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. 2024 Jun 20:9:323.
doi: 10.12688/wellcomeopenres.22347.1. eCollection 2024.

Plasmodium falciparum dhps and dhfr markers of resistance to sulfadoxine-pyrimethamine five years (2016-2020) after the implementation of seasonal malaria chemoprevention in Cameroon

Pacome V K Tchuenkam  1   2 , Lesley N Ngum  2   3   4 , Innocent M Ali  1   2 , Jean Paul K Chedjou  2   5 , Akindeh M Nji  2   3 , Palmer M Netongo  2   3 , Randolph Ngwafor  2 , Peter Thelma N Niba  2   3 , Calvino F Tah  2   3 , William D Nana  2   3 , Germaine Ekoyol  6 , Jude D Bigoga  2   3 , Dorothy F Ashu  6 , Christopher B Tume  1   7 , Wilfried F Mbacham  2   3   8
Affiliations

Plasmodium falciparum dhps and dhfr markers of resistance to sulfadoxine-pyrimethamine five years (2016-2020) after the implementation of seasonal malaria chemoprevention in Cameroon

Pacome V K Tchuenkam et al. Wellcome Open Res. .

Abstract

Background: Antimalarial drug resistance is a major challenge in the fight against malaria. Cameroon implemented seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SPAQ) to over 1.5 million children aged 3-59 months from 2016, raising concerns whether drug pressure may lead to a selection of known parasite resistance mutations. This study aimed at assessing the profiles of plasmodium falciparum dihydrofolate reductase (DHFR) and plasmodium falciparum dihydropteroate synthase (DHPS) gene mutations that encode enzyme targeting SP before and 5 years after the introduction of SMC in the northern part of Cameroon.

Methods: Dried blood spots were prepared from symptomatic P. falciparum-positive children prior to SPAQ administration in 2016 and after the SMC round of 2020. DNA was extracted using the Chelex-100 method, and dhfr and dhps mutations were determined after a nested polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and agarose gel electrophoresis.

Results: 405 children with acute uncomplicated malaria were recruited. Of 405 samples, 201/405 (49.63%) were collected in 2016 and 204/405 (50.37%) were collected in 2020. High levels of mutant alleles S108N, C59R, N51I of dhfr were obtained both in 2016 and 2020 (174 (100%), 166 (95.4%), 131 (75.3%)); (140 (99.4%), 131 (92.2%), 114 (80.3%)) while the frequency of dhps mutant alleles in the A437G and K540E loci stood at 93 (51.9%) and 6 (3.4%) in 2016 and 73 (52.5%) and 4 (2.8%) in 2020, respectively. The quintuple resistant haplotype IRNGE was found in two (1.1%) and one (0.7%) in 2016 and 2020, respectively. No significant difference was observed in the frequency of the studied mutations between the two time points, although we noted a rise in the resistance conferring haplotype IRNG in 2020.

Conclusions: Continuous monitoring is recommended to preempt the widespread occurrence of high-grade resistance bearing parasites in the northern regions of Cameroon.

Keywords: Cameroon; Pfdhps; chemoprevention; drug resistance; plasmodium falciparum; sulfadoxine–pyrimethamine.

Plain language summary

Despite all the efforts to fight against the malaria burden, it continues to be a serious threat to people's life. One of the biggest threats to the elimination and eradication of malaria is the development of resistance to known and established drugs used in the treatment and the prevention of malaria. These resistance markers accounts as a result of mutations on some Plasmodium genes. In this study, we accessed the prevalence of key resistance markers of two genes in a region where a prevention strategy (the Seasonal Malaria Chemoprevention) has been implemented for 5 years. More than 400 (201 in 2016 and 204 in 2020) patients were screened for malaria and blood samples collected to access these markers. High levels of these resistance markers were observed both in 2016 and in 2020. We found a slight increase in the resistance markers from 2016 to 2020 though it was not significant. These results raise the need to continue to closely monitor patterns of resistance.

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Conflict of interest statement

No competing interests were disclosed.

Figures

Figure 1.
Figure 1.. Proportions of haplotypes of dhfr and dhps resistance mutations observed in samples collected in the time points 2016 and 2020.
See this image and copyright information in PMC

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