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Antiamoebic drugs for treating amoebic colitis

  1. Maria Liza M Gonzales1,*,
  2. Leonila F Dans2,
  3. Elizabeth G Martinez1

Editorial Group: Cochrane Infectious Diseases Group

Published Online: 15 APR 2009

Assessed as up-to-date: 4 DEC 2008

DOI: 10.1002/14651858.CD006085.pub2


How to Cite

Gonzales MLM, Dans LF, Martinez EG. Antiamoebic drugs for treating amoebic colitis. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD006085. DOI: 10.1002/14651858.CD006085.pub2.

Author Information

  1. 1

    College of Medicine-Philippine General Hospital, University of the Philippines, Department of Pediatrics, Manila, National Capital Region, Philippines

  2. 2

    Philippine General Hospital, University of the Philippines, Departments of Pediatrics and Clinical Epidemiology, Manila, National Capital Region, Philippines

*Maria Liza M Gonzales, Department of Pediatrics, College of Medicine-Philippine General Hospital, University of the Philippines, Taft Avenue, Manila, National Capital Region, 1000, Philippines. lizmgonzales@yahoo.com.

Publication History

  1. Publication Status: New
  2. Published Online: 15 APR 2009

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Characteristics of included studies [ordered by study ID]
Asrani 1995

MethodsGeneration 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


ParticipantsNumber: 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protocol violators (33 in metronidazole group, 30 in combination therapy group); 1 participant in the combination group withdrawn from the study due to allergic reaction on the first day of treatment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
  1. Metronidazole: 400 mg thrice daily orally for 5 days
  2. 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
  1. Parasitological cure: clearance of E. histolytica in stool specimens at end of treatment
  2. Clinical cure: remission of clinical symptoms on days 5 and 10 after start of treatment
  3. 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)


NotesLocation: 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

Awal 1979

MethodsGeneration of allocation sequence: random-numbers table

Allocation concealment: unclear

Blinding: open

Inclusion of all randomized participants: 100%


ParticipantsNumber: 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
  1. Tinidazole: 2 g single oral dose daily for 3 days
  2. Tinidazole: 2 g single oral dose daily for 2 days
  3. Metronidazole: 2 g single dose for 2 days


Outcomes
  1. Parasitological cure: eradication of E. histolytica from stools on day 30 from start of therapy
  2. Clinical cure: resolution of baseline symptoms of intestinal amoebiasis on day 30 from start of therapy
  3. 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)


NotesLocation: hospital in Bangladesh

Date: 1979 (date of publication only; actual study period not reported)

Source of funding: not stated

Batra 1972

MethodsGeneration of allocation sequence: unclear

Allocation concealment: unclear

Blinding: open

Inclusion of all randomized participants: 100%


ParticipantsNumber: 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


InterventionsMK- 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

  1. 0.5 mg/kg body weight
  2. 1.0 mg/kg body weight
  3. 2.0 mg/kg body weight
  4. 3.0 mg/kg body weight


Outcomes
  1. 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
  2. Clinical response: reduction in clinical signs and symptoms
  3. 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


NotesLocation: hospital in New Delhi, India

Date: 1972 (date of publication only; actual study period not reported)

Source of funding: Merck, Sharp and Dohme

Botero 1974

MethodsGeneration 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)


ParticipantsNumber: 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
  1. Ro 7-0207 (ornidazole): 2 x 250 mg capsules twice daily for 10 days
  2. Metronidazole: 2 x 250 mg capsules twice daily for 10 days


Outcomes
  1. 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
  2. Relapse: reappearance of E. histolytica in the stools within 1 month after becoming negative at the end of treatment
  3. 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
  4. 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)


NotesLocation: hospital in Medellin, Colombia

Date: 1974 (date of publication only; actual study period not reported)

Source of funding: not stated

Botero 1977

MethodsGeneration 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%


ParticipantsNumber: 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
  1. Panidazole: 2 x 250 mg tablets (500 mg), 4 times daily for 6 days
  2. Metronidazole: 2 x 250 mg tablets (500 mg), 4 times daily for 6 days


Outcomes
  1. Parasitological cure: eradication of parasites in any of the post-treatment laboratory examinations
  2. Clinical response: improvement or disappearance of symptoms during weekly follow up for 4 weeks after treatment
  3. 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


NotesLocation: Colombia

Date: 1977 (date of publication only; actual study period not reported)

Source of funding: not stated

Chunge 1989

MethodsGeneration 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


ParticipantsNumber: 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
  1. Tinidazole (Fasigyn): 2 g single oral dose daily for 3 days
  2. Tinidazole (Tynazole): 2 g single oral dose daily for 3 days
  3. Metronidazole (Flagyl): 400 mg thrice daily orally for 5 days
  4. Metronidazole (Metrozol): 400 mg thrice daily orally for 5 days


Outcomes
  1. Parasitological cure: absence of trophozoites or cysts from stool specimens on day 6 after start of treatment
  2. Clinical cure: absence of any 4 of the symptoms initially present at day 6 after start of treatment


NotesLocation: 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

Davila 2002

MethodsGeneration 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%


ParticipantsNumber: 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
  1. Nitazoxanide: 100 mg/5 mL twice daily orally for 3 days
  2. 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
  1. Parasitological cure: eradication of E. histolytica/E. dispar in stool examination 14 days after treatment
  2. 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


