pfk13-Independent Treatment Failure in Four Imported Cases of Plasmodium falciparum Malaria Treated with Artemether-Lumefantrine in the United Kingdom

DOI: 10.1128/AAC.02382-16

Article Figures & Data

TABLE 1

Genotyping data from P. falciparum isolates taken from primary and secondary symptomatic malaria episodes in four UK patients

Patient	Sex and age (yrs)	Travel	Episode 1	Episode 2 (elapsed time since previous episode)	Mutation(s) or haplotype					WGS^f clonality
Patient	Sex and age (yrs)	Travel	Episode 1	Episode 2 (elapsed time since previous episode)	pfk13^b	pfcrt^c	pfmdr1	pfap2mu	pfubp1	WGS^f clonality
1	Male over 65	Angola	August 2015		Lys189Thr	CVIET	Tyr184Phe^d	Ser160Asn	WT
1	Male over 65	Angola		43 days	Lys189Thr	CVIET	Tyr184Phe	Ser160Asn	WT
2	Female under 21	Uganda	January 2016		WT	CVIET	WT	WT	Glu1525Gln
2	Female under 21	Uganda		28 days (cultured)^a	WT	CVIET	WT	WT	Glu1525Gln
3	Male over 21	Liberia	February 2016		WT Gly112Glu	CVIET CVMNK	Tyr184Phe	ins_Lys233,^e ins_Asn233	WT	≥2 clones
3	Male over 21	Liberia		17 days	Gly112Glu	CVMNK	Tyr184Phe	ins_Lys233	WT	1 clone
4	Female under 21	Uganda	January 2016		Lys189Thr	CVIET	WT	ins_Asn226, ins_Asn326	Thr1500Ile
4	Female under 21	Uganda		34 days	Lys189Thr	CVIET	WT	ins_Asn226, ins_Asn326	Thr1500Ile

↵a Parasites from the second malaria episode of patient 2 were successfully established in in vitro culture for estimation of drug susceptibility.
↵b The nomenclature used shows the wild-type (WT) (reference) amino acid encoded at the codon of interest, followed by the amino acid encoded by the observed variant. Mutations in the pfk13 locus previously associated with reduced susceptibility to artemisinin in vitro and in vivo in the Mekong region occur between codon 440 and the 3′ end of the coding region.
↵c The nomenclature used shows the single-letter amino acid code for codons 72 to 76, strongly associated with chloroquine resistance. The CVMNK haplotype has been associated with AL treatment failures in Kenya (5).
↵d The single mutation Tyr to Phe at codon 184 identifies the NFD genotype at codons 86, 184, and 1246 in the pfmdr1 locus, previously associated with AL failure in Tanzania and Kenya (5, 8).
↵e ins, insertion of one amino acid, relative to the reference sequence, after the codon shown.
↵f Whole-genome sequencing results for both parasite isolates from patient 3. In the primary episode, heterozygosity (variant allele frequencies of between 5% and 95% of total reads) was seen in over 4,000 loci. About 50% of reads at informative positions comprised variants also present in the monoclonal recrudescent episode (17 days later).