Summary

Zoonotic diseases are infections that are transmitted from animals to humans. While animals may transmit infection directly, they usually serve as hosts for a pathogen that is then transmitted to humans by a vector (e.g., ticks, fleas). Zoonoses are usually endemic to certain geographical regions, and peaks in incidence often correlate with the life cycle of the transmitting vector. Common diseases include Q fever, Rocky mountain spotted fever, epidemic typhus, ehrlichiosis, and babesiosis. Although these conditions differ in their exact presentation, symptomatic cases typically present with fever, flulike symptoms, and possibly skin rashes. In some cases of fulminant disease, there may be complications such as disseminated intravascular coagulation, shock, and organ failure. Most zoonoses are treated with antibiotics and respond well to treatment.

Q fever

Definition: notifiable zoonotic disease with cattle, sheep, and goats as the primary reservoir
Pathogen: Coxiella burnetii (gram-negative, intracellular)
Epidemiology
- Worldwide occurrence
- 160–170 cases of acute Q fever per year in the US
- 70% of cases occur in men
- Peak incidence from April to June
Route of transmission
- Inhalation of aerosols from the secretions of infected livestock or animals about to give birth
- Ingestion of raw milk produced by infected animals
Risk groups: slaughterhouse workers, farmers, shepherds, veterinarians
Pathophysiology: development of antigens
- Phase I antigens: seen when C. burnetii is highly infectious
- Phase II antigens: seen when C. burnetii is less infectious
  - Antigenic shift essential to differentiating acute Q fever from the chronic variant (see below)
- C. burnetii infection induces a range of immune responses, ranging from autoantibody production to immunosuppression

Type of Q fever		Acute Q fever	Chronic Q fever
Incubation period		2–6 weeks	Months to years
Clinical features		∼ 50% of cases are asymptomatic. Sudden onset of flulike symptoms, which last for 1–2 weeks High-grade fever, chills, malaise, myalgia Headache/retro-orbital pain, photophobia Rhinitis, pharyngitis, laryngitis Nausea, vomiting, diarrhea Atypical pneumonia: generally mild with nonproductive cough and fever Hepatitis, possibly hepatomegaly without jaundice Rare manifestations: meningoencephalitis, acute endocarditis associated with antiphospholipid syndrome and immunosuppression Post-Q fever fatigue syndrome: fatigue, headache, night sweats, arthralgia, myalgia, blurred vision, fasciculations, painful lymphadenopathy Pregnancy: ↑ risk of spontaneous abortion, intrauterine growth retardation, intrauterine fetal death, and premature delivery	Only develops in 1–5% of individuals Low-grade fever Culture-negative endocarditis Culture-negative osteomyelitis
Diagnostics	Serology via IFA (best initial test)	Anti-phase II antibody IgG titers ≥ 200 and IgM titers ≥ 50 In cases of negative IFA but high clinical suspicion, perform PCR on serum or tissue samples before administering antibiotics. IgM antibody titers to phase II antigens much higher than titers to phase I antigens	Anti-phase I antibody IgG titers > 800 or persistently high levels of anti-phase I antibody 6 months after completing therapy Antibodies with titers to phase I antigens are much higher than the titers to phase II antigens.
Diagnostics	Additional findings	↑ Liver enzymes , leukocytosis, thrombocytopenia Chest x-ray: round opacities in patients with atypical pneumonia
Treatment		First-line: doxycycline for 2 weeks Second-line: macrolides (e.g., azithromycin) Among pregnant women or children < 8 years with mild disease: trimethoprim-sulfamethoxazole	First-line: doxycycline and hydroxychloroquine for ≥ 18 months Second-line: rifampin and doxycycline/ciprofloxacin Valve repair may be required in the case of endocarditis.
Prevention		Avoid consuming unpasteurized milk products

References:^[1]^[2]^[3]^[4]^[5]

Rocky Mountain spotted fever (RMSF)

Pathogen: Rickettsia rickettsii; (aerobic, gram-negative, obligate intracellular bacteria )
Epidemiology: Rocky mountains, southeastern, and south central US
Reservoir: dogs, rodents, ticks
Route of transmission: bite of Dermacentor variabilis (dog tick)

Pathophysiology

Infection of endothelial cells is a classic feature of all rickettsial diseases → vasculitis and subsequent endothelial dysfunction → SIRS → shock, peripheral and/or pulmonary edema, DIC, renal failure

Clinical features (incubation period ∼ 7 days, or 2–12 days)
- Fever, headache, myalgia, malaise, conjunctivitis, nausea, and abdominal pain
- Blanching macular rash; (90% of cases): begins on wrists and ankles → spreads to trunk, palms, and soles → becomes petechial and/or hemorrhagic in 50% of cases
- Hepatomegaly, splenomegaly
- Noncardiogenic pulmonary edema with ARDS
Diagnosis: empiric diagnosis based on clinical and epidemiological features
Treatment: doxycycline

