Phenotypic and genotypic characterization of dog tick Rhipicephalus sanguineus sensu lato (Acari: Ixodidae) resistance to deltamethrin in Benin.

The aim of this study was to evaluate the phenotypic and genotypic resistance of Rhipicephalus sanguineus sensu lato to deltamethrin in dogs in the municipality of Natitingou in Benin. In this study, the collection and identification of ticks, Larval Packet Test and specific allele PCR were the main methods used. A total of 41 dogs were examined and 420 ticks were collected in six areas which includes: Tchrimina, Yokossi, Boriyoure, Berécingou, Péporiyakou and Perma. Three species of ticks were identified and they include: R. sanguineus s.l., Rhipicephalus microplus and Haemaphysalis spp. However, R. sanguineus s.l. was the most abundant tick species (9.85) and had the highest parasitic intensity (10.36). The results of the Larval Packet Test showed that the larvae of R. sanguineus s.l. developed a phenotypic resistance against deltamethrin, particularly in the Bérécingou area where resistance ratios of LC50 and LC95 of R. sanguineus s.l. compared to a susceptible strain were 1.591 (1.025-3.054) and 65.339 (20.235-579.825) respectively. The molecular study of the sodium channel gene revealed three genotypes namely the susceptible genotype (SS), the heterozygous genotype (SR) and the resistant genotype (RR), which correlates with the phenotypic results. This information is fundamental to improve monitoring and resistance management strategies of R. sanguineus s.l. ticks to pyrethroids.

Duration of pretomanid/moxifloxacin/pyrazinamide therapy compared with standard therapy based on time-to-extinction mathematics.

OBJECTIVES: Animal models have suggested that the combination of pretomanid with pyrazinamide and moxifloxacin (PaMZ) may shorten TB therapy duration to 3-4 months. Here, we tested that in the hollow-fibre system model of TB (HFS-TB). METHODS: A series of HFS-TB experiments were performed to compare the kill rates of the PaMZ regimen with the standard three-drug combination therapy. HFS-TB experiments were performed with bacilli in log-phase growth treated for 28 days, intracellular bacilli treated daily for 28 days and semi-dormant Mycobacterium tuberculosis treated with daily therapy for 56 days for sterilizing effect. Next, time-to-extinction equations were employed, followed by morphism transformation and Latin hypercube sampling, to determine the proportion of patients who achieved a time to extinction of 3, 4 or 6 months with each regimen. RESULTS: Using linear regression, the HFS-TB sterilizing effect rates of the PaMZ regimen versus the standard-therapy regimen during the 56 days were 0.18 (95% credible interval=0.13-0.23) versus 0.15 (95% credible interval=0.08-0.21) log10 cfu/mL/day, compared with 0.16 (95% credible interval=0.13-0.18) versus 0.11 (95% credible interval=0.09-0.13) log10 cfu/mL/day in the Phase II clinical trial, respectively. Using time-to-extinction and Latin hypercube sampling modelling, the expected percentages of patients in which the PaMZ regimen would achieve sterilization were 40.37% (95% credible interval=39.1-41.34) and 72.30% (95% credible interval=71.41-73.17) at 3 and 4 months duration of therapy, respectively, versus 93.67% (95% credible interval=93.18-94.13) at 6 months for standard therapy. CONCLUSIONS: The kill rates of the PaMZ regimen were predicted to be insufficient to achieve cure in less than 6 months in most patients.

Accelerating the transition of new tuberculosis drug combinations from Phase II to Phase III trials: New technologies and innovative designs.

Geraint Davies and colleagues discuss the potential for innovative early-phase clinical trial methods and technologies to reduce risk and speed up drug development for tuberculosis.

Association of pig UCP3 gene mutations and back fat thickness in the sixth and seventh rib.

Accumulated studies have documented extensive links between UCP3 polymorphisms and pig productive traits, and quantitative trait loci linkage results, on the other hand, provided extensive evidences showing that UCP3 was in the core of several QTLs for carcass and meat quality traits. In this research, we screened two substitutions in coding sequence and one 9-base continuous mutated site in 3'UTR of pig UCP3 gene using the reference population of 293 pigs which were F (2) generation of hybrids between Chinese native Jinhua pigs and European Pietrain. The two missense mutations of G1406A in Exon 3 and T3602C in Exon 5 which led to changes in the G150R and M259T, respectively, were digested by SmaI and introduced Tth111I separately for genotype analysis, and the 9-base continuous mutated site in the 3'UTR was analyzed by an AvaI cleavage. As a result, the 9-base continuous mutated site of 3'UTR manifested significantly close association with the backfat thickness at the sixth and seventh rib, but the polymorphisms of G1406A and T3602C were not associated significantly with any of the seven carcass traits. The same results were shown by RT-qPCR and western blotting. These findings inferred that UCP3 probably has tissue-specific effects on pig carcass traits.