Innovative control tools for the dengue, chikungunya and Zika vector Aedes aegypti, such as genetically modified mosquitoes and biological control and manipulation with the bacteria Wolbachia, are now becoming available and their incorporation into institutional vector control programs is imminent. The objective of this chapter is to examine the technical and organizational mechanisms together with the necessary processes for their introduction and implementation, as well as the indispensable indicators to measure their entomological effect on vector populations and their epidemiological impact in the short, medium and long term as part of an integrated vector management approach.
- entomological surveillance
The tools and strategies that have been implemented in recent decades to control the
Improvements in the quantification and control of this mosquito in urban environments and the transmission of ABD require a reformulation of current control strategies, as well as a stronger focus on reducing vector abundance, preventing human-vector contact and finally, reducing virus transmission [1, 2]. Due to the multiplicity of co-circulating viruses transmitted by the
Traditional mosquito control strategies have consisted of nonintegrated vector management of the immature (larvae) mosquito stage and of the use of insecticides that have fairly low—and temporary—mortality rates in adult female mosquitoes. Effective and sustained control by these methods and intervention is impeded by a number of obstacles: effective coverage of all breeding sources, lack of personnel needed, the need of continuous insecticide re-application, the transitory nature of their effects, the false sense of security that they generate and the dependence fomented in both the affected communities and the mosquito management programs.
On February 1, 2016, the World Health Organization (WHO) declared the Zika virus, along with microcephaly and the other associated neurological disorders, a public health emergency of international importance (public health emergency of international concern, PHEIC) . The Zika outbreak rapidly reached across not only the Americas, but also 75 other countries and territories; its control continues to be a long-term challenge to public health even after the declaration of the end of the state of emergency by the WHO Emergency Committee in November of 2016.
Due to this emergency, the scientific community; entrepreneurs and international, regional, and national governmental programs in areas endemic to
We find ourselves looking to the possible incorporation of various technological innovations whose application in the field of public health offers positive (theoretical) prospects of success along with new opportunities for enhancing the effectiveness of control programs; however, there are also technical and operational challenges that must be considered before incorporating these innovations into the inventory of mosquito management tools .
2. Methods of intervention for
Vector control is a complex task. There are a number of options available for different stages (eggs, larvae, pupae and adult) of the mosquito populations; a variety of available tools (physical/mechanical, environmental, biological, chemical and behavioral preventive measures) and different goals for each strategy (covering containers to avoid egg-laying, eliminating breeding sites in order to diminish larval densities, spraying insecticides to kill and reduce adult mosquitoes or installing barriers that diminish vector-human contact). The ultimate goal of each strategy is diminishing transmission. However, experience has shown that there is no “magic bullet” that is effective, lasting, affordable and easy to implement.
The purpose of vector control is to maintain populations at “acceptable” densities, to minimize vector-human contact (to prevent mosquito bites) and to reduce the longevity of female adult mosquitoes, in order to reduce the health problem to a manageable level that does not surpass the capacities of local health systems. The ambitious campaign (1947–1970) promoted by the Pan American Health Organization (PAHO) to eliminate
We are challenged by different stages of the vector’s life cycle which develop in different environments (air and water) and in different types of breeding sites (natural and artificial), made of a variety of materials (plastic, metal, cement, clay, glass, etc.) and have different productivity, different uses (some may be disposable and others able to be controlled) and can be either permanent or seasonal. This variability in type of vector breeding sites imposes diverse challenges for control—whether it can be sporadic (cleaning campaigns), continuous (use of larvicides or larvivorous fish), or permanent (physical elimination)—and it is not realistic to expect that these differences require a homogenous strategy. The characteristics of the different types of breeding sites require a variety of customized strategies so that the control may be effective and sustainable.
The diversity of available vector control strategies and their implementation in each operation are related to the resources available, the cultural context in which the interventions are performed and the overall capacity for applying them appropriately and with sufficient coverage. These factors can and should be included in the integrated vector management (IVM) approach promoted by the WHO [5, 6]. IVM is based on a spectrum of intervention strategies, frequently utilized in synergy and applied simultaneously, that are selected based off of knowledge of local factors influencing the vector’s biology and the disease’s transmission and morbidity, with the goal of optimizing resources for vector control.
As dengue spread on the last decades, the idea of vector control replaced that of vector elimination, because the magnitude of the problem surpassed the capacity of institutional responses (vertical programs) and incorporated new approaches such as community participation; biological control of larvae (copepods,
Despite new vector control strategies being introduced with the goal of diminishing transmission, entomological monitoring indicators were never adapted to the new demands of the programs, and the traditional indices designed to measure the presence and absence of larvae and containers, which were never linked to the risk of transmission, were maintained .
The introduction of technological innovations—such as the use of
3. Innovations to biological and genetic manipulation of mosquito vectors
The strategies for genetic and biological control/manipulation with
The mechanism of dispersion and coverage that is proposed is the male mosquito vector itself; these male mosquitoes will find their female counterparts and transmit the control measure before these females lay their eggs, undiscriminating as to preferred breeding site and location. The progeny (eggs, larvae and adults) will incorporate the intervention naturally and will maintain it in the population that emerges from their lineage (desirable). In essence, the dispersal and upkeep of the intervention will be a product of biological mechanisms rather than human intervention.
Interventions consisting of biological manipulation and genetic control of vectors, furthermore, share many characteristics that again distinguish them from the traditional methods. Among these are as follows: (1) dependence on vertical (maternal) transmission of heritable elements (resistance genes and
In general, these innovations to vector manipulation are based on two strategies that can be organized according to the results obtained (population elimination vs. replacement) or to the implantation dynamics (self-sustainable or self-limiting).
4. Paradigm shift, focus and objective
One of the most important changes upon incorporating GMM-BCMW into the
Traditional programs of control direct their efforts toward larval stages, reducing breeding sites abundance and the density of larvae in houses and containers, while they attack adult mosquitoes with insecticides that have limited coverage, short duration and low mortality at the population level. The focus and objective of integrated vector management (IVM) are directed to the control of mosquito populations through multi-sector interventions with a multidisciplinary and/or eco-bio-social focus based on changes to community practices, achieved by way of educational interventions.
GMM-BCMW are not technologies that can be used in case of emergency (outbreak control). Focus is directed to the reduction, suppression (elimination) or substitution of
5. Challenges to entomological surveillance
Entomological surveillance has been employed to (1) determine changes in the geographical distribution of
One element of the evolution of control programs has been the slow innovation of entomological monitoring indicators, an area dominated by the traditional
The need for better indicators led to indices of pupae and oviposition, closer life stages to the ideal measure of adult (female) mosquito populations, which would allow for a better approximation of the estimated risk of transmitting dengue [17, 18]. These indicators of entomological risk did not reduce or eliminate the challenges to evaluate the interventions because the need to relate density and/or the threshold of the different vector stages to risk of transmission still persists [19, 20, 21].
The use of “nonentomological” (though associated with infestation and facilitators of vector-human contact and epidemiological risk) indicators has also been proposed and ought to be considered in order to better understand the dynamics of dengue transmission—for example, density and distribution of human populations, socioeconomic conditions, living and public services, climate, etc. [22, 23, 24, 25, 26, 27].
The selection of indicators and surveillance methods depends on the objective of surveillance (density reduction, risk detection and outbreak prevention), the levels of infestation and the capacity for implementation. Nevertheless, there is little evidence showing that the control programs employ systematic monitoring of vector populations—in particular, monitoring of adult females—in order to measure infestation and risk of dengue transmission [18, 28, 29]. In the best of cases, programs still employ indices of infested sites/breeding sites [29, 30] in order to establish “areas” of transmission risk without demonstrating the predictive capacity of these indices as indicators of dengue transmission risk in the last 50 years .
The limitations of these methods for measuring mosquito populations are the absence of a “gold standard,” the fact that all measurements have a range of error (they are not precise) and that only a proportion of the total mosquito population (eggs, larvae or adults) is measured. Furthermore, it must be understood that the risk of transmission can occur in various locations and not necessarily where the measurement and/or intervention is performed and that in the selection of methods of measurement and entomological monitoring, precision is always sacrificed. This is to say that, despite being less precise, easier and cheaper methods are chosen over those (e.g., adult surveys) that require more resources and thus are more expensive .
