Basics
Description
- Human babesiosis is a tick-borne malaria-like illness characterized by fever, malaise, and hemolytic anemia.
- Most infected individuals are asymptomatic.
Epidemiology
- Human babesiosis is a protozoal illness caused by the intraerythrocytic parasite of the Babesia genus.
- Babesia microti is responsible for most cases of babesiosis in the United States.
- Babesia divergens is responsible for most European cases.
- The parasite is transmitted by the tick vector Ixodes scapularis (deer tick), the same vector responsible for transmission of Borrelia burgdorferi (the causative agent in Lyme disease)
- The white-footed mouse (Peromyscus leucopus) is the primary reservoir host of Babesia.
- Most cases in the United States occur in the Northeast and Upper Midwest.
- 96% of reported cases in 2012 occurred in Connecticut, Massachusetts, New Jersey, New York, Rhode Island, Minnesota, and Wisconsin.
- Human infection most commonly occurs in the warm months-late spring to early fall.
Incidence
- In January 2011, babesiosis became a nationally notifiable disease monitored by the Centers for Disease Control and Prevention (CDC).
- According to the CDC, 937 cases were reported in the United States in the year 2012, more cases than meningococcal disease, streptococcal toxic shock syndrome, or botulism combined.
Prevalence
- Prevalence is difficult to ascertain as asymptomatic infection appears to be common in endemic areas. For instance, seroprevalence is as high as 9% in some endemic areas of Rhode Island.
Risk Factors
- Asplenia (functional or anatomic)
- Extremes of age, especially age >50 years
- HIV/AIDS
- Immunosuppressive medications
- Malignancy
- Primary immunodeficiency syndrome
Genetics
There is no known genetic predisposition.
General Prevention
- Prevention begins with avoidance of tick bites.
- Simple measures include wearing long-sleeved shirts and long pants, with pants tucked into the socks in tick-infested areas.
- Avoid endemic regions during the peak months of May to September.
- Light clothing will make ticks easier to see.
- Use DEET-containing insect repellents during outdoor activities.
- Spraying one's clothing with a permethrin tick repellent may be helpful.
- Children and dogs should be inspected daily for ticks after being outside.
- Prophylaxis is not recommended after a tick bite.
- No vaccine is currently available.
- There is currently no universal laboratory screening of blood products.
Pathophysiology
- Babesial infection of the erythrocyte causes membrane damage and lysis, which promotes adherence to the endothelium and microvascular stasis.
- This process results in a hemolytic anemia.
- The spleen plays an important role in decreasing the protozoal load through antibody production and filtering of abnormally shaped infected red blood cells.
Etiology
- A bite from an infected tick transmits the protozoa.
- Incubation period
- Usually 1-4 weeks for tick-transmitted disease
- 1-9 weeks for transfusion-associated disease
- Human-to-human transmission is limited to infection through contaminated blood.
- Babesiosis is currently the most common transfusion-transmitted infection in the United States.
- Rare cases of transplacental and perinatal infection have been reported.
Commonly Associated Conditions
- 11-23% of patients have concurrent Lyme disease.
- Coinfections with Borrelia account for 80% of tick-borne coinfections.
Diagnosis
History
- Few patients recall a tick bite.
- Patients live in or have recently traveled to an endemic region.
- Initial symptoms begin 1-4 weeks after the tick bite and are vague. They may include progressive fatigue, malaise, headaches, and anorexia, accompanied by intermittent fevers as high as 40 °C.
- Chills, myalgias, and arthralgias may follow these symptoms.
- Less common complaints include cough, sore throat, abdominal pain, and emotional lability.
Physical Exam
- Fever and tachycardia are often the only findings.
- Mild conjunctival injection and pharyngeal erythema occasionally occur.
- Mild hepatomegaly and/or splenomegaly may be seen.
- Jaundice or hematuria may also be observed.
- Petechiae and ecchymosis occur in rare cases, most often in the presence of severe illness with associated shock and/or DIC.
Diagnostic Tests & Interpretation
Lab
- Giemsa- or Wright-stained thick and thin blood smears may demonstrate the intraerythrocytic ring form:
- This is often confused with the ring form of Plasmodium falciparum, the etiologic agent of malaria.
- Rarely, the pathognomonic "Maltese cross" forms of the Babesia parasite may be seen on the blood smear.
- Multiple smears should be performed as initial smears may be falsely negative.
- Indirect immunofluorescent assay
- Antigen-specific for B. microti
- In endemic areas, the test has a sensitivity of 91% and a specificity of 99%.
- Can be used when blood smears are negative
- In general, a titer = 1:64 indicates exposure.
- Titer = 1:256 suggests acute infection.
- There is little correlation between titer levels and severity of disease.
- Immunoglobulin levels decline rapidly within months of recovery.
- Polymerase chain reaction is highly sensitive and specific when available.
- Other tests: Most of the abnormal routine test results are the result of hemolysis.
- Urinalysis
- Proteinuria
- Hemoglobinuria
- CBC
- Normal leukocyte count/leukopenia
- Normocytic/normochromic anemia
- Thrombocytopenia
- Atypical lymphocytosis
- Reticulocytosis
- Possible positive Coombs test
- Elevated ESR
- Liver function tests: elevated bilirubin, lactate dehydrogenase, and liver transaminases
- Elevated BUN and creatinine
- In asymptomatic patients, these tests are often normal.
