Babesia
Introduction
Babesia is a protozoan parasite of the blood that causes
a hemolytic disease known as Babesiosis. There are over 100 species of Babesia identified however only a handful of species
have been documented as pathogenic in humans [8]. In the United States, Babesia
microti is the most common
strain associated with humans with other species infecting cattle, livestock
and occasionally domestic animals [1][2]. People who contract Babesiosis suffer
from malaria-like symptoms. As a result malaria is a common misdiagnosis for
the disease.
Agent
(Classification and Taxonomy)
Babesia is a protozoan parasite with a taxonomic
classification as seen in Table 1. Babesia microti (B. microti) and Babesia
divergens (B. divergens) are the two species to most frequently infect
humans. Infections from other species of Babesia have been documented in humans but are not
habitually seen.
Table
1 [3][4]
Kingdom |
Eukaryota |
Phylum |
Alveolata |
Class |
Apicomplexa |
Order |
Aconoidasida |
Family |
Piroplasmida |
Genus |
Babesiidae |
Species |
Over
100 species Babesia
Microti Babesia
divergens |
Synonyms
Babesiosis
can also be known as Prioplasmosis [1]. Due to historical misclassifications,
the protozoa was labeled with many names that are no longer used. Common names
of the disease include Texas Cattle Fever, Redwater Fever, Tick Fever, and
Nantucket Fever [2].
History
of Discovery
For
centuries, Babesiosis was known to be a serious illness for wild and domestic
animals especially cattle. Victor Babes, a Romanian scientist who first
documented the disease in 1888, described symptoms of a severe hemolytic
illness seen uniquely in cattle and sheep [2].
(Image
1 Victor Babes). Some years later, Americans Theobald Smith and Fred Kilborne
identified the parasite as the cause of Texas Cattle Fever, the same disease
described by Babes. Smith and Kilborne also identified the tick as the agent of
transmission, a discovery that first introduced the concept of arthropods
functioning as disease vectors [5]. Long believed to be a disease that only
affected non-human mammals, it wasnÕt until 1957 that the first case of
Babesiosis was seen in humans [1]. The first case was observed in a
splenectomized patient as were all people diagnosed up until 1969. The first
case of Babesiosis seen in a non-splenectomized patient proved that the
protozoan parasite was pathogenic to all people [6].
Clinical
Presentation in Humans
The
severity of B. microti
infections varies. For 25% of cases in adults and half of cases in children,
the disease is asymptomatic or mild with flu-like symptoms. In cases of
symptomatic infection, symptoms are characterized by irregular fevers, chills,
headaches, general lethargy, pain and malaise [1]. In severe cases, hemolytic
anemia, jaundice, shortness of breath, and hemoglobinuria are documented due to
the lytic effects of parasitic multiplication [13][2]. Immunocompetent
individuals with healthy spleens often recover without treatment [1].
Splenectomized patients are more susceptible to contracting the disease and the
course of infection often ends fatally within 5 to 8 days of symptom onset [7].
Parasitemia levels can reach up to 85% in patients without spleens compared to
1-10% in individuals with spleens and effective immune systems. Splenectomized
patients suffer from severe hemolytic anemia with occasional incidences of
hepatomegaly and splenomegaly documented [13].
Complications
that arise from B. microti
infections include acute respiratory failure, congestive heart failure, and
renal failure. Infections can be fatal in 5-10% of hospitalized patients with
increased risk of death in the immunosupressed, the elderly, and those
co-infected with Lyme disease [13].
B.
divergens infections have a much
higher fatality rate (42%) and present with the most severe symptoms. Infected
individuals suffer from hemoglobinuria followed by jaundice, a persistently
high fever, chills and sweats. If left untreated, B. divergens infections can develop into shock-like symptoms
with pulmonary edema and renal failure [13].
Transmission
Babesia is spread through the saliva of a tick when it
bites. At its nymphal stage, a tick will bite into the skin for a blood meal.
