Different origin and dispersal of sulfadoxine-resistant Plasmodium falciparum haplotypes between Eastern Africa and Democratic Republic of Congo
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Different origin and dispersal of sulfadoxine-resistant Plasmodium falciparum haplotypes between Eastern Africa and Democratic Republic of Congo. / Baraka, Vito; Delgado-Ratto, Christopher; Nag, Sidsel; Ishengoma, Deus S; Madebe, Rashid A; Mavoko, Hypolite Muhindo; Nabasumba, Carolyn; Lutumba, Pascal; Alifrangis, Michael; Van Geertruyden, Jean-Pierre.
In: International Journal of Antimicrobial Agents, Vol. 49, No. 4, 04.2017, p. 456-464.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Different origin and dispersal of sulfadoxine-resistant Plasmodium falciparum haplotypes between Eastern Africa and Democratic Republic of Congo
AU - Baraka, Vito
AU - Delgado-Ratto, Christopher
AU - Nag, Sidsel
AU - Ishengoma, Deus S
AU - Madebe, Rashid A
AU - Mavoko, Hypolite Muhindo
AU - Nabasumba, Carolyn
AU - Lutumba, Pascal
AU - Alifrangis, Michael
AU - Van Geertruyden, Jean-Pierre
N1 - Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
PY - 2017/4
Y1 - 2017/4
N2 - Sulfadoxine/pyrimethamine (SP) is still used for malaria control in sub-Saharan Africa; however, widespread resistance is a major concern. This study aimed to determine the dispersal and origin of sulfadoxine resistance lineages in the Democratic Republic of the Congo compared with East African Plasmodium falciparum dihydropteroate synthetase (Pfdhps) haplotypes. The analysis involved 264 isolates collected from patients with uncomplicated malaria from Tanzania, Uganda and DR Congo. Isolates were genotyped for Pfdhps mutations at codons 436, 437, 540, 581 and 613. Three microsatellite loci (0.8, 4.3 and 7.7 kb) flanking the Pfdhps gene were assayed. Evolutionary analysis revealed a shared origin of Pfdhps haplotypes in East Africa, with a distinct population clustering in DR Congo. Furthermore, in Tanzania there was an independent distinct origin of Pfdhps SGEGA resistant haplotype. In Uganda and Tanzania, gene flow patterns contribute to the dispersal and shared origin of parasites carrying double- and triple-mutant Pfdhps haplotypes associated with poor outcomes of intermittent preventive treatment during pregnancy using SP (IPTp-SP). However, the origins of the Pfdhps haplotypes in DR Congo and Eastern Africa sites are different. The genetic structure demonstrated a divergent and distinct population cluster predominated by single-mutant Pfdhps haplotypes at the DR Congo site. This reflects the limited dispersal of double- and triple-mutant Pfdhps haplotypes in DR Congo. This study highlights the current genetic structure and dispersal of high-grade Pfdhps resistant haplotypes, which is important to guide implementation of SP in malaria chemoprevention strategies in the region.
AB - Sulfadoxine/pyrimethamine (SP) is still used for malaria control in sub-Saharan Africa; however, widespread resistance is a major concern. This study aimed to determine the dispersal and origin of sulfadoxine resistance lineages in the Democratic Republic of the Congo compared with East African Plasmodium falciparum dihydropteroate synthetase (Pfdhps) haplotypes. The analysis involved 264 isolates collected from patients with uncomplicated malaria from Tanzania, Uganda and DR Congo. Isolates were genotyped for Pfdhps mutations at codons 436, 437, 540, 581 and 613. Three microsatellite loci (0.8, 4.3 and 7.7 kb) flanking the Pfdhps gene were assayed. Evolutionary analysis revealed a shared origin of Pfdhps haplotypes in East Africa, with a distinct population clustering in DR Congo. Furthermore, in Tanzania there was an independent distinct origin of Pfdhps SGEGA resistant haplotype. In Uganda and Tanzania, gene flow patterns contribute to the dispersal and shared origin of parasites carrying double- and triple-mutant Pfdhps haplotypes associated with poor outcomes of intermittent preventive treatment during pregnancy using SP (IPTp-SP). However, the origins of the Pfdhps haplotypes in DR Congo and Eastern Africa sites are different. The genetic structure demonstrated a divergent and distinct population cluster predominated by single-mutant Pfdhps haplotypes at the DR Congo site. This reflects the limited dispersal of double- and triple-mutant Pfdhps haplotypes in DR Congo. This study highlights the current genetic structure and dispersal of high-grade Pfdhps resistant haplotypes, which is important to guide implementation of SP in malaria chemoprevention strategies in the region.
KW - Africa, Eastern
KW - Antimalarials
KW - Child
KW - Child, Preschool
KW - Democratic Republic of the Congo
KW - Dihydropteroate Synthase
KW - Drug Resistance
KW - Female
KW - Genetic Variation
KW - Genotyping Techniques
KW - Haplotypes
KW - Humans
KW - Infant
KW - Malaria, Falciparum
KW - Male
KW - Microsatellite Repeats
KW - Plasmodium falciparum
KW - Sulfadoxine
KW - Journal Article
U2 - 10.1016/j.ijantimicag.2016.12.007
DO - 10.1016/j.ijantimicag.2016.12.007
M3 - Journal article
C2 - 28237831
VL - 49
SP - 456
EP - 464
JO - International Journal of Antimicrobial Agents
JF - International Journal of Antimicrobial Agents
SN - 0924-8579
IS - 4
ER -
ID: 176620019