**2. Aspects of mosquito behavior and their role on the vectorial capacity**

In mosquitoes, locomotor activity [31–34], host-seeking and blood feeding [35], digestion, mate finding and reproduction, and site choice for oviposition [36–38] are examples of rhythmic patterns that are recognizably modulated by extrinsic factors [39]. While these patterns have been increasingly studied, ecological interactions between hematophagous females and their hosts and pathogens are not well understood [40]. Likewise, how female rhythms affect and are affected by males' biological aspects associated with courtship and mating is still obscure [41, 42]. An emerging field of study, namely, "the causes and consequences of daily rhythms in the interactions between vectors, their hosts and the pathogens they transmit," was reviewed in Rund et al. [40].

Cycles in behavior and physiology have coevolved so that the organism's fitness is optimized. A shift in the rhythm of these traits may disrupt important biological functions leading to impacts on fertility and viability. For instance, in *Drosophila*, a shift in the time of day that food is ingested leads to a reduction in fertility [43], whereas maintaining the expected time for food intake leads to the benefits of an improved cardiac function [44]. In mosquitoes, when females engage in foraging or seeking for hosts, a suite of enzymes responsible for blood digestion must be operating, their immune response must be on to avoid pathogen infection, and their detoxification against insecticides must be active [40]. Therefore, breaking the interlocked pathways for pathogen-vector-host interactions will affect the vectorial capacity and the epidemiology of arboviruses.

The vectorial capacity measures the chance of emergence of new cases of the disease departing from one infected human host. As such, the parameters of behavior and physiology used in the calculation assume that mosquitoes are infected. Other parameters include population density, frequency of bites [26, 40], and transmission competency, which are directly influenced by the vector's behavior and physiology, as well as by the pathogen's behavior and extrinsic incubation period (EIP) [26, 40, 45].

The magnitudes of most parameters of the vectorial capacity equation are highly dependent on the daily variation of locomotor/flight activity behavior. There are several ways of measuring the pattern of locomotor activity of insect species, varying from the traditional method of reporting the presence of one species in field traps, in different times of the day, to activity monitors and video imaging used in the laboratory. Data generated by all these methods are represented with similar graphics, where the amount of locomotor/flight activity registered at each time interval is plotted on a 24-h graph. Variation in activity is studied according to variation in a *Zeitgeber*, a term used for an environmental synchronizer such as light or temperature.

Field and laboratory studies show that *A. aegypti* is active during the day, with activity peaks at dawn and dusk and lack of activity at night [7, 9]. Because flight activity toward hosts is driven by olfactory signals in mosquitoes, one could expect that rhythms in the expression of odorant binding proteins should parallel the olfactory sensitivity to host odors in order to activate the behavioral output [40]. However, in *Aedes aegypti*, rhythms in olfactory sensitivity are not sufficient to explain the daily cycling in behavior toward hosts [39]. The authors performed electroantennography assays and Y-maze olfactometer experiments using five different volatiles (including plants and host odors) and found that the peak of olfactory behavior is decoupled from the variation in olfactory sensitivity. These results suggest that modulation of the behavior associated with olfactory cues happens in both the peripheral (antenna) and central (endogenous clock) levels.

**73**

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

conditions [40].

**vectors**

neurotropic in mosquitoes [58].

Humans are the main hosts for *A. aegypti* females, and humans are most likely

Light and temperature are the major environmental factors affecting the rhythmic behavior of most organisms. As such, variation in these factors has a profound effect on the vectorial capacity. For instance, the biting rate of *A. aegypti*, which is a fundamental parameter in the calculation of the vectorial capacity, is highly influenced by temperature and time of day. Since females need to be active in order to engage in blood seeking, temperatures below 15°C and above 36°C constrain locomotor activity and make the number and intensity of bites to cease [3, 49].

Mating interaction is another element influencing vectorial capacity. Significant alterations in females' physiology and behavior happen after copulation, when male accessory gland peptides are transferred along with sperm [50], though contrasting effects have been reported. Augmented host-seeking and blood-feeding activity [31, 51–53], as well as an increase in oviposition rates [54, 55] and egg development [56], were reported, suggesting that these alterations could boost up the vectorial capacity. On the other hand, Lima-Camara et al. [9] have found a significant decrease in the mean locomotor activity after insemination and after blood feeding in females of *A. aegypti*. Although this result was reported as the daily mean of locomotor activity, the occurrence of a significant increase in the dusk peak of activity, which is the peak associated with biological functions like host-seeking and oviposition, is remarkable.

**3. The effects of infection on behavior and physiology of mosquito** 

Since vectorial capacity suffers major influence of vector behavior, studying the degree of modulation that arbovirus exerts on *A. aegypti*'s behavior is a key factor for understanding infection dynamics and host pathogenesis. In a recent work, Gaburro et al. have shown that infection by Zika virus leads to neuro-excitation in *A. aegypti*'s brain, inducing changes in the mosquito's behavior. The increase in neuronal spikes in infected versus non-infected females reflected on an increase in flight activity when females were studied in pools [57]. The authors found replicating virus in ZIKV-infected female brains, characterizing the tropism for the central nervous system, as well as in sensory organs like antennas and eyes, potentially affecting neuronal communication. Likewise, dengue virus was also found to be

