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恶性疟原虫在蚊子体内发育过程中人类抗体对孢子生殖影响的数学评估。

Mathematical assessment of the impact of human-antibodies on sporogony during the within-mosquito dynamics of Plasmodium falciparum parasites.

作者信息

Teboh-Ewungkem Miranda I, Woldegerima Woldegebriel Assefa, Ngwa Gideon A

机构信息

Department of Mathematics, Lehigh University, Bethlehem, PA 18015, USA.

Department of Mathematics and Applied Mathematics, University of Pretoria, Hatfield, 0028 Pretoria, South Africa; Department of Mathematics, Mekelle University, P.O. Box 231, Mekelle, Ethiopia.

出版信息

J Theor Biol. 2021 Apr 21;515:110562. doi: 10.1016/j.jtbi.2020.110562. Epub 2020 Dec 24.

Abstract

We develop and analyze a deterministic ordinary differential equation mathematical model for the within-mosquito dynamics of the Plasmodium falciparum malaria parasite. Our model takes into account the action and effect of blood resident human-antibodies, ingested by the mosquito during a blood meal from humans, in inhibiting gamete fertilization. The model also captures subsequent developmental processes that lead to the different forms of the parasite within the mosquito. Continuous functions are used to model the switching transition from oocyst to sporozoites as well as human antibody density variations within the mosquito gut are proposed and used. In sum, our model integrates the developmental stages of the parasite within the mosquito such as gametogenesis, fertilization and sporogenesis culminating in the formation of sporozoites. Quantitative and qualitative analyses including a sensitivity analysis for influential parameters are performed. We quantify the average sporozoite load produced at the end of the within-mosquito malaria parasite's developmental stages. Our analysis shows that an increase in the efficiency of the ingested human antibodies in inhibiting fertilization within the mosquito's gut results in lowering the density of oocysts and hence sporozoites that are eventually produced by each mosquito vector. So, it is possible to control and limit oocysts development and hence sporozoites development within a mosquito by boosting the efficiency of antibodies as a pathway to the development of transmission-blocking vaccines which could potentially reduce oocysts prevalence among mosquitoes and hence reduce the transmission potential from mosquitoes to human.

摘要

我们开发并分析了一个用于恶性疟原虫在蚊子体内动态变化的确定性常微分方程数学模型。我们的模型考虑了蚊子在吸食人血时摄入的驻留在血液中的人类抗体在抑制配子受精方面的作用和效果。该模型还捕捉了导致蚊子体内寄生虫不同形态的后续发育过程。我们使用连续函数对从卵囊到子孢子的转换过渡进行建模,并提出并使用了蚊子肠道内人类抗体密度的变化。总之,我们的模型整合了寄生虫在蚊子体内的发育阶段,如配子发生、受精和孢子发生,最终形成子孢子。我们进行了包括对有影响参数的敏感性分析在内的定量和定性分析。我们量化了蚊子体内疟原虫发育阶段结束时产生的平均子孢子负荷。我们的分析表明,摄入的人类抗体在抑制蚊子肠道内受精方面的效率提高,会导致卵囊密度降低,从而最终由每个蚊子传播媒介产生的子孢子密度降低。因此,通过提高抗体效率作为开发传播阻断疫苗的途径,有可能控制和限制蚊子体内卵囊的发育,进而限制子孢子的发育,这可能会降低蚊子中卵囊的流行率,从而降低蚊子向人类传播的可能性。

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