Download Babesiosis Two Atypical Cases From Minnesota and a Review

Microbiology and Infectious Disease / BABESIOSIS
Babesiosis
Two Atypical Cases From Minnesota and a Review
Suman Setty, MD, PhD,1 Zena Khalil, MD,2 Pamela Schori, MT(ASCP),2 Miguel Azar, MD,2
and Patricia Ferrieri, MD1
Key Words: Babesia; Ixodes scapularis; Extraerythrocytic forms; Transfusion-related transmission
DOI: 10.1309/N3DP9MFPNUJD4XJY
Abstract
We present 2 atypical cases of babesiosis and a
review of babesiosis. The first patient was a 72-year-old
man with an intact spleen, who had marked
intravascular hemolysis. His RBCs were parasitized
heavily with trophozoites of Babesia, and he had a large
number of extracellular aggregates of Babesia. The
infection did not respond to oral antibiotic therapy, and
he required an RBC exchange transfusion. The second
patient was a 29-year-old man who had undergone
splenectomy and who had multiple episodes of fever
and gastrointestinal symptoms for 4 months, with
partial response to antibiotics. Thin smears revealed
both intraerythrocytic and extraerythrocytic forms in
very low numbers. The infection responded promptly to
clindamycin and quinine therapy.
The varying clinical manifestations, from acute to
chronic, at a wide range of ages and often the difficulty
of detection by routine blood smears make it necessary
that a high index of clinical suspicion be present for
prompt diagnosis. With increasing numbers of cases of
transfusion-transmitted babesiosis being reported,
protection of the blood supply is essential.
554
554
Am J Clin Pathol 2003;120:554-559
DOI: 10.1309/N3DP9MFPNUJD4XJY
Babesia species are tick-borne, intraerythrocytic
protozoa that are well-known pathogens in animals. During
the past 3 decades, they have been recognized as occasional
pathogens in humans. Most infection passes undetected,
especially in healthy adults with an intact spleen. However,
occasionally in people who have undergone splenectomy and
in immunocompromised people, Babesia infection may be
severe and life-threatening. We report 2 contrasting cases of
babesiosis, one in a 72-year-old man with an intact spleen
who did not respond to oral therapy and the other in a 29year-old man who had undergone splenectomy. They both
had numerous extracellular organisms. We also review the
literature on babesial infection.
Case 1
A 72-year-old man was admitted to the Veterans Affairs
Medical Center, Minneapolis, MN, in mid-August, with fever
and shaking chills for a week. He had been camping several
times during the previous month in the area of Hinckley, MN.
He had no history of insect bite. His hemoglobin concentration dropped 3 g/dL (30 g/L) during the 3 days after admission. His lactate dehydrogenase level was elevated markedly,
and his laboratory test results were consistent with intravascular hemolysis. The patient’s medical history included colon
cancer and subsequent surgery. Physical examination
revealed no hepatomegaly or splenomegaly. The patient was
not taking any medication at the time of admission.
Microscopic examination of a blood smear obtained 3 days
after admission revealed intraerythrocytic ❚Image 1A❚ and extracellular trophozoites of Babesia. Numerous classic “Maltese
© American Society for Clinical Pathology
Microbiology and Infectious Disease / ORIGINAL ARTICLE
cross” forms (tetrads) were identified ❚Image 1B❚. Heavy parasitization of erythrocytes and large extracellular clusters of
trophozoites were present ❚Image 1C❚. Pleomorphism of the
ring forms, lack of synchronous stages, absence of hemozoin,
and a history of exposure to the wooded areas in an endemic
region during the feeding time of the Ixodes scapularis nymph
were consistent with Babesia infection. A search for a simultaneous infection with Ehrlichia was negative on buffy coat
smear. The buffy coat preparation seemed to have numerous
Babesia inclusions in the WBCs, which gave a false impression
of intracellular infection. The findings on the buffy coat were
assumed to be due to the numerous extracellular forms overlying the WBCs. Therapy with oral clindamycin and quinidine
were initiated. The patient’s RBCs continued to hemolyze, and
he received a 1-volume exchange transfusion with packed,
washed RBCs. His hemoglobin rose by 3 g/dL (30 g/L) after
the procedure and remained stable thereafter.
A
C
Case 2
A 29-year-old man was admitted to the University of
Minnesota Hospitals, Minneapolis, in July, with fever
(temperature up to 103°F [39.5°C]), chills, headache, neck
stiffness, and photophobia for 4 days. This was the third
episode during the last 4 months. The previous episode had
been similar, with associated arthralgia, diarrhea, and cough.
