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Drugs for treating giardiasis

  1. Carlos E Granados1,*,
  2. Ludovic Reveiz2,
  3. Luis G Uribe3,
  4. Claudia P Criollo4

Editorial Group: Cochrane Infectious Diseases Group

Published Online: 12 DEC 2012

Assessed as up-to-date: 30 JUL 2011

DOI: 10.1002/14651858.CD007787.pub2


How to Cite

Granados CE, Reveiz L, Uribe LG, Criollo CP. Drugs for treating giardiasis. Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: CD007787. DOI: 10.1002/14651858.CD007787.pub2.

Author Information

  1. 1

    Universidad Nacional de Colombia, Facultad de Medicina, Bogota D.C., Colombia

  2. 2

    Health Systems Based on Primary Health Care (HSS), Pan American Health Organization, Research Promotion and Development Team, Washington DC, USA

  3. 3

    Cardio-Infantil Fundacion, Department of Internal Medicine, Universidad del Rosario, Bogota D. C., Colombia

  4. 4

    Universidad del Valle, Faculty of Medicine, Cali, Valle del Cauca, Colombia

*Carlos E Granados, Facultad de Medicina, Universidad Nacional de Colombia, Tv 38A No 40-04 Facultad de Medicina, Bogota D.C., Colombia. cegranadosg@unal.edu.co. caregra@gmail.com.

Publication History

  1. Publication Status: New
  2. Published Online: 12 DEC 2012

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Characteristics of included studies [ordered by study ID]
Al-Waili 1992 GBR

MethodsUnited Kingdom. No power calculation made. Intention to treat analysis. Duration: 21 days.


Participants44 children (28 males); age: three to 13 years.

Symptoms: anorexia, altered bowel habits, abdominal cramps, flatulence.

Asymptomatic: 0%.

Microscopic stools examination: cysts in all cases and trophozoites in only two cases. Technique: not mentioned.

Exclusion criteria: not mentioned.


InterventionsRx 1. Mebendazole: 200 mg three times daily, 5 days (oral).

Rx 2: Metronidazole: 200 mg three times daily, 5 days (oral).


OutcomesParasitological cure: fecal specimens were examined on days 7 and 14 after treatment. Technique: not mentioned.

Any side effects.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"… were randomly to receive either mebendazole or metronidazole..".

Allocation concealment (selection bias)Unclear riskNot mentioned.

Blinding of outcome assessment (detection bias)
Stools examination
Low risk"The examinations were done blindly.."

Blinding of outcome assessment (detection bias)
Other outcomes
Low risk"…. and the investigators were unaware of the nature of the drugs used..".

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or loss to follow up.

Selective reporting (reporting bias)Unclear riskNo mention of a systematic strategy for collecting side effects.

Other biasLow riskNo comments.

Alizadeh 2006 IRN

MethodsIran. Intention to treat analysis. Duration: 10 days.


Participants120 participants (61 males); age: two to 53 years, mean 22.3 ± 11 years.

Symptoms: were not specified. Asymptomatic: 0%.

Inclusion criteria: acute symptoms of giardiasis and a positive stool examination report for trophozoites of the pathogen.

Microscopic stools examination: cysts in all cases and trophozoites in only two cases. Technique: not mentioned.

Exclusion criteria: not mentioned.


InterventionsRx 1. Albendazole: 400 mg single dose for 5 days (oral).

Rx 2. Metronidazole: 250 mg three times daily for 5 days (oral).


Outcomes"A week after starting the treatment, stool examination to detect trophozoites of G. lamblia was performed three times in three consecutive days for all the patients". Technique: not mentioned.

Parasitological cure: negative stool examination for trophozoites and cysts.

Any side effects.


NotesSample size calculation: "(alpha level of 0.05 and beta level of 0.2), the sample size needed was calculated to be 120 documented cases of the disease"


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"before starting the study one number was assigned for each case. All the numbers were assigned in two groups at random..."

Allocation concealment (selection bias)Low risk"and a physician was assigned to give the needed numbers to the clinics".

Blinding of outcome assessment (detection bias)
Stools examination
Low risk"one parasitologist who was blinded to the treatment received was responsible for detecting the trophozoites in the samples before and after treatment".

Blinding of outcome assessment (detection bias)
Other outcomes
Unclear riskNot mentioned.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll 120 paediatric patients were included in the statistical analysis.

Selective reporting (reporting bias)Unclear riskOne of the expected outcomes is symptomatic improvement, but it was not reported.

Other biasLow riskNo comments.

Bhandari 1972 IND

MethodsIndia. No power calculation made. Intention to treat analysis. Duration: 21 weeks.


Participants54 participants (41 males), from 18 months to 12 years old; There is not any specification about symptoms. However, improvement on clinical symptoms was reported as outcome.

Inclusion criteria: positive stools reports on two successive days.

Exclusion criteria: not mentioned.


InterventionsRx 1. Metronidazole: 35 mg/K single dose, repeated at two weeks (oral).

Rx 2. Metronidazole: 20 mg/K/d three times daily for 5 days, repeated at two weeks (oral).

Metronidazole was administrated mixed with honey, after meals.


OutcomesClinical assessment and stools were repeated on days four, eight,12 and 16 post-treatment. Any side effect volunteered by the patient was noted.

Parasitological cure: stool negative for G. lamblia. The study does not specify the technique of stool examination.

Cure: stool negative for G. lamblia, and complete relief of symptoms or marked clinical improvement.


NotesAny patient with treatment failure was given a third regimen of therapy, which was not specified. None of the patients received treatment before nine weeks.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Treatment schedules in a random manner".

Allocation concealment (selection bias)Unclear riskNot mentioned.

Blinding of outcome assessment (detection bias)
Stools examination
Unclear riskNot mentioned.

Blinding of outcome assessment (detection bias)
Other outcomes
High riskNot mentioned. Probably not, this study compares therapy with metronidazole, 5 days versus 1 day. There is no mention about placebo plus metronidazole in the second group.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data.

Selective reporting (reporting bias)Unclear riskNo mention of a systematic strategy for collecting side effects.

Other biasUnclear riskCharacteristics of included patients were not described in a comparative manner.

Bulut 1996 TUR

MethodsTurkey. No power calculation made. Per protocol analysis. Duration: 14 days.


ParticipantsInformation only on 48 participants (30 males); age: six to 12 years.

Symptoms: two children had diarrhoea. "Nonspecific gastrointestinal symptoms, such as abdominal pain, nausea, and viscid stool, were found in the remaining 46".

Microscopic stools examination: "standard methods" in fresh stool samples. Technique: not mentioned.

Exclusion criteria: not mentioned.


InterventionsRx 1. Mebendazole 100 mg three times daily for one day.

Rx 2: Mebendazole 100 mg three times daily for seven days.

Rx 3: Metronidazole 15mg/kg single dose for seven days.

Rx 4: Ornidazole 40 mg/day single dose.


OutcomesParasitological cure: absence of cystic or trophozoite forms of G. lamblia in the stools (three tests) at two weeks. Technique: not mentioned.

Adverse effects.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomization without more information.

Allocation concealment (selection bias)Unclear riskNot reported.

Blinding of outcome assessment (detection bias)
Stools examination
Low risk"fresh stool samples were examined microscopically for parasites by an examiner blinded".

Blinding of outcome assessment (detection bias)
Other outcomes
High risk"open label".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskStool test were not done in 12 children. However authors reported that symptoms disappeared. No specific information was provided.

Selective reporting (reporting bias)Unclear riskSymptoms outcomes are mentioned but not reported.

Other biasUnclear riskNo information concerning baseline characteristics for each groups.

Cañete 2012 CUB

MethodsCuba. Duration: seven days.


Participants150 participants (73 male); age: 18 to 38 years, mean 30 years.

Symptoms: were not specified. Asymptomatic: 0%.

Inclusion criteria: adults (older than 18 years) with acute symptoms of giardiasis (with or without diarrhoea) and a positive stool examination report. No pregnant women were included.

Microscopic stools examination: cysts or trophozoites.

Technique: "microscopic examination of fecal samples, as wet mounts and/or after Ritchie concentration".

Exclusion criteria: (1) history of sensitivity to benzimidazole compounds or, (2) antiparasitic drugs in the preceding four weeks or, (3) diseases other than giardiasis or, (4) attending other clinical trial.


InterventionsRx 1. Albendazole: 400 mg single dose for five days (oral).

Rx 2. Metronidazole: 250 mg three times daily for 5 five days (oral).


OutcomesStool samples from all cases were examined on the 3rd, 5th and 7th days following completion of treatment.

Adverse events: any reported.


NotesSample size calculation: "statistical power 80%, confidence level 95%, cure rate of alternative drug of 70% and 90% of efficacy for the drug applied to the control group ... "


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"A random-number table was used to allocate each of these 150 adults ..."

Allocation concealment (selection bias)Unclear risk" a random table was developed to (blindly) identify with a number the drug to be administered to each participant, only disclosed at the end of the study".

Blinding of outcome assessment (detection bias)
Stools examination
Low risk"Neither investigators nor patients had information on the drug used throughout the study".

Blinding of outcome assessment (detection bias)
Other outcomes
Unclear risk"Neither investigators nor patients had information on the drug used throughout the study". The frequency of administration of both drugs was different.

Incomplete outcome data (attrition bias)
All outcomes
Low risk"All patients who began treatment completed the study period and were included in the statistical analysis".

Selective reporting (reporting bias)Low riskApparently, all relevant outcomes were reported. Protocol was not available.

Other biasLow riskNo comments.

Chan Del Pino 1999 PER

MethodsPeru. No power calculation was done. Per protocol analysis. Duration: 3 weeks.


Participants79 participants. The mean age was 7.83 ± 2.66 years. The mean weight was 24.06 ± 7.48kg. 38% were preschool children. 67% were malnourished first degree.  

Clinical manifestations were abdominal pain (89.87%), diarrhoea (81.01%), hyporexia (70.88%), and abdominal distension (59,49%). 

Inclusion criteria:

  • Children infected with G. lamblia only. Confirmed by parasitological stool examinations.
  • Children, both sexes, aged three to 15 years of age.
  • Consent of parents or guardians of children.


Exclusion criteria:

  • Children with malnutrition grade II or III.
  • Children who have received antigiardial drugs in the past two months.
  • Children with acute febrile illness.


InterventionsRx 1. Tinidazole: 50 mg/kg/day, single dose (oral).

Rx 2. Metronidazole: 15 mg/kg/day, three times daily for 10 days (oral).

Rx 3. Albendazole: 400 mg/day for five days (oral).

Rx 4. Furazolidone: 5mg/kg/day, every six hours, for 10 days.

Rx 5. Secnidazole: 30 mg/kg/day, single dose (oral).


OutcomesClinical signs and symptoms (cured, improvement, not cured, relapse).

Parasitological (disappearance of cysts or trophozoites, reinfection, infection by other parasites). Coproparasitology examination: direct microscopy, using the technique of Willis. The samples were collected during the first seven days, and days 14 and 21.

Global efficacy (excellent: parasitological cured at 3 days; Good: parasitological cured between three and seven days; moderate: parasitological cured after seven days; bad: parasite presence ).

Tolerance (excellent: no adverse events; good: one mild adverse event with no discontinuation; etc).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom number table.

Allocation concealment (selection bias)High riskFirst, children were randomized to 5 groups and drug subsequently randomized to these groups. 16 children were subsequently excluded after being randomized.

Blinding of outcome assessment (detection bias)
Stools examination
High risk"We performed a prospective, longitudinal, comparative, open and randomised study ..."

Blinding of outcome assessment (detection bias)
Other outcomes
High risk"We performed a prospective, longitudinal, comparative, open and randomised study ..."

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo significant differences in loss to follow up.

Selective reporting (reporting bias)Low riskThe study report include expected outcomes, including those that were pre-specified.

Other biasHigh riskRaw water intake was higher in the groups of children assigned to albendazole and secnidazole.

Dutta 1994 IND

MethodsIndia (multicentre study). No power calculation made. Intention to treat analysis. Duration: 21 days.


Participants150 hospitalised participants (79 males), from two to 10 years old. Diarrhea, abdominal pain and anorexia were the main presenting symptoms.

Inclusion criteria: children (two to 10 years) with proven giardia infection (trophozoites and/or cyst of G lamblia in stool specimens).

Exclusion criteria: "... acute febrile conditions, chronic diarrhoea, severe malnutrition or receiving long term therapy". Treatment of Giardia or intestinal helminthic infection in the previous seven days.


InterventionsRx 1. Albendazole: 400 mg/d, single dose, for five days (oral suspension).

Rx 2. Metronidazole: 7.5mg/kg three times daily (22.5 mg/kg/day) for five days (oral suspension).


OutcomesClinical assessment and stools were repeated on days one to seven, 14 and 21 post-treatment. Stool samples were examined microscopically (direct smear and formal ether concentration tests).

Hematological and biochemical parameters on the 7th and 14th day after treatment.

Reported side-effects.


NotesThis study has a similar methodology to the Misra 1995 IND study, but different patients (different hospitals).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot stated.

Allocation concealment (selection bias)Unclear risk"eligible children were randomised according to pre-determined lists at each site".

Blinding of outcome assessment (detection bias)
Stools examination
Unclear riskNot mentioned.

Blinding of outcome assessment (detection bias)
Other outcomes
High risk"Patient's response to therapy and severity of side-effects were recorded by a co-investigator who was unaware of the treatment given to the patient". However, patients were probably aware about treatment.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data.

Selective reporting (reporting bias)Unclear riskNo mention of a systematic strategy for collecting side effects.

Other biasLow riskNo comments.

Fallah 2007 IRN

MethodsIran. No power calculation made. Intention to treat analysis. Duration: three weeks.


Participants106 participants (69 males). Children, 75% of them were less than 12 years old.

"... from public and private health centres ...". There is no any specification about symptoms

Inclusion criteria: Giardia intestinalis-positive children.

Exclusion criteria: not mentioned.


InterventionsRx 1. Tinidazole: 50 mg/kg, maximum 2 g, once a day, single dose (tablets).

Rx 2. Metronidazole: 15 mg/kg/day, three times daily for seven days (suspension).


OutcomesClinical and parasitological follow-up was carried out before, and at 7, 14, 21 days after treatment.

Parasitological cure was documented when there were three consecutive negative stool examination for G. intestinalis at 1-3 weeks after therapy termination. Stool examination was done by formalin ether concentration technique.

Duration of symptoms of patients.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"were randomly allocated to two groups".

Allocation concealment (selection bias)High risk"a randomised, open-label, clinical trial".

Blinding of outcome assessment (detection bias)
Stools examination
High risk"a randomised, open-label, clinical trial".

Blinding of outcome assessment (detection bias)
Other outcomes
High risk"a randomised, open-label, clinical trial".

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data.

Selective reporting (reporting bias)Unclear risk"Clinical and parasitological follow-up was carried out ...". However, in the outcomes there is no mention about any clinical improvement.

Other biasUnclear riskNo baseline comparison.

Gascon 1989 ESP

MethodsSpain. No power calculation made. Intention to treat analysis. Duration: 30 days.


Participants23 adults; 17 male; Age was not specified. All symptomatic (information provided by author).

Microscopic stools examination: "harbouring G. lamblia". Technique: not mentioned.

Exclusion criteria: not mentioned.


InterventionsRx 1. Mebendazole 200 mg three times daily for one day.

Rx 2: Metronidazole 250 mg every 8 h for seven days.


OutcomesParasitological cure: faecal specimens were examined on days three and seven after treatment, and finally one month later. Technique: not mentioned.


Notes11 patients included from a travellers' clinic. The infections were acquired in Africa (4), Asia (3), Latin America (4).

4 patients were from an acquired immune deficiency syndrome (AIDS) clinic.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"They were all given a random number".

Allocation concealment (selection bias)Unclear riskNot mentioned.

Blinding of outcome assessment (detection bias)
Stools examination
Unclear riskNot mentioned.

Blinding of outcome assessment (detection bias)
Other outcomes
Unclear riskNot mentioned.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThe authors do not specifically mention that there were no losses to follow-up.

Selective reporting (reporting bias)High riskSymptoms outcomes are mentioned but not reported.

Other biasUnclear riskNo information concerning baseline characteristics for each groups.

Gascón 1990 ESP

MethodsSpain. No power calculation made. Intention to treat analysis. Duration: 30 days.


Participants19 participants (10 M); mean age: 29 ± 12 years; 16 adults. All symptomatic (information provided by author).

Microscopic stools examination: "excreting cystics of G. lamblia in their stools". Technique: not mentioned.

Exclusion criteria: not mentioned.


InterventionsRx 1. Mebendazole 200 mg three times daily for five days.

Rx 2: Metronidazole 250 mg every 8 h for seven days.


OutcomesParasitological cure: faecal specimens were examined on days three, seven, and 30 after treatment. Technique: not mentioned.

No mention of adverse events.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"They, were all given a random number..."

Allocation concealment (selection bias)Unclear riskNot mentioned.

