Article

Treatment of Giardiasis

University of Connecticut, Сторс, Connecticut, United States
Clinical Microbiology Reviews (Impact Factor: 17.41). 02/2001; 14(1):114-28. DOI: 10.1128/CMR.14.1.114-128.2001
Source: PubMed

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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    • "The cysts can excyst into trophozoites in the small intestine. Under hostile environment in the small intestine, trophozoites become cysts by secreting a capsule wall, which passes out of the host in its feces, then they can infect new hosts (Adam, 2001; Gardner and Hill, 2001). "
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    ABSTRACT: To study the genetic variation and prokaryotic expression of α18 giardin gene of Giardia lamblia zoonotic assemblage A and host-specific assemblage F, the α18 genes were amplified from G. lamblia assemblages A and F by PCR and sequenced. The PCR product was cloned into the prokaryotic expression vector pET-28a(+) and the positive recombinant plasmid was transformed into Escherichia coli Rosetta (DE3) strain for the expression. The expressed α18 giardin fusion protein was validated by SDS-PAGE and Western blot analysis, and purified by Ni-Agarose resin. The putative sequence of α18 giardin amino acid was analyzed by bioinformatics software. Results showed that the α18 giardin gene was 861 bp in length, encoding 286 amino acids; it was 100% homologous between human-derived and dog-derived G. lamblia assemblage A, but it was 86.8% homologous with G. lamblia assemblage F (cat-derived). Giardin α18 was about 36 kDa in molecular weight, with good reactivity. Prediction based on in silico analyses: it had hydrophobicity, without signal peptide and transmembrane domain, and contained 11 alpha regions, 13 beta sheets, 1 beta turn and 7 random coils in secondary structure. The above information would lay the foundation for research about the subcellular localization and biological function of α18 giardin in G. lamblia.
    No preview · Article · Dec 2015 · Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases
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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.
    Full-text · Article · Apr 2015 · Frontiers in Microbiology
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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.
    Full-text · Research · Feb 2015
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