Article

Treatment of Giardiasis

Division of Infectious Diseases, University of Connecticut Health Center, Farmington, Connecticut 06030-3212, USA.
Clinical Microbiology Reviews (Impact Factor: 16). 02/2001; 14(1):114-28. DOI: 10.1128/CMR.14.1.114-128.2001
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ABSTRACT 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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Available from: David R Hill, Aug 28, 2015
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    • "In spite of its recognition as an important human pathogen for a long time , nearly 5 , 000 people are hospitalized with giardiasis annually in the United States ( see ( Lengerich et al . , 1994 ; Gardner and Hill , 2001 ) and references therein ). The disease spreads through fecal - oral trans mission of the parasite cysts ( Adam , 2001 ) . "
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    ABSTRACT: Giardiasis is a common diarrheal disease worldwide caused by the protozoan parasite Giardia (G.) intestinalis. It is urgent to develop novel drugs to treat giardiasis, due to increasing clinical resistance to the gold standard drug metronidazole (MTZ). New potential antiparasitic compounds are usually tested for their killing efficacy against G. intestinalis under anaerobic conditions, in which MTZ is maximally effective. On the other hand, though commonly regarded as an ‘anaerobic pathogen’, G. intestinalis is exposed to relatively high O2 levels in vivo, living attached to the mucosa of the proximal small intestine. It is thus important to test the effect of O2 when searching for novel potential antigiardial agents, as outlined in a previous study (Bahadur, Mastronicola et al. (2014) Antimicrob. Agents Chemother. 58, 543). Here, forty-five novel chalcone derivatives with triazolyl-quinolone scaffold were synthesized, purified and characterized by high resolution mass spectrometry, 1H and 13C nuclear magnetic resonance and infrared spectroscopy. Efficacy of the compounds against G. intestinalis trophozoites was tested under both anaerobic and microaerobic conditions, and selectivity was assessed in a counter-screen on human epithelial colorectal adenocarcinoma cells. MTZ was used as a positive control in the assays. All the tested compounds proved to be more effective against the parasite in the presence of O2, with the exception of MTZ that was less effective. Under anaerobiosis eighteen compounds were found to be as effective as MTZ or more (up to 3-4 fold); the same compounds proved to be up to > 100 fold more effective than MTZ under microaerobic conditions. Four of them represent potential candidates for the design of novel antigiardial drugs, being highly selective against Giardia trophozoites. This study further underlines the importance of taking O2 into account when testing novel potential antigiardial compounds.
    Frontiers in Microbiology 04/2015; 6. DOI:10.3389/fmicb.2015.00256 · 3.94 Impact Factor
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    • "The main treatments against G. intestinalis are based on derivatives of the following compounds: acridine, mepacrine (Mendelson, 1980) and quinacrine (Harris et al. 2001); nitroimidazoles, including metronidazole (Freeman et al. 1997), tinidazole (Jokipii and Jokipii, 1980), ornidazole (Jokipii and Jokipii, 1982), and other 5-nitroimidazoles (Upcroft et al. 1999); benzimidazoles, albendazole (Dutta et al. 1994), mebendazole (Bulut et al. 1996), nitrofuranes, and furoxone (Pickering, 1985); and more recently, nitazoxanide, a nitrothiazole (Romero et al. 1997; Ponce-Macotela et al. 2001). However, these drugs all produce undesirable secondary effects, ranging from nausea, (Davidson, 1984) and metallic taste in the mouth (Spellman, 1985) to psychosis (Upcroft et al. 1996), carcinogenesis (Gardner and Hill, 2001) and possible genetic damage (Legator et al. 1975; Mitelman et al. 1976). In addition, there is evidence suggesting the selection of resistant strains to antigiardial drugs (Upcroft, 1994; Upcroft and Upcroft, 2001; Sangster et al. 2002; Dunn et al. 2010). "
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    DESCRIPTION: Giardiosis is a neglected parasitic disease that produces diarrhoea and different degrees of malabsorption in humans and animals. Its treatment is based on derivatives of 5-nitroimidazoles, benzimidazoles, nitrofuranes, acridine and nitrotiazoles. These drugs produce undesirable secondary effects, ranging from a metallic taste in the mouth to genetic damage and the selection of resistant strains; therefore, it is necessary to develop new therapeutic alternatives. We demonstrated that a 2-h treatment with 2·87 μg ml(-1) of fraction 6 of Lippia graveolens (F-6) was sufficient to kill half of an experimental Giardia intestinalis (Syn. G. duodenalis, G. lamblia) population, based on the reduction of MTT-tetrazolium salt levels. F-6 breaks the nuclear envelope and injures the ventral suckling disc. The major compounds of F-6 were characterized as naringenin, thymol, pinocembrin and traces of compounds not yet identified. The results suggest that Lippia is a potential source to obtain compounds with anti-Giardia activity. This knowledge is an important starting point to develop new anti-giardial drugs. Future studies will be required to establish the efficacy of F-6 in vivo using an animal model.
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    • "Later estimations showed that it could be responsible for one billion cases annually and is accompanied by an overall worldwide prevalence of 30% [2]. Acute symptoms include diarrhea, gas, abdominal cramps, nausea or vomiting, and dehydration [3, 4]. In some areas of Mexico, the prevalence of giardiosis can reach up to 68% [5] and now G. duodenalis is the most important protozoan parasite causing human intestinal infection in Northwestern Mexico [6]. "
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    ABSTRACT: Human Giardiosis is a public health problem in Mexico, where the national prevalence was estimated to be up to 68%. Misuse of antiprotozoal drugs may result in low effectiveness and undesirable side effects. Research on natural products is a good strategy for discovering more effective antiparasitic compounds. This study evaluated the antigiardial activity of extracts of Yucca baccata, which is native to northwestern Mexico. Forty-two gerbils (females) were weighed and orally inoculated with 5 × 10(6) Giardia trophozoites. Two gerbils were selected at random to confirm infection. Forty living gerbils were randomly allocated into 5 treatment groups (8 per group). Gerbils were randomly assigned to be treated with 24.4 mg/mL, 12.2 mg/mL, and 6.1 mg/mL of extracts, metronidazole (2 mg/mL) or PBS, which were intragastrically administered once per day for 3 days. Nine gerbils died during the study course. On day 10 postinfection, gerbils were euthanized and trophozoites were quantified. Yucca extracts reduced, albeit not significantly, the trophozoite counts in the duodenum segment. Only the high-extract concentration significantly reduced the trophozoite counts in the proximal segment and it was similar to that of metronidazole. Extracts of Y. baccata may represent an effective and natural therapeutic alternative for human giardiosis.
    BioMed Research International 08/2014; 2014:823492. DOI:10.1155/2014/823492 · 2.71 Impact Factor
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