CLINICAL MICROBIOLOGY REVIEWS, Oct. 2008, p. 626638 Vol. 21, No.

4
0893-8512/08/$08.000 doi:10.1128/CMR.00021-08
Copyright 2008, American Society for Microbiology. All Rights Reserved.

Current World Status of Balantidium coli

Frederick L. Schuster1* and Lynn Ramirez-Avila2
California Department of Health, Viral and Rickettsial Disease Laboratory, Richmond, California,1 and
San Francisco General Hospital, University of California Medical Center, San Francisco, California2

INTRODUCTION .......................................................................................................................................................626
History ......................................................................................................................................................................627
MORPHOLOGY .........................................................................................................................................................628
TAXONOMY AND MOLECULAR BIOLOGY.......................................................................................................629
Balantidium spp. Defined .......................................................................................................................................629
Molecular Biology ...................................................................................................................................................629
Balantidium coli versus Balantidium suis..............................................................................................................630
PHYSIOLOGY ............................................................................................................................................................630
CULTIVATION ...........................................................................................................................................................630
Temperature Range for Growth............................................................................................................................631
HOST-PARASITE INTERACTIONS .......................................................................................................................631
Immune Response...................................................................................................................................................631
Immunosuppression ...............................................................................................................................................631
Crossing the Species Barrier: Transfection Attempts .......................................................................................632
DISEASE POTENTIAL..............................................................................................................................................632
Factors Contributing to Disease...........................................................................................................................633
EPIDEMIOLOGY .......................................................................................................................................................633
Outbreaks of Balantidiosis ....................................................................................................................................633
Virulence versus Avirulence in Balantidium ........................................................................................................633
PREVALENCE OF BALANTIDIUM COLI..............................................................................................................633
Infections in Nonhuman Mammals......................................................................................................................633
Swine.....................................................................................................................................................................634
Simians and apes................................................................................................................................................634
Amphibia ..............................................................................................................................................................634
Infections in Humans.............................................................................................................................................634
Areas of endemicity ............................................................................................................................................635
Other possible pathways for transmission......................................................................................................635
Risk factors..........................................................................................................................................................635
Institutional balantidiosis..................................................................................................................................635
LABORATORY DIAGNOSIS....................................................................................................................................635
Pulmonary Infections .............................................................................................................................................635
Balantidiosis versus Dysentery .........................................................................................................................636
Balantidium and Laboratory Infection .................................................................................................................636
PREVENTION OF INFECTION ..............................................................................................................................636
ANTIMICROBIAL THERAPY..................................................................................................................................636
CONCLUSIONS .........................................................................................................................................................636
ACKNOWLEDGMENTS ...........................................................................................................................................637
REFERENCES ............................................................................................................................................................637

INTRODUCTION vehicle for most cases of balantidiosis. Human-to-human

transmission may also occur. Balantidiums habitats in hu-
Protozoan parasitism covers a broad spectrum of diseases.
mans are the cecum and colon. Humans may remain asymp-
Balantidium coli and balantidiosis, the subjects of this review,
tomatic, as does the pig, or may develop dysentery similar to
barely register among infectious protozoan diseases.
that caused by Entamoeba histolytica. Death is an infrequent
Balantidium is the only ciliated protozoon known to infect
consequence of balantidiosis, but in developing countries
humans and is the largest protozoon infecting humans and
with undernourished and overparasitized populations, it can
nonhuman primates. Balantidiosis is a zoonotic disease and
make the difference between a healthy life and chronic de-
is acquired by humans via the fecal-oral route from the
bilitation.
normal host, the pig, where it is asymptomatic. Water is the
The organism is cosmopolitan and can be found wherever
pigs are found. Disease appears to be a problem mostly of
developing countries, where water sources may be contam-
* Corresponding author. Mailing address: California Department of
Health, Viral and Rickettsial Disease Laboratory, Richmond, CA
inated with porcine or human feces. B. coli can become an
94804. Phone: (510) 307-8651. Fax: (510) 307-8599. E-mail: fred.schuster opportunistic parasite in immunosuppressed hosts living in
@cdph.ca.gov. urban environments, where pigs are not a factor in infection.

626
VOL. 21, 2008 BALANTIDIUM COLI 627

FIG. 1. Life cycle of Balantidium infection in humans. The trophozoites and cysts are shed in feces (1), and if the cysts, in particular,
contaminate drinking water or food, the infection can be spread to other humans (2). Fruits and vegetables may also be contaminated by cysts and
serve as a means of transmission. The bottom panel illustrates the pattern of encystment and asexual reproduction in trophic ciliates. (Reprinted
from the CDC-DPDx Parasite Image Library [http://www.dpd.cdc.gov/dpdx/].)

Balantidium is an often-neglected pathogen. Research on History

Balantidium has been sparse. Zaman (80) published an inclu-
sive review on Balantidium 30 years ago, but recently the or-
ganism has come to be regarded as an emerging protozoan
pathogen and has been reviewed by Garcia (22).
Balantidium has a simple life cycle, as follows: dormant cyst
to trophozoite and trophozoite to cyst. Transmission is direct,
from a contaminated water or food supply to humans (Fig. 1).
No intermediate host, as occurs with many other parasitic
species, is needed.
Malmsten (44) was the first to recognize the organism in two
humans with dysentery in the year 1857. Malmsten identified it
as a species of Paramecium and named the organism Parame-
cium coli. Leuckart described a morphologically similar species
from the pig intestine in 1861 (39). Shortly thereafter, Stein
equated the two organisms and placed them in the genus
Balantidium (G. balanto-, bag), and because of priority, the
species name (B. coli) was retained (64). Ironically, Malmsten
628 SCHUSTER AND RAMIREZ-AVILA
FIG. 2. Trophic stage of Balantidium. The surface of the organism
is uniformly covered by cilia, and the lighter areas in the cytoplasm
represent a contractile vacuole (CV) and the macronucleus (Mn). The
oral apparatus (OA) is at the apical end of the organism in this
micrograph. (Reprinted from the CDC-DPDx Parasite Image Library
[http://www.dpd.cdc.gov/dpdx/].)
first described balantidiosis, usually regarded as a disease of
tropic or subtropic regions, from patients in Sweden (44).
Morphologically similar organisms have been detected in a
variety of mammals, including rats, chimpanzees, orangutans,
and infrequently, dogs or cats. The species found in pigs, Bal-
antidium suis, is likely identical to B. coli from humans. Other
species have been isolated from guinea pigs (Balantidium
caviae), cockroaches (Balantidium blattarum), fish, birds, and
amphibia. In all, there have been about 50 species described
(4). Morphology has been the basis for identification to the
species level, and some of the different species that have been
created are in reality B. coli showing polymorphism in different
hosts and under varied growth conditions (41). The taxonomy
will ultimately be resolved once these organisms undergo se-
quencing of their small subunit rRNAs.
MORPHOLOGY
The trophic ciliate measures 30 to 150 m in length by 25 to
120 m in width; the cyst, which may be spherical or slightly
ovoid, measures 40 to 60 m in diameter (41). Size, however,
varies, with some balantidia being up to 200 m in length. The
mouth (oral apparatus) is located at the tapering anterior end,
and the cytopyge (anus) is at the rounded posterior end (Fig.
2). A sausage-shaped macronucleus and a rounded micronu-
cleus are located in the cytoplasm (Fig. 3). Asexual division
CLIN. MICROBIOL. REV.
FIG. 3. View of intestinal lumen with two trophic ciliates. The
prominent macronucleus is seen in this stained section. The upper
ciliate shows the small micronucleus nestled against the macronucleus.
(Reprinted from the CDC-DPDx Parasite Image Library [http://www
.dpd.cdc.gov/dpdx/].)
occurs as it does in most ciliates. A transverse furrow forms,
dividing the mother cell into two asymmetric daughter cells, an
anterior (proter) and a posterior (opisthe) cell. The proter
retains the oral apparatus, and the opisthe develops a new
apparatus. An anterior stomatogenic field appears in the opis-
the, leading to formation of the new oral apparatus, but the old
oral apparatus may also undergo reorganization (37). The
swimming organism exhibits a rotary-type motion by means of
its somatic cilia that may facilitate movement through the
contents of the colon.
Sexual reproduction as conjugation has been reported for
Balantidium, but information is lacking about details of nuclear
events. Two successive fissions (meiosis) occur preceded by
formation of the conjugants, by either equal or unequal divi-
sions (37). The two conjugants attach at the oral apparatus and
exchange micronuclear products of meiosis.
Although the organism lives in an anaerobic environment,
Zaman (80) described mitochondrion-like bodies in electron
micrographs of Balantidium; in contrast, Entamoeba histolytica
and Entamoeba dispar, found in the human colon, are anaer-
obes and lack mitochondria. Cristae or tubuli, however, were
reportedly absent from the mitochondrion-like bodies, raising
the possibility that these organelles are hydrogenosomes (80).
Hydrogenosomes, relict mitochondria, have been identified in
balantidia as well as in other anaerobic ciliates (25, 27). Other
cytoplasmic components include endoplasmic reticulum, ribo-
somes, and numerous vacuoles filled with food particles. A
Golgi apparatus was not seen, but vesicles of endoplasmic
reticulum function in lieu of Golgi vesicles (49). Mucocysts are
also seen (61). Two contractile vacuoles, functioning as osmo-
regulatory organelles, pulsate at a low rate even though the
surrounding environment is isotonic or close to it (79). Undi-
VOL. 21, 2008
FIG. 4. Encysted ciliate. The cytoplasm is protected from environ-
mental stress within a double-walled covering. (Reprinted from the
CDC-DPDx Parasite Image Library [http://www.dpd.cdc.gov/dpdx/].)
gested residue from food vacuoles is eliminated through the
cytopyge.
