Antiamoebic drugs for treating amoebic colitis

 

Characteristics of included studies [ordered by study ID]

Asrani 1995

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: open Inclusion of all randomized participants: 100% for parasitological assessment; 93.4% (898/961) for clinical assessment
Participants	Number: 961 enrolled, 898/961 (93.4%) included in analysis of clinical outcome; 591/591 (100%) positive for E. histolytica on stool examination at baseline included in analysis of parasitological outcome; 63/961 (6.6%) lost to follow up or were protocol violators (33 in metronidazole group, 30 in combination therapy group); 1 participant in the combination group withdrawn from the study due to allergic reaction on the first day of treatment Inclusion criteria: adult male and nonpregnant female patients > 12 years of age with clinical symptoms of intestinal amoebiasis and/or presence of trophozoites or cysts of E. histolytica in stool specimens; laboratory diagnostic method not specified Exclusion criteria: history of alcohol abuse; hypersensitivity or contraindications to any of the study drugs; systemic amoebiasis; severe illness; and/or persistent vomiting
Interventions	Metronidazole: 400 mg thrice daily orally for 5 days Metronidazole and diiodohydroxyquinoline: fixed-drug combination of metronidazole (200 mg) plus diiodohydroxyquinoline (325 mg) (Qugyl by Sil Pharma, Bombay, India) given as 2 tablets thrice daily for 5 days Treatment period was extended to 10 days in both groups when 5 days treatment was inadequate to clear the stools of E. histolytica
Outcomes	Parasitological cure: clearance of E. histolytica in stool specimens at end of treatment Clinical cure: remission of clinical symptoms on days 5 and 10 after start of treatment Adverse events: clinical adverse events monitored by study personnel during treatment Not included in this review: average daily frequency of stools on admission and on day 5 and day 10 of treatment; overall clinical response (rated as "poor" if < 25% relief and not tolerated, "fair" if 25% to 49% relief and not well tolerated, "poor" if 50% to 74% relief and well tolerated, or "excellent" if 75% to 100% relief and well tolerated)
Notes	Location: various cities (not specified) in India Date: 1995 (date of publication only; actual study period not reported) Source of funding: not stated; one of the authors (Dr SJ Phaterpekar) is connected with Searle (India) Limited, Bombay, India Several attempts were made to inquire about the study methods, but no response was obtained from the primary author

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Awal 1979

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Methods	Generation of allocation sequence: random-numbers table Allocation concealment: unclear Blinding: open Inclusion of all randomized participants: 100%
Participants	Number: 66 enrolled and analysed Inclusion criteria: adults and children with clinical signs and symptoms of intestinal amoebiasis and motile haematophagous trophozoites of E. histolytica in fresh stool specimens and on sigmoidoscopy; laboratory diagnostic method for stool examination was not specified Exclusion criteria: antiamoebic treatment during the previous 4 weeks; pregnant women; dehydrated patients; those with evidence of hepatic or renal dysfunction
Interventions	Tinidazole: 2 g single oral dose daily for 3 days Tinidazole: 2 g single oral dose daily for 2 days Metronidazole: 2 g single dose for 2 days
Outcomes	Parasitological cure: eradication of E. histolytica from stools on day 30 from start of therapy Clinical cure: resolution of baseline symptoms of intestinal amoebiasis on day 30 from start of therapy Adverse events: voluntary reporting of side effects by the participants; laboratory tests monitored before and after treatment including complete blood count, serum bilirubin, alkaline phosphatase, and liver transaminase (SGOT)
Notes	Location: hospital in Bangladesh Date: 1979 (date of publication only; actual study period not reported) Source of funding: not stated

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Batra 1972

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: open Inclusion of all randomized participants: 100%
Participants	Number: 40 enrolled; 40 analysed; 2 withdrawn from treatment because of severe gastrointestinal adverse effects Inclusion criteria: acute amoebic dysentery and stool specimens positive for trophozoites of E. histolytica by saline and iodine smears Exclusion criteria: pregnant women; critically ill patients; those with neurological and cardiac abnormalities or disturbed renal functions
Interventions	MK- 910: each arm used 1-methyl-2 -(4'fluorophenyl)-5-nitroimidazole (MK-910) at a different mg/kg body weight day in 3 divided doses orally for 10 days 0.5 mg/kg body weight 1.0 mg/kg body weight 2.0 mg/kg body weight 3.0 mg/kg body weight
Outcomes	Parasitological response: disappearance of E. histolytica from stools on day 5 and day 10 of treatment, both on saline and iodine smear examination and on stool culture using NIH medium Clinical response: reduction in clinical signs and symptoms Adverse events: monitored by study personnel during treatment; laboratory tests monitored before and on day 5 and day 11 of treatment including complete blood count, platelet count, urinalysis, blood urea, blood sugar, serum bilirubin, alkaline phosphatase, liver transaminases (SGOT, SGPT), thymol turbidity tests, and 12-lead electrocardiogram Not included in this review: number of hours from start of treatment to reduction in diarrhoea, tenesmus, and bloody stools; disappearance of colonic ulcers on sigmoidoscopic examination on day 5 and day 11 of treatment
Notes	Location: hospital in New Delhi, India Date: 1972 (date of publication only; actual study period not reported) Source of funding: Merck, Sharp and Dohme

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Botero 1974

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: unclear; reported as "double-blind", but blinding of participants, care provider, and outcome assessors not described Inclusion of all randomized participants: 95.8% (115/120)
Participants	Number: 120 enrolled; 115 analysed; 5 lost to follow up; 1 participant in the Ro 7-0207 terminated treatment after day 6 because of adverse effects Inclusion criteria: adult males with clinical symptoms of intestinal amoebiasis and confirmed by the presence of E. histolytica in the stools examined by direct and Ritchie formalin-ether concentration methods Exclusion criteria: not stated
Interventions	Ro 7-0207 (ornidazole): 2 x 250 mg capsules twice daily for 10 days Metronidazole: 2 x 250 mg capsules twice daily for 10 days
Outcomes	Parasitological response: clearance of E. histolytica from stools at the end of treatment and on at weekly intervals on follow up for at least 1 month Relapse: reappearance of E. histolytica in the stools within 1 month after becoming negative at the end of treatment Clinical response: disappearance or improvement of clinical signs and symptoms on day 5, at the end of treatment, and at weekly intervals during follow up for at least 1 month Adverse events: clinical adverse events monitored for all participants but cardiovascular, neurological, and laboratory monitoring only for the first 20 participants (laboratory tests not specified)
Notes	Location: hospital in Medellin, Colombia Date: 1974 (date of publication only; actual study period not reported) Source of funding: not stated

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Botero 1977

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: unclear; reported as "double-blind", but blinding of participants, care provider, and outcome assessors not described Inclusion of all randomized participants: 100%
Participants	Number: 100 enrolled and 100 analysed Inclusion criteria: adult males with clinical symptoms of intestinal amoebiasis and stools positive for E. histolytica examined by direct and Ritchie formalin-ether concentration methods Exclusion criteria: not stated Concomitant intestinal infection: 26 participants in panidazole group and 27 participants in metronidazole group had concomitant infection with other enteric protozoa and intestinal helminths (Entamoeba coli, Endolimax nana, Iodamoeba butschlii, Ascaris lumbricoides, Trichuris trichiura, Necator americanus, Strongyloides stercoralis)
Interventions	Panidazole: 2 x 250 mg tablets (500 mg), 4 times daily for 6 days Metronidazole: 2 x 250 mg tablets (500 mg), 4 times daily for 6 days
Outcomes	Parasitological cure: eradication of parasites in any of the post-treatment laboratory examinations Clinical response: improvement or disappearance of symptoms during weekly follow up for 4 weeks after treatment Adverse events: clinical adverse events monitored during treatment and on follow up; laboratory tests monitored before and after treatment including complete blood count, erythrocyte sedimentation rate, blood urea nitrogen, liver transaminases, urinalysis, and electrocardiogram Not included in this review: number of stools passed in 24 hours on day 3 and day 6 of treatment and on days 7 and 21 after treatment; clearance of E. histolytica in asymptomatic carriers
Notes	Location: Colombia Date: 1977 (date of publication only; actual study period not reported) Source of funding: not stated

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Chunge 1989

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: double (only participants and laboratory staff examining stools were blinded) Inclusion of all randomized participants: unclear; only those who completed the required stool examinations were included (225 participants) and number randomized not stated
Participants	Number: number enrolled and randomized not stated, 225 analysed Inclusion criteria: adults and children presenting with at least any 4 of the following symptoms of intestinal amoebiasis: abdominal pain, diarrhoea, constipation, mucoid stools, malaise, flatulence, nausea, fever, tenesmus, and stool specimens positive for trophozoites or cysts of E. histolytica by direct smear or formol-ether concentration technique Exclusion criteria: pregnant women
Interventions	Tinidazole (Fasigyn): 2 g single oral dose daily for 3 days Tinidazole (Tynazole): 2 g single oral dose daily for 3 days Metronidazole (Flagyl): 400 mg thrice daily orally for 5 days Metronidazole (Metrozol): 400 mg thrice daily orally for 5 days
Outcomes	Parasitological cure: absence of trophozoites or cysts from stool specimens on day 6 after start of treatment Clinical cure: absence of any 4 of the symptoms initially present at day 6 after start of treatment
Notes	Location: outpatient departments of 3 district hospitals in Kiambo, Kilifi, and Machakos in Kenya Date: 1989 (date of publication only; actual study period not reported) Source of funding: Farmitalia Carlo Erba

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Davila 2002

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: unclear; reported as "double-blind", but blinding of participants, care provider, and outcome assessors not described Inclusion of all randomized participants: 100%
Participants	Number: 275 enrolled; 105/275 (38%) had E. histolytica or E. dispar infection (25 single infection and 80 mixed infection with other intestinal parasites) and were included in the review and analysed Inclusion criteria: children with stool specimens positive for E. histolytica/E. dispar and/or other intestinal parasites by direct smear or Kato-Katz technique Exclusion criteria: not stated
Interventions	Nitazoxanide: 100 mg/5 mL twice daily orally for 3 days Quinfamide: 100 mg/5 mL single oral dose; mebendazole 100 mg/5 mL twice daily orally for 3 days was added to quinfamide when another parasite other than E. histolytica/E. dispar was observed Not stated if placebo was used
Outcomes	Parasitological cure: eradication of E. histolytica/E. dispar in stool examination 14 days after treatment Adverse events: only tolerance to the drugs reported Data for parasitological cure were presented separately for nitazoxandie vs quinfamide for single infections and nitazoxanide vs quinfamide plus mebendazole for mixed infections, and included in a separate meta-analysis
Notes	Location: 3 communities in Colima, Mexico Date: 2002 (date of publication only; actual study period not reported) Source of funding: Instituto Mexicano del Seguro Social (IMSS); nitazoxanide was provided by Laboratories Columbia, S.A. de C.V., Mexico, D.F., Mexico Several attempts were made to contact the primary author, but they were not successful

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Donckaster 1964

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Methods	Generation of allocation sequence: random-numbers table Allocation concealment: unclear Blinding: unclear; reported as "double-blind", but blinding of participants, care provider, and outcome assessors not described Inclusion of all randomized participants: 100%
Participants	Number: 346 enrolled; 346 analysed initially; 21 cases who failed after administration of the primary drugs were randomized a second time to receive a different drug and were analysed twice together with the first group Inclusion criteria: adults and children with clinical symptoms of intestinal amoebiasis and stool specimens positive for cysts and/or trophozoites of E. histolytica examined by the modified Telemann concentration technique (centrifugation with saline formol and ether) for cysts and the polyvinyl alcohol with fixative of Schaudin for the trophozoites Exclusion criteria: those without a source of potable water at home; unable to dispose of their excrement properly; or have other non-parasitic infections and are taking other medications for their infections
Interventions	Dimethychlortetracycline: once daily on an empty stomach for 10 days at the following oral daily doses – children 15 mg/kg and adults 900 mg Oxytetracycline: once daily on an empty stomach for 10 days at the following oral daily doses – children 25 mg/kg and adults 1500 mg Tetracycline: once daily on an empty stomach for 10 days at the following oral daily doses – children 25 mg/kg and adults 1500 mg Chlorphenoxamide: once daily after meals for 10 days at the following oral daily doses – children 125 mg for every 2 years of age and adults 1500 mg Chlorbetamide: once daily after meals for 10 days at the following oral daily doses – children 100 mg/kg and adults 4000 mg Racemic dehydroemetine: once daily after meals for 10 days at the following oral daily doses – children 5 mg for every 2 years of age and adults 40 mg Diiodohydroxyquinoline: once daily after meals for 21 days at the following oral daily doses – children 200 mg for every 2 years of age and adults 1800 mg Phenanthrondione: once daily after meals for 10 days at the following oral daily doses – children 25 mg for every 2 years of age and adults 300 mg Bismuth glycoarsanilate: once daily after meals for 10 days at the following oral daily doses – children 250 mg for every 2 years of age and adults 2000 mg Iodochlorhydroxyquinoline: once daily after meals for 21 days at the following oral daily doses – children 125 mg for every 2 years of age and adults 1000 mg Placebo (starch): once daily after meals for 10 days at the following oral daily doses – children 250 mg for every 2 years of age and adults 1500 mg Not stated which among the drugs, if any, were identical in appearance to the placebo
Outcomes	Parasitological failure: presence of cysts and/or trophozoites in the stool examinations done 10 and 40 days after start of treatment Adverse events: voluntary reporting of clinical adverse events by participants every 3 days during treatment and every 10 to 15 days after treatment
Notes	Location: outpatient clinic of the University of Chile in Santiago, Chile Date: 1963 (date of publication only; actual study period not reported) Source of funding: not stated

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Huggins 1982

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: unclear; reported as "double-blind", but blinding of participants, care provider, and outcome assessors not described Inclusion of all randomized participants: 100%
Participants	Number: 96 enrolled and analysed Inclusion criteria: adults with chronic intestinal amoebiasis and stool specimens positive for E. histolytica by direct smear with Lugol's stain according to the Teleman-Richter or Hoffman, Pons, and Janer methods Exclusion criteria: not stated
Interventions	Win 40.014 (quinfamide): 100 mg single oral dose Win 40.014 (quinfamide): 100 mg twice a day orally at 12-hourly intervals for 1 day Win 40.014 (quinfamide): 100 mg thrice a day orally at 8-hourly intervals for 1 day Placebo: 300 mg daily dose orally, no information given on the frequency of administration of placebo Not stated if Win 40.014 (quinfamide) and placebo tablets were identical in appearance
Outcomes	Parasitological cure: clearance of amoeba from stools on days 2 and 7 after treatment Clinical cure: disappearance of the 4 symptoms recorded at baseline (pain, colic, diarrhoea, and constipation) evaluated on days 2 and 7 after treatment Adverse events: only 2 symptoms (nausea and headache) solicited from participants; laboratory tests were done before and after treatment but results not presented
Notes	Location: Clinical Hospital of the Federal University of Pernambuco, Brazil Date: 1982 (date of publication only; actual study period not reported) Source of funding: not stated

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Joshi 1975

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: open Inclusion of all randomized participants: 100%
Participants	Number: 60 enrolled and analysed Inclusion criteria: adults with clinical symptoms of intestinal amoebiasis and stool specimens positive for trophozoites or cysts of E. histolytica; laboratory diagnostic method not specified Exclusion criteria: those who received antiamoebic treatment in the previous 1 month, pregnant women, dehydrated patients, and those with hepatic, renal, hematologic or EKG abnormalities
Interventions	Tinidazole: 600 mg twice daily orally for 5 days Metronidazole: 400 or 800 mg thrice daily orally for 5 days Treatment period was extended to 10 days in both groups when 5 days treatment was inadequate to relieve symptoms or clear the stools of E. histolytica
Outcomes	Parasitological response: eradication of E. histolytica in stools on day 30 after start of treatment Clinical response: complete or partial relief of symptoms and healing of ulcers on sigmoidoscopy, when carried out Adverse events: voluntary reporting by participants; laboratory tests monitored before and after treatment including haemogram, urinalysis, serum bilirubin, serum transaminases (SGOT, SGPT), alkaline phosphatase, and blood urea Not included in this review: clearance of E. histolytica on day 5 or 10 and day 20 after start of treatment; persistence of clinical symptoms on day 5 or 10 and day 20 after start of treatment
Notes	Location: Ahmedabad, India Date: 1975 (date of publication only; actual study period not reported) Source of funding: not stated Tinidazole tablets (Fasigyn) were supplied by Pfizer Ltd.

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Kapadia 1968

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: unclear Inclusion of all randomized participants: 100%
Participants	Number: 50 enrolled and analysed Inclusion criteria: clinical symptoms of intestinal amoebiasis and stool specimens positive for trophozoites and/or cysts of E. histolytica; laboratory diagnostic method was not specified Exclusion criteria: not stated
Interventions	Chlorhydroxquinoline: 500 mg thrice daily orally for 10 days Di-diiodohydroxyquinoline: 500 mg thrice daily orally for 10 days Not stated if chlorhydroxquinoline and di-diiodohydroxyquinoline were identical in appearance
Outcomes	Parasitological cure: eradication of E. histolytica from stools at the end of the 10-day treatment period Clinical cure: improvement or disappearance of symptoms at the end of the 10-day treatment period Adverse events: clinical adverse events and liver function test monitored before and after treatment including total bilirubin, serum albumin and globulin, and zinc sulfate
Notes	Location: Bombay, India Date: 1968 (date of publication only; actual study period not reported) Source of funding: not stated Supply of chlorhydroxquinoline (Quixalin) from Sarabhai Chemicals

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Karabay 1999

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: open Inclusion of all randomized participants: 100%
Participants	Number: 44 enrolled and analysed Inclusion criteria: acute amoebic dysentery and stool specimens positive for E. histolytica cysts and/or trophozoites examined by 0.85% saline water, Lugol solution, and trichrome stain Exclusion criteria: received treatment for diarrhoea in the last 10 days; those with pathogenic bacteria identified in stool culture
Interventions	Secnidazole: 2 g single oral dose Metronidazole: 750 mg thrice daily orally for 10 days
Outcomes	Parasitological response: clearance of E. histolytica from stools on days 14 and 21 Not included in this review: mean number of days from start of treatment to resolution of clinical symptoms
Notes	Location: military hospital in Erzurum, Turkey Date: July 1998 to November 1998 Source of funding: not stated

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Mansour-Ghanaei 2003

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: double (participants, care providers, and outcome assessors – from personal communication with primary author) Inclusion of all randomized participants: 94.7% (54/57))
Participants	Number: 57 enrolled; 54 analysed; 3 noncompliant participants (2 from the group without Saccharomyces boulardii and 1 from the group with S. boulardii) were excluded from analysis Inclusion criteria: amoebic dysentery presenting with mucous bloody diarrhoea, fever, and abdominal pain; stool specimens positive for haematophagous trophozoites of E. histolytica; laboratory diagnostic method was not specified Exclusion criteria: pregnant women; those on maintenance haemodialysis, steroids, or chemotherapy
Interventions	Metronidazole, iodoquinol, and placebo: metronidazole 750 mg and iodoquinol 650 mg given thrice daily orally with placebo tablets for 10 days Metronidazole, iodoquinol, and S. boulardii: 750 mg and iodoquinol 650 mg thrice daily orally for 10 days plus lyophilized S. boulardii 250 mg orally thrice daily for 10 days S. boulardii and placebo were identical in appearance
Outcomes	Parasitological failure: persistence of amoebic cysts in stool examinations at 4 weeks after treatment Not included in this review: mean duration of diarrhoea, abdominal pain, fever, and headache from start of treatment to resolution of symptoms
Notes	Location: Shahid Beheshti Educational and Therapeutic Center in Shiraz, Iran Date: 21 March 1995 to 21 March 1996 Source of funding: not stated The author was contacted and kindly provided data on method of blinding; however, no response was obtained regarding method of allocation concealment despite several follow-up communications

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Mathur 1976

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: open Inclusion of all randomized participants: 100%
Participants	Number: 60 enrolled and 60 analysed Inclusion criteria: adults and adolescents with clinical symptoms of intestinal amoebiasis and stool specimens positive for trophozoites or cysts of E. histolytica; laboratory diagnostic method was not specified Exclusion criteria: received antiamoebic treatment in the previous 1 month; pregnant women; dehydrated patients; and those with hepatic, renal, hematologic or EKG abnormalities
Interventions	Tinidazole: 600 mg twice daily orally for 5 days Metronidazole: 400 mg thrice daily orally for 5 days (for acute amoebic dysentery) or 800 mg thrice daily for 5 days (for other cases) Treatment period was extended to 10 days in both groups when 5 days treatment was inadequate to relieve symptoms or clear the stools of E. histolytica
Outcomes	Parasitological cure: eradication of E. histolytica from stools on day 30 after start of treatment Clinical cure: relief of presenting clinical signs and symptoms and healing of ulcers on sigmoidoscopy, when carried out Adverse events: voluntary reporting of clinical adverse events by participants; laboratory tests monitored before and after treatment including haemogram, urinalysis, serum bilirubin, transaminases (SGOT, SGPT), alkaline phosphatase, and blood urea
Notes	Location: India Date: 1976 (date of publication only; actual study period not reported) Source of funding: not stated Tinidazole tablets (Fasigyn) were supplied by Pfizer Ltd.

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Misra 1974

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: unclear; reported as "single blind", but it was not stated who among the participants, care provider, or outcome assessor was blinded Inclusion of all randomized participants: 100%
Participants	Number: 60 enrolled and analysed Inclusion criteria: adults and children with clinical symptoms of intestinal amoebiasis and stool specimens positive for trophozoites or cysts of E. histolytica by direct smear or concentration method Exclusion criteria: antiamoebic treatment in the preceding 1 month before enrolment; pregnant women; severe anaemia
Interventions	Tinidazole: 600 mg twice daily orally for 5 days Metronidazole: 400 mg thrice daily orally for 5 days (for acute amoebic dysentery) or 800 mg thrice daily orally for 5 days (for chronic intestinal amoebiases if symptoms were more than 15 days duration) Treatment period was extended to 10 days in both groups when 5 days treatment was inadequate to relieve symptoms or clear the stools of E. histolytica
Outcomes	Parasitological cure: eradication of E. histolytica on follow-up stool examinations on day 30 after start of treatment Clinical cure: disappearance of presenting clinical symptoms and healing of ulcers on sigmoidoscopy on day 30 after start of treatment Adverse events: clinical adverse events monitored during treatment; laboratory tests monitored before and after treatment including complete blood count and platelet count, urinalysis, electrocardiogram, blood urea, serum bilirubin, alkaline phosphatase, and liver transaminases (SGOT, SGPT)
Notes	Location: Medical College Hospital in Bhopal, India Date: 1974 (date of publication only; actual study period not reported) Source of funding: Pfizer Ltd. for support and for supply of study drugs tinidazole (Fasigyn) and metronidazole (Flagyl)

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Misra 1977

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: unclear Inclusion of all randomized participants: 100%
Participants	Number: 60 enrolled and analysed Inclusion criteria: adults with clinical symptoms of intestinal amoebiasis and stool specimens positive for trophozoites or cysts of E. histolytica by direct smear or formol-ether concentration technique, sigmoidoscopy for colonic ulcers, and parasitological examination of sigmoidoscopic scrapings Exclusion criteria: received antiamoebic treatment within the previous 4 weeks; pregnant women; dehydrated patients; evidence of hepatic, renal, hematologic, or EKG abnormalities
Interventions	Tinidazole: 2 g single oral dose daily for 3 days Metronidazole: 2 g single oral dose daily for 3 days Not stated if tinidazole and metronidazole were identical in appearance.
Outcomes	Parasitological response: eradication of E. histolytica from stools on day 30 after start of treatment Clinical response: disappearance of presenting clinical symptoms on day 30 after start of treatment Adverse events: voluntary reporting of clinical adverse events by participants; laboratory tests monitored before and after treatment including urinalysis, complete blood count, serum bilirubin, alkaline phosphatase, liver transaminases (SGOT, SGPT), blood urea, and electrocardiogram
Notes	Location: hospital in Bhopal, India Date: 1977 (date of publication only; actual study period not reported) Source of funding: not stated Unclear if Misra 1977 and Misra 1978 reported the results for same group of participants Several attempts were made to contact the authors, but no response was obtained

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Misra 1978

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: unclear Inclusion of all randomized participants: 98.3% (59/60)
Participants	Number: 60 enrolled; 59 analysed, 1 randomized to tinidazole group excluded because it was discovered later that he had a history of ulcerative colitis Inclusion criteria: adults with clinical symptoms of intestinal amoebiasis and stool specimens positive for trophozoites and cysts of E. histolytica by direct smear or formol-ether concentration technique, sigmoidoscopy for colonic pathology Exclusion criteria: received antiamoebic treatment in the previous 4 weeks before enrolment
Interventions	Tinidazole: 2 g single oral dose daily for 3 days Metronidazole: 2 g single oral dose daily for 3 days Not stated if tinidazole and metronidazole were identical in appearance
Outcomes	Parasitological cure: eradication of E. histolytica from stools on day 30 after start of treatment Clinical cure: disappearance of presenting clinical symptoms on day 30 after start of treatment Adverse events: voluntary reporting of clinical adverse events by participants; laboratory monitoring done before and after treatment including complete blood count, urinalysis, and blood chemistry
Notes	Location: hospital in Bhopal, India Date: 1978 (date of publication only; actual study period not reported) Source of funding: not stated Unclear if Misra 1977 and Misra 1978 reported the results for same group of participants Several attempts were made to contact the author, but no response was obtained

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Mohammed 1998

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Methods	Generation of allocation sequence: random-numbers table Allocation concealment: unclear Blinding: open Inclusion of all randomized participants: 72.5% (50/69)
Participants	Number: 69 enrolled; 50 analysed; 19 lost to follow up (11 in the praziquantel group, 8 in the metronidazole group); 3 in praziquantel group withdrawn from treatment because of lack of response Inclusion criteria: adults with clinical symptoms of intestinal amoebiasis and stool specimens positive for vegetative trophozoite forms (acute amoebic dysentery) or cysts of E. histolytica; laboratory diagnostic method was not specified; those who were cyst passers were treated with praziquantel alone and were not included in the review Exclusion criteria: not stated
Interventions	1. Praziquantel: 40 mg/kg body weight divided into 2 doses orally and taken 4 to 6 hours apart 2. Metronidazole: 800 mg thrice daily orally for 5 days
Outcomes	Parasitological response: disappearance of E. histolytica from stools 1 week after treatment Clinical response: disappearance of baseline clinical signs and symptoms at the end of treatment Adverse events: voluntary reporting of clinical adverse events by participants only for praziquantel
Notes	Location: outpatients in Iraq Date: 1993 to 1995 Source of funding: not stated

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Naoemar 1973

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: double (participants, care providers, and outcome assessors) Inclusion of all randomized participants: 100% at end of treatment; 96.7% at 7 weeks after end of treatment
Participants	Number: 20 enrolled, 20 analysed Inclusion criteria: adults and children with bloody diarrhoea and stools positive for motile haematophagous trophozoites of E. histolytica examined by eosin and iodine smears Exclusion criteria: anaemia or other diseases but exact conditions not stated
Interventions	Ro 7-0207 (ornidazole) Metronidazole Both drugs given as follows: 2 to 6 years of age – 125 mg daily in 3 divided doses for 7 days; 7 to 12 years of age – 250 mg daily in 3 divided doses for 7 days; adults – 1500 mg daily in 3 divided doses for 5 days Ro 7-0207 and metronidazole were identical in appearance (light yellow capsules) and kept in numbered bottles
Outcomes	Parasitological response: clearance of E. histolytica from stools at the end of treatment and 1 month after end of treatment Relapse: reappearance of E. histolytica in stools 1 month after end of treatment Clinical cure: disappearance of symptoms at the end of treatment and at 1 month after end of treatment Adverse events: clinical adverse events monitored during treatment; laboratory tests monitored before and after the end of treatment including complete blood counts, liver transaminase (SGPT), alkaline phosphatase, urinalysis, blood urea, and electrocardiogram Not included in this review: number of days from start of treatment to clearance of E. histolytica in stool specimens and disappearance of symptoms
Notes	Location: outpatient clinics in Jakarta, Indonesia Date: 1973 (date of publication only; actual study period not reported) Source of funding: Roche Far East Research Foundation for supply of drugs and support for the study

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Nnochiri 1967

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: double (participants, care provider, and outcome assessors) Inclusion of all randomized participants: 100% at end of treatment; 96.7% (58/60) at 7 weeks after end of treatment
Participants	Number: 60 with acute amoebic dysentery enrolled; 60 analysed at end of treatment, and 58 (96.8%) analysed 7 weeks after end of treatment Inclusion criteria: military personnel and their families diagnosed with acute amoebic dysentery and stool specimens positive for E. histolytica examined by saline and iodine-stained smears Exclusion criteria: not stated
Interventions	Diloxanide furoate, tetracycline hydrochloride, and chloroquine phosphate (per capsule): diloxanide furoate (187.5 mg), tetracycline hydrochloride (125 mg), and chloroquine phosphate (50 mg) given in 3 dosage regimens of 2 capsules 4 times a day for 5 days, 2 capsules 4 times a day for 7 days, or 2 capsules 4 times a day for 10 days Diloxanide furoate and tetracycline hydrochloride (per capsule): diloxanide furoate (187.5 mg) and tetracycline hydrochloride (125 mg) given in 3 dosage regimens of 2 capsules 4 times a day for 5 days, 2 capsules 4 times a day for 7 days, or 2 capsules 4 times a day for 10 days The 2 drug combinations with and without chloroquine were identical in appearance
Outcomes	Parasitological response: clearance of E. histolytica cysts and trophozoites at end of treatment, then on follow up 7 weeks from completion of treatment; patients whose stools remained negative 7 weeks after treatment were followed up 3 and 6 months from completion of treatment Clinical response: recurrence of symptoms (results were not reported and could not be included in the meta-analysis) Adverse events: clinical adverse events monitored during treatment and on follow up; laboratory tests monitored before and after treatment including urine cytology and presence of protein, blood examination for haemoglobin, total erythrocyte and leucocyte counts and differential count Not included in this review: clearance of E. histolytica from stools of 36 asymptomatic cyst carriers
Notes	Location: Yaba Military Hospital in Lagos, Nigeria Date: August 1965 to July 1966 Source of funding: Messrs Boots Pure Drug Co., Ltd, Nottingham, England

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Padilla 2000

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Methods	Generation of allocation sequence: coin toss Allocation concealment: unclear Blinding: double blind (participants and outcome assessors for clinical and parasitological outcomes blinded; unclear if care provider (main investigator) who administered the medications was blinded) Inclusion of all randomized participants: 100%
Participants	Number: 239 enrolled and analysed Inclusion criteria: children with clinical symptoms of nondysenteric amoebic colitis with at least 1 of 3 stool specimens positive for E. histolytica cysts examined by direct smear using Faust concentration method Exclusion criteria: history of sensitivity to clioquinol or to metronidazole and its derivatives; children who had received antibacterial and/or antiparasitic drugs in the 15 days before their entry into the study; those with amoebic dysentery
Interventions	Secnidazole: 30 mg/kg body weight orally in a single dose Quinfamide: 4.3 mg/kg body weight orally in a single dose
Outcomes	Parasitological response: clearance of E. histolytica cysts on days 5, 6, and 7 after administration of the drugs Adverse events: clinical adverse events were solicited by the investigators through direct questioning for the presence of abdominal pain, nausea, vomiting, headache, diarrhoea, and unpleasant taste in the mouth Not included in this review: acceptability of taste
Notes	Location: 2 urban federal elementary schools in Celaya, Guanajuato, Mexico (Urban Federal Elementary schools 'Carmen Serdan' and 'Juan Jesus de los Reyes') Date: 2000 (date of publication only; actual study period not reported) Source of funding: not stated

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Pamba 1990

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: single (only outcome assessor for parasitological response and rectosigmoidoscopy results were blinded; not stated if assessor for clinical response was blinded) Inclusion of all randomized participants: 88.5% (369/417) 15 days after start of treatment, 67.6% (282/417) 30 days after start of treatment, and 51.3% (214/417) 60 days after start of treatment
Participants	Number: 417 enrolled; 369/417 (88.5%) analysed 15 days after start of treatment, 282/417 (67.6%) analysed 30 days after start of treatment, and 214/417 (51.3%) analysed 60 days after start of treatment; recruitment to the etophamide plus aminosidine group was discontinued because of high incidence of diarrhoea; withdrawals not stated for the other groups Inclusion criteria: children with clinical symptoms of intestinal amoebiasis with stool specimens positive for E. histolytica by direct smear and a concentration method (not specified) Exclusion criteria: pregnant women; known allergy to the drugs; those with co-existing extra-intestinal amoebiasis or other major diseases; treated with antiamoebic drugs in the 30 days before recruitment
Interventions	Aminosidine (A): 500 mg twice daily orally for adults, 15 mg/kg body weight for children given orally for 5 days Etophamide (E): 600 mg twice daily orally for adults,15 mg/kg body weight for children given orally for 5 days Nimorazole (N): 1 g twice daily orally for adults, 20 mg/kg body weight for children given orally for 5 days Combination of nimorazole and aminosidine (NA): same doses as above for 5 days Combination of nimorazole and etophamide (NE): same doses as above for 5 days Combination of etophamide and aminosidine (EA): same doses as above for 5 days
Outcomes	Parasitological cure: disappearance of any form of E. histolytica from stools or ulcer scrapings at the end of treatment Recurrence (relapse): reappearance of E. histolytica during follow up on days 15, 30, and 60 after initial disappearance; due to incomplete data on follow up; results could not be included in the meta-analysis Clinical cure: disappearance of all baseline symptoms at the end of treatment Adverse events: clinical adverse events monitored during treatment Not included in this review: cumulative daily clearance of E. histolytica from stools during treatment, at the end of treatment, and on days 15, 30, and 60 after start of treatment; evolution of mild and severe amoebic ulcers seen on rectosigmoidoscopy; and anatomical cure (healing of previous ulceration)
Notes	Location: 3 district hospitals of Kiambo, Machakos and Kilifi in Kenya, Africa Date: 1990 (date of publication only; actual study period not reported) Source of funding: Farmitalia Carlo Erba

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Panggabean 1980

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: reported as "double-blind", but only care provider was blinded; blinding of participants and outcome assessors not described Inclusion of all randomized participants: 62.5% (25/40) 1 week after treatment, 42.5% (17/40) 2 weeks after treatment, 27.5% (11/40) 3 weeks after treatment, and 15% (6/40) 4 weeks after treatment
Participants	Number: 40 enrolled; 25/40 (62.5%) analysed 1 week after treatment, 17/40 (42.5%) analysed 2 weeks after treatment, 11/40 (27.5%) analysed 3 weeks after treatment, and 6/40 (15%) analysed 4 weeks after treatment Inclusion criteria: children with amoebic dysentery presenting with bloody stools and motile haematophagous trophozoites of E. histolytica in stools examined by direct smear method with eosin 2% stain Exclusion criteria: not stated Concomitant intestinal infection: 35 participants included in the analysis had concomitant intestinal helminthic infection and groups were comparable for numbers and type of concomitant intestinal helminthic infection (tinidazole group: Ascaris lumbricoides 10, Trichuris trichiura 26, Ancylostoma 2; ornidazole group: Ascaris lumbricoides 12, Trichuris trichiura 12, Ancylostoma 3)
Interventions	Tinidazole: 50 mg/kg body weight in a single oral dose daily for 3 days Ornidazole: 50 mg/kg body weight in a single oral dose daily for 3 days Other interventions: children with concomitant intestinal helminthic infection were given single-dose pyrantel pamoate 10 mg/kg and those with trichuriasis were given mebendazole 1 tablet twice daily for 3 consecutive days
Outcomes	Parasitological cure: disappearance of all forms of E. histolytica on stool examinations done weekly until 4 weeks after completion of treatment Reinfection: reappearance of E. histolytica after the second month Clinical cure: disappearance of blood and mucus from stools at follow-up examinations done weekly until 4 weeks after completion of treatment Adverse events: clinical adverse effects reported by participants during treatment
Notes	Location: outpatient clinic of the Sub-department of Gastroenterology, Department of Child Health Medical School, General Hospital, Medan, Indonesia Date: January 1978 to June 1978 Source of funding: PT. Pfizer Indonesia and PT. Hoffman-La Roche

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Pehrson 1983

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Methods	Generation of allocation sequence: unclear (unrecalled by primary author during personal communication) Allocation concealment: inadequate – no attempts to conceal treatment allocation (personal communication with primary author) Blinding: open Inclusion of all randomized participants: 100%
Participants	Number: 41 enrolled and analysed Inclusion criteria: adults and children with clinical symptoms of intestinal amoebiasis but no signs of invasion (eg no fever or acute dysentery) and stool specimens positive for trophozoites or cysts of E. histolytica by direct smear or formol-ether concentration technique by Ridley and Hawgood; had not received any antiamoebic drug during the previous year Exclusion criteria: acute dysenteric amoebiasis; liver abscess Concomitant intestinal infection: 17 patients had concomitant infection with other intestinal organisms (Giardia lamblia 9, Campylobacter jejuni 2, Hymenolepsis nana 1, Ascaris lumbricoides 1, Trichuris trichiura 1, Salmonella paratyphi A 1), but the distribution in the 2 groups was not specified
Interventions	Tinidazole: 40 mg/kg body weight in a single oral dose daily for 5 days Tinidazole plus diloxanide furoate: tinidazole 40 mg/kg body weight in a single oral dose daily for 5 days plus diloxanide furoate 20 mg/kg body weight divided into 3 daily doses for 10 days
Outcomes	Parasitological response: clearance of E. histolytica in any of the 3 stool specimens evaluated 1 month after end of treatment Adverse events: only adverse events severe enough to result in cessation of therapy
Notes	Location: hospital in Stockholm, Sweden Date: 1983 (date of publication only; actual study period not reported) Source of funding: not reported The author was contacted and kindly provided further data. Details on method of randomization could not be recalled by the trial author

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Pehrson 1984

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Methods	Generation of allocation sequence: unclear (unrecalled by primary author during personal communication) Allocation concealment: inadequate – no attempts to conceal treatment allocation (personal communication with primary author) Blinding: open Inclusion of all randomized participants: 100%
Participants	Number: 30 enrolled and analysed Inclusion criteria: adults with clinical symptoms of intestinal amoebiasis but no signs of invasion (eg no fever or acute dysentery) and stool specimens positive for trophozoites or cysts of E. histolytica examined by direct smear or formol-ether concentration technique Exclusion criteria: not stated
Interventions	Tinidazole: 600 mg twice daily orally for 5 days Metronidazole: 800 mg thrice daily orally for 5 days
Outcomes	Parasitological cure: clearance of E. histolytica trophozoites or cysts in any of the 3 stool specimens taken 1 month after end of treatment Adverse events: only adverse events severe enough to result in cessation of therapy
Notes	Location: Stockholm, Sweden Date: 1984 (date of publication only; actual study period not reported) Source of funding: not reported The author was contacted and kindly provided further data. Details on method of randomization could not be recalled by the trial author

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Prasad 1985

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Methods	Generation of allocation sequence: unclear Allocation concealment: coded drug containers; code broken only at the end of the trial Blinding: double (participants, care provider, and outcome assessor) Inclusion of all randomized participants: 91.1% (164/180)
Participants	Number: 180 patients with amoebiasis or giardiasis or both were enrolled; 164/180 (91.1%) analysed, 90 with amoebiasis alone, 47 with giardiasis, and 27 with mixed infection with amoebiasis and giardiasis; 16/180 (8.9%) did not complete treatment and were dropped from the trial but not stated if those who dropped out had amoebiasis, giardiasis, or mixed infection Inclusion criteria: children with clinical symptoms of intestinal amoebiasis or giardiasis (diarrhoea, abdominal pain, dysentery, gastrocolic urgency, etc.) and whose stools were positive for amoeba or giardia; laboratory diagnostic method was not specified Exclusion criteria: not stated Concomitant intestinal infection: Ascaris lumbricoides present in 20%, Ancylostoma duodanale 9.9%, Enterobius vermicularis 1.8%, but distribution in the 2 groups not reported
Interventions	Metronidazole: 100 mg/5 mL suspension, given as 5 mL thrice daily for those 1 to 5 years of age and 10 mL thrice daily for those 6 to 15 years of age for 5 or 10 days depending on severity of disease Metronidazole plus furazolidone: fixed-drug combination suspension of (per 5 mL) metronidazole 75 mg plus furazolidone 25 mg, given as 5 mL thrice daily for those 1 to 5 years of age and 10 mL thrice daily for those 6 to 15 years of age for 5 or 10 days depending on severity of disease
Outcomes	Parasitological and clinical response: evaluated jointly on day 7 after start of therapy; overall outcome was reported as complete cure, partial cure, and no cure but these terms were not defined Adverse events: clinical adverse events reported by participants during treatment Not included in this review: clinical and parasitological response in those with mixed amoebiasis and giardiasis infection
Notes	Location: paediatric outpatient department of S.N. Medical College, Agra, India Date: 1985 (date of publication only; actual study period not reported) Source of funding: not stated Attempts made to contact the authors were unsuccessful

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Pudjiadi 1973

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Methods	Generation of allocation sequence: unclear Allocation concealment: sequentially numbered coded drug containers supplied by Roche Far East Research Foundation, Hong Kong; sealed envelope containing the list of the drugs only opened after the entire trial was finished Blinding: double (participants, care providers, and outcome assessors) Inclusion of all randomized participants: 100%
Participants	Number: 20 enrolled and analysed Inclusion criteria: children with bloody diarrhoea and stools positive for E. histolytica examined by eosin and Lugol's solution Exclusion criteria: not stated Concomitant intestinal infection: Ascaris lumbricoides found in faeces of 6 participants, Trichuris trichiura found in feces of 6 participants, but distribution in the 2 groups not specified
Interventions	Ro 7-0207 (ornidazole): 125 mg capsules Metronidazole: 125 mg capsules Both drugs were given as follows: up to 2 years of age – 62.5 mg, 2 to 6 years of age – 125 mg, and 6 to 12 years of age 250 mg daily, divided into 3 daily doses for 7 days
Outcomes	Parasitological response: clearance of E. histolytica from stools after 7 days of treatment Clinical response: disappearance of clinical symptoms after 7 days of treatment Adverse events: clinical adverse events monitored during treatment; laboratory tests monitored before, during and after treatment including complete blood count, urine analysis, electrocardiogram, liver transaminases (SGPT), and alkaline phosphatase Not included in this review: number of days from start of treatment to disappearance of E. histolytica in the stools; number of days from start of treatment to disappearance of clinical symptoms
Notes	Location: hospital on the Department of Child Health, Medical School University of Indonesia, Jakarta, Indonesia Date: 1973 (date of publication only; actual study period not reported) Source of funding: Roche Far East Research Foundation for supply of drugs and study grant

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Rossignol 2001

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Methods	Generation of allocation concealment: unclear Allocation concealment: unclear Blinding: double (participants, care provider, and outcome assessors) Inclusion of all randomized participants: 100%
Participants	Number: 91 enrolled but only 67 (74%) had Entamoeba histolytica (53 with single and 14 with mixed Giardia and Entamoeba infection); 67 analysed Inclusion criteria: adults and children with diarrhoea and stool specimens positive for cysts or trophozoites of E. histolytica and/or E. dispar alone or with concomitant Giardia intestinalis by direct smear, concentration technique, Ziehl-Neelsen stain, and an immunofluorescent assay (MeriFluor Meridian Diagnostics) Exclusion criteria: pregnant women; using any drug with antiprotozoal activity within 2 weeks of enrolment; and known to have or suspected of having acquired immunodeficiency syndrome (AIDS) Concomitant intestinal infection: mixed Entamoeba histolytica and Giardia intestinalis infection in 6/36 (17%) of participants in the nitazoxanide group and 8/31 (26%) in the placebo group
Interventions	Nitazoxanide: 500 mg twice daily orally for 3 days Placebo tablet (identical): twice daily orally for 3 days
Outcomes	Parasitological response: clearance of E. histolytica from 2 stool specimens collected between days 7 and 10 after start of treatment Clinical response: disappearance of symptoms, resolution of diarrhoea and haematochezia on day 7 after start of treatment Adverse events: clinical adverse events monitored by study personnel Not included in this review: median time from initiation of therapy to passage of the last unformed stools
Notes	Location: outpatient clinic of the Department of Hepatology, Gastroenterology, and Infectious Diseases of the Benha University Hospital, governorate of Kalubia, Nile delta, Egypt Date: 2001 (date of publication only; actual study period not reported) Source of funding: not stated

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Rossignol 2007

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Methods	Generation of allocation sequence: computer-generated randomization Allocation concealment: unclear Blinding: double (participants, care providers, outcome assessors) Inclusion of all randomized participants: 100%
Participants	Number: 100 enrolled and 100 analysed; 2 participants in the placebo group lost to follow up and were considered treatment failures Inclusion criteria: adults and children with diarrhoea; ≥ 1 enteric symptoms; E. histolytica/E. dispar trophozoites identified in stool by microscopic examination using direct smear and concentration technique; stool-positive for E. histolytica by antigen-based ELISA Exclusion criteria: other enteric pathogens identified by Ziehl-Neelsen stain, immunofluorescent assay (MeriFluor Meridian Diagnostics) and stool culture; pregnant and lactating women; using any drug with antiprotozoal activity within 2 weeks of enrolment; and known to have or suspected of having acquired immunodeficiency syndrome (AIDS) or other immune deficiencies
Interventions	Nitazoxanide: for 3 days; adults aged ≥ 12 years, 500 mg tablet twice daily; children 100 mg/5 mL suspension – 1 to 3 years received 5 mL twice daily, 4 to 11 years received 10 mL twice daily Placebo: matching placebo tablet or suspension twice daily for 3 days
Outcomes	Parasitological response: clearance of E. histolytica from 2 stool specimens collected between days 7 to 10 after the start of treatment Clinical response: disappearance of symptoms, resolution of diarrhoea and hematochezia on day 7 after start of treatment Adverse events: monitored by patient diary Not included in this review: time from first dose to passage of last unformed stools
Notes	Location: outpatient clinic of the Benha University Hospital, Benha, Egypt Date: 17 February 2004 to 2 October 2005 Source of funding: Romark Laboratories, L.C.

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Rubidge 1970

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: open Inclusion of all randomized participants: 100%
Participants	Number: 39 enrolled and analysed Inclusion criteria: children with amoebic dysentery presenting with acute onset of diarrhoea with blood, mucus and actively motile haematophagous trophozoites of E. histolytica in stool specimens examined by direct smear and zinc sulfate flotation technique Exclusion criteria: not stated
Interventions	Metronidazole: 50 mg per kg body weight orally for 7 days Dehydroemetine, tetracycline, and diloxanide furoate: dehydroemetine (2 mg/kg body weight daily by subcutaneous injection for 10 days), tetracycline (50 mg/kg body weight daily orally for 7 days), and diloxanide furoate (25 mg/kg body weight daily orally for 10 days)
Outcomes	Parasitological response: clearance of E. histolytica at end of treatment and on subsequent stool specimens during follow up until 28 days after start of treatment Clinical response: disappearance of symptoms at end of treatment and during follow up until 28 days after start of treatment Adverse events: only tolerance to the drugs was reported
Notes	Location: hospital in Durban, South Africa Date: 1970 (date of publication only; actual study period not reported) Source of funding: not stated; metronidazole was supplied by Messrs. May and Baker, Ltd

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Salles 1999

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: open Inclusion of all randomized participants: 90.7% (275/303) included in evaluation for clinical efficacy, 99% (300/303) included in evaluation for parasitological efficacy
Participants	Number: 303 enrolled; 275/303 (90.7%) included in evaluation for clinical efficacy; 300/303 (99%) included in evaluation for parasitological efficacy Inclusion criteria: children with clinical symptoms of intestinal amoebiasis with stool specimens positive for E. histolytica by direct smear using the Faust and Katz method and no history of intolerance to imidazole drugs Exclusion criteria: history of vomiting in the last 48 hours; taken anti-emetic drugs in the last 24 hours; treated with antiamoebic drugs in the last 15 days; symptoms of extraintestinal amoebiasis Concomitant intestinal infection: groups were comparable for presence of other intestinal parasites (Ascaris lumbricoides, Tricuris trichiura, Giardia lamblia, Necator americanus, Ancylostoma, Hymenolepsis nana, Schistosoma. Enterobius vermicularis, Endolimax nana) except for Strongyloides stercoralis which was more frequent in the tinidazole group (3 participants) compared with the secnidazole group (11 participants)
Interventions	Secnidazole: 1 mL/kg body weight orally in a single dose Tinidazole: 0.5 mL/kg body weight once daily orally for 2 days
Outcomes	Parasitological response: clearance of E. histolytica from stool specimens collected on days 7, 14, and 21 following treatment Clinical response: disappearance of all symptoms at the end of the study (day 21) Adverse events: solicited from the participants or their guardians during the follow-up visits
Notes	Location: 5 different centres in Brazil Date: 1999 (date of publication only; actual study period not reported) Source of funding: not stated One author (Valfredo Costa) is connected with Rhodia Farma Ltd, the manufacturer of Secnidal (secnidazole)

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Singh 1977

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: open Inclusion of all randomized participants: 93.3% (56/60)
Participants	Number of participants randomized: 60 to 2 treatment groups Number: 60 enrolled; 56 analysed; 3 participants in the tinidazole group and 1 in the metronidazole group did not comply with the regimen and were excluded from analysis Inclusion criteria: adults with clinical symptoms of intestinal amoebiasis and stool specimens positive for trophozoites or cysts of E. histolytica by direct smear or formol-ether concentration technique Exclusion criteria: received antiamoebic treatment in the previous 4 weeks before enrolment; pregnant women; dehydrated patients; evidence of hepatic, renal, hematologic, or EKG abnormalities Concomitant intestinal infection: 12 had concomitant giardiasis, 6 in each group
Interventions	Tinidazole: 500 mg tablets x 4 (2 g) single-dose daily for 3 days Metronidazole: 400 mg tablets x 5 (2 g) single-dose daily for 3 days
Outcomes	Parasitological response: eradication of E. histolytica on follow-up stool examinations on day 30 after start of treatment Clinical response: disappearance of presenting clinical signs and symptoms on day 30 after start of treatment Adverse events: voluntary reporting of clinical adverse events by the participants; laboratory tests monitored before and after treatment including complete blood count, urinalysis, serum bilirubin, alkaline phosphatase, transaminases, and blood urea
Notes	Location: medical outpatient department of the Government Medical College and Hospital, Patiala India Date: September 1982 to September 1983 Source of funding: not stated; tinidazole was supplied by Pfizer Ltd.

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Sitepu 1982

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Methods	Generation of allocation sequence: random-numbers table Allocation concealment: unclear Blinding: unclear; reported as "double blind", but procedure for blinding participants, care provider, and outcome assessor not described Inclusion of all randomized participants: 82% (41/50) included in analysis on third day or 2 days after treatment, 36% (18/50) 1 week after treatment
Participants	Number: 50 enrolled; 41/50 (82%) analysed on the third day or 2 days after treatment, 18/50 (36%) were analysed 1 week after treatment Losses to follow up: 9/51 (18%) were lost to follow up by the third day or 2 days after treatment, 7 participants in the tinidazole group and 2 in the ornidazole group; 32/50 (64%) were lost to follow up 1 week after treatment, 18 in the tinidazole group and 14 in the ornidazole group Inclusion criteria: children with amoebic dysentery presenting with bloody diarrhoea and motile haematophagous trophozoites of E. histolytica in stools examined by direct smear method with eosin 1% stain Exclusion criteria: not stated Concomitant intestinal infection: trichuriasis (12 in tinidazole group and 15 in ornidazole group)
Interventions	Tinidazole: 50 mg/kg body weight in a single oral dose Ornidazole: 50 mg/kg body weight in a single oral dose
Outcomes	Parasitological response: clearance of E. histolytica from stools on subsequent follow-up visits on days 2 to 4 and 1 week after treatment Clinical response: disappearance of diarrhoea and faeces no longer contained mucus or red blood cells on days 2 to 4 and 1 week after treatment
Notes	Location: outpatient clinic of the Pediatric Gastroenterology Subdivision, Department of Child Health, School of Medicine, University of North Sumatra/Dr Pirngadi Hospital, Medan, Indonesia Date: August 1978 to May 1979 Source of funding: PT. Pfizer Indonesia and PT. Hoffman-La Roche

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Soedin 1985

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: open Inclusion of all randomized participants: 100%
Participants	Number: 80 enrolled and analysed Inclusion criteria: children with clinical symptoms of acute intestinal amoebiasis with stool specimens positive for trophozoites or haematophagous forms of E. histolytica; laboratory diagnostic method was not specified Exclusion criteria: not stated
Interventions	Secnidazole: 2 g orally in a single dose Tetracycline and clioquinol: tetracycline (750 mg) and clioquinol (1 g for 5 days) Co-intervention: 2 cases on secnidazole group were given spasmolytics (unspecified) for stomach cramps
Outcomes	Parasitological response: eradication of E. histolytica in stools examined on days 1 to 7, 7, 14, and 21 after start of treatment Clinical response: disappearance of clinical symptoms on days 1 to 7, 14, 21 and 28 after start of treatment Adverse events: clinical adverse events during follow up
Notes	Location: outpatient in the Padang Bulan Health Centre, Medan, Indonesia Date: September 1982 to September 1983 Source of funding: not stated

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Swami 1977

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: unclear Inclusion of all randomized participants: 93.3% (56/60)
Participants	Number: 60 enrolled; 56/60 (93.3%) analysed; 3/60 (5%) lost to follow up after day 4 (1 in tinidazole group, 2 in metronidazole group); 1 case in the metronidazole group subsequently found to have amoebic liver abscess was excluded from the final analysis Inclusion criteria: adults with clinical symptoms of intestinal amoebiasis and stool specimens positive for trophozoites or cysts of E. histolytica; laboratory diagnostic method was not specified Exclusion criteria: received antiamoebic treatment in previous 4 weeks; pregnant women; patients with marked dehydration; concomitant serious illness (not specified) Type of amoebic colitis: tinidazole group: amoebic dysentery 20/29, nondysenteric amoebic colitis 9/29; metronidazole group: amoebic dysentery 22/27, nondysenteric amoebic colitis 5/27
Interventions	Tinidazole: 2 g single-dose daily for 3 days Metronidazole: 2 g single-dose daily for 3 days Treatment was extended if E. histolytica persisted in the stool on the day following the last treatment period
Outcomes	Parasitological response: eradication of E. histolytica on follow-up stool examinations on day 30 after start of treatment Clinical response: relief of presenting clinical signs and symptoms on day 30 after start of treatment Adverse events: voluntary reporting of adverse events by participants; laboratory tests monitored before and after treatment including blood counts, urinalysis, serum bilirubin, alkaline phosphatase, transaminases (SGOT, SGPT), and blood urea Not included in this review: number of participants who required extension of treatment beyond 3 days
Notes	Geographic location: Visakhapatnam, India Date: 1977 (date of publication only; actual study period not reported) Source of funding: not stated

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Toppare 1994

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: open Inclusion of all randomized participants: 100%
Participants	Number: 102 enrolled and analysed Inclusion criteria: children with gastrointestinal symptoms and stool specimens positive for haematophagous trophozoites of E. histolytica; laboratory diagnostic method not specified Exclusion criteria: not stated Concomitant intestinal infection: all cases in both groups had negative stool cultures for pathogenic bacteria
Interventions	Secnidazole: 30 mg/kg body weight as a single oral dose daily for 3 days Ornidazole 15 mg/kg body weight given twice daily orally for 10 days
Outcomes	Parasitological cure: clearance of E. histolytica cyst or trophozoite from stools 10 days after completion of treatment Clinical response: range and mean number days from start of treatment to resolution of clinical symptoms Adverse events: method for obtaining information on adverse events, specific adverse events, and number of participants who developed any adverse events were not reported
Notes	Location: Medical Center Hospital, Ankara, Turkey Date: 1994 (date of publication only; actual study period not reported) Source of funding: not stated Attempts to contact the authors were unsuccessful

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Tripathi 1986

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Methods	Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: unclear; reported as "double-blind", but procedure for blinding the participants, care provider, and outcome assessor not described Inclusion of all randomized participants: 100%
Participants	Number: 40 enrolled and analysed Inclusion criteria: adults with symptoms of intestinal amoebiasis and stool specimens positive for E. histolytica by direct smear and formol-ether concentration methods, sigmoidoscopy, colonic ulcer scrapings and positive stool culture on NIH media Exclusion criteria: received amoebicidal drugs during the previous 4 weeks; pregnant women; dehydrated patients; liver abscess and any evidence of hepatic, renal, haematological, and ECG abnormalities Concomitant intestinal infection: 4 in each group had concomitant Giardia lamblia in the stools
Interventions	GO 10213 (satranidazole): 150 mg thrice daily for 10 days Metronidazole: 400 mg thrice daily for 10 days
Outcomes	Parasitological response: eradication of E. histolytica on stool examinations on follow up 28 days after start of treatment Clinical response: relief of presenting clinical signs and symptoms and healing of ulcers on sigmoidoscopy on follow up 28 days after start of treatment Adverse events: volunteered by the participants; laboratory tests monitored before and after treatment including complete blood count, liver transaminases (SGOT, SGPT), serum bilirubin, blood urea, urinalysis, and electrocardiogram Not included in this review: frequency of loose stools/day from start of treatment
Notes	Geographic location: hospital in Bhopal, India Date: 1986 (date of publication only; actual study period not reported) Source of funding: Ciba-Geigy India Limited

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Characteristics of excluded studies [ordered by study ID]

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Study	Reason for exclusion
Abd-Rabbo 1969	Not RCT
Abdallah 1969	Not RCT
Achar 1967	Not RCT
Ali Ata 1967	Not RCT
Alterio 1968	Not RCT
Amato Neto 1968	Not RCT
Apt 1976	Not RCT
Apt 1983	Not RCT
Arredondo 1993	Study population: RCT that compared medical treatment with medical treatment plus liver puncture in patients with amoebic liver abscess
Atias 1972	Not RCT
Bakshi 1978	Review of 17 RCTs conducted in India comparing tinidazole with metronidazole over a 2-year period
Banerjee 1976	Not RCT
Baranski 1966	Not RCT
Barroso 1969	Not RCT
Bassily 1987	Not RCT
Belkind 2004	Study population: asymptomatic children positive for intestinal helminths or protozoa
Bezjak 1964	Not RCT
Bhatia 1998	Study population: RCT comparing metronidazole with secnidazole in treating patients with amoebic liver abscess
Biagi 1966	The trial is an RCT comparing clefamide with placebo given not as treatment but as chemoprophylaxis for intestinal amoebiasis among asymptomatic carriers of E. histolytica. Both the primary trial and the subsidiary trial by Biagi are probably duplicate publications of the same study since the 2 trials are similar in all aspects of the study.
Biagi 1978	Not RCT
Blanc 1965	Not a RCT. Both reports (1965 and 1966) by Blanc are probably duplicate publications of the same study since the 2 trials are similar in all aspects of the study
Blessman 2002	Study population: RCT comparing paromomycin with diloxanide furoate for the treatment of asymptomatic carriers of E. histolytica
Blessman 2003a	Intervention and study population: RCT comparing metronidazole alone with ultrasound-guided needle aspiration of the abscess in addition to metronidazole in patients with amoebic liver abscess
Botero 1967	Not RCT
Campos 1969	Not RCT
Cardoso Salles 1970	Not RCT: alternate allocation of patients with intestinal amoebiasis to receive 2 different doses of ethylchlordiphene
Cariry 1969	Not RCT
Chari 1970	Not RCT
Chaudhuri 1966	Not RCT
Cho 1972	Not reported to be randomized but described as a double-blind trial comparing Ro 7-0207 with metronidazole in treating participants with intestinal amoebiasis or E. histolytica asymptomatic carriers; repeated attempts to gather more details from the authors were unsuccessful because the primary author is deceased and the other authors cannot be contacted
Cohen 1975	Study population: RCT comparing chloroquine and metronidazole for the treatment of amoebic liver abscess
da Cunha 1977	Not RCT
Datta 1974	Study population: amoebic liver abscess
de Carvalho 1965	Not RCT
de la Rey 1989	Intervention and study population: RCT that randomized patients with amoebic liver abscess to either metronidazole alone or ultrasound-guided aspiration of the abscess in addition to metronidazole
de Oliveira 1969	Not RCT
Delgado 1971	Not RCT
Devic 1974	Not RCT
Dhariwal 1963	Not RCT
Donckaster 1957	Not RCT
dos Santos 1969	Not RCT
Doshi 1968	Not RCT
el Mofti 1965	Not RCT
Esquivel 1979	Study population: RCT that compared metronidazole, emetine, or both for treating patients with amoebic liver abscess
Ey 1977	Not RCT
Felix 1966	Not a RCT. Both reports by Felix are probably duplicate publications of the same study since the 2 trials are similar in all aspects of the study
Freeman 1990	Intervention and study population: compared efficacy of antiamoebic drug therapy plus needle aspiration with antiamoebic drug therapy alone for patients with amoebic liver abscess
Gilman 1980	Not RCT: diagnostic validity study comparing conventional and immunofluorescent techniques for detection of E. histolytica in rectal biopsies
Gorbea 1989	Not RCT
Hatchuel 1975	Study population: double-blind trial that compared tinidazole and metronidazole for treating patients with amoebic liver abscess
Hoekenga 1951	Not RCT
Holz 1965	Not RCT
Huggins 1965	Not RCT
Huggins 1969	Not RCT
Huggins 1974	Not a RCT. Both reports by Huggins are probably duplicate publications of the same study since the 2 trials are similar in all aspects of the study
Huggins 1977	Not RCT
Huggins 1980	Not RCT
Huggins 1981	Not RCT
Irusen 1992	Study population: amoebic liver abscess
Islam 1975	Not RCT
Islam 1978a	Study population: RCT that compared metronidazole and tinidazole for treating patients with amoebic liver abscess
Islam 1978b	Study population: amoebic liver abscess
Jain 1990	Study population: open clinical trial that compared efficacy of various treatment regimens containing dehydroemetine and/or metronidazole for treating patients with hepatopulmonary amoebiasis
Jayawickrema 1975	Study population: RCT that compared metronidazole with emetine and chloroquine in the treatment of patients with hepatic amoebiasis
Kaur 1972	Not RCT
Khalil 1987	Not RCT
Khokhani 1977	Study population: RCT that compared metronidazole with emetine and chloroquine in the treatment of patients with hepatic amoebiasis
Khokhani 1978	Study population: RCT that compared metronidazole with tinidazole in the treatment of patients with amoebic liver abscess
Konar 1963	Not RCT
Krishnaiah 2003	Not RCT: pharmacokinetic trial comparing 2 formulations of tinidazole given to healthy human volunteers
Kurt 2008	Study population: RCT comparing metronidazole with single-dose ornidazole for treatment of dientamoebiasis
Laham 1951	Not RCT
Levy 1967	Not RCT
Martinez 1969	Not RCT
Masters 1979	Not RCT
Mathur 1974	Not RCT
McAuley 1992	Not RCT
Mendis 1984	Study population: RCT that compared metronidazole with tinidazole in the treatment of patients with hepatic amoebiasis
Misra 1976a	Not RCT
Misra 1976b	Combination of a RCT involving 60 patients randomly assigned to either tinidazole or metronidazole, and a nonrandomized trial involving 30 patients given tinidazole 600 mg twice daily for 5 to 10 days and another 20 patients given tinidazole at 2 g once daily for 3 days. There was no separate analysis for the randomized patients only. Several attempts to contact the authors were unsuccessful
Morales 1975	Study population: RCT that compared intravenous metronidazole with intramuscular emetine in treating patients with amoebic liver abscess
Murray 1980	Intervention: did not study effect of any antiamoebic drug for treating amoebic colitis
Muzzafar 2006	Study population: amoebic liver abscess
Nahrevanian 2008	Study population and not RCT: study to determine prevalence of Cryptosporidium in immunocompromised patients
Naik 1968	Not RCT
Nanavati 1965	Not RCT
Nel 1985	Intervention and study population: study to determine indications for aspiration of amoebic liver abscess
Nel 1986	Intervention and study population: study to determine if aspiration influences course of amoebic liver abscess
O'Holohan 1972	Not RCT
Okeniyi 2007	Study population: no mention of amoebic colitis
Olaeta 1996	Not RCT: alternate allocation of patients with intestinal amoebiasis to receive either quinfamide or etofamide
Omrani 1995	Not RCT
Orozco 1975	Study population: amoebic liver abscess
Padilla 1995	Study population: asymptomatic amoebic infection
Padilla 1998	Unclear if RCT
Padilla 2002	Intervention and study population: RCT where children whose stools became negative for E. histolytica cysts and were asymptomatic after 1 or 2 doses of quinfamide were randomized into 3 groups to determine whether administering quinfamide every 3 to 6 months resulted in reduction in frequency of amoebic infection to below 27%
Pimparkar 1966	Not RCT
Populaire 1980	Pharmacokinetic study of secnidazole given to healthy human volunteers
Powell 1965a	Not RCT
Powell 1965b	Study population: clinical trial of dehydroemetine, emetine, and chloroquine in treating patients with amoebic liver abscess
Powell 1965c	Study population: amoebic liver abscess
Powell 1965d	Not RCT
Powell 1966a	Not RCT
Powell 1966b	Not RCT
Powell 1966c	Not RCT
Powell 1967	Study population: asymptomatic amoebic colitis
Powell 1968	Report of 5 trials using metronidazole in different dosages and durations for the treatment of amoebic dysentery
Powell 1969a	Not RCT
Powell 1969b	Review of several clinical trials using several amoebicides including niridazole, alone or in combination, in the treatment of amoebic dysentery or amoebic liver abscess
Powell 1969c	Guidelines on how to conduct drug trials in amoebiasis
Powell 1971a	Not RCT
Powell 1971b	Letter relaying observation of authors that no cases of liver abscess developed among patients with amoebic dysentery given chloroquine in addition to broad spectrum antibiotics or luminal amoebicides compared to those not given chloroquine
Powell 1972a	Report of clinical trials of new nitroimidazole derivatives for treating patients with amoebic liver abscess
Powell 1972b	Review on the evolution of drug therapy for amoebiasis and also presents the latest developments on niridazole, metronidazole, and other nitroimidazole drugs undergoing clinical trials at that time
Powell 1973	Not RCT
Prakash 1974	Not RCT: alternate allocation of patients with intestinal amoebiasis to receive either tinidazole or metronidazole
Qureshi 1994	Not RCT
Qureshi 1997	Not RCT
Rodrigues 1968	Not RCT
Ruas 1973	Study population: amoebic liver abscess
Ruchko 1978	Not RCT
Saha 1966	Not RCT
Saha 1970	Not RCT
Salem 1964	Not RCT
Salem 1967	Not RCT
Sandia 1977	Not RCT
Sangiuolo 1969	Study population: RCT comparing the efficacy of a combination of canulase and iodochlorhydroxyquinoline (Septo-canulase) with placebo for the treatment of patients who had "acute gastroenteritis, food-borne gastroenteritis, chronic enterocolitis, or ulcerative colitis". There was no mention of amoebic colitis or laboratory diagnosis of amoebic colitis among the included patients
Sankale 1966	Not RCT
Sankale 1969	Not RCT
Sankale 1974	Not RCT
Satpathy 1988	Study population: amoebic liver abscess
Schapiro 1967	Not RCT
Scragg 1968	Study population: amoebic liver abscess
Scragg 1970	Study population: amoebic liver abscess
Segal 1967	Not RCT
Sharma 1989	Intervention and study population: RCT that compared metronidazole alone with needle aspiration of the abscess in addition to metronidazole in patients with amoebic liver abscess
Shrotriya 1985	Not RCT
Simjee 1985	Study population: amoebic liver abscess
Simon 1967	Not RCT
Sinuhaji 1986	Preliminary report of a trial on children with acute amoebic dysentery randomized to receive a single dose of either metronidazole 50 mg/kg body weight/day or secnidazole 30 mg/kg body weight/day. There were incomplete results and no final published report of this trial. Attempts to contact the authors or the institution where the study was conducted were unsuccessful
Sladden 1964	Not RCT
Soh 1980	Study population: amoebic liver abscess
Spellberg 1969	Study population: amoebic liver abscess
Spillman 1976	Study population: RCT that compared metronidazole with tinidazole for treating those with asymptomatic E. histolytica infection and/or E. hartmanni infections
Sutrisno 1978	Not RCT
Tandon 1997	Intervention and study population: RCT that compared metronidazole alone with needle aspiration of the abscess in addition to metronidazole in patients with amoebic liver abscess
Thoren 1990a	Study population: RCT that compared metronidazole, tinidazole, and diloxanide furoate in treating asymptomatic homosexual carriers of E. histolytica
Thoren 1990b	Study population: asymptomatic E. histolytica homosexual carriers
Tjaij 1969	Not RCT
Tjaij 1970	Not RCT
Vaidya 1983	Pharmacokinetic study of Go.10213 and does not compare the drug with placebo or another antiamoebic drug
Vakil 1967	Not RCT: alternate allocation of children and adults with amoebic dysentery, nondysenteric intestinal amoebiasis, or hepatic amoebiasis to receive either intramuscular dehydroemetine or emetine
Vakil 1971	Not RCT
Vakil 1974	Summary report of several clinical trials of various amoebicidal drugs conducted in one medical centre in Bombay, India over the past 12 years
Valencia 1973	Review on use of erythromycin stearate over the last 3 years on 500 patients with intestinal amoebiasis, patients with amoebic cysts, and those with other diseases of the colon
Vanijanonta 1985	Study population: patients with amoebic liver abscess were treated with low dose tinidazole and needle aspiration
Viswanathan 1968	Not RCT
Wang 1971a	Not RCT
Wang 1971b	Report of 2 cases of oxytetracycline resistant amoebic dysentery
Watson 1975	Study population: amoebic infection of the eye
Welch 1978	Not RCT
Widjaya 1991	Intervention and study population: RCT that compared various antiamoebic drug combinations with percutaneous drainage in addition to combination drug therapy for treating patients with amoebic liver abscess
Wilmot 1962	Not RCT
Wolfe 1973	Not RCT
Wolfensberger 1968	Not RCT
Zuberi 1973	Not RCT

