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

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.

Assessment of molecular markers for anti-malarial drug resistance after the introduction and scale-up of malaria control interventions in western Kenya

“…Molecular marker data collected from a 2001 cross-sectional survey in Asembo area [ 17 ] were compared with the 2007 molecular data in Asembo only. The prevalence of mutations at pfmdr1 -86 Y, dhfr -51 I ,108 N and dhps -437 G did not change between time points.…”

“…a The construction of the CQ-SP haplotype included pfcrt -76, pfmdr1 -86, dhfr -51, 59, 108, and dhps -437, 540. *Data are derived from a previous study [ 17 ].…”

“…For the study described here, 253 P. falciparum smear-positive samples, 61 in Asembo, 97 in Gem and 95 in Karemo, collected from participants <15 years old were available for genotyping of anti-malarial drug resistance molecular markers. In order to provide a temporal description in drug resistance markers, the data from the 2007 survey in Asembo were compared with molecular data collected from samples obtained in a 2001 community cross-sectional survey conducted in Asembo area in children < five years old as part of a randomized controlled trial of ITNs between 1996 and 2001 [ 17 , 34 , 35 ].…”

“…In Tanzania, the short-term use of ITNs was linked to decreased prevalence of a molecular marker associated with resistance to SP [ 14 ] and, in Zimbabwe, the implementation of indoor residual spraying (IRS) was associated with a lower risk of CQ treatment failure and reduced prevalence of CQ-resistant parasites [ 15 ]. However, evaluations of insecticide-treated curtains in Burkina Faso [ 16 ] and ITNs in western Kenya five years after their introduction indicated no clear effect of transmission reduction on the prevalence of resistance markers for SP and CQ [ 17 ]. Despite these conflicting findings, these studies suggest that changes in malaria transmission by vector control interventions, which are key elements of malaria control, might influence anti-malarial drug resistance.…”

“…As part of a 2007 annual malaria survey conducted in three areas of western Kenya, this study assessed the prevalence of resistance markers to currently and previously used first-line anti-malarials within the context of drug policy change and scale-up of ITNs. The specific objectives were to: 1) determine the prevalence of drug-resistant molecular markers for CQ, SP and lumefantrine after the introduction of AL; 2) assess the relationship between the observed prevalence of drug resistance markers and differences in transmission intensity, as a result of ITN scale-up, among three geographically contiguous study areas in 2007; and, 3) compare the prevalence of the molecular markers from a subset of 2007 samples with molecular data from a 2001 survey from the same study area [ 17 ].…”