NotesLocation: 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

Donckaster 1964

MethodsGeneration 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%


ParticipantsNumber: 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
  1. Dimethychlortetracycline: once daily on an empty stomach for 10 days at the following oral daily doses – children 15 mg/kg and adults 900 mg
  2. Oxytetracycline: once daily on an empty stomach for 10 days at the following oral daily doses – children 25 mg/kg and adults 1500 mg
  3. Tetracycline: once daily on an empty stomach for 10 days at the following oral daily doses – children 25 mg/kg and adults 1500 mg
  4. 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
  5. Chlorbetamide: once daily after meals for 10 days at the following oral daily doses – children 100 mg/kg and adults 4000 mg
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  1. Parasitological failure: presence of cysts and/or trophozoites in the stool examinations done 10 and 40 days after start of treatment
  2. Adverse events: voluntary reporting of clinical adverse events by participants every 3 days during treatment and every 10 to 15 days after treatment


NotesLocation: 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

Huggins 1982

MethodsGeneration 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%


ParticipantsNumber: 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
  1. Win 40.014 (quinfamide): 100 mg single oral dose
  2. Win 40.014 (quinfamide): 100 mg twice a day orally at 12-hourly intervals for 1 day
  3. Win 40.014 (quinfamide): 100 mg thrice a day orally at 8-hourly intervals for 1 day
  4. 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
  1. Parasitological cure: clearance of amoeba from stools on days 2 and 7 after treatment
  2. Clinical cure: disappearance of the 4 symptoms recorded at baseline (pain, colic, diarrhoea, and constipation) evaluated on days 2 and 7 after treatment
  3. Adverse events: only 2 symptoms (nausea and headache) solicited from participants; laboratory tests were done before and after treatment but results not presented


NotesLocation: 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

Joshi 1975

MethodsGeneration of allocation sequence: unclear

Allocation concealment: unclear

Blinding: open

Inclusion of all randomized participants: 100%


ParticipantsNumber: 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
  1. Tinidazole: 600 mg twice daily orally for 5 days
  2. 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
  1. Parasitological response: eradication of E. histolytica in stools on day 30 after start of treatment
  2. Clinical response: complete or partial relief of symptoms and healing of ulcers on sigmoidoscopy, when carried out
  3. 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


NotesLocation: 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.

Kapadia 1968

MethodsGeneration of allocation sequence: unclear

Allocation concealment: unclear

Blinding: unclear

Inclusion of all randomized participants: 100%


ParticipantsNumber: 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
  1. Chlorhydroxquinoline: 500 mg thrice daily orally for 10 days
  2. Di-diiodohydroxyquinoline: 500 mg thrice daily orally for 10 days


Not stated if chlorhydroxquinoline and di-diiodohydroxyquinoline were identical in appearance


Outcomes
  1. Parasitological cure: eradication of E. histolytica from stools at the end of the 10-day treatment period
  2. Clinical cure: improvement or disappearance of symptoms at the end of the 10-day treatment period
  3. Adverse events: clinical adverse events and liver function test monitored before and after treatment including total bilirubin, serum albumin and globulin, and zinc sulfate


NotesLocation: 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

Karabay 1999

MethodsGeneration of allocation sequence: unclear

Allocation concealment: unclear

Blinding: open

Inclusion of all randomized participants: 100%


ParticipantsNumber: 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
  1. Secnidazole: 2 g single oral dose
  2. Metronidazole: 750 mg thrice daily orally for 10 days


Outcomes
  1. 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


NotesLocation: military hospital in Erzurum, Turkey

Date: July 1998 to November 1998

Source of funding: not stated

Mansour-Ghanaei 2003

MethodsGeneration 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))


ParticipantsNumber: 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
  1. Metronidazole, iodoquinol, and placebo: metronidazole 750 mg and iodoquinol 650 mg given thrice daily orally with placebo tablets for 10 days
  2. 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
  1. 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


NotesLocation: 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

Mathur 1976

MethodsGeneration of allocation sequence: unclear

Allocation concealment: unclear

Blinding: open

Inclusion of all randomized participants: 100%


ParticipantsNumber: 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
  1. Tinidazole: 600 mg twice daily orally for 5 days
  2. 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
  1. Parasitological cure: eradication of E. histolytica from stools on day 30 after start of treatment
  2. Clinical cure: relief of presenting clinical signs and symptoms and healing of ulcers on sigmoidoscopy, when carried out
  3. 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


NotesLocation: 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.

Misra 1974

MethodsGeneration 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%


ParticipantsNumber: 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
  1. Tinidazole: 600 mg twice daily orally for 5 days
  2. 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
  1. Parasitological cure: eradication of E. histolytica on follow-up stool examinations on day 30 after start of treatment
  2. Clinical cure: disappearance of presenting clinical symptoms and healing of ulcers on sigmoidoscopy on day 30 after start of treatment
  3. 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)


NotesLocation: 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)

Misra 1977

MethodsGeneration of allocation sequence: unclear

Allocation concealment: unclear

Blinding: unclear

Inclusion of all randomized participants: 100%


ParticipantsNumber: 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
  1. Tinidazole: 2 g single oral dose daily for 3 days
  2. Metronidazole: 2 g single oral dose daily for 3 days


Not stated if tinidazole and metronidazole were identical in appearance.