Balantidium jocularum, from the herbivorous surgeonfish,
was found to harbor endosymbiotic bacteria in its macronu-
cleus (26). The bacteria were unusually large, measuring up to
4 m in length, but apparently without pathogenic potential
for the ciliate. They are probably gram-positive organisms be-
cause of an endospore-like inclusion within the bacterium. No
other reports of endosymbionts from Balantidium have ap-
peared.
The cyst of Balantidium is the transmissive stage of the
organism. Because of its thickened wall, it is protected from
desiccation and other environmental stress (Fig. 4). It survives
best in humid surroundings protected from direct sunlight. The
trophic ciliate is reportedly unable to survive passage through
the stomach because of the low pH of gastric fluid, but Balan-
tidium trophozoites inoculated into the stomach of guinea pigs
have been found in the colon (56). The process of encystment
begins in the colon and rectum of the host, and cysts are
generally found in formed feces (56). Cysts, however, were not
produced in cultures of balantidia (32, 80), nor are they pro-
duced in cases of acute dysentery. Attempts to simulate in vitro
the colorectal environment in which cysts form (resorption of
water and increased salt concentrations) were unsuccessful in
inducing encystations; overfeeding or starvation was also un-
successful (32). Loss of the ability to encyst is seen in some
other protozoa (e.g., soil amebae) maintained in culture, due
in part to less than optimal growth conditions and/or limiting
amounts of nutrients essential for encystment. E. histolytica, an
agent of amebic dysentery, resembles Balantidium in produc-
ing cysts in formed stools but trophozoites in dysenteric stools.
In vitro encystment of E. histolytica depends upon a number of
factors, including withholding rice starch, the composition of
the bacterial flora, and the encystment medium, and may re-
quire a complex protocol to induce cyst formation (10).
BALANTIDIUM COLI 629
The diet of the ciliate is made up of bacteria and food
particles present or passing through the colon. If extensive
damage has been done to the wall of the colon, red blood cells
may also be seen in trophic organisms, as well as blood in the
stool. The ciliates produce flask-shaped lesions in the submu-
cosa, where they form clusters called nides or nests (4).
TAXONOMY AND MOLECULAR BIOLOGY
Protist taxonomy was recently revised by a committee of the
International Society of Protistologists and allied groups,
based on the wealth of new information that has accumulated
about these organisms since the last official taxonomy pub-
lished in 1980 (1). Since that time, an increased understanding
of ultrastructural morphology, biochemical properties and re-
lationships, studies of nuclear and mitochondrial DNAs, and
protist ecology has developed. The revised taxonomy does not
use the classic categories of phylum, class, order, etc., in order
to maximize taxonomic plasticity as additional information on
phylogenetic relationships, particularly from genomic studies,
becomes available (1).
Balantidium spp. Defined
The following definition is based on the new taxonomy and
represents a characterization of the genus Balantidium, from
the more general ciliate features to those of the genus Balan-
tidium.
Balantidium spp. are ciliated binucleate protozoa with macro-
and micronuclei (features of Ciliophora) covered by uniform
rows of monokinetid somatic ciliation, i.e., rows of cilia arising
from single rows of subsurface kinetosomes and their associ-
ated fibrils; a slit-like anteroventral oral cavity depressed below
the surface (a feature of Litostomea); an oral apparatus with
dense ciliation but lacking specialized oral membranelles, with
features of endosymbiosis in many animals (hairy mouths;
features of Trichostomatia); a vestibular groove leading into
the oral apparatus (feature of Vestibulifera); a vestibular
groove of less than one-half the body length, with features of
commensals of vertebrate, amphibian, and insect hosts or, in
some cases, parasites that may attack the intestinal lining (fea-
ture of the family Balantidiidae). Representative species in
mammals are B. coli, B. suis, and B. caviae.
Molecular Biology
Nucleotide sequences from two studies on Balantidium are
on file at GenBank, one based on small subunit rRNA
(AF029763) and the second based on internal transcribed
spacers 1 and 2 (AF045030) (65, 66, 73). Sequencing was used
to construct a phylogenetic tree placing Balantidium coli with
the trichostome ciliates Isotricha spp. and Dasytricha spp., but
not necessarily in the same subgroup (order Vestibulifera).
These ciliates have a sunken oral apparatus but lack toxic
trichocysts, which aid in subduing prey (51). As yet, a definitive
taxonomy of the group awaits additional information.
630 SCHUSTER AND RAMIREZ-AVILA
Balantidium coli versus Balantidium suis
Are B. coli from humans and B. suis from pigs the same
organism? Persons infected with porcine strains of Balantidium
are usually assumed to have B. coli infections (72). The answer
awaits further studies of the organisms DNAs. Although pigs
are the major reservoir for balantidiosis in humans, laboratory
studies indicate that humans are not readily infected with B.
suis or, for that matter, B. coli. The two organisms appear to be
different from one anotherone is larger (B. coli) and one is
smaller (B. suis)which is evidence enough for some to regard
them as different species. According to Levine (41), however,
a clonal isolate of B. coli showed both morphotypes after being
maintained in culture. The size difference between the two was
attributable to growth conditions of the ciliates. Jameson (32)
favored the view that there is a single species of Balantidium
that splits into two size variations. Similarly, B. caviae from the
guinea pig was described as being indistinguishable in vitro
from B. suis from swine (56). An agar diffusion study of anti-
gens of Balantidium spp. found only minor antigenic differ-
ences between B. coli and B. suis (36).
PHYSIOLOGY
Few studies have examined the energy metabolism of these
organisms. Balantidia are equally able to survive under anaer-
obic as well as aerobic conditions. Carbohydrates are the chief
source of energy for the ciliates growing in vivo (80).
In studies of B. coli combining ultrastructure with cytochem-
istry, peroxisomes were identified in the ciliate. These vesicles
contain peroxidase, an enzyme affording protection from the
destructive effects of highly oxidative compounds, such as hy-
drogen peroxide (60). A comparison of the cytoplasm of cili-
ates from asymptomatic swine and those with acute balantid-
iosis was made. Peroxisomes were more numerous but smaller
(0.6 to 0.8 m) in balantidia from asymptomatic pigs than in
those with acute disease (0.8 m). Likewise, nucleic acid
contents (particularly RNA, but also DNA) from symptomatic
and asymptomatic hogs differ, with the former having more
content (62). The difference may depend on the degree of
metabolic activity of the ciliates and, in the case of RNA, may
be indicative of enhanced protein synthesis. Ciliates with
higher nucleic acid content produced more robust cultures, at
least in the initial stages of in vitro growth (62).
The enzyme glucose-6-phosphatase was present in small ves-
icles attached to the endoplasmic reticulum or in the mem-
brane itself (61). Alkaline phosphatase was found in the ciliate
cortex, nuclear and ciliary membranes, and kinetosomes as
well as in vesicles of the endoplasmic reticulum (61). Phos-
phatase enzymes are important for their role in making glucose
available as an energy source.
Balantidia produce no known toxins, but their ability to
produce ulceration of the colon wall is attributed to hyaluron-
idase, an enzyme that digests hyaluronic acid, a component of
the glue holding mucosal epithelial cells together (68). The
dissolution of group C Streptococcus hyaluronic acid-contain-
ing capsules and the breakdown of potassium hyaluronate by
living B. coli were taken as evidence of hyaluronidase activity.
Entamoeba histolytica, the classic protozoan dysentery agent,
attacks the mucosal surface of the colon and was long claimed
CLIN. MICROBIOL. REV.
to possess hyaluronidase activity. Attempts to demonstrate its
presence, however, using E. histolytica extracts, did not support
the claim (50). In the case of B. coli, other factors may affect
the results, including associated bacteria, waning of virulence
(see next paragraph) in long-term cultures, up- and downregu-
lation of presumptive virulence genes, and strain differences.
Thus, the matter of hyaluronidase production by Balantidium
warrants further study. Levine (41) noted that invasion of co-
lonic epithelium by Balantidium might be secondary to damage
caused by intestinal bacteria.
The term virulence is used here as the degree of patho-
genicity of a parasite and involves substances elaborated by a
pathogen that facilitate infection and disease (e.g., toxins, en-
zymes that promote invasiveness, and adhesive properties).
CULTIVATION
Balantidia are available from fresh pig feces, particularly
from animals with evidence of acute balantidiosis, and from
slaughterhouses. An insulated bottle is used for transport of
porcine intestinal contents to the laboratory. There were a
number of early attempts at maintenance or cultivation in
vitro. Gastric mucin media were developed for Balantidium
and maintained growth for as long as 30 months. Calf serum
and rice starch or rice powder were also required. Starch
grains, if present in culture medium, are ingested and serve as
a carbohydrate source (80). The addition of soluble sugars to
growth media encourages overgrowth of accompanying bacte-
ria, whereas starch particles are efficiently ingested and di-
gested by the phagotrophic ciliates (10). A defined medium
with cysteine HCl and i-inositol was used for short-term phys-
iologic experiments with the organisms, but little in the way
of results appeared in the literature (35). Trophic ciliates,
however, did not survive agitation in attempts at manometric
studies.
