American Journal of Hematology 73:180183 (2003)

Pulmonary Balantidium coli Infection in a

Leukemic Patient
K. Anargyrou,1 G.L. Petrikkos,2 M.T.E. Suller,3* A. Skiada,2 M.P. Siakantaris,1
R.T. Osuntoyinbo,2 G. Pangalis,1 and G. Vaiopoulos1
1

Hematology Section, 1st Department of Internal Medicine, Athens University School of Medicine, Laikon General Hospital, Goudi,
Athens, Greece

Infectious Diseases and Antimicrobial Chemotherapy Research Laboratory G.K. Daikos, 1st Department of Propaedeutic Medicine,
Athens University School of Medicine, Laikon General Hospital, Goudi, Athens, Greece
3
Faculty of Applied Biosciences, University of the West of England, Frenchay Campus, Bristol, United Kingdom

A 59-year-old woman suffering from chronic lymphocytic leukemia developed pulmonary

lesions; bronchoalveolar lavage was performed for possible systemic fungal infection.
However, direct microscopic analysis revealed ciliated protozoa identified as Balantidium
coli. B. coli is the only known pathogenic ciliate, and is usually associated with intestinal
infection in areas associated with pig rearing. On very rare occasions the organisms may
invade extra-intestinal organs, in this case the lungs of an immunocompromised patient.
This case is unusual as balantidiasis is rare in Europe, the patient had no obvious contact
with pigs, and there was no history of diarrhea prior to pulmonary colonization. Metronidazole was rapidly administered, and the condition improved after 2448 hr. Am. J.
2003 Wiley-Liss, Inc.
Hematol. 73:180183, 2003.
Key words: Balantidium coli; pulmonary; leukemia; parasite

CASE HISTORY

A 58-year-old female was diagnosed with chronic

lymphocytic leukemia, Rai stage 0, in September 1997.
The complete blood cell count (CBC) on diagnosis was:
white blood cells 8 109/l (18% neutrophils, 70% lymphocytes, 7% monocytes, 5% eosinophils), hemoglobin
12.5 g/dl, hematocrit 39.5%, platelets 256 109/l.
The patients condition remained stable until November 1999, when neck, axillary, and inguinal lymphadenopathy developed. The CBC was as follows: white
blood cells 61.2 109/l (10% neutrophils, 87% lymphocytes, 1% monocytes, 2% eosinophils), hemoglobin 11.7
g/dl, hematocrit 36.5%, platelets 160 109/l.
In January 2000, because of the lymphadenopathy and
increased lymphocytes, antileukemic therapy with chlorambucil and methylprednisolone (32 mg/day) was initiated in another hospital. She received a total of 7 cycles
of chlorambucil, at a dose of 10 mg per day, for 14 days
per month, without any significant improvement, either
in terms of lymph nodes or CBC. In December 2000,
fludarabine was administered, at a dose of 30 mg/day, for
5 days. The result of the first cycle was severe pancytopenia, and it was interrupted. The patient chose to leave
the center where she was being treated, and she referred
2003 Wiley-Liss, Inc.

herself to our hematological center. At that time she was

taking only prednisolone (40 mg/day). In January 2001 a
neck lymph node was resected for biopsy. The sections
showed effacement of the normal lymph node architecture by a diffuse population of small lymphocytes, within
which there were small, rather indistinct, clusters of
larger cells with nucleoli. The appearance was consistent
with the diagnosis of small lymphocytic lymphoma/BCLL. Bone marrow biopsy showed a markedly hypercellular marrow with a dense interstitial infiltrate of small
lymphocytes similar to those seen in the lymph node.
Myelopoiesis was seen on small clusters of cells adjacent
to the bone, but myelopoietic reserve was much reduced.
Erythroid cells were difficult to identify. Cell marker

*Correspondence to: Dr. Marc T.E. Suller, Faculty of Applied Biosciences, University of the West of England, Frenchay Campus, Coldharbour Lane, Bristol BS16 1QY, United Kingdom. E-mail:
msuller@lycos.com
Received for publication 24 July 2002; Accepted 15 March 2003
Published online in Wiley InterScience (www.interscience.wiley.com).
DOI: 10.1002/ajh.10336

Case Report: Leukemic Balantidium coli Infection

Fig. 1. Chest X ray showing bilateral, diffuse micronodular,

and interstitial lesions in the lungs.

