303
THE LANCET
Pathogenic Entamoeba Histolytica and abscess in man caused by the same creature so often isolated from asymptomatic carriers, or are two parasites involved whose appearance is the same? From the point of view of treatment, the question is vital; yet it remains controversial today. BRUMPT’presented evidence that the human parasitic amoeba known as Entamceba histolytica2consisted of two morphologically indistinguishable but separate speciesEntamceba dysenteriae, a pathogen, and Entamcuba dispar, a more commonly occurring but harmless commensal. This view never gained general acceptance, but, as GARNHAM3 pointed out, it has never been disproved: "One aspect of the problem of etiology has been ignored or passed over lightly: the significance of the asymptomatic carrier strain of E. histolytica. The situation has probably been oversimplified by implying that transformation always occurs between this form and the tissueinvasion amoeba, and in consequence the desirability of treating such cases in regions where amoebiasis occurs. If it is true that some non-pathogenic forms are incapable of such a transformation, then they are intrinsically distinct and Brumpt’s name E. dispar becomes valid." NEAL,4 on the other hand, having summarised the evidence that "virulence is an unstable characteristic in E. histolytica," continues: "On the basis of present evidence, it is my view that amebas are normally avirulent in the intestinal lumen and that, under some stimulus, they change to the invasive form." Till now, despite some limited claims, nobody has succeeded in tracking down this stimulus either to host or parasite. Meanwhile the parasite continues to bite, as it were, on Mondays but not on Tuesdays-a habit distressing to orderly minds. During the first two decades after the 1939-45 war (that is, before ship’s personnel recruited in the tropics were effectively screened) the Dreadnought Seamens Hospital at Greenwich housed a reservoir ARE amoebic
dysentery
1 Brumpt, E.Bull. Acad. Med. Paris, 1925, 94, 943. 2. Schaudinn, F.Arb.K.GesundkAmt. 1903, 19,547. 3 Garnham, P. C. C.World Problems In Leishmaniasis, Amoebiasis, Trypanosomiasis and Toxoplasmosis; p. 31 World Health Organisation, Geneva, 1960. 4. Neal, R. A.Bull.N. Y. Acad. Med. 1971, 47, 462.
of parasites resembling that of a tropical rather than a temperate-zone population, and one of its main problems lay in the diagnosis of amoebic disease. This led to the development of a method for culturing amoebx more suited to hospital conditions than the research methods previously available. It then happened that the chief technician of the Dreadnought hospital laboratory, P. G.
SARGEAUNT, moved to the protozoology department of the London School of Hygiene and Tropical Medicine, where, besides introducing the new amoebic culture medium, he took the opportunity. of trying some of the techniques in current use there (notably in trypanosome work) upon his cultured amcebse. In the demonstration, by the method of WRAXALL and CULLIFORD,5 of the enzyme phosphoglucomutase, he was rewarded by a lucky break. The position of the enzyme band was proved to be associated with the virulence (according to clinical history) of the amoeba.6This relationship held for all 18 strains derived from clinical cases, but for none of the remaining 67 strains from subjects free of amoebic symptoms-a striking result. Some 50 of the series had been collected by a visit to New Delhi arranged for Mr SARGEAUNT with the help of Prof. R. LUMSDEN, and further specimens giving equally definite but as yet unpublished results have been similarly obtained from Mexico. It is too early for this work to have been confirmed by other laboratories. But if, as seems likely, a laboratory method has at last been found for distinguishing the pathogenic from the "dispar" version of E. histolytica, a new territory of exciting further work has been opened up. Apart from the obvious necessity of extending the original work to cover larger numbers, the first question will be that of elucidating the result itself; for some may still object that the association of enzyme difference with virulence need not be intrinsic to the parasite but could be the effect of some cause (e.g.,
ingested bacteria) common to both. A related topic will be that of finding a connection between the pathogenicity of the strain and the chemistry of the "marker" phosphoglucomutase variant that discloses it. Another line of work would be the correlation of the enzyme method with the rat-caecum method7 of detecting virulence. The position of animal and atypical strains awaits investigation by the new method: what would be the enzyme patterns, for instance, of E. ranarum (pathogenic for frogs) and E. invadens (pathogenic for snakes)? Finally, most important of all, is the way going to be cleared for treating, throughout the world, only patients with the pathogenic amoeba? That would be revolutionary indeed. 5. Wraxall,B.G.D.,Culliford,B.J.J.forens.Sci.Soc.1968,8,81. 6. Sargeaunt, P. G., Williams, J. E., Grene, J; D. Trans. R. Soc. trop. Med.
Hyg. 1978, 72, 519. ibid. 1957, 45, 313.
7.Neal, R. A.