The tick, if not removed, will stay attached for 3 to 6 days with longer
periods of feeding associated with a higher probability of acquiring the
parasite. The parasite can survive in the tick as it molts through its various
developmental stages resulting in all stages being potentially infectious. Some
species of Babesia can be
transmitted from a female tick to its offspring before migrating to salivary
glands for feeding [1]. B. microti,
the most common variety of Babesia in
humans however, has not been shown to transmit transovarialy [8].
Most
cases of transmission between humans are attributed to a tick vector. However,
as of 2003 the Centers for Disease Control and Prevention (CDC) acknowledged
more than 40 cases of Babesiosis contracted from packed red blood cell (PRBC)
transfusions and 2 infections documented from organ transplantation. PRBC
transfusions that cause infections were identified through testing of the blood
donor for B. microti
antibodies [9]. The occurrence of PRBC transfusions as a mechanism of Babesia
transmission puts pressure on
governmental organizations, such as the CDC, to heighten standard measures for screening
blood donations.
Reservoir
Many
species of Babesia only
infect non-human mammalian hosts, most commonly cattle, horses, and sheep. B.
microti and B. divergens are the two main pathogenic species in humans.
Their reservoirs are theorized to be the white-footed mouse (Peromuscus
Leucopus Rafinesque), the
microtus vole (Microtus spp.),
and the white-tailed deer (Odocoileus virginianus) [10]. These woodland species are hypothesized
reservoirs because although they are known to harbor the disease, complete
reservoir competence has not yet been shown [11].
Vector:
Babesia
is transmitted by inoculation after the bite of Ixodidae ticks. There are many species of Ixodidae that transmit the disease. In the Americas Ixodidae
scapularis is the most common vector.
This hard tick, commonly known as a deer tick, is also the vector for other
tick-associated illnesses such as Lyme disease.
(Image
2. Drawings of Ixodidae
scapularis female, male, and
nymph)
Incubation
Period
Signs
of infection usually arise 1 to 8 weeks after a bite from an infectious tick
[7]. Infections from B. divergens
have a shorter latent period usually ranging from 1-3 weeks [13].
Morphology
Babesia
enters erythrocytes at the
sporozoite stage. Within the red blood cell, the protozoa become cyclical and
develop into a trophozoite ring seen in the second cell of Image 3.
(Image
3. Morphology of Babesia in an erythrocyte [14]). The trophozoites morph
into merozoites, which have a tetrad structure coined a Maltese-cross form
[14]. The tetrad morphology, which can be seen with Geimsa staining of a thin
blood smear, is unique to Babesia
and serves as a distinguishing feature from Plasmodium falciparum, a protozoan of similar morphology that causes
Malaria. Trophozoite and merozoite growth ruptures the host erythrocyte leading
to the release of vermicules, the infectious parasitic bodies, which rapidly
spread the protozoa throughout the blood [1].
Life
Cycle
The
life cycle of B. microti
requires a biological stage in a rodent or deer host. Beginning from the point
labeled (1) in Figure 1 below, the Ixodidae introduces the sporozoites into the rodent when
taking a blood meal. Sporozoites enter erythrocytes in the blood and begin the
cyclical development between trophozoites and merozoites (point 2). Rather than
producing more trophozoites, some merozoites produce gametocytes (point 3). The
definitive tick host, Ixodidae,
takes up the gametes when attached for a blood meal (point 4). The gametes are
fertilized in the gut of the tick and develop into sporozoites in the salivary
glands. The sporozoites are introduced into a human upon inoculation at the
bite of an infected tick. Even as an incidental host, the phase changes that
occur in the parasite are the same within humans as in the biological hosts. Babesia can be diagnosed at the trophozoite stage and
can be transmitted from human to human either through the tick vector or
through blood transfusions [8].
(Figure
1. Babesia life cycle [8])
Diagnostic
Tests
As
a protozoan parasite, the most effective way to identify Babesia infection though blood sample testing. It is
important to pay specific attention to particular morphologies of Babesia in blood smears because its substantial
similarity to Malaria Plasmodium falciparum results in many patients suffering from
Babesiosis being misdiagnosed. The few distinguishing factors for Babesia include protozoa with varying shapes and sizes,
the potential to contain vacuoles, and the lack of pigment production.
