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Background: The significance of malaria transmission occurring outdoors has risen even in areas where indoor interventions such as long-lasting insecticidal nets and indoor residual spraying are common. The actual contamination rates and effectiveness of recently developed outdoor mosquito control device, the mosquito landing box (MLB), on densities and daily survival of host-seeking laboratory Anopheles arabiensis, which readily bites humans outdoors was demonstrated., Methods: Experiments were conducted in large semi-field systems (SFS) with human volunteers inside, to mimic natural ecosystems, and using MLBs baited with natural or synthetic human odours and carbon dioxide. The MLBs were dusted with 10% pyriproxyfen (PPF) or entomopathogenic fungi (Metarhizium anisopliae) spores to mark mosquitoes physically contacting the devices. Each night, 400 laboratory-reared An. arabiensis females were released in one SFS chamber with two MLBs, and another chamber without MLBs (control). Mosquitoes were individually recaptured while attempting to bite volunteers inside SFS or by aspiration from SFS walls. Mosquitoes from chambers with PPF-treated MLBs and respective controls were individually dipped in water-filled cups containing ten conspecific third-instar larvae, whose subsequent development was monitored. Mosquitoes recaptured from chambers with fungi-treated MLBs were observed for fungal hyphal growth on their cadavers. Separately, effects on daily survival were determined by exposing An. arabiensis in chambers having MLBs treated with 5% pirimiphos methyl compared to chambers without MLBs (control), after which the mosquitoes were recaptured and monitored individually until they died., Results: Up to 63% (152/240) and 43% (92/210) of mosquitoes recaptured inside treatment chambers were contaminated with pyriproxyfen and M. anisopliae, respectively, compared to 8% (19/240) and 0% (0/164) in controls. The mean number of larvae emerging from cups in which adults from chambers with PPF-treated MLBs were dipped was significantly lower [0.75 (0.50-1.01)], than in controls [28.79 (28.32-29.26)], P < 0.001). Daily survival of mosquitoes exposed to 5% pirimiphos methyl was nearly two-fold lower than controls [hazard ratio (HR) = 1.748 (1.551-1.920), P < 0.001]., Conclusion: High contamination rates in exposed mosquitoes even in presence of humans, demonstrates potential of MLBs for controlling outdoor-biting malaria vectors, either by reducing their survival or directly killing host-seeking mosquitoes. The MLBs also have potential for dispensing filial infanticides, such as PPF, which mosquitoes can transmit to their aquatic habitats for mosquito population control.

Background: Large-cage experiments indicate pyriproxifen (PPF) can be transferred from resting sites to aquatic habitats by Anopheles arabiensis--malaria vector mosquitoes to inhibit emergence of their own offspring. PPF coverage is amplified twice: (1) partial coverage of resting sites with PPF contamination results in far higher contamination coverage of adult mosquitoes because they are mobile and use numerous resting sites per gonotrophic cycle, and (2) even greater contamination coverage of aquatic habitats results from accumulation of PPF from multiple oviposition events., Methods and Findings: Deterministic mathematical models are described that use only field-measurable input parameters and capture the biological processes that mediate PPF autodissemination. Recent successes in large cages can be rationalized, and the plausibility of success under full field conditions can be evaluated a priori. The model also defines measurable properties of PPF delivery prototypes that may be optimized under controlled experimental conditions to maximize chances of success in full field trials. The most obvious flaw in this model is the endogenous relationship that inevitably occurs between the larval habitat coverage and the measured rate of oviposition into those habitats if the target mosquito species is used to mediate PPF transfer. However, this inconsistency also illustrates the potential advantages of using a different, non-target mosquito species for contamination at selected resting sites that shares the same aquatic habitats as the primary target. For autodissemination interventions to eliminate malaria transmission or vector populations during the dry season window of opportunity will require comprehensive contamination of the most challenging subset of aquatic habitats [Formula: see text] that persist or retain PPF activity (Ux) for only one week [Formula: see text], where Ux = 7 days). To achieve >99% contamination coverage of these habitats will necessitate values for the product of the proportional coverage of the ovipositing mosquito population with PPF contamination (CM) by the ovitrap-detectable rates of oviposition by wild mosquitoes into this subset of habitats [Formula: see text], divided by the titre of contaminated mosquitoes required to render them unproductive [Formula: see text], that approximately approach unity [Formula: see text]., Conclusions: The simple multiplicative relationship between CM and [Formula: see text], and the simple exponential decay effect they have upon uncontaminated aquatic habitats, allows application of this model by theoreticians and field biologists alike.

Background: In order to sustain the gains achieved by current malaria control strategies, robust surveillance systems that monitor dynamics of vectors and their roles in malaria transmission over time are essential. This longitudinal study demonstrates the trends in malaria vector dynamics and their relative contribution to malaria transmission in hyperendemic transmission settings in Tanzania., Methods: The study was conducted in two villages within the Kilombero Valley, in rural Tanzania for five consecutive years (2008-2012). Seventy-two houses were selected per village and each house was sampled for mosquitoes monthly using a CDC light trap. Collected mosquitoes were assessed for species identity and sporozoite infection status using PCR and ELISA, respectively. Anopheles funestus and Anopheles arabiensis susceptibility to insecticides was assessed using WHO guidelines., Results: A total of 100,810 malaria vectors were collected, of which 76% were Anopheles gambiae s. l. and 24% were An. funestus. Of all An. funestus samples that amplified with PCR (n = 2,737), 97% were An. funestus s.s., 2% were Anopheles rivorulum and 1% Anopheles leesoni. Whereas for An. gambiae s.l. (n = 8,117), 93% were An. arabiensis and 7% were Anopheles gambiae s.s. The proportion of An. gambiae s.s. identified by PCR (2,924) declined from 0.2% in the year 2008 to undetectable levels in 2012. Malaria transmission intensity significantly decreased from an EIR of 78.14 infectious bites/person/year in 2008 to 35 ib/p/yr in 2011 but rebounded to 226 ib/p/yr in 2012 coinciding with an increased role of An. funestus in malaria transmission. Insecticide susceptibility tests indicated high levels of resistance in An. funestus against deltamethrin (87%), permethrin (65%), lambda cyhalothrin (74%), bendiocarb (65%), and DDT (66%). Similarly, An. arabiensis showed insecticide resistance to deltamethrin (64%), permethrin (77%) and lambda cyhalothrin (42%) in 2014., Conclusion: The results indicate the continuing role of An. arabiensis and the increasing importance of An. funestus in malaria transmission, and pyrethroid resistance development in both species. Complementary vector control and surveillance tools are needed that target the ecology, behaviour and insecticide resistance management of these vector species, in order to preserve the efficacy of LLINs.

One of the main challenges to malaria elimination is the resilience of vectors, such as Anopheles arabiensis, that evade lethal exposure to insecticidal control measures or express resistance to their active ingredients. This study investigated a novel technology for population control that sterilizes mosquitoes using pyriproxyfen, a juvenile hormone analogue. Females of An. arabiensis were released in a semifield system divided into four equal sections, and each section had a mud hut sheltering a tethered cow providing a blood source for mosquitoes. In all sections, the inner mud hut walls and roofs were lined with black cotton cloth. In one-half of the sections, the cloth was dusted with pyriproxyfen. An overwhelming 96% reduction in adult production was achieved in pyriproxyfen-treated sections compared with control sections. This unprecedented level of control can be exploited to design new vector control strategies that particularly target existing behaviorally resilient and insecticide-resistant populations.

Background: The suppression of indoor malaria transmission requires additional interventions that complement the use of insecticide treated nets (ITNs) and indoor residual spraying (IRS). Previous studies have examined the impact of house structure on malaria transmission in areas of low transmission. This study was conducted in a high transmission setting and presents further evidence about the association between specific house characteristics and the abundance of endophilic malaria vectors., Methods: Mosquitoes were sampled using CDC light traps from 72 randomly selected houses in two villages on a monthly basis from 2008 to 2011 in rural Southern Tanzania. Generalized linear models using Poisson distributions were used to analyze the association of house characteristics (eave gaps, wall types, roof types, number of windows, rooms and doors, window screens, house size), number of occupants and ITN usage with mean catches of malaria vectors (An.gambiae s.l. and An. funestus)., Results: A total of 36490 female An. gambiae s.l. were collected in Namwawala village and 21266 in Idete village. As for An. funestus females, 2268 were collected in Namwawala and 3398 in Idete. Individually, each house factor had a statistically significant impact (p < 0.05) on the mean catches for An. gambiae s.l. but not An. funestus. A multivariate analysis indicated that the combined absence or presence of eaves, treated or untreated bed-nets, the number of house occupants, house size, netting over windows, and roof type were significantly related (p < 0.05) to An.gambiae s.l. and An. funestus house entry in both villages., Conclusions: Despite significant reductions in vector density and malaria transmission caused by high coverage of ITNs, high numbers of host-seeking malaria vectors are still found indoors due to house designs that favour mosquito entry. In addition to ITNs and IRS, significant efforts should focus on improving house design to prevent mosquito entry and eliminate indoor malaria transmission.

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 Life 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.

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 communal-level 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, community-wide 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.

Background: Near infrared spectroscopy (NIRS) is currently complementing techniques to age-grade mosquitoes. NIRS classifies lab-reared and semi-field raised mosquitoes into < or ≥ 7 days old with an average accuracy of 80%, achieved by training a regression model using partial least squares (PLS) and interpreted as a binary classifier. Methods and findings: We explore whether using an artificial neural network (ANN) analysis instead of PLS regression improves the current accuracy of NIRS models for age-grading malaria transmitting mosquitoes. We also explore if directly training a binary classifier instead of training a regression model and interpreting it as a binary classifier improves the accuracy. A total of 786 and 870 NIR spectra collected from laboratory reared An. gambiae and An. arabiensis, respectively, were used and pre-processed according to previously published protocols. The ANN regression model scored root mean squared error (RMSE) of 1.6 ± 0.2 for An. gambiae and 2.8 ± 0.2 for An. arabiensis; whereas the PLS regression model scored RMSE of 3.7 ± 0.2 for An. gambiae, and 4.5 ± 0.1 for An. arabiensis. When we interpreted regression models as binary classifiers, the accuracy of the ANN regression model was 93.7 ± 1.0% for An. gambiae, and 90.2 ± 1.7% for An. arabiensis; while PLS regression model scored the accuracy of 83.9 ± 2.3% for An. gambiae, and 80.3 ± 2.1% for An. arabiensis. We also find that a directly trained binary classifier yields higher age estimation accuracy than a regression model interpreted as a binary classifier. A directly trained ANN binary classifier scored an accuracy of 99.4 ± 1.0 for An. gambiae and 99.0 ± 0.6% for An. arabiensis; while a directly trained PLS binary classifier scored 93.6 ± 1.2% for An. gambiae and 88.7 ± 1.1% for An. arabiensis. We further tested the reproducibility of these results on different independent mosquito datasets. ANNs scored higher estimation accuracies than when the same age models are trained using PLS. Regardless of the model architecture, directly trained binary classifiers scored higher accuracies on classifying age of mosquitoes than regression models translated as binary classifiers. Conclusion: We recommend training models to estimate age of An. arabiensis and An. gambiae using ANN model architectures (especially for datasets with at least 70 mosquitoes per age group) and direct training of binary classifier instead of training a regression model and interpreting it as a binary classifier. [ABSTRACT FROM AUTHOR]

Background: Near infrared spectroscopy (NIRS) is a high throughput technique that measures absorbance of specific wavelengths of light by biological samples and uses this information to classify the age of lab-reared mosquitoes as younger or older than seven days with an average accuracy greater than 80%. For NIRS to estimate ages of wild mosquitoes, a sample of wild mosquitoes with known age in days would be required to train and test the model. Mark-release-recapture is the most reliable method to produce wild-caught mosquitoes of known age in days. However, it is logistically demanding, time inefficient, subject to low recapture rates, and raises ethical issues due to the release of mosquitoes. Using labels from Detinova dissection results in a mathematical model with poor accuracy. Alternatively, a model trained on spectra from laboratory-reared mosquitoes where age in days is known can be applied to estimate the age of wild mosquitoes, but this would be appropriate only if spectra collected from laboratory-reared and wild mosquitoes are similar. Methods and findings: We performed k-means (k = 2) cluster analysis on a mixture of spectra collected from lab-reared and wild Anopheles arabiensis to determine if there is any significant difference between these two groups. While controlling the numbers of mosquitoes included in the model at each age, we found two clusters with no significant difference in distribution of spectra collected from lab-reared and wild mosquitoes (p = 0.25). We repeated the analysis using hierarchical clustering, and similarly, no significant difference was observed (p = 0.13). Conclusion: We find no difference between spectra collected from laboratory-reared and wild mosquitoes of the same age and species. The results strengthen and support the on-going practice of applying the model trained on spectra collected from laboratory-reared mosquitoes, especially first-generation laboratory-reared mosquitoes. [ABSTRACT FROM AUTHOR]

Background: Despite great achievements by insecticide-treated nets (ITNs) and indoor residual spraying (IRS) in reducing malaria transmission, it is unlikely these tools will be sufficient to eliminate malaria transmission on their own in many settings today. Fortunately, field experiments indicate that there are many promising vector control interventions that can be used to complement ITNs and/or IRS by targeting a wide range of biological and environmental mosquito resources. The majority of these experiments were performed to test a single vector control intervention in isolation; however, there is growing evidence and consensus that effective vector control with the goal of malaria elimination will require a combination of interventions. Method and findings: We have developed a model of mosquito population dynamic to describe the mosquito life and feeding cycles and to optimize the impact of vector control intervention combinations at suppressing mosquito populations. The model simulations were performed for the main three malaria vectors in sub-Saharan Africa, Anopheles gambiae s.s, An. arabiensis and An. funestus. We considered areas having low, moderate and high malaria transmission, corresponding to entomological inoculation rates of 10, 50 and 100 infective bites per person per year, respectively. In all settings, we considered baseline ITN coverage of 50% or 80% in addition to a range of other vector control tools to interrupt malaria transmission. The model was used to sweep through parameters space to select the best optimal intervention packages. Sample model simulations indicate that, starting with ITNs at a coverage of 50% (An. gambiae s.s. and An. funestus) or 80% (An. arabiensis) and adding interventions that do not require human participation (e.g. larviciding at 80% coverage, endectocide treated cattle at 50% coverage and attractive toxic sugar baits at 50% coverage) may be sufficient to suppress all the three species to an extent required to achieve local malaria elimination. Conclusion: The Vector Control Optimization Model (VCOM) is a computational tool to predict the impact of combined vector control interventions at the mosquito population level in a range of eco-epidemiological settings. The model predicts specific combinations of vector control tools to achieve local malaria elimination in a range of eco-epidemiological settings and can assist researchers and program decision-makers on the design of experimental or operational research to test vector control interventions. A corresponding graphical user interface is available for national malaria control programs and other end users. [ABSTRACT FROM AUTHOR]