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A Fatal Case of Babesiosis in Missouri: Identification of Another Piroplasm That Infects Humans

Barbara L. Herwaldt, MD, MPH; David H. Persing, MD, PhD; Eric A. Precigout, PhD; W. L. Goff, PhD; Dane A. Mathiesen, BS; Philip W. Taylor, MD; M. L. Eberhard, PhD; and Andre F. Gorenflot, PhD
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From the Centers for Disease Control and Prevention, Atlanta, Georgia; Mayo Clinic and Foundation, Rochester, Minnesota; Universite Montpellier, Montpellier, France; U.S. Department of Agriculture, Pullman, Washington; and Cape Girardeau Physician Associates, Cape Girardeau, Missouri. Acknowledgments: The authors thank the patient and his family and Patricia A. Conrad, DVM, PhD, Jennifer W. Dickerson, BA, K. Friedhoff, DMV (for provision of B. divergens in vitro antigen), Theodore J. Grieshop, MD, W. Carl Johnson, MS, Donald O. Miles, PhD, Stanley D. Sides, MD, John W. Thomford, PhD, Essie M. Walker, Doris A. Ware, and Marianna Wilson, MS, for their contributions. Grant Support: Dr. Persing is supported by Public Health Service grants AI32403, AR41497, and AI30548. Requests for Reprints: Barbara L. Herwaldt, MD, MPH, Centers for Disease Control and Prevention, Division of Parasitic Diseases, Mailstop F-22, 4770 Buford Highway NE, Atlanta, GA 30341-3724. Current Author Addresses: Drs. Herwaldt and Eberhard: Centers for Disease Control and Prevention, Division of Parasitic Diseases, Mailstop F-22, 4770 Buford Highway NE, Atlanta, GA 30341-3724.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1996;124(7):643-650. doi:10.7326/0003-4819-124-7-199604010-00004
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Objective: To characterize the etiologic agent (MO1) of the first reported case of babesiosis acquired in Missouri.

Design: Case report, serologic testing, animal inoculations, and molecular studies.

Setting: Southeastern Missouri.

Patient: A 73-year-old man who had had a splenectomy and had a fatal case of babesiosis.

Measurements: Serum specimens from the patient were assayed by indirect immunofluorescent antibody testing and immunoprecipitation for reactivity with antigens from various Babesia species. Whole blood obtained from the patient before treatment was inoculated into hamsters and jirds and into calves and bighorn sheep that had had splenectomy and were immunosuppressed with dexamethasone. Piroplasm-specific nuclear small-subunit ribosomal DNA was recovered from the patient's blood by using broad-range amplification with the polymerase chain reaction; a 144 base-pair region of the amplification product was sequenced; and phylogenetic analysis was done to compare MO1 with various Babesia species.

Results: Indirect immunofluorescent antibody testing showed that the patient's serum had strong reactivity with Babesia divergens, which causes babesiosis in cattle and humans in Europe, but that it had minimal reactivity with B. microti and WA1, which are the piroplasms previously known to cause zoonotic babesiosis in the United States. Immunoprecipitations showed that MO1 is more closely related to B. divergens than to B. canis (a canine parasite). None of the experimentally inoculated animals became demonstrably parasitemic. Phylogenetic analyses, after DNA sequencing, showed that MO1 is most closely related to B. divergens (100% similarity).

Conclusions: Although MO1 is probably distinct from B. divergens, the two share morphologic, antigenic, and genetic characteristics; MO1 probably represents a Babesia species not previously recognized to have infected humans. Medical personnel should be aware that patients in the United States can have life-threatening babesiosis even though they are seronegative to B. microti and WA1 antigen.


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Figure 1.
Giemsa-stained blood smear obtained on 2 July from a patient who acquired babesiosis in Missouri.

A. Ring stage, just after invasion of the erythrocyte by a merozoite. B. Trophozoite stage. C. Trophozoite stage with two budding merozoites (empty arrows). D. Two merozoites (empty arrows) joined by a residual body (full arrow). E. Paired piriform parasites. F. Tetrad form (“Maltese cross”). G. Polyparasitism. H. Crisis form. I. Crisis form.

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Figure 2.
Immunoprecipitations of radiolabeled antigens of Babesia divergens and Babesia canis.Top.B. divergensB. divergensBottom.B. divergensB. canis

Exposure time for the autoradiography was 15 days. . Lane 1: human serum collected about 150 days after infection with ; lane 2: serum (2 July) from patient infected with MO1; lane 3: serum from an uninfected human control. Lane 1: serum (2 July) from patient infected with MO1; lane 2: human serum collected about 150 days after infection with ; lane 3: dog immune serum directed against ; lane 4: serum from an uninfected human control; lane 5: serum from an uninfected dog control.

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Figure 3.
DNA sequences of a 144 base-pair region of the nuclear small-subunit ribosomal RNA gene of MO1 compared with those of other piroplasms and of Toxoplasma gondii.

None of the unidentified bases occurred at phylogenetically informative positions, and most were within highly conserved areas. A equals adenine; C equals cytosine; G equals guanine; N equals base that could not be definitively identified; T equals thymine; . equals gap in the sequence alignment.

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Figure 4.
Phylogenetic analysis.[25]Toxoplasma gondiinBabesia odocoileiB. canis[4-6][6]

Maximum parsimony analysis was done in PAUP (phylogenetic analysis using parsimony) version 3.1.1 by bootstrap using the branch and bound search method; was specified as an outgroup. Branch lengths are as indicated, and the percentages of bootstrap replicates ( = 100) associated with each group are shown in parentheses. (deer parasite) and (canine parasite) have not been shown to infect humans. The piroplasms WA1 and CA1 were isolated from persons who acquired babesiosis in Washington and California, respectively.

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