Added CQ vivax drug parameter sets, including hypnozoite drug paramet…

…ers.

Default drug parameters have been relabelled using parasite species names, although the original names have been left in for now, so that it can still be compatable with previous code. All the tests and vignettes use the parasite named parameters sets.

Treatment, MDA and PMC code now includes hypnozoite clearance when these drugs are used.

Added drug prophylaxis effects to human infection, preventing new hypnozoite batch formation.

NAMESPACE

@@ -1,8 +1,13 @@
 # Generated by roxygen2: do not edit by hand
 
 export(AL_params)
+export(AL_params_falciparum)
+export(CQ_PQ_params_vivax)
+export(CQ_params_vivax)
 export(DHA_PQP_params)
+export(DHA_PQP_params_falciparum)
 export(SP_AQ_params)
+export(SP_AQ_params_falciparum)
 export(arab_params)
 export(create_pev_profile)
 export(fun_params)

R/drug_parameters.R

@@ -1,44 +1,95 @@
+#' @title Preset parameters for the DHA-PQP drug
+#' @description From SI of Commun. 5:5606 doi: 10.1038/ncomms6606 (2014)
+#' @details Use a vector of preset parameters for the DHA-PQP drug (dihydroartemisinin-piperaquine)
+#' @details Default parameters, from L to R, are: drug_efficacy: 0.95, drug_rel_c: 0.09434, drug_prophylaxis_shape: 4.4, drug_prophylaxis_scale: 28.1
+#' @export
+DHA_PQP_params_falciparum <- c(.95, 0.09434, 4.4, 28.1)
+
 #' @title Preset parameters for the DHA-PQP drug
 #' @description From SI of Commun. 5:5606 doi: 10.1038/ncomms6606 (2014)
 #' @details Use a vector of preset parameters for the DHA-PQP drug (dihydroartemisinin-piperaquine)
 #' @details Default parameters, from L to R, are: drug_efficacy: 0.95, drug_rel_c: 0.09434, drug_prophylaxis_shape: 4.4, drug_prophylaxis_scale: 28.1
 #' @export
 DHA_PQP_params <- c(.95, 0.09434, 4.4, 28.1)
 
+#' @title Preset parameters for the AL drug
+#' @description From SI of Commun. 5:5606 doi: 10.1038/ncomms6606 (2014)
+#' @details Use a vector of preset parameters for the AL drug (artemether-lumefantrine)
+#' @details Default parameters, from L to R, are: drug_efficacy: 0.95, drug_rel_c: 0.05094, drug_prophylaxis_shape: 11.3, drug_prophylaxis_scale: 10.6
+#' @export
+AL_params_falciparum <- c(.95, 0.05094, 11.3, 10.6)
+
 #' @title Preset parameters for the AL drug
 #' @description From SI of Commun. 5:5606 doi: 10.1038/ncomms6606 (2014)
 #' @details Use a vector of preset parameters for the AL drug (artemether-lumefantrine)
 #' @details Default parameters, from L to R, are: drug_efficacy: 0.95, drug_rel_c: 0.05094, drug_prophylaxis_shape: 11.3, drug_prophylaxis_scale: 10.6
 #' @export
 AL_params <- c(.95, 0.05094, 11.3, 10.6)
 
+#' @title Preset parameters for the SP-AQ drug
+#' @details Use a vector of preset parameters for the SP-AQ drug (sulphadoxine-pyrimethamine and amodiaquine)
+#' @details Default parameters, from L to R, are: drug_efficacy: 0.9, drug_rel_c: 0.32, drug_prophylaxis_shape: 4.3, drug_prophylaxis_scale: 38.1
+#' @export
+SP_AQ_params_falciparum <- c(0.9, 0.32, 4.3, 38.1)
+
 #' @title Preset parameters for the SP-AQ drug
 #' @details Use a vector of preset parameters for the SP-AQ drug (sulphadoxine-pyrimethamine and amodiaquine)
 #' @details Default parameters, from L to R, are: drug_efficacy: 0.9, drug_rel_c: 0.32, drug_prophylaxis_shape: 4.3, drug_prophylaxis_scale: 38.1
 #' @export
 SP_AQ_params <- c(0.9, 0.32, 4.3, 38.1)
 
