**2.4. Venezuelan equine encephalitis**

This disease is caused by the Venezuelan equine encephalitis virus (VEE) or encephalomyelitis in horses, donkeys, zebras, and humans. VEE virus cause acute infections in vertebrates characterized by the presence of high viremia and disease development with varying degrees of severity. Once the equines get the disease, they may die suddenly or present progressive disorders of the central nervous system. Furthermore, in humans, it causes mild to severe influenza-like symptoms, with fever and headache. Around 4–14% of cases develop neuro‐ logical complications and near 1% of reported cases die [20].

The VEE complex contains a number of virus, belonging to the *Alphavirus* genus of the Togaviridae family, which have been classified into six viral subtypes, ranging from I to VI. VEE virus are present in all continents and most often are transmitted by the bite of infected *Culex* (*C. vomerifer*, *C. pedroi*, *C. adamesi*) and *Aedes* (*A. taeniorhynchus*) mosquito vectors and can also be transmitted through aerosols [21]. Although virtually any mosquito can be found infected with VEE virus during epizootics, it is thought that *A. taeniorhynchus* is the main vector responsible for transmitting VEE virus during outbreaks, whereas *Culex* mosquitoes species transmitted enzootic virus strains of VEE [22]. Subcutaneous injection, nasal instillation, and contact with broken skin or bedding contaminated animals are other ways to spread the virus, especially in a lab environment [23].

Epizootic and enzootic strains of VEE virus spread from northern Argentina to Florida and parts of the Rocky Mountains, being more frequent in northern South America. Since 1930, there have been 21 outbreaks of VEE throughout the American continent, being considered an emerging disease naturally due to mutations of the enzootic and endemic virus strains that circulate as a vector-borne disease among mammals host populations, especially in habitats such as forests and wetlands [24]. Some of the strategies used to reduce outbreaks of VEE in horses are through the implementation of the TC-83 vaccine and by protecting against mosquitoes by wearing protective clothing and/or insecticides. Although, the TC-83 vaccine is used in laboratories, there is still no licensed vaccine available to humans for the prevention of infection by the epizootic strains of VEE virus [25].

### **2.5. Japanese encephalitis**

important factors that favor the spread of these mosquitoes and dengue virus from one region

This disease is of major interest to public health because of its great impact on morbidity and mortality in the world since it is the viral disease transmitted by mosquito vectors most common and important worldwide [18]. The World Health Organization estimated that there may be 50 to 100 million dengue infections, a half-million hospitalizations, and 22,000 deaths worldwide every year [19]. Moreover, because of the absence of a vaccine to protect the population at risk, vector control is the most important method for the prevention and interruption of the transmission of the disease. The use of chemical insecticides is a key component in the control of larvae and adult mosquito vector populations. However, derived from overuse for over five decades of these insecticides to interrupt the transmission of the virus, it has generated resistance to different molecules of insecticides by part of mosquito

This disease is caused by the Venezuelan equine encephalitis virus (VEE) or encephalomyelitis in horses, donkeys, zebras, and humans. VEE virus cause acute infections in vertebrates characterized by the presence of high viremia and disease development with varying degrees of severity. Once the equines get the disease, they may die suddenly or present progressive disorders of the central nervous system. Furthermore, in humans, it causes mild to severe influenza-like symptoms, with fever and headache. Around 4–14% of cases develop neuro‐

The VEE complex contains a number of virus, belonging to the *Alphavirus* genus of the Togaviridae family, which have been classified into six viral subtypes, ranging from I to VI. VEE virus are present in all continents and most often are transmitted by the bite of infected *Culex* (*C. vomerifer*, *C. pedroi*, *C. adamesi*) and *Aedes* (*A. taeniorhynchus*) mosquito vectors and can also be transmitted through aerosols [21]. Although virtually any mosquito can be found infected with VEE virus during epizootics, it is thought that *A. taeniorhynchus* is the main vector responsible for transmitting VEE virus during outbreaks, whereas *Culex* mosquitoes species transmitted enzootic virus strains of VEE [22]. Subcutaneous injection, nasal instillation, and contact with broken skin or bedding contaminated animals are other ways to spread the virus,

Epizootic and enzootic strains of VEE virus spread from northern Argentina to Florida and parts of the Rocky Mountains, being more frequent in northern South America. Since 1930, there have been 21 outbreaks of VEE throughout the American continent, being considered an emerging disease naturally due to mutations of the enzootic and endemic virus strains that circulate as a vector-borne disease among mammals host populations, especially in habitats such as forests and wetlands [24]. Some of the strategies used to reduce outbreaks of VEE in horses are through the implementation of the TC-83 vaccine and by protecting against mosquitoes by wearing protective clothing and/or insecticides. Although, the TC-83 vaccine is used in laboratories, there is still no licensed vaccine available to humans for the prevention

to another.

