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Background: Between 2000 and 2019, more than 1.8 billion long-lasting insecticidal nets (LLINs) were distributed in Africa. While the insecticidal durability of LLINs is around 3 years, nets are commonly discarded 2 years post distribution. This study investigated the factors associated with the decision of users to discard LLINs. Methods: A mixed-method sequential explanatory approach using a structured questionnaire followed by focus group discussions (FGDs) to collect information on experiences, views, reasons, how and when LLINs are discarded. Out of 6,526 households that responded to the questionnaire of LLINs durability trial, 160 households were randomly selected from the households in four villages in Bagamoyo Tanzania for FGDs but only 155 households participated in the FGDs. Five of the household representatives couldn't participate due to unexpected circumstances. A total of sixteen FGDs each comprising of 8–10 adults were conducted; older women (40–60 years), older men (40–60 years), younger women (18–39 years), younger men (18–39 years). During the FGDs, participants visually inspected seven samples of LLINs that were "too-torn" based on Proportionate Hole Index recommended by the World Health Organization (WHO) guidelines on LLIN testing, the nets were brought to the discussion and participants had to determine if such LLINs were to be kept or discarded. The study assessed responses from the same participants that attended FGD and also responded to the structured questionnaire, 117 participants fulfilled the criteria, thus data from only 117 participants are analysed in this study. Results: In FGDs, integrity of LLIN influenced the decision to discard or keep a net. Those of older age, women, and householders with lower income were more likely to classify a WHO "too-torn" net as "good". The common methods used to discard LLINs were burning and burying. The findings were seen in the quantitative analysis. For every additional hole, the odds of discarding a WHO "too-torn" LLIN increased [OR = 1.05 (95%CI (1.04–1.07)), p < 0.001]. Younger age group [OR = 4.97 (95%CI (3.25–7.32)), p < 0.001], male-headed households [OR = 6.85 (95%CI (4.44 –10.59)), p < 0.001], and wealthy households [OR = 3.88 (95%CI (2.33–6.46)), p < 0.001] were more likely to discard LLINs. Conclusion: Integrity of LLIN was the main determinant for discarding or keeping LLINs and the decision to discard the net is associated with socioeconomic status of the household, and the age and gender of respondents. WHO "too torn" nets are encouraged to be used instead of none until replacement, and disposal of nets should be based on recommendation. [ABSTRACT FROM AUTHOR]

Background: Spatial repellents that drive mosquitoes away from treated areas, and odour-baited traps, that attract and kill mosquitoes, can be combined and work synergistically in a push-pull system. Push-pull systems have been shown to reduce house entry and outdoor biting rates of malaria vectors and so have the potential to control other outdoor biting mosquitoes such as Aedes aegypti that transmit arboviral diseases. In this study, semi-field experiments were conducted to evaluate whether a push-pull system could be used to reduce bites from Aedes mosquitoes. Methods: The push and pull under investigation consisted of two freestanding transfluthrin passive emanators (FTPE) and a BG sentinel trap (BGS) respectively. The FTPE contained hessian strips treated with 5.25 g of transfluthrin active ingredient. The efficacies of FTPE and BGS alone and in combination were evaluated by human landing catch in a large semi-field system in Tanzania. We also investigated the protection of FTPE over six months. The data were analyzed using generalized linear mixed models with binomial distribution. Results: Two FTPE had a protective efficacy (PE) of 61.2% (95% confidence interval (CI): 52.2–69.9%) against the human landing of Ae. aegypti. The BGS did not significantly reduce mosquito landings; the PE was 2.1% (95% CI: −2.9–7.2%). The push-pull provided a PE of 64.5% (95% CI: 59.1–69.9%). However, there was no significant difference in the PE between the push-pull and the two FTPE against Ae. aegypti (P = 0.30). The FTPE offered significant protection against Ae. aegypti at month three, with a PE of 46.4% (95% CI: 41.1–51.8%), but not at six months with a PE of 2.2% (95% CI: −9.0–14.0%). Conclusions: The PE of the FTPE and the full push-pull are similar, indicative that bite prevention is primarily due to the activity of the FTPE. While these results are encouraging for the FTPE, further work is needed for a push-pull system to be recommended for Ae. aegypti control. The three-month protection against Ae. aegypti bites suggests that FTPE would be a useful additional control tool during dengue outbreaks, that does not require regular user compliance. [ABSTRACT FROM AUTHOR]

Background: Long-lasting insecticidal nets (LLINs) are the most sustainable and effective malaria control tool currently available. Global targets are for 80% of the population living in malaria endemic areas to have access to (own) and use a LLIN. However, current access to LLINs in endemic areas is 56% due to system inefficiencies and budget limitations. Thus, cost-effective approaches to maximize access to effective LLINs in endemic areas are required. This study evaluated whether LLINs that had been stored for 5 years under manufacturer's recommended conditions may be optimally effective against Anopheles mosquitoes, to inform malaria control programmes and governments on the periods over which LLINs may be stored between distributions, in an effort to maximize use of available LLINs. Methods: Standard World Health Organization (WHO) bioassays (cone and tunnel test) were used to evaluate the bio-efficacy and wash resistance of Olyset® and DawaPlus® 2.0 (rebranded Tsara® Soft) LLINs after 5 years of storage at 25 °C to 33.4 °C and 40% to 100% relative humidity. In addition, a small scale Ifakara Ambient Chamber test (I-ACT) was conducted to compare the bio-efficacy of one long stored LLINs to one new LLIN of the same brand, washed or unwashed. LLINs were evaluated using laboratory reared fully susceptible Anopheles gambiae sensu stricto (s.s.) (Ifakara strain) and pyrethroid resistant Anopheles arabiensis (Kingani strain). Results: After 5 years of storage, both unwashed and washed, Olyset® and DawaPlus® 2.0 (Tsara® Soft) LLINs passed WHO bio-efficacy criteria on knockdown (KD60) ≥ 95%, 24-h mortality ≥ 80% and ≥ 90% blood-feeding inhibition in WHO assays against susceptible An. gambiae s.s. DawaPlus® 2.0 LLINs also passed combined WHO bioassay criteria against resistant An. arabiensis. Confirmatory I-ACT tests using whole nets demonstrated that long-stored LLINs showed higher efficacy than new LLINs on both feeding inhibition and mortality endpoints against resistant strains. Conclusions: Even after long-term storage of around 5 years, both Olyset® and DawaPlus® 2.0 LLINs remain efficacious against susceptible Anopheles mosquitoes at optimal storage range of 25 °C to 33.4 °C for temperature and 40% to 100% relative humidity measured by standard WHO methods. DawaPlus® 2.0 (Tsara® Soft) remained efficacious against resistant strain. [ABSTRACT FROM AUTHOR]

It is not surprising that the Library of Congress would be defined as our national monument of art given the scale of the project, its federal sponsorship, and its posture as a public library with access to all Americans. Paralleling the assumption of the Library of Congress as not merely a building for housing books but a ritualistic center of civilization, the ambitious decorative program celebrated Western civilization and, in particular, the evolution of culture through knowledge. This article examines two mural cycles at the Library of Congress, The Evolution of the Book by John White Alexander and The Evolution of Civilization by Edwin Blashfield, considering each as a multivalent construction of American national identity and the critical debates that they generated. The male body was the subject of both cycles and functioned as the ideological armature within which to project current assumptions of and debates about masculinity, labor, imperialism, social reform, national identity, and progress. [ABSTRACT FROM AUTHOR]

Background and purpose A remarkable improvement in patient positioning was observed after the implementation of various process changes aiming to increase the consistency of patient positioning throughout the radiotherapy treatment chain. However, no tool was available to describe these changes over time in a standardised way. This study reports on the feasibility of Statistical Process Control (SPC) to highlight changes in patient positioning accuracy and facilitate correlation of these changes with the underlying process changes. Materials and methods Metrics were designed to quantify the systematic and random patient deformation as input for the SPC charts. These metrics were based on data obtained from multiple local ROI matches for 191 patients who were treated for head-and-neck cancer during the period 2011–2016. Results SPC highlighted a significant improvement in patient positioning that coincided with multiple intentional process changes. The observed improvements could be described as a combination of a reduction in outliers and a systematic improvement in the patient positioning accuracy of all patients. Conclusion SPC is able to track changes in the reproducibility of patient positioning in head-and-neck radiation oncology, and distinguish between systematic and random process changes. Identification of process changes underlying these trends requires additional statistical analysis and seems only possible when the changes do not overlap in time. [ABSTRACT FROM AUTHOR]

Background: Long-lasting insecticidal nets (LLINs) are the first line choice for malaria vector control in sub-Saharan Africa, with most countries adopting universal coverage campaigns. However, there is only limited information on LLIN durability under user conditions. Therefore, this study aimed to assess the durability of Olyset® LLINs distributed during campaigns between 2009 and 2011 in Tanzania. Methods: A retrospective field survey was conducted in eight districts in Tanzania mainland to assess the durability of Olyset campaign nets. Household questionnaires were used to assess attrition, i.e. net loss. All nets remaining in households were collected. A sub-sample of 198 Olyset campaign nets was examined for bio-efficacy against Anopheles gambiae s.s. mosquitoes, permethrin content and physical integrity following standard World Health Organization (WHO) methods. Results: Of 6067 campaign nets reported to have been received between 2009 and 2011, 35 % (2145 nets) were no longer present. Most of those nets had been discarded (84 %) mainly because they were too torn (94 %). Of the 198 sub-sampled Olyset LLINs, 61 % were still in serviceable physical condition sufficient to provide personal protection while 39 % were in unserviceable physical condition according to WHO proportionate Hole Index (pHI). More than 96 % (116/120) of nets in serviceable condition passed WHO bioefficacy criteria while all nets in unserviceable condition passed WHO bioefficacy criteria. Overall mean permethrin content was 16.5 g/kg (95 % CI 16.2–16.9) with 78 % of the sub-sampled nets retaining recommended permethrin content regardless of their age or physical condition. Nets aged 4 years and above had a mean permethrin content of 14 g/kg (95 % CI 12.0–16.0). The only statistically significant predictor of reduced physical net integrity was rats in the house. Conclusions: Two-to-four years after a mass campaign, only 39 % of distributed nets remain both present and in serviceable physical condition, a functional survival considerably below WHO assumptions of 50 % survival of a ‘threeyear’ net. However, the majority of nets still retained substantial levels of permethrin and could still be bio-chemically useful against mosquitoes if their holes were repaired, adding evidence to the value of net care and repair campaigns. [ABSTRACT FROM AUTHOR]

