Glossary

The Epidemiological MODeling software (EMOD) glossary is divided into the following subsections that define terms related to software usage, general epidemiology, and the particular disease being modeled.

Epidemiology terms

antibodies

See antibody.

antibody

A blood protein produced in response to and counteracting a specific antigen. Antibodies combine chemically with substances that the body recognizes as foreign (eg. bacteria, viruses, or other substances).

antigen

A substance that is capable of inducing a specific immune response and that evokes the production of one or more antibodies.

antigens

See antigen.

Clausius-Clayperon relation

A way of characterizing a transition between two phases of matter; provides a method to find a relationship between temperature and pressure along phase boundaries. Frequently used in meteorology and climatology to describe the behavior of water vapor. See Wikipedia - Clausius-Clayperon relation for more information.

compartmental model

A disease model that divides the population into a number of compartments that represent different disease states, such as susceptible, infected, or recovered. Every person in a compartment is considered identical. Many compartmental models are deterministic, but some are stochastic.

deterministic

Characterized by the output being fully determined by the parameter values and the initial conditions. Given the same inputs, a deterministic model will always produce the same output.

diffusive migration

The diffusion of people in and out of nearby nodes by foot travel.

disability-adjusted life years (DALY)

The number of years of life lost due to premature mortality plus the years lost due to disability while infected. Used to quantify the burden of disease.

epidemic

An outbreak of an infectious disease, such that a greater number of individuals than normal has the disease. Epidemics have very high R₀ (Recall R₀>1 for a disease to spread) and are often associated with acute, highly transmissible pathogens that can be directly transmitted. Further, pathogens with lower infectious periods create more explosive epidemics. To control epidemics, it is necessary to reduce R₀. This can be done by:

• Reducing transmissibility.

• Decreasing the number of susceptibles (by vaccination, for example).

• Decreasing the mean number of contacts or the transmissibility, such as by improving sanitation, or limiting the number of interactions sick people have with healthy people.

• Reducing the length of the infectious period.

epitope

The portion of an antigen that the immune system recognizes. An epitope is also called an antigenic determinant.

Euler method

Used in mathematics and computational science, this method is a first-order numerical procedure for solving ordinary differential equations with a given initial value.

exp(

The exponential function, \(e^x\), where \(e\) is the number (approximately 2.718281828) such that the function \(e^x\) is its own derivative. The exponential function is used to model a relationship in which a constant change in the independent variable gives the same proportional change (i.e. percentage increase or decrease) in the dependent variable. The function is often written as \(exp(x)\). The graph of \(y = exp(x)\) is upward-sloping and increases faster as \(x\) increases.

exposed

Individual who has been infected with a pathogen, but due to the pathogen’s incubation period, is not yet infectious.

force of infection (FoI)

A measure of the degree to which an infected individual can spread infection; the per-capita rate at which susceptibles contract infection. Typically increases with transmissibility and prevalence of infection.

herd immunity

The resistance to the spread of a contagious disease within a population that results if a sufficiently high proportion of individuals are immune to the disease, especially through vaccination. The portion of the population that needs to be immunized in order to achieve herd immunity is P > 1 – (1/ R₀), where P = proportion vaccinated * vaccine efficacy.

immune

Unable to become infected/infectious, whether through vaccination or having the disease in the past.

incidence

The rate of new cases of a disease during a specified time period. This is a measure of the risk of contracting a disease.

infectious

Individual who is infected with a pathogen and is capable of transmitting the pathogen to others.

Koppen-Geiger Climate Classification System

A system based on the concept that native vegetation is a good expression of climate. Thus, climate zone boundaries have been selected with vegetation distribution in mind. It combines average annual and monthly temperatures and precipitation, and the seasonality of precipitation. EMOD has several options for configuring the climate, namely air temperature, rainfall, and humidity.

One option utilizes input files that associate geographic nodes with Koppen climate indices. The modified Koppen classification uses three letters to divide the world into five major climate regions (A, B, C, D, and E) based on average annual precipitation, average monthly precipitation, and average monthly temperature. Each category is further divided into sub-categories based on temperature and precipitation. While the Koppen system does not take such things as temperature extremes, average cloud cover, number of days with sunshine, or wind into account, it is a good representation of our earth’s climate.

loss to follow-up (LTFU)

Patients who at one point were actively participating in disease treatment or clinical research, but have become lost either by error or by becoming unreachable at the point of follow-up.