+#' @title Preset parameters for the CQ drug acting on P. vivax
+#' @description Efficacy from SI of Nekkab et al., DOI: 10.1371/journal.pmed.1003535 (2021),
+#' shape and scale consistent with a longer prophylaxis time: 28 days, decreasing gradually
+#' @details Use a vector of preset parameters for the CQ drug (chloroquine) acting on P. vivax
+#' @details Default parameters, from L to R, are: drug_efficacy: 0.899, drug_rel_c: 0.5, drug_prophylaxis_shape: 20, drug_prophylaxis_scale: 5
+#' @export
+CQ_params_vivax <- c(0.899, 0.5, 5, 20)
+
+#' @title Preset parameters for the CQ-PQ drug acting on P. vivax
+#' @description Efficacy from SI of Nekkab et al., DOI: 10.1371/journal.pmed.1003535 (2021),
+#' BS shape and scale consistent with a longer prophylaxis time: 28 days, decreasing gradually,
+#' LS shape are scale consistent with a 7 day PQ treatment, with rapid decay.
+#' @details Use a vector of preset parameters for the CQ-PQ drug (chloroquine and primaquine) acting on P. vivax
+#' @details Default parameters, from L to R, are: drug_efficacy: 0.948, drug_rel_c: 0.5, drug_prophylaxis_shape: 5, drug_prophylaxis_scale: 20,
+#' drug_hypnozoite_efficacy: 0.713, drug_hypnozoite_prophylaxis_shape: 10, drug_hypnozoite_prophylaxis_scale: 5.5
+#' @export
+CQ_PQ_params_vivax <- c(0.948, 0.5, 5, 20, 0.713, 10, 5.5)
+
+#' @title Preset parameters for the CQ-TQ drug acting on P. vivax
+#' @description Efficacy from SI of Nekkab et al., DOI: 10.1371/journal.pmed.1003535 (2021),
+#' BS shape and scale consistent with a longer prophylaxis time: 28 days, decreasing gradually,
+#' LS shape are scale consistent with a single TQ treatment, with longer prophylaxis: 45 days.
+#' @details Use a vector of preset parameters for the CQ-TQ drug (chloroquine and tafenoquine) acting on P. vivax
+#' @details Default parameters, from L to R, are: drug_efficacy: 1, drug_rel_c: 0.5, drug_prophylaxis_shape: 5, drug_prophylaxis_scale: 20,
+#' drug_hypnozoite_efficacy: 0.713, drug_hypnozoite_prophylaxis_shape: 5.5, drug_hypnozoite_prophylaxis_scale: 30
+CQ_TQ_params_vivax <- c(1, 0.5, 5, 20, 0.713, 5, 30)
+
 #' @title Parameterise drugs to use in the model
 #'
 #' @param parameters the model parameters
 #' @param drugs a list of drug parameters, can be set using presets
 #' @export
 set_drugs <- function(parameters, drugs) {
-  stopifnot(is.list(drugs))
+  stopifnot("is.list(drugs) is not TRUE" = is.list(drugs))
   keys <- c(
     'drug_efficacy',
     'drug_rel_c',
     'drug_prophylaxis_shape',
-    'drug_prophylaxis_scale'
+    'drug_prophylaxis_scale',
+    # hypnozoite parameters
+    'drug_hypnozoite_efficacy',
+    'drug_hypnozoite_prophylaxis_shape',
+    'drug_hypnozoite_prophylaxis_scale'
   )
+
   for (drug in seq_along(drugs)) {
     for (i in seq_along(drugs[[drug]])) {
-      parameters[[keys[[i]]]] <- c(parameters[[keys[[i]]]], drugs[[drug]][[i]])
+      parameters[[keys[[i]]]][drug] <- drugs[[drug]][[i]]
     }
   }
   parameters
 }
-
 #' @title Parameterise clinical treatment
 #'
 #' @param parameters the model parameters

R/human_infection.R

@@ -519,13 +519,33 @@ relapse_bite_infection_hazard_resolution <- function(
   ## all bitten humans with an infectious bite (incorporating prophylaxis) get a new batch of hypnozoites
   if(bite_infections$size()>0){
 
+    ## drug prophylaxis may limit formation of new hypnozoite batches
+    ls_prophylaxis <- rep(0, bite_infections$size())
+    if(length(parameters$drug_hypnozoite_efficacy) > 0){
+
+      ls_drug <- variables$ls_drug$get_values(bite_infections)
+      ls_medicated <- (ls_drug > 0)
+      ls_medicated[ls_drug > 0] <- !is.na(parameters$drug_hypnozoite_efficacy[ls_drug])
+
+      if (any(ls_medicated)) {
+        ls_drug <- ls_drug[ls_medicated]
+        ls_drug_time <- variables$ls_drug_time$get_values(bite_infections)[ls_medicated]
+        ls_prophylaxis[ls_medicated] <- weibull_survival(
+          timestep - ls_drug_time,
+          parameters$drug_hypnozoite_prophylaxis_shape[ls_drug],
+          parameters$drug_hypnozoite_prophylaxis_scale[ls_drug]
+        )
+      }
+    }
+
     # make sure batches are capped
-    current_batches <- variables$hypnozoites$get_values(bite_infections)
+    new_hypnozoite_batch_formed <- bitset_at(bite_infections, bernoulli_multi_p(1 - ls_prophylaxis))
+    current_batches <- variables$hypnozoites$get_values(new_hypnozoite_batch_formed)
     new_batch_number <- pmin(current_batches + 1, parameters$kmax)
 
     variables$hypnozoites$queue_update(
       new_batch_number,
-      bite_infections
+      new_hypnozoite_batch_formed
     )
   }
 }
@@ -729,6 +749,15 @@ calculate_treated <- function(
     )
   }
 
