A note on the duration of infections with Entamœba histolytica

168

A NOTE

ON T H E

DUI~ATION

ENTAM(EBA

OF

INFECTIONS

WITH

HISTOLYTICA.* BY

CLIFFO]:I,D

DO:BELL,

31:.A.,

Im~eria~ CoZtege of Science, AND A. C. S T E V E N S O N , lg,B,, D.IP.tI.,

Wcllcome Bu,rea~ of Scientific I~eseareh.

We propose to give very briefly in the following note an account of three persons infected with Entameeba histolytica who have come under our observation during the last two years. These cases are of interest chiefly because they supply some evidence as to the length of" time during-which infection with the dysentery amoeba may persist ; and they are of interest, secondarily, because they also throw some light upon certain subsidiary problems which arise from a consideration of the duration of such infections. We will first note the .histories, so far as they are relevant, of these three cases; and we wilt afterwards discuss these and indicate the conclusions which may be drawn from them. The first two cases were included in the series of " d y s e n t e r y " patients invalided to England in 1915 frona the Eastern Mediterranean war area, and studied bacteriologically by Dr. L. ~AJO~AN and Dr. G. T. WESTEUX1 at the London Hospital, and from the protozoological aspect by :Lieut.-Colonel C. IV[. WE~¥oN ~ and ourselves ~ at the Wellcome Bureau of Scientific :Research. Neither of these cases properly belongs, however, to this series. The patients were both civilians, and they were included in the series simply because they entered hospital at * T h e e a s e s h e r e i n d e s c r i b e d w e r e s~udied b y u s in t h e c o u r s e of w o r k u n d e r t a k e n d u r i n g t h e l a s t t w o y e a r s for f h e M:edical :Research C o m m i t t e e . T h e N o t e itself is s u p p i e t n e n t a r y to t h e t w o R e p o r t s to t h e C o m m i t t e e (Nos. 1 a n d 2 in list of r e f e r e n c e s at end) w h i c h h a v e a l r e a d y b e e n p u b l i s h e d .

NOTE

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INFECTIONS

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ENTAMCEBA

YIISTOLYTICA.

169

the same time, and with the same ailments, as the other eases. No detailed account of these two patients has previously been published, though the results of the baeteriologiea,1 examinations of their blood and stools are already on record 1, and likewise the protozoological findings from the examination of the stools of the first ~. Case 1 (No. 762 in London Hospital Series 1 ) . - T h i s patient contracted dysentery in E g y p t in 1882, when he was serving in the army. He was sent to hospital at Cairo, where he spent three months and was " treated with pills." He relapsed seven weeks later and was sent home to England. I-Iere he recovered for the time being, and since his return he has not left this country. About ten years ago he began to suffer from recurrent attacks of diarrhoea, which persisted, with varying severity and for variable periods, until January 28th, 1916, when he entered the London Hospital for treatment. At this time he stated that he had been suffering from diarrhoea, sometimes accompanied by the passage of blood and mucus, for eleven weeks. Examinations of his stools and blood bacteriologically were negative ~. Microscopical examinations of his stools on February 1st, however, shewed the presence of cysts of E. Aistolytica and also some free amcsb~e. (E. coli also present.) The patient was treated with emetine hydrochloride hypodermically (1 grain daily for twenty-one consecutive days); and after his stools had been examined five more times with consistently negative results, and his clinical syrnptoms had completely disappeared, he was discharged from hospital as cured. Case 2 (No. 59i, London Hospital Series ~, 2).--This patient, an old soldier, first suffered from " dysentery " in Egypt in 1887. It is not certain whether this first attack was true dysentery, since it might, from the patient's own account of it, have been due to a typhoid or parstyphoid infection. However, in 1899 he had a severe attack of undoubted dysentery in In&a, and shortly afterwards returned to England. Here he was emplo]ced as an attendant in a lunatic asylum, and after six years' service in this capacity he had another acute attack of dysentery (1899). This was described as " colitis " and "ulceration of the bowels," and was supposed to have been acquired from contact with inmates suffering from " asylum colitis," but its true character can hardly be in doubt. After six weeks in hospital he was discharged as cured, and a few months later rejoined the army and went to South Africa (Boer War). Eight months after his arrivM he had another acute t~ttack of dysentery (1900), as a

170

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ENTAM(EBA

HISTOLYTICA.

result of which he was invalided to England. He recovered clinically on the voyage home, and resumed his former occupation on reaching this country. For the next ten years he suffered periodically from attacks of Severe abdominal pains, which were invariably followed by diarrhoea. He was admitted to the London Hospital on November 29th, 1910, suffering from a liver abscess. About seven or eight weeks previously he had had a severe attack of " diarrhoea," with blood and alucus in his stools, which l~sted for a fortnight. The abscess was opened and drained, about " eight ounces of thick creamy pus " being evacuated. The Clinical Laboratory report states that the cultures from this were sterile bacteriologically, and " no amoebae were detected." The patient returned to the London Hospital on December 25th, 1915, with a second liver abscess. He had been ill for three weeks previously with (?) bronchopneumonia, rigors, and pain in the right side. T h e liver abscess was opened and a quantity of typical amoebm abscess pus drained from it. Examination of this pus bacteriologically by Drs. RAJCH~IAN and WESTERN gave negative results ; but microscopic examination by Dr. WENYON, and later by ourselves, shewed that it contained numerous active E . h i s t o l y t i c a amoebae. Cysts of this parasite were also present in the patient's stools on January 3rd, 1916. Emetine hydrochloride was administered hypodermically. The amoebae gradually disappeared from the liver, and no more cysts were discoverable in the stools. In March the patient was finally discharged from hospital as Cured. Bacteriological examinations Of his fmces and agglutination tesbs of his blood--carried out in 1915 and 1916, at the London Hospital, by Drs. RAJCH~AN and WESTEI~N~ gave negative results. The third case is a private one under the c~re of Capt S. R. DouGLAS, I.M.S. (ret.), who has kindly given us the facts. The history of this case is peculiarly precise and trustworthy, since the patient is himself a medical ,nan with a wide knowledge and experience of dysentery. Case 3 . ~ T h e patient, who had previously been in India, contracted dysentery originally in China, July, 1901. Soon afterwards, and before he had recovered, he returned to India. On the way there h e developed an abscess of the liver, for which he underwent an operation shortly after landing (August, 1901). In December of the same year he came home to England, where he has since lived. After his return his dysenteric symptoms disappeared for a time, but then returned, and from 1905 until

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1911 he suffered almost continuously from dysentery. He passed from five to twenty stools daily, usually containing blo9d, mucus, and large numbers of amoebae. His abdomen was opened in 1906 and his liver examined. It was found to have recovered completely from the first operation, though numerous ~dhesions had been formed, which were broken down. His abdomen was again opened in 1908, when his appendix was removed. Examination of the patient's large intestine, in the course of these operations, shewed that its wall had no~ undergone any considerable thickening. I n 1911 the long period of persistent dysentery suddenly ended, its termination coinciding with the patient's recovery from an attack of pneumonia. F r o m this time (1911) until 1917 he has suffered from several slight attacks of dysentery, which yielded to hypodermic treatment with emetine hydrochloride. In September, 1917, the case came under the observation of one of us (C. D.), who then found large numbers of cysts of E. his~olYtica accompanied by many free amoebae in his stools. Since his return to :England from India in 1901, the patient has paid several short visits to the Continent, and in 1910 he spent several months in :Egypt. This was during the long period of dysentery (1905 to 1911), from which he suffered continuously before, during, and immediately after his visit. It should be added that the patient has had no further liver trouble since he recovered fl'oin his original abscess and the adhesions which followed. Before discussing these three cases, we would note that there are two considerations which make it usually very difficult to prove conclusively that infections with E. histolytica may persist for long periods of time. The first is that the eetiology of the dysenteries is a matter of comparatively recent knowledge ; so that it will usually be impossible to ascertain precisely what particular pathogenic organism was responsible for an attack of dysentery which occurred many years ago. The second difficulty is the fact, which is now well known, that a person may become, and long remain, infected with E. histolytica without displaying any dysenteric symptoms or outward sign of infection. The question of the duration of E. histolytica~ infections is of some practical importance, and has recently been raised by Low, 8 and WENYO~ and O'ConNor. 4 The former describes a case believed to have been infected for twenty years, and the lat~er note the occurrence of infections

17'2

~

NO~E

o~

I~F]~C~IO~S

WITH

]~A~(~]~A

~ISTOL~TIC~.