114 Insecticides Resistance

vectors [19].

**2.4. Venezuelan equine encephalitis**

especially in a lab environment [23].

of infection by the epizootic strains of VEE virus [25].

logical complications and near 1% of reported cases die [20].

Japanese encephalitis (JE) is a viral disease transmitted to humans by mosquitoes of the *Aedes* and *Culex* genera, where main vectors are *C. tritaeniorhynchus*, *C. annulus*, *C. annulirostris*, *C. vishnui*, *C. fuscocephala*, and *C. gelidus* [26]. This disease affects horses, donkeys, pigs, and humans. Due to low qualifications and shorter duration of the viremia, humans or horses transmit the virus to other biting mosquitoes and are considered as terminal hosts [27]. The reservoirs of JE virus are pigs and wild birds. The incubation period is around 4–14 days. In pigs, JE causes reproductive losses (stillbirths and abortions), in horses, it causes encephalitis, and in humans, the disease can range from very serious to no symptoms. Neurologic sequelae occur in up to 80% of human cases and about 15,000 deaths annually [28].

JE is distributed across several areas of temperate and tropical Asia, with a higher incidence in rural areas of Southeast Asia, the Indian subcontinent and parts of Northern Asia. It also occurs, but less frequently in Japan, Taiwan, Singapore, Hong Kong, eastern Russia, and Australia [29]. Although the virus affects all age-groups, regions where there have been widespread childhood vaccination campaigns against the disease, the age distribution has changed, increasing the proportion of cases in older children and adults [27]. Therefore, the best alternative for control of JE it is the application of the vaccine, which is associated with the generation of neutralizing antibodies.

#### **2.6. Lymphatic filariasis**

Lymphatic filariasis, also know elephantiasis, is a parasitic disease caused by nematodes of the *Filarioidea* family, which is transmitted to humans by mosquitoes of the genus *Anopheles*, *Culex*, *Aedes*, and *Mansonia*, which inject various nematode larvae while feed on blood [30]. The disease is present in sub-Saharan Africa and Southeast Asia. It is a chronic parasitic disease in which adult worms lodge in the lymphatic vessels where they release microfilariae from the bloodstream. Filariasis can produce a wide variety of clinical manifestations whose symptoms include fever, lymphadenitis, and retrograde lymphangitis and thickening of the skin and underlying areas, caused by obstruction of the lymphatic system by the parasite. Although, the mortality associated with filariasis is low, the social and health consequences generated by their chronic manifestations are important because they cause severe disability in those subjects who suffer (blindness, deformities), which gives rise to a decrease in working capacity and in the economy [30]. Filariasis is classified as a neglected disease by the World Health Organization due to the limited investment by pharmaceutical companies for research into new treatments and the low professional interest on the part of health personnel in the countries of first world [31]. Against lymphatic filariasis, a combination of two drugs alben‐ dazole and ivermectin is used [32]

#### **2.7. Rift Valley fever**

The disease is caused by the Rift Valley fever virus, an RNA virus belonging to the *Bunyavir‐ idae* genus of the Phlebovirus family. The Rift Valley fever (RVF) is a peracute or acute, febrile, mosquito-borne disease that causes fever of viral origin that affects domestic animals like cows, buffaloes, sheep, goats, camels, and humans [33]. The route of transmission of the disease commonly is associated with mosquito-borne epidemics during the rainy season. RVF has been isolated from more than 30 mosquito species, of which it is considered that the *Aedes* and *Culex* genera are the main disease vectors [34]. The presence of RVF virus has been detected in most countries of East, West, and Southern parts of the African continent, being the disease endemic in Southern and Eastern Africa, but also epidemics have been reported in Egypt, Saudi Arabia, and Yemen [35]. The high genetic diversity observed in the RVF virus in the East, West, and Southern Africa shows the ancestral origin of the disease for these regions. Further, since outbreaks found outside these African regions have limited genetic diversity, these outbreaks are the result of the introduction of a single strain of the virus from the center of Africa, followed by its spread by mosquitoes between the vulnerable animal and human population [36]. Most cases of this disease occur in veterinarians, slaughterhouse workers, laboratory personnel, and other employees who work directly with blood and tissues of animals. Therefore, an inacti‐ vated vaccine is available against this disease; nevertheless, it is only available to laboratory personnel and veterinarians not being yet available to general public.