This male patient presented with a scrotal abscess and urinary obstruction. The patient’s history included a perineal abscess and the development of urethrocutaneous fistulae (watering-can perineum). He underwent multiple debridement procedures without resolution. During the fifth debridement for Fournier’s gangrene, a biopsy revealed invasive squamous cell carcinoma. The patient was bedridden because of the large mass, a wide en bloc resection with lymphadenectomy and reconstruction was performed revealing a large (22 cm) squamous cell carcinoma originating from the urethra. He also received palliative chemoradiotherapy and hip hemiarthroplasty. Unfortunately, he succumbed to the disease. Given the recognized relationship between inflammation and the development of cancer, it is important to entertain a differential diagnosis of cancer, especially with erosive infections. This case report highlights the all too common late presentation of urethral cancer. Interestingly, despite correction of the bedridden state with palliative surgery, the patient did not perceive an improvement in quality of life based on the FACT-G questionnaire. [ABSTRACT FROM AUTHOR]

Purpose: This article identifies, prioritizes, and summarizes the published literature on the medication use process (MUP) from calendar year 2012 that can impact health-system pharmacists’ daily practice. Summary: The MUP is the foundational system that provides the framework for safe patient care within the health care environment. The MUP is defined in this article as having the following components: prescribing/transcribing, dispensing, administration, and monitoring. A PubMed search was conducted in January 2013 for calendar year 2012 using targeted Medical Subject Headings (MeSH) keywords, providing a total of 944 articles. A thorough review identified 46 potentially significant articles: 14 for prescribing/transcribing, 12 for dispensing, 10 for administration, and 10 for monitoring. Peer review led to the selection of key articles from each category. These articles are briefly summarized, with a mention of why this article is important within health-system pharmacy. The other articles are listed for further review and evaluation. Conclusion: It is important to routinely review the published literature and to incorporate significant findings into daily practice. Health-system pharmacists have an active role in improving the MUP in their institution and awareness of the significant published studies can assist in changing practice at the institutional level. [ABSTRACT FROM AUTHOR]

Central nervous system tumors carry grave clinical prognoses due to limited effectiveness of surgical resection, radiation, and chemotherapy. Thus, improved strategies for brain tumor visualization and targeted treatment are critically needed. We demonstrate that mouse cerebellar medulloblastoma (MB) can be targeted and illuminated with a fluorescent, engineered cystine knot (knottin) peptide that binds with high affinity to αvβ3, αvβ5, and α5β1 integrin receptors. This integrin-binding knottin peptide, denoted EETI 2.5F, was evaluated as a molecular imaging probe in both orthotopic and genetic models of MB. Following tail vein injection, fluorescence arising from dye-conjugated EETI 2.5F was localized to the tumor compared with the normal surrounding brain tissue, as measured by optical imaging. The imaging signal intensity correlated with tumor volume. Due to its unique ability to bind to α5β1 integrin, EETI 2.5F showed superior in vivo and ex vivo brain tumor imaging contrast compared with other engineered integrin-binding knottin peptides and with c(RGDfK), a well-studied integrin-binding peptidomimetic. Next, EETI 2.5F was fused to an antibody fragment crystallizable (Fc) domain (EETI 2.5F-Fc) to determine if a larger integrin-binding protein could also target intracranial brain tumors. EETI 2.5F-Fc, conjugated to a fluorescent dye, illuminated MB following i.v. injection and was able to distribute throughout the tumor parenchyma. In contrast, brain tumor imaging signals were not detected in mice injected with EETI 2.5F proteins containing a scrambled integrin-binding sequence, demonstrating the importance of target specificity. These results highlight the potential of using EETI 2.5F and EETI 2.5-Fc as targeted molecular probes for brain tumor imaging. [ABSTRACT FROM AUTHOR]

Background: Cystine-knot miniproteins, also known as knottins, have shown great potential as molecular scaffolds for the development of targeted therapeutics and diagnostic agents. For this purpose, previous protein engineering efforts have focused on knottins based on the Ecballium elaterium trypsin inhibitor (EETI) from squash seeds, the Agouti-related protein (AgRP) neuropeptide from mammals, or the Kalata B1 uterotonic peptide from plants. Here, we demonstrate that Agatoxin (AgTx), an ion channel inhibitor found in spider venom, can be used as a molecular scaffold to engineer knottins that bind with high-affinity to a tumor-associated integrin receptor. Methodology/Principal Findings: We used a rational loop-grafting approach to engineer AgTx variants that bound to αvβ3 integrin with affinities in the low nM range. We showed that a disulfide-constrained loop from AgRP, a structurally-related knottin, can be substituted into AgTx to confer its high affinity binding properties. In parallel, we identified amino acid mutations required for efficient in vitro folding of engineered integrin-binding AgTx variants. Molecular imaging was used to evaluate in vivo tumor targeting and biodistribution of an engineered AgTx knottin compared to integrin-binding knottins based on AgRP and EETI. Knottin peptides were chemically synthesized and conjugated to a near-infrared fluorescent dye. Integrin-binding AgTx, AgRP, and EETI knottins all generated high tumor imaging contrast in U87MG glioblastoma xenograft models. Interestingly, EETI-based knottins generated significantly lower non-specific kidney imaging signals compared to AgTx and AgRP-based knottins. Conclusions/Significance: In this study, we demonstrate that AgTx, a knottin from spider venom, can be engineered to bind with high affinity to a tumor-associated receptor target. This work validates AgTx as a viable molecular scaffold for protein engineering, and further demonstrates the promise of using tumor-targeting knottins as probes for in vivo molecular imaging. [ABSTRACT FROM AUTHOR]

Mosquito coils, vaporizer mats and emanators confer protection against mosquito bites through the spatial action of emanated vapor or airborne pyrethroid particles. These products dominate the pest control market; therefore, it is vital to characterize mosquito responses elicited by the chemical actives and their potential for disease prevention. The aim of this review was to determine effects of mosquito coils and emanators on mosquito responses that reduce human-vector contact and to propose scientific consensus on terminologies and methodologies used for evaluation of product formats that could contain spatial chemical actives, including indoor residual spraying (IRS), long lasting insecticide treated nets (LLINs) and insecticide treated materials (ITMs). PubMed, (National Centre for Biotechnology Information (NCBI), U.S. National Library of Medicine, NIH), MEDLINE, LILAC, Cochrane library, IBECS and Armed Forces Pest Management Board Literature Retrieval System search engines were used to identify studies of pyrethroid based coils and emanators with key-words "Mosquito coils" "Mosquito emanators" and "Spatial repellents". It was concluded that there is need to improve statistical reporting of studies,and reach consensus in the methodologies and terminologies used through standardized testing guidelines. Despite differing evaluation methodologies, data showed that coils and emanators induce mortality, deterrence, repellency as well as reduce the ability of mosquitoes to feed on humans. Available data on efficacy outdoors, dose-response relationships and effective distance of coils and emanators is inadequate for developing a target product profile (TPP), which will be required for such chemicals before optimized implementation can occur for maximum benefits in disease control. [ABSTRACT FROM AUTHOR]

Plant-based repellents have been used for generations in traditional practice as a personal protection measure against host-seeking mosquitoes. Knowledge on traditional repellent plants obtained through ethnobotanical studies is a valuable resource for the development of new natural products. Recently, commercial repellent products containing plant-based ingredients have gained increasing popularity among consumers, as these are commonly perceived as "safe" in comparison to long-established synthetic repellents although this is sometimes a misconception. To date insufficient studies have followed standard WHO Pesticide Evaluation Scheme guidelines for repellent testing. There is a need for further standardized studies in order to better evaluate repellent compounds and develop new products that offer high repellency as well as good consumer safety. This paper presents a summary of recent information on testing, efficacy and safety of plant-based repellents as well as promising new developments in the field. [ABSTRACT FROM AUTHOR]

Background: Malaria control in remote, forested areas of the Mekong region relies on personal protection from mosquito bites. Uptake of these methods may be limited by knowledge of the link between mosquitoes and malaria as well as social and economic aspects. Understanding barriers to uptake will inform malaria control programmes on targets for improvement of delivery. Methods: A total 748 key respondents: health providers and village heads, from 187 villages and 25 different ethnic groups, were interviewed using structured questionnaires. Differences in use of personal protection, and knowledge of malaria between groups were analysed using chi-square; and binary logistic regression used for multivariate analysis. Results: Malaria knowledge was poor with 19.4% of women and 37.5% of men linking mosquitoes with malaria, although 95.6% knew one or more methods of mosquito control. Virtually all respondents used personal protection at some time during the year; and understanding of malaria transmission was strongly associated with bednet use. Those working in forest agriculture were significantly more likely to know that mosquitoes transmit malaria but this did not translate into a significantly greater likelihood of using bednets. Furthermore, use of personal protection while woing outdoors was rare, and less than 3% of respondents knew about the insecticide impregnation of bednets. The use of bednets, synthetic repellents and mosquito coils varied between ethnic groups, but was significantly more frequent among those with higher income, more years of education and permanent housing. The reported use of repellents and coils was also more common among women despite their low knowledge of malaria transmission, and low likelihood of having heard information on malaria within the last year. Conclusion: The use of personal protection must be increased, particularly among outdoor workers that have higher malaria risk. However, personal protection is widely used and widely accepted to prevent nuisance biting mosquitoes, with the major barrier to use being affordability. Therefore, social marketing campaigns aimed at women and those that work outdoors that provide highly subsidised products, especially insecticide impregnation kits for bednets and hammock nets are most likely to succeed in lowering malaria morbidity among non Han-Chinese groups in rural China. [ABSTRACT FROM AUTHOR]

Background: The cost of mosquito repellents in Latin America has discouraged their wider use among the poor. To address this problem, a low-cost repellent was developed that reduces the level of expensive repellent actives by combining them with inexpensive fixatives that appear to slow repellent evaporation. The chosen actives were a mixture of para-menthane-diol (PMD) and lemongrass oil (LG). Methods: To test the efficacy of the repellent, field trials were staged in Guatemala and Peru. Repellent efficacy was determined by human-landing catches on volunteers who wore the experimental repellents, control, or 15% DEET. The studies were conducted using a balanced Latin Square design with volunteers, treatments, and locations rotated each night. Results: In Guatemala, collections were performed for two hours, commencing three hours after repellent application. The repellent provided >98% protection for five hours after application, with a biting pressure of >100 landings per person/hour. The 15% DEET control provided lower protection at 92% (p < 0.0001). In Peru, collections were performed for four hours, commencing two hours after repellent application. The PMD/LG repellent provided 95% protection for six hours after application with a biting pressure of >46 landings per person/hour. The 20% DEET control provided significantly lower protection at 64% (p < 0.0001). Conclusion: In both locations, the PMD/LG repellent provided excellent protection up to six hours after application against a wide range of disease vectors including Anopheles darlingi. The addition of fixatives to the repellent extended its longevity while enhancing efficacy and significantly reducing its cost to malaria-endemic communities. [ABSTRACT FROM AUTHOR]

Presents a case study on the Great Big Sea band as an example of Newfoundland and Labrador's popular music and cultural identity. Reasons for the success of the band; Features of popular music in Newfoundland which are reflected in the music of the Great Big Sea; Musical identity of the band.

Discusses how two international expositions in the United States in 1898 and 1901 collided with the realities and implications of the Spanish-American War. Discussion on the Trans-Mississippi and International Exposition in Omaha, Nebraska in 1898 and the Pan-American Exposition in Buffalo, New York in 1901; Implications of the conduct of the international expositions on American colonialism.

Background: Indoor residual spraying (IRS) is one of the most effective malaria control tools. However, its application has become limited to specific contexts due to the increased costs of IRS products and implementation programmes. Selective spraying—selective spray targeted to particular areas/surfaces of dwellings—has been proposed to maintain the malaria control and resistance-management benefits of IRS while decreasing the costs of the intervention. Methods: A literature search was conducted to find (1) studies that assessed the resting behaviour of Anopheles mosquitoes and (2) studies that evaluated the impact of selective spraying on entomological and malaria outcomes. Additional articles were identified through hand searches of all references cited in articles identified through the initial search. A cost model was developed from PMI VectorLink IRS country programmes, and comparative cost analysis reports to describe the overall cost benefits of selective IRS. Results: In some studies, there appeared to be a clear resting preference for certain Anopheles species in terms of the height at which they rested. However, for other species, and particularly the major African malaria vectors, a clear resting pattern was not detected. Furthermore, resting behaviour was not measured in a standardized way. For the selective spray studies that were assessed, there was a wide range of spray configurations, which complicates the comparison of methods. Many of these spray techniques were effective and resulted in reported 25–68% cost savings and reduced use of insecticide. The reported cost savings in the literature do not always consider all of the IRS implementation costs. Using the IRS cost model, these savings ranged from 17 to 29% for programs that targeted Anopheles spp. and 18–41% for programmes that targeted Aedes aegypti. Conclusions: Resting behaviour is generally measured in a simplistic way; noting the resting spot of mosquitoes in the morning. This is likely an oversimplification, and there is a need for better monitoring of resting mosquitoes. This may improve the target surface for selective spray techniques, which could reduce the cost of IRS while maintaining its effectiveness. Reporting of cost savings should be calculated considering the entire implementation costs, and a cost model was provided for future calculations. [ABSTRACT FROM AUTHOR]

Cambodia’s goal to eliminate malaria by 2025 is challenged by persistent transmission in forest and forest fringe areas, where people are exposed to Anopheles mosquito bites during the day and night. Volatile pyrethroid spatial repellents (VPSRs) and insecticide-treated clothing (ITC) could address these gaps. This study evaluated the outdoor application of one passive transfluthrin-based VPSR, four etofenprox-ITCs paired with a picaridin topical repellent, and a combination of VPSR and ITC against wild Anopheles landing in Cambodia. A 7 × 7 Latin-square study was conducted over 49 collection nights in temporary open structures in Mondulkiri Province. All interventions substantially reduced Anopheles landing, with protective efficacy ranging from 61 to 95%. Mathematical modeling showed significant reductions in vectoral capacity, especially with the combined ITC and VPSR and VPSR alone, albeit with decreased effectiveness over time. These interventions have the potential to reduce outdoor and daytime Anopheles biting, offering valuable contributions to malaria elimination efforts in Cambodia and the Greater Mekong Subregion, contingent upon achieving effective coverage and adherence. [ABSTRACT FROM AUTHOR]

The availability of nutrients from mosquito blood meals accelerates the development of Plasmodium falciparum laboratory strains in artificially infected Anopheles gambiae mosquitoes. The impact of multiple blood meals on the number of P. falciparum genotypes developing from polyclonal natural human malaria infections (field-isolates) remains unexplored. Here, we experimentally infect An. gambiae with P. falciparum field-isolates and measure the impact of an additional non-infectious blood meal on parasite development. We also assess parasite genetic diversity at the blood stage level of the parasite in the human host and of the sporozoites in the mosquito. Additional blood meals increase the sporozoite infection prevalence and intensity, but do not substantially affect the genetic diversity of sporozoites in the mosquito. The most abundant parasite genotypes in the human blood were transmitted to mosquitoes, suggesting that there was no preferential selection of specific genotypes. This study underlines the importance of additional mosquito blood meals for the development of parasite field-isolates in the mosquito host. [ABSTRACT FROM AUTHOR]

Provides information about the National Women Suffrage Pageant in 1913 sponsored by the National American Women Suffrage Association. Analysis on the pageant craze that swept United States; Focus of the pageants staged by the American Pageant Association (APA); Significance of Alice Paul on National Women Suffrage Pageant; Two elements of the pageant.

Background: Effective testing for malaria, including the detection of infections at very low densities, is vital for the successful elimination of the disease. Unfortunately, existing methods are either inexpensive but poorly sensitive or sensitive but costly. Recent studies have shown that mid-infrared spectroscopy coupled with machine learning (MIRs-ML) has potential for rapidly detecting malaria infections but requires further evaluation on diverse samples representative of natural infections in endemic areas. The aim of this study was, therefore, to demonstrate a simple AI-powered, reagent-free, and user-friendly approach that uses mid-infrared spectra from dried blood spots to accurately detect malaria infections across varying parasite densities and anaemic conditions. Methods: Plasmodium falciparum strains NF54 and FCR3 were cultured and mixed with blood from 70 malaria-free individuals to create various malaria parasitaemia and anaemic conditions. Blood dilutions produced three haematocrit ratios (50%, 25%, 12.5%) and five parasitaemia levels (6%, 0.1%, 0.002%, 0.00003%, 0%). Dried blood spots were prepared on Whatman™ filter papers and scanned using attenuated total reflection-Fourier Transform Infrared (ATR-FTIR) for machine-learning analysis. Three classifiers were trained on an 80%/20% split of 4655 spectra: (I) high contrast (6% parasitaemia vs. negative), (II) low contrast (0.00003% vs. negative) and (III) all concentrations (all positive levels vs. negative). The classifiers were validated with unseen datasets to detect malaria at various parasitaemia levels and anaemic conditions. Additionally, these classifiers were tested on samples from a population survey in malaria-endemic villages of southeastern Tanzania. Results: The AI classifiers attained over 90% accuracy in detecting malaria infections as low as one parasite per microlitre of blood, a sensitivity unattainable by conventional RDTs and microscopy. These laboratory-developed classifiers seamlessly transitioned to field applicability, achieving over 80% accuracy in predicting natural P. falciparum infections in blood samples collected during the field survey. Crucially, the performance remained unaffected by various levels of anaemia, a common complication in malaria patients. Conclusion: These findings suggest that the AI-driven mid-infrared spectroscopy approach holds promise as a simplified, sensitive and cost-effective method for malaria screening, consistently performing well despite variations in parasite densities and anaemic conditions. The technique simply involves scanning dried blood spots with a desktop mid-infrared scanner and analysing the spectra using pre-trained AI classifiers, making it readily adaptable to field conditions in low-resource settings. In this study, the approach was successfully adapted to field use, effectively predicting natural malaria infections in blood samples from a population-level survey in Tanzania. With additional field trials and validation, this technique could significantly enhance malaria surveillance and contribute to accelerating malaria elimination efforts. [ABSTRACT FROM AUTHOR]