He had an intermittent, blotchy, red rash on the epigastrium.
He received an amoxicillin–clavulanate potassium combination drug for the first 2 episodes, which resulted in partial
relief of symptoms. The intervals between acute episodes
were associated with fatigue, night sweats, and loss of
appetite. He had no history of insect bite. His hemoglobin
concentration at the last admission was 9.2 g/dL (92 g/L),
with slightly elevated total bilirubin and liver enzyme levels.
His medical history included a splenectomy 15 years earlier
B
❚Image 1❚ A, Thin smear of venous blood showing
pleomorphism of Babesia trophozoites (arrows) in RBCs
(Wright-Giemsa, ×100). B, A blood smear showing a classic
tetrad (arrow) in an RBC arranged in the form of a Maltese
cross (Wright-Giemsa, ×100). C, Extracellular ring trophozoites
(arrow) (Wright-Giemsa, ×100).
Am J Clin Pathol 2003;120:554-559
© American Society for Clinical Pathology
555
DOI: 10.1309/N3DP9MFPNUJD4XJY
555
555
Setty et al / BABESIOSIS
for a posttraumatic rupture of the spleen. The physical examination revealed no hepatomegaly. The patient was not taking
any medication at the time of admission.
Microscopic examination of a Giemsa-stained blood
smear obtained at admission revealed a low number of
intraerythrocytic and extracellular trophozoites of Babesia.
A rare classic “Maltese cross” (tetrads) was identified. Small
extracellular clusters of trophozoites were present. A search
for a simultaneous infection with Ehrlichia was negative on
thin- and thick-smear preparations. The Lyme antibody titer
was negative. Therapy with oral clindamycin and quinine
was initiated. His condition improved within 8 days, and he
was discharged from the hospital.
Epidemiology and Life Cycle
Babesiosis is a zoonotic disease caused by protozoa in
the phylum Apicomplexa, order Piroplasmorida that parasitize erythrocytes of wild and domestic animals. The first
epidemic of Babesia probably occurred in biblical times
when it resulted in infection of the cattle of Pharaoh Ramses
II. In 1888, Babes described “intraerythrocytic bacteria” as
responsible for the death of 30,000 to 50,000 head of
Romanian cattle with febrile hemoglobinuria.1 In 1893,
Smith and Kilborne2 recognized Babesia as a protozoan
transmitted by a blood-sucking tick. The first human case of
babesiosis, believed to be caused by Babesia bovis, was
reported in 1957 in a 33-year-old asplenic farmer from the
former Yugoslavia.3 In 1969, the first case of babesiosis in a
patient with an intact spleen was reported from Nantucket
Island, MA, and was caused by Babesia microti.4
Babesiosis is endemic to Europe and the northeastern
islands, mainland, upper Midwest, and the West Coast of the
United States. Of the approximately 99 species of Babesia,
few are known to infect humans. In Europe, Babesia divergens and B bovis are cattle strains that cause a severe and
often fatal disease, particularly in people who have undergone splenectomy, whereas B microti, in North America,
infects patients with intact spleens and produces a milder and
often asymptomatic disease. Two newly described strains of
Babesia affect immunocompetent patients in the United
States: WA1 described in Washington State and Babesia
MO1 in Missouri.5-7
Ixodes dammini is the vector for transmission of
babesiosis in the northeastern areas of the United States. In
the southern United States, the name I scapularis has been
used for the same vector. The vector in the western United
States is Ixodes pacificus. The sexual stage occurs in the tick
where transmission from larva to nymph (transstadial transmission) occurs. The larval and nymph stages of the tick
feed on the naturally infected white-footed mouse
556
556
Am J Clin Pathol 2003;120:554-559
DOI: 10.1309/N3DP9MFPNUJD4XJY
(Peromyscus leucopus, the reservoir host), which remains
parasitemic for life, while the adult tick favors the whitetailed deer, Odocoileus virginianus.
Transmission, Clinical Findings, and
Pathogenesis
Babesia sporozoites are transmitted to humans mostly
by the bite of the Ixodes nymph and occasionally by the
adult tick. In the infected nymph, the organism migrates to
the salivary gland. The nymph then seeks a blood meal and
infects another rodent or human by injecting sporozoites into
the bloodstream. The sporozoites enter the erythrocytes,
possibly by binding to the C3 in the circulation and attaching
to the erythrocytic C3b receptors, as observed in Babesia
rodhaini.8 The sporozoites undergo asexual budding into 4
merozoites, followed by perforation of the RBC membrane,
leading to hemolysis. The merozoites then infect other
RBCs; the parasites become trophozoites and can divide by
binary fission, creating the ring forms and tetrads seen in
erythrocytes on stained blood smears. Usually, 1% to 10% of
the RBCs are parasitized. However, up to 85% parasitemia
has been noted.9 The disease is mild to asymptomatic in
healthy people. However, overwhelming infection is seen in
immunocompromised and asplenic patients in the United
States and in most cases in Europe.
