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The treatment of pinworm infection (Enterobiasis)
T H E T R E A T M E N T OF P I N W O R M I N F E C T I O N
(ENTEROBIASIS)
A COMPARATIVE STUDY OF THREE 0XYURICIDES THOMAS S. BUMB~m0, M.D., FRANCIS J . GUSTINA, M.D., AND ROSE E . OLEKSIAK, B . A . BUFFALO, N. Y.
N T H E p a s t two y e a r s we have exa m i n e d 1,768 p a t i e n t s in the w a r d s a n d the clinics of the E. J. M e y e r M e m o r i a l H o s p i t a l in Buffalo, N. Y., f o r p i n w o r m infection. Of this number, 1,737 were children and thirtyone were adults. Using a modifieation of the G r a h a m Scotch Tape swab technique, which we have m i n u t e l y described in our published reports, we f o u n d t h a t 523 or 30 p e r cent of the 1,768 patients were infected. Of the 523 infected, 513 or 98 per cent were children and ten or 2 per cent were aduIts. I n our search for an ideal oxyurieide, one t h a t is easy to take, well t o l e r a t e d and inexpensive, we have to date evaluated these nine d r u g s : Egressin, Diphenan, gentian violet, T e r r a m y c i n , papain, Cremothalidine, M a g n a m y e i n , garlic, and piperazine. The results obtained with five of these have been published. P a p a i n 1 was effective in 10 per cent of t h i r t y eases, E g r e s s i n 2 in 54 p e r cent of thirtynine cases, D i p h e n a n in 30 per cent of f o r t y eases, gentian violet in 84 per cent of t h i r t y - e i g h t eases, and Terr a m y c i n in 85 per cent of thirty-nine p a t i e n t s treatedY Gentian violet and T e r r a m y c i n , the most effective of these oxyurieides, were not completely satisfactory. The y o u n g e r children were not able to swallow
I
the intact enteric-coated gentian violet tablets, and in some p a t i e n t s it caused nausea and vomiting, with a b d o m i n a l cramps. The cost of Terr a m y c i n and the possibility of establishing sensitivity to a n i m p o r t a n t antibiotic are decided d r a w b a c k s in treating' p i n w o r m infections w i t h this drug. The percentages o f cures obtained with Egressin, Diphenan, papain, Cremothalidine, and Magnamycin were sufficiently low to make them of questionable value. CLINICAL MATERIAL AND METHOD
One h u n d r e d and fifty-five children infected with p i n w o r m s were t r e a t e d with one of three oxyuricides. All o f these children, r a n g i n g in age f r o m 21/2 to 16 years, were residents of the G e r m a n R o m a n Catholic O r p h a n a g e in Buffalo, N. Y. F o r t y - s e v e n of these infected children were t r e a t e d w i t h piperazine h e x a h y d r a t e , fifty were t r e a t e d with T e r r a m y c i n , and fifty-eight with d e h y d r a t e d garlic powder. E a c h t r e a t m e n t g r o u p contained an almost equal n u m b e r of children f r o m 1 to 5 years, 6 to 10 y e a r s and 11 to 16 y e a r s of age. The diagnosis in all eases was established b y the use of a modification of the G r a h a m Scotch T a p e swab technique which we have described in detail in earlier publications. I n this study, we used a new Scotch T a p e which is From the Department of Pediatrics, E. J. Meyer Memorial Hospital and University of Buffalo, School of Medicine. m o r e t r a n s p a r e n t , with a crystal-clear 3s6
BUMBALO ET AL. :
adhesive that makes the identification of the pinworm eggs much easier. This tape is designated as' Scotch acetate film tape No. 800. Seven days after treatment, Scotch Tape swab smears were made daily for one week to determine the results of the treatment. Those patients who had seven consecutive negative smears were declared cured. The remaining eightyone children of the orphanage had negative diagnostic Scotch Tape smears. These children, even though they were considered free of pinworm infection, were also treated with either Terramycin or garlic. F i f t y were treated with Terramycin and fifty-eight with garlic. By treating the entire pediatric population of the orphanage we hoped to minimize the possibility of allowing infected children who had negative diagnostic smears to go untreated and possibly reinfect the treated cases. The adult population of the orphanage was not treated since none of them presented symptoms that suggested pinworm infection. Piperazine hexahydrate, a white crystalline substance, has the following structural formula: l ~ N ( Cl=f2 - C I - I 2 ) H N 9 6 II~O \ C I I ~ CH~.
