Effect of Transmission Reduction by Insecticide-Treated Bednets (ITNs) on Antimalarial Drug Resistance in Western Kenya

Monica Shah,Kimberly Garner,William A Hawley,Bernard Nahlen,Wangeci Gatei,Anna J Blackstock,Laurence Slutsker,Kim Lindblade,Ya Ping Shi,Edward Walker,Feiko Ter Kuile,Simon Kariuki,Penelope Phillips-Howard,Jodi Vanden Eng,Mary J Hamel,John E Gimnig,Dianne Terlouw

doi:10.1371/journal.pone.0026746

Abstract

Despite the clear public health benefit of insecticide-treated bednets (ITNs), the impact of malaria transmission-reduction by vector control on the spread of drug resistance is not well understood. In the present study, the effect of sustained transmission reduction by ITNs on the prevalence of Plasmodium falciparum gene mutations associated with resistance to the antimalarial drugs sulfadoxine-pyrimethamine (SP) and chloroquine (CQ) in children under the age of five years was investigated during an ITN trial in Asembo area, western Kenya. During the ITN trial, the national first line antimalarial treatment changed from CQ to SP. Smear-positive samples collected from cross sectional surveys prior to ITN introduction (baseline, n = 250) and five years post-ITN intervention (year 5 survey, n = 242) were genotyped for single nucleotide polymorphisms (SNPs) at dhfr-51, 59, 108, 164 and dhps-437, 540 (SP resistance), and pfcrt-76 and pfmdr1-86 (CQ resistance). The association between the drug resistance mutations and epidemiological variables was evaluated. There were significant increases in the prevalence of SP dhps mutations and the dhfr/dhps quintuple mutant, and a significant reduction in the proportion of mixed infections detected at dhfr-51, 59 and dhps-437, 540 SNPs from baseline to the year 5 survey. There was no change in the high prevalence of pfcrt-76 and pfmdr1-86 mutations. Multivariable regression analysis further showed that current antifolate use and year of survey were significantly associated with more SP drug resistance mutations. These results suggest that increased antifolate drug use due to drug policy change likely led to the high prevalence of SP mutations 5 years post-ITN intervention and reduced transmission had no apparent effect on the existing high prevalence of CQ mutations. There is no evidence from the current study that sustained transmission reduction by ITNs reduces the prevalence of genes associated with malaria drug resistance.

Highlights

Worldwide, three billion people are at risk of malaria infection
Of the 503 randomly selected parasite positive samples, 492 (97.8%) samples were successfully genotyped for all drug resistance single nucleotide polymorphisms (SNPs), 250 (96.5%) for baseline and 242 (99.2%) for year 5 survey samples
Prevalence of SNP Mutations and SP and CQ Genotypes The prevalence of mutations and proportion of mixed infections by SNP at baseline and the year 5 survey are summarized in figure 1

Summary

Introduction

Three billion people are at risk of malaria infection. Over 85% of the approximately 250 million cases and one million deaths due to malaria occur in Africa each year [1]. The international community has emphasized the use of malaria prevention to reduce the global burden of malaria as well as to preserve the efficacy of the limited set of antimalarial treatment drugs that are threatened by the emergence and spread of drug resistance [2,3]. Current World Health Organization (WHO)recommended malaria control strategies include prompt access to effective treatment, vector control with long lasting insecticidetreated bednets (LLITNs) and indoor residual spraying (IRS), and prevention of malaria in pregnancy [1]. In subSaharan Africa, the use of ITNs has been associated with a 70–90% decrease in malaria transmission, reduction in childhood malaria morbidity and all-cause mortality, and significant decrease in adverse effects of malaria in pregnancy [6,7,8]

Methods

Results

Conclusion