title: Spatial Effects on the Multiplicity of Plasmodium falciparum Infections.
abstract: As malaria is being pushed back on many frontiers and global case numbers are declining, accurate measurement and prediction of transmission becomes increasingly difficult. Low transmission settings are characterised by high levels of spatial heterogeneity, which stands in stark contrast to the widely used assumption of spatially homogeneous transmission used in mathematical transmission models for malaria. In the present study an individual-based mathematical malaria transmission model that incorporates multiple parasite clones, variable human exposure and duration of infection, limited mosquito flight distance and most importantly geographically heterogeneous human and mosquito population densities was used to illustrate the differences between homogeneous and heterogeneous transmission assumptions when aiming to predict surrogate indicators of transmission intensity such as population parasite prevalence or multiplicity of infection (MOI). In traditionally highly malaria endemic regions where most of the population harbours malaria parasites, humans are often infected with multiple parasite clones. However, studies have shown also in areas with low overall parasite prevalence, infection with multiple parasite clones is a common occurrence. Mathematical models assuming homogeneous transmission between humans and mosquitoes cannot explain these observations. Heterogeneity of transmission can arise from many factors including acquired immunity, body size and occupational exposure. In this study, we show that spatial heterogeneity has a profound effect on predictions of MOI and parasite prevalence. We illustrate, that models assuming homogeneous transmission underestimate average MOI in low transmission settings when compared to field data and that spatially heterogeneous models predict stable transmission at much lower overall parasite prevalence. Therefore it is very important that models used to guide malaria surveillance and control strategies in low transmission and elimination settings take into account the spatial features of the specific target area, including human and mosquito vector distribution.
authors.affiliation: Population-Based Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.|Vector-borne Diseases Unit, Papua New Guinea Insititute of Medical Research, Madang, Madang Province, Papua New Guinea.
authors.forename: Stephan
authors.initials: S
authors.lastname: Karl
authors.affiliation: Population-Based Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|MRC Centre for Outbreak Analysis & Modelling, Department of Infectious Disease Epidemiology, Imperial College, London, United Kingdom.
authors.forename: Michael T
authors.initials: MT
authors.lastname: White
authors.affiliation: School of Computer Science and Software Engineering, The University of Western Australia, Perth, WA, Australia.
authors.forename: George J
authors.initials: GJ
authors.lastname: Milne
authors.affiliation: Department of Mathematics, Applied Mathematics and Statistics, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Gurarie
authors.affiliation: Institute for Health Metrics and Evaluation, Seattle, Washington, United States of America.|Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Simon I
authors.initials: SI
authors.lastname: Hay
authors.affiliation: Population-Based Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Alyssa E
authors.initials: AE
authors.lastname: Barry
authors.affiliation: Department of Medical Parasitology and Infection Biology Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Felger
authors.affiliation: Population-Based Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.|Malaria: Parasites and Hosts Unit, Department of Parasites & Insect Vectors, Institut Pasteur, Paris, France.
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
mesh_terms: D000483:Alleles; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D009033:Culicidae / Q000502:physiology; D006801:Humans; D007303:Insect Vectors / Q000502:physiology; D016778:Malaria, Falciparum / Q000635:transmission*; D015233:Models, Statistical; D010963:Plasmodium falciparum / Q000235:genetics / Q000502:physiology*; D015800:Protozoan Proteins / Q000235:genetics; D062206:Spatial Analysis
chemical_list: D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium