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This approach helped to eliminate Ae. However, these activities required enormous human resources and costs to support, making them unsustainable in the long term. Today, the scale of continuing urban expansion abnegates such an approach. Current mosquito control techniques based on larval habitat source reduction, larviciding, and space spray are costly, laborious, and of debatable efficacy depending on the circumstances [ 10 , 11 ]; therefore, there remains an urgent need for the development of intervention methods that could be reasonably implemented in the context of modern day urban environments and with some measure of possible sustainability.

One of the major challenges in large, condensed urban settings is achieving sufficient coverage of aquatic habitats preferred by Ae. Identifying and treating all possible breeding sites manually is not a realistic solution even with considerable organised community support and resources.

One potential solution, originally proposed by Itoh et al. Furthermore, given the relatively indiscriminate dissemination of the insecticide, it must also be non-toxic to vertebrates and have a relatively narrow range of action against other aquatic invertebrates. Pyriproxyfen PPF ticks all the boxes [ 16 ]. This World Health Organization WHO approved pupacide can be safely used in drinking water and is recommended as part of conventional programmes against Ae.

It is a synthetic analogue of juvenile hormone which, at very low concentrations, prevents larval and pupal development as well as female fertility and male spermiogenesis [ 19 , 20 ]. Currently it is applied as either granular or liquid formulations directly to water containers and drains in South America and South East Asia with documented success in reducing immature and adult mosquito numbers and has been associated with a reduction in dengue incidence [ 21 , 22 ].

The potential of PPF application via AD has been demonstrated in a variety of small-scale trials in Peru and Italy [ 12 , 15 ] and on a larger scale in the Amazon [ 23 ]. However, whilst entomological efficacy of PPF has been demonstrated when applied through AD, ground space spray, or container treatment, evidence of actual epidemiological impact infection reduction is generally inconclusive [ 24 , 25 ]. The lethal and pre-lethal e.

The fungal infection also interferes with DENV replication within the mosquito, thus having a profound effect on mosquito vectorial capacity i. Previous studies have estimated that, to account for the unpredictable spatio-temporal heterogeneity in dengue transmission, PCRTs are the most effective study design and that a larger number of clusters with fewer children per cluster provide the optimal strategy—in effect, a bet-hedging approach for a statistically sufficient coverage of an area [ 31 ].

As the population density in clusters will vary, it is possible that there will not be sufficient children within a prescribed area. In this case, we will increase the circle radius to reach the required sample number. Intervention and sampling strategy. The yellow region includes recruited children for the sero-conversion study and the outer peripheral region is the buffer zone also treated with AD devices blue jar icons but without sero-conversion saliva sampling.

GATs are more efficient in capturing gravid Ae. Clusters will be stratified according to historical dengue incidence and population density. In the Philippines, a barangay is the smallest administrative division in the Philippines urban or rural , but which can be subdivided into puroks zones consisting of 20 to 50 households depending on the location and density of the households in an area.

This will generate maps with which to choose clusters for the intervention study and assign clusters to either treatment or control groups according to broad similarities. The sample size is calculated using the following standard formula when considering proportions incidence rate :. The final sample size will depend on the dengue transmission rate in the study areas as estimated from the historical mean rate.

Recent sero-conversion studies in Cebu City, Philippines, have observed a symptomatic incidence rate of 1. Reported incidence rates in our study area under administrative Region IV-A are consistently amongst the highest in the country. Thus, the total number of children to be recruited is , distributed over 46 clusters of children each.

The principle evaluation criterion is the epidemiological efficacy read out: dengue infection sero-conversion. These time points are designated Pre-, Post1, and Post2 within each year. The secondary evaluation criterion is the entomological read out. Aedes spp. Traps will be placed both inside and outside 10 randomly selected houses within each site.

Traps placed outside will be positioned against the wall of the house in an area with shelter from direct sunlight. Traps placed inside the house will be positioned in a suitably unobstructed area but where there is air movement. In each barangay pre-selected to participate in the study, Research Institute for Tropical Medicine RITM team members will hold general information meetings on the project with the population in the presence of the community barangay health workers BHWs and local public health officials.

