Whole-Genome Sequencing to Evaluate the Resistance Landscape Following Antimalarial Treatment Failure With Fosmidomycin-Clindamycin

被引：21

作者：

Guggisberg, Ann M. ^{[1
]}

Sundararaman, Sesh A. ^{[3
,4
]}

Lanaspa, Miguel ^{[5
,6
]}

Moraleda, Cinta ^{[5
,6
]}

Gonzalez, Raquel ^{[5
,6
]}

Mayor, Alfredo ^{[5
,6
]}

Cistero, Pau ^{[6
]}

Hutchinson, David ^{[7
]}

Kremsner, Peter G. ^{[8
,9
]}

Hahn, Beatrice H. ^{[3
,4
]}

Bassat, Quique ^{[5
]}

Odom, Audrey R. ^{[1
,2
]}

机构：

[1] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA

[3] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA

[4] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA

[5] Ctr Invest Saude Manhica, Maputo, Mozambique

[6] Hosp Clin Univ Barcelona, Barcelona Ctr Int Hlth Res, Barcelona Inst Global Hlth, Barcelona, Spain

[7] Jomaa Pharma, Hamburg, Germany

[8] Univ Tubingen, Inst Tropenmed, Tubingen, Germany

[9] Ctr Rech Med Lambarene, Lambarene, Gabon

来源：

JOURNAL OF INFECTIOUS DISEASES | 2016年 / 214卷 / 07期

基金：

美国国家卫生研究院;

关键词：

Malaria; fosmidomycin; recrudescence; Plasmodium; clindamycin; whole genome amplification; PLASMODIUM-FALCIPARUM; MOZAMBICAN CHILDREN; DNA-POLYMERASE; MALARIA; DRUG; SYNTHASE; POLYMORPHISMS; CHLOROQUINE; COMBINATION; INFECTIONS;

D O I：

10.1093/infdis/jiw304

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Novel antimalarial therapies are needed in the face of emerging resistance to artemisinin combination therapies. A previous study found a high cure rate in Mozambican children with uncomplicated Plasmodium falciparum malaria 7 days after combination treatment with fosmidomycin-clindamycin. However, 28-day cure rates were low (45.9%), owing to parasite recrudescence. We sought to identify any genetic changes underlying parasite recrudescence. To this end, we used a selective whole-genome amplification method to amplify parasite genomes from blood spot DNA samples. Parasite genomes from pretreatment and postrecrudescence samples were subjected to whole-genome sequencing to identify nucleotide variants. Our data did not support the existence of a genetic change responsible for recrudescence following fosmidomycin-clindamycin treatment. Additionally, we found that previously described resistance alleles for these drugs do not represent biomarkers of recrudescence. Future studies should continue to optimize fosmidomycin combinations for use as antimalarial therapies.

引用

页码：1085 / 1091

页数：7

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