Collection of zoonotic diseases

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, endemic 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.

• 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)
  • Virulence factors of C. burnetii
    • C. burnetii escapes macrophage phagocytosis by:
      • Producing superoxide dismutase to inactive phagolysosomal enzymes
      • Inhibiting cathepsin fusion
  • C. burnetii infection induces a range of immune responses, ranging from autoantibody production to immunosuppression
  • One of two syndromes develop depending on the host's immune response:
    • Acute Q fever: few C. burnetii organisms and stronger cell response to the pathogen
    • Chronic Q fever: multiple C. burnetii organisms and weaker cell response; C. burnetii survives in monocytes and macrophages

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.
	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]}

• 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]

Endemic typhus (also known as murine typhus)

• Definition: An exanthematous typhus fever caused by Rickettsia typhi
• Etiology: Rickettsia typhi
• Transmission: : via vector: rat and cat fleas
• Epidemiology: occurs worldwide, mainly warm coastal regions, southern US
• Clinical features
  • Incubation period: 8–16 days
  • Fever, severe headache, malaise
  • Maculopapular or petechial rash; erupts on the trunk → spreads to extremities
  • No eschar (scab at site of flea bite)
  • Brill-Zinser disease: exacerbated recurrence many years after the primary episode
• Diagnosis
  • Serology (four-fold rise in antibodies)
  • Positive Weil-Felix reaction
• Treatment: doxycycline, chloramphenicol

Scrub typhus

• Definition: An exanthematous typhus fever caused by Orientia tsutsugamushi. Not to be confused with epidemic typhus, which is caused by Rickettsia prowazekii.
• Etiology: Orientia tsutsugamushi
• Transmission: via vector: Trombicula mites larvae (chiggers) from rodents
• Epidemiology: occurs mainly in central, eastern, and southeast Asia; northern Australia, South Pacific
• Clinical features
  • Incubation period: 7–10 days
  • Fever, severe headache, myalgias, arthralgia, cough
  • Maculopapular rash
  • Eschar at site of mite attachment
  • Lymphadenopathy
  • Relative bradycardia despite fever
• Diagnosis
  • Serology (four-fold rise in antibodies)
  • Positive Weil-Felix reaction
• Treatment: doxycycline, chloramphenicol

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

• 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]

• 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]

• 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]