Impact of a spatial repellent intervention on Anopheles kdr insecticide resistance allele in Sumba, Indonesia.

BACKGROUND: The emergence of insecticide resistance and outdoor transmission in malaria-endemic areas underlines the urgent need to develop innovative tools, such as spatial repellents (SR), that may circumvent this residual transmission. With limited options for effective insecticides, regular resistance monitoring is warranted for selecting and using appropriate tools. This study evaluates the pyrethroid knockdown resistance (kdr) allele before and after implementing a transfluthrin-based spatial repellent (SR) intervention in placebo-treated clusters. METHODS: This study looks at the frequency distribution of the kdr allele in Sumba Island from June 2015 to August 2018. Insecticide susceptibility tests were carried out on female Anopheles sp. aged 3-5 days against permethrin 21.5 µg/ml, deltamethrin 12.5 µg/ml, and transfluthrin 10 µg/ml using CDC bottle assay. PCR sequencing of representative samples from adult mosquito collections and insecticide tests revealed the presence of kdr mutations (L1014F and L1014S) in the VGSC gene. RESULTS: A total of 12 Anopheles species, Anopheles tesselatus, Anopheles. aconitus, Anopheles barbirostris, Anopheles kochi, Anopheles annularis, Anopheles maculatus, Anopheles sundaicus, Anopheles flavirostris, Anopheles balabacensis, Anopheles indefinitus, Anopheles subpictus, and Anopheles vagus were analysed. Anopheles vagus and An. sundaicus predominated in the larval populations. Susceptibility assays for all insecticides identified fully susceptible phenotypes in all species examined. Anopheles increasing frequency of kdr mutant alleles during the 3 year SR deployment was observed in both SR-treated and placebo areas, a statistically significant increase occurred in each arm. However, it is unclear how significant SR is in causing the increase in mutant alleles. The L1014S, knockdown resistance east type (kdr-e) allele was detected for the first time among the mosquito samples in this study. The L1014F, knockdown resistance west type (kdr-w) allele and heteroduplex form (wild-type-mutant) were found in almost all Anopheles species examined, including An. vagus, An. aconitus, An. subpictus, An. tesselatus, An. annularis, An. flavirostris and An. sundaicus. CONCLUSION: The presence of fully susceptible phenotypes over time, along with an increase in the frequency distribution of the L1014F/S mutations post-intervention, suggest drivers of resistance external to the study, including pyrethroid use in agriculture and long-lasting insecticidal nets (LLINs). However, this does not negate possible SR impacts that support resistance. More studies that enable the comprehension of possible SR-based drivers of resistance in mosquitoes need to be conducted.

Human behavior determinants of exposure to Anopheles vectors of malaria in Sumba, Indonesia.

Malaria vector control interventions in Sumba, Indonesia, have not been able to eliminate malaria. Human drivers of exposure to Anopheles bites were investigated as part of a larger clinical trial evaluating the impact of a spatial repellent product on malaria incidence. Human behavioral observations (HBOs) evaluating temporal and spatial presence, sleeping behaviors, and insecticide treated net (ITN) use, were collected parallel to entomological collections-indoor and outdoor human landing catches (HLCs), and house hold surveys. Data demonstrates that mosquito access to humans, enabled by structurally open houses, is evident by the similar entomological landing rates both inside and outside households. The presence of animals inside houses was associated with increased mosquito entry-however, the number of humans present inside houses was not related to increased mosquito landing. Analyzing mosquito landing rates with human behavior data enables the spatial and temporal estimation of exposure to Anopheles bites, accounting for intervention (ITN) presence and usage. Human behavior adjusted exposure to Anopheles bites was found to be highest in the early in the evening, but continued at lower levels throughout the night. Over the night, most exposure (53%) occurred when people were indoors and not under the protection of nets (asleep or awake) followed by exposure outside (44%). Characterized gaps in protection are outdoor exposure as well as exposure indoors-when awake, and when asleep and not using ITNs. Interestingly, in the primary trial, even though there was not a significant impact of the spatial repellent on vector biting rates by themselves (16%), when factoring in human behavior, there was approximately 28% less exposure in the intervention arm than in the placebo arm. The treated arm had less human behavior adjusted bites in all spaces evaluated though there was proportionally higher exposure indoors. This analysis points to the importance of using HBOs both towards understanding gaps in protection as well as how interventions are evaluated. To mitigate ongoing transmission, understanding context specific spatial and temporal exposure based on the interactions of vectors, humans and interventions would be vital for a directed evidence-based control or elimination strategy.