Because the volunteers to be recruited are of school age, additional information meetings will be held in the local schools. Once clusters are identified and randomly assigned with appropriate stratification, the study team will perform household visits with the Lipa City public health staff and respective area BHWs. Following signed consent, a short questionnaire pertaining to the participant will be completed and the individual assigned a unique identifier barcode.

During field investigations, a file with a name and address and corresponding barcode assigned to the subject identity will be used. This file will only be accessible to the field investigations team members who have direct contact with the participants.

To ensure confidentiality, the file will be kept in an access-limited and secured locked cabinet. Upon completion of the field work, the address of the individual will be removed from the database, with irreversible anonymisation. Fieldwork will involve initial paper files that will then be input into an electronic file which will be accessible only to the field investigation team. Study compliance will strictly adhere to the Republic Act No.

Participants can request their personal information to be removed and destroyed at any time during the study, which will also result in the withdrawal of the participant from the study. Throughout the study period, local health authorities will continue with their routine government approved dengue control strategies. Our intervention study will in no way replace the current mosquito control methods in use. HH Household. For the intervention study, 46 clusters will be selected each covering an area with at least children.

Before geolocalisation of historical dengue cases, however, we cannot predict which sites will be selected, nor their actual human densities, and thus the initial calculations are based on mean densities. One pesticide-treated netting removed from the active ingredient sachet will then be placed on the floater and the remaining contents of the sachet tipped into the water.

The tablets are added to the trap tap water to emit organic odours attractive for egg-laying mosquitoes. GATs will be placed inside and outside houses at designated locations. A sticky strip is placed inside the GAT and used to capture entering mosquitoes Additional file 3. Likewise, the dried grass and water in the GATs will be replaced during the weekly survey.

At the end of the 4-month treatment period, all mosquito traps will be removed, properly cleaned, and stored until the following year. A saliva sample will be taken by spitting into a sterile urine collection container, kept on ice, and transported to RITM for further processing. Although IgM titres will rise during a secondary DENV infection, a significant increase in IgM titres only systematically occurs in primary dengue infections and is relatively short lived; therefore, changes in IgG titres will be measured [ 38 ].

Exposure to dengue virus will produce an increase in IgG titre compared with the baseline titre in an individual, irrespective of whether they have been vaccinated or not or having been previously exposed to any DENV serotype See Statistical analyses below. The technicians performing the ELISAs will have no prior knowledge whether the samples come from a treatment or control site. Upon study completion, analyses, and publication, all saliva samples will be destroyed and coding files erased.

For each participating child, information on their name, age, sex, address, barangay , cluster number, dengue vaccination status, school, class, and subsequent dengue ELISA titres will be recorded using a paper case report form that will be subsequently input into a study electronic database.

Unique bar codes will be used as identifiers. Statistical analysis will be performed in RITM. Study volunteers and their parents will be informed on their specific sero-conversion ELISA findings during an annual feedback meeting. Whilst not providing a definitive diagnostic for infection, at a minimum this will inform individuals whether they are sero-positive for dengue and whether they have had a primary or post-primary infection. Because there is an increased risk of severe disease in post-primary infections, this information could enable individuals to enhance their efforts for personal protection from mosquito bites.

Emerging innovative information technologies, such as data management system software packages, can assist disease control programmes to better manage and analyse data, and thus make it easier to carry out routine surveillance, monitor interventions, and evaluate control programme performance. This will lead to better informed decision making and actions on the part of health authorities.

Population density at the barangay level will be acquired. Only spots with no geographical overlap will be accepted. Areas that are neither hotspots nor coldspots will be classified as intermediate. Hot and cold spots will contain a variable number of purok s and it is possible, and indeed likely, that hot and cold spots vary year to year. Therefore, purok s will be classified by annual similarity, in other words year 1 in hotspot, year 2 not, year 3 coldspot, and so on. In this way purok s can be classified into a risk designation and matched for treatment and control site selection.

