Pediatric Babesiosis 

Human babesiosis is an emerging tick-borne zoonotic disease caused by the protozoan parasites of the genus Babesia.^[1] Babesial parasites and those of the closely related genus Theileria have worldwide distribution, parasitizing the erythrocytes of wild and domestic animals. These parasites are commonly called piroplasms because of the pear-shaped forms found within infected RBCs. Babesial infections in humans are infrequent and occur in limited geographic locations. Disease manifestations range from asymptomatic infection in healthy individuals to severe illness and death in those who are asplenic, elderly, or immunocompromised.

Babes first described babesiosis in Romanian cattle in 1888. Skrabalo was the first to identify a human infection caused by Babesia in 1957 in the former Yugoslavia. Earlier reports involved splenectomized patients with fulminant babesiosis. In 1969, infection with Babesia microti was described in a patient with an intact spleen from Nantucket Island off the coast of Massachusetts. Babesiosis is endemic in the Northeast, particularly in the areas of Nantucket Island, Martha's Vineyard, Shelter Island, and parts of Long Island. Cases have been reported from the Midwest and West Coast of the United States.

Of the more than 70 species worldwide in the genus Babesia, human infections are largely due to the rodent strain B microti (found only in the United States) and the cattle strains Babesia divergens and Babesia bovis (found only in Europe). Sporadic cases of babesiosis due to Babesia duncani (isolates WA-1 and CA-5) have been reported in Washington and northern California. Genetic sequence analysis of WA-1 strain has revealed piroplasm-specific, small-subunit ribosomal DNA. Phylogenetically, WA-1 strain Babesia is closely related to Babesia gibsoni, a canine pathogen. A fatal case of babesiosis was recently described in Missouri from a strain (MO-1) that was closely related to B divergens. Serologic studies that test for B microti do not detect infections due to these other strains of Babesia.

Babesia species in the host erythrocyte vary in size from 1-5 mm in length. B microti measures 2 X 1.5 mm, B divergens measures 4 X 1.5 mm, and B bovis measures 2.4 X 1.5 mm. They are pear-shaped, oval, or round. Their ring form and peripheral location in the erythrocyte frequently lead to their being mistaken for Plasmodium falciparum.

Babesiosis is a zoonotic disease and requires transmission from an animal reservoir to humans via a tick vector.^[2] In the northeastern United States, the black-legged deer tick Ixodes scapularis, also called Ixodes dammini (see the image below), is the principal vector for transmitting the etiologic agent B microti. I scapularis is the same vector that transmits Lyme disease.

Babesia species from rodents, primarily the white-footed deer mouse but also the field mouse, vole, rat, and chipmunk, are transmitted to humans during tick bites in endemic areas. Babesiosis is understandably more prevalent during the periods of tick activity such as spring and summer.

The tick I scapularis has 3 developmental stages, the larva, the nymph, and the adult, with each stage requiring a blood meal for development into the next stage. As a larva and nymph, the tick feeds on rodents; however, as an adult, the tick prefers to feed on the white-tailed deer. Female ticks are impregnated while obtaining their blood meal on the deer, with the formation of up to 20,000 eggs.

Although rodents are infected with Babesia (60% on Nantucket Island), the white-tailed deer does not carry the organism. B microti is transmitted from the larval phase of the tick to the nymphal phase (transstadial transmission) but not transovarially. Human infection is primarily produced by the bite of an infected nymph during a blood meal. Restocking of deer populations and curtailment of hunting has increased deer herds in certain areas. The proximity of deer, mouse, and tick create the conditions for human infection. Babesiosis is rarely acquired through blood transfusion.^[3] In transfusion-associated cases, sources of babesiosis have included platelets and frozen erythrocytes. The incubation period in transfusion-associated disease appears to be 6-9 weeks. Transplacental transmission has also occurred rarely.

The hard-bodied cattle tick Ixodes ricinus is thought to transmit bovine babesiosis from the cattle reservoir to humans in Europe.

Sporozoites enter the patient's blood stream during the tick bite and become intraerythrocytic. Upon infection of the host erythrocyte, mature B microti trophozoites undergo asynchronous asexual budding and divide into 2 or 4 merozoites. As parasites leave the erythrocyte, the membrane is damaged. The precise mechanism of hemolysis is unknown. Unlike in Plasmodium, the schizogony is asynchronous, and massive hemolysis does not occur.

The spleen offers a critical host defense against this infection, as suggested by the higher incidence and greater severity of babesiosis in asplenic patients. The spleen traps the infected erythrocytes, and their ingestion by the macrophages follows.

Complement activation by Babesia may lead to the generation of tumor necrosis factor (TNF) and interleukin-1 (IL-1). Decreased complement levels, increased circulating C1q-binding activity and decreased C4, C3, and CH50 levels are observed in patients with babesiosis. The generation of these primarily macrophage-produced mediators may explain many of the clinical features, such as fever, anorexia, arthralgias, myalgias, and the fulminant shock syndrome of bovine babesiosis.

The disease itself alters cellular immune function. Patients with acute babesiosis have an increase in T-suppressor lymphocytes, T-cytotoxic lymphocytes, or both and decreased responses to lymphocyte mitogens with a polyclonal hypergammaglobulinemia.

Frequency

United States

Human babesiosis is endemic in the northeastern coastal region of the United States, particularly Nantucket Island, Martha's Vineyard, Cape Cod (Massachusetts), Block Island (Rhode Island), eastern Long Island, Shelter Island, and Fire Island (New York). More recently, cases have been described from the Connecticut mainland and Washington State. In addition, infections with Babesia species have been reported in New Jersey, Maryland, Virginia, California, Wisconsin, Minnesota, Missouri, Washington State, Georgia, and Mexico. Disease prevalence in Cape Cod, as suggested by antibody to B microti, has been reported as 3.7%, whereas on Shelter Island in individuals with a high risk of exposure to ticks, it was 4.4% in June and reached 6.9% by October.

International

Babesiosis is rare in Europe, with cases reported from the former Yugoslavia, France, Russia, Ireland, and Scotland. All of the cases involved bovine Babesia and occurred in individuals who were splenectomized. One recent report describes human Babesia infection in Columbia.

Mortality/Morbidity

In a healthy individual with an intact spleen, babesiosis is rarely fatal; however, in a patient who is asplenic, babesiosis is generally quite severe and frequently fatal. In a 1998 review by White and colleagues, babesiosis was fatal in 9 of 139 (6.5%) patients who were hospitalized for the disease in New York from 1982-1993.^[4]

Age

Patients with clinical illness and intact spleens are usually aged 50 years or older, suggesting that age plays a factor in the severity of the clinical response. Previously healthy individuals with babesiosis are generally older (mean >60 y) than are patients with babesiosis with antecedent medical problems (mean 48 y). Vannier et al suggested that the age-associated decline in resistance to B microti is genetically determined.