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1. Modeling Seasonal Malaria Transmission: A Methodology Connecting Regional Temperatures to Mosquito and Parasite Developmental Traits

   Prosper, O.; Gurski, K.; Teboh-Ewungkem, M.; Peace, A.; Feng, Z.; Reynolds; M.; and Manore, C. (January 2023, Letters in biomathematics)

   Increasing temperatures have raised concerns over the potential effect on disease spread. Temperature is a well known factor affecting mosquito population dynamics and the development rate of the malaria parasite within the mosquito, and consequently, malaria transmission. A sinusoidal wave is commonly used to incorporate temperature effects in malaria models, however, we introduce a seasonal malaria framework that links data on temperature-dependent mosquito and parasite demographic traits to average monthly regional temperature data, without forcing a sinusoidal fit to the data. We introduce a spline methodology that maps temperature-dependent mosquito traits to time-varying model parameters. The resulting non-autonomous system of differential equations is used to study the impact of seasonality on malaria transmission dynamics and burden in a high and low malaria transmission region in Malawi. We present numerical simulations illustrating how temperature shifts alter the entomological inoculation rate and the number of malaria infections in these regions. 

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2. The impact of within-vector parasite development on the extrinsic incubation period

   https://doi.org/10.1098/rsos.192173  

   Childs, Lauren M.; Prosper, Olivia F. (October 2020, Royal Society Open Science)

   null (Ed.)

   Mosquito-borne diseases, in particular malaria, have a significant burden worldwide leading to nearly half a million deaths each year. The malaria parasite requires a vertebrate host, such as a human, and a vector host, the Anopheles mosquito, to complete its full life cycle. Here, we focus on the parasite dynamics within the vector to examine the first appearance of sporozoites in the salivary glands, which indicates a first time of infectiousness of mosquitoes. The timing of this period of pathogen development in the mosquito until transmissibility, known as the extrinsic incubation period, remains poorly understood. We develop compartmental models of within-mosquito parasite dynamics fitted with experimental data on oocyst and sporozoite counts. We find that only a fraction of oocysts burst to release sporozoites and bursting must be delayed either via a time-dependent function or a gamma-distributed set of compartments. We use Bayesian inference to estimate distributions of parameters and determine that bursting rate is a key epidemiological parameter. A better understanding of the factors impacting the extrinsic incubation period will aid in the development of interventions to slow or stop the spread of malaria. 

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3. Plasmodium falciparum Calcium-Dependent Protein Kinase 4 is Critical for Male Gametogenesis and Transmission to the Mosquito Vector

   https://doi.org/10.1128/mBio.02575-21  

   Kumar, Sudhir; Haile, Meseret T.; Hoopmann, Michael R.; Tran, Linh T.; Michaels, Samantha A.; Morrone, Seamus R.; Ojo, Kayode K.; Reynolds, Laura M.; Kusebauch, Ulrike; Vaughan, Ashley M.; et al (December 2021, mBio)

   Weiss, Louis M. (Ed.)

   ABSTRACT Gametocytes of the malaria parasite Plasmodium are taken up by the mosquito vector with an infectious blood meal, representing a critical stage for parasite transmission. Calcium-independent protein kinases (CDPKs) play key roles in calcium-mediated signaling across the complex life cycle of the parasite. We sought to understand their role in human parasite transmission from the host to the mosquito vector and thus investigated the role of the human-infective parasite Plasmodium falciparum CDPK4 in the parasite life cycle. P. falciparum cdpk4 − parasites created by targeted gene deletion showed no effect in blood stage development or gametocyte development. However, cdpk4 − parasites showed a severe defect in male gametogenesis and the emergence of flagellated male gametes. To understand the molecular underpinnings of this defect, we performed mass spectrometry-based phosphoproteomic analyses of wild-type and Plasmodium falciparum cdpk4 − late gametocyte stages to identify key CDPK4-mediated phosphorylation events that may be important for the regulation of male gametogenesis. We further employed in vitro assays to identify these putative substrates of Plasmodium falciparum CDPK4. This indicated that CDPK4 regulates male gametogenesis by directly or indirectly controlling key essential events, such as DNA replication, mRNA translation, and cell motility. Taken together, our work demonstrates that PfCDPK4 is a central kinase that regulates exflagellation and thereby is critical for parasite transmission to the mosquito vector. IMPORTANCE Transmission of the malaria parasite to the mosquito vector is critical for the completion of the sexual stage of the parasite life cycle and is dependent on the release of male gametes from the gametocyte body inside the mosquito midgut. In the present study, we demonstrate that PfCDPK4 is critical for male gametogenesis and is involved in phosphorylation of proteins essential for male gamete emergence. Targeting PfCDPK4 and its substrates may provide insights into achieving effective malaria transmission-blocking strategies. 