#### **2.8. West Nile fever**

West Nile fever (WNF) is transmitted to humans through the bite of *Culex* and *Aedes* mosqui‐ toes vectors of West Nile virus (WNV). This disease can affect birds, horses, and humans causing an unapparent infection, mild febrile illness, meningitis, encephalitis, an acute poliomyelitis-like syndrome, or death [37]. WNV is a member of the genus *Flavivirus* in the Flaviviridae family. This arbovirus is maintained in nature by cycling between several bird species and mosquitoes that support the WNV replication. The resulting symptoms of WNV is variable, and the disease does not cause obvious signs in some species but often kills them after suffering a fatal systemic disease in other species [38]. Among mammals, the cyclical disease occurs mainly in horses and humans. In horses, this disease is characterized by the presence of ataxia ranging from mild to severe, besides presenting weakness, muscle twitching, and cranial nerve deficits [39]. The mortality rate is about one in three clinically affected horses unvaccinated [40]. In humans, most infection cases are asymptomatic and are usually mild and flulike if symptoms occur. The development of severe disease characterized by neurological signs and appears to be rare in most outbreaks. However, since the 1990s, this situation changed since the WNV became an important human and veterinary pathogen. WNV has a broad geographic range that includes portions of Europe, Asia, Africa, Australia (Kunjin virus), and North, Central, and South America. The incubation period of this disease ranges from 3 to 14 days with severe symptoms, in one of every 150 people infected. Symptoms may last from a few days to several weeks and have reported that approximately 80% of infected people show no symptoms at all. Although all persons are able to acquire the WNV, people older than 50 years are at higher risk of developing more severe forms of the disease. Over the past decade, the understanding gained about the clinical spectrum of the disease as well as the short- or long-term associated with human WNV infection has been substantially increased. Presently, a vaccine is available only for horses, but not for humans.[41].

#### **2.9. Chikungunya fever**

buffaloes, sheep, goats, camels, and humans [33]. The route of transmission of the disease commonly is associated with mosquito-borne epidemics during the rainy season. RVF has been isolated from more than 30 mosquito species, of which it is considered that the *Aedes* and *Culex* genera are the main disease vectors [34]. The presence of RVF virus has been detected in most countries of East, West, and Southern parts of the African continent, being the disease endemic in Southern and Eastern Africa, but also epidemics have been reported in Egypt, Saudi Arabia, and Yemen [35]. The high genetic diversity observed in the RVF virus in the East, West, and Southern Africa shows the ancestral origin of the disease for these regions. Further, since outbreaks found outside these African regions have limited genetic diversity, these outbreaks are the result of the introduction of a single strain of the virus from the center of Africa, followed by its spread by mosquitoes between the vulnerable animal and human population [36]. Most cases of this disease occur in veterinarians, slaughterhouse workers, laboratory personnel, and other employees who work directly with blood and tissues of animals. Therefore, an inacti‐ vated vaccine is available against this disease; nevertheless, it is only available to laboratory

West Nile fever (WNF) is transmitted to humans through the bite of *Culex* and *Aedes* mosqui‐ toes vectors of West Nile virus (WNV). This disease can affect birds, horses, and humans causing an unapparent infection, mild febrile illness, meningitis, encephalitis, an acute poliomyelitis-like syndrome, or death [37]. WNV is a member of the genus *Flavivirus* in the Flaviviridae family. This arbovirus is maintained in nature by cycling between several bird species and mosquitoes that support the WNV replication. The resulting symptoms of WNV is variable, and the disease does not cause obvious signs in some species but often kills them after suffering a fatal systemic disease in other species [38]. Among mammals, the cyclical disease occurs mainly in horses and humans. In horses, this disease is characterized by the presence of ataxia ranging from mild to severe, besides presenting weakness, muscle twitching, and cranial nerve deficits [39]. The mortality rate is about one in three clinically affected horses unvaccinated [40]. In humans, most infection cases are asymptomatic and are usually mild and flulike if symptoms occur. The development of severe disease characterized by neurological signs and appears to be rare in most outbreaks. However, since the 1990s, this situation changed since the WNV became an important human and veterinary pathogen. WNV has a broad geographic range that includes portions of Europe, Asia, Africa, Australia (Kunjin virus), and North, Central, and South America. The incubation period of this disease ranges from 3 to 14 days with severe symptoms, in one of every 150 people infected. Symptoms may last from a few days to several weeks and have reported that approximately 80% of infected people show no symptoms at all. Although all persons are able to acquire the WNV, people older than 50 years are at higher risk of developing more severe forms of the disease. Over the past decade, the understanding gained about the clinical spectrum of the disease as well as the short- or long-term associated with human WNV infection has been substantially increased.

personnel and veterinarians not being yet available to general public.

Presently, a vaccine is available only for horses, but not for humans.[41].

**2.8. West Nile fever**

116 Insecticides Resistance

Chikungunya fever is a viral disease, manifested by fever and severe arthralgia, prevalent in Africa, Asia, and Europe, and now emerging and little studied in the Americas and the Caribbean Islands since 2013 [42]. Chikungunya virus is transmitted to humans by *Aedes* vectors. There are two main vectors *A. aegypti* and *A. albopictus*, which are present in the tropics and temperate zones. Although *A. aegypti* has always been the main vector transmitter of the disease, in most recent outbreaks, *A. albopictus* has become the main vector. Chikungunya word comes from the makonde dialect spoken by an ethnic group of southeast Tanzania and northern Mozambique, which means the man who walks hunched over, due to the appearance shown by patients due to the severity of joint pain that they suffer [43].

The Chikungunya virus is an enveloped positive-strand RNA virus, belonging to the *Alpha‐ virus* genus, group arbovirus A, of the Togaviridae family. The virus affects all humans without distinction, being susceptible to contracting the disease individuals not previously infected with the virus, after individuals are infected, immunity is prolonged. Chikungunya fever epidemics spread rapidly within infected community until the development of immunity in the population affected stops transmission. In general, about 3–28% of infected people are asymptomatic, although they contribute to the spread of the disease. On the other hand, in the symptomatic forms, the clinical manifestations may be acute, subacute, or chronic. After the bite, the incubation period of the disease is 1–12 days characterized by fever, severe arthralgias, back pain, incapacitating myalgia, and conjunctivitis. Subsequently, after 2 or 3 days, macu‐ lopapular exanthem is described (sometimes only macular) in half of the cases, distributed on the trunk and extremities. Fever usually takes between 2 and 3 days, and leukopenia is the rule. Since there is no specific antiviral treatment or vaccine, treatment against the disease should be symptomatic against the symptoms presented by the patient and can be applied antipyretics, analgesics, anti-inflammatory, and ribavirin [44].

#### **2.10. St. Louis encephalitis**

St. Louis encephalitis (SLE) is a viral disease transmitted by mosquitoes of the *Culex* genus, where birds are the normal hosts of this disease that affects humans. Other potential vectors, which can become infected and transmit the SLE to vertebrate hosts, include the mosquito species of the *Aedes*, *Mansonia*, and *Sabethes* genera [45]. The SLE is a disease of greatest medical importance in North America prior the introduction of WNV in 1999. According to studies conducted in the United States, the sparrow has a key role in the chain of infection, and doves, blue jay, and robin are important too, being the young of these species most important that adults [6]. The SLEV may be enzootic in some places but eventually can occur epizootic in which a large number of birds become infected, also being able to cause infections in humans as isolated cases or epidemics, by the bite of mosquitoes infected with the virus. Under optimal conditions, the extrinsic incubation period of the virus is about 10 days, staying active throughout the life of the mosquito. Human infections with SLEV not always result in clinical manifestations of encephalitis, which is why it often goes unnoticed, except during epidemics [46]. The most susceptible population is of children and the elderly, and the mortality rate of SLE is between 5% and 20%. Currently, SLE is widely distributed throughout American continent, from Canada, Mexico, Central and South America, and the Caribbean [6]. To date, a vaccine against SLE has not been developed [41] because antibiotics are not effective against this virus. Therefore, the best form of protection against the transmission of SLEV is to avoid mosquito bites as much as possible.

## **2.11. Eastern equine encephalitis**

Eastern equine encephalitis (EEE) is caused by the eastern equine encephalitis virus (EEEV), an RNA virus classified in the family Togaviridae. EEE infections are characterized by symptoms such as fever, headache, nausea and vomiting, malaise and weakness, confusion, myalgia, arthralgia, and neck stiffness. The main vector species involved in outbreaks of disease are *Coquillettidia perturbans, Culiseta melanura*, *Ochlerotatus canadensis*, *Aedes vexans*, and *Culex* mosquito's species [47]. The cycle of transmission of EEE occurs between wild birds and mosquito vectors, and when mosquitoes bit humans they transmit the virus. Disease incuba‐ tion period varies from 4 to 10 days, and the infection can result in one of two types of disease, systemic or encephalitis, depending on the age of the person and other host factors. The illness lasts one to two weeks, and recovery is complete when the central nervous system is not affected. In humans, the rate of mortality is around 3%, and many of those recovering suffer some form of mental disability for life, and death usually occurs from 2 to 10 days after onset of symptoms. EEEV is found throughout the Western Hemisphere and North America in areas of the east of the Mississippi River in the US, southeastern Canada to Argentina, and Peru. The EEE was first recognized in humans in 1938 [48]. Since then, cases have been produced sporadically as small epidemics with a total of 223 reports between 1955 and 1993 [49], including a peak of 36 cases in 1959 [50]. Of this case, the third part of the patients affected died because of the disease. The diagnosis of the symptoms of EEE is difficult because the symptoms that occur in patients are nonspecific. Currently, the only available vaccine is for horses, and there is still no human vaccine for the general public.

#### **2.12. Western equine encephalitis**

The causal agent of Western equine encephalitis (WEE) is the WEE virus (WEEV), which is an arbovirus of the Togaviridae family, transmitted by mosquitoes of the *Culex* and *Culise‐ ta* genres [51, 52], of which *Culex tarsalis* is the main vector of WEEV in western North America [53]. The natural cycle of WEEV is maintained through alternating infection between birds and ornithophilic mosquitoes. WEE primarily affects birds, mosquitoes, humans, and horses. The clinical form of WEE occurs in humans and horses, which are dead-end hosts [54]. Clinical disease can result in febrile disease of variable severity associated with neurological symptoms that range from headache to aseptic meningitis or encephalitis. The WEE has been reported in the Western United States, Canada, Mexico, and Central and South America [54]. WEEV in humans results in mild disease in adults but can become serious encephalitis in children and elderly people. The mortality rate is between 5% and 15%, of which about 50% of infants who survive have permanent brain damage. People can prevent WEE infection by avoiding outdoor activities at the primary feeding period of *Culex* and *Culiseta* mosquitoes or using mosquito repellents. For horses, a vaccine for WEE exists in the market, but there is no vaccine for humans [55].

#### **2.13. La Crosse encephalitis**

continent, from Canada, Mexico, Central and South America, and the Caribbean [6]. To date, a vaccine against SLE has not been developed [41] because antibiotics are not effective against this virus. Therefore, the best form of protection against the transmission of SLEV is to avoid

Eastern equine encephalitis (EEE) is caused by the eastern equine encephalitis virus (EEEV), an RNA virus classified in the family Togaviridae. EEE infections are characterized by symptoms such as fever, headache, nausea and vomiting, malaise and weakness, confusion, myalgia, arthralgia, and neck stiffness. The main vector species involved in outbreaks of disease are *Coquillettidia perturbans, Culiseta melanura*, *Ochlerotatus canadensis*, *Aedes vexans*, and *Culex* mosquito's species [47]. The cycle of transmission of EEE occurs between wild birds and mosquito vectors, and when mosquitoes bit humans they transmit the virus. Disease incuba‐ tion period varies from 4 to 10 days, and the infection can result in one of two types of disease, systemic or encephalitis, depending on the age of the person and other host factors. The illness lasts one to two weeks, and recovery is complete when the central nervous system is not affected. In humans, the rate of mortality is around 3%, and many of those recovering suffer some form of mental disability for life, and death usually occurs from 2 to 10 days after onset of symptoms. EEEV is found throughout the Western Hemisphere and North America in areas of the east of the Mississippi River in the US, southeastern Canada to Argentina, and Peru. The EEE was first recognized in humans in 1938 [48]. Since then, cases have been produced sporadically as small epidemics with a total of 223 reports between 1955 and 1993 [49], including a peak of 36 cases in 1959 [50]. Of this case, the third part of the patients affected died because of the disease. The diagnosis of the symptoms of EEE is difficult because the symptoms that occur in patients are nonspecific. Currently, the only available vaccine is for

