Menicive Copyright © 1977 by The Williams & Wilkins Co. Vol. 56, No. 4 Printed in USA. INVASIVE AMEBIASIS IL Amesic Liver ABSCESS AND ITs COMPLICATIONS E, B. ADAMS and J, N. MacLEOD Like amebic dysentery, liver abscess caused by E. histolytica is a common disease in Natal. Of 5087 patients with invasive amebiasis ad- mitted to one medical unit at King Edward VIIT Hospital, Durban, over a 20-year period (1955 1974), the liver was involved in 2074. If recog- nized and treated appropriately, amebic liver abscess carries a good prognosis but extension into neighboring structures, especially the peri- cardium, conspicuously alters the risk to life (ee Table 1). In two-thirds of these patients proof that the disease was invasive amebiasis came from aspi- ration of amebic pus from the liver, from identi- fication of E. histolytica in pleural effusions or sputum in those with thoracic involvement, or from post-mortem examination. The remaining third lacked definitive proof but were almost certainly cases of amebie liver abscess because of appropriate clinical features, typical findings on radiological examination including in many cases isotopic scanning of the liver, a positive amebic gel diffusion test, and satisfactory re- sponse to treatment with a tissue amebicide. Clinical features. The main clinical features in 400 consecutive admissions are listed in Ta- ble 2. It will be seen that only a minority of patients with amebic liver abscess also have active intestinal disease. Others have recently had proven amebic dysentery or give a history of diarrhea or dysentery which has cleared up. In the majority there is no clue as to when the initial invasive phase in the bowel occurred. ‘The duration of symptoms denoting liver in- volvement varies from a few days to many months, Pain, the commonest symptom, might be in the right upper quadrant of the abdomen, the epigastrium, the right lower chest or the right shoulder tip—singly or in various combi: nations. Of these, right upper quadrant pain referred to the right shoulder tip is highly suggestive. Much less commonly the pain is left-sided. This has special significance despite its infrequent occurrence since liver abscesses From the Department of Medicine, University of Natal, Durban, South Africa. in the left lobe carry the added risk of extension into the pericardium, a dangerous complication (eee Table 1). Although usually dull in type, the pain may be stabbing or pleuritic. Patients may also complain of swelling in the upper abdomen or over the right lower chest, cough, sweating, malaise, loss of weight, anorexia, flatulence and hiccough. Sometimes there is backache or pain might be felt in the axilla, below the right scapula or in the lower abdomen. Enlargement of the liver with pain on palpa- tion is the most important sign; finding a site of maximal tenderness (point-tenderness) either over the liver below the ribs or in the intercos- tal spaces is typical. A localized swelling in the epigastrium or right upper abdomen may be seen. Sometimes the liver is not apparently enlarged because the abscess is situated high up under the diaphragm, the enlargement being upwards. In such cases there may be intercostal tenderness, dullness to percussion over the right lower chest and diminished breath sounds. In suspected cases inspection of the chest for bulging or fullness and careful palpation of the intercostal spaces (using only one finger) between mid-axillary and mid-clavi- cular lines may give a clue to the correct diag- nosis. The point of maximal tenderness should be determined by questioning the patient dur- ing the examination or watching his face for an expression of discomfort. Frequently the signs of downward and upward expansion of the liver are combined. Fever is usual and often sus- tained but low-grade pyrexia is not uncommon. Occasionally there are rigors. Long-standing cases show weight-loss, anemia and cachexia. Diagnosis. Much weight should be given to the clinical features already described. Finding point-tenderness on palpation of the liver is a most useful sign as is intercostal tenderness, but the latter might also occur in other condi- tions such as tuberculous pleural effusions and lobar pneumonia, both of which come into the differential diagnosis of hepatic amebiasis with extension into the thorax. In hepatoma (pri- mary carcinoma of the liver) hepatic enlarge- ment and pain are also features but the liver is,326 TABLE 1 Amebic Liver Abscess and its Complications (1955-1974) Cases Death Uncomplicated liver abscess 1888 0m Complicated by extension into ‘The chest 46 962%) Peritoni 2” 718.4%) Complicated by extension into Pericardium 2 R96) Rupture into bowel 2eI Tar Hemobilia 1 ° Brain abscess 1 1 2074 3911.98) “* Rupture into pericardium and stomach. TABLE 2 Main clinical features in 400 consecutive admissions with amebic liver abscess % Length of history 0-2 weeks 59 2-4 weeks 20 4-12 weeks 16 2 weeks 5 Symptoms Pain 99 Right hypochondrium cr Right chest 28 Epigastrium a Right shoulder 9 Previous dysentery 19 Present diarrhea or dysentery u Cough n Dyspnea 4 Signs ‘Tenderness in right hypochondrium 85 Liver palpable and tender 80 Fever % Signs at right lung base a7 Localized intercostal tenderness 38 Epigastric tenderness 2 Localized swelling over liver 10 more often diffusely tender and much harder in consistency. A hard liver does not exclude a diagnosis of amebic liver abscess because con- comitant citthosis is by no means uncommon. When the liver cannot be palpated, unex- plained pain in the epigastrium, right upper quadrant or lower chest, or shoulder-tip pain in a patient in whom radiology shows a raised dome of the diaphragm with some shadowing ADAMS AND MACLEOD above it and immobility on screening are also ikely to be due to an amebic liver abscess. When there is no point tenderness and facilities for further investigation are lacking, relief after a therapeutic trial of a tissue amebicide virtually proves the diagnosis. ‘The main laboratory aids to diagnosis are summarized in Table 3. Mild degrees of anemia are common, the anemia being that of chronic infection (11). The severity is related to the duration of symptoms. It may be either normo- chromic or hypochromie. In the latter case ex- amination of the plasma-iron pattern or the bone marrow for iron stores will help to rule out iron-deficiency anemia. Occasionally anemia is profound, the lowest hemoglobin in this series being 3.8 g/100 ml. Leukocytosis is present in a majority of cases Although jaundice does not exclude the diag- nosis, its presence makes amebic liver abscess unlikely. We rarely found jaundice in our pa- tients and only once was it obstructive (when, the abscess was very large). As an aid to diag- nosis, liver function tests, although sometimes abnormal, are unhelpful, presumably because so much liver tissue is unaffected. In doubtful cases (e.g., no point-tenderness and no elevation of the diaphragm on x-ray) relief after a therapeutic trial of a tissue amebi- cide is good evidence in favor of amebic liver abscess. This is preferred to blind needling of the liver which can be dangerous. Serological tests can be particularly helpful in such cases. We have largely relied on the gel-diffusion test (10). A positive result, which denotes present or past invasive amebiasis, was found in 96% of proven cases of amebie liver abscess (18). The importance of the test is that when negative, amebic liver abscess is an unlikely diagnosis. TABLE 3 Summary of main laboratory aids to diagnosis in 400 consecutive admissions a Positive serology (amebie gel diffusion 94 test) Aspiration of typical amebic pus 85 Leucocytosis >10,000/mm" 1 Anemia <12 g/100 ml Hb 63 Elevated right diaphragm on x-ray 56 Radio-isotopie scanning * Ultrasonic scanning Not available when these patients were admit- ted but now in constant use for diagnostic purposes,INVASIVE AMEBIASIS ‘The latex agglutination test, which is quicker, has similar significance (12), Finding what has come to be known as ame- bic pus at aspiration virtually proves the diag- nosis. The material is variable in color and consistency but typically it is opaque and red- dish, dirty brown or pink. Those who delight in such analogies would add the appellation “an- chovy sauce.” Amebic pus is almost always sterile except in those instances in which sec- ‘ondary infection has occurred. In our experi- ence the latter is rare on the first aspiration. Aspiration of thinner material, yellow or green- ish in color, does not rule out the diagnosis, indeed, fluid of this kind is commonly seen at necropsy in cases of amebic liver abscess which had not been aspirated during life. Direct proof of the diagnosis may be obtained by finding E. histolytica on direct microscopy or culture of the aspirated pus. ‘The value of radiology has already been men- tioned. The diaphragm is raised in about half the eases and shadowing may be seen above it, usually representing discoid atelectasis unless there is extension into the thorax. Scanning of the liver after the administration of an isotope such as technesium-labelled sulphur colloid is, very valuable in doubtful cases, a liver abscess 327 showing up as a “cold” area. The scope of this investigation in hepatic amebiasis, using the isotope I Rose Bengal, has been fully dis- cussed by others (2). It is particularly useful when the indications for aspiration are absent or dubious. Recently we have found ultrasonic scanning of great value. If the liver scan sug- gests amebic liver abscess and response to met- ronidazole is poor, exploratory needling in the direction of the cold area is justified. Treatment. We prefer to combine a tissue amebicide with aspiration at the point of maxi- mal tenderness, a policy which has given us the favorable results reflected in Table 1. As re- gards the choice of drug, our current practice is based on a series of therapeutic trials carried out over the period 1958-1972 (15-17, 20, 23-25, 33-35), The admission criteria were