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The presently used therapy for Babesia microti infections, a combination of quinine and clindamycin, does not always result in parasitologic cures. To identify possible alternative chemotherapeutic agents for such infections, we screened, in the hamster-B. microti system, 12 antiprotozoal drugs that have either recently been released for human use or were in experimental stages of development at the Walter Reed Army Institute of Research for the treatment of malaria and leishmaniasis. Several well-recognized antimalarial drugs, such as mefloquine, halofantrine, artesunate, and artelenic acid, exhibited little or no effect on parasitemia. Two 8-aminoquinolines, WR006026 [8-(6-diethylaminohexylamino)-6-methoxy-4-methylquinoline dihydrochloride] and WR238605 [8-[(4-amino-1-methylbutyl)amino]-2,6-dimethoxy-4-methyl-5 -(3-trifluoromethylphenoxy-7) quinoline succinate], produced clearance of patent parasitemia. Furthermore, blood from infected hamsters treated with WR238605 via an intramuscular injection failed to infect naive hamsters on subpassage, thus producing a parasitologic cure. These two compounds merit further screening in other systems and may prove useful in treating human babesiosis.

Blood smears from 13 patients infected with Babesia microti were reviewed to define the range of morphologic characteristics of the organism. Organisms resembling rings of Plasmodium falciparum were the predominant forms in all patients' blood smears. Babesia microti and Plasmodium spp. may be differentiated by the presence of pigment deposits in erythrocytes parasitized with mature stages of Plasmodium.

An indirect immunofluorescent test was used to determine antibody titers to Babesia microti in serum samples collected from 16 patients between 1 week and 1 year after the onset of illness. Titers rose to greater than or equal to 1:1,024 during the first few weeks of illness and then fell gradually to 1:16 to 1:256 over the next 5-6 months.

A 65-year-old man infected with Babesia microti failed to respond to therapy with oral chloroquine phosphate. He was then successfully dreated with diminazene aceturate, an experimental anti-protozoal agent. After his recovery from babesiosis, the patient developed acute idiopathic polyneuritis (Landry-Guillain-Barré Syndrome), which was probably related to his diminazene therapy.

An indirect immunofluorescence (IIF) test was performed with human sera to detect cross-reactivity of Babesia microti antibodies with other species of Babesia parasites, with other blood and tissue parasites, and with various tick-borne organisms. Antisera to B. microti cross reacted with other Babesia species, but at lower dilutions than with the homologous antigens, and occurred most often during the acute phase of the disease. Cross-reactions with antibodies to malaria, Colorado tick fever, and a variety of other parasitic diseases were uncommon. However, acute and convalescent phase sera from 4 patients with suspected or confirmed Rocky Mountain spotted fever showed a rise in titer to B. microti antigen. In addition, 6 of 185 serum samples from children on an Indian reservation in North Carolina had IIF titers of greater than or equal to 1:256, suggesting a possible focus of B. microti infections in humans.

We compared various methods for detecting Babesia microti infection in white-footed mice (Peromyscus leucopus) captured in enzootic regions of Massachusetts. The most sensitive method tested involved inoculating blood from wild rodents into hamsters. One month postinoculation proved to be the optimal time for microscopically examining blood of inoculated hamsters. With this method, as few as 300 organisms produced patent infection. Prior splenectomy of hamsters did not increase susceptibility to infection. For direct study of captured animals, a Giemsa-stained, thin blood-film prepared from the animal's tail was the most convenient method tested. However, this method detected only 61% of infections identified by hamster inoculation.

The host range of Babesia microti was studied on Nantucket Island in order to identify the enzootic reservoir of this human pathogen. White-footed mice (Peromyscus leucopus) were more frequently parasitized than were other indigenous animals. Infection was ubiquitous in locations where deer were abundant. Mice were most frequently parasitemic during spring and summer and adults more frequently than juveniles. Parasitemia, which was rarely intense, was sustained for as long as 4 months. Mice lived as long as 10 months, and juveniles were most abundant during early summer. Prevalence of zoonotic infection, in certain locations, appeared to be inversely correlated with abundance of mice. B. microti was present solely in regions harboring deer.

To learn more about the course of Babesia microti infections in primates, six Macaca mulatta monkeys with blood-induced B. microti infections were followed for 270 days with regular thick blood smears. Three of the monkeys experienced from 1--3 recurrences of parasitemia defined here as greater than or equal to 200 organisms/mm3 blood. Following splenectomy on day 297, parasitemia recurred in all animals, reaching levels of 1.9 x 10(5) to 2.7 x 10(6) organisms/mm3, and was associated with a moderately severe hemolytic anemia. These findings suggest that similar recurrences of parasitemia may occur in human cases, and that splenectomy may present a risk to persons with a past history of B. microti infection.

Between 1969 and 1977, 14 persons with parasitologically confirmed Babesia microti infections and seven persons with antibody titers to B. microti greater than or equal to 1:1,024 were identified on Nantucket Island, Massachusetts. Nineteen of these 21 persons were interviewed. About half were permanent residents of Nantucket; the others spent most of their summers on the island. There were 12 women and seven men. Patients ranged in age from 23 to 86 years; all of those with parasitologically confirmed infections were at least 49 years old. Fifteen patients had illnesses characterized by fever, chills, myalgia and fatigue. Five reported being bitten by a tick from 7 to 28 days before the onset of illness. Most cases occurred during July or August. There appeared to be no association between B. microti infection and direct contact with wild or domestic animals or specific outdoor activities. The unusual age distribution of patients with parasitologically confirmed B. microti infections may result because older persons tend to have more severe illnesses and thus are more likely to come to medical attention.

An indirect immunofluorescent antibody test was used to detect antibody to Babesia microti in human sera. Nine patients from Nantucket Island, Massachusetts infected with B. microti had serum titers greater than or equal to 1,024. Of 84 control sera from New York City residents, 246 sera from patients with possible exposure to ticks, and 36 sera from patients with suspected or confirmed tick bites, none was reactive at titers of 1:16 or above. The within-test reproducibility was within one fourfold dilution in 95% of trials. Test-to-test reproducibility was within one fourfold dilution in 33% of trials and within two fourfold dilutions in 100% of trials. Although cross-reactions among infected patients' sera and antigens of B. argentina, B. equi, B. bigemina, Plasmodium vivax, P. falciparum, and P. brasilianum were common, titers were highest to the homologous antigen.

For identifying drugs which might be effective in the treatment of human Babesia microti infections, 20 selected antiprotozoal agents or combinations of agents were tested for activity against B. microti in Mongolian jirds (meriones unguiculatus). 4-Methyl-primaquine and aromatic diamidines, including diminazene and pentamidine, were the most effective compounds tested.

To determine whether Ixodes dammini is capable of transmitting Babesia microti to primates, infected nymphal ticks were allowed to feed on five Macaca mulatta. The monkeys were then followed for at least 60 days with daily thick blood smears for evidence of infection. Patent B. microti parasitemia developed in four of the five animals. Prepatent periods were 13, 18, 20, and 28 days. Maximum parasitemia ranged from 83 to 7,068 organisms/mm3 blood. Splenectomy 15-17 months after exposure to ticks results in recurrences of parasitemia in three of the four infected monkeys.

Eight non-splenectomized Macaca mulatta were inoculated intravenously with strains of Babesia microti that originally were isolated from 2 human cases of babesiosis and then were maintained in hamsters in the laboratory. Patent infections developed in 7 animals with peak parasitemias of 496 to 3,906 organisms/mm3 blood. Prepatent periods ranged from 15 to 46 days. Parasitemia persisted for at least 90 days in all animals and in one, organisms were still present 559 days after inoculation.