The causal agent of Western equine encephalitis (WEE) is the WEE virus (WEEV), which is an arbovirus of the Togaviridae family, transmitted by mosquitoes of the *Culex* and *Culise‐ ta* genres [51, 52], of which *Culex tarsalis* is the main vector of WEEV in western North America [53]. The natural cycle of WEEV is maintained through alternating infection between birds and ornithophilic mosquitoes. WEE primarily affects birds, mosquitoes, humans, and horses. The clinical form of WEE occurs in humans and horses, which are dead-end hosts [54]. Clinical disease can result in febrile disease of variable severity associated with neurological symptoms that range from headache to aseptic meningitis or encephalitis. The WEE has been reported in the Western United States, Canada, Mexico, and Central and South America [54]. WEEV in humans results in mild disease in adults but can become serious encephalitis in children and elderly people. The mortality rate is between 5% and 15%, of which about 50% of infants who survive have permanent brain damage. People can prevent WEE infection by avoiding outdoor activities at the primary feeding period of *Culex* and *Culiseta* mosquitoes or using mosquito repellents. For horses, a vaccine for WEE exists in the market, but there

horses, and there is still no human vaccine for the general public.

mosquito bites as much as possible.

118 Insecticides Resistance

**2.11. Eastern equine encephalitis**

**2.12. Western equine encephalitis**

is no vaccine for humans [55].

La Crosse encephalitis (LAC) is a disease caused by the La Crosse encephalitis virus (LACV). LACV is spread through the bite of infected mosquitoes of the *Aedes* genus, where *A. triseria‐ tus* is the principal vector and reservoir of LACV in nature [56]. The vertebrate of the Sciuridae family are its normal hosts in forest habitats throughout the range of the disease [57]. Subse‐ quently, the virus can be passed to humans by feeding on infected rodents with the virus, or transovarially from an infected female to offspring. LACV is distributed in the United States from the upper Midwestern states, primarily Illinois, Iowa, Indiana, Minnesota, Ohio, and Wisconsin to New York, and South to Texas, Alabama, and Georgia [58], with confirmed human cases of LAC in 29 of the lower 48 states [59]. The disease affects the central nervous system being able to become severe and fatal in rare cases [57]. After an incubation period of 5–15 days, LAC symptoms include fever, headache, nausea, vomiting, and fatigue and initially presents as a nonspecific summertime illness. Severe cases involving encephalitis occur more often in children under 16 years accompanied commonly of seizures and in some cases coma, paralysis, and long-term disability or death. There is no specific treatment against LACV infection, so care is based on symptoms. The best way to reduce the risk of becoming infected with LACV is to avoid mosquito bites, use insect repellents, wear clothes to avoid bites, or even stay indoors during peak hours of mosquito activity. Another preventive measure that provides good results is to eliminate mosquito breeding sites. There is no antiviral drugs or vaccine available against the LAC because antibiotics are not effective against viruses [57].

#### **2.14. Zika fever**

Zika fever (ZIKF) is caused by Zika virus (ZIKV), a flavivirus belonging to the family Flavi‐ viridae. It is a disease of monkeys and humans spread through the bite of infected *Aedes* mosquito [60]. Where *A. africanus* and *A*. *aegypti* are the principal probable vectors [61]. Clinical symptoms are mild headache, maculopapular eruption in different parts of the body, transient fever, malaise, and joint pain. ZIKV is common in West and Central Africa but also occurs in Pakistan, India, Vietnam, Thailand, the Philippines, Malaysia, Indonesia and Micronesia. In 2014, the presence of ZIKV in some American regions was reported. There is no vaccine, drugs or specific treatment for ZIKF, so the strategies for prevention and control the disease include insect repellents and mosquito elimination [62].