Biphasic media in tubes were often used with an agar, in-
spissated egg yolk, or serum butt overlaid with nutrient me-
dium. Bacteria present in the sample can overgrow in an en-
riched medium, requiring the addition of antibiotics (e.g.,
penicillin-streptomycin) to suppress bacterial proliferation.
When growing in tubes, balantidia favor the bottom of the
tube, where conditions are microaerophilic or anaerobic. Za-
man maintained monoxenic cultures of B. coli with Escherichia
coli, using antibiotics to control bacterial overgrowth (80). Di-
amonds TYSGM medium for Entamoeba and other enteric
parasites will also support the xenic (with bacteria) growth of
balantidia (10). The medium contains Trypticase (casein di-
gest), yeast extract, serum, and porcine gastric mucin. Starch
powder is added to tubes at the time of inoculation of medium.
Zaman (80) noted that B. suis from the pig is not as readily
cultured as B. coli from humans. Others apparently encoun-
tered no difficulties with cultivation of B. suis (62). Among the
variables involved in cultivation are the growth medium and
pH (optimal range, 5.4 to 8.0) (32), associated undefined bac-
terial flora, strain differences, and differences in nutritional
requirements between ciliates from different hosts.
In the case of many pathogens maintained in vitro, pro-
longed cultivation attenuates virulence, and animal passage
may be required to restore it. The difficulty in infecting labo-
ratory animals (e.g., the guinea pig) and the absence of an
VOL. 21, 2008
animal model of disease are obstacles in attempts to study the
pathogenicity of the ciliate.
Temperature Range for Growth
Balantidium grows at temperatures between 20C and 40C,
a range that is adaptive for mammalian endosymbionts but can
also allow for survival and growth outside the host (10). Tro-
phic ciliates did not survive longer than 24 to 48 h in cultures
maintained at temperatures over 40C (12). The trophic or-
ganism from pig intestine has been reported to survive room
temperature and exposure to air for 24 h to as long as 10 days
(56). There is no information about the ability of balantidia
from poikilothermic animals to make the transition to mam-
malian body temperature.
HOST-PARASITE INTERACTIONS
In pigs, as in some humans and other mammals, Balantidium
infects but causes no serious disease of the gastrointestinal
tract. It can thrive there in balance with its host without causing
dysenteric symptoms, such as severe diarrhea and bloody
stools. The problem with this detente is that malnutrition,
alcoholism, or a compromised immune system (as in human
immunodeficiency virus [HIV]/AIDS, etc.) can tip the balance
in favor of the ciliate, leading to disease (3, 20, 70). In acute
disease, explosive diarrhea may occur as often as every 20 min
(38). Perforation of the colon may also occur in acute disease,
with life-threatening consequences.
Hosts vary in their susceptibility to Balantidium, and at-
tempts at infecting humans have been disappointing (76). This
may be due to virulence of the particular strain used for infec-
tion, the intrinsic health of the host, and/or the dosage of the
ciliate administered to the host. There is no evidence that
other intestinal flora of humans, whether bacteria, protozoa, or
viruses, render the host more susceptible to infection. It is
known, however, that the presence of pathogenic bacteria (e.g.,
Salmonella) in the intestine can worsen an infection by invad-
ing colonic lesions caused by balantidia (41, 57, 59, 60).
Nonhuman primates, particularly the great apes and Old
World monkeys, can develop Balantidium infections. This is of
concern since some of these animals are endangered species or
close to it because of disease, encroachment by humans on
their natural habitats, and resultant density-dependent changes
in their populations. Orangutans, for example, are less likely to
be infected by Balantidium in their natural setting, while those
in rehabilitation centers for injured or orphaned animals
have a higher prevalence of the ciliate (34). Reasons for this
include overcrowding at the centers, with increased stress on
individuals; contacts with humans and other animal species
and their associated bacterial, viral, and protozoan organisms;
and water sources contaminated by fecal material in confined
areas (34). In the wild, the orangutan population density is 2
individuals km2 (34).
Immune Response
Few intensive studies have been carried out on the hosts
immune response to Balantidium. One study examined a pop-
ulation of captive rhesus macaque monkeys with and without
BALANTIDIUM COLI 631
chronic diarrhea (57). The study detected a broad array of
bacterial and protozoan organisms, as well as viruses. A sig-
nificantly larger proportion of animals with chronic diarrhea
harbored pathogenic bacteria (Campylobacter spp., Shigella
flexneri, and Yersinia enterocolitica) than those without diar-
rhea. The prevalence of Balantidium was 12% (estimated
from the graph in reference 57). The presence of Balantidium
in the colon appeared not to be the cause of disease. Monkeys
with chronic diarrhea showed a significantly increased produc-
tion of interleukin-1, interleukin-3, and tumor necrosis factor
alpha, to a level of 60 to 70% from about 20 to 30% in
nondiarrheic animals. This was not necessarily due to Balan-
tidium, however, because of the variety of other intestinal or-
ganisms.
Experiments to demonstrate an immune response to Balan-
tidium were done by Zaman, who studied an immobilization
reaction to Balantidium (78). Using anti-Balantidium antibod-
ies raised in rabbits, the serum immobilized the ciliates within
less than a minute (titers of 1:4 and 1:8); higher dilutions took
longer to immobilize. Heat-inactivated rabbit serum did not
immobilize. Ultimately, the treated organisms disintegrated.
Demonstrating a humoral response to the ciliates in patients
with balantidiosis by indirect fluorescent-antibody (IFA) stain-
ing would be of interest. Dzebenski (18) tested pigs for anti-
Balantidium antibodies by IFA staining but had difficulty in
detecting any activity in pig sera. He attributed the lack of
response to the small sample of animals tested and the absence
of evidence of tissue invasion in the animals used.
Availability of an IFA test would sidestep the labor-intensive
examination of stool samples (except for validation) and might
give a better estimate of Balantidium exposure if applied to
persons living in regions of endemicity and to groups at risk.
Populations with constant exposure to Balantidium may de-
velop some degree of immunity (19). In areas where contact
with pigs is common, such as the Altiplano region of Bolivia,
most of the schoolchildren examined had asymptomatic infec-
tions, but few had diarrheic stools, suggesting resistance to
fulminant disease (19). In an outbreak of balantidiosis on the
Western Pacific island of Truk (see below), immunity may have
been a factor in the relatively rapid resolution (estimated at 6
weeks) of the outbreak among inhabitants (72).
Immunosuppression
Immunocompromised individuals appear to be less resistant
to balantidiosis. There have been no concerted studies, how-
ever, to determine the prevalence of balantidia in immunosup-
pressed hosts. Reports in the literature are more of an anec-
dotal nature. Two reports of balantidiosis in HIV/AIDS
patients point to Balantidium as both a pathogen and an op-
portunist (8, 11).
There have been several reports in the literature of Balan-
tidium spreading to the lungs, causing a pneumonia-like dis-
ease. Most of these infections have occurred in elderly or
otherwise immunocompromised persons. A 71-year-old woman
(Greece) with anal cancer, diabetes, fever, and intermittent di-
arrhea was found to have Balantidium in her lungs when a
bronchial secretion was examined as a wet mount slide prep-
aration (70). Although the patient was treated with metroni-
dazole, a drug of choice for treating balantidiosis, and several
632 SCHUSTER AND RAMIREZ-AVILA
other antimicrobials, she died of cardiac arrest. Computerized
tomography scans and X-rays showed lung lesions in a 58-year-
old woman (Greece) with leukemia who also suffered weight
loss, weakness, abdominal cramps, and a cough. Since a fungal
infection was suspected, bronchoalveolar lavage was per-
formed, and balantidia were found in the wash fluid (3). The
authors postulated that the ciliates were spread hematog-
enously from the site of colonic ulceration to the lungs. Anti-
microbial treatment with metronidazole was successful in
resolving the infection.
Nonpulmonary infections have also developed in immuno-
suppressed patients. A 54-year-old alcoholic pork butcher
(France) with acute diarrhea suffered colonic perforation but
recovered after doxycycline treatment and colectomy (20). Bal-
antidia were detected in stools of a 47-year-old female (Tur-
key) with non-Hodgkins lymphoma, accompanied by abdom-
inal pain and bloody diarrhea; she, too, was treated successfully
with metronidazole (75).
Except for the pork butcher in the preceding paragraph, the
other patients had no contact with pigs and lived in urban
areas. The leukemic patient had also received corticosteroids
and chemotherapy, which may have increased vulnerability to
opportunistic infections by muting the immune response.
Other possible sources of infection may have been consump-
tion of uncooked vegetables and/or food contaminated by rat
droppings or mechanically by cockroaches or flies.
A Barbary sheep (Korea) from a zoological park died after
showing signs of emaciation, lethargy, and weakness (9). At
autopsy, B. coli was found in the gastric lymph ducts and in the
submucosa of the abomasum of the animal. The sheep was also
infected with the coccidian Eimeria and with parasitic worms.
Balantidia, however, were not found in the animals stool. It
was hypothesized that balantidia initially infected the aboma-
sum, where damage to the mucosal surface by Eimeria facili-
tated invasion of the lymphatics.
Among possible pathways by which balantidia in the colon
wall could colonize the lungs are the circulatory (hepatic portal
circuit) or lymphatic systems (3, 9, 70), perforation of the colon
and spread through the peritoneal cavity (70), invasion of the
lungs across the diaphragm (58), and colonization of the na-
sopharynx with spread to the lungs, resulting from aspiration of
fluid from the oral cavity (58). It is interesting that there was no
indication of Balantidium trophic ciliates or cysts in the stool
samples of most of these individuals.
Crossing the Species Barrier: Transfection Attempts
A parasite passing from one species to another faces the
problem of species specificity, both for the host and for the
parasite. Although humans are susceptible hosts for balantidia,
efforts to infect humans have not been successful (76). Balan-
tidium has no problem in passing from pigs to humans under
appropriate conditions (e.g., the outbreak in Truk). For trans-
mission to be successful, it would appear that proximity and
persistent contact between pigs and humans are factors.
Gelatin capsules containing human feces with active ciliates
and cysts were given to volunteers (76). The capsules contained
250 trophic ciliates and 250 cysts. Volunteers were followed
over a period of 10 years, but no evidence of infection based on
stool examination was found. The study may have been ex-
CLIN. MICROBIOL. REV.
tended to detect asymptomatic or cryptic infections that were
not readily apparent in stool samples from the volunteers. In
another study, a human fecal homogenate containing consid-
erably larger numbers of cysts of B. coli (1.2 104 to 4.8 104)
was used to infect piglets and monkeys (74). Severe diarrhea
developed in about half of the piglets (4 of 10) and in monkeys
that had been pretreated with hydrocortisone (2 of 4). Other
animals suffered moderate diarrhea (piglets) or were asymp-
tomatic (monkeys).
Attempts were also made to infect guinea pigs by using
porcine balantidia (56). Ciliates harvested from culture, con-
taining starch grains as markers, were injected into the stom-
ach of a guinea pig. Starch-filled ciliates were subsequently
found in its esophagus and cecum. A second attempt trans-
ferred ciliates directly from the pig by use of a stomach tube,
and trophic ciliates were detected in the ileum, jejunum, and
cecum. Both animals died soon after infection as a result of the
experimental procedure.
DISEASE POTENTIAL
Balantidiosis has a range of mild to severe clinical presen-
tations. The following three clinical manifestations of balan-
tidiosis can occur (71): (i) asymptomatic hosts who are carriers
of disease and serve as reservoirs of infection in the commu-
nity; (ii) chronic infection that presents with nonbloody diar-
rhea, cramping, halitosis, and abdominal pain secondary to
trophozoite invasion of the large intestine (71, 75); and (iii)
patients with fulminating balantidiosis passing mucoid, bloody
stools.
The most severe presentation of B. coli occurs with weight
loss, tenesmus, and bloody stools (71). Intestinal hemorrhage
and perforation can also occur and are mediated by the pro-
duction of B. coli proteolytic enzymes (3). Direct evidence for
the presence of proteolytic enzymes is lacking, but proteolysis
is generally assumed to be a factor in digesting the mucous
coating of the colon and facilitating tissue invasion, abscess
formation, ulceration, and perforation of the intestine (3).
Entamoeba histolytica, which has a similar pattern of pathoge-
nicity, has been shown to possess and secrete cysteine, serine,
aspartic, and metallo-proteases, some of which can target the
mucus layer of the intestinal wall and aid in penetration of the
underlying tissue (43, 69).
Hemorrhage and perforation were reported for fatal cases of
B. coli infections (17). Fulminating balantidiosis has a case
fatality rate of 30% (19). Vasquez and Vidal (71) described the
case of a 60-year-old pig farmer with pancolonic damage and
microperforation who died despite antiparasitic treatment.
Another fatal case of balantidiosis occurred in a 63-year-old
pig farmer, who died of dysentery and subsequent hemorrhage
after 8 days; an autopsy revealed ulcerative colitis (54). Fatal
cases of balantidiosis have also been associated with sepsis
secondary to intestinal disease (51, 58). A malnourished
2-year-old girl with an anorectal malformation who was diag-
nosed with balantidiosis developed septic shock and died de-
spite antimicrobial treatment with ampicillin and amikacin for
sepsis and metronidazole for balantidiosis (7).
Although the intestine is the most common site of B. coli
disease, there are extraintestinal sites of infection. These in-
clude the appendix but rarely the liver (16). Dodd (16) re-
VOL. 21, 2008
ported a case of a 16-year-old who presented with abdominal
pain, fever, and elevated white blood cell count and who had a
gangrenous appendix. Pathological examination of the appen-
dix revealed inflammation, ulceration, necrosis, and B. coli
trophozoites (16). Genitourinary sites of infection, including
uterine infection, vaginitis, and cystitis, are thought to occur via
direct spread from the anal area or secondary to rectovaginal
fistulas created from infection with B. coli (58). Lung infections
with Balantidium are infrequent but noteworthy. A necrotizing
lung infection was reported for a 42-year-old organic farmer
who routinely used pig manure to fertilize his vegetables, prob-
ably as a result of aerosolizing the manure and inhaling air-
borne cysts (58). Airborne transmission of cysts is unlikely.
Cysts of Balantidium are large and would not be carried over
great distances, either on air currents or in water droplets.
Thus, infection by inhalation would require direct contact with
aerosol droplets.
Factors Contributing to Disease
Nutritional status, intestinal bacterial flora, parasite load,
achlorhydria, alcoholism, or any chronic disease may affect the
severity of disease (19). As previously noted, some degree of
immunity may be present in populations that are exposed to
Balantidium on a regular basis (19, 72).
EPIDEMIOLOGY
B. coli infection is uncommon in humans despite its potential
for worldwide distribution. The organism, though pathogenic,
is of low virulence. The worldwide prevalence is estimated at
0.02 to 1% (19), but it varies widely by geographic location (3).
Areas of high prevalence include regions of Latin America,
the Philippines, Papua New Guinea and West Irian, and areas
of the Middle East (63, 75). In New Guinea, the rate of infec-
tion among pig farmers is as high as 28% (53), and in the
Altiplano area of Bolivia, balantidiosis rates range between 6
and 29% (19).
The major factors leading to human balantidiosis include (i)
close contact between pigs and humans, (ii) a lack of appro-
priate waste disposal such that swine and human excrement
contaminate drinking water sources (e.g., wells and streams)
and food, and (iii) subtropical and/or tropical climatic condi-
tions (e.g., warmth and humidity) favoring survival of cysts.
Balantidia, however, are adaptive to less than ideal conditions,
as evidenced by their ability to infect compromised hosts living
in urban settings and to survive in hogs in decidedly nontrop-
ical locations, such as Denmark (31) and Poland (62). Human-
to-human spread by the fecal-oral route can take place as with
other enteric diseases.
Outbreaks of Balantidiosis
What factors are responsible for balantidiosis outbreaks in
humans? What is regarded as the largest outbreak of balan-
tidiosis occurred following a typhoon that hit the island of Truk
in the Caroline Islands (Western Pacific), where many of the
residents kept pigs. A typhoon destroyed homes and rooftop
catchment systems for collection of rainwater, leaving people
without a source of uncontaminated water. Instead, they used
BALANTIDIUM COLI 633
water from streams and wells that were contaminated with pig
and human feces, resulting in balantidiosis in 110 persons on
the island, as well as an increase in E. histolytica and Ascaris
infections (72). Neither age nor gender was a factor in infec-
tion and disease, as it appears to be in normal transmission
in areas of endemicity. Symptoms of disease appeared an av-
erage of 6 days (range, 0 to 27 days) before laboratory diag-
nosis was made by stool examination (72).
In institutional populations (mental hospitals, prisons, and
orphan asylums), where pigs are an unlikely source of infec-
tion, outbreaks are the result of asymptomatic carriers and the
difficulties involved in maintaining hygienic control (6). Cases
developing in urban areas generally occur in immunocompro-
mised hosts and are self-limiting outbreaks (3, 9, 20, 70, 75).
The bacterial flora of the host can influence its susceptibility
and course of infection, particularly if pathogenic or poten-
tially pathogenic bacteria are found in the gut. This has been
the case for nonhuman primates (57) and supports a secondary
role of Balantidium in causing disease (41, 59, 62).
Virulence versus Avirulence in Balantidium
Are there virulent and avirulent strains of B. coli and B. suis?
What factor(s) triggered the balantidiosis outbreak in Truk
described above? Because the prevalence of Balantidium in the
population was low before the typhoon hit the island, Walzer
et al. (72) postulated that the source of the infection was pigs
rather than humans.
In theory, a virulent strain entering a population, whether
from contaminated water or human or pig contacts, is a likely
source of disease outbreak. In contrast, avirulent strains are
either ineffectual in causing disease or produce asymptomatic
infections. But no evidence for such a dichotomy in balantidia
is available. Humans are not easily infected, and the preva-
lence of Balantidium among humans (estimated at 1% world-
wide) is lower than that in pigs, which can be as high as 100%
in surveyed swine populations (31). The distribution of patho-
genic Entamoeba histolytica and its nonpathogenic look-alike
E. dispar in human populations helps to explain the anomaly of
persons having entamoebae in stools without symptoms of
invasive disease (15). Many more persons are infected asymp-
tomatically with E. dispar than with the pathogenic organism E.
histolytica. Among those diagnosed as having Entamoeba in
their stools, only 10 to 20% exhibit diarrheic disease. Further-
more, even the avirulent organism E. dispar may erode the
colon wall and cause symptoms such as bloating and cramps
(15).
PREVALENCE OF BALANTIDIUM COLI
Infections in Nonhuman Mammals
Although pigs are a major source of balantidiosis, a number
of other mammalian species have been found to harbor the
ciliate. In a study done in Japan with fecal samples from 56
mammalian species, 6 were found to harbor the ciliate (49).
