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      A Meta-analysis of the Effectiveness of Albendazole Compared with Metronidazole as Treatments for Infections with Giardia duodenalis

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          Abstract

          Background

          Metronidazole is the most commonly used drug for the treatment of giardiasis in humans. In spite of its therapeutic efficacy for giardiasis, low patient compliance, especially in children, side effects, and the emergence of metronidazole-resistant strains may restrict its use. Albendazole has been used to treat Giardia duodenalis infections in recent years. However, efficacy studies in vivo and in vitro have produced diverse results as to its effectiveness. A moderately benign side effect profile, combined with established efficacy against many helminths, renders it promising for treatment of giardiasis in humans.

          Methodology and Principal Findings

          We performed a search in the PubMed, Scopus, EMBASE, the ISI Web of Science, LILIACS, and Cochrane Controlled Trials Register for trials published before February 2010 as well as in references of relevant research and review articles. Eight randomized clinical trials (including 900 patients) comparing the effectiveness of albendazole with that of metronidazole were included in meta-analysis. After extracting and validating the data, the pooled risk ratio (RR) was calculated using an inverse-variance random-effects model. Albendazole was found to be equally as effective as metronidazole in the treatment of giardiasis in humans (RR 0.97; 95% CI, 0.93, 1.01). In addition, safety analysis suggested that patients treated with albendazole had a lower risk of adverse effects compared with those who received metronidazole (RR 0.36; 95% CI, 0.10, 1.34), but limitations of the sample size precluded a definite conclusion.

          Conclusions/Significance

          The effectiveness of albendazole, when given as a single dose of 400 mg/day for 5 days, was comparable to that of metronidazole. Patients treated with albendazole tended to have fewer side effects compared with those who took metronidazole. Given the safety, effectiveness, and low costs of albendazole, this drug could be potentially used as an alternative and/or a replacement for the existing metronidazole therapy protocols in the treatment of giardiasis in humans.

          Author Summary

          Giardiasis is one of the most common intestinal protozoal infections worldwide. Although metronidazole is the most common drug used to treat giardiasis in humans, its use is associated with a variety of side effects. Poor compliance and the emergence of metronidazole-resistant strains may restrict use of the drug. Albendazole is an orally administered broad-spectrum anthelmintic agent. The use of albendazole has fewer side effects than metronidazole. The anthelmintic has been used against Giardia duodenalis both in vivo and in vitro with different results. However, the current meta-analysis assessed the effectiveness and safety of albendazole compared with metronidazole for the treatment of giardiasis in humans. After searching different databases, eight comparative randomized clinical trials, including 900 patients, met our criteria and were selected for the current meta-analysis. Results showed that albendazole was as effective as metronidazole for the treatment of giardiasis in humans and people receiving the drug tended to have fewer side effects compared with those who received metronidazole. Given the safety, effectiveness, and low costs of albendazole, this drug may be considered a potential alternative and/or a replacement for the existing widely used metronidazole in the treatment of giardiasis in humans.

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          Biology of Giardia lamblia.

          R D Adam (2001)
          Giardia lamblia is a common cause of diarrhea in humans and other mammals throughout the world. It can be distinguished from other Giardia species by light or electron microscopy. The two major genotypes of G. lamblia that infect humans are so different genetically and biologically that they may warrant separate species or subspecies designations. Trophozoites have nuclei and a well-developed cytoskeleton but lack mitochondria, peroxisomes, and the components of oxidative phosphorylation. They have an endomembrane system with at least some characteristics of the Golgi complex and encoplasmic reticulum, which becomes more extensive in encysting organisms. The primitive nature of the organelles and metabolism, as well as small-subunit rRNA phylogeny, has led to the proposal that Giardia spp. are among the most primitive eukaryotes. G. lamblia probably has a ploidy of 4 and a genome size of approximately 10 to 12 Mb divided among five chromosomes. Most genes have short 5' and 3' untranslated regions and promoter regions that are near the initiation codon. Trophozoites exhibit antigenic variation of an extensive repertoire of cysteine-rich variant-specific surface proteins. Expression is allele specific, and changes in expression from one vsp gene to another have not been associated with sequence alterations or gene rearrangements. The Giardia genome project promises to greatly increase our understanding of this interesting and enigmatic organism.
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            Treatment of giardiasis.

