Pharmacological studies of malaria in pregnancy, infancy and childhood in Papua New Guinea

[Truncated abstract] With half the world’s population still at risk of malaria, it remains one of the most important global health concerns. In highly endemic areas such as coastal Papua New Guinea (PNG), adults develop immunity to symptomatic infection, while pregnant women, infants and children bear the burden of clinical disease. Antimalarial drugs still play an important role in the treatment and prevention of malaria. In pregnancy and infancy prevention of disease is afforded, to some extent, by the use of Intermittent Preventive Treatment (IPT). In childhood, effective treatments are required to prevent recrudescence and early re‐infection. To enable optimal dosing of pharmacological therapy, studies performed in these specific at‐risk groups are required. This primary aims of this thesis were, in samples of at‐risk populations, to describe the pharmacokinetic (PK) properties of a number of antimalarial drugs using a population approach and to provide preliminary information regarding their efficacy, safety and tolerability. These studies were intended to guide future large clinical trials and assist in determining health policies. The first of these studies evaluated the PK of azithromycin (AZI) in pregnant and nonpregnant women. AZI is one of the few antimalarial drugs known to be safe in pregnancy and it is conventionally given with chloroquine or sulfadoxinepyrimethamine (SP). The effect of pregnancy on the PK parameters of AZI was not large enough to justify a dose adjustment. A timed single blood sample that could be used as a surrogate for overall exposure was identified.