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Clin Evid (Online). 2011; 2011: 0918.
Published online Jan 13, 2011.
PMCID: PMC3275292
Amoebic dysentery
Nicole M Mackey-Lawrence# and William Arthur Petri Jr., MD, PhD, Professor#
Nicole M Mackey-Lawrence, University of Virginia, Charlottesville, USA;
#Contributed equally.
NMML declares that she has no competing interests. WP receives loyalty income for diagnosis of Amoebiasis. This is donated in its entirety to the American Society of tropical Medicine & Hygiene, at no benefit to WP.
NMML and WP would like to acknowledge the contribution of the previous author, Elizabeth Martinez.
Introduction
Amoebic dysentery is caused by the protozoan parasite Entamoeba histolytica. It is transmitted in areas where poor sanitation allows contamination of drinking water and food with faeces. In these areas, up to 40% of people with diarrhoea may have amoebic dysentery.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of drug treatments for amoebic dysentery in endemic areas? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 6 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: diiodohydroxyquinoline (iodoquinol), diloxanide, emetine, metronidazole, nitazoxanide, ornidazole, paromomycin, secnidazole, and tinidazole.
Invasive infection with the parasite Entamoeba histolytica can be asymptomatic, or can cause diarrhoea with blood and mucus, abdominal pains, and fever.
  • Amoebic dysentery is transmitted in areas where poor sanitation allows contamination of drinking water and food with faeces. In these areas, up to 40% of people with diarrhoea may have amoebic dysentery.
  • Fulminant amoebic dysentery is often fatal. Other complications include perforation of the colon, colonic ulcers, amoeboma, or chronic carriage.
Ornidazole may be effective at curing amoebic dysentery compared with placebo, but can cause nausea and vomiting.
  • Secnidazole, tinidazole, and metronidazole may be as effective as ornidazole at curing amoebic dysentery.
  • Metronidazole may be less effective than tinidazole at reducing clinical symptoms, but may be as effective at clearing parasites. Metronidazole may be more likely than tinidazole to cause adverse effects such as nausea.
Nitazoxanide is likely to be more effective than placebo at reducing clinical failure. Nitazoxanide may not be more effective than placebo at preventing parasitological failure.
We don't know whether emetine, paromomycin, diloxanide, or diiodohydroxyquinoline are effective in treating amoebic dysentery as we found no trials. However, paromomycin, diloxanide, and diiodohydroxyquinoline are luminal amoebicides and there is consensus that they have insufficient tissue penetration to be effective against invasive disease.
Definition
Amoebic dysentery is caused by the protozoan parasite Entamoeba histolytica. Invasive intestinal parasitic infection can result in symptoms of fulminant dysentery, such as fever, chills, bloody or mucous diarrhoea, and abdominal discomfort. The dysentery can alternate with periods of constipation or remission. This review focuses on amoebic dysentery only, and includes populations with both suspected and documented disease in endemic areas where levels of infection do not exhibit wide fluctuations through time.[1] The term "amoebic dysentery" encompasses people described as having symptomatic intestinal amoebiasis, amoebic colitis, amoebic diarrhoea, or invasive intestinal amoebiasis. Extraintestinal amoebiasis (e.g., amoebic liver abscess) and asymptomatic amoebiasis are not covered.
Incidence/ Prevalence
We found no accurate global prevalence data for E histolytica infection and amoebic dysentery. Estimates on the prevalence of Entamoeba infection range from 1% to 40% of the population in Central and South America, Africa, and Asia, and from 0.2% to 10.8% in endemic areas of developed countries such as the USA.[2] [3] [4] [5] However, these estimates are difficult to interpret, mainly because infection can remain asymptomatic or go unreported,[6] and because many older reports do not distinguish E histolytica from the non-pathogenic, morphologically identical species Entamoeba dispar. Development and availability of more sophisticated methods (such as the enzyme-linked immunosorbent assay [ELISA]-based test) to differentiate the two species might give a more accurate estimate of its global prevalence.[7] Infection with E histolytica is a common cause of acute diarrhoea in developing countries. One survey conducted in Egypt found that 38% of people with acute diarrhoea in an outpatient clinic had amoebic dysentery.[8]
Aetiology/ Risk factors
Ingestion of cysts from food or water contaminated with faeces is the main route of E histolytica transmission. Low standards of hygiene and sanitation, particularly those related to crowding, tropical climate, contamination of food and water with faeces, and inadequate disposal of faeces, all account for the high rates of infection seen in developing countries.[9] [10] In developed countries, risk factors include communal living, oral and anal sex, compromised immune system, and migration or travel from endemic areas.[9] [11] [12]
Prognosis
Amoebic dysentery may progress to amoeboma, fulminant colitis, toxic megacolon, and colonic ulcers, and may lead to perforation.[13] Amoeboma may be mistaken for colonic carcinoma or pyogenic abscess. Amoebic dysentery may also result in chronic carriage and the chronic passing of amoebic cysts. Fulminant amoebic dysentery is reported to have 55% to 88% mortality.[14] [15] It is estimated that more than 500 million people are infected with E histolytica worldwide.[10] Between 40,000 and 100,000 will die each year, placing this infection second to malaria in mortality caused by protozoan parasites.[16]
Aims of intervention
To reduce the infectious period, length of illness, risks of dehydration, risks of transmission to others, and rates of severe illness; to prevent complications and death, with minimal adverse effects.
Outcomes
Mortality; quality of life; hospitalisation: length of hospital stay, rate of hospital admission; complications (i.e., amoeboma, extension to pleural cavity, chronic cyst carriage); treatment effectiveness: therapeutic cure (defined as absence of parasites in stools, disappearance of symptoms, and healing of ulcers); clinical failure (defined as persistence of symptoms), and parasitological failure (defined as persistence of parasites in stools or in other diagnostic tests); and adverse effects of treatment.
Methods
Clinical Evidence search and appraisal April 2010. The following databases were used to identify studies for this systematic review: Medline 1966 to April 2010, Embase 1980 to April 2010, and The Cochrane Database of Systematic Reviews 2010, Issue 3 (1966 to date of issue). An additional search within The Cochrane Library was carried out for the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using pre-determined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews of RCTs and RCTs in any language, including open studies, with no minimum number of participants. There was no minimum length of follow-up required to include studies, and no maximum loss to follow-up. We included systematic reviews of RCTs and RCTs where harms of an included intervention were studied, applying the same study design criteria for inclusion as we did for benefits. In addition we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table
Table
GRADE Evaluation of interventions for Amoebic dysentery.
Glossary
Amoeboma A granulomatous lesion of the caecum or ascending colon caused by localised chronic Entamoeba histolytica infection.
Enzyme linked immunosorbent assay (ELISA) A testing method using immune responses to detect substances such as hormones, bacterial antigens, and antibodies.
Helminthiasis Presence in the body of parasitic worms, including nematode worms such as Ascaris, Trichuris, and Ancylostoma.
Low-quality evidenceFurther 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 evidenceAny estimate of effect is very uncertain.

Notes
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
Contributor Information
Nicole M Mackey-Lawrence, University of Virginia, Charlottesville, USA.
William Arthur Petri Jr., University of Virginia, Charlottesville, USA.
1. Last JM (ed). A dictionary of epidemiology. 3rd ed. New York, NY: Oxford University Press; 1995.
2. Rivera WL, Tachibana H, Kanbara H. Field study on the distribution of Entamoeba histolytica and Entamoeba dispar in the northern Philippines as detected by the polymerase chain reaction. Am J Trop Med Hyg1998;59:916–921. [PubMed]
3. Haque R, Faruque ASG, Hahn P, et al. Entamoeba histolytica and Entamoeba dispar infection in children in Bangladesh. J Infect Dis1997;175:734–736. [PubMed]
4. Braga LL, Mendonca Y, Paiva CA, et al. Seropositivity for and intestinal colonization with Entamoeba histolytica and Entamoeba dispar in individuals in Northeastern Brazil. J Clin Microbiol1998;36:3044–3045. [PMC free article] [PubMed]
5. Chacin-Bonilla L, Bonillla E, Parra AM, et al. Prevalence of Entamoeba histolytica and other intestinal parasites in a community from Maracaibo, Venezuela. Ann Trop Med Parasitol1992;86:373–380. [PubMed]
6. Anonymous. Amoebiasis. Wkly Epidemiol Rec1997;72:97–99. [PubMed]
7. Huston CD, Petri WA. Amoebiasis: clinical implications of the recognition of Entamoeba dispar Curr Infect Dis Rep1999;1:441–447. [PubMed]
8. Abd-Alla MD, Ravdin JI. Diagnosis of amoebic colitis by antigen capture ELISA in patients presenting with acute diarrhoea in Cairo, Egypt. Trop Med Int Health2002;7:365–370. [PubMed]
9. Davis AN, Haque R, Petri WA Jr. Update on protozoan parasites of the intestine. Curr Opin Gastroenterol2002;18:10–14. [PubMed]
10. Lucas R, Upcroft JA. Clinical significance of the redefinition of the agent of amoebiasis. Rev Latinoam Microbiol2001;43:183–187. [PubMed]
11. Petri WA Jr, Singh U. Diagnosis and management of amebiasis. Clin Infect Dis1999;29:1117–1125. [PubMed]
12. Stanley SL. Amoebiasis. Lancet2003;361:1025–1034. [PubMed]
13. Haque R, Huston CD, Hughes M, et al. Amebiasis. N Engl J Med2003;348:1565–1573. [PubMed]
14. Singh B, Moodley J, Ramdial PK. Fulminant amoebic colitis: a favorable outcome. Int Surg2001;86:77–81. [PubMed]
15. Vargas M, Pena A. Toxic amoebic colitis and amoebic colon perforation in children: an improved prognosis. J Pediatr Surg1976;11:223–225. [PubMed]
16. Espinosa-Cantellano M, Martínez-Palomo A. Recent developments in amoebiasis research. Curr Opin Infect Dis2000;13:451–456. [PubMed]
17. Gonzales-Maria LM, Dans LF, Martinez EG. Antiamoebic drugs for treating amoebic colitis. In: The Cochrane Library, Issue 3, 2010. Chichester, UK: John Wiley & Sons, Ltd. Search date 2008.
18. Misra NP, Gupta RC. A comparison of a short course of single daily dosage therapy of tinidazole with metronidazole in intestinal amoebiasis. J Int Med Res1977;5:434–437. [PubMed]
19. Misra NP. A comparative study of tinidazole with metronidazole as a single daily dose for three days in symptomatic intestinal amoebiasis. Drugs1978;15(suppl 1):19–22. [PubMed]
20. Toppare MF, Kitapci F, Senses DA, et al. Ornidazole and secnidazole in the treatment of symptomatic intestinal amoebiasis in childhood. Trop Doct1994;24:183–184. [PubMed]
21. Apt W, Perez C, Miranda C, et al. Treatment of intestinal amebiasis and giardiasis with ornidazole. [In Spanish.] Rev Med Chil1983;111:1130–1133. [PubMed]
22. Panggabean A, Sutjipto A, Aldy D, et al. Tinidazole versus ornidazole in amebic dysentery in children (a double blind trial). Paediatr Indones1980;20:229–235. [PubMed]
23. Gupta YK, Gupta M, Aneja S, et al. Current drug therapy of protozoal diarrhoea. Indian J Pediatr2004;71:55–58. [PubMed]
24. Pantenburg B, Cabada MM, White AC Jr. Treatment of cryptosporidiosis. Expert Rev Anti Infect Ther2009;7:385–391. [PubMed]
25. Di Perri G, Strosselli M, Rondanelli EG. Therapy of entamebiasis. J Chemother1989;1:113–122. [PubMed]
26. Bhopale KK, Pradhan KS, Masani KB, et al. A comparative study of experimental caecal amoebiasis and the evaluation of amoebicides. Ann Trop Med Parasitol1995;89:253–259. [PubMed]

