Epidemiologic Notes and Reports Clindamycin and Quinine Treatment for Babesia microti Infections

Two cases of Babesia microti infection have recently been reported from Massachusetts. Both patients recovered after treatment with clindamycin and quinine.

Case 1: On July 22, 1982, a 73-year-old man residing in Nantucket, Massachusetts, had onset of fever (temperature of 38.3-39.4 C (101-103 F)) accompanied by malaise and weakness. Blood films on July 28 were negative for parasites. His symptoms continued, and he was hospitalized on July 31. His temperature was 39.7 C (103.4 F); he had no rash, and his spleen was not palpable. Hemoglobin was 14.9 g/dL, hematocrit, 44, and white blood cells (WBC), 4,600/mm((3)); B. microti were found in the blood film. Tetracycline was given orally (250 mg every 6 hours) but discontinued after 1 day and replaced by chloroquine (500 mg every 12 hours). Parasites were present after 2 days of treatment; chloroquine was replaced with ampicillin (500 mg orally every 6 hours) and trimethoprim (160 mg) plus sulfamethoxazole (800 mg orally every 12 hours). Serum obtained on August 2 had a 2048 were found in the blood film. Tetracycline was given orally (250 mg every 6 hours) but discontinued after 1 day and replaced by chloroquine (500 mg every 12 hours). Parasites were present after 2 days of treatment; chloroquine was replaced with ampicillin (500 mg orally every 6 hours) and trimethoprim (160 mg) plus sulfamethoxazole (800 mg orally every 12 hours). Serum obtained on August 2 had a 2048 antibody titer to B. microti by the indirect fluorescence antibody (IFA) test. On August 5, 50% of red blood cells (RBC) were parasitized. The next day, ampicillin and trimethoprim-sulfamethoxazole were discontinued, and clindamycin (300 mg intravenously (IV) every 6 hours) and quinine (650 mg orally every 6 hours) were given, along with two units of packed RBC. On August 7, parasitemia was 20%, and the patient's highest temperature was 38.1 C (100.6 F). On August 8, he was tachypneic with signs of mild pulmonary edema, but his temperature was normal, and the parasitemia had decreased to 5%. After blood had been obtained for parasitologic examination, the patient was given two additional units of packed RBC on August 8. Blood films on August 11 and thereafter during hospitalization were negative for parasites. Clinical improvement was apparent on August 11, with no further temperature elevations, and oral clindamycin (150 mg every 6 hours) was substituted for IV clindamycin. Quinine and clindamycin were discontinued on August 16, and the patient was discharged on August 17.

Blood films prepared on October 27 were still negative for parasites, and the patient's antibody titer to Babesia had decreased to 256 (specimen run in parallel with August 2 specimen). Hamsters inoculated with blood collected the same day were negative for parasites when tested on November 15 and 22.

Case 2: On August 22, 1982, a 60-year-old man was hospitalized in Concord, Massachusetts, with a splenic rupture. He was given four blood transfusions and was splenectomized the day after admission. He was discharged on August 30 after an uneventful post-operative course. On September 11, his temperature rose to 38.9 C (102 F). The patient was readmitted on September 13 with a temperature of 40 C (104 F) and shaking chills. Physical examination was normal. Hematologic values were as follows: hematocrit 34.6, hemoglobin 11.6 g, RBC 3.75 million, WBC 5200, and platelets 324,000/mm((3)). Blood films were positive for B. microti, with approximately 2.4% of RBC parasitized. Urine was 1+ for hemoglobin; total bilirubin was 1.6 and direct bilirubin, 0.6 mg/dL. Serum glutamic-pyruvic transaminase was 118, serum glutamic-oxaloacetic transaminase, 427 IU/L, and plasma hemoglobin, 10 mg dL. Chemotherapy with quinine (650 mg orally every 8 hours) and clindamycin (750 mg IV every 6 hours) was begun on September 13. Three days later, parasitemia was 1.4%, and 5 days after initiation of therapy, it had decreased to 0.1%. Blood films examined on September 18 and thereafter until discharge were negative for parasites. Low-grade fever continued until September 17, but signs of hemolysis had decreased and disappeared rapidly over the next 8 hours) and clindamycin (750 mg IV every 6 hours) was begun on September 13. Three days later, parasitemia was 1.4%, and 5 days after initiation of therapy, it had decreased to 0.1%. Blood films examined on September 18 and thereafter until discharge were negative for parasites. Low-grade fever continued until September 17, but signs of hemolysis had decreased and disappeared rapidly over the next few days. The patient was discharged on September 24 after completing a 10-day course of quinine-clindamycin treatment.

Serum specimens collected on September 13 and 14 had a B. microti antibody titer of 256 by IFA. Blood obtained on September 14 produced infection in hamsters in 1 week. Hamsters inoculated with blood collected from the patient on October 6 showed no evidence of infection 10 weeks later.

Blood from the four donors inoculated into hamsters resulted in no infections during a 6-week observation period. None of the donors had antibody to B. microti. Reported by GJ Dammin, MD, A Spielman, SD, Harvard School of Public Health; EB Mahoney, MD, Nantucket Cottage Hospital, Nantucket Island, MA; EF Bracker, MD, K Kaplan, MD, Emerson Hospital, Concord, MA; Protozoal Diseases Br, Div of Parasitic Diseases, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: B. microti is an intraerythrocytic protozoan parasite resembling Plasmodium falciparum. Natural transmission occurs through the bite of an infected tick (Ixodes dammini), but transfusion-induced infections have been recognized since 1979 (1,2). A spectrum of infections, ranging from asymptomatic to severe, life-threatening disease with fever, chills, and hemolytic anemia may occur. Splenectomized patients are more likely to have severe infections, but as this report illustrates, high parasitemia with hemolysis may also occur in spleen-intact patients (2,3). Most cases occur in late summer and early fall. Of the 17 patients with babesiosis reported to CDC in 1982, most were visitors or residents of Long Island or Shelter Island, New York, and Nantucket, Massachusetts.

Treatment of severe infection has had only limited success. Although chloroquine has been reported to give symptomatic relief, the drug does not appreciably affect parasitemia in hamsters or humans (4,5). Other anti-malarial drugs, such as quinacrine, primaquin, pyrimethamine, pyrimethamine-sulfadoxine, sulfadiazine, and tetracycline, have no effect on parasitemia in animals (5,6). Similarly, pentamidine is of questionable efficacy in humans (3,7,8) and is ineffective against B. microti in animals (5,6). Another anti-trypanosomal drug (diminazene aceturate) seemed effective against B. microti in one patient; however, his recovery was complicated by development of Guillain-Barre syndrome (7). Guillain-Barre was never definitively linked to the drug, but there has been reluctance to use it again.

The effectiveness of quinine-clindamycin against B. microti was first suggested when the drug combination was used to treat a patient with presumed chloroquine-resistant P. falciparum malaria, but in whom babesiosis was later diagnosed. Parasitemia was 8% at the beginning of therapy and decreased to 0% by day 7 of treatment (1). The efficacy of clindamycin and quinine in treating malaria caused by multidrug-resistant strains of P. falciparum was reported in 1974 (6). Why this drug combination should be effective against B. microti is unclear, since quinine alone has been reported to be ineffective against B. microti in humans and animals (8,10), and clindamycin alone has produced contradictory results in experimentally infected animals. Clindamycin was effective against B. microti in hamsters, but had no appreciable effect on parasitemia in mongolian jirds (6,10). Quinine plus clindamycin was reported more effective against B. microti than clindamycin alone in hamsters (10).

Cases 1 and 2 in the current report provided the first opportunity to evaluate prospectively the efficacy of quinine-clindamycin. Parasitemia decreased more rapidly than has been observed after using any other chemotherapeutic agent. Failure to infect hamsters with blood from these patients after treatment provides strong evidence that parasites were eradicated from their blood rather than reduced to a number undetectable by blood smears. While these results are encouraging, it must be emphasized that many patients with babesiosis have a mild clinical course and recover without specific anti-babesia chemotherapy. Therefore, it is recommended that treatment be reserved for seriously ill patients and that parasitologic response, as well as adverse reactions to treatment, be carefully recorded to provide a better picture of the efficacy of this drug regimen in a larger group of patients.

References

1. Wittner M, Rowin KS, Tanowitz HB, et al. Successful chemotherapy of transfusion babesiosis. Ann Intern Med 1982; 96:601-4.

2. Jacoby GA, Hunt JV, Kosinski KS, et al. Treatment of transfusion-transmitted babesiosis by exchange transfusion. N Eng J Med 1980; 303:1098-100.

3. Cahill KM, Benach JL, Reich LM, et al. Red cell exchange: treatment of babesiosis in a splenectomized patient. Transfusion 1981; 21:193-8.

4. Ruebush TK, 2d, Cassaday PB, Marsh HJ, et al. Human babesiosis on Nantucket Island: clinical features. Ann Intern Med l977; 86:6-9.

5. Miller LH, Neva FA, and Gill F. Failure of chloroquine in human babesiosis (Babesia microti): case report and chemotherapeutic trials in hamsters. Ann Intern Med l978; 88:200-2.

6. Ruebush TK, 2d, Contacos PG, Steck EA. Chemotherapy of Babesia microti infections in mongolian jirds. Antimicrob Agents Chemother 1980; 18: 289-91.

7. Ruebush TK, 2d, Rubin RH, Wolpow ER, Cassady PB, Schultz MG. Neurologic complications following the treatment of human Babesia microti infection with diminazene aceturate. Am J Trop Med Hyg 1979; 28: 184-9. microti infections in mongolian jirds. Antimicrob Agents Chemother 1980; 18: 289-91.

8. Ruebush TK, 2d, Rubin RH, Wolpow ER, Cassady PB, Schultz MG. Neurologic complications following the treatment of human Babesia microti infection with diminazene aceturate. Am J Trop Med Hyg 1979; 28: 184-9.

9. Francioli PB, Keithly JS, Jones TC, Brandstetter RD, Wolf DJ. Response of babesiosis to pentamidine therapy. Ann Intern Med 1981; 94: 326-30.

10. Miller LH, Glew RH, Wyler DJ, et al. Evaluation of clindamycin in combination with quinine against multidrug-resistant strains of Plasmodium falciparum. Am J Trop Med Hyg 1974; 23:565-9.

11. Rowin KS, Tanowitz HB, Wittner M. Therapy of experimental babesiosis. Ann Intern Med 1982;97:556-8.

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