LTFU

See loss to follow-up.

ordinary differential equation (ODE)

A differential equation containing one or more functions of one independent variable and its derivatives.

prevalence

The rate of all cases of a disease during a specified time period. This is a measure of how widespread a disease is.

recovered

Individual who is either no longer infectious, or “removed” from the population.

reproductive number

In a fully susceptible population, the basic reproductive number R₀ is the number of secondary infections generated by the first infectious individual over the course of the infectious period. R₀=S*L* \(\beta\) (where S = the number of susceptible hosts, L = length of infection, and \(\beta\) = transmissibility). When R₀> 1, disease will spread. It is essentially a measure of the expected or average outcome of transmission. The effective reproductive number takes into account non-susceptible individuals. This is the threshold parameter used to determine whether or not an epidemic will occur, and determines:

• The initial rate of increase of an epidemic (the exponential growth phase).

• The final size of an epidemic (what fraction of susceptibles will be infected).

• The endemic equilibrium fraction of susceptibles in a population (1/ R₀).

• The critical vaccination threshold, which is equal to 1-(1/ R₀), and determines the number of people that must be vaccinated to prevent the spread of a pathogen.

routine immunization (RI)

The standard practice of vaccinating the majority of susceptible people in a population against vaccine-preventable diseases.

SEIR model

A generic epidemiological model that provides a simplified means of describing the transmission of an infectious disease through individuals where those individuals can pass through the following five states: susceptible, exposed, infectious, and recovered.

SEIRS model

A generic epidemiological model that provides a simplified means of describing the transmission of an infectious disease through individuals where those individuals can pass through the following five states: susceptible, exposed, infectious, recovered, and susceptible.

SI model

A generic epidemiological model that provides a simplified means of describing the transmission of an infectious disease through individuals where those individuals can pass through the following five states: susceptible and infectious.

simulation burn-in

A modeling concept in which a simulation runs for a period of time before reaching a steady state and the output during that period is not used for predictions. This concept is borrowed from the electronics industry where the first items produced by a manufacturing process are discarded.

SIR model

A generic epidemiological model that provides a simplified means of describing the transmission of an infectious disease through individuals where those individuals can pass through the following five states: susceptible, infectious, and recovered.

SIRS model

A generic epidemiological model that provides a simplified means of describing the transmission of an infectious disease through individuals where those individuals can pass through the following five states: susceptible, infectious, recovered, and susceptible.

SIS model

A generic epidemiological model that provides a simplified means of describing the transmission of an infectious disease through individuals where those individuals can pass through the following five states: susceptible, infectious, and susceptible.

stochastic

Characterized by having a random probability distribution that may be analyzed statistically but not predicted precisely.

stochastic die-out

When an disease outbreak ends, despite having an effective R₀ above 1, due to randomness. A deterministic model cannot estimate the probability of stochastic die- out, but a stochastic model can.

subpatent

When an individual is infected but asymptomatic, so the infection is not readily detectable.

superinfection

The simultaneous infection with multiple strains of the same pathogen.

supplemental immunization activity (SIA)

In contrast to routine immunization (RI), SIAs are large-scale operations with a goal of delivering vaccines to every household.

susceptible

Individual who is able to become infected.

transmissibility (\(\beta\))

Also known as the effective contact rate, is the product of the contact rate and the probability of transmission per contact.

virulence

The capacity of a pathogen to produce disease. It is proportional to parasitemia, or the number of circulating copies of the pathogen in the host. The higher the virulence (given contact between S and I individuals), the more likely transmission is to occur. However, higher virulence means contact may be less likely as infected hosts show more symptoms of the disease. There is a trade-off that occurs between high transmissibility and disease- induced mortality.

WAIFW matrix

A matrix of values that describes the rate of transmission between different population groups. WAIFW is an abbreviation for Who Acquires Infection From Whom.

Weibull distribution

A probability distribution often used in EMOD and that requires both a shape parameter and a scale parameter. The shape parameter governs the shape of the density function. When the shape parameter is equal to 1, it is an exponential distribution. For shape parameters above 1, it forms a unimodal (hump-shaped) density function. As the shape parameter becomes large, the function forms a sharp peak. The inverse of the shape parameter is sometimes referred to here as the “heterogeneity” of the distribution (heterogeneity = 1/shape), because it can be helpful to think about the degree of heterogeneity of draws from the distribution, especially for hump-shaped functions with heterogeneity values between 0 and 1 (i.e., shape parameters greater than 1). The scale parameter shifts the distribution from left to right. When heterogeneity is small (i.e., the shape parameter is large), the scale parameter sets the location of the sharp peak.

EMOD software terms

agent-based model

A type of simulation that models the actions and interactions of autonomous agents (both individual and collective entities such as organizations or groups).

Boost

Free, peer-reviewed, portable C++ source libraries aimed at a wide range of uses including parallel processing applications (Boost.MPI). For more information, please see the Boost website, http://www.boost.org.

boxcar function

A mathematical function that is equal to zero over the entire real line except for a single interval where it is equal to a constant.

campaign

A collection of events that use interventions to modify a simulation.

campaign event

A JSON object that determines when and where an intervention is distributed during a campaign.

campaign file

A JSON (JavaScript Object Notation) formatted file that contains the parameters that specify the distribution instructions for all interventions used in a campaign, such as diagnostic tests, the target demographic, and the timing and cost of interventions. The location of this file is specified in the configuration file with the Campaign_Filename parameter. Typically, the file name is campaign.json.

channel

A property of the simulation (for example, “Parasite Prevalence”) that is accumulated once per simulated time step and written to file, typically as an array of the accumulated values.

class factory

A function that instantiate objects at run-time and use information from JSON-based configuration information in the creation of these objects.

configuration file

A JSON (JavaScript Object Notation) formatted file that contains the parameters sufficient for initiating a simulation. It controls many different aspects of the simulation, such as population size, disease dynamics, and length of the simulation. Typically, the file name is config.json.

core

In computing, a core refers to an independent central processing unit (CPU) in the computer. Multi-core computers have more than one CPU. However, through technologies such as Hyper- Threading Technology (HTT or HT), a single physical core can actually act like two virtual or logical cores, and appear to the operating system as two processors.

demographics file

A JSON (JavaScript Object Notation) formatted file that contains the parameters that specify the demographics of a population, such as age distribution, risk, birthrate, and more. IDM provides demographics files for many geographic regions. This file is typically named <region>_demographics.json.

disease-specific build

A build of the EMOD executable (Eradication.exe) built using SCons without any dynamic link libraries (DLLs).

dynamic link library (DLL)

Microsoft’s implementation of a shared library, separate from the EMOD executable (Eradication.exe), that can be dynamically loaded (and unloaded when unneeded) at runtime. This loading can be explicit or implicit.

EMODule

A modular component of EMOD that are consumed and used by the EMOD executable (Eradication.exe). Under Windows, a EMODule is implemented as a dynamic link library (DLL) and, under CentOS, EMODules are currently not supported. EMODules are primarily custom reporters.

Epidemiological MODeling software (EMOD)

The modeling software from the Institute for Disease Modeling (IDM) for disease researchers and developers to investigate disease dynamics, and to assist in combating a host of infectious diseases. You may see this referred to as Disease Transmission Kernel (DTK) in the source code.

Eradication.exe

Typical (default) name for the EMOD executable (Eradication.exe), whether built using monolithic build or modular (EMODule-enabled) build.

event coordinator

A JSON object that determines who will receive a particular intervention during a campaign.

flattened file

A single campaign or configuration file created by combining a default file with one or more overlay files. Multiple files must be flattened prior to running a simulation. Configuration files are flattened to a single-depth JSON file without nesting, the format required for consumption by the EMOD executable (Eradication.exe). Separating the parameters into multiple files is primarily used for testing and experimentation.

Heterogeneous Intra-Node Transmission (HINT)

A feature for modeling person-to-person transmission of diseases in heterogeneous population segments within a node for generic simulations.

high-performance computing (HPC)

The use of parallel processing for running advanced applications efficiently, reliably, and quickly.

individual properties

Labels that can be applied to individuals within a simulation and used to configure heterogeneous transmission, target interventions, and move individuals through a health care cascade.

input files

The JSON and binary files used as inputs to an EMOD simulation. The primary input files are the JSON-formatted configuration, demographics, and campaign files. They may also include the binary files for migration, climate, population serialization, or load- balancing.

inset chart

The default JSON output report for EMOD that includes multiple channels that contain data at each time step of the simulation. These channels include number of new infections, prevalence, number of recovered, and more.

intervention

An object aimed at reducing the spread of a disease that is distributed either to an individual; such as a vaccine, drug, or bednet; or to a node; such as a larvicide. Additionally, initial disease outbreaks and intermediate interventions that schedule another intervention are implemented as interventions in the campaign file.

JSON

See JavaSCript Object Notation.

JSON (JavaScript Object Notation)

A human-readable, open standard, text-based file format for data interchange. It is typically used to represent simple data structures and associative arrays, and is language-independent. For more information, see https://www.json.org.

Keyhole Markup Language (KML)

A file format used to display geographic data in an Earth browser, for example, Google Maps. The format uses an XML-based structure (tag-based structure with nested elements and attributes). Tags are case-sensitive.

Link-Time Code Generation (LTCG)

A method for the linker to optimize code (for size and/or speed) after compilation has occurred. The compiled code is turned not into actual code, but instead into an intermediate language form (IL, but not to be confused with .NET IL which has a different purpose). The LTCG then, unlike the compiler, can see the whole body of code in all object files and be able to optimize the result more effectively.

Message Passing Interface (MPI)

An interface used to pass information between computing cores in parallel simulations. One example is the migration of individuals from one geographic location to another within EMOD simulations.

microsolver

A type of “miniature model” that operates within the framework of EMOD to compute a particular set of parameters. Each microsolver, in effect, is creating a microsimulation in order to accurately capture the dynamics of that particular aspect of the model.

monolithic build

A single EMOD executable (Eradication.exe) with no DLLs that includes all components as part of Eradication.exe itself. You can still use EMODules with the monolithic build; for example, a custom reporter is a common type of EMODule. View the documentation on EMODules and emodules_map.json for more information about creation and use of EMODules.

Monte Carlo method

A class of algorithms using repeated random sampling to obtain numerical results. Monte Carlo simulations create probability distributions for possible outcomes, which provides a more realistic way of describing uncertainty.

node

A grid size that is used for modeling geographies. Within EMOD, a node is a geographic region containing simulated individuals. Individuals migrate between nodes either temporarily or permanently using mobility patterns driven by local, regional, and long- distance transportation.

node properties

Labels that can be applied to nodes within a simulation and used to target interventions based on geography.

node-targeted intervention

An intervention that is distributed to a geographical node rather than to a single individual. One example is larvicides, which affect all mosquitoes living and feeding within a given node.

nodes

See node.

output report

A file that is the output from an EMOD simulation. Output reports are in JSON, CSV, or binary file format. You must pass the data from an output report to graphing software if you want to visualize the output of a simulation.

overlay file

An additional configuration, campaign, or demographic file that overrides the default parameter values in the primary file. Separating the parameters into multiple files is primarily used for testing a nd experimentation. In the case of configuration and campaign files, the files can use an arbitrary hierarchical structure to organize parameters into logical groups. Configuration and campaign files must be flattened into a single file before running a simulation.

preview

Software that undergoes a shorter testing cycle in order to make it available more quickly. Previews may contain software defects that could result in unexpected behavior. Use EMOD previews at your own discretion.

regression test

A test to verify that existing EMOD functionality works with new updates, located in the Regression subdirectory of the EMOD source code repository. Directory names of each subdirectory in Regression describe the main regression attributes, for example, “1_Generic_Seattle_MultiNode”. Also can refer to the process of regression testing of software.

release

Software that includes new functionality, scientific tutorials leveraging new or existing functionality, and/or bug fixes that have been thoroughly tested so that any defects have been fixed before release. EMOD releases undergo full regression testing.

reporter

Functionality that extracts simulation data, aggregates it, and saves it as an output report. EMOD provides several built-in reporters for outputting data from simulations and you also have the ability to create a custom reporter.

scenario

A collection of input files that describes a real-world example of a disease outbreak and interventions. Many scenarios are included with EMOD source installations or are available to download at EMOD scenarios to learn more about epidemiology and disease modeling.

schema

A text or JSON file that can be generated from the EMOD executable (Eradication.exe) that defines all configuration and campaign parameters.

simulation

An execution of the EMOD software using an associated set of input files.

simulation type

The disease or disease class to model.

