Etiology

There are more than 90 species of Babesia that infect a wide variety of wild and domestic animals throughout the world. Only a few of these species have been reported to infect humans, including Babesia microti, Babesia divergens (and Babesia divergens–like species), Babesia duncani (previously known as WA1), Babesia venatorum (previously know as EU1), KO1, and TW1.

Epidemiology

Babesia are transmitted to humans from vertebrate reservoir hosts by the Ixodes ricinus family of ticks. B. microti is the most common cause of babesiosis in humans. The primary reservoir for B. microti is the white-footed mouse, Peromyscus leucopus, and the primary vector is the black legged tick, Ixodes scapularis. I. scapularis also transmits the causative agents of Lyme disease and human granulocytic anaplasmosis and may simultaneously transmit all 3 microorganisms. White-tailed deer (Odocoileus virginianus) serve as the host on which adult ticks feed most abundantly but are incompetent reservoirs. Babesiosis may be transmitted through blood transfusion, and B. microti is the most frequently reported transfusion-transmitted microbial agent in the USA. Rarely, babesiosis is acquired by transplacental transmission.

Human B. microti infection is endemic in the northeastern and upper midwestern USA and in Europe. Human babesial infections caused by the cattle parasite, Babesia divergens, have been described in many countries in Europe, while B. divergens–like infections have been described in Kentucky, Missouri, and Washington. B. duncani infects humans along the Pacific coast. B. venatorum infection has been documented among people in Austria, Germany, and Italy. Human babesiosis cases also have been documented in Asia, Africa, and South America, including KO1 in Korea and TW1 in Taiwan.

In certain sites and in certain years of high transmission, babesiosis constitutes a significant public health burden. Nantucket Island reported 21 such cases in 1994, which translates to 280 cases/100,000 population, placing the community burden of disease in a category with gonorrhea as “moderately common.” Comparable incidence rates have been described elsewhere on the southern New England coast.

Pathogenesis

The pathogenesis of human babesiosis is not well understood. Cytoadherence and lysis of infected erythrocytes and excessive production of proinflammatory cytokines such as tumor necrosis factor and interleukin-1 probably account most of the clinical manifestations and complications of the disease. The spleen has an important role in clearing parasitemia as do T and B cells, macrophages, polymorphonuclear leukocytes, cytokines, antibody, and complement.

Clinical Manifestations

The clinical severity of babesiosis ranges from subclinical infection to fulminating disease and death. In clinically apparent cases, symptoms of babesiosis begin after an incubation period of 1-9 wk from the beginning of tick feeding or 6-9 wk after transfusion. Typical symptoms in moderate to severe infection include intermittent fever as high as 40°C (104°F) accompanied by any combination of chills, sweats, myalgias, arthralgias, nausea, and vomiting. Less commonly noted are emotional lability, hyperesthesia, headache, sore throat, abdominal pain, conjunctival injection, photophobia, weight loss, and nonproductive cough. The findings on physical examination generally are minimal, often consisting only of fever. Splenomegaly, hepatomegaly, or both are noted occasionally. Rash is seldom present. Abnormal laboratory findings include moderately severe hemolytic anemia, elevated reticulocyte count, thrombocytopenia, proteinuria, and elevated bilirubin, blood urea nitrogen, and creatinine levels. The leukocyte count is normal to slightly decreased, with increased bands. Symptoms usually last for a week to several months, with prolonged recovery of up to a year or more in severe cases. Complications include respiratory failure, disseminated intravascular coagulation, heart failure, renal failure, liver failure, and coma. A prolonged relapsing course of illness despite multiple courses of antibabesial therapy has been described in highly immunocompromised hosts, such as those with cancer, asplenia, and immuosuppressive therapy. About 25% of these patients die, while the remainder are cured after an average of 3 mo (range 1-24 mo) of antibabesial therapy.

Risk factors for severe disease include anatomic or functional asplenia, concomitant malignancy or HIV infection, immunosuppressive drugs, age of more than 40 yr, or infection with B. divergens or B. duncani. Concurrent babesiosis and Lyme disease infection occurs in 3-11% of patients experiencing Lyme disease, depending on location in southern New England and the northern Midwest. Such co-infection results in more severe illness than with either disease alone. Moderate to severe babesiosis may occur in children, but infection generally is less severe than in adults. About 50% of infected children are asymptomatic or experience minimal symptoms. Neonates may develop severe illness and usually acquire infection from blood transfusion.

Diagnosis

Diagnosis of B. microti infection in human hosts is by microscopic demonstration of organisms using Giemsa-stained thin blood films. Parasitemia may be exceedingly low, especially early in the course of illness. Thick blood smears may be examined, but the organisms may be mistaken for stain precipitate or iron inclusion bodies. The polymerase chain reaction is a sensitive and specific test for detection of Babesia DNA. Subinoculation of blood into hamsters or gerbils and in vitro cultivation are too specialized for all but the most experienced laboratories. Serologic testing is useful, particularly for diagnosing B. microti infection. The indirect immunofluorescence serologic assay for both IgG and IgM antibodies is sensitive and specific and generally can confirm a diagnosis of babesiosis when parasites are scarce or undetectable. The diagnosis of babesiosis is most reliably made in patients who have lived in or traveled to an area where babesiosis is endemic, experience viral infection–like symptoms, and have identifiable parasites on blood smear or amplifiable Babesia DNA in blood and antibabesial antibody in serum. The diagnosis of active babesial infection based on seropositivity alone is suspect.

Treatment

The combination of clindamycin (7-10 mg/kg given every 6-8 hr [up to a maximum of 600 mg per dose] intravenously or orally) and quinine (8 mg/kg given every 8 hr [up to a maximum of 650 mg per dose]) for 7-10 days was the first effective therapeutic combination for the treatment of babesiosis and remains the treatment of choice for severe disease. Adverse reactions are common, especially tinnitus and abdominal distress. The combination of atovaquone (20 mg/kg every 12 hr [up to a maximum of 750 mg per dose]) and azithromycin (10 mg/kg per day, once per day on day 1 [up to a maximum of 500 mg per dose] and 5 mg/kg once per day [up to a maximum of 250 mg per dose] thereafter orally) for 7-10 days is as effective as clindamycin and quinine but with fewer adverse effects. Atovaquone and azithromycin successfully treats babesiosis in infants and should be considered for initial use in children experiencing mild to moderate infection. Treatment failure with clindamycin and quinine and with atovaquone and azithromycin may occur in highly immunocompromised hosts. Consultation with an infectious diseases expert is recommended in these cases. Exchange blood transfusion can decrease parasitemia rapidly and remove toxic by-products of infection and should be considered for all patients experiencing severe Babesia infection.

Prognosis

Moderate to severe disease is frequently observed in some highly endemic areas. The case fatality rate was estimated at 5% in a retrospective study of 136 New York cases but may as high as 20% in immunocompromised hosts. Immunity is sometimes incomplete, with low-level asymptomatic parasitemia persisting for as long as 26 mo after symptoms have resolved or with relapsing symptomatic disease in immunocompromised hosts.

Prevention

Prevention of babesiosis can be accomplished by avoiding areas where ticks, deer, and mice are known to thrive. Use of clothing that covers the lower part of the body and that is sprayed or impregnated with diethyltoluamide (DEET), dimethyl phthalate, or permethrin (Permanone) is recommended for those who travel in the foliage of endemic areas. A search for ticks on people and pets should be carried out and the ticks removed using tweezers to grasp the mouth parts without squeezing the body of the tick. Prospective blood donors with a history of babesiosis are excluded from giving blood to prevent transfusion-related cases.