METHODS: We collected a total of 125 bat flies from three Pteropus species (Pteropus vampyrus, P. hypomelanus, and P. lylei) from eight localities in Malaysia, Cambodia, and Vietnam. We identified specimens morphologically and then sequenced three mitochondrial DNA gene fragments (CoI, CoII, cytB; 1744 basepairs total) from a subset of 45 bat flies. We measured genetic diversity, molecular variance, and population genetic subdivision (FST), and used phylogenetic and haplotype network analyses to quantify parasite genetic structure across host species and localities.
RESULTS: All flies were identified as Cyclopodia horsfieldi with the exception of two individuals of Eucampsipoda sundaica. Low levels of population genetic structure were detected between populations of Cyclopodia horsfieldi from across a wide geographic range (~1000 km), and tests for isolation by distance were rejected. AMOVA results support a lack of geographic and host-specific population structure, with molecular variance primarily partitioned within populations. Pairwise FST values from flies collected from island populations of Pteropus hypomelanus in East and West Peninsular Malaysia supported predictions based on previous studies of host genetic structure.
CONCLUSIONS: The lack of population genetic structure and morphological variation observed in Cyclopodia horsfieldi is most likely due to frequent contact between flying fox species and subsequent high levels of parasite gene flow. Specifically, we suggest that Pteropus vampyrus may facilitate movement of bat flies between the three Pteropus species in the region. We demonstrate the utility of parasite genetics as an additional layer of information to measure host movement and interspecific host contact. These approaches may have wide implications for understanding zoonotic, epizootic, and enzootic disease dynamics. Bat flies may play a role as vectors of disease in bats, and their competence as vectors of bacterial and/or viral pathogens is in need of further investigation.
OBJECTIVE: We have conducted a systematic review of two major (FIGHT and LIVE) placebo-controlled trials of liraglutide and its clinical effect on the ejection fraction of subjects with heart failure.
METHODS: Medline data was retrieved for trials involving liraglutide from 2012 to 2020. The inclusion criteria for trials were: subjects with or without type 2 diabetes mellitus (T2DM), subjects with heart failure with rLVEF, major trials (phase II or III) on liraglutide, trials included liraglutide with defined efficacy primary outcome of patients with heart failure with rLVEF. The search was limited to the English language, whereby two trials [FIGHT and LIVE] had been included and two trials were excluded due to different primary outcomes. Participants (541) had been randomized for either liraglutide or placebo for 24 weeks.
RESULTS: In the FIGHT trial the primary intention-to-treat, sensitivity, and diabetes subgroup analyses have shown no significant between-group difference in the global rank scores (mean rank of 146 in the liraglutide group versus 156 in the placebo group; Wilcoxon rank-sum P=.31), number of deaths, re-hospitalizations for heart failure, or the composite of death or change in NT-pro BNP level (P= .94). In the LIVE trial, the change in the left ventricular ejection fraction (LVEF) from baseline to week 24 was not significantly different between treatment groups. The overall discontinuation rate of liraglutide was high in the FIGHT trial (29%, 86) as compared to that in the LIVE trial (11.6%, 28).
CONCLUSION: FIGHT and LIVE trials have demonstrated that liraglutide use in subjects with heart failure and rLVEF was implicated with an increased adverse risk of heart failure-related outcomes.