Outcomes
  1. Parasitological response: eradication of E. histolytica from stools on day 30 after start of treatment
  2. Clinical response: disappearance of presenting clinical symptoms on day 30 after start of treatment
  3. 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


NotesLocation: 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

Misra 1978

MethodsGeneration of allocation sequence: unclear

Allocation concealment: unclear

Blinding: unclear

Inclusion of all randomized participants: 98.3% (59/60)


ParticipantsNumber: 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
  1. Tinidazole: 2 g single oral dose daily for 3 days
  2. Metronidazole: 2 g single oral dose daily for 3 days


Not stated if tinidazole and metronidazole were identical in appearance


Outcomes
  1. Parasitological cure: eradication of E. histolytica from stools on day 30 after start of treatment
  2. Clinical cure: disappearance of presenting clinical symptoms on day 30 after start of treatment
  3. 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


NotesLocation: 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

Mohammed 1998

MethodsGeneration of allocation sequence: random-numbers table

Allocation concealment: unclear

Blinding: open

Inclusion of all randomized participants: 72.5% (50/69)


ParticipantsNumber: 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. 1. Praziquantel: 40 mg/kg body weight divided into 2 doses orally and taken 4 to 6 hours apart
  2. 2. Metronidazole: 800 mg thrice daily orally for 5 days


Outcomes
  1. Parasitological response: disappearance of E. histolytica from stools 1 week after treatment
  2. Clinical response: disappearance of baseline clinical signs and symptoms at the end of treatment
  3. Adverse events: voluntary reporting of clinical adverse events by participants only for praziquantel


NotesLocation: outpatients in Iraq

Date: 1993 to 1995

Source of funding: not stated

Naoemar 1973

MethodsGeneration 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


ParticipantsNumber: 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
  1. Ro 7-0207 (ornidazole)
  2. 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
  1. Parasitological response: clearance of E. histolytica from stools at the end of treatment and 1 month after end of treatment
  2. Relapse: reappearance of E. histolytica in stools 1 month after end of treatment
  3. Clinical cure: disappearance of symptoms at the end of treatment and at 1 month after end of treatment
  4. 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


NotesLocation: 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

Nnochiri 1967

MethodsGeneration 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


ParticipantsNumber: 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
  1. 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
  2. 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
  1. 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
  2. Clinical response: recurrence of symptoms (results were not reported and could not be included in the meta-analysis)
  3. 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


NotesLocation: Yaba Military Hospital in Lagos, Nigeria

Date: August 1965 to July 1966

Source of funding: Messrs Boots Pure Drug Co., Ltd, Nottingham, England

Padilla 2000

MethodsGeneration 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%


ParticipantsNumber: 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
  1. Secnidazole: 30 mg/kg body weight orally in a single dose
  2. Quinfamide: 4.3 mg/kg body weight orally in a single dose


Outcomes
  1. Parasitological response: clearance of E. histolytica cysts on days 5, 6, and 7 after administration of the drugs
  2. 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


NotesLocation: 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

Pamba 1990

MethodsGeneration 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


ParticipantsNumber: 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
  1. Aminosidine (A): 500 mg twice daily orally for adults, 15 mg/kg body weight for children given orally for 5 days
  2. Etophamide (E): 600 mg twice daily orally for adults,15 mg/kg body weight for children given orally for 5 days
  3. Nimorazole (N): 1 g twice daily orally for adults, 20 mg/kg body weight for children given orally for 5 days
  4. Combination of nimorazole and aminosidine (NA): same doses as above for 5 days
  5. Combination of nimorazole and etophamide (NE): same doses as above for 5 days
  6. Combination of etophamide and aminosidine (EA): same doses as above for 5 days


Outcomes
  1. Parasitological cure: disappearance of any form of E. histolytica from stools or ulcer scrapings at the end of treatment
  2. 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
  3. Clinical cure: disappearance of all baseline symptoms at the end of treatment
  4. 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)


NotesLocation: 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

Panggabean 1980

MethodsGeneration 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


ParticipantsNumber: 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
  1. Tinidazole: 50 mg/kg body weight in a single oral dose daily for 3 days
  2. 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
  1. Parasitological cure: disappearance of all forms of E. histolytica on stool examinations done weekly until 4 weeks after completion of treatment
  2. Reinfection: reappearance of E. histolytica after the second month
  3. Clinical cure: disappearance of blood and mucus from stools at follow-up examinations done weekly until 4 weeks after completion of treatment
  4. Adverse events: clinical adverse effects reported by participants during treatment


NotesLocation: 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

Pehrson 1983

MethodsGeneration 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%


ParticipantsNumber: 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
  1. Tinidazole: 40 mg/kg body weight in a single oral dose daily for 5 days
  2. 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
  1. Parasitological response: clearance of E. histolytica in any of the 3 stool specimens evaluated 1 month after end of treatment
  2. Adverse events: only adverse events severe enough to result in cessation of therapy


NotesLocation: 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

Pehrson 1984

MethodsGeneration 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%


ParticipantsNumber: 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
  1. Tinidazole: 600 mg twice daily orally for 5 days
  2. Metronidazole: 800 mg thrice daily orally for 5 days


Outcomes
  1. Parasitological cure: clearance of E. histolytica trophozoites or cysts in any of the 3 stool specimens taken 1 month after end of treatment
  2. Adverse events: only adverse events severe enough to result in cessation of therapy


NotesLocation: 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

Prasad 1985

MethodsGeneration 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)


ParticipantsNumber: 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
  1. 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
  2. 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
  1. 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
  2. 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


NotesLocation: 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

Pudjiadi 1973

MethodsGeneration 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%


ParticipantsNumber: 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
  1. Ro 7-0207 (ornidazole): 125 mg capsules
  2. 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
  1. Parasitological response: clearance of E. histolytica from stools after 7 days of treatment
  2. Clinical response: disappearance of clinical symptoms after 7 days of treatment
  3. 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


NotesLocation: 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

Rossignol 2001

MethodsGeneration of allocation concealment: unclear

Allocation concealment: unclear

Blinding: double (participants, care provider, and outcome assessors)

Inclusion of all randomized participants: 100%


ParticipantsNumber: 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
  1. Nitazoxanide: 500 mg twice daily orally for 3 days
  2. Placebo tablet (identical): twice daily orally for 3 days