Impact of a spatial repellent product on Anopheles and non-Anopheles mosquitoes in Sumba, Indonesia.

BACKGROUND: The East Nusa Tenggara province, Indonesia, contributed to 5% of malaria cases nationally in 2020, with other mosquito-borne diseases, such as dengue and filariasis also being endemic. Monitoring of spatial and temporal vector species compositions and bionomic traits is an efficient method for generating evidence towards intervention strategy optimization and meeting disease elimination goals. METHODS: The impact of a spatial repellent (SR) on human biting mosquitoes was evaluated as part of a parent cluster-randomized, double-blinded, placebo-controlled trial, in Sumba, East Nusa Tenggara. A 10-month (June 2015-March 2016) baseline study was followed by a 24-month intervention period (April 2016 to April 2018)-where half the clusters were randomly assigned either a passive transfluthrin emanator or a placebo control. RESULTS: Human-landing mosquito catches documented a reduction in landing rates related to the SR. Overall, there was a 16.4% reduction (21% indoors, and 11.3% outdoors) in human biting rates (HBR) for Anopheles. For Aedes, there was a 44.3% HBR reduction indoors and a 35.6% reduction outdoors. This reduction was 38.3% indoors and 39.1% outdoors for Armigeres, and 36.0% indoors and 32.3% outdoors for Culex species. Intervention impacts on the HBRs were not significant and are attributed to large inter-household and inter cluster variation. Anopheles flavirostris, Anopheles balabacensis and Anopheles maculatus individually impacted the overall malaria infections hazard rate with statistically significance. Though there was SR-based protection against malaria for all Anopheles species (except Anopheles sundaicus), only five (Anopheles aconitus, Anopheles kochi, Anopheles tessellatus, An. maculatus and An. sundaicus) demonstrated statistical significance. The SR numerically reduced Anopheles parity rates indoors and outdoors when compared to the placebo. CONCLUSION: Evidence demonstrating that Anopheles vectors bite both indoors and outdoors indicates that currently implemented indoor-based vector control tools may not be sufficient to eliminate malaria. The documented impact of the SR intervention on Aedes, Armigeres and Culex species points to its importance in combatting other vector borne diseases. Studies to determine the impact of spatial repellents on other mosquito-borne diseases is recommended.

An inventory of human night-biting mosquitoes and their bionomics in Sumba, Indonesia.

Mosquitoes are important vectors that transmit pathogens to human and other vertebrates. Each mosquito species has specific ecological requirements and bionomic traits that impact human exposure to mosquito bites, and hence disease transmission and vector control. A study of human biting mosquitoes and their bionomic characteristics was conducted in West Sumba and Southwest Sumba Districts, Nusa Tenggara Timur Province, Indonesia from May 2015 to April 2018. Biweekly human landing catches (HLC) of night biting mosquitoes both indoors and outdoors caught a total of 73,507 mosquito specimens (59.7% non-Anopheles, 40.3% Anopheles). A minimum of 22 Culicinae species belonging to four genera (Aedes, Armigeres, Culex, Mansonia), and 13 Anophelinae species were identified. Culex quinquefasciatus was the dominant Culicinae species, Anopheles aconitus was the principal Anopheles species inland, while An. sundaicus was dominant closer to the coast. The overall human biting rate (HBR) was 10.548 bites per person per night (bpn) indoors and 10.551 bpn outdoors. Mosquitoes biting rates were slightly higher indoors for all genera with the exception of Anopheles, where biting rates were slightly higher outdoors. Diurnal and crepuscular Aedes and Armigeres demonstrated declining biting rates throughout the night while Culex and Anopheles biting rates peaked before midnight and then declined. Both anopheline and non-anopheline populations did not have a significant association with temperature (p = 0.3 and 0.88 respectively), or rainfall (p = 0.13 and 0.57 respectively). The point distribution of HBR and seasonal variables did not have a linear correlation. Data demonstrated similar mosquito-human interactions occurring outdoors and indoors and during early parts of the night implying both indoor and outdoor disease transmission potential in the area-pointing to the need for interventions in both spaces. Integrated vector analysis frameworks may enable better surveillance, monitoring and evaluation strategies for multiple diseases.