Metronidazole
Summary
Metronidazole may be less effective than tinidazole at reducing clinical symptoms, but may be as effective at clearing parasites. Metronidazole may be more likely than tinidazole to cause adverse effects such as nausea.
Metronidazole seems as effective as ornidazole at treating both clinical and parasitological signs. Both interventions exhibited similar rates of adverse effects.
We found no direct information from RCTs about whether metronidazole is better than no active treatment. We found no clinically important results from RCTs about metronidazole compared with secnidazole, emetine, paromomycin, diloxanide, nitazoxanide, or diiodohydroxyquinoline in people with amoebic dysentery.
Benefits and harms
Metronidazole versus placebo:
We found no systematic review or RCTs.
Metronidazole versus tinidazole:
We found one systematic review (search date 2008, 10 RCTs) comparing metronidazole versus tinidazole.[17]
Treatment effectiveness
Metronidazole compared with tinidazole Metronidazole may be less effective than tinidazole in decreasing clinical failure at 15–60 days after completion of treatment. However, we don't know how effective metronidazole and tinidazole are, compared with each other, at decreasing parasitological failure (very low-quality evidence).
Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Clinical failure
[17]
Systematic review
285 people
2 RCTs in this analysis
Clinical failure 1–14 days after completion of treatment
6/132 (5%) with metronidazole
1/153 (1%) with tinidazole

