No abstract

African Animal Trypanosomiasis (AAT), caused predominantly by Trypanosoma brucei brucei, T. vivax and T. congolense, is a fatal livestock disease throughout Sub-Saharan Africa. Treatment options are very limited and threatened by resistance. Tubercidin (7-deazaadenosine) analogs have shown activity against individual parasites but viable chemotherapy must be active against all three species. Divergence in sensitivity to nucleoside antimetabolites could be caused by differences in nucleoside transporters. Having previously characterized the T. brucei nucleoside carriers, we here report the functional expression and characterization of the main adenosine transporters of T. vivax (TvxNT3) and T. congolense (TcoAT1/NT10), in a Leishmania mexicana cell line (‘SUPKO’) lacking adenosine uptake. Both carriers were similar to the T. brucei P1-type transporters and bind adenosine mostly through interactions with N3, N7 and 3′-OH. Expression of TvxNT3 and TcoAT1 sensitized SUPKO cells to various 7-substituted tubercidins and other nucleoside analogs although tubercidin itself is a poor substrate for P1-type transporters. Individual nucleoside EC50s were similar for T. b. brucei, T. congolense, T. evansi and T. equiperdum but correlated less well with T. vivax. However, multiple nucleosides including 7-halogentubercidines displayed pEC50>7 for all species and, based on transporter and anti-parasite SAR analyses, we conclude that nucleoside chemotherapy for AAT is viable.

Objectives The emergence of colistin-resistant Enterobacteriaceae from human and animal sources is one of the major public health concerns as colistin is the last-resort antibiotic for treating infections caused by multidrug-resistant Gram-negative bacteria. We aimed to determine the prevalence of the prototype widespread colistin resistance genes (mcr-1 and mcr-2) among commensal and pathogenic Escherichia coli strains isolated from food-producing and companion animals in Iran. Results A total of 607 E. coli isolates which were previously collected from different animal sources between 2008 and 2016 used to uncover the possible presence of plasmid-mediated colistin resistance genes (mcr-1 and mcr-2) by PCR. Overall, our results could not confirm the presence of any mcr-1 or mcr-2 positive E. coli among the studied isolates. It is concluded that despite the important role of food-producing animals in transferring the antibiotic resistance, they were not the main source for carriage of mcr-1 and mcr-2 in Iran until 2016. This study suggests that the other mcr variants (mcr-3 to mcr-9) might be responsible for conferring colistin resistance in animal isolates in Iran. The possible linkage between pig farming industry and high level of mcr carriage in some countries needs to be clarified in future prospective studies.

BackgroundFoot-and-mouth disease (FMD) is an acute viral disease of cloven-hoofed animals with high economic impact. FMD remains endemic in Iran particularly in the livestock-dense province of Khorasan Razavi in northeastern Iran where FMD outbreaks continuously occur. In this study, we aimed to quantify risk factors for the recurrence of FMD outbreaks in Iran by analyzing a time-series of FMD outbreak data from the province of Khorasan Razavi.ResultsThis study used FMD outbreak data collected from 2012 to 2014. Data were collected by local offices of the Iranian Animal Disease Department and the veterinarian of the veterinary council of the Khorasan Razavi province. An outbreak investigation questionnaire was delivered to 127 farms, including 46 case farms (FMD-infected) and 81 control farms (FMD-free). To quantify and compare the odds of exposure to a risk factor in FMD-infected farms versus FMD-free farms, logistic regression models were built using SPSS software version 16.Our results of multivariable logistic regression indicate that hygienic status of the farm (OR = 11.83; CI = 3.38–41.43), FMD vaccination status (OR = 0.06; CI = 0.01–0.68), transportation of livestock (OR = 0.40; CI = 0.163–0.981) and inhibition of livestock dealers’ entry into the farm (OR = 0.36; CI = 0.12–1.09) were identified as important risk factors for farm-level FMD infection.ConclusionThis study generated much needed evidence on a set of modifiable risk factors for the recurrence of FMD outbreaks in the high risk province of Khorasan Razavi. This information can be used to improve existing national FMD control program and suggest new guidelines to prevent FMD outbreaks in the country.

Trypanosomes and Leishmania are parasitic protozoans that affect millions of people globally. Herein we report the synthesis of 2‐aroyl quinazolinones and their antiprotozoal efficacy against Trypanosoma brucei, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania infantum. These compounds were counter‐screened against a human cell line for cytotoxicity. Thirteen of the twenty target compounds in this study inhibited the growth of these parasites, with compounds KJ1, and KJ10 exhibiting IC50 values of 4.7 μM (T. b. brucei) and 1.1 μM (T. b. rhodesiense), respectively.