Efficacy evaluation of Veeralin LN, a PBO-incorporated alpha-cypermethrin long-lasting insecticidal net against Anopheles culicifacies in experimental huts in Odisha State.

BACKGROUND: The success of malaria control using long-lasting insecticidal nets (LLINs) is threatened by pyrethroid resistance developed by the malaria vectors, worldwide. To combat the resistance, synergist piperonyl butoxide (PBO) incorporated LLINs is one of the available options. In the current phase II hut trial, the efficacy of Veeralin®LN (an alpha-cypermethrin and PBO-incorporated net) was evaluated against Anopheles culicifacies, a pyrethroid resistant malaria vector. METHODS: The performance of Veeralin®LN was compared with MAGNet®LN and untreated net in reducing the entry, induced exit, mortality and blood feeding inhibition of target vector species. RESULTS: The performance of Veeralin was equal to MAGNet in terms of reducing hut entry, inhibiting blood feeding and inducing exophily, and with regard to causing mortality Veeralin was better than MAGNet. When compared to untreated net, a significant reduction in hut entry and blood feeding and an increase in exophily and mortality were observed with Veeralin. In cone bioassays, unwashed Veeralin caused > 80% mortality of An. culicifacies. CONCLUSIONS: Veeralin performed equal to (entry, exit, feeding) or better than (mortality in huts and cone bioassays) MAGNet and could be an effective tool against pyrethroid resistant malaria vectors.

VectorInfo: A web resource for medically important Indian arthropod disease vectors.

VectorInfo is a freely accessible web resource, emphasised on medically important Indian arthropods funded by Indian Council of Medical Research (ICMR) and maintained by one of its premier institute, Vector Control Research Centre (VCRC). VectorInfo elucidates and curates medically important Indian arthropod's biological, omics technologies to adopt a holistic view of the molecules that make up an organism, aimed at the detection of genomics, transcriptomics, proteomics, enzymes & pathways and immune specific genes. The nitty-gritty of VectorInfo is aimed at scrutinizing all the possible information on Indian disease vectors in a single window for the scientific community. The database affords 53 medically important Indian arthropod's biological and omics information well-structured and provided with downloadable facilities. In addition to this, huge number of research articles were mined in the quest for gathering the recommended insecticide targets and their mechanisms, that pave ways to design and develop novel lead molecules through computational means. This current up-to-date database contains 2,498 omics entries beneficial for the molecular studies and analysis. In order to maintain regular updates, user forms were provided for the scientific community to submit research data to the database administrator. The VectorInfo furthermore conveys various resources for vector control and diagnostics and the links to the crucial software tools used for the Bioinformatics analysis.

Intensity of pyrethroid resistance in Anopheles culicifacies s.l. (Diptera: Culicidae) in Odisha State, India.

ANOPHELES CULICIFACIES S.L: . is the principal malaria vector in India and has recently developed resistance to synthetic pyrethroids. For identifying the possible operational impact, quantitative measure of the intensity of this resistance is required. The purpose of this study was to measure the intensity of pyrethroid resistance in An. culicifacies s.l. The intensity bioassays with wild caught An. culicifacies s.l were carried out in 10 districts of east central India using 5x and 10x diagnostic concentrations of deltamethrin following WHO insecticides susceptibility guidelines. The results showed that the mortality of An. culicifacies s.l. ranged from 70% to 80% while exposed to 1x DC of deltamethrin (0.05%). Further bioassays conducted with 5x concentration of deltamethrin (0.25%) showed that the mortality of An. culicifacies s.l. in all the 10 districts varied from 92% to 97% indicating moderate resistance. While exposing to 10x concentration (0.5%) of this insecticide, 100% mortality was observed in all the districts; thereby confirmed moderate resistance intensity of this species. Since resistance was not confirmed at the 10x concentration, operational failure of this insecticide was unlikely. Hence, it is recommended to continue the use of LLINs for malaria vector control in these areas.

Evidence of natural infection of Orientia tsutsugamushi in vectors and animal hosts - Risk of scrub typhus transmission to humans in Puducherry, South India.