RR 0.17
95% CI 0.02 to 1.30
P = 0.088
Not significant
[17]
Systematic review
477 people
8 RCTs in this analysis
Clinical failure 15–60 days after completion of treatment
48/229 (21%) with metronidazole
13/248 (5%) with tinidazole

RR 0.28
95% CI 0.15 to 0.51
P less than or equal to 0.001
Moderate effect sizeTinidazole
Parasitological failure
[17]
Systematic review
285 people
2 RCTs in this analysis
Parasitological failure 1–14 days after completion of treatment
63/132 (48%) with metronidazole
79/153 (52%) with tinidazole

RR 1.01
95% CI 0.58 to 1.74
P = 0.98
Not significant
[17]
Systematic review
507 people
9 RCTs in this analysis
Parasitological failure 15–60 days after completion of treatment
34/245 (14%) with metronidazole
26/262 (10%) with tinidazole

RR 0.64
95% CI 0.25 to 1.64
P = 0.35
Significant heterogeneity present in analysis (P = 0.007). Subgroup analysis revealed that analysis by clinical group reduced some of the observed heterogeneity (see further information on studies)
Not significant
Mortality
No data from the following reference on this outcome.[17]
Quality of life
No data from the following reference on this outcome.[17]
Hospitalisation
No data from the following reference on this outcome.[17]
Complications
No data from the following reference on this outcome.[17]
Adverse effects
Metronidazole compared with tinidazole Metronidazole may be more likely to be associated with adverse effects than tinidazole (low-quality evidence).
Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects
[17]
Systematic review
477 people
8 RCTs in this analysis
Proportion of people with adverse effects
103/229 (45%) with metronidazole
72/248 (30%) with tinidazole

RR 0.65
95% CI 0.46 to 0.92
P = 0.015
Small effect sizetinidazole
Metronidazole versus ornidazole:
We found one systematic review (search date 2008, 3 RCTs) comparing metronidazole versus ornidazole.[17]
Treatment effectiveness
Metronidazole compared with ornidazole We don't know how effective metronidazole and ornidazole are, compared with each other, in clearance of both clinical symptoms and parasitological signs (very low-quality evidence).
Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Clinical failure
[17]
Systematic review
40 people
2 RCTs in this analysis
Clinical failure 1–14 days after completion of treatment
0/20 (0%) with metronidazole
0/20 (0%) with ornidazole

The review reported that the number of trials was too small to detect any difference
[17]
Systematic review
118 people
2 RCTs in this analysis
Clinical failure 15–60 days after completion of treatment
0/59 (0%) with metronidazole
1/59 (2%) with ornidazole

RR 3.00
95% CI 0.13 to 71.89
P = 0.50
The review reported that the number of trials was too small to detect any difference
Not significant
Parasitological failure
[17]
Systematic review
40 people
2 RCTs in this analysis
Parasitological failure 1–14 days after completion of treatment
0/20 (0%) with metronidazole
0/20 (0%) with ornidazole

The review reported that the number of trials was too small to detect any difference
[17]
Systematic review
135 people
2 RCTs in this analysis
Parasitological failure 15–60 days after completion of treatment
6/69 (9%) with metronidazole
1/66 (2%) with ornidazole

RR 0.18
95% CI 0.02 to 1.41
P = 0.10
The review reported that the number of trials was too small to detect any difference
Not significant
Mortality
No data from the following reference on this outcome.[17]
Quality of life
No data from the following reference on this outcome.[17]
Hospitalisation
No data from the following reference on this outcome.[17]
Complications
No data from the following reference on this outcome.[17]
Adverse effects
Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects
[17]
Systematic review
20 people
Data from 1 RCT
Proportion of people with adverse effects
3/10 (30%) with metronidazole
2/10 (20%) with ornidazole

RR 0.67
95% CI 0.14 to 3.17
P = 0.61
Not significant
Metronidazole versus secnidazole, emetine, paromomycin, diloxanide, nitazoxanide, or diiodohydroxyquinoline:
We found no systematic review or RCTs.
Further information on studies
The quality of the RCTs included in the analysis was generally low, with a lack of standardised methods for inclusion, diagnosis, and outcome reporting. Many of the RCTs included in the meta-analysis were not blinded, while those studies that used blinding did so with diverse methods. Diagnosis of amoebic dysentery was predominately achieved by direct visualisation of either trophozoites or cysts in stool. Other diagnostic methods included ELISA detection from stool, concentration of sample for increased sensitivity for cyst detection, flotation techniques, and trophozoite fixation. While some trials reported on concomitant infection with other intestinal pathogens (parasite or bacteria), not all trials determined if Entamoeba histolytica was the single likely cause of dysentery. Metronidazole versus tinidazole The review reported that it was not clear whether two RCTs involved the same group of people or different groups sampled from the same population. The meta-analysis demonstrated that removal of a possible duplicate study () along with exclusion of trials funded by pharmaceutical companies did not significantly change the overall results of tinidazole versus metronidazole. The fact that not all trials determined if E histolytica was the single likely cause of dysentery could impact on data interpretation and could account for some of the difference observed between tinidazole and metronidazole in clinical failures outcome, while no significant difference was observed in the parasitological failure outcome. The RCTs displayed significant heterogeneity, as reported in the meta-analysis. When analysed by subgroup, the meta-analysis found reduced heterogeneity in three groups: those who used WHO diagnostic criteria, "unspecified amoebic colitis", and "non-dysenteric amoebic colitis"; this could affect the interpretation of included RCTs as a whole.
Comment
Clinical guide:
While tinidazole had reduced clinical failure rates when compared with metronidazole, tinidazole did not differ significantly from metronidazole in the parasitological failure outcome. Furthermore, metronidazole is the established drug of choice for treatment of amoebic dysentery. While we found no studies that show metronidazole efficacy compared with placebo, this is likely to be due to the ethical questions involved in treatment of a potentially fatal condition with placebo. Therefore, metronidazole is likely to be beneficial, as are tinidazole and ornidazole.
Substantive changes
Metronidazole New evidence added.[17] Categorisation changed from Unlikely to be beneficial to Likely to be beneficial.

Secnidazole
Summary
Secnidazole may have similar efficacy as ornidazole at reducing parasitological or clinical failure in treatment of amoebic dysentery.
We found no direct information from RCTs about whether secnidazole is better than no active treatment. We found no clinically important results from RCTs about secnidazole compared with metronidazole, tinidazole, emetine, paromomycin, diloxanide, diiodohydroxyquinoline, or nitazoxanide in people with amoebic dysentery.
Benefits and harms
Secnidazole versus placebo:
We found no systematic review or RCTs.
Secnidazole versus ornidazole:
We found one systematic review (search date 2008),[17] which identified one unblinded RCT comparing secnidazole (30 mg/kg daily for 3 days) versus ornidazole (15 mg/kg daily for 10 days).[20]
Treatment effectiveness
Secnidazole compared with ornidazole We don't know how effective secnidazole and ornidazole are, compared with each other, at reducing clinical or parasitological failure (very low-quality evidence).
Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Clinical failure
[20]
RCT
102 children with amoebic dysentery
In review [17]
Persistence of diarrhoea and abdominal discomfort 10 days after treatment ended
3/60 (5%) with secnidazole
2/42 (5%) with ornidazole

Significance assessment not performed
Parasitological failure
[20]
RCT
102 children with amoebic dysentery
In review [17]
Failure to clear parasites 10 days after treatment ended
19/60 (32%) with secnidazole
10/42 (24%) with ornidazole

Significance assessment not performed
Mortality
No data from the following reference on this outcome.[20]
Quality of life
No data from the following reference on this outcome.[20]
Hospitalisation
No data from the following reference on this outcome.[20]
Complications
No data from the following reference on this outcome.[20]
Adverse effects
Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects
[20]
RCT
102 children with amoebic dysentery
In review [17]
Adverse effects
with secnidazole
with ornidazole
Secnidazole versus metronidazole, tinidazole, emetine, paromomycin, diloxanide, diiodohydroxyquinoline, or nitazoxanide:
We found no systematic review or RCTs.
Further information on studies
None.
Comment
None.
Substantive changes
Secnidazole New evidence added.[17] Categorisation unchanged (Likely to be beneficial).

Ornidazole
Summary
Ornidazole may be effective at curing amoebic dysentery compared with placebo, but can cause nausea and vomiting.
Ornidazole may be as effective as tinidazole, metronidazole, and secnidazole at curing amoebic dysentery.
We found no direct information from RCTs about ornidazole compared with emetine, paromomycin, diloxanide, diiodohydroxyquinoline, or nitazoxanide in people with amoebic dysentery.
Benefits and harms
Ornidazole versus placebo:
We found one RCT.[21]
Treatment effectiveness
Ornidazole compared with placebo Ornidazole may be more effective than placebo in clearing parasites at 8 to 10 days (very low-quality evidence).
Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Parasitological failure
[21]
RCT
55 people Failure to clear parasites 8 to 10 days
7/35 (20%) with ornidazole
20/20 (100%) with placebo

Significance assessment not performed
Mortality
No data from the following reference on this outcome.[21]
Quality of life
No data from the following reference on this outcome.[21]
Hospitalisation
No data from the following reference on this outcome.[21]
Complications
No data from the following reference on this outcome.[21]
Adverse effects
Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects
[21]
RCT
55 people Proportion of people with adverse effects
3/35 (8.6%) with ornidazole
0/20 (0%) with placebo

Significance assessment not performed
Ornidazole versus tinidazole:
We found one systematic review (search date 2008, 2 RCTs).[17]
Treatment effectiveness
Ornidazole compared with tinidazole We don't know how effective ornidazole and tinidazole are, compared with each other, in reducing both clinical and parasitological failure at 1 to 14 days after completion of treatment (very low-quality evidence).
Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Clinical failure
[17]
Systematic review
66 children
2 RCTs in this analysis
Clinical failure 1–14 days after completion of treatment
0/35 (0%) with ornidazole
3/31 (10%) with tinidazole

RR 0.23
95% CI 0.03 to 1.96
P = 0.18
Not significant
Parasitological failure
[17]
Systematic review
66 children
2 RCTs in this analysis
Parasitological failure 1–14 days after completion of treatment
1/35 (3%) with ornidazole
0/31 (0%) with tinidazole

Significance assessment not performed
Mortality
No data from the following reference on this outcome.[17]
Quality of life
No data from the following reference on this outcome.[17]
Hospitalisation
No data from the following reference on this outcome.[17]
Complications
No data from the following reference on this outcome.[17]
Adverse effects
Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects
[22]
RCT
40 children
In review [17]
Adverse effects
with ornidazole
with tinidazole
Ornidazole versus metronidazole:
See option on metronidazole.
Ornidazole versus secnidazole:
See option on secnidazole.
Ornidazole versus emetine, paromomycin, diloxanide, diiodohydroxyquinoline, or nitazoxanide:
We found no systematic review or RCTs.
Further information on studies
Ornidazole versus tinidazole: The review reported that both RCTs had high withdrawal rates. Most of the children in one of the RCTs also had helminthiasis (presence of Ascaris, Trichuris, or Ancylostoma: 17/20 [85%] in the tinidazole group v 18/20 [90%] in the ornidazole group).
Comment
None.
Substantive changes
Ornidazole New evidence added.[17] Categorisation unchanged (Likely to be beneficial).

Tinidazole
Summary
Tinidazole may be more effective than metronidazole at reducing clinical symptoms, but may be as effective at clearing parasites. Tinidazole may be less likely to cause adverse effects than metronidazole.
Tinidazole may be as effective as ornidazole at preventing clinical and parasitological failure.
We found no clinically important results from RCTs about tinidazole compared with secnidazole, emetine, paromomycin, diloxanide, nitazoxanide, or diiodohydroxyquinoline in people with amoebic dysentery.
Benefits and harms
Tinidazole versus placebo:
We found no systematic review or RCTs.
Tinidazole versus metronidazole:
See option on metronidazole.
Tinidazole versus ornidazole:
See option on ornidazole.
Tinidazole versus secnidazole, emetine, paromomycin, diloxanide, nitazoxanide, or diiodohydroxyquinoline:
We found no systematic review or RCTs.
Further information on studies
None.
Comment
None.
Substantive changes
Tinidazole New evidence added.[17] Categorisation unchanged (Likely to be beneficial).

Nitazoxanide
Summary
Nitazoxanide is likely to be more effective than placebo at reducing clinical failure. Nitazoxanide may be no more effective than placebo at preventing parasitological failure.
We found no clinically important results from RCTs about nitazoxanide compared with metronidazole, secnidazole, ornidazole, tinidazole, emetine, paromomycin, diloxanide, or diiodohydroxyquinoline in people with amoebic dysentery.
Benefits and harms
Nitazoxanide versus placebo:
We found one systematic review (search date 2008, 2 RCTs).[17]
Treatment effectiveness
Nitazoxanide compared with placebo Nitazoxanide may be more effective than placebo at reducing clinical failure at 1 to 14 days after completion of treatment, but we don't know whether it is more effective at reducing parasitological failure (low-quality evidence).
Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Clinical failure
[17]
Systematic review
153 people
2 RCTs in this analysis
Clinical failure 1–14 days after completion of treatment
9/80 (11%) with nitazoxanide
40/73 (55%) with placebo

RR 0.21
95% CI 0.06 to 0.81
P = 0.023
Moderate effect sizeNitazoxanide
Parasitological failure
[17]
Systematic review
167 people
2 RCTs in this analysis
Parasitological failure 1–14 days after completion of treatment
14/86 (16%) with nitazoxanide
46/81 (57%) with placebo

