A model for malaria treatment evaluation in the presence of multiple species

C R Walker; R I Hickson; E Chang; P Ngor; S Sovannaroth; J A Simpson; D J Price; J M McCaw; R N Price; J A Flegg; A Devine

doi:10.1016/j.epidem.2023.100687

A model for malaria treatment evaluation in the presence of multiple species

Epidemics. 2023 Sep:44:100687. doi: 10.1016/j.epidem.2023.100687. Epub 2023 May 18.

Authors

C R Walker¹, R I Hickson², E Chang³, P Ngor⁴, S Sovannaroth⁵, J A Simpson⁶, D J Price⁷, J M McCaw⁸, R N Price⁹, J A Flegg³, A Devine¹⁰

Affiliations

¹ School of Mathematics and Statistics, University of Melbourne, Australia. Electronic address: camelia.walker@unimelb.edu.au.
² School of Mathematics and Statistics, University of Melbourne, Australia; Australian Institute of Tropical Health and Medicine, and College of Public Health, Medical & Veterinary Sciences, James Cook University, Australia; Health and Biosecurity, CSIRO, Australia.
³ School of Mathematics and Statistics, University of Melbourne, Australia.
⁴ Cambodian National Center for Parasitology, Entomology and Malaria Control, Cambodia; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Thailand.
⁵ Cambodian National Center for Parasitology, Entomology and Malaria Control, Cambodia.
⁶ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Australia.
⁷ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Australia; Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Australia.
⁸ School of Mathematics and Statistics, University of Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Australia.
⁹ Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Thailand; Division of Global and Tropical Health, Menzies School of Health Research and Charles Darwin University, Australia; Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, UK.
¹⁰ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Australia; Division of Global and Tropical Health, Menzies School of Health Research and Charles Darwin University, Australia.

Abstract

Plasmodium falciparum and P. vivax are the two most common causes of malaria. While the majority of deaths and severe morbidity are due to P. falciparum, P. vivax poses a greater challenge to eliminating malaria outside of Africa due to its ability to form latent liver stage parasites (hypnozoites), which can cause relapsing episodes within an individual patient. In areas where P. falciparum and P. vivax are co-endemic, individuals can carry parasites of both species simultaneously. These mixed infections complicate dynamics in several ways: treatment of mixed infections will simultaneously affect both species, P. falciparum can mask the detection of P. vivax, and it has been hypothesised that clearing P. falciparum may trigger a relapse of dormant P. vivax. When mixed infections are treated for only blood-stage parasites, patients are at risk of relapse infections due to P. vivax hypnozoites. We present a stochastic mathematical model that captures interactions between P. falciparum and P. vivax, and incorporates both standard schizonticidal treatment (which targets blood-stage parasites) and radical cure treatment (which additionally targets liver-stage parasites). We apply this model via a hypothetical simulation study to assess the implications of different treatment coverages of radical cure for mixed and P. vivax infections and a "unified radical cure" treatment strategy where P. falciparum, P. vivax, and mixed infections all receive radical cure after screening glucose-6-phosphate dehydrogenase (G6PD) normal. In addition, we investigated the impact of mass drug administration (MDA) of blood-stage treatment. We find that a unified radical cure strategy leads to a substantially lower incidence of malaria cases and deaths overall. MDA with schizonticidal treatment was found to decrease P. falciparum with little effect on P. vivax. We perform a univariate sensitivity analysis to highlight important model parameters.

Keywords: Malaria; Plasmodium falciparum; Plasmodium vivax; Stochastic modelling; Unified treatment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Coinfection*
Humans
Malaria* / drug therapy
Malaria* / epidemiology
Malaria* / parasitology
Malaria, Falciparum* / drug therapy
Malaria, Falciparum* / epidemiology
Malaria, Falciparum* / parasitology
Malaria, Vivax* / drug therapy
Malaria, Vivax* / epidemiology
Malaria, Vivax* / parasitology
Plasmodium vivax
Recurrence

Abstract

Publication types

MeSH terms

Grants and funding