A randomized, comparative study of supervised and unsupervised artesunate–amodiaquine, for the treatment of uncomplicated malaria in Ghana

Abstract

Although the use of artesunate-amodiaquine treatment is growing in Africa, data on its effectiveness are limited. In only the second published comparison of supervised and unsupervised treatments with this combination, Ghanaian children with uncomplicated malaria have recently been investigated in an open-label, randomized, comparative study. Children aged 6-120 months attending the Navrongo War Memorial hospital between November 2005 and December 2006 were enrolled if they had uncomplicated Plasmodium falciparum malaria and at least one of their parents/guardians gave their informed consent. Overall, 638 patients were screened, 357 were found to have P. falciparum infection, and 308 of these satisfied the other selection criteria and were enrolled. The subjects were divided randomly into two treatment arms. All the children were scheduled to receive 10 mg amodiaquine/kg and 4 mg artesunate/kg daily for 3 days but only 154 (the 'supervised') were given all their treatments in hospital, with each dose directly observed. Although the other 154 children (the 'unsupervised') were given their first dose in hospital, under supervision, they were then sent home with the tablets they required to complete treatment. Study participation lasted for 28 days, with follow-up on days 3, 7, 14, 21 and 28. During follow-up, axillary temperatures, any emergent signs and symptoms, and concomitant drug consumption were recorded and haemoglobin concentrations and malarial parasitaemias and gametocytaemias were measured. All but seven of the 308 subjects completed the study. At enrolment the subjects had a mean age of 45.0 months, a mean weight of 14.8 kg, a mean axillary temperature of 37.9 degrees C and a geometric mean parasitaemia of 11,367 asexual stages/microl. About 55% of the children investigated were girls. There were no significant baseline difference between the two treatment arms. Although there was also no difference in the clearance of fever and parasitaemia between the two arms by day 14, a supervised child was significantly more likely to show an adequate clinical and parasitological response, by day 21 (91.3% v. 84.1%; P= 0.05) or day 28 (80.0% v. 64.9%; P<0.01), than an unsupervised child. The reported adverse effects following treatment and the trend in haemoglobin recovery were, however, similar in the two arms. Although artesunate-amodiaquine appeared very effective in the treatment of uncomplicated P. falciparum malaria in children, whether supervised or not, it appears that supervised treatment provided stronger prevention against re-infection and recrudescence. At least in the present study, treatment at home, without medical supervision, probably led to relatively poor compliance.

Adherence to Artesunate-Amodiaquine Therapy for Uncomplicated Malaria in Rural Ghana: A Randomised Trial of Supervised versus Unsupervised Drug Administration

“…In these children, there was an initial drop in haemoglobin followed by an increase by day 14 [20]. A similar pattern of haematological recovery post malaria treatment has been reported among other children in northern Ghana [18] and Kenyan children [21]. In this study, haemoglobin levels were determined only on days 0 and 2.…”

“…Body weakness was commonly reported within the first two days posttreatment. Generally, the reported symptoms among this cohort of adults are less than that reported among children who were treated with AS+AQ in northern Ghana [18]. Compliance among participants in both supervised and unsupervised groups was high irrespective of side-effects they experienced during treatment phase.…”

Prediction of Improved Antimalarial Chemoprevention with Weekly Dosing of Dihydroartemisinin-Piperaquine

“…Supervised dosing does ensure good treatment adherence, but it places a logistic and financial burden on health care providers, policy makers, and the patients, especially in rural areas where heath care access is difficult. This limits the implementation of IPT on a wider scale and might prevent an efficacious protection against new malaria infections (14). It is possible that adherence could be increased with simplified dosing regimens such as weekly dosing (15, 16).…”

Artesunate plus amodiaquine combination therapy: reviewing the evidence

“…On the other hand, in infants and young children less than 30 months participating in a sulphadoxine-pyrimethamine/Placebo Intermittent Preventive Treatment (IPTi) trial who developed uncomplicated malaria and were treated with supervised or unsupervised AS/AQ [Oyakhirome et al, 2007], a significant difference in the risk of treatment failure between the two regimens in favor of the supervised treatment was reported. Similarly, in a comparison of supervised versus unsupervised AS/AQ in children 5 years or younger [Oduro et al, 2008], children treated with supervised AS/AQ were more likely to show an adequate clinical and parasitological response than children treated unsupervised.…”

“…The AS/AQ combination is more efficacious than amodiaquine monotherapy, and clinical trials from various countries, mainly in children, have reported high PCR-corrected, day-28 cure rates (Table 2) [Adjei et al, 2008b;Bonnet et al, 2007;Faucher et al, 2009;Faye et al, 2007;Grandesso et al, 2006;Guthmann et al, 2006;Kayentao et al, 2009;Kobbe et al, 2008;Koram et al, 2008;Martensson et al, 2005;Mutabingwa et al, 2005;Ndiaye et al, 2009;Oduro et al, 2008;Osorio et al, 2007;Owusu-Agyei et al, 2008;Oyakhirome et al, 2007;Sirima et al, 2009;Swarthout et al, 2006;Thanh et al, 2009;van den Broek et al, 2006]. However, comparative studies of the AS/AQ combination with other ACT regimens such as artemether-lumefantrine [Bukirwa et al, 2006;Martensson et al, 2005;Mutabingwa et al, 2005;van den Broek et al, 2006], or dihydroartemisinin-piperaquine [Hasugian et al, 2007], have shown a tendency towards a higher risk of recurrent parasitaemia after AS/AQ treatment, despite the high day-28 cure rates.…”