Trends in Molecular Markers Associated with Resistance to Sulfadoxine-Pyrimethamine (SP) Among Plasmodium falciparum Isolates on Bioko Island, Equatorial Guinea: 2011-2017

Infect Drug Resist. 2020 Apr 28:13:1203-1212. doi: 10.2147/IDR.S236898. eCollection 2020.

Abstract

Purpose: Antimalarial drug resistance is one of the major challenges in global efforts to control and eliminate malaria. In 2006, sulfadoxine-pyrimethamine (SP) replaced with artemisinin-based combination therapy (ACT) on Bioko Island, Equatorial Guinea, in response to increasing SP resistance, which is associated with mutations in the dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes.

Patients and methods: To evaluate the trend of molecular markers associated with SP resistance on Bioko Island from 2011 to 2017, 179 samples collected during active case detection were analysed by PCR and DNA sequencing.

Results: Pfdhfr and Pfdhps gene sequences were obtained for 90.5% (162/179) and 77.1% (138/179) of the samples, respectively. For Pfdhfr, 97.5% (158/162), 95.7% (155/162) and 98.1% (159/162) of the samples contained N51I, C59R and S108N mutant alleles, respectively. And Pfdhps S436A, A437G, K540E, A581G, and A613S mutations were observed in 25.4% (35/138), 88.4% (122/138), 5.1% (7/138), 1.4% (2/138), and 7.2% (10/138) of the samples, respectively. Two classes of previously described Pfdhfr-Pfdhps haplotypes associated with SP resistance and their frequencies were identified: partial (IRNI-SGKAA, 59.4%) and full (IRNI-SGEAA, 5.5%) resistance. Although no significant difference was observed in different time periods (p>0.05), our study confirmed a slowly increasing trend of the frequencies of these SP-resistance markers in Bioko parasites over the 7 years investigated.

Conclusion: The findings reveal the general existence of SP-resistance markers on Bioko Island even after the replacement of SP as a first-line treatment for uncomplicated malaria. Continuous molecular monitoring and additional control efforts in the region are urgently needed.

Keywords: dihydrofolate reductase; dihydropteroate synthase; drug resistance; malaria; sulfadoxine-pyrimethamine.

Grants and funding

This work was partially supported by the Natural Science Foundation of Guangdong Province (Grant No. 2016A03031311 to Jiang-Tao Chen; 2018A030307074 to Yu-Zhong Zheng), the Guangdong Science and Technology Project (Grant No. 2016A030303064 to Guang-Cai Zha), the Foundation for Innovative Research Team of Hubei University of Medicine (Grant No. FDFR201603 to Jian Li), the National Natural Science Foundation of China (Grant No. 81802046 to Jian Li), 2020 Chaozhou’s First Batch of Special Science and Technology Plans, and 2019 Guangdong Province Key Discipline Research Project.