standard- ized. Each patient had uncomplicated amebic liver abscess, proved by the aspiration of bacte- riologically sterile pus; patients seriously ill and those who had recently received amebi- cides or had co-existing disease were excluded. Table 4 sets out the best results obtained in these trials. From it will be seen that emetine {two courses), the combination of emetine or dehydroemetine with chloroquine, and metro- nidazole are equally effective. Our most recent ‘TABLE 4 ‘Trial Drugs) 1. Wilmot, Powell, Adams, _Emetine 1958 (33) Chloroquine 2, Wilmot, Powell, Adams, Emetine and 1959 (34) chloroquine Chloroquine 3. Wilmot, Powell, MacLeod, Dehydroemetine Elsdan-Dew, 1964 (35) ‘and chloroquine fmetine and chloroquine 4, Powell, Wilmot, Elsdon- Metronidazole Dew, 1967 (23) Clinical trials showing best results in the treatment of amebic liver abscess Number” cure Regimen (duration in days) of se my Rett (65 mg im. x 10; 14 days later, 19100 65 mg im. x 6 600 mg, 300 mg 6 hours later, 6 63 then 150 mg bd. x 29 As above, emetine for 10 days only 22,91 ‘As above 23 80 mgi.m. x 10 50 100 ‘As above ‘As above, emetine for 10 days only 49100 5 regimens, 20 in each: 100 100 (i) 2.4 g, 1.2 g 6 hours later, ‘then 800 mg t.d.s. x 9 (i) 2.4 g, 12g 6 hours later, then 800 mg t.d.s. x 4 (iii) 800 mg t.d.s. x 10 (iv) 800 mg tds. x 5 (¥) 400 mg tds. x328 experience with metronidazole confirms the value of this drug. There were no deaths in 112 consecutive patients with uncomplicated ame- bic liver abscess, proved in each case by a posi- tive gel-diffusion test and the aspiration of bac- teriologically sterile pus. 800 mg thrice daily for 5 days was superior to 400 mg thrice daily: all 53 patients on the 800 mg regimen were cured without additional drug therapy whereas 2 out of 59 patients treated on the lower dosage schedule required dehydroemetine as well for the abolition of all symptoms and signs of liver disease. Although the first, metronidazole is not the only nitroimidazole which is effective as a tis- cide. Other drugs in this group pro- duce similar results as regards cure but a rather higher cyst-passing rate (16), a conclu- sion which has recently been challenged (7) in the case of tinidazole. From the results shown in Table 4 it is clear that the choice may be one of individual prefer- ence, Emetine produces a number of toxic ef- fects such as pain and tenderness at the site of injection, nausea, muscular weakness and car- diovascular changes, which have been fully dis- cussed by Wilmot (32). Powell (13) showed that dehydroemetine is similarly cardiotoxic. De- spite their toxicity, these are two valuable drugs. Precautions to be observed are to keep the patient at rest, to ensure correct daily dos- age and duration of treatment, and to discon- tinue their use if significant tachycardia oc- curs. It is best to avoid emetine or dehydroeme- tine in patients with established heart disease; we make an exception in the case of amebic pericarditis (q.v.). Metronidazole has fewer side effects (see p. 318), is equally effective, is eaay to administer and will cure concomitant amebic dysentery. We, therefore, regard it as the drug of choice for amebic liver abscess. Although other dosage regimens, some of them shorter and using a single dose of metronida- zole each day (24), may also be effective, our current practice is to give 800 mg thrice daily for 5 days. Second courses are occasionally nec- essary and for patients whose progress is slow despite metronidazole and repeated aspiration we do not hesitate to use emetine or dehydroe- metine in addition. A small proportion of patients remain cyst- passers after clinical cure of amebic liver ab- scess with any tissue amebicide: in the case of metronidazole 6 out of 45 patients (13%) re- ADAMS AND MACLEOD ported by Powell and Elsdon-Dew (16) and 10 of the 53 patients mentioned above (19%). While this state does not constitute disease we believe cysts should be eradicated in such cases because the patient often returns to the same envi- romental conditions which might previously have contributed to invasiveness. We recom- mend that one of the lumenal amebicides, diio- dohydroxyquinoline (600 mg t.d.s. for 20 days) or diloxanide furoate (500 mg t.d.s. for 10 days) should also be given. In all cases of suspected liver abscess a point of maximal tenderness should be carefully sought by digital palpation in the lower inter- costal spaces and over the liver below the rib margins, the relative frequency of the sites for aspiration being shown in Table 5. When a point of maximal tenderness is present, aspira- tion with a medium-bore needle should be at- tempted at this site, preparing the patient with subcutaneous morphine or pethidine and local anesthesia. The needle is seldom introduced to a depth of more than 8 em and when the posi- tion of the abscess has been established by aspi- ration of pus, a wide-bore needle can be intro- duced for further evacuation. If pus is not ob- tained after needling in two or three