17.7 — Malaria and the Mosquito-Borne Diseases

Mosquitoes kill more humans than any other animal. Malaria alone has probably killed more people than any other single cause in human history, and it has shaped the human genome more than any other pathogen — sickle cell, thalassaemia, G6PD deficiency and Duffy negativity are all its fingerprints (Chapter 3.3).

And it is being pushed back. Deaths fell from around 900,000 a year in 2000 to around 600,000 today, despite population growth. Europe and North America eliminated it entirely. The first malaria vaccines are now being deployed.

Malaria

Caused by Plasmodium, a protozoan, transmitted by female Anopheles mosquitoes — which bite between dusk and dawn.

That timing is the basis of the single most effective control measure: insecticide-treated bed nets, which work because the vector bites at night.

Five species infect humans, and the distinction matters.

P. falciparum — the dangerous one. Responsible for the great majority of deaths, and dominant in Africa.

P. vivax — widespread in Asia and South America, rarely fatal, and it forms dormant liver stages that reactivate months or years later.

P. ovale — similar, with liver stages.

P. malariae — mild, and can persist for decades.

P. knowlesi — a monkey parasite that infects humans in Southeast Asia.

The life cycle, briefly

Mosquito bite → parasites travel to the liver → multiply there for 1 to 2 weeks → burst out into the blood → invade red cells → multiply → rupture the cells synchronously → repeat.

And the synchronous rupture is what produces the classic fever pattern — spikes every 48 or 72 hours depending on the species, because the whole population of parasites completes its cycle together.

In practice the fever is often irregular, particularly early and in falciparum, which is why waiting for a textbook pattern delays diagnosis.

Why falciparum is the lethal one:

It infects red cells of all ages, so parasite loads can become enormous, while the others prefer young or old cells only.

And it makes infected cells sticky. Proteins on the cell surface bind to blood vessel linings, so infected cells adhere in small vessels rather than circulating.

That sequestration is the mechanism of severe malaria. In the brain it causes cerebral malaria; in the placenta it causes pregnancy complications; and it explains why the visible parasite count in the blood underestimates the true burden.

Recognising it

Fever in anyone who has been in a malarial area in the past year is malaria until proven otherwise.

And "the past year" is deliberate. Falciparum usually presents within 3 months and vivax can present a year or more later from liver stages.

Symptoms are non-specific: fever, chills, sweats, headache, muscle aches, nausea. It is routinely mistaken for influenza, and that mistake is how people die.

Severe malaria — impaired consciousness, seizures, breathing difficulty, jaundice, severe anaemia, low blood sugar, kidney failure, shock.

Falciparum malaria can progress from mild symptoms to death within 24 hours. This is the single most important fact in the chapter, and it is why a fever after travel is an urgent rather than a routine presentation.

Diagnosis: blood film microscopy remains the standard and identifies the species and the parasite count. Rapid diagnostic tests detect parasite antigen in minutes, need no laboratory, and have transformed diagnosis in rural settings.

And a single negative film does not exclude it — three films over 48 hours are standard if suspicion remains.

Treatment

Artemisinin-based combination therapy is first-line for uncomplicated falciparum.

Artemisinin was found by Tu Youyou working through classical Chinese medical texts (Chapter 3.7), and she shared the 2015 Nobel Prize for it.

Combination rather than single-agent is deliberate, to slow resistance — the same logic as HIV treatment.

Severe malaria: intravenous artesunate, which replaced quinine after trials showed a substantial mortality reduction.

Vivax and ovale need a second drug — primaquine or tafenoquine — to clear the dormant liver stages, otherwise it relapses.

And G6PD testing is required first, because these drugs cause severe haemolysis in deficiency (Chapter 7.1) — one of the clearest examples of a genetic test changing a prescription.

Resistance is the live concern. Artemisinin partial resistance emerged in Southeast Asia and has now been detected in East Africa, which is the development the field is watching most closely.

Prevention

And the layered approach is what works — no single measure is sufficient.

Insecticide-treated bed nets — the single most effective intervention. Distribution campaigns are credited with a large share of the mortality reduction since 2000.

Indoor residual spraying.

Repellents containing DEET or picaridin, and covering up at dusk and dawn.

Chemoprophylaxis for travellers — several options, chosen by destination, resistance pattern and individual factors. All must be started before travel and continued after return, which is where compliance most often fails.

