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Tuesday, January 20, 2009

BABESIOSIS

BABESIOSIS - Eleftherios Mylonakis, MD; Vassiliki Syriopoulou, MD
BASICS
DESCRIPTION
• Babesiosis is a tick-borne hemolytic disease that is caused by intra-erythrocytic protozoan parasites of the genus Babesia.
• Rarely reported outside the United States. Sporadic cases have been reported from a number of countries, including France, Italy, the former Yugoslavia, the United Kingdom, Ireland, the former Soviet Union, and Mexico. In the United States, infections have been reported in many states, but the most endemic areas are the islands off the coast of Massachusetts (including Nantucket and Martha's Vineyard), New York (including Long Island, Shelter Island, and Fire Island), and in Connecticut. In these areas, asymptomatic human infection seems to be common. (1-4, 6-9)
• Incubation period of babesiosis varies from 5-33 days. Most patients do not recall recent tick exposure. After an infected blood transfusion, the incubation period can be up to 9 weeks.
• System(s) Affected: Cardiovascular Gastrointestinal; Hemic/Lymphatic/Immunologic; Musculoskeletal; Nervous; Pulmonary; Renal/Urologic
ALERT
Geriatric Considerations
Morbidity and mortality is higher in patients >65.
GENERAL PREVENTION
• Avoid endemic regions during the peak transmission months of May to September (especially relevant for asplenic or immunocompromised persons, in whom babesiosis can be a devastating illness).
• Using insect repellant is advised during outdoor activities, especially in wooded or grassy areas
- Products with 10-35% N-diethyl-meta-toluamide (DEET) will provide adequate protection under most conditions.
• Early removal of ticks is important; the tick must remain attached for at least 24 hours before the transmission of Babesia microti occurs. Daily self-examination is recommended for persons who engage in outdoor activities in endemic areas.
• Pets must be examined for ticks because they may carry ticks into the home.
EPIDEMIOLOGY
Predominant age: All ages; most patients present in their 40s or 50s.
Incidence
• Between 1968 and 1993, >450 Babesia infections were confirmed in the United States by blood smears or serologic testing. Prevalence is difficult to estimate because of lack of surveillance, and because infections are often asymptomatic (1,2).
• In a recent 1-year seroconversion study of patients in New York State who were at high risk for tick-borne diseases, antibodies to Babesia microti were seen in 7 of 671 participants (1%). (3)
Prevalence
High-level parasitemia is more common in asplenic patients. Such patients have been treated successfully with exchange transfusion in addition to drugs.
RISK FACTORS
• Exposure to endemic areas
• Transfusion-associated babesiosis and transplacental/perinatal transmission have been reported.
ETIOLOGY
• Babesia microti (in the United States) and Babesia divergens and Babesia bovis (in Europe) cause most infections in humans. Recently, one case of Babesia divergens was reported in the United States.
• A previously unknown species of Babesia (WA-1) was isolated from an immunocompetent man in Washington State who had clinical babesiosis. Researchers also described another probable new babesial species (MO1) associated with the first reported case of babesiosis acquired in the state of Missouri. MO1 is probably distinct from B. divergens, but the two share morphologic, antigenic, and genetic characteristics.
• Ixodid (or hard-bodied) ticks, in particular, Ixodes dammini (Ixodes scapularis) and Ixodes ricinus, are the vectors of the parasite.
ASSOCIATED CONDITIONS
• Coinfection with Borrelia burgdorferi and Babesia microti is relatively common in endemic areas.
• Coinfection with Ehrlichia species may also be seen. Three species of Ehrlichia have been described that infect humans, Ehrlichia chaffeensis, Ehrlichia phagocytophila, and Ehrlichia ewingii. Typically, patients have a nonspecific febrile illness. Rash is uncommon with human granulocytic ehrlichiosis but common with human monocytic ehrlichiosis. Laboratory findings often include leukopenia, thrombocytopenia, and increases in serum hepatic enzyme activities. (4)


