Travel and the emergence of high-level drug resistance in Plasmodium falciparum in southwest Uganda: results from a population-based study.


Lynch, CA; Pearce, R; Pota, H; Egwang, C; Egwang, T; Bhasin, A; Cox, J; Abeku, TA; Roper, C; (2017) Travel and the emergence of high-level drug resistance in Plasmodium falciparum in southwest Uganda: results from a population-based study. Malar J, 16 (1). p. 150. ISSN 1475-2875 DOI: 10.1186/s12936-017-1812-1

[img]
Preview
Text - Published Version
License:

Download (1700Kb) | Preview

Abstract

The I164L mutation on the dhfr gene confers high level resistance to sulfadoxine-pyrimethamine (SP) but it is rare in Africa except in a cluster of reports where prevalence >10% in highland areas of southwest Uganda and eastern Rwanda. The occurrence of the dhfr I164L mutation was investigated in community surveys in this area and examined the relationship to migration. A cross-sectional prevalence survey was undertaken in among villages within the catchment areas of two health facilities in a highland site (Kabale) and a highland fringe site (Rukungiri) in 2007. Sociodemographic details, including recent migration, were collected for each person included in the study. A total of 206 Plasmodium falciparum positive subjects were detected by rapid diagnostic test; 203 in Rukungiri and 3 in Kabale. Bloodspot samples were taken and were screened for dhfr I164L. Sequence analysis confirmed the presence of the I164L mutations in twelve P. falciparum positive samples giving an estimated prevalence of 8.6% in Rukungiri. Of the three parasite positive samples in Kabale, none had I164L mutations. Among the twelve I164L positives three were male, ages ranged from 5 to 90 years of age. None of those with the I164L mutation had travelled in the 8 weeks prior to the survey, although three were from households from which at least one household member had travelled during that period. Haplotypes were determined in non-mixed infections and showed the dhfr I164L mutation occurs in both as a N51I + S108N + I164L haplotype (n = 2) and N51I + C59R + S108N + I164L haplotype (n = 5). Genotyping of flanking microsatellite markers showed that the I164L occurred independently on the triple mutant (N51I, C59R + S108N) and double mutant (N51I + S108N) background. There is sustained local transmission of parasites with the dhfr I164L mutation in Rukungiri and no evidence to indicate its occurrence is associated with recent travel to highly resistant neighbouring areas. The emergence of a regional cluster of I164L in SW Uganda and Rwanda indicates that transmission of I164L is facilitated by strong drug pressure in low transmission areas potentially catalysed in those areas by travel and the importation of parasites from relatively higher transmission settings.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Disease Control
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Malaria Centre
Antimicrobial Resistance Centre (AMR)
PubMed ID: 28415996
URI: http://researchonline.lshtm.ac.uk/id/eprint/4086899

Statistics


Download activity - last 12 months
Downloads since deposit
0Downloads
4Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item