Abstract
BackgroundWith effective vector control and case management, substantial progress has been made towards eliminating malaria on the islands of São Tomé and Príncipe (STP). This study assessed the dynamic changes in the genetic diversity of Plasmodium falciparum, the anti-malarial drug resistance mutations, and malaria treatment outcomes between 2010 and 2016 to provide insights for the prevention of malaria rebounding.MethodsPolymorphic regions of merozoite surface proteins 1 and 2 (msp1 and msp2) were sequenced in 118 dried blood spots (DBSs) collected from malaria patients who had visited the Central Hospital in 2010–2016. Mutations in the multi-drug resistance I (pfmdr1), chloroquine resistance transporter (pfcrt), and kelch 13 (pfk13) genes were analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) and sequencing in 111 DBSs. A total of 7482 cases that completed a 28-day follow-up were evaluated for treatment outcomes based on the microscopic results. Regression models were used to characterize factors associated with levels of parasite density and treatment failures.ResultsParasite strains in STP showed significant changes during and after the peak incidence in 2012. The prevalent allelic type in msp1 changed from K1 to MAD20, and that in msp2 changed from 3D7/IC to FC27. The dominant alleles of drug-resistance markers were pfmdr1 86Y, 184F, D1246, and pfcrt 76 T (Y-F-D-T, 51.4%). The average parasite density in malaria cases declined threefold from low-transmission (2010–2013) to pre-elimination period (2014–2016). Logistic regression models showed that patients with younger age (OR for age = 0.97–0.98, p < 0.001), higher initial parasite density (log10-transformed, OR = 1.44, p < 0.001), and receiving quinine treatment (compared to artemisinin-based combination therapy, OR = 1.91–1.96, p < 0.001) were more likely to experience treatment failures during follow-up.ConclusionsPlasmodium falciparum in STP had experienced changes in prevalent strains, and increased mutation frequencies in drug-resistance genes from the low-transmission to the pre-elimination settings. Notably, patients with younger age and receiving quinine treatment were more likely to show parasitological treatment failure during follow-up. Therapeutic efficacy should be carefully monitored to inform future treatment policy in STP.
Highlights
With effective vector control and case management, substantial progress has been made towards eliminating malaria on the islands of São Tomé and Príncipe (STP)
Sequence diversity of msp1 block 2 in P. falciparum isolates from STP Twenty-two haplotypes were identified in msp1 block 2 from 118 samples collected between 2010 and 2016 (GenBank accession numbers MW001371–MW001392)
Nine haplotypes belonged to the K1 family (KH1–KH9), nine belonged to the MAD20 family (MH1–MH8, haplotype MH3 was translated from two nucleotide sequences, MH3-1 and MH3-2), and four belonged to the RO33 family (RH1–RH4)
Summary
With effective vector control and case management, substantial progress has been made towards eliminating malaria on the islands of São Tomé and Príncipe (STP). STP’s progress towards malaria elimination is being threatened by a potential rebound in malaria cases, emergence of insecticide resistant vectors and increased human mobility [4, 7]. In response to this situation, the Taiwan Anti-Malaria Advisory Mission has partnered with the government of STP to reinforce case follow-up by establishing a realtime electronic case management system, and preserving residual dried blood spots (DBSs) from malaria patients for implementation research. By integrating case surveillance data and parasite’s genetic information, the dynamic changes of parasites over the control period can be tracked, mainly focusing on the genetic diversity, antimalarial drug resistance, and treatment effectiveness in Plasmodium falciparum
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