---

 E. histolytica: Entamoeba histolytica; RCT: randomized controlled trial.

 

Characteristics of studies awaiting assessment [ordered by study ID]

Guevara 1980

---

Methods	Unclear (reported as double-blind in the title)
Participants	Nondysenteric amoebic colitis (from abstract)
Interventions	Quinfamide given at 3 doses (300 mg, 600 mg, and 1200 mg) vs teclozan (from abstract)
Outcomes	Eradication of amoeba in stools and rectosigmoidoscopic findings (from abstract)
Notes	Full paper not available

---

Soedin 1989

---

Methods	Unknown
Participants	intestinal amoebiasis
Interventions	Single-dose secnidazole versus 5-day regimen of a combination of tetracycline and clioquinol
Outcomes	Unknown
Notes	Full paper not available; may possibly be the same study as Soedin 1985

---

 

Comparison 1. Alternative drug vs metronidazole

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 Clinical failure: 1 to 14 days after end of treatment

5

375

Risk Ratio (M-H, Random, 95% CI)

0.41 [0.11, 1.64]

---

1.1 Ornidazole

2

40

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

1.2 Praziquantel

1

50

Risk Ratio (M-H, Random, 95% CI)

0.69 [0.17, 2.78]

---

1.3 Tinidazole

2

285

Risk Ratio (M-H, Random, 95% CI)

0.17 [0.02, 1.30]

---

 2 Clinical failure: 15 to 60 days after end of treatment

12

679

Risk Ratio (M-H, Random, 95% CI)

0.39 [0.21, 0.73]

---

2.1 Ornidazole

2

118

Risk Ratio (M-H, Random, 95% CI)

3.00 [0.13, 71.89]

---

2.2 Panidazole

1

44

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

2.3 Satranidazole (GO 10213)

1

40

Risk Ratio (M-H, Random, 95% CI)

0.8 [0.40, 1.60]

---

2.4 Tinidazole

8

477

Risk Ratio (M-H, Random, 95% CI)

0.28 [0.15, 0.51]

---

 3 Parasitological failure: 1 to 14 days after end of treatment

6

419

Risk Ratio (M-H, Random, 95% CI)

1.05 [0.85, 1.29]

---

3.1 Ornidazole

2

40

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

3.2 Praziquantel

1

50

Risk Ratio (M-H, Random, 95% CI)

0.69 [0.17, 2.78]

---

3.3 Secnidazole

1

44

Risk Ratio (M-H, Random, 95% CI)

0.31 [0.01, 7.12]

---

3.4 Tinidazole

2

285

Risk Ratio (M-H, Random, 95% CI)

1.01 [0.58, 1.74]

---

 4 Parasitological failure: 15 to 60 days after end of treatment

13

Risk Ratio (M-H, Random, 95% CI)

Subtotals only

---

4.1 Ornidazole

2

135

Risk Ratio (M-H, Random, 95% CI)

0.18 [0.02, 1.41]

---

4.2 Panidazole

1

86

Risk Ratio (M-H, Random, 95% CI)

1.71 [0.81, 3.60]

---

4.3 Satranidazole (GO 10213)

1

40

Risk Ratio (M-H, Random, 95% CI)

0.33 [0.01, 7.72]

---

4.4 Tinidazole

9

507

Risk Ratio (M-H, Random, 95% CI)

0.64 [0.25, 1.64]

---

 5 Relapse (ornidazole)

2

Risk Ratio (M-H, Random, 95% CI)

Totals not selected

---

 6 Adverse events

11

Risk Ratio (M-H, Random, 95% CI)

Subtotals only

---

6.1 Ornidazole

1

20

Risk Ratio (M-H, Random, 95% CI)

0.67 [0.14, 3.17]

---

6.2 Panidazole

1

100

Risk Ratio (M-H, Random, 95% CI)

1.12 [0.87, 1.45]

---

6.3 Satranidazole (GO 10213)

1

40

Risk Ratio (M-H, Random, 95% CI)

0.71 [0.27, 1.88]

---

6.4 Tinidazole

8

477

Risk Ratio (M-H, Random, 95% CI)

0.65 [0.46, 0.92]

---

 

Comparison 2. Any antiamoebic drug vs placebo

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 Clinical failure: 1 to 14 days after end of treatment

3

Risk Ratio (M-H, Random, 95% CI)

Subtotals only

---

1.1 Quinfamide

1

40

Risk Ratio (M-H, Random, 95% CI)

0.35 [0.21, 0.60]

---

1.2 Nitazoxanide

2

153

Risk Ratio (M-H, Random, 95% CI)

0.21 [0.06, 0.81]

---

 2 Parasitological failure: 1 to 14 days after end of treatment

4

Risk Ratio (M-H, Random, 95% CI)

Subtotals only

---

2.1 Nitazoxanide

2

167

Risk Ratio (M-H, Random, 95% CI)

0.25 [0.05, 1.27]

---

2.2 Quinfamide

1

96

Risk Ratio (M-H, Random, 95% CI)

0.30 [0.19, 0.47]

---

2.3 10 different drugs belonging to 6 drug classes

1

367

Risk Ratio (M-H, Random, 95% CI)

0.37 [0.26, 0.53]

---

 3 Other adverse events

3

Risk Ratio (M-H, Random, 95% CI)

Totals not selected

---

3.1 Nitazoxanide

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

3.2 Quinfamide

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

3.3 10 different drugs belonging to 6 drug classes

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

 

Comparison 3. Combination regimen vs monotherapy

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 Clinical failure: 1 to 14 days after end of treatment

5

Risk Ratio (M-H, Random, 95% CI)

Totals not selected

---

1.1 Dehydroemetine and tetracycline and diloxanide furoate vs metronidazole

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

1.2 Metronidazole and diiodohydroxyquinoline vs metronidazole

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

1.3 Metronidazole and furazolidone vs metronidazole

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

1.4 Combinations vs nimorazole, aminosidine, and etofamide

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

1.5 Tetracycline and clioquinol vs secnidazole

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

 2 Parasitological failure: 1 to 14 days after end of treatment

6

Risk Ratio (M-H, Random, 95% CI)

Totals not selected

---

2.1 Dehydroemetine and tetracycline and diloxanide furoate vs metronidazole

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

2.2 Metronidazole and diiodohydroxyquinoline vs metronidazole

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

2.3 Metronidazole and furazolidone vs metronidazole

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

2.4 Combinations vs nimorazole, aminosidine, and etofamide

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

2.5 Quinfamide and mebendazole vs nitazoxanide (mixed infections only)

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

2.6 Tetracycline and clioquinol vs secnidazole

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

 

Comparison 4. Single dose regimen vs longer regimen

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 Clinical failure: 1 to 14 or 15 to 60 days after end of treatment, combined

3

Risk Ratio (M-H, Random, 95% CI)

Totals not selected

---

1.1 Quinfamide: 1 dose vs 2 or 3 doses

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

1.2 Secnidazole (1 dose) vs tetracycline and clioquinol (5 days)

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

1.3 Secnidazole (1 dose) vs tinidazole (2 days)

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

 2 Parasitological failure: 1 to 14 days after end of treatment

4

Risk Ratio (M-H, Random, 95% CI)

Totals not selected

---

2.1 Quinfamide (1 dose) vs nitazoxanide (3 days)

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

2.2 Quinfamide: 1 dose vs 2 or 3 doses

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

2.3 Secnidazole (1 dose) vs metronidazole (10 days)

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

2.4 Secnidazole (1 dose) vs tetracycline and clioquinol (5 days)

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

 

Comparison 5. Other antiamoebic drug comparisons

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 Clinical failure: 1 to 14 days after end of treatment

5

Risk Ratio (M-H, Random, 95% CI)

Subtotals only

---

1.1 Ornidazole vs tinidazole

2

66

Risk Ratio (M-H, Random, 95% CI)

0.23 [0.03, 1.96]

---

1.2 Ornidazole vs secnidazole

1

102

Risk Ratio (M-H, Random, 95% CI)

0.95 [0.17, 5.45]

---

1.3 Chlorhydroxyquinoline vs diiodohydroxyquinoline

1

100

Risk Ratio (M-H, Random, 95% CI)

0.24 [0.11, 0.53]

---

1.4 MK-910 (4 dosages)

1

40

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

 2 Parasitological failure: 1 to 14 days after end of treatment

9

Risk Ratio (M-H, Random, 95% CI)

Totals not selected

---

2.1 Ornidazole vs tinidazole

2

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

2.2 Ornidazole vs secnidazole

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

2.3 Chlorhydroxyquinoline vs diiodohydroxyquinoline

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

2.4 MK-910 (4 dosages)

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

2.5 Quinfamide vs secnidazole

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

2.6 Quinfamide vs nitazoxanide

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

2.7 Metronidazole and iodoquinol vs Saccharomyces boulardii or placebo

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

2.8 2 fixed-drug combinations of diloxanide furoate and tetracycline with or without chloroquine

1

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

 

Comparison 6. Subgroup analyses: alternative drug vs metronidazole

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 Parasitological failure 15 to 60 days after end of treatment, by clinical category

13

768

Risk Ratio (M-H, Random, 95% CI)

0.81 [0.45, 1.48]

---

1.1 Amoebic dysentery

3

162

Risk Ratio (M-H, Random, 95% CI)

0.79 [0.07, 8.68]

---

1.2 Nondysenteric amoebic colitis

3

89

Risk Ratio (M-H, Random, 95% CI)

1.63 [1.09, 2.42]

---

1.3 Amoebic colitis or intestinal amoebiasis, unspecified

9

517

Risk Ratio (M-H, Random, 95% CI)

0.56 [0.29, 1.10]

---

 2 Parasitological failure 15 to 60 days after end of treatment, by age group

13

Risk Ratio (M-H, Random, 95% CI)

Subtotals only

---

2.1 Adults (age ≥ 15 years)

10

622

Risk Ratio (M-H, Random, 95% CI)

0.63 [0.25, 1.54]

---

2.2 Children (age < 15 years)

0

0

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

2.3 Both adults and children

3

146

Risk Ratio (M-H, Random, 95% CI)

0.79 [0.34, 1.85]

---

 3 Parasitological failure 15 to 60 days after end of treatment, single or mixed intestinal infection

13

Risk Ratio (M-H, Random, 95% CI)

Subtotals only

---

3.1 Amoebic infection only

10

586

Risk Ratio (M-H, Random, 95% CI)

0.63 [0.25, 1.59]

---

3.2 Mixed intestinal infection

3

182

Risk Ratio (M-H, Random, 95% CI)

0.63 [0.10, 3.91]

---

 4 Parasitological failure 15 to 60 days after end of treatment, by criteria

13

Risk Ratio (M-H, Random, 95% CI)

Subtotals only

---

4.1 WHO criteria

9

517

Risk Ratio (M-H, Random, 95% CI)

0.56 [0.29, 1.10]

---

4.2 Other criteria

4

251

Risk Ratio (M-H, Random, 95% CI)

1.31 [0.58, 2.94]

---

 

Comparison 7. Subgroup analyses: any antiamoebic drug vs placebo

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 Parasitological failure 1 to 14 days after end of treatment, by clinical category

4

Risk Ratio (M-H, Random, 95% CI)

Subtotals only

---

1.1 Nondysenteric amoebic colitis

1

96

Risk Ratio (M-H, Random, 95% CI)

0.30 [0.19, 0.47]

---

1.2 Amoebic colitis or intestinal amoebiasis, unspecified

3

534

Risk Ratio (M-H, Random, 95% CI)

0.33 [0.17, 0.62]

---

 2 Clinical failure 1 to 14 days after end of treatment, by age group

3

193

Risk Ratio (M-H, Random, 95% CI)

0.27 [0.14, 0.51]

---

2.1 Adults (age ≥ 15 years)

3

143

Risk Ratio (M-H, Random, 95% CI)

0.31 [0.16, 0.60]

---

2.2 Children (age < 15 years)

1

50

Risk Ratio (M-H, Random, 95% CI)

0.14 [0.04, 0.56]

---

 3 Parasitological failure 1 to 14 days after end of treatment, by age group

4

630

Risk Ratio (M-H, Random, 95% CI)

0.33 [0.23, 0.48]

---

3.1 Adults (age ≥ 15 years)

3

213

Risk Ratio (M-H, Random, 95% CI)

0.34 [0.20, 0.56]

---

3.2 Children (age < 15 years)

1

50

Risk Ratio (M-H, Random, 95% CI)

0.08 [0.01, 0.54]

---

3.3 Both adults and children

1

367

Risk Ratio (M-H, Random, 95% CI)

0.37 [0.26, 0.53]

---

 

Comparison 8. Subgroup analyses: combination regimen vs monotherapy

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 Clinical failure: 1 to 14 days after end of treatment, by intervention

5

Risk Ratio (M-H, Random, 95% CI)

Subtotals only

---

1.1 Combination vs metronidazole

3

1025

Risk Ratio (M-H, Random, 95% CI)

0.33 [0.11, 0.98]

---

1.2 Combination vs alternative drugs

2

480

Risk Ratio (M-H, Random, 95% CI)

2.60 [0.20, 33.80]

---

 2 Parasitological failure: 1 to 14 days after end of treatment, by intervention

6

Risk Ratio (M-H, Random, 95% CI)

Subtotals only

---

2.1 Combination vs metronidazole

3

720

Risk Ratio (M-H, Random, 95% CI)

0.36 [0.15, 0.86]

---

2.2 Combination vs alternative drugs

3

577

Risk Ratio (M-H, Random, 95% CI)

1.84 [0.41, 8.37]

---

 

Comparison 9. Subgroup analyses: any single dose regimen vs longer regimen

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 Parasitological failure: 1 to 14 days after end of treatment, by intervention

4

221

Risk Ratio (M-H, Random, 95% CI)

0.73 [0.11, 4.91]

---

1.1 Secnidazole single dose vs longer duration

2

124

Risk Ratio (M-H, Random, 95% CI)

0.14 [0.06, 0.35]

---

1.2 Quinfamide single dose vs longer duration

2

97

Risk Ratio (M-H, Random, 95% CI)

2.13 [1.02, 4.46]

---

 

Table 1. Amoebicide classes and examples

---

Amoebicide	Class	Example
Luminal	Arsenical compounds	Carbarsone, acetarsone or acetarsol, treparsol, diphetarsone, glycobiarsol or bismuth glycolylarsanilate, stovarsol, and thioarsenite, thiocarbarsone or thiocarabazone, arsthinol
	Hydroxyquinoline derivatives	Chiniofon or quinoxyl, clioquinol or iodochlorhydroxyquin, and iodoquinol or diiodohydroxyquin
	Dichloroacetamide derivatives	Diloxanide furoate or entamide furoate, clefamide, eticlordifene or ethylchlordiphene or etofamide or etophamide, and quinfamide
	Benzylamine derivatives	Teclozan, chlorbetamide or mantomide, and chlorphenoxamide or mebinol
	Antibiotic amoebicides	Tetracycline, oxytetracycline, chlortetracycline, erythromycin, paromomycin, and fumagillin
	Nithrothiazole salicylamide	Nitazoxanide
Tissue	Emetine and its derivatives	Emetine hydrochloride, emetine bismuth iodide, dehydroemetine dihydrochloride, and dehydroemetine resinate
	Aminoquinoline	Chloroquine
	Thiazole derivative	Niridazole
	Nitroimidazoles	Metronidazole, tinidazole, ornidazole, secnidazole, and nimorazole

---