Antigiardial Activity of Novel Guanidine Compounds.

From four focused compound libraries based on the known anticoccidial agent robenidine, 44 compounds total were synthesised and screened for antigiardial activity. All active compounds were counter-screened for antibiotic and cytotoxic action. Of the analogues examined, 21 displayed IC50 <5 µM, seven with IC50 <1.0 µM. Most active were 2,2'-bis{[4-(trifluoromethoxy)phenyl]methylene}carbonimidic dihydrazide hydrochloride (30), 2,2'-bis{[4-(trifluoromethylsulfanyl)phenyl]methylene}carbonimidic dihydrazide hydrochloride (32), and 2,2'-bis[(2-bromo-4,5-dimethoxyphenyl)methylene]carbonimidic dihydrazide hydrochloride (41) with IC50 =0.2 µM. The maximal observed activity was a 5 h IC50 value of 0.2 µM for 41. The clinically used metronidazole was inactive at this timepoint at a concentration of 25 µM. Robenidine off-target effects at bacteria and cell line toxicity were removed. Analogue 41 was well tolerated in mice treated orally (100 mg/kg). Following 5 h treatment with 41, no Giardia regrowth was noted after 48 h.

Molecular Detection and Epidemiological Features of Selected Bacterial, Viral, and Parasitic Enteropathogens in Stool Specimens from Children with Acute Diarrhea in Thi-Qar Governorate, Iraq.

Knowledge of etiology causes of diarrheal illness is essential for development and implementation of public health measures to prevent and control this disease syndrome. There are few published studies examining diarrhea in children aged <5 years in Iraq. This study aims to investigate the occurrences and epidemiology of selected bacterial (Salmonella spp. and Campylobacter spp.), viral (adenovirus, norovirus GI and GII, and astrovirus), and parasitic (Entamoeba spp. and Giardia spp.) agents in stool samples from 155 child diarrheal cases enrolled between March and August 2017, in a hospital-based cross-sectional study in Thi-Qar, southeastern Iraq. Using molecular techniques and sequence-based characterization, adenovirus was the most frequently detected enteropathogen (53/155 (34.2%)), followed by Salmonella spp. (23/155 (14.8%)), Entamoeba spp. (21/155 (13.5%)), and Campylobacter spp. (17/155 (10.9%)). Mixed infection with Salmonella spp. and Campylobacter spp. was evident, and the same was revealed between various enteric viruses, particularly adenovirus and norovirus. The most frequent co-infection pattern was between adenovirus and Campylobacter spp., in seven cases (7/155 (4.5%)). Whole-genome sequencing-derived typing data for Salmonella isolates (n = 23) revealed that sequence type 49 was the most prevalent in this sample set (15/23 (65.2%)). To the best of our knowledge, this study provides the first report on detection and identification of floR, blaCARB-2, and mphA antimicrobial resistance genes in Salmonella isolated from children in the Middle East region. Logistic regression analysis pointed to few enteropathogen-specific correlations between child age, household water source, and breastfeeding patterns in relation to the outcome of detection of individual enteropathogens. This study presents the first published molecular investigation of multiple enteropathogens among children <5 years of age in Iraq. Our data provide supporting evidence for planning of childhood diarrhea management programs. It is important to build on this study and develop future longitudinal case-control research in order to elaborate the epidemiology of enteropathogens in childhood diarrhea in Iraq.

Carriage of critically important antimicrobial resistant bacteria and zoonotic parasites amongst camp dogs in remote Western Australian indigenous communities.

Camp dogs in indigenous communities in the Western Australian Kimberley Region, share the domestic environment with humans and have the potential to act as carriers of, and sentinels for, a wide range of zoonotic agents, including intestinal parasites and antimicrobial resistant bacteria. In this study, we investigated the carriage of extended-spectrum-cephalosporin-resistant (ESC-resistant) Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA) and species of hookworm and Giardia among camp dogs in remote Western Australian Aboriginal communities. A total of 141 canine faecal samples and 156 nasal swabs were collected from dogs in four communities of the Western Australian Kimberley region. Overall, ESC-resistant E. coli was detected in 16.7% of faecal samples and MRSA was isolated from 2.6% of nasal swabs. Of most significance was the presence of the community-associated Panton-Valentine leucocidin (PVL)-positive MRSA ST93 and ST5 clones and ESC-resistant E. coli ST38 and ST131. The most prevalent zoonotic intestinal parasite infection was Ancylostoma caninum (66%). The prevalence of Giardia was 12.1%, with the main genotypes of Giardia detected being dog specific assemblages C and D, which are unlikely to cause disease in humans.

Giardia duodenalis mouse model for the development of novel antigiardial agents.

This study describes a neonatal mouse model of Giardia infection for development of novel antigiardials. Mice were infected with the axenically cultured Assemblage A BAH2c2 strain, with 105 trophozoites per animal recovered. This model proved to be robust and consistent for use in preliminary drug efficacy trials and drug development.