Sero-conversion of individuals to DENV will be analysed yearly using three saliva samples taken from each individual during each year six total samples per volunteer. This double analysis will enable assessment of change in IgG OD beyond that using the classical threshold of an arbitrary four-fold increase. All analyses will be performed using Genstat version 15 [ 41 ]. We will test for over-dispersion in the response variable and, if it exists, an over-dispersion parameter will be estimated and applied.

Otherwise, a Poisson distribution will be assumed. Two models will be constructed, one for each Aedes dengue vector species. Because the extent to which an area is built up can impede mosquito flight i. In the context of the Ecomore 2 project www. All modifications must be clearly stated and formally accepted by the Consortium members Project coordinator and partners in each participating country.

Results will be communicated to trial participants through general dissemination meetings and language-adapted leaflets in Tagalog the national language of the Philippines. Scientific publishing will be in open access, peer-reviewed journals and involve all scientific collaborators, the authors of this manuscript, and others as appropriate.

It is commonly accepted that an integrated approach to vector control is required to be effective in reducing transmission risk. Currently, the majority of countries adhere, at least as published policy, to WHO recommendations on mosquito control including source reduction environmental hygiene and community-based clean-up campaigns , larvicidal treatment of water storage containers, and peridomestic space spraying of insecticides around homes of recent dengue cases [ 44 ].

However, there is currently no definitive evidence that these measures have any demonstrable effect on reducing dengue transmission [ 11 , 24 , 25 ]. This efficacy trial of the first commercial product using the AD approach will be highly informative as to the general utility of AD in reducing not only vector mosquito densities but, more importantly, actually reducing the risk of dengue infection. The AD technique may complement typical source reduction practices and larviciding campaigns by more efficiently targeting the most productive containers upon which the female mosquito fixes and contaminates the larval habitat, and importantly those sites beyond access for human manual treatment.

AD is potentially a more effective intervention than adult mosquito lethal traps because its impact is amplified between the dissemination devices and the larval habitats, in other words a small number of devices can contaminate a much wider number of habitats [ 12 , 16 ]. Despite some evidence that PPF disseminated by AD can be effective [ 12 , 15 , 23 ], there remain several obstacles to be overcome.

Firstly, the AD devices need to attract sufficient mosquitoes and thus depend not only on the local abundance of mosquitoes but also on the attractiveness of the AD device in the face of other competitive sites. Secondly, studies in urban areas have shown that topography is important for the movement of mosquitoes e. This implies that AD devices may have to be deployed at very high and operationally impracticable densities. This high trap density is unlikely to be feasible or even welcome by a community.

Thus, there is need for the development of more operationally useful and practical strategies for incorporation of AD approaches into larger, integrated mosquito control programmes. Finally, as with all insecticides, the risk of resistance developing against PPF is a real possibility; therefore, resistance management strategies are required to mitigate this threat.

The evolution of resistance to PPF has been well documented for agricultural pests, most notably for the cotton whitefly Bemisia tabaci where PPF resistance became so high in some areas of Israel that it was discontinued [ 46 ]. Learning from this unfortunate outcome, an insecticide resistance management IRM programme was implemented in the US with recommendations for early season, single application, threshold-based treatments of PPF, coupled with a later season application of broad-spectrum insecticides [ 47 ].

Metabolic resistance in both housefly and whitefly to PPF was attributed to mutations in enzyme activities of cytochrome P mono-oxygenases and glutathione S-transferases [ 48 , 49 ], but resulting in a fitness cost that may have helped retard the development of resistance under field conditions when IRM is applied [ 46 , 49 ].

Using an alternating application of several insecticides with different physiological modes of action has long been a strategy to combat resistance of insects to chemical control agents. The addition of the slower-acting entomopathogenic fungus against adult mosquitoes may contribute to a reduction in the rate of selection pressure for resistance against PPF, in addition to its lethal and pre-lethal effects on the mosquito.

