Published by : PROFESSIONAL MEDICAL PUBLICATIONS
|January - March 2007||
Comparison between efficacy of a single dose of tinidazole with a
7-day standard dose course of metronidazole in Giardiasis
Mohammad Fallah1, Soghra Rabiee2, Ali Akbar Moshtaghi3
Objective: Giardia intestinalis is the most common intestinal protozoan in the under developed countries. Treatment of infection has some difficulties by metronidazole because of long course of therapy and various side effects. The objective of this study was to determine efficacy and side effects of tinidazole compared with metronidazole in the treatment of giardiasis in children.
Patients and Methods: A randomized controlled clinical trial, 106 subjects (69 males, 37 females) with Giardia intestinalis infection admitted to out patients or private clinics in Hamdan, West of Iran, was treated with tinidazole or metronidazole. The study period was May 2002 to January 2003. Tinidazole 50 mg/kg single dose and metronidazole 15 mg/kg three times a day for seven days were given orally to children. Parasitological cure was documented when there was 3 times negative stool examination for giardiasis at 1-2 weeks after therapy.
Results: Thirty-seven of 42 individuals (88.1%) treated with tinidazole and 43 of 64 children (67.2%) treated with metronidazole had parasitological cure. Cure rates between two groups were significant statistically (P<0.01). No major side effect were observed except two cases in metronidazole group who had mild headache and abdominal pain for two days and some had metallic taste. Three cases in tinidazole group had nausea, dizziness and headache.
Conclusion: Tinidazole was more effective than metronidazole, produced fewer and mild side effects and is recommended as drug of choice in single dose therapy for giardiasis. Because of single dose administration, short course of therapy and good compliance of patients, this preparation is preferred to metronidazole in the treatment of giardiasis.
KEY WORDS: Giardiasis, Tinidazole, Clinical trial.
Pak J Med Sci January - March 2007 Vol. 23 No.1 43-46
1. Dr. Mohammad Fallah
Department of Parasitology
2. Dr. Soghra Rabiee
Department of Obstetrics & Gynecology
3. Dr. Ali Akbar Moshtaghi
Department of Pediatrics
1-3: School of Medicine,
Hamadan University of Medical Sciences,
Hamadan – Iran.
Correspondences:Dr. Mohammad Fallah
* Received for Publication: December 22, 2005
* Revision Accepted: May 26, 2006
Giardia intestinalis is a protozoan parasite of the small intestine that causes extensive morbidity worldwide. Giardiasis is a cosmopolitan parasitosis. Diarrhea, abdominal colic and flatulence are the main clinical symptoms, however, malabsorption, and impairment of growth of children may occur.1 Despite the recognition of G. intestinalis clinical illness for the last 40 years, no definitive treatment protocols have been published. There is at present only a limited range of chemotherapeutic agents for the treatment of Giardia infection. These comprise metronidazole and related nitroimidazoles, quinacrine and furazolidone. The 5-nitroimidazoles are the drug of choice in the treatment of giardiasis. Metronidazole is not completely effective, exhibits undesirable side effects sometimes and, is carcinogenic in the laboratory animals.2 In human giardiasis, therapeutic failure occurs more and more frequently, due to low compliance with drug therapy, reinfection or parasite resistance to metronidazole.3-4 Treatment failures are common (5-20%), repeated courses of therapy are often required, and there is evidence of variable drug sensitivity between strains of Giardia.5 On the other hand, long period of therapy (7-10 days, three times a day) is a disadvantage for this drug. Therefore, the adverse effects and treatment failures of some of the currently recommended drugs for Giardia infection suggests need for alternative antigiardial agents. Investigation for compounds with short course of therapy, single dose as far as possible, is a recent outstanding recommendation of the World Health Organization.6 A most attractive feature of tinidazole is that when used as single dose regimen according to some reports has produced excellent results.7,8 The aim of this study was to evaluate the efficacy of tinidazole, single dose, and standard therapy of metronidazole in giardiasis.
PATIENTS AND METHODS
The efficacy and tolerability of metronidazole and tinidazole were evaluated in a randomized, open-label, clinical trial performed with 106 Giardia intestinalis-positive children enrolled from public and private health centers by convenience sampling. The study period was nine months from May 2002 to January 2003 on patients admitted in Hamadan, West of Iran. The subjects (37 females and 69 males) were randomly allocated to two groups: experiment group (n=42) were given tinidazole and control group (n=64) were given metronidazole. In group one, metronidazole suspension as standard oral dose (15 mg/kg/day, three divided doses, for seven days), and in group two, tinidazole tablets, single dose (50 mg/kg of body of weight to a maximum 2g, once a day) were prescribed respectively.9 Patients were followed for three weeks after the end of therapy for the presence of G. intestinalis in their stool. Clinical and parasitological follow-up was carried out before, and at 7, 14, 21 days after treatment and the outcome of treatment was noted. Stool examination was done by formalin ether concentration technique in the research laboratory of Department of Parasitology, School of Medicine Hamdan University Iran. Parasitological cure was documented when there were three consecutive negative stool examination for G. intestinalis at 1-3 weeks after therapy termination.10
Thirty-seven of 42 children (88.1%) treated with tinidazole and 43 of 64 children (67.2%) treated with metronidazole had parasitological cure. Cure rate between two groups was significant statistically (P<0.01). No major side effect were observed except two cases in metronidazole group who had mild headache and abdominal pain for two days metallic taste after drug ingestion was more commonly reported in both groups and there was significant difference in both groups. No major side effect were observed except two cases in 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 terms of weight, age, duration of symptoms and drug are presented in [Tables I-IV]. Tinidazole appears to be safe having a few ignorable side effects and produced a significant cure rate, more effective than metronidazole against Giardia, comparable with other antigiardial agents used as a single dose therapy.
A single dose regimen of tinidazole had excellent effectiveness in treatment of giardiasis 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.11 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.12,13 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.14,15 Some evidence suggests that drug resistance may be responsible for these failures.16,17
Unfortunately, failures in treatment of giardiasis with standard metronidazole therapy have been reported in five to 20% cases.18 In the event of overt clinical resistance to metronidazole in G. intestinalis strains, tinidazole could be an alternative treatment. Unfortunately, this drug is not available in some countries, including Islamic Republic of Iran. A key issue should be keeping in mind the documented cross-resistance between currently used nitroimidazole drugs.4 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. More ever, perhaps treatment of all asymptomatic G. intestinalis infections in developing countries hyperendemic for the disease is doubtful because of rapid reinfection.19
Clinical metronidazole resistance in Trichomonas vaginalis has also been documented previously.12 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 mertronidazole, produced fewer and mild side effects, and good compliance of patients. We recommend tinidazole as drug of choice for treatment of giardiasis because of its efficacy, desirable tolerance, single dose regimen and short course of therapy and good compliance of patients. This preparation is preferred to metronidazole in the treatment of G. intestinalis 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 giardiasis.
This study was supported in parts by a grant from National Center for Medical Sciences Research, Deputy of Research and Technology, Ministry of Health and Medical Education, Islamic Republic of Iran which is hereby acknowledged.
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