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Explain the concept of “One Health.”

Relationship between animal and human health and disease

Positives of animal interactions:
o Psychological well-being, companionship
o Food, nutrition
o Warmth and protection
o Power and transportation
o Fertilizer

Potential threats:
o Environmental hazards
o Traumatic injuries
o Infectious diseases


Define the term zoonosis and explain the role of animals in human disease.

1) Classic: disease caused by infectious agents that are transmitted from animals to humans
2) Broader: disease caused by infectious agents that are transmitted from animals to humans OR are shared by animals and humans

The role of animals in zoonotic diseases:
Animals = direct source of infection
• Ex: bite wounds, rabies, plague, tularemia, bartonellosis, brucellosis
Animals = indirect source for contamination of food or water supplies
• Ex: salmonellosis, campylobacteriosis, yersiniosis, leptorspirosis
Animals and humans share the infection
• Ex: Lyme disease, blastomycosis, West Nile fever, equine encephalitis, leishmaniasis, Chagas disease


Bartonellosis: characteristics

Bartonella henselae (Rochalimaea henselae)
o 2 different genotypes (genotype II may be more pathogenic for humans)

Gram Stain:
o Curved
o Gram negative rods

o Slow-growing, motile
o Oxidase and catalase-negative
o Grow best at 35°C with CO2
o Grow on chocolate-, rabbit-heart-, or Columbia-blood agar

Other Bartonella species pathogenic for humans:
o B. clarridgeiae, koehlerae, vinsonii, washoensis, elizabethae, alsatica, rochalimae and tribocorum


Bartonellosis: clinical disease

Papules or pustules at site of scratch/bite
o 4-6 days after wound
o Persistent, non-healing wound

Regional lymphadenopathy (7-50 days after)
o >90% of patients
o Histology: necrotizing, granulomatous inflammation, micro-abscess formation
On biopsy:
• 26% nodes = evidence of neoplasia
• 4% = evidence of Mycobacterium infections

Fever (<29%)

Chronic systemic manifestations:
o Endocarditis
o Osteomyelitis
o Uveitis and other eye manisfestations
o Prolonged bacteremia and fever
o Breast abscesses

CNS diseases:
• Includes: cerebral arteritis, stroke, encephalitis, seizures, coma; myelitis
• Evidence of headaches and/or neurologic disease with or without cognitive dysfunction in patients with cat or biting insect contacts
• Association with Bartonella seropositivity or bacteremia being referred to neurologists/rheumatologists
• Neurologic symptoms, myalgia, arthropathy
• May contribute to neurocognitive decline in AIDS (AIDS dementia)


Bartonellosis: risk factors

Children < 10 years = highest prevalence of CSD (57-80% cases)
More likely to develop complications:
• Persistent fevers and fevers of unknown origin
• Parinaud’s oculoglandular syndrome: Ocular granuloma or conjunctivitis, Preauricular lymphadenopathy
• Spread to abdominal lymph nodes, liver/spleen (7%), bones
• Encephalitis (12%): 1-6 weeks after onset of lymphadenopathy; Seizure or coma may occur

Immunocompromised patients
1) Bacillary angiomatosis:
• Bartonella stimulates vEFG and angiogenesis
• Lobular proliferation of small blood vessels and inflammatory infiltrates
2) Peliosis hepatitis:
• Blood-filled cystic lesions develop in liver (sometimes spleen)
• Associated with: hepatomegaly, abdominal pain, nausea
3) Hepatitis and splenitis
• Granulomatous
• Necrotizing
• Can progress to spontaneous rupture and hemoperitoneum (bleeding into peritoneum)


Bartonellosis: vectors

Widespread infection in cats
• 15-30% seropositive (especially in southeastern U.S.)
• Maintain prolonged (up to 22 months) bacteremia
Often asymptomatic
o In 90% human CSD cases = cat contact
• 75% = scratch or bite
• Greater risk = kittens (more likely to cause scratches)
Other animal vectors also possible


Bartonellosis: diagnosis

Clinical presentation + history of animal contact + lab measure:

Serologically: IFA, ELISA assays
• Single high IgG titer
• 4x rise in IgG titers
• Positive IgM titer

• Confirmation and exclusion of other potential causes of lymphadenitis
• Skin lesion punch biopsies

PCR for bacteremia


Bartonellosis: treatment

Adenopathy resolves in 2-6 months
Antibiotics = prevent other complications from occurring (but do not alter course of disease significantly)
• Azithromycin for CSD
• Doxycycline or erythromycin for 8-12 weeks for bacillary angiomatosis
Aspirate nodes if fluctuant (rarely)


Bartonellosis: prevention

o Avoid rough play with cats
o Wash scratches/bites well (bacteria present in saliva)
o Flea control
o Antibiotic therapy in cats = unlikely to immediately eliminate organism and reduce risk of transmission
o Negative serologic test in cat = highly predictive that cat is NOT bacteremic
• Immune-compromised patients should adopt only seronegative adult cats