Outcomes
  1. Parasitological response: clearance of E. histolytica from 2 stool specimens collected between days 7 and 10 after start of treatment
  2. Clinical response: disappearance of symptoms, resolution of diarrhoea and haematochezia on day 7 after start of treatment
  3. 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


NotesLocation: 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

Rossignol 2007

MethodsGeneration of allocation sequence: computer-generated randomization

Allocation concealment: unclear

Blinding: double (participants, care providers, outcome assessors)

Inclusion of all randomized participants: 100%


ParticipantsNumber: 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
  1. 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
  2. Placebo: matching placebo tablet or suspension twice daily for 3 days


Outcomes
  1. Parasitological response: clearance of E. histolytica from 2 stool specimens collected between days 7 to 10 after the start of treatment
  2. Clinical response: disappearance of symptoms, resolution of diarrhoea and hematochezia on day 7 after start of treatment
  3. Adverse events: monitored by patient diary


Not included in this review: time from first dose to passage of last unformed stools


NotesLocation: outpatient clinic of the Benha University Hospital, Benha, Egypt

Date: 17 February 2004 to 2 October 2005

Source of funding: Romark Laboratories, L.C.

Rubidge 1970

MethodsGeneration of allocation sequence: unclear

Allocation concealment: unclear

Blinding: open

Inclusion of all randomized participants: 100%


ParticipantsNumber: 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
  1. Metronidazole: 50 mg per kg body weight orally for 7 days
  2. 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
  1. 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
  2. Clinical response: disappearance of symptoms at end of treatment and during follow up until 28 days after start of treatment
  3. Adverse events: only tolerance to the drugs was reported


NotesLocation: 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

Salles 1999

MethodsGeneration 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


ParticipantsNumber: 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
  1. Secnidazole: 1 mL/kg body weight orally in a single dose
  2. Tinidazole: 0.5 mL/kg body weight once daily orally for 2 days


Outcomes
  1. Parasitological response: clearance of E. histolytica from stool specimens collected on days 7, 14, and 21 following treatment
  2. Clinical response: disappearance of all symptoms at the end of the study (day 21)
  3. Adverse events: solicited from the participants or their guardians during the follow-up visits


NotesLocation: 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)

Singh 1977

MethodsGeneration of allocation sequence: unclear

Allocation concealment: unclear

Blinding: open

Inclusion of all randomized participants: 93.3% (56/60)


ParticipantsNumber 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
  1. Tinidazole: 500 mg tablets x 4 (2 g) single-dose daily for 3 days
  2. Metronidazole: 400 mg tablets x 5 (2 g) single-dose daily for 3 days


Outcomes
  1. Parasitological response: eradication of E. histolytica on follow-up stool examinations on day 30 after start of treatment
  2. Clinical response: disappearance of presenting clinical signs and symptoms on day 30 after start of treatment
  3. 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


NotesLocation: 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.

Sitepu 1982

MethodsGeneration 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


ParticipantsNumber: 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
  1. Tinidazole: 50 mg/kg body weight in a single oral dose
  2. Ornidazole: 50 mg/kg body weight in a single oral dose


Outcomes
  1. Parasitological response: clearance of E. histolytica from stools on subsequent follow-up visits on days 2 to 4 and 1 week after treatment
  2. 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


NotesLocation: 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

Soedin 1985

MethodsGeneration of allocation sequence: unclear

Allocation concealment: unclear

Blinding: open

Inclusion of all randomized participants: 100%


ParticipantsNumber: 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
  1. Secnidazole: 2 g orally in a single dose
  2. 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
  1. Parasitological response: eradication of E. histolytica in stools examined on days 1 to 7, 7, 14, and 21 after start of treatment
  2. Clinical response: disappearance of clinical symptoms on days 1 to 7, 14, 21 and 28 after start of treatment
  3. Adverse events: clinical adverse events during follow up


NotesLocation: outpatient in the Padang Bulan Health Centre, Medan, Indonesia

Date: September 1982 to September 1983

Source of funding: not stated

Swami 1977

MethodsGeneration of allocation sequence: unclear

Allocation concealment: unclear

Blinding: unclear

Inclusion of all randomized participants: 93.3% (56/60)


ParticipantsNumber: 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
  1. Tinidazole: 2 g single-dose daily for 3 days
  2. 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
  1. Parasitological response: eradication of E. histolytica on follow-up stool examinations on day 30 after start of treatment
  2. Clinical response: relief of presenting clinical signs and symptoms on day 30 after start of treatment
  3. 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


NotesGeographic location: Visakhapatnam, India

Date: 1977 (date of publication only; actual study period not reported)

Source of funding: not stated

Toppare 1994

MethodsGeneration of allocation sequence: unclear

Allocation concealment: unclear

Blinding: open

Inclusion of all randomized participants: 100%


ParticipantsNumber: 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
  1. Secnidazole: 30 mg/kg body weight as a single oral dose daily for 3 days
  2. Ornidazole 15 mg/kg body weight given twice daily orally for 10 days


Outcomes
  1. Parasitological cure: clearance of E. histolytica cyst or trophozoite from stools 10 days after completion of treatment
  2. Clinical response: range and mean number days from start of treatment to resolution of clinical symptoms
  3. Adverse events: method for obtaining information on adverse events, specific adverse events, and number of participants who developed any adverse events were not reported


NotesLocation: 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

Tripathi 1986

MethodsGeneration 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%


ParticipantsNumber: 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
  1. GO 10213 (satranidazole): 150 mg thrice daily for 10 days
  2. Metronidazole: 400 mg thrice daily for 10 days


Outcomes
  1. Parasitological response: eradication of E. histolytica on stool examinations on follow up 28 days after start of treatment
  2. Clinical response: relief of presenting clinical signs and symptoms and healing of ulcers on sigmoidoscopy on follow up 28 days after start of treatment
  3. 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


