TY - JOUR
T1 - Drug-Resistance and population structure of plasmodium falciparum across the democratic Republic of Congo using high-Throughput molecular inversion probes
AU - Aydemir, Ozkan
AU - Janko, Mark
AU - Hathaway, Nick J.
AU - Verity, Robert
AU - Mwandagalirwa, Melchior Kashamuka
AU - Tshefu, Antoinette K.
AU - Tessema, Sofonias K.
AU - Marsh, Patrick W.
AU - Tran, Alice
AU - Reimonn, Thomas
AU - Ghani, Azra C.
AU - Ghansah, Anita
AU - Juliano, Jonathan J.
AU - Greenhouse, Bryan R.
AU - Emch, Michael
AU - Meshnick, Steven R.
AU - Bailey, Jeffrey A.
N1 - Publisher Copyright:
© The Author(s) 2018.
PY - 2018/8/14
Y1 - 2018/8/14
N2 - A better understanding of the drivers of the spread of malaria parasites and drug resistance across space and time is needed. These drivers can be elucidated using genetic tools. Here, a novel molecular inversion probe (MIP) panel targeting all major drug-resistance mutations and a set of microsatellites was used to genotype Plasmodium falciparum infections of 552 children from the 2013–2014 Demographic and Health Survey conducted in the Democratic Republic of the Congo (DRC). Microsatellite-based analysis of population structure suggests that parasites within the DRC form a homogeneous population. In contrast, sulfadoxine-resistance markers in dihydropteroate synthase show marked spatial structure with ongoing spread of double and triple mutants compared with 2007. These findings suggest that parasites in the DRC remain panmictic despite rapidly spreading antimalarial-resistance mutations. Moreover, highly multiplexed targeted sequencing using MIPs emerges as a cost-effective method for elucidating pathogen genetics in complex infections in large cohorts.
AB - A better understanding of the drivers of the spread of malaria parasites and drug resistance across space and time is needed. These drivers can be elucidated using genetic tools. Here, a novel molecular inversion probe (MIP) panel targeting all major drug-resistance mutations and a set of microsatellites was used to genotype Plasmodium falciparum infections of 552 children from the 2013–2014 Demographic and Health Survey conducted in the Democratic Republic of the Congo (DRC). Microsatellite-based analysis of population structure suggests that parasites within the DRC form a homogeneous population. In contrast, sulfadoxine-resistance markers in dihydropteroate synthase show marked spatial structure with ongoing spread of double and triple mutants compared with 2007. These findings suggest that parasites in the DRC remain panmictic despite rapidly spreading antimalarial-resistance mutations. Moreover, highly multiplexed targeted sequencing using MIPs emerges as a cost-effective method for elucidating pathogen genetics in complex infections in large cohorts.
KW - Democratic Republic of the Congo
KW - Drug resistance
KW - Malaria
KW - Molecular inversion probe
KW - Targeted sequencing
UR - http://www.scopus.com/inward/record.url?scp=85054999488&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiy223
DO - 10.1093/infdis/jiy223
M3 - Article
C2 - 29718283
AN - SCOPUS:85054999488
SN - 0022-1899
VL - 218
SP - 946
EP - 955
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -