Molecular measures for declining malaria transmission in Papua New Guinea

In the last decades malaria control strategies have led to a dramatic decrease of malaria prevalence and many endemic countries are moving towards elimination. Despite such great achievements, the current control progress is challenged by a high prevalence of asymptomatic low density parasite infections, especially in areas of low transmission. These low-density submicroscopic infections can infect mosquitoes and thus contribute to malaria transmission, but often remain undetectable by microscopy or rapid diagnostic tests. Molecular diagnostics are crucial to characterise this submicroscopic parasite reservoir. Understanding the true picture of submicroscopic parasite infections and their role for transmission in different transmission settings is vital to design adequate interventions and progress towards elimination.
This PhD thesis provides improved molecular diagnostic tools for detection and quantification of submicroscopic and low-density P. falciparum and P. vivax parasite infections. The novel P. vivax ultra-sensitive qPCR assay, together with the established P. falciparum qPCR assay, provide more accurate prevalence data and improve malaria diagnosis in epidemiological studies across all transmission settings. Mapping of accurate malaria prevalence is particularly relevant in pre- and elimination settings to plan and evaluate the impact of interventions in order to prevent the resurgence of the malaria parasite.
The development of new highly sensitive male-specific gametocyte assays allows to study the transmission potential of ultra-low density P. falciparum infections. Quantification of male and female gametocyte densities in P. falciparum infections improves the precision of mathematical models to predict human-to-mosquito infectivity. Identification of the infectious parasite reservoir in endemic communities can guide targetted interventions to reduce transmission and accelarate elimination.
The third project of this thesis presents a new AmpSeq-based approach to determine drug treatment outcome in antimalarial clinical trials. AmpSeq overcomes drawbacks inherent to standard length-polymorphic genotyping and permits robust characterisation of clone dynamics during trial follow up. AmpSeq also provides a valuable tool for genomic surveillance of malaria parasites and can fundamentally contribute to understand the spread of drug-resistant malaria parasites.