Blinding of outcome assessment (detection bias)
Stools examination
Unclear riskNot mentioned.

Blinding of outcome assessment (detection bias)
Other outcomes
Unclear riskNot mentioned.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThe authors do not specifically mention that there were no losses to follow-up.

Selective reporting (reporting bias)High riskNo mention of symptoms or adverse events.

Other biasUnclear riskNo information concerning baseline characteristics for each groups.

Hall 1993 IND

MethodsIndia. No power calculation made. Per protocol analysis. Duration: 15 days.


ParticipantsChildren between 5 and 10 years old. Confirmed presence of Giardia cysts or trophozoites in faeces. 426 children (222 in the first phase, and 204 in the second phase)

There is not any specification about symptoms.

Exclusion criteria: not mentioned.


InterventionsPhase 1:

Rx 1. Albendazole: 600 mg single dose (chewable tablets).

Rx 2. Albendazole: 400 mg single dose, for three days (chewable tablets).

Rx 3. Metronidazole: 125 mg three times daily (375 mg/d) for five days (oral).

Phase 2:

Rx 4. Albendazole: 800 mg single dose (chewable tablets).

Rx 5. Albendazole: 400 mg single dose, for five days (chewable tablets).

Rx 6. Metronidazole: 125 mg three times daily (375 mg/d) for five days (oral).


OutcomesDirect microscopy of faeces in saline. Three stools samples collected from each child over a period of 10 days after treatment.

Cure: Stool negative for G. lamblia.

Adverse events.


NotesThis study took into account as the unit of analysis "infections" (one child could participate more than once). However, also considered as the unit of analysis "children in their first (and / or unique) infection". For this systematic review, we consider data from the first Infection of children.

Similarly, for this systematic review, we consider treatments Rx 5 and Rx 6. Since this scheme albendazole is used more frequently, and it was the best response rate in this study.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"A list of the numbers 1, 2 and 3 was randomly generated by a computer program".

Allocation concealment (selection bias)Low risk"… sealed in serially numbered envelopes by someone not concerned with treatment. The envelopes were opened in the field by the project physician, case by case, …".

Blinding of outcome assessment (detection bias)
Stools examination
Low risk"… each of the 3 stool samples collected after treatment was identified only by a unique serial number when examined microscopically, …".

Blinding of outcome assessment (detection bias)
Other outcomes
High risk"Because of the very different drug regimens being used in the investigation, a double-blind study was considered impracticable.".

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data.

Selective reporting (reporting bias)High riskThe outcomes of adverse events were incompletely reported. Adverse events were not specified for each treatment group.

Other biasUnclear riskNo baseline comparison.

Kalayci 1995 TUR

MethodsTurkey. No power calculation made. Intention to treat analysis. Duration: 10 days.


Participants45 children; ages 34 months to 16 years. All symptomatic.

Symptoms: abdominal cramps (82%), vomiting (27%), greasy stools (24%), flatulence (18%), weight loss (18%), and anorexia (67%). The children had these complaints for 45 to 120 days (mean 86 days).

Microscopic stools examination: ".. within one hour after being passed for both cysts and trophozoites of G. lamblia". G. lamblia cysts were seen in all cases and trophozoites in 14 cases. Technique: not mentioned.

Exclusion criteria: children with a history of any treatment for giardiasis.


InterventionsRx 1. Mebendazole 200 three times daily for 10 days (oral).

Rx 2. Metronidazole 5mg/kg three times daily for 10 days.

Rx 3. Furazolidone 2mg/kg four times daily for 10 days.


OutcomesClinical monitoring and three fecal specimens were re-examined (technique not mentioned.) for 7 to 10 days after treatment.

Side-effects.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk".. and chosen randomly to receive.."

Allocation concealment (selection bias)Unclear riskNot mentioned.

Blinding of outcome assessment (detection bias)
Stools examination
Low risk".. by investigators who were unaware of the drugs used or the results of the treatment".

Blinding of outcome assessment (detection bias)
Other outcomes
Unclear riskNot mentioned.

Incomplete outcome data (attrition bias)
All outcomes
Low riskThere were no losses to follow-up.

Selective reporting (reporting bias)Low riskAll outcomes were included in the analyses.

Other biasLow riskNo comments.

Karabay 2004 TUR

MethodsTurkey. No power calculation made. Per protocol analysis. Duration: 15 days.


ParticipantsAdults with diarrhoea at the outpatient clinic of the Department of Infectious Diseases of Social Security Hospital in Turkey: 67 patients (29 male).

Inclusion criteria: adults with diarrhoea (more than four times of unformed stools per day) and G intestinalis cyst or trophozoites (direct faecal microscopic examination).

Exclusion criteria: antiparasitic drugs during the 10 days prior to beginning the study; fever, pregnant women, mothers who were breast feeding, known hypersensitivity to either treatments, patients for whom any of the treatments used in the study were contraindicated.


InterventionsRx 1. Albendazole: 400 mg/day single dose, for five days (oral).

Rx 2. Metronidazole: 500 mg three times daily (1500 mg/d), for five days (oral).


OutcomesClinical response and parasitological response with 2 stool samples between days 7 and 15 after initiation of treatment (direct faecal microscopic examination).

Noncompliance: failure to attend the controls, or inappropriate use of medications (dose, duration).

After starting treatment, healing of symptoms in hours.

Side effects.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomization without more information.

Allocation concealment (selection bias)High risk"An open randomised clinical study".

Blinding of outcome assessment (detection bias)
Stools examination
High risk"An open randomised clinical study".

Blinding of outcome assessment (detection bias)
Other outcomes
High risk"An open randomised clinical study".

Incomplete outcome data (attrition bias)
All outcomes
Low riskMissing outcome data balanced in numbers across intervention groups (with similar reasons).

Selective reporting (reporting bias)Unclear riskIn the methods section, the authors do not describe all outcomes that subsequently reported in results section.

Other biasLow riskNo comments.

Misra 1995 IND

MethodsIndia. No power calculation made. Per protocol analysis. Duration: 21 days.


Participants64 hospitalised participants (38 males), from twp to 10 years old; Diarrhea, abdominal pain, anorexia, nausea, and vomiting were the more frequent symptoms.

Inclusion criteria: Children (twp to 12 years) with proven Giardia infection (trophozoites and/or cyst of G lamblia in stool specimens).

Exclusion criteria: "... acute febrile conditions, chronic diarrhoea, severe malnutrition or receiving long term therapy". Treatment of Giardia or intestinal helminthic infection in the previous seven days.


InterventionsRx 1. Albendazole: 400 mg/d, single dose, for five days (oral suspension).

Rx 2. Metronidazole: 7.5mg/kg three times daily (22.5 mg/kg/day), for five days (oral suspension).


OutcomesClinical assessment and stools were repeated on days one to seven, 14 and 21 post-treatment. Stool samples were examined microscopically (direct smear and formal ether concentration tests).

Hematological and biochemical parameters on the 7th and 14th day after treatment.

Reported side-effects.


NotesMore severe presenting symptoms (abdominal pain, vomiting and watery stools) in children in the group treated with metronidazole.

This study has a similar methodology to the Dutta 1994 IND study, but different patients (different hospitals).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"An open randomised parallel..."

Allocation concealment (selection bias)High risk"An open ..."

Blinding of outcome assessment (detection bias)
Stools examination
High risk"An open ..."

Blinding of outcome assessment (detection bias)
Other outcomes
High risk"An open ..."

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe losses were distributed similarly in both groups. "All these children had responded to the therapy and parents did not want the children to be hospitalised any further"

Selective reporting (reporting bias)Unclear riskNo results were reported hematological and biochemical variables. The report mentions that there were no significant differences in these variables.

Other biasHigh riskMore severe presenting symptoms (abdominal pain, vomiting and watery stools) in children in the group treated with metronidazole.

Ortiz 2001 PER

MethodsPeru. Intention to treat and per protocol analysis. Duration: 14 days.


Participants110 (54 males); ages two to 11 years, mean of age 5.67 (±2.56). All symptomatic.

Symptoms: duration of diarrhoea: 2 to 154 days. Pain, distension, and/or tenderness in 32.7%. Diarrhea was defined as more than three unformed stools per day or unformed stools without increased stool frequency for more than four weeks.

Enzyme immunoassay (Triage Parasite Panel, Biosite Diagnostic, San Diego, California) for G. lamblia, Entamoeba histolytica or Cryptosporidium parvum. Positive results for G. lamblia were confirmed using a direct examination and a Ritchie concentration technique.

Exclusion criteria: children with positive enzyme immunoassay of faecal samples for E. histolytica or C. parvum; children using any drug with antiprotozoal activity within two weeks of enrolment; children known to have or suspected of having AIDS were excluded from the study; patients with positive coprocultures for bacterial causes of diarrhoea were excluded from the analysis of clinical response.


InterventionsRx 1. Nitazoxanide: 5 mL (ages 2 to 3 years) or 10 mL (ages four to 11 years) of nitazoxanide (100 mg per 5 mL) strawberry-flavoured oral suspension, BID for three days.

Rx 2: Metronidazole: 5 mL of 125 mg per 5 mL (ages two to five years) or 250 mg per 5 mL (ages six to 11 years) of metronidazole suspension BID for five days.


OutcomesClinical response (at the day 7 follow-up): "well" (no symptoms, no watery stools and no more than two soft stools, and has no hematochezia within the past 24 h or no symptoms and no unformed stools within the past 48 h); or "continuing illness" (any number of watery stools, more than two soft stools per 24 h, or hematochezia or enteric symptoms plus the passage of any number of soft or watery stools during the past 48 h); or "clinical treatment failure" (clinical deterioration or worsening of symptoms after at least 24 h of treatment resulting in the patients being removed from the study).

Parasitological response: "eradicated" (no cysts observed in either post-treatment stool sample); or "persistence" (cysts observed in either or both post-treatment stool samples). Two stool samples were collected on consecutive days between day 7 and 10, following the initiation of treatment for evaluation of parasitological response . Stool samples collected at follow-up were examined for G. lamblia using a direct examination and a Ritchie concentration technique.


NotesSample size calculation: For the two treatment groups (n 55) (80% of power; 20% in risk differences).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Computer-generated randomisation list".

Allocation concealment (selection bias)Unclear riskNot mentioned.

Blinding of outcome assessment (detection bias)
Stools examination
Low risk"parasitologist conducting the stool examinations was blinded to the patients treatment group assignment".

Blinding of outcome assessment (detection bias)
Other outcomes
Unclear riskNot mentioned.

Incomplete outcome data (attrition bias)
All outcomes
Low riskLosses to follow up were reported.

Selective reporting (reporting bias)Low riskAll outcomes were included in the analyses.

Other biasLow riskNo comments.

Perez-Choliz 1989 ESP

MethodsSpain. No power calculation made. Per protocol analysis. Duration: 1 month.


Participants52 children (30 male) with parasitological diagnosis of giardiasis (paediatric outpatient). The mean age was 7.62 ± 3.23 (1.4 to 14.1 years).

There is not any specification about baseline symptoms, they were presumably 100% symptomatics.

Exclusion criteria: Not mentioned.


InterventionsRx 1. Tinidazole: 50 mg/kg, maximum 1.5g, single dose (oral). During or after a main meal.

Rx 2. Metronidazole: 20-25 mg/kg/d, max 0.5 g per day (oral). Three cycles of eight days with seven days between them.


OutcomesExamination of four stool samples, one month after treatment ends. The study does not specify the technique of stool examination.

