Several studies have analysed the efficacy and tolerability of AL and DP and all show very good results [1, 4, 6, 7, 12, 14, 25]. In the present study, the two drugs showed to be similar with respect to effectiveness and tolerability compared to other studies. However, most of these studies have a follow up of 42 days which makes a direct comparison of the results difficult. No adverse events other than those related to malaria itself were observed in the current study, which is in line with other reports. In the present study, all children experienced haemoglobin convalescence without difference between the two treatment arms, in contrast to the study of Kamya et al, who found a greater increase in the DP treated patients . The difference in follow-up time and the numbers of patients included in both studies may be responsible for this difference. Further studies with comparable study length should be done to give an answer to these discrepancies.
The effects on gametocytaemia and possibly malaria transmission deserve further study. Whereas asexual parasites were cleared in three days after the initiation of the two treatment schedules, gametocytaemia appeared different when assessed by microscopy as well as with NASBA. Gametocytes were present in low numbers throughout follow-up in both study groups. Artemisinin derivatives have in general a negative effect on gametocyte development and survival and thus influence malaria transmission, at least in low transmission areas [15–17]. In this study, the actual infectiousness of the remaining gametocyte populations in both treatment arms was not assessed; the presence of gametocytes does not necessarily mean that they actually contribute to transmission. Several studies have shown that gametocytes persist in a large population of previously infected and treated children [5, 19, 26, 27]. A large proportion of these carriers has a parasite load below microscopical detection limit, a load that can be detected with molecular assays like NASBA. Patients with submicroscopic parasite densities may still be infectious to mosquitoes and may contribute to transmission [14, 19], as confirmed with membrane feeding experiments [18, 28]. Studies that include reduction of transmission as a component of efficacy of drugs, thus need to incorporate highly sensitive molecular assays to reliably assess gametocyte densities.
The present study showed a limited effect of DP on gametocyte development in comparison with AL when a sensitive tool like NASBA is used for gametocyte detection, which could limit the usefulness of DP to areas with low transmission but this finding should be further investigated in larger studies in different study sites with different transmission intensities. It is not clear if plasma concentrations of dihydroartemisinin in the blood could play a role. Dihyrodartemisinin is the major and the active metabolite of artemether. So far, no studies have been performed that compare the plasma levels of dihydroartemisinin when given as such or after administration of artemether and subsequent metabolisation. This should be further investigated together with effect on gametocytogenesis, which should incorporate a sensitive detection tool for gametocytes such as NASBA.
The effect that drugs can have on gametocyte clearance as measured with NASBA could have some implications for the introduction drugs and especially the introduction of new drugs. This study showed that with sensitive detection tools a difference in parasite clearance can be observed but these results should be confirmed in larger studies and in other study areas with different malaria transmission intensities. Transmission intensity varies significantly in the different African countries and within a country high and low transmission areas can often be identified. Malaria endemic countries generally have a national malaria drug policy for the whole country. Although this is logical from a practical and logistical point of view, it may not be the best approach for effective malaria control. It could, therefore, be more effective if a country develops specific drug policies to suit regional instead of national requirements.