New developments in the therapy of amoebiasis.

Progress report New developments in the therapy of amoebiasis Although frequently overlooked in practice, it has long been taught that for the adequate therapy of invasive amoebiasis treatment should be directed at all the sites where Entamoeba histolytica may be present. Hence the ideal amoebicide should be active within the bowel lumen, in the bowel wall, and systemically, particularly in the liver. Until quite recently all available amoebicides were selective in their sites of action. They consisted of a small number of reliable tissue amoebicides (chiefly emetine preparations and chloroquine), indirect-acting broad-spectrum antibiotics, and a great many predominantly luminal amoebicides. Inadequate assessment of the latter on inappropriate clinical material often led to misleading claims of their efficacy in invasive amoebiasis. However, almost all forms of amoebiasis could be treated effectively provided the correct combinations of drugs were used, although therapy was often a little complicated and prolonged, and occasionally associated with toxicity. In 1964 a preliminary report of the effect of niridazole in amoebic liver abscess led to the introduction of a new series of compounds in therapy'. It was found that niridazole alone was capable of curing both intestinal and hepatic amoebiasis but it was soon evident that this drug possessed an undesirable degree of toxicity2. It was not, however, long before another nitroheterocyclic compound was shown to yield even better results. This was the nitro-imidazole derivative, metronidazole. At a dosage of 200 mg three times daily for seven days the drug had been widely and safely used since 1959 for the treatment of tri-chomoniasis, but this regimen in amoebic dysentery had been disappointing. It was only in 1966, after considerably higher dosage regimens were used, that successful clinical trials in amoebic dysentery and amoebic liver abscess were reported3. Further studies showed that extremely small amounts of the drug were effective in liver abscess4 5 but at such low doses eradication of amoebae in the bowel is uncertain. During the past four years metronidazole has been extensively investigated, particularly in invasive amoebiasis, and has been the subject of numerous favourable reports although the dosages used have varied widely6'7'8'9. The drug has proved effective at a dosage of 40-50 mg/kg daily for amoebiasis in childhood'0"11"12. Good results have also been reported with relatively small doses in symptomless cyst-passers and in chronic intestinal amoebiasiSl3'l4. However, in this respect it should be borne in mind that the drug is highly absorbed and …