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Amebiasis in children
AMEBIASIS SAMUEL J.
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CHILDREN
NICItA~JJ[Ih~, M.D., H E ~ a u G. PONC~R, M.D., AND iV[AR.ION HOOD CHICAGO~ ILL.
M E B I C d y s e n t e r y with its classical gastrointestinal symptomatology is relatively uncommon in infancy and childhood DeBuys 1 reported t h a t out of 313 cases of amebic d y s e n t e r y a d m i t t e d to Charity Hospital, N e w Orleans, only f o u r o c c u r r e d in children u n d e r twelve years of age. D o u g h e r t y 2 stated t h a t in the H e n r i e t t a Eggleston Hosp i t a l for Children in A t l a n t a only one case of amebic d y s e n t e r y occ u r r e d in 3,180 admissions, including o v e r 200 cases of diarrhea. The prevalence of infection with Endameba histolytica cannot, however, be gauged b y the incidence of one clinical f o r m of amebiasis. Amebic d y s e n t e r y is only one of the more severe clinical expressions of the infection while the t e r m amebiasis represents the state of infection in m a n b y Endameba histolytica regardless of the n a t u r e or degree o~ clinical manifestations. This differentiation is an i m p o r t a n t one. I f the incidence of amebiasis in ~nfants and children were judged b y the n u m b e r of cases of amebic dysentery one would obtain a false impression of the clinical and public health problem. T h a t such problems actually exist was evidenced in a careful s t u d y of patients admitted to our d i s p e n s a r y this p a s t year. The recent Chicago epidemic has served to m a k e the medical profession, especially in the n o r t h e r n p a r t s of the U n i t e d Sta~es, " a m e b i c c o n s c i o u s . " As a resfilt t h e r e has bee~ a r e l e a r n i n g a n d a r e a l i g n m e n t of p r e c o n c e i v e d impressions a b o u t the disease. The u n s u s p e c t e d finding of Endameba histolytica ill the stools in a few cases t h a t presented vague abdominal symptoms s i m u l a t i n g chronic appendicitis p r o m p t e d us to i n v e s t i g a t e furr o t h e r cases in children p r e s e n t i n g similar complaints. No a t t e m p t w a s m a d e in this s t u d y to conduct a s y s t e m a t i c s t u d y or s u r v e y of the disease. I t has been definitely established b y n u m e r o u s iJavestigators t h a t amebiasis is p r e v a l e n t t h r o u g h o u t the w o r l d a n d should not be considerecl as solely a t r o p i c a l disease. I n the U n i t e d States most of the r e p o r t s on the incidence of the infection h a v e come f r o m the s o u t h e r n states a n d P~cific Coast. I n an analysis of cases of amebiasis in the ~'rom the ]:)ep~rtments of Pediatrics and Internal l~1edicine, College of Medicine, University of Illinois, Chicago. 741
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hospitals of t h i r t e e n southern cities Dougherty'-' f o u n d t h a t clinical amebiasis o c c u r r e d in children u n d e r fifteen y e a r s of age in 8 p e r cent of the cases. The incidence of infection w i t h Endameba histoIytica in children f r o m one m o n t h to five years of age was 16.5 p e r cent, and f r o m six years to fifteen years, 20 p e r cent, according to F a u s P in a su~wey u n d e r t a k e n in southwestern Virginia. The, percentage of infection varied greatly in different localities. Milam and Meleney 4 fo.und an incidence of 15.4 p e r cent: of infection u n d e r one y e a r of age, 27.5 per cent f r o m one to f o u r y e a r s ; and 30.5 p e r cent f r o m five to nine years in an epidemiologic study of amebiasis in a r u r a l community in Tennessee. Sumer]in ~ found an incidence of infection with Endameba histolytica of 0.4 p e r cent among" 513 children in private practice in San Diego, California. I t is thus seen t h a t the incidence of amebic infection in children varies widely with the economic status of the patients and the locality. Statistics covering the incidence of infection with Endameba histoIytica in children for t h e northern p a r t s of the country have been v e r y m e a g e r . Owen, Honess, a n d Simon ~ r e c e n t l y r e p o r t e d a s u r v e y f o r intestinal p r o t o z o a in ei{~'hty-three A m e r i c a n I n d i a n b o y s living in a mission school on a r e s e r v a t i o n in central W y o m i n g . T h e y f o u n d Endameba histolytica in 26.5 per cent of the total n u m b e r of cases examined. Owen ~ also investigated children in an orphanage in Oregon for protozoan infestations. H e f o u n d in a group of f o r t y d w o boys a protozoan infestation of 7] p e r cent, 4.7 p e r cent of which were positive for Endaqneba h,istolytica. Tansinsin s f o u n d a percentage of infection with Enda.meba histolytica of 3.0 p e r cent in 115 children in Pennsylvania. This percentage was based on only one l a b o r a t o r y examination on the stool specimen of each patient for Endameba histolytica. Boeck and Stiles 9 found a percentage of infection with Endamebcb histolytica of 17.6 in the age group of five to nineteen years in training schools in Washington, D. C. Obviously such data concerning restricted groups living u n d e r supervision with we]Lestablished s a n i t a r y and hygienic practices are of limited value. No accnrate conclusions can be d r a w n f r v m them as regards the general incidence of infection in children with Endamebic hlstolytica. However, they do indicate timt there m u s t be an appreciable percentage of infection in children in these areas. I n adults residing in the northern states the. percentage of infection with this parasite has been f o u n d to v a r y between 4.5 p e r cent and 22.5 per cent according" to Sistrunk, ~~ Giffin, ~ and Sanford, ~ each of whom reported surveys f r o m the s a m e institution in different years. Recognized authorities h a v e e s t i m a t e d t h a t f r o m 5 to 10 p e r cent of individuals in this c o u n t r y are infected with Endamebc~ histolytica. T h e r e is u n d o u b t e d and established evidence as to the p a t h o g e n i c i t y o f t h i s p a r a s i t e f o r man. h l v a s i o n of the intestinal tissues p r o b a b l y
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occurs in all individuals h a r b o r i n g the parasite, the extent of the lesion being dependent upon the various factors t h a t influence the n a t u r a l resistance o f the host, such as i m p r o p e r food, overwork, rep e a t e d exposure to infections, climate, etc. S t u a r t 1~ called attention to the t h e o r y t h a t there is a biologic equilibrium established between host and parasite. Acute cases are rare and indicate a lack of equilibrium. These may develop acute symptoms a f t e r surgical operations, shock, malnutrition, and causes that u n d e r m i n e the general well-being of the patient. Ill the tropics w h e r e the incidence of amebas is high, acute cases are usually associated with bacillary dysentery. I n the epidemiologic r e p o r t of the L e a g u e of Nations 14 it was felt t h a t the problem of acute eases of amebiasis seemed to depend upon the determination of the efficient causes of d y s e n t e r y among the ameba carriers, both in t e m p e r a t e and w a r m regions, or th~ causes for the change of the amebas from a saprophytic to a parasitic mode of existence. The opinion was expressed t h a t such a change was most p r o b a b l y b r o u g h t about by a cessation of tolerance on the p a r t of the h u m a n host. Because of the n a t u r a l resistance of a great m a j o r i t y of the individuals harboring Endamcba histolytica, the minute lesions continually being produced are rapidly healed so t h a t the clinically recognizable symptom-complex associated with amebic dysentery does not develop. Such individuals have been called " c a r r i e r s " with the implication