INFECTIONS BY AEDES AEGYPTI MOSQUITO
Creators: name: Aziz, Owais
name: Fatima, Zarrien
name: Khaliq, Hafiz Muhammad Haseeb
Publisher: name: Zenodo
Year: 2024

description: Species name/classification: Aedes aegypti 

Common name: Yellow fever mosquito

1. Morphological characters and similar species

Adults of Ae. aegypti are relatively small and show a black and white pattern due to the presence of white/silver scale patches on a black background on the legs and other parts of the body. However, Ae. aegypti could be mixed up with other invasive (Ae. albopictus, Ae. japonicus) or (Ae. cretinus, restricted to Cyprus, Greece, Turkey). The prevailing diagnostic character is the presence of silver scales in a shape of a lyre on a black background on the scutum (dorsal part of the thorax). The domestic form (Ae. aegypti aegypti) is paler than its ancestor (Ae. aegypti formosus) and has white scales on the first abdominal tergite (1). 

1.1 Seasonal abundance

Ae. aegypti is active throughout the year, with a peak in abundance from August to October.

1.2 Voltinism (generations per season)

Multivoltine

1.3 Host preferences (e.g. birds, mammals, humans)

Aedes aegypti prefer mammalian hosts and will preferentially feed on humans, even in the presence of alternative hosts. They also feed multiple times during one gonotrophic cycle (feeding, egg-producing cycle). Which has implications for disease transmission (2).

1.4 Aquatic/terrestrial habitats

Historically, Ae. aegypti was found in forested areas, using tree holes as habitats. As an adaptation to urban domestic habitats, it is nowadays exploiting a wide range of artificial containers such as vases, water tanks and tyres. It is also found utilising underground aquatic habitats, such as septic tanks, and adapting to use both indoor and outdoor aquatic container habitats in the same area. Adaptation to breeding outdoors may allow for increased population numbers and difficulty in implementation of control methods. A study in Brazil found high numbers of eggs in oviposition sites close to human populations. Eggs which are laid on or near the water surface are resistant to desiccation (3).

1.5 Biting/resting habits

The domestic form is often not found further than 100m from human habitations although some studies have shown that breeding habitats can also be found away from human dwellings. Aedes aegypti prefer human habitations as they provide resting and host-seeking possibilities and as a result will readily enter buildings. Their activity is both diurnal and crepuscular (4).

1.6Epidemiology and transmission of pathogens

Aedes aegypti is known to transmit dengue virus, yellow fever virus, chikungunya virus, and Zika virus (4).

2.1 Chikungunya

Aedes aegypti is the principle vector of chikungunya virus(Ojeda Rodriguez et al., n.d.). Aedes aegypti has been involved in virtually all chikungunya epidemics from Africa, India and other countries in Southeast Asia. They caused an outbreak of chikungunya virus in Kenya (2004) and the Comoros islands (2005) where in the latter, 63% of the population was affected. 

A recent entomological investigation following an outbreak of chikungunya virus in Yemen (2010/2011) revealed the presence of chikungunya virus in field collected Ae. aegypti in the outbreak area (4). 

2.1.1 Definition

            The virus is known for causing an acute febrile illness, rash, and arthralgia known as Chikungunya fever followed by potentially chronic and debilitating arthritic symptoms that may last for months or years.

            The most common symptoms of CHIKV infection are fever, headache, rash and polyarthralgia, the virus appears to present tropism for the nervous system in the ocular tissue. In fact, eye alterations are recognized as important complications of Chikungunya fever (5).

2.1.2 Pathophysiology

There are two methods by which CHIKV transmit, one is Urban mode in which the transmission path is human to mosquito to human, other is sylvatic transmission in which path is animal to mosquito to human (6). 

 

 

2.1.3 Pathology

The route of infection used by CHIKV starts after inoculation and infection of human epithelial and endothelial cells, primary fibroblasts, and monocyte-derived macrophages. After an initial immune response and sheltering in the lymph nodes, CHIKV travels through the lymphatic and circulatory system causing significant viremia. Transportation into target organs (muscles, joints, liver, and brain) has been found to be caused by infected monocyte-derived macrophages. Inflammatory reaction mediated by CD8+ (acute), CD4+ T lymphocytes, and pro-inflammatory cytokines are thought to be responsible for the acute symptoms, while a persistent reservoir of infected monocytes in the joints may be responsible for chronic joint disease (7).

2.2 Dengue

Aedes aegypti is the primary vector of dengue. All four dengue serotypes have been isolated from field-collected Ae. Aegypti (7). 

Aedes aegypti has long been recognised as a vector of dengue, causing major dengue fever epidemics in the Americas and South East Asia. Global incidence of dengue has also increased in the past 25 years. 

Arbovirus is the cause of dengue fever (disease) according to WHO (World Health Organization) this term of arbovirus is refer to such diseases which are spread by arthropods (arthropods borne diseases) i.e. mosquitos, flies etc (7). 

Taxonomy of Dengue virus (DENV) is, Family Flaviviridae; Genus Flavivirus; Dengue Virus has four different serotypes (DENV1-4) (Salles et al., 2018). DENV infection is a major cause of disease in tropical and subtropical areas, with an estimated 50 million infections occurring each year and more than 2.5 billion people being at risk of infection (Martina et al., 2009). Infection with any of the DENV serotypes may be asymptomatic in the majority of cases or may result in a wide spectrum of clinical symptoms, ranging from a mild flu-like syndrome (known as dengue fever [DF]) to the most severe forms of the disease, which are characterized by coagulopathy, increased vascular fragility, and permeability (dengue hemorrhagic fever [DHF]). The latter may progress to hypovolemic shock (dengue shock syndrome [DSS]). In Asia the risk of developing severe disease is greater in DENV-infected children ( £15 years) than in adults (7).

2.2.1 Pathology

Cell and tissue tropism of DENV may have a major impact on the outcome of DENV infections. In vitro data and autopsy studies suggest that three organ systems play an important role in the pathogenesis of DHF/DSS: the immune system, the liver, and endothelial cell (EC) linings of blood vessels. The tropism of DENV for cells of the respective systems, the corresponding pathological effects of DENV infection of these systems, and the relevance of these events for the overall pathogenesis of DENV infection will be described.

Cells of the immune system. During the feeding of mosquitoes on humans, DENV is presumably injected into the bloodstream, with spillover in the epidermis and dermis, resulting in infection of immature Langerhans cells (epidermal dendritic cells [DC]), and keratinocytes. Infected cells then migrate from site of infection to lymph nodes, where monocytes and macrophages are recruited, which become targets of infection. Consequently, infection is amplified and virus is disseminated through the lymphatic system. As a result of this primary viremia, several cells of the mononuclear lineage, including blood-derived monocytes (59), myeloid DC, and splenic and liver macrophages are infected. DENV has also been shown to have tropism for circulating mononuclear cells in blood and for cells residing in the spleen, lymph nodes, and bone marrow. Leukocytes also have been shown to be infected with DENV in experimentally infected nonhumans primates. It should be noted that during secondary infections with heterologous DENV, high concentrations of DENV-specific immunoglobulin G (IgG) will complex newly produced virus that adheres to and is taken up by mononuclear cells. Following infection, mononuclear cells predominantly die by apoptosis, while abortively infected or bystander DC are stimulated to produce the bulk of mediators that are involved in inflammatory and hemostatic responses of the host. In this regard, factors that influence the amount of target cells infected, and consequently the levels of viremia, may determine the ratio of different proinflammatory and anti-inflammatory cytokines, chemokines, and other mediators, as well as the way in which the inflammatory response affects the hemostatic system. Bone marrow stromal cells have also been shown to be susceptible to infection with DENV (8).

2.2.2 Organ pathology 

The presence of DENV in cells in the skin, liver, spleen, lymph node, kidney, bone marrow, lung, thymus, and brain are reported by researchers. In general, the presence of DENV in several organs was not associated with gross or microscopic evidence of severe organ pathology, which agrees with the pathogenesis of DHF/DSS. 

The liver is commonly involved in DENV infections in humans as there is an association between elevated liver enzyme levels and spontaneous bleeding tendencies. Cases of dengue-associated hepatitis have been described, which were characterized by moderate midzonal hepatocyte necrosis, microvesicular steatosis, and councilman bodies.

Although DENV was found in a significant proportion of human hepatocytes and Kupffer cells, little inflammation was seen within the liver, indicating that much of the observed apoptosis and necrosis was virally induced. The higher prevalence of apoptosis over necrosis could explain the limited inflammation seen in the liver, a picture similar to what is observed in the early phase of yellow fever or Rift Valley fever.  Although severe hepatic damage is not common in DENV infections, elevated liver enzymes suggest that the liver is affected, but the role of hepatic damage in coagulopathy and disease severity remains to be established (9). 

2.3 Yellow fever

Yellow fever is maintained in sylvatic cycle between monkeys and mosquitoes of Aedes or Haemagogus genera. Aedes aegypti is the vector involved in urban yellow fever transmission where only human is the amplifying host. Aedes aegypti has been shown to transmit yellow fever virus to F1 progeny under laboratory conditions and field collection studies have also confirmed this in nature (10).

2.3.1 Definition

            Yellow fever can present with varying clinical features ranging from a self-limited, mild febrile illness to severe hemorrhage and liver disease. The “yellow” comes from jaundice that affects some patients with severe disease.

2.3.2 Epidemiology

            Vaccination has decreased worldwide epidemics of yellow fever, but the infection has reemerged in many parts of Africa and South America. No one is immune from yellow fever, and it occurs in people of all ages and races. The highest mortality rates are reported in infants and the elderly, who often have depressed immune systems. Most cases are diagnosed in unvaccinated travelers to sub-Saharan Africa or South America (11). 

2.3.3 Pathophysiology

The incubation period is 3 to 6 days. Once acquired, the virus quickly spreads to multiple organs in the body. The liver is the most important organ affected by yellow fever. It produces profound jaundice due to liver damage. The kidneys also undergo similar pathological alterations and can lead to acute renal failure. When the upper gastrointestinal (GI) tract is involved, the gastric acid mixed with blood produces what is known as black vomit. Central nervous system (CNS) features include cerebral edema and hemorrhage. Encephalopathy is also a common feature of yellow fever (12).

2.3.4 Pathology

·                Midzonal hepatitis (can extend to periportal area and centrilobular area in patients with severe and prolonged disease, treated in intensive care)

·                Apoptotic (Councilman bodies) and steatotic hepatocytes

·                Minimal inflammatory reaction in the liver, mainly located in portal area

·                Hyperplasia of Kupffer cells; hemophagocytosis can be seen

·                Villela bodies: bright ochre colored bodies in Kupffer cells, mainly in the midzone; these granular bodies are believed to result from disintegration of Councilman bodies and bile pigment in the cytoplasm of Kupffer cells

·                Torres bodies: eosinophilic intranuclear inclusion, rarely observed in human YF; it is a cytopathic change induced by YFV in the hepatocytes, commonly seen in Rhesus monkeys (experimental YF)

·                Regeneration and ductular reaction are not common in fatal cases

·                Preserved reticulin framework even in fulminant cases

·                Other organs: direct damage caused by the YFV (kidneys, spleen and heart); congestion and hemorrhages; lesions due to ischemic hypoxic injury and secondary infections

·                Livers in yellow fever related orthotropic liver transplantation show similar histological findings (infection of the graft), with more extensive ischemic lesions (13).

2.3.5. Treatment / Management

Yellow fever is a reportable infection. Once the virus is contracted, symptoms develop after 3 to 6 days. There is no specific treatment, but severe cases require aggressive supportive care and hydration. Patients should be managed in the intensive care unit (ICU) and closely monitored for disseminated intravascular coagulation (DIC), hemorrhage, kidney, and liver dysfunction. Coagulopathy is managed with fresh frozen plasma, and renal failure may require dialysis. Even though yellow fever is not transmitted from person to person, isolation of the individual should be undertaken until the diagnosis is confirmed. Universal precautions are required when looking after patients with yellow fever although person-person transmission of the virus is unlikely. Infected patients should avoid mosquitoes, as they may transmit the virus to mosquitoes, which can serve as vectors for infection other patients.

Since there is no effective treatment or vaccine, prevention is critical. This is best accomplished by avoiding mosquito bites entirely. Even very short periods outdoors can lead to exposure to mosquito bites, so people should wear proper protective clothing. This protection includes long sleeves, long pants, socks, and closed-toe shoes. Pant legs can be tucked into socks to prevent bites to exposed ankles. Transmission is common during the warmer months, and mosquitoes may bite through very thin clothing, so treating clothing with repellents containing permethrin, DEET, oil of lemon eucalyptus, or other EPA-registered insect repellants will reduce this risk. Permethrin should not be applied directly to the skin, but when applied to clothing, it provides protection even after the clothing is washed.

Transmission is most frequent when mosquitoes feed, between dawn and dusk, so outdoor activities during this period should be avoided. However, one of the mosquitos responsible for transmitting the virus, Aedes Aegypty, feeds during the daytime; so there is no safe time during the day for a traveler without repellent and wearing protective clothing.

Travelers should sleep in air-conditioned spaces or use mosquito nets or screens to prevent bites during sleep. Standing water is a breeding ground for mosquitoes, so flowerpots, buckets, and other containers should be drained. Children’s wading pools should be emptied and stored on their sides, and tire swings should have holes drilled into the bottom to allow trapped water to drain.

There is a safe and highly effective live-attenuated vaccine available to prevent yellow fever. A single dose confers lifelong immunity and is effective within 30 days for 99% of patients. Patients with relative contraindications to live attenuated vaccine who plan to travel to endemic areas should review the recommendations for vaccination prior to travel (14).

2.4 Zika virus

Zika virus is maintained in a sylvatic cycle involving non-human primates and a wide variety of sylvatic and peri-domestic Aedes mosquitoes. Aedes aegypti is considered the most important vector for Zika virus transmission to humans. Aedes aegypti mosquitoes were found infected in the wild. 

Zika virus is a single-stranded RNA virus of the family and the genus Flavivirus. In the majority of people, infection by the Zika virus is mild and self-limiting (15).

2.4.1 Etiology

Diseases caused by Zika virus are predominately arboviral and transmitted by the bite of female Aedes aegypti and Aedes albopictus mosquitoes. Person-to-person contact (e.g., sexual contact), blood transfusion, organ transplantation, and perinatally (maternal-fetal vertical transmission) may also transmit infection .

2.4.2 Pathophysiology

The Zika virus is transmitted by the Aedes mosquito and several other Aedes species. Besides a mosquito bite, the virus can also be transmitted sexually.

            Zika virus infection should be considered if the patient has a history of recent travel to an area with suspected Zika virus transmission or a sexual partner with recent travel to such an area. The duration of infectivity of bodily fluids following infection is unknown. However, Zika virus has been cultured from semen up to 90 days after symptom onset, and viral RNA has been detected in blood after 58 days and in semen up to 188 days. Most patients with acute Zika virus infections are either asymptomatic (60% to 80%) or have only mild symptoms.

For Zika disease due to a mosquito bite, the estimated incubation phase between bite and symptoms is two to 14 days. In symptomatic infections, the most common symptoms\signs include: rash (90% or more), conjunctivitis (55% to 82%), fever (65% to 80%), and headache (45% to 80%). The rash is typically maculopapular, and the fever is often low grade, and short-lived. Other common symptoms and signs include arthralgia (65% to 70%, myalgia (48% to 65%), and retro-orbital pain (39% to 48%). Less commonly seen are edema, vomiting, and abdominal pain. In areas with dengue fever and chikungunya, which have many symptoms and signs in common, it may be difficult to diagnose the etiology of the illness correctly. Conjunctivitis and rash more commonly are seen in Zika virus infections than dengue fever and chikungunya.

An increase in cases of the acute Guillain-Barre syndrome (a type of acute paralytic neuropathy) was observed during the French Polynesia outbreak. Although not proven to be the cause, it is suspected that Zika virus infection is likely a trigger of Guillain-Barre syndrome. Cases of acute myelitis and meningoencephalitis have also been reported following Zika virus infection. A complete neurologic examination is recommended when Zika virus is suspected.

Zika virus infection during pregnancy is the cause of a variety of congenital disabilities, including microcephaly and other brain abnormalities. For any women of reproductive age and areas conducive to possible Zika virus infection, the patient’s pregnancy status and short-term reproductive plans should be determined (11).

2.4.3 Treatment / Management

As noted, most cases of Zika virus disease is asymptomatic or mild. Treatment is supportive, encouraging rest, maintaining adequate hydration and the use of analgesics and antipyretics. If dengue fever is a possible etiology of the patient’s symptoms, aspirin and other nonsteroidal anti-inflammatory drugs should be avoided due to the hypothetical risk of hemorrhage and Reye syndrome. Individuals with Zika infection should be protected from mosquito exposure to reduce the risk of local transmission (16).

 

 

Reference:

 

1.         Sarwar MS, Jahan N, Ali A, Yousaf HK, Munzoor I. Establishment of Wolbachia infection in Aedes aegypti from Pakistan via embryonic microinjection and semi-field evaluation of general fitness of resultant mosquito population. Parasites & Vectors. 2022;15(1):191.

2.         Santos MC, Viana JL, Monteiro JD, Freire RC, Freitas DL, Câmara IM, et al. Infrared spectroscopy (NIRS and ATR-FTIR) together with multivariate classification for non-destructive differentiation between female mosquitoes of Aedes aegypti recently infected with dengue vs. uninfected females. Acta Tropica. 2022;235:106633.

3.         Ross PA, Robinson KL, Yang Q, Callahan AG, Schmidt TL, Axford JK, et al. A decade of stability for wMel Wolbachia in natural Aedes aegypti populations. PLoS pathogens. 2022;18(2):e1010256.

4.         Reitmayer CM, Levitt E, Basu S, Atkinson B, Fragkoudis R, Merits A, et al. Mimicking superinfection exclusion disrupts alphavirus infection and transmission in the yellow fever mosquito Aedes aegypti. Proceedings of the National Academy of Sciences. 2023;120(37):e2303080120.

5.         Merkling SH, Crist AB, Henrion-Lacritick A, Frangeul L, Couderc E, Gausson V, et al. Multifaceted contributions of Dicer2 to arbovirus transmission by Aedes aegypti. Cell Reports. 2023;42(8).

6.         Mehmood N, Hassan A, Zhou W, Usman HM, Ai H, Huang Q. Behavioural alterations in female Aedes aegypti mosquito in response to entomopathogenic fungal infections. Pest Management Science. 2022;78(5):2065-73.

7.         Logan RA, Quek S, Muthoni JN, von Eicken A, Brettell LE, Anderson ER, et al. Vertical and horizontal transmission of cell fusing agent virus in Aedes aegypti. Applied and Environmental Microbiology. 2022;88(18):e01062-22.

8.         Leandro AS, de Castro WAC, Lopes RD, Delai RM, Villela DA, De-Freitas RM. Citywide integrated Aedes aegypti mosquito surveillance as early warning system for arbovirus transmission, Brazil. Emerging Infectious Diseases. 2022;28(4):707.

9.         Chotiwan N, Brito-Sierra CA, Ramirez G, Lian E, Grabowski JM, Graham B, et al. Expression of fatty acid synthase genes and their role in development and arboviral infection of Aedes aegypti. Parasites & vectors. 2022;15(1):233.

10.       do Nascimento RM, Campolina TB, Chaves BA, Delgado JLF, Godoy RSM, Pimenta PFP, et al. The influence of culture-dependent native microbiota in Zika virus infection in Aedes aegypti. Parasites & Vectors. 2022;15(1):57.

11.       Alomar AA, Alto BW. Temperature-mediated effects on Mayaro virus vector competency of Florida Aedes aegypti mosquito vectors. Viruses. 2022;14(5):880.

12.       Gómez M, Martinez D, Muñoz M, Ramírez JD. Aedes aegypti and Ae. albopictus microbiome/virome: new strategies for controlling arboviral transmission? Parasites & Vectors. 2022;15(1):1-13.

13.       Erb SM, Butrapet S, Roehrig JT, Huang CY-H, Blair CD. Genetic Adaptation by Dengue Virus Serotype 2 to Enhance Infection of Aedes aegypti Mosquito Midguts. Viruses. 2022;14(7):1569.

14.       Egid BR, Coulibaly M, Dadzie SK, Kamgang B, McCall PJ, Sedda L, et al. Review of the ecology and behaviour of Aedes aegypti and Aedes albopictus in Western Africa and implications for vector control. Current research in parasitology & vector-borne diseases. 2022;2:100074.

15.       Dong S, Dimopoulos G. Aedes aegypti Argonaute 2 controls arbovirus infection and host mortality. Nature communications. 2023;14(1):5773.

16.       Algamdi AG, Shaher FM, Mahyoub JA. Biological comparative study between Wolbachia-infected Aedes aegypti mosquito and Wolbachia-uninfected strain, Jeddah city, Saudi Arabia. Saudi Journal of Biological Sciences. 2023;30(3):103581.