Correspondence

Treatment of Asymptomatic Intestinal Entamoeba histolytica Infection

N Engl J Med 2002; 347:1384October 24, 2002

Article

To the Editor:

Paromomycin and diloxanide furoate are the drugs recommended for the treatment of asymptomatic Entamoeba histolytica infection.1 These agents have been used in clinical practice for more than 30 years. The efficacy of either agent against E. histolytica is reported to be greater than 80 percent,2 although some have suggested that paromomycin is preferable because of a lower cure rate reported with the use of diloxanide furoate in symptomatic patients.3 However, the efficacy of these medications was evaluated before the identification of E. dispar as a separate nonpathogenic species, which is morphologically indistinguishable from E. histolytica and which also colonizes the human gut.4 Because the prevalence of E. dispar worldwide is believed to be 10 times as high as that of E. histolytica, previous studies may have reflected primarily the effectiveness of these medications against E. dispar.

We report the results of a randomized trial comparing the efficacy of diloxanide furoate with that of paromomycin for the treatment of asymptomatic carriers of E. histolytica. Subjects were identified by screening adult members of 372 households in Phu Cat, Hué, Vietnam (33 percent of all households). Stool specimens were obtained from 1040 subjects (87 percent of those eligible) and analyzed with the use of a real-time polymerase-chain-reaction (PCR) assay that is specific for E. histolytica, according to a method described previously.5 A total of 93 asymptomatic carriers of E. histolytica were identified, of whom 71 agreed to participate in the study. The study was approved by the scientific review board of the Medical College of the University of Hué. Written informed consent was obtained from all subjects.

Thirty-four subjects (13 men with a mean [±SD] age of 37.6±11.2 years and 21 women with a mean age of 36.8±10.5 years) were randomly assigned to receive paromomycin, and 37 subjects (18 men with a mean age of 39.2±11.2 years and 19 women with a mean age of 36.8±11.0 years) were assigned to receive diloxanide furoate. Both drugs were given at the recommended oral dose of 500 mg three times a day for 10 days. The taking of medication was directly observed in 44 of the subjects (62 percent). For all subjects, the presence of E. histolytica in the stool was reassessed with the use of the PCR assay 10 and 20 days after the termination of therapy. There was no loss to follow-up.

Evaluation on day 20 indicated a significantly higher cure rate among the subjects randomly assigned to treatment with paromomycin than among those assigned to treatment with diloxanide furoate (85 percent vs. 51 percent, P=0.003) (Table 1Table 1Efficacy of Paromomycin as Compared with Diloxanide Furoate for the Treatment of Asymptomatic Entamoeba histolytica Infection.). The findings were similar when the comparison was limited to the subjects whose regular intake of medication was directly observed. In two subjects who received paromomycin and one subject who received diloxanide furoate, stool samples were negative for parasites on day 10 after therapy but were positive on day 20. Since the reinfection rate for E. histolytica in the studied population is only 4 percent per year, it is likely that the reappearance of the parasite was due to incomplete efficacy of the drug, resulting in a transient reduction of the parasite load to a level below the threshold of detection. Since both drugs are well tolerated and their costs are similar, the results support the use of paromomycin as the first-line agent for the treatment of asymptomatic E. histolytica infection.

Joerg Blessmann, M.D.
Egbert Tannich, M.D.
Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany
tannich@bni.uni-hamburg.de

5 References

1. 1

   World Health Organization. Amoebiasis. Wkly Epidemiol Rec 1997;72:97-99
   Medline

2. 2

   McAuley JB, Herwaldt BL, Stokes SL, et al. Diloxanide furoate for treating asymptomatic Entamoeba histolytica cyst passers: 14 years' experience in the United States. Clin Infect Dis 1992;15:464-468
   CrossRef | Web of Science | Medline

3. 3

   McAuley JB, Juranek DD. Luminal agents in the treatment of amebiasis. Clin Infect Dis 1992;14:1161-1162
   CrossRef | Web of Science | Medline

4. 4

   Diamond LS, Clark CG. A redescription of Entamoeba histolytica Schaudinn, 1903 (Emended Walker, 1911) separating it from Entamoeba dispar Brumpt, 1925. J Eukaryot Microbiol 1993;40:340-344
   CrossRef | Web of Science | Medline

5. 5

   Verweij JJ, Blotkamp J, Brienen EA, Aguirre A, Polderman AM. Differentiation of Entamoeba histolytica and Entamoeba dispar cysts using polymerase chain reaction on DNA isolated from faeces with spin columns. Eur J Clin Microbiol Infect Dis 2000;19:358-361
   CrossRef | Web of Science | Medline

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   J BLESSMANN, A LEVAN, E TANNICH. (2006) Epidemiology and Treatment of Amebiasis in Hué, Vietnam. Archives of Medical Research 37:2, 269-271
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   Egbert Tannich. (2004) Zur Labordiagnostik von Entamoeba histolytica -Infektionen. The laboratory diagnosis of Entamoeba histolytica -infections. LaboratoriumsMedizin 28:6, 491-497
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   William Stauffer, Jonathan I. Ravdin. (2003) Entamoeba histolytica: an update. Current Opinion in Infectious Diseases 16:5, 479-485
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   Haque, Rashidul, Huston, Christopher D., Hughes, Molly, Houpt, Eric, Petri, William A. Jr., . (2003) Amebiasis. New England Journal of Medicine 348:16, 1565-1573
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