Abstract
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 July 2006 (BMJ 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 11 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: emetine, metronidazole, ornidazole, paromomycin, secnidazole, and tinidazole.
Key Points
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.
We don't know whether tinidazole is better than placebo, but it seems to be more effective than metronidazole at reducing symptoms and clearing the infection, with fewer adverse effects.
Secnidazole and tinidazole may be as effective as ornidazole at curing amoebic dysentery in children.
We don't know whether emetine or paromomycin are beneficial in treating amoebic dysentery.
About this condition
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. 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 1-40% of the population in Central and South America, Africa, and Asia, and from 0.2-10.8% in endemic areas of developed countries such as the USA. However, these estimates are difficult to interpret, mainly because infection can remain asymptomatic or go unreported, 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. 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.
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. It has been suggested that some animals, such as dogs, pigs, and monkeys, may act as reservoir hosts to the protozoa, but this has not been proven. In resource rich countries, risk factors include communal living, oral and anal sex, compromised immune system, and migration or travel from endemic areas.
Prognosis
Amoebic dysentery may progress to amoeboma, fulminant colitis, toxic megacolon and colonic ulcers, and may lead to perforation. 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 55-88% mortality. It is estimated that more than 500 million people are infected with E histolytica worldwide. Between 40 000 and 100 000 will die each year, placing this infection second to malaria in mortality caused by protozoan parasites.
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; severity of diarrhoea (duration, time to formed stools, number of loose stools per day, stool volume); rate of complications (i.e. amoeboma, extension to pleural cavity, chronic cyst carriage); length of hospital stay; rate of hospital admission; relief from symptoms (i.e. cramps, nausea, vomiting); therapeutic cure (defined as absence of parasites in stools, disappearance of symptoms, and healing of ulcers); failure of treatment (defined as either persistence of symptoms or persistence of parasites, or both); and adverse effects of treatment.
Methods
BMJ Clinical Evidence search and appraisal July 2006. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and National Institute for Health and Clinical Excellence (NICE) clinical guidelines. Abstracts of the studies retrieved were assessed independently by two information specialists using pre-determined criteria to identify relevant studies. Study design criteria for inclusion in this chapter were: published systematic reviews and RCTs in any language. RCTs could be from ‘open' studies upwards and there was no minimum trial size, loss to follow up or length of follow up required. In addition we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are continually added to the review as required. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).
Table.
GRADE evaluation of interventions for Amoebic dysentery
| Important outcomes | Cure rates, treatment failure, symptom relief, adverse effects | ||||||||
| Number of studies (participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of drug treatments for amoebic dysentery in endemic areas? | |||||||||
| 9 (at least 711 people) | Treatment failure | Metronidazole v tinidazole | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for incomplete reporting of results and methodological flaws. Consistency point deducted for conflicting results |
| 8 (477) | Adverse effects | Metronidazole v tinidazole | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for incomplete reporting of results and methodological flaws. Consistency point deducted for conflicting results |
| 1 (102) | Treatment failure | Secnidazole v ornidazole | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and sparse data |
| 1 (55) | Treatment failure | Ornidazole v placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and sparse data |
| 1 (40) | Treatment failure | Ornidazole v tinidazole | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for incomplete reporting of results and sparse data. Directness point deducted for inclusion of population with additional diseases |
Type of evidence: 4 = RCT; 2 = Observational; 1 = Non-analytical/expert opinion.Consistency: similarity of results across studies.Directness: generalisability of population or outcomes.Effect size: based on relative risk or odds ratio.
Glossary
- Amoeboma
A granulomatous lesion of the caecum or ascending colon caused by localised chronic E histolytica infection.
- Enzyme linked immunosorbent assay [ELISA]
A testing method using immune responses to detect substances such as hormones, bacterial antigens and antibodies.
- Low-quality evidence
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 evidence
Any estimate of effect is very uncertain.
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
Leonila F Dans, Department of Pediatrics and Clinical Epidemiology, University of Philippines, Manila, Philippines.
Elizabeth G Martínez, Department of Pediatrics and Clinical Epidemiology, University of Philippines, Manila, Philippines.
