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A 7-month-old girl developed cutaneous amebiasis of the perianal and genital areas in association with amebic dysentery. The diagnosis was based on the identification of Entamoeba histolytica by skin biopsy. She was treated with dehydroemetine and metronidazole with excellent results. This is only the eighth reported case of this disease in a child.

Infection with single or multiple species of intestinal protozoa is common in humans and can result in either asymptomatic colonization or symptoms of intestinal disease. Entamoeba histolytica serves as a paradigm for invasive colonic protozoal infection. The key to diagnosis and treatment of amebiasis is knowledge of the epidemiologic risk factors and clinical manifestations, a rational approach to diagnosis, and an understanding of the sites of action and uses of anti-amebic drugs. This knowledge of treatment provides a context for consideration of intestinal infection with less common protozoan pathogens such as Dientamoeba fragilis and Balantidium coli and 'nonpathogenic' protozoa such as Blastocystis hominis and Entamoeba coli.

Ivermectin is a safe, effective, and relatively well-tolerated drug for the treatment of human onchocerciasis. However, due to side effects of the drug, large-scale ivermectin distribution without medical supervision is not recommended. The mechanisms involved in the pathogenesis of ivermectin-induced adverse reactions are not yet known. Since onchocerciasis patients are likely to have concurrent parasitic infections, we investigated whether side effects that occur after ivermectin treatment could be related to the presence of parasite eggs and cysts in stool samples prior to treatment. One hundred twenty-nine onchocerciasis patients were treated with a single dose of ivermectin (150 micrograms/kg) and side effects were graded according to the classification of Greene and others. Stool samples were collected before and three days after treatment. A high percentage (80.5%) of the patients reported adverse effects (57% mild, 14.1% moderate, and 9.4% severe reactions). Most (95.1%) of the patients had one or more concurrent parasitic infections. No relationship could be found between the occurrence and extent of side effects and the severity of concurrent intestinal parasitic infections. However, side effects were significantly correlated with pretreatment microfilarial counts. Ivermectin treatment did not induce significant short-term changes in Trichuris trichiura or Schistosoma mansoni egg counts. However, a significant reduction in Ascaris lumbricoides egg counts and Entamoeba coli cyst loads was observed; a cure rate of 46% for cysts was reached. In contrast, hookworm egg production increased after ivermectin treatment. Further studies are required to verify ivermectin-induced changes in cyst and hookworm loads as well as the significance of these findings.

We report a case of double primary amoebic brain abscess in a 22 year old man, with signs of intracranial hypertension and deficit. Computed tomography found two hypodense lesions, not suggestive of pyogenic abscesses. Aspiration of one of the two abscesses, revealed the organism, and the two abscesses regressed in response to medical treatment. The authors insist on the rarity of these abscesses, their gravity, and the difficulty of the diagnosis.

Entamoeba histolytica, the causative agent of amebiasis, was first described in 1875. Although a large number of people throughout the world are infected with this organism, only a small percentage will develop clinical symptoms. Morbidity and mortality due to E. histolytica vary from area to area and person to person. Recent findings have suggested that there are pathogenic and nonpathogenic strains of E. histolytica that can be differentiated by isoenzyme (zymodeme) analysis, monoclonal antibodies, and DNA probes. Whether pathogenicity is a genotypic trait or can be changed by environmental influences has not been resolved. Exchange of genetic material between strains of amebae can influence zymodeme patterns. Currently, detection of E. histolytica infections depends on examinations for ova and parasites and on serologic tests; however, the development of monoclonal antibodies and DNA probes specific for pathogenic zymodemes may be beneficial for clinical laboratory testing and therapeutic decisions when approved tests become available. A better understanding of the mechanisms of pathogenicity at the molecular level is evolving and should promote the development of vaccines and better target selection for therapeutic agents.

Amoebae were isolated from an arthritic knee of a male patient. The organisms grew in Egg Yolk Infusion medium, and in Diamond's Biosate Iron-Serum-33 medium, which contained Trypanosoma cruzi, and were identified microscopically as Entamoeba histolytica. Furthermore, amoebae-like organisms in aspirate and cultures were immunocytochemically identified using monoclonal antibodies against E. histolytica. On the basis of the morphologic and immunologic observations, it was concluded that the knee lesion was caused by infection with E. hystolytica. The knee lesion resolved following treatment with metronidazole. This case is the first report of an amoebic infection of the knee joint.

Diloxanide furoate is used for treating asymptomatic or mildly symptomatic persons who are passing cysts of Entamoeba histolytica. The Centers for Disease Control (Atlanta) released this drug for 4,371 treatment courses from 1977 through 1990. Of the 2,815 report forms (64%) returned, 656 adverse effects were reported for 390 treatment courses (14%); they included flatulence (260), diarrhea or cramping (100), nausea (93), headache (17), disorientation or dizziness (9), and diplopia (4). During 1984-1990 uniform collection of data allowed more detailed analysis of toxicity and efficacy; fewer adverse effects were reported for persons aged 20 months to 10 years than for persons aged greater than 10 years (6 of 206 [3%] vs. 89 of 763 [12%], relative risk = 0.27, 95% confidence interval = 0.12 less than relative risk less than 0.61). Parasitological cures were achieved during 497 (86%) of the 575 treatment courses (52%) administered to asymptomatic persons who were passing cysts, who had received a full 10-day treatment course, and for whom results of a follow-up stool examination (greater than or equal to 14 days post-treatment) were available. Diloxanide furoate is safe and effective for treating asymptomatic persons who are passing E. histolytica cysts and may be particularly well tolerated in children.

Granulomatous hepatitis make up a group of conditions of various aetiologies. The diagnosis of granulomatous hepatitis is histologic, since the aspect of the granulomatous lesion is not always indicative of a specific disease. It is important to take into consideration for the aetiologic diagnosis a good response to a specific therapy or the execution of complementary examinations. The 25% of granulomatous hepatitis remain undiagnosed.

The importance and limitations of microscopic differential diagnosis of Entamoeba histolytica in asymptomatic carriers is reviewed. The possibility that some nonpathogenic strains of E. histolytica could be Entamoeba hartmanni is discussed. The imperative necessity to encourage research in epidemiology and diagnosis is emphasized. The need to know the prevalence in Mexico and distinguish E. histolytica from E. hartmanni is also discussed. This differential diagnosis is fundamental in the treatment of carriers and in epidemiological studies. Treatment must be directed only to acute and chronic patients and asymptomatic carries who prepare food. Appropriate drugs are still metronidazole and quinolines.

Invasive amebiasis is a very serious health problem in Mexico as it is presumably related to the presence of virulent strains of Entamoeba histolytica and poor hygienic and sanitary conditions; other factors related to invasive amebiasis are undernutrition, alcoholism, and homosexuality. We present three patients with pulmonary amebic hematogenous abscess. Clinically all patients had the typical "chocolate" exudate. The three patients had pulmonary consolidations by chest roentgenogram; one of them had multiple opacities with air fluid level, and the others had an isolated opacity with air fluid level. The ultrasound and hepatogammagram were negative for diaphragmatic communication in all; in one of them the pneumoperitoneum was negative for diaphragmatic communication. The transthoracic needle biopsy of the lesions was positive to ameba in two patients. The serologic tests were positive in all. We treated the patients with metronidazole and emetine during 10 days; since the clinical picture and the radiologic findings did not remit completely, we gave a second course of metronidazole during 10 days more and achieved complete resolution.

A middle-aged female with an atrial septal defect (secundum type) presented with a primary pulmonary amoebic abscess. She was successfully treated with antiamoebic therapy. One year later she presented with a similar lung abscess which again responded to antiamboebic treatment. Attention is drawn to the fact that a patient with a left to right shunt can present with a recurrent rare primary parasitic infection of the lung.

We performed a retrospective review of screening parasitology examinations on a Cambodian refugee population served by an urban neighborhood health center. Five-hundred twenty of 1084 patients were examined for ova and parasites either by purged stool, which was examined immediately, or preserved stool, examined at a teaching hospital and proprietary laboratories. Overall, 335 (64 percent) of the tested patients had at least one parasite. The prevalence of infection varied by test technique (purged stool examined immediately, 86 percent; preserved stool examined at a hospital, 65 percent; preserved stool sent to a proprietary laboratory, 31 percent, P less than 0.01). In this population where Entamoeba histolytica infection was 44 percent as measured by the purged warm stool technique, the cold preserved stool test had a measured relative sensitivity of 33 percent. Assuming a selectivity of 99 percent, it would take eight negative tests to reach a greater than 95 percent negative predictive value. The high rate of intestinal carriage of pathogenic parasites in this population and the insensitivity of commonly available diagnostic tests make routine presumptive treatment of intestinal parasites an option when the purged stool examination is unavailable.

A cohort of 99 subjects, members of the flight staff of Lufthansa German airlines, all infected with Entamoeba histolytica, were followed over a period of 2.5 years to monitor their clinical and parasitological status. All but 4 of the subjects were infected with non-pathogenic zymodemes of E. histolytica and had negative amoebic serology, and most were clinically well. One male heterosexual carrying a pathogenic zymodeme was found, despite massive treatment regimes, to carry the infection persistently for 12 months. Most non-pathogenic infections were left untreated.

417 patients suffering from intestinal amoebiasis were randomly allocated to 6 different treatment groups in a controlled study in 3 District Hospitals in Kenya. The patients received either aminosidine (A), etophamide (E), nimorazole (N), or the combinations NA, NE, EA. Treatment in all cases was given twice daily for 5 days. Before and after treatment, rectosigmoidoscopy was done in each patient, and stool examination with characterization of invasive (IF) and non invasive (NIF) forms of amoeba was done daily throughout treatment, and on Days 15, 30 and 60 of follow-up. Clinical cure was good after all the treatments, varying from 90 to 100%; parasitological cure at the end of treatment was 100% in the NA and EA treatments groups, and 98% in A group. The incidence of relapses was nil in the EA group, followed by 3% in NA and 6% in A groups. Anatomical cure (healing of ulcers) was 97.8% in the NA group, 95.5% in the N group and 88.5% in the A group. Drug tolerance was excellent or good after all the treatments, except that the EA combination produced diarrhoea in 76.5% of patients. Overall analysis of the findings, including tolerance of the various treatments, showed that aminosidine either alone or in combination with nimorazole gave the best results. Ulcers seen on rectosigmoidoscopy were more common in patients excreting invasive forms of amoebae in their stools.

The authors have treated: a) 48 cases of E. histolytica histolytica intestinal amoebiasis by a single dose of 35 mg/kg of secnidazole with 98 p. 100 of parasitological success; b) 122 cases of E. histolytica minuta with several procedures: a unique dose of 25 mg/kg gives no success in 16.6 p. 100 of the cases, but the same single dose during three days gets only 2 p. 100 of failure; c) 22 cases of hepatic amoebiasis by a daily dose of 25 to 33 mg/kg during 5 days with success in every cases. Tolerance has been excellent. These short cures, facilitated by the long half-life of secnidazole are particularly easy to apply in developing countries.

General descriptions and monographs of the five parasites most likely to be seen in U. S. patients are presented. The appended monographs are designed to be a starting reference for answering drug information questions regarding these parasites. The drugs covered in the monographs are listed in the order of suggested use.

Diphetarsone is an arsenical used in the treatment of intestinal amoebiasis and trichuriasis. It is an efficacious drug with minimal toxicity. However, in this report, a heretofore undescribed reaction, that of generalized angioedema, is presented. A review of diphetarsone toxicity is also presented.

Recently, Entamoeba polecki was identified for the first time in our parasitology laboratory in stool specimens from eight Southeast Asian refugees. This ameba has been reported infrequently in the Western world; most reported cases have been from the New Guinea region. In most previously described patients and in our patients, no definite gastrointestinal symptoms could be directly attributed to E. polecki infection. Morphologically, E. polecki may mimic the pathogen E. histolytica and also nonpathogens such as E. coli. These species are most readily distinguished by studying encysted forms. In contrast to E. histolytica and E. coli, E. polecki characteristically has uninucleate cysts. Both pigs and monkeys naturally harbor E. polecki, but four of the patients in this series had no apparent contact with these animals. Other modes of infection may be human-to-human transmission or acquisition from other domestic animals. Six of our eight patients were treated successfully with one course of metronidazole in a regimen similar to that used for E. histolytica infection. In the two other patients, repeated courses of therapy eradicated the infection. Because of the recent increase in number of Southeast Asian immigrants to the United States, E. polecki may be identified more frequently than in the past. Physicians and laboratory personnel should be familiar with this organism, because it may be confused with E. histolytica or may act as a pathogen.

Eighty-nine patients infected with Entamoeba histolytica, non-pathogenic amoebae or Trichuris trichiura were studied prospectively to determine the safety and efficacy of diphetarsone therapy. An additional 75 patients were studied retrospectively to assess further the efficacy of diphetarsone in the treatment of E. histolytica cyst passers. Side effects were noted in 9% and included gastrointestinal upset, lightheadedness and headache. Transient liver function abnormalities were recorded in 5.6%. diphetarsone was completely effective in the treatment of Dientamoeba fragilis, Entamoeba hartmanni, Iodamoeba buetschlii and Trichuris trichiura. 99% of the patients with E. histolytica, 97% of those with E. coli and 98% of those with Endolimax nana were cured.

A series of bisamidines of 2,6-diaminoanthraquinone was synthesized and tested against cecal and hepatic forms of Entamoeba histolytica infections in rats and hamsters, respectively. A number of compounds were found to have good activity against infections in both species.

A case of cutaneous amoebic ulcer, a rare extra-intestinal lesion in the skin of the leg, is presented. The diagnosis was made after examination of ulcer exudate and skin biopsy. The possible mode of infection of the skin is discussed.

An epizootic of reptilian amebiasis seems to have caused the death of 15 to 16 large and valuable captive snakes (boas, pythons, and anacondas) occupying one of 5 large display dioramas in the Steinhart Aquarium of the California Academy of Science, Golden Gate Park, San Francisco. Subsequent review of previous snake deaths in the colony indicated that of 464 snakes that had died since early 1969, 89 snakes had intestinal or hepatic lesions, and 80 of these snakes had pathologic features which involved severe intestinal ulceration, hemorrhage, and massive enteritis, with or without hepatic necrosis and destruction, condition compatible with Entamoeba invadens infection. The present epizootic began in November, 1972, with the death by acute enteritis of a red-tailed boa constrictor (Boa constrictor amarali) and was followed by the loss of 15 other large boids and pythonids. The affected snakes became immobile, refused to feed, and began to die 10 weeks after the death of the red-tailed boa. Seven boa constrictors, 4 pythons, and 4 anacondas from the same diorama died during the ensuing 10 weeks. Entamoeba invadens trophozoites were identified in the stool of the remaining living snake, a 3-m boa constrictor, and in the liver and the intestinal tissue of 1 of the dead boas examined microscopically. The parasite was also found in the stool of a giant Burmese python (Python molurus bivittatus) that died in the adjacent diorama and in the tissues of a blue-tongued skink (Tiliqua scincoides), separately housed, that died of enteritis during this period. Amebic cysts were recovered from turtle and alligator fecal samples taken from a central "swamp," or reservoir, draining the dioramas, water that is returned to the snake display areas after passage through a biological sand-gravel filter and ultraviolet radiation exposure. Cultures from these stools were positive and proved lethal to an experimentally infected boa constrictor. Treatment of the surviving snake in the affected diorama with metronidazole at the dose rate of 275 mg/kg proved rapidly effective; toxicosis was not observed. Other snakes and lizards suspected of having the infection were similarly treated and returned to normal behavior and feeding patterns. Epidemiologic considerations review the probable mode of introduction and spread of this highly lethal snake pathogen and recommendations are made for avoiding infection, prophylactic treatment, and handling of similar epizootics when they do occur among captive reptiles in aquariums, zoos, and research laboratories.

The second symptomatic case of Entamoeba polecki infection, the first to respond to therapy, is reported. The patient experienced intermittent episodes of abdominal cramps, diarrhea, nausea, and malaise associated with large numbers of E. polecki cysts in the stool. Following treatment with diloxanide furoate and metronidazole, all symptoms cleared and the parasite was no longer present in the stool.

Since 1961, when Cosar pointed out for the first time that metronidazol was a useful pharmacological agent against E. histolytica, several authors have demonstrated its effectiveness against invasive amebiasis in its colonic or extraintestinal variety. The obtained results with metronidazol were so far better compared with the rest of the known amebecides, that in 1974, Elsdon Dew stated that a new era in the medical treatment of the amebiasis had started with the forthcoming use of the agent. However, the frequent and important adverse collateral effects produced in a good number of patients have forced to look for other nitroimidazole derivates, hopefully more efficient and, of course, better tolerated. Thus, the tinidazole, ornidazole, flunidazole, romidazole, ornidazole, flunidazole, dimetridazole, satranidazole, nitrimidazine, panidazole, have been tried and some others are still subject to experimentation, such as the Ro 7-0207 (alpha-chlorometil-2-metil-5-nitro-1-imidazol), the phexinidazole (HOE 239) and the CG 10213-Go from CIBA-Geigy and no significant advantage has been found over the metronidazol. The phexinidazole turned out to be twice as effective as the metronidazole in the experimental hepatic amebiasis of the golden hamster. This fact must be confirmed or discarded in the human hepatic amebiasis.

More than 135 new 2-methyl-5-nitroimidazoles substituted in 1-position and 1-methyl-5-nitroimidazoles substituted in 2-position were investigated for their activity against various protozoan species, in particular Entamoeba histolytica in the golden hamster, Trichomonas fetus, Trypanosoma brucei and T. cruzi in the NMRI mouse. Among the nitroimidazoles substituted in the 1-position only two preparations exhibited a similar effect as metronidazole preparations exhibited a similar effect as metronidazole against T. fetus. In the class of the nitroimidazoles substituted in the 2-position 16 compounds were as effective as metronidazole, 19 showed an effect superior to metronidazole, 1 was as good as tinidazole and 2 exhibited an activity superior to tinidazole against T. fetus. Only few compounds displayed any amoebicidal activity. Of the mono and bis-hydrazones of 1-methyl-5-nitroimidazole-2-aldehyde substituted in the 2-position 3 compounds had an amoebicidal effect 2 to 8 times stronger than that of metronidazole. Only few representatives of the 1-methyl-5-nitroimidazoles substituted in the 2-position produced a useful trypanocidal effect when given in relatively high doses. The structure-activity relationship of 5-nitroimidazole derivatives has been discussed.