The fungus has been shown to counter the effect of insecticide resistance in anopheline mosquitoes [ 50 , 51 ]. The extent to which resistance can develop against entomopathogenic fungi remains uncertain; whilst it can be selected for, the associated fitness cost to the insect suggests that it is less likely to arise in field settings [ 52 , 53 , 54 ]. The temporal requirement of evolution-proof insecticides is to allow mosquitoes time to develop and oviposit viable eggs but prevent them from transmitting pathogens.

This balance is, however, fine and predicated on the circumstances. In conclusion, a resistance management programme should be envisaged if AD mosquito traps prove effective. Whilst the epidemiological efficacy of the new tool is fundamental, community involvement and optimising strategies for the public health sector can greatly enhance the utility and success of an intervention. In addition to combining different mosquito control tools, the WHO IVM strategy emphasises the necessity to consider the societal impact, public opinion, and awareness in the viability and acceptability of any intervention strategy [ 56 ].

The IVM approach also emphasises the importance of strengthening the public and private sectors involved in decision-making and implementation of mosquito control strategies. Carrying out the trial in close collaboration with the local public health sector and included communities is an important step in enabling local support and continuity for vector control. Surveillance is also an essential component of dengue control because it provides spatial-temporal information on the number and distribution of disease cases and the relative intensity of transmission.

Reliable and timely surveillance data allow programmes to target interventions appropriately and to respond to outbreaks quickly. However, integrated epidemiological, entomological, and intervention data are often unavailable and are time-consuming to collate and analyse. This poses a significant challenge to dengue control because the most effective control programmes will likely utilise several complementary interventions.

The public health sector is a domain under continuous change and development, and novel methods for improving capacity are increasingly available. Emerging information technologies are improving our capacity to predict, prevent, and control vector-borne and other infectious diseases [ 57 ]. Data-rich epidemiological studies and robust surveillance programmes will benefit enormously from such technological advances that will enable rapid collection and analysis of standardised disease and vector data.

Continuous surveillance, monitoring, and evaluation using real-time data enables vector-borne disease control programmes to rapidly identify disease occurrence, monitor specific intervention effectiveness, and plan appropriate interventions. In conclusion, there is a suite of technological tools for the development of more up-to-date approaches to vector mosquito control to reduce viral pathogens transmitted by Aedes aegypti and similar species.

However, new tools require validation under field conditions before optimisation for wide-scale and routine application. Well-executed evaluations for assisting local public health sectors to achieve technologically advanced management of their mosquito control strategies are a sine qua non for reducing the burden of mosquito-borne disease. The major concern of the study will be the dependency on there being sufficient dengue activity during at least one of the study years and that the cluster design is sufficient to account for the recognised spatio-temporal heterogeneity in dengue [ 58 , 59 ].

To maximise power and somewhat alleviate this concern, sero-conversion rather than dengue case incidence will be used as the measure of epidemiological outcome, capturing the sub-clinical infections that form the majority of dengue infections [ 60 , 61 ]. Considerable effort will be given to continuous dialogue with the community to maintain adherence throughout the study.

Global Strategy for dengue prevention and control, — Geneva: World Health Organization; Google Scholar. The global distribution and burden of dengue. Epidemic arboviral diseases: priorities for research and public health. Lancet Infect Dis. Article Google Scholar. Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial.

Immunogenicity, safety, and tolerability of a recombinant measles-virus-based chikungunya vaccine: a randomised, double-blind, placebo-controlled, active-comparator, first-in-man trial. Vaccine protection against Zika virus from Brazil.

Impact of combined vector-control and vaccination strategies on transmission dynamics of dengue fever: a model-based analysis. Health Care Manag Sci. Mosquito control might not bolster imperfect dengue vaccines. Soper FL. Aedes aegypti and Yellow Fever. Bull WHO. Effectiveness of peridomestic space spraying with insecticide on dengue transmission; systematic review. Tropical Med Int Health. Assessing dengue transmission risk and a vector control intervention using entomological and immunological indices in Thailand: study protocol for a cluster-randomized controlled trial.

