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article · The Journal of Infectious Diseases

Drug-Resistance and Population Structure of Plasmodium falciparum Across the Democratic Republic of Congo Using High-Throughput Molecular Inversion Probes

2018143 citationsOpen accessUniversité de Kinshasa (UNIKIN)

In plain language

Understanding how malaria parasites spread and develop drug resistance requires robust genetic tools. A study evaluated a novel molecular inversion probe panel designed to target key drug-resistance mutations alongside microsatellite markers. This panel was used to genotype Plasmodium falciparum infections in 552 children from a national survey conducted in the Democratic Republic of the Congo between 2013 and 2014. Microsatellite analysis indicated that the parasite population across the country is genetically homogeneous. In contrast, markers linked to sulfadoxine resistance in dihydropteroate synthase displayed distinct spatial structuring, marked by an ongoing spread of double and triple mutant strains compared with 2007 data. The findings indicate that antimalarial resistance mutations can spread rapidly despite an underlying panmictic parasite population. Furthermore, high-throughput targeted sequencing using molecular inversion probes offers an efficient, cost-effective method for profiling complex pathogen genetics in large patient cohorts.

Key takeaways

  • A novel molecular inversion probe panel successfully genotyped Plasmodium falciparum infections from 552 children in the Democratic Republic of the Congo.
  • Microsatellite analysis indicates that the parasite population across the country remains genetically homogeneous and panmictic.
  • Sulfadoxine-resistance mutations showed distinct spatial structuring and an ongoing increase in double and triple mutants compared with 2007.
  • Multiplexed targeted sequencing with molecular inversion probes is a cost-effective method for studying pathogen genetics in large population cohorts.

Why it matters

Malaria remains a severe health burden, and the rapid spread of drug resistance threatens global control efforts. By showing that resistance mutations can expand across an otherwise uniform parasite population, this work aids public health planning. It also establishes a practical, cost-effective genetic sequencing approach that helps disease surveillance programmes monitor emerging antimalarial resistance across large populations.

Commercialisation angle

The molecular inversion probe panel offers an applied genetic tool for public health bodies, diagnostic developers, and epidemiological surveillance programmes. It enables cost-effective, high-throughput tracking of drug resistance in large population cohorts. Having been tested on field survey samples, the method is technically validated, though its wider routine deployment depends on integration into regional monitoring networks and laboratory workflows.

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Abstract

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.

Research topics

  • Malaria Research and Control
  • vaccines and immunoinformatics approaches
  • Antibiotic Resistance in Bacteria

Sustainable Development Goals

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DOI: 10.1093/infdis/jiy223

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