HEXYLRESORCINOL AS AN By P. A. MAPLESTONE, d.s.o., m.b., ch.u., d.t.m. and A. Iv. MUKERJI, m.b. (Cal.) (From the Hookworm Research Laboratory, School oj Tropical Medicine and Hygiene, Calcutta) The history of the use of hexylresorcinol as an anthelmintic is only of about two and a half years duration, and, up to date, all that has been published on the subject is by Lamson and his co-workers in America. The study of this drug in the treatment of intestinal worm is part of an extensive systematic search for efficient and non-toxic anthelmin- tics that is being carried out in America. This is an extremely valuable investigation, and one which in the end we hope will furnish us with much improved remedies for the treatment of these conditions. Lamson, Ward and Brown (1930) in a pre- liminary paper first drew attention to the possi- bilities of hexylresorcinol as an anthelmintic, and this paper was followed by one written by Lamson, Caldwell, Brown and Ward (1931) giving details of treatment and its results. They found that doses of one gramme were the optimum for adults, and they gave the drug in hard gelatine capsules, to avoid its irritating action on the buccal mucous membrane. It was also soon discovered that food cither shortly Nov., 1932] HEXYLRESORCINOL : MAPLESTONE & MUKERJI 611

before or after the treatment lowered greatly moisture, so they now recommend using sugar- its In one of cases on efficiency. series treated coated pills. In our use of the drug this recent the above with a of lines, purgative magnesium finding is of no importance for the capsules two sulphate hours after the drug was given, were only filled as required and administered seven out of ten cases of were com- immediately. cured and there was a pletely total egg reduc- All our patients were admitted to hospital at tion of 96.4 and in five other cases per cent., least on the day prior to treatment, so that our in which the was not magnesium sulphate given trials of this treatment could be properly con- until hours were twenty-four afterwards, all trolled; and most of them had a preliminary cured with of course an reduction of one egg purge. On the evening before treatment a meal, hundred cent. In both these instances as per consisting of bread and milk only, was allowed. well as in the Lamson figures quoted below, The capsules containing the drug were given and his collaborators either the Stoll used, egg- at six a.m. in the morning and not more than or its counting method, modification by Stoll two ounces of water were permitted, to assist and for both the Hausheer, estimating egg in swallowing them. Nothing more was taken reduction and cure rate. In another series of until a meal at ten-thirty a.m., and no purga- tests carried out under field conditions Lamson, tive was given. In fact from our personal ex- Robbins and Ward obtained Brown, (1931) perience of the drug and that of a large number results similar to the above in the case of of our patients, hexylresorcinol appeared to have also treated a number of ascariasis; they a definite cathartic action of its own, its ad- children infected with hookworm, and they ministration frequently being followed by three obtained an reduction of 80 to 90 cent, egg per or four copious watery stools in the course of with a of single dose hexylresorcinol, but the six or seven hours. These evacuations were not actual number treated and the percentage cured accompanied by the least discomfort or abdo- is not given. minal pain. Lamson, Caldwell, Brown and Ward (1932) We have treated twenty-one cases of asca- carried out comparative tests between hexylre- riasis with a cure rate of 66.6 per cent., and an sorcinol and heptylresorcinol and came to the egg reduction, estimated by the original Stoll conclusion that the latter drug was not as effi- counting method, of 94 per cent. In the case cient as the former. Among the figures given of hookworm we have treated twenty- in this paper there is a table showing fifteen six cases with 7.7 per cent, of cures, and 71.4 cases of ascariasis that were given one gramme per cent, of egg reduction. These results com- and two cases that were given 0.8 gramme of pare fairly closely with those quoted above. hexylresorcinol with 29.4 per cent, of complete In the present instance, as on former occasions, cures and an egg reduction of 73.5 per cent. In we have relied on examination of stools by the case of hookworm infection twenty-five cases Lane's centrifuge at least ten days after treat- were given one gramme of hexylresorcinol, ment, in testing for complete cure, and while none were cured and there was an egg reduc- using the egg-counting method as well, we con- tion of 62.7 per cent. sider our results by Lane's technique much the The next paper on the subject was a general more valuable of the two. one on by Lamson and Ward We have also treated ten cases of Tcenia (1932) in which considerable space is devoted sacjivata infection, using the same dose and the to hexylresorcinol and several tables are given same method of administration as in the case from which it is difficult to abstract informa- of round-worm infection. In no case did we tion for comparison with other results. In a recover the complete worm, but five of the cases final paper on anthelmintics Lamson, Brown have reported that they have been free from and Ward (1932) state that they consider a passing segments for over three months, four single dose of hexylresorcinol will remove 90 have not been cured) and one case has not been to 95 per cent, of , 80 to 85 per cent, of