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Anopheles is a genus of mosquitoes in the family Culicidae, and the principal genus of the subfamily Anophelinae, which also contains the smaller genera Bironella and Chagasia. The name, given by Johann Wilhelm Meigen in 1818, derives from the Ancient Greek anōphelēs, meaning "useless" or "profitless". Of the roughly 480 to 500 described species, many of which are groups of closely related forms that cannot be told apart by appearance, about 70 are capable of transmitting human malaria parasites, and roughly 40 are considered dominant vectors.

Anopheles is the only genus whose members transmit human malaria, caused by Plasmodium falciparum, P. vivax, P. ovale, P. malariae, and the monkey parasite P. knowlesi. Some species also transmit the nematodes Wuchereria bancrofti and Brugia malayi, which cause lymphatic filariasis, and O'nyong-nyong virus, the only arbovirus of major human importance transmitted principally by Anopheles rather than by Aedes or Culex.

Because Anopheles mosquitoes are small-bodied ectotherms whose larvae develop in surface water and whose adult survival depends on temperature and humidity, the distribution, seasonality, and transmission potential of the genus are closely tied to climate, land use, and climate change.

Evolutionary divergence and subgenera

Molecular dating and fossils preserved in amber suggest that the subfamily Anophelinae, containing Anopheles, separated from the Culicinae, which contains Aedes, Culex, and related genera, in the Jurassic or Early Cretaceous, broadly 150 to 200 million years ago. Estimates vary considerably with the method used. The timing overlaps the breakup of Gondwana, which has been proposed as a cause of the group's early geographic division, though the association is not firmly established.

The genus is divided into seven or eight subgenera, distinguished by the structure of the male genitalia, wing venation, the armature of the foregut, and genetic relationships. All the dominant vectors of human malaria belong to just four subgenera, each largely confined to its own part of the world. The species counts below are approximate, and new species continue to be described.

The subgenera of Anopheles

Morphological comparison across life stages

At every stage of life, Anopheles mosquitoes can be told apart from Aedes and Culex:

Comparison of Anopheles with the two main culicine genera

Chromosomes and comparative genomics

Anopheles species have three pairs of chromosomes: two pairs of autosomes, designated 2 and 3, each with a left and right arm, and a pair of sex chromosomes, XX in females and XY in males. The Anopheles maculipennis group is unusual in having undergone rearrangements that exchanged material between chromosome arms.

Maleness is determined by a gene on the Y chromosome, called Yob in the An. gambiae complex and Guy1 in An. stephensi. Expressed early in the embryo, it adjusts the activity of the X chromosome and directs the male pattern of splicing of the gene doublesex. Embryos without a Y chromosome produce the female form of the protein instead.

Comparison of 16 Anopheles genomes, led by Nora Besansky, Daniel Neafsey, and colleagues, revealed two notable features:

1. Rapid change on the X chromosome. Genes rarely move between chromosome arms, so the overall arrangement has been preserved over tens of millions of years. The X chromosome is the exception: it rearranges frequently, loses genes to the autosomes, and diverges rapidly in sequence. It is correspondingly important in the formation of barriers to interbreeding between related species.
2. Adaptation through chromosomal inversions. In several vector groups, large inverted segments of chromosome suppress recombination in individuals carrying one inverted and one standard copy. This keeps sets of co-adapted genes together, and the frequency of such inversions often varies along gradients of temperature and humidity.

Larval habitats

All Anopheles species have aquatic larvae, but the species that transmit malaria occupy very different kinds of water. This explains why measures that eliminate malaria on one continent can make it worse on another.

• Sunlit temporary pools, such as rain puddles and hoofprints, are used by An. gambiae and An. arabiensis in Africa and by An. punctulatus in New Guinea. These species need open sunlight, warm water, and the absence of predators.
• Permanent vegetated water, including marshes, swamps, and lake margins, is used by An. funestus, the second most important African vector, whose larvae shelter among reeds and so sustain transmission through the dry season after temporary pools have dried. The North American An. quadrimaculatus and the South American An. darlingi, which prefers shaded, clear, slightly acidic water at forest river margins, occupy similar habitats.
• Shaded forest streams and seepages are used by An. minimus and An. dirus in Southeast Asia, giving rise to what is called forest malaria. Clearing forest in Southeast Asia historically reduced these species, whereas clearing forest in Africa or the Amazon creates the sunlit pools that favour An. gambiae and An. darlingi.
• Irrigated farmland, particularly rice fields and canals, supports An. coluzzii in West Africa, An. sinensis in East Asia, An. culicifacies in India, and An. freeborni in California.
• Water containers in towns are used by An. stephensi, which lays its eggs in rooftop tanks, cisterns, wells, and discarded tyres alongside Aedes aegypti.
• Brackish coastal water supports species able to tolerate salt, including An. melas in West Africa, An. merus in East Africa, An. sundaicus in Southeast Asia, An. atroparvus and An. sacharovi in Europe, and An. aquasalis and An. albimanus in the Americas.
• Water held by bromeliads in the forest canopy supports the subgenus Kerteszia.

Blood feeding and the gonotrophic cycle

Newly emerged Anopheles adults of both sexes feed on plant sugars, from nectar, damaged fruit, and honeydew, which fuel flight. Males feed only on sugar throughout their lives, which are short. Females of all vector species must also take blood, which supplies the amino acids, lipids, and iron needed to produce eggs. Blood feeding activates hormonal signalling that causes the fat body to make yolk proteins, allowing a batch of roughly 50 to 200 eggs to mature.

As blood passes through the foregut, it crosses a row of small teeth in species of the subgenus Cellia, known as the cibarial armature. These have little effect on malaria parasites, which are only a few micrometres across, but they damage a proportion of the much larger microfilariae of Wuchereria bancrofti. This has been proposed as the reason why Anopheles transmits filariasis inefficiently at low worm densities, a pattern called facilitation, whereas Culex transmits efficiently even at low densities, called limitation. The correspondence between armature and transmission pattern is imperfect, and other explanations have been suggested.

While feeding, the female concentrates the blood meal by excreting fluid from the rear of the abdomen. The evaporation of these droplets also helps her avoid overheating from a meal at 37 °C. The blood is enclosed in a membrane secreted by the gut and digested over two to four days, after which the female seeks a place to lay her eggs. This interval is the gonotrophic cycle.

Overwintering and dry-season survival

Unlike Aedes, whose eggs survive cold and drought, Anopheles eggs cannot. These mosquitoes therefore survive unfavourable seasons mainly as adult females, and occasionally as larvae.

• Winter dormancy in temperate species. In Europe and North America, shortening days and falling temperatures in autumn cause newly emerged females to enter a dormant state. They mate in autumn and store sperm through the winter, feed heavily on nectar to build up fat reserves, accumulate compounds that protect against cold, and shelter in caves, hollow trees, cellars, and animal sheds. Two patterns occur:

1. Complete dormancy, as in An. messeae and An. quadrimaculatus, in which females take no blood through the winter and live on stored fat.
2. Partial dormancy, as in An. atroparvus and An. sacharovi, in which females sheltering in heated houses and stables produce no eggs but continue to take blood meals to replenish their reserves. This behaviour allowed P. vivax to be transmitted indoors through the winter in the Netherlands, England, Germany, and Russia, a phenomenon known as winter malaria.

• Dry-season survival in the tropics. In the African Sahel, where no rain falls for six months or more, An. coluzzii survives locally in a dormant state in humid shelters, thickening the waxy layer of its cuticle to reduce water loss. An. gambiae and An. arabiensis instead largely disappear and return by flying at night at heights of 100 to 300 m, carried by winds over distances of a hundred kilometres or more.

Because Anopheles has adapted to very different conditions on every continent except Antarctica, the intensity of malaria transmission varies by orders of magnitude between regions.

Dominant malaria vectors by region

Thermal performance curves

Every rate that governs Anopheles populations and transmission depends on temperature: how fast eggs hatch, how quickly larvae develop and whether they survive, how large the adults are, how fast blood is digested and therefore how often the female bites, how long adults live, and how quickly the malaria parasite develops inside the mosquito.

As shown by Erin Mordecai, Matthew Thomas, Krijn Paaijmans, and colleagues, these do not increase steadily with warming. Each rises to an optimum and then falls, a pattern often described by the Briere function, _f_(T) = _cT_(T − T_min)(T_max − T)^1/2.

• Larvae. In tropical species, development stops below roughly 12 to 14 °C, is most efficient between about 24 and 28 °C, and fails above 35 to 38 °C. Species adapted to hot springs or to urban water containers tolerate higher temperatures. Larvae reared in warmer water also mature faster than they accumulate mass, so the adults are smaller, a general pattern among ectotherms. Smaller females take smaller blood meals, which reduces the chance of picking up parasites, and lay fewer eggs. Whether they also die faster is disputed.
• Adult survival against parasite development. Warming shortens the time the parasite needs to develop, which favours transmission. But adult mosquitoes live longest at moderate temperatures, around 20 to 25 °C, and their survival falls steeply above about 30 °C. Since a mosquito must survive the whole of the parasite's development to transmit at all, and since the proportion that do so falls exponentially with both mortality and incubation time, the combined effect peaks at a moderate temperature:
• For An. gambiae with P. falciparum, transmission becomes possible at about 17 °C, peaks near 25 °C, and ceases around 33 °C.
• For An. stephensi, which evolved in hotter regions, the optimum is higher, near 26 to 28 °C, and transmission continues to about 36 °C.

Desiccation and vapor pressure deficit

Adult Anopheles weigh only a milligram or two and have a large surface area relative to their volume, so they lose water rapidly, mostly through the cuticle and partly through the breathing openings. The rate depends on how dry the air is, measured as the vapor pressure deficit.

Because warm air can hold much more water vapour, roughly 7% more per degree, warming raises this deficit during hot seasons and droughts. Beyond about 1.5 to 2.5 kPa, mosquito mortality rises sharply unless the insect can compensate:

1. A more waterproof cuticle. Species adapted to dry regions, including An. arabiensis and An. stephensi, produce longer-chain waxy compounds on the cuticle that reduce water loss.
2. Sheltering. Resting inside houses, animal shelters, or burrows reduces exposure to the hottest and driest conditions by several degrees and raises humidity substantially.
3. Drinking blood for water. Mild dehydration makes females more likely to seek a blood meal, which supplies water as well as nutrients, so biting may briefly increase at the start of a drought.

Range shifts and invasive expansion

Climate change and human transport have shifted Anopheles distributions along three primary axes:

• Movement upslope and toward the poles. Analysis by Colin Carlson and colleagues of more than a century of African collection records found that the range limits of African Anopheles species have moved upslope by about 6.5 m a year on average, and away from the equator by about 4.7 km a year, with wide variation between species. Populations of An. gambiae, An. arabiensis, and An. funestus are now established in highland valleys of East Africa and Madagascar at 1,600 to 2,500 m. In South America, An. darlingi and An. pseudopunctipennis have moved into Andean valleys, and in Asia An. minimus and An. maculatus into the Himalayan foothills.
• Longer seasons in temperate regions. Warmer autumns and milder winters lengthen the active season and delay the onset of winter dormancy in temperate species, allowing additional generations each summer and widening the period in which an imported case could start local transmission. Small clusters of locally acquired malaria have occurred recently in Greece, Italy, Spain, and the United States.
• The spread of An. stephensi. Native to South Asia and the Arabian Peninsula, this urban species was detected in Djibouti in 2012, where malaria cases subsequently rose from a few dozen a year to tens of thousands, though other factors contributed. It has since been found in Ethiopia, Sudan, Somalia, Eritrea, Kenya, Nigeria, and Ghana. Its spread has been assisted by shipping and road transport and by rapid urban growth, and its preference for warmer conditions suits it to cities. One modelling study estimated that unchecked spread could place an additional 126 million urban residents at risk.

Historical larval and adult interventions

After Ronald Ross and Giovanni Battista Grassi established the role of Anopheles in 1897 and 1898, control concentrated on the larvae, with methods tailored to the local species. Examples include the drainage and oiling of breeding sites during the construction of the Panama Canal under William Gorgas, Malcolm Watson's drainage of hillside seepages in Malaya, and the draining of the Pontine Marshes in Italy. Larvae were also killed with Paris green, an arsenic compound applied as a dust that surface-feeding Anopheles larvae ingest, and with introduced fish.

The discovery of the insecticidal properties of DDT by Paul Hermann Müller in 1939, together with George Macdonald's mathematical analysis, shifted attention from larvae to adults. Because a female must rest for a day or two after feeding while she digests blood and develops eggs, spraying the inside walls of houses, or sleeping under a treated net, kills a large proportion of the population at its most vulnerable point. Transmission falls steeply as a result, since it depends on the square of the biting rate and declines exponentially as mosquito survival falls. This approach underpinned the WHO Global Malaria Eradication Programme of 1955 to 1969, which removed malaria from Europe, North America, the Caribbean, Australia, and parts of Asia and Latin America. The programme excluded most of Sub-Saharan Africa and was abandoned after resistance to DDT emerged and transmission resumed in several countries.

Insecticide and behavioral resistance

Sustained use of insecticides, both in public health and in agriculture, has produced resistance in more than 80 Anopheles species. The two main African vectors have taken different routes.

• Changes to the insecticide's target. In the An. gambiae complex, An. stephensi, An. culicifacies, and An. sinensis, resistance to pyrethroids and DDT arises largely from changes in the sodium channel of nerve cells, known as knockdown resistance. Resistance to carbamates and organophosphates arises from a change in the enzyme acetylcholinesterase.

Anopheles funestus is strikingly different: it has none of these sodium channel mutations and lacks the usual acetylcholinesterase change, having instead acquired a different one.

• Increased breakdown of the insecticide. In An. funestus, resistance comes almost entirely from greatly increased production of two cytochrome P450 enzymes and of a glutathione transferase, through duplication of the genes and changes to their control regions. In An. gambiae and An. coluzzii, a different set of P450 enzymes is involved, together with a thickened cuticle and a protein in the legs that binds pyrethroids before they reach the nervous system.
• Changes in behaviour. In Africa, the Americas, and the Pacific, decades of indoor control have favoured mosquitoes that avoid it:

1. Biting earlier or later, shifting from the middle of the night, when people are under nets, to the early evening or early morning.
2. Biting and resting outdoors, avoiding treated surfaces altogether.
3. Feeding on animals such as cattle, goats, or dogs instead of entering houses.

Together these sustain what is called residual transmission, which persists even where net coverage exceeds 80%.

Next-generation control tools

To counter resistance in Anopheles, modern control programs integrate chemical, biological, and genetic tools:

• Improved nets and sprays.
• Nets combining a pyrethroid with piperonyl butoxide, which blocks the P450 enzymes that break the insecticide down, restoring its effect against resistant mosquitoes.
• Nets combining a pyrethroid with chlorfenapyr. Chlorfenapyr is inactive until the mosquito's own P450 enzymes convert it into a compound that disrupts energy production in the mitochondria. Resistant mosquitoes, which have more of these enzymes, therefore activate it more readily, and there is no overlap with the mutations that confer pyrethroid resistance.
• Nets combining a pyrethroid with pyriproxyfen, which sterilizes surviving females, and new compounds for indoor spraying, including pirimiphos-methyl, clothianidin, and broflanilide, which acts at a site on the insect nerve receptor unaffected by existing resistance.
• Methods aimed at outdoor transmission.
• Sugar baits. Because both sexes must feed on plant sugars regardless of where they bite, bait stations containing an attractant, sugar, and an insecticide can kill mosquitoes that never enter a house.
• Ivermectin. Given to people or livestock, it circulates in the blood and paralyses mosquitoes that feed on them, whether indoors or out, and reduces egg production in survivors.
• Blocking house entry. Mosquitoes follow rising currents of warm, odour-laden air into houses through the open gaps beneath the roof. Closing these gaps, or fitting tubes treated with insecticide or with fungi that kill mosquitoes, intercepts them at the point of entry. Volatile repellents can also disrupt host-seeking in the space around houses.
• Biological and genetic methods.
• Bacterial larvicides. Preparations of Bacillus thuringiensis israelensis and Lysinibacillus sphaericus produce toxins that destroy the gut lining of larvae and are used in water containers, rice fields, and dry-season refuges.
• Microbial symbionts. Microsporidia MB, a symbiont passed from female mosquitoes to their offspring, was found in Kenyan populations and appeared to prevent malaria infection without harming the mosquito, though the numbers studied were small. The gut bacterium Delftia tsuruhatensis produces a compound that blocks parasite development and can be acquired from treated surfaces or sugar.
• Gene drives. Genetic systems designed to spread through wild populations faster than ordinary inheritance allows are in development. Some aim to suppress populations, by disrupting a gene required for female fertility or by biasing offspring heavily toward males. Others aim to leave populations in place while spreading genes that block the parasite. All remain at the laboratory and contained-trial stage.

Why is *Anopheles* the only mosquito genus that transmits human malaria?

Human *Plasmodium* parasites have co-evolved specifically with *Anopheles* midgut and salivary gland receptors required for sporogonic development. When ingested by culicine mosquitoes (*Aedes* or *Culex*), human *Plasmodium* ookinetes either fail to recognize and traverse the midgut epithelial ligands or are lysed by complement-like immune responses and melanotic encapsulation, preventing oocyst maturation and salivary gland invasion.

How does the cibarial armature of subgenus *Cellia* affect filariasis transmission?

Female *Anopheles* in the subgenus *Cellia* possess rows of sclerotized chitinous teeth lining the cibarial pump of the foregut. When blood is drawn into the gut, these teeth mechanically lacerate a high proportion of ingested *Wuchereria bancrofti* microfilariae (which measure 240–300 μm in length), creating an epidemiological facilitation threshold where transmission becomes inefficient at low human microfilarial densities, unlike *Plasmodium* gametocytes (≈10 μm), which pass undamaged.

Why does *Anopheles stephensi* pose a distinct threat to urban malaria control in Africa?

Unlike native African malaria vectors (*Anopheles gambiae* and *Anopheles funestus*), which breed predominantly in rural sunlit pools or vegetated marshes, *Anopheles stephensi* is an invasive urban vector that oviposits in anthropogenic water storage containers, cisterns, and wells alongside *Aedes aegypti*. Furthermore, *Anopheles stephensi* exhibits a higher thermal optimum (26–28 °C), greater adult heat tolerance (up to 36 °C), and widespread resistance to multiple insecticide classes.

• Malaria
• Mosquito
• Vector control
• Insecticide resistance
• Mosquito-borne disease