**Abstract**

Most organisms live in a rhythmic world, where daily environmental variation has a profound effect on their behavior and physiology. In addition to abiotic influence, interactions with other organisms that have their own particular cycles are also part of circadian rhythm formation. In this chapter, we present aspects of the biology of mosquito vectors, more precisely *Aedes aegypti*, which is a vector of arboviruses of great epidemiological importance, like dengue, Zika, and chikungunya. The successful transmission of the virus depends on the coordination of several behavioral and physiological traits involved in the virus-vector-host interaction. Thus, understanding the mechanisms of endogenous control of rhythmic traits of the mosquito vector and the impact that both environmental variation and virus infection can have on this regulation is key for a reliable estimate of the vectorial capacity. We discuss the infection-driven changes in traits used to calculate parameters of the vectorial capacity, and finally, we review the current knowledge on the molecular mechanisms underlying vector rhythmic behavior and the potential cellular targets of arbovirus infection.

**Keywords:** *Aedes aegypti*, arbovirus, behavior, vectorial capacity, physiology, neurotropism, Zika, dengue, chikungunya, circadian clocks

### **1. Introduction**

#### **1.1 The** *Aedes aegypti* **mosquito as a vector of arboviruses**

*Aedes aegypti* (Diptera: Culicidae) is an insect belonging to the family Culicidae and subgenus *Stegomyia*. The species was originally found in Egypt, hence its specific name; but it is currently distributed worldwide, occurring mainly in tropical and subtropical regions [1, 2]. *Aedes aegypti* life cycle is composed of four phases: egg, four larval instars, pupa, and adult (**Figure 1**).

Since they spend most of their life cycle in water, mosquitoes are considered to be primarily aquatic; they gain the terrestrial environment only in adulthood, when they fly in order to seek for food and mates [3–5]. Easy to distinguish for taxonomists, *A. aegypti* is a dark-bodied mosquito in the adult phase, with white spots on the dorsal abdomen and legs and a white pattern composed of a lira-shaped drawing on its scutum (**Figure 2**) [1, 6].

The mosquito *A. aegypti* is considered a major disease vector in urban habitats, being able to host and transmit various arbovirus. Females of anautogenous

**Figure 1.** *Life cycle of the Aedes aegypti mosquito (credits of the photos on each image—out of ratio).*

#### **Figure 2.**

*Aedes aegypti mosquito. The arrow points to the scutum region that displays the lira-shaped (out of ratio). The three body parts, common to all insects, are indicated above. Adapted from [6].*

mosquitoes, like *A. aegypti*, need a blood meal in order to mature their eggs and to perpetuate the species. Because of this, this mosquito is indubitably one of the most pathologically important arthropod vectors. One *A. aegypti* female is able to produce approximately 100 eggs after blood feeding on a vertebrate host, in each gonotrophic cycle (interval between blood meal and egg laying). Even being a diurnal mosquito, the female prefers to lay eggs in dark/shaded sites and in the dark phase of the day [7–10]. *Aedes aegypti* is an anthropophilic species, preferring to feed on human blood than the blood of other vertebrates [11, 12]. This feature is responsible for the role of *A. aegypti* as transmitter of many pathogens that cause important human diseases. The markedly anthropophilic and endophilic behaviors of *A. aegypti* make it a very efficient vector of yellow fever, dengue, chikungunya, and Zika viruses [3, 11, 13–16]. Many other factors related to behavior and physiology of vector and pathogens are significant for the success in arbovirus transmission, such as (i) the habit of laying eggs in multiple breeding sites; (ii) the diversity of posture sites; (iii) the gonotrophic discordance, that is, the ability to blood feed on more than one host for each batch of eggs produced; and (iv) the ability of the eggs in remaining viable, in quiescence state, for up to 1 year in dry conditions (called "egg resistance to desiccation") and in large temperature variation (i.e., 16–35°C) [1, 3, 17–20]. All these features can be associated to vector competence and vectorial capacity [7].

**71**

**Figure 3.**

mosquito vector tissues.