Correction: Anopheles sundaicus complex and the presence of Anopheles epiroticus in Indonesia.

[This corrects the article DOI: 10.1371/journal.pntd.0008385.].

Anopheles sundaicus complex and the presence of Anopheles epiroticus in Indonesia.

Anopheles sundaicus s.l. is an important malaria vector primarily found in coastal landscapes of western and central Indonesia. The species complex has a wide geographical distribution in South and Southeast Asia and exhibits ecological and behavioural variability over its range. Studies on understanding the distribution of different members in the complex and their bionomics related to malaria transmission might be important guiding more effective vector intervention strategies. Female An. sundaicus s.l. were collected from seven provinces, 12 locations in Indonesia representing Sumatra: North Sumatra, Bangka-Belitung, South Lampung, and Bengkulu; in Java: West Java; and the Lesser Sunda Islands: West Nusa Tenggara and East Nusa Tenggara provinces. Sequencing of ribosomal DNA ITS2 gene fragments and two mitochondrial DNA gene markers, COI and cytb, enabled molecular identification of morphologically indistinguishable members of the complex. Findings allowed inference on the distribution of the An. sundaicus s.l. present in Indonesia and further illustrate the phylogenetic relationships of An. epiroticus within the complex. A total of 370 An. sundaicus s.l specimens were analysed for the ITS2 fragment. The ITS2 sequence alignment revealed two consistent species-specific point mutations, a T>C transition at base 479 and a G>T transversion at base 538 that differentiated five haplotypes: TG, CG, TT, CT, and TY. The TG haplotype matched published An. epiroticus-indicative sequences from Thailand, Vietnam and peninsular Malaysia. The previously described insertion event (base 603) was observed in all identified specimens. Analysis of the COI and cytb genes revealed no consistent nucleotide variations that could definitively distinguish An. epiroticus from other members in the Sundaicus Complex. The findings indicate and support the existence of An. epiroticus in North Sumatra and Bangka-Belitung archipelago. Further studies are recommended to determine the full distributional extent of the Sundaicus complex in Indonesia and investigate the role of these species in malaria transmission.

Efficacy of a Spatial Repellent for Control of Malaria in Indonesia: A Cluster-Randomized Controlled Trial.

A cluster-randomized, double-blinded, placebo-controlled trial was conducted to estimate the protective efficacy (PE) of a spatial repellent (SR) against malaria infection in Sumba, Indonesia. Following radical cure in 1,341 children aged ≥ 6 months to ≤ 5 years in 24 clusters, households were given transfluthrin or placebo passive emanators (devices designed to release vaporized chemical). Monthly blood screening and biweekly human-landing mosquito catches were performed during a 10-month baseline (June 2015-March 2016) and a 24-month intervention period (April 2016-April 2018). Screening detected 164 first-time infections and an accumulative total of 459 infections in 667 subjects in placebo-control households, and 134 first-time and 253 accumulative total infections among 665 subjects in active intervention households. The 24-cluster protective effect of 27.7% and 31.3%, for time to first-event and overall (total new) infections, respectively, was not statistically significant. Purportedly, this was due in part to zero to low incidence in some clusters, undermining the ability to detect a protective effect. Subgroup analysis of 19 clusters where at least one infection occurred during baseline showed 33.3% (P-value = 0.083) and 40.9% (P-value = 0.0236, statistically significant at the one-sided 5% significance level) protective effect to first infection and overall infections, respectively. Among 12 moderate- to high-risk clusters, a statistically significant decrease in infection by intervention was detected (60% PE). Primary entomological analysis of impact was inconclusive. Although this study suggests SRs prevent malaria, additional evidence is required to demonstrate the product class provides an operationally feasible and effective means of reducing malaria transmission.

Host attraction and biting behaviour of Anopheles mosquitoes in South Halmahera, Indonesia.

