Efficacy of combination therapy with artesunate plus amodiaquine compared to monotherapy with chloroquine, amodiaquine or sulfadoxine–pyrimethamine for treatment of uncomplicated Plasmodium falciparum in Afghanistan

Abstract

Summaryintroduction In South and Central Asia resistance to chloroquine (CQ) has reached unmanageable levels, and resistance to sulfadoxine-pyrimethamine (SP) is emerging. Amodiaquine (AQ) is widely used in the region, and elsewhere shows only partial resistance to CQ. In Afghanistan, one option for slowing the spread of resistance and improving treatment outcomes is the use of artemisinin combination therapy (ACT).methods The efficacy of CQ, AQ, SP and amodiaquine plus artesunate (AQ/AS) in the treatment of uncomplicated falciparum malaria was investigated using standard World Health Organization (WHO) procedures. Malaria patients were randomized to four treatment groups: 268 were enrolled and 240 completed the trial.results There was a high level of cross-resistance between CQ and AQ resistance: adequate clinical and parasitological response by day 42 was 11% after CQ treatment and 9% after AQ treatment. The trend of treatment failure between AQ and CQ was almost identical. Cure rates were considerably improved by the addition of artesunate to AQ or by use of SP; adequate clinical and parasitological response being 72% for AQ/AS and 92% for SP. The combination of AS/AQ substantially reduced the odds of treatment failure relative to AQ monotherapy by day 42 [odds ratio (OR) ¼ 0.03, 95% confidence interval (CI) 0.01-0.1] in addition to reducing the proportion of patients with gametocytes throughout the 42-day period. Gametocyte carriage rate was only marginally higher in the SP than in the CQ-and AQ-treated groups.conclusion The therapeutic and parasitological cure rates with AS/AQ were inadequate, and the criteria for deploying ACT -namely to prevent further selection of drug resistance from a position of low frequency -was not met in the region. An alternative drug combination to AQ/AS is required for Afghanistan.

Dramatically decreased therapeutic efficacy of chloroquine and sulfadoxine‐pyrimethamine, but not mefloquine, in southern Benin

“…The choice seems motivated by both efficacy and coformulation. Of note, ACT efficacy is reliant on the efficacy of the partner drug (Durrani et al 2005, Int art study group 2004). According to our results, MQ constitutes a serious candidate for ACTs in Benin, and probably in most sub-Saharan African countries.…”

Large-Scale Surveillance of Plasmodium falciparum crt ( K76T ) in Northern Ghana

“…The overrepresentation of Pfcrt(K76T) parasites in areas of low-density infections might suggest reduced fitness of resistant parasites; however, in the context of ongoing selection, recombinations, and potential compensatory mechanisms, this hypothesis cannot be confirmed in a cross-sectional study (14). Efficacy and, equally important, the useful therapeutic life span of any ACT critically depend on the choice of the partner drug and preexisting resistance patterns (4,9). The high prevalence of Pfcrt(K76T) parasites in northern Ghana and the possibility of even further distribution could produce a frightening scenario: given that the abundance of the Pfcrt(K76T) mutation is confirmed to translate into impaired AQ efficacy (study in progress), the useful life span of AQ-AS may be shortened considerably.…”

Amodiaquine Resistance in Plasmodium falciparum Malaria in Afghanistan Is Associated with the pfcrt SVMNT Allele at Codons 72 to 76

“…The clinical and parasitological results of drug efficacy testing have been reported elsewhere (4). Amodiaquine (Basoquin) was supplied by Parke-Davis.…”