probably lasting for periods up to six years in persons displaying clinical signs of infection. But, as they very justly remark, " the length of time that a person may remain a healthy carrier is much more difficult to decide, for there is no history of repeated dysentery to guide us." I n the case of unhealthy carriers, they conclude that infections once acquired may persist " over long periods, and, so far as we can judge, it may be for the rest of life." The ease recorded by :Lows well illustrates the two elements of uncertainty to which we have previously referred. The patient in question was a seaman, who had travelled all over the world. He had one attack of dysentery in Egypt twenty years ago, but no others, before or since. In 1916 he entered hospital in England suffering from a typical amoebic liver abscess, and passing cysts of E. histolytica in his stools. He was certainly infected with E. histolytica at this time, therefore, but proof that he became infected at the time when he suffered from dysentery twenty years ago is lacking. It is quite possible that his original and only attack of dysentery was bacillary,, and not amoebic; and that he acquired his infection with E. histolytica at some period of his travels during the following twenty years. It is not possible, therefore, to obtain a conclusive proof that an amoebic infection may persist for twenty years from cases such as this. Criticisms along similar lines may be made of all such histories, including those which we ourselves have just recorded. Nevertheless, we think that, as regards our cases, the evidence of long duration of infection is rather more satisfactory. Case 1 had acute dysentery in E g y p t 34 years before we examined him. Shortly after the original attack he suffered from a relapse. Since then he has resided in England, where the chances of acquiring infection with E. histolyticcb are very small. Ten years ago he began to suffer from "diarrhoea" once more, and had continued to do so until the time when he came under our observation. The " diarrhoea" h'om which he was suffering when we examined h i m - - a s is evident from the finding of E. histolyticc~ in his stools, and his response to emetine t r e a t m e n t - - w a s subaeute amoebic dysentery. That the case had suffered from bacillary dysentery is rendered improbable from the agglutination reactions of his blood. There was thus evidence that this case was suffering, when we examined him, from infection with E. histolytica, ; that the original attack of dysentery 34: years ago was likewise due to this organism,

A

NOTE

ON

INFECTIONS

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HISTOLYTICA.

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since the dysentery had relapsed, and there was but little chance of an infection being acquired during this period; and there was, moreover, evidence that the patient had not been infected with dysentery bacilli. W e think it highly probable, therefore, that this ease had been a carrier of E. histolytic~ for the 34 years of his residence in England after his return from Egypt, where he originally acquired his infection. If this conclusion is correct, then we think this ease constitutes the longest duration of infection with E. histolyticc~ which has yet been recorded. The evidence obtainable from Case 2 is in some respects similar. The patient had " d y s e n t e r y " in E g y p t some 28 years before we examined him. This was followed by a definite acute attack (? relapse) in India about five years later; and for the following 23 years he continned to suffer from periodic recurrences of intestinal disorder, which strongly suggest that they were relapses of dysentery due to an amoebic infection acquired originally either in Egypt or in India. The culmination of this intestinal trouble in two liver abscesses (1910 and 1915), and the ultimate proof of the presence of active E. histolytica in the second abscess, and of its cysts in the stools, substantiates this interpretation. The patient, it is true, may possibly have acquired his amoebic infection at a date later than ]892. H e had been abroad since then (S. Africa) where he suffered from dysentery of unknown sstiology. It may have been a relapse of his original amoebic dysentery or due to a newly acquired amoebic, or even bacillary infection; for the prevailing type of dysentery during the Boer W a r is generally believed to have been bacillary. His attack of " asylum colitis" may also possibly have been due to a bacillary infection, and not a relapse of amoebic dysentery. Nevertheless, the fact that his agglutination reactions give no indication of his having suffered from bacillary dysentery, supplies further evidence that his intestinal ailments have been due to the same amoebic cause throughout. The evidence appears to us strong that this case, therefore, had been a carrier of E. histolyticc~ for a period of probably at least 23 and possibly even 28 years before he came under our observation. The information concerning Case 3 enables us to determine the minimum duration of his E. histolyticc~ infection with considerable accuracy. Almost immediately after the patient experienced his first attack of dysentery i n China 16 years ago, he developed an abscess of the liver. Frequent relapses of acute and snbaeute dysentery since, and

174

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ENTAM(2~BA tIISTO:LYTICA.

