Different origin and dispersal of sulfadoxine-resistant Plasmodium falciparum haplotypes between Eastern Africa and Democratic Republic of Congo

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 - 2017/4/1

Y1 - 2017/4/1

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

SN - 0924-8579

VL - 49

SP - 456

EP - 464

JO - International Journal of Antimicrobial Agents

JF - International Journal of Antimicrobial Agents

IS - 4

ER -