different directions, the procedure is abandoned. An- other attempt may be made several days later if the patient's condition has not improved on metronidazole. Scanning of the liver with a Tadioisotope or ultrasonic scanning helps con- siderably in identifying the situation of the ab- scess, The amount of amebic pus obtained var- ies considerably. In the present series the range was from 2 ml to 5000 ml; more than 2 liters was removed in 37 patients with uncomplicated liver abscess (2%), usually in not more than 4 aspirations, In approximately half, the abscess was relatively small (ess than 200 ml) and only one aspiration was necessary. Relief after nee- dling is usual, and repeated aspirations should only be done if more than 250 ml of pus is removed at the first aspiration, pain does not subside, or when other constitutional symp- toms persist. TABLE 5 Site of aspiration of amebic * Right lower intercostal spaces 65 Right hypochondrium 20 Epigastrium 15INVASIVE AMEBIASIS If there is no point of maximal tenderness, aspiration is best avoided for a few days until the effect of treatment with metronidazole can be judged. Many patients with small abscesses will recover very satisfactorily on drug therapy alone, proof of the diagnosis in such cases rest- ing on circumstantial evidence (raised dome of the diaphragm, positive serology, results of iso- tope scanning of the liver). Sometimes symp- toms persist despite metronidazole. Careful re- examination for a point of maximal tenderness is often rewarding after several days of treat- ment. In other patients with radiological evi- dence of a raised diaphragm but without point tenderness, needling is justifiable and often yields amebic pus. Death occurred in only 13 of the 1859 patients with uncomplicated amebic liver abscess (0.7%) managed by aspiration when indicated and the use of a tissue amebicide. One of these patients was admitted moribund and another also had pneumonia and heart failure. Five had multi- ple liver abscesses. The diagnosis was first made post-mortem in two cases. Complications Extension into the thorax. The commonest way in which an amebic abscess extends into the chest is by contiguity. Extension via lym- phatic channels has also been postulated (3). Before actual rupture occurs pleural irritation may give rise to a pleural friction rub, a “pleural reaction” on the x-ray film, or to a serous pleural effusion. Prior to rupture radio- logical changes suggestive of linear atelectasis or circumscribed consolidation may be seen in the right lower lobe adjacent to the diaphragm. Rupture into the pleural space leads to an ame- bic empyema. Rupture into the lung may result in consolidation, abscess formation, or a he- pato-bronchial fistula. Radiology shows that the pulmonary changes are almost always in the right lower lobe adjacent to an elevated or deformed right diaphragm. With the occur- rence of a hepato-bronchial fistula large quanti- ties of amebic pus may be coughed with rapid relief of symptoms. Prior to the advent of spe- cific amebicides such an event gave the best chance of spontaneous cure (27). Rarely, pulmonary lesions and abscesses re- mote from the diaphragm in patients with known hepatic amebiasis have been attributed toE. histolytica. Whereas blood-borne infection undoubtedly occurs, the portal venous circula- 329 tion being the usual route from bowel to liver, spread by systemic vessels to the lungs is rare (81). One should be wary of accepting without question a connection between isolated pulmo- nary shadows well removed from the dia- phragm in cases of amebic liver abscess since there are more common causes for such lesions. ‘Among the 146 patients with thoracic ame- biasis in this series four types could be recog- nized —hepato-bronchial fistula (47%), pleural effusion and empyema (29%), lung abscess (14%) and consolidation (10%); but there was considerable overlap. Right-sided lesions were the commonest, radiological appearances vary- ing from a raised diaphragm with a little pleural reaction above it or with minimal basal consolidation, to pleural effusion of various de- grees (up to three liters or more), well-marked basal and middle-lobe opacities and lung ab- scesses (usually single). Most patients complain of some of the follow- ing symptoms: pain, cough, hemoptysis or dyspnea, the first three being more common. Pain may be pleuritic in type, situated in the right lower chest or the tip of the shoulder, but it may be absent altogether or felt only in the right upper quadrant of the abdomen. Left- sided pain is much less common (but much more important since it may represent pericar- dial involvement). Cough may be non-produc- tive. More often it is productive, the sputum varying from a small amount of whitish mate- rial or blood-stained spittle to larger quantities ‘of expectorate which is reddish-brown, dirty brown, purulent or frank amebic pus. ‘The physical signs are those of the underly- ing lesion, the commonest being an elevated right diaphragm, signs of consolidation or those of a pleural effusion. Like other thin-walled abscesses, those of amebie origin may produce few physical signs. The liver need not be palpa- ble since a liver abscess with thoracic extension is usually high up in the right lobe. When the liver can be felt below the costal margin it is frequently tender. This sign together with hem- optysis and other chest symptoms and signs in an area where invasive amebiasis is known to occur should immediately raise suspicion of the correct diagnosis. Many patients start their ill- ness with cough, chest pain and slightly blood- stained sputum; in most cases coughing up frank amebie pus comes later, an event which usually heralds clinical improvement. Some pa- tients when first seen are already coughing330 copious reddish-brown, dirty brown or “an- chovy-sauce” material, strongly suggesting a diagnosis of amebic hepato-bronchial fistula. Metronidazole or other tissue amebicide should be administered and where possible the liver abscess aspirated. Pleural effusions should also be aspirated, the procedure being repeated when there is evidence of reaccumula- tion. Occasionally many aspirations are neces- sary. The combination of metronidazole with spontaneous emptying of the liver abscess via an hepato-bronchial fistula or needle aspiration of liver or pleural fluid (or both) usually gives good results. Surgical intervention is rarely called for. The case-fatality rate in this series was 6.2%. Missing the diagnosis altogether or making it too late were important causes of death In our experience pulmonary fibrosis was rarely a complication of the pathological proc- ess of invasive amebiasis. In a few instances residual bronchiectasis was shown in the basal segments of the right lung. We have only en- countered residual pleural thickening and fi- brosis when aspiration of amebic pus from the pleural cavity has been inadequately per- formed. Peritonitis. There were 38 cases with 7 deaths (case-fatality rate 18.4%). The usual way in which this occurs is as a sudden event, giving rise to severe pain and the signs of the “acute abdomen.” Previous hepatic pain, when pres- ent, helps in the diagnosis. In a minority of cases there is a slow leak producing walled off abscesses, In both cases laparotomy is indicated for diagnostic purposes and treatment is by surgical drainage and the use of tissue amebi- cides. Amebic peritonitis arising from a liver abscess carries a better prognosis than peritoni- tis occurring in amebic dysentery, presumably because the pus is free of bacteria and the sur- geon does not have to cope with the problem of friable bowel Amebic pericarditis. This complication, the most dangerous hazard of amebic liver abscess, has been fully discussed elsewhere (1, 9). Ex- tension from the left lobe is the usual cause. Rarely, spread may also occur from the right lobe or the disease may reach the pericardium via an amebic lung abscess. Before actual rup- ture takes place, irritation of the pericardium by a contiguous liver abscess leads to serous effusion, Since this heralds rupture of amebic pus into the pericardial sac ("suppurative ame- ADAMS AND MACLEOD bic pericarditis") and should be a warning of this imminent catastrophe, it is best described as the "presuppurative” phase, a term which is preferred (for this reason) to others such as “sympathetic” and “reactive.” Suppurative amebic pericarditis may occur insidiously, a gradual leak into the pericardium causing pro- gressive deterioration in the patient's condi- tion. Sometimes rupture is rapid, usually a calamitous event. Constrictive pericarditis oc- casionally follows suppurative amebic pericar- ditis. This series includes 27 patients, an incidence of 1.3%, The duration of symptoms ranged from 3 days to 6 months, most patients having been il for many weeks. There were three modes of presentation, he- patic, cardiac and in shock. (1) Hepatic presentation. Eight patients first presented with signs and symptoms of amebic liver abscess, most often in the left lobe, Each later developed pericarditis with effusion, ex- tension to the pericardium being suggested by one or more of the following: deterioration in the patient's general condition, the onset of retrosternal or left chest pain, dyspnea, eleva- tion of the jugular venous pressure, a rising pulse rate, a pulse of small volume, pulsus paradoxus, a pericardial friction rub. (2) Cardiac presentation. Considerably more patients, 18 in all, first presented with cardiac signs, either those of pericarditis with effusion or congestive cardiac failure, or both, the signs of the causative liver abscess being incon- spicuous. The two diseases most often diag- nosed in error were tuberculous pericarditis ‘(when pericardial signs were obvious) and con- gestive cardiomyopathy (when pericardial signs were insignificant or dubious). These di- agnoses were justified because both conditions are much more common among African pa- tients. Chest. pain, left shoulder tip pain, a pericardial rub combined with point-tenderness over the liver in the midline or in the left hypochondrium rather than diffuse hepatic pain (as in congestive cardiac failure) led to the correct diagnosis in most cases. In others, the diagnosis became obvious after aspiration of typical amebic pus from the pericardial sac when tuberculous pericarditis had been sus- pected. The diagnosis is readily missed. In one pa- tient, congestive cardiac failure due to tubercu- lous pericarditis was diagnosed on radiologicalINVASIVE AMEBIASIS evidence of pulmonary infiltration of the left Tung, cavitation in the midzone and partial pneumothorax. Despite appropriate treatment, the patient became shocked and died on the fifth day. At necropsy there was an amebic liver abscess which had spread to the left thorax and ruptured into the pericardium. (3) Presentation in shock. Rapid cardiac tam- ponade is occasionally the first detectable event in the natural history of amebic pericarditis (5, 9). One patient presented in this way. He had complained of abdominal and chest pain for 3 days and on the morning of admission had felt cold, sweated profusely and passed blood per rectum, The main features on examination were an enlarged liver, cold extremities, im- palpable pulses and unrecordable blood pres- sure. A rub, thought to be pleural, was audible in the left chest anteriorly and a rectal ulcer was seen on proctoscopy. Cardiac tamponade was diagnosed, resuscitation commenced and 80 ml amebic pus aspirated from the pericar- dium but the patient died some hours later. Necropsy confirmed amebic pericarditis due to amebic liver abscess; amebie dysentery was also present. Rapid cardiac tamponade with resulting shock may also come on at a later stage during treatment of an amebic liver abscess or pericar- ditis, as it did in three other cases (all fatal). The only possible therapeutic measure is in- stant aspiration of the pericardium. ‘The most useful diagnostic aids are a positive serological test, electrocardiographic evidence of pericarditis, a high and immobile left dia- phragm on radiology, a cold area in the left lobe of the liver on radioisotopic scanning of the liver and diagnostic aspiration of the pericar- dium under electrocardiographic control. The last is the only way of confirming the diagnosi ‘Treatment comprises the use of effective ti sue amebicides and adequate drainage of the pericardial sac by needle aspiration. If the elini- cal signs and radioisotopie scanning suggest that the liver abscess is of appreciable size, this, should also be aspirated. Both procedures must be repeated if the patient does not make good progress. Constriction may supervene but con- servative management is advised since fibrous constriction is an unlikely event and resolution often occurs without recourse to surgery. Nev- ertheless, surgery is occasionally necessary. In this series treatment was based on these principles. Three patients were given only one 331 drug and two died. Thereafter two tissue ame- bicides were used in combination; emetine and chloroquine until 1967 after which metronida- zole was given with dehydroemetine. Numbers were small but there was no difference between the two combinations. Eight patients died. Of the four in whom the correct diagnosis was made during life, one ran a prolonged course in hospital, constricted, re- quired pericardectomy after 2 months’ treat- ment but died after operation. Another col- lapsed and died on the day of admission. Two others died despite the regimen of treatment, outlined above. ‘Two of the four patients in whom amebic pericarditis was not diagnosed were treated for tuberculous pericarditis. Another patient had presented with an enlarged, tender liver, with- out cardiac involvement but soon afterwards collapsed and died from rapid cardiac tampon- ade. Failure to think of invasive amebiasis was thus partly or fully responsible for death in these three patients. A fourth patient, reported elsewhere (6), was admitted with pneumoperi- cardium due to rupture of a left lobe liver ab- scess which had also eroded into the stomach. Rupture into bowel. This occurred in only three patients, one of whom survived rupture into lung and gut, the sign that the latter had taken place being sudden evacuation of amebic pus per rectum, Of the two fatal cases one involved rupture into duodenum and kidney; the liver abscess in the other, already referred to, had ruptured into stomach and pericardium. ‘These few cases may underestimate the fre- queney of this complication of amebic liver ab- seess since rupture into the bowel, like hepato- bronchial fistula, favors recovery provided tis- sue amebicides are used. Unlike the latter which is suspected when there is radiological evidence of extension into the thorax and con- firmed if the patient coughs up brownish spu- tum containing E. histolytica, rupture into the bowel may pass unsuspected in a patient se- verely ill from amebic liver abscess. Hemobilia producing