Infection severity across scales in multi-strain immuno-epidemiological Dengue model structured by host antibody level

Abstract

Infection by distinct Dengue virus serotypes and host immunity are intricately linked. In particular, certain levels of cross-reactive antibodies in the host may actually enhance infection severity leading to Dengue hemorrhagic fever (DHF). The coupled immunological and epidemiological dynamics of Dengue calls for a multi-scale modeling approach. In this work, we formulate a within-host model which mechanistically recapitulates characteristics of antibody dependent enhancement (ADE) in Dengue infection. The within-host scale is then linked to epidemiological spread by a vector-host partial differential equation model structured by host antibody level. The coupling allows for dynamic population-wide antibody levels to be tracked through primary and secondary infections by distinct Dengue strains, along with waning of cross-protective immunity after primary infection. Analysis of both the within-host and between-host systems are conducted. Stability results in the epidemic model are formulated via basic and invasion reproduction numbers as a function of immunological variables. Additionally, we develop numerical methods in order to simulate the multi-scale model and assess the influence of parameters on disease spread and DHF prevalence in the population.

Pathogen Infection Recovery Probability (PIRP) Versus Proinflammatory Anti-Pathogen Species (PIAPS) Levels: Modelling and Therapeutic Strategies

“…Pathogen infection modeling could be very useful for understanding the infection mechanisms and processes, and for preventive or therapeutic strategies. However, most of the existing modeling works are mainly focusing on multiple host infection and transmittance statistics over time domain [13][14][15][16][17] , very few modeling work provide insights on pathogen infection recovery probability (PIRP) over anti-pathogens species (APS), particularly over proinflammatory anti-pathogen species (PIAPS) which is the focus of this study. A pathogen infection in a host may result in pathogen un-controlled growth if the host immune system is too weak, deficient, or dysregulated (including immunoparalysis and a series of immune deficiency syndromes) that could result in sepsis or septic shocks 20 .…”

“…A pathogen infection in a host may result in pathogen un-controlled growth if the host immune system is too weak, deficient, or dysregulated (including immunoparalysis and a series of immune deficiency syndromes) that could result in sepsis or septic shocks 20 . In a host with normal immune response system, as illustrated in Figure 1, a pathogen infection at time t0 (end of incubation period) typically trigger a normal and efficient growth (clonal expansion) of immune system generated anti-pathogen species (APS, including PIAPS at an initial level x0 and time t0) and ideally shall result in pathogen being eliminated/cleared at te 13 . Once the pathogen is eliminated by the APS or PIAPS at te, the APS or PIAPS growth are supposed to cease and either remain at their equilibrium levels xe or decrease (shown by blue solid lines).…”

Pathogen Infection Recovery Probability (PIRP) Versus Proinflammatory Anti-Pathogen Species (PIAPS) Levels: Modelling and Therapeutic Strategies

“…Pathogen infection modeling could be very useful for understanding the infection mechanisms and processes, and for preventive or therapeutic strategies. However, most of the existing modeling works are mainly focusing on multiple host infection and transmittance statistics over time domain [13][14][15][16][17], very few modeling work provide insights on pathogen infection recovery probability (PIRP) over anti-pathogens species (APS), particularly over proinflammatory anti-pathogen species (PIAPS) that is the focus of this study.…”

“…A pathogen infection in a host may result in pathogen un-controlled growth if the host immune system is too weak, deficient, or dysregulated (including immunoparalysis and a serious immune deficiency syndromes) that could result in sepsis or septic shocks [20]. In a host with normal immune response system, as illustrated in Figure 1, the pathogen infection at time t0 (end of incubation period) typically trigger a normal and efficient growth (clonal expansion) of immune system generated anti-pathogen species (APS at an initial level x0) and ideally shall result in pathogen being eliminated/cleared at te [13]. Once the pathogen is eliminated by the APS at te, the APS (including PIAPS) growth are expected to cease and remain at their equilibrium levels xe.…”

“…Once the pathogen is eliminated by the APS at te, the APS (including PIAPS) growth are expected to cease and remain at their equilibrium levels xe. Certain APS (such as certain pathogen specific antibodies) are expected to remain at their equilibrium levels for certain period of time so the same pathogen infection can be prevented or inhibited (principle of vaccination), though antibody equilibrium level slow decay in long period of time are normal or expected [13][14][15][16][17]. However, in certain immunodysfunction disorders, particularly certain hyperinflammatory disorders, such as cytokine release syndromes (CRS) or cytokine storm (CS) [4][5][6][7][8][9][10][11][12], macrophage activation syndromes (MAS) or macrophage-cytokine self-amplifying loop (MCSAL) [11], WBS proliferative disorders [4], certain PIAPS can grow out of control or not being efficiently dampened by the host anti-inflammatory species (e.g., IL-10) even after te where the pathogen may have been eliminated.…”