traced. These results are not nearly as satis- hookworms, and 40 to 45 per cent, of trichuris. factory as those reported with carbon tetra- The number of cases estimated to be actually chloride by Maplestone and Mukerj i (1931). cured in these instances is not given, but in It should also be noted that although the greater most recent cases of asca- their scries of 263 part of a tapeworm was usually evacuated a riasis they state that 75 per cent, were cured few hours after treatment with hexylresorcinol, and that there is an egg reduction of 90 per the worms were always alive and moved active- cent. ly when placed in water. In our own series of cases we have followed The assumption of the American workers and his the reccommendations of Lamson that the percentage of egg reduction may be of co-workers regarding regulation diet, directly interpreted as a percentage of worm and we also gave all our treatments in destruction seems to be hardly justified for the hard in doses of one gelatine capsules worms supplying the eggs in the post-treatment gramme. Lamson and Ward (1932) reported counts are the survivors of severe poisoning to that gelatine capsules are not suitable which they have been subjected a short time for large scale treatments because gelatine and before, and it seems extremely likely that their of hexylresorcinol interact in the presence functions, of which egg laying is probably the 612 THE INDIAN MEDICAL GAZETTE [Nov!, 1932

most important, will be at least seriously upset if not altogether suspended for a considerable time. Support is lent to this view by a study of the figures in this paper, especially in the case of hookworm, for if we combine our results with those of Lamson, Caldwell, Brown and Ward (1932) we have fifty-one cases with 3.7 per cent, of cures and sixty-seven per cent, in egg reduction. If reduction in the number of eggs were a direct index of the number of worms destroyed one would expect to find a fairly close correlation between the percentage of egg re- duction and percentage of complete cures when a large number of cases are taken, and there is no evidence of this in these figures. - One point that has not been touched on by the American workers is the cost of hexylresor- cinol. We obtained our supply of the drug from England and it cost us thirty shillings an ounce, (I.e., a dose of one gramme cost approximately one shilling, so unless increased demand brings about a great reduction in cost this factor alone will make hexylresorcinol unsuitable for treat- ments on a large scale. Another serious objec- tion to its use in large scale treatments is the great diminution in efficiency of the drug when given shortly before or after food. In all the papers quoted above the principal advantage claimed for this drug over other anthelmintics is its safety, and to us this seems to be the only advantage. However, the advo- cates of this form of treatment themselves admit that dogs may show petechial haimor- rhages in the stomach mucosa after hexylresor- cinol, and the superficial layers of the buccal mucosa may be removed by it, so it is clearly not without some injurious action on patients. Another point claimed in its favour is that many times the optimum dose may be given and may be repeated at short intervals without any harm done. being (Continued from previous column) So far as can two be gathered only between Lambert, S. M. (1923). Carbon Tetrachlorid in the and three thousand cases treated with hexylre- Treatment of Hookworm Disease. Observations on sorcinol in anthelmintic doses have been re- Fifty Thousand Cases. Ibid., Vol. LXXX, p. 526. P. ported upon, and it should be remembered that Lamson, D., Brown, H. W., Robbins, B. H., and Ward, C. B. (1931). Field Treatments of Ascariasis, carbon tetrachloride was ushered in with very Ancylostomiasis, and Trichuriasis with Hexylresorcinol. similar favourable notices a few only years ago, Amer. Journ. Ilyg., Vol. XIII, p. 803. and it was not until after more than forty Lamson, P. D., Brown, H. W., and Ward, C. B. (1932). thousand cases had been treated by Lambert Anthelmintics. Some Therapeutic and Practical Con- siderations on their Use. Journ. Amer. Med. (1922 and 1923), (to quote only one of the Assoc., early Vol. XCIX, p. 292. users of this before a drug) death from it was P. E. H. and recorded. Lamson, D., Caldwell, L., Brown, W., Ward, C. B. (1931). Hexylresorcinol in the Treatment In view of the results of treatment given of Human Ascariasis. Amer. Journ. Hug., Vol. XIII, above, the very high cost of and p. 575. hexylresorcinol P. D., E. H. and the othei aspects of the matter which Lamson, Caldwell, L., Brown, W., have been C. B. (1932). A of the Anthel- discussed we are of the Ward, Comparison opinion that hexylre- mintic Properties of and sorcinol is not Hexylresorcinol Heptyl- yet proved to be an efficient sub- resorcinol. Ibid., Vol. XV, p. 306. stitute for the older anthelmintics. Lamson. P. D., and Ward, C. B. (1932). The Chemo- therapy of Helminth Infestations. Journ. Parasitol., References Vol. XVIII, p. 173. P. C. and H. W. Lambert, S M (1922). Carbon Tetrachlorid in (ho Lamson, D., Ward, B., Brown, (1930). Treatment of Hookworm An Ascaricide. Proc. Soc. Disease. Observations in Effective Hexylresorcinol. Thousand Cases. J num. Biol, and Vol. 1017. Twenty Amer. Med. Assoc., Expcr. Med., XXVII, p. Vol. LXXIX, p. 2055. Maplestone, P. A., and Mukerji, A. K. (1931). Carbon Tetrachloride in the Treatment of Tamia (Coiiliiiucd at foot of next column) Infections. Indian Med. Gaz., Vol. LXVI, p. 667.