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Probabilistic modeling for an integrated temporary acquired immunity with norovirus epidemiological data.

ABSTRACT: Integration of acquired immunity into microbial risk assessment for illness incidence is of no doubt essential for the study of susceptibility to illness. In this study, a probabilistic model was set up as dose response for infection and a mathematical derivation was carried out by integrating immunity to obtain probability of illness models. Temporary acquire immunity from epidemiology studies which includes six different Norovirus transmission scenarios such as symptomatic individuals infectious, pre- and post-symptomatic infectiousness (low and high), innate genetic resistance, genogroup 2 type 4 and those with no immune boosting by asymptomatic infection were evaluated. Simulated results on illness inflation factor as a function of dose and exposure indicated that high frequency exposures had immense immunity build up even at high dose levels; hence minimized the probability of illness. Using Norovirus transmission dynamics data, results showed, and immunity included models had a reduction of 2-6 logs of magnitude difference in disease burden for both population and individual probable illness incidence. Additionally, the magnitude order of illness for each dose response remained largely the same for all transmission scenarios; symptomatic infectiousness and no immune boosting after asymptomatic infectiousness also remained the same throughout. With integration of epidemiological data on acquired immunity into the risk assessment, more realistic results were achieved signifying an overestimation of probable risk of illness when epidemiological immunity data are not included. This finding supported the call for rigorous integration of temporary acquired immunity in dose-response in all microbial risk assessments.

SUBMITTER: Owusu-Ansah EDJ

PROVIDER: S-EPMC6503004 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Probabilistic modeling for an integrated temporary acquired immunity with norovirus epidemiological data.

Owusu-Ansah Emmanuel de-Graft Johnson EDJ Barnes Benedict B Abaidoo Robert R Tine Hald H Dalsgaard Anders A Permin Anders A Schou Torben Wilde TW

Infectious Disease Modelling 20190427

Integration of acquired immunity into microbial risk assessment for illness incidence is of no doubt essential for the study of susceptibility to illness. In this study, a probabilistic model was set up as dose response for infection and a mathematical derivation was carried out by integrating immunity to obtain probability of illness models. Temporary acquire immunity from epidemiology studies which includes six different <i>Norovirus</i> transmission scenarios such as symptomatic individuals i ...[more]

PMID: 31080934

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Project description:BackgroundCancer patients with advanced disease routinely exhaust available clinical regimens and lack actionable genomic medicine results, leaving a large patient population without effective treatments options when their disease inevitably progresses. To address the unmet clinical need for evidence-based therapy assignment when standard clinical approaches have failed, we have developed a probabilistic computational modeling approach which integrates molecular sequencing data with functional assay data to develop patient-specific combination cancer treatments.MethodsTissue taken from a murine model of alveolar rhabdomyosarcoma was used to perform single agent drug screening and DNA/RNA sequencing experiments; results integrated via our computational modeling approach identified a synergistic personalized two-drug combination. Cells derived from the primary murine tumor were allografted into mouse models and used to validate the personalized two-drug combination. Computational modeling of single agent drug screening and RNA sequencing of multiple heterogenous sites from a single patient's epithelioid sarcoma identified a personalized two-drug combination effective across all tumor regions. The heterogeneity-consensus combination was validated in a xenograft model derived from the patient's primary tumor. Cell cultures derived from human and canine undifferentiated pleomorphic sarcoma were assayed by drug screen; computational modeling identified a resistance-abrogating two-drug combination common to both cell cultures. This combination was validated in vitro via a cell regrowth assay.ResultsOur computational modeling approach addresses three major challenges in personalized cancer therapy: synergistic drug combination predictions (validated in vitro and in vivo in a genetically engineered murine cancer model), identification of unifying therapeutic targets to overcome intra-tumor heterogeneity (validated in vivo in a human cancer xenograft), and mitigation of cancer cell resistance and rewiring mechanisms (validated in vitro in a human and canine cancer model).ConclusionsThese proof-of-concept studies support the use of an integrative functional approach to personalized combination therapy prediction for the population of high-risk cancer patients lacking viable clinical options and without actionable DNA sequencing-based therapy.

Dataset Information

Probabilistic modeling for an integrated temporary acquired immunity with norovirus epidemiological data.

Publications

Probabilistic modeling for an integrated temporary acquired immunity with norovirus epidemiological data.

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