the presence of numerous amoebae in his fmces up to the time when he came under our observation--when typical alncebm and cysts of E. histolytica were present in abundance--render it almost certain that this case had been infected with the dysentery amoebae for at least 16 years. From these three cases we think it justifiable to conclude that an infection with /~. histolyticct may persist certainly for 16, and probably for as long as 34 years. They supply no evidence to support the contention that persons who acquire an infection abroad, and then return to live in this country, get rid of their infections spontaneously without specific treatment. On the other hand, they afford good evidence of the remarkably persistent character and long duration of E. histolytica infections when the amoebm have once established themselves in the body. It has recently been asserted by M a i m s and MERClEa 5 that there is nothing to fear from the introduction of large numbers of carriers of amoebic dysentery into :Prance, from the colonies and tropical countries, during the war. The infection, they say, dies out sooner or later, and without specific treatment, in cold or temperate climates. -They further state that this is due to the fact that the amoebm can only live in the presence of certain intestinal bacteria, which abound in persons living in the tropics, but which become reduced in number or disappear altogether when the infected persons return to temperate regions. We know of no evidence to support such statements, and at least two of the three cases cited in the present note--and many o~hers that we could cite, of shorter duration--are flatly contradictory, w e have,, no desire to exaggerate or emphasize the risk incurred by the introduction of amoebic dysentery carriers into this country during or after the war; for we regard the spread of infection as dependent chiefly upon inadequate sanitary conditions, and we are fully alive to the fact that a large number of carriers are, and probably may remain, in apparently excellent health. Nevertheless, we would ask for evidence, in the first place, to prove that the intestinal flora undergoes a complete change in passing from a temperate to a tropical climate, or vice versa. And secondly, we think it desirable that the authors should publish accounts of actual eases which have recovered spontaneously from E. histolyfiec~ infections, acquired abroad, without specific tvea~lnent and merely as a result of change of residence. It will, of course, be necessary for them to furnish proofs thai the cases really were at one time infected with E. histoly~iec~; that they have undergone no specific treatment; and that their infections have now

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completely disappeared. At present we ourselves know of no such cases ; and from our own experience we think that convincing evidence of their existence will not be easily obtained. Before we conclude, we would call attention once more to the curious and still obscure rele,tion of liver abscesses to intestinal infections with E. histolytica, since the three cases here recorded are of interest in this respect. The case (Case 1) in which the duration of the infection appears to have been the longest (34 years), has never had a liver abscess. The amcebEe appear to have been restricted in their distribution to the intestine for the whole period. Case 2, however, appears to have been a carrier similarly for at least 18 years before the amcebee gained access to his liver. He had one liver abscess probably at least 18 years, and a second at least 23 years, after the amcebee had originally established themselves in his intestine. Case 3 is a curious counterpart to Case 2. Almost immediately after he became infected, apparently, he suffered from an abscess of the liver. For the following 16 years, however, although the intestinal infection has persisted, and given rise to repeated dysenteric attacks, he has had no recurrence of the liver infection. The factors which determine the passage of the amoebae from the gut to the liver still require elucidation; and such facts as the foregoing make it a p p e a r - a t least superficially--as though it were entirely a matter of chance whether a person who acquires an intestinal infection with E. histolytica does, or does not, acquire a liver abscess subsequently. I n conclusion, we take the opportunity of thanking Dr. G. T. WESTERN for supplying us with information concerning Cases 1 and 2. Through him we would also convey our thanks to the medical officers under whose care these patients were at the London Hospital, since we owe their permission to record these cases to his good offices. We would also offer our best thanks to Captain S. 1%. DouGnAS for giving us, and allowing us to publish, the very interesting details concerning the history of the third case which we have here described. .REFERENCES. 1.

2. 3. 4. 5.

L. RAJCHMAN a n d G. T. WESTERN. Medical R e s e a r c h Committee, Special Report Series, No. 5, 1917. (Report upon 878 cases of bacillary e n t e r i t i s , w i t h A p p e n d i x on the protozoal findings by C. DOBELL and A. C, STEVENSON). C . M . Wt~NYON. Journ. l~oy. A r m y Med. CorNs , April, 1916. G . C . L o w . B r i t i s h Med. Journ., Dec. 23rd, 1916. C. ]K. WENYON a n d F. W. O'CONNOR. Journ. Roy. A r m y Med. Corps, Feb. 1917. C. MATHIS a n d L. ~,~ERCiER, Bali, Soc, P a t h o l Exot., ¥ol. X., /go. 4, 1917.