Simple Summary: Mosquito traps are widely used for the monitoring and surveillance of mosquito vectors in many mosquito-borne disease-endemic countries. However, the costs and efficacy of traps remain a great challenge. In this study, we compared the trapping efficacy of locally modified Gravid Aedes Trap (GAT) and Autocidal Gravid Ovitrap (AGO) for dengue vector (Aedes aegypti) in a semi-field and field settings. The GAT was lined with pyrethroid-treated nets as a killing agent, while the AGO adhered with a sticky board to capture mosquitoes. We also compared the locally modified traps baited with either yeast or grass infusion with BG-Sentinel (BGS) with BG lure (a standard trap for capturing Aedes mosquitoes). Our findings showed that the GAT was more efficacious than the AGO in both semi-field and field settings. Additionally, there was no significant difference between yeast-baited and grass-baited GAT traps in capturing mosquitoes, although yeast was easier to use. When compared to a standard trap (BGS), GAT showed no difference in capturing Aedes mosquitoes in a semi-field; however, in the field setting, BGS outperformed the modified GAT. The study assessed the trapping efficacy of locally modified (1) Gravid Aedes Trap (GAT) lined with insecticide-treated net (ITN) as a killing agent and (2) Autocidal Gravid Ovitrap (AGO) with sticky board in the semi-field system (SFS) and field setting. Fully balanced Latin square experiments were conducted to compare GAT lined with ITN vs. AGO, both with either yeast or grass infusion. Biogent-Sentinel (BGS) with BG-Lure and no CO2 was used as a standard trap for Aedes mosquitoes. In the SFS, GAT outperformed AGO in collecting both nulliparous (65% vs. 49%, OR = 2.22, [95% CI: 1.89–2.60], p < 0.001) and gravid mosquitoes (73% vs. 64%, OR = 1.67, [95% CI: 1.41–1.97], p < 0.001). Similar differences were observed in the field. Yeast and grass infusion did not significantly differ in trapping gravid mosquitoes (OR = 0.91, [95% CI: 0.77–1.07], p = 0.250). The use of ITN improved mosquito recapture from 11% to 70% in the SFS. The same trend was observed in the field. Yeast was chosen for further evaluation in the optimized GAT due to its convenience and bifenthrin net for its resistance management properties. Mosquito density was collected when using 4× GATs relative to BGS-captured gravid mosquitoes 64 vs. 58 (IRR = 0.82, [95% CI: 0.35–1.95], p = 0.658) and showed no density dependence. Deployment of multiple yeast-baited GAT lined with bifenthrin net is cost-effective (single GAT < $8) compared to other traps such as BGS ($160). [ABSTRACT FROM AUTHOR]

Entomological evaluations of vector control tools often use human landing catches (HLCs) as a standard measure of a direct human-vector contact. However, some tools have additional characteristics, such as mortality, and HLCS are not sensitive for measuring other effects beyond landing inhibition. Therefore, additional measures may need to be considered when evaluating these tools for public health use. This study has two main aims (1) the evaluate the accuracy of HLCs as a proxy for feeding and (2) to compare the predicted reduction in vectorial capacity when we do and do not consider these additional characteristics. To achieve this, we analyse previously published semi-field data from an experiment which used HLCs and another where mosquitoes were allowed to feed in the presence of different dosages of the volatile pyrethroid spatial repellent, transfluthrin. We compare results for two mathematical models: one which only considers the reduction in feeding effect and one which also considers mortality before and after feeding (using data gathered by the aspiration of mosquitoes after the semi-field feeding/landing period and 24 h survival monitoring). These Bayesian hierarchical models are parameterised using Bayesian inference. We observe that, for susceptible mosquitoes, reduction in landing is underestimated by HLCs. For knockdown resistant mosquitoes the relationship is less clear; with HLCs sometimes appearing to overestimate this characteristic. We find HLCs tend to under-predict the relative reduction in vectorial capacity in susceptible mosquitoes while over-predicting this impact in knockdown-resistant mosquitoes. Models without secondary effects have lower predicted relative reductions in vectorial capacities. Overall, this study highlights the importance of considering additional characteristics to reduction in biting of volatile pyrethroid spatial repellents. We recommend that these are considered when evaluating novel vector control tools. [ABSTRACT FROM AUTHOR]

The article discusses an integrated investigational drug service (IDS) model for the preparation of inpatient, outpatient, investigational and commercial oncology doses. It mentions the importance of an integrated IDS model within an oncology service line to ensure the dispensation of the correct therapies at the correct time, factors considered for model implementation including content experts, access to protocol information and standard practices, and the operational structure of the model.

Background: Pyrethroid resistance in the key malaria vectors threatens the success of pyrethroid-treated nets. To overcome pyrethroid resistance, Interceptor® G2 (IG2), a 'first-in-class' dual insecticidal net that combines alpha-cypermethrin with chlorfenapyr, was developed. Chlorfenapyr is a pro-insecticide, requiring bio-activation by oxidative metabolism within the insect's mitochondria, constituting a mode of action preventing cross-resistance to pyrethroids. Recent epidemiological trials conducted in Benin and Tanzania confirm IG2's public health value in areas with pyrethroid-resistant Anopheles mosquitoes. As chlorfenapyr might also interfere with the metabolic mechanism of the Plasmodium parasite, we hypothesised that chlorfenapyr may provide additional transmission-reducing effects even if a mosquito survives a sub-lethal dose. Methods: We tested the effect of chlorfenapyr netting to reduce Plasmodium falciparum transmission using a modified WHO tunnel test with a dose yielding sub-lethal effects. Pyrethroid-resistant Anopheles gambiae s.s. with L1014F and L1014S knockdown resistance alleles and expression levels of pyrethroid metabolisers CYP6P3, CYP6M2, CYP4G16 and CYP6P1 confirmed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) prior to conducting experiments were exposed to untreated netting and netting treated with 200 mg/m3 chlorfenapyr for 8 h overnight and then fed on gametocytemic blood meals from naturally infected individuals. Prevalence and intensity of oocysts and sporozoites were determined on day 8 and day 16 after feeding. Results: Both prevalence and intensity of P. falciparum infection in the surviving mosquitoes were substantially reduced in the chlorfenapyr-exposed mosquitoes compared to untreated nets. The odds ratios in the prevalence of oocysts and sporozoites were 0.33 (95% confidence interval; 95% CI 0.23–0.46) and 0.43 (95% CI 0.25–0.73), respectively, while only the incidence rate ratio for oocysts was 0.30 (95% CI 0.22–0.41). Conclusion: We demonstrated that sub-lethal exposure of pyrethroid-resistant mosquitoes to chlorfenapyr substantially reduces the proportion of infected mosquitoes and the intensity of the P. falciparum infection. This will likely also contribute to the reduction of malaria in communities beyond the direct killing of mosquitoes. [ABSTRACT FROM AUTHOR]

Background: Pyrethroid resistance in the key malaria vectors threatens the success of pyrethroid-treated nets. To overcome pyrethroid resistance, Interceptor® G2 (IG2), a 'first-in-class' dual insecticidal net that combines alpha-cypermethrin with chlorfenapyr, was developed. Chlorfenapyr is a pro-insecticide, requiring bio-activation by oxidative metabolism within the insect's mitochondria, constituting a mode of action preventing cross-resistance to pyrethroids. Recent epidemiological trials conducted in Benin and Tanzania confirm IG2's public health value in areas with pyrethroid-resistant Anopheles mosquitoes. As chlorfenapyr might also interfere with the metabolic mechanism of the Plasmodium parasite, we hypothesised that chlorfenapyr may provide additional transmission-reducing effects even if a mosquito survives a sub-lethal dose. Methods: We tested the effect of chlorfenapyr netting to reduce Plasmodium falciparum transmission using a modified WHO tunnel test with a dose yielding sub-lethal effects. Pyrethroid-resistant Anopheles gambiae s.s. with L1014F and L1014S knockdown resistance alleles and expression levels of pyrethroid metabolisers CYP6P3, CYP6M2, CYP4G16 and CYP6P1 confirmed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) prior to conducting experiments were exposed to untreated netting and netting treated with 200 mg/m3 chlorfenapyr for 8 h overnight and then fed on gametocytemic blood meals from naturally infected individuals. Prevalence and intensity of oocysts and sporozoites were determined on day 8 and day 16 after feeding. Results: Both prevalence and intensity of P. falciparum infection in the surviving mosquitoes were substantially reduced in the chlorfenapyr-exposed mosquitoes compared to untreated nets. The odds ratios in the prevalence of oocysts and sporozoites were 0.33 (95% confidence interval; 95% CI 0.23–0.46) and 0.43 (95% CI 0.25–0.73), respectively, while only the incidence rate ratio for oocysts was 0.30 (95% CI 0.22–0.41). Conclusion: We demonstrated that sub-lethal exposure of pyrethroid-resistant mosquitoes to chlorfenapyr substantially reduces the proportion of infected mosquitoes and the intensity of the P. falciparum infection. This will likely also contribute to the reduction of malaria in communities beyond the direct killing of mosquitoes. [ABSTRACT FROM AUTHOR]

Novel malaria vector control strategies targeting the odour-orientation of mosquitoes during host-seeking, such as 'attract-and-kill' or 'push-and-pull', have been suggested as complementary tools to indoor residual spraying and long-lasting insecticidal nets. These would be particularly beneficial if they can target vectors in the peri-domestic space where people are unprotected by traditional interventions. A randomized double-blind placebo-control study was implemented in western Kenya to evaluate: a 'push' intervention (spatial repellent) using transfluthrin-treated fabric strips positioned at open eave gaps of houses; a 'pull' intervention placing an odour-baited mosquito trap at a 5 m distance from a house; the combined 'push–pull' package; and the control where houses contained all elements but without active ingredients. Treatments were rotated through 12 houses in a randomized-block design. Outdoor biting was estimated using human landing catches, and indoor mosquito densities using light-traps. None of the interventions provided any protection from outdoor biting malaria vectors. The 'push' reduced indoor vector densities dominated by Anopheles funestus by around two thirds. The 'pull' device did not add any benefit. In the light of the high Anopheles arabiensis biting densities outdoors in the study location, the search for efficient outdoor protection and effective pull components needs to continue. [ABSTRACT FROM AUTHOR]

Background: The mosquito landing rate measured by human landing catches (HLC) is the conventional endpoint used to evaluate the impact of vector control interventions on human-vector exposure. Non-exposure based alternatives to the HLC are desirable to minimize the risk of accidental mosquito bites. One such alternative is the human-baited double net trap (HDN), but the estimated personal protection of interventions using the HDN has not been compared to the efficacy estimated using HLC. This semi-field study in Sai Yok District, Kanchanaburi Province, Thailand, evaluates the performance of the HLC and the HDN for estimating the effect on Anopheles minimus landing rates of two intervention types characterized by contrasting modes of action, a volatile pyrethroid spatial repellent (VSPR) and insecticide-treated clothing (ITC). Methods: Two experiments to evaluate the protective efficacy of (1) a VPSR and (2) ITC, were performed. A block randomized cross-over design over 32 nights was carried out with both the HLC or HDN. Eight replicates per combination of collection method and intervention or control arm were conducted. For each replicate, 100 An. minimus were released and were collected for 6 h. The odds ratio (OR) of the released An. minimus mosquitoes landing in the intervention compared to the control arm was estimated using logistic regression, including collection method, treatment, and experimental day as fixed effects. Results: For the VPSR, the protective efficacy was similar for the two methods: 99.3%, 95% CI (99.5–99.0) when measured by HLC, and 100% (100, Inf) when measured by HDN where no mosquitoes were caught (interaction test p = 0.99). For the ITC, the protective efficacy was 70% (60–77%) measured by HLC but there was no evidence of protection when measured by HDN [4% increase (15–27%)] (interaction test p < 0.001). Conclusions: Interactions between mosquitoes, bite prevention tools and the sampling method may impact the estimated intervention protective efficacy. Consequently, the sampling method must be considered when evaluating these interventions. The HDN is a valid alternative trapping method (relative to the HLC) for evaluating the impact of bite prevention methods that affect mosquito behaviour at a distance (e.g. VPSR), but not for interventions that operate through tarsal contact (e.g., ITC). [ABSTRACT FROM AUTHOR]

Background: Asymptomatic malaria infections (Plasmodium falciparum) are common in school-aged children and represent a disease transmission reservoir as they are potentially infectious to mosquitoes. To detect and treat such infections, convenient, rapid and reliable diagnostic tools are needed. In this study, malaria rapid diagnostic tests (mRDT), light microscopy (LM) and quantitative polymerase chain reaction (qPCR) were used to evaluate their performance detecting asymptomatic malaria infections that are infectious to mosquitoes. Methods: One hundred seventy asymptomatic school-aged children (6–14 years old) from the Bagamoyo district in Tanzania were screened for Plasmodium spp. infections using mRDT (SD BIOLINE), LM and qPCR. In addition, gametocytes were detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR) for all qPCR-positive children. Venous blood from all P. falciparum positive children was fed to female Anopheles gambiae sensu stricto mosquitoes via direct membrane feeding assays (DMFAs) after serum replacement. Mosquitoes were dissected for oocyst infections on day 8 post-infection. Results: The P. falciparum prevalence in study participants was 31.7% by qPCR, 18.2% by mRDT and 9.4% by LM. Approximately one-third (31.2%) of asymptomatic malaria infections were infectious to mosquitoes in DMFAs. In total, 297 infected mosquitoes were recorded after dissections, from which 94.9% (282/297) were derived from infections detected by mRDT and 5.1% (15/297) from subpatent mRDT infections. Conclusion: The mRDT can be used reliably to detect children carrying gametocyte densities sufficient to infect high numbers of mosquitoes. Subpatent mRDT infections contributed marginally to the pool of oocyts-infected mosquitoes. [ABSTRACT FROM AUTHOR]

Presently, the most common malaria control tools–i.e., long lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS)–are limited to targeting indoor biting and resting behaviors of Anopheles mosquito species. Few interventions are targeted towards malaria control in areas where transmission is driven or persists due to outdoor biting behaviors. This study investigated a volatile pyrethroid-based spatial repellent (VPSR) designed to bridge this gap and provide protection from mosquito bites in outdoor spaces. Southern Province, Zambia, is one such environment where outdoor biting is suspected to contribute to malaria transmission, where people are active in the evening in open-walled outdoor kitchens. This study assessed the VPSR in replica kitchens within a controlled semi-field environment. Endpoints included effects on mosquito host seeking, immediate and delayed mortality, deterrence, blood feeding inhibition, and fertility. Host-seeking was reduced by approximately 40% over the course of nightly releases in chambers containing VPSR devices. Mosquito behavior was not uniform throughout the night, and the modeled effect of the intervention was considerably higher when hourly catch rates were considered. These two observations highlight a limitation of this overnight semi-field design and consideration of mosquito circadian rhythms is recommended for future semi-field studies. Additionally, deterrence and immediate mortality were both observed in treatment chambers, with evidence of delayed mortality and a dose related response. These results demonstrate a primarily personal protective mode of action with possible positive and negative community effects. Further investigation into this primary mode of action will be conducted through a field trial of the same product in nearby communities. [ABSTRACT FROM AUTHOR]

Background: Mass distributions of long-lasting insecticidal nets (LLINs) have contributed to large reductions in the malaria burden. However, this success is in jeopardy due in part to the increasing pyrethroid-resistant mosquito population as well as low LLINs coverage in various areas because the lifespan of LLINs is often shorter than the interval between replenishment campaigns. New insecticide-treated nets (ITNs) containing pyrethroid and piperonyl-butoxide (PBO) have shown a greater reduction in the incidence of malaria than pyrethroid LLINs in areas with pyrethroid-resistant mosquitoes. However, the durability (attrition, bio-efficacy, physical integrity and chemical retainment) of pyrethroid-PBO ITNs under operational settings has not been fully characterized. This study will measure the durability of pyrethroid-PBO ITNs to assess whether they meet the World Health Organization (WHO) three years of operational performance criteria required to be categorized as "long-lasting". Methods: A prospective household randomized controlled trial will be conducted simultaneously in Tanzania, India and Côte d'Ivoire to estimate the field durability of three pyrethroid-PBO ITNs (Veeralin®, Tsara® Boost, and Olyset® Plus) compared to a pyrethroid LLIN: MAGNet®. Durability monitoring will be conducted up to 36 months post-distribution and median survival in months will be calculated. The proportion of ITNs: (1) lost (attrition), (2) physical integrity, (3) resistance to damage score, (4) meeting WHO bio-efficacy (≥ 95% knockdown after 1 h or ≥ 80% mortality after 24 h for WHO cone bioassay, or ≥ 90% blood-feeding inhibition or ≥ 80% mortality after 24 h for WHO Tunnel tests) criteria against laboratory-reared resistant and susceptible mosquitoes, and insecticidal persistence over time will be estimated. The non-inferiority of Veeralin® and Tsara® Boost to the first-in-class, Olyset® Plus will additionally be assessed for mortality, and the equivalence of 20 times washed ITNs compared to field aged ITNs will be assessed for mortality and blood-feeding inhibition endpoints in the Ifakara Ambient Chamber Test, Tanzania. Conclusion: This will be the first large-scale prospective household randomized controlled trial of pyrethroid-PBO ITNs in three different countries in East Africa, West Africa and South Asia, simultaneously. The study will generate information on the replenishment intervals for PBO nets. [ABSTRACT FROM AUTHOR]

Today, malaria prevention hinges upon two domestic interventions: insecticide-treated bed nets and indoor residual spraying. As mosquitoes grow resistant to these tools, however, novel approaches to vector control have become a priority area of malaria research and development. Spatial repellency, a volumetric mode of action that seeks to reduce disease transmission by creating an atmosphere inimical to mosquitoes, represents one way forward. Drawing from research that sought to develop new repellent chemicals in conversation with users from sub-Saharan Africa and the United States, we consider the implications of a non-insecticidal paradigm of vector control for how we understand the political ecology of malaria. [ABSTRACT FROM AUTHOR]

Background: On-going malaria transmission is increasingly mediated by outdoor-biting vectors, especially where indoor insecticidal interventions such as long-lasting insecticide treated nets (LLINs) are widespread. Often, the vectors are also physiologically resistant to insecticides, presenting major obstacles for elimination. We tested a combination of electrocuting grids with synthetic odours as an alternative killing mechanism against outdoor-biting mosquitoes. Methods: An odour-baited device, the Mosquito Landing Box (MLB), was improved by fitting it with low-cost electrocuting grids to instantly kill mosquitoes attracted to the odour lure, and automated photo switch to activate attractant-dispensing and mosquito-killing systems between dusk and dawn. MLBs fitted with one, two or three electrocuting grids were compared outdoors in a malaria endemic village in Tanzania, where vectors had lost susceptibility to pyrethroids. MLBs with three grids were also tested in a large semi-field cage (9.6×9.6×4.5m), to assess effects on biting-densities of laboratory-reared Anopheles arabiensis on volunteers sitting near MLBs. Results: Significantly more mosquitoes were killed when MLBs had two or three grids, than one grid in wet and dry seasons (P<0.05). The MLBs were highly efficient against Mansonia species and malaria vector, An. arabiensis. Of all mosquitoes, 99% were non-blood fed, suggesting host-seeking status. In the semi-field, the MLBs reduced mean number of malaria mosquitoes attempting to bite humans fourfold. Conclusion: The improved odour-baited MLBs effectively kill outdoor-biting malaria vector mosquitoes that are behaviourally and physiologically resistant to insecticidal interventions e.g. LLINs. The MLBs reduce human-biting vector densities even when used close to humans, and are insecticide-free, hence potentially antiresistance. The devices could either be used as surveillance tools or complementary mosquito control interventions to accelerate malaria elimination where outdoor transmission is significant. [ABSTRACT FROM AUTHOR]