An additional challenge is the combination of strategies (not yet their integration) and the differentiated evaluation of their impact, since while one intervention can modify the physical availability of breeding sites, it does not necessarily result in a decrease of vector density nor control the most stable and productive breeding sites. On the other hand, there is insufficient evidence to support the idea that achieving a lower egg or larval density through a variety of available interventions has an impact on the rate of disease transmission. Nevertheless, the combined use of old strategies and/or the incorporation of new vector control tools imposes various challenges: (1) the use of indicators that measure more specifically the density of mosquitoes in all stages of development in order to more concretely evaluate all available modes of intervention, (2) the definition of risk thresholds and (3) that the programs demonstrate their capacity (in terms of human resources, equipment and finances) to be executed with the coverage and frequency necessary to make them valid [1, 2].
6. Challenges to epidemiological surveillance
The evaluation of interventions to control
Systems of epidemiological surveillance now have the task of measuring, in the most precise manner possible, three infections transmitted by
The estimate of the actual number of dengue cases, and now of Zika and chikungunya, is very difficult to calculate due to
Only patients with severe symptoms go to the doctor, and these are the best detected by the surveillance system. An additional operational problem is the lack of sensibility to clinical diagnoses of fever and the limited collection of samples in order to confirm diagnosis—even during an epidemic—now that normative processes restrict the collection of samples to only severe cases or those at the onset of an outbreak. Only those cases confirmed by diagnostic methods available in regional labs (serology and viral isolation) are recorded .
These circumstances impact the opportunity for vector control interventions (operational problem) since the presence of asymptomatic cases and unspecified or febrile patients are not registered early, and it is not until the accumulation of many cases that an increase in transmission is detected; it is at this point that control actions are initiated . Among the
In the health services sector, diagnosis and documentation related to cases should be improved by strengthening the capacities of health personnel and local laboratories. To accomplish this, the following are indispensable: (1) counting on clinical guidelines that facilitate the health personnel in the identification and treatment of clinical cases under surveillance (dengue, Zika and chikungunya) and that reduce the identification of false negatives, (2) establishing criteria for the collection of samples and having the supplies necessary for serological and/or viral confirmation of suspected cases, (3) improving the reporting of cases unconfirmed in the laboratory (probable/suspected) following the algorithms of differential diagnosis for the three illnesses, (4) encouraging the reporting of cases by epidemiological association in the case of an outbreak and (5) seeking mechanisms for notification of cases identified by private medical services .
7. Operational changes to the programs of control with
Evidence indicates that technological innovations should be viewed as tools complementary to vector control programs—tools whose introduction would be performed in carefully selected sites until the detection of evidence of the sustained impact and the reduction of potential risks of evolution in the manipulated species and introduced genetic or biological marker. It is believed that innovations would be used in places where traditional measures of control have little to no effect and where they may have an important epidemiological impact on transmission dynamics. However, as with any intervention—and especially with innovative interventions—there are some operational changes that will need to be considered for the programs of control with
An additional challenge is the integration of abovementioned interventions in order to perform them in a combined and sequential manner and differential intensity in accordance with the epidemiology of each area vulnerable to transmission. Although the available human and financial resources will generally define this, we must pursue on the objective to direct efforts to high-risk areas. The selection of localities in which to introduce these innovations for control should take into account the degree of risk in that area as well as the impact produced by the illnesses.
The incorporation of GMM-BCMW into the vector control programs involves the components proposed for IVM, but also requires adaptation of the technology to the local conditions, as well as the development of an infrastructure of basic technology (insectariums and laboratories) to permit mass, sustained production, implementation and appropriate evaluation of the interventions. In this case, a specialized multidisciplinary group—in addition to technical personnel—is needed to achieve the introduction, monitoring and evaluation of new interventional strategies.
