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"Anushrita"
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Knockdown-resistance (kdr) mutations in Indian Aedes aegypti populations: Lack of recombination among haplotypes bearing V1016G, F1534C, and F1534L kdr alleles
by
Kona, Madhavinadha P.
,
Singh, Om P.
,
Weetman, David
in
Aedes - drug effects
,
Aedes - genetics
,
Alleles
2025
Knockdown resistance (kdr) mutations in the voltage-gated sodium channel (VGSC) gene are a key mechanism of insecticide resistance in mosquitoes. In Asian Aedes aegypti populations two main VGSC haplogroups with kdr mutations have been identified: one carrying the F1534C mutation and another with V1016G and/or S989P mutations. Previous functional studies have demonstrated that these three mutations on a single haplotype confer up to a 1100-fold increase in pyrethroid resistance, underscoring the importance of monitoring these triple mutations in distinct populations. This study investigates the prevalence of kdr mutations in Indian populations and explores the linkage association between these mutations and two distinct conserved types of introns located between exons 20 and 21.
Ae. aegypti specimens collected from eight different locations were genotyped for kdr alleles and intron (between exons 20 and 21) haplotypes using PCR-based assays. Representative samples underwent DNA sequencing of VGSC regions.
Five kdr mutations namely S989P, V1016G, T1520I, F1534C, and F1534L were identified, each exhibiting varying distribution and frequencies across different geographical regions. Two distinct and stably-diverged intron haplotypes, designated as intron-A and intron-B, were identified between exons 20 and 21. Seven haplotypes, including two wild-type variants, were observed among Indian populations. The kdr-bearing haplotypes can be classified into three distinct haplogroups: haplogroup G (V1016G with/or without S989P and with intron-A), haplogroup L (F1534L and intron-A), and haplogroup C (F1534C with/or without T1520I and with intron-B). Importantly, no evidence of recombination within Indian populations was detected among these three haplogroups.
Five kdr mutations were identified in the VGSC of Indian Ae. aegypti populations, each showing a definitive linkage with one of the two types of intron haplotypes. The lack of recombination among haplogroups bearing 1016G with 989P, 1534C and 1534L mutations suggests that the most potent insecticide resistance haplotype, bearing the triple kdr mutation, is currently absent. This finding has significant operational implications, as it may indicate that current vector control measures remain effective against these populations, potentially delaying the emergence of highly resistant phenotypes.
Journal Article
Knockdown-resistance
2025
Background Knockdown resistance (kdr) mutations in the voltage-gated sodium channel (VGSC) gene are a key mechanism of insecticide resistance in mosquitoes. In Asian Aedes aegypti populations two main VGSC haplogroups with kdr mutations have been identified: one carrying the F1534C mutation and another with V1016G and/or S989P mutations. Previous functional studies have demonstrated that these three mutations on a single haplotype confer up to a 1100-fold increase in pyrethroid resistance, underscoring the importance of monitoring these triple mutations in distinct populations. This study investigates the prevalence of kdr mutations in Indian populations and explores the linkage association between these mutations and two distinct conserved types of introns located between exons 20 and 21. Methods Ae. aegypti specimens collected from eight different locations were genotyped for kdr alleles and intron (between exons 20 and 21) haplotypes using PCR-based assays. Representative samples underwent DNA sequencing of VGSC regions. Results Five kdr mutations namely S989P, V1016G, T1520I, F1534C, and F1534L were identified, each exhibiting varying distribution and frequencies across different geographical regions. Two distinct and stably-diverged intron haplotypes, designated as intron-A and intron-B, were identified between exons 20 and 21. Seven haplotypes, including two wild-type variants, were observed among Indian populations. The kdr-bearing haplotypes can be classified into three distinct haplogroups: haplogroup G (V1016G with/or without S989P and with intron-A), haplogroup L (F1534L and intron-A), and haplogroup C (F1534C with/or without T1520I and with intron-B). Importantly, no evidence of recombination within Indian populations was detected among these three haplogroups. Conclusions Five kdr mutations were identified in the VGSC of Indian Ae. aegypti populations, each showing a definitive linkage with one of the two types of intron haplotypes. The lack of recombination among haplogroups bearing 1016G with 989P, 1534C and 1534L mutations suggests that the most potent insecticide resistance haplotype, bearing the triple kdr mutation, is currently absent. This finding has significant operational implications, as it may indicate that current vector control measures remain effective against these populations, potentially delaying the emergence of highly resistant phenotypes.
Journal Article
Knockdown-resistance (kdr) mutations in Indian Aedes aegypti populations: Lack of recombination among haplotypes bearing V1016G, F1534C, and F1534L kdr alleles
2025
BackgroundKnockdown resistance (kdr) mutations in the voltage-gated sodium channel (VGSC) gene are a key mechanism of insecticide resistance in mosquitoes. In Asian Aedes aegypti populations two main VGSC haplogroups with kdr mutations have been identified: one carrying the F1534C mutation and another with V1016G and/or S989P mutations. Previous functional studies have demonstrated that these three mutations on a single haplotype confer up to a 1100-fold increase in pyrethroid resistance, underscoring the importance of monitoring these triple mutations in distinct populations. This study investigates the prevalence of kdr mutations in Indian populations and explores the linkage association between these mutations and two distinct conserved types of introns located between exons 20 and 21.MethodsAe. aegypti specimens collected from eight different locations were genotyped for kdr alleles and intron (between exons 20 and 21) haplotypes using PCR-based assays. Representative samples underwent DNA sequencing of VGSC regions.ResultsFive kdr mutations namely S989P, V1016G, T1520I, F1534C, and F1534L were identified, each exhibiting varying distribution and frequencies across different geographical regions. Two distinct and stably-diverged intron haplotypes, designated as intron-A and intron-B, were identified between exons 20 and 21. Seven haplotypes, including two wild-type variants, were observed among Indian populations. The kdr-bearing haplotypes can be classified into three distinct haplogroups: haplogroup G (V1016G with/or without S989P and with intron-A), haplogroup L (F1534L and intron-A), and haplogroup C (F1534C with/or without T1520I and with intron-B). Importantly, no evidence of recombination within Indian populations was detected among these three haplogroups.ConclusionsFive kdr mutations were identified in the VGSC of Indian Ae. aegypti populations, each showing a definitive linkage with one of the two types of intron haplotypes. The lack of recombination among haplogroups bearing 1016G with 989P, 1534C and 1534L mutations suggests that the most potent insecticide resistance haplotype, bearing the triple kdr mutation, is currently absent. This finding has significant operational implications, as it may indicate that current vector control measures remain effective against these populations, potentially delaying the emergence of highly resistant phenotypes.
Journal Article
Impact of urbanization on the abundance and distribution of Anophelines population in Ghaziabad district, Uttar Pradesh, India
by
Gupta, Abhishek
,
Prasad, Pooja
,
Rani, Alka
in
Agricultural land
,
Animal Distribution
,
Animals
2024
Background & objectives:
In urban areas, upsurge in population has resulted in more breeding sites for malaria vectors, and hence this scenario potentially undermine malaria elimination and control programs. The change in land use due to urbanization may result in the presence and distribution of malaria vectors. Understanding potential malaria vectors is essential for current and future malaria transmission control strategies. This study investigated the effects of rapid urbanization on malaria vectors An. culicifacies s.l. and An. stephensi L. in Ghaziabad district.
Methods:
Ghaziabad district which presents several levels of urbanization was selected for this study. Entomological investigations were conducted seasonally from 2014-2016 in the rural, urban, and peri-urban regions. Vector incrimination study was done using ELISA (confirmation by PCR) on suspected Anopheles vectors viz. An. culicifacies, An. stephensi, An. annularis and An. subpictus.
Results:
An. culicifacies showed alteration in distribution influenced by rural and agricultural land whereas An. stephensi was found to be influenced by artificial habitats and population growth.
Interpretation & conclusion:
The study also confirms the association between the abundance of malaria vectors and land use change.
Journal Article
Health Impact Assessment of Indira Sagar Project: a paramount to studies on Water Development Projects
2017
Background
Very limited studies on Health Impact Assessment (HIA) of Water Development Projects (WDP) in relation to mosquito-borne diseases have been carried out in India. The current study focuses on using HIA as a tool for finding impact of Indira Sagar Project, Madhya Pradesh on human health in relation to mosquito borne diseases, and emphasizing its incorporation as an integral part of any WDP.
Methods
Screening, scoping, assessment, recommendation, reporting, and evaluation were carried out in selected study areas. Entomological, epidemiological, socio-economic and knowledge, attitudes and practices data related to malaria transmission in three dam components: Submergence (SUB), Command (CMD) and Resettlement and Rehabilitation (RR) colonies were generated for the period of January 2013–December 2014. Statistical analysis was attempted to compare data among dam components and to identify risk factors. Component-specific mitigation measures were suggested based on observations.
Results
Anopheles culicifacies
was the dominating species in all three dam components and its man-hour density in CMD areas was higher compared to SUB and RR. The odds of finding a positive malaria case was much higher in CMD compared to SUB (OR 1.24, CI 95% 0.71–2.43) and RR (OR 5.48, CI 95% 0.73–40.63). Respondents of CMD stated more previous episodes of malaria (81.8%) compared to RR (61.4%) and SUB (55.7%). The canonical discriminant analysis concluded that distance from reservoir/Indira Sagar canal had the highest discriminating ability of malaria cases in different components followed by treatment-seeking behaviour and malaria history. The analysis identified these risk factors with 70% accuracy.
Conclusion
Engineering manipulations may be carried out in CMD areas to control seepage and RR colonies should be established beyond 3 km from reservoir/Indira Sagar canal considering the flight range of
A. culicifacies
. Strengthening of surveillance with early detection and complete treatment was recommended for CMD areas. To avoid future transmission in other areas and projects HIA should be carried out at planning stage for planning better control activities.
Journal Article
A Randomized, Multiple-Dose, Multicenter, Comparative Parallel Study to Evaluate the Safety and Efficacy of Intravenous Infusion of Rituximab (Hetero) and Reference Medicinal Product (Rituximab, Roche) in Indian Patients of Non-Hodgkin's Lymphoma (HERILY)
by
Biswas, Ghanashyam
,
Tripathi, Santanu
,
Advani, Suresh
in
Accreditation
,
Antigens
,
Chemotherapy
2018
Abstract
Objective:
To compare the antitumor efficacy, safety, and pharmacodynamic (PD) characteristics of Hetero-rituximab (test) with reference medicinal product (rituximab, Roche) in non-Hodgkin's lymphoma.
Patients and Methods:
One hundred and thirty-five patients with diffuse large B-cell lymphoma (DLBCL) were randomized to receive intravenous infusion of either test or reference product. Efficacy (best overall response [BOR] rate [primary end point]), safety, PD (CD19), and immunological assessments (secondary end points) were done at the end of cycle 3 and cycle 6.
Results:
: At the end of 6 cycles, BOR rate was 73.47% in Hetero-rituximab test arm compared to the 69.09% in reference arm. Anti-rituximab antibodies were found to be negative at cycle 3 and cycle 6 for all patients. Patients treated with Hetero-rituximab show a significant depletion in CD19+ cell which was comparable with reference drug. Safety and immunogenic potential of the test drug was comparable to the reference drug in the patients of DLBCL.
Conclusion:
BOR rate at cycle 3, cycle 6, and end of the study lies within the prespecified limit for noninferiority which concludes that test product is therapeutically noninferior to reference medicinal product.
Journal Article
Detection of dengue virus in individual Aedes aegypti mosquitoes in Delhi, India
by
Vikram, Kumar
,
Anushrita
,
Yadav, NK
in
Aedes - virology
,
Aedes aegypti; dengue virus; immunofluorescent assay; minimum infection rate
,
Animals
2015
Delhi, the capital city of India, has so far witnessed several outbreaks of dengue fever since 1967 (last one reported in 2013). Improved virological and entomological surveillance are the only tools that can help in prevention of dengue as well as in the development of dengue control programmes. The aim of the study was to conduct a prospective field study to detect dengue virus in adult Aedes aegypti mosquitoes collected from various localities represented by different socioeconomic groups in Delhi.
The study areas were selected and categorized into high, medium and low income groups on the basis of socioeconomical characteristics of the resident population, where dengue cases were reported during the past three years by MCD. Dengue viral infection was detected in the head squash of each adult mosquito by immunofluorescent assay (IFA) employing monoclonal antibodies against dengue virus (DENV). A total of 2408 females and 1206 males of Ae. aegypti were collected and tested by IFA.
Out of 2408 Ae. aegypti females, 14 were found positive, with minimum infection rate (MIR) of 5.8 per 1000 mosquitoes. Among the 18 study areas, 11 localities were found positive for dengue virus infection. Low income group (LIG) areas showed highest mosquito infectivity (9.8), followed by medium income group (MIG), i.e. 6.2; while least was observed in high income group (HIG), i.e. 1.3. No vertical transmission of dengue virus could be detected in 1206 Ae. aegypti males collected.
The study concludes that there was high MIR in the identified localities of low and medium income groups. Estimation of MIR in a female Aedes mosquito in the existing arsenals for dengue surveillance would be an added advantage for early warning of dengue outbreak. The presence of infected mosquitoes in identified localities of Delhi was alarming and require rigorous vector surveillance so that the severe outbreaks can be prevented.
Journal Article
Knockdown-resistance (kdr) mutations in Indian Aedes aegypti populations: lack of recombination among haplotypes bearing V1016G, F1534C, and F1534L kdr alleles
2024
Background Knockdown resistance (kdr) mutations in the voltage-gated sodium channel (VGSC) gene are a key mechanism of insecticide resistance in mosquitoes. In Asian Aedes aegypti populations two main VGSC haplogroups with kdr mutations have been identified: one carrying the F1534C mutation and another with V1016G and/or S989P mutations. Functional studies have demonstrated that these three mutations on a single haplotype confer up to a 1100-fold increase in pyrethroid resistance, underscoring the need to monitor these triple mutations within distinct populations. This study investigates the prevalence of kdr mutations in Indian populations and explores the linkage association between these mutations and two distinct conserved types of introns located between exons 20 and 21. Methods Ae. aegypti specimens collected from eight different locations were genotyped for kdr alleles and intron (between exons 20 and 21) haplotypes using PCR-based assays. Representative samples underwent DNA sequencing of VGSC regions. Results Five kdr mutations namely S989P, V1016G, T1520I, F1534C, and F1534L, were identified, each exhibiting varying distribution and frequencies across different geographical regions. Two distinct and stably-diverged intron haplotypes, designated as intron-A and intron-B, were identified between exons 20 and 21. Seven haplotypes, including two wild-type variants, were observed among Indian populations. The kdr-bearing haplotypes can be classified into three distinct haplogroups: haplogroup G (V1016G with/or without S989P and with intron-A), haplogroup L (F1534L and intron-A), and haplogroup C (F1534C with/or without T1520I and with intron-B). Importantly, no evidence of recombination within Indian populations was detected among these three haplogroups. Conclusions Five kdr mutations were identified in the VGSC of Indian Ae. aegypti populations, each showing a definitive linkage with one of the two types of intron haplotypes. The lack of recombination among haplogroups bearing 1016G with 989P, 1534C and 1534L mutations suggests that the most potent insecticide resistance haplotype, bearing the triple kdr mutation, is currently absent. This finding has significant operational implications, as it may indicate that current vector control measures remain effective against these populations, potentially delaying the emergence of highly resistant phenotypes.Competing Interest StatementThe authors have declared no competing interest.