Evaluating putative repellent 'push' and attractive 'pull' components for manipulating the odour orientation of host-seeking malaria vectors in the peri-domestic space

BACKGROUND: Novel malaria vector control approaches aim to combine tools for maximum protection. This study aimed to evaluate novel and re-evaluate existing putative repellent 'push' and attractive 'pull' components for manipulating the odour orientation of malaria vectors in the peri-domestic space. METHODS: Anopheles arabiensis outdoor human landing catches and trap comparisons were implemented in large semi-field systems to (i) test the efficacy of Citriodiol((R)) or transfluthrin-treated fabric strips positioned in house eave gaps as push components for preventing bites; (ii) understand the efficacy of MB5-baited Suna-traps in attracting vectors in the presence of a human being; (iii) assess 2-butanone as a CO2 replacement for trapping; (iv) determine the protection provided by a full push-pull set up. The air concentrations of the chemical constituents of the push-pull set-up were quantified. RESULTS: Microencapsulated Citriodiol((R)) eave strips did not provide outdoor protection against host-seeking An. arabiensis. Transfluthrin-treated strips reduced the odds of a mosquito landing on the human volunteer (OR 0.17; 95% CI 0.12-0.23). This impact was lower (OR 0.59; 95% CI 0.52-0.66) during the push-pull experiment, which was associated with low nighttime temperatures likely affecting the transfluthrin vaporisation. The MB5-baited Suna trap supplemented with CO2 attracted only a third of the released mosquitoes in the absence of a human being; however, with a human volunteer in the same system, the trap caught < 1% of all released mosquitoes. The volunteer consistently attracted over two-thirds of all mosquitoes released. This was the case in the absence ('pull' only) and in the presence of a spatial repellent ('push-pull'), indicating that in its current configuration the tested 'pull' does not provide a valuable addition to a spatial repellent. The chemical 2-butanone was ineffective in replacing CO2. Transfluthrin was detectable in the air space but with a strong linear reduction in concentrations over 5 m from release. The MB5 constituent chemicals were only irregularly detected, potentially suggesting insufficient release and concentration in the air for attraction. CONCLUSION: This step-by-step evaluation of the selected 'push' and 'pull' components led to a better understanding of their ability to affect host-seeking behaviours of the malaria vector An. arabiensis in the peri-domestic space and helps to gauge the impact such tools would have when used in the field for monitoring or control

Semi-field evaluation of the exposure-free mosquito electrocuting trap and BG-Sentinel trap as an alternative to the human landing catch for measuring the efficacy of transfluthrin emanators against Aedes aegypti

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

Human landing catches provide a useful measure of protective efficacy for the evaluation of volatile pyrethroid spatial repellents

BACKGROUND: The human landing catch (HLC) method, in which human volunteers collect mosquitoes that land on them before they can bite, is used to quantify human exposure to mosquito vectors of disease. Comparing HLCs in the presence and absence of interventions such as repellents is often used to measure protective efficacy (PE). Some repellents have multiple actions, including feeding inhibition, whereby mosquitoes may be unable to bite even if they land on a host. A comparison was made between the PE of the volatile pyrethroid spatial repellent (VPSR) transfluthrin determined using a landing method (HLC) and a biting method (allowing the mosquitoes that landed to blood-feed) to evaluate whether HLC is a suitable method for the estimation of the personal PE of a VPSR. METHODS: A fully balanced, two-arm crossover design study was conducted using a 6 x 6 x 2-m netted cage within a semi-field system. Hessian strips (4 m x 0.1 m) treated with a 5-, 10-, 15-, or 20-g dose of transfluthrin were evaluated against a paired negative control for three strains of laboratory-reared Anopheles and Aedes aegypti mosquitoes. Six replicates were performed per dose using either the landing or the biting method. The number of recaptured mosquitoes was analysed by negative binomial regression, and the PEs calculated using the two methods were compared by Bland-Altman plots. RESULTS: For Anopheles, fewer mosquitoes blood-fed in the biting arm than landed in the landing arm (incidence rate ratio = 0.87, 95% confidence interval 0.81-0.93, P < 0.001). For Ae. aegypti, biting was overestimated by around 37% with the landing method (incidence rate ratio = 0.63, 95% confidence interval 0.57-0.70, P = 0.001). However, the PEs calculated for each method were in close agreement when tested by the Bland Altman plot. CONCLUSIONS: The HLC method led to underestimation of mosquito feeding inhibition as a mode of action of transfluthrin, and there were species- and dose-dependent differences in the relationship between landing and biting. However, the estimated PEs were similar between the two methods. The results of this study indicate that HLC can be used as a proxy for personal PE for the evaluation of a VPSR, especially when the difficulties associated with enumerating blood-fed mosquitoes in a field setting are taken into consideration

The development and evaluation of a self-marking unit to estimate malaria vector survival and dispersal distance

Background A clear understanding of mosquito biology is fundamental to the control efforts of mosquito-borne diseases such as malaria. Mosquito mark-release-recapture (MMRR) experiments are a popular method of measuring the survival and dispersal of disease vectors; however, examples with African malaria vectors are limited. Ethical and technical difficulties involved in carrying out MMRR studies may have held back research in this area and, therefore, a device that marks mosquitoes as they emerge from breeding sites was developed and evaluated to overcome the problems of MMRR. Methods A modified self-marking unit that marks mosquitoes with fluorescent pigment as they emerge from their breeding site was developed based on a previous design for Culex mosquitoes. The self-marking unit was first evaluated under semi-field conditions with laboratory-reared Anopheles arabiensis to determine the marking success and impact on mosquito survival. Subsequently, a field evaluation of MMRR was conducted in Yombo village, Tanzania, to examine the feasibility of the system. Results During the semi-field evaluation the self-marking units successfully marked 86% of emerging mosquitoes and there was no effect of fluorescent marker on mosquito survival. The unit successfully marked wild male and female Anopheles gambiae sensu lato (s.l.) in sufficiently large numbers to justify its use in MMRR studies. The estimated daily survival probability of An. gambiae s.l. was 0.87 (95% CI 0.69–1.10) and mean dispersal distance was 579 m (95% CI 521–636 m). Conclusions This study demonstrates the successful use of a self-marking device in an MMRR study with African malaria vectors. This method may be useful in investigating population structure and dispersal of mosquitoes for deployment and evaluation of future vector control tools, such as gene drive, and to better parameterize mathematical models

A randomized, double-blind placebo-control study assessing the protective efficacy of an odour-based 'push-pull' malaria vector control strategy in reducing human-vector contact

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

Predicting the impact of outdoor vector control interventions on malaria transmission intensity from semi-field studies

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

Semi-field evaluation of freestanding transfluthrin passive emanators and the BG sentinel trap as a "push-pull control strategy" against Aedes aegypti mosquitoes

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.; 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.; 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%).; 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

Inter-annual decrease in pulse rate and peak frequency of Southeast Pacific blue whale song types

The decrease in the frequency of two southeast Pacific blue whale song types was examined over decades, usingacoustic data from several different sources ranging between the Equator and Chilean Patagonia. The pulse rate ofthe song units as well as their peak frequency were measured using two different methods (summed auto-correlationand Fourier transform). The sources of error associated with each measurement were assessed. There was a lineardecline in both parameters for the more common song type (southeast Pacific song type n ◦ 2). An abbreviated analysisalso showed a frequency decline in the scarcer southeast Pacific song type n ◦ 1 between 1970 to 2014, revealing thatboth song types are declining at similar rates. We discussed the use of measuring both pulse rate and peak frequencyto examine the frequency decline. Finally, a comparison of the rates of frequency decline with other song typesreported in the literature is presented.La décroissance en fréquence des deux chants de baleine bleue de l'océan pacifique sud est est examiné sur plusieurs décennies en utilisant comme source des données acoustiques de l'Equateur à la Patagonie chilienne. La fréquence de pulsation et la fréquence pic des signaux sont mesurés en utilisant deux méthodes distinctes (auto-corrélation sommée et transformée de Fourier rapide). Les sources d'erreur associées à chaque mesure sont estimées. Il y a un déclin linéaire de ces deux fréquences pour le chant le plus commun de cette zone (chant du Pacifique Sud Est n°2, SEP2). Un analyse plus rapide montre aussi une baisse linéaire, entre 1970 et 2014, de la fréquence du chant SEP1, plus rarement enregistré dans cette zone. Ces deux baisses ont des amplitudes similaires. L'intérêt de mesurer la fréquence de pulsation et la fréquence pic de façon concomitante est estimé. Enfin, une comparaison globale des déclins en fréquence de tous les types de chants de baleines bleues est fournie

Developing a Wellbeing Framework for Aboriginal and Torres Strait Islander Peoples Living with Chronic Disease (Wellbeing Study)

Addressing a need identified by Aboriginal and Torres Strait Islander peoples and their primary healthcare providers, this study developed a Wellbeing Framework for managing chronic disease in a manner that also supports wellbeing. Chronic care models that are currently in use usually focus upon the systems, resources and policies that are required to deliver care. The important roles of culture, spirituality, Country and family in maintaining health and wellbeing are notably absent from such models. Re-defining the way in which care is delivered to reflect Aboriginal and Torres Strait Islander peoples’ needs and values is essential for improving the accessibility and acceptability of primary healthcare services.The research reported in this paper is a project of the Australian Primary Health Care Research Institute which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research Evaluation and Development Strategy