*The Effects of Infection on Mosquito Rhythmic Behavior DOI: http://dx.doi.org/10.5772/intechopen.89409*

*aegypti* competence to DENV transmission [15, 22, 23].

mosquitoes to control programs [24].

help to assess the risk of arbovirus emergence [24].

sion by mosquitoes make similar assumptions [28, 29].

*the extrinsic incubation period (EIP). Adapted from Refs. [26, 27].*

Both vector competence and vectorial capacity are critical for arbovirus transmission. Vector competence is the intrinsic ability of a vector to acquire, maintain, and transmit a pathogen to another host. In mosquitoes, a species is considered vector competent when females transmit the pathogen from one vertebrate to another during blood feeding [21]. This competence is related to intrinsic features of the vector, as well as the pathogen, such as pathogen genotype, pathogen strain, and vector strain. Specifically, for the viruses DENV and CHIKV, vector competence has been tested and confirmed in *A. aegypti* and *A. albopictus* laboratory strains. To DENV, environmental factors as daily temperature fluctuations have been demonstrated to impact vector-pathogen interactions, being able to modulate the *A.* 

Although the number of studies on *A. aegypti* behavior and physiology, as well as arbovirus-mosquito interactions, has been growing, additional information is needed in order to promote the development of better mosquito control actions. Variation in the vector competence for different arboviruses highlights the existence of different virus-vector interactions. For example, both *A. aegypti* and *A. albopictus* show the competence to transmit the arboviruses DENV, ZIKV, YFV, and CHIKV; however these vectors do not exhibit the same transmission efficiency. Likewise, within-population genetic variation may explain the varied vector competence for different arboviruses and may also be related to the response of

Other factors may be involved in the vector competence, for example, two different insecticide resistance mechanisms were described to enhance the vector competence of *Culex quinquefasciatus* for West Nile virus, which can impact on transmission dynamics of arboviruses for other mosquito vector species [25]. Measuring the vector competence of field mosquitoes for different arbovirus can

Vectorial capacity, in turn, is the estimated value through a formula that takes into account a set of parameters of intraspecific physiology and behavior that, associated with environmental conditions, favor natural transmission of a given disease. The vectorial capacity is mainly influenced by population density, biting behavior (frequency of host contact for blood feeding), and mosquito vector survivorship [26]. The concept of vectorial capacity was initially established for the transmission of malaria by vectors of the genus *Anopheles* and calculated by the formula shown in **Figure 3**, where the total number of potentially infectious bites a day is one of the parameters. Many studies of mathematical models describing pathogen transmis-

The World Health Organization emphasizes that mosquito vector control plays an important role in blocking the propagation of critical arboviruses. This is particularly relevant when no vaccines or specific drug treatments are available, as is the case for dengue, Zika, and chikungunya, which have the *A. aegypti* as the main vector [13, 14, 30]. Understanding vector competence and vector capacity mechanisms is important in designing safer vaccines and new strategies to prevent the transmission of pathogens. Specifically for the mosquito vector *A. aegypti*, many barriers hamper infection, dissemination, and transmission of arboviruses through

*Vectorial capacity formula: here m is the number of female mosquitoes per host, a is the daily blood feeding rate, b is the transmission rate among exposed mosquitoes, p is the probability of daily survival, and n is* 

*Vector-Borne Diseases - Recent Developments in Epidemiology and Control*

mosquitoes, like *A. aegypti*, need a blood meal in order to mature their eggs and to perpetuate the species. Because of this, this mosquito is indubitably one of the most pathologically important arthropod vectors. One *A. aegypti* female is able to produce approximately 100 eggs after blood feeding on a vertebrate host, in each gonotrophic cycle (interval between blood meal and egg laying). Even being a diurnal mosquito, the female prefers to lay eggs in dark/shaded sites and in the dark phase of the day [7–10]. *Aedes aegypti* is an anthropophilic species, preferring to feed on human blood than the blood of other vertebrates [11, 12]. This feature is responsible for the role of *A. aegypti* as transmitter of many pathogens that cause important human diseases. The markedly anthropophilic and endophilic behaviors of *A. aegypti* make it a very efficient vector of yellow fever, dengue, chikungunya, and Zika viruses [3, 11, 13–16]. Many other factors related to behavior and physiology of vector and pathogens are significant for the success in arbovirus transmission, such as (i) the habit of laying eggs in multiple breeding sites; (ii) the diversity of posture sites; (iii) the gonotrophic discordance, that is, the ability to blood feed on more than one host for each batch of eggs produced; and (iv) the ability of the eggs in remaining viable, in quiescence state, for up to 1 year in dry conditions (called "egg resistance to desiccation") and in large temperature variation (i.e., 16–35°C) [1, 3, 17–20]. All these features can be associated to vector competence

