- Email: [email protected]
Entamide furoate in the treatment of acute amoebic dysentery
469 TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL M E D m t ~ S AND HYoxZl~.
Vol. 54. No. 5. September, 1960.
ENTAMIDE
FUROATE
IN THE TREATMENT
OF ACUTE AMOEBIC
DYSENTERY BY
S. SHALDON, M.A., M.B., M.mc.e.*
Department of Medidne, Royal Free Hospital, London (late Captain, Royal Army Medical Corps) Entamide, dichloroacet-4-hydroxy-N-methylanilide, showed amoebicidal activity in in vivo experiments with rats (WoOLFE, 1957) with no toxic effects. Although Entamide was reasonably effective in clearing the stools of cysts of E. histolytica in chronic or asymptomatic colonic amoebiasis (WooDRUFF et al., 1956 ; FOLL, 1957 ; S~'~J!W and THIRUVENGADAM, 1958), it was found to be disappointing in acute cases where trophozoites of E. histolytica were present in the stool. Because of the high relapse rate in acute cases, its use was limited in the treatment of amoebic dysentery. T h e furoic acid ester, Entamide furoate, has recently become available for clinical trial, and as it possesses more than four times the amoebicidal activity of Entamide in vivo and is just as non-toxic (MAIN, pers. commun.), it was considered justified to investigate its therapeutic effect in acute amoebic dysentery. MATERIAL
Four Nigerian soldiers with acute amoebic dysentery, all passing trophozoites in their stools, were treated with Entamide furoate in a dosage of 30 mg./kg, body weight/day in four divided doses for 10 days. The ages of the patients ranged from 19 years to 23 years, and apart from their presenting symptoms of pain and bloody diarrhoea, no relevant history was obtained. One man had had treatment with emetine hydrochloride grain 1 daily by injection for 10 days, 6 months previously for acute amoebic dysentery, but otherwise no amoebieidal treatment had been given in the cases before the trial with Entamide furoate. Symptoms had persisted for 2-3 weeks in each case before diagnosis. Two subjects were sigmoidoscoped before treatment, and early amoebic ulcers were seen in the colon in both. None of the four showed any evidence of hepatic amoebiasis. RESULTS All patients were symptom-free within 5 days, although one developed a mild oesophagitis on the 6th day of treatment, which responded to antacids and did not require stopping Entamide furoate. Stool examinations at 12, 14 and 16 days after Commencing Entamide furoate, showed no trophozoites or cysts of E. histolytica present in any of the four. During the course of treatment the patients were in hospital under careful observation, and were allowed to get up as soon as they were symptom-free. Apart from the mild oesophagitis s I wish to thank Dr. P. T. Main of Messrs. Boots Pure Drug Co. Ltd., for his help and for supplying the Entamide furoate used in the trial.
470
ENTAMIDEFLVROATEIN ACUTEAMOEBICDYSENTERY
in one case, no side effects were observed, and the absence of depression and abdominal discomfort associated with emetine and emetine bismuth iodide therapy was particularly noticeable. Follow-up at 6 weeks revealed no trophozoites or cysts in the stools of the four men, and sigmoidoscopy of the two who were sigmoidoscoped before treatment, showed complete healing of the ulcers previously seen. DISCUSSION Emetine bismuth iodide is the most effective oral amoebicidal drug in use (WooDaUFF et al., 1956), but the unpleasant side effects of abdominal discomfort and diarrhoea often result in the patients' refusing to complete the course of treatment, especially if out-patients. In endemic areas of amoebiasis, the shortage of hospital beds often precludes in-patient therapy for acute amoebic dysentery, and the need for an effective oral non-toxic amoebicidal drug is very great. Entamide furoate was effective in treating four acute cases of colonic amoebiasis and no unpleasant side effects were observed. Follow-up at 6 weeks after treatment revealed no evidence of relapse, but this is too short a period to draw any definite conclusions about relapse rates. However, in comparison with Entamide, where relapse rates of 20-50 per cent. in cases of acute amoebic dysentery were observed within 6 weeks of treatment (FOLL, 1957 ; S~JIVI and TmRUVENCADAiVi, 1958), Entamide furoate would appear to be more effective. Larger trials with longer follow-up per!ods will be necessary to estimate the incidence of relapse, although in any endemic area of amoebiasis the possibility of reinfection rather than relapse must always be considered in determining relapse rates. The reason why Entamide furoate appears to be more effective than Entamide may be related to the fact that it is less soluble than Entamide, and may, therefore, be more slowly absorbed from the gut and more slowly excreted from the body, thus providing a higher concentration in the bowel wall and lumen for a longer period than Entamide. SUMMARY
Four cases of acute amoebic dysentery were treated with Entamide furoate with a dose of 30 mg./kg, body weight/day, for 10 days. One patient developed a mild oesophagitis which cleared on symptomatic treatment, otherwise no side effects were observed. Symptoms were relieved completely in all cases by the 5th day, and stool observation at the conclusion of treatment showed no evidence of trophozoites or cysts of E. histolytica. Follow-up examinations at 6 weeks showed no evidence of relapse in any of the cases. The drug appears to be effective in the treatment of acute amoebic dysentery and non-toxic. Further follow-up studies would be necessary to exclude the possibility of relapse. REFERENCES FOLL, C. V. (1957). J. trop. Med. Hyg., 60, 216. SANJIVI, K. S. & THIRUVENGADAM,K. V. (1958). J. Ass. Physicians India, 6, 365. WOODRUFF,A. W., BELL, S. & SCI-IOFIELD,F. D. (1956). Trans. R. Soc. trop. Med. Hyg., 50, 114. WOOLFE, G. (1957). Ibid., 51, 320.