References
- 1.Last JM (editor). A dictionary of epidemiology, 3rd ed. New York: Oxford University Press; 1995. [Google Scholar]
- 2.Rivera WI, Tachibana H, Kanbara H. Field study on the distribution of Entamoeba histolytica and Entamoeba dispar in the northern Philippines as detected by PCR. Am J Trop Med Hyg 1998;59:916–921. [DOI] [PubMed] [Google Scholar]
- 3.Haque R, Faruque ASG, Hahn P, et al. Entamoeba histolytica and Entamoeba dispar infection in children in Bangladesh. J Infect Dis 1997;175:734–736. [DOI] [PubMed] [Google Scholar]
- 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 Microbiol 1998;36:3044–3045. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Chacin-Bonilla L, Bonillla E, Parra AM, et al. Prevalence of Entamoeba histolytica and other intestinal parasites in a community from Maracaibo, in Venezuela. Ann Trop Med Parasitol 1992;86:373–380. [DOI] [PubMed] [Google Scholar]
- 6.Anonymous. Amoebiasis. Wkly Epidemiol Rec 1997;72:97–99. [PubMed] [Google Scholar]
- 7.Huston CD, Petri WA. Amoebiasis: clinical implications of the recognition of Entamoeba dispar Curr Infect Dis Rep 1999;1:441–447. [DOI] [PubMed] [Google Scholar]
- 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 Health 2002;7:365–370. [DOI] [PubMed] [Google Scholar]
- 9.Davis AN, Haque R, Petri WA. Update on protozoan parasites of the intestine. Curr Opin Gastroenterol 2002;18:10–14. [DOI] [PubMed] [Google Scholar]
- 10.Lucas R, Upcroft JA. Clinical significance of the redefinition of the agent of amoebiasis. Rev Latinoam Microbiol 2001;43:183–187. [PubMed] [Google Scholar]
- 11.Petri WA, Singh U. Diagnosis and management of amebiasis. Clin Infect Dis 1999;29:1117–1125. [DOI] [PubMed] [Google Scholar]
- 12.Stanley SL. Amoebiasis. Lancet 2003;361:1025–1034. [DOI] [PubMed] [Google Scholar]
- 13.Haque R, Huston CD, Hughes M, et al. Amebiasis. N Engl J Med 2003;348:1565–1573. [DOI] [PubMed] [Google Scholar]
- 14.Singh B, Moodley J, Ramdial PK. Fulminant amoebic colitis: a favorable outcome. Int Surg 2001;86:77–81. [PubMed] [Google Scholar]
- 15.Vargas M, Pena A. Toxic amoebic colitis and amoebic colon perforation in children: an improved prognosis. J Pediatr Surg 1976;11:223–225. [DOI] [PubMed] [Google Scholar]
- 16.Espinosa-Cantellano M, Martínez-Palomo A. Recent developments in amoebiasis research. Curr Opin Infect Dis 2000;13:451–456. [DOI] [PubMed] [Google Scholar]
- 17.Singh G, Kumar S. Short course of single daily dosage treatment with tinidazole and metronidazole in intestinal amoebiasis: a comparative study. Curr Med Res Opin 1977;5:157–160. [DOI] [PubMed] [Google Scholar]
- 18.Swami B, Lavakusulu D, Sitha Devi C. Tinidazole and metronidazole in the treatment of intestinal amoebiasis. Curr Med Res Opin 1977;5:152–156. [DOI] [PubMed] [Google Scholar]
- 19.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 Res 1977;5:434–437. [DOI] [PubMed] [Google Scholar]
- 20.Misra NP. A comparative study of tinidazole with metronidazole as a single daily dose for three days in symptomatic intestinal amoebiasis. Drugs 1978;15(suppl 1):19–22. [DOI] [PubMed] [Google Scholar]
- 21.Chunge CN, Estambale BBA, Pamba HO, et al. Comparison of four nitroimidazole compounds for treatment of symptomatic amoebiasis in Kenya. East Afr Med J 1989;66:724–727. [PubMed] [Google Scholar]
- 22.Misra NP, Laiq SM. Comparative trial of tinidazole and metronidazole in intestinal amebiasis. Curr Ther Res Clin Exp 1974;16:1255–1263. [PubMed] [Google Scholar]
- 23.Joshi HD, Shah BM. A comparative study of tinidazole and metronidazole in treatment of amoebiasis. Indian Pract 1975:295–302. [Google Scholar]
- 24.Awal ARMA, Ali S. Tinidazole in the treatment of symptomatic intestinal amoebiasis. Curr Ther Res Clin Exp 1979;26:962–966. [Google Scholar]
- 25.Mathur SN, Itigi A, Rao PD, et al. Evaluation of tinidazole in treatment of amoebiasis. Ind Med Gaz 1976;361–364. [Google Scholar]
- 26.Toppare MF, Kitapci F, Senses DA, et al. Ornidazole and secnidazole in the treatment of symptomatic intestinal amoebiasis in childhood. Trop Doct 1994;24:183–184. [DOI] [PubMed] [Google Scholar]
- 27.Apt W, Perez C, Miranda C, et al. Tratamiento de la amebiasis intestinal y giardiasis con ordinazol [in Spanish]. Rev Med Chile 1983;111:1130–1133. [PubMed] [Google Scholar]
- 28.Panggabean A, Sutjipto A, Aldy D, et al. Tinidazole versus ornidazole in amebic dysentery in children (a double blind trial). Paediatr Indones 1980;20:229–235. [PubMed] [Google Scholar]