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Diphyllobothriasis, a rare cause of profuse diarrhea following autologous transplantation

Diphyllobothriasis is a zoonosis acquired by humans after the ingestion of plerocercoid larvae present in raw and undercooked fish. In North America, Diphyllobothrium latum (D. latum) infection is limited mostly to areas with cold water lakes.1 Various species of freshwater or anadromous (living in both fresh and saltwater) fishes may be infected by D. latum plerocercoid larvae, including perch, trout, salmon, char and pike.2 We report herein the first case of D. latum infection in an immunocompromised patient who presented with profuse diarrhea.

The patient was a 60-year-old man who lived in the north-east area of the Province of Quebec, Canada, and who had never traveled outside the country. This patient with anaplastic T-cell lymphoma had achieved minimal residual disease with ESHAP (etoposide, methylprednisolone, cytosine arabinoside and cis-platinum) chemotherapy. He was admitted to our institution in December 2005 to undergo auto-SCT. His disease initially presented with widespread abdominal lymph nodes and multiple hepatic nodular lesions, which progressed after eight cycles of CHOP (CY, doxorubicin, VCR and prednisone). His medical history was significant for mild, chronic diarrhea (2–3 loose stools/day) of 1-year duration; complete investigation by a gastroenterologist, including upper and lower endoscopies, was negative.

After conditioning with BEAC (bis-chloronitrosourea, etoposide, cytosine arabinoside and CY), the patient received his autologous stem cell graft on 29 December 2005. On day +3, though neutropenic, he developed fever, diffuse abdominal pain and profuse diarrhea, which reached a maximum of 5025 ml/day (Figure 1). A computed tomography scan of the abdomen revealed right colitis as well as a thickening of the cecum and distal parts of the small bowel. Coprological cultures were negative for pathogenic bacteria or viruses; quantitative PCR in blood leukocytes for CMV was also negative. The patient recovered from aplasia on day +18 with decreased diarrhea. However, the improvement was of short duration, with recurrence of both diarrhea and fever on day +28 despite the resolution of aplasia (Figure 1). Multiple repeat stool cultures were unable to identify any specific pathogen. A careful physical examination showed a new right cervical lymph node. Repeat computed tomography scans of the chest and abdomen were suggestive of lymphoma relapse with recurrence of several lymph nodes in previously involved areas. Biopsy of the right cervical lymph node confirmed relapse of anaplastic T-cell lymphoma.

Figure 1
figure1

Evolution of stool output in ml after autologous transplant. Arrows indicate Praziquantel treatment.

A microbiology consultation was obtained on day +42; three stool specimens were sent for parasitic examination. A diagnosis of D. latum infection was made after identification of numerous characteristic parasite eggs (Figure 2). The patient received a single dose of praziquantel (10 mg/kg) on day +43 with initial improvement in stool output. Two stool specimens became negative for parasite eggs after the first treatment. However, on day +49, profuse diarrhea recurred and eggs in two separate stool specimens were again identified. A second dose of praziquantel on day +57 led to complete resolution of diarrhea; all stool examinations remained negative after the second dose. Owing to early relapse after transplant, the patient was offered palliative care and died on day +82.

Figure 2
figure2

Eggs of Diphyllobothrium latum found in the feces of the patient (Microscopy × 10).

This is the first report of D. latum infection in an immunocompromised host. The major symptoms encountered by D. latum infection in immunocompetent patients include abdominal pain, vomiting, dyspepsia, diarrhea and discharge of proglottids in feces.3 Patients often seek medical advice after observing tapeworm segments in feces. Other symptoms are nonspecific and include fatigue, anorexia, fever and myalgia.3, 4 Megaloblastic anemia has been described as a complication of long-term infestation, as a result of vitamin B12 malabsorption.5 In our patient, it is difficult to determine whether the initial symptoms (fever, abdominal pain) before autologous transplant were due to lymphoma or parasitic infection. There was no evidence of eosinophilia, megaloblastic anemia or vitamin B12 deficiency in blood analyses before transplant. Following further questioning on life habits, we discovered that the most likely source of contamination was the consumption of raw trout in the months before autograft.

Since 1987, the medication of choice for D. latum infection has been praziquantel. Single-dose treatment with praziquantel 5–10 mg/kg produces high cure rates in patients with D. latum infection. However, in many instances, a second dose is given when the tapeworm is not evacuated. In our patient, a second dose was given after the recurrence of diarrhea and relapse of eggs on stool examination. It is noted that the whole worm was not observed in feces after the first praziquantel dose.6, 7

Diarrhea is often observed after autologous or allogeneic transplantation. Identification of the specific cause is important for appropriate management. Diarrhea may have multiple causes, including infectious agents, drugs, GVHD and metabolic conditions. Among infectious agents, the bacterial, viral and parasitic organisms can all cause diarrhea. In the first 30 days after transplantation, Clostridium difficile is the most common pathogen.8 After 30 days, CMV disease predominates. Herpes virus, enterovirus and rotavirus have also been reported. Cryptosporidium spp, Entamoeba histolytica and Blastocystis hominis are parasites most commonly seen in immunocompromised patients. Cryptosporidiosis has been reported, especially in renal transplant recipients. Strongyloides and Ascaris are rare, whereas Mycobacterium avium and Candida albicans are uncommon etiological agents of diarrhea.8, 9

Drug-induced diarrhea also occurs frequently among transplant patients. Both chemotherapeutic agents, such as melphalan, thiotepa, anthracyclines and etoposide, and antibiotics have been incriminated. The impact of multiple concomitant medications should also be considered. In our patient, the stool output was much greater than what is usually expected following a BEAC conditioning regimen. In addition, diarrhea recurred without the introduction of any new therapeutic agent, a finding dismissing a drug-related side effect.

In summary, we report the first case of D. latum infection in an immunocompromised host. This report is of particular importance in view of the widespread increase in consumption of raw fish, especially sushis or fish tartare, in developed countries. Search for parasites should clearly be a part of stool examinations in patients who develop diarrhea after transplant.

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Detrait, M., Poirier, L., Roy, DC. et al. Diphyllobothriasis, a rare cause of profuse diarrhea following autologous transplantation. Bone Marrow Transplant 44, 131–132 (2009). https://doi.org/10.1038/bmt.2008.439

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