The species were mainly nonhuman primates but also included
wild boars. Rodents and carnivores (cats and dogs) tested
negative. From the small number of infections found, Nakau-
634 SCHUSTER AND RAMIREZ-AVILA
chi (49) concluded that the disease was not a veterinary con-
cern in Japan.
Swine. Studies that have examined the prevalence of Balan-
tidium in pigs in the United States are few. Morris et al. (47)
studied intestinal parasites of pigs, including B. coli, from
Oklahoma hog farms. Balantidium was detected in 55.1% of
pigs examined, with adult swine having a higher prevalence
(18.6%) than shoats (14.6%) and nursing pigs (5%). Pigs on
pasture land or dirt lots had a somewhat higher percentage
(16.4%) of balantidia than pigs kept on wood slats (13.2%) or
on cement surfaces (7.4%) (36). A study of hogs in southern
Georgia found a higher prevalence of B. suis in gestating hogs
than in lactating animals, but differences were attributed to
locations (different units) where hogs were confined and to age
differences (45). Weaned pigs were negative for balantidia but
soon became infected either from the mother or from caproph-
agy of residual fecal material in the holding pens. In general,
however, prevalence increased in pigs with age, as also shown
in the Oklahoma survey.
In two reports from Europe, the prevalence of Balantidium
in pigs from a Danish research farm increased from 57% for
suckling piglets to 100% for most other age groups (31). In a
survey of 15 of 20 pig-raising farms (n 514 fecal samples) in
Germany, the prevalence of infection was 60% for suckling
pigs (13).
Wild boars in rural Western Iran were a reservoir for Bal-
antidium, and since wild boars scavenge farms, Solaymani-
Mohammadi et al. (63) examined boars to assess the potential
for spread of ciliates to livestock and humans. Sixty-seven
percent of the animals were infected, with females and older
animals carrying a heavier parasite load than males and
younger boars. Because pork is proscribed for Moslems, rais-
ing pigs in Iran is not an important factor in zoonotic infec-
tions, and cases that occur are assumed to be the result of
human-to-human transmission. A study of fecal material from
292 feral pigs in water catchment areas in southwest Australia
identified 10 positive cases (3%) in genetically distinct popu-
lations (29). Infections were not uniformly distributed among
all genetic groups; most of the infected pigs (nine animals)
were from a single genetic subpopulation. Balantidium was
uncommon or absent from other subgroups. It was concluded
that feral pigs pose a public health threat to drinking water
supplies, as the animals wallow in creeks feeding into reser-
voirs providing water to local municipalities.
Simians and apes. A study of 910 fecal samples from 222
nonhuman primates confined in groups was carried out at four
zoological gardens in Belgium (40). Entamoeba spp. and Giar-
dia were the most common endocommensals, with infection
rates of 44% and 41%, respectively, and Balantidium was de-
tected in 13% of the fecal samples, mostly from Old World
monkeys (Celebes crested macaques, mandrills, and hamadr-
yas baboons); prosimians (e.g., lemurs) and New World mon-
keys were uninfected. Thus, though infection with the ciliate
was found in some groups, it was not a pervasive problem in
zoo populations. Its incidence in Old World monkeys might
relate to these simians spending more time on the ground than
other animals and being more likely to come into contact with
feces containing Balantidium cysts (40).
Nursing rhesus macaque monkeys at a research center were
studied for milk production (30). Animals with B. coli infec-
CLIN. MICROBIOL. REV.
tions produced milk with a lower fat content than that in
animals without B. coli. Furthermore, the heavier the infection,
the less fat was in the milk (about 6.5% in clean animals
versus 4.2% in animals with heavy infections). The lower fat
concentration, however, did not affect infants weights.
Baboons (Papio doguera) captured in the wild in Kenya were
the basis for a study of intestinal protozoa (48). At the time of
capture, 63% of the animals harbored Balantidium, the most
frequently found protozoon. After transfer and captivity in the
United States for a year and a half, none of the animals were
infected, although most other intestinal protozoa (e.g., Ent-
amoeba spp.) did not diminish in numbers.
A comparative survey of parasites of semicaptive (at a re-
habilitation center) versus free-ranging orangutans in Sabah,
Malaysia, found that the prevalence of B. coli was 14% in the
free-ranging group, while it was 42% among semicaptive young
animals (34).
Amphibia. A number of species of Balantidium have been
described from amphibia (e.g., Rana, Xenopus, and Bufo spe-
cies). A recent finding by Li et al. showed that Balantidium
occurred in the feces of the giant Chinese salamander (42). A
new species, Balantidium andianusis, was described from a
single animal; a second species from the salamander, Balan-
tidium sinensis, had previously been described from the frog.
The basis of identification to the species level was detailed
measurements of the oral apparatus, length, width, etc.
Infections in Humans
The prevalence of human balantidiosis is higher in popula-
tions in regions of endemicity having close contact with pigs or
pig feces, such as farmers and workers in abattoirs (51, 58).
Contacts between humans and pigs are necessary but not suf-
ficient to cause disease. Other factors must be taken into ac-
count, such as (i) host factors, including resistance and/or pos-
sible immunity; and (ii) the etiologic agent itself and its ability
to invade host tissues.
Balantidiosis is an uncommon human disease mostly re-
stricted to tropical and subtropical regions because of sanitary
standards, climatic conditions, and cultural mores. The major
factors in spread of the disease to humans are the presence of
infected swine and little or no means of disposal of animal and
human waste. It is a disease of poor, rural areas where people
are likely to live in close proximity to their livestock, with their
homes offering protection not only for themselves but also for
their domestic animals. It is the close association of people and
pigs that leads to infection. Pigs pass Balantidium cysts in their
feces, which can contaminate wells and groundwaters, serving
as a vehicle for transmission of parasites.
In a survey of 325 waterborne diseases in North America and
Europe, Balantidium infections accounted for 0.3% (n 1) of
the outbreaks (33).
A comprehensive study of stool samples from 2,000 Ay-
mara Indian children from the Altiplano region of Bolivia
found widespread infection with balantidia but a low level of
fulminant disease among the children (19). The overall prev-
alence of B. coli was 1.2% (range, 1.0 to 5.3%). More than half
of the pigs (n 50) in the same communities were infected
with balantidia, as determined by examination of stool sam-
ples. One-third of the children in the survey showed stunted
VOL. 21, 2008
growth as a result of chronic malnutrition. The authors of the
study concluded that the children were asymptomatic carriers
of balantidia but showed the consequences of long-term infec-
tions.
Areas of endemicity. Areas of endemicity are regions where
balantidiosis is a present and constant threat. Included among
these are the Philippines, parts of Papua New Guinea and
West Irian (Irian Jaya) in the western Pacific, and rural areas
of South America. As described above, conditions for spread
of disease are close contact with pigs and water contaminated
by human and porcine feces. Tropical temperatures and high
humidity favor survival of excreted Balantidium cysts in pig or
human feces. The disease is also in found in highland areas of
Papua New Guinea and Irian Jaya, where temperatures are
cooler than in the lowlands. Because of the highland temper-
atures, pigs often seek shelter and warmth in human habitats.
Prevalence studies based on surveys carried out in the 1950s
and onward have put the numbers at 28%, 20%, 11%, and in
more recent times (1970s), 1.7%, in only 3 of a total of 60
villages (53). Other studies found prevalence rates of 1% to
20% among people in the Central Highlands of Papua New
Guinea (5). Infections among women were twice as common as
those among men because women tend to the pigs.
Other possible pathways for transmission. Balantidiosis is a
cosmopolitan disease with potential for developing almost any-
where. The absence of pigs in strict Moslem societies makes
human-to-human transmission more likely. Rats may be carri-
ers of Balantidium, but it is not known if the rat Balantidium
species can infect humans. The cockroach, which has its own
species of Balantidium, may serve as a mechanical agent of
transmission from feces to food (67).
Sewage sludge may be another source of infection. Activated
sludge, a by-product of sewage treatment, can contain bacte-
rial, protozoan, and metazoan parasites and is a potential
threat to health if it is applied as a fertilizer. Such was the case
in Bahrain (Arabian Gulf), where sludge was found to contain
balantidia (range of 66 to 528 ml1, with a mean of 234 ml1).
The origin of the balantidia remained uncertain, since neither
pigs nor monkeys, both possible sources, are found in the
country. The occurrence of the ciliate appeared to have been a
one-time event, since ciliates were not found in subsequent
sludge samples (2).
Risk factors. The major risk factor for humans is close con-
tact with pigs. This is particularly so in areas of endemicity
(e.g., Papua New Guinea), where swine are kept in dirt lots; pig
and human feces are scattered indiscriminately, allowing con-
tamination of water sources; and residents may suffer from
chronic malnutrition or other predisposing factors, such as
parasitic infections. Crowding in dwellings can facilitate the
spread of infection. Others at risk are workers in abattoirs
where pig intestines are handled. Farmers working with pig
feces are at risk of contracting the infection. Given the num-
bers of simians carrying balantidia, zookeepers are another
such group, but at low or containable risk. Likewise, veterinar-
ians and veterinary students working with sick hogs are at risk
of infection.
Institutional balantidiosis. Both residents and workers in
asylums, orphanages, and prisons are potential candidates for
balantidiosis. A study of four mental institutions in Italy exam-
ined the prevalence of parasites in stool samples from 238
BALANTIDIUM COLI 635
residents (24). About 13 different, mostly protozoan parasites,
including B. coli, were found in stool samples. B. coli and the
more common organism Cryptosporidium parvum were de-
tected in 9.2% of the residents. A study done in the United
States found a 5% incidence of B. coli infections at a mental
hospital, and this appeared to increase with length of residence
(77). Poor hygiene among residents of the mental institution
was associated with spread of parasites on hands, tableware,
and dishes and with the practices of pica, coprophagy, and
geophagy. The conclusion is that hygienic surveillance and
antimicrobial therapy are necessary in such facilities to limit
the spread of parasites among institutional residents.
LABORATORY DIAGNOSIS
Because of their large size and spiraling motility, balantidia
can readily be recognized in wet mount slide preparations,
even at a low magnification (100). This is the case with
freshly collected diarrheic stool samples, which are likely to
contain actively swimming trophic ciliates, as well as bron-
choalveolar wash fluid. Stool samples for examination should
be collected over several days because excretion of parasites
can be erratic. Cyst stages are more common in formed stools.
To search for cysts, a portion of formed stool is broken up in
phosphate-buffered saline or fixative (10% phosphate-buffered
formalin or polyvinyl alcohol) and coarsely filtered through
gauze or a sieve to remove large pieces of debris. The resulting
fluid can be examined microscopically for cysts in formed
stools or for trophozoites in diarrheic stools. A phase-contrast
microscope is helpful for viewing internal structures of un-
stained living or fixed ciliates. Staining can be done using
Lugols iodine (1:5 to 1:100 dilutions), but the stain concen-
trates progressively in the cytoplasm, obscuring details such as
the macronucleus. The same is true for permanent stains, such
as hematoxylin-eosin, as cells can take up excess stain, obscur-
ing all internal detail. Heavily stained cysts can be mistaken for
helminth ova, leading to misdiagnosis. Biopsy of the colon, if
performed, followed by hematoxylin-eosin staining of sections
may be useful in evaluating the extent of damage to the wall
(Fig. 4). Methods for concentration of parasites from stool
samples, making them easier to find, include sedimentation
and flotation (21). Since balantidiosis is a rare disease in de-
veloped countries, most technicians would not normally be
looking for trophozoites or cysts of Balantidium in examining
stool samples. Thus, it is particularly important that balantid-
iosis be considered a possibility for patients from areas of
endemicity and travelers returning from such areas. The num-
ber of balantidia in a stool sample may be high; 1,230 organ-
isms g1 feces was reported for the stool of a chimpanzee in
Japan (49). A Danish study of pigs at a research farm found an
average of 865 cysts g1 feces from pigs of 28 to 52 weeks of
age (31).
Pulmonary Infections
Diagnosing lung infections with B. coli can present a prob-
lem because of possible confusion between ciliated epithelial
cells (CEC) and trophic balantidia. Bronchoalveolar wash fluid
containing Balantidium has been reported (3, 58, 70) but may
also contain motile CEC from the trachea that can be mistaken
636 SCHUSTER AND RAMIREZ-AVILA
for ciliates in wet mounts. CEC have relatively few cilia on
their surfaces compared to the uniformly ciliated surfaces of
balantidia, and the cilia may be clumped in the case of colum-
nar epithelial cells; CEC are smaller (30 m) than balantidia
(150 to 200 m), elongated rather than ovoid, and more likely
to swim aimlessly in circles, unlike the pronounced spiraling
movements of ciliates (14, 28). The use of a phase-contrast
microscope can help to visualize Balantidium features, such as
the oral apparatus, uniform somatic ciliation, and the macro-
nucleus. During a search for respiratory syncytial virus in the
nasopharynx of an infant, unusual ciliated cells were seen in
wet mounts and initially thought to be parasites, most likely B.
coli. Subsequent examination after staining showed ciliary dis-
tribution along one edge of the cell and identified the cells as
ciliocytophthoria, degenerative fragments of epithelial cells
(28). CEC can also be confused with other motile pathogens, in
this case the flagellate stage of the ameboflagellate Naegleria
fowleri in cerebrospinal fluid samples (14).
Balantidiosis versus Dysentery
Most cases of dysentery, regardless of the causal agent, in-
cluding balantidial, amebic, and bacterial dysenteries, present
with similar clinical profiles, including abdominal pain and
diarrhea leading to dehydration and bloody stools. Balantidi-
osis outside areas of endemicity is relatively rare; amebiosis is
more likely to be encountered, particularly in travelers from
developed countries visiting areas of the world with poor san-
itation and contaminated drinking water. A travel history of
the patient can be helpful in making a preliminary diagnosis.
Bacillary dysentery is a constant and major public health men-
ace in developed and underdeveloped countries, with contam-
inated water and food and asymptomatic food handlers being
involved in disease transmission. Diagnosis is made using dif-
ferential or selective agars or manual or automated identifica-
tion systems. Among differential diagnoses of dysenteric dis-
eases are ulcerative colitis, diverticulosis, and inflammatory
bowel disease.
The cystic organism E. histolytica, found in formed stools,
measures 10 to 20 m and has a nucleus with a small central
endosome and peripheral chromatin connected to the endo-
some by a delicate fibrillar network. Four nuclei are typical of
the mature cyst. RNA-containing club-shaped chromatoid
bodies are seen in newly formed cysts but disappear as the cysts
age. There may be cysts of other amebae, such as E. dispar and
E. coli, both of which are harmless commensals that can be
mistaken for E. histolytica, in the stool. Balantidium cysts are
larger (40 to 60 m) than ameba cysts and are binucleate
(macro- and micronuclei), and at times the trophic organism
can be seen spinning within the cyst wall due to ciliary activity.
The two organisms are found in the trophic state in diarrheic
stools. Balantidia in wet mounts are active swimmers with
uniform ciliation and a spiraling swimming pattern. Trophic
Entamoeba can be seen moving on the slide surface by means
of an anterior ectoplasmic pseudopod and is smaller (25 m
in diameter) than Balantidium. Food vacuoles containing
erythrocytes differentiate trophic E. histolytica from other ame-
bae in stools. Both trophic organisms are seen optimally in
freshly collected feces that have not been refrigerated or al-
lowed to sit on a laboratory bench for hours.
CLIN. MICROBIOL. REV.
Balantidium and Laboratory Infection
In developed countries, fecal samples containing balantidia
are unusual, and the risk of laboratory infections is very low.
No laboratory-acquired infections have ever been reported.
Because the cysts pose more of a risk than do trophic ciliates,
precautions should be taken in handling formed porcine or
human fecal matter that might contain cysts. The numbers of
cysts in stool samples may be such that small amounts of
material can be highly infective. Cysts may also survive drying
on bench tops, instruments, and other laboratory surfaces.
Sodium hypochlorite (1%) is an effective disinfectant (55).
Procedures that produce aerosols should be avoided. Gloves
and a laboratory coat are appropriate protective clothing. Bio-
safety level 2 precautions are recommended.
PREVENTION OF INFECTION
The best means of protecting human populations from bal-
antidiosis is by providing a source of clean, uncontaminated
water for drinking and other purposes. Chlorine, at the con-
centrations normally used for ensuring water safety, is not
effective against cysts of Balantidium. Pigs should not be al-
lowed to roam in and around feeder streams or rivers that
empty into reservoirs that are used for providing municipal
water supplies (29). Likewise, spreading of sludge from sewage
processing as fertilizer can lead to contamination of produce or
water sources with cysts of balantidia (2). Pigs should not have
access to areas where crops are being raised. Judging from the
occurrence of balantidiosis in immunosuppressed individuals
living in urban settings, there are additional sources of infec-
tion besides pig-to-human transmission. Raising Balantidium-
free pigs is an unrealistic goal. Piglets become infected from
their mother or, if not that, through coprophagy.
ANTIMICROBIAL THERAPY
Tetracyclines and metronidazole are treatments of choice
for human Balantidium infection. A number of different dos-
age regimens and treatment durations exist in the literature (3,
20, 23, 75). For metronidazole (Flagyl), the treatment is typi-
cally 5 days (adult dosage, 750 mg three times a day; pediatric
dosage, 35 to 50 mg kg of body weight1 day1 in three doses
[maximum dosage, 2 g]), in contrast to tetracycline (adult dos-
age, 500 mg four times a day; pediatric dosage, 40 mg kg1
dose1 in four doses) treatment over 10 days. Iodoquinol, for
a 20-day treatment course (adult dosage, 650 mg three times a
day; pediatric dosage, 40 mg kg1 dose1 in three doses), and
doxycycline are alternatives (3, 58). There is some evidence
that nitazoxanide (Alinia), a broad-spectrum antiparasitic and
antihelminthic drug, may be another treatment for balantidi-
osis (52). The reader may wish to consult The Medical Letter on
Drugs and Therapeutics, Drugs for Parasitic Infections (46). Dos-
ages given here are from the 2004 edition but are unchanged in
the latest edition (2007).
CONCLUSIONS
Balantidium coli is a cosmopolitan parasitic-opportunistic
pathogen that can be found throughout the world. Its reservoir
host is the pig, and humans become infected through direct or
VOL. 21, 2008
indirect contact with pigs. In rural areas and in some develop-
ing countries where pig and human fecal matter contaminates
the water supply, there is a greater likelihood that balantidiosis
may develop in humans. The infection may be subclinical in
humans, as it mostly is in pigs, or may develop as a fulminant
infection with bloody and mucus-containing diarrhea; this can
lead to perforation of the colon. The disease responds to treat-
ment with tetracycline or metronidazole.