To examine whether Entamoeba histolytica is the cause of a variety of intestinal disorders, as often implicated, a two-part study was conducted. In part 1, 184 patients attending a gastroenterology clinic and needing a sigmoidoscopy had a rectal biopsy specimen and a stool sample cultured for E histolytica. Part of the biopsy specimen was examined histologically. In addition, serum was tested for antibody to E histolytica. 34 (18.7%) patients were culture positive. There was no correlation between the culture results and patients' symptoms except for diarrhoea, which was more common in the culture-negative group, or with histological or serological findings. In the second part of the study, 15 culture-positive patients were followed up untreated for a mean (+/- SD) of 8.6 (+/- 4.9) months, range 1-18. In all 15 patients spontaneous eradication of the parasite occurred, and in none did symptoms of invasive amoebiasis develop. Thus E histolytica seems not to be responsible for many of the bowel complaints commonly attributed to it. In these cyst passers the cysts are probably incidental to an irritable bowel syndrome or some other organic disease. There seems to be little justification for treating cyst passers since eradication of the parasite occurs spontaneously and the danger of invasive amoebiasis is negligible. Such a practice would result in an enormous saving on the cost of drugs.

The anti-amoebic action of the bipyridyl antibiotic caerulomycin was assessed in vitro and in vivo using various strains of Entamoeba histolytica from polyxenic, axenic and monoxenic cultures. Minimum inhibition concentrations of caerulomycin (metronidazole) were 7.5 (5), 15.6(1.95) and 60 (2.5) micrograms/ml against polyxenic, axenic and monoxenic cultures of E. histolytica, respectively. The ED50 values ascertained in golden hamsters (extraintestinal amoebiasis) and rats (intestinal amoebiasis) after the oral route were 136 and 199 mg/kg (X4), respectively. Metronidazole proved to be approximately four times more active against tissue forms of E. histolytica than caerulomycin [ED50 of metronidazole: less than 40 mg/kg (X4)]. The antibiotic was slightly superior to metronidazole in its action on lumen forms of E. histolytica [ED50 of metronidazole: 233 mg/kg (X4)]. The antibiotic was in some cases toxic to hamsters and rats within the therapeutic range.

1,4-Bis-[1-methyl-5-nitroimidazolyl-(2-methyleneimino)]-piperazine (HOE 316) administered orally produces an effect which is clearly superior to that of metronidazole against Entamoeba histolytica in the golden hamster and slightly inferior against Trichomonas fetus and T. vaginalis in the mouse. The acute tolerance of the compound is very good (LD 50% greater than 10 g/kg body weight). It is assumed that the possible main metabolite of HOE 316 is a monohydrazone: 1-methyl-2-(4-amino-piperazino-1-imino-methyl)-5-nitroimidazole.

Five to nine-year-old Aboriginal children on Mitchell River Community maintained a satisfactory growth rate in the presence of multiple infections with intestinal parasites. Intensive treatment was successful in eliminating Giardia lamblia, Entamoeba histolytica, and Strongyloides stercoralis infections, but reinfection with G. lamblia was rapid. Treatment failed to produce any growth spurt in the group. This may have been due to the rapidity of reinfection, but raises the question of whether intestinal parasites contribute significantly to growth retardation or whether growth retarded children have an immune deficit rendering them more susceptible to parasitic infections.

Basically substituted 2,6-diacetaminoanthraquinones proved to have an interesting in vivo effect against Entameba histolytica, but this effect was markedly exceeded by that of the series of the 2,6-diamidinoanthraquinones. A number of compounds of this series revealed a significantly stronger extraintestinal effect in the golden hamster than the standard amebicides metronidazole and tinidazole, but they were not superior to these compounds in their trichomonacidal effect, which was in general only a moderate one. In both substance classes, the amebicidal effect was confined to 2,6-disubstitution. Variations of the anthraquinone system resulted in a loss of activity. The structure-activity relationships are discussed.

On a global scale, 480 million people were recently estimated to be infected with Entamoeba histolytica and some 48 million people suffer from invasive amoebiasis. The latter, in the intestinal and extra-intestinal forms, accounts for 40 000 to 110 000 deaths annually. In view of this considerable mortality and morbidity, more research is urgently needed so that more effective control strategies may be introduced.This Update article reviews the magnitude of the problem, clinical and laboratory diagnosis, present treatment and prevention measures, possible control strategies, and research priorities.