Seasonal malaria chemoprevention and the spread of Plasmodium falciparum quintuple-mutant parasites resistant to sulfadoxine-pyrimethamine: a modelling study.

Background: Seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine prevents millions of clinical malaria cases in children younger than 5 years in Africa's Sahel region. However, Plasmodium falciparum parasites partially resistant to sulfadoxine-pyrimethamine (with quintuple mutations) potentially threaten the protective effectiveness of SMC. We evaluated the spread of quintuple-mutant parasites and the clinical consequences.

Design and selection of drug properties to increase the public health impact of next-generation seasonal malaria chemoprevention: a modelling study.

Background: Seasonal malaria chemoprevention (SMC) is recommended for disease control in settings with moderate to high Plasmodium falciparum transmission and currently depends on the administration of sulfadoxine-pyrimethamine plus amodiaquine. However, poor regimen adherence and the increased frequency of parasite mutations conferring sulfadoxine-pyrimethamine resistance might threaten the effectiveness of SMC. Guidance is needed to de-risk the development of drug compounds for malaria prevention.

Patient variability in the blood-stage dynamics of Plasmodium falciparum captured by clustering historical data.

Background: Mathematical models provide an understanding of the dynamics of a Plasmodium falciparum blood-stage infection (within-host models), and can predict the impact of control strategies that affect the blood-stage of malaria. However, the dynamics of P. falciparum blood-stage infections are highly variable between individuals.

The influence of biological, epidemiological, and treatment factors on the establishment and spread of drug-resistant .

The effectiveness of artemisinin-based combination therapies (ACTs) to treat malaria is threatened by resistance. The complex interplay between sources of selective pressure-treatment properties, biological factors, transmission intensity, and access to treatment-obscures understanding how, when, and why resistance establishes and spreads across different locations. We developed a disease modelling approach with emulator-based global sensitivity analysis to systematically quantify which of these factors drive establishment and spread of drug resistance.