void IndividualHumanVector::UpdateInfectiousness(float dt)
{
infectiousness = 0;
float tmp_infectiousness = 0;
typedef std::map< StrainIdentity, float > strain_infectivity_map_t;
typedef strain_infectivity_map_t::value_type strain_infectivity_t;
strain_infectivity_map_t infectivity_by_strain;
StrainIdentity tmp_strainIDs;
// Loop once over all infections, caching strains and infectivity.
// If total infectiousness exceeds unity, we will normalize all strains down accordingly.
for (auto infection : infections)
{
release_assert( infection );
tmp_infectiousness = infection->GetInfectiousness();
infectiousness += tmp_infectiousness;
if ( tmp_infectiousness > 0 )
{
infection->GetInfectiousStrainID(&tmp_strainIDs);
infectivity_by_strain[tmp_strainIDs] += tmp_infectiousness;
}
}
// Effects of transmission-reducing immunity. N.B. interventions on vector success are not here, since they depend on vector-population-specific behavior
release_assert( susceptibility );
release_assert( interventions );
float modtransmit = susceptibility->GetModTransmit() * interventions->GetInterventionReducedTransmit();
// Maximum individual infectiousness is set here, capping the sum of unmodified infectivity at prob=1
float truncate_infectious_mod = (infectiousness > 1 ) ? 1.0f/infectiousness : 1.0f;
infectiousness *= truncate_infectious_mod * modtransmit;
// Host weight is the product of MC weighting and relative biting
float host_vector_weight = float(GetMonteCarloWeight() * GetRelativeBitingRate());
// 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" );
}
// Loop again over infection strains, depositing (downscaled) infectivity modified by vector intervention effects etc. (indoor + outdoor)
for (auto& infectivity : infectivity_by_strain)
{
const StrainIdentity *id = &(infectivity.first);
parent->DepositFromIndividual( const_cast<StrainIdentity*>(id), host_vector_weight * infectivity.second * truncate_infectious_mod * modtransmit * ivie->GetblockIndoorVectorTransmit(), &NodeVector::human_to_vector_indoor );
parent->DepositFromIndividual( const_cast<StrainIdentity*>(id), host_vector_weight * infectivity.second * truncate_infectious_mod * modtransmit * ivie->GetblockOutdoorVectorTransmit(), &NodeVector::human_to_vector_outdoor );
}
}
void IndividualHumanVector::Expose( const IContagionPopulation* cp, float dt, TransmissionRoute::Enum transmission_route )
{
release_assert( cp );
release_assert( susceptibility );
release_assert( interventions );
#if 1
// get rid of this. but seems to be needed for malaria garki. :( :( :(
if( !vector_interventions )
{
vector_interventions = static_cast<VectorInterventionsContainer*>(interventions);
}
#endif
release_assert( vector_interventions );
float acqmod = GetRelativeBitingRate() * susceptibility->getModAcquire() * interventions->GetInterventionReducedAcquire();
switch( transmission_route )
{
case TransmissionRoute::TRANSMISSIONROUTE_VECTOR_TO_HUMAN_INDOOR:
acqmod *= vector_interventions->GetblockIndoorVectorAcquire();
break;
case TransmissionRoute::TRANSMISSIONROUTE_VECTOR_TO_HUMAN_OUTDOOR:
acqmod *= vector_interventions->GetblockOutdoorVectorAcquire();
break;
default:
throw BadEnumInSwitchStatementException( __FILE__, __LINE__, __FUNCTION__, "transmission_route", transmission_route, "Stringified enum value not available" );
}
// Accumulate vector of pairs of strain ids and cumulative infection probability
float infection_probability = cp->GetTotalContagion() * acqmod * dt;
if ( infection_probability > 0 )
{
// Increment total exposure
m_total_exposure += infection_probability;
// With a weighted random draw, pick a strain from the ContagionPopulation CDF
StrainIdentity strain_id;
strain_id.SetAntigenID(cp->GetAntigenId());
cp->ResolveInfectingStrain(&strain_id);
// Push this exposure and strain back to the storage array for all vector-to-human pools (e.g. indoor, outdoor)
m_strain_exposure.push_back( std::make_pair(strain_id, m_total_exposure) );
}
}
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);
}
}
}
}
