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Contributor Information

Author

Arlo Pelegrin, BA, MSc
Entomologist

Disclosure: Arlo Pelegrin, BA, MSc, has disclosed no relevant financial relationships.

Reviewer

Bret A Nicks, MD, MHA, FACEP
CMO, Davie Medical Center
Associate Dean, Global Health
Director, EM Global Health Fellowship
Associate Professor, Emergency Medicine
Wake Forest Baptist Health
Winston-Salem, North Carolina

Disclosure: Bret A Nicks, MD, MHA, FACEP, has disclosed no relevant financial relationships.

Editor

Olivia Wong, DO
Section Editor
Medscape Drugs & Diseases
New York, New York

Disclosure: Olivia Wong, DO, has disclosed no relevant financial relationships.

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6 Mosquito-Borne Illnesses

Arlo Pelegrin, BA, MSc  |  March 15, 2016

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Slide 1

Most people flinch at the buzz of a mosquito near the ear, and for good reason. These small delicate insects are, at best, a summer nuisance whose calling card is an infuriating itchy bump. At their worst, mosquitoes can be deadly. They deploy an array of highly-refined sensory and locomotor tools that enable them to successfully attack humans.[1,2] In doing so, mosquitoes transmit a variety of microbes and viruses that may cause immeasurable human suffering.[3]

Image of a female Aedes aegypti mosquito obtaining a blood meal from a human host courtesy of the Centers for Disease Control and Prevention (CDC)/James Gathany.

Slide 2

Mosquito Bite–Related Mortality

Deaths resulting from mosquito bites outnumber all other animal-related deaths combined. A staggering more than 1 million people die each year from diseases transmitted by mosquitoes.[5] In addition to mortality, mosquito-borne vectors are responsible for the suffering of hundreds of millions of people. Each year, an estimated 700 million people are infected by mosquito bites, with almost all serious cases of mosquito-borne illnesses occurring in developing countries.[6]

Image courtesy of Medscape. Data sources: American Mosquito Control Association (AMCA)[5]; Lozano R, Naghavi M, Foreman K, et al. Lancet. 2012;380(9859):2095-128. PMID: 23245604[7]; and Kasturiratne A, Wickremasinghe AR, de Silva N, et al. PLoS Med. 2008;5(11):e218. PMID: 18986210.[8]

Slide 3

Mosquitos Basics

Mosquitoes (family Culicidae) are related to flies, gnats, crane flies, and midges.[9,10] They can usually be distinguished with the naked eye by the obvious presence of a long proboscis and, microscopically, by the abundance of scales on their bodies. Over 3500 mosquito species have been described,[11] most of which are harmless. Although several hundred species are capable of transmitting disease, only a handful are responsible for the major mosquito-related illnesses.

Despite their fragile and delicate appearance, mosquitoes are in fact extremely capable survivors. They lay their eggs in pools of stagnant water, where the larvae (top left) use comblike mouthparts to glean nourishment from algae, bacteria, and other minuscule organisms.[11] The air-breathing larva is equipped with a snorkel-like breathing tube coated in waxy hydrofuge hairs on the tip of its tail, so it can thrive in dirty and hypoxic water.[12] The comma-shaped pupae (bottom left) also breathe through snorkels and, unusually for pupating insects, retain the ability to move, ducking below the water if alarmed. Adults (right) emerge directly from the water surface.[11] Mosquitoes are excellent at airborne maneuvers, able to beat their wings up to 500 times per second.[13]

Images of a Culex quinquefasciatus mosquito larva (top left) and an adult flying female A aegypti mosquito (right) courtesy of the CDC and CDC/James Gathany, respectively; image of a mosquito pupa (bottom left) courtesy of M Phillis/Haslemere Natural History Society.