Another mode of transmission to humans is via blood
transmission, with longer incubation periods (6-9 weeks)
than after a bite (1-3 weeks).10 Transmission of more than 20
cases of babesiosis by RBC and blood component transfusion has been reported.11-13 In addition, the variant WA1 also
has been associated with transfusion-associated babesiosis.12
Parasitemia in humans is transient and episodic. For this
reason, there is a risk of asymptomatic donors transmitting
the disease to recipients. These parasites can remain viable
under blood bank conditions, at a temperature of 4°C for up
to 35 days in packed RBCs and platelet concentrates that
contain residual erythrocytes. Because Babesia has been
described as an intraerythrocytic parasite, plasma transfusion
has not usually been believed to be associated with a risk of
transmission.
When symptoms occur, they are nonspecific and include
fatigue, anorexia, myalgia, nausea, headache, sweating
rigors, abdominal pain, emotional lability, depression, and
dark urine.14 Acute respiratory symptoms, including edema,
may appear during the course of the disease.15 Renal function also is affected occasionally. Reduced platelet counts are
observed, with a direct Coombs test result occasionally being
positive. The mechanism for this is not known.
Pathogenesis has not been defined clearly. Abnormal
erythrocytes are retained by the spleen and ingested by
© American Society for Clinical Pathology
Microbiology and Infectious Disease / ORIGINAL ARTICLE
macrophages; therefore, disease is more severe in asplenic
patients. Complement activation by Babesia may lead to
generation of tumor necrosis factor and interleukin-1 release,
causing fulminant symptoms. 16 Decreased complement
levels of C3, C4, and CH50 are seen in Babesia infection.
Also, increased C1q binding activity owing to immune
complexes is present.17
Prevalence
The prevalence of human babesiosis is difficult to
measure, owing to the asymptomatic nature of the infection.
Several surveys have shown the presence of Babesia antibodies in asymptomatic individuals. Krause et al18 demonstrated that the prevalence of Babesia increased in
Connecticut during a 30-year period (1959-1989). In their
study, there was no evidence of babesial infection in residential college students between 1959 and 1963, whereas 2.9%
were positive for Babesia antibodies between 1986 and
1989, and the prevalence remained constant during the
following 5 years. A serosurvey in Block Island, RI, where
Babesia is endemic, showed that 9% of the population (12%
of children and 8% of adults) was seropositive; in
Connecticut, 21% of the population (16% of children and
22% of adults) was seropositive.19
The parasite that once was confined to a circumscribed
area in New England has been now reported in Maryland,
Virginia, Wisconsin, Minnesota, Washington State (WA1),
and Missouri (MO1). The reason for this geographic spread
seems, in part, to be linked to the expanding population of
white-tailed deer in the eastern half of the United States. As
the deer population has increased, so has the habitat range of
I dammini. As a consequence, more people will be exposed
to infection with Babesia in the coming years. More cases of
transfusion-associated transmission also are likely, given the
increase in the range of the tick, the increase in the deer
population, and the general increase in travel by North
Americans. Since the same tick and primary host also harbor
the organisms for Lyme disease and ehrlichiosis, many
donors may have dual or triple infections.20-22
Krause et al23 reported that 24 of 46 Babesia-infected
subjects, who received no specific treatment, had Babesia
DNA detectable in their blood for an average of 82 days. One
subject in that study had recrudescent disease after 2 years, at
a time when the risk of reinfection was nil. The recrudescence
occurred when the patient became immunocompromised after
developing cancer. It, therefore, seems that when left
untreated, silent babesial infection may persist for months or
even years. Parasitemia has been observed to wax and wane
in infected asymptomatic donors, even without treatment. For
example, a donor with WA1 infection was parasitemic more
than 7 months after donation and was found, in retrospect, to
have been parasitemic more than 6 months before donation.6
Diagnosis
Diagnosis is based on clinical suspicion and history of
exposure. Thin and thick smears stained with Giemsa will
demonstrate the presence of trophozoites in the RBCs.24 It is
necessary to examine 200 to 300 oil immersion fields before
declaring a specimen negative. Also, a single negative set of
blood smears does not rule out a Babesia infection. As in the