Balantidiosis is a disease that need never exist given access
to clean water and a public health infrastructure that monitors
the water supply and tracks infections. Its spread can be limited
by sanitary measures and personal hygiene, but it is a disease
that will be around as long as there are pigs. Immunocompro-
mised individuals have developed balantidiosis without any
direct contact with pigs, perhaps with rats or contaminated
produce as a possible source of infection. For the clinician,
balanatidiosis should be included in the differential diagnosis
for persistent diarrhea in travelers to or from Southeast Asia,
the Western Pacific islands, rural South America, or commu-
nities where close contact with domestic swine occurs.
Warming of the earths surface may provide a more favor-
able environment, even in the now temperate areas of the
world, for survival of trophic and cystic stages of Balantidium,
and its prevalence may increase. Effective sanitation and un-
contaminated water are the most useful weapons against in-
fection. Fortunately, balantidiosis responds to antimicrobial
therapy, and there have been no reports of resistance to the
drugs of choice.
ACKNOWLEDGMENTS
We thank Carol Glaser (Viral and Rickettsial Disease Laboratory)
for her enthusiastic support of this project. We also thank Blaine
Mathison and the CDC-DPDx Parasite Image Library (http://www.dpd
.cdc.gov/dpdx/), which was the source of illustrations used in this paper,
for parasite identification. F.L.S. is grateful to Govinda S. Visvesvara
(Division of Parasitic Diseases, CDC) for informative discussions
about Balantidium.
Neither author of this paper has any conflict of interest or financial
relationship relevant to the study.
REFERENCES
1. Adl, S. M., A. G. B. Simpson, M. A. Farmer, R. A. Andersen, O. R. Anderson,
J. R. Barta, S. S. Bowser, G. Brugerolle, R. A. Fensome, S. Fredericq, T. Y.
James, S. Karpov, P. Kugrens, J. Krug, C. E. Lewis, J. Lodge, D. H. Lynn,
D. G. Mann, R. M. McCourt, L. Mendoza, O. Mestrup, S. E. Mozley-
Standridge, T. A. Nerad, C. A. Shearer, A. V. Smirnov, F. W. Spiegel, and
M. F. J. R. Taylor. 2005. The new higher level classification of eukaryotes
with emphasis on the taxonomy of protists. J. Eukaryot. Microbiol. 52:399
451.
2. Amin, O. M. 1988. Pathogenic micro-organisms and helminths in sewage
products, Arabian Gulf, country of Bahrain. Am. J. Public Health 78:314
315.
3. Anargyrou, K., G. L. Petrikkos, M. T. E. Suller, A. Skiada, M. R. Siakan-
taris, R. T. Osuntoyinbo, G. Pangalis, and G. Vaiopoulos. 2003. Pulmonary
Balantidium coli infection in a leukemic patient. Am. J. Hematol. 73:180
183.
4. Baker, J. R. 1973. Parasitic protozoa. Hutchinson University Library, Lon-
don, United Kingdom.
5. Barnish, G., and R. W. Ashford. 1989. Occasional parasitic infections of man
in Papua New Guinea and Irian Jaya (New Guinea). Ann. Trop. Med.
Parasitol. 83:121135.
6. Baskerville, L., Y. Ahmed, and S. Ramchand. 1970. Balantidium colitis.
Report of a case. Am. J. Dig. Dis. 15:727731.
7. Cano Rosales, M., J. Medina Flores, and J. Narvaez Soto. 2000. Balantidiasis
en ninosreporte de un caso fatal. Diagnostico 39:221224.
8. Cermen o, J. R., I. Herna
ndez de Cuesta, O. Uzcategui, J. Pa
ez, M. Rivera,
and N. Baliachi. 2003. Balantidium coli in a HIV-infected patient with
chronic diarrhea. AIDS 17:941942.
9. Cho, H.-S., S.-S. Shin, and N.-Y. Park. 2006. Balantidiasis in the gastric
BALANTIDIUM COLI 637
lymph nodes of Barbary sheep (Ammotragus lervia): an incidental finding. J.
Vet. Sci. 7:207209.
10. Clark, C. G., and L. S. Diamond. 2002. Methods for cultivation of luminal
parasitic protists of clinical importance. Clin. Microbiol. Rev. 15:329341.
11. Clyti, E., C. Aznar, P. Coopie, M. el Gueedj, B. Carme, and R. Pradinaud.
1998. A case of coinfection by Balantidium coli and HIV in French Guiana.
Bull. Soc. Pathol. Exot. 91:309311.
12. Cox, F. E. G. 1961. The cultivation of Balantidium coli throughout its viable
temperature range. Ann. Trop. Med. Parasitol. 55:305308.
13. Damriyasa, I. M., and C. Bauer. 2006. Prevalence and age-dependent oc-
currence of intestinal protozoan infections in suckling pigs. Berl. Mu nch.
Tieraztl. Wochenschr. 119:287290.
14. Davis, L. E., G. S. Visvesvara, D. L. McLaren, R. Randell, C. C. Fenoglio,
L. C. McLaren, M. Purdy, V. Cooper, and G. R. Healy. 1985. Respiratory
epithelial cell masquerading as agents of primary amebic meningoencepha-
litis: distinguishing features. Neurology 35:14871490.
15. Diamond, L. S., and C. G. Clark. 1993. A redescription of Entamoeba
histolytica Schaudinn, 1903 (emended Walker, 1911) separating it from
Entamoeba dispar Brumpt, 1925. J. Eukaryot. Microbiol. 40:340344.
16. Dodd, L. G. 1991. Balantidium coli infestation as a cause of acute appendi-
citis. J. Infect. Dis. 163:1392.
17. Dorfman, S., O. Rangel, and L. G. Bravo. 1984. Balantidiasis: report of a
fatal case with appendicular and pulmonary involvement. Trans. R. Soc.
Trop. Med. Hyg. 78:833834.
18. Dzebenski, T. H. 1966. Immunofluorescent studies on Balantidium coli.
Trans. R. Soc. Trop. Med. Hyg. 60:387389.
19. Esteban, J.-G., C. Aguirre, R. Angles, L. R. Ash, and S. Mas-Coma. 1998.
Balantidiasis in Aymara children from the northern Bolivian altiplano.
Am. J. Trop. Med. Hyg. 59:922927.
20. Ferry, T., D. Bouhour, F. De Monbrison, F. Laurent, H. Domouchel-Cham-
pagne, S. Picot, M. A. Piens, and P. Granier. 2004. Severe peritonitis due to
Balantidium coli acquired in France. Eur. J. Clin. Microbiol. Infect. Dis.
23:393395.
21. Garcia, L. S. 2007. Diagnostic medical parasitology, 5th ed. ASM Press,
Washington, DC.
22. Garcia, L. S. 2008. Balantidium coli, p. 353366. In N. A. Khan (ed.),
Emerging protozoan pathogens. Taylor & Francis, New York, NY.
23. Garcia-Lavarde, A., and L. de Bonilla. 1975. Clinical trials with metronida-
zole in human balantidiasis. Am. J. Trop. Med. Hyg. 24:781783.
24. Giacometti, A., O. Cirioni, M. Balducci, D. Drenaggi, M. Quarta, M. De
Federicis, P. Ruggeri, D. Colapinto, G. Ripani, and G. Scalize. 1997. Epi-
demiologic features of intestinal parasitic infections in Italian mental insti-
tutions. Eur. J. Epidemiol. 13:825830.
25. Grain, J. 1994. Classe vestibuliferea de Puytorac et al., 1974, p. 311379. In
P. de Puytorac (ed.), Traite de Zoologie, vol. 2. Masson, Paris, France.
26. Grim, J. N. 1993. Endonuclear symbionts within a symbiont: the surgeonfish
intestinal symbiont, Balantidium jocularum (Ciliophora) is host to a gram-
positive macronuclear inhabiting bacterium. Enterocytobiosis Cell Res.
9:209214.
27. Hackstein, J. H. P., R. H. de Graaf, J. J. van Hellemond, and A. G. M.
Tielens. 2008. Hydrogenosomes of anaerobic ciliates. Microbiol. Monogr.
9:97112.
28. Hadziyannis, E., B. Yen-Lieberman, G. Hall, and G. W. Procop. 2000. Cilio-
cytophthoria in clinical virology. Arch. Pathol. Lab. Med. 124:12201223.
29. Hampton, J., P. B. S. Spencer, A. D. Elliot, and R. C. A. Thompson. 2006.
Prevalence of zoonotic pathogens from feral pigs in major public drinking
water catchments in Western Australia. EcoHealth 3:103108.
30. Hinde, K. 2007. Milk composition varies in relation to the presence and
abundance of Balantidium coli in the mother in captive rhesus macaques
(Macaca mulatta). Am. J. Primatol. 69:625634.
31. Hindsbo, O., C. V. Nielsen, J. Andressen, A. L. Willingham, M. Bendixen, M.
Nielsen, and N. O. Nielsen. 2000. Age-dependent occurrence of the intestinal
ciliate Balantidium coli in pigs at a Danish research farm. Acta Vet. Scand.
41:7983.
32. Jameson, A. P. 1927. The behaviour of Balantidium coli Malm. in cultures.
Parasitology 19:411419.
33. Karanis, P., C. Kourenti, and H. Smith. 2007. Waterborne transmission of
protozoan parasites: a worldwide review of outbreaks and lessons learnt. J.
Water Health 5:138.
34. Kilbourn, A. M., W. B. Karesh, N. D. Wolfe, E. J. Bosi, R. A. Cook, and M.
Andau. 2003. Health evaluation of free-ranging and semi-captive orangutans
(Pongo pygmaeus pygmaeus) in Sabah, Malaysia. J. Wildl. Dis. 39:7383.