studies showed a typical CLL immunophenotype

(CD19+/CD5+, CD23+, FMC7).
In March 2001 she developed low-grade fever of
37.8C and was treated, at home, with ciprofloxacin, 1
g/day, for 8 days. She remained febrile and in the week
prior to admission to the hospital (16th23rd May 2001),
the patient developed a high-fever of 39.9C with rigors
and a headache that did not respond to analgesics. She
also complained of weakness, weight loss (23 kg in 1
month), abdominal cramps and bloating, a persistent,
nonproductive cough, and dyspnea.
On May 23 she was admitted to our hospital. The
patient was pale and in distress. Her blood pressure was
110/60 mmHg, the pulse rate was 120/min and her temperature 36.6C. Arterial blood gases were as follows:
pO2 42.7 mmHg, pCO2 31.6 mmHg, pH 7.5, HCO3 24.9
mmol/l, saturation 83.3%. Enlarged lymph nodes were
palpated in the cervical, axillary, and inguinal areas. Examination of the head and neck was otherwise normal.
Physical examination of the respiratory and cardiovascular system revealed no significant findings. The abdomen
was soft and nontender, with no palpable organomegaly,
with normal sounds. Her laboratory blood tests were as
follows: hemoglobin 10.5 g/dl, hematocrit 33.8%, white
blood count 28600/l (polymorphonuclear leucocytes
3%, lymphocytes 97%), platelets 84000/l, urea 38 mg/
dl, creatinine 0.9 mg/dl, sodium 138 mEq/l, potassium
4.4 mEq/l, AST 50 U/l, ALT 22 U/l, lactic dehydrogenase 1,344 U/l. A chest X ray showed bilateral, diffuse
micronodular and interstitial lesions in the lungs (Fig. 1).
A chest CT-scan showed enlarged lymph nodes of the
mediastinum, on the right, by the trachea and on the left,

181

near the aortic arch. The axillary lymph nodes were also
enlarged. Bilateral, diffuse micronodular, and interstitial
lesions were seen in the lungs. An abdominal CT scan
showed small enlargement of the liver and spleen, with
no focal lesions, and enlarged para-aortic lymph nodes.
Pancreas and kidneys were normal.
Treatment with ceftriaxone, 2 g/day, and amikacin, 1
g/day, was started. In view of the findings, a fungal (including Pneumocystis carinii) infection of the lung was
suspected, and subsequently a bronchoalveolar lavage
was performed. Direct microscopic examination of the
specimen revealed numerous protozoa that were 50 m
or more in diameter. They had an outer membrane covered by short cilia and a single large kidney-bean-shaped
nucleus. They exhibited a rotary/boring motility, which
became more vigorous with continued illumination. They
were identified as Balantidium coli. Trying to identify a
possible source of infection, multiple questions were
asked, but the patient confirmed that she lived only in
Athens, denied any contact with pigs or other mammals,
and her diet did not include any raw meat.
A stool sample was obtained from the patient which
was nondiarrheal and nonmucoid in appearance, and no
parasites were observed microscopically. Stains and PCR
for P. carinii were repeatedly negative. The patient was
treated for the parasitic infection with metronidazole at
750 mg, administered intravenously 3 times a day for 15
days. After 24 hr the patient was afebrile with a normal
body temperature, and upon the completion of antiparasitic therapy, X rays and CT scans revealed that the lung
lesions had receded (Fig. 2). During the next 6 months
there was no clinical or radiological relapse of the infection, and this led us to the conclusion that the organism
was effectively eliminated. Following the infection, the
patient was again treated with fludarabine, at a reduced
dose, 25 mg/day/month for 1 cycle and then continued
with COP (cyclophosphamide, Oncovin, prednisolone).
DISCUSSION

B. coli is the largest protozoan parasite and the only

ciliated protozoa known to infect humans. Human infection is relatively rare and occurs mainly in tropical regions, especially Latin America, the Far East, and New
Guinea, usually associated with areas of pig rearing [1].
B. coli colonizes the intestine of the pig and then multiplies by asexual reproduction, during which each parasitic cell divides into two daughter cells, by transverse
binary fission. However, the trophozoite will encyst as it
passes through the intestine and is excreted in feces. A
definitive host may ingest the encysted organism and
consequently become infected after de-encystation in the
stomach. Although the pig is the major host for B. coli,
the organism is capable of adapting to new host species,
such as humans, guinea pigs, and other mammals, and

182

Case Report: Anargyrou et al.