+  # Update liver stage drug effects
+  if(length(parameters$drug_hynozoite_efficacy) > 0){
+    if(successfully_treated$successfully_treated_hypnozoites$size() > 0){
+      variables$hypnozoites$queue_update(0, successfully_treated$successfully_treated_hypnozoites)
+      variables$ls_drug$queue_update(drug, successfully_treated$successfully_treated_hypnozoites)
+      variables$ls_drug_time$queue_update(timestep, successfully_treated$successfully_treated_hypnozoites)
+    }
+  }
+
   successfully_treated$successfully_treated
 
 }
@@ -808,6 +837,16 @@ calculate_successful_treatments <- function(
       successfully_treated = successfully_treated)
 
   }
+
+  if(length(parameters$drug_hypnozoite_efficacy) > 0){
+    effectively_treated_hypnozoites_index <- bernoulli_multi_p(parameters$drug_hypnozoite_efficacy[drugs])
+    successfully_treated_hypnozoites <- bitset_at(target, effectively_treated_hypnozoites_index)
+    successfully_treated_list <- c(
+      successfully_treated_list,
+      successfully_treated_hypnozoites = successfully_treated_hypnozoites
+    )
+  }
+
   successfully_treated_list
 }
 

R/mda_processes.R

@@ -137,6 +137,15 @@ update_mass_drug_admin <- function(
     variables$drug_time$queue_update(timestep, target$successfully_treated)
 
   }
+
+  # Update liver stage drug effects
+  if(length(parameters$drug_hypnozoite_efficacy) > 0){
+    if(target$successfully_treated_hypnozoites$size() > 0){
+      variables$hypnozoites$queue_update(0, target$successfully_treated_hypnozoites)
+      variables$ls_drug$queue_update(drug, target$successfully_treated_hypnozoites)
+      variables$ls_drug_time$queue_update(timestep, target$successfully_treated_hypnozoites)
+    }
+  }
 }
 
 #' @title Calculate asymptomatic detectable individuals

R/parameters.R

@@ -403,6 +403,9 @@ get_parameters <- function(overrides = list(), parasite = "falciparum") {
       drug_rel_c             = numeric(0),
       drug_prophylaxis_shape = numeric(0),
       drug_prophylaxis_scale = numeric(0),
+      drug_hypnozoite_efficacy = numeric(0),
+      drug_hypnozoite_prophylaxis_shape = numeric(0),
+      drug_hypnozoite_prophylaxis_scale = numeric(0),
       clinical_treatment_drugs     = list(),
       clinical_treatment_timesteps = list(),
       clinical_treatment_coverages = list(),

R/pmc.R

@@ -63,6 +63,5 @@ create_pmc_process <- function(
       timestep,
       drug
     )
-
   }
 }

R/processes.R

@@ -47,7 +47,7 @@ create_processes <- function(
     immunity_process = create_exponential_decay_process(variables$ica,
                                                         parameters$rc)
   )
-  
+
   if(parameters$parasite == "falciparum"){
     processes <- c(
       processes,

R/variables.R

@@ -35,6 +35,8 @@
 #' * infectivity - The onward infectiousness to mosquitos
 #' * drug - The last prescribed drug
 #' * drug_time - The timestep of the last drug
+#' * ls_drug - The last prescribed drug
+#' * ls_drug_time - The timestep of the last drug
 #'
 #' Antimalarial resistance variables are:
 #' * dt - the delay for humans to move from state Tr to state S
@@ -286,6 +288,11 @@ create_variables <- function(parameters) {
   drug <- individual::IntegerVariable$new(rep(0, size))
   drug_time <- individual::IntegerVariable$new(rep(-1, size))
 
+  if(length(parameters$drug_hypnozoite_efficacy) > 0){
+    ls_drug <- individual::IntegerVariable$new(rep(0, size))
+    ls_drug_time <- individual::IntegerVariable$new(rep(-1, size))
+  }
+
   last_pev_timestep <- individual::IntegerVariable$new(rep(-1, size))
   last_eff_pev_timestep <- individual::IntegerVariable$new(rep(-1, size))
   pev_profile <- individual::IntegerVariable$new(rep(-1, size))