examination of smears for the presence of malarial parasites,
multiple sets of blood films must be examined before
concluding that a patient does not have babesiosis. The parasite often is undetectable in the thin-smear preparation,
which makes careful examination of the thick-smear preparation imperative. Automated instruments have been reported
to fail to detect Babesia.25 The organism may be misdiagnosed as Plasmodium species owing to its ring conformation,
the presence of a single chromatin dot, and a peripheral location in the erythrocytes. However, it can be distinguished
from Plasmodium species by the absence of travel history
outside the United States, pleomorphism of the ring forms,
Maltese cross formation, lack of hemozoin, and lack of
stages other than the ring form. Additionally, the presence of
smaller rings without central pigment can help distinguish
Babesia species from Plasmodium species. Although the
presence of tetrad formations often is mentioned as a diagnostic aid, the forms often are not found, and, therefore,
diagnosis must be based on the pleomorphic appearance of
the ring forms. Occasionally, trophozoites may be seen
outside erythrocytes with Babesia infection.9
Indirect fluorescent antibody titers of more than 1:1,024
indicate active infection; a titer of 1:256 or more is diagnostic, and a titer of 1:32 or more indicates previous infection.26 Various polymerase chain reaction detection assays
are available for detection of B microti and other
species.6,23,27-30 A study by Homer and coworkers27 has
demonstrated that species-specific primers can be designed
for B microti. Confirmation can be obtained by intraperitoneal inoculation of 1.0 mL of EDTA-anticoagulated whole
blood into the peritoneum of golden hamsters followed by
smear positivity in 2 to 4 weeks.
Prevention
Prevention consists of avoiding tick habitats during the
tick-biting season, protective clothing, and use of diethyltoluamide insect repellent or permethrin spray. Inspection of pets
for ticks and removal of ticks with tweezers are appropriate.
Am J Clin Pathol 2003;120:554-559
© American Society for Clinical Pathology
557
DOI: 10.1309/N3DP9MFPNUJD4XJY
557
557
Setty et al / BABESIOSIS
Effective measures for prevention of transfusion-transmitted babesiosis are needed. Babesia is the most commonly
reported cause of transfusion-transmitted parasitic infection in
the United States. Microscopic methods are not very sensitive,
since the level of parasitemia may be low. Clinically overt
cases of babesiosis should not pose a risk of transmitting the
disease via blood transfusion since the affected patients are
unlikely to be blood donors. It is the asymptomatic infected
would-be donor who is important to identify. No test is in
routine use for mass screening of blood donors for Babesia
infection. Donor-screening methods include a subjective evaluation of the donor’s health and objective methods such as the
measurement of temperature and hemoglobin concentration,
each of which would exclude some individuals with a Babesia
infection. The results of some studies indicate that additional
medical history would not be useful.31
Another approach would be to avoid collecting blood in
endemic areas, particularly during the spring and summer.
Studies have shown this approach to have limited value,31
based on a statistically insignificant difference in seropositivity in endemic and nonendemic areas. In addition, the loss
of healthy donors would adversely affect the blood supply.
Finally, donors who have a history of babesiosis are
currently deferred indefinitely because of the possibility of
ongoing infection.32 More data are needed to determine the
efficacy of antimicrobials in eradicating the parasite. In areas
where babesiosis is endemic, blood-donor screening for B
microti and other species by means of polymerase chain
reaction–based methods is being studied. A higher degree of
safety of blood transfusion would be reached if new methods
were available for inactivating these parasites. Inactivation of
Babesia in RBC and platelet preparations, by photosensitization using lipophilic pheophorbide derivatives, seems to be a
promising approach.33,34
Treatment
The standard regimen for the treatment of Babesia
infection consists of a combination of antibiotics, clindamycin, and quinine. This regimen is fairly effective for
most cases of Babesia infection. However, with high levels
of parasitemia (more than 10%), marked hemolysis occurs.
In these cases, there is a role for the blood bank in treatment.
Exchange transfusion, accompanied by clindamycin and
quinine therapy, is a lifesaving procedure.35 This technique
simultaneously lowers the parasite load and replaces the
patient’s plasma.
