Immunity

The following parameters determine the immune system response for the disease being modeled, including waning immunity after an infection clears.

Note

Parameters are case-sensitive. For Boolean parameters, set to 1 for true or 0 for false. Minimum, maximum, or default values of “NA” indicate that those values are not applicable for that parameter.

EMOD does not use true defaults; that is, if the dependency relationships indicate that a parameter is required, you must supply a value for it. However, many of the tools used to work with EMOD will use the default values provided below.

JSON format does not permit comments, but you can add “dummy” parameters to add contextual information to your files. Any keys that are not EMOD parameter names will be ignored by the model.

Parameter

Data type

Minimum

Maximum

Default

Description

Example

Acquisition_Blocking_Immunity_Decay_Rate

float

0

1

0.001

The rate at which acquisition-blocking immunity decays after the initial period indicated by the base acquisition-blocking immunity offset. Only used when Enable_Immunity and Enable_Immune_Decay parameters are set to true (1).

 
{
    "Acquisition_Blocking_Immunity_Decay_Rate": 0.05
}

Acquisition_Blocking_Immunity_Duration_Before_Decay

float

0

45000

0

The number of days after infection until acquisition-blocking immunity begins to decay. Enable_Immunity and Enable_Immune_Decay must be set to true (1).

 
{
    "Acquisition_Blocking_Immunity_Duration_Before_Decay": 10
}

Antibody_Capacity_Growth_Rate

float

0

1

0.1

The maximum daily rate of specific antibody capacity increase. Antibody production begins at a capacity of 0.3., and hyperimmunity results at 0.4. The actual growth rate tends to be lower and is a function of antigen concentrations.

 
{
    "Antibody_Capacity_Growth_Rate": 0.09
}

Antibody_CSP_Decay_Days

float

1

3.40E+38

90

Exponential decay time for the circumsporozoite protein (CSP) antibody concentration (in days) when boosted above natural maximum concentrations.

 
{
    "Antibody_CSP_Decay_Days": 80
}

Antibody_CSP_Killing_Inverse_Width

float

1.00E-0

1000000

1.5

The inverse width of the sigmoidal sporozoite killing function of circumsporozoite protein (CSP) antibody concentration.

 
{
    "Antibody_CSP_Killing_Inverse_Width": 1.7
}

Antibody_CSP_Killing_Threshold

float

1.00E-0

1000000

10

The threshold value on circumsporozoite protein (CSP) antibody concentration for sporozoite killing.

 
{
    "Antibody_CSP_Killing_Threshold": 20
}

Antibody_IRBC_Kill_Rate

double

NA

NA

2

The scale factor multiplied by antibody level to produce the rate of clearance of the infected red blood cell (IRBC) population.

 
{
    "Antibody_IRBC_Kill_Rate": 1.595
}

Antibody_Memory_Level

float

0

0.35

0.2

The limiting level of antibody capacity that remains after a prolonged absence of a specific antigen. The antibody capacity decays to this level gradually after infection is cleared. The decay rate in antibody capacity is set so that hyperimmunity is lost within 4 months, and capacity continues to decay to this level. The antibody memory level is relevant for year-scale dynamics, but not for long-term dynamics (10-20 years).

 
{
    "Antibody_Memory_Level": 0.3
}

Antibody_Stimulation_C50

float

0.1

10000

10

The concentration of an antigen, measured in IRBC/ul at which growth in antibody capacity against the antigen increases at half the maximum rate specified by Antibody_Capacity_Growth_Rate.

 
{
    "Antibody_Stimulation_C50": 30,
    "Antibody_Capacity_Growth_Rate": 0.09
}

Antigen_Switch_Rate

double

NA

NA

2.00E-09

The antigenic switching rate per infected red blood cell per asexual cycle. See Parasite_Switch_Type for different switching patterns.

 
{
    "Antigen_Switch_Rate": 5e-09
}

Cytokine_Gametocyte_Inactivation

float

0

1

0.02

The strength of inflammatory response inactivation of gametocytes.

 
{
    "Cytokine_Gametocyte_Inactivation": 0.0167
}

Enable_Immunity

boolean

0

1

1

Controls whether or not an individual has protective immunity after an infection clears.

