COMPARATIVE THERAPEUTIC EFFICACY OF ARTEMETHER-LUMEFANTRINE AND ARTESUNATE-AMODIAQUINE FOR THE TREATMENT OF UNCOMPLICATED PLASMODIUM FALCIPARUM MALARIA IN CHILDREN OF BARKI-LADI LGA OF PLATEAU STATE

Abstract

Background: The World Health Organization recommended artemisinin based combination therapy (ACT) for the treatment of uncomplicated Plasmodium falciparum malaria and it is widely used in most malaria endemic countries in tropical Africa. It is also recommended that efficacy, tolerability and safety of ACT should be continuously monitored in all the malaria endemic regions where they are used mostly as the first line antimalaria drugs for the clinical cure of uncomplicated Plasmodium falciparum malaria.
Objective: This study was undertaken to compare the therapeutic efficacy, tolerability and safety of artemether-lumefantrine and artesunate-amodiaquine for the clinical cure of uncomplicated Plasmodium falciparum malaria mono-infection in children of Barki-Ladi LGA of Plateau State using a 28-day protocol.
Subjects and Methods: The subjects consisted of children age 6 to 60 months old. Prior to screening, the subjects were randomized into two study arms to receive 6-dose regimen of artemether-lumefantrine (AL) versus 3-day course of daily amodiaquine-artesunate (AA). In each arm, there were a total of 57 subjects.
Following endorsement of written informed consent, eligible study subjects were given weight-dependent study medications. They were then longitudinally evaluated clinically, parasitologically, haematologically and biochemically. Clinical and parasitological evaluations were carried out on Days 0, 1, 2, 3, 7, 14, 21 and 28 for primary and secondary outcomes. The outcomes assessed were adequate clinical and parasitological response, fever and parasite clearance times, gametocyte carriage rate before and after treatment and gametocyte clearance time. Safety profile was simultaneously assessed clinically and using laboratory parameters in all participants. The results were entered into case record forms and subsequently transferred into computer using software SPSS versions 15.0 and 17.0 and then analyzed at the end of the study.
Results: Of a total of 649 subjects screened for parasitaemia in the study, 282 (43.5%) were febrile (temperature  37.5oC). Out of 649 subjects, 252 (38.8%) had parasitaemia. Only P. falciparum was identified. No cases of mixed infections. Parasite count varied from 1000 – 200,000 asexual forms/µL. Of the parasitaemic subjects, 114 (17.6%) met the enrollment criteria. One hundred and eleven (97.4%) of the 114 subjects completed the study. Three subjects (2.7%) did not complete the study; one subject from AA study arm was excluded because he developed signs of severe malaria, one subject from AA study arm had missing
PCV and parasite data and one subject from AL relocated from the study area to his home state.
The Day 28 PCR-corrected parasitological cure rates were 50(89.3%) and 50(90.9%) for AL and AA respectively (p=0.089), fever clearance times (FCT) were 16.7 hours and 18.3 hours for AL and AA respectively (p=0.32). Parasite clearance times (PCT) were 26.1 hours and 28.8 hours for AL and AA respectively (p=0.06). Gametocyte carriage rates (GCR) were 10.7% and 10.9% for AL and AA treatment arms respectively (p=0.32). Gametocyte clearance times (GCT) were 104 hours and 152 hours for AL and AA respectively (p= 0.44).
There was no early treatment failure (ETF) and no late clinical failure (LCF). Late parasitological failure (LPF) at D28 were 6(10.7%) and 5(9.1%) for AL and AA respectively, (p=0.486).
The most frequently reported adverse event (AE) was coughing (18%) while vomiting (6%) was the least. No patients reported serious adverse events (SAEs) and there was no laboratory evidence of toxicity.
Conclusions: Artemether-lumefantrine (AL) and artesunate-amodiaquine (AA) have comparable therapeutic efficacy for clinical cure of uncomplicated P. falciparum malaria mono-infection. AL and AA were safe and tolerable in children. Overall, it appears that there is reduced P. falciparum malaria parasite sensitivity to both AL and AA.

COMPARATIVE THERAPEUTIC EFFICACY OF ARTEMETHER-LUMEFANTRINE AND ARTESUNATE-AMODIAQUINE FOR THE TREATMENT OF UNCOMPLICATED PLASMODIUM FALCIPARUM MALARIA IN CHILDREN OF BARKI-LADI LGA OF PLATEAU STATE