*Aedes aegypti mosquito. The arrow points to the scutum region that displays the lira-shaped (out of ratio). The* 

*Life cycle of the Aedes aegypti mosquito (credits of the photos on each image—out of ratio).*

*three body parts, common to all insects, are indicated above. Adapted from [6].*

**70**

**Figure 1.**

**Figure 2.**

and vectorial capacity [7].

Both vector competence and vectorial capacity are critical for arbovirus transmission. Vector competence is the intrinsic ability of a vector to acquire, maintain, and transmit a pathogen to another host. In mosquitoes, a species is considered vector competent when females transmit the pathogen from one vertebrate to another during blood feeding [21]. This competence is related to intrinsic features of the vector, as well as the pathogen, such as pathogen genotype, pathogen strain, and vector strain. Specifically, for the viruses DENV and CHIKV, vector competence has been tested and confirmed in *A. aegypti* and *A. albopictus* laboratory strains. To DENV, environmental factors as daily temperature fluctuations have been demonstrated to impact vector-pathogen interactions, being able to modulate the *A. aegypti* competence to DENV transmission [15, 22, 23].

Although the number of studies on *A. aegypti* behavior and physiology, as well as arbovirus-mosquito interactions, has been growing, additional information is needed in order to promote the development of better mosquito control actions. Variation in the vector competence for different arboviruses highlights the existence of different virus-vector interactions. For example, both *A. aegypti* and *A. albopictus* show the competence to transmit the arboviruses DENV, ZIKV, YFV, and CHIKV; however these vectors do not exhibit the same transmission efficiency. Likewise, within-population genetic variation may explain the varied vector competence for different arboviruses and may also be related to the response of mosquitoes to control programs [24].

Other factors may be involved in the vector competence, for example, two different insecticide resistance mechanisms were described to enhance the vector competence of *Culex quinquefasciatus* for West Nile virus, which can impact on transmission dynamics of arboviruses for other mosquito vector species [25]. Measuring the vector competence of field mosquitoes for different arbovirus can help to assess the risk of arbovirus emergence [24].

Vectorial capacity, in turn, is the estimated value through a formula that takes into account a set of parameters of intraspecific physiology and behavior that, associated with environmental conditions, favor natural transmission of a given disease. The vectorial capacity is mainly influenced by population density, biting behavior (frequency of host contact for blood feeding), and mosquito vector survivorship [26]. The concept of vectorial capacity was initially established for the transmission of malaria by vectors of the genus *Anopheles* and calculated by the formula shown in **Figure 3**, where the total number of potentially infectious bites a day is one of the parameters. Many studies of mathematical models describing pathogen transmission by mosquitoes make similar assumptions [28, 29].

The World Health Organization emphasizes that mosquito vector control plays an important role in blocking the propagation of critical arboviruses. This is particularly relevant when no vaccines or specific drug treatments are available, as is the case for dengue, Zika, and chikungunya, which have the *A. aegypti* as the main vector [13, 14, 30]. Understanding vector competence and vector capacity mechanisms is important in designing safer vaccines and new strategies to prevent the transmission of pathogens. Specifically for the mosquito vector *A. aegypti*, many barriers hamper infection, dissemination, and transmission of arboviruses through mosquito vector tissues.

#### **Figure 3.**

*Vectorial capacity formula: here m is the number of female mosquitoes per host, a is the daily blood feeding rate, b is the transmission rate among exposed mosquitoes, p is the probability of daily survival, and n is the extrinsic incubation period (EIP). Adapted from Refs. [26, 27].*
