Rosen & Barkin's 5-Minute Emergency Medicine Consult (89 page)

• Tick-borne, infectious disease caused by intraerythrocytic protozoa of the genus
  Babesia
  , infects wide array of vertebrate animals, causes lysis of host RBCs
  
• Asymptomatic to severe, life-threatening infection depending on the species of
  Babesia
  and the immune status of the patient
  
  • Asymptomatic infection:
    
    • 50% of children and 25% of adults with infection have no symptoms
      
  • Mild–moderate disease:
    
    • Usually immune competent patients
      
    • Infections typically self-limited or resolve with antibiotic therapy
      
    • Mortality usually <5%
      
  • Severe disease:
    
    • Defined as hospitalization >2 wk, ICU stay >2 days, or ending in death
      
    • Typically associated with immune compromise: Splenectomy; cancer; HIV; hemoglobinopathy; chronic heart, lung, or liver disease
      
    • Other groups at higher risk for severe disease: Neonates, >50 yr old, on immune-suppressive drugs (e.g., rituximab or anticytokine therapy [e.g., etanercept, infliximab])
      
    • Mortality can be as high as 21% among immune-suppressed patients
      
• Complications develop in approximately one-half of the hospitalized patients:
  
  • ARDS, DIC most common
    
  • Can also see CHF, coma, liver failure, renal failure, splenic rupture
    
• Co-occurrence with other tick-borne diseases should be considered in endemic regions under the following conditions:
  
  • Lyme disease (
    Borrelia burgdorferi
    ) – associated rash
    
  • Human granulocytic anaplasmosis (
    Anaplasma phagocytophilum
    ) – protracted symptoms with leukopenia
    

• Babesia
  :
  
  • Species causing human disease:
    
    • Babesia microti
      – Northern and Midwestern US (most common cause of disease in US)
      
    • Babesia divergens
      – Europe
      
    • Babesia duncani
      – Northern US Pacific coast
      
  • Case reports of Babesiosis in Asia, Africa, Australia, and South America
    
  • Animal reservoirs:
    
    • B. microti
      – white-footed mouse, white-tailed deer
      
    • B. divergens
      – cattle, rats
      
• Transmission via
  Ixodes
  tick vector:
  
  • Most common vector for transmission of babesiosis to humans
    
  • Ixodes
    requires blood meal from a vertebrate host to pass through each stage of life cycle (larva, nymph, adult)
    
    • Most cases result from nymphal tick bites in late spring through summer, adult ticks can also transmit disease
      
• Pathogen life cycle, pathogenesis:
  
  • Protozoa pass from tick salivary glands to mammalian bloodstream where they penetrate erythrocytes, mature and divide.
    
  • Mature protozoa exit from RBC resulting in membrane damage, lysis, hemolytic anemia, and hemoglobinuria.
    
  • Damaged RBCs become less deformable, enhancing removal by spleen; however, asplenic patients less able to clear infected RBCs, leading to more severe disease.
    
  • Damaged RBCs may result in microvascular stasis with secondary ischemic organ injury to liver, spleen, heart, kidney, or brain.
    
• Transmission via transfusion of RBCs, platelets:
  
  • >150 cases since 1979, 75% of these since 2000
    
  • B. microti
    is the most common pathogen
    
  • Low-level parasitemia may not be visible on donor blood smears, yet can still transmit disease
    
  • Often results in severe cases as recipients of blood products often immune compromised or have significant comorbidities
    

Transmission can occur in utero and during delivery; youngest reported case was a 4-wk-old infant.

DIAGNOSIS

Gradual onset of malaise and fatigue, associated with fever as high as 105°F (40.6°C), 1–4 wk after tick bite, or 1–9 wk after transfusion with contaminated blood products

• Common symptoms include chills and sweats, headache, anorexia, nonproductive cough, arthralgia, and nausea
  
• Less common symptoms include vomiting, sore throat, abdominal pain, conjunctival injection, photophobia, weight loss, emotional lability, depression, and hyperesthesia
  

• Febrile, flu-like illness in patients who
  
  • live in, or traveled to an endemic area within past 2 mo (especially during spring, summer)
    
  • have had blood product transfusions within past 6 mo
    
• Shock or sepsis presentation in patients with above history, especially in presence of risk factors for severe disease (see above)
  

• Fever (most common finding)
  
• Hepatosplenomegaly
  
• Pharyngeal erythema
  
• Jaundice
  
• Retinopathy with splinter hemorrhages
  
• Retinal infarcts
  
• Rash may be seen:
  
  • Petechiae, ecchymosis
    
  • Erythema chronicum migrans (suggests concurrent Lyme disease)
    
• Severe disease:
  
  • Tachypnea
    
  • Hypoxia
    
  • Hypotension
    
  • Altered mental status
    

• Microscopy of thin blood smear with Giemsa or Wright staining to demonstrate
  Babesia
  organisms
  
• When smears are negative, polymerase chain reaction (PCR) assay can be used
  
• Indirect immunofluorescent antibody testing can be used to recognize babesial antigens when microscopy and PCR assays are negative
  

• Microscopy:
  
  • Intraerythrocytic parasites can be round, oval, or pear shaped.
    