It is readily soluble in water to give a clear colorless alkalhm solution. It is not hygroscopic and is stable in solid form. Piperazine has been used for many years in the treatment of gout and urinary calculi. It produces no symptoms and is practically nontoxic.~ The acute and chronic toxicity tests of piperazine conducted by the Wellcome Research Laboratories have established its nontoxicity in the normal dosage range.
ENTEROBIASIS
387
Mouriquand and associates s treated ,nice infected with Aspicularis tetraptera and Syphacea with piperazine hexahydrate and reported satisfactory anthelminthic properties toward these mouse oxyurids. They also treated a group of children ranging in age from 3 to 15 years with a high proportion of cures and reported that piperazine was "easily accepted by children and very well tolerated even by the very small." Standen Ghas also successfully treated Aspieuluris tetraptera with piperazine and recommended that it be used in the treatment of human pinworm infection. White and Standen 7 treated a group of thirty-one children with piperazine hexahydrate syrup at a dose level of 50 to 75 rag. per kilogram per day with a 97 per cent cure rate. They also reported no toxic effects in dose levels as high as 150 rag. per kilogram daily and found that piperazine was extremely well tolerated by all but one o~ the thirtyone children treated. Brown s in this country has also found piperazine quite effective against the mouse pinworm, Aspiculuris tetraptera. So far as we can determine, there are no reported series of cases of enterobiasis treated with piperazine in this country. Forty-seven of the infected children were treated with a palatable 10 per cent syrup containing 100 rag. of piperazine hexahydrate per cubic centimeter. Without any previous preparation these patients were treated for seven days, rested for seven days, and then treated for seven more days. A f t e r a lapse of seven days, following the last day of treatment, one Scotch Tape swab smear was taken daily, early in the morning, before the patients were bathed, to determine the
388
THE J O U R N A L 0 F PEDIATRICS
results of the t r e a t m e n t . I n addition to t h e piperazine h e x a h y d r a t e s y r u p t r e a t m e n t , the usually r e c o m m e n d e d personal and e n v i r o n m e n t a l hygienic measures were a d h e r e d to as closely as possible. This same routine was followed in t r e a t i n g the children w i t h T e r r a m y c i n and garlic. Table I Iists the n u m b e r of eases t r e a t e d with these three oxyuricides, the dosage used, the d u r a t i o n of t r e a t m e n t , and the result of t r e a t m e n t . F o r m a n y y e a r s r a w garlic has been used in m a n y p a r t s of the w o r l d as a " p o p u l a r r e m e d y " for p i n w o r m infection. M a n y clinicians consider r a w garlic as one of the best oxyurieides. E c k e r l e u in his s t u d y (personal c o m m u n i c a t i o n used r a w garlic, one
8 grains of d e h y d r a t e d garlic powder* to the teaspoonful. I n addition to the garlic t r e a t m e n t , the usually teeo m m e n d e d personal and e n v i r o n m e n tal hygienic measures were c a r r i e d out as best as possible. Table I indicates the n u m b e r of cases treated, dosage, and per cent of cures with the garlic syrup, The garlic s y r u p was v e r y well accepted and t o l e r a t e d b y all the children and no u n t o w a r d effects were noted in all f i f t y - e i g h t children treated. I n a recent s t u d y 3 on the t r e a t m e n t of enterobiasis w i t h T e r r a m y c i n we r e p o r t e d a cure r a t e of 85 per cent of f o r t y infected children t r e a t e d with 10 rag. of T e r r a m y c i n p e r p o u n d of b o d y weight, divided into t h r e e daily
TABLE I
DRUG Piperazine hexahydrato
I
CASES 47
Garlic s y r u p
58
Terramycin
50
I 1-5 yr. 1~ 5-10 yr. 1 10 yr. a n d 1-10 yr. 1 10 yr. a n d
DOSAGE tsp. t.i.d. tsp. t.l.d. up, 11~ tsp. t.i.d. tsp. t.i.d. up, 2 tsp. t.l.d.
