Clinical trials of artesunate plus sulfadoxine-pyrimethamine for Plasmodium falciparum malaria in Afghanistan: maintained efficacy a decade after introduction

Abstract

BackgroundCombination therapy with artesunate plus sulfadoxine-pyrimethamine (SP) was adopted as recommended treatment for Plasmodium falciparum infection in Afghanistan in 2003.MethodsA series of prospective clinical studies examining the efficacy of artesunate plus sulfadoxine-pyrimethamine (AS + SP) against P. falciparum were undertaken in sentinel sites in Afghanistan from 2007 to 2014, accompanied by relevant molecular studies. The first study was a randomized trial of AS + SP versus dihydroartemisinin-piperaquine, while two subsequent studies were standard therapeutic efficacy studies of AS + SP.ResultsThree hundred and three patients were enrolled across four provinces in the north and east of the country. Curative efficacy was high in all the trials, with an adequate clinical and parasitological response (ACPR) of more than 95 % in all groups and trial stages. Genotyping for drug-resistance alleles at dhfr indicated fixation of the S108 N mutation and a prevalence of the C59R mutation of approximately 95 % across all sites. Other mutations in dhfr and dhps remained rare or absent entirely, although five isolates from the first trial carried the dhps triple mutant SGEGA haplotype. In the last study undertaken in 2012–2014 the K13 artemisinin resistance marker was examined; only two of 60 successfully sequenced samples carried a K13-propeller mutation.ConclusionsThese data confirm maintained efficacy 10 years after introduction of artesunate plus SP as combination treatment of P. falciparum in Afghanistan. The molecular data indicate that despite a substantial fall in incidence, resistance has not developed to artemisinins, or intensified to the ACT partner drug components.Trial Registrationhttp://www.clinicaltrials.gov/ct NCT00682578, NCT01115439 and NCT01707199

Prevalence of molecular markers of sulfadoxine–pyrimethamine and artemisinin resistance in Plasmodium falciparum from Pakistan

“…Moreover, a therapeutic efficacy study conducted in Zhob, Kech, Khairpur, Thatta, Khrram agency, and Khyber agency also reported near fixation of the PfDHFR double mutant [22]. Similar results have also been reported in the neighboring countries of Iran [34], Afghanistan [35], India [36] and China [37].…”

Efficacy of artesunate + sulphadoxine/pyrimethamine and artemether + lumefantrine and dhfr and dhps mutations in Somalia: evidence for updating the malaria treatment policy

“…Currently, nine countries recommend AS + SP as their first‐line treatment (Afghanistan, Djibouti, India, Islamic Republic of Iran, Pakistan, Saudi Arabia, Somalia, Sudan and Yemen). Recent evidence has shown that AS + SP treatment was failing in north‐east India, leading to its subsequent replacement , while high cure rates (> 95% ACPR) of the combination have been reported in Yemen and Afghanistan .…”

Chloroquine–Primaquine versus Chloroquine Alone to Treat Vivax Malaria in Afghanistan: An Open Randomized Superiority Trial

“…Patients were censored from analysis if there was stated withdrawal of consent, severe malaria or persistent vomiting during the acute phase (necessitating parenteral treatment) or development of concomitant disease interfering with classification of treatment outcome. Patients who developed P. falciparum infections were treated with artesunate plus sulphadoxine-pyrimethamine 16 and retained in the study. Patients failing to attend follow-up were visited at home and asked to reattend the center.…”