  • Parasites in budding tetrad formation (Maltese cross) are pathognomonic for babesiosis, but not commonly seen.
    
  • Most common finding is intraerythrocytic round or oval (pyriform) rings with pale blue cytoplasm and red-staining nucleus.
    
  • Extracellular parasites may be seen with high levels of parasitemia.
    
  • Parasitemia levels are generally between 1% and 10%, but can be as high as 80%; may be <1% in early stages of disease.
    
  • Ring forms may appear similar to
    Plasmodium falciparum
    (malaria); in babesiosis there are no pigment deposits (hemozoin) that are usually seen with malaria.
    
• PCR:
  
  • Amplification of babesial 18s rRNA gene is more sensitive than microscopy
    
  • Results can be available within 24 hr
    
  • Useful in cases with low levels of parasitemia
    
• Serology:
  
  • Indirect immunofluorescent antibody testing may be useful when microscopy and PCR testing are negative.
    
  • IgM antibody usually detectable 2 wk after onset of illness
    
  • IgG titers ≥1:256 suggest active or recent infections; IgM titers ≥1:64 suggest acute infection.
    
• Nonspecific lab abnormalities that may be seen in babesiosis:
  
  • Mild-to-moderate hemolytic anemia (low hematocrit/hemoglobin, low haptoglobin, elevated reticulocyte count, elevated lactate dehydrogenase, elevated total bilirubin)
    
  • Thrombocytopenia is common
    
  • LFTs (elevated alkaline phosphatase, transaminases, lactate dehydrogenase, bilirubin)
    
  • Urinalysis (hemoglobinuria, proteinuria)
    
  • Elevated BUN, creatinine suggests renal insufficiency
    
  • Hyperkalemia may result from massive hemolysis
    

• Malaria
  
• Other tick-borne diseases:
  
  • Lyme disease
    
  • Human granulocytic anaplasmosis
    
  • Ehrlichiosis
    
  • Rocky Mountain spotted fever
    
  • Colorado tick fever
    
  • Q fever
    
  • Tularemia
    
  • Relapsing fever
    
• Typhoid fever
  
• Acute hemolytic anemia
  

TREATMENT

• Ensure a patent airway in patients with respiratory distress.
  
• Provide supplemental oxygen and ventilatory assistance as needed.
  
• If patient presents in shock, establish IV access and administer a fluid bolus of 0.9% NS 500 mL (peds: 20 mL/kg) IV.
  

• Airway management, ventilatory support for patients with acute respiratory distress
  
• IV access should be established in patients with evidence or risk factors for severe disease.
  
• IV fluids, pressor support for patients in shock
  
• Cardiac monitor: Patients with severe disease may develop cardiac ischemia, arrhythmias.
  

• Antipyretics for fever
  
• Start antibiotic therapy in symptomatic patients after confirming diagnosis on microscopy or PCR
  
• Mild–moderate disease:
  
  • Oral atovaquone + azithromycin for 7–10 days is the regimen of choice.
    
  • Clindamycin + quinine is an effective alternative, but associated with significant side effects (tinnitus, vertigo, gastroenteritis) that may require reduced dosing or stopping medication in up to one-third of patients.
    
• Severe disease:
  
  • IV clindamycin + oral quinine for 7–10 days is regimen of choice (IV quinine may be used, but may cause ventricular arrhythmias and requires QT monitoring)
    
  • RBC exchange transfusion is indicated in patients with parasitemia >10%; hemoglobin <10 g/dL; or pulmonary, renal, or hepatic complications.
    
  • Persistent or relapsing disease may be seen in immunocompromised patients; these patients should receive antibiotic therapy for at least 6 wk, continuing for 2 wk after the last positive blood smear; can use standard combinations (see above).
    
• Asymptomatic infection:
  
  • Antibiotics are not indicated unless parasitemia on blood smears persists >3 mo.
    

• Acetaminophen: 500 mg (peds: 10–15 mg/kg, do not exceed 5 doses/24 h) PO q4–6h, do not exceed 4 g/24 h
  
• Atovaquone: 750 mg (peds: 20 mg/kg; max. 750 mg/dose) PO BID for 7 days
  
• Azithromycin: 500 mg (peds: 10 mg/kg; max. 500 mg) PO on day 1, followed by 250 mg (peds: 5 mg/kg; max. 250 mg) PO per day: 6 days
  
• Clindamycin: 300–600 mg (peds: 7–10 mg/kg q6–8h) IV q6h; 600 mg (peds: 7–10 mg/kg q6–8h) PO q8h for 7–10 days
  
• Ibuprofen: 400 mg (peds: 20–40 mg/kg/d) PO q6–8h PRN
  
• Quinine: 650 mg (peds: 25 mg/kg/d) PO q8h for 7–10 days
  

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