Arch Dis Child: first published as 10.1136/adc.43.227.121 on 1 February 1968. Downloaded from

Arch. Dis. Childh., 1968, 43, 121.

Emetine Hydrochloride and Dehydroemetine Combined with Chloroquine in the Treatment of Children with Amoebic Liver Abscess

J. N. SCRAGG and S. J. POWELL* From the Departments of Paediatrics and Child Health, and Medicine, University of Natal, and the Amoebiasis Research Unitt, Durban, South Africa

A combination of emetine hydrochloride with amoebic liver abscess was confirmed by the aspiration chloroquine yields better results than either drug of characteristic pus from the liver in all patients: in 17 alone in the treatment of amoebic liver abscess in of the 24 aspirates trophozoites of Entamoeba histolytica adults (Wilmot, Powell, and Adams, 1959). A were identified. In all except one patient, a 7-week-old infant, the amoebic gel-diffusion test was positive. similar combination of dehydroemetine with chloro- All patients received chloroquine, 15 mg. base/kg. day, quine is equally satisfactory (Wilmot, Powell, orally for 21 days, and in addition were randomly placed MacLeod, and Elsdon-Dew, 1964; Powell, Wilmot, on either emetine hydrochloride, 1 mg./kg. day, or MacLeod, and Elsdon-Dew, 1967). Dehydro- dehydroemetine, 2 mg./kg. day, by subcutaneous emetine is claimed to be less cardiotoxic than injection for 10 days. Those with active dysentery also emetine (Schwartz and Herrero, 1965), and in received oral tetracycline to combat intestinal amoebiasis. adults it produces fewer electrocardiographic In 22 patients repeated aspirations of the liver were copyright. changes when given in identical dosage (Powell, required, and in 6 surgical drainage of the abscess was 1967) so that up to 2 mg./kg. day have been given eventually necessary, but no additional amoebicides were with apparent safety (Powell, Wilmot, MacLeod, given. and Elsdon-Dew, 1965). In children, amoebic liver abscess carries a high Results mortality (Scragg, 1960), but a comparative trial of The results are summarized in the Table. emetine hydrochloride and chloroquine did not Necropsy findings. It will be noted that 3 show that cardiac toxicity from emetine was a factor patients who received emetine combined with http://adc.bmj.com/ in causing death (Scragg and Powell, 1966). The chloroquine died. One, a malnourished 16-month- results suggested that emetine was well tolerated old infant with active dysentery, died 48 hours by children and that, as in adults, emetine combined after beginning treatment; necropsy showed mul- with chloroquine might provide the most effective tiple abscesses which had destroyed most of the treatment. right lobe of the liver. A second patient, aged 14 The present trial reports the results of combining months, was critically ill with kwashiorkor and either emetine hydrochloride or dehydroemetine bronchopneumonia and died following surgical on September 28, 2021 by guest. Protected with chloroquine in children with amoebic liver drainage on the 24th day; a chronic non-liquefied abscess. abscess in the left lobe of the liver was found at Material and Methods TABLE Studies were made on 24 African children, their ages ranging from 1 month to 11 years. The diagnosis of Results of Treatment

Received June 9, 1967. No. of No. of No. of No. of Patients Cures Deaths Relapses * Requests for reprints should be addressed to S. J. Powell, Amoebiasis Research Unit, P.O. Box 1035, Durban, South Africa. Emetine hydro- chloride. . 12 9 3O t The Amoebiasis Research Unit is sponsored by the following Dehydroemetine 12 1 1 1 O bodies: The South African Council for Scientific and Industrial ..I Research; The Natal Provincial Administration; The University of Natal; and the United States Public Health Service (Grant AI 01592). Both drugs were given in combination with chloroquine. 121 Arch Dis Child: first published as 10.1136/adc.43.227.121 on 1 February 1968. Downloaded from

122 Scragg and Powell necropsy. The third infant, 1 month old, died on intervention is undesirable, but in selected instances the 9th day; necropsy was refused. open drainage has a more important place in the One patient who received dehydroemetine and management of children than of adults. chloroquine died on the 5th day. This was an In view of such clinical variations, comparison of extremely ill 13-month-old infant with profound the efficacy of drugs must be interpreted with anaemia and jaundice; at necropsy multiple abscesses caution. Nevertheless, it appears that either in the liver were present, one occupying the whole emetine or dehydroemetine can be combined with of the right lobe. chloroquine with safety and advantage. Although the immediate case fatality rate may not be signifi- Electrocardiographic findings. Electrocar- cantly influenced by combined therapy, the absence diograms were obtained before and after completion of relapse in our present trial contrasts with our of treatment in 8 of the group who received emetine previous experience using single drugs. and in 11 of those given dehydroemetine. No For the treatment of adults dehydroemetine is arrhythmias, conduction defects, or significant marginally preferred to emetine (Powell et al., 1965). tachycardia were observed. However, T wave Only long usage will tell if it is more effective in inversion developed in 6 children given emetine children though we believe that it is. Because it and in 3 who received dehydroemetine. may be slightly more effective and can be given in larger dosage, dehydroemetine is the drug of Follow-up. Ten children attended for follow- choice and should be given with chloroquine for up from 1 to 8 months after discharge. None the treatment of amoebic liver abscess in children. had relapsed. Summary Discussion Emetine hydrochloride combined with chloro- The results of therapy are difficult to assess in quine cured 9 of 12 children with amoebic liver children with amoebic liver abscess for several abscess. An alternative combination of dehydro- reasons. Even in areas where the disease is emetine with chloroquine produced cure in 11 of copyright. frequent in adults it is relatively rare in children, 12 children. No relapses were observed. so that large-scale studies are not possible. More- Electrocardiographic changes, consisting only of over, standardization of clinical criteria and manage- T wave inversion, were noted in 6 who received ment is more difficult than in adults. Age alone is emetine and in 3 given dehydroemetine. a most important factor in prognosis and can readily Although the immediate case fatality rate may not affect evaluation of treatment. In this study all be significantly influenced, a combination of either 4 deaths occurred among the 13 infants aged 16 preparation with chloroquine appears to reduce the months or less, whereas none of the remaining 11 relapse rate. Dehydroemetine is preferred to http://adc.bmj.com/ older children died. Regardless of the nature of emetine hydrochloride since not only may it be the therapy, mortality is higher in infants. more effective but it is possibly safer even in higher Some infants are only brought to hospital when dosage. the disease is so far advanced that it is difficult to imagine any form of therapy affecting cure. The We wish to thank Professor H. L. Wallace for advice necropsy appearances in the two infants who died and access to patients, and Dr. H. Wannenburg, Medical on the 2nd and 5th days of treatment suggested Superintendent, King Edward VIII Hospital, Durban, on September 28, 2021 by guest. Protected that the prognosis was hopeless from the outset. A for facilities. liver abscess of medium size in an adult is relatively enormous in an infant and causes extensive liver REFERENCES destruction. Consequently, the mortality of liver Powell, S. J. (1967). The cardiotoxicity of systemic amebicides: a abscess is to comparative electrocardiographic study. Amer. J. trop. Med. likely remain higher in infants despite Hyg., 16, 447. effective amoebicides. -, Wilmot, A. J., MacLeod, I. N., and Elsdon-Dew, R. (1965). The place of surgical drainage in management A comparative trial of dehydroemetine, emetine hydrochloride and chloroquine in the treatment of amoebic liver abscess. is not well defined. In our present study we Ann. trop. Med. Parasit., 59, 496. tended to resort to it at an earlier stage than previous- and - (1967). A comparative trial of dehydro- emetine and emetine hydrochloride in identical dosage in ly. Although it was only considered necessary in amoebic liver abscess. ibid., 61, 26. 6 patients, one of whom suddenly died, earlier Schwartz, D. E., and Herrero, J. (1965). Comparative pharmaco- surgery may have a in kinetic studies of dehydroemetine and emetine in guinea pigs been factor reducing both using spectrofluorometric and radiometric methods. Amer. the death and relapse rates. Premature surgical trop. Mod. Hyg., 14, 78. Arch Dis Child: first published as 10.1136/adc.43.227.121 on 1 February 1968. Downloaded from

Emetine Hydrochloride and Dehydroemetine with Chloroquine in Amoebic Liver Abscess 123 Scragg, J. (1960). Amoebic liver abscess in African children. compared with chloroquine and emetine combined in amebic Arch. Dis. Childh., 35, 171. liver abscess. Amer. J. trop. Med. Hyg., 8, 623. -, and Powell, S. J. (1966). Emetine hydrochloride and chloro- quine in the treatment of children with amoebic liver abscess. -, -, MacLeod, I. N., and Elsdon-Dew, R. (1964). The ibid., 41, 549. treatment of amoebic liver abscess with dehydroemetine. Proc. Wilmot, A. J., Powell, S. J., and Adams, E. B. (1959). Chloroquine 3rd int. Congr. Chemother., Stuttgart, 1963, 2, 1528. copyright. http://adc.bmj.com/ on September 28, 2021 by guest. Protected

9