Culex pipiens and Culex restuans larval interactions shape the bacterial communities in container aquatic habitats.

Container aquatic habitats host a community of aquatic insects, primarily mosquito larvae that browse on container surface microbial biofilm and filter-feed on microorganisms in the water column. We examined how the bacterial communities in these habitats respond to feeding by larvae of two container-dwelling mosquito species, Culex pipiens and Cx. restuans. We also investigated how the microbiota of these larvae is impacted by intra- and interspecific interactions. Microbial diversity and richness were significantly higher in water samples when mosquito larvae were present, and in Cx. restuans compared to Cx. pipiens larvae. Microbial communities of water samples clustered based on the presence or absence of mosquito larvae and were distinct from those of mosquito larvae. Culex pipiens and Cx. restuans larvae harbored distinct microbial communities when reared under intraspecific conditions and similar microbial communities when reared under interspecific conditions. These findings demonstrate that mosquito larvae play a major role in structuring the microbial communities in container habitats and that intra- and interspecific interactions in mosquito larvae may shape their microbiota. This has important ecological and public health implications since larvae of the two mosquito species are major occupants of container habitats while the adults are vectors of West Nile virus.

Specific phytochemicals in floral nectar up-regulate genes involved in longevity regulation and xenobiotic metabolism, extending mosquito life span.

During nectar feeding, mosquitoes ingest a plethora of phytochemicals present in nectar. The ecological and physiological impacts of these ingested phytochemicals on the disease vectors are poorly understood. In this study, we evaluated the effects of three nectar phytochemicals-- caffeine, p-coumaric acid, and quercetin--on longevity, fecundity, and sugar-feeding behavior of the Asian tiger mosquito (Aedes albopictus). Adult females of Ae. albopictus were provided continuous access to 10% sucrose supplemented with one of the three phytochemicals and their fecundity, longevity, and the amount of sucrose consumed determined. Transcriptome response of Ae. albopictus females to p-coumaric acid and quercetin was also evaluated. Dietary quercetin and p-coumaric acid enhanced the longevity of female Ae. albopictus, while caffeine resulted in reduced sugar consumption and enhanced fecundity of gravid females. RNA-seq analyses identified 237 genes that were differentially expressed (DE) in mosquitoes consuming p-coumaric acid or quercetin relative to mosquitoes consuming an unamended sucrose solution diet. Among the DE genes, several encoding antioxidant enzymes, cytochrome P450s, and heat shock proteins were upregulated, whereas histones were downregulated. Overall, our findings show that consuming certain nectar phytochemicals can enhance adult longevity of female Asian tiger mosquitoes, apparently by differentially regulating the expression level of genes involved in longevity and xenobiotic metabolism; this has potential impacts not only on life span but also on vectorial capacity and insecticide resistance.

Heartland Virus in Humans and Ticks, Illinois, USA, 2018-2019.

In 2018, Heartland disease virus infected 2 persons in Illinois, USA. In 2019, ticks were collected at potential tick bite exposure locations and tested for Heartland and Bourbon viruses. A Heartland virus-positive pool of adult male Amblyomma americanum ticks was found at 2 locations, 439 km apart, suggesting widespread distribution in Illinois.

Alteration of plant species assemblages can decrease the transmission potential of malaria mosquitoes.

Knowledge of the link between a vector population's pathogen-transmission potential and its biotic environment can generate more realistic forecasts of disease risk due to environmental change. It also can promote more effective vector control by both conventional and novel means.This study assessed the effect of particular plant species assemblages differing in nectar production on components of the vectorial capacity of the mosquito Anopheles gambiae s.s., an important vector of African malaria.We followed cohorts of mosquitoes for three weeks in greenhouse mesocosms holding nectar-poor and nectar-rich plant species by tracking daily mortalities and estimating daily biting rates and fecundities. At death, a mosquito's insemination status and wing length were determined. These life history traits allowed incorporation of larval dynamics into a vectorial capacity estimate. This new study provided both novel assemblages of putative host plants and a human blood host within a nocturnal period of maximum biting.Survivorship was significantly greater in nectar-rich environments than nectar-poor ones, resulting in greater total fecundity. Daily biting rate and fecundity per female between treatments was not detected. These results translated to greater estimated vectorial capacities in the nectar-rich environment in all four replicates of the experiment (means: 1,089.5 ± 125.2 vs. 518.3 ± 60.6). When mosquito density was made a function of survival and fecundity, rather than held constant, the difference between plant treatments was more pronounced, but so was the variance, so differences were not statistically significant. In the nectar-poor environment, females' survival suffered severely when a blood host was not provided. A sugar-accessibility experiment confirmed that Parthenium hysterophorus is a nectar-poor plant for these mosquitoes.Synthesis and applications. This study, assessing the effect of particular plant species assemblages on the vectorial capacity of malaria mosquitoes, highlights the likelihood that changes in plant communities (e.g. due to introduction of exotic or nectar-rich species) can increase malaria transmission and that a reduction of favourable nectar sources can reduce it. Also, plant communities' data can be used to identify potential high risk areas. Further studies are warranted to explore how and when management of plant species assemblages should be considered as an option in an integrated vector management strategy.

Would the control of invasive alien plants reduce malaria transmission? A review.

Vector control has been the most effective preventive measure against malaria and other vector-borne diseases. However, due to concerns such as insecticide resistance and budget shortfalls, an integrated control approach will be required to ensure sustainable, long-term effectiveness. An integrated management strategy should entail some aspects of environmental management, relying on coordination between various scientific disciplines. Here, we review one such environmental control tactic: invasive alien plant management. This covers salient plant-mosquito interactions for both terrestrial and aquatic invasive plants and how these affect a vector's ability to transmit malaria. Invasive plants tend to have longer flowering durations, more vigorous growth, and their spread can result in an increase in biomass, particularly in areas where previously little vegetation existed. Some invasive alien plants provide shelter or resting sites for adult mosquitoes and are also attractive nectar-producing hosts, enhancing their vectorial capacity. We conclude that these plants may increase malaria transmission rates in certain environments, though many questions still need to be answered, to determine how often this conclusion holds. However, in the case of aquatic invasive plants, available evidence suggests that the management of these plants would contribute to malaria control. We also examine and review the opportunities for large-scale invasive alien plant management, including options for biological control. Finally, we highlight the research priorities that must be addressed in order to ensure that integrated vector and invasive alien plant management operate in a synergistic fashion.

How much will it cost to eradicate lymphatic filariasis? An analysis of the financial and economic costs of intensified efforts against lymphatic filariasis.

INTRODUCTION: Lymphatic filariasis (LF), a neglected tropical disease (NTD) preventable through mass drug administration (MDA), is one of six diseases deemed possibly eradicable. Previously we developed one LF elimination scenario, which assumes MDA scale-up to continue in all countries that have previously undertaken MDA. In contrast, our three previously developed eradication scenarios assume all LF endemic countries will undertake MDA at an average (eradication I), fast (eradication II), or instantaneous (eradication III) rate of scale-up. In this analysis we use a micro-costing model to project the financial and economic costs of each of these scenarios in order to provide evidence to decision makers about the investment required to eliminate and eradicate LF. METHODOLOGY/KEY FINDINGS: Costing was undertaken from a health system perspective, with all results expressed in 2012 US dollars (USD). A discount rate of 3% was applied to calculate the net present value of future costs. Prospective NTD budgets from LF endemic countries were reviewed to preliminarily determine activities and resources necessary to undertake a program to eliminate LF at a country level. In consultation with LF program experts, activities and resources were further reviewed and a refined list of activities and necessary resources, along with their associated quantities and costs, were determined and grouped into the following activities: advocacy and communication, capacity strengthening, coordination and strengthening partnerships, data management, ongoing surveillance, monitoring and supervision, drug delivery, and administration. The costs of mapping and undertaking transmission assessment surveys and the value of donated drugs and volunteer time were also accounted for. Using previously developed scenarios and deterministic estimates of MDA duration, the financial and economic costs of interrupting LF transmission under varying rates of MDA scale-up were then modelled using a micro-costing approach. The elimination scenario, which includes countries that previously undertook MDA, is estimated to cost 929 million USD (95% Credible Interval: 884m-972m). Proceeding to eradication is anticipated to require a higher financial investment, estimated at 1.24 billion USD (1.17bn-1.30bn) in the eradication III scenario (immediate scale-up), with eradication II (intensified scale-up) projected at 1.27 billion USD (1.21bn-1.33bn), and eradication I (slow scale-up) estimated at 1.29 billion USD (1.23bn-1.34bn). The economic costs of the eradication III scenario are estimated at approximately 7.57 billion USD (7.12bn-7.94bn), while the elimination scenario is projected to have an economic cost of 5.21 billion USD (4.91bn-5.45bn). Countries in the AFRO region will require the greatest investment to reach elimination or eradication, but also stand to gain the most in cost savings. Across all scenarios, capacity strengthening and advocacy and communication represent the greatest financial costs, whereas mapping, post-MDA surveillance, and administration comprise the least. CONCLUSIONS/SIGNIFICANCE: Though challenging to implement, our results indicate that financial and economic savings are greatest under the eradication III scenario. Thus, if eradication for LF is the objective, accelerated scale-up is projected to be the best investment.

Seeing beyond 2020: an economic evaluation of contemporary and emerging strategies for elimination of Trypanosoma brucei gambiense.

BACKGROUND: Trypanosoma brucei (T b) gambiense is targeted to reach elimination as a public health problem by 2020 and full elimination by 2030. To achieve these goals, stakeholders need to consider strategies to accelerate elimination. Hence, we aimed to model several options related to current and emerging methods for case detection, treatment, and vector control across settings to assess cost-effectiveness and the probability of elimination. METHODS: Five intervention strategies were modelled over 30 years for low, moderate, and high transmission settings. Model parameters related to costs, efficacy, and transmission were based on available evidence and parameter estimation. Outcomes included disability-adjusted life-years (DALYs), costs, and long-term prevalence. Sensitivity analyses were done to calculate the uncertainty of the results. FINDINGS: To reach elimination targets for 2020 across all settings, approaches combining case detection, treatment, and vector control would be most effective. Elimination in high and moderate transmission areas was probable and cost-effective when strategies included vector control and novel methods, with incremental cost-effectiveness ratios (ICERs) ranging from US$400 to $1500 per DALY averted. In low transmission areas, approaches including the newest interventions alone or in combination with tiny targets (vector control) were cost-effective, with ICERs of $200 or $1800 per DALY averted, respectively, but only strategies including vector control were likely to lead to elimination. Results of sensitivity analyses showed that allowing for biennial surveillance, reducing vector control maintenance costs, or variations of active surveillance coverage could also be cost-effective options for elimination, depending on the setting. INTERPRETATION: Although various strategies might lead to elimination of T b gambiense, cost-effective approaches will include adoption of emerging technologies and, in some settings, increased surveillance or implementation of vector control. FUNDING: Bill & Melinda Gates Foundation.

Modelling the health impact and cost-effectiveness of lymphatic filariasis eradication under varying levels of mass drug administration scale-up and geographic coverage.

BACKGROUND: A global programme to eliminate lymphatic filariasis (GPELF) is underway, yet two key programmatic features are currently still lacking: (1) the extension of efforts to all lymphatic filariasis (LF) endemic countries, and (2) the expansion of geographic coverage of mass drug administration (MDA) within countries. For varying levels of scale-up of MDA, we assessed the health benefits and the incremental cost-effectiveness ratios (ICERs) associated with LF eradication, projected the potential savings due to decreased morbidity management needs, and estimated potential household productivity gains as a result of reduced LF-related morbidity. METHODS: We extended an LF transmission model to track hydrocele and lymphoedema incidence in order to obtain estimates of the disability adjusted life years (DALYs) averted due to scaling up MDA over a period of 50 years. We then estimated the ICERs and the cost-effectiveness acceptability curves associated with different rates of MDA scale-up. Health systems savings were estimated by considering the averted morbidity, treatment-seeking behaviour and morbidity management costs. Gains in worker productivity were estimated by multiplying estimated working days lost as a result of morbidity with country-specific per-worker agricultural wages. RESULTS: Our projections indicate that a massive scaling-up of MDA could lead to 4.38 million incremental DALYs averted over a 50-year time horizon compared to a scenario which mirrors current efforts against LF. In comparison to maintaining the current rate of progress against LF, massive scaling-up of MDA-pursuing LF eradication as soon as possible-was most likely to be cost-effective above a willingness to pay threshold of US$71.5/DALY averted. Intensified MDA scale-up was also associated with lower ICERs. Furthermore, this could result in health systems savings up to US$483 million. Extending coverage to all endemic areas could generate additional economic benefits through gains in worker productivity between US$3.4 and US$14.4 billion. CONCLUSIONS: In addition to ethical and political motivations for scaling-up MDA rapidly, this analysis provides economic support for increasing the intensity of MDA programmes.

What Is Needed to Eradicate Lymphatic Filariasis? A Model-Based Assessment on the Impact of Scaling Up Mass Drug Administration Programs.

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease for which more than a billion people in 73 countries are thought to be at-risk. At a global level, the efforts against LF are designed as an elimination program. However, current efforts appear to aim for elimination in some but not all endemic areas. With the 2020 goal of elimination looming, we set out to develop plausible scale-up scenarios to reach global elimination and eradication. We predict the duration of mass drug administration (MDA) necessary to reach local elimination for a variety of transmission archetypes using an existing model of LF transmission, estimate the number of treatments required for each scenario, and consider implications of rapid scale-up. METHODOLOGY: We have defined four scenarios that differ in their geographic coverage and rate of scale-up. For each scenario, country-specific simulations and calculations were performed that took into account the pre-intervention transmission intensity, the different vector genera, drug regimen, achieved level of population coverage, previous progress toward elimination, and potential programmatic delays due to mapping, operations, and administration. PRINCIPAL FINDINGS: Our results indicate that eliminating LF by 2020 is unlikely. If MDA programs are drastically scaled up and expanded, the final round of MDA for LF eradication could be delivered in 2028 after 4,159 million treatments. However, if the current rate of scale-up is maintained, the final round of MDA to eradicate LF may not occur until 2050. CONCLUSIONS/SIGNIFICANCE: Rapid scale-up of MDA will decrease the amount of time and treatments required to reach LF eradication. It may also propel the program towards success, as the risk of failure is likely to increase with extended program duration.

Contemporary and emerging strategies for eliminating human African trypanosomiasis due to Trypanosoma brucei gambiense: review.

OBJECTIVES: To review current and emerging tools for Gambiense HAT control and elimination, and propose strategies that integrate these tools with epidemiological evidence. METHODS: We reviewed the scientific literature to identify contemporary and emerging tools and strategies for controlling and eliminating Gambiense HAT. Through an iterative process involving key stakeholders, we then developed comprehensive scenarios leading to elimination, considering both established and new tools for diagnosis, case treatment and vector control. RESULTS: Core components of all scenarios include detecting and treating cases with established or emerging techniques. Relatively more intensive scenarios incorporate vector control. New tools considered include tiny targets for tsetse fly control, use of rapid diagnostic tests and oral treatment with fexinidazole or oxaboroles. Scenarios consider the time when critical new tools are expected to become ready for deployment by national control programmes. Based on a review of the latest epidemiological data, we estimate the various interventions to cover 1,380,600 km(2) and 56,986,000 people. CONCLUSIONS: A number of new tools will fill critical gaps in the current armamentarium for diagnosing and treating Gambiense HAT. Deploying these tools in endemic areas will facilitate the comprehensive and sustainable control of the disease considerably and contribute to the ultimate goal of elimination.

How effective is integrated vector management against malaria and lymphatic filariasis where the diseases are transmitted by the same vector?

BACKGROUND: The opportunity to integrate vector management across multiple vector-borne diseases is particularly plausible for malaria and lymphatic filariasis (LF) control where both diseases are transmitted by the same vector. To date most examples of integrated control targeting these diseases have been unanticipated consequences of malaria vector control, rather than planned strategies that aim to maximize the efficacy and take the complex ecological and biological interactions between the two diseases into account. METHODOLOGY/PRINCIPAL FINDINGS: We developed a general model of malaria and LF transmission and derived expressions for the basic reproductive number (R0) for each disease. Transmission of both diseases was most sensitive to vector mortality and biting rate. Simulating different levels of coverage of long lasting-insecticidal nets (LLINs) and larval control confirms the effectiveness of these interventions for the control of both diseases. When LF was maintained near the critical density of mosquitoes, minor levels of vector control (8% coverage of LLINs or treatment of 20% of larval sites) were sufficient to eliminate the disease. Malaria had a far greater R0 and required a 90% population coverage of LLINs in order to eliminate it. When the mosquito density was doubled, 36% and 58% coverage of LLINs and larval control, respectively, were required for LF elimination; and malaria elimination was possible with a combined coverage of 78% of LLINs and larval control. CONCLUSIONS/SIGNIFICANCE: Despite the low level of vector control required to eliminate LF, simulations suggest that prevalence of LF will decrease at a slower rate than malaria, even at high levels of coverage. If representative of field situations, integrated management should take into account not only how malaria control can facilitate filariasis elimination, but strike a balance between the high levels of coverage of (multiple) interventions required for malaria with the long duration predicted to be required for filariasis elimination.

Transient population dynamics of mosquitoes during sterile male releases: modelling mating behaviour and perturbations of life history parameters.

The release of genetically-modified or sterile male mosquitoes offers a promising form of mosquito-transmitted pathogen control, but the insights derived from our understanding of male mosquito behaviour have not fully been incorporated into the design of such genetic control or sterile-male release methods. The importance of aspects of male life history and mating behaviour for sterile-male release programmes were investigated by projecting a stage-structured matrix model over time. An elasticity analysis of transient dynamics during sterile-male releases was performed to provide insight on which vector control methods are likely to be most synergistic. The results suggest that high mating competitiveness and mortality costs of released males are required before the sterile-release method becomes ineffective. Additionally, if released males suffer a mortality cost, older males should be released due to their increased mating capacity. If released males are of a homogenous size and size-assortative mating occurs in nature, this can lead to an increase in the abundance of large females and reduce the efficacy of the population-suppression effort. At a high level of size-assortative mating, the disease transmission potential of the vector population increases due to male releases, arguing for the release of a heterogeneously-sized male population. The female population was most sensitive to perturbations of density-dependent components of larval mortality and female survivorship and fecundity. These findings suggest source reduction might be a particularly effective complement to mosquito control based on the sterile insect technique (SIT). In order for SIT to realize its potential as a key component of an integrated vector-management strategy to control mosquito-transmitted pathogens, programme design of sterile-male release programmes must account for the ecology, behaviour and life history of mosquitoes. The model used here takes a step in this direction and can easily be modified to investigate additional aspects of mosquito behaviour or species-specific ecology.

Effects of plant-community composition on the vectorial capacity and fitness of the malaria mosquito Anopheles gambiae.

Dynamics of Anopheles gambiae abundance and malaria transmission potential rely strongly on environmental conditions. Female and male An. gambiae use sugar and are affected by its absence, but how the presence or absence of nectariferous plants affects An. gambiae abundance and vectorial capacity has not been studied. We report on four replicates of a cohort study performed in mesocosms with sugar-poor and sugar-rich plants, in which we measured mosquito survival, biting rates, and fecundity. Survivorship was greater with access to sugar-rich plant species, and mortality patterns were age-dependent. Sugar-poor populations experienced Weibull mortality patterns, and of four populations in the sugar-rich environment, two female and three male subpopulations were better fitted by Gompertz functions. A tendency toward higher biting rates in sugar-poor mesocosms, particularly for young females, was found. Therefore, vectorial capacity was pulled in opposing directions by nectar availability, resulting in highly variable vectorial capacity values.

An effective indoor mesocosm for studying populations of Anopheles gambiae in temperate climates.

To study the indoor behavior of Anopheles gambiae populations in a temperate climate, we have devised a walk-in mesocosm, built within a greenhouse. The structure provides conditions more natural than laboratory cages, including sufficient room for swarming and for flight between resting sites, sugar-bearing plants, a human host, and an oviposition site. These activities impose energy demands closer to those encountered in the field. The structure also has predators, fluctuating temperatures, natural daylight, and an evening crepuscular period. Most important, its resting sites comprise a bank of tubes that can be inspected or removed individually to obtain, at regular time intervals, random representative samples of an experimental population while all individuals are inactive. Samples from aging cohorts of mosquitoes, released at emergence, can yield information on behavioral sequences, mate competition, reproductive success, and survival under different nutritional regimes.