Slide 4

Only female mosquitoes are blood-feeders.[13] They find their prey by visual recognition and by several types of odor and carbon dioxide (CO2) receptors on the antennae and palps.[1,13,14]

The feeding tube is a conglomeration of paired, specialized appendages.[15] The labium is a scaly support sheath that bends during feeding. The mandibles and maxillae are thin and wiry, tipped with bladelike teeth for carving a hole into the host integument. The flexible hypopharynx is a two-way tube inserted into the host tissue.[15] Once a host blood vessel is located, blood is pumped out and mosquito saliva is pumped in. The saliva contains many inhibitors that prevent blood coagulation, platelet aggregation, host immunity, inflammation, and other host defense processes.[16] Pathogens are also transmitted with the saliva. Infected mosquitoes spend more time searching for a blood vessel, and consequently injecting saliva, than noninfected mosquitoes do.[17]

Image courtesy of Martin Heigan.

Slide 5

The typical mosquito bite causes an elevated pruritic wheal surrounded by inflamed flare.[18,19] Left alone, the lesion usually disappears within a couple of days, but relentless scratching can create an enlarged wheal or tear the epidermis and leave the victim vulnerable to secondary infections.[20]

Reactions to mosquito bites vary in severity from person to person.[20] In themselves, however, such bites are rarely more than an irritation.[18,20]

Image courtesy of DermNet NZ.

Slide 6

Aedes Aegypti

Although there are hundreds of mosquito species that feed on human blood, two species, A aegypti (shown) and Aedes albopictus, are responsible for the transmission of numerous arboviruses.[21] A aegypti, the yellow fever mosquito, originated in Africa, and A albopictus, the Asian tiger mosquito, originated in Asia, but both species have expanded to new geographic locations and become cosmopolitan.

In addition to yellow fever, A aegypti is the primary vector for transmitting dengue fever, Zika virus, and chikungunya virus,[22] as well as several other viral pathogens. A albopictus also transmits dengue fever, Zika virus, and chikungunya.[21,23,24]

Image courtesy of the CDC/James Gathany.

Slide 7

Dengue fever

Dengue fever, also known as breakbone fever and dengue hemorrhagic fever,[25] typically occurs in tropical and subtropical regions, primarily in urban and semi-urban areas, and it affects an estimated 390 million people worldwide each year.[26]

The disease is not typically fatal; however, its signs/symptoms are excruciating. These include high fever, intense headache, severe eye pain, joint pain, nosebleeds, rash, and low white blood cell counts.[26,27] Treatment involves supportive care. Some severe cases can lead to life-threatening dengue hemorrhagic fever or dengue shock syndrome.[26,27]

The image depicts a confluent erythematosus rash with islands of sparing in a patient with dengue fever.

Image courtesy of Thomas EA, John M, Kanish B. Indian J Dermatol. 2010;55(1):79-85 [Open access.] PMID: 20418984, PMCID: PMC2856380.

Slide 8

Zika virus disease

Zika virus was first detected in Ugandan monkeys in 1947.[28] It is transmitted by mosquitoes in the genus Aedes, especially A aegypti and A albopictus.[23] Since its discovery, Zika virus has steadily increased its territory eastward, from Africa to Yap Island and French Polynesia in the Pacific and, eventually, to the Americas.[28]

Physicians in outbreak areas reported mild dengue-like signs/symptoms that quickly resolved, including back pain, fever, rash, arthralgia, and headache.[28] In addition, outbreaks in French Polynesia (2013) and Brazil (2015) showed increases in neurologic and autoimmune complications. More recently, Brazilian health authorities noted a relatively high incidence of Guillain-Barré syndrome during the current Zika virus outbreak[28]; the association between the two conditions was confirmed through antibody assay in a retrospective case-control study of the 2013-2014 French Polynesia outbreak.[29,30] The researchers also found large numbers of individuals who demonstrated the Zika antibody but had not reported any illness.[30]

The current outbreak in Central and South America was first detected in May of 2015.[31] Zika virus is making inroads into the United States but, thus far, all cases have been related to travelers returning from infected areas; there have been no reported autochthonous (native) infections.[32]

Image courtesy of CDC/Cynthia Goldsmith.

Slide 9

In 2015, concurrent with the Zika outbreak, the number of microcephalic infants born in Brazil skyrocketed to approximately 20 times the reported numbers from previous years.[33] However, prior outbreaks of the virus did not correlate with microcephaly. Some medical professionals attributed the rise in cases of microcephaly to pyriproxyfen, a larvicide that had been introduced into the drinking water in areas most affected by microcephaly,[34] whereas others suggested the spike may be due to an increased awareness of the association between Zika virus and microcephaly.[35] Pyriproxyfen is an analogue to an insect hormone that keeps immature insects from undergoing metamorphosis.[36] Still others continue to blame Zika virus, pointing to decades of safe use and extensive laboratory testing of pyriproxyfen.[37]

Mounting evidence continues to indicate a correlation between Zika virus infection and microcephaly, but establishing one as the cause of the other remains difficult.[38,39] The CDC and World Health Organization (WHO) have issued a travel advisory against pregnant women traveling to affected areas.[40,41]

Adapted image courtesy of the CDC.

Slide 10

Sexual transmission of Zika virus has been confirmed in the United States,[42] and the WHO indicates that this mode of transmission may be more common than previously thought.[43] The possibility of sexual transmission of Zika virus was considered as early as 2008.[44]

Standard procedures for avoiding sexually-transmitted diseases (eg, condoms) should also be effective against Zika virus.[45,46]

Current management is supportive and preventive measures.[47]

Adapted image courtesy of the WHO.

Slide 11

Yellow fever

Yellow fever is caused by a virus belonging to the genus Flavivirus, which includes dengue, Zika, and West Nile viruses.[48] This disease can be transmitted from a mother mosquito to her young, which is instrumental in large-scale epidemics of yellow fever.[49] Annually, an estimated 200,000 people are infected, causing about 30,000 deaths, primarily in Africa.[48] An outbreak of yellow fever in Angola that began in December 2015 is ongoing, with 75-125 deaths reported through February 2016.[50,51]

Typically, signs/symptoms begin 3-6 days after a bite from an infected mosquito, manifesting as fever, chills, myalgia with back pain, headache, anorexia, nausea, and vomiting.[48] Such cases generally last only a few days. Approximately 15% of patients enter a subsequent, more toxic phase, exhibiting jaundice (hence the name of the condition), abdominal pain, and vomiting. Hemorrhaging occurs from the eyes, nose, mouth, or stomach, and kidney function deteriorates. About half of those who experience the toxic phase die within 2 weeks; the remainder recover without serious sequelae.[48]

Treatment is limited to mitigation of symptoms and supportive care. Although a vaccine exists, the minimum effective threshold is not always reached in developing countries due to logistical difficulties.

Image of multiple virions of the yellow fever virus at a magnification of 234,000× courtesy of the CDC.

Slide 12

Historically, yellow fever was a significant threat to Europeans traveling around the globe. European settlers in Africa died during outbreaks, whereas native populations, who had acquired immunity after centuries of exposure, only suffered the initial phase of infection.[52] Among British sailors in the 19th century, an assignment to the West Indies carried a high risk of contracting "Yellow Jack."

Yellow fever was probably carried to the Americas by way of the slave trade. The disease appears to have been instrumental in decimating French troops sent to quell a slave uprising in Haiti, leading to that country's eventual independence.[52]

In 1864, a bioterrorist plotted the spread of yellow fever via clothing and blankets, targeting Abraham Lincoln and northern cities in the United States.[53] The scheme was foiled by a disgruntled fellow conspirator; nevertheless, it would ultimately have been unsuccessful due to a complete misunderstanding of how the disease is spread.[53]

Image of cemetery marker courtesy of Wikimedia Commons/Marque1313, and image of "Yellow Jack" signal flag (inset) courtesy of Wikipedia/Denelson83.