that the parasites are nonpathogenie and produce no lesions i n their intestinal tract. The weight of clinical, pathologic, and experimental evidence is certainly opposed to such a view. In fact, Craig ~5 has repeatedly stated that the great proportion of so-called "carriers" of Endamebc~ histoIytica present symptoms some time during the course of their infection. Strictly speaking it is preferable to consider the carrier state in amebiasis as latent amebic i.nfection in which the symptoms of the presence of the parasites m a y or m a y not impress themselves on the consciousness o f the host. There seems to be no definite correlation between the extent of the intestinal lesions, which m a y r a n g e from minute defects microscopic in size to extensive ulcerations, and the severity of the clinical symptoms. lVfarked amebic ulcerations, and even amebic liver abscesses, have been r e p e a t e d l y f o u n d in individuals who p r e s e n t e d no classical symptoms of infection with Endameba histolytica. I t follows, there~ fore, that the presence of Endameba histolytica in the intestinal tract of an individual is a f a r from harmless condition and is a potential danger to the well-being of the host. Disturbances of health of v a r y i n g degrees have been r e p o r t e d by m a n y investigators in most of the patients with amebiasis. On the whole, t h e i r complaints have been associated with disturbances in the
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gastrointestinal t r a c t ; chiefly constipation with occasional attacks of mild diarrhea, vague, colicky pain, especially in the right lower quadrant, with tenderness present both diffusely or over the colon, anorexia, and loss of weight. Headaches, irritability, lethargy, and neuralgic pains in the extremities have also been described in latent amebic infections. In the past few years the above mentioned considerations regarding the incidence of infection and the pathogenicity of Endamebc~ histolytica have been often stressed by students of this disease; they have pointed out to the medical profession that an amebiasis problem does exist in this country. The importance of recognition and treatment of the so-called " c a r r i e r s , " who are responsible for spreading the Endameba histolytica in the form of cysts (the only infective forms of the ameba), is obvious from the standpoint of both the patient and the general public. Just how this problem should be attacked has not been definitely decided by local and state heMth authorities. Obviously, the epidemiologic aspects of amebiasis cannot be adequately dealt with until the incidence of the infection is known and some of the disputed points regarding the pathology of the carrier state, are definitely settled. Clinically, the attention of the profession has been focussed for the most part upon the adult population. The imPortance of the problem of latent amebic infection in infancy and childhood has not been adequately appreciated. This has been partially due to unfamiliarity of many practitioners with certain phases of amebic infection or amebiasis. As aforementioned, a few surveys have been made to determine the incidence of infection of children in various communities in the United States. In additiozl there are a number of report s in the literature recording cases of classic amebic dysentery in infants and children. No attempt, however, has thus far been made to elucidate and emphasize the milder symptoms with relation to the gastrointestinal tract t hat may occur in children as a result of infection with this parasit 9, aside from the familiar dysenteric symptoms. Undoubtedly children are as susceptible to the infection as adults, and it is questionable whether they are less exposed to the etiologic factors in this disease. The realization Of the prevalence of amebic infection in this country, together with the knowledge of its pathogenicity, should lead more often to a consideration of amebiasis in the differential diagnosis relating to obscure or vague abdominal symptoms in childhood. Owen, Honess, and Simon G stated that their data in Indian children which revealed the high incidence of infection with Endameba histolytica of 26.5 per cent should prompt the physician to " b e a r in mind the possibility of the presence of Endameba histolytica in making a diagnosis of all obscure intestinal complaints." Kessel and Mason 16 made a study with a view toward comparing laboratory and clinical
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observations in protozoan infection of the h u m a n gastrointestinal tract. A m o n g t h e i r conclusions they noted t h a t patients h a r b o r i n g Endameba histolytica had colitis symptoms about three times as f r e q u e n t l y as those in whom the parasites were not found. They therefore stressed tl/e importance of routine stool examinations for Endameba histolytica in patients exhibiting intestinal symptoms. The causes of obscure abdominal p a i n in children are m a n y and of diverse origins. A large p e r c e n t a g e of cases p r e s e n t i n g this s y m p t o m are due to simple and benign causes such as euterospasm and meteorism as a result of d i e t a r y indiscretion. 17 There is reason to believe, however, that intestinal parasites have seldom received adequate consideration except in regions where infestation is endemic. I n m a n y cases where amebiasis has been considered, the care and method of collection of the stool specimen would certain]y make for a negative report. I t is or/ly a f t e r m a n y c a r e f u l e x a m i n a t i o n s b y e x p e r i e n c e d w o r k e r s on a freshly passed, w a r m stool t h a t the diagnosis of amebiasis can be ruled out. C r a i g 18 states that at least six specimens of feces collected at different times should be examined before a negative resu]t Call be regarded as final. I t has also been emphasized b y m a n y workers that a single stool examination reveals only about one-third of the total incidence of intestinal protozoa. This percentage m i g h t be increased if, as Sumerlin ~ points out, liquid stool specimens following a saline cathartic are examined while warm. I n the m a j o r i t y of cases in children the diagnosis of amebiasis cannot be made without the finding of parasites in the feces: The clinical symptoms of vague abdominal pain associated with constipation or' diarrhea are f a r f r o m characteristic or pathognomonie of a n y one intestinal or abdominal ailment. Obscure types of abdominal p a i n in children occurring as a p a r t of the variable, symptomatology of amebiasis m a y simulate m a n y abdominal conditions. Appendicitis is one of the most frequent diseases confused with the vague gastrointestinal s y m p t o m s of amebiasis. This is a common prob;lem for differential diagnosis in the tropics, or wherever amebiasis is found. I n two of the cases of our series appendectomies h a d been p e r f o r m e d and later, a f t e r careful search, Endamebcb histolytica were found. I n a t h i r d p a t i e n t the parasites were discovered while operation was being contemplated. I n the following cases the diagnosis of amebiasis was established only a f t e r diligent search for the parasite was made. I n several cases, two or three examinations were necessal~r, and in one case the parasites were noted f o r the first time on the f o u r t h examination. I t is of interest to note that, in addition to Endc~meba histolyticG Endameba coli cysts were f o u n d in all of our patients. The latter were especially noted in those stool examinations preceding the specimen which finally revealed the pathogenic parasite. Such an association between a pathogenic and nonpathogenic parasite is more t h a n of aca-
