• In the U.S., cases caused by B. microti are acquired on offshore islands of the northeastern coast, including Nantucket Island, Cape Cod, and Martha’s Vineyard in Massachusetts; Block Island in Rhode Island; and Long Island, Fire Island, and Shelter Island in New York; as well as the nearby mainland including Connecticut.
• Sporadic cases reported from California, Georgia, Maryland, Minnesota, Virginia, Wisconsin, and most recently the WA-1 strain from Washington State and the
MO-1 strain from Missouri.
• B. divergens and B. bovis are implicated in human disease in Europe, where the disease remains rare and predominantly associated with asplenia.
• Majority of cases are symptomatic.
• May be transmissible by transfusion, through platelets and erythrocytes.
• Mixed infections (B. microti and Borrelia burgdorferi) are estimated to occur in 10% (Rhode Island and Connecticut) to 60% (New York) of cases.
DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
• Ambeiasis
• Ehrlichiosis
• Hepatic abscess
• Leptospirosis
• Malaria
• Salmonellosis, including typhoid fever
• Acute viral hepatitis
• Hemorrhagic fevers
The diagnosis can be made by visualizing the parasites in the blood with the light microscope, detecting the antibody serologically, or verifying the parasite with molecular genetic methods. The intra-erythrocytic forms of Babesia can be confused morphologically with malaria.
WORKUP
Should be suspected in any febrile patient living or traveling in an endemic area, irrespective of exposure history to ticks or tick bites, especially if asplenic
LABORATORY TESTS
• CBC to reveal mild to moderate pancytopenia
• Abnormally elevated serum chemistries, including creatinine, liver function profile, lactate dehydrogenase, and direct and total bilirubin levels
• Urinalysis to reveal proteinuria and hemoglobinuria
• Examination of Giemsa- or Wright-stained thick and thin blood films for intraerythrocytic parasites
1. In its classic, though infrequently seen, form a “tetrad” or “Maltese Cross” composed of four daughter cells attached by cytoplasmic strands is observed
2. More commonly, smaller forms composed of a single chromatin dot are eccentrically located within bluish cytoplasm.
3. Parasitized erythrocytes may be multiply infected but not enlarged, or they may show evidence of pigment deposition, seen with Plasmodium species.
• Diagnosis achieved serologically by indirect immunofluorescence assay (IFA) is specific for B. microti.
1. Titer of =1:64 is indicative of seropositivity, whereas one =1:256 is considered diagnostic of acute infection.
2. Assay is hampered by the inability to distinguish between exposed patients and those who are actively infected.
3. Immunoglobulin M indirect immunofluorescent-antibody test may be highly sensitive and specific for diagnosis.
TREATMENT
NONPHARMACOLOGIC THERAPY
Supportive care with adequate hydration
ACUTE GENERAL Rx
• In patients with intact spleens: predominantly asymptomatic or if symptomatic, generally self-limited
• Therapy reserved for the severely ill patient, especially if asplenic or immunosuppressed
• Combination of quinine sulfate 650 mg PO tid plus clindamycin 600 mg PO tid (1.2 g parenterally bid) taken for 7 to 10 days: effective but may not eliminate parasites
• Exchange transfusions in addition to therapy with quinine and clindamycin: successful treatment for severe infections in asplenic patients associated with high levels of B. microti or B. divergens parasitemia
DISPOSITION
Prognosis is usually good and fatal outcomes are rare.
REFERRAL
• For prompt consultation with an infectious disease specialist if the diagnosis is acutely suspected, especially in the asplenic, elderly, or immunocompromised patient
• For hospitalization for the severely ill patient who may require exchange transfusions in addition to antibiotic therapy

Babesiosis

BASIC INFORMATION
DEFINITION
Babesiosis is a tick-transmitted protozoan disease of animals, caused by intraerythrocytic parasites of the genus Babesia. Humans are incidentally infected, resulting in a nonspecific febrile illness.
EPIDEMIOLOGY & DEMOGRAPHICS
United States Babesiosis due to B. microti is an emerging infection in the United States. Most of the >300 documented cases have occurred in coastal southern New England (from eastern Connecticut to Cape Cod, MA) and the chain of islands off the coast, particularly Nantucket Island and Martha’s Vineyard (MA); Block Island (RI); and eastern Long Island, Shelter Island, and Fire Island (NY). Several cases have been reported from upstate New York, New Jersey, and Pennsylvania and from the upper Midwest (Wisconsin, Minnesota). Because babesiosis is not a notifiable disease in every state and asymptomatic infection is common, the incidence of B. microti infection is greatly underestimated. In New York state alone, >800 cases have been reported in the past decade. In Washington state and northern California, nine cases have been attributed to B. duncani (isolates WA1 and CA5), B. duncani-type parasites (WA2 and CA6), and other closely related babesial parasites (CA1-4). These organisms are antigenically distinct from B. microti and belong to the clade of piroplasms found in dogs (B. conradae) and wild animals in the western United States. As asymptomatic infection may persist for months without detectable parasitemia, babesiosis may be transmitted by blood transfusion, especially in endemic areas. More than 50 transfusion- transmitted cases have been attributed to B. microti and two to B. duncani (WA1 and WA2). Neonatal babesiosis is rare and has been acquired by vertical transmission, blood transfusion, or tick bite. Lastly, B. divergens-like parasites have been implicated in three cases of acute babesiosis (one each in Missouri, Kentucky, and Washington state).
Other Countries Babesiosis is rare in Europe, with half of the >35 cases documented in France and the British Isles. In addition to the original case from Croatia, cases have been reported from the central Alpine region (Austria, Italy, Switzerland) and from southern Europe (Spain, Portugal). Most cases have involved asplenic patients and have been attributed to B. divergens. B. microti has been implicated in only a handful of cases, although serologic evidence of B. microti infection has emerged from Switzerland and midwestern Germany. A study of two patients from Austria and Italy has identified Babesia EU1 as a novel pathogen that belongs to the B. divergens clade and is closely related to B. odocoilei, a parasite of white-tailed deer. Sporadic cases of human babesiosis have been described in Mexico, Colombia, the Canary Islands, Ivory Coast, Egypt, Mozambique, South Africa, and India. Cases due to B. microti-like piroplasms have been reported from Taiwan and Japan.
PREVALENCE (IN U.S.):
• In areas of high endemicity, seropositivity ranging from 9% (Rhode Island) to 21% (Connecticut)
• Highest number of reported cases in New York
PREDOMINANT SEX: Males (most likely through increased exposure to vectors during recreational or occupational activities)
PREDOMINANT AGE: Severity apparently increasing with age >40 yr
PEAK INCIDENCE: Spring and summer months, May through September
GENETICS: None known
CONGENITAL INFECTION: At least one case of probable vertical transmission
NEONATAL INFECTION: At least two cases of perinatal transmission
PHYSICAL FINDINGS & CLINICAL PRESENTATION
• Incubation period 1 to 4 wk, or 6 to 9 wk in transfusion-associated disease
• Gradual onset of irregular fever, chills, diaphoresis, headache, myalgia, arthralgia, fatigue, and dark urine
• On physical examination: petechiae, frank or mild hepatosplenomegaly, and jaundice
• Infection with B. divergens producing a more severe illness with a rapid onset of symptoms and increasing parasitemia progressing to massive intravascular hemolysis and renal failure
Clinical Features. The occasionally severe clinical manifestations include fever, shivering,myalgia, fatigue, and jaundice as a consequence of hemolytic anemia. Furthermore, many infections probably follow an asymptomatic course.
ETIOLOGY
• Vector: Deer tick, Ixodes scapularis (also known as I. dammini)
1. Feeds on rodents during the spring and summer while in its larval and nymphal stages and on deer as an adult
2. During the warmer months in endemic areas, humans are readily infected while engaging in outdoor activities
• B. microti, along with B. divergens and B. bovis, account for most human infections.