Seasonal chemoprevention in children in areas with a defined transmission season.

And vaccines, finally.

RTS,S/AS01 was recommended by the WHO in 2021 — the first malaria vaccine ever approved — followed by R21/Matrix-M in 2023, which is cheaper and can be produced at larger scale.

Efficacy is around 40 to 75 percent depending on the vaccine and the schedule, which is modest by vaccine standards and substantial against a disease of this scale. Rollout across African countries is underway.

The other mosquito-borne diseases

Different mosquitoes, different times of day, which matters for prevention.

Aedes mosquitoes bite during the day, particularly early morning and late afternoon. Bed nets are far less useful against them, and repellent during daylight matters more.

Dengue

Four related viruses, spread by Aedes, and around 400 million infections a year — rising.

High fever, severe headache, pain behind the eyes, and intense muscle and joint pain — hence "breakbone fever". A rash appears as the fever settles.

And dengue has a feature that is genuinely unusual and important.

A second infection with a different serotype carries a substantially higher risk of severe disease than the first.

The mechanism is antibody-dependent enhancement: antibodies from the first infection bind the new serotype without neutralising it, and the antibody-coated virus is then taken up more efficiently by immune cells — the antibody helps it in.

Which is why severe dengue is more common in second infections, and why dengue vaccines have been genuinely difficult. One vaccine was withdrawn from routine use in the Philippines after it increased severe disease in previously uninfected recipients — the vaccine acted like a first infection. It is now given only to those with confirmed prior infection, and newer vaccines are being assessed against the same concern.

Severe dengue — plasma leakage, bleeding and organ impairment, appearing as the fever falls rather than at its peak.

And the warning signs, which are what to watch for: severe abdominal pain, persistent vomiting, bleeding gums or nose, lethargy or restlessness, and rapid breathing.

Treatment is supportive, with careful fluid management — and NSAIDs and aspirin are avoided because of bleeding risk. Paracetamol only.

Chikungunya

Aedes-borne. Fever and severe joint pain, and the joint pain is the defining feature — it can persist for months or years in a substantial minority, which is what distinguishes it from dengue in retrospect.

Zika

Usually mild or asymptomatic. Its importance is in pregnancy — congenital Zika syndrome including severe microcephaly (Chapter 4.6), established during the 2015–16 South American epidemic.

It is also sexually transmissible, which is unusual for an arbovirus and which affects travel advice for couples planning pregnancy.

Yellow fever

Fever, jaundice, bleeding, and a mortality of 20 to 50 percent in severe cases.

And there is an excellent vaccine — a single dose giving lifelong protection, required for entry to many countries.

Japanese encephalitis and West Nile virus

Mostly asymptomatic, occasionally causing severe encephalitis. A vaccine exists for Japanese encephalitis.

Lymphatic filariasis

Worms transmitted by mosquitoes, lodging in lymphatics (Chapter 7.8). Mass drug administration has eliminated it from multiple countries.

Non-mosquito vectors, briefly

Ticks — Lyme disease, tick-borne encephalitis, and several rickettsial infections.

And the practical advice is specific: check for ticks after being in long grass or woodland, and remove them promptly with fine-tipped tweezers, grasping close to the skin and pulling steadily upward. Transmission risk rises with attachment time, so prompt removal matters more than the technique.

Sandflies — leishmaniasis. Tsetse flies — sleeping sickness. Triatomine bugs — Chagas disease. Fleas — plague, which still occurs and is treatable with antibiotics.

What is improving, and what is not

Improving: malaria deaths down by around a third since 2000. Vaccines finally available. Guinea worm nearly eradicated. River blindness and filariasis eliminated from multiple countries.

Not improving: dengue is spreading, and its range is expanding with warming temperatures and urbanisation. Insecticide resistance in mosquitoes is widespread. Artemisinin resistance is spreading.

And the interventions in development are interesting. Wolbachia — a bacterium introduced into Aedes populations that blocks dengue transmission — has produced large reductions in trials. Gene drives that could suppress mosquito populations exist technically and raise genuine ecological and governance questions.

The practical summary for a traveller is short. Check what is endemic where you are going. Take prophylaxis if advised, and take it properly. Use repellent and nets. And treat any fever within a year of travel as urgent, not routine.

What the next page fixes

Chapter 17.8 covers the infection that has killed more people than any other in history and is still, quietly, the leading infectious cause of death worldwide.