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

Autor: Amit Bhasin, Tarekegn A. Abeku, Jonathan Cox, Richard Pearce, Connie Egwang, Cally Roper, Hirva Pota, Thomas G. Egwang, Caroline A. Lynch
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Veterinary medicine
Drug Resistance
Drug resistance
Sulfadoxine–pyrimethamine (SP)
0302 clinical medicine
Gene Frequency
Surveys and Questionnaires
Prevalence
dhfr
Uganda
Malaria
Falciparum
Child
Migration
Aged
80 and over
Genetics
Travel
Rapid diagnostic test
Middle Aged
Infectious Diseases
Child
Preschool
Female
Adult
lcsh:Arctic medicine. Tropical medicine
Adolescent
lcsh:RC955-962
Plasmodium falciparum
030106 microbiology
030231 tropical medicine
Mutation
Missense
Biology
Disease cluster
lcsh:Infectious and parasitic diseases
Young Adult
03 medical and health sciences
parasitic diseases
medicine
Humans
lcsh:RC109-216
Selection
Genetic
Genotyping
Aged
Research
Haplotype
Infant
Newborn
Infant
Sequence Analysis
DNA
medicine.disease
biology.organism_classification
Malaria
Tetrahydrofolate Dehydrogenase
Cross-Sectional Studies
Haplotypes
Parasitology
Zdroj: Malaria Journal
Malaria Journal, Vol 16, Iss 1, Pp 1-9 (2017)
ISSN: 1475-2875
Popis: Background 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. Methods 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. Results 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. Conclusions 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.
Databáze: OpenAIRE
Externí odkaz: