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تميز دراسي و بحثي + جائزة تفوقية
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البحوث المنشورة
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البحث (1):
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عنوان البحث:
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Combined Target Site (Kdr)
Mutations Play A Primary Role In Highly Pyrethroid Resistant Phenotypes Of Aedes
Aegypti From Saudi Arabia
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رابط إلى البحث:
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Click here
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تاريخ النشر:
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27/03/2017
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موجز عن البحث:
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Background
Pyrethroid resistance is a threat to
effective vector control of Aedes aegypti, the vector of dengue, Zika
and other arboviruses, but there are many major knowledge gaps on the
mechanisms of resistance. In Jeddah and Makkah, the principal dengue-endemic
areas of Saudi Arabia, pyrethroids are used widely for Ae. aegypti control
but information about resistance remains sparse, and the underlying genetic
basis is unknown. Findings from an ongoing study in this internationally
significant area are reported here.
Methods
Aedes aegypti collected
from each city were raised to adults and assayed for resistance to permethrin,
deltamethrin (with and without the synergist piperonyl butoxide, PBO),
fenitrothion, and bendiocarb. Two fragments of the voltage-gated sodium
channel (Vgsc), encompassing four previously identified mutation
sites, were sequenced and subsequently genotyped to determine associations
with resistance. Expression of five candidate,genes(CYP9J10, CYP9J28,
CYP9J32, CYP9M6, ABCB4) previously associated with
pyrethroid resistance was compared between assay survivors and controls.
Results
Jeddah and Makkah populations exhibited
resistance to multiple insecticides and a similarly high prevalence of
resistance to deltamethrin compared to a resistant Cayman strain, with a
significant influence of age and exposure duration on survival. PBO
pre-exposure increased pyrethroid mortality significantly in the Jeddah, but
not the Makkah strain. Three potentially interacting Vgsc mutations
were detected: V1016G and S989P were in perfect linkage disequilibrium in
each strain and strongly predicted survival, especially in the Makkah strain,
but were in negative linkage disequilibrium with 1534C, though some females
with the Vgsctriple mutation were detected. The candidate
gene CYP9J28 was significantly over-expressed in Jeddah
compared to two susceptible reference strains, but none of the candidate
genes was consistently up-regulated to a significant level in the Makkah
strain.
Conclusions
Despite their proximity, Makkah and Jeddah
exhibit significant differences in pyrethroid resistance phenotypes, with
some evidence to suggest a different balance of mechanisms, for example with
more impact associated with CYP450s in the Jeddah strain, and the dual kdrmutations
989P and 1016G in the more resistant Makkah strain. The results overall
demonstrate a major role for paired target site mutations in pyrethroid
resistance and highlight their utility for diagnostic monitoring.
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المؤتمرات العلمية:
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المؤتمر (1):
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عنوان المؤتمر:
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2nd Gulf Congress Of Clinical Microbiology And
Infection Diseases
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تاريخ الإنعقاد:
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01/11/2017
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مكان الإنعقاد:
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Manama, Bahrain
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طبيعة المشاركة:
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paper presentation
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عنوان المشاركة:
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Insecticide Resistance And
Mechanisms In Aedes Aegypti Dengue Endemic Areas Of Saudi Arabia
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ملخص المشاركة:
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In Saudi Arabia, dengue has been endemic
since the 1990s and control programme relies on vector “Ae.
aegypti” control using insecticides. Insecticide resistance is a growing
concern but is poorly characterised in Saudi and resistance mechanisms have
not been studied. The study aimed to determine insecticide resistance in
Ae.aegypti from Jeddah and Makkah and investigated the role of target site
mutations and metabolic mechanisms. Three kdr mutations S989P, V1016G, F1534C
were observed for the first time in Saudi Arabia. Microarray data identified
multiple differentially expressed genes. Aedes mosquitoes are highly
resistant to pyrethroids. Voltage-gated sodium channel (Vgsc) mutations are
strongly associated with deltamethrin resistance and, though P450 enzymes
seem to be the dominant metabolic mechanism, our data suggest a greater
importance of target site mutations. This proposes that the Vgsc mutations,
provide a valuable monitoring tool; however further investigation is required
to determine the importance of other resistance mechanisms.
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المؤتمر ( 2 ):
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عنوان المؤتمر:
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American Society Of Tropical
Medicine And Hygiene
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تاريخ الإنعقاد:
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05/11/2017
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مكان الإنعقاد:
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Baltimore, Maryland. USA
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طبيعة المشاركة:
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Poster presentation
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عنوان المشاركة:
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Mechanisms Of Pyrethroid
Resistance In Aedes Aegypti From Dengue Endemic Areas Of Saudi Arabia: A
Primary Role For Target Site Mutations
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ملخص المشاركة:
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Control of Aedes aegypti using insecticides is the main method to reduce the
prevalence of dengue in the disease-foci cities of Makkah and Jeddah, Saudi
Arabia. Despite potential impacts on control, little is known about
insecticide resistance in Ae. aegypti
in the Middle Eastern Region, and nothing about underlying mechanisms . We
characterized insecticide resistance in Ae.
aegypti from the dengue foci of Jeddah and Makkah and investigated the
role of the two main resistance mechanisms anticipated, target site mutations
and metabolic detoxification. WHO bioassays were performed on adult Ae. aegypti reared from eggs or
immature stages collected in Jeddah and Makkah. Portions of the voltage-gated
sodium channel (Vgsc) gene were
sequenced to identify target site mutations. Microarray analyses were
performed to identify transcriptome variation potentially linked to
deltamethrin resistance and qPCR of candidate genes applied to investigate
mechanistic cross-resistance in lines selected for other insecticides.
Adults bioassays revealed resistance/
suspected resistance to all insecticides tested in Makkah and Jeddah Ae. aegypti with significantly higher
levels of deltamethrin resistance in Makkah compared to a reference resistant
Cayman strain. Three kdr mutations
(S989P, V1016G, F1534C) were detected for the first time in the Middle
Eastern region, with S989P and V1016G markers in perfect linkage
disequilibrium (LD) and strongly predicting deltamethrin resistance, but in
negative LD with F1534C. The synergist PBO, which is applied primarily to
block the action of P450 enzymes, caused a moderate increase in deltamethrin
mortality in Jeddah but had a non-significant effect on Makkah female
mortality. Transcriptional analysis identified multiple differentially
expressed genes, numerically dominated by P450s, more highly expressed in
Jeddah than Makkah, consistent with the synergist test results.
Ae.
aegypti
female mosquitoes from Jeddah and Makkah are highly resistant to pyrethroids,
and insecticide resistance appears to be increasing. Vgsc mutations are strongly associated with deltamethrin
resistance and, whilst P450 enzymes appear to be the dominant metabolic
mechanism, our findings suggest a greater importance of target site
mutations. This suggests that the Vgsc
mutations, which are easily screened, provide a valuable monitoring tool;
however further investigation is required to determine the importance of
metabolic and other resistance mechanisms.
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الرابط:
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Click here
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المؤتمر (3):
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عنوان المؤتمر:
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2nd WIN International Conference On ”Integrated Approaches
And Innovative Tools For Combating Insecticide Resistance In Arbovirus
Vectors”
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تاريخ الإنعقاد:
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01/03/2018
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مكان الإنعقاد:
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Singapore
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طبيعة المشاركة:
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Poster presentation
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عنوان المشاركة:
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Characterizing Mechanisms
Associated With Pyrethroid Resistance In Aedes Aegypti In Saudi Arabia
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ملخص المشاركة:
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Pyrethroids are routinely used as a control
measure for dengue fever spread by Aedes aegypti in Saudi Arabia.
Effectiveness of control may be impacted by resistance but there is limited
information on insecticide resistance in Ae. aegypti in the middle eastern
region and less still on mechanisms underlying resistance phenotypes. Aedes
aegypti from Jeddah and Makkah, the two primary dengue-endemic areas of Saudi
Arabia, were assayed for resistance phenotypes; their target site mutations
investigated using sequencing and genotyping; and metabolic resistance
mechanisms investigated using microarrays. Both the Jeddah and Makkah field
strains were resistant to multiple insecticides, with especially high
deltamethrin resistance in Makkah. Three kdr mutations were detected (S989P,
V1016G, F1534C), two of which were previously only identified in Asia. The
S989P and V1016G mutations were in perfect linkage disequilibrium (LD) and
strongly predicted deltamethrin resistance. Microarray analysis sought to
identify genes consistently differentially expressed between susceptible
strains and both Saudi Arabian strains. Results showed enrichment of P450s,
some previously identified as pyrethroid metabolisers. However, the lead
candidate gene statistically, CYP9J7 has not previously been
functionally-investigated and we investigated its metabolic capacity via in
vitro insecticide metabolism assays. No depletion of either deltamethrin or
permethrin was observed, but surprisingly CYP9J7 metabolised the
organophosphate malathion. Mosquitoes from Jeddah and Makkah are highly
resistant to pyrethroids. The gene expression and target site mutation data
suggest that the Jeddah strain relies on both metabolic and target site
resistance mechanisms, with evidence suggesting the latter may be more
prominent at present. Further work is required to identify whether the organophosphate
metabolism detected represents detoxification or activation, which have
opposing implications for resistance management
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الرابط:
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Click here
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المؤتمر (4):
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عنوان المؤتمر:
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XIEuropean Congress of
Entomology
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تاريخ الإنعقاد:
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02/07/2018
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مكان الإنعقاد:
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Napoli,Italy
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طبيعة المشاركة:
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Poster presentation
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عنوان المشاركة:
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A Novel Wind Tunnel Assay For
Evaluating The Behaviour Of Pyrethroid Resistant Aedes Aegypti From Areas Of Saudi
Arabia
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ملخص المشاركة:
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Pyrethroids are routinely used as a control
measure for dengue fever spread by Aedes aegypti in Saudi Arabia.
Effectiveness of control may be impacted by resistance but there is limited
information on insecticide resistance in Ae. aegypti in the middle eastern
region and less still on mechanisms underlying resistance phenotypes. Aedes
aegypti from Jeddah and Makkah, the two primary dengue-endemic areas of Saudi
Arabia, were assayed for resistance phenotypes; their target site mutations
investigated using sequencing and genotyping; and metabolic resistance
mechanisms investigated using microarrays. Both the Jeddah and Makkah field
strains were resistant to multiple insecticides, with especially high
deltamethrin resistance in Makkah. Three kdr mutations were detected (S989P,
V1016G, F1534C), two of which were previously only identified in Asia. The S989P
and V1016G mutations were in perfect linkage disequilibrium (LD) and strongly
predicted deltamethrin resistance. Microarray analysis sought to identify
genes consistently differentially expressed between susceptible strains and
both Saudi Arabian strains. Results showed enrichment of P450s, some
previously identified as pyrethroid metabolisers. However, the lead candidate
gene statistically, CYP9J7 has not previously been functionally-investigated
and we investigated its metabolic capacity via in vitro insecticide
metabolism assays. No depletion of either deltamethrin or permethrin was
observed, but surprisingly CYP9J7 metabolised the organophosphate malathion.
Mosquitoes from Jeddah and Makkah are highly resistant to pyrethroids. The
gene expression and target site mutation data suggest that the Jeddah strain
relies on both metabolic and target site resistance mechanisms, with evidence
suggesting the latter may be more prominent at present. Further work is
required to identify whether the organophosphate metabolism detected
represents detoxification or activation, which have opposing implications for
resistance management.
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الرابط:
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Click here
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جوائز التكريم:
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الجائزة (1):
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مسمى الجائزة:
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Best Poster Presentation.
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الجهة المانحة:
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Royal Entomological Society’s
postgraduate forum organising committee
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تاريخ الجائزة:
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16 Feb 2015
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مجال التكريم:
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Study behavioural and
Physiological insecticide resistance of dengue vector in the Kingdom of Saudi
Arabia
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الجائزة (2):
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مسمى الجائزة:
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SSMMID Best Abstract Award
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الجهة المانحة:
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2nd Gulf congress of
Clinical Microbiology and infectious diseases 2017
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تاريخ الجائزة:
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1-4/11/2017
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مجال التكريم:
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1st Best Abstract
Award
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الجائزة (3):
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مسمى الجائزة:
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Award for Best oral presentation
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الجهة المانحة:
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Liverpool School of Tropical
Medicine
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تاريخ الجائزة:
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04/05/2017
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مجال التكريم:
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Best oral presentation for the
biological sciences deanery at the Annual LSTM Postgraduate research student
conference 2016/2017
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