Babesia are intraerythrocytic, tick-transmitted, protozoan parasites that infect a broad range of wild and domesticated mammals including cattle, horses, dogs, and rodents. Human babesial infection is uncommon, caused by B. microti in North America and B. divergens in Europe, with most infections occurring in asplenic people. Presentation is typically with nonspecific ‘viral-type’ symptoms. Haemolytic anaemia is a characteristic feature and can be severe, particularly with B. divergens. Diagnosis is by discovering babesia organisms in Giemsa-stained blood smears, or detection of its DNA in blood by PCR. Aside from supportive care, treatment is usually with combinations of clindamycin, quinine, atovaquone and azithromycin. Mortality ranges from 5 to 40%. Prevention is by use of repellents, removing ticks from the skin, and avoidance of exposure in asplenic and immunocompromised individuals: there is no vaccine.
Although several species of babesia may infect humans, two species, Babesia microti and B. divergens, are responsible for most cases of human babesiosis. In the United States of America, thousands of cases of B. microti infections have been reported since 1988, mostly from the north-east coast including Nantucket, Martha’s Vineyard, and Block Island. B. microti is transmitted by Ixodes scapularis (previously I. dammini) and its reservoir host is the common white-footed mouse Peromyscus leucopus. B. duncani, a new species, has been identified in 9 patients in Washington State. B. equi cases have been identified in California and a single fatal case of B. divergens infection in Missouri. The zoonotic Borrelia burgdorferi, causing Lyme disease, is also transmitted by I. scapularis and coinfections are documented. The risk of both babesiosis and Lyme disease is highest in June when nymphal I. scapularis are most abundant. More than 20 cases of transfusion-transmitted babesiosis have been reported in the United States of America. A number of cases have been reported of infection exported to other countries in visitors from the United States.
Since the first description of human babesiosis in Europe in 1957, more than 40 cases have been reported. Most of them were due to B. divergens, a common cattle pathogen transmitted by I. ricinus. France, the United Kingdom, and Ireland account for more than 50% of the cases reported in Europe. Farmers, foresters, campers, and hikers are affected, usually between May and October, the season of activity of I. ricinus. Most infections (83%) occur in asplenic people. Only one autochthonus case of B.microti transfusion-transmitted has been reported in Europe in a german patient with a myeloid leukemia, but the risk exists for B. divergens which may survive in packed red blood cells for several weeks at 4°C. B. venatorum, closely related to but distinct from B. odocoilei that infects white-tail deer in United States of America has been isolated in 3 asplenic patients in Italy, Austria and Germany.
Ticks infected with babesia inoculate parasites while feeding on a vertebrate. Babesia enter red blood cells directly and multiply by budding to form two or four parasites, rarely more, in 8 to 10 h. They are released and invade other erythrocytes. The spleen plays a major role in resistance to babesial infections, especially in the case of B. divergens babesiosis.
B. microti infection
In humans, B. microti babesiosis is characterized by gradually developing malaise, anorexia, and fatigue with subsequent development of fever, sweats, and generalized myalgia, starting from 1 to 4 weeks after a tick bite; 95% of those infected have intact spleens. Headache, shaking chills, nausea, depression, and hyperaesthesia are less frequent. Mild hepatomegaly and splenomegaly may be detected and spontaneous splenic rupture may occur. A mild to severe haemolytic anaemia, sometimes complicated by acute kidney injury, thrombocytopenia and normal white blood cell count are generally present. Lactate dehydrogenase, liver enzymes, and unconjugated bilirubin levels may be increased. Parasites are found in peripheral blood of 1 to 20% of patients with intact spleens, but in up to 80% of those who are asplenic. The illness is usually more severe in asplenic and older patients. Complications are more likely in the immunocompromised. Acute illness lasts from 1 to 4 weeks, but weakness and malaise often persist for several months. A low, asymptomatic parasitaemia may persist for several weeks after recovery. Case fatality is about 5%.
B. divergens infection
In Europe, B. divergens infections are usually more severe than those caused by B. microti, with a case fatality up to 42%. After an incubation period of 1 to 3 weeks, there is sudden severe intravascular haemolysis resulting in haemoglobinuria, severe anaemia, and jaundice, associated with nonperiodic high fever (40–41°C), hypotension, shaking chills, intense sweats, headache, myalgia, lumbar pain, vomiting, and diarrhoea. Peripheral blood B. divergens parasitaemia varies from 5 to 80%. Patients rapidly develop renal failure, which may be associated with pulmonary oedema, coma, and death.
Babesiosis should be suspected in any patient from any area who presents with fever and a history of tick bite. Initially, Plasmodium falciparum malaria may be suspected, but lack of recent travel in malaria-endemic areas or recent blood transfusion and lack of a spleen should lead to suspicion of babesiosis. Diagnosis is based on discovering babesia in Giemsa-stained blood smears (Fig. 22.214.171.124). Babesia can be distinguished from plasmodia by the absence of gametocytes and pigment in erythrocytes.
B. microti is characterized by multiple basket-shaped parasites. In some cases, parasitaemia is sparse and detection of antibodies, using an indirect fluorescent antibody assay, may be useful for diagnosis. Antibody titres rise during the first weeks and fall after 5 months, but correlation between antibody titre and severity of the disease is poor. A real-time polymerase chain reaction (RT-PCR) assay targeting the 18S rRNA gene of B. microti has been developed.
B. divergens is characterized in Giemsa-stained blood smears by double piriform intraerythrocytic parasites or tetrads, but annular, punctiform, and filamentous forms may also be encountered. Serology cannot be used for a rapid diagnosis of B. divergens infection. Amplification of babesial DNA by polymerase chain reaction, using species-specific primers may establish the diagnosis of both B. microti and B. divergens within 24 h. These assays are more sensitive than, but equally specific as, smear detection. Clearance of DNA seems to be related to disappearance of parasites.
Treatment and prevention
Chloroquine, sulphadiazine, co-trimoxazole, pentamidine, or diminazene aceturate appear ineffective in completely eliminating babesia parasites. For B. microti infection, the standard treatment is a combination of atovaquone (750 mg every 12 h) and azithromycin (500–1000 mg orally on day 1, and 250–1000 mg therafter) for 7 days. Alternatively, a combination of clindamycin (600 mg intravenously or orally) with quinine (650 mg orally) every 6 to 8 h for at least 7 days in adults; treatment for children is atovaquone (20 mg/kg every 12 h, maximum 750 mg/dose) and azithromycin (10 mg/kg per day on day 1 and 5 mg/kg per day thereafter) or alternatively a combination of clindamycin (7–10 mg/kg) and quinine (8 mg/kg) every 6 to 8 h for at least 7 days. For immunocompromised patients, a treatment for 6 weeks and 2 additional weeks after blood parasite clearance is recommended. For patients with high parasitaemias (≥ 10%), haemolysis, or renal failure or those that are immunocompromised, these therapies might not be sufficient and exchange transfusion should be considered.
In Europe, babesiosis should be treated as a medical emergency. Immediate chemotherapy with either a combination of clindamycine and quinine or clindamycin alone reduces parasitaemia and prevents extensive haemolysis and renal failure. Exchange transfusion should be used in fulminating B. divergens cases. Imidocarb dipropionate, which has been used for treatment of cattle babesiosis, has been successfully used in two patients in Ireland, although this drug is not approved for human treatment.
Preventive measures consist of use of repellents containing N,N-diethyl-3-methylbenzamide for clothing or skin, removing ticks from the skin, and avoiding exposure for asplenic and immunocompromised individuals. To date, no vaccine against human babesiosis is available.
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