Vol. 54. No. 5. September, 1960.
ENTAMIDE
FUROATE
IN THE TREATMENT
OF ACUTE AMOEBIC
DYSENTERY BY
S. SHALDON, M.A., M.B., M.mc.e.*
Department of Medidne, Royal Free Hospital, London (late Captain, Royal Army Medical Corps) Entamide, dichloroacet-4-hydroxy-N-methylanilide, showed amoebicidal activity in in vivo experiments with rats (WoOLFE, 1957) with no toxic effects. Although Entamide was reasonably effective in clearing the stools of cysts of E. histolytica in chronic or asymptomatic colonic amoebiasis (WooDRUFF et al., 1956 ; FOLL, 1957 ; S~'~J!W and THIRUVENGADAM, 1958), it was found to be disappointing in acute cases where trophozoites of E. histolytica were present in the stool. Because of the high relapse rate in acute cases, its use was limited in the treatment of amoebic dysentery. T h e furoic acid ester, Entamide furoate, has recently become available for clinical trial, and as it possesses more than four times the amoebicidal activity of Entamide in vivo and is just as non-toxic (MAIN, pers. commun.), it was considered justified to investigate its therapeutic effect in acute amoebic dysentery. MATERIAL
Four Nigerian soldiers with acute amoebic dysentery, all passing trophozoites in their stools, were treated with Entamide furoate in a dosage of 30 mg./kg, body weight/day in four divided doses for 10 days. The ages of the patients ranged from 19 years to 23 years, and apart from their presenting symptoms of pain and bloody diarrhoea, no relevant history was obtained. One man had had treatment with emetine hydrochloride grain 1 daily by injection for 10 days, 6 months previously for acute amoebic dysentery, but otherwise no amoebieidal treatment had been given in the cases before the trial with Entamide furoate. Symptoms had persisted for 2-3 weeks in each case before diagnosis. Two subjects were sigmoidoscoped before treatment, and early amoebic ulcers were seen in the colon in both. None of the four showed any evidence of hepatic amoebiasis. RESULTS All patients were symptom-free within 5 days, although one developed a mild oesophagitis on the 6th day of treatment, which responded to antacids and did not require stopping Entamide furoate. Stool examinations at 12, 14 and 16 days after Commencing Entamide furoate, showed no trophozoites or cysts of E. histolytica present in any of the four. During the course of treatment the patients were in hospital under careful observation, and were allowed to get up as soon as they were symptom-free. Apart from the mild oesophagitis s I wish to thank Dr. P. T. Main of Messrs. Boots Pure Drug Co. Ltd., for his help and for supplying the Entamide furoate used in the trial.
470
ENTAMIDEFLVROATEIN ACUTEAMOEBICDYSENTERY
in one case, no side effects were observed, and the absence of depression and abdominal discomfort associated with emetine and emetine bismuth iodide therapy was particularly noticeable. Follow-up at 6 weeks revealed no trophozoites or cysts in the stools of the four men, and sigmoidoscopy of the two who were sigmoidoscoped before treatment, showed complete healing of the ulcers previously seen. DISCUSSION Emetine bismuth iodide is the most effective oral amoebicidal drug in use (WooDaUFF et al., 1956), but the unpleasant side effects of abdominal discomfort and diarrhoea often result in the patients' refusing to complete the course of treatment, especially if out-patients. In endemic areas of amoebiasis, the shortage of hospital beds often precludes in-patient therapy for acute amoebic dysentery, and the need for an effective oral non-toxic amoebicidal drug is very great. Entamide furoate was effective in treating four acute cases of colonic amoebiasis and no unpleasant side effects were observed. Follow-up at 6 weeks after treatment revealed no evidence of relapse, but this is too short a period to draw any definite conclusions about relapse rates. However, in comparison with Entamide, where relapse rates of 20-50 per cent. in cases of acute amoebic dysentery were observed within 6 weeks of treatment (FOLL, 1957 ; S~JIVI and TmRUVENCADAiVi, 1958), Entamide furoate would appear to be more effective. Larger trials with longer follow-up per!ods will be necessary to estimate the incidence of relapse, although in any endemic area of amoebiasis the possibility of reinfection rather than relapse must always be considered in determining relapse rates. The reason why Entamide furoate appears to be more effective than Entamide may be related to the fact that it is less soluble than Entamide, and may, therefore, be more slowly absorbed from the gut and more slowly excreted from the body, thus providing a higher concentration in the bowel wall and lumen for a longer period than Entamide. SUMMARY
Four cases of acute amoebic dysentery were treated with Entamide furoate with a dose of 30 mg./kg, body weight/day, for 10 days. One patient developed a mild oesophagitis which cleared on symptomatic treatment, otherwise no side effects were observed. Symptoms were relieved completely in all cases by the 5th day, and stool observation at the conclusion of treatment showed no evidence of trophozoites or cysts of E. histolytica. Follow-up examinations at 6 weeks showed no evidence of relapse in any of the cases. The drug appears to be effective in the treatment of acute amoebic dysentery and non-toxic. Further follow-up studies would be necessary to exclude the possibility of relapse. REFERENCES FOLL, C. V. (1957). J. trop. Med. Hyg., 60, 216. SANJIVI, K. S. & THIRUVENGADAM,K. V. (1958). J. Ass. Physicians India, 6, 365. WOODRUFF,A. W., BELL, S. & SCI-IOFIELD,F. D. (1956). Trans. R. Soc. trop. Med. Hyg., 50, 114. WOOLFE, G. (1957). Ibid., 51, 320.