Drug Resistance in the Microaerophilic Parasite Giardia lamblia

Abstract

The microaerophilic parasite Giardia lamblia is a causative agent of dysentery affecting hundreds of millions of people around the globe every year. The symptoms of the disease, commonly referred to as giardiasis, are diarrhea, nausea, and malabsorption. Treatment of giardiasis is exclusively based on chemotherapy with antigiardial drugs, including metronidazole, albendazole, and nitazoxanide. In this review, all drugs currently used in the treatment of Giardia infections are discussed with a special emphasis on treatment failure and drug resistance.

Giardia intestinalis infection associated with malnutrition in children living in northeastern Brazil

“…Importantly, giardiasis has not been effectively targeted by the intestinal parasite control initiatives recently implemented by the Brazilian Ministry of Health [27], which have consisted of the distribution of a single 400 mg albendazole dose in schools and health centers. Although albendazole is effective and has been successfully used to control STHs, a five-day regimen is required to treat giardiasis [28]. Thus, the persistence of endemic giardiasis in rural areas may be due to limitations in the policies to control intestinal parasites.…”

“…The 5-nitroimidazolic compound most widely used to treat giardiasis, metronidazole, cannot be administered in a single dose. Instead, a five-day course is needed [28], which poses logistical hurdles. Although three other 5-nitroimidazolic derivatives -secnidazole, ornidazole and tinidazole, all of which are marketed in many countries [28] -are effective in single doses against G. intestinalis, the cost of these drugs, their poor tolerability, and their adverse effects preclude their use in large-scale chemoprevention strategies.…”

Giardiasis

“…However, tinidazole or metronidazole should still be used as first line treatment for travellers returning from these areas despite cross resistance between these drugs. 65 Patients with treatment failure should be discussed with or referred to a specialist, who should exclude underlying problems such as coeliac disease, inherited disaccharidase deficiency, and immunodeficiency disorders, particularly of total and IgA antibody production. Combination treatment with the above agents may be used under specialist care.…”

Click Chemistry-Facilitated Structural Diversification of Nitrothiazoles, Nitrofurans, and Nitropyrroles Enhances Antimicrobial Activity against Giardia lamblia

“…Resistance to the common clinical nitroheterocyclic drugs has been reported for G. lamblia in vitro and in vivo (12,13,20,29), yet it has also been demonstrated that specific nitroimidazole derivatives can overcome existing forms of resistance to different degrees (22,24), suggesting that resistance is relative and not a universal phenotype that equally impacts all nitroheterocyclic compounds. To evaluate the activity of the new nitroheterocyclic compounds against nitro drug-resistant G. lamblia, we tested two independently derived lines, 713M3 and WB-M2, which exhibit stable resistance in form of a 5-to 20-fold increase in EC 50 compared to susceptible lines against the three reference drugs, nitazoxanide, furazolidone, and metronidazole (28) (Fig.…”