Correspondence

Case 4-1996: Paralysis Due to Schistosomiasis

N Engl J Med 1996; 334:1548-1549June 6, 1996

Article

To the Editor:

In Case Record 4-1996, the discussion by Liu and Compton (Feb. 8 issue)1 of a patient with paralysis due to schistosomiasis deserves comment on two points.

The first concerns Dr. Liu's final sentence, which states that there is “evidence of the resistance of S. [Schistosoma] mansoni to praziquantel in areas of endemic disease where the drug has been used widely.” Although there have been case reports of increased tolerance to praziquantel, resistance (in the sense of single-step complete resistance, as seen in bacterial infections) has not been reported. Tolerance to praziquantel is possible, but resistance has not been reported to be a problem.

Second, we are surprised that the treating physicians did not try oxamniquine. The authors noted that the patient received three courses of treatment with praziquantel, but they did not provide details of the tapering dose that ultimately resulted in the patient's ability to walk unassisted. Following the recurrence of symptoms after a second course of treatment with praziquantel, it might have been prudent to try oxamniquine, which as the authors note, has been especially effective against the S. mansoni species in this hemisphere. Oxamniquine has formed the backbone of the Brazilian national program of control of schistosomiasis and is reportedly effective in patients whose disease is not cured by praziquantel.2 Oxamniquine might have been effective against this patient's parasite.

Joseph Cook, M.D.
Edna McConnell Clark Foundation, New York, NY 10177

Michael R. Reich, Ph.D.
Harvard School of Public Health, Boston, MA 02115

2 References

1. 1

   Case Records of the Massachusetts General Hospital (Case 4-1996). N Engl J Med 1996;334:382-389
   Full Text | Web of Science | Medline

2. 2

   Katz N, Rocha RS, de Souza CP, et al. Efficacy of alternating therapy with oxamniquine and praziquantel to treat Schistosoma mansoni in children following failure of first treatment. Am J Trop Med Hyg 1991;44:509-512
   Web of Science | Medline

To the Editor:

In his comprehensive discussion of a case of S. mansoni myelopathy, Liu claims that praziquantel has been used successfully in patients with spinal cord schistosomiasis and later states that “the patient's clinical response to treatment was striking” and that her relapse suggested that the initial treatment with praziquantel had not killed all the adult worms. I believe that these statements are debatable, since there is no convincing evidence that schistosomicides reverse the neurologic manifestations of spinal cord involvement in schistosomiasis.

In the pathophysiology of schistosomiasis caused by S. mansoni, the eggs — not the adult worms — are important. Since neither praziquantel nor oxamniquine is ovicidal,1,2 the basis for the use of antischistosomal drugs is, by killing the female worms, to prevent further oviposition and damage caused by new eggs.3 Theoretically, killing the worms should not directly improve the neurologic symptoms in patients with spinal cord schistosomiasis. Early treatment is said to be associated with a better prognosis,1 but it is not possible to decide whether this is due to the effects of antischistosomal drugs or corticosteroids.

Sérgio de A. Nishioka, M.D.
Universidade Federal de Uberlandia, 38400-902 Uberlandia, Brazil

3 References

1. 1

   Haribhai HC, Bhigjee AI, Bill PL, et al. Spinal cord schistosomiasis: a clinical, laboratory and radiological study, with a note on therapeutic aspects. Brain 1991;114:709-726
   CrossRef | Web of Science | Medline

2. 2

   Shekhar KC. Schistosomiasis drug therapy and treatment considerations. Drugs 1991;42:379-405
   CrossRef | Web of Science | Medline

3. 3

   Scrimgeour EM, Gajdusek DC. Involvement of the central nervous system in Schistosoma mansoni and S. haematobium infection: a review. Brain 1985;108:1023-1038
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Liu replies:

To the Editor: Drs. Cook and Reich are correct in stating that genetic resistance to praziquantel has not yet been reported in human schistosome infections, although experiments in mice indicate that schistosome parasites can become tolerant to praziquantel with heavy drug use.1 In some large series a small percentage of infected patients continued to excrete schistosome eggs (albeit in much reduced numbers) after a conventional course of treatment, suggesting that clinical tolerance to praziquantel may occur in areas of endemic disease. Nevertheless, with retreatment most of these patients are cured.2 Oxamniquine is indeed effective in treating schistosomiasis due to S. mansoni; perhaps because its efficacy is limited to S. mansoni, the drug is underused in this country as compared with praziquantel, which enjoys greater clinical use as an agent effective against a broad range of trematode and cestode parasites.3

The majority of reported cases of S. mansoni myelopathy treated with praziquantel or oxamniquine have improved after anthelmintic therapy. As Dr. Nishioka points out, in most of these cases there was also concomitant treatment with corticosteroids and supportive care, so it is difficult to assess the specific effects of antischistosomal and antiinflammatory therapy on the basis of these uncontrolled studies (and a controlled study in which anthelmintic treatment is withheld will probably never be done). The tissue damage caused by schistosomiasis is largely due to immunopathologic granulomatous host responses mediated by T-cell–derived cytokines against parasite-egg antigens,4 rather than any directly toxic effects of the eggs themselves. By killing the adult female worms and terminating egg production, praziquantel and oxamniquine can interrupt the ongoing deleterious host immune responses against eggs deposited in the tissues; indeed, extensive clinical experience has shown that the condition of patients with established hepatic schistosomiasis improves after anthelmintic treatment in the absence of corticosteroid administration. There is no evidence to suggest that anthelmintic treatment can worsen the acute clinical course of central nervous system schistosomiasis (as may occur with chemotherapy in neurocysticercosis). Thus, it remains clinically prudent to administer praziquantel or oxamniquine, together with or shortly after the initiation of a course of corticosteroids, in cases of schistosomal myelopathy.

Leo Liu, M.D., D.T.M.H.
Beth Israel Hospital, Boston, MA 02215

4 References

1. 1

   Fallon PG, Doenhoff MJ. Drug-resistant schistosomiasis: resistance to praziquantel and oxamniquine induced in Schistosoma mansoni in mice is drug specific. Am J Trop Med Hyg 1994;51:83-88
   Web of Science | Medline

2. 2

   Ismail M, Tao L, Bennett JL. Characterization of isolates of Schistosoma mansoni from Egyptian villagers that tolerate high doses of praziquantel. Am J Trop Med Hyg (in press).
   

3. 3

   Liu LX, Weller PF. Antiparasitic drugs. N Engl J Med 1996;334:1178-1184
   Full Text | Web of Science | Medline

4. 4

   Capron A, Dessaint JP. Immunologic aspects of schistosomiasis. Annu Rev Med 1992;43:209-218
   CrossRef | Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   Somchai Pinlaor, Yusuke Hiraku, Puangrat Yongvanit, Saeko Tada-Oikawa, Ning Ma, Porntip Pinlaor, Paiboon Sithithaworn, Banchob Sripa, Mariko Murata, Shinji Oikawa, Shosuke Kawanishi. (2006) iNOS-dependent DNA damagevia NF-κB expression in hamsters infected withOpisthorchis viverrini and its suppression by the antihelminthic drug praziquantel. International Journal of Cancer 119:5, 1067-1072
   CrossRef

2. 2

   May H. Han, Joseph R. Zunt. (2005) Neurologic Aspects of Infections in International Travelers. The Neurologist 11:1, 30-44
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