Alterations in mosquito behaviour by malaria parasites: potential impact on force of infection

BACKGROUND: A variety of studies have reported that malaria parasites alter the behaviour of mosquitoes. These behavioural alterations likely increase transmission because they reduce the risk of vector death during parasite development and increase biting after parasites become infectious. METHODS: A mathematical model is used to investigate the potential impact of these behavioural alterations on the lifetime number of infectious bites delivered. The model is used to explore the importance of assumptions about the magnitude and distribution of mortality as well as the importance of extrinsic incubation period and gonotrophic cycle length. Additionally, the model is applied to four datasets taken from actual transmission settings. RESULTS: The impact of behavioural changes on the relative number of lifetime bites is highly dependent on assumptions about the distribution of mortality over the mosquito-feeding cycle. Even using fairly conservative estimates of these parameters and field collected data, the model outputs suggest that altered feeding could easily cause a doubling in the force of infection. CONCLUSIONS: Infection-induced behavioural alterations have their greatest impact on the lifetime number of infectious bites in environments with high feeding-related adult mortality and many pre-infectious feeding cycles. Interventions that increase feeding-associated mortality are predicted to amplify the relative fitness benefits and hence enhance the strength of selection for behavioural alteration.This study was supported by the NIH-NIAID ICEMR award (#U19AI089676-01)

Eave tubes for malaria control in Africa: a modelling assessment of potential impact on transmission.

BACKGROUND: Novel interventions for malaria control are necessary in the face of problems such as increasing insecticide resistance and residual malaria transmission. One way to assess performance prior to deployment in the field is through mathematical modelling. Modelled here are a range of potential outcomes for eave tubes, a novel mosquito control tool combining house screening and targeted use of insecticides to provide both physical protection and turn the house into a lethal mosquito killing device. METHODS: The effect of eave tubes was modelled by estimating the reduction of infectious mosquito bites relative to no intervention (a transmission metric defined as relative transmission potential, RTP). The model was used to assess how RTP varied with coverage when eave tubes were used as a stand-alone intervention, or in combination with either bed nets (LLINs) or indoor residual spraying (IRS). RESULTS: The model indicated the impact of eave tubes on transmission increases non-linearly as coverage increases, suggesting a community level benefit. For example, based on realistic assumptions, just 30 % coverage resulted in around 70 % reduction in overall RTP (i.e. there was a benefit for those houses without eave tubes). Increasing coverage to around 70 % reduced overall RTP by >90 %. Eave tubes exhibited some redundancy with existing interventions, such that combining interventions within properties did not give reductions in RTP equal to the sum of those provided by deploying each intervention singly. However, combining eave tubes and either LLINs or IRS could be extremely effective if the technologies were deployed in a non-overlapping way. CONCLUSION: Using predictive models to assess the benefit of new technologies has great value, and is especially pertinent prior to conducting expensive, large scale, randomized controlled trials. The current modelling study indicates eave tubes have considerable potential to impact malaria transmission if deployed at scale and can be used effectively with existing tools, especially if they are combined strategically with, for example, IRS and eave tubes targeting different houses.This work was supported by European Union Seventh Framework Programme Grant 306105, FP7-HEALTH-2012-INNOVATION-1

VUV frequency combs from below-threshold harmonics

Recent demonstrations of high-harmonic generation (HHG) at very high repetition frequencies (~100 MHz) may allow for the revolutionary transfer of frequency combs to the vacuum ultraviolet (VUV). This advance necessitates unifying optical frequency comb technology with strong-field atomic physics. While strong-field studies of HHG have often focused on above-threshold harmonic generation (photon energy above the ionization potential), for VUV frequency combs an understanding of below-threshold harmonic orders and their generation process is crucial. Here we present a new and quantitative study of the harmonics 7-13 generated below and near the ionization threshold in xenon gas. We show multiple generation pathways for these harmonics that are manifested as on-axis interference in the harmonic yield. This discovery provides a new understanding of the strong-field, below-threshold dynamics under the influence of an atomic potential and allows us to quantitatively assess the achievable coherence of a VUV frequency comb generated through below threshold harmonics. We find that under reasonable experimental conditions temporal coherence is maintained. As evidence we present the first explicit VUV frequency comb structure beyond the 3rd harmonic.Comment: 16 pages, 4 figures, 1 tabl

The influence of electromagnetic fields from two commercially available water-treatment devices on calcium carbonate precipitation

CaCO3 precipitation profiles, tracked by absorbance at 350 nm, showing accelerated precipitation upon exposure of the parent solutions to a pulsed electromagnetic field (PEMF) from a commercially available device.</p

Comparison of Methods for Xenomonitoring in Vectors of Lymphatic Filariasis in Northeastern Tanzania.

Monitoring Wuchereria bancrofti infection in mosquitoes (xenomonitoring) can play an important role in determining when lymphatic filariasis has been eliminated, or in focusing control efforts. As mosquito infection rates can be low, a method for collecting large numbers of mosquitoes is necessary. Gravid traps collected large numbers of Culex quinquefasciatus in Tanzania, and a collection method that targets mosquitoes that have already fed could result in increased sensitivity in detecting W. bancrofti-infected mosquitoes. The aim of this experiment was to test this hypothesis by comparing U.S. Centers for Disease Control and Prevention (CDC) light traps with CDC gravid traps in northeastern Tanzania, where Cx. quinquefasciatus is a vector of lymphatic filariasis. After an initial study where small numbers of mosquitoes were collected, a second study collected 16,316 Cx. quinquefasciatus in 60 gravid trap-nights and 240 light trap-nights. Mosquitoes were pooled and tested for presence of W. bancrofti DNA. Light and gravid traps collected similar numbers of mosquitoes per trap-night, but the physiological status of the mosquitoes was different. The estimated infection rate in mosquitoes collected in light traps was considerably higher than in mosquitoes collected in gravid traps, so light traps can be a useful tool for xenomonitoring work in Tanzania

Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents

Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs) was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs

Effective computational methods for hybrid stochastic gene networks

At the scale of the individual cell, protein production is a stochastic process with multiple time scales, combining quick and slow random steps with discontinuous and smooth variation. Hybrid stochastic processes, in particular piecewise-deterministic Markov processes (PDMP), are well adapted for describing such situations. PDMPs approximate the jump Markov processes traditionally used as models for stochastic chemical reaction networks. Although hybrid modelling is now well established in biology, these models remain computationally challenging. We propose several improved methods for computing time dependent multivariate probability distributions (MPD) of PDMP models of gene networks. In these models, the promoter dynamics is described by a finite state, continuous time Markov process, whereas the mRNA and protein levels follow ordinary differential equations (ODEs). The Monte-Carlo method combines direct simulation of the PDMP with analytic solutions of the ODEs. The push-forward method numerically computes the probability measure advected by the deterministic ODE flow, through the use of analytic expressions of the corresponding semigroup. Compared to earlier versions of this method, the probability of the promoter states sequence is computed beyond the naive mean field theory and adapted for non-linear regulation functions