The standard regimen of clindamycin and quinine
frequently causes adverse reactions. An alternative treatment
with atovaquone and azithromycin was noted to be as effective and associated with significantly fewer adverse effects.36
558
558
Am J Clin Pathol 2003;120:554-559
DOI: 10.1309/N3DP9MFPNUJD4XJY
Discussion
The spread of Babesia infection and blood transmission
of the organism have renewed our interest in studying this
organism. Fevers of unknown origin in patients with a
history of travel to areas endemic for the Ixodes tick should
result in a high index of suspicion, and a search for Babesia,
Borrelia, and Ehrlichia infections should be instituted, since
they might occur simultaneously, particularly with the latter
2 genera.
Historically, Babesia has been described predominantly
as an intracellular parasite. An earlier abstract and a subsequent report from Massachusetts described the presence of
extracellular forms detected by blood smears.37,38 Both of
our cases, with low and high parasite numbers, had extracellular forms, which suggests the possibility of transmission by
plasma and platelet products. There is a risk of asymptomatic
blood donors transmitting the parasite to recipients of their
blood products. This is important to note since Babesia
infection reportedly can recur for up to 2 years without a new
exposure. The first line of treatment is oral therapy with both
clindamycin and quinine. In case of a high level of parasitemia (above 10%), an RBC exchange transfusion may be
lifesaving.
From the 1Department of Laboratory Medicine and Pathology,
University of Minnesota Medical School, and the 2Department of
Laboratory Medicine, Veterans Affairs Medical Center,
Minneapolis.
Address correspondence to Dr Setty: Box 609, UMHC, 420
Delaware St SE, Minneapolis, MN 55455.
References
1. Babes V. Sur l’hemoglobinurie bacterienne boeuf. Comptes
Rendus de Acad Sci III. 1888;107:692-694.
2. Smith T, Kilborne FL. Investigations Into Nature, Causation and
Prevention of Texas or Southern Cattle Tick Fever. Washington,
DC: US Department of Agriculture; 1893:177-304. Bureau of
Animal Industries Bulletin 1.
3. Skrabalo Z, Deanovic Z. Piroplasmosis in man: report on a
case. Doc Med Geogr Trop. 1957;9:11-16.
4. Western KA, Benson GD, Gleason NN, et al. Babesiosis in a
Massachusetts resident. N Engl J Med. 1970;283:854-856.
5. Quick RE, Herwaldt BL, Thomford JW, et al. Babesiosis in
Washington State: a new species of Babesia. Ann Intern Med.
1993;119:284-290.
6. Thomford JW, Conrad PA, Telford SR III, et al. Cultivation
and phylogenetic characterization of a newly recognized human
pathogenic protozoan. J Infect Dis. 1994;169:1050-1056.
7. Herwaldt BL, Persing DH, Precigout EA, et al. A fatal case of
babesiosis in Missouri: identification of another piroplasm
that infects humans. Ann Intern Med. 1996;124:643-650.
8. Jack RM, Ward PA. Babesia rodhaini interactions with
complement: relationship to parasitic entry into red cells.
J Immunol. 1980;124:1566-1573.
© American Society for Clinical Pathology
Microbiology and Infectious Disease / ORIGINAL ARTICLE
9. Gelfand, JA. Babesia. In: Mandell GL, Bennett JE, Douglas
RG, et al, eds. Mandell, Douglas, and Bennett’s Principles and
Practice of Infectious Diseases. 5th ed. New York, NY:
Churchill Livingstone; 2000:2899-2902.
10. Anderson JF, Mintz ED, Gadbaw JJ, et al. Babesia microti,
human babesiosis, and Borrelia burgdorferi in Connecticut.
J Clin Microbiol. 1991;29:2779-2783.
11. McQuiston JH, Childs JE, Chamberland ME, et al, for the
Working Group on Transfusion Transmission of Tick-Borne
Diseases. Transmission of tick-borne agents of disease by
blood transfusion: a review of known and potential risks in
the United States. Transfusion. 2000;40:274-284.
12. Herwaldt BL, Kjemtrup AM, Conrad PA, et al. Transfusion
transmitted babesiosis in Washington State: first reported case
caused by a WA1-type parasite. J Infect Dis. 1997;175:12591262.
13. Linden JW, Wong SJ, Chu FK, et al. Transfusion-associated
transmission of babesiosis in New York State. Transfusion.
2000;40:285-289.
14. Gelfand JA, Callahan MV. Babesiosis. Current Clin Top Infect
Dis. 1998;18:201-216.
15. Boustani MR, Lepore TJ, Gelfand JA, et al. Acute respiratory
failure in patients treated for babesiosis. Am J Respir Crit Care
Med. 1994;149:1689-1691.
