Dynamic changes in genetic diversity, drug resistance mutations, and treatment outcomes of falciparum malaria from the low-transmission to the pre-elimination phase on the islands of São Tomé and Príncipe

Malaria Journal

Arlindo Vicente de Assunção Carvalho¹  Ying-An Chen²  Kun-Hsien Tsai³  Tsen-Ju Shiu⁴  Wei-Liang Shih⁵  Lien-Fen Tseng⁶  Chien-Fu Cheng⁶ 

[1] Centro Nacional de Endemias, Ministério da Saúde de São Tomé e Príncipe, São Tomé, São Tomé and Príncipe;Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Taipei, Taiwan;Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Taipei, Taiwan;Taiwan Anti-Malaria Advisory Mission, São Tomé, São Tomé and Príncipe;Infectious Diseases Research and Education Center, Ministry of Health and Welfare and National Taiwan University, Taipei, Taiwan;Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan;Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan;Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan;Infectious Diseases Research and Education Center, Ministry of Health and Welfare and National Taiwan University, Taipei, Taiwan;Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan;Taiwan Anti-Malaria Advisory Mission, São Tomé, São Tomé and Príncipe;

关键词: São Tomé and Príncipe;    Malaria;    Plasmodium falciparum;    Merozoite surface proteins;    Antimalarial drug resistance mutations;    Recurrence;   

DOI  :  10.1186/s12936-021-04007-3

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY