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Phenothiazine in the treatment of human intestinal helminthic infestations
163 TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL 1V[EDICINE AND" HYGIENE. Vol. X X X V I I . No. 2. S e p t e m b e r , 1943.
P H E N O T H I A Z I N E IN T H E T R E A T M E N T OF H U M A N INTESTINAL HELMINTHIC INFESTATIONS BY
MOUNTJOY ELLIOT F, M.A., M.D., M.R.C.P.I. The pharmacology and antiparasitic action of phenothiazine (thiodiphenyl amine) in the human and veterinary fields of helminthology have been recently reviewed and summarized by DAVEY and INr~Es (1942). It has proved itself a powerful weapon against certain intestinal parasites of animals but as yet no careful survey as to its potentialities in the human subject has been .made. Our limited observations amongst the natives of West Africa have convinced us that this drug may be a s p o t e n t a destroyer of hookworms as any of the drugs at present used for this purpose. We were also impressed by its action against Strongyloides stercoralis, parasites which up to this have been very difficult to deal with in some patients. KtUTtrr~EN-EI~BAUM,in Canada (1941), studied its action against threadworms and found it exercised a powerful destructive action on these worms.
Toxicity and Dosage. The drug must be given in strictly controlled dosage, especially to children, as toxic sequellae have been reported following its use in children. Inhibition of haemopoesis, haemolysis or hepatitis were recorded (HOBBLE 1941, and HuMPrmvrs 1942). I have given the drug to over seventy adult natives and have been impressed by its lack of unpleasant sequellae as compared with fifty control patients to whom santonin, oil of chenopodium or carbon tetrachloride had been given. The American standard of dosage was put at 1"0 gramme per 10 lb. of body weight. This appeared a safe adult level because I gave the phenothiazine in doses usually more than double this standard and had no cases of intolerance. Our total adult dosage varied between 20 and 30 grammes and it was spread out over a period of 4 to 5 days. Results are very poor if attempts at " shock therapy " are attempted by giving the total dosage in 1 day as is the custom with most other antiparasitic drugs. The reason for this has not yet been explained but there is evidence that phenothiazine acts as a tissue toxin only after it has been ingested by the parasite and not as an environmental poison. If this is the case, its action against those parasites who derive their nutrition by sucking lymph and blood from the intestinal mucosa, can only be brought about by the minute quantities of the drug absorbed into the blood stream.
164
PHENOTHIAZINE IN HELMINTHIC INFESTATIONS.
Method of Administration.
.The drug is put up in 1 gramme tablets and was given to our patients in three equally divided daily doses after meals, i.e., two tablets three times a day after meals for 4 to 5 days. It is important to give the large tablets crushed up, otherwise they may be passed unchanged in the stools. The diet during the period of treatment should not be too heavy. ASSESSMENT OF CURE Owing to shortage of laboratory staff, we were unable tq make ova or worm counts on unit bulk weight of faeces but used simple cover glass preparations instead. If two successive preparations failed to show any ova, the pa'ient was considered cured. The first examinations were not made until at least a week had elapsed since the completion of treatment. Results.
On the basis of the above' assessment, the following infections were con• sidered cured by the administration of phenothiazine. Parasite. Ancylostoma duodenale Strongyloides stercoralis Ascaris lumbricoides Taenia saginata ...... Trichuris trichiura . . . . . . Entamoeba histolytica
... ... ...
Number Treated. 36 8
...
Number Cured.
26 5
15
9
8 8 9
4 5 6
~UMMARY.
Phenothiazine appears to be well tolerated by the adult native if given in accordance with the American standard of dosage. This preliminary investigation suggests that phenothiazine 'has aft antiparasitic action against A . duodenale and other common intestinal parasites. A further detailed clinical investigation into its potentialities might yield much valuable information. REFERENCES. DAVEY, D . G . & INNES, J. R . M . (19a2). Vet. Bull., 12 (8). R. 7. HUBBLE, D. (1941). Lancet, 2,600. HUMPHREYS, D. R. (1942). Ibid., 2, 39. KUITUNEN-EKBAUM. (1941). Ganad. publ. Hlth ft., 82, 308.
