An open randomized controlled trial to compare the efficacy of two fixed dose combinations of artemesinin based combinations for uncomplicated falciparum malaria in Bangladesh

Abstract

National Malaria Control Program (NMCP) of Bangladesh has introduced Artemisinin Based Combination (ACT), Coartem (R) (Artemether-Lumefantrine (AL), fixed dose combination, in the confirmed cases of uncomplicated P. falciparum malaria since 2004. Despite the reduction of mortality due to malaria, the development and spread of anti-malarial drug resistance wordwide posing a threat to the health services and will make it difficult to control malaria in Bangladesh in future. We need to have an alternative to Coartem which could be Artesunate-amodiaquine (AA) in a fixed dose combination (FDC), a cheaper altenative not yet evidenced to be effective and safe to our population. In this study we compared the efficacy and safety of Artemether + Lumefantrene (FDC, Coartem®) with Artesunate +Amodiaquine tablets (100/270 mg FDC) for the treatment of uncomplicated P. falciparum malaria in three high risk multi-drug resistant malaria prevalent areas of Bangladesh. It was an open label randomized controlled trial conducted between December 2008 and November 2009 in 4 upazillas in patients over the age 12 to 60 years diagnosed as a case of uncomplicated P.falciparum malaria. The outcome of the cases were measured as clinical response, parasitological response, defervescence time and parasite clearance time. Drug safety was assessed by comparing the adverse events. A total of 252 cases were randomized to receive Artesunate + Amodiaquine (AA group, 147 cases) and Artemether + Lumefantrene (AL group, 106 cases), one lost to follow up at day 28 in AA group. The distribution of the cases was comparable by age, sex and study sites. Treatment success' response was observed 100% in the AL group and AA group had 99%, two failures with AA were late treatment failures and the difference was not statistically significant (p>.1). The parasitological sensitive (S) response was observed in 97% of cases in AL group and 95% in the AA group, and was not a statistically significant difference. There was no significant difference in deffervescence time and parasite clearance time between two groups of cases. No serious adverse events were observed. The frequencies of minor adverse events were insignificantly different between the two treatment groups. The two ACT regimen, AA and AL had no significant difference in efficacy and safety for treatment of Uncomplicated Malaria in Bangladesh. However, there were few more failures with AA regimen compared to AL regimen, which was not statistically significant. Both these regimens can be used alternatively by the NMCP of Bangladesh as first-line treatment option.

G6PD Deficiency and Antimalarial Efficacy for Uncomplicated Malaria in Bangladesh: A Prospective Observational Study

“…Reassuringly, in patients with P . falciparum the parasite clearance half-life was 2.75 hours with a median PCT of 22.0 hours, values well within the range expected of fully sensitive parasites and similar to earlier reports from this region [ 14 , 32 , 36 , 37 , 9 ].…”

“…vivax parasitaemia within 12 hours and all by 36 hours. A recent meta–analysis found that clearance of parasites in >95% of participants within 48 hours (as was seen in the current study) is highly indicative of CQ sensitivity [ 14 ].…”

“…The CHT are located on the Bangladesh- Myanmar border and are a potential gateway for the spread of artemisinin resistance from the Mekong region into the Indian subcontinent and onwards into Africa. The last systematic evaluation of the national guidelines for the treatment of uncomplicated malaria was conducted in 2009 [ 14 ], with a subsequent trial of artesunate monotherapy in 2012 [ 15 ]. Both studies demonstrated the high efficacy of artemisinin against P .…”

Persistence of Markers of Chloroquine Resistance in Plasmodium falciparum in Bangladesh

“…20 In Bangladesh, clinical trials of ACTs, for example, AL, artesunate-mefloquine, artesunate-amodiaquine, and artesunate-azithromycin, have shown excellent efficacy, with rapid parasite clearance and high rates of treatment success. [21][22][23][24][25] Although AL is the mandated treatment for uncomplicated malaria, CQ remains available as an over-thecounter medication for self-treatment of malaria, as well as for vivax malaria treatment in some parts of the country. 26,27 Several drug resistance mechanisms have been reported in P. falciparum; CQ resistance (CQR) has been linked to the mutation in the P. falciparum chloroquine resistance transporter gene (pfcrt) at codon 76.…”