Impact of insecticidetreated curtains ITCs on the prevalence of genetic markers of resistance to chl

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Impact of insecticide-treated curtains (ITCs) on
the prevalence of genetic markers of resistance
to chloroquine and sulfadoxine pyrimethamine in
Burkina Faso________________________ DA
Diallo1,2, C Sutherland2 I Nebié1, C Roper, AT
Konaté1, E Ilboudo-Sanogo1, BM Greenwood2 SN
Cousens21Centre National de Recherche et de
Formation sur le Paludisme (CNRFP), Burkina
Faso 2London School of Hygiene Tropical
Medecine (LSHTM), United Kingdom
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Background

• Malaria control threatened by drug resistance
• Several approaches to delaying resistance
• Rational use of drugs
• Combination therapy
• Use of vector control measures (Molineux et al.,
  1999)
• Limited field data on vector control and drug
  resistance
• Lower frequency of wild type alleles of dhfr
  associated with treated bed nets (Alifrangis et
  al., 2003)
• Reductions in clinical failure to CQ and in the
  prevalence of pfcrt-76, pfmdr1 (86Y and 1246)
  with indoor spraying (Mahraburwa et al., 2004)

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Objectives

• To assess the impact of ITCs on the prevalence of
  genetic markers of resistance to chloroquine (CQ)
  in children with symptomatic and asymptomatic
  malaria
• pfcrt-76 and pfmdr1-86
• To assess the impact of ITCs on the prevalence of
  genetic markers of resistance to sulfadoxine
  pyrimethamine (SP) in children with symptomatic
  malaria
• dhfr (51, 59, 108) and dhps (437G, 540E)

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Study design methods

• In vivo study of CQ efficacy in 18 villages
• 9 villages protected with ITC for up to 8 years
  (1994-2002)
• Entomological inoculation rate (EIR) lt1 infective
  bite/person/month
• 9 unprotected villages
• No history of ITMs use
• EIR about 30 infective bites/person/month
• Filter filter paper blood spots collected before
  treatment in children 6-59 months with
  uncomplicated malaria
• Cross-sectional surveyrandom sample of
  asymptomatic children
• Filter paper blood spots
• Genotyping of pfcrt-76 and pfmdr1-86
• RFLP and SSOP PCR on samples from symptomatic and
  asymptomatic children
• Genotyping of dhfr(51, 59, 108) and dhps (437,
  540)
• SSOP PCR on random sample of symptomatic children

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Study Site
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ITC protected area
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Door curtain
Eaves curtain
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Proportions of infections carrying a mutation at
the pfcrt-76 gene locus by age and ITC use
Odds ratios adjusted for age, sex, and baseline
parasitaemia (Generalized Estimating
Equations) 95CI were constructed using robust
standard errors.
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Proportions of infections carrying a parasites
with the pfmdr1-86Y mutation by age and ITC use
Odds ratios adjusted for age, sex, and baseline
parasitaemia (Generalized Estimating
Equations) 95CI were constructed using robust
standard errors.
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Proportions of infections carrying pfcrt-76T or
pmdr1-86Y by age and ITC use in children with
asymptomatic malaria
Odds ratios adjusted for age, sex, and baseline
parasitaemia (Generalized Estimating
Equations) 95CI were constructed using robust
standard errors.
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Prevalence of combinations of dhfr-108-51-59
alleles in children with uncomplicated malaria in
ITC and non-ITC villages
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Prevalence of combinations of dhps-437-540
alleles in children with uncomplicated malaria in
ITC and non-ITC villages
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Conclusion

• Use of ITCs did not affect the proportion of
  infections carrying genetic mutations associated
  with resistance to CQ or SP
• At least, children using ITCs were NOT at
  increased risk of carrying resistant parasites a
  consequence of ITC use
• ITC use was NOT associated with increased drug
  pressure on the parasite population

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Acknowledgments

• CNRFP (Burkina Faso)
• CNRFP staff
• GMP LSHTM
• Carol Aldous
• Amit Bhasin
• Daniel Chandramohan
• Rachel Hallett
• Heather Naylor
• Rosalynn Ord
• Geoffrey Targett
• Hirva Potta

Communities involved in the study Ziniaré,
Boussé district staff MoH, Burkina
Faso UNDP/World Bank/WHO/MIM/TDR
The study was funded by the Gates Malaria
Partnership