scholarly journals Synergistic and antagonistic interactions between bednets and vaccines in the control of malaria

2015 ◽  
Vol 112 (10) ◽  
pp. 3014-3019 ◽  
Author(s):  
Yael Artzy-Randrup ◽  
Andrew P. Dobson ◽  
Mercedes Pascual
Keyword(s):  
Mathematical Model ◽  
Malaria Transmission ◽  
Malaria Control ◽  
Added Value ◽  
Transmission Blocking ◽  
Malaria Vaccines ◽  
General Mathematical Model ◽  
Straightforward Solution ◽  
Detrimental Impact ◽  
Antagonistic Interactions

It is extremely likely that the malaria vaccines currently in development will be used in conjunction with treated bednets and other forms of malaria control. The interaction of different intervention methods is at present poorly understood in a disease such as malaria where immunity is more complex than for other pathogens that have been successfully controlled by vaccination. Here we develop a general mathematical model of malaria transmission to examine the interaction between vaccination and bednets. Counterintuitively, we find that the frailty of malaria immunity will potentially cause both synergistic and antagonistic interactions between vaccination and the use of bednets. We explore the conditions that create these tensions, and outline strategies that minimize their detrimental impact. Our analysis specifically considers the three leading vaccine classes currently in development: preerythrocytic (PEV), blood stage (BSV), and transmission blocking (TBV). We find that the combination of BSV with treated bednets can lead to increased morbidity with no added value in terms of elimination; the interaction is clearly antagonistic. In contrast, there is strong synergy between PEV and treated bednets that may facilitate elimination, although transient stages are likely to increase morbidity. The combination of TBV with treated bednets is synergistic, lowering both morbidity and elimination thresholds. Our results suggest that vaccines will not provide a straightforward solution to malaria control, and that future programs need to consider the synergistic and antagonistic interactions between vaccines and treated bednets.

scholarly journals Optimizing systemic insecticide use to improve malaria control

2019 ◽  
Author(s):  
Hannah R. Meredith ◽  
Luis Furuya-Kanamori ◽  
Laith Yakob
Keyword(s):  
Mathematical Model ◽  
Malaria Transmission ◽  
Malaria Control ◽  
Mass Drug Administration ◽  
Mosquito Control ◽  
Pyrethroid Resistance ◽  
Control Strategies ◽  
Systemic Insecticide ◽  
Systemic Insecticides ◽  
Long Lasting Insecticidal Nets

AbstractLong lasting insecticidal nets and indoor residual sprays have significantly reduced the burden of malaria. However, several hurdles remain before elimination can be achieved: mosquito vectors have developed resistance to public health insecticides, including pyrethroids, and have altered their biting behaviour to avoid these indoor control tools. Systemic insecticides, drugs applied directly to blood-hosts to kill mosquitoes that take a blood meal, offer a promising vector control option. To date, most studies focus on repurposing ivermectin, a drug used extensively to treat river blindness. There is concern that over-dependence on a single drug will inevitably repeat past experiences with the rapid spread of pyrethroid resistance in malaria vectors. Diversifying the arsenal of systemic insecticides used for mass drug administration would improve this strategy’s sustainability. Here, a review was conducted to identify systemic insecticide candidates and consolidate their pharmacokinetic/pharmacodynamic properties. The impact of alternative integrated vector control options and different dosing regimens on malaria transmission reduction are illustrated through a mathematical model simulation. The review identified drugs from four classes commonly used in livestock and companion animals: avermectics, milbemycins, isoxazolines, and spinosyns. Simulations predicted that isoxazoline and spinosyn drugs were promising candidates for mass drug administration, as they were predicted to need less frequent application than avermectins and milbemycins to maintain mosquitocidal blood concentrations. These findings will provide a guide for investigating and applying different systemic insecticides to achieve better mosquito control strategies.SignificanceThe widespread use of long lasting insecticidal nets (LLINs) and indoor residual spray has selected for mosquitoes that are resistant to pyrethroids or avoid exposure by feeding outdoors or on livestock. Systemic insecticides, drugs that render a host’s blood toxic to feeding mosquitoes, could be an effective control strategy for mosquitoes with pyrethroid resistance and/or outdoor feeding tendencies. Here, a number of existing systemic insecticide candidates are identified and their pharmacokinetic properties in different drug-host-route scenarios consolidated. These data were used to parameterise a mathematical model that illustrated the projected gains achievable in malaria control programmes already employing LLINs. The findings provide a guide for investigating and applying different systemic insecticides to improve mosquito control strategies and reduce malaria transmission.

scholarly journals Molecular interactions between parasite and mosquito during midgut invasion as targets to block malaria transmission

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Yacob Keleta ◽  
Julian Ramelow ◽  
Liwang Cui ◽  
Jun Li
Keyword(s):  
Malaria Transmission ◽  
Molecular Interactions ◽  
Molecular Mechanisms ◽  
Considerable Effort ◽  
Transmission Blocking ◽  
Public Health Burden ◽  
Mosquito Midgut ◽  
Malaria Vaccines ◽  
Effective Transmission ◽  
Transmission Blocking Vaccines

AbstractDespite considerable effort, malaria remains a major public health burden. Malaria is caused by five Plasmodium species and is transmitted to humans via the female Anopheles mosquito. The development of malaria vaccines against the liver and blood stages has been challenging. Therefore, malaria elimination strategies advocate integrated measures, including transmission-blocking approaches. Designing an effective transmission-blocking strategy relies on a sophisticated understanding of the molecular mechanisms governing the interactions between the mosquito midgut molecules and the malaria parasite. Here we review recent advances in the biology of malaria transmission, focusing on molecular interactions between Plasmodium and Anopheles mosquito midgut proteins. We provide an overview of parasite and mosquito proteins that are either targets for drugs currently in clinical trials or candidates of promising transmission-blocking vaccines.

Development and analysis of a malaria transmission mathematical model with seasonal mosquito life‐history traits

2019 ◽  
Vol 144 (4) ◽  
pp. 389-411 ◽  
Author(s):  
Ramsés Djidjou‐Demasse ◽  
Gbenga J. Abiodun ◽  
Abiodun M. Adeola ◽  
Joel O. Botai
Keyword(s):  
Mathematical Model ◽  
Life History ◽  
Malaria Transmission ◽  
Life History Traits

scholarly journals Incidence of Plasmodium falciparum malaria infection in 6-month to 45-year-olds on selected areas of Bioko Island, Equatorial Guinea

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Vicente Urbano Nsue Ndong Nchama ◽  
Ali Hamad Said ◽  
Ali Mtoro ◽  
Gertrudis Owono Bidjimi ◽  
Marta Alene Owono ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Control ◽  
Malaria Infection ◽  
Age Groups ◽  
Control Measures ◽  
Equatorial Guinea ◽  
Safety And Efficacy ◽  
Bioko Island ◽  
Malaria Vaccines

Abstract Background Extensive malaria control measures have been implemented on Bioko Island, Equatorial Guinea over the past 16 years, reducing parasite prevalence and malaria-related morbidity and mortality, but without achieving elimination. Malaria vaccines offer hope for reducing the burden to zero. Three phase 1/2 studies have been conducted successfully on Bioko Island to evaluate the safety and efficacy of whole Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccines. A large, pivotal trial of the safety and efficacy of the radiation-attenuated Sanaria® PfSPZ Vaccine against P. falciparum is planned for 2022. This study assessed the incidence of malaria at the phase 3 study site and characterized the influence of socio-demographic factors on the burden of malaria to guide trial design. Methods A cohort of 240 randomly selected individuals aged 6 months to 45 years from selected areas of North Bioko Province, Bioko Island, was followed for 24 weeks after clearance of parasitaemia. Assessment of clinical presentation consistent with malaria and thick blood smears were performed every 2 weeks. Incidence of first and multiple malaria infections per person-time of follow-up was estimated, compared between age groups, and examined for associated socio-demographic risk factors. Results There were 58 malaria infection episodes observed during the follow up period, including 47 first and 11 repeat infections. The incidence of malaria was 0.25 [95% CI (0.19, 0.32)] and of first malaria was 0.23 [95% CI (0.17, 0.30)] per person per 24 weeks (0.22 in 6–59-month-olds, 0.26 in 5–17-year-olds, 0.20 in 18–45-year-olds). Incidence of first malaria with symptoms was 0.13 [95% CI (0.09, 0.19)] per person per 24 weeks (0.16 in 6–59-month-olds, 0.10 in 5–17-year-olds, 0.11 in 18–45-year-olds). Multivariate assessment showed that study area, gender, malaria positivity at screening, and household socioeconomic status independently predicted the observed incidence of malaria. Conclusion Despite intensive malaria control efforts on Bioko Island, local transmission remains and is spread evenly throughout age groups. These incidence rates indicate moderate malaria transmission which may be sufficient to support future larger trials of PfSPZ Vaccine. The long-term goal is to conduct mass vaccination programmes to halt transmission and eliminate P. falciparum malaria.

The Generation Principle and Mathematical Models of Double-Enveloping Internal Gear Pairs

2015 ◽  
Author(s):  
Xuan Li ◽  
Bingkui Chen ◽  
Yawen Wang ◽  
Guohua Sun ◽  
Teik C. Lim
Keyword(s):  
Mathematical Model ◽  
Load Capacity ◽  
Geometrical Shape ◽  
Gear Pair ◽  
Numerical Examples ◽  
Proposed Model ◽  
General Mathematical Model ◽  
Meshing Characteristics ◽  
Internal Gear ◽  
Tooth Pair

In this paper, the planar double-enveloping method is presented for the generation of tooth profiles of the internal gear pair for various applications, such as gerotors and gear reducers. The main characteristic of this method is the existence of double contact between one tooth pair such that the sealing property, the load capacity and the transmission precision can be significantly improved as compared to the conventional configuration by the single-enveloping theory. Firstly, the generation principle of the planar double-enveloping method is introduced. Based on the coordinate transformation and the envelope theory, the general mathematical model of the double-enveloping internal gear pair is presented. By using this model, users can directly design different geometrical shape profiles to obtain a double-enveloping internal gear pair with better meshing characteristics. Secondly, to validate the effectiveness of the proposed model, specific mathematical formulations of three double-enveloping internal gear pairs which apply circular, parabolic and elliptical curves as the generating curves are given. The equations of tooth profiles and meshing are derived and the composition of tooth profiles is analyzed. Finally, numerical examples are provided for an illustration.

scholarly journals Heterogeneous exposure and hotspots for malaria vectors at three study sites in Uganda

2018 ◽  
Vol 2 ◽  
pp. 32 ◽  
Author(s):  
Su Yun Kang ◽  
Katherine E. Battle ◽  
Harry S. Gibson ◽  
Laura V. Cooper ◽  
Kilama Maxwell ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Malaria Vector ◽  
Malaria Control ◽  
Negative Binomial ◽  
Indoor Residual Spraying ◽  
Housing Quality ◽  
Environmental Covariates ◽  
Vector Density ◽  
Vector Abundance ◽  
Study Sites

Background: Heterogeneity in malaria transmission has household, temporal, and spatial components. These factors are relevant for improving the efficiency of malaria control by targeting heterogeneity. To quantify variation, we analyzed mosquito counts from entomological surveillance conducted at three study sites in Uganda that varied in malaria transmission intensity. Mosquito biting or exposure is a risk factor for malaria transmission. Methods: Using a Bayesian zero-inflated negative binomial model, validated via a comprehensive simulation study, we quantified household differences in malaria vector density and examined its spatial distribution. We introduced a novel approach for identifying changes in vector abundance hotspots over time by computing the Getis-Ord statistic on ratios of household biting propensities for different scenarios. We also explored the association of household biting propensities with housing and environmental covariates. Results: In each site, there was evidence for hot and cold spots of vector abundance, and spatial patterns associated with urbanicity, elevation, or other environmental covariates. We found some differences in the hotspots in rainy vs. dry seasons or before vs. after the application of control interventions. Housing quality explained a portion of the variation among households in mosquito counts. Conclusion: This work provided an improved understanding of heterogeneity in malaria vector density at the three study sites in Uganda and offered a valuable opportunity for assessing whether interventions could be spatially targeted to be aimed at abundance hotspots which may increase malaria risk. Indoor residual spraying was shown to be a successful measure of vector control interventions in Tororo, Uganda.  Cement walls, brick floors, closed eaves, screened airbricks, and tiled roofs were features of a house that had shown reduction of household biting propensity. Improvements in house quality should be recommended as a supplementary measure for malaria control reducing risk of infection.

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