P H E N O T H I A Z I N E IN T H E T R E A T M E N T OF H U M A N INTESTINAL HELMINTHIC INFESTATIONS BY
MOUNTJOY ELLIOT F, M.A., M.D., M.R.C.P.I. The pharmacology and antiparasitic action of phenothiazine (thiodiphenyl amine) in the human and veterinary fields of helminthology have been recently reviewed and summarized by DAVEY and INr~Es (1942). It has proved itself a powerful weapon against certain intestinal parasites of animals but as yet no careful survey as to its potentialities in the human subject has been .made. Our limited observations amongst the natives of West Africa have convinced us that this drug may be a s p o t e n t a destroyer of hookworms as any of the drugs at present used for this purpose. We were also impressed by its action against Strongyloides stercoralis, parasites which up to this have been very difficult to deal with in some patients. KtUTtrr~EN-EI~BAUM,in Canada (1941), studied its action against threadworms and found it exercised a powerful destructive action on these worms.
Toxicity and Dosage. The drug must be given in strictly controlled dosage, especially to children, as toxic sequellae have been reported following its use in children. Inhibition of haemopoesis, haemolysis or hepatitis were recorded (HOBBLE 1941, and HuMPrmvrs 1942). I have given the drug to over seventy adult natives and have been impressed by its lack of unpleasant sequellae as compared with fifty control patients to whom santonin, oil of chenopodium or carbon tetrachloride had been given. The American standard of dosage was put at 1"0 gramme per 10 lb. of body weight. This appeared a safe adult level because I gave the phenothiazine in doses usually more than double this standard and had no cases of intolerance. Our total adult dosage varied between 20 and 30 grammes and it was spread out over a period of 4 to 5 days. Results are very poor if attempts at " shock therapy " are attempted by giving the total dosage in 1 day as is the custom with most other antiparasitic drugs. The reason for this has not yet been explained but there is evidence that phenothiazine acts as a tissue toxin only after it has been ingested by the parasite and not as an environmental poison. If this is the case, its action against those parasites who derive their nutrition by sucking lymph and blood from the intestinal mucosa, can only be brought about by the minute quantities of the drug absorbed into the blood stream.
164
PHENOTHIAZINE IN HELMINTHIC INFESTATIONS.
Method of Administration.
.The drug is put up in 1 gramme tablets and was given to our patients in three equally divided daily doses after meals, i.e., two tablets three times a day after meals for 4 to 5 days. It is important to give the large tablets crushed up, otherwise they may be passed unchanged in the stools. The diet during the period of treatment should not be too heavy. ASSESSMENT OF CURE Owing to shortage of laboratory staff, we were unable tq make ova or worm counts on unit bulk weight of faeces but used simple cover glass preparations instead. If two successive preparations failed to show any ova, the pa'ient was considered cured. The first examinations were not made until at least a week had elapsed since the completion of treatment. Results.
On the basis of the above' assessment, the following infections were con• sidered cured by the administration of phenothiazine. Parasite. Ancylostoma duodenale Strongyloides stercoralis Ascaris lumbricoides Taenia saginata ...... Trichuris trichiura . . . . . . Entamoeba histolytica
... ... ...
Number Treated. 36 8
...
Number Cured.
26 5
15
9
8 8 9
4 5 6
~UMMARY.
Phenothiazine appears to be well tolerated by the adult native if given in accordance with the American standard of dosage. This preliminary investigation suggests that phenothiazine 'has aft antiparasitic action against A . duodenale and other common intestinal parasites. A further detailed clinical investigation into its potentialities might yield much valuable information. REFERENCES. DAVEY, D . G . & INNES, J. R . M . (19a2). Vet. Bull., 12 (8). R. 7. HUBBLE, D. (1941). Lancet, 2,600. HUMPHREYS, D. R. (1942). Ibid., 2, 39. KUITUNEN-EKBAUM. (1941). Ganad. publ. Hlth ft., 82, 308.