This study showed an overall 28-day cure rate of 79.3% for the fixed dose combination of artemisinin-naphthoquine. It was not possible to perform polymerase chain reaction (PCR) to confirm the genetic characteristics of the species reported as treatment failures in this study to determine whether these were due to recrudescence or actually new infections. This cure rate is lower than those reported in other efficacy studies on the same drug, most of which were between 97% and 98%
[9–11, 16]. Treatment failures in all these studies were confirmed with PCR thereby excluding new infections. It is possible that the failure to exclude possible new infections in this Nigerian study with molecular techniques has contributed to the lower cure rate reported.
Single dose artemisinin-naphthoquine has also been shown to have an efficacy rate comparable to that of artemether-lumefantrine
. This study did not compare artemisinin- naphthoquine with another ACT, but an earlier study in the same locality showed comparable cure rates for artemether-lumefantrine (87.0%) and artesunate/amodiaquine (82.5%)
. The rapid decrease in the number of persons with parasitaemia by Day 2 of follow-up is indicative of the high therapeutic efficacy characteristic of other forms of ACT already in use. An adequately powered comparative trial of established formulations of ACT with this agent will be required to establish non-inferiority or otherwise, as well as tolerability and adherence to treatment.
The recommended artemisinin-naphthoquine dose for those aged 15 years and above is a single blister (1,000/400 mg) comprising eight tablets (125/50 mg). The exploratory dose-finding assessment performed in this study showed that the treatment arm that received the total recommended dose in two split doses of four tablets (500/200 mg) per dose had a higher 28-day cure rate than those that received the recommended single dose regimen without any difference in tolerability. This observation is limited by the lack of pharmacokinetics data to adequately investigate bioequivalence.
The unique advantage of artemisinin-naphthoquine is its simple dosage schedule, a characteristic which is more likely to be associated with better patient adherence to treatment than ACT regimens that required multiple dosing schedules
[19, 20]. The second drug in this artemisinin combination therapeutic regimen, naphthoquine has a long elimination half-life and has not been used widely in this environment as a single agent for the treatment of P. falciparum malaria and, therefore, is able to sustain and complete elimination long after the artemisinin component has waned to below therapeutic levels
. While the use of this combination regimen on naive parasite populations may achieve high cure rates, there is however significant risk that widespread single dose use of naphthoquine in this combination regimen could create sufficient pressure on the parasites leading to emergence of increasingly less susceptible mutants and ultimately varying degrees of parasite resistance
[14, 21]. This raises significant concern about the continued use of this drug combination as a single dose regimen among populations resident in areas with intense perennial transmission where there is likely to be a rapid increase in the pool of people with mutant species of P. falciparum. Recent evidence from clinical evaluation of a large cohort of children treated with artemether-lumefantrine and artesunate-amodiaquine showed that these artemisinin-based combination treatments are still highly efficacious in Nigeria
. However, reports of emergence of strains of P falciparum resistant to the artemisinin compound in south-east Asia calls for greater attention to rationale use of ACT regimens
In order to prevent or delay the emergence and spread of P. falciparum resistance to the component drugs of this potentially beneficial combination regimen (arteminisin-naphthoquine), it would be advisable to use a once daily regimen for a period long enough to ensure complete elimination of all susceptible parasites in each treatment course. In this study, the use of a single-dose regimen of half the recommended dose was explored and revealed a fairly good 28-day cure rate but lower than the rate obtained with the recommended dose. It is likely that administration of single daily dose of 500/200 mg for three days will achieve high cure rates with much lower risk of recrudescence than would be the case with the current practice of single dose of 1,000/400 mg give only for one day. A well designed trial to test this dosage option would be of immense public health importance to avert the likely deterioration of this combination regimen from widespread use as single dose regimen.
One of the key elements in any drug development and evaluation is the issue of safety of the population for which the drug is intended. Artemisinin-naphthoquine was well tolerated and no serious adverse event was recorded in the study. The commonest adverse events were weakness and headache which were reported more in the group that took the recommended dosage. Since both symptoms could also be caused by malaria, it is not certain whether these symptoms were due to the drug alone or caused by the illness itself. This is in keeping with findings from earlier studies in China that showed that this drug is safe and well tolerated
[9, 10, 16]. Larger studies are needed to define the safety and efficacy in different population including children and pregnant women.