EMOD supports the following simulation types for modeling a variety of diseases:

• Generic disease (GENERIC_SIM), which can be used for modeling a variety of diseases such as influenza or measles

• Vector-borne diseases (VECTOR_SIM), which can be used for modeling vector-borne diseases such as dengue

• Malaria (MALARIA_SIM), which adds features specific to malaria biology and treatment

• Tuberculosis with HIV coinfection (TBHIV_SIM), which can be used for modeling TB transmission, with the option to add HIV coinfection as a contributing factor

• Sexually transmitted infections (STI_SIM), which adds features for sexual relationship networks

• HIV (HIV_SIM), which adds features specific to HIV biology and treatment

• Environmental transmission (ENVIRONMENTAL_SIM), which adds features for diseases transmitted through contaminated food or water

• Typhoid (TYPHOID_SIM), which adds features specific to typhoid biology and treatment

solvers

Solvers are used to find computational solutions to problems. In simulations, they can be used, for example, to determine the time of the next simulation step, or to compute the states of a model at particular time steps.

Standard Template Library (STL)

A library that contains a set of common C++ classes (including generic algorithms and data structures) that are independent of container and implemented as templates, which enables compile-time polymorphism (often more efficient than run-time polymorphism). For more information and discussion of STL, see Wikipedia - Standard Template Library for more information.

state transition event

A change in state (e.g. healthy to infected, undiagnosed to positive diagnosis, or birth) that may trigger a subsequent action, often an intervention. “Campaign events” should not be confused with state transition events.

time step

A discrete number of hours or days in which the “simulation states” of all “simulation objects” (interventions, infections, immune systems, or individuals) are updated in a simulation. Each time step will complete processing before launching the next one. For example, a time step would process the migration data for populations moving between nodes via rail, airline, and road. The migration of individuals between nodes is the last step of the time step after updating states.

tutorial

A set of instructions in the documentation to learn more about epidemiology and disease modeling. Tutorials are based on real-world scenarios and demonstrate the mechanics of the the model. Each tutorial consists of one or more scenarios.

working directory

The directory that contains the configuration and campaign files for a simulation. You must be in this directory when you invoke Eradication.exe at the command line to run a simulation.

Vector terms

cohort model

A vector model that tracks properties of mosquito “cohorts”, for example, population, age, gender, fertility, etc.

entomological inoculation rate (EIR)

The commonly-used measure of the intensity of vector-borne disease transmission. EIR is equal to the number of mosquito bites per night times the proportion of those bites that test positive for infectious agents, such as sporozoites in malaria.

gene drive mosquito

Gene drive is a genetic technique that promotes the inheritance of particular genes or specific genetic elements. In mosquitoes, approaches are being tested that work to suppress the spread of malaria by creating mosquito lines through fertility suppression, driving-Y chromosomes, or express genes that limit malaria transmission.

gonotrophic

A female mosquito’s feeding and egg-laying cycle, where the duration is defined as the average number of days that gravid mosquitoes take to oviposit after taking a blood meal.

homing endonuclease gene (HEG)

A “selfish” genetic element that can spread through the mosquito population even at a cost to the host. The HEG allele status is a tracked property of mosquitoes. Large numbers of HEG- positive mosquitoes may be introduced into the simulation by a MosquitoRelease intervention.

individual mosquito model

A vector model simulation where every individual mosquito in the population is modeled, as well as a simulation of a sampled subset of mosquitoes to represent the population as the whole.

indoor residual spraying (IRS)

The process of spraying insecticide on the interior surfaces of dwellings in order to repel or kill mosquitoes.

insecticide-treated nets (ITN)

Bednets hung over sleeping areas that are treated with insecticide to repel mosquitoes and kill those that land on them.

larval habitat

Mosquito larval ecology includes several habitat types including brackish swamp, constant, human population, temporary rainfall, and semi-permanent water vegetation.

larvicide

A node-targeted intervention that may be configured to have a direct killing effect on the larval population and a temporary reduction on available larval habitat.

oviposition

To deposit or lay eggs.

spatial repellent

An intervention that may be individually-distributed (protective indoors and outdoors), or node-distributed at the community-level, that repels mosquitoes from biting.

