The changing landscape of Plasmodium falciparum drug resistance in the Democratic Republic of Congo

Abstract

Background: Drug resistant malaria is a growing concern in the Democratic Republic of the Congo (DRC), where previous studies indicate that parasites resistant to sulfadoxine/pyrimethamine or chloroquine are spatially clustered. This study explores longitudinal changes in spatial patterns to understand how resistant malaria may be spreading within the DRC, using samples from nation-wide population-representative surveys. Methods: We selected 552 children with PCR-detectable Plasmodium falciparum infection and identified known variants in the pfdhps and pfcrt genes associated with resistance. We compared the proportion of mutant parasites in 2013 to those previously reported from adults in 2007, and identified risk factors for carrying a resistant allele using multivariate mixed-effects modeling. Finally, we fit a spatial-temporal model to the observed data, providing smooth allele frequency estimates over space and time. Results: The proportion of co-occurring pfdhps K540E/A581G mutations increased by 16% between 2007 and 2013. The spatial-temporal model suggests that the spatial range of the pfdhps double mutants expanded over time, while the prevalence and range of pfcrt mutations remained steady. Conclusions: This study uses population-representative samples to describe the changing landscape of SP resistance within the DRC, and the persistence of chloroquine resistance. Vigilant molecular surveillance is critical for controlling the spread of resistance.

Molecular surveillance of artemisinin resistance-related pfK13 and pfcrt polymorphisms in imported Plasmodium falciparum isolates reported in eastern China from 2015–2019

“…Despite of the high prevalence of pfcrt K76T observed in GMS [40], as well as the China-Myanmar border [41,42], the low prevalence rate (4.2%) of pfcrt K76T mutation in African countries reported by the present study re ects high susceptibility of P. falciparum to the CQ. The codons at 72-76 with CVIET was the dominant mutant haplotypes in pfcrt genotype and it was common found in African isolates [43][44][45]. Similarity, we found CVIET were mainly distributed in Central Africa (7.8%) and Eastern Africa (7.8%).…”

Shifts in antimalarial drug policy since 2006 have rapidly selectedP. falciparumresistance alleles in Angola

“…The most rapid change observed in this study was the increase in total SP-resistance alleles per isolate (Fig 3). Similar increases over time have been reported in a number of other African countries [42][43][44] , likely in response to the implementation of WHO recommendations for SP during pregnancy. It is now clear that more than five mutations in dhfr/dhps contribute to SP resistance: in our sample, seven such mutations were present, and three infections (7.0%) carried six of them.…”

Nontargeted metabolomics integrated with1H NMR and LC–Q‐TOF–MS/MS methods to depict a more comprehensive metabolic profile in response to chrysosplenetin and artemisinin co‐treatment against artemisinin‐sensitive and ‐resistantPlasmodium bergheiK173

“…Artemisinin resistance is defined as delayed clearance of malaria parasites following treatment with either artesunate monotherapy or ACTs (WHO, 2018). Recently, studies have attempted to clarify the molecular mechanisms of antimalarial drug resistance, including that due to pfatp6 (Nagasundaram et al, 2016), pfcrt and pfmdr1 (Gil & Krishna, 2017; Kim et al, 2019; Njokah et al, 2016; Otienoburu et al, 2019) and pfdhps (Deutsch‐Feldman et al, 2019) mutations and changes in the Kelch13 ‐mediated endocytosis pathway (Birnbaum et al, 2020; Siddiqui et al, 2017) and heme metabolism (Witkowski et al, 2012). However, no effective inhibitors are available to prevent the emergence and spread of resistance, which can lead to the decreased efficacy of almost all existing antimalarial drugs.…”