BACKGROUND: Scrub typhus infection is endemic in India and reported to be the major cause for acute encephalitis syndrome (AES) in humans. Periodic occurrence of scrub typhus cases and presence of pathogen in rodents were also reported in areas with human cases of scrub typhus in Puducherry. OBJECTIVES: This study was carried out to screen Orientia tsutsugamushi in rodent/shrew reservoirs and vectors in villages of Puducherry with no reports of human scrub typhus cases. METHODS: This study was conducted during October 2017 to January 2018 in ten randomly selected villages in Puducherry. Rodents/shrews in the peridomestic area were trapped using Sherman traps. Screening of O. tsutsugamushi in rodents/shrews and mite vectors was done by polymerase chain reaction (PCR). Weil-Felix test was done to screen antibodies against O. tsutsugamushi in rodent serum samples. RESULTS: Among the 54 rodents trapped, Suncus murinus was the major small animal and Leptotrombidium deliense was the major mite species retrieved. PCR screening revealed pathogen positivity in 8 rodent blood and 3 pooled mite samples. Phylogenetic analysis has shown that Kato was the circulating serotype of O. tsutsugamushi. None of the rodent serum samples was tested positive for antibodies against O. tsutsugamushi by Weil-Felix test. CONCLUSIONS: The presence of pathogen in both vectors and reservoir animal hosts imposes a risk for scrub typhus transmission to the inhabitants; hence, initiation of vector control measures before the start of winter is recommended in the study area. It is also recommended to screen scrub typhus in patients with undifferentiated acute febrile illness and AES.

Evaluation of long-lasting indoor residual spraying of deltamethrin 62.5 SC-PE against malaria vectors in India.

BACKGROUND: Deltamethrin 62.5 polymer-enhanced suspension concentrate (SC-PE) is one of the World Health Organization-approved insecticides for indoor residual spraying and was recommended to evaluate its residual activity for determination of appropriate spray cycles in different eco-epidemiologic settings. In the current study, efficacy of deltamethrin 62.5 SC-PE was evaluated against vectors of malaria and its impact on malaria incidence in a Plasmodium falciparum hyper-endemic area in Koraput district, Odisha State, India. METHODS: The trial had two comparable arms, arm 1 with residual spraying of deltamethrin 62.5 SC-PE and arm 2 with deltamethrin 2.5% WP (positive control). Comparative assessment of the impact of each intervention arm on entomological (density, parity, infection and human blood index), epidemiological (malaria incidence) parameters, residual efficacy and adverse effects were evaluated. RESULTS: Both the arms were comparable in terms of entomological and epidemiological parameters. While, deltamethrin 62.5 SC-PE was found to be effective for 150 days in mud and wood surfaces and 157 days in cement surfaces; deltamethrin 2.5% was effective only for 105 days on mud surfaces and 113 days on cement and wood surfaces. CONCLUSIONS: Deltamethrin 62.5 SC-PE had prolonged killing effectiveness up to 5 months. Hence, one round of IRS with deltamethrin 62.5 SC-PE would be sufficient to cover two existing malaria peak transmission seasons (July-August and October-November) in many parts of India.

Comparative efficacy of two rounds of indoor residual spraying of DDT 75% @ 1g/m2 with that of DDT 50% @ 1g/m2 against the malaria vectors in India.

While, dichlorodiphenyl-trichloroethane (DDT) water dispersible powder (WDP) 75% is considered as the high performance long lasting formulation for indoor residual spraying (IRS), no information is available regarding the comparative epidemiological effectiveness of the two DDT formulations when used for IRS in Indian conditions. The current study was undertaken to compare the effectiveness of IRS using DDT WDP 75% @ one g active ingredient (AI)/m2 with that using DDT WDP 50% @ one g AI/m2 in controlling Anopheles fluviatilis and An. culicifacies, the primary vectors of malaria in the selected endemic areas of Odisha State. Although, cone-bioassay mortality after 8 months of post spraying on DDT 75% sprayed surfaces as well as on sprayed but mud plastered surfaces was higher than DDT 50%, the six entomological parameters viz. resting density indoors and outdoors, trap density indoors, parous rate, human blood index and infection rate of An. fluviatilis and An. culicifacies did not show any statistically significant difference in reduction/ changes from pre- to post-spray period between the two DDT formulations.

Evaluation of MAGNet, a long-lasting insecticidal mosquito net against Anopheles fluviatilis in experimental huts in India.

BACKGROUND: MAGNet LN is a wash resistant long-lasting insecticidal (polyethylene) net (LLIN) in which the alpha-cypermethrin insecticide is incorporated within the 150 denier high density polyethylene monofilaments of the nets. The bio-efficacy of MAGNet LN was reported to be high even after 25 washes. The LN met the WHO criteria of Phase I evaluation and obtained recommendation from the World Health Organization Pesticide Evaluation Scheme (WHOPES) for Phase II trial. For registration of the LN in India, the current study was conducted to evaluate its efficacy after 20 or 25 washes compared to negative control (untreated net) and positive control (Duranet LN) in experimental huts against a wild, free flying pyrethroid susceptible population of Anopheles fluviatilis in terms of deterrence, blood-feeding inhibition, mortality and induced exophily. METHODS: The evaluation was carried out in six experimental huts located at Kandhaguda village in Malkangiri district, Odisha state following the WHO guidelines. RESULTS: The study showed that 25 times washed MAGNet LN produced 100% mortality in cone bioassays before and after hut evaluation. MAGNet washed 25 times did not differ significantly from all other treated nets in terms of deterring hut entry, induced exophily, blood feeding inhibition and causing mortality of An. fluviatilis. CONCLUSIONS: MAGNet LN showed extended wash resistance retaining its bio-efficacy up to 25 washes and met the WHOPES requirement of passing Phase II evaluation.

Multiple insecticide resistance in Anopheles culicifacies s.l. (Diptera: Culicidae) in east-central India.

Development of resistance among the vectors to different insecticides poses a potential threat to vector control programme. Regular monitoring of susceptibility status of vector species to commonly used insecticides is recommended for planning appropriate vector control measures. In this communication, we have determined the phenotypic resistance of Anopheles culicifacies s.l., the major malaria vector against commonly used various insecticides in ten highly malaria endemic districts of Odisha State in east-central India. Bioassays were conducted before and after mass distribution of long-lasting insecticidal nets (LLINs) on field caught female mosquitoes with dichlorodiphenyl-trichloroethane (DDT), malathion and deltamethrin following the standard World Health Organization (WHO) guidelines. From the bioassays using 1x diagnostic concentrations (DC) recommended by WHO, we confirmed a higher frequency of resistant phenotype in An. culicifacies s.l. against DDT (range: 72% to 90%; average: 82%) compared to that against malathion(range: 17% to 34%; average: 26.7%) and deltamethrin (range: 14% to 24%; average: 19.1%) during 2018. Since, resistance to pyrethroid is detected; it is recommended to carry out bioassays of An. culicifacies s.l. exposing to higher concentrations of deltamethrin which would yield relevant information on the intensity of resistance and be useful to select suitable insecticide for resistance management vector control interventions.

Molecular modelling studies of kdr mutations in voltage gated sodium channel revealed significant conformational variations contributing to insecticide resistance.

Voltage gated sodium channels (VGSC) of mosquito vectors are the primary targets of dichlorodiphenyltrichloroethane (DDT) and other synthetic pyrethroids used in public health programmes. The knockdown resistant (kdr) mutations in VGSC are associated with the insecticide resistance especially in Anophelines. The present study is aimed to emphasize and demarcate the impact of three kdr-mutations such as L1014S, L1014F and L1014H on insecticide resistance. The membrane model of sodium transport domain of VGSC (STD-VGSC) was constructed using de novo approach based on domain and trans-membrane predictions. The comparative molecular modelling studies of wild type and mutant models of STD-VGSC revealed that L1014F mutant was observed to be near native to the wild type model in all the respects, but, L1014S and L1014H mutations showed drastic variations in the energy levels, root mean square fluctuations (RMSF) that resulted in conformational variations. The predicted binding sites also showed variable cavity volumes and RMSF in L1014S and L1014H mutants. Further, DDT also found be bound in near native manner to wild type in L1014F mutant and with variable orientation and affinities in L1014S and L1014H mutants. The variations and fluctuations observed in mutant structures explained that each mutation has its specific impact on the conformation of VGSC and its binding with DDT. The study provides new insights into the structure-function-correlations of mutant STD-VGSC structures and demonstrates the role and effects of kdr mutations on insecticide resistance in mosquito vectors.