Using adult mosquitoes to transfer insecticides to Aedes aegypti larval habitats. Utilization of bloodfed females of Aedes aegypti as a vehicle for the transfer of the insect growth regulator pyriproxyfen to larval habitats. J Am Mosq Control Assoc. Reiter P. Oviposition, dispersal, and survival in Aedes aegypti : implications for the efficacy of control strategies. Vector Borne Zoonotic Dis. Devine G. Auto-dissemination of pyriproxyfen for the control of container-inhabiting mosquitoes—a progress review.

Outlooks Pest Manag. World Health Organization. Pesticides and their application—for the control of vectors and pest of public health importance. Guidelines for drinking-water quality. Pyriproxyfen as a mosquito larvicide.

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Consumers will continue to demand three key things in healthcare—access, price and outcomes. As part of access, consumers expect patient experience in healthcare that is on par with tech, retail and financial industries. Patients expect a seamless digital experience as they navigate scheduling, medication orders and follow-up communication.

To create this experience, we need data seamlessly integrated between electronic medical records and technology platforms to support the patient journey. At the same time, the question remains—how do we combine customer experience lessons from tech leaders with effective healthcare delivery? The pandemic and the response in the United States exposed fault lines within the healthcare industry when it comes to underserved populations.

Digital health companies are starting to address previously unmet needs for underserved populations as social consciousness shifts. Examples of unique companies in the social determinants of health space include socially determined mapping social determinants of health needs, cost and utilization at a granular level , eMocha inhaler and medication monitoring for pediatric asthma patients in Baltimore and LiveChair leveraging the barbershop setting to engage Black men around their healthcare, particularly chronic conditions like hypertension and diabetes.

Looking ahead, it will be interesting to see how future solutions add risk-sharing models to align outcomes, especially related to Medicare and Medicaid populations. Telehealth: We should expect to see add-ons to telemedicine platforms like pairing with clinical decision support for providers, use of AI such as chatbots and triage tools , and platform pairing with remote patient monitoring devices.

Private payers have also begun to reimburse for remote patient monitoring for chronic disease such as congestive heart failure, COPD and diabetes. At Sinai Hospital in Baltimore, for instance, employees are using GetWell Loop, a patient engagement and communication platform, to monitor vaccination symptoms and COVID symptoms prior to arriving on campus.

Beyond the digital front door, we can also expect more forward-facing solutions, like health concierge services and more patient-friendly provider directories. It will be interesting to see how best practices from other industries make their way into healthcare. Access to care and health equity will continue to be a priority in healthcare and funding in the future should reflect that.

We can expect a rise in the number of startups in the space and we might see growing markets in social entrepreneurship and impact investing. This is also a space ripe for public-private partnerships and joint ventures between interdisciplinary players to generate stronger and more sustainable impact together. The pandemic has increased demand in a dramatic way for digital health solutions, especially as it relates to access to care.

Massive increases in the funding of virtual care and telemedicine were somewhat predictable, but it revealed more nuanced trends. With millions confined to their homes and isolated from social channels, a stronger demand for behavioral health intervention surfaced. As the pandemic continues, mental health challenges will continue to grow more complex and require greater sophistication from digital health platforms in the wellness space. The challenge for providers moving forward, however, is to implement these services while improving experience and quality over time.

This is precisely why provider partnerships with tech startups and payers are so essential to navigating this next wave of transformation. To date, the primary infrastructure platform for healthcare is the EHR; virtually everything flows through an EHR at some point. However, we should expect additional infrastructure platforms and protocols to emerge this year. These infrastructure platforms likely will encompass core functions ranging from scheduling to billing, to dozens of other use cases.

By narrowing the set of product features to be built, new companies can focus on solving deep healthcare problems and not waste energy rebuilding tools that already function well. Hopefully this will make it easier to launch new health IT products. There have been some wonderful advancements in diagnostics, including the ability to detect disease earlier and with increased accuracy.