Parasitological cure: stool negative for G. lamblia.

Symptoms collected in unsystematically through medical charts.

Side effects: questioning the patient and family, especially: headache, allergic reactions or any gastrointestinal symptoms.


NotesThe study provides no explanation for the loss to follow up.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"The allocation was set so random and alternating with tinidazole and metronidazole".

Allocation concealment (selection bias)Unclear riskNot mentioned.

Blinding of outcome assessment (detection bias)
Stools examination
Unclear risk"Randomized, double blind trial". Not specified. Both treatments are different in terms of duration of therapy.

Blinding of outcome assessment (detection bias)
Other outcomes
Unclear risk"Randomized, double blind trial". Not specified. Both treatments are different in terms of duration of therapy.

Incomplete outcome data (attrition bias)
All outcomes
High riskTwo losses to follow up in tinidazole group, and nine in the metronidazole group.

Selective reporting (reporting bias)Unclear riskSymptoms collected in unsystematically through medical charts.

Other biasUnclear riskNo baseline comparison.

Rodríguez 1996 MEX

MethodsMexico. No power calculation made. Intention to treat analysis. Duration: three weeks.


Participants49 participants (25 males). Ages 3 to 12 years.   

The main clinical manifestations were abdominal pain (65%), diarrhoea (35%), and hyporexia (49%). 8% of children were asymptomatic. 

Inclusion criteria:

  • Children between three and 12 years old
  • Children infected with G. lamblia. Confirmed by parasitological stool examinations (Faust's technique).
  • Consent of parents or guardians of children.


Exclusion criteria:

  • Children who have received antigiardial drugs in the past three months.


InterventionsRx 1. Albendazole: 200 mg three times daily for 5 days (oral).

Rx 2. Metronidazole: 30 mg/kg/day, three times daily, for 5 days (oral).


OutcomesParasitological (disappearance of cysts or trophozoites). Coproparasitology examination: direct microscopy, using the technique of Faust. The samples were collected on days 14 and 21, and he/she was considered cured if both samples were negative.

Reported side-effects.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Two groups were formed randomly".

Allocation concealment (selection bias)Unclear riskNot mentioned.

Blinding of outcome assessment (detection bias)
Stools examination
Unclear riskNot mentioned.

Blinding of outcome assessment (detection bias)
Other outcomes
Unclear riskNot mentioned.

Incomplete outcome data (attrition bias)
All outcomes
Low riskThere were no losses to follow-up.

Selective reporting (reporting bias)Unclear riskNo mention of a systematic strategy for collecting side effects.

Other biasHigh riskThere are differences in baseline characteristics of both groups. For example, preschool children were 51% in the albendazole group and 40% for metronidazole arm. Similarly, 74% of the children complained of abdominal pain in the albendazole group and 54% did so in the metronidazole group.

Romero-Cabello 1995 MEX

MethodsMexico. No power calculation made. Intention to treat analysis. Duration: 21 days.


Participants100 participants (49 males), from four to 11 years old (median: eight years old); symptoms (93%): 42% abdominal pain, 39% hyporexia, 8% diarrhoea, 2% nausea, and 2% debility.

Inclusion criteria: children infected with G. lamblia. Stool samples were examined microscopically.

Exclusion criteria: any drug with antiprotozoal activity in the last two months; or another class of treatment in children with denutrition II or III grade.


InterventionsRx 1. Albendazole: 400 mg/day single dose, for five days (oral).

Rx 2. Metronidazole: 7.5 mg/kg three times daily, for five days (oral).


OutcomesParasitological cure: absence of the cystic or trophozoite form of G. lamblia in the stools. Stools were repeated on days one to seven, 14, and 21 after beginning the treatment. Direct microscopy (three successive days).

Clinical response at one to seven days after beginning of treatment. Time to recovery.

Side-effects: on days one to seven, 14, and 21.

Cell blood count and blood chemistry after treatment.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot stated.

Allocation concealment (selection bias)Unclear risk"using an aleatory code A and B".

Blinding of outcome assessment (detection bias)
Stools examination
High risk"Open label".

Blinding of outcome assessment (detection bias)
Other outcomes
High risk"Open label".

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo reported losses to follow up.

Selective reporting (reporting bias)Low riskApparently, all outcomes were reported.

Other biasLow riskNo comments.

Yereli 2004 TUR

MethodsTurkey. No power calculation made. Intention to treat analysis. Duration: 21 days (14 days after completing treatment).


Participants107 children, from three to 15 years old; Symptoms (gastrointestinal complaints, diarrhoea, weight loss, anorexia, and fatigue) and G. lamblia cysts and or trophozoites in stools.

Stool samples were assessed for giardiasis by the saline–Lugol, formalin ethyl acetate concentration, and trichrome staining methods.

Exclusion criteria: not mentioned.


InterventionsRx 1. Albendazole: 10 mg/kg/day, single dose, for five days (tablets).

Rx 2. Metronidazole: 20 mg/kg/day, three times daily, for seven days (tablet or liquid).


OutcomesStool samples from all cases were examined on the 7th, 10th and 14th days following completion of treatment.

Clinical symptoms: the method was not specified.

Side-effects: the method was not specified.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"was divided into two random groups".

Allocation concealment (selection bias)Unclear riskNot mentioned.

Blinding of outcome assessment (detection bias)
Stools examination
Unclear riskNot mentioned.

Blinding of outcome assessment (detection bias)
Other outcomes
High riskNo masking of drugs.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or loss to follow up.

Selective reporting (reporting bias)High riskSymptoms were not adequately reported.

Other biasLow riskNo comments.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Bakshi 1978It is not a randomized clinical trial. Meta-analysis of clinical trials in India.

Baqai 2001No randomization.

Bassily 1987It is not a randomized clinical trial.