Background: Quality assurance (QA) of insecticide-treated nets (ITNs) delivered to malaria-endemic countries is conducted by measuring physiochemical parameters, but not bioefficacy against malaria mosquitoes. This study explored utility of cone bioassays for pre-delivery QA of pyrethroid ITNs to test the assumption that cone bioassays are consistent across locations, mosquito strains, and laboratories. Methods: Double-blinded bioassays were conducted on twenty unused pyrethroid ITNs of 4 brands (100 nets, 5 subsamples per net) that had been delivered for mass distribution in Papua New Guinea (PNG) having passed predelivery inspections. Cone bioassays were performed on the same net pieces following World Health Organization (WHO) guidelines at the PNG Institute of Medical Research (PNGIMR) using pyrethroid susceptible Anopheles farauti sensu stricto (s.s.) and at Ifakara Health Institute (IHI), Tanzania using pyrethroid susceptible Anopheles gambiae s.s. Additionally, WHO tunnel tests were conducted at IHI on ITNs that did not meet cone bioefficacy thresholds. Results from IHI and PNGIMR were compared using Spearman's Rank correlation, Bland–Altman (BA) analysis and analysis of agreement. Literature review on the use of cone bioassays for unused pyrethroid ITNs testing was conducted. Results: In cone bioassays, 13/20 nets (65%) at IHI and 8/20 (40%) at PNGIMR met WHO bioefficacy criteria. All nets met WHO bioefficacy criteria on combined cone/tunnel tests at IHI. Results from IHI and PNGIMR correlated on 60-min knockdown (KD60) (rs = 0.6,p = 0.002,n = 20) and 24-h mortality (M24) (rs = 0.9,p < 0.0001,n = 20) but BA showed systematic bias between the results. Of the 5 nets with discrepant result between IHI and PNGIMR, three had confidence intervals overlapping the 80% mortality threshold, with averages within 1–3% of the threshold. Including these as a pass, the agreement between the results to predict ITN failure was good with kappa = 0.79 (0.53–1.00) and 90% accuracy. Conclusions: Based on these study findings, the WHO cone bioassay is a reproducible bioassay for ITNs with > 80% M24, and for all ITNs provided inherent stochastic variation and systematic bias are accounted for. The literature review confirms that WHO cone bioassay bioefficacy criteria have been previously achieved by all pyrethroid ITNs (unwashed), without the need for additional tunnel tests. The 80% M24 threshold remains the most reliable indicator of pyrethroid ITN quality using pyrethroid susceptible mosquitoes. In the absence of alternative tests, cone bioassays could be used as part of pre-delivery QA. [ABSTRACT FROM AUTHOR]

Simple Summary: Membrane feeding assays have been widely used in malaria transmission research and insectary colony maintenance. Here, we investigate whether a membrane feeder can replace animal baits for evaluating insecticide-treated nets (ITNs) bio-efficacy in the World Health Organization (WHO) tunnel test. The effect of (1) alternative baits, (2) exposure time, and (3) mosquito density on the endpoints of mosquito mortality and feeding inhibition or feeding success was investigated. Our results show that similar mortality at 24-h (M24) or 72-h (M72) is estimated using either a membrane feeder or a rabbit bait with an overnight (12 h) exposure. However, the membrane measured higher blood feeding inhibition than the rabbit, likely due to the absence of host cues, notably carbon dioxide. Therefore, the membrane feeder may be used instead of an animal bait to test mortality endpoints in WHO tunnel tests and blood feeding rates need to be improved. Experimental results demonstrated that using 50 or 100 mosquitoes per replicate measure the same for mortality and feeding inhibition endpoints with an animal bait. Therefore, WHO tunnel tests may be run with lower mosquito densities. This will reduce strain on insectaries to produce sufficient mosquitoes to meet the large sample sizes needed for bio-efficacy durability monitoring of chlorfenapyr ITNs that must be evaluated in "free-flying" bioassays. The standard World Health Organization (WHO) tunnel test is a reliable laboratory bioassay used for "free-flying" testing of insecticide-treated nets (ITNs) bio-efficacy where mosquitoes pass through a ITN sample to reach a live animal bait. Multiple parameters (i.e., bait, exposure time, and mosquito density) may affect the outcomes measured in tunnel tests. Therefore, a comparison was conducted of alternative hosts, exposure time, and lower mosquito density against the current gold standard test (100 mosquitoes, animal bait, and 12-h exposure) as outlined in the WHO ITN evaluation guideline. This was done with the aim to make the tunnel test cheaper and with higher throughput to meet the large sample sizes needed for bio-efficacy durability monitoring of chlorfenapyr ITNs that must be evaluated in "free-flying" bioassays. Methods: A series of experiments were conducted in the WHO tunnel test to evaluate the impact of the following factors on bio-efficacy endpoints of mosquito mortality at 24-h (M24) and 72-h (M72) and blood-feeding success (BFS): (1) baits (rabbit, membrane, human arm); (2) exposure time in the tunnel (1 h vs. 12 h); and (3) mosquito density (50 vs. 100). Finally, an alternative bioassay using a membrane with 50 mosquitoes (membrane-50) was compared to the gold standard bioassay (rabbit with 100 mosquitoes, rabbit-100). Pyrethroid-resistant Anopheles arabiensis and pyrethroid susceptible Anopheles gambiae were used to evaluate Interceptor® and Interceptor® G2 ITNs. Results: Using a human arm as bait gave a very different BFS, which impacted measurements of M24 and M72. The same trends in M24, M72 and BFS were observed for both Interceptor® ITN and Interceptor® G2 unwashed and washed 20 times measured using the gold standard WHO tunnel test (rabbit-100) or rabbit with 50 mosquitoes (rabbit-50). M24, M72 and BFS were not statistically different when either 50 or 100 mosquitoes were used with rabbit bait in the tunnel bioassay for either the susceptible or resistant strains. No systematic difference was observed between rabbit-50 and rabbit-100 in the agreement by the Bland and Altman method (B&A). The mean difference was 4.54% (−22.54–31.62) in BFS and 1.71% (−28.71–32.12) in M72 for rabbit-50 versus rabbit-100. Similar M24, M72 and lower BFS was measured by membrane-50 compared to rabbit-100. No systematic difference was observed in the agreement between membrane-50 and rabbit-100, by B&A. The mean difference was 9.06% (−11.42–29.64) for BSF and −5.44% (−50.3–39.45) for M72. Both membrane-50, rabbit-50 and rabbit-100 predicted the superiority of Interceptor® G2 over Interceptor® ITN for the resistant strain on M72. Conclusion: These results demonstrate that WHO tunnel tests using rabbit bait may be run with 50 mosquitoes to increase sample sizes needed for bio-efficacy durability monitoring of ITNs in "free-flying" bioassays. Using a membrane feeder with 50 mosquitoes is a potential replacement for the WHO tunnel bioassay with animal bait if control blood feeding rates can be improved to 50% because blood feeding impacts mosquito survival after exposure to insecticides. [ABSTRACT FROM AUTHOR]

Students in the Rural Clinical School of Western Australia (RCSWA) spend one year of clinical study learning in small groups while embedded in rural or remote communities. This aims to increase the locally trained rural medical workforce. Their learning environment, the clinical context of their learning, and their rural doctor-teachers all contrast with the more traditional learning setting in city hospitals. The RCSWA has succeeded in its outcomes for students and in rural medical workforce impact; it has grown from 4 pilot sites to 14 in 12 years. This reflective piece assimilates observations of the formation of the RCSWA pedagogy and of the strategic alignment of education technologies with learning environment and pedagogy over a seven-year period. Internal and external influences, driving change in the RCSWA, were considered from three observer perspectives in a naturalistic setting. Flexibility in both education technologies and organizational governance enabled education management to actively follow pedagogy. Peter Senge's learning organization (LO) theory was overlaid on the strategies for change response in the RCSWA; these aligned with those of known LOs as well with LO disciplines and the archetypal systems thinking. We contend that the successful RCSWA paradigm is that of an LO. [ABSTRACT FROM AUTHOR]

Background: Vector mosquito biting intensity is an important measure to understand malaria transmission. Human landing catch (HLC) is an effective but labour-intensive, expensive, and potentially hazardous entomological surveillance tool. The Centres for Disease Control light trap (CDC-LT) and the human decoy trap (HDT) are exposure-free alternatives. This study compared the CDC-LT and HDT against HLC for measuring Anopheles biting in rural Tanzania and assessed their suitability as HLC proxies. Methods: Indoor mosquito surveys using HLC and CDC-LT and outdoor surveys using HLC and HDT were conducted in 2017 and in 2019 in Ulanga, Tanzania in 19 villages, with one trap/house/night. Species composition, sporozoite rates and density/trap/night were compared. Aggregating the data by village and month, the Bland–Altman approach was used to assess agreement between trap types. Results: Overall, 66,807 Anopheles funestus and 14,606 Anopheles arabiensis adult females were caught with 6,013 CDC-LT, 339 indoor-HLC, 136 HDT and 195 outdoor-HLC collections. Indoors, CDC-LT caught fewer An. arabiensis (Adjusted rate ratio [Adj.RR] = 0.35, 95% confidence interval [CI]: 0.27–0.46, p < 0.001) and An. funestus (Adj.RR = 0.63, 95%CI: 0.51–0.79, p < 0.001) than HLC per trap/night. Outdoors, HDT caught fewer An. arabiensis (Adj.RR = 0.04, 95%CI: 0.01–0.14, p < 0.001) and An. funestus (Adj.RR = 0.10, 95%CI: 0.07–0.15, p < 0.001) than HLC. The bias and variability in number of mosquitoes caught by the different traps were dependent on mosquito densities. The relative efficacies of both CDC-LT and HDT in comparison to HLC declined with increased mosquito abundance. The variability in the ratios was substantial for low HLC counts and decreased as mosquito abundance increased. The numbers of sporozoite positive mosquitoes were low for all traps. Conclusions: CDC-LT can be suitable for comparing mosquito populations between study arms or over time if accuracy in the absolute biting rate, compared to HLC, is not required. CDC-LT is useful for estimating sporozoite rates because large numbers of traps can be deployed to collect adequate mosquito samples. The present design of the HDT is not amenable for use in large-scale entomological surveys. Use of HLC remains important for estimating human exposure to mosquitoes as part of estimating the entomological inoculation rate (EIR). [ABSTRACT FROM AUTHOR]

The article presents hitting the right note at the right time: Circadian control of audibility in Anopheles mosquito mating swarms is mediated by flight tones. It mentions that the flight tones of individual mosquitoes occupy narrow, partly non-overlapping frequency ranges, suggesting that the audibility of individual females varies across males.

