Malaria and the Mosquito Diseases

TL;DR. Malaria is caused by a single-celled parasite injected into your blood by a mosquito. It multiplies first in the liver, then inside red blood cells, bursting out in synchronised waves that produce the classic cycles of chills, fever, and drenching sweat. The deadliest species, Plasmodium falciparum, makes infected red cells sticky so they jam in small vessels, and when that happens in the brain it causes cerebral malaria, which kills children within hours. It remains one of the largest causes of childhood death on earth, and about 95 percent of malaria deaths occur in Africa. The tools that work best are unglamorous: a treated bed net, a rapid test, and a three-day course of tablets.

Key takeaways

• In 2024 there were an estimated 282 million malaria cases and 610,000 deaths, with roughly 95 percent of deaths in the WHO African Region and most in children under 5.
• Malaria is not contagious between people. It needs a female Anopheles mosquito as an intermediate host.
• The fever pattern is mechanical: parasites burst out of red cells in synchrony every 48 or 72 hours depending on species.
• Insecticide-treated nets are the single most effective intervention, and the scale-up from 2000 to 2015 is credited with the majority of the lives saved in that period.
• Two vaccines (RTS,S/AS01 and R21/Matrix-M) are now being deployed in African countries. They are partially effective, which is enough to matter at this scale.
• Resistance is the recurring threat: to chloroquine historically, to artemisinin now, and to insecticides in the mosquitoes themselves.

What it is

Malaria is infection with a protozoan parasite of the genus Plasmodium. Five species infect humans:

The vector is the female Anopheles mosquito, which bites mainly between dusk and dawn. That single behavioural fact is why bed nets work so well and why daytime-biting mosquito diseases like dengue need different tools.

The history

In short: From cinchona bark in the 1600s to a Chinese military programme that found artemisinin in a fourth-century text.

Malaria is old enough to have shaped the human genome (Chapter 62). Chinese, Indian, Egyptian, and Greek texts describe periodic fevers with enlarged spleens. The name comes from medieval Italian mala aria, "bad air," from the belief that swamp vapours caused it. Rome's periodic fevers depopulated stretches of the Campagna for centuries.

Progress has stalled since about 2015, and cases have risen recently, driven by funding gaps, insecticide and drug resistance, an invasive urban-adapted mosquito (Anopheles stephensi) spreading in the Horn of Africa, and conflict and climate disruption.

What actually goes wrong

In short: The parasite multiplies in the liver, then bursts out of red cells in synchronised waves, and the deadliest species makes those cells sticky enough to block small vessels.

The life cycle explains the disease.

1. Bite. An infected mosquito injects sporozoites with its saliva. Perhaps a few dozen parasites enter.
2. Liver stage. Sporozoites travel to the liver and invade liver cells, where each multiplies silently into tens of thousands of merozoites over about a week. No symptoms yet. In P. vivax and P. ovale, some become dormant hypnozoites that can wake months or years later, which is why these species relapse without any new bite.
3. Blood stage. Merozoites burst out and invade red blood cells, consuming haemoglobin, multiplying, and rupturing the cell to invade more. Each cycle takes 48 hours for falciparum, vivax, and ovale, and 72 for malariae.
4. Fever. The synchronised rupture of billions of red cells releases parasite material that triggers a massive cytokine response: chills and rigors, then high fever, then profuse sweating as it breaks. Hence the classic tertian (every third day, counting inclusively) pattern, though in practice, especially in falciparum, the cycles are often not synchronised and the fever is continuous.
5. Transmission back. Some parasites become sexual forms (gametocytes), taken up by the next biting mosquito, where they mate and complete the cycle.

Why falciparum kills. Infected red cells express a parasite protein called PfEMP1 on their surface, which binds receptors on blood vessel walls. The infected cells stick to the endothelium and to each other (cytoadherence and rosetting), which keeps them out of the spleen where they would be destroyed. The consequence is that small vessels become packed with infected cells, obstructing flow. In the brain, this causes cerebral malaria: coma, seizures, and death within hours if untreated. PfEMP1 is also encoded by around 60 variant genes that the parasite switches between, so antibodies against one version do not recognise the next, which is why immunity develops slowly and never completely.

What it does to the body

Uncomplicated malaria: fever, chills, headache, muscle aches, nausea, vomiting. It is easily mistaken for flu, and in a returning traveller that mistake is a common cause of preventable death.

Anaemia: from destruction of infected red cells, destruction of uninfected ones, and suppressed marrow production. Severe anaemia is a leading cause of malaria death in young children.

Severe malaria (any of these makes it an emergency): impaired consciousness or seizures (cerebral malaria), respiratory distress from metabolic acidosis, hypoglycaemia, severe anaemia, kidney failure, jaundice, shock, or very high parasite density.

Malaria in pregnancy: parasites sequester in the placenta, causing maternal anaemia, low birth weight, prematurity, and stillbirth. First pregnancies are worst affected. This is why intermittent preventive treatment in pregnancy is a standard programme.

Chronic consequences: repeated infection causes enlarged spleen, chronic anaemia, and in children who survive cerebral malaria, lasting neurological and cognitive impairment in a substantial minority.

Is it deadly?

Yes, and disproportionately to children.

• About 610,000 deaths in 2024, from an estimated 282 million cases.
• Roughly 95 percent of deaths occur in the WHO African Region, and most are in children under 5.
• Nigeria and the Democratic Republic of the Congo alone account for a large share of the global total.
• Severe malaria treated promptly with intravenous artesunate has mortality around 8 to 15 percent; untreated cerebral malaria is nearly always fatal.
• People repeatedly exposed from childhood develop partial immunity: they still get infected but are much less likely to develop severe disease. This is why malaria deaths in high-transmission areas concentrate in young children and in non-immune visitors, and why people who leave an endemic area for a few years lose that protection and can become severely ill on return.

Is it contagious?

Not person to person. Malaria requires a mosquito to complete part of its life cycle. You cannot catch it by contact with someone who has it.

The exceptions are direct blood routes: transfusion, shared needles, organ transplant, and mother to child across the placenta. Airport malaria, in which infected mosquitoes arriving on aircraft bite people near airports in non-endemic countries, is documented and rare.

Who gets it

In short: Overwhelmingly young children in sub-Saharan Africa, plus pregnant women, and travellers who have lost their partial immunity.

Geographically, sub-Saharan Africa carries the overwhelming majority of the burden, with substantial transmission also in South and Southeast Asia, Papua New Guinea, the Amazon basin, and parts of Central America.

Within endemic areas, risk falls on young children (before partial immunity develops), pregnant women, people with HIV, and travellers or migrants returning after time away.

Genetics. Malaria has exerted more selective pressure on the human genome than any other infectious disease. Sickle cell trait, thalassemia traits, G6PD deficiency, and other red cell variants all persist at high frequency in historically malarious regions because carriers are protected against severe malaria, at the cost of disease in those who inherit two copies. The Duffy-negative blood group, near-universal in West and Central Africa, prevents P. vivax from entering red cells at all, which is why vivax is largely absent there. These are examples of balanced polymorphism, and they are the clearest demonstration in human biology that a genetic disease can be the price of a genetic defence.

Treatment, and how it works

In short: Test before treating, then artemisinin combinations for three days, intravenous artesunate for severe disease, and a G6PD test before clearing the dormant liver stages.

Diagnosis first. Rapid diagnostic tests detecting parasite antigens give an answer in 15 minutes from a finger prick, and microscopy remains the standard where laboratories exist. Treating fever presumptively as malaria without testing wastes drugs and misses other causes, and WHO policy has for years been to test before treating.

Uncomplicated falciparum malaria: artemisinin-based combination therapy (ACT), such as artemether-lumefantrine or artesunate-amodiaquine, for three days. Artemisinin derivatives kill parasites extremely fast (reducing parasite numbers about 10,000-fold per life cycle) but clear from the body quickly; the partner drug has a longer half-life and finishes off the survivors. The combination both cures faster and protects against resistance.

Severe malaria: intravenous artesunate, which replaced quinine after two large trials (SEAQUAMAT in Asia and AQUAMAT in African children) showed substantial mortality reductions. Supportive care matters: careful fluid management, glucose, transfusion for severe anaemia, and treatment of seizures.

P. vivax and P. ovale: treating the blood stage is not enough, because hypnozoites in the liver will relapse. Primaquine (14 days) or tafenoquine (single dose) clears them, and both cause severe haemolysis in people with G6PD deficiency, so G6PD testing before treatment is required. This is a textbook example of pharmacogenomics in routine global health practice.

Chemoprevention for defined groups: seasonal malaria chemoprevention for children in the Sahel during the transmission season, intermittent preventive treatment in pregnancy, and prophylaxis for travellers (atovaquone-proguanil, doxycycline, or mefloquine, chosen by destination, duration, and tolerability).

Vaccines: RTS,S/AS01 and R21/Matrix-M target the sporozoite stage. Efficacy against clinical malaria is roughly 40 to 75 percent in the first year depending on the vaccine, schedule, and seasonality, waning thereafter. That is modest by the standards of measles vaccine and substantial by the standards of a disease killing hundreds of thousands of children, particularly combined with nets and chemoprevention.

What treatment costs

• Artemisinin combinations are generally well tolerated: nausea, dizziness, and, for lumefantrine, a requirement to take it with fatty food for absorption.
• Primaquine and tafenoquine: haemolysis in G6PD deficiency, which can be severe.
• Mefloquine: neuropsychiatric effects including vivid dreams, anxiety, and, rarely, serious psychiatric reactions, which is why it has fallen out of favour for travellers.
• Doxycycline: photosensitivity and oesophageal irritation, and it must not be used in pregnancy or young children.
• Quinine: cinchonism, a syndrome of tinnitus, deafness, and nausea, plus dangerous hypoglycaemia.

The other mosquito diseases

In short: A daytime-biting urban mosquito carries dengue, Zika, chikungunya, and yellow fever, and dengue's second infection is more dangerous than its first.

