**7. Operational changes to the programs of control with** *Wolbachia* **and GMM**

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 *Wolbachia* and GMM.

fever/exanthema and discriminating diagnosis is reduced when complications are severe and chronic manifestations of each infection are observed. The *operational problems* are evidenced through the low demand of health services—especially during outbreaks—which results in under registration of cases when the person does not demand or lacks access to health services, medicates himself or opts for treatments of symptoms they already recognize through

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

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 [34]. Among the *cultural problems*, or problems of perception, we find the familiarity with the sickness and its management given prior experience; fever is not considered an important risk to one's health

*The necessity of improving detection, diagnosis and notification*: Epidemiological surveillance of arboviruses faces two importance problems that occur in two different spaces: the community and health services. Given the clinical characteristics, an important number of cases do not demand health services due to their asymptomatic status or the unspecified fever that does not merit a visit to a doctor. Even many clinical cases do not consult medical services due to the patient having recognized and identified the case and knowing how to treat it. Due to this situation, we underestimate the number of cases and the detection of the illness and detection

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 [37].

**7. Operational changes to the programs of control with** *Wolbachia*

Evidence indicates that technological innovations should be viewed as tools complementary to vector control programs—tools whose introduction would be performed in carefully

methods available in regional labs (serology and viral isolation) are recorded [33].

and does not merit a visit to a doctor unless accompanied by more serious symptoms.

previous exposure to the problem.

102 Dengue Fever - a Resilient Threat in the Face of Innovation

for those affected should be improved [35, 36].

**and GMM**

*Integration of interventions by level of application:* A central element is the organization of interventions by level of application. We must keep on with simple practices, such as domestic hygiene (personal level); routine broad procedures such as breeding sites elimination campaigns; technically elaborated entomological sampling and larvicide application (community level); and even specialized, high-cost actions that require equipped, professional personnel, such as insecticide sprays (town level) or programs of medical attention for the correct handling of severe cases (national level). On the other hand, interventions aimed at urban infrastructure (access to potable water, garbage collection and a recycling system) ought to be incorporated bearing in mind that require high-level political commitment and substantial investments (municipal level).

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.

*Program structure*: The organization of the control programs has evolved from a vertical centralized structure ("Top-down")—independent of health services and with a "militarized" organization—to a more horizontal and decentralized structure, more tightly linked to services of surveillance and medical care and more participatory ("Bottom-up"). The advances toward a horizontal organization are variable, and in many programs, there exists a combination of both structures, in which the coordination is centralized. The need of coordinating all these processes—including the application of GMM/BCMW-based strategies—implies that programs that adopt these innovations ought to incorporate a centralized perspective, although the host communities ought to participate in the operational unfolding of the new technologies.

*Implementation*: The traditional control programs have an established procedural routine repeated each year, in the same season, with the same resources (human resources as well as physical, chemical and biological); however, the areas of control must be expanded and the actions intensified due to the increase in at-risk zones. In the case of IVM, it has been proposed that actions implemented should be differential in frequency and intensity in accordance with epidemiological risk.

*Human resources and operational infrastructure*: The vertical focus of traditional control programs developed a whole line of training for technical vector control personnel totally apart from promotional, preventative and educational health activities. This operational personnel was integrated in brigades separated from other health activities that were not exclusively linked to vector control. This resulted in an independent organization with equipment, vehicles, machinery and supplies (insecticides) that has been growing hand-in-hand with the problem. With IVM, a more rational use of resources is proposed, starting with the multi-sector and multidisciplinary nature (social participation) of the approach, where the social communication component is incorporated as a substantial element of this strategy.

*Efficiency in large-scale production*: In order to obtain the desired results, it is necessary to release a large quantity of mosquitoes (sterile, genetically manipulated or infected) into the environment in a reasonably short period of time that will allow for reduction and substitution of wild mosquito populations. Production, handling (separation), distribution and release may affect the capacity and competence of freed vectors. Production is easy to evaluate, but the

Challenges for the Introduction and Evaluation of the Impact of Innovative *Aedes aegypti*…

http://dx.doi.org/10.5772/intechopen.79862

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*Quality*: The performance, or *fitness*, of the vector should be evaluated, and there is not much experience with this sort of evaluation. Some factors to be evaluated are physical distinctions (pupa and/or adult size), survival rate, dispersal, mating capabilities, sperm quality, competition with wild or native species, and so on. Training of technical personnel and a specialized

