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

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.

Host density and habitat structure influence host contact rates and Batrachochytrium salamandrivorans transmission.

Batrachochytrium salamandrivorans (Bsal) is an emerging invasive pathogen that is highly pathogenic to salamander species. Modeling infection dynamics in this system can facilitate proactive efforts to mitigate this pathogen's impact on North American species. Given its widespread distribution and high abundance, the eastern newt (Notophthalmus viridescens) has the potential to significantly influence Bsal epidemiology. We designed experiments to 1) estimate contact rates given different host densities and habitat structure and 2) estimate the probability of transmission from infected to susceptible individuals. Using parameter estimates from data generated during these experiments, we modeled infection and disease outcomes for a population of newts using a system of differential equations. We found that host contact rates were density-dependent, and that adding habitat structure reduced contacts. The probability of Bsal transmission given contact between newts was very high (>90%) even at early stages of infection. Our simulations show rapid transmission of Bsal among individuals following pathogen introduction, with infection prevalence exceeding 90% within one month and >80% mortality of newts in three months. Estimates of basic reproductive rate (R0) of Bsal for eastern newts were 1.9 and 3.2 for complex and simple habitats, respectively. Although reducing host density and increasing habitat complexity might decrease transmission, these management strategies may be ineffective at stopping Bsal invasion in eastern newt populations due to this species' hyper-susceptibility.

Simulating within-vector generation of the malaria parasite diversity.

Plasmodium falciparum, the most virulent human malaria parasite, undergoes asexual reproduction within the human host, but reproduces sexually within its vector host, the Anopheles mosquito. Consequently, the mosquito stage of the parasite life cycle provides an opportunity to create genetically novel parasites in multiply-infected mosquitoes, potentially increasing parasite population diversity. Despite the important implications for disease transmission and malaria control, a quantitative mapping of how parasite diversity entering a mosquito relates to diversity of the parasite exiting, has not been undertaken. To examine the role that vector biology plays in modulating parasite diversity, we develop a two-part model framework that estimates the diversity as a consequence of different bottlenecks and expansion events occurring during the vector-stage of the parasite life cycle. For the underlying framework, we develop the first stochastic model of within-vector P. falciparum parasite dynamics and go on to simulate the dynamics of two parasite subpopulations, emulating multiply infected mosquitoes. We show that incorporating stochasticity is essential to capture the extensive variation in parasite dynamics, particularly in the presence of multiple parasites. In particular, unlike deterministic models, which always predict the most fit parasites to produce the most sporozoites, we find that occasionally only parasites with lower fitness survive to the sporozoite stage. This has important implications for onward transmission. The second part of our framework includes a model of sequence diversity generation resulting from recombination and reassortment between parasites within a mosquito. Our two-part model framework shows that bottlenecks entering the oocyst stage decrease parasite diversity from what is present in the initial gametocyte population in a mosquito's blood meal. However, diversity increases with the possibility for recombination and proliferation in the formation of sporozoites. Furthermore, when we begin with two parasite subpopulations in the initial gametocyte population, the probability of transmitting more than two unique parasites from mosquito to human is over 50% for a wide range of initial gametocyte densities.