Following the inclusion of artemether - lumefantrine combination as one of the first-line drugs for the treatment of uncomplicated malaria in Ghana in 2008 , there was the need to study its therapeutic efficacy in four sentinel sites representing the three main ecological zones of the country during the 2010/2011 surveillance period.
The study has shown that the overall PCR-corrected cure rate for Ghana is 95.4% (95% CI: 90.3, 98.0) with the savannah zone showing a significantly lower rate of 90.4% (95% CI: 78.2, 96.4). The over 90% cure rate of AL in Ghana is comparable with findings from other studies in Africa within the past decade [5, 14–20], and suggests that Ghana as a whole has not reached the 10% cut-off failure rate necessary for the review of AL as one of the first line drugs in the treatment of uncomplicated malaria in the country . However, the 9.6% early treatment failure rate observed in the savannah zone is worrying and suggests the need for conduct of pharmacokinetic studies during subsequent efficacy studies to determine the adequacy of plasma drug concentrations, which is necessary for describing treatment failures .
Fever and parasite clearance were slower among children enrolled in the savannah zone. Whereas no child was febrile on day-3 and day-7 in the forest and coastal zones, febrile cases were reported on all days among children in the savannah zone during the first follow-up week. The proportion of children still febrile on day-1 post-treatment was significantly highest in the savannah zone (42.9%; 95% CI: 30.0, 56.7) compared with the forest zone (16.7%; 95% CI: 9.5, 27.2) and the coastal zone (10.5%; 95% CI: 3.4, 25.7) (p < 0.001). Additionally, 8/55 or 14.5% (95% CI: 6.9, 27.2) of the children enrolled in the savannah zone were parasitaemic on day-2 post-treatment whilst no child was parasitaemic on the same day in the forest and coastal zones. Out of the 8 parasitaemic children 5 (62.5%; 95% CI: 25.9, 89.8) had parasite count greater than the day-0 count but remained aparasitaemic on days 3, 7, 14, 21, and 28 post-treatment without any rescue treatment. The rapid rise in asexual parasitaemia after commencement of ACT treatment has been reported in Nigeria and attributed to a possible larger load of sequestered parasites in deep tissues in some patients. In the Nigeria study, parasitaemia levels peaked at one hour after the first dose of AL, and by 16 hours post-treatment all parasites had been cleared among children with initial rise in parasitaemia . In our study, total asexual parasite clearance for children with increased parasitaemia on day-2 was achieved on day-3. This observation, coupled with the known phenomenon of parasite mobilization from deep tissues by ACT raises concern about the WHO criteria for ETF classification in relation to parasite densities . It may be worthwhile shifting the criteria from day-2 to day-3 post-treatment in areas of intense transmission. This notwithstanding, the delayed clearance of fever and parasites in the savannah zone need to be further studied taking into account the possible effects of ACT usage on parasite dynamics within the population .
Pre-treatment gametocytaemia was prevalent only in the savannah zone (7.1%) and declined to 0% by day-2 post-treatment whilst gametocytaemia was prevalent on day-2 post-treatment in the coastal zone (10.5%), halved by day-3 (5.3%), and declined to 0% by day-7 post-treatment. This finding suggests that ACT remains efficacious in gametocyte clearance in Ghana. The efficacy in gametocyte clearance has the advantage of potentially slowing down the transmission of resistant alleles .
Post-treatment mean haemoglobin concentration was significantly higher than pre-treatment concentration in the coastal zone but not the forest and savannah zones. This finding suggests that the therapeutic efficacy of AL resulting from rapid parasite clearance may not necessarily translate into significant post-treatment increases in haemoglobin concentrations during a 28-day follow up period. A couple of studies in Africa have reported non-significant post-treatment increases in haemoglobin concentrations with AL treatment during a 28-day follow-up period of patients treated for acute uncomplicated malaria [15, 26] whilst a couple of studies in Ghana have reported significant increases during the same follow-up period [5, 27].