hematemesis and me- lena. One patient with amebic liver abscess, mild jaundice and severe anemia (hemoglobin 5.1 g/100 ml), who was apparently successfully treated with metronidazole, blood transfusion and the aspiration of 355 ml amebic pus, was readmitted 3 days after discharge with hemate- mesis and melena (hemoglobin 4.8 g/100 mb) After transfusion and further treatment with332 metronidazole and dehydroemetine, gastros- copy and barium meal examination were done without revealing the origin of the bleeding. At laparotomy a large empty right lobe cavity was demonstrated. Aortography and right hepatic angiography showed contrast material entering the cavity from the right hepatic artery and emptying rapidly. He made an excellent recov- ery after ligation of this vessel. This rare com- plication of amebic liver abscess has been more fully reported elsewhere (21) Brain abscess. This is also a rare complica- tion of invasive amebiasis. It usually arises by blood spread from lesions in liver or lung (31) but may develop without such lesions being demonstrable, presumably from gut via the paravertebral plexus of veins (19) One patient in this series developed epilepti- form seizures and was admitted in coma a week after being discharged from hospital apparently cured of an amebic liver abscess (1400 ml pus aspirated). He died three weeks later despite further treatment with tissue amebicides and antibiotics. At necropsy a brain abscess was found, presumably amebic although E. histoly- tica was not observed. As is the case elsewhere, in this hospital suspicion of the amebie etiology of brain ab- scesses has been confirmed by finding the para- site in the lesion postmortem (19) and E. histo- Iytica has been found in brain abscesses in rou- tine necropsy material (J. Wainwright, 1975 unpublished data). DISCUSSION Alll the patients reported here were regarded as having actual liver abscess, the diagnosis “amebic hepatitis” being avoided. This term appears to have been introduced to describe a presuppurative phase of amebic liver abscess, i.e., focal rather than diffuse disease. Unfortu- nately, the term “amebic hepatitis” is often used to describe a hypothetical situation of dif- fuse involvement of the liver in patients with chronic discomfort in the right upper quadrant and a slightly enlarged tender liver. The eondi- tion lacks histological proof (22). Patients dying of amebic liver abscess show no evidence of involvement of liver tissue remote from the abscess and examination of biopsy material in patients diagnosed clinically as having “amebic hepatitis” likewise denies its existence (32). Sometimes patients with amebic dysentery de- velop discomfort and enlargement of the liver, ADAMS AND MACLEOD suggesting hepatic invasion. Liver biopsy in such patients reveals either a liver abscess or normal tissue; those shown to have no liver abscess after exploratory needling can be cured by a drug such as tetracycline which has no effect on E. histolytica in the liver although its use leads to cure of bowel amebiasis, ‘A comparison of the low case-fatality rate in amebie abscesses which remain confined to the liver (0.7%) with the high rates when there is extension into the chest (6.2%), the peritoneal cavity (18.4%) or the pericardium (29.6%) un- derlines the importance of early diagnosis and effective treatment. In endemic areas such as Natal awareness of the high incidence of the disease and the dangers of its complications encourages early diagnosis. The disease, al- though by no means rare in temperate climates (29), is often missed and should not be over- looked in these days of international travel and migration, especially since such effective ther- apy is available. Is aspiration really necessary in uncompli- cated amebic liver abscess? Many workers rely largely on tissue amebicides, avoiding aspira- tion unless diagnosis has been delayed and rup- ture seems imminent (26, 28) or, as in the large series of Tsai in Taiwan (30), reserving the procedure for patients who are “critically ill.” Our policy of aspirating the abscess when it can be localized clinically means in practice doing so in two-thirds of patients. Since he adopted a policy of restricting aspiration to critically i patients, Tsai has had good results, with case- fatality rates of 3.1% (831 cases, 14% aspirated) using emetine and chloroquine and 2.3% (132 cases, 13% aspirated) using metronidazole in addition to these two drugs. Comparison be- tween the results obtained in one center with those in another is of no great value. Neverthe- less it is worth repeating that there were no deaths among the 122 patients most recently admitted to our care with uncomplicated ame- bic liver abscess, all of whom were aspirated and treated with metronidazole. In view of this experience and the overall case-fatality rates in uncomplicated liver abscess (0.7%) and in the series as a whole, complications included (1.9%), it would appear unethical to abandon the procedure without good evidence that it is unnecessary. ‘There are two other reasons why frequent recourse to aspiration is preferred. One is that while it is hoped that metronidazole immedi-INVASIVE AMEBIASIS ately prevents further tissue invasion, proof that it does so is lacking. If rupture into thorax, peritoneum or pericardium is imminent when the patient is first seen, it seems reasonable to assume that this may still occur in the next day or so and also reasonable to believe that evacu- ation of the abscess via needle aspiration will prevent these highly dangerous complications. In one reported case (8) metronidazole without aspiration did not prevent rupture into the thorax. The other reason is that pyogenic liver abscess may give rise to a similar clinical and radiological picture, the only difference being that serological tests will be negative unless there has been past invasive amebiasis. If aspi- ration is avoided in such cases until metronida- zole has failed, or until the effect of other tissue ambecides is known, there will be an unjustifia- ble delay in making the correct diagnosis and commencing appropriate treatment. We be- lieve that aspiration serves two very useful functions: diagnosis and treatment. ‘A review of the literature of amebie pericar- ditis 25 years ago showed that the disease was, almost always fatal; indeed it had been recog- nized before death in only 2 out of 44 cases (4). The results of treatment in this series are in striking contrast and confirm those obtained in 25 cases collected over a three-year period from various wards of this hospital and treated simi- larly (9). Good results can be achieved by awareness that this dangerous complication of amebic liver abscess may masquerade as peri- carditis or heart failure or both, with incon- spicuous liver signs; by vigilance for the onset, of pericardial complications in patients with amebic liver abscess; by using diagnostic aids such as serological tests and liver scanning in cases of pericarditis of obscure etiology; and by relieving cardiac tamponade, preferably by needle aspiration. Our experience suggests that a combination of two tissue amebicides is bet- ter than one given alone but the numbers are too small for conclusive proof. SUMMARY Analysis of the records of 2074 patients with hepatic amebiasis admitted to one medical unit over a twenty-year period showed not only the efficacy of treatment with tissue amebicides and aspiration of the abscess when clinically indicated, but also the dangers of some of the complications. When the abscess remained confined to the 333 liver the case-fatality rate was low (0.7%). Met- ronidazole combined with aspiration appears to be the treatment of choice. In contrast the case-fatality rate was high (29.6%) when there was extension into the peri- cardium. Amebic pericarditis presents in three ‘ways: as pericarditis complicating a known case of amebic liver abscess, as cardiac failure of ‘obscure etiology and in shock from rapid car- diac tamponade. The latter two varieties are readily missed. When the pleurae and lungs are involved, the prognosis is relatively good (case-fatality rate 6.2%), probably because, hepato-bronchial fistula being common, amebic pus is often coughed up providing spontaneous drainage, and also because pleural effusions are readily Giagnosed and aspirated. Peritonitis arising from the rupture of a liver abscess carries a better prognosis than the in- testinal variety. Here the treatment of choice is, surgical drainage, since friable bowel wall does not complicate the procedure. ACKNOWLEDGMENTS ‘These analyses were undertaken as a tribute to the work of our colleagues, A. J. Wilmot and S. J. Powell, who are deceased. We wish to thank Prof. . Elsdon-Dew, until recently Director of the Amoe- biasis Research Unit, Durban, and his staff, espe- cially Dr. 8. E. Maddison and Dr. E. M. Proctor, who provided expert laboratory support; and Dr. H. R. J. Wannenburg, Medical Superintendent, King Edward VIII Hospital, for clinical facilities. Much of the laboratory work was aided by grants from the South African Medical Research Council, the United States Public Health Service and the Natal Provincial Administration, whose assistance we ac- knowledge with gratitude. REFERENCES 1, Adams, E. B.: Amoebie pericarditis. Medicine 8.A.,17; 1013, 1974 2. Bieler, E. U., Meyer, B. J., Jansen, C. R. and du Toit, D.: The liver in amoebic disease. A re- port on clinical and scintigraphic observations in 247 patients. S. Afr. Med. J., 48: 308, 1974. 3. Bookless, A. S.: Thoracic amoebiasis. J. R. ‘Army Med. Corps, 94: 52, 1950. 4. Carter, M. G. and Korones, 8. B.: Amebic peri- carditis, Review of the literature and report of acase, N. Engl. J. Med., 242: 390, 1950. 5. D'Cruz, I. A. and Ramamoorthy, K.: Amoebic pericarditis. J. Indian Med. Assoc., 49: 342, 1967, 6. Freeman, A. L. and Bhoola, K. D.: Pneumoperi- cardium complicating amoebic liver abscess. 8. Afr. Med. J., 50: 426, 1976.334 7. 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