sugar-baited trap

Bait stations, often placed inside houses, that have an attractive and toxic sugar used to attract and kill sugar-feeding male and female mosquitoes.

vector

Insect or other living carrier that transmits an infectious agent. The vector life cycle and feeding cycle in the model are described in the article Eckhoff, Malaria Journal 2011, 10:303.

vector model

The vector model includes both a cohort model and an individual mosquito model. The model is a closed-loop feeding cycle where successful animal feeds (both indoors and outdoors) produce eggs, larva, vector mating, and then, adult mosquitoes. The vector model inherits the same human- infection model structure from the generic simulation type: uninfected, latent incubation, infectious, multiple immune variables, and superinfection. However, the transmission of infections is not between individual humans, but rather via the human-to-vector and vector- to-human pathways.

vectorial capacity

The daily rate of all mosquitoes that would be infected after biting a single infectious host. This measure can be used to describe the transmission intensity of malaria, and serves as a rate at which future infections arise from a currently infected host.

Wolbachia

This is a genus of bacteria that infects many arthopod species (especially insects). It has been discovered that insects infected with Wolbachia have increased resistance to viral or other parasitic infections. Work is underway to determine if strains of modified Wolbachia can be used to control malaria, by effectively preventing mosquitoes from becoming infected with Plasmodium parasites.

Malaria terms

circumsporozoite protein (CSP)

One of two proteins (the other being thrombospondin-related adhesive protein) involved in sporozoite recognition of host cells in malaria.

CRISPR

A genome-editing technique that utilizes the CRISPR/Cas9 system (a prokaryotic immune system) that can be used to splice DNA sequences in very specific target locations, enabling the precise insertion or removal of genes of interest.

cytokine

Cytokines are small secreted proteins that are released by cells, and have specific effects on interactions and communications between cells. They are especially important in the immune system, and can function in inflammatory (and anti-inflammatory) response.

gametocyte

The male and female sexual forms of the blood-stage malaria parasite. During blood-feeding, gametocytes are taken up into the mosquito mid-gut where they commence the mosquito-phase of the parasite life cycle.

gametocytes

The plural of gametocyte.

hepatocyte

The cell type that comprises liver tissue.

mass drug administration (MDA)

The treatment of an entire population in a geographic area with a curative dose of an antimalarial drug without first testing for infection, and regardless of the presence of symptoms.

merozoite

The malaria parasite stage that invades red blood cells. After each cycle of asexual reproduction within the infected red blood cell, merozoites are released into the bloodstream to invade new red blood cells.

merozoite surface protein (MSP)

A type of protein integral to red blood cell invasion by malaria parasites that is an important target of the human immune response.

merozoites

See merozoite.

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1)

A protein encoded by the malaria parasite and expressed on the surface of infected red blood cells. PfEMP1 adheres to various human receptors, allowing sequestration of parasitized red blood cells and avoidance of clearance in the spleen. PfEMP1 is an important antigenic target of the human adapted immune response. It exhibits a high degree of antigenic variation via a genetic switching mechanism evolved to escape immune pressure.

pre-erythrocytic

Stages of a malaria parasite that occur before the red blood cells are invaded. This includes the period starting from inoculation with sporozoites, through the liver-stage multiplication, up to infected hepatocyte rupture, and the first invasion of erythrocytes by merozoites.

pre-erythrocytic vaccine (PEV)

A vaccine targeted at the earliest stage of malaria parasite development, namely before the blood-stage infection. Other vaccines target the asexual and sexual stages of the parasite.

schizont

Cells formed during the asexual stage of the life cycle of sporozoan protozoans, such as the malaria parasite.

sporogony

The asexual process of spore formation in parasitic sporozoans.

sporozoite

a motile, spore-like stage of the malaria parasite that is the infectious agent introduced into the host.

transmission-blocking vaccine (TBV)

A vaccine that blocks gametocytes from infected humans by producing viable sporozoites in mosquitoes. Also referred to as a “sexual-stage” vaccine, since vaccines in this class block gametocytes from infected humans by producing viable sporozoites in mosquitoes.

vaccine intervention types

In EMOD, vaccine intervention types are either “AcquisitionBlocking”, “TransmissionBlocking” or “MortalityBlocking”. For example, “mode-of-action”, “targeted parasite stages”, (such as pre-erythrocytic, asexual, or sexual), etc.