Moving towards improved malaria control The position of molecular diagnostics and evaluating the efficacy of a novel treatment option

Even though wide-scale interventions have led to important reductions in malaria morbidity and mortality, the disease still has a large impact on human health. Scaling up existing interventions and developing new methods for malaria control are essential to eventually eliminate malaria in most endemic settings. Prevention, diagnosis and treatment play crucial roles in this respect. The focus of this thesis lies on the latter two and the described work can be grouped into two main sections. Section A comprises (molecular) diagnostics. Microscopy and/or rapid diagnostic tests are highly suitable for case detection but lack sensitivity to detect low-density infections. It is important to diagnose and treat these submicroscopic infections, particularly in low transmission areas targeting elimination. Highly sensitive molecular diagnostics may play an important role, but technical requirements and costs hamper their implementation in resource-limited settings. In this thesis, the diagnostic accuracy of different molecular malaria diagnostics is discussed and the development and evaluation of direct-on-blood PCR Nucleic Acid Lateral Flow Immunoassay is described, a molecular tool designed to overcome some implementation challenges of conventional diagnostics. It was found to be a sensitive, specific and easy method for the detection and species differentiation of Plasmodium. In section B, the efficacy, safety and gametocyte dynamics of pyronaridine-artesunate (PA) were described, a novel artemisinin-based combination therapy. Pyronaridine-artesunate was found to be well-tolerated and efficacious for the treatment of uncomplicated P. falciparum malaria in Kenyan children. The duration of gametocyte carriage and gametocyte circulation time were slightly longer for pyronaridine-artesunate, compared to artemether-lumefantrine.