Trophozoites within an erythrocyte that appear in a tetrad formation are also
indicative of Babesia. A
trained eye is necessary to distinguish the two species seen below.
(Image 4. Geimsa-stained thin blood smear of Plasmodium falciparum)
(Image 5. Babesia tetrad
seen in a blood smear)
Even
with much study of Babesiosis and Malaria, misdiagnosis with blood smear can be
frequent and problematic. To supplement a blood smear, diagnoses should be made
with an indirect fluorescent antibody (IFA) test. IFA testing has a much higher
specificity than stained blood smears with antibody detection in 88-96 % of
infected patients [8]. Diagnostic measures through antibody testing are also
particularly useful for identifying serum prevalence in asymptomatic
individuals. Due to the transmissibility of Babesia through blood transfusions, IFA testing would be
an effective means of screening for the disease in blood donations.
Historically,
Babesiosis diagnosis was
carried out with xenodiagnosis in hamsters for B. microti and in gerbils for B.divergens [1]. While successful at identifying the
disease, this diagnostic technique has been abandoned for faster diagnostic
measures.
Management
and Therapy
There
are several ways to manage and treat Babesiosis. In many cases, patients
spontaneously recover having only experienced mild symptoms undiagnosed as the
disease. This occurrence is almost always seen in B. microti infections, which are generally more common in
the United States. For B. divergens
and more severe B. microti infections,
the standard treatment historically for symptomatic individuals was oral or
intravenous Clindamycin with oral quinine [8]. With the results of research
completed in 2000 however, treatment regimens have been increasingly leaning
towards oral Atovaquone with oral azithromycin. The latter medications are
preferred as they are equally effective and exhibit fewer associated adverse
reactions [12].
(Image
6. Molecular Structure of
Clindamycin)
(Image
7. Molecular Structure of
Atovaquone)
In
severe cases, blood exchange transfusions have been performed to lower the
parasitic load in the individual [1]. Other rudimentary treatment measures
include addressing and correcting abnormal clinical signals [2].
Epidemiology
Of
the species to infect humans, B. microti is most common in the Americas whereas B. divergens is the predominant strain found in Europe.
Endemic areas are regions of tick habitat, including the forest regions of the
Northeastern United States and temperate regions of Europe [7]. Ixodidae, the tick vector of B. microti, also transmits the better-known Lyme disease.
For reasons that remain unclear, in areas endemic to both Lyme disease and
Babesiosis, Lyme disease transmission prevails and is more predominant in the
region [1]. Prevalence of Babesiosis is regions endemic to Malaria remains
unknown due to the likelihood of misdiagnosis as Malaria [13]. As the disease
results in a high number of asympomatic individuals, many populations can
possess high seroprevalence without much documentation of illness. For example,
in Rhode Island and Nantucket, seroprevalence has been measured to be 20-25%
[1]. Prevalence of Babesiosis is most documented during the months of May to
September where there is high tick activity in endemic regions [7].
Public
Health and Prevention Strategies or Vaccines
(Image 8)
The most effective public health measure for Babesia is avoidance of tick exposure. This can be performed through personal prevention strategies such as avoiding tick infested areas (especially during high tick season between May and September), remaining covered with light clothing, searching for ticks after being outdoors and removing discovered ticks from the skin [13]. Other preventative measures include applying Diethyltoluamide (DEET), a common bug repellent that is effective against ticks amongst other insects. On a state level, if health
|
Useful
Web Links
- Lyme and Tick-Borne
Diseases Research Center: Babesiosis
http://www.columbia-lyme.org/patients/tbd_babesia.html
- Connecticut Department
of Public Health: Babesiosis Fact Sheet
http://www.ct.gov/dph/cwp/view.asp?a=3136&q=388254
- New York State
Department of Health: Babesiosis
http://www.health.state.ny.us/diseases/communicable/babesiosis/fact_sheet.htm
- Centers for Disease
Control and Prevention:
http://www.cdc.gov/ncidod/dpd/parasites/babesia/default.htm
- DPDx: Laboratory
Identification of Parasites of Public Health Concern: Babesiosis
http://www.dpd.cdc.gov/dpdx/HTML/Babesiosis.htm
References
[1] Despommier, Dickson D. et al. Parasitic
Diseases. Ed 3. Spinger-Verlag Inc: New York City, New York, 1995, p
224-226
[2] M. Ristic et al, Ed. Malaria and Babesiosis:
New Perspectives in Clinical Microbiology. Martinus Nijhoff Publishers:
Dordrecht, The Netherlands, 1984, 100-170
[3] Abeer Khayat and Mobeen Rathore. The
Neurological Manifestations of Pediatric Infectious Diseases and
Immunodeficiency Syndromes. Humana Press, 2008, Chapter 36, 343-346
[4] National Center for Biotechnology Information:
Taxonomy Browser.
[5] Centers for Disease Control and Prevention. Theobald
Smith. <http://www.cdc.gov/eid/content/14/12/1939.htm>
[6] Beaver, PhD., Sc.D., Paul Chester, et al. Clinical
Parasitology. Ed 9. Lea and Febiger: Philadelphia, Pennsylvania, p 205-208
[7] National Institute of Allergy and Infectious
Diseases, National Institutes of Health. Babesiosis. <http://www3.niaid.nih.gov/topics/babesiosis/>
[8] DPDx: Laboratory Identification of Parasites of
Public Health Concern. Babesiosis
<http://www.dpd.cdc.gov/dpdx/HTML/Babesiosis.htm>
[9] Joseph Z. Lux, Don Weiss, Jeanne V. Linden,
Debra Kessler, Barbara L. Herwaldt, Susan J. Wong, Jan Keithly, Phyllis
Della-Latta, and Brian E. Scully. Transfusion-Associated Babesiosis
Infection after Heart Transplant.
Emerging Infectious Diseases, Vol. 9, No. 2, 2003 <http://www.cdc.gov/ncidod/EID/vol9no1/02-0149.htm>
[10] G Karbowiak. Zoonotic reservoir of Babesia
microti in Poland. Polish
Journal of Microbiology, 2004 <http://www.ncbi.nlm.nih.gov/pubmed/15787199?dopt=Abstract>
[11] CAT.INST: Centre Nationale de Recherche
Scientifique <http://cat.inist.fr/?aModele=afficheN&cpsidt=4605007>
[12] Peter J. Krause, M.D., Timothy Lepore, M.D.,
Vijay K. Sikand, M.D., Joseph Gadbaw, M.D., Georgine Burke, Ph.D., Sam R.
Telford, Sc.D., Peter Brassard, M.D., Diane Pearl, M.D., Jaber Azlanzadeh,
Ph.D., Diane Christianson, R.N., Debra McGrath, R.N., and Andrew Spielman,
Sc.D. Atovaquone and Azithromycin for the Treatment of Babesiosis. New England Journal of Medicine, Vol 343:
1454-1458, 2000. <http://content.nejm.org/cgi/content/full/343/20/1454 >
[13] Jeffrey A. Gelfand and Edouard Vannier. Chapter
204: Babesiosis. McGraw-HillÕs
Access Medicine. <http://www.accessmedicine.com/content.aspx?aID=2892931>
[14] Barbara L. Herwaldt, Simone Cacci, Filippo
Gherlinzoni, Horst Aspck, Susan B. Slemenda, PierPaolo Piccaluga, Giovanni
Martinelli, Renate Edelhofer, Ursula Hollenstein, Giovanni Poletti, Silvio
Pampiglione, Karin Lschenberger, Sante Tura, and Norman J. Pieniazek. Molecular
Characterization of a Non–Babesia divergens Organism Causing Zoonotic
Babesiosis in Europe. Emerging
Infectious Diseases, Vol 9:8, 2003
<http://www.cdc.gov/ncidod/EID/vol9no8/02-0748.htm#Figure2>
Images