Treatment Efficacy and Malaria TRANSmission After Artemisinin Combination Therapy 2 (TRANSACT2)

Accurate diagnosis followed by prompt and efficacious treatment is the backbone of any malaria control programme. However, malaria treatment has been facing huge challenges in recent years. A number of affordable antimalarial drugs have been used to cure malaria since the 1940s: these include chloroquine (CQ), sulphadoxine-pyrimethamine (SP; Fansidar®), mefloquine (MQ), amodiaquine (AQ) and quinine. The emergence and spread of resistance to these commonly-used drugs has been largely responsible for the worsening of the malaria situation observed in the past decades.

Across the African continent, guidelines have recently been changed. The World Health Organization (WHO) recommends for falciparum malaria the use of combination therapies, preferably those containing artemisinin derivatives (ACT, artemisinin-based combination therapy). Artemisinin derivatives, e.g. artesunate, artemether and dihydroartemisinin, being extremely potent antimalarial agents are the ideal partners in combinations with other antimalarials. ACTs have three demonstrable advantages over conventional therapy, they i) are efficacious in clearing asexual parasites, ii) substantially reduce post-treatment gametocyte carriage and iii) "protect" the partner drug from selecting resistant parasites.

In Kenya, both CQ and SP have lost clinical efficacy. CQ was replaced by SP in 1998 and in the year 2006, SP was effectively replaced by Artemether-Lumefantrine (AL: Coartem®). The policy change to the artemisinin-based drug AL is in line with the WHO recommendations to shift to ACT as first line antimalarial treatment.The most efficacious ACT, however, needs local comparisons in terms of treatment efficacy and transmission-reducing activity.

Inclusion criteria

• Age 6 months - 10 years
• Residents of research area (5 km around the clinic)
• Willingness to come for complete scheduled follow-up.
• Uncomplicated malaria with P. falciparum mono-infection
• Parasitaemia of 1000-200,000 parasites/ul
• Temperature > 37.5°C and < 39.5°C, or history of fever in previous 24 hours.
• No history of adverse reactions to AL
• Understanding of the procedures of the study by parent or guardian and willing to participate by signing informed consent forms.

Exclusion criteria

• General signs of severe malaria
• Haemoglobin concentration < 5g/dl
• Presence of disease other than malaria causing febrile conditions
• Mixed infection with P. malariae or other non-falciparum malaria species
• Unwilling to participate and sign informed consent forms.