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demic interest. Various representative surveys in different par~s of the world in which the comparative incidence of Endameba colt, Endameba histolytica, and Endolimax ha,ha were noted were analyzed b y Faust. a9 Such a s t u d y revealed a definite correlation between the Endameba histolyticc~ index and Endameba colt and E n d o l i m a x n~nc~ index. A low E n d a m e b a histo~ytica index was usually associated with a relatively low Endameba co li and Endoli~nax n~na index. F a u s t ~9 accumulated additional data f r o m various regions a n d showed t h a t in about 60 per cent of the cases in which Endamebr histolytica was no~ed, Endameba coli was also found. I I e concluded thas the Endameba coli index of a c o m m u n i t y was a r e l a t i v e l y a c c u r a t e indication of the a m o u n t of End~meba histolyticc~ in t h a t area. H e f u r t h e r suggested the possibility of considering seriously the presence of Endamebc~ h@tolytica whenever Endameba coli was found. The following case reports are representative of some of the clinical problems of amebiasis in children. CASE REPORTS CASE 1.--A. ~r white female patient, aged twelve years, was admitted to the hospital on Feb. 27, 1933, with the history of pain of one y e a r ' s duration i n the r i g h t lower quadrant, occasionally associated with fever and vomiting, occurring about every month and lasting about a weck. She passed pinworms three or fore' times in the past two years. Bright red blood was noted in the stools on several occasions. The physical examination was essentially negative except for slight tenderness of the abdomen on deep pressure over the r i g h t lower quadrant, right upper quadrant, and eplgastrium. Rectal examination was negative. White blood count was 10,550; polymorphonuclears, 41 per cent; monocytes, 7 per cent; lymphocytes, 52 per cent; and eosinophi]s, 2 per cent. P a t i e n t was discharged and referred to the out-patient department for f u r t h e r laboratory and clinical examination. The findings remained essentially negative, and it was felt at t h a t time t h a t a diagnosis of chronic appendicitis was very questionable and t h a t surgery was not indicated. About five months later, Aug. 30, 1933, she was readmitted to the hospital on the surgical service with the complaint of pain in tile right lower q u a d r a n t of twenty h o u r s ' duration, nausea., but no vomiting, lY[other stated t h a t the child had had several similar attacks during the past year. She presented acute tenderness in the r i g h t lower q u a d r a n t in the region of lV~cBurney's Point, with no rigidity. The white blood "count was 12,350. Appendectomy was considered advisable. The appendix was found long and kinked in the middle, but it did not appear to be acutely i n f l a m e d . . P a t i e n t was discharged Sept. 9, 1933, in good condition. She was seen in the dispensary again one month later, a t which time she complained of pain in the right lumbar region. Urine showed one plus albumin, occasional red blood cells, and numerous pus and epithelial cells. Blood examination showed a white blood count of 8,350; polymorphonuclears, 24 per cent; lymphocytes, 64 per cent; monocytes, 2 per cent; and eosinophils, 10 per cent. Stool examination was negative for ova and parasites. On later visits, tenderness on palpation over abdomen persisted. Repeated stool examinations revealed first En~azaeba oo~l~ cysts, and later Enda~eba~ hivto~yt~va. P a t i e n t received the routine treatment for amebiasis at the Municipal Contagious Hospital with complete subsidence of symptoms. CAS~ 2.--B. J. H., white female~ aged seven years, was admitted to the dispensary July 3, 1933, with complaint o f abdominal pain of two y e a r s ' duration~ located
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around the umbilicus. The pain was intermittent and cramplike in character; attacks occurred every few weeks, and were associated with nausea, occasional vomiting, and slight fever. Appetite was only fair, and bowel movements were regular. No attacks of diarrhea or bloody stools had been present. Recurring attacks of Jvague abdominal pain were noted at frequent intervals during the visits to the disp~nsary. Physical findings were essentially negative, except for tenderness on deep palpation over the right lower quadrant. I n October, three months after the first visit to the clinic, the child still complained of pain in the right lower quadrant of abdomen with 11o new objective manifestations. At this time the gastrointestinal tract was examined with an opaque meal and revealed the appendix apparently adherent and kinked, with tenderness to pressure over it, and prolonged retention of its contents. The findings were consistent with pathologic appendix. Patient was then referred to surgery for an opinion as to the advisability of performing an appendectomy. Urine was negative. The white blood count was 15,150; polymorphonuclears, 29 per cent; lymphoeytes, 63 per cent; monoeytes, 5 per cent; and eosinophils, 3 per cent. P a t i e n t was seen in the surgical dispensary, and later admitted to the hospital on their service, Nov. 17, 1933, when it was noted that she had been having an exacerbation of the right lower quadrant pain over a two-week period. Appendectomy was performed on the following day. The appendix was found injected but not adherent. Th~ patient made an uneventful recovery. In view of the fact that a sister of the patient had an attack of abdominal pain associated with the passag~ of bloody, mucoid stools in J a n u a r y of this year, the p a t i e n t ' s stools were repeatedly examined for Ene~a~neba h~sta~yt~oa. Several examinations revealed only En~azaebaL eoIi cysts. A f t e r administration of a saline cathartic on Apr. 24, 1934, Enda~neba~ his'to~ytiea was found. Patient was referred for treatment. CAS~ 3.---~ary G., white~ a~'ed twelve years, was admitted on the surgical service on Dec. 4, 1933, with complaint of pain in the right lower quadrant of abdomen for two days. I n addition a history of vague, generalized abdominal pain of many months' duration was obtained. There was no relation to the ingestion of food or bowel movement. Vomiting occurred only occasionally~ Constipation was noted, and patient had been given cathartics frequently. Physical examination was essentially negative, except for moderate tenderness on deep palpation over the course of the colon, more marked on the right side. There was no rigidity. Rectal examination was negative. The white blood count was 6,650; polymorphonuclears, 50 per cent; ]ymphocytes, 46 per cent; monoeytes, 2 per cent; and eosinophils, 2 per cent. l~resh, warm stools revealed the presence of vegetative forms of ]~qzda~eba histolyt{ca) with occasional ~n~a~n~ba~ e'ol~ cysts on repeated examinations. Proctoscopie examination revealed typical amebic ulcerations in the rectum. Fatien~ was transferred to Municipal Contagious Hospital where she received treatment over a period of six weeks. Since then, child has been perfectly well and has had no complaints. CAs~ 4 . ~ E . H., aged ten years (sister of B. J. It., Case 2)~ was first seen in the pediatric dispensary Jan. 15, 1934. Mother stated that the patient had been perfectly well until two days before admission when she woke up with severe abdominal pain followed by sewral vomiting spells. Three bloody, mucoid stools were passed during the day. The pain was intermittent and located around the umbilicus. Improvement occurred later in the day. Physical examination was negative except for slight exophthalmos and slightly enlarged thyroid. The white blood count was 10,800; polymorphonuelears, 60 per cent; Iymphocytes, 28 per cent; monocytes, 12 per cent. Examination of stool at this time revealed no parasites, l%bruary 22, one month later, the vegetative forms of E n d a ~ e b a h~sto%yt{ea were demonstrated in addition to Endameba, voli cysts. When this was written, patient was under treatment.