If I need a recent negative COVID result or proof of vaccination to board a flight or send my child to school, how can I effectively get that information to the appropriate third parties? One to two years ago, physician experience PX was almost considered a stand-alone category within digital health. Companies would even pitch themselves as patient or physician experience companies. Experience is closely linked to outcomes, so companies gaining traction are solving bigger health challenges and embedding experience into the core of their product, rather than selling experience alone.

Executives and leaders across companies of all sizes, who previously may have only focused on employee wellness during open enrollment, are now realizing that the health of their employees is vital. When combined with it becoming easier to launch healthcare solutions, I expect to see the number of deals, as well as total invested capital to set records. COVID has injected a strong sense of urgency across the healthcare ecosystem, leading to dramatic change in a short period of time.

I think COVID laid bare that healthcare organizations are slow to move, not because they lacked the capability to move quickly, but rather because there was never a sufficient incentive or catalyst to move quickly. Organizations that were slowly adopting telemedicine saw their share of telemedicine appointments soar overnight. Were there some hiccups along the way?

Sure, but one of the most important learnings is that even the largest healthcare organizations can move quickly when promoted to do so. During the pandemic, many Americans experienced a virtual healthcare visit for the first time ever, and found the process to be faster, easier and as effective as in-person care. We believe that Medicare will make permanent telemedicine coverage that was enacted as a result of the COVID public health emergency, leading many seniors to embrace virtual visits for a majority of their care.

Virtual visits offer some clinical advantages. Clinicians can check in with patients more frequently, track biomarkers remotely and continuously, and intervene faster when problems arise—leading to better outcomes and reduced costs. It will be tough for brick and mortar healthcare businesses to replicate these features, since they have strong incentives for keeping the in-person status quo to cover their large overhead costs. In the United States, 50 million people suffer from mental health issues , and that number is growing rapidly due to the demands of the ongoing pandemic , recession and social unrest.

As investors in Lyra Health, which enables companies to provide mental health resources to their employees, we think greater access to behavioral healthcare and tech-enabled care for more complex mental health needs is a huge opportunity. Increased access and usage of mental health resources will result in lower employee turnover and overall lower medical care costs.

Lastly, we think that AI for healthcare will move out of buzzword territory and into useful products. Companies like Suki and Virta Health are making it easier for physicians to work more efficiently thanks to AI. Large opportunities exist to apply AI to reduce administrative costs, reduce medical errors, and incorporate genetic data into clinical care.

This will add pressure for health IT companies to grow even faster in this environment so they can potentially go public sooner or be acquired while multiples are high. We also think that there will continue to be many promising companies created, particularly in virtual care, mental health, and primary care for Medicare and Medicaid populations. These are sectors where we think economic incentives and tech-enablement plus data are well aligned for new entrants to succeed.

There was a jump in health IT deals last year and funding in this space continues to break records. We think that this growth will continue to be driven by businesses and business-models that are created with better-aligned economic incentives and information. For many healthcare providers, patients and payers, the ultimate goal of innovation is creating lower-cost care options and increasing access to data that removes barriers to excellent care.

However, the rapid and successful adoption of telemedicine in and stronger incentives for the healthcare industry to become more efficient and affordable will continue to drive demand for health IT startups to disrupt the old guard.

We think that the best care models are likely to be hybrid models that incorporate in-person care, remote monitoring of data, and virtual care. At Providence Ventures, our top three areas of focus center on what we call Distributed Care. Essentially, transitioning the care model from a primarily in-office model, to one where patients get care at the most appropriate venue of care, for their specific concern, at that particular point in time led by virtual care in every clinically appropriate care setting.

With COVID induced pressures toward value-based care, accelerated consumer acceptance and pressure for regulatory changes—the time is now for this industry disruption. The real opportunity, however, is moving the industry from Telehealth 1.

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N2Care designs and builds mobile medical homes that are placed on the care-giving family's property. Number of Investors. Money Raised. Lead Investors. Predict your next investment The CB Insights tech market intelligence platform analyzes millions of data points on venture capital, startups, patents. N2CareInternational School of Management Paris Founder and CEO of N2Care Investment Manager at Gerber Kawasaki Wealth & Investment Managment.