The coverage of a vector control program functions at the level of the individual, the household, the block or neighborhood, but rarely at the town level. With the IVM programs, the target for intensive application of control efforts will be the neighborhood and towns at greatest risk; there are no claims that all affected areas, neighborhoods or towns will be covered. Coverage in the case of GMM-BCMW can include areas, towns, or medium-sized urban centers, since the mass release of treated mosquitoes cannot limit itself to blocks or a neighborhood. Thus, monitoring and maintenance in such broad areas is complicated by the necessity of technical and (specially trained) human resources and not presently contemplated by surveillance programs.
Their application for control of mosquitoes that transmit disease is today only viewed within the context of the strategy of integrated vector management (IVM). This implies necessary adaptations in control programs as regard production of biological materials as well as in relation to the operation, which should be designed in accordance with the technical specifications of the modified organisms.
8. Final considerations
During the last decade, the WHO has been promoting IVM but has been using only those intervention methods traditionally available. Several innovative methods are being developed to complement the current control of
Vector control programs do not use “single” methods. Innovations should be considered complementary tools to control programs, not substitutes. Traditional and/or new interventions of greater complexity can be implemented proactively using a risk stratification approach calling for different intensity and greater coverage in priority areas. However, we can anticipate complications on monitoring and evaluation, since there is little evidence and experience of multiple or combined interventions with intersectoral participation and IVM.
Traditional vector control has demonstrated limited impacts and transitory decreases in larval and adult mosquito populations. Monitoring of these traditional control programs is performed on an irregular basis throughout the year, without taking into account that there are important seasonal effects on vector populations. Furthermore, these evaluations are unstructured and usually not conduced at the time intervals necessary in order to estimate the magnitude and longevity of the effects on vector populations. In the case of GMM-BCMW, in addition to performing entomological monitoring to estimate the effects of suppression on target populations, in the case of substitution or population replacement strategies, it is necessary to include measurements of the reproductive and biological performance of the introduced populations.
Estimates of the effect of traditional actions (larval density) do not imply impacts on disease transmission (incidence). The IVM strategies share these limitations, although they diversify the indicators due to the multidisciplinary nature of their interventions. In the case of GMM-BCMW, the evaluations ought to incorporate continuous monitoring of adult mosquito populations (wild and introduced): their survival, performance (or
Despite intense research on
Entomological surveillance is indispensable in order to monitor vector populations and to count on the basic parameters that allow for evaluation of direct impact on affected populations. Larval densities are not sufficient for evaluating the effects expected with the inclusion of these innovations, since the introduced populations are competing adults; as a result, it is necessary to evaluate adult density (males and females) as well as vector survival, mating habits, reproductive capacities (fecundity) and so on.
Last but not least, the success of any control intervention should be measured ultimately in terms of resultant decrease in infection transmission and in the impact of the illness on the community. This process entails decreased herd immunity in human populations and would introduce the risk of greater epidemics if the intervention measures lost intensity or effectiveness or were no longer applied. Decreased immunity augments the population’s susceptibility, which results in lower vector density thresholds for transmission or risk of transmission.
Here, we have exposed some of the major challenges for the introduction, implementation and evaluation of innovative
Other basic requirements for the adoption of technological innovations include a regulatory and legislative framework for their use in public health (Environmental, Biosecurity and Bioethics); following a set of Protocols & Portfolio having to do with safety, quality control, efficacy, and so on; and necessary integration with local vector control programs including agreement/acceptance by institutions and communities. In terms of administrative and financial requirements, we still need to resolve whether these technological innovations can be acquired under the current budget structure (as a product or service). In order to more quickly implement these new technologies, we need to develop a medium to long-term implementation and financing plan; production, distribution, monitoring and evaluation logistics and private-public partnerships.
To the Canadian Institutes of Health Research (CIHR) and IDRC (Preventing Zika disease with novel vector control approaches Project 108412) and Fondo Mixto CONACYT–Gobierno del Estado De Yucatán (Project YUC-2017-03-01-556). Abdiel Martin-Park is supported by the Cátedras–CONACYT program. Special thanks to Ana García-Moreno Malcolm for grammar corrections.