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Experimental amoebiasis and the development of anti-amoebic compounds

Published online by Cambridge University Press:  06 April 2009

R. A. Neal
R. A. Neal
Affiliation:
Department of Parasitology, Wellcome Research Laboratories, Beckenham, Kent
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Extract

In the ideal situation, the development of new amoebicides, or more accurately anti-amoebic compounds which are compounds with activity against Entamoeba histolytica, should initially proceed with the study of parasite-specific metabolic pathways and their inhibition, followed by whole parasite in vitro studies, experimental in vivo models and finally clinical trial. However, there are considerable gaps in our knowledge which will be discussed below, and consequently many investigators consider that empirically selected compounds should be tested experimentally in addition to specifically designed compounds. Before clinical trials can begin, extensive examination of the candidate amoebicide in experimental animals is required in order to investigate possible toxicological hazards.

In addition to inhibiting the amoebic parasite, the drug has to reach the parasite in several different sites in the body, thus there is also a problem of pharmacokinetics and distribution. Prior to the discovery of the nitroimidazole class of amoebicides, the multi-site attack was solved by the use of several drugs, sometimes in sequence during the treatment of an individual case (Powell, 1972). The discovery of the nitroimidazole class of compound changed the situation dramatically and these have shown a clinical and parasitological effect against extra-intestinal and intestinal wall infections. The effect on intralumenal infection (that is mildly symptomatic or asymptomatic infections) of the large intestine is, however, less certain (Finegold, 1977; Spillman, Ayala & Sanchez, 1976).

Although the treatment of amoebiasis appears to be satisfactory at the present time, it is difficult to predict problems which might arise in the future, and therefore it is valuable to continue the pre-clinical development, especially the investigation of parasite metabolism, in order to define parasite-specific points of chemotherapeutic attack.

The chemotherapy of amoebiasis was reviewed comprehensively by Woolf (1963, 1965). The present account of the development of amoebicides therefore starts from the Woolfe reviews.

Type
Trends and Perspectives
Information
Parasitology , Volume 86 , Issue 1 , February 1983 , pp. 175 - 191
Copyright
Copyright © Cambridge University Press 1983

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References

Albach, R. A., Shaffer, J. G. & Watson, R. H. (1966). A comparison of in vitro drug sensitivities of strains of Entamoeba which grow at 37 °C and at room temperature. American Journal of Tropical Medicine and Hygiene 15, 855–9.CrossRefGoogle Scholar
Amyx, H. L., Asher, D. M., Nash, T. E., Gibbs, C. J. & Gajdusek, B. C. (1978). Hepatic amebiasis in spider monkeys. American Journal of Tropical Medicine and Hygiene 27, 888–91.CrossRefGoogle ScholarPubMed
Anderson, H. H., Nelson, T. L., Hrenoff, A. K. & Fish, C. H. (1954). Antibiotic synergism in amebiasis. American Journal of Tropical Medicine and Hygiene 3, 254–61.CrossRefGoogle ScholarPubMed
Biagi, F. F., Robledo, E., Servin, H. & Martuscelli, A. (1962). The effect of cholesterol on the pathogenicity of Entamoeba histolytica. American Journal of Tropical Medicine and Hygiene 11, 333–40.CrossRefGoogle ScholarPubMed
Basit, N., Siddiquiz, M. A. & Ahmed, Z. (1977). In vitro effect of extracts of Euphorbia hirta Linn. on Entamoeba histolytica. rivista Parassitologia 38, 259–62.Google Scholar
Benazet, F. & Guillaume, L. (1976). Activités antiamibienne et trichomonacide du secnidazole au laboratoire Bulletin Societé Pathologie Exotique 69, 309–19.Google Scholar
Berberian, D. A., Slighter, R. G. & Surrey, A. R. (1960). In vitro and in vivo amebicidal activity of N, N′-bis (dichloroacetyl) diamines. Antibiotics and Chemotherapy 11, 245–55.Google Scholar
Bos, H. J. (1979). Entamoeba histolytica: cytopathogenicity of intact amoebae and cell-free extracts; isolation and characterization of an intracellular tox in. Experimental Parasitology 47, 369–77.CrossRefGoogle Scholar
Bos, H. J. & van de Griend, R. J. (1977). Virulence and toxicity of axenic Entamoeba histolytica. Nature, London 265, 341–3.CrossRefGoogle ScholarPubMed
Bradner, W. T. & Rawson, G. W. (1951). An in vitro method of screening amebicidal agents using the Phillips culture. Science 113, 674–6.CrossRefGoogle Scholar
Brand, T. von (1979). Biochemistry and Physiology of Endoparasites. Amsterdam: Elsevier/North Holland and Biomedical Press.Google Scholar
Burden, E. J., Carvajal, S. G., Fabio, P. F., Fields, T. L., Yang-l, Lin, Murdock, K. C. & Lang, S. A. Jr. (1979). The effect of bisamidines of 2,6-diaminoanthroquinone on Entamoeba histolytica infections in rats and hamsters. Experientia 35, 33–5.CrossRefGoogle Scholar
Buzas, A., Cavier, R., Cossais, F., Finet, J.-P., Jacquet, J.-P., Lavielle, G. & Platzer, N. (1977). Synthèse et propiétés amoebicides d'analogues de l'émétine. Analyse des composés nouveaux en 13C-RMN. (±) Alkyl-l-déséthyl-3-émétine à jonction B/C cis ou trans. Helvetica Chimica Acta 60, 2122–34.CrossRefGoogle Scholar
Campos, R. (1973). Estudo comparative de actividade in vitro do nifuratel e de outros medicamentos sobre a cepa brasileira patogênica da Entamoeba histolytica. Revista Brasileira Clinica Terapêutica 2, 587–8.Google Scholar
Carneri, l. de (1976). Taxonomy of amoebae and antiprotozoal activity of nitromidazoles and dichloroacetamide derivatives. In Memorias Conferencia International Amibiasis, México City (ed. Sepulveda, B. and Diamond, L. S.). Institute Méxicano Seguar Social: Mexico.Google Scholar
Carneri, I. de, Candia Carnevali, M. D., Trane, F. & Meinardi, G. (1976). Aspetti morfologici e sistemici dell'azione antiamebica dell'Etofamide Giornale Malatlie Infettive Parassitarie 28, 229–40.Google Scholar
Carneri, I. de, Cantone, A., Giraldi, P. N., Logemann, W., Meinardi, G. & Trane, F. (1970). Ethychlordiphene: a new antiamebic agent. Progress in Antimicrobial and Anticancer Chemotherapy 1, 155–8.Google Scholar
Carneri, I. de & Casinovi, C. G. (1968). Un potente antiamebico d'origine vegetale: l'ailantone, principio attivo di Ailanthus glandulosa. Parassitologia 10, 215–17.Google Scholar
Chaia, G., da Silva, E. F., Vilela, C. C. & Chiari, L. (1977). Isolation and maintenance of a strain of Entamoeba histolytica Schaudinn 1903 and the possibility of its utilization in screening of drugs. Revista Instituto Medicina Tropical, São Paulo 19, 195–201.Google ScholarPubMed