Aedes aegypti, a daytime-biting, urban, container-breeding mosquito, transmits a different family of viral diseases that are expanding rapidly as cities grow and the climate warms.

Dengue is now the fastest-growing mosquito-borne disease. There are four serotypes, and the crucial and dangerous feature is that infection with one gives lifelong immunity to that serotype and only temporary protection against the others. A second infection with a different serotype carries a substantially higher risk of severe dengue, in which plasma leaks from blood vessels, causing shock and bleeding, through a mechanism called antibody-dependent enhancement: antibodies from the first infection bind the new virus without neutralising it and help it enter cells. 2024 was the largest dengue year on record, with over 14 million reported cases. Treatment is careful fluid management, and there is no antiviral. Vaccines exist and their use is complicated precisely by the enhancement problem, since vaccinating someone never previously infected can mimic a first infection.

Chikungunya causes fever and severe joint pain that can persist for months or years. Zika is usually mild in adults and causes severe congenital brain malformations when it infects a pregnant woman, which is why a mild disease triggered a global emergency in 2015 to 2016. Yellow fever causes liver failure and haemorrhage, has a highly effective single-dose vaccine that gives lifelong protection, and still causes outbreaks where coverage lapses. West Nile virus is mostly mild and occasionally causes encephalitis.

Wolbachia is the most interesting new tool. Wolbachia bacteria, introduced into Aedes mosquito populations, block the mosquito's ability to transmit dengue and spread through the population by themselves. A cluster-randomised trial in Yogyakarta, Indonesia, found a 77 percent reduction in dengue cases in treated areas, and deployments are expanding.

Other vector-borne diseases worth naming: lymphatic filariasis (mosquito-borne worms causing elephantiasis, a major target for mass drug administration), leishmaniasis (sandflies), Chagas disease (triatomine bugs in the Americas, a leading cause of cardiomyopathy there), and Lyme disease (ticks in North America, Europe, and Asia).

What the person can do

• Sleep under an insecticide-treated net in endemic areas. It is the highest-value action available and it works because Anopheles bites at night.
• Get tested for any fever in or after travel to a malarious area, urgently. Falciparum malaria can go from mild to fatal in a day, and a fever within three months of return from a malarious area is malaria until proven otherwise.
• Take prophylaxis as prescribed, including the doses after leaving the area, which people routinely skip and which matter.
• Cover skin at dusk, use DEET or picaridin repellent, and screen windows.
• Remove standing water around the home. This is the main lever for Aedes-borne diseases such as dengue, since the mosquito breeds in buckets, tyres, and plant saucers rather than swamps.
• Complete the full course of any antimalarial, since partial treatment selects resistant parasites.

Living with it

In high-transmission areas, malaria is not a discrete event but a recurring tax on childhood: repeated episodes of fever, missed school, anaemia, and medical costs, on top of the deaths. Its economic drag is large enough to be visible in national accounts, and the historical association between malaria and poverty runs in both directions.

What's next

• Artemisinin partial resistance, first detected in Southeast Asia and now confirmed in East Africa, is the most serious threat. If artemisinin combinations fail in Africa the way chloroquine did, deaths will rise sharply. Triple combination therapies are being trialled in response.
• Monoclonal antibodies given as a single seasonal injection to prevent infection in children, in early trials.
• Next-generation vaccines, including whole-sporozoite and transmission-blocking approaches.
• Gene drives: genetically engineered mosquitoes designed to spread a gene that either suppresses the population or blocks parasite transmission. Technically demonstrated in the laboratory, and raising serious governance and ecological questions that are being worked through before field release.
• New insecticides and dual-active nets, since pyrethroid resistance is now widespread.
• Funding, which is again the limiting factor: WHO's own assessment is that current financing falls far short of what the targets require.

Sources and notes

Case and death figures are from the WHO World Malaria Report 2025 (2024 data): approximately 282 million cases and 610,000 deaths, with about 95 percent of deaths in the African Region. Artemisinin discovery: Tu Youyou, Nobel Lecture, 2015. Severe malaria treatment: SEAQUAMAT (The Lancet, 2005) and AQUAMAT (The Lancet, 2010). Bed net attribution: Bhatt et al., Nature, 2015, which estimated insecticide-treated nets accounted for the largest share of cases averted from 2000 to 2015. RTS,S: WHO recommendation 2021, based on phase 3 and pilot implementation data. R21/Matrix-M: WHO recommendation 2023. Wolbachia dengue trial: Utarini et al., NEJM, 2021 (77 percent reduction). Dengue 2024 case counts: WHO and PAHO surveillance. Duffy negativity and P. vivax: Miller et al., NEJM, 1976.

Open questions. How fast artemisinin partial resistance will spread in Africa, and whether triple therapies will hold it, is the field's central uncertainty. The ecological consequences and governance of gene drives are unresolved. Long-term durability of the current vaccines is not yet known.

Next: the organ that quietly processes everything you swallow, and the viruses that live in it. 👉