Novel and promising compounds to treat Cryptosporidium parvum infections

No fully effective approved drug therapy exists for Cryptosporidium infections of immunocompetent and immunocompromised patients. Here, we investigated 11 benzimidazole derivatives carrying substituted thioalkyl and thiobenzyl groups at position 2 of benzimidazole nucleus and additional substituents at the benzene part of benzimidazole for inhibition of the in vitro growth of the intestinal protozoan parasite, Cryptosporidium parvum. Three of them, i.e., 5-carboxy-2-(4-nitrobenzylthio)-1H-benzimidazole, 5,6-dichloro-2-(4-nitrobenzylthio)-1H-benzimidazole, and 4,6-dichloro-2-(4-nitrobenzylthio)-1H-benzimidazole, (compounds 5, 7, and 8) were the most active (IC50 28–31 μM). The concentration of compounds 5, 7, and 8 that caused 50% growth inhibition in human enterocytic HCT-8 cells by a quantitative alkaline phosphatase immunoassay was comparable with those obtained for paromomycin

Novel and promising compounds to treat Cryptosporidium parvum infections

No fully effective approved drug therapy exists for Cryptosporidium infections of immunocompetent and immunocompromised patients. Here, we investigated 11 benzimidazole derivatives carrying substituted thioalkyl and thiobenzyl groups at position 2 of benzimidazole nucleus and additional substituents at the benzene part of benzimidazole for inhibition of the in vitro growth of the intestinal protozoan parasite, Cryptosporidium parvum. Three of them, i.e., 5-carboxy-2-(4-nitrobenzylthio)-1H-benzimidazole, 5,6-dichloro-2-(4-nitrobenzylthio)-1H-benzimidazole, and 4,6-dichloro-2-(4-nitrobenzylthio)-1H-benzimidazole, (compounds 5, 7, and 8) were the most active (IC50 28–31 μM). The concentration of compounds 5, 7, and 8 that caused 50% growth inhibition in human enterocytic HCT-8 cells by a quantitative alkaline phosphatase immunoassay was comparable with those obtained for paromomycin

Prevalence of soil transmitted nematodes on Nukufetau, a remote Pacific island in Tuvalu

BACKGROUND: The population of Nukufetau, a remote coral atoll island in Tuvalu in the Western Pacific, received annual mass drug administration (MDA) of diethylcarbamazine and albendazole under the Pacific Elimination of Lymphatic Filariasis program in 2001, 2002 and 2003, with the last MDA occurring six months before a cross-sectional survey of the whole population for soil transmitted helminths (STH). METHODS: A cross-sectional survey in May 2004 recruited 206 residents (35.2% of the population) who provided a single faecal sample that was preserved, concentrated and examined microscopically. RESULTS: Overall prevalence of STH was 69.9%; only hookworm and Trichuris trichiura were diagnosed. Trichuris was present in 68.4% with intensity of infection being light in 56.3%, medium in 11.7% and heavy in 0.5%. Hookworm occurred in 11.7% with intensity of infection 11.2% being light and medium in 0.5%. Twenty individuals (9.7%) had dual infections. The prevalence of Trichuris was constant across all ages while the prevalence of hookworm was significantly lower in residents below 30 years of age. In the age group 5–12 years comparison of results with a 2001 survey [1] suggested that the prevalence of STH has declined minimally, due to sustained high prevalence of Trichuris, while hookworm has declined dramatically from 34.4% to 1.6%. CONCLUSION: The results of this survey suggest that although the MDA appears to have reduced hookworm prevalence in residents below 30 years of age, there has been minimal effect on Trichuris prevalence. An integrated program to control STH is required

Bacillus thuringiensis Cry5B Protein Is Highly Efficacious as a Single-Dose Therapy against an Intestinal Roundworm Infection in Mice

Intestinal parasitic nematode diseases infect over one billion people and cause significant disease burden in children (growth and cognitive stunting, malnutrition), in pregnant women, and via their dampening of the immune system in infected individuals. In over thirty years, no new classes of anti-roundworm drugs (anthelmintics) for treating humans have been developed. Because of limitations of the current drugs and the threat of parasite resistance, new anthelmintics are needed. The soil bacterium Bacillus thuringiensis (Bt) produces crystal (Cry) proteins that specifically target and kill insects and nematodes and is used around the world as a safe insecticide. Here we test the effects of the Bt Cry protein Cry5B on a chronic, natural intestinal roundworm infection in mice, namely the helminth parasite Heligmosomoides bakeri. We find that a single dose of Cry5B can eliminate 70% of the parasites and can almost completely block the ability of the parasites to produce progeny. Comparisons of Cry5B's efficacy with known anthelmintics suggest its activity is as good as or perhaps even better than those currently used. Furthermore, this protein is rapidly digested by simulated stomach juices, suggesting that protecting it from these juices would reveal a superior anthelmintic