5 rag. p e r p o u n d of b o d y weight divided into 3 d a i l y doses
clove e v e r y other night for f o u r t e e n days, i n t e r r u p t e d b y a one-week rest period. H e r e c o m m e n d s r a w garlic m i x e d with g r a t e d carrots and mayonnaise, served in a sandwich. F r e s h p a r s l e y eaten i m m e d i a t e l y a f t e r the g a r l i c sandwich acts as a n a t u r a l deodorizer. Vanni 1~ also r e p o r t e d deodorized garlic tablets as the treatm e n t of choice for enterobiasis. Kill i n g s w o r t h and associates 11 used r a w garlic in the t r e a t m e n t of p i n w o r m infection with 87 per cent cures. I n o u r study, fifty-eight of the inf e c t e d children at the G e r m a n R o m a n Catholic O r p h a n a g e were t r e a t e d with a mint-flavored s y r u p containing
I 7 7 7 7 7 7 7 7 7
DURATION [ % CURED day s treatment 85 d a y s rest days treatment days t r e a t m e n t 7 d a y s rest days t r e a t m e n t days t r e a t m e n t 38 days rest days treatment
doses for a period of seven days. L o u g h l i n and co-workers 12 t r e a t e d t h i r t y patients with enterobiasis with 1 to 2 Gm. of T e r r a m y M n base for five d a y s with a 100 per cent cure rate. I n this s t u d y we t r e a t e d fifty of the infected children at the Germ a n R o m a n Catholic O r p h a n a g e with 5 nag. of T e r r a m y e i n t p e r pound of b o d y weight, divided into three daily doses for a period of f o u r t e e n days w i t h a seven-day rest period at the end of the first week of t r e a t m e n t . *Garlic powder as a mint-flavored s y r u p w a s supplied by t h e V a n P a t t e n P h a r m a c e u t i cal Co. ~ T e r r a m y c i n w a s supplied by t h e Chas. Pfizer & Co., Inc.
BUMBALO ET AL. :
The same precautions and routines were used in the t r e a t m e n t of this group of patients t h a t were used with the piperazine and garlic treatment. The same rigid measure of cure, seven consecutive negative Scotch Tape smears t a k e n seven days a f t e r the termination of the treatment, was also carried out. The p e r c e n t a g e of cures obtained with the decreased dose of T e r r a m y c i n is indicated in Table I. RESULTS AND DISCUSSION Of the forty-seven patients treated with piperazine h e x a h y d r a t e , f o r t y had seven consecutive negative posttreatment Scotch Tape smears, the remaining seven patients had one to seven positive post-treatment smears. The cure rate in this series of patients t r e a t e d with piperazine h e x a h y d r a t e was 85 per cent. All the patients in this series took the palatable syrup of piperazine readily and tolerated it very well. Sample post-treatment blood counts done on ten of the patients were normal, and sample post-treatment urinalyses done on twenty of the patients were negative, except for three female children who showed evidence of cystitis which we believe was not caused by, nor related to, the piperazine treatment. Even though the percentage of cures obtained in the group of fiftyeight patients t r e a t e d with garlic was only 7 per cent, we are of the opinion. t h a t garlic should not be discarded as an oxyuricide. Two errors made in our garlic s t u d y might have, at least in part, contributed to this low percentage of cures. The 8 grains of d e h y d r a t e d garlic, given three times daily, m a k i n g a total daily dose of 24 grain.s of d e h y d r a t e d powder,
389
ENTEROBIASIS
could have been an inadequate dose. Since most of the studies on the garlic t r e a t m e n t of enterobiasis used one " p o d " or " c l o v e " of garlic, we weighed m a n y " c l o v e s " of garlic to arrive at an average weight of a clove of garlic. A f t e r weighing m a n y cloves of garlic t h a t were obtained in local food shops, we concluded that the average weight of a clove was 11 grains. W e p r e p a r e d a mintflavored s y r u p containing approxim a t e l y 8 grains of d e h y d r a t e d garlic powder to the teaspoon. This was the syrup we used in treating fifty-eight of the infected children at the German Roman Catholic Orphanage. At the conclusion of the s t u d y we learned that garlic cloves most usually available t h r o u g h food shops average 46 grains. This information has been confirmed b y the U.S. D e p a r t m e n t of Agriculture? x' Since the completion of this study, we again obtained samples of garlic cloves f r o m local food shops and f o u n d t h a t the average weight of these cloves was 60 grains. However, the replacement ratio between raw and d e h y d r a t e d garlic is 1 to 6, on the average, one p a r t of dehyd r a t e d garlic equals six parers of raw garlic. On this basis, even with the error made in computing the average weight of a clove of garlic, the dosage used in our study could well have been an adequate dose. The possibility that some active principle of garlic is lost in the dehydration process should also be considered in evaluating the garlic treatment of enterobiasis. The second error which we feel we should explain is that the bottles containing the garlic syrup were not carefully shaken be*Leaflet
Garlic.
No.
138,
entitled
Product~o~
of
390
THE JOURNAL
fore a dose was administered and for this reason the individual doses of garlic syrup could have varied considerably. How much this error contributed to the low percentage of cures in the garlic group we are not able to state with any degree of accuracy. Of the fifty patients treated with the reduced dose of Terramycin, 5 rag. per pound of body weight, only 38 per cent had seven consecutive negative post-treatment Scotch Tape smears. This percentage of cures is less than one-hail the percentage of cures obtained in our earlier study in which we used 10 rag. of Terramycin per pound of body weight. This study suggests that the 5 rag. per pound of body weight dose is not adequate to produce the direct deleterious action upon the mature gravid female worms and on the fertilized eggs as suggested by Loughlin and associates. 12 SUl~IMARY
1. The percentage of cures with piperazine,~.85 per cent, obtained in this series of forty-seven patients compares very favorably with the cures obtained with Terramycin and gentian rio]at. S~nce the syrup of piperazine used in this study was easy to take, well tolerated, and, we are assured, can be made available inexpensively, we are of the opinion that of the nine oxyuricides that we have tested to date, piperazine hexahydrate v ~ the closest to our standard of an ideal oxyuricide. 2. We have been able to confirm the study of White and Standen, as reported in the English literature, that piperazine hexahydrate is a nontoxic, safe, and effective oxyuricide. *Piperazine hexahydrate as syrup of Antepar Citrate was supplied by the BurroughsWellcome Company.
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PEDIATRICS
3. The 7 per cent cures obtained with dehydrated garlic powder in this series of fifty-eight infected children was the lowest of all the oxyuriaides we have tested to date. 4. However, because of the ancient reputation of garlic as a " p o p u l a r r e m e d y " for pinworm infection substantiated in part by medical research, and because of the possibility of some error in our garlic study, we are of the opinion that garlic should be tried again both by us and other groups after some of the details of dehydrated garlic powder dosage have been confirmed. The complete lack of toxicity and the low cost of dehydrated garlic powder would make it, in our opinion, a n ideal oxyuricide if repeated studies could confirm the high cure rates obtained by other researchers. 5. Terramycin in a reduced dose of 5 rag. per pound of body weight cured only 38 per cent of fifty-nine infected children, This dose, onehalf of the dose we reported on in an earlier study, apparently is not enough to produce an effective cure rate. The authors express their appreciation to Dr. Samuel Milite]lo, the medical director of the German Roman Catholic Orphanage, for his permission to conduct this study at the German l~oman Catholic Orphanage. REFERENCES 1. Bumbalo, T, S., Gustina, F. J., and Oleksiak, 1~. E. : The Treatment of Pinworm Infection (Enterobiasis) With Papain, J. PEDIAT. 42: 576, 1953. 2. Bumbalo, T. S., Gustina, F. J., and Oleksiak, R. E.: The T r e a t m e n t of Enterobiasis W i t h Egressin, J. Parasitol. 39: 66, 1953. 3. Bumbalo, T. S., a n d Gustina, F. J.: The T r e a t m e n t of P i n w o r m I n f e c t i o n in Children, Postgrad. Mad. 14: 83, 1953. 4. So]lman, I. : A Manual of Pharmacology a n d I t s Application to Therapeutics and Toxicology, Philadelphia, 1948, W. B. Saunders Co.
BUMBAL0 ET AL. : 5. Mouriquand, G., Roman, E., and Coisnard, J.: Analysis of Treatment of Oxyuriasis W i t h Piperazine, J. Med. Lyon 32: 189, 1951. 6. Standen, O. D.: E x p e r l m e n t a l Chemot h e r a p y of Oxyuriasls, Brit. M. J. 2: 755, 1953. 7. White, R. H. R.~ and Standen, O. l).: Piperazine in the T r e a t m e n t of Thread worms in Children, Report on a Clinical Trial, Brit. M. J. 2: 755, ]953. 8. Brown, H . W . : P e r s o n a l communication (Columbia U n i v e r s i t y School of Public Health, New York, New York).
ENTEROBIASIS
391
9. Eekerle, W. J.: Personal eommunication a n d p a p e r presented at the 102nd. a n n u a l m e e t i n g of the A. M. A , J u n e 1-5, New York, 1953. 10. Vanni, u Therapy of Oxyuriasis, M i n e r v a Med. 33: 280, 1942. 11. Killingsworth, W. P., Meyer, P. R., McFadden, I. M., and Boardman, H. L.: Treatmeng of Pinworms (Oxyuriasis). Clinical E v a l u a t i o n Based on 1,005 Cases, Texas J. Med. 48: 27, 1952. 12. Loughlin, E. H., Rappaport, I., Mullir., W. G., Wells, H. S., Joseph, A. A., and Shookhoff, tI. B . : The T r e a t m e n t of E n t e r o b i a s i s W i t h Terramycin Base, Antibiotics & Chemother. 1: 588, 1951.
(ENTEROBIASIS)
A COMPARATIVE STUDY OF THREE 0XYURICIDES THOMAS S. BUMB~m0, M.D., FRANCIS J . GUSTINA, M.D., AND ROSE E . OLEKSIAK, B . A . BUFFALO, N. Y.
N T H E p a s t two y e a r s we have exa m i n e d 1,768 p a t i e n t s in the w a r d s a n d the clinics of the E. J. M e y e r M e m o r i a l H o s p i t a l in Buffalo, N. Y., f o r p i n w o r m infection. Of this number, 1,737 were children and thirtyone were adults. Using a modifieation of the G r a h a m Scotch Tape swab technique, which we have m i n u t e l y described in our published reports, we f o u n d t h a t 523 or 30 p e r cent of the 1,768 patients were infected. Of the 523 infected, 513 or 98 per cent were children and ten or 2 per cent were aduIts. I n our search for an ideal oxyurieide, one t h a t is easy to take, well t o l e r a t e d and inexpensive, we have to date evaluated these nine d r u g s : Egressin, Diphenan, gentian violet, T e r r a m y c i n , papain, Cremothalidine, M a g n a m y e i n , garlic, and piperazine. The results obtained with five of these have been published. P a p a i n 1 was effective in 10 per cent of t h i r t y eases, E g r e s s i n 2 in 54 p e r cent of thirtynine cases, D i p h e n a n in 30 per cent of f o r t y eases, gentian violet in 84 per cent of t h i r t y - e i g h t eases, and Terr a m y c i n in 85 per cent of thirty-nine p a t i e n t s treatedY Gentian violet and T e r r a m y c i n , the most effective of these oxyurieides, were not completely satisfactory. The y o u n g e r children were not able to swallow
I
the intact enteric-coated gentian violet tablets, and in some p a t i e n t s it caused nausea and vomiting, with a b d o m i n a l cramps. The cost of Terr a m y c i n and the possibility of establishing sensitivity to a n i m p o r t a n t antibiotic are decided d r a w b a c k s in treating' p i n w o r m infections w i t h this drug. The percentages o f cures obtained with Egressin, Diphenan, papain, Cremothalidine, and Magnamycin were sufficiently low to make them of questionable value. CLINICAL MATERIAL AND METHOD
One h u n d r e d and fifty-five children infected with p i n w o r m s were t r e a t e d with one of three oxyuricides. All o f these children, r a n g i n g in age f r o m 21/2 to 16 years, were residents of the G e r m a n R o m a n Catholic O r p h a n a g e in Buffalo, N. Y. F o r t y - s e v e n of these infected children were t r e a t e d w i t h piperazine h e x a h y d r a t e , fifty were t r e a t e d with T e r r a m y c i n , and fifty-eight with d e h y d r a t e d garlic powder. E a c h t r e a t m e n t g r o u p contained an almost equal n u m b e r of children f r o m 1 to 5 years, 6 to 10 y e a r s and 11 to 16 y e a r s of age. The diagnosis in all eases was established b y the use of a modification of the G r a h a m Scotch T a p e swab technique which we have described in detail in earlier publications. I n this study, we used a new Scotch T a p e which is From the Department of Pediatrics, E. J. Meyer Memorial Hospital and University of Buffalo, School of Medicine. m o r e t r a n s p a r e n t , with a crystal-clear 3s6
BUMBALO ET AL. :
adhesive that makes the identification of the pinworm eggs much easier. This tape is designated as' Scotch acetate film tape No. 800. Seven days after treatment, Scotch Tape swab smears were made daily for one week to determine the results of the treatment. Those patients who had seven consecutive negative smears were declared cured. The remaining eightyone children of the orphanage had negative diagnostic Scotch Tape smears. These children, even though they were considered free of pinworm infection, were also treated with either Terramycin or garlic. F i f t y were treated with Terramycin and fifty-eight with garlic. By treating the entire pediatric population of the orphanage we hoped to minimize the possibility of allowing infected children who had negative diagnostic smears to go untreated and possibly reinfect the treated cases. The adult population of the orphanage was not treated since none of them presented symptoms that suggested pinworm infection. Piperazine hexahydrate, a white crystalline substance, has the following structural formula: l ~ N ( Cl=f2 - C I - I 2 ) H N 9 6 II~O \ C I I ~ CH~.