References:^[6]^[7]^[8]^[9]

Typhus

	Epidemic typhus	Endemic typhus	Scrub typhus
Pathogen	Rickettsia prowazekii	Rickettsia typhi	Orientia tsutsugamushi
Reservoir	Humans, flying squirrels	Rats, mice, cats	Rodents
Vector	Human body lice (feces)	Rat and cat fleas , flea feces	Trombicula mites larvae (chiggers)
Geographical distribution	Worldwide (esp. the Andes, Africa, Southeast Asia)	Worldwide, warm coastal regions, southern US	Central, eastern, and southeast Asia; northern Australia, South Pacific
Incubation period	7–14 days	8–16 days	7–10 days
Clinical findings	Fever, severe headache, malaise Maculopapular or petechial rash erupts on the trunk → spreads to extremities No eschar (scab at site of flea bite) Relative bradycardia despite fever Brill-Zinser disease: exacerbated reccurence many years after the primary episode		Fever, severe headache, myalgias, arthralgia, cough Maculopapular rash Eschar at site of mite attachment Lymphadenopathy Relative bradycardia
Diagnostics	Serology (four-fold rise in antibodies) Positive Weil-Felix reaction
Treatment	Doxycycline, chloramphenicol

References:^[1]^[10]^[11]

Ehrlichiosis

Pathogen: Ehrlichia; chaffeensis, Ehrlichia ewingii (intracellular, gram-negative bacteria)
Epidemiology: southeastern and south central US, mid-Atlantic States
Reservoir: white tail deer
Route of transmission: bite of the lone star tick; (Amblyomma americanum) → infection of monocytes and macrophages
Clinical infection (incubation period of 1–2 weeks)
- Fever, headaches, malaise, myalgias
- Similar to RMSF, but usually without a rash (“spotless” RMSF)
- Possibly neurologic symptoms (altered mental status, stiff neck, clonus)
- May cause renal failure and GI bleeding
Diagnosis
- Leukopenia, thrombocytopenia
- Wright-Giemsa stain of blood smear: detection of morulae inside the infected monocytes
- Serology via IFA: IgG Ehrlichia titer
Treatment: PO doxycycline or tetracycline

References:^[12]

Babesiosis

Pathogen: Babesia species, especially Babesia microti (protozoan parasites)
Epidemiology
- Worldwide occurrence; endemic in the Northeast, Northwest, and upper Midwest of the US
- Seasonal distribution: most cases in July and August when tick populations reach their peak
Route of transmission
- Natural reservoir: wild animals (especially rodents), cattle
- Transmission to humans via tick bites: Ixodes scapularis (black-legged deer tick)
Clinical features (incubation period of 1–6 weeks)
- Most cases asymptomatic or mild, but may be severe or even fatal
- Flulike symptoms (fever, malaise, myalgia, headache)
- Hemolytic anemia with dark urine and icterus
- Mild splenomegaly and hepatomegaly
- Severe infection may lead to DIC, ARDS, congestive heart failure, splenic rupture, and death.
- Clinical features similar to malaria infections
Diagnostics
- Laboratory findings: signs of hemolytic anemia; , thrombocytopenia; , normal WBC or mild leukopenia; , ↑ transaminases, and alkaline phosphatase
- Confirmatory test: Giemsa stain reveals thin blood smear intraerythrocyte rings with a maltese cross.
- PCR, serology
- Coinfection with other tick-borne pathogens (e.g., Borrelia, A. phagocytophilum) should be considered
Treatment
- Atovaquone and azithromycin for mild disease
- Quinine and clindamycin for severe infections

References:^[13]^[14]^[15]

Plague

Pathogen: Yersinia pestis
Epidemiology: western US (as scattered cases in rural areas)
Reservoir: prairie dogs, squirrels, rodents
Route of transmission: flea bites
Clinical features
- Bubonic plague (most common): sudden onset of fever, headache, myalgias, chills, and painful swollen lymph nodes (buboes) → may progress to sepsis, pneumonia, and meningitis
- Septicemic plague: signs and symptoms of sepsis, abdominal pain, possible shock, DIC
- Pneumonic plague : rapidly progressing pneumonia with possible respiratory failure and shock
Diagnostics: : cultures with Wayson stain taken from buboes, blood, or sputum → shows bipolar staining of bacteria (appearance of “closed safety pin”)
Treatment
- Do not delay treatment for diagnosis!
- Isolation with droplet precautions until pneumonic plague is ruled out
- First-line: IV gentamicin or fluoroquinolones for 10–14 days
- Second-line: doxycycline, tetracycline

References:^[16]^[17]

Previously important diseases

Smallpox is a highly contagious disease caused by the virus Variola major or Variola minor. The last natural case occurred in the seventies. Since that time, the disease has officially been eradicated by smallpox vaccine programs.