Plague: causative organism and characteristics

Yersinia pestis
o Gram-negative bipolar rod

o Aerobic growth on most media (including blood agar and MacConkey’s)
• Forms small colonies on MacConkey’s
o Oxidase-negative, catalase-positive
o Does NOT ferment lactose
o Does NOT utilize citrate, urease or indole
o Non-motile
o Grows better at 28°C than at higher temperatures
o Triple-sugar-iron (TSI) slants = produces alkaline slant and acid butt


Plague: modes of transmission/reservoir

Cause of Black Death in Middle Ages

o Currently: Asia, Africa, Andean countries of South America
o In U.S: Western states: New Mexico, Arizona, Colorado, Texas, California, Nevada

o Primarily rodents (rats)
o Seasonal summer pattern in temperate regions

Transmission via:
Fleas from infected rodent
• Blood meal in foregut clots
• Y. pestis expresses phospholipase enzyme = able to survive in flea midgut → replicates
• Blockage of gut → regurgitation of organisms at next feeding
Ingestion of infected rodents (Ex: cats)
• Also = ingestion of guinea pigs by humans in Andes
Direct contact with blood, pus, aerosols

At risk:
o Veternarians = handling infected cats


Plague: clinical forms

Bubonic plague
o Most common (81% cases)
o 2-8 day incubation
o High fever, headache, malaise
o Warm, painful, swollen lymph nodes (“buboes”)
• Hemorrhagic necrosis on histology
o May be tachycardic and hypotensive
Meningitis if not treated:
• Fever, headache, meningismus
• PMN pleocytosis in CSF

Septicemic plague
o Hematogenous spread throughout body
• Y. pestis replicates within mononuclear leukocytes
o Shock, DIC and death within 2 days
o 30% mortality if untreated

Pneumonic plague
o Lung infection after inhaling organism or hematogenous spread
o Cough (often with hemoptysis) and chest pain
o Bronchopneumonia and lung consolidation
o 100% fatal if untreated
o Potential as a bioterrorism agent


Plague: diagnosis

Gram statin of an aspirate or bacterial culture
• Bipolar rod (NOT a diplococcus)
• Use Wayson’s or Wright’s stain = accentuates bipolar look
• Fluorescent Ab staining can confirm


Plague: treatment

Aminoglycosides: DOC is streptomycin
• Alternative = gentamicin
Also effective: tetracyclines, fluoroquinolones, chloramphenicol
• Recommended for meningitis, pleuritis, endophthalmitis, myocarditis cases
Levofloxacin recently approved

NOTE: penicillins (beta-lactams) NOT effective
Aspirate buboes if fluctuant


Plague: prevention

Formalin-inactivated vaccine available
• Travelers to endemic areas
• People in high risk occupations
Cat vaccination developed but not commercially available

o Insecticides
o Rodent control
o Personal protective devices


Tularemia: causative agent and characteristics

Francisella tularensis
• Gram negative bipolar rod

Type A (F. tularensis tularensis):
o Restricted to North America (in southeast and Martha’s Vineyard)
o Rabbits (“Rabbit fever”) and tick transmission
• Can pass transovarially in ticks (maintains organism population in nature)

Type B (F. tularensis holoartica):
o Wider range of animals: rabbits, squirrels, muskrats, beavers, etc.; also reptiles and birds


Tularemia: transmission/location/at risk

Located: northern hemisphere

At risk:
o Veterinarians handling infected animals
o Zoonotic risk to hunters
o Laboratory workers

o People eating undercooked game meats (need 108 organisms)
o Inhalation of organism (only need 10-100 organisms)
o Waterborne infection: Can survive weeks to months in water and mud; May use amoebae as host


Tularemia: clinical forms

Prodrome: fever/chills, headache, malaise after 3-5 day incubation

After skin (tick bite) contact = Ulceroglandular form
o 21-87% cases
o Ulcerative skin lesions
o Regional lymphadenopathy

After conjunctival contamination = Oculoglandular form
o <12%)
• Severe pharyngitis and lymphadenopathy
Systemic typhoidal (5-30%)
• Multi-organ dysfunction
• GI signs: loose, watery, non-bloody diarrhea, vomiting, abdominal pain
Pneumonic form (7-20%)
• Cough, chest pain
• Potential use in bioterrorism


Tularemia: diagnosis

Clinical suspicion!
• Rarely seen on smears
• Requires specialized culture and detection methods

• Agglutination, ELISA


Tularemia: treatment

• DOC: streptomycin (alternative = gentamycin)
Others: Ciprofloxacin, doxyclycine


Tularemia: prevention

o Live attenuated vaccine for high risk people (ex: lab workers)
o Insecticides/tick repellents
o Personal protective devices
o Thorough cooking of game meats


Leptospirosis: Causative agent and characteristics

Leptospira interrogans (kirschneri) spirochete
o 250+ serovars
o Spirochete with bent or hooked ends

• Needs specialized media: Fletcher’s EMJH, Tween 80-albumin
• Needs 5-6 weeks at 28-30°C in the dark

Does NOT replicate outside human host


Leptospirosis: reservoir and transmission

Animal reservoirs
o Persistent infection in renal tubules → prolonged excretion in urine
o Water contamination
o Host-adapted strains (not cause disease in animals)

Globally = rats
o Outbreaks associated with tropics, heavy rainfall due to increase in rodent population
U.S. = dogs > livestock (cattle, pigs) > rodents > wild animals

o Direct contact with infected animals (especially their urine)
o Indirect exposure (ex: via contaminated water)


Leptospirosis: those at risk

• Vets, farmers slaughterhouse workers
• Sewer workers, military members, zoo keepers, rice and sugar cane plantation employees


Leptospirosis: clinical disease

“Rice-field fever,” “can-cutters fever,” “swine herder’s disease”
Incubation ~7-12 days
Biphasic fever

Anicteric leptospirosis (85-90%)
Flu-like illness
• Headache, myalgia, malaise
• Abdominal pain, nausea, diarrhea
• Petechiae (vasculitis)
• Conjunctival hemorrhage
Potential sequalae = immune-mediated, aseptic meningitis

Weil disease
o Associated with L. icterohaemorrhagiae
o Flu-like illness
o Liver dysfunction → jaundice
o Renal insufficiency (from renal tubular damage)
o More extensive hemorrhages
o Recovery can take months

Mystery disease
o Severe pulmonary hemorrhage syndrome (SPHS)
Outbreak in Nicaragua in 1995; other cases in Asia, Argentina, Brazil
• Following flooding
• Rats and dogs with titer >400
Unique feature = pulmonary hemorrhage
Associated with specific strains: Copenhageni, icterohemorrhagic


Leptospirosis: diagnosis

• Micro-agglutination test confirmatory
• Note: antibiotic therapy may suppress/delay seroconversion
• Positive by 10 days post infection

• In first 10-14 days = blood, CSF
• After 14 days = urine

Dark-field microscopy
• Only good if see organisms
• Negative results do not rule out diagnosis


Leptospirosis: treatment

o Doxycycline
o Ampicillin, amoxicillin
o For severe disease = IV penicillin G
o Note: cephalosporins generally NOT effective

Potential adverse effect = Jarisch-Herxheimer reaction
• Type III immune complex-mediated hypersensitivity
• Due to release of proteins from death of bacteria
• Results in sepsis


Leptospirosis: prevention

o Vaccinating animals does NOT prevent infection and shedding of organisms, but DOES prevent clinical disease in animal
o Avoid stagnant water
o Avoid mucosal or abraded skin contact with animal urine
o Post-exposure and preventative doxycycline (200 mg/week)


Brucellosis: Causative bacteria and Gram stain reaction

• Brucella spp. = each animal vector as typical type
o B. abortus in cattle (Latin America)
o B. melitensis in goats (Mediterranean/Middle East)
o B. suis in pigs
o B. canis in dogs

Small Gram negative coccobacillus
Facultative intracellular pathogen
o Survives and replicated in leukocytes
o Virulence from LPS


Brucellosis: transmission and reservoir

• Direct exposure = Contact with animal reproductive tissues/fluids
• Foodborne disease (pre-pasteurization)
• Aerosolization
• Self-vaccination risk for vets


Brucellosis: those at risk

• Occupational contact with domestic animals
• Consumption of unpasteurized milk and cheese
o Hispanic soft cheeses = queso fresco


Brucellosis: clinical disease

• “Undulant,” “Malta,” or “Mediterranean Fever”
• Incubation generally 1-2 months

o Undulating fever
o Night sweats (malodorous)
o Profound weakness
o Arthralgia and myalgia
o Headaches
o Men: epididymitis, orchitis
o Women: spontaneous abortion
o Long term sequelae: Sacroiliitis, hepatitis, colitis, encephalitis, psychoses
o Endocarditis (with B. melitensis → mortality)

Often lasts for months = very debilitating
Low case fatality rate


Brucellosis: diagnosis

o Culture and serology


Brucellosis: treatment

o Doxycycline (children = use TMP-sulfa) + rifampin for 6 weeks


Brucellosis: prevention

o Current RB51 vaccine for cattle can cause disease in humans
o Accidental self-injection can occur
o Prophylaxis with 3 weeks of doxycycline
o Note: older Strain 19 vaccine caused more significant disease so needed more doxycycline + rifampin