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

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.
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Emergence of a dhfr mutation conferring high-level drug resistance in Plasmodium falciparum populations from southwest Uganda.

Authors

Mayor MeshTerms

Drug Resistance

Mutation, Missense

Travel

Keywords

Drug resistance

Malaria

Migration

Sulfadoxine–pyrimethamine (SP)

Travel

dhfr

Journal Title malaria journal
Publication Year Start




PMID- 28415996
OWN - NLM
STAT- MEDLINE
DA  - 20170418
DCOM- 20170501
LR  - 20170501
IS  - 1475-2875 (Electronic)
IS  - 1475-2875 (Linking)
VI  - 16
IP  - 1
DP  - 2017 Apr 17
TI  - Travel and the emergence of high-level drug resistance in Plasmodium falciparum
      in southwest Uganda: results from a population-based study.
PG  - 150
LID - 10.1186/s12936-017-1812-1 [doi]
AB  - 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.
FAU - Lynch, Caroline A
AU  - Lynch CA
AD  - Faculty of Epidemiology and Population Health, London School of Hygiene and
      Tropical Medicine, London, UK. [email protected]
FAU - Pearce, Richard
AU  - Pearce R
AD  - Faculty of Infectious and Tropical Diseases, London School of Hygiene and
      Tropical Medicine, London, UK.
FAU - Pota, Hirva
AU  - Pota H
AD  - Faculty of Infectious and Tropical Diseases, London School of Hygiene and
      Tropical Medicine, London, UK.
FAU - Egwang, Connie
AU  - Egwang C
AD  - Medical Biotechnology Laboratories, Kampala, Uganda.
FAU - Egwang, Thomas
AU  - Egwang T
AD  - Medical Biotechnology Laboratories, Kampala, Uganda.
FAU - Bhasin, Amit
AU  - Bhasin A
AD  - Faculty of Infectious and Tropical Diseases, London School of Hygiene and
      Tropical Medicine, London, UK.
FAU - Cox, Jonathan
AU  - Cox J
AD  - Faculty of Infectious and Tropical Diseases, London School of Hygiene and
      Tropical Medicine, London, UK.
FAU - Abeku, Tarekegn A
AU  - Abeku TA
AD  - Malaria Consortium, London, UK.
FAU - Roper, Cally
AU  - Roper C
AD  - Faculty of Infectious and Tropical Diseases, London School of Hygiene and
      Tropical Medicine, London, UK.
LA  - eng
PT  - Journal Article
DEP - 20170417
PL  - England
TA  - Malar J
JT  - Malaria journal
JID - 101139802
RN  - EC 1.5.1.3 (Tetrahydrofolate Dehydrogenase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Child
MH  - Child, Preschool
MH  - Cross-Sectional Studies
MH  - *Drug Resistance
MH  - Female
MH  - Gene Frequency
MH  - Haplotypes
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Malaria, Falciparum/epidemiology/*parasitology
MH  - Male
MH  - Middle Aged
MH  - *Mutation, Missense
MH  - Plasmodium falciparum/drug effects/*enzymology/isolation & purification
MH  - Prevalence
MH  - Selection, Genetic
MH  - Sequence Analysis, DNA
MH  - Surveys and Questionnaires
MH  - Tetrahydrofolate Dehydrogenase/*genetics
MH  - *Travel
MH  - Uganda/epidemiology
MH  - Young Adult
PMC - PMC5392983
OTO - NOTNLM
OT  - Drug resistance
OT  - Malaria
OT  - Migration
OT  - Sulfadoxine-pyrimethamine (SP)
OT  - Travel
OT  - dhfr
EDAT- 2017/04/19 06:00
MHDA- 2017/05/02 06:00
CRDT- 2017/04/19 06:00
PHST- 2016/11/29 [received]
PHST- 2017/04/08 [accepted]
AID - 10.1186/s12936-017-1812-1 [doi]
AID - 10.1186/s12936-017-1812-1 [pii]
PST - epublish
SO  - Malar J. 2017 Apr 17;16(1):150. doi: 10.1186/s12936-017-1812-1.

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