bioRxiv Science⌕ Search

Biology subjects

Cecilia, H.

Publications and source records attributed to Cecilia, H..

6 recordsLinked to original sources

Multiscale Modeling of Vector-Borne Diseases: The Role of Dose-Dependent Transmission

The transmission of infectious diseases involves complex interactions across multiple biological scales, from within-host immunological processes to between-host transmission dynamics. While multiscale models have the potential to capture these interactions more accurately, they are often hindered by increased complexity and limited data availability. In this study, we develop a multiscale epidemic model linking host-vector population-level transmission dynamics to within-host and within-vector pathogen dynamics. Our model captures key features of within-vector viral progression and allows bidirectional coupling between within-host and between-host processes. The scales are linked under the assumption of dose-dependent transmission, with the functional form informed by empirical viremia-infectiousness data from arbovirus transmission. Focusing on Dengue, Zika, and West Nile viruses as case studies, we assess how different functional forms of the coupling affect the number of equilibria of the epidemic model. We find that when the transmission is modeled using linear coupling functions, the multiscale model yields the same bifurcation structure of the simpler, uncoupled model, indicating that the linking of scales does not alter the range of possible long-term epidemiological states in such cases. However, nonlinear coupling can induce complex behaviors such as multiple endemic equilibria and backward bifurcations, which the uncoupled model does not capture. These results underscore the importance of carefully selecting coupling functions and provide guidance on when multiscale modeling is essential for understanding and managing vector-borne diseases.

systems biology↗

Inside-Out: Modeling the link between Zika virus viral dynamics within hosts and transmission to vectors across host species and virus strains

Epidemiological models of mosquito-borne virus transmission often lack accurate estimates of host-to-vector transmission probability. Here, we estimated this probability for two strains of Zika virus (ZIKV)--one sylvatic and one human-endemic--from two monkey species to Aedes albopictus mosquitoes using experimental infection data. Viral dynamics did not differ between monkey species, although one (cynomolgus macaque) is a native ZIKV host and the other (squirrel monkey) a novel host, but differed between strains, with viremia for the human-endemic strain peaking later and lower than the sylvatic strain. Only the sylvatic strain was transmitted to mosquitoes. In mosquitoes, anatomical barriers influence viral progression to salivary glands, complicating host infectiousness estimation. We quantified the probability of viral dissemination to the legs in Ae. albopictus, which increased with host viral load and was higher after feeding on squirrel monkeys than on cynomolgus macaques. We also found a positive relationship between virus titer in mosquito legs and virus detection in saliva after a 14-day extrinsic incubation period. Combining these factors, we found that squirrel monkeys were on average 1.5 times more infectious to Ae. albopictus than cynomolgus macaques. These estimates will help assess ZIKVs potential to establish an enzootic, sylvatic cycle in the Americas.

systems biology↗

Aedes albopictus is not an arbovirus aficionado - Impacts of sylvatic flavivirus infection in vectors and hosts on mosquito engorgement on non-human primates

The contact structure between vertebrate hosts and arthropod vectors plays a key role in the spread of arthropod-borne viruses (arboviruses); thus, it is important to determine whether arbovirus infection of either host or vector alters vector feeding behavior. Here we leveraged a study of the replication dynamics of two arboviruses isolated from their ancestral cycles in paleotropical forests, sylvatic dengue-2 (DENV-2) and Zika (ZIKV), in one non-human primate (NHP) species from the paleotropics (cynomolgus macaques, Macaca fascicularis) and one from the neotropics (squirrel monkeys, Saimiri boliviensis) to test the effect of both vector and host infection with each virus on completion of blood feeding (engorgement) of the mosquito Aedes albopictus. Although mosquitoes were starved and given no choice of hosts, engorgement rates varied dramatically, from 0% to 100%. While neither vector nor host infection systematically affected engorgement, NHP species and body temperature at the time of feeding did. We also interrogated the effect of repeated mosquito bites on cytokine expression and found that epidermal growth factor (EGF) and macrophage migration inhibitory factor (MIF) concentrations were dynamically associated with exposure to mosquito bites. This study highlights the importance of incorporating individual-level heterogeneity of vector biting in arbovirus transmission models.

systems biology↗

Immunologically mediated trade-offs shaping transmission of sylvatic dengue and Zika viruses in native and novel non-human primate hosts

Mosquito-borne dengue (DENV) and Zika (ZIKV) viruses originated in Old World sylvatic cycles involving monkey hosts, spilled over into human transmission, and were translocated to the Americas, creating potential for spillback into neotropical sylvatic cycles. Studies of the trade-offs that shape within-host dynamics and transmission of these viruses are lacking, hampering efforts to predict spillover and spillback. We exposed native (cynomolgus macaque) or novel (squirrel monkey) hosts to mosquitoes infected with either sylvatic DENV or ZIKV and monitored viremia, natural killer cells, transmission to mosquitoes, cytokines, and neutralizing antibody titers. Unexpectedly, DENV transmission from both host species occurred only when serum viremia was undetectable or near the limit of detection. ZIKV replicated in squirrel monkeys to much higher titers than DENV and was transmitted more efficiently but stimulated lower neutralizing antibody titers. Increasing ZIKV viremia led to greater instantaneous transmission and shorter duration of infection, consistent with a replication-clearance trade-off.

microbiology↗

Heterogeneity of Rift Valley fever virus transmission potential across livestock hosts, quantified through a model-based analysis of host viral load and vector infection

Rift Valley fever (RVF) is a viral, vector-borne, zoonotic disease. The relative contributions of livestock species to RVFV transmission has not been previously quantified. To estimate their potential to transmit the virus over the course of their infection, we 1) fitted a within-host model to viral RNA and infectious virus measures, obtained daily from infected lambs, calves, and young goats, 2) estimated the relationship between vertebrate host infectious titers and probability to infect mosquitoes, and 3) estimated the net infectiousness of each host species over the duration of their infectious periods, taking into account different survival outcomes for lambs. Our results indicate that the efficiency of viral replication, along with the lifespan of infectious particles, could be sources of heterogeneity between hosts. For similar infectious titers, we found that infection rates in Aedes spp. vectors were significantly higher than in Culex spp. vectors. Consequently, for Aedes infections, we estimated the net infectiousness of lambs to be 2.93 (median) and 3.65 times higher than that of calves and goats, respectively. Among lambs, individuals which eventually died from the infection were 1.93 times more infectious than lambs recovering. Beyond infectiousness, the relative contributions of host species to transmission depend on local ecological factors, including relative abundances and vector host-feeding preferences. Quantifying these contributions will ultimately help design efficient, targeted, surveillance and vaccination strategies.

systems biology↗

Environmental heterogeneity drives tsetse fly population dynamics

A spatially and temporally heterogeneous environment may lead to unexpected population dynamics, and knowledge still is needed on which of the local environment properties favour population maintenance at larger scale. As regards pathogen vectors, such as tsetse flies transmitting human and animal African trypanosomosis, such a knowledge is crucial for proposing relevant management strategy. We developed an original mechanistic spatio-temporal model of tsetse fly population dynamics, accounting for combined effects of spatial complexity, density-dependence, and temperature on the age-structured population, and parametrized with field and laboratory data. We confirmed the strong impact of temperature and adult mortality on tsetse populations. We showed that patches with the lowest mean temperatures and lowest variations act as refuges when adult mortality is homogeneously increased. Our results highlighted the importance of baseline data collection to characterize the targeted ecosystem before any control measure is implemented to maximize its efficiency.

ecology↗