Background: Indoor residual insecticide spraying (IRS) and long-lasting insecticide treated nets (LLINs) are commonly used together even though evidence that such combinations confer greater protection against malaria than either method alone is inconsistent. Methods: A deterministic model of mosquito life cycle processes was adapted to allow parameterization with results from experimental hut trials of various combinations of untreated nets or LLINs (Olyset®, PermaNet 2.0®, Icon Life® nets) with IRS (pirimiphos methyl, lambda cyhalothrin, DDT), in a setting where vector populations are dominated by Anopheles arabiensis, so that community level impact upon malaria transmission at high coverage could be predicted. Results: Intact untreated nets alone provide equivalent personal protection to all three LLINs. Relative to IRS plus untreated nets, community level protection is slightly higher when Olyset® or PermaNet 2.0® nets are added onto IRS with pirimiphos methyl or lambda cyhalothrin but not DDT, and when Icon LifeW nets supplement any of the IRS insecticides. Adding IRS onto any net modestly enhances communal protection when pirimiphos methyl is sprayed, while spraying lambda cyhalothrin enhances protection for untreated nets but not LLINs. Addition of DDT reduces communal protection when added to LLINs. Conclusions: Where transmission is mediated primarily by An. arabiensis, adding IRS to high LLIN coverage provides only modest incremental benefit (e.g. when an organophosphate like pirimiphos methyl is used), but can be redundant (e.g. when a pyrethroid like lambda cyhalothin is used) or even regressive (e.g. when DDT is used for the IRS). Relative to IRS plus untreated nets, supplementing IRS with LLINs will only modestly improve community protection. Beyond the physical protection that intact nets provide, additional protection against transmission by An. arabiensis conferred by insecticides will be remarkably small, regardless of whether they are delivered as LLINs or IRS. The insecticidal action of LLINs and IRS probably already approaches their absolute limit of potential impact upon this persistent vector so personal protection of nets should be enhanced by improving the physical integrity and durability. Combining LLINs and non-pyrethroid IRS in residual transmission systems may nevertheless be justified as a means to manage insecticide resistance and prevent potential rebound of not only An. arabiensis, but also more potent, vulnerable and historically important species such as Anopheles gambiae and Anopheles funestus. [ABSTRACT FROM AUTHOR]

Background: While there is strong evidence that bite protection methods such as permethrin-treated clothing and topical insect repellents are protective against insect bites, there are few studies assessing the impact on malaria infection. This study will estimate the protective efficacy of treated uniforms and DEET insect repellent on the incidence of malaria infection among military personnel in an operational setting. Permethrin-treated uniforms used with DEET lotion will be compared to etofenprox-treated uniforms with DEET lotion. The effect of DEET lotion will be estimated by comparing permethrin-treated uniforms with DEET or placebo lotion.Method: A cluster randomised double-blind placebo-controlled trial is planned to evaluate the effectiveness of the interventions on preventing malaria infections in soldiers on active duty at Mgambo National Service Camp in Tanga, Tanzania. The arms are (1) permethrin-treated uniform with 30% DEET liposome formula; (2) permethrin-treated uniform with placebo lotion; (3) candidate insect repellent system, i.e. etofenprox-treated uniform with 30% DEET liposome formula; and (4) placebo, i.e. untreated uniforms with placebo lotion. The primary outcome is the incidence of Plasmodium falciparum malaria infection detected by polymerase chain reaction (PCR) by active case detection using surveys every 2 weeks for 12 months. Rapid diagnostic tests will be used for the diagnosis of participants with symptoms. The unit of randomisation will be combania: companies formed by recruits aged 18 to 25 years; combania do activities together and sleep in the same dormitory. Unequal randomisation will be used to optimise statistical power for the primary comparison between permethrin-treated uniforms with DEET and etofenprox-treated uniforms with DEET.Discussion: This trial will provide the estimate of the effects of permethrin with DEET compared to those of the new fabric treatment etofenprox with DEET and any additional effect of using DEET. The results will inform strategies to protect military personnel and civilians who have more outdoor or occupational malaria exposure than the general public.Trial Registration: ClinicalTrials.gov NCT02938975 . [ABSTRACT FROM AUTHOR]

Background: The human landing catch (HLC) measures human exposure to mosquito bites and evaluates the efficacy of vector control tools. However, it may expose volunteers to potentially infected mosquitoes. The mosquito electrocuting trap (MET) and BG-Sentinel traps (BGS) represent alternative, exposure-free methods for sampling host-seeking mosquitoes. This study investigates whether these methods can be effectively used as alternatives to HLC for measuring the efficacy of transfluthrin emanator against Aedes aegypti. Methods: The protective efficacy (PE) of freestanding passive transfluthrin emanators (FTPEs), measured by HLC, MET and BGS, was compared in no-choice and choice tests. The collection methods were conducted 2 m from an experimental hut with FTPEs positioned at 3 m on either side of them. For the choice experiment, a competitor HLC was included 10 m from the first collection point. One hundred laboratory-reared Ae. aegypti mosquitoes were released and collected for 3 consecutive h. Results: In the no-choice test, each method measured similar PE: HLC: 66% (95% confidence interval [CI]: 50–82), MET: 55% (95% CI: 48–63) and BGS: 64% (95% CI: 54–73). The proportion of mosquitoes recaptured was consistent between methods (20–24%) in treatment and varied (47–71%) in the control. However, in choice tests, the PE measured by each method varied: HLC: 37% (95% CI: 25–50%), MET: 76% (95% CI: 61–92) and BGS trap: 0% (95% CI: 0–100). Recaptured mosquitoes were no longer consistent between methods in treatment (2–26%) and remained variable in the control (7–42%). FTPE provided 50% PE to the second HLC 10 m away. In the control, the MET and the BGS were less efficacious in collecting mosquitoes in the presence of a second HLC. Conclusions: Measuring the PE in isolation was fairly consistent for HLC, MET and BGS. Because HLC is not advisable, it is reasonable to use either MET or BGS as a proxy for HLC for testing volatile pyrethroid (VP) in areas of active arbovirus-endemic areas. The presence of a human host in close proximity invalidated the PE estimates from BGS and METs. Findings also indicated that transfluthrin can protect multiple people in the peridomestic area and that at short range mosquitoes select humans over the BGS. [ABSTRACT FROM AUTHOR]

Background: Semi-field experiments with human landing catch (HLC) measure as the outcome are an important step in the development of novel vector control interventions against outdoor transmission of malaria since they provide good estimates of personal protection. However, it is often infeasible to determine whether the reduction in HLC counts is due to mosquito mortality or repellency, especially considering that spatial repellents based on volatile pyrethroids might induce both. Due to the vastly different impact of repellency and mortality on transmission, the community-level impact of spatial repellents can not be estimated from such semi-field experiments. Methods: We present a new stochastic model that is able to estimate for any product inhibiting outdoor biting, its repelling effect versus its killing and disarming (preventing host-seeking until the next night) effects, based only on time-stratified HLC data from controlled semi-field experiments. For parameter inference, a Bayesian hierarchical model is used to account for nightly variation of semi-field experimental conditions. We estimate the impact of the products on the vectorial capacity of the given Anopheles species using an existing mathematical model. With this methodology, we analysed data from recent semi-field studies in Kenya and Tanzania on the impact of transfluthrin-treated eave ribbons, the odour-baited Suna trap and their combination (push–pull system) on HLC of Anopheles arabiensis in the peridomestic area. Results: Complementing previous analyses of personal protection, we found that the transfluthrin-treated eave ribbons act mainly by killing or disarming mosquitoes. Depending on the actual ratio of disarming versus killing, the vectorial capacity of An. arabiensis is reduced by 41 to 96% at 70% coverage with the transfluthrin-treated eave ribbons and by 38 to 82% at the same coverage with the push–pull system, under the assumption of a similar impact on biting indoors compared to outdoors. Conclusions: The results of this analysis of semi-field data suggest that transfluthrin-treated eave ribbons are a promising tool against malaria transmission by An. arabiensis in the peridomestic area, since they provide both personal and community protection. Our modelling framework can estimate the community-level impact of any tool intervening during the mosquito host-seeking state using data from only semi-field experiments with time-stratified HLC. [ABSTRACT FROM AUTHOR]

Background: High coverage of personal protection measures that kill mosquitoes dramatically reduce malaria transmission where vector populations depend upon human blood. However, most primary malaria vectors outside of sub-Saharan Africa can be classified as "very zoophagic,'' meaning they feed occasionally (<10% of blood meals) upon humans, so personal protection interventions have negligible impact upon their survival. Methods and Findings: We extended a published malaria transmission model to examine the relationship between transmission, control, and the baseline proportion of bloodmeals obtained from humans (human blood index). The lower limit of the human blood index enables derivation of simplified models for zoophagic vectors that (1) Rely on only three field-measurable parameters. (2) Predict immediate and delayed (with and without assuming reduced human infectivity, respectively) impacts of personal protection measures upon transmission. (3) Illustrate how appreciable indirect communallevel protection for non-users can be accrued through direct personal protection of users. (4) Suggest the coverage and efficacy thresholds required to attain epidemiological impact. The findings suggest that immediate, indirect, communitywide protection of users and non-users alike may linearly relate to the efficacy of a user's direct personal protection, regardless of whether that is achieved by killing or repelling mosquitoes. High protective coverage and efficacy ($80%) are important to achieve epidemiologically meaningful impact. Non-users are indirectly protected because the two most common species of human malaria are strict anthroponoses. Therefore, the small proportion of mosquitoes that are killed or diverted while attacking humans can represent a large proportion of those actually transmitting malaria. Conclusions: Simplified models of malaria transmission by very zoophagic vectors may be used by control practitioners to predict intervention impact interventions using three field-measurable parameters; the proportion of human exposure to mosquitoes occurring when an intervention can be practically used, its protective efficacy when used, and the proportion of people using it. [ABSTRACT FROM AUTHOR]

Background: Traps baited with synthetic human odors have been proposed as suitable technologies for controlling malaria and other mosquito-borne diseases. We investigated the potential benefits of such traps for preventing malaria transmission in Africa and the essential characteristics that they should possess so as to be effective. Methods and Principal Findings: An existing mathematical model was reformulated to distinguish availability of hosts for attack by mosquitoes from availability of blood per se. This adaptation allowed the effects of pseudo-hosts such as odor-baited mosquito traps, which do not yield blood but which can nonetheless be attacked by the mosquitoes, to be simulated considering communities consisting of users and non-users of insecticide-treated nets (ITNs), currently the primary malaria prevention method. We determined that malaria transmission declines as trap coverage (proportion of total availability of all hosts and pseudo hosts that traps constitute) increases. If the traps are more attractive than humans and are located in areas where mosquitoes are most abundant, 20-130 traps per 1000 people would be sufficient to match the impact of 50% community-wide ITN coverage. If such traps are used to complement ITNs, malaria transmission can be reduced by 99% or more in most scenarios representative of Africa. However, to match cost-effectiveness of ITNs, the traps delivery, operation and maintenance would have to cost a maximum of US$4.25 to 27.61 per unit per year. Conclusions and Significance: Odor-baited mosquito traps might potentially be effective and affordable tools for malaria control in Africa, particularly if they are used to complement, rather than replace, existing methods. We recommend that developers should focus on super-attractive baits and cheaper traps to enhance cost-effectiveness, and that the most appropriate way to deploy such technologies is through vertical delivery mechanisms. [ABSTRACT FROM AUTHOR]

Background: Insecticide-treated nets (ITNs) undergo a series of tests to obtain listing by World Health Organization (WHO) Prequalification. These tests characterize the bioefficacy, physical and chemical properties of the ITN. ITN procurers assume that product specifications relate to product performance. Here, ITN test methods and their underlying assumptions are discussed from the perspective of the ITN manufacturing process and product characteristics. Methods: Data were extracted from WHO Pesticide Evaluation Scheme (WHOPES) meeting reports from 2003 to 2017, supplemented with additional chemical analysis to critically evaluate ITNs bioassays with a focus on sampling, washing and wash resistance, and bioefficacy testing. Production methods for ITNs and their impact on testing outcomes are described. Results and recommendations: ITNs are not homogenous products. They vary within panels and between the sides and the roof. Running tests of wash resistance using a before/after tests on the same sample or band within a net reduces test variability. As mosquitoes frequently interact with ITN roofs, additional sampling of the roof when evaluating ITNs is advisable because in nets where roof and sides are of the same material, the contribution of roof sample (20–25%) to the average is less than the tolerance for the specification (25%). Mosquito mortality data cannot be reliably used to evaluate net surface concentration to determine regeneration time (RT) and resistance to washing as nets may regenerate beyond the insecticide concentrations needed to kill 100% of susceptible mosquitoes. Chemical assays to quantify surface concentration are needed. The Wash Resistance Index (WRI) averaged over the first four washes is only informative if the product has a log linear loss rate of insecticide. Using a WRI that excludes the first wash off gives more reliable results. Storage conditions used for product specifications are lower than those encountered under product shipping and storage that may exceed 50 °C, and should be reconsidered. Operational monitoring of new ITNs and linking observed product performance, such as bioefficacy after 2 or 3 years of use, with product characteristics, such as WRI, will aid the development of more robust test methods and product specifications for new products coming to market. [ABSTRACT FROM AUTHOR]

Background: Semi-field experiments with human landing catch (HLC) measure as the outcome are an important step in the development of novel vector control interventions against outdoor transmission of malaria since they provide good estimates of personal protection. However, it is often infeasible to determine whether the reduction in HLC counts is due to mosquito mortality or repellency, especially considering that spatial repellents based on volatile pyrethroids might induce both. Due to the vastly different impact of repellency and mortality on transmission, the community-level impact of spatial repellents can not be estimated from such semi-field experiments. Methods: We present a new stochastic model that is able to estimate for any product inhibiting outdoor biting, its repelling effect versus its killing and disarming (preventing host-seeking until the next night) effects, based only on time-stratified HLC data from controlled semi-field experiments. For parameter inference, a Bayesian hierarchical model is used to account for nightly variation of semi-field experimental conditions. We estimate the impact of the products on the vectorial capacity of the given Anopheles species using an existing mathematical model. With this methodology, we analysed data from recent semi-field studies in Kenya and Tanzania on the impact of transfluthrin-treated eave ribbons, the odour-baited Suna trap and their combination (push–pull system) on HLC of Anopheles arabiensis in the peridomestic area. Results: Complementing previous analyses of personal protection, we found that the transfluthrin-treated eave ribbons act mainly by killing or disarming mosquitoes. Depending on the actual ratio of disarming versus killing, the vectorial capacity of An. arabiensis is reduced by 41 to 96% at 70% coverage with the transfluthrin-treated eave ribbons and by 38 to 82% at the same coverage with the push–pull system, under the assumption of a similar impact on biting indoors compared to outdoors. Conclusions: The results of this analysis of semi-field data suggest that transfluthrin-treated eave ribbons are a promising tool against malaria transmission by An. arabiensis in the peridomestic area, since they provide both personal and community protection. Our modelling framework can estimate the community-level impact of any tool intervening during the mosquito host-seeking state using data from only semi-field experiments with time-stratified HLC. [ABSTRACT FROM AUTHOR]

Over 2.2 billion long-lasting insecticidal nets (LLINs) for malaria control have been delivered to recipient countries. LLINs are the largest single item in the global malaria control budget. To be eligible for donor-funded procurement and distribution schemes, LLIN products must attain and retain World Health Organization (WHO) prequalification status by passing safety, quality, and efficacy benchmarks. Predelivery inspections further test product quality before distribution. We have shown that, despite these quality-assurance measures, substandard LLINs were distributed in Papua New Guinea (PNG) for at least 6 years (2013–2019). Other countries may have received similar LLINs. Here, we discuss the most important weaknesses of the current LLIN quality-assurance framework that have made this possible. Based on a series of concerning observations of a sudden decrease in the bioefficacy of long-lasting insecticidal nets (LLINs) in Papua New Guinea in 2013, we discuss the urgent need for a revision of the framework for the quality assessment of LLINs for both prequalification (PQ) purposes and post-PQ monitoring. The most important deficiencies of the current system include the absence of regular bioefficacy assessment for quality assurance, the ambivalence of the currently recommended bioassay methodologies, and the lack of capacity in many recipient countries for basic LLIN quality assurance. It is in the interest of manufacturers, donors, recipient countries, and most importantly, those relying on LLINs for protection against malaria, that the quality-assurance framework for these important commodities remains rigorous, adaptive, and transparent. [ABSTRACT FROM AUTHOR]

Background: The human landing catch (HLC) measures human exposure to mosquito bites and evaluates the efficacy of vector control tools. However, it may expose volunteers to potentially infected mosquitoes. The mosquito electrocuting trap (MET) and BG-Sentinel traps (BGS) represent alternative, exposure-free methods for sampling host-seeking mosquitoes. This study investigates whether these methods can be effectively used as alternatives to HLC for measuring the efficacy of transfluthrin emanator against Aedes aegypti. Methods: The protective efficacy (PE) of freestanding passive transfluthrin emanators (FTPEs), measured by HLC, MET and BGS, was compared in no-choice and choice tests. The collection methods were conducted 2 m from an experimental hut with FTPEs positioned at 3 m on either side of them. For the choice experiment, a competitor HLC was included 10 m from the first collection point. One hundred laboratory-reared Ae. aegypti mosquitoes were released and collected for 3 consecutive h. Results: In the no-choice test, each method measured similar PE: HLC: 66% (95% confidence interval [CI]: 50–82), MET: 55% (95% CI: 48–63) and BGS: 64% (95% CI: 54–73). The proportion of mosquitoes recaptured was consistent between methods (20–24%) in treatment and varied (47–71%) in the control. However, in choice tests, the PE measured by each method varied: HLC: 37% (95% CI: 25–50%), MET: 76% (95% CI: 61–92) and BGS trap: 0% (95% CI: 0–100). Recaptured mosquitoes were no longer consistent between methods in treatment (2–26%) and remained variable in the control (7–42%). FTPE provided 50% PE to the second HLC 10 m away. In the control, the MET and the BGS were less efficacious in collecting mosquitoes in the presence of a second HLC. Conclusions: Measuring the PE in isolation was fairly consistent for HLC, MET and BGS. Because HLC is not advisable, it is reasonable to use either MET or BGS as a proxy for HLC for testing volatile pyrethroid (VP) in areas of active arbovirus-endemic areas. The presence of a human host in close proximity invalidated the PE estimates from BGS and METs. Findings also indicated that transfluthrin can protect multiple people in the peridomestic area and that at short range mosquitoes select humans over the BGS. [ABSTRACT FROM AUTHOR]