Slide 13

Chikungunya virus disease

Chikungunya translates to "that which bends up" (ie, becomes contorted) in the Makonde or Kimakonde language of Mozambique and Tanzania, where the disease was described after an outbreak in 1952.[54,55] The primary vector has been A aegypti[22]; however, in 2005, researchers discovered a mutation that allows the virus to be carried by A albopictus, a highly-invasive temperate species.[56] Thus, formerly confined to tropical and subtropical climates, the chikungunya virus has accessed a significantly expanded area.

In 2013, the WHO reported the first local transmission of the virus in the Western Hemisphere (St. Martin), triggering the Caribbean epidemic.[54] By April 2015, nearly 1.4 million cases of suspected chikungunya were reported in the Caribbean islands, Latin America, and United States.

Signs/symptoms include sudden onset of fever, morbilliform rash,[57] headache, myalgia, and crippling joint pain (which results in the contorted posture that gives the disease its name).[54,57,58] Most patients recover after 1 week,[55] but the joint pain can persist for months or years.[54] In rare cases, neurologic disorders (eg, encephalitis) have been associated with chikungunya.[59-61] The disease is occasionally fatal to patients who are elderly, very young, or otherwise already immune compromised.[54,55,61,62]

Treatment consists of supportive care.[54,55]

Chikungunya virus can also be carried by birds, monkeys, cattle, and rodents.[54,63]

Image of a foot from a Filipino patient infected with chikungunya virus courtesy of Wikimedia Commons/Nsaa; image of chikungunya virus particles (inset) courtesy of the CDC/Cynthia Goldsmith.

Slide 14

Japanese encephalitis

Japanese encephalitis is caused by another member of the genus Flavivirus, and it usually occurs in pigs and wading birds.[64,65] The virus is transmitted to humans, cows, and horses primarily via two mosquito species, Culex tritaeniorhynchus and Culex vishnui.[66]

Most infections result in mild symptoms (fever, headache) or are asymptomatic; however, approximately 1 in 250 infected individuals presents with severe symptoms, such as high fever, headache, neck stiffness, disorientation, coma, seizures, spastic paralysis and, ultimately, death.[64,65] An estimated 13,000-20,000 annual deaths occur from this condition (case-fatality rate, ≤30% in symptomatic disease), primarily in children.[64] About 20%-30% of survivors of symptomatic Japanese encephalitis suffer permanent neurologic and/or psychiatric sequelae.[64,65]

Major outbreaks of Japanese encephalitis occur every 2-15 years.[64] Treatment involves supportive measures. Inactivated Vero cell-derived, live attenuated, and live recombinant vaccines are in current use.[64] A mouse brain–derived vaccine is also available, but the high cost of production has limited its availability in more poor regions.[67]

Adapted image courtesy of the CDC.

Slide 15

Malaria

Even among mosquitoes, the marsh mosquitoes in the genus Anopheles are exceptionally detrimental to humans; they are the carriers of malaria.[11,68] Anopheles mosquitos are found on all continents, except Antarctica, with approximately 460 species recognized.[69] Only a few dozen species transmit malaria, but members of this genus also carry canine heartworm,[70] filiariasis, and o'nyong'nyong fever.[71]

Image of a female A gambiae mosquito courtesy of the CDC/James Gathany.

Slide 16

An estimated 214 million people contracted malaria in 2015, resulting in 438,000 deaths, predominantly children in Africa.[68] Although there are several species of malarial parasites, Plasmodium falciparum and Plasmodium vivax are responsible for the most human misery.[68] Anopheles gambiae females carrying malarial parasites are more attracted to human odors than uninfected mosquitos, suggesting that the parasites may play a less passive role in the transmission process.[72]

Plasmodia (phylum Apicomplexa, due to the apical complex structure used to penetrate host cells) have several discrete life stages, passing part of their complex life cycle in a dipteran insect host and part in a mammal host.[73] Parasites in the mosquito's saliva enter the mammal host via biting, and then they invade the liver, multiply, and differentiate into blood-infecting forms, before being released into the bloodstream. The parasites bind to erythrocytes and invade them; once inside, they multiply again into new parasites that are then released to infect more erythrocytes.[73] During this process, parasite-derived surface proteins cause the erythrocytes to stick to the walls of the blood vessels; this can become critical if many erythrocytes bind to blood vessels in the brain (cerebral malaria).[74] During the blood infection stage, some of the parasites differentiate into reproductive forms, which are taken up by feeding mosquitoes.[73]

Image courtesy of Dreamstime/Decade3d.