It is readily soluble in water to give a clear colorless alkalhm solution. It is not hygroscopic and is stable in solid form. Piperazine has been used for many years in the treatment of gout and urinary calculi. It produces no symptoms and is practically nontoxic.~ The acute and chronic toxicity tests of piperazine conducted by the Wellcome Research Laboratories have established its nontoxicity in the normal dosage range.
ENTEROBIASIS
387
Mouriquand and associates s treated ,nice infected with Aspicularis tetraptera and Syphacea with piperazine hexahydrate and reported satisfactory anthelminthic properties toward these mouse oxyurids. They also treated a group of children ranging in age from 3 to 15 years with a high proportion of cures and reported that piperazine was "easily accepted by children and very well tolerated even by the very small." Standen Ghas also successfully treated Aspieuluris tetraptera with piperazine and recommended that it be used in the treatment of human pinworm infection. White and Standen 7 treated a group of thirty-one children with piperazine hexahydrate syrup at a dose level of 50 to 75 rag. per kilogram per day with a 97 per cent cure rate. They also reported no toxic effects in dose levels as high as 150 rag. per kilogram daily and found that piperazine was extremely well tolerated by all but one o~ the thirtyone children treated. Brown s in this country has also found piperazine quite effective against the mouse pinworm, Aspiculuris tetraptera. So far as we can determine, there are no reported series of cases of enterobiasis treated with piperazine in this country. Forty-seven of the infected children were treated with a palatable 10 per cent syrup containing 100 rag. of piperazine hexahydrate per cubic centimeter. Without any previous preparation these patients were treated for seven days, rested for seven days, and then treated for seven more days. A f t e r a lapse of seven days, following the last day of treatment, one Scotch Tape swab smear was taken daily, early in the morning, before the patients were bathed, to determine the
388
THE J O U R N A L 0 F PEDIATRICS
results of the t r e a t m e n t . I n addition to t h e piperazine h e x a h y d r a t e s y r u p t r e a t m e n t , the usually r e c o m m e n d e d personal and e n v i r o n m e n t a l hygienic measures were a d h e r e d to as closely as possible. This same routine was followed in t r e a t i n g the children w i t h T e r r a m y c i n and garlic. Table I Iists the n u m b e r of eases t r e a t e d with these three oxyuricides, the dosage used, the d u r a t i o n of t r e a t m e n t , and the result of t r e a t m e n t . F o r m a n y y e a r s r a w garlic has been used in m a n y p a r t s of the w o r l d as a " p o p u l a r r e m e d y " for p i n w o r m infection. M a n y clinicians consider r a w garlic as one of the best oxyurieides. E c k e r l e u in his s t u d y (personal c o m m u n i c a t i o n used r a w garlic, one
8 grains of d e h y d r a t e d garlic powder* to the teaspoonful. I n addition to the garlic t r e a t m e n t , the usually teeo m m e n d e d personal and e n v i r o n m e n tal hygienic measures were c a r r i e d out as best as possible. Table I indicates the n u m b e r of cases treated, dosage, and per cent of cures with the garlic syrup, The garlic s y r u p was v e r y well accepted and t o l e r a t e d b y all the children and no u n t o w a r d effects were noted in all f i f t y - e i g h t children treated. I n a recent s t u d y 3 on the t r e a t m e n t of enterobiasis w i t h T e r r a m y c i n we r e p o r t e d a cure r a t e of 85 per cent of f o r t y infected children t r e a t e d with 10 rag. of T e r r a m y c i n p e r p o u n d of b o d y weight, divided into t h r e e daily
TABLE I
DRUG Piperazine hexahydrato
I
CASES 47
Garlic s y r u p
58
Terramycin
50
I 1-5 yr. 1~ 5-10 yr. 1 10 yr. a n d 1-10 yr. 1 10 yr. a n d
DOSAGE tsp. t.i.d. tsp. t.l.d. up, 11~ tsp. t.i.d. tsp. t.i.d. up, 2 tsp. t.l.d.
5 rag. p e r p o u n d of b o d y weight divided into 3 d a i l y doses
clove e v e r y other night for f o u r t e e n days, i n t e r r u p t e d b y a one-week rest period. H e r e c o m m e n d s r a w garlic m i x e d with g r a t e d carrots and mayonnaise, served in a sandwich. F r e s h p a r s l e y eaten i m m e d i a t e l y a f t e r the g a r l i c sandwich acts as a n a t u r a l deodorizer. Vanni 1~ also r e p o r t e d deodorized garlic tablets as the treatm e n t of choice for enterobiasis. Kill i n g s w o r t h and associates 11 used r a w garlic in the t r e a t m e n t of p i n w o r m infection with 87 per cent cures. I n o u r study, fifty-eight of the inf e c t e d children at the G e r m a n R o m a n Catholic O r p h a n a g e were t r e a t e d with a mint-flavored s y r u p containing
I 7 7 7 7 7 7 7 7 7
DURATION [ % CURED day s treatment 85 d a y s rest days treatment days t r e a t m e n t 7 d a y s rest days t r e a t m e n t days t r e a t m e n t 38 days rest days treatment
doses for a period of seven days. L o u g h l i n and co-workers 12 t r e a t e d t h i r t y patients with enterobiasis with 1 to 2 Gm. of T e r r a m y M n base for five d a y s with a 100 per cent cure rate. I n this s t u d y we t r e a t e d fifty of the infected children at the Germ a n R o m a n Catholic O r p h a n a g e with 5 nag. of T e r r a m y e i n t p e r pound of b o d y weight, divided into three daily doses for a period of f o u r t e e n days w i t h a seven-day rest period at the end of the first week of t r e a t m e n t . *Garlic powder as a mint-flavored s y r u p w a s supplied by t h e V a n P a t t e n P h a r m a c e u t i cal Co. ~ T e r r a m y c i n w a s supplied by t h e Chas. Pfizer & Co., Inc.
BUMBALO ET AL. :
The same precautions and routines were used in the t r e a t m e n t of this group of patients t h a t were used with the piperazine and garlic treatment. The same rigid measure of cure, seven consecutive negative Scotch Tape smears t a k e n seven days a f t e r the termination of the treatment, was also carried out. The p e r c e n t a g e of cures obtained with the decreased dose of T e r r a m y c i n is indicated in Table I. RESULTS AND DISCUSSION Of the forty-seven patients treated with piperazine h e x a h y d r a t e , f o r t y had seven consecutive negative posttreatment Scotch Tape smears, the remaining seven patients had one to seven positive post-treatment smears. The cure rate in this series of patients t r e a t e d with piperazine h e x a h y d r a t e was 85 per cent. All the patients in this series took the palatable syrup of piperazine readily and tolerated it very well. Sample post-treatment blood counts done on ten of the patients were normal, and sample post-treatment urinalyses done on twenty of the patients were negative, except for three female children who showed evidence of cystitis which we believe was not caused by, nor related to, the piperazine treatment. Even though the percentage of cures obtained in the group of fiftyeight patients t r e a t e d with garlic was only 7 per cent, we are of the opinion. t h a t garlic should not be discarded as an oxyuricide. Two errors made in our garlic s t u d y might have, at least in part, contributed to this low percentage of cures. The 8 grains of d e h y d r a t e d garlic, given three times daily, m a k i n g a total daily dose of 24 grain.s of d e h y d r a t e d powder,
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could have been an inadequate dose. Since most of the studies on the garlic t r e a t m e n t of enterobiasis used one " p o d " or " c l o v e " of garlic, we weighed m a n y " c l o v e s " of garlic to arrive at an average weight of a clove of garlic. A f t e r weighing m a n y cloves of garlic t h a t were obtained in local food shops, we concluded that the average weight of a clove was 11 grains. W e p r e p a r e d a mintflavored s y r u p containing approxim a t e l y 8 grains of d e h y d r a t e d garlic powder to the teaspoon. This was the syrup we used in treating fifty-eight of the infected children at the German Roman Catholic Orphanage. At the conclusion of the s t u d y we learned that garlic cloves most usually available t h r o u g h food shops average 46 grains. This information has been confirmed b y the U.S. D e p a r t m e n t of Agriculture? x' Since the completion of this study, we again obtained samples of garlic cloves f r o m local food shops and f o u n d t h a t the average weight of these cloves was 60 grains. However, the replacement ratio between raw and d e h y d r a t e d garlic is 1 to 6, on the average, one p a r t of dehyd r a t e d garlic equals six parers of raw garlic. On this basis, even with the error made in computing the average weight of a clove of garlic, the dosage used in our study could well have been an adequate dose. The possibility that some active principle of garlic is lost in the dehydration process should also be considered in evaluating the garlic treatment of enterobiasis. The second error which we feel we should explain is that the bottles containing the garlic syrup were not carefully shaken be*Leaflet
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fore a dose was administered and for this reason the individual doses of garlic syrup could have varied considerably. How much this error contributed to the low percentage of cures in the garlic group we are not able to state with any degree of accuracy. Of the fifty patients treated with the reduced dose of Terramycin, 5 rag. per pound of body weight, only 38 per cent had seven consecutive negative post-treatment Scotch Tape smears. This percentage of cures is less than one-hail the percentage of cures obtained in our earlier study in which we used 10 rag. of Terramycin per pound of body weight. This study suggests that the 5 rag. per pound of body weight dose is not adequate to produce the direct deleterious action upon the mature gravid female worms and on the fertilized eggs as suggested by Loughlin and associates. 12 SUl~IMARY
1. The percentage of cures with piperazine,~.85 per cent, obtained in this series of forty-seven patients compares very favorably with the cures obtained with Terramycin and gentian rio]at. S~nce the syrup of piperazine used in this study was easy to take, well tolerated, and, we are assured, can be made available inexpensively, we are of the opinion that of the nine oxyuricides that we have tested to date, piperazine hexahydrate v ~ the closest to our standard of an ideal oxyuricide. 2. We have been able to confirm the study of White and Standen, as reported in the English literature, that piperazine hexahydrate is a nontoxic, safe, and effective oxyuricide. *Piperazine hexahydrate as syrup of Antepar Citrate was supplied by the BurroughsWellcome Company.
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3. The 7 per cent cures obtained with dehydrated garlic powder in this series of fifty-eight infected children was the lowest of all the oxyuriaides we have tested to date. 4. However, because of the ancient reputation of garlic as a " p o p u l a r r e m e d y " for pinworm infection substantiated in part by medical research, and because of the possibility of some error in our garlic study, we are of the opinion that garlic should be tried again both by us and other groups after some of the details of dehydrated garlic powder dosage have been confirmed. The complete lack of toxicity and the low cost of dehydrated garlic powder would make it, in our opinion, a n ideal oxyuricide if repeated studies could confirm the high cure rates obtained by other researchers. 5. Terramycin in a reduced dose of 5 rag. per pound of body weight cured only 38 per cent of fifty-nine infected children, This dose, onehalf of the dose we reported on in an earlier study, apparently is not enough to produce an effective cure rate. The authors express their appreciation to Dr. Samuel Milite]lo, the medical director of the German Roman Catholic Orphanage, for his permission to conduct this study at the German l~oman Catholic Orphanage. REFERENCES 1. Bumbalo, T, S., Gustina, F. J., and Oleksiak, 1~. E. : The Treatment of Pinworm Infection (Enterobiasis) With Papain, J. PEDIAT. 42: 576, 1953. 2. Bumbalo, T. S., Gustina, F. J., and Oleksiak, R. E.: The T r e a t m e n t of Enterobiasis W i t h Egressin, J. Parasitol. 39: 66, 1953. 3. Bumbalo, T. S., a n d Gustina, F. J.: The T r e a t m e n t of P i n w o r m I n f e c t i o n in Children, Postgrad. Mad. 14: 83, 1953. 4. So]lman, I. : A Manual of Pharmacology a n d I t s Application to Therapeutics and Toxicology, Philadelphia, 1948, W. B. Saunders Co.
BUMBAL0 ET AL. : 5. Mouriquand, G., Roman, E., and Coisnard, J.: Analysis of Treatment of Oxyuriasis W i t h Piperazine, J. Med. Lyon 32: 189, 1951. 6. Standen, O. D.: E x p e r l m e n t a l Chemot h e r a p y of Oxyuriasls, Brit. M. J. 2: 755, 1953. 7. White, R. H. R.~ and Standen, O. l).: Piperazine in the T r e a t m e n t of Thread worms in Children, Report on a Clinical Trial, Brit. M. J. 2: 755, ]953. 8. Brown, H . W . : P e r s o n a l communication (Columbia U n i v e r s i t y School of Public Health, New York, New York).
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9. Eekerle, W. J.: Personal eommunication a n d p a p e r presented at the 102nd. a n n u a l m e e t i n g of the A. M. A , J u n e 1-5, New York, 1953. 10. Vanni, u Therapy of Oxyuriasis, M i n e r v a Med. 33: 280, 1942. 11. Killingsworth, W. P., Meyer, P. R., McFadden, I. M., and Boardman, H. L.: Treatmeng of Pinworms (Oxyuriasis). Clinical E v a l u a t i o n Based on 1,005 Cases, Texas J. Med. 48: 27, 1952. 12. Loughlin, E. H., Rappaport, I., Mullir., W. G., Wells, H. S., Joseph, A. A., and Shookhoff, tI. B . : The T r e a t m e n t of E n t e r o b i a s i s W i t h Terramycin Base, Antibiotics & Chemother. 1: 588, 1951.