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Sam Salman


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Sam Salman

Thesis

Pharmacokinetics of antimalarial compounds for infants, children and pregnant women in Papua New Guinea

Summary

The development of new drug regimens requires investigating the pharmacokinetics (PK) of these agents. As the pharmacokinetics can vary depending on age, race, illness, pregnancy and many other factors it is important to define the disposition of a drug in the setting in which it will be used. This project will define the PK of a number of different antimalarial agents with the view to provide information that will aid in optimum treatment of malaria. In infants the drug combination sulphadoxine/pyrimethamine (Fansidar®)will be investigated to better understand their use in intermittent preventative treatment in infants (IPTi). The artemisinin combination treatments Coartem® (artemether/lumefantrine) and Artequick® (artemisinin/piperaquine) will be investigated in children to ensure adequate dosing occurs in this population. The commonly used antibacterial azithromycin, that also possesses antimalarial activity, will be investigated in pregnant women to determine the effect of pregnancy on its disposition. These studies will provide new information that will aid in future treatment decisions for malaria.

Why my research is important

Malaria is an important global public health concern with around 100 countries or territories still affected, representing 3.2 billion people still at risk of the infection. There is an estimated 300-500 million clinical cases each year and 1.1-2.7 million deaths due to malaria, of these 60% of cases and 80% of deaths are found in sub-Saharan Africa. It is also the ninth leading cause of death in low to middle income countries and amongst the top five leading causes of child death globally.

In PNG there is a range of malaria endemicity due to variability in the altitude around the country. Highest levels of malaria transmission are found in coastal areas where the rainfall and temperatures are ideal for mosquito vectors, as altitude increases temperatures decrease along with malaria transmission. In some coastal areas, especially those closer to the equator on the north coast of the country, there is rainfall throughout the year capable of supporting perennial transmission with levels comparable to those found in sub-Saharan Africa. Four of the five human malarias are found in the country namely falciparum, vivax, malariae and ovale, with falciparum and vivax being most important clinically. Immunity to malaria is gained over a number of infections due to the complexity of the parasite’s immune evasion capabilities. As with other areas of high endemicity this means that young children who are still developing this immunity are most at risk of a symptomatic infection. Pregnant women rarely have symptomatic infections in these areas, due to pre-existing immunity, however an infection can cause maternal anaemia and have negative consequences for the infant especially in primigravidae.

Like many other countries the rate and spectrum of resistance to antimalarial agents in PNG is increasing. New treatments are thus required in PNG as resistance makes traditional drugs ineffective. Investigating the pharmacokinetics of these agents represents one step in establishing new treatment protocols.

Funding

  • NHMRC
  • IPTi consortium
  • MiP Consortium