16. Okusawa S, Yancey KB, van der Meer JWM, et al. C5a
stimulates secretion of tumor necrosis factor from human
mononuclear cells in vitro: comparison with secretion of
interleukin 1 beta and interleukin 1 alpha. J Exp Med.
1988;168:443-448.
17. Benach JL, Habicht GS, Hamburger MI.
Immunoresponsiveness in acute babesiosis in humans. J Infect
Dis. 1982;146:369-380.
18. Krause PJ, Telford SR III, Ryan R, et al. Geographical and
temporal distribution of babesial infection in Connecticut.
J Clin Microbiol. 1991;29:1-4.
19. Krause PJ, Telford SR III, Pollack RJ, et al. Babesiosis: an
underdiagnosed disease of children. Pediatrics. 1992;89(6 pt
1):1045-1048.
20. Meldrum SC, Birkhead GS, White DJ, et al. Human
babesiosis in New York State: an epidemiological description
of 136 cases. Clin Infect Dis. 1992;15:1019-1023.
21. Stafford KC, Massung RF, Magnarelli LA, et al. Infection
with agents of human granulocytic ehrlichiosis, Lyme disease,
and babesiosis in wild white-footed mice (Peromyscus
leucopus) in Connecticut. J Clin Microbiol. 1999;37:28872892.
22. Varde S, Beckley J, Schwartz I. Prevalence of tick-borne
pathogens in Ixodes scapularis in a rural New Jersey County.
Emerg Infect Dis. 1998;4:97-99.
23. Krause PJ, Spielman JA, Telford SR III, et al. Persistent
parasitemia after acute babesiosis. N Engl J Med.
1998;339:160-165.
24. Seabolt JP. Babesia: challenges for the medical technologist.
Lab Med. 1982;13:547-551.
25. Brucker DA, Garcia LS, Shimizu RY, et al. Babesiosis:
problems in diagnosis using autoanalyzers. Am J Clin Pathol.
1985;83:520-521.
26. Ruebush TK II, Chisolm ES, Sulzer AJ, et al. Development
and persistence of antibody in persons infected with Babesia
microti. Am J Trop Med Hyg. 1981;30:291-292.
27. Homer MJ, Bruinsma ES, Lodes MJ, et al. A polymorphic
multigene family encoding an immunodominant protein from
Babesia microti. J Clin Microbiol. 2000;38:362-368.
28. Homer MJ, Aguilar-Delfin I, Telford SR III, et al. Babesiosis.
Clin Microbiol Rev. 2000;13:451-469.
29. Persing DH, Mathiesen D, Marshall WF, et al. Detection of
Babesia microti by polymerase chain reaction. J Clin Microbiol.
1992;30:2097-2103.
30. Persing DH, Herwaldt BL, Glaser C, et al. Infection with a
Babesia-like organism in northern California. N Engl J Med.
1995;332:298-303.
31. Popovsky MA, Lindberg LE, Syrek AL, et al. Prevalence of
Babesia antibody in a selected blood donor population.
Transfusion. 1988;28:59-61.
32. Vengelen-Tyler V, ed. Infectious complications of blood
transfusion. In: Technical Manual. 13th ed. Bethesda, MD:
American Association of Blood Banks; 1999:625.
33. Grellier P, Santus R, Mouray E, et al. Photosensitized
inactivation of Plasmodium falciparum and Babesia
divergens–inactivated erythrocytes in whole blood by
lipophilic pheophorbide derivatives. Vox Sang. 1997;72:211220.
34. Corash L. Inactivation of viruses, bacteria, protozoa and
leucocytes in platelet concentrates. Vox Sang. 1998;74(suppl
2):173-176.
35. Dorman SR, Cannon ME, Telford SR III, et al. Fulminant
babesiosis treated with clindamycin, quinine and whole blood
exchange transfusion. Transfusion. 2000;40:375-380.
36. Krause PJ, Lepore T, Sikand VK, et al. Atovaquone and
azithromycin for the treatment of babesiosis. N Engl J Med.
2000;343:1454-1458.
37. Setty S, Khalil Z, Schori P, et al. Babesiosis: two contrasting
cases [abstract]. Am J Clin Pathol. 2000;114:300.
38. Pantanowitz L, Cannon ME. Extracellular Babesia microti
parasites. Transfusion. 2001;41:440.
Am J Clin Pathol 2003;120:554-559
© American Society for Clinical Pathology
559
DOI: 10.1309/N3DP9MFPNUJD4XJY
559
559