Fig. 2. Chest X ray after treatment with metronidazole at

750 mg, administered intravenously 3 times a day for 15
days, revealing that the lung lesions had receded.

cause serious disease. Human balantidiosis is most

prevalent where pigs are raised and slaughtered. Colonization is usually noninvasive and asymptomatic but may
lead to acute or chronic diarrhea [2]. Proteolytic enzymes, e.g., hyaluronidases, are produced that can break
down the intestinal epithelium, resulting in invasion of
the mucosa and colon ulceration [3]. The production of
these proteolytic enzymes might be the factor that differentiates B. coli from other ciliate protozoa, allowing it
to infect humans. As a result, hemorrhaging and secondary bacterial infections may occur. Occasionally, the organisms will perforate the large intestine and affect the
small intestine, [4] the appendix, [3] the vagina, uterus,
and bladder, [5] and on very rare occasions the liver [6]
and lungs [79]. Currently, precise information about
exact morbidity and mortality rates of balantidiasis is
lacking. A study performed in Amerindian populations of
Amazonia [10] found both a low prevalence of the disease and absence of symptoms or signs referable to this
organism. In another study, performed in San Cayetano,
Corrientes, Argentina, 207 stool samples were collected
from children and examined; 83% contained one or more
parasites. The prevalence of B. coli was 0.5% [11]. Immunologic factors, such as IgA and T-cell responses, are
important for giardiasis and spore-forming protozoa, but
there are no studies regarding B. coli and immunosuppression. There is little information about balantidiasis in
HIV-infected patients. In parts of the world where pigs
are the principal domestic animals and standards of hy-

giene are suboptimal, infection rates of Balantidium in

the population can be high, and it is likely that immunodeficiency can lead to exacerbation of this disease. A
case of co-infection by B. coli and HIV has been reported
from French Guiana [12].
Diagnosis of B. coli is established by observing trophozoites in stool or tissue samples. It is relatively easy
to recognize in clinical specimens due to its large size
(50100 m long and 4070 m wide), an outer membrane covered by short cilia and a single large kidneybean-shaped nucleus. In wet mount preparations, it exhibits a rotary/boring motility, and the macronucleus may
be apparent. Iodine may be used to stain the organism,
and the nucleus becomes clearly visible (other staining).
There are several drugs that can be used in the treatment
of balantidiasis: tetracycline, 500 mg qid, for 10 days;
metronidazole, 750 mg tid, for 5 days; or iodoquinol, 650
mg tid, for 20 days [13]. In this case, metronidazole was
chosen because it can be given intravenously and it was
readily available
This case is unusual for three reasons: (i) The incidence of the disease in Europe is very low, so physicians
may not have considered the possibility of balantidiasis.
Several interesting articles, originating in the U.S. [14
16], include discussions about B. coli, but there are no
similar articles from Europe. (ii) B. coli infection in humans is usually associated with poor sanitation and close
proximity to pigs. However, there was no evidence to
suggest any interaction of this patient with pigs. Ladas et
al. [8] reported a balantidium infection of the lungs and
the intestine of a 70-year-old Greek male with bronchial
asthma, who was not immunocompromised, and who
also claimed to have had no contact with pigs. (iii) There
was no history of bloody or mucoid diarrhea leading up
to the diagnosis of balantidiasis, although invasion of the
intestinal mucosa does not always lead to ulceration [8].
There are three other reports of lung balantidiasis in the
literature. The most common site of infection is the intestine. A possible mechanism for lung infection could be
initial colonization of the intestine, ulceration, and subsequent hematological dissemination, although this hypothesis remains to be proven. In our case diagnosis was
established as a consequence of the results of the CT
scan, which revealed lesions in the lungs. As the patient
was suffering from leukemia, and thus was immunocompromised, a systemic mold infection was suspected. For
this reason, a BAL specimen was collected, in which the
parasite was observed microscopically. Without rapid
initiation of therapy, the patients condition would probably have rapidly deteriorated. Treatment with the appropriate antibiotic (metronidazole) and rapid improvement confirm the diagnosis of B. coli as the etiology of
the febrile pulmonary disease of this immunocompromised patient. The patient was immunocompromised
from having leukemia, from being on long-term cortico-

Case Report: Leukemic Balantidium coli Infection

steroids, and from receiving chemotherapy, which affects

lymphocyte function. It would seem logical to conclude
that the above factors played a role in the infection, but
no studies about balantidiasis in immunocompromised
patients exist. Parasites pose a serious problem in the
patient with impaired lymphocyte function, and further
studies are needed to elucidate their mode of action.
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