The results of this study show, both clinically and parasitologically, that SP is significantly superior to AQ in terms of efficacy, with day-28 PCR-corrected failure rates of 11.6% and 28.2% respectively. SP also was more effective than AQ for preventing recurrent infections. Both regimens were safe and well-tolerated, with no serious adverse reaction recorded during the course of the study. Although protocols of previous studies were not in conformity with the standard WHO protocol, our data concerning SP efficacy are consistent with those reported in other parts of the country, such as in Bakoumba (Haut-Ogooué province) indicating a treatment failure rate of 14% at day 28 without PCR-adjustment in children under 10 years [
14]. A good efficacy of SP was also observed in neighbouring Congo, Cameroon and Equatorial Guinea [
9,
10,
24]. The absence of the
dhps K540E mutation observed in the present study was already described in Gabon [
25] and in neighbouring countries [
17,
25,
26]. There is now a clear evidence that the principal role attributed to the
dhps K540E mutation as a molecular marker predicting clinical SP-treatment failures is not true either in the existing literature or in the present study where 11.6% of SP resistance was found without a single instance of
dhps K540E mutation. The AQ-resistance level reported in the study is too high, according to WHO guidelines (AQ-treatment failures >25%). The present results regarding AQ efficacy are consistent with other studies from Lambarané (Moyen-Ogooué province) and Bakumba (Haut-Ogooué province), reporting worse AQ efficacy with PCR-uncorrected resistance rates ranging from 34.7% to 47% on day 28 [
13,
14]. In contrast, the results from Libreville (Estuaire Province) have reported low AQ-failure rates ranging from 0% to 13% on day 14 [
1,
2,
12]. Though these data are lacking PCR-adjustment, it seems that AQ efficacy is creating geographic differences in Gabon. Further AQ efficacy studies carefully carried out according to standard WHO protocol in other parts of the country, including settings reporting high AQ-failure rates, are urgently needed. Geographic differences of AQ efficacy cannot be directly explained by differences in malaria transmission levels between different regions of the country, because it was reported that transmission intensity does not directly affect the evolution of drug-resistance [
27]. However, the relative importance of immunity in determining the response to therapy has been demonstrated in other studies, which had shown that age, a surrogate marker of acquired immunity, is associated with the ability to clear parasites with resistant genotypes [
28]. It has been reported that cytochrome P450 CYP2C8 is involved in the metabolism of AQ, and additionally some information is currently available concerning its variation among ethnic groups as in Zanzibar and in Ghana [
29,
30]; this also needs to be investigated in Gabon in order to understand these inter-provincial differences of AQ efficacy.
In conclusion, geographical differences of AQ efficacy discussed in this study are a major concern in Gabon now that the AQ/AS combination has been selected as the new malaria first-line treatment policy. Thus, further investigations carefully conducted in the respect of good clinical practices are necessary to ascertain AQ-resistance at the national level.
In a country where ACTs are implemented, classical antimalarial drugs, including AQ and SP, must be monitored by recruiting persons with asymptomatic P. falciparum infection. The results of this longitudinal prospective study will provide an essential baseline of the parasitological efficacy of those monotherapies and also to be able to understand, at a later stage, the natural history of the evolution of resistance to ACTs.