35. Klaas, J., II. 1974. Two new gastric mucin cultivation media and a chemically
defined maintenance medium for Balantidium coli. J. Parasitol. 60:907910.
36. Krascheninnikow, S., and E. L. Jeska. 1961. Agar diffusion studies on the
species specificity of Balantidium coli, B. caviae and B. wenrichi. Immunology
4:282288.
37. Krascheninnikow, S., and D. H. Wenrich. 1958. Some observations on mor-
phology and division of Balantidium coli and Balantidium caviae. J. Proto-
zool. 5:196202.
38. Lerman, R. H., W. T. Hall, and O. Barret, Jr. 1970. Balantidium coli infection
in a Vietnam returnee. Calif. Med. 112:1718.
638 SCHUSTER AND RAMIREZ-AVILA
39. Leuckart, R. 1857. Ueber Paramecium (?) coli Malmst. Arch. Naturgesch.
27:80.
40. Levecke, B., P. Dorny, T. Geurden, F. Vercammen, and J. Vercruysse. 2007.
Gastrointestinal protozoa in non-human primates of four zoological gardens
in Belgium. Vet. Parasitol. 148:236246.
41. Levine, N. D. 1961. Protozoan parasites of domestic animals and of man.
Burgess Publishing Co., Minneapolis, MN.
42. Li, M., J. Wang, Z. Gu, F. Ling, X. Ke, and X. Gong. 2008. First report of two
Balantidium species from the Chinese giant salamander, Andrias davidianus:
Balantidiuim sinensis Nie 1935 and Balantidium andianusis n. sp. Parasitol.
Res. 102:605611.
43. Lidell, M. E., D. M. Moncada, K. Chadee, and G. C. Hansson. 2006. Ent-
amoeba histolytica cysteine proteases cleave the MUC2 mucin in its C-
terminal domain and dissolve the protective colonic mucus gel. Proc. Natl.
Acad. Sci. USA 103:92989303.
44. Malmsten, P. H. 1857. Infusorien als Intestinal-Thiere beim Menschen.
Arch. Pathol. Anat. Physiol. Klin. Med. 12:302309.
45. Marti, O. G., Jr., and O. M. Hale. 1986. Parasite transmission in confined
hogs. Vet. Parasitol. 19:301314.
46. Medical Letter, Inc. 2004. The medical letter on drugs and therapeutics.
Drugs for parasitic infections. The Medical Letter, Inc., New Rochelle, NY.
47. Morris, R. G., H. E. Jordan, W. G. Luce, T. C. Coburn, and C. V. Maxwell.
1984. Prevalence of gastrointestinal parasitism in Oklahoma swine. Am. J.
Vet. Res. 45:24212423.
48. Myers, B. J., and R. E. Kuntz. 1968. Intestinal protozoa of the baboon Papio
doguera Pucheran, 1856. J. Protozool. 15:361365.
49. Nakauchi, K. 1999. The prevalence of Balantidium coli infection in fifty-six
mammalian species. J. Vet. Med. Sci. 61:6365.
50. Nickel, R., R. Stern, and M. Lieppe. 2000. Evidence that hyaluronidase is not
involved in tissue invasion of the protozoan parasite Entamoeba histolytica.
Infect. Immun. 68:30533055.
51. Oberhuber, G., G. Karpitschka, and M. Stolte. 1993. Balantidium coli: a rare
cause of colonic ulcer. Eur. J. Gastroenterol. Hepatol. 5:755757.
52. Ochoa, T. J., and C. White. 2005. Nitazoxide for treatment of intestinal
parasites in children. Pediatr. Infect. Dis. 24:641642.
53. Owen, L. L. 2005. Parasitic zoonoses in Papua New Guinea. J. Helminthol.
79:114.
54. Pinheiro, M. C., and M. A. Lima. 1991. Caso fatal de balantiase intestinal.
Rev. Soc. Bras. Med. Trop. 24:173176.
55. Public Health Agency of Canada. 1999. Material safety data sheet. Public
Health Agency of Canada, Ottawa, Ontario, Canada. http://www.phac.aspc
.gc.ca/msds15e.html.
56. Rees, C. W. 1927. Balantidia from pigs and guinea pigs: their viability, cyst
production and cultivation. Science 61:8991.
57. Sestak, K., C. K. Merritt, J. Borda, E. Saylor, S. R. Schwamberger, F.
Cogswell, E. S. Didier, P. J. Didier, G. Plauche, R. P. Bohn, P. P. Aye, P.
Alexa, R. L. Ward, and A. A. Lackner. 2003. Infectious agent and immune
response characteristics of chronic enterocolitis in captive rhesus macaques.
Infect. Immun. 71:40794086.
58. Sharma, S., and G. Harding. 2003. Necrotizing lung infection caused by the
protozoan Balantidium coli. Can. J. Infect. Dis. 14:163166.
59. Skotarczak, B. 1997. Bacterial-flora in acute and symptom-free balantidiosis.
Acta Parasitol. 42:230233.
CLIN. MICROBIOL. REV.
60. Skotarczak, B. 1997. Ultrastructural and cytochemical identification of per-
oxisomes in Balantidium coli, Ciliophora. Folia Biol. 45:117120.
61. Skotarczak, B., and L. Kolodziejczyk. 2005. An electron microscopic study of
the phosphatases in the ciliate Balantidium coli. Folia Morphol. 64:282286.
62. Skotarczak, B., and R. Zielinski. 1997. A comparison of nucleic acid content
in Balantidium coli trophozoites from different isolates. Folia Biol. (Krakow)
45:121124.
63. Solaymani-Mohammadi, S., M. Rezaian, H. Hooshyar, G. R. Molavi, Z.
Babaei, and M. A. Anwar. 2004. Intestinal protozoa in wild boars (Sus scrofa)
in western Iran. J. Wildl. Dis. 40:801803.
64. Stein, F. 1863. Ueber Paramecium (?) coli Malmsten. Amtl. Berl. Dtsch.
Chem. Ges. 37:165.
65. Struder-Kypke, M. C., A.-D. G. Wright, W. Foissner, A. Chatzinotas, and D.
Lynn. 2006. Molecular phylogeny of litostome ciliates (Ciliophora, Litosto-
matea) with emphasis on free-living haptorian genera. Protist 157:261278.
66. Struder-Kypke, M. C., O. A. Kornilova, and D. Lynn. 2007. Phylogeny of
trichostome ciliates (Ciliophora, Litostomatea) endosymbiotic in the Yakut
horse (Equus caballus). Eur. J. Protistol. 43:319328.
67. Tatfeng, Y. M., M. U. Usuanlele, A. Orukpe, A. K. Digban, M. Okodua, F.
Oviasogie, and A. A. Turay. 2005. Mechanical transmission of pathogenic
organisms: the role of cockroaches. J. Vector Borne Dis. 42:129134.
68. Templis, C. H., and M. G. Lysenko. 1957. The production of hyaluronidase
by Balantidium coli. Exp. Parasitol. 6:3136.
69. Tillack, M., L. Biller, H. Irmer, M. Freitas, M. A. Gomes, E. Tannich, and I.
Bruchhaus. 2007. The Entamoeba histolytica genome: primary structure and
expression of proteolytic enzymes. BMC Genomics 8:170. http://www
.biomedcentral.com/1471-2164/8/170.
70. Vasilakopolou, A., K. Dimarongona, A. Samakovli, K. Papadimitris, and A.
Avlami. 2003. Balantidium coli pneumonia in an immunocompromised pa-
tient. Scand. J. Infect. Dis. 35:144146.
71. Vasquez, W., and J. Vidal. 1999. Colitis balantidiasica: a proposito de un caso
fatal en el departamento de Huancavelica. An. Fac. Med. 60:119123.
72. Walzer, P. D., F. N. Judson, K. B. Murphy, G. R. Healy, D. K. English, and
M. G. Schultz. 1973. Balantidiasis outbreak in Truk. Am. J. Trop. Med. Hyg.
22:3341.
73. Wright, A.-D. G. 1999. Analysis of intraspecific sequence variation among
eight isolates of the rumen symbiont, Isotricha prostoma (Ciliophora), from
two continents. J. Eukaryot. Microbiol. 46:445446.
74. Yang, Y., L. Zeng, and J. Zhou. 1995. Diarrhoea in piglets and monkeys
experimentally infected with Balantidium coli isolated from human feces. J.
Trop. Med. Hyg. 98:6972.
75. Yazar, S., F. Altuntas, I. Sahin, and M. Atambay. 2004. Dysentery caused by
Balantidium coli in a patient with non-Hodgkins lymphoma from Turkey.
World J. Gastroenterol. 10:458459.
76. Young, M. 1950. Attempts to transmit human Balantidium coli. Am. J. Trop.
Med. Hyg. 30:7172.
77. Young, M. D., and C. Ham. 1941. The incidence of intestinal parasites in a
selected group at a mental hospital. J. Parasitol. 27:7174.
78. Zaman, V. 1964. Studies on the immobilization reaction in the genus Bal-
antidium. Trans. R. Soc. Trop. Med. Hyg. 58:255259.
79. Zaman, V. 1970. Activity of contractile vacuole in the parasitic ciliate, Bal-
antidium coli. Experientia 26:806807.
80. Zaman, V. 1978. Balantidium coli, p. 633653. In J. P. Kreier (ed.), Parasitic
protozoa, vol. 2. Academic Press, New York, NY.