 
{
    "Enable_Immunity": 1
}

Enable_Initial_Susceptibility_Distribution

boolean

0

1

0

Controls whether or not individuals in the population have immunity at the beginning of the simulation. If set to 0, individuals are not initialized with immunity but may acquire immunity. If set to 1, you must indicate the type of distribution to use for immunity in the configuration parameter Immunity_Initialization_Distribution_Type and the distribution values in the demographics file. Enable_Immunity must be set to 1.

 
{
    "Enable_Immunity": 1,
    "Enable_Initial_Susceptibility_Distribution": 1,
    "Immunity_Initialization_Distribution_Type": "DISTRIBUTION_SIMPLE"
}

Enable_Maternal_Antibodies_Transmission

boolean

0

1

0

Controls whether or not mothers pass antibodies to their infants. When enabled, you must set Maternal_Antibodies_Type,**Maternal_Antibody_Protection**, and Maternal_Antibody_Decay_Rate. Enable_Birth must be set to 1.

 
{
    "Enable_Maternal_Antibodies_Transmission": 1,
    "Maternal_Antibodies_Type": "SIMPLE_WANING",
    "Maternal_Antibody_Protection": 0.23,
    "Maternal_Antibody_Decay_Rate": 0.03
}

Enable_Maternal_Protection

boolean

0

1

0

Controls whether or not mothers pass immunity on to their infants. Setting to 1 (true) enables maternal protection as defined by Maternal_Protection_Type. Enable_Birth must be set to 1 (true).

 
{
    "Enable_Maternal_Protection": 1,
    "Maternal_Protection_Type": "LINEAR_FRACTIONAL"
}

Erythropoiesis_Anemia_Effect

float

0

1000

3.5

The exponential rate of increased red-blood-cell production from reduced red-blood-cell availability.

 
{
    "Erythropoiesis_Anemia_Effect": 3
}

Falciparum_MSP_Variants

integer

0

1000

100

The number of distinct merozoite surface protein (MSP) variants for P. falciparum malaria in the overall parasite population in the simulation, not necessarily in an individual.

 
{
    "Falciparum_MSP_Variants": 4
}

Falciparum_Nonspecific_Types

integer

0

1000

20

The number of distinct non-specific types of P. falciparum malaria.

 
{
    "Falciparum_Nonspecific_Types": 92
}

Falciparum_PfEMP1_Variants

integer

0

100000

1000

The number of distinct Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants for P. falciparum malaria in the overall parasite population in the simulation.

 
{
    "Falciparum_PfEMP1_Variants": 300
}

Fever_IRBC_Kill_Rate

float

0

1000

0.15

The maximum kill rate for infected red blood cells due to the inflammatory innate immune response. As fever increases above 38.5 degrees Celsius, the kill rate becomes successively higher along a sigmoidal curve approaching this rate.

 
{
    "Fever_IRBC_Kill_Rate": 1.4
}

Immune_Threshold_For_Downsampling

float

0

1

0

The threshold on acquisition immunity at which to apply immunity-dependent downsampling; individuals who are more immune than this this threshold are downsampled. A value of 1 is equivalent to full susceptibility and 0 is equivalent to full immunity. If the acquisition immunity modifier is larger than the threshold, no downsampling occurs. Individual_Sampling_Type must set to ADAPTED_SAMPLING_BY_IMMUNE_STATE.

 
{
    "Relative_Sample_Rate_Immune": 0.1,
    "Immune_Threshold_For_Downsampling": 0.5,
    "Individual_Sampling_Type": "ADAPTED_SAMPLING_BY_IMMUNE_STATE"
}

Innate_Immune_Variation_Type

enum

NA

NA

NONE

The type of innate immunity on which to apply individual-level variation. Possible values are:

NONE

No variation in innate immunity between individuals.

PYROGENIC_THRESHOLD

Applies individual variation using the susceptibility distribution values set in SusceptibilityDistributionFlag, SusceptibilityDistribution1, and SusceptibilityDistribution2 in the demographics file to the average threshold for infected red blood cells resulting in fever, as set in Pyrogenic_Threshold.

PYROGENIC_THRESHOLD_VS_AGE

Ignores the demographic file settings and applies an age-dependent threshold for infected red blood cells resulting in fever.

CYTOKINE_KILLING

Applies individual variation using the susceptibility distribution values set in SusceptibilityDistributionFlag, SusceptibilityDistribution1, and SusceptibilityDistribution2 in the demographics file to the effectiveness of cytokines in killing infected red blood cells, as set in Fever_IRBC_Kill_Rate.

 
{
    "Innate_Immune_Variation_Type": "PYROGENIC_THRESHOLD"
}

Maternal_Antibodies_Type

enum

NA

NA

OFF

The type of maternal antibody protection. Enable_Maternal_Antibodies_Transmission must be set to 1 (true). Possible values are:

OFF

No maternal antibody protection provided.

SIMPLE_WANING

The protection from maternal antibodies is a function of the configured maximum fraction protection (Maternal_Antibody_Protection) and the age of the child (through Maternal_Antibody_Decay_Rate), but also of the transmission-intensity in the simulation. In particular, the protection is modified by a factor corresponding to the fraction of PfEMP1 antigenic variants to which possible mothers (14 to 45-year-old females) have been exposed in their lifetimes.

CONSTANT_INITIAL_IMMUNITY

Protection is independent of acquired immunity in possible mothers.

 
{
    "Maternal_Antibodies_Type": "CONSTANT_INITIAL_IMMUNITY"
}

Maternal_Antibody_Decay_Rate

float

0

3.40E+38

0.01

The decay rate per day in protection from maternal antibodies. Maternal_Antibodies_Type must be set to SIMPLE_WANING or CONSTANT_INITIAL_IMMUNITY.

 
{
    "Maternal_Antibodies_Type": "SIMPLE_WANING",
    "Maternal_Antibody_Decay_Rate": 0.01,
    "Maternal_Antibody_Protection": 0.1327
}

Maternal_Antibody_Protection

float

0

1

0.1

The strength of protection from maternal antibodies as a multiple of full antibody killing effect. Maternal_Antibodies_Type must be set to SIMPLE_WANING or CONSTANT_INITIAL_IMMUNITY.

 
{
    "Maternal_Antibodies_Type": "SIMPLE_WANING",
    "Maternal_Antibody_Decay_Rate": 0.01,
    "Maternal_Antibody_Protection": 0.1327
}

Maternal_Linear_Slope

float

0.0001

1

0.01

Slope parameter describing the rate of waning for maternal protection, must be positive. The per-day increase in susceptibility. Maternal_Protection_Type must be set to LINEAR_FRACTIONAL or LINEAR_BINARY.

 
{
    "Maternal_Protection_Type": "LINEAR_FRACTIONAL",
    "Maternal_Linear_SusZero": 0.45,
    "Maternal_Linear_Slope": 0.02
}

Maternal_Linear_SusZero

float

0

1

0.2

The initial level of maternal protection at age 0, given as susceptibility. A value of 0.0 implies total protection, a value of 1.0 implies no protection. Maternal_Protection_Type must be set to LINEAR_FRACTIONAL or LINEAR_BINARY.

 
{
    "Maternal_Protection_Type": "LINEAR_FRACTIONAL",
    "Maternal_Linear_SusZero": 0.45,
    "Maternal_Linear_Slope": 0.02
}

Maternal_Protection_Type

enum

NA

NA

NONE

The type of maternal protection afforded to infants. Enable_Maternal_Protection must be set to 1 (true). Possible values are:

NONE

No immune protection is passed on to infants.

LINEAR

Susceptibility is a function of age and governed by a linear equation. Susceptibility = Maternal_Linear_Slope * age + Maternal_Linear_SusZero

SIGMOID

Susceptibility is a function of age and governed by a sigmoidal equation. Susceptibility = Maternal_Sigmoid_SusInit + (1.0 - Maternal_Sigmoid_SusInit) / * (1.0 + EXP(( Maternal_Sigmoid_HalfMaxAge - age) / Maternal_Sigmoid_SteepFac))

You must set Susceptibility_Type to determine if susceptibility at a particular age is interpreted as a fractional value or the probability of complete immunity or susceptibility.

