DOI: 10.5061/dryad.k0p2ngfhq
title: Heterogeneous mosquito exposure increases Plasmodium vivax and Plasmodium falciparum coinfections: a modelling study

description: In malaria-endemic regions, Plasmodium vivax and Plasmodium falciparum
 coexist and may interact. For instance, fevers induced by P. falciparum
 might activate dormant P. vivax parasites and concurrent radical cure of
 both species has been proposed to prevent relapses. Heterogeneous mosquito
 exposure may contribute to the dependence of both parasites. We conducted
 a literature review on their respective prevalence and that of
 coinfections. The data revealed a positive correlation between P. vivax
 and P. falciparum prevalence and coinfection prevalences exceeding
 expectations assuming infections occur independently. We used the review
 data to fit a compartmental model of coinfections that features
 heterogeneous mosquito exposure. The fit suggests that heterogeneous
 exposure sufficiently explains the observed departure from independence.
 Finally, we performed simulations under the model assessing the impact on
 P. vivax prevalence of the activation-by-fever hypothesis and the radical
 cure proposition. We demonstrated a moderate impact of allowing P.
 falciparum fevers to reactivate P. vivax and a substantial impact of
 treating P. falciparum cases with radical cure. Our model highlights the
 dependence between P. falciparum and P. vivax and emphasises the
 influence of heterogeneous mosquito exposure. This simple framework can
 inform the design of more complex models assessing integrated malaria
 control strategies in co-endemic regions.
description: We performed a literature review on PubMed to collect data from
 field epidemiology studies recording <em>P. vivax</em>,
 <em>P. falciparum</em>, and coinfection prevalence, among the
 general population. Specifically, we defined those studies as
 cross-sectional and active infection-detection studies performed in
 communities, unrestricted by age, sex, or symptomatic status. The keywords
 we used were: Title: (Malaria OR Vivax OR Falciparum)
 NOT (Health-care facility OR Hospital OR Health centre OR Systematic
 Review OR Meta*) Abstract: Prevalence OR Distribution
 OR Epidemiology OR Cross-section Text: Vivax AND
 Falciparum After title and abstract screening with
 “Rayyan”, we screened the main text and extracted the
 <em>P. vivax</em>, <em>P. falciparum,</em> and
 coinfection prevalence from each study, as well as the sample size and
 diagnostic method used to generate prevalence. We excluded studies that
 failed to report all those metrics or that did not screen the general
 population. A spreadsheet of the details of all the studies retained after
 title and abstract screening is available as a supplementary
 file. We defined different metrics related to the
 coupled dynamics of <em>P. vivax</em>, <em>P.
 falciparum,</em> and coinfections. First, we introduced the notion
 of expected coinfection prevalence under the independence of <em>P.
 vivax</em> and <em>P. falciparum</em>. That is, we
 assumed that if <em>P. vivax</em> and <em>P.
 falciparum</em> transmission are independent, coinfection prevalence
 should be the product of <em>P. falciparum</em> and
 <em>P. vivax</em> prevalence. We then defined the proportional
 excess coinfection prevalence as the difference between observed and
 expected coinfection prevalence, normalized by different measures of local
 transmission intensity: <em>P. vivax</em> prevalence,
 <em>P. falciparum</em> prevalence, or overall malaria
 prevalence.
