Six challenges in modelling for public health policy.

The World Health Organisation's definition of public health refers to all organized measures to prevent disease, promote health, and prolong life among the population as a whole (World Health Organization, 2014). Mathematical modelling plays an increasingly important role in helping to guide the most high impact and cost-effective means of achieving these goals. Public health programmes are usually implemented over a long period of time with broad benefits to many in the community. Clinical trials are seldom large enough to capture these effects. Observational data may be used to evaluate a programme after it is underway, but have limited value in helping to predict the future impact of a proposed policy. Furthermore, public health practitioners are often required to respond to new threats, for which there is little or no previous data on which to assess the threat. Computational and mathematical models can help to assess potential threats and impacts early in the process, and later aid in interpreting data from complex and multifactorial systems. As such, these models can be critical tools in guiding public health action. However, there are a number of challenges in achieving a successful interface between modelling and public health. Here, we discuss some of these challenges

Controlled Phenylhydrazine-Induced Reticulocytosis in the Rat

Author Institution: Department of Physiology, Ohio State University, College of Medicine, Columbus, Ohio 43210The pattern of development of phenylhydrazine-induced rat reticulocytosis was studied over a period of nine days. Intraperitoneal injections of phenylhydrazine (4 mg/100 gm) every other day caused a fall in hematocrit which leveled off at 60% of normal by the fifth day. Increased erythropoiesis was indicated by a three-fold increase in the number of circulating reituclocytes after the first three injections. The immediate response was the release of stored mature reticulocytes from the bone marrow. As the anemia progressed, more and more young reticulocytes appeared until 70 to 85% of the red cells in the peripheral circulation were reticulocytes and 20% of these were juvenile forms

Urban Cholera transmission hotspots and their implications for Reactive Vaccination: evidence from Bissau city, Guinea Bissau

Use of cholera vaccines in response to epidemics (reactive vaccination) may provide an effective supplement to traditional control measures. In Haiti, reactive vaccination was considered but, until recently, rejected in part due to limited global supply of vaccine. Using Bissau City, Guinea-Bissau as a case study, we explore neighborhood-level transmission dynamics to understand if, with limited vaccine and likely delays, reactive vaccination can significantly change the course of a cholera epidemic

Seven challenges for model-driven data collection in experimental and observational studies

Infectious disease models are both concise statements of hypotheses and powerful techniques for creating tools from hypotheses and theories. As such, they have tremendous potential for guiding data collection in experimental and observational studies, leading to more efficient testing of hypotheses and more robust study designs. In numerous instances, infectious disease models have played a key role in informing data collection, including the Garki project studying malaria, the response to the 2009 pandemic of H1N1 influenza in the United Kingdom and studies of T-cell immunodynamics in mammals. However, such synergies remain the exception rather than the rule; and a close marriage of dynamic modeling and empirical data collection is far from the norm in infectious disease research. Overcoming the challenges to using models to inform data collection has the potential to accelerate innovation and to improve practice in how we deal with infectious disease threats

What Now? Epidemiology in the Wake of a Pandemic

The coronavirus disease 2019 (COVID-19) pandemic and the coming transition to a postpandemic world where COVID-19 will likely remain as an endemic disease present a host of challenges and opportunities in epidemiologic research. The scale and universality of this disruption to life and health provide unique opportunities to study phenomena and health challenges in all branches of epidemiology, from the obvious infectious disease and social consequences to less clear impacts on chronic disease and cancer. If we are to both take advantage of the largest natural experiment of our lifetimes and provide evidence to inform the numerous public health and clinical decisions being made every day, we must act quickly to ask critical questions and develop new methods for answering them. In doing so, we should build on each of our strengths and expertise and try to provide new insights rather than become yet another voice commenting on the same set of questions with limited evidence

Opportunities and challenges in modeling emerging infectious diseases

The term “pathogen emergence” encompasses everything from previously unidentified viruses entering the human population to established pathogens invading new populations and the evolution of drug resistance. Mathematical models of emergent pathogens allow forecasts of case numbers, investigation of transmission mechanisms, and evaluation of control options. Yet, there are numerous limitations and pitfalls to their use, often driven by data scarcity. Growing availability of data on pathogen genetics and human ecology, coupled with computational and methodological innovations, is amplifying the power of models to inform the public health response to emergence events. Tighter integration of infectious disease models with public health practice and development of resources at the ready has the potential to increase the timeliness and quality of responses

Seven challenges for model-driven data collection in experimental and observational studies.

Infectious disease models are both concise statements of hypotheses and powerful techniques for creating tools from hypotheses and theories. As such, they have tremendous potential for guiding data collection in experimental and observational studies, leading to more efficient testing of hypotheses and more robust study designs. In numerous instances, infectious disease models have played a key role in informing data collection, including the Garki project studying malaria, the response to the 2009 pandemic of H1N1 influenza in the United Kingdom and studies of T-cell immunodynamics in mammals. However, such synergies remain the exception rather than the rule; and a close marriage of dynamic modeling and empirical data collection is far from the norm in infectious disease research. Overcoming the challenges to using models to inform data collection has the potential to accelerate innovation and to improve practice in how we deal with infectious disease threats

Analysis of Vaccine Effectiveness against COVID-19 and the Emergence of Delta and Other Variants of Concern in Utah

Since the emergence of SARS-CoV-2, vaccines have been heralded as the best way to curtail the COVID-19 pandemic. Clinical trials have shown SARS-CoV-2 vaccines to be highly efficacious against both disease and infection. However, those vaccines currently in use were primarily tested against early lineages. Data on vaccine effectiveness against variants of concern (VOCs) remains limited, including the Delta variant (B.1.617.2)

Improving propensity score weighting using machine learning

Machine learning techniques such as classification and regression trees (CART) have been suggested as promising alternatives to logistic regression for the estimation of propensity scores. The authors examined the performance of various CART-based propensity score models using simulated data. Hypothetical studies of varying sample sizes (n=500, 1000, 2000) with a binary exposure, continuous outcome, and 10 covariates were simulated under seven scenarios differing by degree of non-linear and non-additive associations between covariates and the exposure. Propensity score weights were estimated using logistic regression (all main effects), CART, pruned CART, and the ensemble methods of bagged CART, random forests, and boosted CART. Performance metrics included covariate balance, standard error, per cent absolute bias, and 95 per cent confidence interval (CI) coverage. All methods displayed generally acceptable performance under conditions of either non-linearity or non-additivity alone. However, under conditions of both moderate non-additivity and moderate non-linearity, logistic regression had subpar performance, whereas ensemble methods provided substantially better bias reduction and more consistent 95 per cent CI coverage. The results suggest that ensemble methods, especially boosted CART, may be useful for propensity score weighting

Sample size calculation for phylogenetic case Linkage

Sample size calculations are an essential component of the design and evaluation of scientific studies. However, there is a lack of clear guidance for determining the sample size needed for phylogenetic studies, which are becoming an essential part of studying pathogen transmission. We introduce a statistical framework for determining the number of true infector- infectee transmission pairs identified by a phylogenetic study, given the size and population coverage of that study. We then show how characteristics of the criteria used to determine linkage and aspects of the study design can influence our ability to correctly identify transmission links, in sometimes counterintuitive ways. We test the overall approach using outbreak simulations and provide guidance for calculating the sensitivity and specificity of the linkage criteria, the key inputs to our approach. The framework is freely available as the R package phylosamp, and is broadly applicable to designing and evaluating a wide array of pathogen phylogenetic studies