 
{
    "Enable_Maternal_Protection": 1,
    "Maternal_Protection_Type": "LINEAR_FRACTIONAL"
}

Maternal_Sigmoid_HalfMaxAge

float

-270

3650

180

The age in days that the level of maternal protection is half of its initial value. Maternal_Protection_Type must be set to SIGMOID_FRACTIONAL or SIGMOID_BINARY.

 
{
    "Maternal_Protection_Type": "SIGMOID_BINARY",
    "Maternal_Sigmoid_SteepFac": 30,
    "Maternal_Sigmoid_HalfMaxAge": 365,
    "Maternal_Sigmoid_SusInit": 0.0002
}

Maternal_Sigmoid_SteepFac

float

0.1

1000

30

The steepness factor describing the rate of waning for maternal protection, must be positive. Small values imply rapid waning.**Maternal_Protection_Type** must be set to SIGMOID_FRACTIONAL or SIGMOID_BINARY.

 
{
    "Maternal_Protection_Type": "SIGMOID_BINARY",
    "Maternal_Sigmoid_SteepFac": 30,
    "Maternal_Sigmoid_HalfMaxAge": 365,
    "Maternal_Sigmoid_SusInit": 0.0002
}

Maternal_Sigmoid_SusInit

float

0

1

0

The initial level of maternal protection at age -INF, given as susceptibility. A value of 0.0 implies total protection, a value of 1.0 implies no protection. Maternal_Protection_Type must be set to SIGMOID_FRACTIONAL or SIGMOID_BINARY.

 
{
    "Maternal_Protection_Type": "SIGMOID_BINARY",
    "Maternal_Sigmoid_SteepFac": 30,
    "Maternal_Sigmoid_HalfMaxAge": 365,
    "Maternal_Sigmoid_SusInit": 0.0002
}

Max_MSP1_Antibody_Growthrate

float

0

1

0.02

The maximum increase in MSP1 antibody capacity during each asexual cycle. The higher this value, the sooner early clearances are observed and the earlier the parasite density envelope decreases.

 
{
    "Max_MSP1_Antibody_Growthrate": 0.045
}

Min_Adapted_Response

float

0

1

0.02

The minimum level of antibody stimulation to a novel antigen. The value sets the low-range asymptote for antibody capacity growth, which is calculated from Antibody_Capacity_Growth_Rate and antigen density, in the presence of any nonzero antigen level.

 
{
    "Min_Adapted_Response": 0.01
}

Mortality_Blocking_Immunity_Decay_Rate

float

0

1

0.001

The rate at which mortality-blocking immunity decays after the mortality-blocking immunity offset period. Enable_Immune_Decay must be set to 1.

 
{
    "Mortality_Blocking_Immunity_Decay_Rate": 0.1
}

Mortality_Blocking_Immunity_Duration_Before_Decay

float

0

45000

0

The number of days after infection until mortality-blocking immunity begins to decay. Enable_Immunity and Enable_Immune_Decay must be set to 1.

 
{
    "Mortality_Blocking_Immunity_Duration_Before_Decay": 270
}

MSP1_Merozoite_Kill_Fraction

double

NA

NA

0.5

The fraction of merozoites inhibited from invading new erythrocytes when MSP1-specific antibody level is 1.

 
{
    "MSP1_Merozoite_Kill_Fraction": 0.4364623975644405
}

Nonspecific_Antibody_Growth_Rate_Factor

float

0

1000

0.5

The factor that adjusts Antibody_Capacity_Growth_Rate for less immunogenic surface proteins, called minor epitopes.

 
{
    "Nonspecific_Antibody_Growth_Rate_Factor": 0.5
}

Nonspecific_Antigenicity_Factor

double

NA

NA

0.2

The nonspecific antigenicity factor that adjusts antibody IRBC kill rate to account for IRBCs caused by antibody responses to antigenically weak surface proteins.

 
{
    "Nonspecific_Antigenicity_Factor": 0.39192559432597257
}

Post_Infection_Acquisition_Multiplier

float

0

1

0

The multiplicative reduction in the probability of reacquiring disease. At the time of recovery, the immunity against acquisition is multiplied by Acquisition_Blocking_Immunity_Decay_Rate x (1 - Post_Infection_Acquisition_Multiplier). Enable_Immunity must be set to 1 (true).

 
{
    "Enable_Immunity": 1,
    "Enable_Immune_Decay": 1,
    "Post_Infection_Acquisition_Multiplier": 0.9
}

Post_Infection_Mortality_Multiplier

float

0

1

0

The multiplicative reduction in the probability of dying from infection after getting reinfected. At the time of recovery, the immunity against mortality is multiplied by Mortality_Blocking_Immunity_Decay_Rate x (1 - Post_Infection_Mortality_Multiplier). Enable_Immunity must be set to 1 (true).

 
{
    "Enable_Immunity": 1,
    "Enable_Immune_Decay": 1,
    "Post_Infection_Mortality_Multiplier": 0.5
}

Post_Infection_Transmission_Multiplier

float

0

1

0

The multiplicative reduction in the probability of transmitting infection after getting reinfected. At the time of recovery, the immunity against transmission is multiplied by Transmission_Blocking_Immunity_Decay_Rate x (1 - Post_Infection_Transmission_Multiplier). Enable_Immunity must be set to 1 (true).

 
{
    "Enable_Immunity": 1,
    "Enable_Immunity_Decay": 1,
    "Post_Infection_Transmission_Multiplier": 0.9
}

RBC_Destruction_Multiplier

double

NA

NA

9.5

The number of total red blood cells destroyed per infected rupturing schizont.

 
{
    "RBC_Destruction_Multiplier": 3.291048711
}

Susceptibility_Initialization_Distribution_Type

enum

NA

NA

DISTRIBUTION_OFF

The method for initializing the susceptibility distribution in the simulated population. Enable_Initial_Susceptibility_Distribution must be set to 1 (true). Possible values are:

DISTRIBUTION_OFF

All individuals default to no susceptibility.

DISTRIBUTION_SIMPLE

Individual susceptibilities are drawn from a distribution whose functional form and parameters are specified in the demographics file in IndividualAttributes using SusceptibilityDistributionFlag, SusceptibilityDistribution1, and SusceptibilityDistribution2 (see Simple distributions parameters).

DISTRIBUTION_COMPLEX

Individual susceptibilities are drawn from an age-dependent piecewise linear function for each specific antibody in the demographics file (see Complex distributions parameters).

 
{
    "Enable_Immunity": 1,
    "Enable_Initial_Susceptibility_Distribution": 1,
    "Susceptibility_Initialization_Distribution_Type": "DISTRIBUTION_COMPLEX"
}

Susceptibility_Type

enum

NA

NA

FRACTIONAL

Controls implementation of an individual’s susceptibility. Currently only relevant to Maternal_Protection_Type parameter. Possible values are:

FRACTIONAL

All agents are assigned equal values between 0 and 1 according to a governing equation as specified by Maternal_Protection_Type.

BINARY

Agents receive a value of either 0 or 1 (complete immunity or susceptibility) with the probability determined by a governing equation as specified by Maternal_Protection_Type.

 
{
    "Susceptibility_Type": "FRACTIONAL",
    "Enable_Maternal_Protection": 1,
    "Maternal_Protection_Type": "LINEAR_FRACTIONAL"
}

Transmission_Blocking_Immunity_Decay_Rate

float

0

1000

0.001

The rate at which transmission-blocking immunity decays after the base transmission-blocking immunity offset period. Used only when Enable_Immunity and Enable_Immune_Decay parameters are set to true (1).

 
{
    "Transmission_Blocking_Immunity_Decay_Rate": 0.01
}

Transmission_Blocking_Immunity_Duration_Before_Decay

float

0

45000

0

The number of days after infection until transmission-blocking immunity begins to decay. Only used when Enable_Immunity and Enable_Immune_Decay parameters are set to true (1).

 
{
    "Transmission_Blocking_Immunity_Duration_Before_Decay": 90
}