Severe Babesiosis

Severe babesiosis is infection with intraerythrocytic Babesia protozoa (Babesia microti, Babesia divergens, Babesia duncani and Babesia venatorum) with high parasitaemia, haemolysis and organ dysfunction. It is transmitted by Ixodes ticks, and also by blood transfusion and transplacentally.

Epidemiology. Babesia microti is endemic in the northeastern and upper midwestern United States, and Babesia divergens in Europe (mostly in splenectomised patients). Severe disease affects older adults, asplenic patients, those with HIV, cancer, immunosuppression or on rituximab, and patients with chronic heart, lung, liver or kidney disease. Mortality of hospitalised patients is about 6 to 9%, and higher in immunocompromised hosts.

Definition of severe disease. Parasitaemia of 10% or more, or organ complications: acute respiratory distress, disseminated intravascular coagulation, haemolytic anaemia (haemoglobin under 100 g/L), renal failure, hepatic compromise, heart failure or shock.

Pathophysiology. Parasites invade and lyse red cells, causing haemolytic anaemia and cytokine release. Infected red cells adhere to endothelium and cause microvascular obstruction, with an absent spleen preventing clearance.

Presentation is fever, drenching sweats, rigors, fatigue, myalgia, headache, anorexia, nausea, dark urine, jaundice, splenomegaly and hepatomegaly, after an incubation of 1 to 4 weeks (up to 9 weeks after transfusion). Severe cases develop ARDS, DIC, haemolytic crisis, acute kidney injury, congestive heart failure, splenic rupture and coma.

Red flags.

• Parasitaemia of 10% or more, or haemoglobin falling.
• Asplenia, immunosuppression or older age.
• Respiratory distress, renal failure or shock.

Thin blood film (intraerythrocytic rings, tetrads, "Maltese cross" forms) with percentage parasitaemia (repeat every 12 to 24 hours), nucleic acid amplification testing for Babesia, and serology (IgG, IgM). Full blood count (anaemia, thrombocytopenia), reticulocytes, lactate dehydrogenase, bilirubin, haptoglobin, direct antiglobulin test, creatinine, liver tests, coagulation, chest radiograph and blood cultures. Check for co-infection with Borrelia burgdorferi (Lyme disease), Anaplasma phagocytophilum and Powassan virus.

Differential diagnosis. Malaria (travel history, species identification), haemolytic anaemias, sepsis, anaplasmosis, ehrlichiosis, Lyme disease, leptospirosis and thrombotic microangiopathy.

Antimicrobial therapy (for 7 to 10 days; longer in immunocompromised patients).

• Preferred for severe disease: azithromycin 500 mg IV daily for the first day (or 250 to 500 mg daily) then 250 mg daily, plus atovaquone 750 mg orally every 12 hours.
• Alternative: clindamycin 600 mg IV every 6 hours plus quinine 650 mg orally every 8 hours (monitor QT, hypoglycaemia and cinchonism). Convert to oral clindamycin 600 mg every 8 hours.
• Immunocompromised hosts: treat for at least 6 weeks, including 2 weeks after parasites are no longer seen on smear, with consideration of higher doses of azithromycin (600 to 1000 mg daily) and specialist input for relapse.

Red cell exchange transfusion. Indications: parasitaemia of 10% or more, or severe haemolysis (haemoglobin under 100 g/L), or pulmonary, renal or hepatic compromise, and in asplenic patients. Aim to reduce parasitaemia to under 5%. Continue until parasitaemia is under 5% and clinical improvement. Simple transfusion for severe anaemia.

Supportive care. Oxygen, lung protective ventilation for ARDS, renal replacement for renal failure, fluids and vasopressors for shock, and treatment of DIC.

Co-infection. Add doxycycline 100 mg twice daily for 10 to 14 days for Lyme disease or anaplasmosis.

Prevention and reporting. Tick avoidance, blood donor screening in endemic regions, and notification where required.

Monitoring. Parasitaemia every 12 to 24 hours, haemoglobin, lactate dehydrogenase, creatinine, electrolytes, oxygen saturation, blood pressure and glucose (quinine).

Referral and escalation. Infectious disease specialists, haematology (exchange transfusion) and intensive care at once.

Special groups. In pregnancy, clindamycin with quinine or azithromycin with atovaquone, with obstetric input, and neonates are screened. In splenectomised patients, severe disease is likely and early exchange is considered. In renal impairment, adjust quinine.