BACKGROUND: Indonesia is home to a variety of malaria vectors whose specific bionomic traits remain largely uncharacterized. Species-specific behaviours, such as host feeding preferences, impact the dynamics of malaria transmission and the effectiveness of vector control interventions. METHODS: To examine species-specific host attraction and feeding behaviours, a Latin square design was used to compare Anopheles mosquitoes attracted to human, cow, and goat-baited tents. Anopheles mosquitoes were collected hourly from the inside walls of each baited tent. Species were morphologically and then molecularly identified using rDNA ITS2 sequences. The head and thorax of individual specimens were analysed for Plasmodium DNA using PCR. Bloodmeals were identified using a multiplex PCR. RESULTS: A total of 1024, 137, and 74 Anopheles were collected over 12 nights in cow, goat, and human-baited tents, respectively. The species were identified as Anopheles kochi, Anopheles farauti s.s., Anopheles hackeri, Anopheles hinesorum, Anopheles indefinitus, Anopheles punctulatus, Anopheles tessellatus, Anopheles vagus, and Anopheles vanus, many of which are known to transmit human malaria. Molecular analysis of blood meals revealed a high level of feeding on multiple host species in a single night. Anopheles kochi, An. indefinitus, and An. vanus were infected with Plasmodium vivax at rates comparable to primary malaria vectors. CONCLUSIONS: The species distributions of Anopheles mosquitoes attracted to human, goat, and cow hosts were similar. Eight of nine sporozoite positive samples were captured with animal-baited traps, indicating that even predominantly zoophilic mosquitoes may be contributing to malaria transmission. Multiple host feeding and flexibility in blood feeding behaviour have important implications for malaria transmission, malaria control, and the effectiveness of intervention and monitoring methods, particularly those that target human-feeding vectors.

eEvidence: Information Seeking Support for Evidence-based Practice: An Implementation Case Study.

We propose to collect freely available articles from the web to build an evidence-based practice resource collection with up-to-date coverage, and then apply automated classification and key information extraction on the collected articles to provide means for sounder relevance judgments. We implement these features into a dual-interface system that allows users to choose between an active or passive information seeking process depending on the amount of time available.

Improving Search for Evidence-based Practice using Information Extraction.

The search for applicable and valid research evidence-based practice articles is not supported well in common EBP resources, as some crucial study data, such as patient details, study design and results, are not available or presented explicitly. We propose to extract these data from research articles using a two-step supervised soft classification method. Compared to manual annotation, our approach is less labor-intensive and more flexible, hence opening up the possibility of utilizing these data to facilitate the evidence selection process in information seeking support systems.

eEvidence: supplying evidence to the patient interaction.

Nursing demands that all care offered to patients is appropriately assessed, delivered and evaluated; the care offered must be up to date and supported by adequately researched published evidence. A basic logic suggests that information and communications technology can help the nurse in maintaining his/her care provision to the highest level through presenting relevant evidence. The nursing need for evidence to support the delivery of care is a global phenomenon. Within the project this is demonstrated by the fact that the project lead is resident in England and the project is being carried out in Singapore with the help of the National University Hospital, the Alice Lee Centre of Nursing Studies and the School of Computing at the National University of Singapore. The project commenced in January 2008, this paper will present the background thinking to the project design and will describe the outcomes which will provide nurses with individual supportive evidence for their practice gleaned from quality assured sources. The project will use information and communications technology to provide the evidence on an individual basis. The paper will outline the four key elements of the project, these being the development of user (professional) profiles; the design and development of an automatic crawler search engine to deliver quality assured evidence sources and software design; there will be some mention of hardware design and maintenance which is the fourth key element. Within the paper, consideration will be given to the added value of the project to the nurses, their patients/clients, the research agenda and the employing organisation: The drive for information is determined by the nurses in clinical and community practice. Evidence available immediately at the point of intervention with patient/client. No patient information stored within structure. All technology and almost all support software already available. Additional information can flow both ways for quality and activity audits. Identification of areas weak in evidence requiring supportive research will be driven by practice. Immediate dissemination of new generic practices and principles can be delivered to each nurse on syncopation, removing the requirements for paper updates etc. Process can be transferred across all healthcare clinical professions In conclusion, information will be given on progress to date in terms of technical applicability and user acceptance by the nursing staff. In addition, an insight will be given as to managing a multiprofessional, multi-organisational project from a distance.