Slide 17

The initial presentation of malaria, which may be delayed depending on the parasite species, is flulike and difficult to distinguish from many other conditions.[68,75] Signs/symptoms may include fever, shivering, and mild jaundice, followed by cyclical periods of sudden onset of chills and shivering, and then fever and sweating, over 2-3 days.[75]

Severe malaria may manifest as neurologic abnormalities, severe anemia, hemoglobinuria ("blackwater fever"[76]), acute respiratory distress syndrome, hypotension, acute kidney failure, metabolic acidosis, and hypoglycemia.[75]

Malaria remains a treatable illness with early and appropriate antimalarial medications,[68,77] as well as supportive measures. Although malaria has been eradicated in many countries, the risk of reinfestation remains.[68] No licensed vaccine exists[68]; however, some pharmaceutical compounds can be taken prophylactically.[78]

Images of a P falciparum microgametocyte (left) and a red blood cell containing four P vivax rings, next to a growing trophozoite (right), courtesy of the CDC.

Slide 18

Other Mosquito-Borne Illnesses

As noted earlier, many other diseases are spread by mosquitoes, such as canine heartworm (Dirofilaria immitis) (shown), which affects dogs and, occasionally, cats and humans. West Nile Virus, another virus in the Flavivirus group, is responsible for epidemics in recent years in developed regions.[79] Less-severe viruses, such as eastern and western equine encephalitis and St. Louis encephalitis, are also spread by mosquitoes.[5,13]

Climate change and expansion of standing-water agricultural practices (eg, rice) may bring more people into contact with disease-bearing mosquitoes in the future.[80-83]

Image of (1) D immitis in the heart of a dog (left) courtesy of Otranto D, Capelli G, Genchi C. Parasit Vectors. 2009;2 suppl 1:S2. [Open access.] PMID: 19426441, PMCID: PMC2679394; and (2) D immitis under microscopy at 400× (right) courtesy of Wikimedia Commons/Joelmills.

Slide 19

Prevention of Mosquito Bites

Sometimes, mosquitoes are impossible to avoid. However, personal efforts towards defense can be very effective.

Wear light-colored clothing that covers as much exposed skin as possible.[84,85] Apply DEET (N,N-diethyl-meta-toluamide)–containing insect repellents to vulnerable areas. Sleep under mosquito nets, and don a net hood in areas where mosquitoes teem.

Eat generous helpings of the most pungent local foods. Be mindful of your immediate surroundings and, remember, mosquitoes are present during the day and night. Your ears will often detect a mosquito before it is close enough to bite you.

Adapted image courtesy of the CDC.

Slide 20

Local mosquito mitigation efforts can keep the population down. Because mosquito larvae don't need dissolved oxygen, they can thrive in small volumes of water. Ditches, buckets, empty cups, old tires, tarp folds, birdbaths, and derelict bins are all excellent nurseries for young mosquitoes.[85] Patrol your environs after rainfalls, and pour out accumulations of water wherever you see them.

In poorly-draining areas, dig channels to pool the water in a single deep place. Deeper, more-permanent water will attract diving beetles, backswimmers, dragonflies, and other aquatic predators that deal very efficiently with prey that is obliged to come up for air.[86,87]

Mosquitoes are never welcome, but during warm and damp weather, they're seldom far away.

Images courtesy of Arlo Pelegrin. The mosquito in the right image is a woodland floodwater mosquito (Aedes punctor).

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