Corresspondence to:
Dr Suleiman Muneizel
Email: slmuneizel@yahoo.com

Entamoeba histolytica is the etiological agent of amoebic dysentery. Worldwide, 40-50 million symptomatic cases of amoebiasis occur annually and 70,000 to 100,000 deaths are due to this infection.^[1] Molecular phylogeny places entamoeba on one of the lowermost branches of the eukaryotic tree, closest to dictyostelium. Although the organism was originally thought to lack mitochondria, nuclear-encoded mitochondrial genes and a remnant organelle have now been identified.^[2,3] Unusual features of entamoeba include polyploid chromosomes that vary in length; multiple origins of DNA replication; abundant, repetitive DNA; closely spaced genes that largely lack introns; a novel GAAC element controlling the expression of messenger RNA; and unique endocytic pathways.^[4,5,6,7] There are two distinct, but morphologically identical species of Entamoeba: Entamoeba histolytica, which is pathogenic and Entamoeba dispar, which is non-pathogenic.^[15]

Ingestion of the quadrinucleate cyst of E. histolytica from fecally contaminated food or water initiates infection. Infection with E. histolytica may be asymptomatic or may cause dysentery or extra intestinal disease. Asymptomatic infection should be treated because of its potential to progress to invasive disease. Patients with amebic colitis typically present with a several-week history of cramping abdominal pain, weight loss, and watery or bloody diarrhea. The insidious onset and variable signs and symptoms make diagnosis difficult, with fever and grossly bloody stool absent in most cases.^[8,9,10] Therapy for invasive infection differs from therapy for noninvasive infection. Noninvasive infections may be treated with paromomycin. Nitroimidazoles, particularly metronidazole, are the mainstay of therapy for invasive amebiasis.^[11] Nitroimidazoles with longer half-lives (namely, tinidazole, secnidazole, and ornidazole) are better tolerated and allow shorter periods of treatment.

Approximately 90 percent of patients who present with mild-to-moderate amebic dysentery have a response to nitroimidazole therapy. Parasites persist in the intestine in as many as 40 to 60 percent of patients who receive nitroimidazole. Therefore, nitroimidazole treatment should be followed with paromomycin or the second-line agent diloxanide furoate to cure luminal infection. Metronidazole and paromomycin should not be given at the same time, since the diarrhea that is a common side effect of paromomycin may make it difficult to assess the patient's response to therapy.^[12,13,14] In this study we assess the efficacy of the 2 nitroimidazoles available in Jordan, tinidazole and metronidazole.

The efficacy and tolerability of metronidazole and tinidazole were evaluated in a randomized clinical trial performed with 66 patients who attended the out-patient clinic and emergency room in QAMH. The study period was 12 months from July 2005 to July 2006. The subjects (24 females and 42 males) were randomly allocated to two groups: experiment group (n=32) were given tinidazole and control group (n=34) were given metronidazole [Table 1]. In group one, metronidazole 2gm as a single dose orally for 3 days), and in group two, tinidazole 2 gm single dose orally were prescribed respectively.[16] Patients were followed for three weeks after the end of therapy for the presence of entamoeba histolytica in their stool. Clinical and parasitological follow-up was carried out before, and at 7, 14, and 21 days after treatment and the outcome of treatment was noted. Parasitological cure was documented when there were three consecutive negative stool examinations for entamoeba histolytica at 1-3 weeks after therapy termination.

As illustrated in Table 1 the sample size of both groups was almost identical 32 (48.5%)and 34 (51.5%)of tinidazole and metronidazole respectively. The males constituted the majority of patients 42 (63.6%)while the females were 24 forming 36.4% of the patients, The male to female ratio was 1.75:1.

The age distribution of patients ranged from 16 years to 68 years, the commonest age group was among 20 years-40 years making up around half of all patients (48.5%) as shown in Table 2.

28 of 32 patients (87.5%) treated with tinidazole and 23 of 34 patients (67.5%) treated with metronidazole had parasitological cure. Cure rate between the two groups was statistically significant (P<0.01). No major side effects were observed except two cases in the metronidazole group who had mild headache and abdominal pain for two days and three cases in tinidazole group who reported nausea, dizziness and headache. Efficacy of two regimens in term of drug are presented in [Table 3]. Tinidazole appears to be safe having a few ignorable side effects and produced a significant cure rate, more effective than metronidazole.

A 2 gm single dose for 3 days regimen of tinidazole had excellent effectiveness in treatment of amoebiasis as compared with metronidazole. Introduction of nitroheterocyclic drugs in the late 1950s and the 1960s heralded a new era in the treatment of infections caused by a range of pathogenic protozoan parasites.^[17] Metronidazole is the drug now most widely used in the treatment of anaerobic protozoan parasitic infections caused by G. intestinalis, Trichomonas vaginalis and Entamoeba histolytica.^[18,19] Although various drugs have been available for several decades to treat this infection, none of them is entirely satisfactory due to high incidence of undesirable side effects and a significant failure rate in clearing parasites from the gastrointestinal tract.^[19,20] Some evidence suggests that drug resistance may be responsible for these failures.^[21,22] Unfortunately, failures in treatment of amoebiasis with standard metronidazole therapy have been reported in five to 20% cases. In the event of overt clinical resistance to metronidazole in entamoeba histolytica strains, tinidazole could be an alternative treatment. A key issue should be keeping in mind the documented cross-resistance between currently used nitroimidazole drugs .As such the choice of drug will differ in each case depending on the local conditions and keeping in view the sensitivity of parasite strain. Moreover, perhaps treatment of all asymptomatic entamoeba histolytica infections in developing countries hyperendemic for the disease is doubtful because of rapid reinfection. Clinical metronidazole resistance in Trichomonas vaginalis has also been documented previously.^[22] Single dose therapy with tinidazole is effective in the metronidazole-resistant strains of T. vaginalis which could be another advantage of this drug.

Tinidazole was more effective than metronidazole produced fewer and mild side effects. We recommend tinidazole as drug of choice for treatment of amoebiasis because of its efficacy, and desirable tolerance. This preparation is preferred to metronidazole in the treatment of entamoeba histolytica infection as a considerable advantage in low socio-economic communities. Moreover, this drug may be tried and used if other agents failed in the treatment of clinical amoebiasis.

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