A seven-year surveillance of epidemiology of malaria reveals travel and gender are the key drivers of dispersion of drug resistant genotypes in Kenya

Abstract

Malaria drug resistance is a global public health concern. Though parasite mutations have been associated with resistance, other factors could influence the resistance. A robust surveillance system is required to monitor and help contain the resistance. This study established the role of travel and gender in dispersion of chloroquine resistant genotypes in malaria epidemic zones in Kenya. A total of 1,776 individuals presenting with uncomplicated malaria at hospitals selected from four malaria transmission zones in Kenya between 2008 and 2014 were enrolled in a prospective surveillance study assessing the epidemiology of malaria drug resistance patterns. Demographic and clinical information per individual was obtained using a structured questionnaire. Further, 2 mL of blood was collected for malaria diagnosis, parasitemia quantification and molecular analysis. DNA extracted from dried blood spots collected from each of the individuals was genotyped for polymorphisms in Plasmodium falciparum chloroquine transporter gene (Pfcrt 76), Plasmodium falciparum multidrug resistant gene 1 (Pfmdr1 86 and Pfmdr1 184) regions that are putative drug resistance genes using both conventional polymerase chain reaction (PCR) and real-time PCR. The molecular and demographic data was analyzed using Stata version 13 (College Station, TX: StataCorp LP) while mapping of cases at the selected geographic zones was done in QGIS version 2.18. Chloroquine resistant (CQR) genotypes across gender revealed an association with chloroquine resistance by both univariate model (p = 0.027) and by multivariate model (p = 0.025), female as reference group in both models. Prior treatment with antimalarial drugs within the last 6 weeks before enrollment was associated with carriage of CQR genotype by multivariate model (p = 0.034). Further, a significant relationship was observed between travel and CQR carriage both by univariate model (p = 0.001) and multivariate model (p = 0.002). These findings suggest that gender and travel are significantly associated with chloroquine resistance. From a gender perspective, males are more likely to harbor resistant strains than females hence involved in strain dispersion. On the other hand, travel underscores the role of transport network in introducing spread of resistant genotypes, bringing in to focus the need to monitor gene flow and establish strategies to minimize the introduction of resistance strains by controlling malaria among frequent transporters.

Polymorphism analysis of pfmdr1 gene in Plasmodium falciparum isolates 11 years post-adoption of artemisinin-based combination therapy in Saudi Arabia

“…The current findings suggest that there has been a significant decline in the prevalence of pfmdr1 86 Y (and conversely an increase in the wild N86 allele) since the implementation of the ACT treatment policy in Saudi Arabia, which is consistent with previous reports elsewhere 15 , 17 , 28 , 29 . However, a conclusion based on two previous studies 26 , 27 and the current study might not be reliable.…”

“…In contrast, a study in Kenya found that males are more likely to harbour CQ-resistant P. falciparum parasites with high pfmdr1 mutations as compared females. This difference was attributed to a practice among males of delayed treatment seeking, which may have placed them at higher risk of accumulating super-infections and developing resistance 29 .…”

Polymorphism Analysis of pfmdr1 Gene in Plasmodium falciparum Isolates 11 Years Post-adoption of Artemisinin-based Combination Therapy in Saudi Arabia

“…The current ndings suggest that there has been a signi cant decline in the prevalence of pfmdr1 86Y (and conversely an increase in the wild N86 allele) since the implementation of the ACT treatment policy in Saudi Arabia, which is consistent with previous reports elsewhere 15,17,28,29 . However, a conclusion based on two previous studies 26, 27 and the current study might not be reliable.…”

Synergism in Antiplasmodial Activities of Artemether and Lumefantrine in Combination with Securidaca longipedunculata Fresen (Polygalaceae)

“…First, conventional PCR was used to amplify a fragment of Pfmdr 1, Pfcrt , Pfdhfr , Pfdhps, and Pfmrp 1 genes on an Applied Biosystems’ GenAmp PCR system 9700 (Foster City, CA, USA). The primary reaction was done as earlier described [ 38 ]. The SNPs were then determined by amplification of a fragment of the respective gene as earlier described [ 38 ] using real-time PCR machine Applied Biosystems’ prism 7500 Fast real-time PCR system (Foster City, CA, USA).…”

“…The primary reaction was done as earlier described [ 38 ]. The SNPs were then determined by amplification of a fragment of the respective gene as earlier described [ 38 ] using real-time PCR machine Applied Biosystems’ prism 7500 Fast real-time PCR system (Foster City, CA, USA).…”