NotesGeographic location: hospital in Bhopal, India

Date: 1986 (date of publication only; actual study period not reported)

Source of funding: Ciba-Geigy India Limited

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Abd-Rabbo 1969Not RCT

Abdallah 1969Not RCT

Achar 1967Not RCT

Ali Ata 1967Not RCT

Alterio 1968Not RCT

Amato Neto 1968Not RCT

Apt 1976Not RCT

Apt 1983Not RCT

Arredondo 1993Study population: RCT that compared medical treatment with medical treatment plus liver puncture in patients with amoebic liver abscess

Atias 1972Not RCT

Bakshi 1978Review of 17 RCTs conducted in India comparing tinidazole with metronidazole over a 2-year period

Banerjee 1976Not RCT

Baranski 1966Not RCT

Barroso 1969Not RCT

Bassily 1987Not RCT

Belkind 2004Study population: asymptomatic children positive for intestinal helminths or protozoa

Bezjak 1964Not RCT

Bhatia 1998Study population: RCT comparing metronidazole with secnidazole in treating patients with amoebic liver abscess

Biagi 1966The 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 1978Not RCT

Blanc 1965Not 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 2002Study population: RCT comparing paromomycin with diloxanide furoate for the treatment of asymptomatic carriers of E. histolytica

Blessman 2003aIntervention 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 1967Not RCT

Campos 1969Not RCT

Cardoso Salles 1970Not RCT: alternate allocation of patients with intestinal amoebiasis to receive 2 different doses of ethylchlordiphene

Cariry 1969Not RCT

Chari 1970Not RCT

Chaudhuri 1966Not RCT

Cho 1972Not 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 1975Study population: RCT comparing chloroquine and metronidazole for the treatment of amoebic liver abscess

da Cunha 1977Not RCT

Datta 1974Study population: amoebic liver abscess

de Carvalho 1965Not RCT

de la Rey 1989Intervention 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 1969Not RCT

Delgado 1971Not RCT

Devic 1974Not RCT

Dhariwal 1963Not RCT

Donckaster 1957Not RCT

dos Santos 1969Not RCT

Doshi 1968Not RCT

el Mofti 1965Not RCT

Esquivel 1979Study population: RCT that compared metronidazole, emetine, or both for treating patients with amoebic liver abscess

Ey 1977Not RCT

Felix 1966Not 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 1990Intervention and study population: compared efficacy of antiamoebic drug therapy plus needle aspiration with antiamoebic drug therapy alone for patients with amoebic liver abscess

Gilman 1980Not RCT: diagnostic validity study comparing conventional and immunofluorescent techniques for detection of E. histolytica in rectal biopsies

Gorbea 1989Not RCT

Hatchuel 1975Study population: double-blind trial that compared tinidazole and metronidazole for treating patients with amoebic liver abscess

Hoekenga 1951Not RCT

Holz 1965Not RCT

Huggins 1965Not RCT

Huggins 1969Not RCT

Huggins 1974Not 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 1977Not RCT

Huggins 1980Not RCT

Huggins 1981Not RCT

Irusen 1992Study population: amoebic liver abscess

Islam 1975Not RCT

Islam 1978aStudy population: RCT that compared metronidazole and tinidazole for treating patients with amoebic liver abscess

Islam 1978bStudy population: amoebic liver abscess

Jain 1990Study population: open clinical trial that compared efficacy of various treatment regimens containing dehydroemetine and/or metronidazole for treating patients with hepatopulmonary amoebiasis

Jayawickrema 1975Study population: RCT that compared metronidazole with emetine and chloroquine in the treatment of patients with hepatic amoebiasis

Kaur 1972Not RCT

Khalil 1987Not RCT

Khokhani 1977Study population: RCT that compared metronidazole with emetine and chloroquine in the treatment of patients with hepatic amoebiasis

Khokhani 1978Study population: RCT that compared metronidazole with tinidazole in the treatment of patients with amoebic liver abscess

Konar 1963Not RCT

Krishnaiah 2003Not RCT: pharmacokinetic trial comparing 2 formulations of tinidazole given to healthy human volunteers

Kurt 2008Study population: RCT comparing metronidazole with single-dose ornidazole for treatment of dientamoebiasis

Laham 1951Not RCT

Levy 1967Not RCT

Martinez 1969Not RCT

Masters 1979Not RCT

Mathur 1974Not RCT

McAuley 1992Not RCT

Mendis 1984Study population: RCT that compared metronidazole with tinidazole in the treatment of patients with hepatic amoebiasis

Misra 1976aNot RCT

Misra 1976bCombination 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 1975Study population: RCT that compared intravenous metronidazole with intramuscular emetine in treating patients with amoebic liver abscess

Murray 1980Intervention: did not study effect of any antiamoebic drug for treating amoebic colitis

Muzzafar 2006Study population: amoebic liver abscess

Nahrevanian 2008Study population and not RCT: study to determine prevalence of Cryptosporidium in immunocompromised patients

Naik 1968Not RCT

Nanavati 1965Not RCT

Nel 1985Intervention and study population: study to determine indications for aspiration of amoebic liver abscess

Nel 1986Intervention and study population: study to determine if aspiration influences course of amoebic liver abscess

O'Holohan 1972Not RCT

Okeniyi 2007Study population: no mention of amoebic colitis

Olaeta 1996Not RCT: alternate allocation of patients with intestinal amoebiasis to receive either quinfamide or etofamide

Omrani 1995Not RCT

Orozco 1975Study population: amoebic liver abscess

Padilla 1995Study population: asymptomatic amoebic infection

Padilla 1998Unclear if RCT

Padilla 2002Intervention 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 1966Not RCT

Populaire 1980Pharmacokinetic study of secnidazole given to healthy human volunteers

Powell 1965aNot RCT

Powell 1965bStudy population: clinical trial of dehydroemetine, emetine, and chloroquine in treating patients with amoebic liver abscess

Powell 1965cStudy population: amoebic liver abscess

Powell 1965dNot RCT

Powell 1966aNot RCT

Powell 1966bNot RCT

Powell 1966cNot RCT

Powell 1967Study population: asymptomatic amoebic colitis

Powell 1968Report of 5 trials using metronidazole in different dosages and durations for the treatment of amoebic dysentery

Powell 1969aNot RCT

Powell 1969bReview of several clinical trials using several amoebicides including niridazole, alone or in combination, in the treatment of amoebic dysentery or amoebic liver abscess

Powell 1969cGuidelines on how to conduct drug trials in amoebiasis

Powell 1971aNot RCT

Powell 1971bLetter 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 1972aReport of clinical trials of new nitroimidazole derivatives for treating patients with amoebic liver abscess

Powell 1972bReview 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 1973Not RCT

Prakash 1974Not RCT: alternate allocation of patients with intestinal amoebiasis to receive either tinidazole or metronidazole

Qureshi 1994Not RCT

Qureshi 1997Not RCT

Rodrigues 1968Not RCT

Ruas 1973Study population: amoebic liver abscess

Ruchko 1978Not RCT

Saha 1966Not RCT

Saha 1970Not RCT

Salem 1964Not RCT

Salem 1967Not RCT

Sandia 1977Not RCT

Sangiuolo 1969Study 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 1966Not RCT

Sankale 1969Not RCT

Sankale 1974Not RCT

Satpathy 1988Study population: amoebic liver abscess

Schapiro 1967Not RCT

Scragg 1968Study population: amoebic liver abscess

Scragg 1970Study population: amoebic liver abscess

Segal 1967Not RCT

Sharma 1989Intervention 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 1985Not RCT

Simjee 1985Study population: amoebic liver abscess

Simon 1967Not RCT

Sinuhaji 1986Preliminary 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 1964Not RCT

Soh 1980Study population: amoebic liver abscess

Spellberg 1969Study population: amoebic liver abscess

Spillman 1976Study population: RCT that compared metronidazole with tinidazole for treating those with asymptomatic E. histolytica infection and/or E. hartmanni infections

Sutrisno 1978Not RCT

Tandon 1997Intervention 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 1990aStudy population: RCT that compared metronidazole, tinidazole, and diloxanide furoate in treating asymptomatic homosexual carriers of E. histolytica

Thoren 1990bStudy population: asymptomatic E. histolytica homosexual carriers

Tjaij 1969Not RCT

Tjaij 1970Not RCT

Vaidya 1983Pharmacokinetic study of Go.10213 and does not compare the drug with placebo or another antiamoebic drug

Vakil 1967Not RCT: alternate allocation of children and adults with amoebic dysentery, nondysenteric intestinal amoebiasis, or hepatic amoebiasis to receive either intramuscular dehydroemetine or emetine

Vakil 1971Not RCT

Vakil 1974Summary report of several clinical trials of various amoebicidal drugs conducted in one medical centre in Bombay, India over the past 12 years

Valencia 1973Review 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 1985Study population: patients with amoebic liver abscess were treated with low dose tinidazole and needle aspiration

Viswanathan 1968Not RCT

Wang 1971aNot RCT

Wang 1971bReport of 2 cases of oxytetracycline resistant amoebic dysentery

Watson 1975Study population: amoebic infection of the eye

Welch 1978Not RCT

Widjaya 1991Intervention 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 1962Not RCT

Wolfe 1973Not RCT

Wolfensberger 1968Not RCT

Zuberi 1973Not RCT

 
Characteristics of studies awaiting assessment [ordered by study ID]
Guevara 1980

MethodsUnclear (reported as double-blind in the title)

ParticipantsNondysenteric amoebic colitis (from abstract)

InterventionsQuinfamide given at 3 doses (300 mg, 600 mg, and 1200 mg) vs teclozan (from abstract)

OutcomesEradication of amoeba in stools and rectosigmoidoscopic findings (from abstract)

NotesFull paper not available

Soedin 1989

MethodsUnknown

Participantsintestinal amoebiasis

InterventionsSingle-dose secnidazole versus 5-day regimen of a combination of tetracycline and clioquinol

OutcomesUnknown

NotesFull paper not available; may possibly be the same study as Soedin 1985

 
Comparison 1. Alternative drug vs metronidazole

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Clinical failure: 1 to 14 days after end of treatment5375Risk Ratio (M-H, Random, 95% CI)0.41 [0.11, 1.64]

    1.1 Ornidazole
240Risk Ratio (M-H, Random, 95% CI)Not estimable

    1.2 Praziquantel
150Risk Ratio (M-H, Random, 95% CI)0.69 [0.17, 2.78]

    1.3 Tinidazole
2285Risk Ratio (M-H, Random, 95% CI)0.17 [0.02, 1.30]

 2 Clinical failure: 15 to 60 days after end of treatment12679Risk Ratio (M-H, Random, 95% CI)0.39 [0.21, 0.73]

    2.1 Ornidazole
2118Risk Ratio (M-H, Random, 95% CI)3.00 [0.13, 71.89]

    2.2 Panidazole
144Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.3 Satranidazole (GO 10213)
140Risk Ratio (M-H, Random, 95% CI)0.8 [0.40, 1.60]

    2.4 Tinidazole
8477Risk Ratio (M-H, Random, 95% CI)0.28 [0.15, 0.51]

 3 Parasitological failure: 1 to 14 days after end of treatment6419Risk Ratio (M-H, Random, 95% CI)1.05 [0.85, 1.29]

    3.1 Ornidazole
240Risk Ratio (M-H, Random, 95% CI)Not estimable

    3.2 Praziquantel
150Risk Ratio (M-H, Random, 95% CI)0.69 [0.17, 2.78]

    3.3 Secnidazole
144Risk Ratio (M-H, Random, 95% CI)0.31 [0.01, 7.12]

    3.4 Tinidazole
2285Risk Ratio (M-H, Random, 95% CI)1.01 [0.58, 1.74]

 4 Parasitological failure: 15 to 60 days after end of treatment13Risk Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 Ornidazole
2135Risk Ratio (M-H, Random, 95% CI)0.18 [0.02, 1.41]

    4.2 Panidazole
186Risk Ratio (M-H, Random, 95% CI)1.71 [0.81, 3.60]

    4.3 Satranidazole (GO 10213)
140Risk Ratio (M-H, Random, 95% CI)0.33 [0.01, 7.72]

    4.4 Tinidazole
9507Risk Ratio (M-H, Random, 95% CI)0.64 [0.25, 1.64]

 5 Relapse (ornidazole)2Risk Ratio (M-H, Random, 95% CI)Totals not selected

 6 Adverse events11Risk Ratio (M-H, Random, 95% CI)Subtotals only

    6.1 Ornidazole
120Risk Ratio (M-H, Random, 95% CI)0.67 [0.14, 3.17]

    6.2 Panidazole
1100Risk Ratio (M-H, Random, 95% CI)1.12 [0.87, 1.45]

    6.3 Satranidazole (GO 10213)
140Risk Ratio (M-H, Random, 95% CI)0.71 [0.27, 1.88]

    6.4 Tinidazole
8477Risk Ratio (M-H, Random, 95% CI)0.65 [0.46, 0.92]

 
Comparison 2. Any antiamoebic drug vs placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Clinical failure: 1 to 14 days after end of treatment3Risk Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Quinfamide
140Risk Ratio (M-H, Random, 95% CI)0.35 [0.21, 0.60]

    1.2 Nitazoxanide
2153Risk Ratio (M-H, Random, 95% CI)0.21 [0.06, 0.81]

 2 Parasitological failure: 1 to 14 days after end of treatment4Risk Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Nitazoxanide
2167Risk Ratio (M-H, Random, 95% CI)0.25 [0.05, 1.27]

    2.2 Quinfamide
196Risk Ratio (M-H, Random, 95% CI)0.30 [0.19, 0.47]

    2.3 10 different drugs belonging to 6 drug classes
1367Risk Ratio (M-H, Random, 95% CI)0.37 [0.26, 0.53]

 3 Other adverse events3Risk Ratio (M-H, Random, 95% CI)Totals not selected

    3.1 Nitazoxanide
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    3.2 Quinfamide
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    3.3 10 different drugs belonging to 6 drug classes
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 
Comparison 3. Combination regimen vs monotherapy

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Clinical failure: 1 to 14 days after end of treatment5Risk Ratio (M-H, Random, 95% CI)Totals not selected

    1.1 Dehydroemetine and tetracycline and diloxanide furoate vs metronidazole
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    1.2 Metronidazole and diiodohydroxyquinoline vs metronidazole
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    1.3 Metronidazole and furazolidone vs metronidazole
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    1.4 Combinations vs nimorazole, aminosidine, and etofamide
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    1.5 Tetracycline and clioquinol vs secnidazole
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 2 Parasitological failure: 1 to 14 days after end of treatment6Risk Ratio (M-H, Random, 95% CI)Totals not selected

    2.1 Dehydroemetine and tetracycline and diloxanide furoate vs metronidazole
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.2 Metronidazole and diiodohydroxyquinoline vs metronidazole
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.3 Metronidazole and furazolidone vs metronidazole
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.4 Combinations vs nimorazole, aminosidine, and etofamide
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.5 Quinfamide and mebendazole vs nitazoxanide (mixed infections only)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.6 Tetracycline and clioquinol vs secnidazole
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 
Comparison 4. Single dose regimen vs longer regimen

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Clinical failure: 1 to 14 or 15 to 60 days after end of treatment, combined3Risk Ratio (M-H, Random, 95% CI)Totals not selected

    1.1 Quinfamide: 1 dose vs 2 or 3 doses
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    1.2 Secnidazole (1 dose) vs tetracycline and clioquinol (5 days)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    1.3 Secnidazole (1 dose) vs tinidazole (2 days)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 2 Parasitological failure: 1 to 14 days after end of treatment4Risk Ratio (M-H, Random, 95% CI)Totals not selected

    2.1 Quinfamide (1 dose) vs nitazoxanide (3 days)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.2 Quinfamide: 1 dose vs 2 or 3 doses
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.3 Secnidazole (1 dose) vs metronidazole (10 days)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.4 Secnidazole (1 dose) vs tetracycline and clioquinol (5 days)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 
Comparison 5. Other antiamoebic drug comparisons

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Clinical failure: 1 to 14 days after end of treatment5Risk Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Ornidazole vs tinidazole
266Risk Ratio (M-H, Random, 95% CI)0.23 [0.03, 1.96]

