Topics in Infectious Diseases Newsletter

October 2002 Amoebiasis

Amoebiasis is rare in developed countries, being most common among travellers, but is common in less developed countries, incidence approaching 100% in some populations. It is caused by the protozoan, Entamoeba histolytica. Reports of global prevalence of 480 million and incidence of 500 million were based on the misidentification of the morphologically indistinguishable Entamoeba dispar as Entamoeba histolytica. Entamoeba dispar is entirely nonpathogenic, while 5-15% of Entamoeba histolytica infections are symptomatic. The true global prevalence and incidence is 35-50 million, with an annual death rate of 40-110,000. The most common manifestation is intestinal amoebiasis. As mentioned, this is usually asymptomatic. On microscopy, no haematophagous trophozoites are seen, there are no changes observable at endoscopy and no specific antibodies are elicited. In the invasive form (amoebic colitis), there may be intermittent diarrhoea or acute dysentery with bloody, mucoid stools, colicky pains and rectal tenesmus. Weight loss, dehydration, fever, constipation, headache and drowsiness also occur in some cases. Onset is gradual, lasting one to several weeks. Colonic lesions and perforations and amoeboma (amoebic granuloma), a granulomatous tumour-like mass on the intestinal wall, may develop. Fulinating amoebic colitis is a severe form characterised by the passage of numerous bloody stools, generalised abdominal discomfort, colicky pains preceding evacuation, and rectal tenesmus (often constant and intense), with fever, dehydration and prostration. There may be intestinal haemorrhage or perforation. The most severe form is acute necrotising colitis with toxic megacolon, which often requires surgical intervention, occurs in 0.5% of cases and may be associated with > 40% of deaths. Peritonitis, appendicitis, cecitis, rectovaginal amoebic cutis and rectovesicular fistulas can all occur. Diagnosis in most laboratories is still by microscopic examination of fresh, warm, liquid faeces for haematophagous trophozoites. Sensitivity is only 30-50%. This may be improved by merthiolate iodine formalin concentration and staining of multiple stool specimens, by modified Ritchie formalin-ether concentration and examination of wet mounts and preparations stained by iron haematoxylin or trichrome for trophozoites and cysts, or by examining sigmoidoscopic swabs and scrpaings from large bowel ulcers and biopsies of rectal mucosa. Unfortunately, most laboratories still do not differentiate between E.histolytica and E.dispar - which can be done by indirect immunofluorescence with monoclonal antibodies. Culture adds little in the way of sensitivity or precision to microscopic methods. The most sensitive and specific method is antigen detection by ELISA on stool (sensitivity and specificity both >95%). The liver is the organ most affected outside the colon. It is invaded via the intrahepatic portal vessels. The infection may be self-limiting or may progress to a liver abscess. Amoebic liver abscess is much more common in men than in women or children. Liver enlargement is seen in 95-100% of cases (presenting complaint in 40%), right upper quadrant pain and tenderness in 66-100% (presenting complaint in 30%), nausea and vomiting in 60-75%, raised right diaphragm in 60%, epigastric pain and tenderness in 48-52%, chills in 42%, right

shoulder pain in 40% (presenting complaint in 3%), fever in 35-95% (presenting complaint in 40%), anorexia, weight loss and fatigue in 33-100% (presenting complaint in 5%), back pain in 30%, diarrhoea in 25-66% (presenting complaint in 15%), right chest pain in 6-50%, hiccoughs occasionally. Male gender, insidious onset, fever, history of chronic diarrhoea (only in 30-40% of patients), right pleuritic pain, single hepatic lesion of right lobe, liver enlargement, liver tenderness and liver filling defect favour the diagnosis, which is best confirmed by ELISA detection of antigen. The test on serum has sensitivity of 96% and specificity of 75-100%, while that on saliva has specificity of 70%. When performed on abscess fluid or pus, the specificity is 100%. Complications include rupture into the peritoneum (2-10% of cases), pleuropulmonary involvement and secondary bacterial infections. Other extraintestinal complications include splenic abscess, empyema and pericarditis. Diagnosis in these cases is similar to that for liver abscess. Cutaneous amoebiasis usually arises as an extension of intestinal amoebiasis, hepatic amoebiasis or amoebic lung abscess but on occasion results from primary infection. It manifests as a painful, rapidly spreading edematous ulceration of the skin, usually with fever and leucocytosis. Diagnosis is by examination of a biopsy. Genital amoebiasis may lead to destruction of the external genitalia. Metronidazole is the treatment of choice for all cases of invasive amoebiasis. Tinidazole is as effective as metronidazole and is better tolerated but is not available in the United States. Ornidazole is also just as effectve as metronidazole and better tolerated but is available in only a few countries. Chloroquine sulphate may be useful in the treatment of liver abscess when metronidazole fails. Emetine may be used as a last resort but has potentially fatal side effects. In amobeic colitis and in other invasive infections where cysts are present in the faeces, treatment with metronidazole should be followed by paromomycin, iodoquinol or diloxanide furoate (available only from the CDC in the USA) to destroy cysts. Nonsymptomatic cyst passers should be similarly treated to prevent the carrier state. This is one of the prime facets of prevention and control, others being public education on hygiene, feces disposal, food handling and sexual practices, provision of uncontaminated drinking water, and thorough washing of fruits and vegetables with effective disinfectants before consumption.

PERITONITIS http://www.bhj.org/books/liver/s3c05.htm Akses: 30 juli 2003

. CHAPTER CONTENTS

Acute peritonitis Clinical Features Investigations Treatment Chronic generalised peritonitis Localised peritonitis

Superimposed local and generalised peritonitis Bile peritonitis Mortality Table I

Amoebic peritonitis is considered to be the second most common complication of amoebic liver abscess after pleuropulmonary amoebiasis.1 The incidence varies from 5-10%.2-4 Vergoz and Hermanjat Guerins found it to be the most common form of rupture into the serous cavities. Manson-Bahr6 reported that the highest percentage (26%) of ruptures occurred into the peritonium. (Table I in Chapter I, Section Vl gives further data on the relative frequency of this condition.) Rogers7 found that this complication occurred more frequently in the left lobe abscesses (7.14%) than in the right (3.7%). Out of the seven cases of frank rupture of the abscess with generalized peritonitis, Ramchandran et al 4 found that the abscess was situated in the left lobe in three. Alkan et al 8 in 1961 noted that 4 out of 8 cases of perforation into the peritoneal cavity were associated with a left lobe abscess. This could probably be explained by the smaller bulk of the left lobe and its consequent inability in containing the rapidly expanding abscess. Moreover the anatomical relations of the left lobe reduce the chances of the formation of firm adhesions. The right lobe can easily accommodate an expanding abscess due to its larger volume. Leakage of the abscess appears to be as frequent a cause of peritonitis in right lobe abscesses as a frank rupture. Acute peritonitis When an abscess ruptures suddenly the natural restrictive factors like adhesions and paralytic ileus do not come into play early enough to restrict the spread of the pus. Thus, acute generalised peritonitis occurs. Very rarely in a case of liver abscess, an associated silent amoebic ulcer of the colon may perforate causing acute peritonitis. This complication is more likely in patients who also complain of associated diarrhoea or dysentery and whose colon is extensive studded with amoebic ulcers.

ClINICAL FEATURES The initial picture is similar to that of any peritonitis caused by perforation of a hollow viscus acute pancreatitis. 'Shock' is often considerable and the classical signs of an 'acute abdomen' are present. Death may occur at this stage. However,

if the patient survives, abdominal distension and signs of free fluid in the abdomen, very soon replace those of generalised guarding and board-like rigidity of the abdominal wall. At this stage perforation of a typhoid or tuberculous ulcer of the small bowel would be a very close differential diagnosis. The diagnosis depends upon a high index of suspicion. In the tropical countries every case of acute abdomen should be scrutinised for evidence of amoebic liver abscess by looking for intercostal tenderness, hepatomegaly, lump in the upper abdomen, presence of icterus, and suggestive investigations. INVESTIGATIONS Acute abdomen being an emergency, at the slightest suspicion of amoebic liver abscess it is prefers to institute the appropriate treatment even bed diagnostic confirmation becomes available. It must be emphasized here that every effort should be m to confirm the diagnosis of amoebic peritonitis when suspected, in view of the reports of reduced mortality in cases diagnosed early.9,10 in plain X-ray of abdomen elevation of right dome of diaphragm should be looked for. It is a common observation that often in cases of acute abdomen duff amoebic liver abscess, a plain X-ray of the abdomen does not show air under the diaphragm. Proctoscopic and sigmoidoscopic demonstration of amoebic ulcers in the bowel (observed in 30-40% cases) would aid the diagnosis. Liver scan and serological tests should be done if time and the patient's condition permit. Elevated serum alkaline phosphatase and serum bilirubin levels if already done in the early part of the illness, may help in the diagnosis. Finally, diagnostic tapping in all the four quadrants of the abdomen with a de Verres spring loaded needle should be tried. Detection of brownish pus would indicate the diagnosis of an amoebic liver abscess. TREATMENT The treatment of acute generalised peritonitis is surgical. This constitutes one of the most serious abdominal emergencies in tropical countries. Careful peritoneal toilette, drainage of the peritoneal cavity, drainage of the abscess cavity (if possible, through an extra-peritoneal route), careful aspiration of the subdiaphragmatic spaces and exclusion of multiple abscesses, must all be meticulously, yet speedily carried out. Pre- and post-operatively a course of emetine must be started together with parenteral tetracycline. When the patient can take drugs orally, chloroquine and a luminal amoebicide should be added.2 Chronic generalised peritonitis This is a very rare presentation. The pus leaking out of an abscess may spread slowly to cause chronic generalised peritonitis. In this case, the peritoneal cavity is a mass of adhesions and there are multiple small pockets of greyish yellow pus. 2 The main features are abdominal discomfort and distension and a progressive loss of weight. The abdomen, on palpation feels doughy. We have seen such patients but we could never make up our mind whether a colonic ulcer or a leak from an associated liver abscess had led to amoebic peritonitis. Yet again differentiating a perforated typhoid or tuberculous ulcer would be very problematic. Serological tests more than liver scanning could be of help in these cases. Peritoneal aspiration of brownish pus, and the demonstration of E. Histolytica in the same, may at times afford a clue to the diagnosis. As in acute peritonitis, laparotomy with meticulous peritoneal toilette is very essential although some authorities11 consider it to be indicated only for the establishment of a diagnosis.