            Alan Gardner, D. Hill (2000)
            Giardia lamblia is both the most common intestinal parasite in the United States and a frequent cause of diarrheal illness throughout the world. In spite of its recognition as an important human pathogen, there have been relatively few agents used in therapy. This paper discusses each class of drugs used in treatment, along with their mechanism of action, in vitro and clinical efficacy, and side effects and contraindications. Recommendations are made for the preferred treatment in different clinical situations. The greatest clinical experience is with the nitroimidazole drugs, i.e., metronidazole, tinidazole, and ornidazole, which are highly effective. A 5- to 7-day course of metronidazole can be expected to cure over 90% of individuals, and a single dose of tinidazole or ornidazole will cure a similar number. Quinacrine, which is no longer produced in the United States, has excellent efficacy but may be poorly tolerated, especially in children. Furazolidone is an effective alternative but must be administered four times a day for 7 to 10 days. Paromomycin may be used during early pregnancy, because it is not systematically absorbed, but it is not always effective. Patients who have resistant infection can usually be cured by a prolonged course of treatment with a combination of a nitroimidazole with quinacrine.
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              Neurocysticercosis: an update.

              Arturo Carpio (2002)
              Taeniosis and cysticercosis, diseases caused by the parasitic tapeworm Taenia solium, are distributed worldwide where pigs are eaten and sanitation is poor, and also in the more developed countries as a result of increasing migration. Neurocysticercosis is the commonest parasitic disease of the human nervous system. Immunological assays detect positivity for human cysticercosis in 8-12% of people in some endemic regions, which indicates the presence of antibodies against the parasite but not necessarily active or central-nervous-system infection. The only reliable tool for diagnosis of neurocysticercosis is imaging by CT or MRI. The presence of viable cysts with a mural nodule, associated with degenerative cysts and calcifications, is typical. Classification of neurocysticercosis into active, transitional, and inactive forms gives a good clinical-imaging correlation and facilitates medical and surgical treatment. The main clinical manifestations of neurocysticercosis are seizures, headache, and focal neurological deficits, and it can have such sequelae as epilepsy, hydrocephalus, and dementia. Treatment should be individually fitted for each patient, with antiepileptic drugs, analgesics, corticosteroids, or a combination of these. Anthelmintic drugs (praziquantel and albendazole) are used routinely, but so far no controlled clinical trial has established specific indications or definitive doses of treatment. Parenchymal forms of neurocysticercosis have a good prognosis in terms of clinical remission. The most effective approach to taeniosis and cysticercosis is prevention, which should be a primary public-health focus for less developed countries.
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                Author and article information

                Contributors
                : Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS Negl Trop Dis
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosntds
                Title: PLoS Neglected Tropical Diseases
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Print): 1935-2727
                ISSN (Electronic): 1935-2735
                Publication date Collection: May 2010
                Publication date (Electronic): 11 May 2010
                Volume: 4
                Issue: 5
                Electronic Location Identifier: e682
                Affiliations
                [1 ]Department of Biology, Georgetown University, Washington, D. C., United States of America
                [2 ]Department of Oncology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, D. C., United States of America
                Swiss Tropical Institute, Switzerland
                Author notes

                Conceived and designed the experiments: SSM JMG CAL. Performed the experiments: SSM SMS. Analyzed the data: SSM JMG CAL SMS. Contributed reagents/materials/analysis tools: SSM. Wrote the paper: SSM SMS.

                Article
                Publisher ID: 09-PNTD-RA-0435R2
                DOI: 10.1371/journal.pntd.0000682
                PMC ID: 2867942
                PubMed ID: 20485492
                SO-VID: 288971c1-a88f-46bd-b281-c4f0d5f140e3
                Copyright © Solaymani-Mohammadi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                Date received : 21 August 2009
                Date accepted : 25 March 2010
                Page count
                Pages: 10
                Categories
                Subject: Research Article
                Subject: Infectious Diseases/Protozoal Infections
                Subject: Microbiology/Parasitology

                ScienceOpen disciplines: Infectious disease & Microbiology
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology

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