Malaria remains one of the greatest causes of morbidity and mortality in the world. Globally, there are between 300–500 million cases of clinical malaria every year, with 85% of these from Africa . Currently, 1.5 to 2.7 million deaths are attributable to malaria annually, 90% of them in Africa . In Nigeria, malaria is holoendemic hence clinical cases of the disease are seen throughout the year. It is the commonest cause of outpatient hospital attendance in all age-groups in the country . Under five children are especially prone to develop the severe forms of the disease which, if not treated promptly can lead to death. Drug Therapeutic Efficacy Tests (DTET) conducted in different parts of Nigeria on chloroquine and sulphadoxine-pyrimethamine combination in 2002 showed adequate clinical and parasitological response (ACPR) of 39.2% and 56.7% respectively . Thus, chloroquine and sulphadoxine-pyrimethamine are no longer efficacious in treating malaria in Nigeria [4, 5]. The global malaria control strategy advocates prompt and adequate treatment with an effective antimalarial drug as an essential measure to reduce the morbidity and mortality arising from the disease . In line with above findings, the Federal Ministry of Health considered a change in policy to artemisinin-based combination therapy (ACT), which has been shown to be effective in other countries. The rationale for the use of ACTs is to reduce the probability of resistance developing simultaneously to two drugs with independent mechanisms of action [5, 6].
The artemisinin drugs are developed from the Chinese wormwood (Artemisia annua) and the derivatives, namely, artemether, artesunate and dihydroartemisinin have now gained popularity as short acting drugs which could be used in combination with drugs which have longer half-life [7, 8]. Mefloquine has been reported to consistently show high treatment efficacy in African children [9, 10] and in pregnant women . This was in the era of antimalarial monotherapy. At that time, mefloquine, a 4-quinoline carbinol, was reported to be one of the most effective drugs in the treatment of malaria in Nigeria . It was also found to be an effective suppressive prophylactic drug, when administered weekly or fortnightly against drug-resistant Plasmodium falciparum . The successful treatment of falciparum malaria with regimens of artemisinin derivatives plus mefloquine has been reported in other countries [14–17]. The pharmacokinetics of mefloquine combined with artesunate in children with acute falciparum malaria in Thailand has also been studied . Li et al  showed that artesunate has a broader stage-specificity of action than other antimalarial drugs. After oral artesunate, relative bioavailability of the drug was 82.0%. The parasite clearance time (PCT) and fever clearance time (FCT) were 6.5 hours and 24 hours respectively  and parasitaemia was reduced by 90% within 24 hours after starting treatment.
The rationale was based on the convincing evidence that a combination of two or more schizontocidal drugs will not only improve cure rate but could help reduce the rate of development of parasite resistance to either of the drugs in the combination. Thus, the combination of short-acting artemisinin derivative (artesunate) with longer acting mefloquine is expected to constitute a good ACT.
The Drug Therapeutic Efficacy tests (DTET) conducted on two such combinations, namely, artesunate + amodiaquine and artemether + lumefantrine in 2004 showed adequate clinical and parasitological response (ACPR) of 94.6% and 96.8% respectively . The Federal ministry of health then changed the policy on malaria treatment to artemisinin-based combination therapy (ACT) .
However, there is the challenge of availability and affordability of ACTs. To improve better access to ACTs at affordable prices, Roll Back Malaria partners in the pharmaceutical industries were encouraged to pre-package ACTs, which could be used if found effective, approved and duly registered by the regulatory authorities. One such combination drug is Artequin™, a combination of artesunate and mefloquine, manufactured by MEPHA Ltd (Aesch, Basel, Switzerland). Although this combination has been reported to be efficacious elsewhere, there is need to determine the efficacy, safety and tolerability of this ACT among Nigerians.
This co-packaged formulation of artesunate and mefloquine has not been used before now in Nigeria. The outcome of therapeutic efficacy tests could be different in Nigeria, or even in different geographic zones of the country. It is, therefore, important to determine the efficacy, safety and tolerability of this co-packaged formulation of AM among Nigerian population. There is also the need to provide more options for malaria control in Nigeria.
The objectives of the study were:
To evaluate therapeutic efficacy of a combination of artesunate plus mefloquine (AM) using the modified WHO seven-day in vivo test extended to 14 and 28 day follow-up period.
To determine the safety and tolerability of AM in the treatment of acute uncomplicated P. falciparum malaria.
To estimate gametocyte carriage and its reduction during treatment.