Chiari, L., Guerrero, J. & Negrão dos Santos, C. (1978). Experimental muscular amebiasis in hamsters as a biological model. Zeitschrift für Parasitenkunde 56, 107–14.CrossRefGoogle ScholarPubMed
Cosar, C., Ganter, P. & Julun, L. (1961). Experimental study on metronidazole (RP-8823). Trichomonacidal and amoebicidal activities. Toxicity and general pharmacological properties. Presse Medicine 69, 1069–72.Google Scholar
Cuckler, A. C., Malanga, C. M. & Conroy, J. (1970). Therapeutic efficacy of new nitroimid-azoles for experimental trichomoniasis, amebiasis and trypanosomiasis. American Journal of Tropical Medicine and Hygiene 19, 916–25.CrossRefGoogle ScholarPubMed
Das, S. R., Das, P. & Rai, G. P. (1979). Revival of pathogenicity of axenically grown Entamoeba histolytica for the rat. Australian Journal of Experimental Biology and Medical Science 57, 241–4.CrossRefGoogle ScholarPubMed
Das, S. R. & Ghoshal, S. (1976). Restoration of virulence to rat of axenically grown Entamoeba histolytica by cholesterol and hamster liver passage. Annals of Tropical Medicine and Parasitology 70, 439–43.CrossRefGoogle ScholarPubMed
Das, S. R. & Singh, B. N. (1965). Virulence of strains of Entamoeba histolytica to rats and guinea pigs and effect of cholesterol on virulence. Indian Journal of Experimental Biology 3, 106–9.Google ScholarPubMed
Diamond, L. S. (1968). Techniques ofaxenic cultivation of Entamoeba histolytica Schaudinn, 1903 and E. histolytica-like amoebae. Journal of Parasitology 54, 1047–56.CrossRefGoogle Scholar
Diamond, L. S., Harlow, D. R. & Cunnick, C. C. (1978). A new medium for the axenic cultivation of Entamoeba histolytica and other Entamoeba. Transactions of the Royal Society of Tropical Medicine and Hygiene 72, 431–2.CrossRefGoogle ScholarPubMed
Diamond, L. S., Phillips, B. P. & Bartgis, I. L. (1974 a). A comparison of the virulence of nine strains of axenically cultivated E. histolytica in hamster liver. Achivos Investigación Medica 5 (suppl 2), 423–6.Google ScholarPubMed
Diamond, L. S., Phillips, B. P. & Bartgis, I. L. (1974 b). The clawed jird (Meriones unguiculatus) as an experimental animal for the study of hepatic amebiasis. Archivos Investigación Medica 5 (suppl. 2), 465–70.Google Scholar
Dutta, D. & Khare, R. L. (1971). Antiamoebic activity of anacardic acid and its sodium salt. Indian Journal of Pharmacy 33, 112–14.Google Scholar
Dutta, G. P. (1976). Cultivation of axenic Entamoeba histolytica from small inocula Indian Journal of Medical Research 64, 573–8.Google ScholarPubMed
Dutta, G. P. & Narain, L. (1978). Influence of pH on the amoebicidal activity of systemically active amoebicides against axenic Entamoeba histolytica. Indian Journal of Experimental Biology 16, 838–40.Google ScholarPubMed
Entner, N. (1979). Emetine binding to ribosomes of Entamoeba histolytica – inhibition of protein synthesis and amoebicidal action. Journal of Protozoology 26, 324–8.CrossRefGoogle Scholar
Entner, N., Evans, L. A. & Gonzalez, C. (1962). Genetics of Entamoeba histolytica: differences in drug sensitivity between Laredo and other strains of Entamoeba histolytica. Journal of Protozoology 9, 466–8.CrossRefGoogle Scholar