A consequence of the neurotropic characteristic of these arboviruses is the alteration in the patterns of locomotor activity and feeding behavior. For instance, *A. triseriatus* becomes more avid for refeeding when infected by La Crosse virus [59, 60], while *Aedes aegypti* becomes more active when infected with serotype 2 of dengue virus [61] and with Zika virus when females are monitored in groups in cages (**Figure 4**) [57]. However, the assumption that virus infection would modulate behavior in a way to increase virus transmission and vectorial capacity is not always met. The example of West Nile virus indicates a possible decrease in virus transmission, where the mosquito vector *Culex pipiens* becomes less avid for host-seeking when infected with the virus [63]. Likewise, for individually monitored females of *A. aegypti*, Zika virus infection reduces flight activity, suggesting that infected mosquitoes may remain

associated with closely distributed human hosts (**Figure 4**) [62].

awake and active when these females are trying to land and blood feed. This imposes a risk for the mosquito. Body heat and carbon dioxide are the human factors that are the most attractive for mosquitoes [46]. The availability of these factors varies in a circadian way [40, 47, 48] and are subjected to changes in environmental

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

reviewed in Rund et al. [40].

period (EIP) [26, 40, 45].

or temperature.

capacity and the epidemiology of arboviruses.

**2. Aspects of mosquito behavior and their role on the vectorial capacity**

In mosquitoes, locomotor activity [31–34], host-seeking and blood feeding [35], digestion, mate finding and reproduction, and site choice for oviposition [36–38] are examples of rhythmic patterns that are recognizably modulated by extrinsic factors [39]. While these patterns have been increasingly studied, ecological interactions between hematophagous females and their hosts and pathogens are not well understood [40]. Likewise, how female rhythms affect and are affected by males' biological aspects associated with courtship and mating is still obscure [41, 42]. An emerging field of study, namely, "the causes and consequences of daily rhythms in the interactions between vectors, their hosts and the pathogens they transmit," was

Cycles in behavior and physiology have coevolved so that the organism's fitness is optimized. A shift in the rhythm of these traits may disrupt important biological functions leading to impacts on fertility and viability. For instance, in *Drosophila*, a shift in the time of day that food is ingested leads to a reduction in fertility [43], whereas maintaining the expected time for food intake leads to the benefits of an improved cardiac function [44]. In mosquitoes, when females engage in foraging or seeking for hosts, a suite of enzymes responsible for blood digestion must be operating, their immune response must be on to avoid pathogen infection, and their detoxification against insecticides must be active [40]. Therefore, breaking the interlocked pathways for pathogen-vector-host interactions will affect the vectorial

The vectorial capacity measures the chance of emergence of new cases of the disease departing from one infected human host. As such, the parameters of behavior and physiology used in the calculation assume that mosquitoes are infected. Other parameters include population density, frequency of bites [26, 40], and transmission competency, which are directly influenced by the vector's behavior and physiology, as well as by the pathogen's behavior and extrinsic incubation

The magnitudes of most parameters of the vectorial capacity equation are highly dependent on the daily variation of locomotor/flight activity behavior. There are several ways of measuring the pattern of locomotor activity of insect species, varying from the traditional method of reporting the presence of one species in field traps, in different times of the day, to activity monitors and video imaging used in the laboratory. Data generated by all these methods are represented with similar graphics, where the amount of locomotor/flight activity registered at each time interval is plotted on a 24-h graph. Variation in activity is studied according to variation in a *Zeitgeber*, a term used for an environmental synchronizer such as light

Field and laboratory studies show that *A. aegypti* is active during the day, with activity peaks at dawn and dusk and lack of activity at night [7, 9]. Because flight activity toward hosts is driven by olfactory signals in mosquitoes, one could expect that rhythms in the expression of odorant binding proteins should parallel the olfactory sensitivity to host odors in order to activate the behavioral output [40]. However, in *Aedes aegypti*, rhythms in olfactory sensitivity are not sufficient to explain the daily cycling in behavior toward hosts [39]. The authors performed electroantennography assays and Y-maze olfactometer experiments using five different volatiles (including plants and host odors) and found that the peak of olfactory behavior is decoupled from the variation in olfactory sensitivity. These results suggest that modulation of the behavior associated with olfactory cues happens in both

the peripheral (antenna) and central (endogenous clock) levels.

**72**

Humans are the main hosts for *A. aegypti* females, and humans are most likely awake and active when these females are trying to land and blood feed. This imposes a risk for the mosquito. Body heat and carbon dioxide are the human factors that are the most attractive for mosquitoes [46]. The availability of these factors varies in a circadian way [40, 47, 48] and are subjected to changes in environmental conditions [40].

Light and temperature are the major environmental factors affecting the rhythmic behavior of most organisms. As such, variation in these factors has a profound effect on the vectorial capacity. For instance, the biting rate of *A. aegypti*, which is a fundamental parameter in the calculation of the vectorial capacity, is highly influenced by temperature and time of day. Since females need to be active in order to engage in blood seeking, temperatures below 15°C and above 36°C constrain locomotor activity and make the number and intensity of bites to cease [3, 49].

Mating interaction is another element influencing vectorial capacity. Significant alterations in females' physiology and behavior happen after copulation, when male accessory gland peptides are transferred along with sperm [50], though contrasting effects have been reported. Augmented host-seeking and blood-feeding activity [31, 51–53], as well as an increase in oviposition rates [54, 55] and egg development [56], were reported, suggesting that these alterations could boost up the vectorial capacity. On the other hand, Lima-Camara et al. [9] have found a significant decrease in the mean locomotor activity after insemination and after blood feeding in females of *A. aegypti*. Although this result was reported as the daily mean of locomotor activity, the occurrence of a significant increase in the dusk peak of activity, which is the peak associated with biological functions like host-seeking and oviposition, is remarkable.