RR 0.25
95% CI 0.05 to 1.27
P = 0.095
Not significant
Mortality
No data from the following reference on this outcome.[17]
Quality of life
No data from the following reference on this outcome.[17]
Hospitalisation
No data from the following reference on this outcome.[17]
Complications
No data from the following reference on this outcome.[17]
Adverse effects
Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects
[17]
Systematic review
67 people
Data from 1 RCT
Proportion of people with adverse effects
6/36 (17%) with nitazoxanide
4/31 (13%) with placebo

RR 1.29
95% CI 0.40 to 4.16
Not significant
Nitazoxanide versus metronidazole, secnidazole, ornidazole, tinidazole, emetine, paromomycin, diloxanide, or diiodohydroxyquinoline:
We found no systematic review or RCTs.
Further information on studies
The review commented that the RCT participants had clinical symptoms of intestinal amoebiasis, without distinguishing between amoebic dysentery and non-dysenteric amoebic colitis.
Comment
More high-quality studies are needed to determine whether nitazoxanide is significantly more effective than placebo at reducing parasitological signs of amoebic dysentery. Furthermore, studies comparing nitazoxanide and other currently used interventions (metronidazole, tinidazole, ornidazole, and secnidazole) will be useful in demonstrating efficacy.
Substantive changes
Nitazoxanide New option.[17] Categorised as Likely to be beneficial.

Summary
We don't know whether emetine is beneficial in treating amoebic dysentery.
Benefits and harms
Emetine:
We found no systematic review or RCTs comparing emetine versus placebo, metronidazole, tinidazole, secnidazole, ornidazole, paromomycin, diloxanide, diiodohydroxyquinoline, or nitazoxanide.
Further information on studies
None.
Comment
None.
Substantive changes
No new evidence

Paromomycin
Summary
We don't know whether paromomycin is effective in treating amoebic dysentery as we found no studies.
Paromomycin would not be expected to be beneficial in treating amoebic dysentery since it achieves therapeutic levels solely in the lumen of the gut (and not in the intestinal mucosa).
Benefits and harms
Paromomycin:
We found no systematic review or RCTs comparing paromomycin versus placebo, metronidazole, tinidazole, secnidazole, ornidazole, emetine, diloxanide, diiodohydroxyquinoline, or nitazoxanide.
Further information on studies
None.
Comment
Paromomycin is a luminal amoebicide that is not recommended for treatment of symptomatic amoebic infection as it does not penetrate into the intestinal epithelium.[23] [24]
Substantive changes
Paromomycin Evidence reassessed. Categorisation changed from Unknown effectiveness to Unlikely to be beneficial.

Diloxanide
Summary
We don't know whether diloxanide is effective in treating amoebic dysentery as we found no trials.
There is consensus that diloxanide has insufficient tissue penetration to be effective.
Benefits and harms
Diloxanide:
We found no systematic review or RCTs comparing diloxanide versus placebo, metronidazole, tinidazole, secnidazole, ornidazole, emetine, paromomycin, diiodohydroxyquinoline, or nitazoxanide.
Further information on studies
None.
Comment
Diloxanide is a luminal amoebicide that is not recommended for treatment of symptomatic amoebic infection as it does not penetrate into the intestinal epithelium.[23] [25] [26]
Substantive changes
Diloxanide New option. Categorised as Unlikely to be beneficial.

Diiodohydroxyquinoline (iodoquinol)
Summary
We don't know whether diiodohydroxyquinoline is effective in treating amoebic dysentery as we found no trials.
There is consensus that diiodohydroxyquinoline may have insufficient tissue penetration to be effective.
Benefits and harms
Diiodohydroxyquinoline:
We found no systematic review or RCTs comparing diiodohydroxyquinoline versus placebo, metronidazole, tinidazole, secnidazole, ornidazole, emetine, paromomycin, diloxanide, or nitazoxanide.
Further information on studies
None.
Comment
Diiodohydroxyquinoline is a luminal amoebicide that is not recommended for treatment of symptomatic amoebic infection as it does not penetrate into the intestinal epithelium.[23]
Substantive changes
Diiodohydroxyquinoline New option. Categorised as Unlikely to be beneficial.
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