Entner, N. & Grollman, A. P. (1973). Inhibition of protein synthesis: a mechanism of amoebicide action of emetine and other related compounds. Journal of Protozoology 20, 160–3.CrossRefGoogle Scholar
Finegold, S. M. (1977). Metronidazole. In Proceedings of the International Metronidazole Conference Montreal, Quebec, 1976. Amsterdam: International Congress Series 438, Excerpta Medica.Google Scholar
Ghadirian, E. & Meerovitch, E. (1979). Pathogenicity of axenically cultivated Entamoeba histolytica strain 200:NIH, in the hamster. Journal of Parasitology 65, 768–71.CrossRefGoogle ScholarPubMed
Gillin, F. D. & Diamond, L. S. (1978 a). Clonal growth of Entamoeba in agar: some applications of this technique to the study of their cell biology. Achivos Investigation Medica 9 (suppl. 1), 237–46.Google Scholar
Gillin, F. D. & Diamond, L. S. (1978 b). Clonal growth of Entamoeba histolytica and other species of Entamoeba in agar. Journal of Protozoology 25, 539–43.CrossRefGoogle ScholarPubMed
Gillin, F. D. & Diamond, L. S. (1980). Attachment and short-term maintenance of motility and viability of Entamoeba histolytica in a defined medium. Journal of Protozoology 27, 220–5.CrossRefGoogle Scholar
Gold, D. & Kagan, I. G. (1978). Susceptibility of various strains of mice to Entamoeba histolytica. Journal of Parasitology 64, 937–8.CrossRefGoogle ScholarPubMed
Gold, D. & Norman, L. (1979). Studies on the preservation and enhancement of the virulence of some strains of Entamoeba histolytica in axenic and monoxenic cultures. Journal of Parasitology 65, 970–2.CrossRefGoogle ScholarPubMed
Gordeeva, L. M. (1975). Experimental study of changes in the sensitivity of Entamoeba histolytica to flagyl (metronidazole). In Problemy parazitologii. Materialy VIII nauchoi konferentsii parazitologii UkSSR, Chast′ 1, KIV USSR, pp. 125–127. Only seen in Protozoological Abstracts 1979 vol. 3 Abstract no. 902.Google Scholar
Gordeeva, L. M. (1981). Entamoeba histolytica and studies on the biological patterns of amoeba long term cultivation with metronidazole. Seventh International Congress Protozoology,Warsaw. Abstract no. 120.Google Scholar
Gordeeva, L. & Yusupova, R. (1968). Experimental chemotherapy of amoebiasis. 1. Determination in vitro and in vivo of antiamoebal activity of flagyl and monomycin in combination with other chemotherapeutic drugs. Medical Parasitology and Parasitic Diseases 37, 643–7.Google Scholar
Grunberg, E., Cleeland, R., Prince, H. N. & Titsworth, E. (1970). α-Chloromethyl-2-methyl-5-nitro-l-imidazoleethanol (Ro7–0207), a substance exhibiting antiparasitic activity against amebae, trichomonads and pinworms. Proceedings of the Society of Experimental Biology and Medicine 133, 490–2.CrossRefGoogle Scholar
Jayaswal, S. B. (1976). Amoebicidal activity of steroidal alkaloids of Wrightia tomentosa in vitro. Inidan Journal of Pharmacy 38, 112–13.Google Scholar
Knight, R. C., Skolimowski, I. M. & Edwards, D. I. (1978). The interaction of reduced metronidazole with DNA. Biochemical Pharmacology 27, 2089–93.CrossRefGoogle ScholarPubMed
Kradolfer, F. & Jarumilinta, R. (1965). CIBA 32, 644-Ba a new systematically active amoebicide. Annals of Tropical Medicine and Parasitology 59, 210–18.CrossRefGoogle Scholar
Kuntz, R. E. & Myers, B. J. (1972). Parasites of South American primates. International Zoo Yearbook 12, 61–8.CrossRefGoogle Scholar
