Aedes aegypti is a primary vector of viral pathogens and is responsible for millions of human infections annually that represent critical public health and economic costs. Pyrethroids are one of the ...most commonly used classes of insecticides to control adult A. aegypti. The insecticidal activity of pyrethroids depends on their ability to bind and disrupt the voltage-sensitive sodium channel (VSSC). In mosquitoes, a common mechanism of resistance to pyrethroids is due to mutations in Vssc (hereafter referred as knockdown resistance, kdr). In this study, we found that a kdr (410L+V1016I+1534C) allele was the main mechanism of resistance in a pyrethroid-resistant strain of A. aegypti collected in Colombia. To characterize the level of resistance these mutations confer, we isolated a pyrethroid resistant strain (LMRKDR:RK, LKR) that was congenic to the susceptible Rockefeller (ROCK) strain. The full-length cDNA of Vssc was cloned from LKR and no additional resistance mutations were present. The levels of resistance to different pyrethroids varied from 3.9- to 56-fold. We compared the levels of resistance to pyrethroids, DCJW and DDT between LKR and what was previously reported in two other congenic strains that share the same pyrethroid-susceptible background (the ROCK strain), but carry different kdr alleles (F1534C or S989P + V1016G). The resistance conferred by kdr alleles can vary depending on the stereochemistry of the pyrethroid. The 410L+1016I+1534C kdr allele does not confer higher levels of resistance to six of ten pyrethroids, relative to the 1534C allele. The importance of these results to understand the evolution of insecticide resistance and mosquito control are discussed.
Individuals and communities that are closest to a problem are often the most powerful advocates for public policy change.6 In the case of global surgery, one of these individuals is the front-line ...surgical or anaesthesia provider who struggles to deliver care to patients in the most challenging circumstances. ...the front-line surgeon, anaesthetist or nurse at the district hospital understands all too well the realities of conducting an emergency laparotomy using the light from a mobile phone because the operating room lamps are non-functional, or the challenge of providing anaesthesia with limited training, inadequate medicines and oxygen supply shortages. ...medical and nursing schools must consider offering elective courses in policy and advocacy so that students can gain the fundamentals of public policy and acquire essential advocacy skills. After years of working in dire situations, they become frustrated and burnt out.23 24 The repercussions of this burnout and frustrations can be lower quality care, emigration to HICs for better opportunities, the so-called brain drain problem or perhaps moving out of healthcare practice altogether.25 The frustrations can be compounded when policymakers attempt to enact legislation contrary to the interests of healthcare workers, such as the recent bill introduced in the Nigerian parliament mandating doctors to work in the country for at least 5 years postgraduation before being licensed.26 It is also important to note that policy change is a complex process.
Data suggest that the malaria vector mosquito Anopheles coluzzii persists during the dry season in the Sahel through a dormancy mechanism known as aestivation; however, the contribution of ...aestivation compared with alternative strategies such as migration is unknown. Here we marked larval Anopheles mosquitoes in two Sahelian villages in Mali using deuterium (
H) to assess the contribution of aestivation to persistence of mosquitoes through the seven-month dry season. After an initial enrichment period, 33% of An. coluzzii mosquitoes were strongly marked. Seven months following enrichment, multiple analysis methods supported the ongoing presence of marked mosquitoes, compatible with the prediction that the fraction of marked mosquitoes should remain stable throughout the dry season if local aestivation is occurring. The results suggest that aestivation is a major persistence mechanism of An. coluzzii in the Sahel, contributing at least 20% of the adults at the onset of rains. This persistence strategy could influence mosquito control and malaria elimination campaigns.
Recent studies have reported
mosquitoes captured at high-altitude (40-290 m above ground) in the Sahel. Here, we describe this migration modality across genera and species of African Culicidae and ...examine its implications for disease transmission and control. As well as
, six other genera-
, and
comprised 90% of the 2,340 mosquitoes captured at altitude. Of the 50 molecularly confirmed species (
= 2,107), 33 species represented by multiple specimens were conservatively considered high-altitude windborne migrants, suggesting it is a common migration modality in mosquitoes (31-47% of the known species in Mali), and especially in
(45-59%). Overall species abundance varied between 2 and 710 specimens/species (in
and
, respectively). At altitude, females outnumbered males 6:1, and 93% of the females have taken at least one blood meal on a vertebrate host prior to their departure. Most taxa were more common at higher sampling altitudes, indicating that total abundance and diversity are underestimated. High-altitude flight activity was concentrated between June and November coinciding with availability of surface waters and peak disease transmission by mosquitoes. These hallmarks of windborne mosquito migration bolster their role as carriers of mosquito-borne pathogens (MBPs). Screening 921 mosquitoes using pan-
assays revealed that thoracic infection rate in these high-altitude migrants was 2.4%, providing a proof of concept that vertebrate pathogens are transported by windborne mosquitoes at altitude. Fourteen of the 33 windborne mosquito species had been reported as vectors to 25 MBPs in West Africa, which represent 32% of the MBPs known in that region and include those that inflict the heaviest burden on human and animal health, such as malaria, yellow fever, dengue, and Rift Valley fever. We highlight five arboviruses that are most likely affected by windborne mosquitoes in West Africa: Rift Valley fever, O'nyong'nyong, Ngari, Pangola, and Ndumu. We conclude that the study of windborne spread of diseases by migrating insects and the development of surveillance to map the sources, routes, and destinations of vectors and pathogens is key to understand, predict, and mitigate existing and new threats of public health.
Spread options are contingent claims with payoffs dependent on the difference of two market variables. Although their uses have widespread over the years and across every sector of the financial ...markets, their valuation has remained a challenging task for both academics and practitioners. To date, with the exception of the exchange option, spread option prices do not admit an analytical expression outside the geometric Brownian motion paradigm. This dissertation proposes an almost closed-form approximation for the valuation of this class of instruments under several multi-factor stochastic volatility models. We develop analytical approximations for the spread option price under jump-diffusion models and mean-reverting models as well. The numerical methods combine closed form approximations, Monte Carlo methods and conditioning techniques. Algorithms for the exact simulation of stochastic volatility models are presented.
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