DIAGNOSIS
SIGNS AND SYMPTOMS (3)
• Asymptomatic
• High fever (up to 40C [104F])
• Chills
• Diaphoresis
• Gastrointestinal (anorexia, nausea, abdominal pain, vomiting, diarrhea)
• Generalized weakness
• Fatigue
• Myalgia
• Respiratory (cough, shortness of breath)
• Headache
• Hepatomegaly and splenomegaly or evidence of shock
• Rash (uncommon)
• Central nervous system involvement includes headache, photophobia, neck and back stiffness, altered sensorium, and emotional lability
• Jaundice and dark urine may develop later in course of illness
TESTS
Lab
• Mild to severe hemolytic anemia (common nonspecific finding)
• Normal to slightly depressed leukocyte count (common nonspecific finding)
• Typical morphologic picture on the blood smear
• A Wright- or Giemsa-stained peripheral blood smear is most commonly used to demonstrate the presence of intraerythrocytic parasites.
• Rarely, tetrads of merozoites are visible.
• Serologic evaluation with the indirect immunofluorescent antibody test with use of Babesia microti antigen is available in a few laboratories. The cut-off titer for determination of a positive result varies with the particular laboratory protocol used, but in most laboratories, titers of more than 1:64 are considered consistent with Babesia microti infection. Tenfold to 20-fold higher titers can be observed in the acute setting, with a gradual decline over weeks to months. The correlation between the level of the titer and the severity of symptoms is poor.
• Detection of Babesia microti by polymerase chain reaction (PCR) is more sensitive and equally specific for the diagnosis of acute cases, in comparison with direct smear examination and hamster inoculation. PCR-based methods may also be indicated for monitoring of the infection.
Diagnostic Procedures/Surgery
Based on typical morphologic picture on the blood smear in conjunction with epidemiologic information
DIFFERENTIAL DIAGNOSIS
• Bacterial sepsis
• Hepatitis
• Lyme disease
• Ehrlichiosis
• Leishmaniasis
• Malaria
TREATMENT
GENERAL MEASURES
• Appropriate health care: Outpatient or inpatient, depending on symptoms
• Supportive care
MEDICATION (DRUGS)
First Line
• Atovaquone (Mepron): Suspension 750 mg b.i.d. plus azithromycin (Zithromax) 500-1,000 mg/d (5)[B]
• Combination of quinine (Quinamm): 650 mg of salt orally t.i.d. and clindamycin (Cleocin) 600 mg orally t.i.d., or 1.2 g parenterally b.i.d. for 7-10 days is the most commonly used treatment. (Pediatric: Dosage is 20-40 mg/kg/d for quinine and 25 mg/kg/d for Clindamycin.)
• In areas endemic for Lyme disease and ehrlichiosis, it may be advisable to add doxycycline (Vibramycin) 100 mg b.i.d. PO in the management of patients with babesiosis until serologic testing is completed.
• Exchange transfusion, together with antibabesial chemotherapy, may be necessary in critically ill patients. This treatment is usually reserved for patients who are extremely ill (blood parasitemia >10%, massive hemolysis and asplenia).
• Precautions: Clindamycin can lead to Clostridium difficile associated diarrhea.
Second Line
Several other drugs have been evaluated, including tetracycline, primaquine, sulfadiazine (Microsulfon), and pyrimethamine (Fansidar). Results have varied. Pentamidine (Pentam) has proved to be moderately effective in diminishing symptoms and decreasing parasitemia.
FOLLOW-UP
PROGNOSIS
• When left untreated, silent babesial infection may persist for months or even years.
• 139 hospitalized cases in New York State between 1982 and 1993 (3)
- 9 patients (6.5%) died.
- 1/4 of the patients were admitted to the ICU.
- 1/4 of the patients required hospitalization for more than 14 days.
• Alkaline phosphatase levels greater than 125 U/L, white blood cell counts greater than 5  109/L, history of cardiac abnormality, history of splenectomy, presence of heart murmur, and parasitemia values of 4% or higher were associated with disease severity.
COMPLICATIONS
• Congestive heart failure
• Disseminated intravascular coagulation
• Acute respiratory distress syndrome (can occur even a few days after the onset of effective antimicrobial treatment)
• Renal failure and myocardial infarction also have been associated with severe babesiosis.
PATIENT MONITORING
Monitor for complications (congestive heart failure, etc.) and follow parasitemia as needed.
REFERENCES
1. Quick RE, Herwaldt BL, Thomford JW, et al. Babesiosis in Washington State: A new species of Babesia? Ann Intern Med. 1993;119:284-290.
2. Persing DH, Herwaldt BL, Glaser C, et al. Infection with a Babesia-like organism in northern California. N Engl J Med. 1995;332:298-303.
3. White DJ, Talarico J, Chang HG, et al. Human babesiosis in New York State: A review of 139 hospitalized cases and analysis of prognostic factors. Arch Intern Med. 1998;158:2149-2154.
4. Mylonakis E. When to suspect and how to monitor babesiosis. Amer Fam Physician. 2001;63:1969-1974.
5. Krause PJ, Lepore T, Sikand VK, et al. Atovaquone and azithromycin for the treatment of babesiosis. N Engl J Med. 2000 Nov 16;343(20):1454-8.
6. Beattie JF, Michelson ML, Holman PJ. Acute babesiosis caused by Babesia divergens in a resident of Kentucky. N Engl J Med. 2002;29;347(9):697-698.
7. Gelfand JA. Babesia species. In: Mandell GL, Douglas RG, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 6th ed. New York, NY: Churchill Livingstone, 2005:3209-3215.
8. Gutman JD, Kotton CN, Kratz A. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 29-2003. A 60-year-old man with fever, rigors, and sweats. N Engl J Med. 2003;349(12):1168-1175.
9. Pruthi RK, Marshall WF, Wiltsie JC, Persing DH. Human babesiosis. Mayo Clin Proc. 1995;70:853-862.
MISCELLANEOUS
See also: Lyme Disease

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