void IndividualHumanMalaria::CountPositiveSlideFields( RANDOMBASE * rng, int nfields, float uL_per_field, int& positive_asexual_fields, int& positive_gametocyte_fields) const
{
float asexual_density = GetMalariaSusceptibilityContext()->get_parasite_density();
float gametocyte_density = (m_female_gametocytes + m_male_gametocytes) * m_inv_microliters_blood;
float asexual_prob_per_field = EXPCDF(-asexual_density * uL_per_field);
float gametocyte_prob_per_field = EXPCDF(-gametocyte_density * uL_per_field);
// binomial random draw (or poisson/normal approximations thereof)
positive_asexual_fields = rng->binomial_approx2(nfields, asexual_prob_per_field);
positive_gametocyte_fields = rng->binomial_approx2(nfields, gametocyte_prob_per_field);
}
void VectorProbabilities::SetNodeProbabilities(INodeVectorInterventionEffects* invie, float dt)
{
outdoorareakilling = EXPCDF( -dt * invie->GetOutdoorKilling() );
outdoorareakilling_male = EXPCDF( -dt * invie->GetOutdoorKillingMale() );
kill_PFV = invie->GetPFVKill();
attraction_ADIV = invie->GetADIVAttraction();
attraction_ADOV = invie->GetADOVAttraction();
spatial_repellent = invie->GetVillageSpatialRepellent();
sugarTrapKilling = invie->GetSugarFeedKilling();
kill_livestockfeed = invie->GetAnimalFeedKilling();
outdoorRestKilling = invie->GetOutdoorRestKilling();
}
void VectorProbabilities::SetNodeProbabilities(INodeVectorInterventionEffects* invie, float dt)
{
outdoorareakilling = EXPCDF( -dt * invie->GetOutdoorKilling() );
outdoorareakilling_male = EXPCDF( -dt * invie->GetOutdoorKillingMale() );
kill_PFV = invie->GetPFVKill();
attraction_ADIV = invie->GetADIVAttraction();
attraction_ADOV = invie->GetADOVAttraction();
spatial_repellent = invie->GetVillageSpatialRepellent();
sugarTrapKilling = invie->GetSugarFeedKilling();
kill_livestockfeed = invie->GetAnimalFeedKilling();
outdoorRestKilling = invie->GetOutdoorRestKilling();
ADbiocontrol_additional_mortality = 0.0f; // AD biocontrol not implemented (this would be for non-immediate mortality, i.e. an increased mortality over the days following exposure)
}
void IndividualHumanVector::ApplyTotalBitingExposure()
{
// Make random draw whether to acquire new infection
// dt incorporated already in ExposeIndividual function arguments
float acquisition_probability = float(EXPCDF(-m_total_exposure));
if ( randgen->e() >= acquisition_probability ) return;
// Choose a strain based on a weighted draw over values from all vector-to-human pools
float strain_cdf_draw = randgen->e() * m_total_exposure;
std::vector<strain_exposure_t>::iterator it = std::lower_bound( m_strain_exposure.begin(), m_strain_exposure.end(), strain_cdf_draw, compare_strain_exposure_float_less());
AcquireNewInfection(&(it->first));
}
bool ClimateByData::IsPlausible()
{
// check to see whether fewer than 2.5% of the values will exceed the upper- and lower-bounds
int low_index = int(num_datapoints * 0.025);
int high_index = int(num_datapoints * 0.975);
std::vector<float> sorted = airtemperature_data;
sort(sorted.begin(), sorted.end());
if( sorted[high_index] + (2 * airtemperature_variance) > max_airtemp ||
sorted[low_index] - (2 * airtemperature_variance) < min_airtemp )
{
return false;
}
sorted = landtemperature_data;
sort(sorted.begin(), sorted.end());
if( sorted[high_index] + (2 * landtemperature_variance) > max_landtemp ||
sorted[low_index] - (2 * landtemperature_variance) < min_landtemp )
{
return false;
}
sorted = humidity_data;
sort(sorted.begin(), sorted.end());
if( sorted[high_index] > 1.0 || sorted[low_index] < 0.0 )
return false;
sorted = rainfall_data;
sort(sorted.begin(), sorted.end());
if(sorted[low_index] < 0)
return false;
if((rainfall_variance_enabled && (EXPCDF(-1 / sorted[high_index] * resolution_correction * max_rainfall) < 0.975)) ||
(!rainfall_variance_enabled && sorted[high_index] * resolution_correction > max_rainfall))
{
return false;
}
return true;
}
bool ClimateConstant::IsPlausible()
{
if( base_airtemperature + (2 * airtemperature_variance) > max_airtemp ||
base_airtemperature - (2 * airtemperature_variance) < min_airtemp ||
base_landtemperature + (2 * landtemperature_variance) > max_landtemp ||
base_landtemperature - (2 * landtemperature_variance) < min_landtemp ||
base_rainfall < 0.0 ||
base_humidity > 1.0 ||
base_humidity < 0.0 )
{
LOG_DEBUG( "IsPlausible returning false\n" );
return false;
}
if((rainfall_variance_enabled && (EXPCDF(-1 /base_rainfall * max_rainfall) < 0.975)) ||
(!rainfall_variance_enabled && base_rainfall > max_rainfall))
{
LOG_DEBUG( "IsPlausible returning false\n" );
return false;
}
return true;
}
void IndividualHumanMalaria::DepositInfectiousnessFromGametocytes()
{
release_assert( malaria_susceptibility );
m_inv_microliters_blood = malaria_susceptibility->get_inv_microliters_blood();
// Now add a factor to limit inactivation of gametocytes by inflammatory cytokines
// Important for slope of infectivity v. gametocyte counts
double fever_effect = malaria_susceptibility->get_cytokines();
fever_effect = Sigmoid::basic_sigmoid(SusceptibilityMalariaConfig::cytokine_gametocyte_inactivation, float(fever_effect));
// fever_effect*=0.95;
// Infectivity is reviewed by Sinden, R. E., G. A. Butcher, et al. (1996). "Regulation of Infectivity of Plasmodium to the Mosquito Vector." Advances in Parasitology 38: 53-117.
// model based on data from Jeffery, G. M. and D. E. Eyles (1955). "Infectivity to Mosquitoes of Plasmodium Falciparum as Related to Gametocyte Density and Duration of Infection." Am J Trop Med Hyg 4(5): 781-789.
// and Schneider, P., J. T. Bousema, et al. (2007). "Submicroscopic Plasmodium falciparum gametocyte densities frequently result in mosquito infection." Am J Trop Med Hyg 76(3): 470-474.
// 2 due to bloodmeal and other factor due to conservative estimate for macrogametocyte ookinete transition, can be a higher reduction due to immune response
// that factor also includes effect of successful fertilization with male gametocytes
infectiousness = float(EXPCDF(-double(m_female_gametocytes) * m_inv_microliters_blood * MICROLITERS_PER_BLOODMEAL * SusceptibilityMalariaConfig::base_gametocyte_mosquito_survival * (1.0 - fever_effect))); //temp function, see vector_parameter_scratch.xlsx
LOG_DEBUG_F("Gametocytes: %lld (male) %lld (female). Infectiousness=%0.2g\n", m_male_gametocytes, m_female_gametocytes, infectiousness);
// Effects of transmission-reducing immunity. N.B. interventions on vector success are not here, since they depend on vector-population-specific behavior
float modtransmit = susceptibility->GetModTransmit() * interventions->GetInterventionReducedTransmit();
infectiousness *= modtransmit;
// Host weight is the product of MC weighting and relative biting
float host_vector_weight = float(GetMonteCarloWeight() * GetRelativeBitingRate());
float weighted_infectiousnesss = host_vector_weight * infectiousness;
// Effects from vector intervention container
IVectorInterventionsEffects* ivie = nullptr;
if ( s_OK != interventions->QueryInterface(GET_IID(IVectorInterventionsEffects), (void**)&ivie) )
{
throw QueryInterfaceException( __FILE__, __LINE__, __FUNCTION__, "interventions", "IVectorInterventionsEffects", "IndividualHumanVector" );
}
// Here we deposit human-to-vector infectiousness based on proportional outcrossing of strain IDs
gametocytes_strain_map_t::const_iterator gc1,gc2,end=m_female_gametocytes_by_strain.end();
for (gc1=m_female_gametocytes_by_strain.begin(); gc1!=end; ++gc1)
{
for (gc2=gc1; gc2!=end; ++gc2)
{
// Fractional weight is product of component weights
float strain_weight;
if (gc1==gc2)
{
strain_weight = pow( float(gc1->second) / float(m_female_gametocytes), 2 );
DepositFractionalContagionByStrain( weighted_infectiousnesss * strain_weight, ivie, gc1->first.GetAntigenID(), gc1->first.GetGeneticID() );
continue;
}
// Two off-diagonal contributions given how pairwise iteration is done in this loop
strain_weight = 2.0f * gc1->second * gc2->second / pow( float(m_female_gametocytes), 2 );
LOG_DEBUG_F("Crossing two strains with weight %0.2f and %0.2f\n", gc1->second/float(m_female_gametocytes), gc2->second/(float)m_female_gametocytes);
// Genetic ID from first component
int geneticID = gc1->first.GetGeneticID();
if ( geneticID != gc2->first.GetGeneticID() )
{
// One outcrossing realization if genetic IDs are different
geneticID = MalariaBarcode::getInstance()->fromOutcrossing( geneticID, gc2->first.GetGeneticID() );
LOG_DEBUG_F("Crossing geneticID %d + %d --> %d\n", gc1->first.GetGeneticID(), gc2->first.GetGeneticID(), geneticID);
}
// Deposit fractional infectiousness to each of indoor and outdoor pools
if ( gc1->first.GetAntigenID() == gc2->first.GetAntigenID() )
{
DepositFractionalContagionByStrain( weighted_infectiousnesss * strain_weight, ivie, gc1->first.GetAntigenID(), geneticID );
}
else
{
// Deposit half the weight to each if antigenIDs are different.
// Note that geneticID is not outcrossed independently for the different antigen IDs.
DepositFractionalContagionByStrain( 0.5f * weighted_infectiousnesss * strain_weight, ivie, gc1->first.GetAntigenID(), geneticID );
DepositFractionalContagionByStrain( 0.5f * weighted_infectiousnesss * strain_weight, ivie, gc2->first.GetAntigenID(), geneticID );
LOG_DEBUG_F("Depositing contagion with antigenIDs %d and %d for geneticID=%d\n", gc1->first.GetAntigenID(), gc2->first.GetAntigenID(), geneticID);
}
}
}
}
void IndividualHumanMalaria::UpdateGametocyteCounts(float dt)
{
// Check for mature gametocyte drug killing
float drugGametocyteKill = 0;
IMalariaDrugEffects* imde = nullptr;
if (s_OK == GetInterventionsContext()->QueryInterface(GET_IID(IMalariaDrugEffects), (void **)&imde))
{
drugGametocyteKill = imde->get_drug_gametocyteM();
}
else
{
throw QueryInterfaceException( __FILE__, __LINE__, __FUNCTION__, "GetInterventionsContext()", "IMalariaDrugEffects", "IIndividualHumanInterventionsContext" );
}
// Older mature gametocytes die; then add in the newly matured ones
double pkill = 0;
double numkilled = 0;
// Decay half-life--Sinden, R. E., G. A. Butcher, et al. (1996). "Regulation of Infectivity of Plasmodium to the Mosquito Vector." Advances in Parasitology 38: 53-117.
// Smalley, M. E. and R. E. Sinden (1977). "Plasmodium falciparum gametocytes: their longevity and infectivity." Parasitology 74(01): 1-8.
pkill = EXPCDF(-dt * (0.277 + drugGametocyteKill));// half-life of 2.5 days corresponds to a decay time constant of 3.6 days, 0.277 = 1/3.6
m_male_gametocytes = 0;
for( gametocytes_strain_map_t::iterator gc = m_male_gametocytes_by_strain.begin(); gc != m_male_gametocytes_by_strain.end(); )
{
// Gaussian approximation of binomial errors for each strain that is present
numkilled = (randgen->eGauss() * sqrt(pkill * gc->second * (1.0 - pkill)) + pkill * gc->second); // halflife of 2.5 days
numkilled = max(0.0, numkilled); //can't add by killing
gc->second = int64_t(gc->second - numkilled);
gc->second = max(0L, gc->second);
if ( gc->second == 0 )
{
gc = m_male_gametocytes_by_strain.erase(gc); // remove empty strains from map
}
else
{
m_male_gametocytes += gc->second;
++gc;
}
}
m_female_gametocytes = 0;
for( gametocytes_strain_map_t::iterator gc = m_female_gametocytes_by_strain.begin(); gc != m_female_gametocytes_by_strain.end(); )
{
numkilled = (randgen->eGauss() * sqrt(pkill * gc->second * (1.0 - pkill)) + pkill * gc->second); // halflife of 2.5 days
numkilled = max(0.0, numkilled); //can't add by killing
gc->second = int64_t(gc->second - numkilled);
gc->second = max(0L, gc->second);
if ( gc->second == 0 )
{
gc = m_female_gametocytes_by_strain.erase(gc); // remove empty strains from map
}
else
{
m_female_gametocytes += gc->second;
++gc;
}
}
infectiousness = 0;
int64_t tmp_male_gametocytes = 0;
int64_t tmp_female_gametocytes = 0;
StrainIdentity tmp_strainIDs;
// Loop over infections and add newly matured male and female gametocytes by strain
for (auto infection : infections)
{
// Cast from Infection --> InfectionMalaria
IInfectionMalaria *tempinf = nullptr;
if( infection->QueryInterface( GET_IID(IInfectionMalaria), (void**)&tempinf ) != s_OK )
{
throw QueryInterfaceException( __FILE__, __LINE__, __FUNCTION__, "Infection", "IInfectionMalaria", "tempinf" );
}
//InfectionMalaria *tempinf = static_cast<InfectionMalaria *>(infection);
// Get gametocytes that have matured in this timestep
// N.B. malariaCycleGametocytes is called once per asexual cycle (several days),
// so the stage-5 counter is reset to avoid multiple counting.
tmp_male_gametocytes = tempinf->get_MaleGametocytes(5);
tempinf->reset_MaleGametocytes(/* stage */5);
tmp_female_gametocytes = tempinf->get_FemaleGametocytes(5);
tempinf->reset_FemaleGametocytes(/* stage */5);
// No new gametocytes
if ( tmp_male_gametocytes==0 && tmp_female_gametocytes==0 ) continue;
// Add new gametocytes to those carried over (and not killed) from the previous time steps
infection->GetInfectiousStrainID(&tmp_strainIDs);
m_male_gametocytes_by_strain[tmp_strainIDs] += tmp_male_gametocytes;
m_male_gametocytes += tmp_male_gametocytes;
m_female_gametocytes_by_strain[tmp_strainIDs] += tmp_female_gametocytes;
m_female_gametocytes += tmp_female_gametocytes;
}
}