Lajudie, P. de, Alberto, O., Aurousseau, M., Forgacs, P., Collins, M. & Tiberghien, R. (1970). Étude des effets antiamibiens et trichomonacides de steroïdes d'hemisynthèse dérivés de la paravallarine alcaloide du Paravallaris microphylla Pitard (Apocynacées). Chimie Therapeutique, Mars-Avril, 129–37.Google Scholar
Lancastre, F., Bazin, J.-C., Le Fichoux, Y., Mougeot, G. & Gargotjri, M. (1968). Amibiase experimentale. Obtention du type pathogene de E. histolytica chez la souris blanche rendre immunotolerante. Annates Parasitologic (Paris) 43, 623–8.Google Scholar
LaRusso, N. F., Tomasz, M., Müller, M. & Lipman, R. (1977). Interaction of metronidazole with nucleic acids in vitro. Molecular Pharmacology 13, 872–82.Google ScholarPubMed
Latour, N. G. & Reeves, R. E. (1965). An iron-requirement for growth of Entamoeba histolytica in culture, and the antiamebal activity of 7-iodo-8-hydroxyquinoline-5-sulfonic acid Experimental Parasitology 17, 203–9.CrossRefGoogle Scholar
Legator, M. S., Connor, T. H. & Stoeckel, M. (1975). Detection of mutagenic activity of metronidazole and niridazole in body fluids of humans and mice. Science 188, 1118–19.CrossRefGoogle ScholarPubMed
Lushbaugh, W. B., Kairalla, A. B., Cantey, J. R., Hofbauer, A. F. & Pittman, F. E. (1979). Isolation of a cytotoxic-enterotoxin from Entamoeba histolytica Journal of Infectious Diseases 139, 9–17.CrossRefGoogle Scholar
Lushbaugh, W. B., Kairalla, A. B., Loadholt, C. B. & Pitmman, F. E. (1978). Effect of hamster liver passage on the virulence of axenically cultivated Entamoeba histolytica. American Journal of Tropical Medicine and Hygiene 27, 248–54.CrossRefGoogle ScholarPubMed
Mattekn, C. F. T. & Keister, D. B. (1977 a). Experimental amebiasis. I. Pathogenicity of axenically cultured Entamoeba histolytica in the brain of the newborn mouse. American Journal of Tropical Medicine and Hygiene 26, 393–401.CrossRefGoogle Scholar
Mattern, C. F. T. & Keister, D. B. (1977 b). Experimental amebiasis. II. Hepatic amebiasis in the newborn hamster. American Journal of Tropical Medicine and Hygiene 26, 402–11.CrossRefGoogle ScholarPubMed
Meerovitch, E. & Ghadirian, E. (1978). Restoration of virulence of axenically cultivated Entamoeba histolytica by cholesterol. Canadian Journal of Microbiology 24, 63–5.CrossRefGoogle ScholarPubMed
Michel, R. & Hohmann, R. (1979). Der Einfluss von Cytochalasin B, Colchicin und Vinblastin auf die Adhäsion von Entamoeba histolytica an Glasoberflächen. Zeitschrift für Parasitenkunde 60, 123–33.CrossRefGoogle Scholar
Miller, M. J. & Bray, R. S. (1966). Entamoeba histolytica infections in the chimpanzee (Pan satyrus). Journal of Parasitology 52, 386–8.CrossRefGoogle Scholar
Müller, M. & Lindmark, D. G. (1976). Uptake of metronidazole and its effect on viability in trichomonads and Entamoeba invadens under anaerobic and aerobic conditions. Antimicrobial Agents and Chemotherapy 9, 696–700.CrossRefGoogle ScholarPubMed
Müller, M., Nseka, V., Mack, S. R. & Lindmark, D. G. (1979). Effects of 2:4-dinitrophenol on trichomonads and Entamoeba invadens Comparative Biochemistry and Physiology B 64, 97–100.Google Scholar
Myers, B. J., Kuntz, R. E. & Malherbe, H. (1971). Intestinal commensals and parasites of the South African baboon (Papis cynocephalus). Transactions of the American Microscopical Society 90, 80–3.CrossRefGoogle Scholar
Nakamura, M. & Anderson, H. H. (1951). Evidence of direct amebicidal action of agents tested in vitro against Entamoeba histolytica. Journal of Parasitology 37, 421–3.CrossRefGoogle Scholar
Nakamura, M., Hrenoff, A. K. & Anderson, H. H. (1953). Drug effects on the mechanism of Entamoeba histolytica; in vitro and in vivo tests of synergism. American Journal of Tropical Medicine and Hygiene 2, 206–11.CrossRefGoogle Scholar
Neal, R. A. (1967). The in vitro cultivation of Entamoeba. Problems of in vitro culture. In Fifth Symposium of the British Society for Parasitology pp. 9–36. Oxford: Blackwells Scientific Publications.Google Scholar
Neal, R. A. (1971). Pathogenesis of amoebiasis. Bulletin of the New York Academy of Medicine 47, 462–8.Google Scholar
Neal, R. A. (1978). Antiamoebic activity of drugs given singly and in combination against axenically grown Entamoeba histolytica. Archivos Investigacion Medica 9 (suppl. 1), 387–92.Google ScholarPubMed
Neal, R. A. & Harris, W. G. (1977). Attempts to infect inbred strains of rats and mice with Entamoeba histolytica. Protozoology 3, 197–9.Google Scholar
Phillips, B. P. (1951). Measurements of direct amebicidal potential by a micromethod for the screening of drugs in vitro. American Journal of Tropical Medicine and Hygiene 31, 561–5.CrossRefGoogle ScholarPubMed
Phillips, B. P. (1973). Entamoeba histolytica: concurrent irreversible loss of infectivity/pathogenicity and encystment potential after prolonged maintenance in axenic culture in vitro. Experimental Parasitology 34, 163–7.CrossRefGoogle ScholarPubMed
Powell, S. J. (1969). Current therapy of amoebiasis. Indian Practitioner 22, 19–22.Google Scholar
Powell, S. J. (1972). Latest developments in the treatment of amebiasis. Advances in Pharmacology and Chemotherapy 10, 91–103.CrossRefGoogle ScholarPubMed
Raether, W. (1971). Intrahepatikale Infektionversuche am Goldhamster mit Entamoeba histolytica – Crithidia-Kulturen mit und ohne Beteiligung von Bakterien. Zeitschrift für Parasitenkunde 36, 335–45.CrossRefGoogle Scholar
Raether, W., Scheubert, G. & Vanderbeke, O. (1967). Vergleichende Untersuchungen über den Verhalten der Glutamat-Oxalacetat-und der Glutamat-Pyruvat-Transaminase in Serum vom Goldhamster unter verschiendenen Versuchsbedingungen der extraintestinalen Amöbi-asis. Zeitschrift für Tropenmedizin und Parasitologic 18, 304–20.Google Scholar
Raether, W., Seidenath, H. & Winkelman, E. (1977). 1, 4-Bis [l-methyl-5-nitroimidazole- (2-methyleneimino)]-piperazine, a new drug with marked activity against Entamoeba histolytica. Drug Research 27, 968–9.Google ScholarPubMed
Ravdin, J. I., Croft, B. Y. & Guerrant, R. L. (1980). Cytopathogenic mechanisms of Entamoeba histolytica. Journal of Experimental Medicine 152, 377–90.CrossRefGoogle ScholarPubMed
Ray, D. K., Chatterjee, D. K., Bhopale, K. K. & Shrivastava, V. B. (1979). Simultaneous hepatic and intestinal infections of golden hamsters by Entamoeba histolytica trophozoites. Indian Journal of Parasitology 3, 203–4.Google Scholar
Reardon, L. V. & Rininger, B. F. (1968). A survey of parasites in laboratory primates. Laboratory Animal Care 18, 577–80.Google ScholarPubMed
Ross, G. W. & Knight, R. (1973). Dietary factors affecting the pathogenicity of Entamoeba histolytica in rats. Transactions ojtke Royal Society of Tropical Medicine and Hygiene 67, 560–7.CrossRefGoogle ScholarPubMed