Alert
False negatives:
- Blood smears may not demonstrate the protozoa at low levels of parasitemia.
- Serologic false positives for B. microti include cross-reactivity with other Babesia sp. or malarial organisms
Differential Diagnosis
- Ehrlichiosis
- Influenza
- Lyme disease
- Malaria
- Nonspecific viral syndrome
Treatment
Medication
- No treatment is required for asymptomatic patients who are otherwise healthy.
- For symptomatic patients, treatment is generally for 7-10 days regardless of regimen; more severely ill patients may require a longer duration of therapy.
First Line
- Clindamycin in combination with quinine
- Standard therapy for asplenic, immunodeficient, or severely ill patients
- Pediatric dosing:
- Clindamycin: 20-40 mg/kg/day IV/PO divided q6-8h (max 600 mg/dose)
- Quinine: 30 mg/kg/day PO divided into 3 doses
- Adult dosing:
- Clindamycin: 600 mg PO q8h or 300-600 mg IV q6h
- Quinine: 650 mg PO q8h
Second Line
- Atovaquone in combination with azithromycin
- Has similar treatment effectiveness with fewer side effects (such as vertigo, tinnitus, and GI upset) than clindamycin and quinine in adults
- Use of atovaquone and azithromycin has not been studied in the pediatric population; clindamycin and quinine are the recommended treatment choice for symptomatic children.
- Pediatric dosing:
- Atovaquone 40 mg/kg/day PO divided into 2 doses (max 750 mg q12h)
- Azithromycin 10 mg/kg/day (max 500 mg) PO on day 1 and 5 mg/kg/day (max 250 mg) PO daily thereafter
- Adult dosing:
- Atovaquone 750 mg PO q12h
- Azithromycin 500-1,000 mg PO on day 1 and 250-1,000 mg PO daily thereafter
- In areas endemic for Lyme disease and ehrlichiosis, consider adding doxycycline to either regimen until lab confirmation of absence of either disease in the patient with babesiosis.
Additional Therapies
General Measures
Those with mild clinical disease usually recover without treatment.
Additional Therapies
- For life-threatening infections, exchange transfusion has been successful. Consider in patients with severe parasitemia (≥10%), severe hemolysis, or renal/hepatic/pulmonary compromise.
- Progressive respiratory distress may require mechanical ventilation.
Alert
- Signs to watch for:
- Respiratory distress, especially after treatment has begun
- Pancytopenia and lymphadenopathy: may indicate the development of hemophagocytic syndrome
- Pitfalls
- Children who are from endemic areas and have an acute febrile illness may be misdiagnosed with a nonspecific viral illness.
- One should be suspicious for a coinfection with Lyme disease or ehrlichiosis in those who are not responding to standard therapy.
- Delayed recognition of this uncommon disease may be life threatening in the immunocompromised patient.
- In endemic areas, babesiosis should be considered in a posttransfusion febrile illness in at-risk populations.
Ongoing Care
Follow-up Recommendations
When to expect improvement:
- Some improvement of symptoms should be noted within 24-48 hours of onset of therapy.
- Those who are only mildly affected usually have resolution of their symptoms over a few weeks.
- For severely affected and immunodeficient patients, the convalescent period may be as long as 18 months.
- In untreated asymptomatic individuals, parasitemia may persist for months to years.
- Long-term complications are rare.
- Recrudescence has been reported.
Complications
- Rarely fatal in the United States
- Pancytopenia and overwhelming secondary bacterial sepsis may occur.
- Serious and fulminant complications have been described:
- Pulmonary edema and adult respiratory distress syndrome, often happening after treatment has begun.
- CHF
- Renal failure
- Hemophagocytic syndrome/DIC
- Seizures/coma
- Those coinfected with Lyme disease are susceptible to more severe disease and complications.
Additional Reading
- American Academy of Pediatrics. Babesiosis. In: Pickering LK, Baker CJ, Kimberlin DW, et al, eds. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012:244-245.
- Centers for Disease Control and Prevention. Summary of notifiable diseases-United States, 2010. MMWR Morb Mortal Wkly Rep. 2012;59(53):1-111. [View Abstract]
- Vannier E, Gewurz BE, Krause PJ. Human babesiosis. Infect Dis Clin North Am. 2008;22(3):469-488, viii-ix. [View Abstract]
- Vannier E, Krause PJ. Human babesiosis. N Engl J Med. 2012;366(25):2397-2407. [View Abstract]
- Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43(9):1089-1134. [View Abstract]
Codes
ICD09
ICD10
SNOMED
- 21061004 Babesiosis (disorder)
- 73908004 Infection by Babesia microti (disorder)
- 51613008 Infection by Babesia divergens (disorder)
FAQ
- Q: How long does a tick have to be attached for infection to occur?
- A: In general, successful transmission requires at least 24 hours of attachment.
- Q: How should a tick be removed?
- A: The tick should be grasped with forceps as close to its head as possible and pulled straight up. If possible, it should be saved for identification.
- Q: Does infection confer lifetime immunity?
- A: Reinfection is possible.