NAMESPACE

@@ -5,6 +5,7 @@ export(alpha_r)
 export(baseline_parameters)
 export(beta)
 export(calculate_irbc_ratio)
+export(calculate_urbc_loss_ratio)
 export(credible_intervals)
 export(define_derived_parameters)
 export(delta_i)

R/outputs.R

@@ -135,6 +135,36 @@ infection_flows_and_loss <- function(results) {
 }
 
 
+#' Calculate the ratio of (a) the unparasitised RBC loss due to malaria
+#' (additional uRBC retention in the spleen); to (b) the parasitised RBC loss
+#' due to RBC infection.
+#'
+#' @param results A dataframe of simulation results.
+#'
+#' @return
+#' A dataframe that includes the following column, in addition to those in
+#' `results`:
+#'
+#' \describe{
+#'   \item{uRBC_Loss_Ratio}{The ratio of uRBC loss (from the circulation) due
+#'     to splenic retention and due to parasitisation.}
+#' }
+#'
+#' @export
+calculate_urbc_loss_ratio <- function(results) {
+  results |> dplyr::mutate(
+    flow_uc_to_r_inf = flow_uc_to_r - flow_uc_to_r_no_inf,
+    inf_total = inf_from_ic + inf_from_iq + inf_from_ir,
+    uRBC_Loss_Ratio = dplyr::case_when(
+      inf_total > 0 ~ flow_uc_to_r_inf / inf_total,
+      .default = 0
+    ),
+    flow_uc_to_r_inf,
+    inf_total = NULL
+  )
+}
+
+
 #' Calculate the ratio of (a) the fraction of RBCs in the spleen that are
 #' infected; to (b) the fraction of RBCs in the circulation that are infected.
 #'

R/state.R

@@ -344,6 +344,24 @@ step_spleenrbc_model <- function(p, s, t) {
     * (1 - exp_lambda_i)
   )
 
+  # Limit RBC infections in the spleen to the spleen uRBC population.
+  Drr_t_1[2:p$T_urbc] <- pmin(Drr_t_1[2:p$T_urbc], U_r_to_r + U_c_to_r)
+
+  # Limit RBC infections in the circulation to the circulating uRBC population.
+  # Calculate the difference between the intended RBC infections and the
+  # circulating uRC population.
+  net_Dc <- Dc_t_1[2:p$T_urbc] + Dq_t_1[2:p$T_urbc] + Drc_t_1[2:p$T_urbc]
+  net_Uc <- U_c_to_c + U_r_to_c
+  # Calculate the number of possible RBC infections in the circulation.
+  actual_Dc <- pmin(net_Dc, net_Uc)
+  # Down-scale the infections from each source (circulation, microvasculature,
+  # and spleen) where intended infections exceed available uRBCs.
+  frac_Dc <- actual_Dc / net_Dc
+  frac_Dc[net_Dc == 0] <- 0
+  Dc_t_1[2:p$T_urbc] <- frac_Dc * Dc_t_1[2:p$T_urbc]
+  Dq_t_1[2:p$T_urbc] <- frac_Dc * Dq_t_1[2:p$T_urbc]
+  Drc_t_1[2:p$T_urbc] <- frac_Dc * Drc_t_1[2:p$T_urbc]
+
   # Update reticulocyte population in the bone marrow.
   r_at <- numeric(p$T_R)
   r_at[1] <- s$n_at_1[p$T_n]

data-raw/input-parameters-pf.csv

@@ -17,7 +17,7 @@ delta_iS_scale,2,removal rate of infected schizonts from circulation by the sple
 zeta_sl,10,related to calculating sequestered iRBC in the microvasculature
 zeta_a50,26,related to calculating sequestered iRBC in the microvasculature
 kM,0.01,Parameters for macrophages dynamics
-lambdaI.sel,1.778E-11,for determining Phagocytosis rate of the iRBCs retained in the spleen by macrophages
+lambdaI.sel,1.5E-11,for determining Phagocytosis rate of the iRBCs retained in the spleen by macrophages
 lambdaU.sel,5.00E-07,for determining Phagocytosis rate of the uRBCs retained in the spleen by macrophages
 w_rc,0.1,Proportion of merozoites released from retained retics that infect circulating uRBCs
 PMF,8,Parasite multiplication factor

data-raw/parameters.R

@@ -71,17 +71,7 @@ parameters_pf <- dplyr::left_join(ordered_names, parameters_pf, by = "name")
 
 usethis::use_data(parameters_pf, overwrite = TRUE)
 
-# For Pv, we increase delta_iR and preserve the values of delta_i{R,S}_prime
-# by adjusting the scaling parameters k_i{R,S}.
-pv_scale <- 0.4 / 0.15
-parameters_pv <- parameters_pf |>
-  dplyr::mutate(
-    baseline = dplyr::case_when(
-      name == "delta_iR" ~ baseline * pv_scale,
-      name == "k_iR" ~ baseline / pv_scale,
-      name == "k_iS" ~ baseline / pv_scale,
-      .default = baseline
-    )
-  )
+# We use the same parameter values for Pv.
+parameters_pv <- parameters_pf
 
 usethis::use_data(parameters_pv, overwrite = TRUE)

run-sensitivity-analysis.R

@@ -46,9 +46,23 @@ run_sensitivity_analysis <- function(species, days = 150, n_samples = 1000) {
   # Save the credible intervals for all simulations.
   cint_all_file <- file.path("outputs", paste0(prefix, "-rbc-cints-all.rds"))
   cint_all <- results |>
-    select(scenario, time, U_t, Ur_t, I_t, Iq_t, Ir_t) |>
+    select(
+      scenario, time,
+      U_t, Ur_t, I_t, Iq_t, Ir_t,
+      flow_uc_to_r, flow_uc_to_r_no_inf,
+      inf_from_ic, inf_from_iq, inf_from_ir
+    ) |>
     # Calculate ratio of iRBC % in the spleen to iRBC % in the circulation.
     calculate_irbc_ratio() |>
+    # Calculate ratio of unparasitised uRBC loss to parasitised uRBC loss.
+    calculate_urbc_loss_ratio() |>
+    # Drop intermediate values.
+    select(
+      scenario, time,
+      U_t, Ur_t, I_t, Iq_t, Ir_t,
+      iRBC_Ratio,
+      uRBC_Loss_Ratio
+    ) |>
     credible_intervals() |>
     mutate(Species = !!species)
   saveRDS(cint_all, cint_all_file)
@@ -61,9 +75,23 @@ run_sensitivity_analysis <- function(species, days = 150, n_samples = 1000) {
   cint_nonz_file <- file.path("outputs", paste0(prefix, "-rbc-cints-nonz.rds"))
   cint_nonz <- results |>
     filter(! scenario %in% zero_scenarios) |>
-    select(scenario, time, U_t, Ur_t, I_t, Iq_t, Ir_t) |>
+    select(
+      scenario, time,
+      U_t, Ur_t, I_t, Iq_t, Ir_t,
+      flow_uc_to_r, flow_uc_to_r_no_inf,
+      inf_from_ic, inf_from_iq, inf_from_ir
+    ) |>
     # Calculate ratio of iRBC % in the spleen to iRBC % in the circulation.
     calculate_irbc_ratio() |>
+    # Calculate ratio of unparasitised uRBC loss to parasitised uRBC loss.
+    calculate_urbc_loss_ratio() |>
+    # Drop intermediate values.
+    select(
+      scenario, time,
+      U_t, Ur_t, I_t, Iq_t, Ir_t,
+      iRBC_Ratio,
+      uRBC_Loss_Ratio
+    ) |>
     credible_intervals() |>
     mutate(Species = !!species)
   saveRDS(cint_nonz, cint_nonz_file)
@@ -72,9 +100,23 @@ run_sensitivity_analysis <- function(species, days = 150, n_samples = 1000) {
   cint_zero_file <- file.path("outputs", paste0(prefix, "-rbc-cints-zero.rds"))
   cint_zero <- results |>
     filter(scenario %in% zero_scenarios) |>
-    select(scenario, time, U_t, Ur_t, I_t, Iq_t, Ir_t) |>
+    select(
+      scenario, time,
+      U_t, Ur_t, I_t, Iq_t, Ir_t,
+      flow_uc_to_r, flow_uc_to_r_no_inf,
+      inf_from_ic, inf_from_iq, inf_from_ir
+    ) |>
     # Calculate ratio of iRBC % in the spleen to iRBC % in the circulation.
     calculate_irbc_ratio() |>
+    # Calculate ratio of unparasitised uRBC loss to parasitised uRBC loss.
+    calculate_urbc_loss_ratio() |>
+    # Drop intermediate values.
+    select(
+      scenario, time,
+      U_t, Ur_t, I_t, Iq_t, Ir_t,
+      iRBC_Ratio,
+      uRBC_Loss_Ratio
+    ) |>
     credible_intervals() |>
     mutate(Species = !!species)
   saveRDS(cint_zero, cint_zero_file)

vignettes/articles/model-description.Rmd

@@ -795,8 +795,6 @@ Table: Model parameters for RBC destruction and macrophage populations.
 
 - The two species have different age-dependent merozoite preferences for uninfected RBCs; see [RBC infection] for details.
 
-- Infected RBCs are removed from the circulation at a higher rate for Pv; see [Infected RBC removal from circulation] for details.
-
 - Pf-infected RBCs can become sequestered in the microvasculature; see [Infected RBC sequestration] for details.
 
 \clearpage