Wheat germ supplement reduces cyst and trophozoite passage in people with giardiasis.

JENNIFER GRANT 0 SIDDHARTHA MAHANTY 0 AMIR KHADIR 0 J. DICK MACLEAN 0 EVELYNE KOKOSKIN 0 BETH YEAGER 0 LAWRENCE JOSEPH 0 JUDITH DIAZ 0 EDUARDO GOTUZZO 0 NORMAN MAINVILLE 0 BRIAN J. WARD 0 0 Center for the Study of Host Resistance, McGill University , Montreal, Quebec , Canada; McGill Tropical Diseases Center and Division of Clinical Epidemiology, Montreal General Hospital , Montreal, Quebec , Canada; Instituto des Investigacions Nutricional , La Molina, Lima , Peru; Tropical Medicine Institute, Universidad Peruana Cayetano Heredia , Lima , Peru The protozoan parasite Giardia lamblia is a major cause of waterborne enteric disease worldwide. Lectins are proteins that bind to carbohydrate (sugar) moieties. Potential targets for lectins are found on the surface of most single-celled organisms. Modest concentrations of wheat germ agglutinin (WGA) have been shown to inhibit G. lamblia excystation and trophozoite growth in vitro and can reduce cyst passage in mice infected with the closely related protozoan parasite, G. muris. Commercial preparations of wheat germ (WG) contain 13-53 g of WGA per gram. We performed a double-masked, placebo-controlled study of dietary supplementation with WG in 63 subjects with giardiasis in Montreal and Lima (25 asymptomatic patients passing cysts; 38 patients with symptoms). Asymptomatic subjects received WG (2 g, 3 times a day) or placebo (cornstarch, 2 g, 3 times a day) for 10 days, followed by metronidazole (250 mg 3 times a day) for 7 days. Symptomatic subjects received metronidazole (250 mg 3 times a day) plus either WG or placebo for 7 days. Stool specimens were collected every day (Montreal) or every other day (Lima) for 10 days and on Day 35 for microscopic examination and coproantigen determination. Subjects kept a diary of symptoms for 10 days after recruitment. In asymptomatic subjects, both cyst passage and coproantigen levels were reduced by 50% in those taking WG compared with the placebo group (P 0.01 and P 0.06, respectively). In symptomatic subjects, cyst passage and coproantigen levels fell precipitously in response to metronidazole therapy, and there were no clinically important differences between those receiving supplemental WG or placebo. However, symptoms appear to have resolved more rapidly in the subjects taking WG in addition to metronidazole. The WG supplement was well tolerated in both symptomatic and asymptomatic subjects. These data suggest that components of WG, possibly WGA, either alone or in combination with antiprotozoal agents, can influence the course of human giardiasis. - Giardia lamblia is among the most common protozoan parasites of the human intestinal tract and is a major cause of waterborne enteric disease worldwide.1,2 Giardia infects a wide range of mammalian hosts, including both domestic and wild animals and humans.1,3 Surface water in many regions of the world is heavily contaminated with G. lamblia cysts.4 Upon ingestion, G. lamblia excysts and colonizes the upper gastrointestinal tract, where it can cause a spectrum of disease, from asymptomatic cyst passage to explosive or chronic diarrhea.1,5 Although G. lamblia is not invasive, infection can result in extensive damage to the small bowel mucosa, leading to malabsorption.1,5 Without treatment, people can remain infected for months.1 Many subjects have difficulty tolerating the drugs available for the treatment of giardiasis (e.g., metronidazole), and 1015% need repeated courses of therapy to be cured.1 In hyperendemic regions of the world, reinfection frequently occurs within a matter of weeks after treatment.6 Lectins are proteins that bind to carbohydrate (sugar) moieties. Lectins were originally recognized because of their ability to agglutinate blood cells7 (hence the term agglutinins). A wide range of biological actions is mediated by lectin-glycoprotein interactions, including intracellular sorting of proteins, control of morphogenesis, cellular differentiation, fertilization, binding of microorganisms to target tissues, and cell-cell interactions such as adhesion and trafficking of leukocytes, metastasis, and inhibition of natural killer cell activity.810 Many lectins are derived from plant seeds,11 and some of the best known are components of common human foods such as kidney beans (Phaseolus vulgaris agglutinin), lima beans (lima bean agglutinin) and wheat (WG agglutinin, or WGA).11 Some dietary lectins are poorly absorbed in the gastrointestinal tract and are relatively nontoxic at moderate concentrations.11 The precise role of lectins in plants is unknown.12,13 The surface proteins of many intestinal protozoa, including G. lamblia, are glycosylated.14,15 At modest concentrations (10100 g/mL), WGA can arrest G. lamblia trophozoite growth in axenic cultures,16 inhibit excystation,17 and decrease cyst passage in mice infected with the closely related organism G. muris.16 These observations prompted us to initiate a small clinical trial to evaluate the potential for WGA to influence the course of human giardiasis. In human terms, the doses of WGA used in the studies mentioned above were large but not massive. As much as 1012% of the protein content of WG is WGA, and common wheatbased cereals contain up to 50 g of WGA per gram.16 At very high doses, some lectins (including WGA) can have antinutritive effects.11 For this reason, and because our interest in practical solutions for problems in the developing world, we chose to use WG in the current study rather than purified lectin. MATERIALS AND METHODS Human subjects. Subjects were recruited at several travel clinics in Montreal (McGill Center for Tropical Diseases, St. Luc Hospital, Maisonneuve Rosemont Hospital) and in public outpatient clinics located in San Juan de Lurigancho, a periurban area of Lima, Peru. Stool samples submitted to the parasitology laboratories of the participating institutions were screened for the presence of G. lamblia by microscopy and coproantigen detection (see below), and people were contacted to determine their willingness to participate in the study. A total of 63 otherwise healthy adults were recruited in Montreal, Canada (n 31), and Lima, Peru (n 32). Subjects who sought consultation in these clinics for any gastrointestinal complaint were considered to be symptomatic (n 38), whereas those for whom stool examination had been performed for other reasons (e.g., posttravel screening, weakness, parasites found in a family member) were classified as asymptomatic (n 25). Informed consent was obtained from subjects, and human experimentation guidelines of the Medical Research Council of Canada were followed. This study was approved by the ethics review committees of McGill University (Montreal, Canada) and Universidad Peruana Cayetano Heredia (Lima, Peru). Treatment protocol. After obtaining informed consent, subjects were block randomized to receive either WG (2 g) or cornstarch (2 g) orally 3 times a day for 10 days. Block randomization was acco (...truncated)