Título:
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Whole genome sequencing to evaluate the resistance landscape
following antimalarial treatment failure with
fosmidomycin-clindamycin
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Autor/a:
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Guggisberg, Ann M.; Sundararaman, Sesh A.; Lanaspa, Miguel; Moraleda Redecilla, Cinta; González, Raquel; Mayor Aparicio, Alfredo Gabriel; Cisteró, Pau; Hutchinson, David; Kremsner, Peter G.; Hahn, Beatrice H.; Bassat Orellana, Quique; Odom, Audrey R.
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Abstract:
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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 post
treatment with a fosmidomycin-clindamycin combination. However,
28-day cure rates were low (45.9%), due to parasite
recrudescence. We sought to identify any genetic changes
underlying parasite recrudescence. To this end, we utilized a
selective whole genome amplification method to amplify parasite
genomes from blood spot DNA samples. Parasite genomes from
pre-treatment and post-recrudescence samples were subjected to
whole genome sequencing to identify nucleotide variants. We find
that our data do not support the existence of a genetic change
responsible for recrudescence following fosmidomycin-clindamycin
treatment. Additionally, we find 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. |
Materia(s):
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-Malària -Plasmodium falciparum -Vacuna de la malària -Malaria -Plasmodium falciparum -Malaria vaccine |
Derechos:
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(c) Guggisberg et al., 2016
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Tipo de documento:
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Artículo Artículo - Versión aceptada |
Editor:
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Oxford University Press
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Compartir:
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