THE LANCET
Pathogenic Entamoeba Histolytica and abscess in man caused by the same creature so often isolated from asymptomatic carriers, or are two parasites involved whose appearance is the same? From the point of view of treatment, the question is vital; yet it remains controversial today. BRUMPT’presented evidence that the human parasitic amoeba known as Entamceba histolytica2consisted of two morphologically indistinguishable but separate speciesEntamceba dysenteriae, a pathogen, and Entamcuba dispar, a more commonly occurring but harmless commensal. This view never gained general acceptance, but, as GARNHAM3 pointed out, it has never been disproved: "One aspect of the problem of etiology has been ignored or passed over lightly: the significance of the asymptomatic carrier strain of E. histolytica. The situation has probably been oversimplified by implying that transformation always occurs between this form and the tissueinvasion amoeba, and in consequence the desirability of treating such cases in regions where amoebiasis occurs. If it is true that some non-pathogenic forms are incapable of such a transformation, then they are intrinsically distinct and Brumpt’s name E. dispar becomes valid." NEAL,4 on the other hand, having summarised the evidence that "virulence is an unstable characteristic in E. histolytica," continues: "On the basis of present evidence, it is my view that amebas are normally avirulent in the intestinal lumen and that, under some stimulus, they change to the invasive form." Till now, despite some limited claims, nobody has succeeded in tracking down this stimulus either to host or parasite. Meanwhile the parasite continues to bite, as it were, on Mondays but not on Tuesdays-a habit distressing to orderly minds. During the first two decades after the 1939-45 war (that is, before ship’s personnel recruited in the tropics were effectively screened) the Dreadnought Seamens Hospital at Greenwich housed a reservoir ARE amoebic
dysentery
1 Brumpt, E.Bull. Acad. Med. Paris, 1925, 94, 943. 2. Schaudinn, F.Arb.K.GesundkAmt. 1903, 19,547. 3 Garnham, P. C. C.World Problems In Leishmaniasis, Amoebiasis, Trypanosomiasis and Toxoplasmosis; p. 31 World Health Organisation, Geneva, 1960. 4. Neal, R. A.Bull.N. Y. Acad. Med. 1971, 47, 462.
of parasites resembling that of a tropical rather than a temperate-zone population, and one of its main problems lay in the diagnosis of amoebic disease. This led to the development of a method for culturing amoebx more suited to hospital conditions than the research methods previously available. It then happened that the chief technician of the Dreadnought hospital laboratory, P. G.
SARGEAUNT, moved to the protozoology department of the London School of Hygiene and Tropical Medicine, where, besides introducing the new amoebic culture medium, he took the opportunity. of trying some of the techniques in current use there (notably in trypanosome work) upon his cultured amcebse. In the demonstration, by the method of WRAXALL and CULLIFORD,5 of the enzyme phosphoglucomutase, he was rewarded by a lucky break. The position of the enzyme band was proved to be associated with the virulence (according to clinical history) of the amoeba.6This relationship held for all 18 strains derived from clinical cases, but for none of the remaining 67 strains from subjects free of amoebic symptoms-a striking result. Some 50 of the series had been collected by a visit to New Delhi arranged for Mr SARGEAUNT with the help of Prof. R. LUMSDEN, and further specimens giving equally definite but as yet unpublished results have been similarly obtained from Mexico. It is too early for this work to have been confirmed by other laboratories. But if, as seems likely, a laboratory method has at last been found for distinguishing the pathogenic from the "dispar" version of E. histolytica, a new territory of exciting further work has been opened up. Apart from the obvious necessity of extending the original work to cover larger numbers, the first question will be that of elucidating the result itself; for some may still object that the association of enzyme difference with virulence need not be intrinsic to the parasite but could be the effect of some cause (e.g.,
ingested bacteria) common to both. A related topic will be that of finding a connection between the pathogenicity of the strain and the chemistry of the "marker" phosphoglucomutase variant that discloses it. Another line of work would be the correlation of the enzyme method with the rat-caecum method7 of detecting virulence. The position of animal and atypical strains awaits investigation by the new method: what would be the enzyme patterns, for instance, of E. ranarum (pathogenic for frogs) and E. invadens (pathogenic for snakes)? Finally, most important of all, is the way going to be cleared for treating, throughout the world, only patients with the pathogenic amoeba? That would be revolutionary indeed. 5. Wraxall,B.G.D.,Culliford,B.J.J.forens.Sci.Soc.1968,8,81. 6. Sargeaunt, P. G., Williams, J. E., Grene, J; D. Trans. R. Soc. trop. Med.
Hyg. 1978, 72, 519. ibid. 1957, 45, 313.
7.Neal, R. A.