Sawyer, P. R., Brogden, R. N., Pinder, R. M., Speight, T. M. & Avery, G. S. (1976). Tinidazole: a review of its antiprotozoal activity and therapeutic efficacy. Drugs 11, 423–40.CrossRefGoogle ScholarPubMed
Seneca, H. & Bergendahl, E. (1954). The synergistic amebicidal effect of tetracycline, oxytetracycline and carbomycin on cultures of Endamoeba histolytica. American Journal of Medical Sciences 228, 16–20.CrossRefGoogle Scholar
Shapero, M., Jefferies, H. S. & Ryan, D. M. (1972). Laboratory evaluation of panidazole (l-(2′-[α-pyridyl] ethyl-2-methyl)-5-nitroimidazole), a new amoebicide. Annals of Tropical Medicine and Parasitology 66, 187–92.CrossRefGoogle Scholar
Singh, B. N., Das, S. R. & Dutta, G. P. (1973). Importance of O-R potential in initiating cultures of axenically grown Entamoeba histolytica from small inocula. Current Science 42, 227–30.Google Scholar
Slighter, R. G., Yarinsky, A., Drobeck, H. P. & Bailey, D. M. (1980). Activity of quinfamide against natural infections of Entamoeba criceti in hamsters: a new potent agent for intestinal amoebiasis. Parasitology 81, 157–68.CrossRefGoogle ScholarPubMed
Spillman, R., Ayala, S. C. & Sanchez, C. E. de (1976). Double-blind test of metronidazole and tinidazole in the treatment of asymptomatic Entamoeba histolytica and Entamoeba hartmanni carriers. American Journal of Tropical Medicine and Hygiene 25, 549–51.CrossRefGoogle Scholar
Subbaiah, T. V. & Amin, A. H. (1967). Effect of berberine sulphate on Entamoeba histolytica. Nature, London 215, 527–8.CrossRefGoogle ScholarPubMed
Szudarski, M. & Myjak, P. (1968). A trial to obtain in vitro a metronidazole-resistant strain of Entamoeba histolytica. Bulletin of the Institute of Marine Medicine, Gdansk 20, 221–6.Google Scholar
Teodorovic, S. D. (1961). Usefulness of single lesion infection in experimental amoebiasis. Proceedings of the 1st International Conference on Protozoology Prague, pp. 592–594.Google Scholar
Thompson, P. E. (1971). Experimental amebiasis and chemotherapy. Archivos Investigacion Medica 2 (suppl.), 245–54.Google Scholar
Treviño-Garciá Manzo, N., de la Torre, M., Ruiz de Chávez, I. & Sepúlveda, B. (1970). Cambios morfologicos de Entamoeba histolytica bajo el efecto del clorhidrato de emetine in vitro. Archivos Investigacion Medica 1 (suppl), 81–90.Google ScholarPubMed
Viel, C., Rumpe, P. & Lamy, L. (1966). Synthèse et propriétés de deux nouveaux antiamibiens succédanés de l'émétine. Bulletin Chimie Therapeutique, Mai–Juin, p. 228.Google Scholar
Westphal, A. (1970). Die intrazäkale Infektion der Maus mit Entamoeba histolytica. Zeitschrift für Parasitenlcunde 21, 220–30.Google ScholarPubMed
Woolfe, G. (1963). Chemotherapy of amebiasis In Experimental Chemotherapy vol. 1 (ed. Schnitzer, R. J. and Hawking, F.), pp. 355–443. London: Academic Press.CrossRefGoogle Scholar
Woolfe, G. (1965). The chemotherapy of amoebiasis. Progress in Drug Research 8, 12–52.Google Scholar
Yadava, J. N. S. & Dutta, G. P. (1973 a). Comparison of amoebicidal action of antibiotics on Entamoeba histolytica grown axenically and with bacterial or typanosome associates. Indian Journal of Experimental Biology 11, 105–7.Google ScholarPubMed
Yadava, J. N. S. & Dutta, G. P. (1973 b). Combined action of antiamoebic drugs and antibiotics on axenically grown Entamoeba histolytica. Indian Journal of Medical Research 61, 971–5.Google ScholarPubMed