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4. Impacts of host availability and temperature on mosquito‐borne parasite transmission

   https://doi.org/10.1002/ecm.1603  

   Dahlin, Kyle J‐M; O'Regan, Suzanne M; Han, Barbara A; Schmidt, John Paul; Drake, John M (May 2024, Ecological Monographs)

   Abstract Global climate change is predicted to cause range shifts in the mosquito species that transmit pathogens to humans and wildlife. Recent modeling studies have sought to improve our understanding of the relationship between temperature and the transmission potential of mosquito‐borne pathogens. However, the role of the vertebrate host population, including the importance of host behavioral defenses on mosquito feeding success, remains poorly understood despite ample empirical evidence of its significance to pathogen transmission. Here, we derived thermal performance curves for mosquito and parasite traits and integrated them into two models of vector–host contact to investigate how vertebrate host traits and behaviors affect two key thermal properties of mosquito‐borne parasite transmission: the thermal optimum for transmission and the thermal niche of the parasite population. We parameterized these models for five mosquito‐borne parasite transmission systems, leading to two main conclusions. First, vertebrate host availability may induce a shift in the thermal optimum of transmission. When the tolerance of the vertebrate host to biting from mosquitoes is limited, the thermal optimum of transmission may be altered by as much as 5°C, a magnitude of applied significance. Second, thresholds for sustained transmission depend nonlinearly on both vertebrate host availability and temperature. At any temperature, sustained transmission is impossible when vertebrate hosts are extremely abundant because the probability of encountering an infected individual is negligible. But when host biting tolerance is limited, sustained transmission will also not occur at low host population densities. Furthermore, our model indicates that biting tolerance should interact with vertebrate host population density to adjust the parasite population thermal niche. Together, these results suggest that vertebrate host traits and behaviors play essential roles in the thermal properties of mosquito‐borne parasite transmission. Increasing our understanding of this relationship should lead us to improved predictions about shifting global patterns of mosquito‐borne disease. 

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5. Parasitism of Aedes albopictus by Ascogregarina taiwanensis lowers its competitive ability against Aedes triseriatus

   https://doi.org/10.1186/s13071-021-04581-0  

   Stump, Emma; Childs, Lauren M.; Walker, Melody (December 2021, Parasites & Vectors)

   null (Ed.)

   Abstract Background Mosquitoes are vectors for diseases such as dengue, malaria and La Crosse virus that significantly impact the human population. When multiple mosquito species are present, the competition between species may alter population dynamics as well as disease spread. Two mosquito species, Aedes albopictus and Aedes triseriatus , both inhabit areas where La Crosse virus is found. Infection of Aedes albopictus by the parasite Ascogregarina taiwanensis and Aedes triseriatus by the parasite Ascogregarina barretti can decrease a mosquito’s fitness, respectively. In particular, the decrease in fitness of Aedes albopictus occurs through the impact of Ascogregarina taiwanensis on female fecundity, larval development rate, and larval mortality and may impact its initial competitive advantage over Aedes triseriatus during invasion. Methods We examine the effects of parasitism of gregarine parasites on Aedes albopictus and triseriatus population dynamics and competition with a focus on when Aedes albopictus is new to an area. We build a compartmental model including competition between Aedes albopictus and triseriatus while under parasitism of the gregarine parasites. Using parameters based on the literature, we simulate the dynamics and analyze the equilibrium population proportion of the two species. We consider the presence of both parasites and potential dilution effects. Results We show that increased levels of parasitism in Aedes albopictus will decrease the initial competitive advantage of the species over Aedes triseriatus and increase the survivorship of Aedes triseriatus . We find Aedes albopictus is better able to invade when there is more extreme parasitism of Aedes triseriatus . Furthermore, although the transient dynamics differ, dilution of the parasite density through uptake by both species does not alter the equilibrium population sizes of either species. Conclusions Mosquito population dynamics are affected by many factors, such as abiotic factors (e.g. temperature and humidity) and competition between mosquito species. This is especially true when multiple mosquito species are vying to live in the same area. Knowledge of how population dynamics are affected by gregarine parasites among competing species can inform future mosquito control efforts and help prevent the spread of vector-borne disease. 

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