*Social participation*: Social and community participation are essential to the acceptance, monitoring and evaluation of GMM strategies. Given the nature of the new GMM methods, communication with the communities is necessary in order to introduce these methods, which are

*Sustainability*: The re-introduction of an eliminated species is possible if control interventions cease or diminish in intensity and frequency. Invasion or re-introduction from other nontreated areas requires a containment plan with geographical barriers to inhibit vector migration. The concerns are more environmental than health-related. The emptied niche may

*Costs*: Cost-effectiveness studies of traditional control methods begin to be an important strategy in evaluating their potential and their degree of incorporation, and in defining the conditions that create for their maximum usefulness. The success of an intervention in terms of costs is subject to the context of where it is applied, the scale of implementation, the availability of personnel and appropriate equipment and the scale of the problem (endemic, epidemic, hyperendemic and introduction of new agents). Traditional control programs require resources in response to the growing magnitude and breadth of the problem. The investments associated with IVM increase costs because of the community and multi-sector participation and the necessary social communication, which touch on other relevant community issues. The incorporation of GMM-MBW needs to be accompanied by an important investment in infrastructure, personnel training, equipment and supplies, along with a strong social communication component that ought to be considered within the comprehensive cost of the program.

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 *Ae. aegypti* populations and affect the transmission of ABD. Some show great potential, such as the use of GMM-BCMW, but are not yet available as

same may not be said for the competence of the generated mosquitoes.

conceptually very different from traditional methods of control.

promote the invasion of a more dangerous, competent and effective species.

multidisciplinary group is needed.

**8. Final considerations**

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.

*Coverage*: A problem inherent to the traditional programs of control in urban and suburban areas in countries where ABD are endemic is their limited coverage; not all breeding sites can be protected or removed, and their productive potential cannot be eliminated with biological, chemical or physical agents. It is not possible to protect or control the totality of the most productive and stable breeding sites in urban centers due to their number, seasonal productivity, location and access ("cryptic" breeding sites).

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.

*Scale*: One of the most important challenges for any vector control intervention is reaching a level of sufficient coverage (breeding sites, houses, people or communities) in order to effectively limit transmission. These technological innovations are proposed as intervention at a scale larger than that established by traditional vector control strategies. However, all of the processes of production, introduction and maintenance must be initially evaluated at an intermediate scale before considering their application at the regional or national level.

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.

*Efficiency in large-scale production*: In order to obtain the desired results, it is necessary to release a large quantity of mosquitoes (sterile, genetically manipulated or infected) into the environment in a reasonably short period of time that will allow for reduction and substitution of wild mosquito populations. Production, handling (separation), distribution and release may affect the capacity and competence of freed vectors. Production is easy to evaluate, but the same may not be said for the competence of the generated mosquitoes.

*Quality*: The performance, or *fitness*, of the vector should be evaluated, and there is not much experience with this sort of evaluation. Some factors to be evaluated are physical distinctions (pupa and/or adult size), survival rate, dispersal, mating capabilities, sperm quality, competition with wild or native species, and so on. Training of technical personnel and a specialized multidisciplinary group is needed.

*Social participation*: Social and community participation are essential to the acceptance, monitoring and evaluation of GMM strategies. Given the nature of the new GMM methods, communication with the communities is necessary in order to introduce these methods, which are conceptually very different from traditional methods of control.

*Sustainability*: The re-introduction of an eliminated species is possible if control interventions cease or diminish in intensity and frequency. Invasion or re-introduction from other nontreated areas requires a containment plan with geographical barriers to inhibit vector migration. The concerns are more environmental than health-related. The emptied niche may promote the invasion of a more dangerous, competent and effective species.

*Costs*: Cost-effectiveness studies of traditional control methods begin to be an important strategy in evaluating their potential and their degree of incorporation, and in defining the conditions that create for their maximum usefulness. The success of an intervention in terms of costs is subject to the context of where it is applied, the scale of implementation, the availability of personnel and appropriate equipment and the scale of the problem (endemic, epidemic, hyperendemic and introduction of new agents). Traditional control programs require resources in response to the growing magnitude and breadth of the problem. The investments associated with IVM increase costs because of the community and multi-sector participation and the necessary social communication, which touch on other relevant community issues. The incorporation of GMM-MBW needs to be accompanied by an important investment in infrastructure, personnel training, equipment and supplies, along with a strong social communication component that ought to be considered within the comprehensive cost of the program.