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Another sister in this family, thirteen years old, had had her appendix removed four years ago for chronic appendicitis, according to the mother. Thus far only Endameba ooli cysts have been found. CASE 5.--M. A., white female, aged ten years, was first seen in the dispensary on Jan. 30, 1934, with the complaint of eramplike pains in the abdomen of three weeks' duration. One year ago she had an attack of diarrhea which lasted three weeks, the stools containing mucus but no blood. I n addition she suffered from dizzy spells and nausea, which were associated with the generalized abdominal pain. There was no vomiting and no fever. Physical examination was essentially negative, except for tenderness on palpation and slightly increased resistance in the right lower quadrant of abdomen. Urine was negative. The white blood count was 7,650 ; polymorphonue]ears, 57 per cent; lymphoeytes, 37 per cent; monocytes, 3 per cent; and eosinophils, 3 per cent. During the following six weeks, the child continued to complain of vague pains in both lower quadrants of abdomen, especially on the right side. Stool examination showed encysted forms of E~a~neb~ eoI~. A second stool examination showed many giardia cysts, frequent Euda~ne~ba vo~i cysts, and frequent Chareot-Leyden crystals. No Enda~eb~ histo~yt~va, trophozoites, or cysts were found. One week later another stool examination showed similar findings. However, on the fourth examination a few days later a cathartic stool was obtained, and it revealed, ia addition to thd trophozoites, precystic forms, and cysts of Enc~a~neba hivtolyt~aal. Patient was under treatment a~ the time this was written. CAs~. 6.~l~Iae G., white, aged eight years, was admitted to the dispensary l~arch 6, 1934. She was brought in for a general physical examination. However, on questioning, a history of vomiting soon after taking food, vague, generalized abdominal pains, and constipation was elicited. Physical findings were essentially those associated with malnutrition. The white blood cell count was 6,550; polymorphonuclears, 52 per cent; ]ymphocytes, 30 per cent; monocytes, 9 per cent; and eosinophils, 9 per cent. Stool examination showed numerous encysted forms of Enda~neba vo~. Another stool examination, one week later~ revealed frequent Enc?a~neba vo~ cysts and occasional En~a~meba hi~tolyt~ca cysts, in addition to Chareot-Leyden crystals. A cathartic stool specimen revealed the vegetative forms of E ~ a ~ e b a his toIyt~ca.
SUIV[MARY The available data on the incidence of amebiasis in children in the zlorthern stas and the recent evidence of amebic infection in and about Chicago warrant the attention of the medical profession to the problem of latent amebic infection in childhood. In the past few years the symptomatoiogy and pathology in such infections in adults have been repeatedly stressed, especially by Craig. From the cases c i t e d i n t h i s r e p o r t it is a p p a r e n t t h a t c h i l d r e n i n f e c t e d w i t h E n d a m e b a histolytica may likewise manifest obscure and unexplained gastrointest i n a l s y m p t o m s w h i c h a t t i m e s m a y l e a d to f a u l t y d i a g n o s e s o f a c u t e o r chronic appendicitis and other diseases of the alimentary tract. Careful and repeated examinations for parasites in the stools of children exhibiting vague abdominal complaints should be undertaken whenever possible.
REFEREIqECS i. DeBuys, L. i~.: J.A. IVl.A. 63: 1806, 191~. 2. Dougherty, l~ark S., Jr.- Am. J. Trop. lYied. 13: 317, 1933. 3. Faust, E. C.: Am. J. Trop. Med. II: 231, 1931.
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4. Milam, Daniel F., and Meleney, Henry E.: Am. J. Hyg. 14: 325, 1931. 5. Sumerlin, I{. S.: J . A . M . A . 102: 363, 1934. 6. Owen~ William B., Honess, Ralph F., and Simon, James R.: J . A . M . A . 102: 913, 1934. 7. Owen, W. B.: Northwest. Med. 31: 186, 1932. 8. Tansinsin, Manuel S.: Arch. Pedlar. 47: 113, 1930. 9. Boeek, W. C., a n d Stiles, C . W . : Bull. 133, Hyg. Lab. U. S. Public Health Service, 1923. 10. Sistrunk, W . E . : J. A. iVL A. 57: 1507, 1911. 11. Giffm, H. Z.: J . A . M . A . 61: 675, 1913. 12. Sanford, A . H . : 3. A. M. A. 67: 1923, 1916. 13. Stuart, 1VL A.: ~ . S. Nav. M. Bull. 26: 411, 1928. 14. League of Nations. (General Review of Dysentery, Its Geographical Distribution, League of Nations Epidemiological Report.) ]~{arch--April, 1933, pp. 48-86. 15. Craig, Charles F . : J . A . M . A . 98: 1615, 1932. 16. ]~essel, J. F., and Mason, V. R.: J . A . 1V[. A. 94: 1, 1930. 17. Schlutz, Frederick, W.: g. I~ED~AT. 2: 41, 1933. 18. Craig, Charles F.: Internat. Clin. 1: 77, 1929. ]9. Faust, Ernest Carroll: Am. ft. Trop. Med. 10: 137, ]930. 1819 WEST POLK STREET
IN
CHILDREN
NICItA~JJ[Ih~, M.D., H E ~ a u G. PONC~R, M.D., AND iV[AR.ION HOOD CHICAGO~ ILL.
M E B I C d y s e n t e r y with its classical gastrointestinal symptomatology is relatively uncommon in infancy and childhood DeBuys 1 reported t h a t out of 313 cases of amebic d y s e n t e r y a d m i t t e d to Charity Hospital, N e w Orleans, only f o u r o c c u r r e d in children u n d e r twelve years of age. D o u g h e r t y 2 stated t h a t in the H e n r i e t t a Eggleston Hosp i t a l for Children in A t l a n t a only one case of amebic d y s e n t e r y occ u r r e d in 3,180 admissions, including o v e r 200 cases of diarrhea. The prevalence of infection with Endameba histolytica cannot, however, be gauged b y the incidence of one clinical f o r m of amebiasis. Amebic d y s e n t e r y is only one of the more severe clinical expressions of the infection while the t e r m amebiasis represents the state of infection in m a n b y Endameba histolytica regardless of the n a t u r e or degree o~ clinical manifestations. This differentiation is an i m p o r t a n t one. I f the incidence of amebiasis in ~nfants and children were judged b y the n u m b e r of cases of amebic dysentery one would obtain a false impression of the clinical and public health problem. T h a t such problems actually exist was evidenced in a careful s t u d y of patients admitted to our d i s p e n s a r y this p a s t year. The recent Chicago epidemic has served to m a k e the medical profession, especially in the n o r t h e r n p a r t s of the U n i t e d Sta~es, " a m e b i c c o n s c i o u s . " As a resfilt t h e r e has bee~ a r e l e a r n i n g a n d a r e a l i g n m e n t of p r e c o n c e i v e d impressions a b o u t the disease. The u n s u s p e c t e d finding of Endameba histolytica ill the stools in a few cases t h a t presented vague abdominal symptoms s i m u l a t i n g chronic appendicitis p r o m p t e d us to i n v e s t i g a t e furr o t h e r cases in children p r e s e n t i n g similar complaints. No a t t e m p t w a s m a d e in this s t u d y to conduct a s y s t e m a t i c s t u d y or s u r v e y of the disease. I t has been definitely established b y n u m e r o u s iJavestigators t h a t amebiasis is p r e v a l e n t t h r o u g h o u t the w o r l d a n d should not be considerecl as solely a t r o p i c a l disease. I n the U n i t e d States most of the r e p o r t s on the incidence of the infection h a v e come f r o m the s o u t h e r n states a n d P~cific Coast. I n an analysis of cases of amebiasis in the ~'rom the ]:)ep~rtments of Pediatrics and Internal l~1edicine, College of Medicine, University of Illinois, Chicago. 741
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hospitals of t h i r t e e n southern cities Dougherty'-' f o u n d t h a t clinical amebiasis o c c u r r e d in children u n d e r fifteen y e a r s of age in 8 p e r cent of the cases. The incidence of infection w i t h Endameba histoIytica in children f r o m one m o n t h to five years of age was 16.5 p e r cent, and f r o m six years to fifteen years, 20 p e r cent, according to F a u s P in a su~wey u n d e r t a k e n in southwestern Virginia. The, percentage of infection varied greatly in different localities. Milam and Meleney 4 fo.und an incidence of 15.4 p e r cent: of infection u n d e r one y e a r of age, 27.5 per cent f r o m one to f o u r y e a r s ; and 30.5 p e r cent f r o m five to nine years in an epidemiologic study of amebiasis in a r u r a l community in Tennessee. Sumer]in ~ found an incidence of infection with Endameba histolytica of 0.4 p e r cent among" 513 children in private practice in San Diego, California. I t is thus seen t h a t the incidence of amebic infection in children varies widely with the economic status of the patients and the locality. Statistics covering the incidence of infection with Endameba histoIytica in children for t h e northern p a r t s of the country have been v e r y m e a g e r . Owen, Honess, a n d Simon ~ r e c e n t l y r e p o r t e d a s u r v e y f o r intestinal p r o t o z o a in ei{~'hty-three A m e r i c a n I n d i a n b o y s living in a mission school on a r e s e r v a t i o n in central W y o m i n g . T h e y f o u n d Endameba histolytica in 26.5 per cent of the total n u m b e r of cases examined. Owen ~ also investigated children in an orphanage in Oregon for protozoan infestations. H e f o u n d in a group of f o r t y d w o boys a protozoan infestation of 7] p e r cent, 4.7 p e r cent of which were positive for Endaqneba h,istolytica. Tansinsin s f o u n d a percentage of infection with Enda.meba histolytica of 3.0 p e r cent in 115 children in Pennsylvania. This percentage was based on only one l a b o r a t o r y examination on the stool specimen of each patient for Endameba histolytica. Boeck and Stiles 9 found a percentage of infection with Endamebcb histolytica of 17.6 in the age group of five to nineteen years in training schools in Washington, D. C. Obviously such data concerning restricted groups living u n d e r supervision with we]Lestablished s a n i t a r y and hygienic practices are of limited value. No accnrate conclusions can be d r a w n f r v m them as regards the general incidence of infection in children with Endamebic hlstolytica. However, they do indicate timt there m u s t be an appreciable percentage of infection in children in these areas. I n adults residing in the northern states the. percentage of infection with this parasite has been f o u n d to v a r y between 4.5 p e r cent and 22.5 per cent according" to Sistrunk, ~~ Giffin, ~ and Sanford, ~ each of whom reported surveys f r o m the s a m e institution in different years. Recognized authorities h a v e e s t i m a t e d t h a t f r o m 5 to 10 p e r cent of individuals in this c o u n t r y are infected with Endamebc~ histolytica. T h e r e is u n d o u b t e d and established evidence as to the p a t h o g e n i c i t y o f t h i s p a r a s i t e f o r man. h l v a s i o n of the intestinal tissues p r o b a b l y
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occurs in all individuals h a r b o r i n g the parasite, the extent of the lesion being dependent upon the various factors t h a t influence the n a t u r a l resistance o f the host, such as i m p r o p e r food, overwork, rep e a t e d exposure to infections, climate, etc. S t u a r t 1~ called attention to the t h e o r y t h a t there is a biologic equilibrium established between host and parasite. Acute cases are rare and indicate a lack of equilibrium. These may develop acute symptoms a f t e r surgical operations, shock, malnutrition, and causes that u n d e r m i n e the general well-being of the patient. Ill the tropics w h e r e the incidence of amebas is high, acute cases are usually associated with bacillary dysentery. I n the epidemiologic r e p o r t of the L e a g u e of Nations 14 it was felt t h a t the problem of acute eases of amebiasis seemed to depend upon the determination of the efficient causes of d y s e n t e r y among the ameba carriers, both in t e m p e r a t e and w a r m regions, or th~ causes for the change of the amebas from a saprophytic to a parasitic mode of existence. The opinion was expressed t h a t such a change was most p r o b a b l y b r o u g h t about by a cessation of tolerance on the p a r t of the h u m a n host. Because of the n a t u r a l resistance of a great m a j o r i t y of the individuals harboring Endamcba histolytica, the minute lesions continually being produced are rapidly healed so t h a t the clinically recognizable symptom-complex associated with amebic dysentery does not develop. Such individuals have been called " c a r r i e r s " with the implication that the parasites are nonpathogenie and produce no lesions i n their intestinal tract. The weight of clinical, pathologic, and experimental evidence is certainly opposed to such a view. In fact, Craig ~5 has repeatedly stated that the great proportion of so-called "carriers" of Endamebc~ histoIytica present symptoms some time during the course of their infection. Strictly speaking it is preferable to consider the carrier state in amebiasis as latent amebic i.nfection in which the symptoms of the presence of the parasites m a y or m a y not impress themselves on the consciousness o f the host. There seems to be no definite correlation between the extent of the intestinal lesions, which m a y r a n g e from minute defects microscopic in size to extensive ulcerations, and the severity of the clinical symptoms. lVfarked amebic ulcerations, and even amebic liver abscesses, have been r e p e a t e d l y f o u n d in individuals who p r e s e n t e d no classical symptoms of infection with Endameba histolytica. I t follows, there~ fore, that the presence of Endameba histolytica in the intestinal tract of an individual is a f a r from harmless condition and is a potential danger to the well-being of the host. Disturbances of health of v a r y i n g degrees have been r e p o r t e d by m a n y investigators in most of the patients with amebiasis. On the whole, t h e i r complaints have been associated with disturbances in the
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gastrointestinal t r a c t ; chiefly constipation with occasional attacks of mild diarrhea, vague, colicky pain, especially in the right lower quadrant, with tenderness present both diffusely or over the colon, anorexia, and loss of weight. Headaches, irritability, lethargy, and neuralgic pains in the extremities have also been described in latent amebic infections. In the past few years the above mentioned considerations regarding the incidence of infection and the pathogenicity of Endamebc~ histolytica have been often stressed by students of this disease; they have pointed out to the medical profession that an amebiasis problem does exist in this country. The importance of recognition and treatment of the so-called " c a r r i e r s , " who are responsible for spreading the Endameba histolytica in the form of cysts (the only infective forms of the ameba), is obvious from the standpoint of both the patient and the general public. Just how this problem should be attacked has not been definitely decided by local and state heMth authorities. Obviously, the epidemiologic aspects of amebiasis cannot be adequately dealt with until the incidence of the infection is known and some of the disputed points regarding the pathology of the carrier state, are definitely settled. Clinically, the attention of the profession has been focussed for the most part upon the adult population. The imPortance of the problem of latent amebic infection in infancy and childhood has not been adequately appreciated. This has been partially due to unfamiliarity of many practitioners with certain phases of amebic infection or amebiasis. As aforementioned, a few surveys have been made to determine the incidence of infection of children in various communities in the United States. In additiozl there are a number of report s in the literature recording cases of classic amebic dysentery in infants and children. No attempt, however, has thus far been made to elucidate and emphasize the milder symptoms with relation to the gastrointestinal tract t hat may occur in children as a result of infection with this parasit 9, aside from the familiar dysenteric symptoms. Undoubtedly children are as susceptible to the infection as adults, and it is questionable whether they are less exposed to the etiologic factors in this disease. The realization Of the prevalence of amebic infection in this country, together with the knowledge of its pathogenicity, should lead more often to a consideration of amebiasis in the differential diagnosis relating to obscure or vague abdominal symptoms in childhood. Owen, Honess, and Simon G stated that their data in Indian children which revealed the high incidence of infection with Endameba histolytica of 26.5 per cent should prompt the physician to " b e a r in mind the possibility of the presence of Endameba histolytica in making a diagnosis of all obscure intestinal complaints." Kessel and Mason 16 made a study with a view toward comparing laboratory and clinical
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observations in protozoan infection of the h u m a n gastrointestinal tract. A m o n g t h e i r conclusions they noted t h a t patients h a r b o r i n g Endameba histolytica had colitis symptoms about three times as f r e q u e n t l y as those in whom the parasites were not found. They therefore stressed tl/e importance of routine stool examinations for Endameba histolytica in patients exhibiting intestinal symptoms. The causes of obscure abdominal p a i n in children are m a n y and of diverse origins. A large p e r c e n t a g e of cases p r e s e n t i n g this s y m p t o m are due to simple and benign causes such as euterospasm and meteorism as a result of d i e t a r y indiscretion. 17 There is reason to believe, however, that intestinal parasites have seldom received adequate consideration except in regions where infestation is endemic. I n m a n y cases where amebiasis has been considered, the care and method of collection of the stool specimen would certain]y make for a negative report. I t is or/ly a f t e r m a n y c a r e f u l e x a m i n a t i o n s b y e x p e r i e n c e d w o r k e r s on a freshly passed, w a r m stool t h a t the diagnosis of amebiasis can be ruled out. C r a i g 18 states that at least six specimens of feces collected at different times should be examined before a negative resu]t Call be regarded as final. I t has also been emphasized b y m a n y workers that a single stool examination reveals only about one-third of the total incidence of intestinal protozoa. This percentage m i g h t be increased if, as Sumerlin ~ points out, liquid stool specimens following a saline cathartic are examined while warm. I n the m a j o r i t y of cases in children the diagnosis of amebiasis cannot be made without the finding of parasites in the feces: The clinical symptoms of vague abdominal pain associated with constipation or' diarrhea are f a r f r o m characteristic or pathognomonie of a n y one intestinal or abdominal ailment. Obscure types of abdominal p a i n in children occurring as a p a r t of the variable, symptomatology of amebiasis m a y simulate m a n y abdominal conditions. Appendicitis is one of the most frequent diseases confused with the vague gastrointestinal s y m p t o m s of amebiasis. This is a common prob;lem for differential diagnosis in the tropics, or wherever amebiasis is found. I n two of the cases of our series appendectomies h a d been p e r f o r m e d and later, a f t e r careful search, Endamebcb histolytica were found. I n a t h i r d p a t i e n t the parasites were discovered while operation was being contemplated. I n the following cases the diagnosis of amebiasis was established only a f t e r diligent search for the parasite was made. I n several cases, two or three examinations were necessal~r, and in one case the parasites were noted f o r the first time on the f o u r t h examination. I t is of interest to note that, in addition to Endc~meba histolyticG Endameba coli cysts were f o u n d in all of our patients. The latter were especially noted in those stool examinations preceding the specimen which finally revealed the pathogenic parasite. Such an association between a pathogenic and nonpathogenic parasite is more t h a n of aca-
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demic interest. Various representative surveys in different par~s of the world in which the comparative incidence of Endameba colt, Endameba histolytica, and Endolimax ha,ha were noted were analyzed b y Faust. a9 Such a s t u d y revealed a definite correlation between the Endameba histolyticc~ index and Endameba colt and E n d o l i m a x n~nc~ index. A low E n d a m e b a histo~ytica index was usually associated with a relatively low Endameba co li and Endoli~nax n~na index. F a u s t ~9 accumulated additional data f r o m various regions a n d showed t h a t in about 60 per cent of the cases in which Endamebr histolytica was no~ed, Endameba coli was also found. I I e concluded thas the Endameba coli index of a c o m m u n i t y was a r e l a t i v e l y a c c u r a t e indication of the a m o u n t of End~meba histolyticc~ in t h a t area. H e f u r t h e r suggested the possibility of considering seriously the presence of Endamebc~ h@tolytica whenever Endameba coli was found. The following case reports are representative of some of the clinical problems of amebiasis in children. CASE REPORTS CASE 1.--A. ~r white female patient, aged twelve years, was admitted to the hospital on Feb. 27, 1933, with the history of pain of one y e a r ' s duration i n the r i g h t lower quadrant, occasionally associated with fever and vomiting, occurring about every month and lasting about a weck. She passed pinworms three or fore' times in the past two years. Bright red blood was noted in the stools on several occasions. The physical examination was essentially negative except for slight tenderness of the abdomen on deep pressure over the r i g h t lower quadrant, right upper quadrant, and eplgastrium. Rectal examination was negative. White blood count was 10,550; polymorphonuclears, 41 per cent; monocytes, 7 per cent; lymphocytes, 52 per cent; and eosinophi]s, 2 per cent. P a t i e n t was discharged and referred to the out-patient department for f u r t h e r laboratory and clinical examination. The findings remained essentially negative, and it was felt at t h a t time t h a t a diagnosis of chronic appendicitis was very questionable and t h a t surgery was not indicated. About five months later, Aug. 30, 1933, she was readmitted to the hospital on the surgical service with the complaint of pain in tile right lower q u a d r a n t of twenty h o u r s ' duration, nausea., but no vomiting, lY[other stated t h a t the child had had several similar attacks during the past year. She presented acute tenderness in the r i g h t lower q u a d r a n t in the region of lV~cBurney's Point, with no rigidity. The white blood "count was 12,350. Appendectomy was considered advisable. The appendix was found long and kinked in the middle, but it did not appear to be acutely i n f l a m e d . . P a t i e n t was discharged Sept. 9, 1933, in good condition. She was seen in the dispensary again one month later, a t which time she complained of pain in the right lumbar region. Urine showed one plus albumin, occasional red blood cells, and numerous pus and epithelial cells. Blood examination showed a white blood count of 8,350; polymorphonuclears, 24 per cent; lymphocytes, 64 per cent; monocytes, 2 per cent; and eosinophils, 10 per cent. Stool examination was negative for ova and parasites. On later visits, tenderness on palpation over abdomen persisted. Repeated stool examinations revealed first En~azaeba oo~l~ cysts, and later Enda~eba~ hivto~yt~va. P a t i e n t received the routine treatment for amebiasis at the Municipal Contagious Hospital with complete subsidence of symptoms. CAS~ 2.--B. J. H., white female~ aged seven years, was admitted to the dispensary July 3, 1933, with complaint o f abdominal pain of two y e a r s ' duration~ located
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around the umbilicus. The pain was intermittent and cramplike in character; attacks occurred every few weeks, and were associated with nausea, occasional vomiting, and slight fever. Appetite was only fair, and bowel movements were regular. No attacks of diarrhea or bloody stools had been present. Recurring attacks of Jvague abdominal pain were noted at frequent intervals during the visits to the disp~nsary. Physical findings were essentially negative, except for tenderness on deep palpation over the right lower quadrant. I n October, three months after the first visit to the clinic, the child still complained of pain in the right lower quadrant of abdomen with 11o new objective manifestations. At this time the gastrointestinal tract was examined with an opaque meal and revealed the appendix apparently adherent and kinked, with tenderness to pressure over it, and prolonged retention of its contents. The findings were consistent with pathologic appendix. Patient was then referred to surgery for an opinion as to the advisability of performing an appendectomy. Urine was negative. The white blood count was 15,150; polymorphonuclears, 29 per cent; lymphoeytes, 63 per cent; monoeytes, 5 per cent; and eosinophils, 3 per cent. P a t i e n t was seen in the surgical dispensary, and later admitted to the hospital on their service, Nov. 17, 1933, when it was noted that she had been having an exacerbation of the right lower quadrant pain over a two-week period. Appendectomy was performed on the following day. The appendix was found injected but not adherent. Th~ patient made an uneventful recovery. In view of the fact that a sister of the patient had an attack of abdominal pain associated with the passag~ of bloody, mucoid stools in J a n u a r y of this year, the p a t i e n t ' s stools were repeatedly examined for Ene~a~neba h~sta~yt~oa. Several examinations revealed only En~azaebaL eoIi cysts. A f t e r administration of a saline cathartic on Apr. 24, 1934, Enda~neba~ his'to~ytiea was found. Patient was referred for treatment. CAS~ 3.---~ary G., white~ a~'ed twelve years, was admitted on the surgical service on Dec. 4, 1933, with complaint of pain in the right lower quadrant of abdomen for two days. I n addition a history of vague, generalized abdominal pain of many months' duration was obtained. There was no relation to the ingestion of food or bowel movement. Vomiting occurred only occasionally~ Constipation was noted, and patient had been given cathartics frequently. Physical examination was essentially negative, except for moderate tenderness on deep palpation over the course of the colon, more marked on the right side. There was no rigidity. Rectal examination was negative. The white blood count was 6,650; polymorphonuclears, 50 per cent; ]ymphocytes, 46 per cent; monoeytes, 2 per cent; and eosinophils, 2 per cent. l~resh, warm stools revealed the presence of vegetative forms of ]~qzda~eba histolyt{ca) with occasional ~n~a~n~ba~ e'ol~ cysts on repeated examinations. Proctoscopie examination revealed typical amebic ulcerations in the rectum. Fatien~ was transferred to Municipal Contagious Hospital where she received treatment over a period of six weeks. Since then, child has been perfectly well and has had no complaints. CAs~ 4 . ~ E . H., aged ten years (sister of B. J. It., Case 2)~ was first seen in the pediatric dispensary Jan. 15, 1934. Mother stated that the patient had been perfectly well until two days before admission when she woke up with severe abdominal pain followed by sewral vomiting spells. Three bloody, mucoid stools were passed during the day. The pain was intermittent and located around the umbilicus. Improvement occurred later in the day. Physical examination was negative except for slight exophthalmos and slightly enlarged thyroid. The white blood count was 10,800; polymorphonuelears, 60 per cent; Iymphocytes, 28 per cent; monocytes, 12 per cent. Examination of stool at this time revealed no parasites, l%bruary 22, one month later, the vegetative forms of E n d a ~ e b a h~sto%yt{ea were demonstrated in addition to Endameba, voli cysts. When this was written, patient was under treatment.
