, myalgia, abdominal pain

(mimicking cholecystitis) ii. Rash (macular, petechial) begins on palms and soles,

ankles/wrists and spread to truck. iii. Aseptic meningitis, conjunctivitis, ARDS.

c. Diagnosis – i. Clinical diagnosis by typical rash ii. Immunofluorescent stain of skin/tissue biopsy. iii. serological test iv. (old Weil-Felix test - detect cross-reactive antibodies to

Proteus vulgaris).

d. Encounter/entry - wood tick and dog tick from dogs or rodents; tick is both vector and reservoir

e. Spread - yes - through body causing vasculitis; use actin polymerization like Listeria and Shigella

f. Multiplication - requires tissue culture; no developmental stages, but escapes vacuole to live within cytoplasm

g. Evades defenses - intracellular

h. Damage - 2 - 6 day incubation period; infection of vascular endothelium resulting is rash, hemorrhage, thrombosis, and edema (macules progressing to petechial lesions); rash spreads from hands and feet to trunk (presence of rash on palms and soles - unique characteristic); can be fatal if untreated

i. Spread to humans - no

Other Rickettsia: (do not need to memorize; just recognize the name)

Rickettsia sp. Vector Disease

R. prowazekii Louse Louse-borne typhus (epidemic typhus)- rash: trunk spreading to extremites; spares palms and soles

R. typhi Flea Endemic (murine) typhus- less severe than epidemic typhus

R. tsutsugamushi Mite Scrub typhus-similar clinically to epidemic typhus

Ehrlichia chaffeensis – - transmitted by tick

- asymptomatic to fatal

- Classic presentation: fever, headache, myalgia.

- Important lab test: thrombocyopenia, leukopenia. <50% develop rash.

- Infects white blood cells.

Bartonella henselae

1. cat scratch disease - benign local lymphadenopathy

2. bacillary angiomatosis (AIDS)- proliferative vascular lesions in

dermis and internal organs (stimulation of vascular endothelial growth via cytokine production)

Bacillus anthracisA. Gram-positive rod, aerobic spore former

B. Disease - anthrax: cutaneous, inhalation, ingestion - (usually only a few cases of cutaneous in U.S. each year)

C. Diagnosis - epidemiology, culture, chest X-ray for inhalation

D. Encounter - exposure to animal products contaminated with stable sporesE. Entry - breaks in skin and lungsF. Spread - yes throughout blood with inhalation, possible with cutaneous

G. Evasion of defenses - poly-glutamate capsule (exception to carbohydrate rule) – antiphagocytic

H. Multiplication - spores germinate in macrophages, then cells replicate extracellularly

I. Damage - potent exotoxins (PA, EF, LF) - cytotoxic 1. cutaneous - entry at skin: papule progressing to vesicle, ulcer, ultimately an eschar (black lesion) and edema - called a "malignant pustule"; rarely fatal 2. lung: (Wool sorter's disease) flu-like illness progressing rapidly to respiratory distress, cyanosis, edema of neck and chest, shock, fatal if untreated

J. Spread to humans - No

Brucella abortus. A. Gram negative rod, coccobacilliB. Disease - Brucellosis (undulate fever, Malta fever) - very rare (couple of 100 cases in U.S.); fever, back or limb pain; splenomegaly; long course (months)C. Diagnosis - culture or serologyD. Encounter - occupational exposure to infected animals (ranchers, slaughterhouse, veterinarians), contaminated milk; no arthropod vectorE. Entry - inhalation, ingestion, cuts in skinF. Multiplication, evade defenses - lives within macrophages in reticuloendothelial system (spleen, liver, lymph nodes, bone marrow), avoid killing by PMNs; likes erythritol

“Eh, what’s up Doc?”

Yersinia pestisA. Gram-negative rod (bipolar staining on Gram-stain)

B. Disease - Bubonic or pneumonic plague1. bubonic - swollen, painful lymph nodes, fever,

septic shock in later stages2. pneumonic - flu-like illness progressing to mucoid,

bloody sputum; dyspnea, cyanosis; rapidly fatal

C. Diagnosis - culture, stain of tissue/sputum, or serology

D. Encounter1. urban cycle (none in U.S.) - fleas from rats

(bubonic), human-human (pneumonic)- with pneumonic plague - a human with pneumonic

disease can spread the organisms via respiratory droplet - highly communicable (requires isolation)

2. sylvatic cycle - fleas from prairie dogs, deer mice, or rats; less than 50 cases per year in western U.S.

E. Entry - bite on skin (sylvatic) or lungs (pneumonic)

F. Spread - yes - to draining lymph nodes causing buboes (swollen, painful), through blood throughout body (lungs can become infected by septic emboli to for pneumonic plague)

G. Evade defenses, multiplication - grows within macrophages

H. Damage - endotoxin shock-like symptoms due to infection throughout the body (high fever, myalgia), bubonic usually fatal if untreated; pneumonic 100% fatal if untreated

I. Spread to new human hosts - yes in pneumonic plague

“Eh, what’s up Doc?”

Francisella tularensisA. Gram-negative rodB. Disease - Tularemia (Rabbit Fever) after ingestion - influenza-like to typhoid fever-like syndrome with fever; ulceroglandular form - ulcer at inoculation, adenopathy at regional nodes; other localized sites possibleC. Diagnosis - usually NOT cultured to prevent lab infections; serology usually doneD. Encounter and entry - many different wild animals - rabbits deer, rodents; usually through arthropod vector but also by direct contact with animal (e.g. skinning a rabbit), inhalation (very low i.d.) or eatingE. Spread - yes, from the site of inoculation into the regional lymph nodesF. Evasion of defenses/multiplication - multiplication in macrophages

“Lawnmower” Tularemia

The term “lawmower tularemia” was first used about a decade ago to describe two cases of pneumonic tularemia in adolescent males who ran over a dead rabbit while mowing a grassy area. Neither youth touched the remains of the animal, suggesting an aerosol of bacteria was sufficient to cause infection. Both individuals were hospitalized, treated with streptomycin, and recovered.

Hence, in endemic areas, use of protective clothing and face masks may be warranted.

(A.S.M. News)