Besirbellioglu 2006This study included two groups treated with metronidazole plus Saccharomyces boulardii.

Botero 1974The study was presented in a congress. No data available.

Gazder 1978This study compared single dose of metronidazole against single dose of tinidazole.

Grant 2001This study included two groups treated with metronidazole plus wheat germ, or placebo.

Guerrero 2000Authors were contacted. The study was presented in a congress, data were not provided.

Jokipii 1978It is not a randomized clinical trial.

Jokipii 1979It is not a randomized clinical trial.

Krishnamurthy 1978This study compared single dose of metronidazole against single dose of tinidazole.

Kyrönseppä 1981This study compared treatment with single dose tinidazole, against treatment with metronidazole for two days.

Leary 1974This study compared treatment with metronidazole for one day, against treatment with metronidazole for two days.

Levi 1977It is not a randomized clinical trial.

Morrone 2004It is not a randomized clinical trial.

Nigam 1991This study compared single dose of metronidazole against single dose of tinidazole.

Sabchareon 1980It is not a randomized clinical trial.

Sadjjadi 2001Asymptomatic children.

Speelman 1985This study compared single dose tinidazole against single dose metronidazole, and another arm with metronidazole for three days.

Suntornpoch 1981It is not a randomized clinical trial.

 
Comparison 1. Albendazole (once daily) versus metronidazole (three times daily)

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

 1 Parasitological cure (at 1 to 3 weeks)10932Risk Ratio (M-H, Fixed, 95% CI)0.99 [0.95, 1.03]

 2 Time to achieve parasitological cure (hours)157Mean Difference (IV, Fixed, 95% CI)-19.0 [-34.72, -3.28]

 3 Clinical improvement (at 2 to 3 weeks)5483Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.93, 1.04]

 4 Time of symptomatic improvement (hours)297Mean Difference (IV, Fixed, 95% CI)-5.69 [-22.10, 10.73]

 5 Other adverse events (gastrointestinal at 1 to 3 weeks)8717Risk Ratio (M-H, Random, 95% CI)0.29 [0.13, 0.63]

 6 Other adverse events (neurological at 1 to 3 weeks)5453Risk Ratio (M-H, Fixed, 95% CI)0.34 [0.18, 0.64]

 7 Other adverse events (metallic taste at 3 weeks)3327Risk Ratio (M-H, Fixed, 95% CI)0.03 [0.01, 0.13]

 8 Other adverse events (allergic/cutaneous at 3 weeks)2154Risk Ratio (M-H, Fixed, 95% CI)0.2 [0.01, 4.08]

 9 Other adverse events (fever at 3 weeks)134Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.23, 4.27]

 10 Other adverse events (transient elevation of liver enzymes at 3 weeks)1150Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.06, 15.69]

 11 Other adverse (transient neutropenia at 3 weeks)1150Risk Ratio (M-H, Fixed, 95% CI)5.0 [0.24, 102.42]

 12 Non-compliance to treatment (at 2 weeks)157Risk Ratio (M-H, Fixed, 95% CI)0.74 [0.27, 2.06]

 
Comparison 2. Mebendazole (three times daily) versus metronidazole (three times daily)

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

 1 Parasitological cure (at 1 to 2 weeks)5142Risk Ratio (M-H, Random, 95% CI)0.58 [0.32, 1.06]

    1.1 Children
3100Risk Ratio (M-H, Random, 95% CI)0.85 [0.62, 1.17]

    1.2 Children and adults
242Risk Ratio (M-H, Random, 95% CI)0.15 [0.05, 0.44]

 2 Other adverse events (nausea/vomiting at 1 to 2 weeks)3100Risk Ratio (M-H, Fixed, 95% CI)0.32 [0.05, 1.90]

 3 Other adverse events (headache at 1 to 2 weeks)274Risk Ratio (M-H, Fixed, 95% CI)0.24 [0.03, 2.06]

 4 Other adverse events (urticaria at 1 to 2 weeks)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 3. Tinidazole (single dose) versus metronidazole (three times daily)

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

 1 Parasitological cure (at 3 weeks to 1 month)3179Risk Ratio (M-H, Random, 95% CI)1.23 [0.87, 1.73]

 2 Clinical improvement (at 3 weeks to 1 month)3179Risk Ratio (M-H, Fixed, 95% CI)1.20 [1.06, 1.36]

 3 Other adverse events (gastrointestinal at 3 weeks to 1 month)3179Risk Ratio (M-H, Fixed, 95% CI)0.58 [0.21, 1.62]

 4 Other adverse events (neurological at 3 weeks to 1 month)2138Risk Ratio (M-H, Fixed, 95% CI)1.30 [0.29, 5.92]

 5 Other adverse events (allergic/cutaneous at 3 weeks to 1 month)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 6 Other adverse events (fever at 3 weeks to 1 month)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 7 Serious adverse events (at 3 weeks to 1 month)3179Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 4. Metronidazole (single dose) versus metronidazole (three times daily)

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

 1 Parasitological cure (at 2 weeks)154Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.93, 1.08]

 2 Other adverse events (gastrointestinal at 2 weeks)154Risk Ratio (M-H, Fixed, 95% CI)2.70 [0.26, 27.96]

 3 Serious adverse events (at 2 weeks)154Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 5. Nitazoxanide (twice daily) versus metronidazole (twice daily)

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

 1 Parasitological cure (at 1 week)1110Risk Ratio (M-H, Random, 95% CI)0.95 [0.76, 1.20]

 2 Reduction in symptoms of diarrhea (at 1 week)1110Risk Ratio (M-H, Random, 95% CI)1.07 [0.90, 1.27]

 3 Other adverse events (at 1 week)1110Risk Ratio (M-H, Fixed, 95% CI)1.1 [0.51, 2.38]

 4 Other adverse events (abdominal pain at 1 week)1110Risk Ratio (M-H, Fixed, 95% CI)1.67 [0.65, 4.27]

 5 Other adverse events (nausea/vomiting at 1 week)1110Risk Ratio (M-H, Fixed, 95% CI)0.33 [0.01, 8.01]

 6 Other adverse events (headache at 1 week)1110Risk Ratio (M-H, Fixed, 95% CI)0.14 [0.01, 2.70]

 
Summary of findings for the main comparison.

Albendazole (5+ days) compared to metronidazole (5+ days) for treating giardiasis

Patient or population: People with giardiasis infection
Settings: Endemic settings
Intervention: Albendazole once daily for five or more days
Comparison: Metronidazole three times daily for five or more days

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Metronidazole
(three times daily for 5 to 10 days)
Albendazole
(once daily for 5 to 10 days)

Parasitological cure (Follow-up: 1 to 2 weeks)91 per 10090 per 100
(86 to 94)
RR 0.99
(0.95 to 1.03)
932
(10 studies)
⊕⊕⊕⊝
moderate1,2,3

Clinical improvement (Follow-up: 2 to 3 weeks)91 per 10089 per 100
(85 to 95)
RR 0.98
(0.93 to 1.04)
483
(5 studies)
⊕⊕⊕⊝
moderate1,2,3

Gastrointestinal side effects (Follow-up: 1 to 3 weeks)29 per 1008 per 100
(4 to 18)
RR 0.29
(0.13 to 0.63)
717
(8 studies)
⊕⊕⊕⊝
moderate1,2

Neurological side effects (Follow-up: 1 to 3 weeks)15 per 1005 per 100
(3 to 10)
RR 0.34
(0.18 to 0.64)
453
(5 studies)
⊕⊕⊝⊝
low1,2,4

*The basis for the assumed risk (eg the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk Ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 These trials were conducted in adults and children in India, Mexico, Peru, Cuba, and Turkey. The dose of metronidazole was 250 mg to 500 mg three times daily for 5 to 10 days. The dose of albendazole was 400 mg once daily for five to 10 days.
2 Downgraded by 1 for risk of bias as none of these trials adequately described allocation concealment or blinding.
3 The finding of no difference between treatments is consistent across trials, and the 95% CI excludes clinically important differences.
4 Downgraded by 1 for imprecision as the number of neurological side effects in these trials was very low.
 
Summary of findings 2.

Mebendazole (5+ days) compared to metronidazole (5+ days) for treating giardiasis

Patient or population: People with giardiasis infection
Settings: Endemic settings
Intervention: Mebendazole once daily for five or more days
Comparison: Metronidazole three times daily for five or more days

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Metronidazole
(three times daily for 5 to 10 days)
Mebendazole
(three times daily for 5 to 10 days)

Parasitological cure

(Follow-up: 1 to 2 weeks)
90 per 10052 per 100
(29 to 95)
RR 0.58
(0.32 to 1.06)
142
(5 studies)
⊕⊝⊝⊝
very low1,2,3

Clinical improvement---(0 studies)-Not reported

Side effects: nausea/vomiting8 per 1003 per 100
(0 to 15)
RR 0.32
(0.05 to 1.9)
100
(3 studies)
⊕⊝⊝⊝
very low1,2,3

Side effects: headache8 per 1002 per 100
(0 to 17)
RR 0.24
(0.03 to 2.06)
74
(2 studies)
⊕⊝⊝⊝
very low1,2,3

Serious adverse events---142
(5 studies)
-Not reported

*The basis for the assumed risk (eg the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk Ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1These trials were conducted in adults and children from Spain, Turkey, and the UK. The usual dose of mebendazole was 200 mg three times daily for five to 10 days, and metronidazole 5 mg/kg (or 250 mg) three times daily for five to 10 days.
2 Downgraded by 1 for risk of bias. None of these trials adequately described allocation concealment or blinding.
3 Downgraded by 2 for imprecision. The trials were very small and underpowered to detect differences. The 95% CI is wide and includes no difference between treatments.
 
Summary of findings 3.

Tinidazole (single dose) compared to metronidazole (5+ days) for treating giardiasis

Patient or population: People with giardiasis infection
Settings: Endemic settings
Intervention: Tinidazole single dose
Comparison: Metronidazole three times daily for five or more days

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Metronidazole
(three times daily for 5 to 10 days)
Tinidazole
(single dose)

Parasitological cure
(Follow-up: 3 to 4 weeks)
73 per 10089 per 100
(63 to 100)
RR 1.23
(0.87 to 1.73)
179
(3 studies)
⊕⊝⊝⊝
very low1,2,3

Clinical improvement
(Follow-up: 3 to 4 weeks)
76 per 10087 per 100
(76 to 100)
RR 1.15
(1 to 1.32)
179
(3 studies)
⊕⊝⊝⊝
very low1,2,3

Gastrointestinal side effects
(Follow-up: 3 to 4 weeks)
8 per 1005 per 100
(2 to 13)
RR 0.58
(0.21 to 1.62)
179
(3 studies)
⊕⊝⊝⊝
very low1,2,3

Neurological side effects
(Follow-up: 3 to 4 weeks)
4 per 1005 per 100
(1 to 22)
RR 1.3
(0.29 to 5.92)
138
(2 studies)
⊕⊝⊝⊝
very low1,2,3

Serious adverse events---179
(3 studies)
-Not reported

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1These trials were conducted in Iran, Spain and Peru. The usual dose of tinidazole was 50mg/kg as a single dose, and metronidazole 5 mg/kg (or 250 mg) three times daily for five to 10 days.
2 Downgraded by 1 for risk of bias. None of these trials adequately described allocation concealment or blinding.
3 Downgraded by 2 for imprecision. The trials were very small and underpowered to detect differences. The 95% CI is wide and includes no difference between treatments.