Moreover, in the past, conservative drug therapy with emetine and chloroquine had been found to result in slow improvement and eventual recovery. 11 Some authorities consider the above entity to be hypothetical . Localised peritonitis Sometimes, when slow leakage occurs from a liver abscess, adhesions of the intestines and omentum to the site of the leak, restrict the spread of the pus and a mass is formed. An intra-abdominal mass in a patient suffering from amoebic liver abscess should suggest a localised intraperitoneal collection of pus. When the leak is into the lesser sac, initial acute epigastric pain and tenderness are marked. These may settle down after few days if the infection is walled off, the patient then presenting with "pyrexia of unknown origin" When the leak is posterior, the diagnosis of perinephric suppuration is often made, the amoebic pathology in the liver being diagnosed at the operation table. A 'leak' from an amoebic abscess may similarly be walled off in any of the subphrenic spaces leading to "pyrexia of unknown origin". A localised collection of pus, calls for surgical drainage which, however, is not urgent.2 Superimposed local and generalised peritonitis In such a presentation, the signs may be predominantly local, but there is some evidence of a wider peritoneal spread. Ileus and abdominal distension may develop. As the etiology is uncertain such a case would warrant early surgery with subsequent drainage, if necessary.12 However, the choice between the two lines of management remains a matter of individual preference. Gaseous abdominal distention calls for decompression by intermittent or continuous suction. Bile peritonitis Sometimes pure bile may seep into the abscess cavity from exposed biliary canaliculi in the absence of significant fibrous tissue reaction in the wall of the abscess.13 When such an abscess ruptures, bile peritonitis occurs. This is a particularly severe form of peritonitis.13 Bile laden peritoneal fluid is an excellent culture medium for the growth of gram-negative organisms. Thus, the risk of developing secondary bacterial infection and consequent gram-negative septicaemia is quite high.14 The treatment of bile peritonitis is particularly urgent though in no way different from that of acute generalised peritonitis. A broad spectrum antibiotic must always be added. Culture and sensitivity of the organism, if isolated should guide the institution of specific antibiotics. Mortality Peritonitis is one of the dreaded complications of amoebic liver abscess. 10,11 and has been associated with a high mortality in the past. Earlier workers like MansonBahr6 and Rogers7 regarded this complication as most serious and likely to terminate fatally.15 (Table I) Lamont and Pooler16 feel that provided the patient survives the initial effect of rupture, the prognosis seems favourable and the after effects are slight. Recently, more reports of timely diagnosis and good recovery from this condition are being published.3 Biliary peritonitis has a graver prognosis. Septicaemia and secondary bacterial peritonitis would appreciably increase morbidity and mortality.13 If on opening up the abdomen, the surgeon

finds the abscess intact, but sees a perforation of an acutely inflamed amoebic colon, the prognosis of the patient would be grave, as even handling this colon, which is like a wet blotting paper, is hazardous. TABLE I Mortality rate in amoebic peritonitis due to amoebic liver abscess Author Vergoz and Hermanjat Guerins5 Wilmot, A J11 DeBakey and Ochsner1 Archampong3 DeBakey and Jordans15 References: Year 1932 Mortality rate 46.1%

1949 1951 1973 1977

21 .00% 75.00% 50.75% 75.00%

1. Ochsner, A, and DeBakey, M E, Surg. Gyn. Obst. (I A S. ), 1951,92, 209

2. Wilmot, A J, Clinical Amoebiasis, Blackwell Scientific Publications, Oxford, 1962. 3. Archampong, E Q. and Clark, C G. Ann. Roy. Coll. Surg. Eng., 1973, 52, 36. 4. Ramachandran, S. and Coonatillake, H D, Brit.J. Surg., 1974, 61, 353 5. Vergoz, P. and Hermanjat Guerin, R P. Rev Chir., 1932, 70, 680. 6. Manson-Bahr, P. Lancet, 1923, 1, 941 7. Rogers, L, Lancet, 1922, 1, 463. 8. Alkan, W I, Kalmi, B. et al, Ann Int Med., 1961, 55, 800. 9. Sherlock Sheila, Diseases of the Liver and Biliary System, Blackwell Scientific Publications, Oxford,1975. 613 10. Macleod, J, Davidson's Principles and Practice of Medicine, Churchill Livingstone, Edinburgh, 1974. 11. Wilmot AJ, DM Thesis, University of Oxford, 1949. 12. McCarty, R B. and Schnedorf, I G, Am J Surg, 1946, 71, 401 13. Ramachandran, S. Induruwa, P A C, et al, J Trop Med Hyg., 1975, 78, 236 14. Miles, R M, and Jack, M S. Surgery, 1953, 34,445. 15. DeBakey M E and Jordan G L Surg Clin N.Am, 1977, 57, 325

16. Lamont, N M, and Pooler N R. Quart. J Med. 1958, 27, 389