Artemisinins are known to be highly potent anti-malarial drugs that are active against immature gametocytes [13, 14], hence pivotal in reduction of malaria transmission and elimination/eradication agenda. To the best of authors’ knowledge, there is no evidence of clinical resistance to AL. However tolerance or increased parasite clearence time and reduced susceptibility to artemisinins and artesunate-mefloquine has been observed in Thai-Cambodia and Thai-Mynmar boarder [5, 6]. This is the same locus where chloroquine resistance first emerged and subsequently spread all over the world. Emergence of artermisinin resistance would be disastrous for global malaria control. Therefore, regular surveillance and prompt response to any indication of compromised efficacy is required .
This study recorded high (100%) efficacy of AL. The reported efficacy level is more or less similar to >98% recorded in Tanzania, prior to introduction of AL , and elsewere in Africa [16–20]. However, in these other studies, the high efficacy rates were reached after exclusion of new infection by molecular genotyping. Therefore, it is obvious that the cause of alarm that prompted this exploratory study in Tabora was not malaria recurrence or compromised AL efficacy but malaria overdiagnosis. This practice has been reported previously elsewhere in Africa [21, 22] as a cause of inappropriate malaria case managment . Overdiagnosis is attributable to incompetency of laboratory workers, work overload, and pressure from patients with fever accepting malaria diagnosis .
In this study, none of the patients reported to have taken AL prior to hospital presentation, which was confirmed by lack of lumefantrine traces in the plasma. In addition, all patients had adequate therapautic levels of lumefantrine on Day 7. However, the Day 7 plasma lumefantrine levels showed wide variation between individuals. Indeed, it is known that the efficacy of AL combination is strongly influenced by wide variation in the pharmacokinetics of lumefantrine among individuals . The maximum therapeutic cure rate is achieved when the plasma drug concentration is adequately available for at least three parasite life cycles that is equal to six days . The impact of pharmacokinetic variation on selection for resistance to residual parasites in high transmission areas needs to be carefully evaluated.
Artemether-lumefantrine showed short fever and parasites clearence time and quick recovery of haemoglobin levels. Only one patient had fever up to Day 1 and neither fever nor parasitaemia was reported on Day 2, contrary to a report in central Ethiopia where fever and parasitaemia persisted to Day 3 . Haemoglobin levels significantly increased on Day 7 as reported in other studies in this region, but the second haemoglobin measurement was done on Day 14 [27, 28]. The complete 28 days’ follow up to all patients was achieved by using mobile phone calls to remind parents or guardians about their appointment dates and days. Mobile phone contacts might minimize loss to follow up in efficacy studies.
The Day 0 gametocyte prevalence (30%) recorded in this study is higher compared with those reported previously in Tanzania [29, 30]. Furthermore, as observed elsewhere in Africa [27, 31–33], no new gametocytaemic cases were observed during the follow-up period. Admittedly, this could be attributable to small sample size, which is a limitation of this study, and microscopy detection limit. Gametocytaemia persisted for seven to 14 days, (as recorded previously), against 55 days for non-ACT drugs .
ACT is effective against immature sequestered gametocytes [32, 34, 35], hence they reduce gametocyte carriage as well as gametocytes density [31, 36, 37]. Apparently, ACT does not affect the viability of mature gametocytes [31, 36]. Consequently, persistence of mature gametocytes might still play a role on maintianing transmission cycle. Hence, combination with a strong gametocytocidal drug such as primaquine will maximize ACT usefulness.
The phenomenon of increase in gametocytaemia in this study and of sexual stage count in Nigeria  despite drug treatment, might be a sign of tolerance or emergence of parasites with reduced drug sensitivity in the region. Another plausible explanation for the increase in gametocytaemia is coincidence between drug administration and maturation release of mature gametocytes into the peripheral circulation. These observations of increased gametocytaemia after treatment need to be verified in a larger study.