description: # Heterogeneous mosquito exposure increases *Plasmodium vivax* and
 *Plasmodium falciparum* coinfections: a modelling study
 [https://doi.org/10.5061/dryad.k0p2ngfhq](https://doi.org/10.5061/dryad.k0p2ngfhq) ## Description of the data and file structure The present repository includes data collected via a literature review of field studies recording *P. vivax* and *P. falciparum* infection, and coinfection prevalence. This data was used for: 1. An analysis of the statistical dependence between *P. vivax* and *P. falciparum* infection prevalence 2. Fitting a compartmental model of coinfections with *P. vivax* and *P. falciparum* ### Files and variables #### File: Review\_data.Rdata **Description:** This file contains the information extracted from each study included after the literature review. **Variables:** * **method**: The diagnostic method used for species identification in the included study. * **sample size**: The number of samples evaluated in the included study. * **country of study site(s)**: The country in which study was the included study was performed. * **Pf_prev (%)**: The prevalence of *P. falciparum* single infections recorded in the included study. * **Pv_prev (%)**: The prevalence of *P. vivax* single infections recorded in the included study. * **Mixed_prev (%)**: The prevalence of *P. falciparum* and *P. vivax* mixed infections recorded in the included study. * **Pf_prev (%) all**: The prevalence of all *P. falciparum* infections (single or mixed) recorded in the included study. * **Pv_prev (%) all**: The prevalence of all *P. vivax* infections (single or mixed) recorded in the included study. * **All_prev (%)**: The prevalence of any *Plasmodium* infections (single or mixed) recorded in the included study. * **mixed/Pf_prev all**: The ratio between the prevalence of mixed infections and the prevalence of all *P. falciparum* infections (single or mixed) recorded in the included study. * **mixed/Pv_prev all**: The ratio between the prevalence of mixed infections and the prevalence of all *P. vivax* infections (single or mixed) recorded in the included study. * **mixed/PvPf_prev all**: The ratio between the prevalence of mixed infections and the prevalence of any *Plasmodium* infections (single or mixed) recorded in the included study. * **Mixed_prev (%) exp**: The prevalence of mixed infections expected from the prevalence of *P. vivax* infections (single or mixed) and of *P. falciparum* infections (single or mixed) recorded in the included study, i.e. the product of the prevalence of *P. vivax* infections (single or mixed) and of *P. falciparum* infections recorded in the included study. * **mixed_exp/Pf_prev all**: The ratio between the expected prevalence of mixed infections (defined above) and the prevalence of all *P. falciparum* infections (single or mixed) recorded in the included study. * **mixed_exp/Pv_prev all**: The ratio between the expected prevalence of mixed infections (defined above) and the prevalence of all *P. vivax* infections (single or mixed) recorded in the included study. * **mixed_exp/PvPf_prev**: The ratio between the expected prevalence of mixed infections (defined above) and the prevalence of any *Plasmodium* infections (single or mixed) recorded in the included study. * **Region**: The country where the included study was conducted, classified into "Africa", "Indian/Pacific Ocean", "South America", "South Asia", or "South-East Asia". * **method2**: The diagnostic method used for species identification in the included study, classified as "PCR", or "Other". * **Sizes**: The number of samples evaluated in the included study, scaled between 0 and 1 (for plotting purposes). ## Code/software The data analysis and model fitting were done in R version 4.4.1 (2024-06-14). Necessary R-packages to run the code are *deSolve*, *statmod*, *scales*, and *dplyr*. * **Helper.R** is a script containing helper functions and recurring parameters. * **Heterogeneity_model_coinfection.R** is the script encoding the coinfection model under heterogeneous exposure to mosquito bites, which is presented in the article. * **Heterogeneity_febrile_trigger_model_coinfection.R** is the script encoding the same model but allowing for febrile *P. falciparum* infections to trigger *P. vivax* hypnozoite reactivation (relapse). * **Heterogeneity_radical_cure_model_coinfection.R**s the script encoding the same model but allowing for blood-stage or radical cure treatment of *P. falciparum* and *P. vivax*. * **Null_model.R**  is the script encoding the model of coinfection under no heterogeneity. * **ABC_prior_sampling.R** is a script sampling from parameter priors, which are plugged into the compartmental model to output equilibrium prevalences of *P. vivax*, *P. falciparum* and coinfection. This script outputs the R object *sample.rds*. * **ABC_nearest_neighbor.R** is a script selecting the 100 nearest neighbors of each review data point among the prior sampled prevalence triplets. This script outputs the R object *5800_nearest_neighbors.rds*. * **Het_febrile_trigger_simulations.R** is the script running simulations under different scenarios of hypnozoite activation by *P. falciparum* fevers. * **Het_radical_cure_simulations.R** is the script running scenario simulations of different blood-stage treatments or radical cure regimens. * **Identifyability.R** is the script diagnosing issues with identifiability for the 3 fitted parameters. * **Sensitivity.R** is the script of a sensitivity analysis around each of the assumed (not estimated) parameters.