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Another sister in this family, thirteen years old, had had her appendix removed four years ago for chronic appendicitis, according to the mother. Thus far only Endameba ooli cysts have been found. CASE 5.--M. A., white female, aged ten years, was first seen in the dispensary on Jan. 30, 1934, with the complaint of eramplike pains in the abdomen of three weeks' duration. One year ago she had an attack of diarrhea which lasted three weeks, the stools containing mucus but no blood. I n addition she suffered from dizzy spells and nausea, which were associated with the generalized abdominal pain. There was no vomiting and no fever. Physical examination was essentially negative, except for tenderness on palpation and slightly increased resistance in the right lower quadrant of abdomen. Urine was negative. The white blood count was 7,650 ; polymorphonue]ears, 57 per cent; lymphoeytes, 37 per cent; monocytes, 3 per cent; and eosinophils, 3 per cent. During the following six weeks, the child continued to complain of vague pains in both lower quadrants of abdomen, especially on the right side. Stool examination showed encysted forms of E~a~neb~ eoI~. A second stool examination showed many giardia cysts, frequent Euda~ne~ba vo~i cysts, and frequent Chareot-Leyden crystals. No Enda~eb~ histo~yt~va, trophozoites, or cysts were found. One week later another stool examination showed similar findings. However, on the fourth examination a few days later a cathartic stool was obtained, and it revealed, ia addition to thd trophozoites, precystic forms, and cysts of Enc~a~neba hivtolyt~aal. Patient was under treatment a~ the time this was written. CAs~. 6.~l~Iae G., white, aged eight years, was admitted to the dispensary l~arch 6, 1934. She was brought in for a general physical examination. However, on questioning, a history of vomiting soon after taking food, vague, generalized abdominal pains, and constipation was elicited. Physical findings were essentially those associated with malnutrition. The white blood cell count was 6,550; polymorphonuclears, 52 per cent; ]ymphocytes, 30 per cent; monocytes, 9 per cent; and eosinophils, 9 per cent. Stool examination showed numerous encysted forms of Enda~neba vo~. Another stool examination, one week later~ revealed frequent Enc?a~neba vo~ cysts and occasional En~a~meba hi~tolyt~ca cysts, in addition to Chareot-Leyden crystals. A cathartic stool specimen revealed the vegetative forms of E ~ a ~ e b a his toIyt~ca.
SUIV[MARY The available data on the incidence of amebiasis in children in the zlorthern stas and the recent evidence of amebic infection in and about Chicago warrant the attention of the medical profession to the problem of latent amebic infection in childhood. In the past few years the symptomatoiogy and pathology in such infections in adults have been repeatedly stressed, especially by Craig. From the cases c i t e d i n t h i s r e p o r t it is a p p a r e n t t h a t c h i l d r e n i n f e c t e d w i t h E n d a m e b a histolytica may likewise manifest obscure and unexplained gastrointest i n a l s y m p t o m s w h i c h a t t i m e s m a y l e a d to f a u l t y d i a g n o s e s o f a c u t e o r chronic appendicitis and other diseases of the alimentary tract. Careful and repeated examinations for parasites in the stools of children exhibiting vague abdominal complaints should be undertaken whenever possible.
REFEREIqECS i. DeBuys, L. i~.: J.A. IVl.A. 63: 1806, 191~. 2. Dougherty, l~ark S., Jr.- Am. J. Trop. lYied. 13: 317, 1933. 3. Faust, E. C.: Am. J. Trop. Med. II: 231, 1931.
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4. Milam, Daniel F., and Meleney, Henry E.: Am. J. Hyg. 14: 325, 1931. 5. Sumerlin, I{. S.: J . A . M . A . 102: 363, 1934. 6. Owen~ William B., Honess, Ralph F., and Simon, James R.: J . A . M . A . 102: 913, 1934. 7. Owen, W. B.: Northwest. Med. 31: 186, 1932. 8. Tansinsin, Manuel S.: Arch. Pedlar. 47: 113, 1930. 9. Boeek, W. C., a n d Stiles, C . W . : Bull. 133, Hyg. Lab. U. S. Public Health Service, 1923. 10. Sistrunk, W . E . : J. A. iVL A. 57: 1507, 1911. 11. Giffm, H. Z.: J . A . M . A . 61: 675, 1913. 12. Sanford, A . H . : 3. A. M. A. 67: 1923, 1916. 13. Stuart, 1VL A.: ~ . S. Nav. M. Bull. 26: 411, 1928. 14. League of Nations. (General Review of Dysentery, Its Geographical Distribution, League of Nations Epidemiological Report.) ]~{arch--April, 1933, pp. 48-86. 15. Craig, Charles F . : J . A . M . A . 98: 1615, 1932. 16. ]~essel, J. F., and Mason, V. R.: J . A . 1V[. A. 94: 1, 1930. 17. Schlutz, Frederick, W.: g. I~ED~AT. 2: 41, 1933. 18. Craig, Charles F.: Internat. Clin. 1: 77, 1929. ]9. Faust, Ernest Carroll: Am. ft. Trop. Med. 10: 137, ]930. 1819 WEST POLK STREET