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ACT recommended for P. falciparum malaria warrants improvement
Artemether-lumefantrine, a recommended artemisinin-based combination therapy, failed to treat four imported cases of Plasmodium falciparum malaria in the U.K., suggesting the efficacy of this front-line defense could deteriorate in the future, according to a brief report.
“In Asia, reduced artemisinin susceptibility mediated by specific mutations in the parasite pfk13 locus may indicate a threat to [artemisinin-based combination therapy (ACT)] efficacy,” Colin J. Sutherland, PhD MPH, from the Public Health England malaria reference laboratory at the London School of Hygiene and Tropical Medicine, and colleagues wrote. “However, these specific pfk13 variants have not been seen in Africa, where variable ACT efficacy appears to be independent of pfk13 polymorphism, but may be linked to multi-locus genotypes encompassing pfcrt, pfmdr1, pfap2mu and pfubp1.”
In two U.K. hospitals, researchers assessed four cases of recurrent P. falciparum malaria in patients treated with artemether-lumefantrine (AL) occurring 17 to 43 days after the original episode was recorded in the Malaria Reference Laboratory (MRL) between October 2015 and February 2016. In their article, Sutherland and colleagues presented brief case reports with genotyping of parasites isolated from both episodes for each patient.
Patient 1, a man aged over 65 years, presented with 1.4% P. falciparum parasitemia in 2015 after returning from Angola. Less than 2 months after treatment and discharge, the patient returned with recurrent symptoms and presented with variants associated with the recurrent parasitemia found in African patients treated with AL. Patient 2, a woman aged under 21 years, presented with acute P. falciparum hyperparasitemia at over 30% in early 2016 following travel to Uganda. After treatment and discharge, symptoms recurred, possibly reflecting inadequate clearance of the original hyperparasitemia. Researchers found that the genotype of both parasite isolates was consistent with AL sensitivity at pfk13, pfcrt, pfmdr1 and pfap2mu.
At the time of hospital admission in 2016, patient 3, a man aged over 21 years, had 0.4% P. falciparum parasitemia after travel to Liberia. He received AL treatment, but returned with recurrent symptoms 17 days after discharge. Examination suggests that the recurrent infection comprised a single parasite clone, differing from the pfcrt and pfap2mu loci isolates observed in the primary episode. Lastly, patient 4, another woman under 21 years, was diagnosed with 0.08% P. falciparum parasitemia and treated with oral AL following travel to Uganda in early 2016. One month later, her symptoms recurred and the hospital confirmed 0.03% P. falciparum parasitemia. When researchers evaluated the parasite loci, they saw both episodes appeared identical.
“Treatment failure cannot be unequivocally ascribed to parasite resistance in these four patients, although three harbored parasites with variant alleles of loci previously linked to reduced susceptibility to artemisinin or lumefantrine,” Sutherland and colleagues wrote. “The parasites we describe may represent adaptive Africa genotypes that have evolved pfk13-independent mechanisms for post-treatment survival in vivo… [suggesting that], in non-endemic countries with imported malaria cases from Africa, vigilance is required to protect the efficacy of our front-line ACT.” – by Savannah Demko
Disclosure: Chiodini is supported by the National Institute for Health Research at University College London Hospitals Biomedical Research Center. Sutherland reports no other relevant financial disclosures.