    1.2 Ornidazole vs secnidazole
1102Risk Ratio (M-H, Random, 95% CI)0.95 [0.17, 5.45]

    1.3 Chlorhydroxyquinoline vs diiodohydroxyquinoline
1100Risk Ratio (M-H, Random, 95% CI)0.24 [0.11, 0.53]

    1.4 MK-910 (4 dosages)
140Risk Ratio (M-H, Random, 95% CI)Not estimable

 2 Parasitological failure: 1 to 14 days after end of treatment9Risk Ratio (M-H, Random, 95% CI)Totals not selected

    2.1 Ornidazole vs tinidazole
2Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.2 Ornidazole vs secnidazole
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.3 Chlorhydroxyquinoline vs diiodohydroxyquinoline
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.4 MK-910 (4 dosages)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.5 Quinfamide vs secnidazole
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.6 Quinfamide vs nitazoxanide
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.7 Metronidazole and iodoquinol vs Saccharomyces boulardii or placebo
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.8 2 fixed-drug combinations of diloxanide furoate and tetracycline with or without chloroquine
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 
Comparison 6. Subgroup analyses: alternative drug vs metronidazole

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure 15 to 60 days after end of treatment, by clinical category13768Risk Ratio (M-H, Random, 95% CI)0.81 [0.45, 1.48]

    1.1 Amoebic dysentery
3162Risk Ratio (M-H, Random, 95% CI)0.79 [0.07, 8.68]

    1.2 Nondysenteric amoebic colitis
389Risk Ratio (M-H, Random, 95% CI)1.63 [1.09, 2.42]

    1.3 Amoebic colitis or intestinal amoebiasis, unspecified
9517Risk 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 group13Risk Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Adults (age ≥ 15 years)
10622Risk Ratio (M-H, Random, 95% CI)0.63 [0.25, 1.54]

   2.2 Children (age < 15 years)
00Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.3 Both adults and children
3146Risk 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 infection13Risk Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Amoebic infection only
10586Risk Ratio (M-H, Random, 95% CI)0.63 [0.25, 1.59]

    3.2 Mixed intestinal infection
3182Risk Ratio (M-H, Random, 95% CI)0.63 [0.10, 3.91]

 4 Parasitological failure 15 to 60 days after end of treatment, by criteria13Risk Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 WHO criteria
9517Risk Ratio (M-H, Random, 95% CI)0.56 [0.29, 1.10]

    4.2 Other criteria
4251Risk Ratio (M-H, Random, 95% CI)1.31 [0.58, 2.94]

 
Comparison 7. Subgroup analyses: any antiamoebic drug vs placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure 1 to 14 days after end of treatment, by clinical category4Risk Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Nondysenteric amoebic colitis
196Risk Ratio (M-H, Random, 95% CI)0.30 [0.19, 0.47]

    1.2 Amoebic colitis or intestinal amoebiasis, unspecified
3534Risk 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 group3193Risk Ratio (M-H, Random, 95% CI)0.27 [0.14, 0.51]

    2.1 Adults (age ≥ 15 years)
3143Risk Ratio (M-H, Random, 95% CI)0.31 [0.16, 0.60]

    2.2 Children (age < 15 years)
150Risk 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 group4630Risk Ratio (M-H, Random, 95% CI)0.33 [0.23, 0.48]

    3.1 Adults (age ≥ 15 years)
3213Risk Ratio (M-H, Random, 95% CI)0.34 [0.20, 0.56]

    3.2 Children (age < 15 years)
150Risk Ratio (M-H, Random, 95% CI)0.08 [0.01, 0.54]

    3.3 Both adults and children
1367Risk Ratio (M-H, Random, 95% CI)0.37 [0.26, 0.53]

 
Comparison 8. Subgroup analyses: combination regimen vs monotherapy

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Clinical failure: 1 to 14 days after end of treatment, by intervention5Risk Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Combination vs metronidazole
31025Risk Ratio (M-H, Random, 95% CI)0.33 [0.11, 0.98]

    1.2 Combination vs alternative drugs
2480Risk Ratio (M-H, Random, 95% CI)2.60 [0.20, 33.80]

 2 Parasitological failure: 1 to 14 days after end of treatment, by intervention6Risk Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Combination vs metronidazole
3720Risk Ratio (M-H, Random, 95% CI)0.36 [0.15, 0.86]

    2.2 Combination vs alternative drugs
3577Risk 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 titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure: 1 to 14 days after end of treatment, by intervention4221Risk Ratio (M-H, Random, 95% CI)0.73 [0.11, 4.91]

    1.1 Secnidazole single dose vs longer duration
2124Risk Ratio (M-H, Random, 95% CI)0.14 [0.06, 0.35]

    1.2 Quinfamide single dose vs longer duration
297Risk Ratio (M-H, Random, 95% CI)2.13 [1.02, 4.46]

 
Table 1. Amoebicide classes and examples

AmoebicideClassExample

LuminalArsenical compoundsCarbarsone, acetarsone or acetarsol, treparsol, diphetarsone, glycobiarsol or bismuth glycolylarsanilate, stovarsol, and thioarsenite, thiocarbarsone or thiocarabazone, arsthinol

Hydroxyquinoline derivativesChiniofon or quinoxyl, clioquinol or iodochlorhydroxyquin, and iodoquinol or diiodohydroxyquin

Dichloroacetamide derivativesDiloxanide furoate or entamide furoate, clefamide, eticlordifene or ethylchlordiphene or etofamide or etophamide, and quinfamide

Benzylamine derivativesTeclozan, chlorbetamide or mantomide, and chlorphenoxamide or mebinol

Antibiotic amoebicidesTetracycline, oxytetracycline, chlortetracycline, erythromycin, paromomycin, and fumagillin

Nithrothiazole salicylamideNitazoxanide

TissueEmetine and its derivativesEmetine hydrochloride, emetine bismuth iodide, dehydroemetine dihydrochloride, and dehydroemetine resinate

AminoquinolineChloroquine

Thiazole derivativeNiridazole

NitroimidazolesMetronidazole, tinidazole, ornidazole, secnidazole, and nimorazole