Malaria: The preventable, curable disease that kills millions

When we talk about malaria, we’re dealing with a surprisingly sophisticated enemy. This ancient disease is caused by tiny protozoan parasites from the Plasmodium genus—think of them as microscopic hitchhikers with a complex life plan.

Malaria parasites that infect humans: the Plasmodium parasite

Malaria is not a single entity. The disease is caused by single-celled parasites belonging to the Plasmodium genus. Five species are known to cause disease in humans:

• Plasmodium falciparum: This is the most prevalent malaria parasite on the African continent and is responsible for the most severe and life-threatening cases of malaria globally
• Plasmodium vivax: The dominant parasite outside of Africa, particularly in Asia and Latin America. P. vivax is notorious for its ability to cause relapsing malaria
• Plasmodium ovale: Also capable of causing relapses, this species is found mainly in West Africa and some islands in the Western Pacific
• Plasmodium malariae: This species can cause a long-lasting, chronic infection that may remain in the blood for decades if left untreated
• Plasmodium knowlesi: A species primarily found in Southeast Asia that normally infects macaques but can be transmitted to humans

The ability of P. vivax and P. ovale to cause relapses is due to a unique feature: they can form dormant stages in the liver called hypnozoites. These “sleeping” parasites can reactivate weeks, months, or even years after the initial mosquito bite, causing the person to become sick again. This makes treating these types of malaria more complex.

These parasites recruited accomplices to help them spread far and wide: female Anopheles mosquitoes. When one of these infected mosquitoes bites into someone like you or me, they inject the malarial parasites straight into your bloodstream. 

Causing human infections

While mosquito bites are the main highway for transmission, malaria rarely spreads through blood transfusions, shared needles, or from a mother to her baby during birth.

Once the parasites are in your system, they head straight to the liver, where they begin to multiply fast. Once they reach a particular limit, they burst out and invade your red blood cells, hijacking your body’s oxygen-delivery system and making you seriously ill.

From the parasite’s point of view, it’s a remarkably efficient process that’s been perfected over millennia, which is exactly why malaria remains such a formidable global health challenge.

The term “malaria” comes from the medieval Italian words mala aria, meaning “bad air.” People once believed the disease came from the foul-smelling air rising from swamps and marshlands. For centuries, the true cause remained a mystery.

The first major breakthrough came in 1880, when French army surgeon Charles Louis Alphonse Laveran observed parasites inside the red blood cells of a malaria patient in Algeria, identifying a microorganism as the cause for the first time.

Nearly two decades later, in 1897, British officer Ronald Ross, working in India, proved that mosquitoes were the vector, demonstrating that the Anopheles mosquito transmitted the parasites. 

These discoveries laid the groundwork for our modern understanding of the disease and its control.

Malaria is endemic in many countries. Large outbreaks and epidemics can occur when control measures fail or when weather changes. Understanding the epidemiology of the disease can help clinicians and public health agencies prevent or curtail outbreaks.

Notable malaria outbreaks

• 2024, Ethiopia: 7.3 million cases reported with 1,157 deaths. P. falciparum was responsible for over two-thirds of these cases.
• 2023, Ethiopia: 4.1 million malaria cases reported with 527 deaths.
• 2023-2024: Madagascar: 1.5 million malaria cases reported with 212 deaths.
• Global surge in 2020: Disruptions from the COVID-19 pandemic led to a sharp increase in malaria cases. The World Malaria Report 2021 found 241 million cases in 2020 (14 million more than in 2019) and 627,000 deaths.
• Burundi 2019: A national epidemic infected more than 8.5 million people in one year
• Venezuela 2015–2018: During a health system collapse, Venezuela reported over 1.2 million cases over 3 years
• Uganda 2015–2016: A district in northern Uganda saw malaria cases explode in 2015-16. The previous year, the number of cases per 1,000 people was 7. It rose over 16-fold to 113 per 1,000 in 2015.
• 1934-1935 Ceylon (modern day: Sri Lanka): 1.5 million malaria cases reported

The source of the malaria outbreaks data is GIDEON Informatics. Comprehensive outbreak details and related academic sources are found on the GIDEON platform, a leading infectious disease database.

Where is malaria found (endemic regions)?

Malaria is found in tropical and subtropical regions. The highest burden is in sub-Saharan Africa. 

• In 2023, about 94% of cases and 95% of malaria-related deaths were reported in the WHO African Region. Within Africa, Nigeria, the Democratic Republic of the Congo, Tanzania, and Niger account for the majority of cases.
• Outside Africa, malaria is also endemic in Central and South America, Southeast Asia, and parts of Oceania (such as Papua New Guinea). 
• P. falciparum dominates in Africa while P. vivax is more common outside sub-Saharan Africa.

Public health campaigns have successfully eliminated malaria from temperate regions like Europe and North America, marking a major victory over the parasitic infection.

But the threat isn’t completely gone. Travelers still bring the parasite back from endemic areas. Since Anopheles mosquitoes are still present in these regions, there is always a risk that they could bite an infected person and restart local transmission.

In our connected world, even “eliminated” diseases are just one plane ride away from making a comeback.

Who is most at risk?

Anyone living in or traveling to malaria-endemic areas can get malaria. However, certain groups are especially vulnerable:

• Children under the age of 5: Young children are at the highest risk of severe disease and death, especially in endemic regions
• Pregnant people: Malaria can cause severe anemia and complications in pregnancy
• People with weakened immune systems: People with HIV or AIDS are at high risk for malaria
• Travelers lacking immunity: Non-immune migrants, mobile populations, and travelers are at higher risk

Malaria is a parasitic disease spread by vectors. It is not contagious and cannot be spread from person to person like the flu.

How the Anopheles mosquito spreads malaria 

Malaria is transmitted to humans through the bites of infected female Anopheles mosquitoes. When a mosquito bites a person with malaria, it ingests microscopic parasites along with the blood.

These parasites mature inside the mosquito over a week or two. When the infected mosquito takes its next blood meal, it injects the parasites into a new person, and the cycle continues.

Symptoms of malaria typically appear 10 to 15 days after the infective mosquito bite.

Early, flu-like signs

The initial symptoms are often nonspecific and can be mistaken for a common cold or flu. These include:

• Fever
• Headache
• Chills
• Muscle aches and fatigue
• Nausea and vomiting

The classic malaria cycle: Chills, fever, and sweats

As the infection progresses, some people experience the “classic” malaria paroxysm, a cycle of symptoms that lasts 6-10 hours:

1. A cold stage (shivering, feeling cold)
2. A hot stage (high fever, headaches, vomiting)
3. A sweating stage (profuse sweating, return to normal temperature, tiredness)

This cycle often repeats every two days for P. falciparum, P. vivax, and P. ovale infections, and every three days for P. malariae infections.

Severe malaria: Complications of falciparum malaria

If a P. falciparum infection is not treated promptly, it can progress to severe malaria, which is a medical emergency. 

Complications can include:

• Cerebral malaria: Seizures, confusion, and loss of consciousness as parasites block small blood vessels in the brain.
• Severe anemia: Caused by the destruction of red blood cells.
• Acute respiratory distress syndrome (ARDS): Difficulty breathing due to fluid in the lungs.
• Organ failure: Particularly affecting the kidneys or liver

Anyone who has traveled to a malaria-endemic area and develops a fever should seek immediate medical attention.

The gold standard: Blood smears

The most reliable way to diagnose malaria is by examining a drop of the patient’s blood under a microscope. A blood smear is stained to make the parasites more visible. 

This method, known as microscopy, is the gold standard because it can confirm the presence of parasites, identify the specific species, and quantify the parasite density (the number of parasites in the blood).

Rapid diagnostic tests (RDTs)

Rapid diagnostic tests (RDTs) are another crucial tool. RDTs work like a pregnancy test, detecting specific antigens (proteins) produced by malaria parasites in a person’s blood. 

They provide results in just 15-20 minutes and are widely used in remote areas where microscopy is not available.

Note: Polymerase Chain Reaction (PCR) tests or molecular assays are highly sensitive but are mostly used in research or reference labs, not for routine diagnosis.

Early diagnosis and treatment of malaria are critical to prevent uncomplicated cases from progressing to severe disease and death.

Artemisinin-based combination therapies (ACTs)

These are first-line drugs for P. falciparum malaria worldwide. ACTs pair a fast-acting artemisinin derivative with a longer-acting partner drug, reducing the chance of resistance.

Other drug regimens

In areas where P. vivax, ovale, malariae, or knowlesi are present (or if ACTs are unavailable), other treatments may be used. Chloroquine is still effective for P. malariae and many P. vivax/ovale infections outside of regions with chloroquine resistance.

Eliminating the dormant stage in the liver

P. vivax and P. ovale have a dormant liver stage (hypnozoite) that causes relapses. Therefore, after treating the blood-stage infection, patients with vivax or ovale also receive primaquine (or tafenoquine) to kill the liver hypnozoites. 

Severe malaria treatment

When a person has severe or complicated malaria (for example, if they experience coma, organ failure, or very high parasite levels), urgent intensive care is needed. The recommended therapy is intravenous artesunate. If IV artesunate is not immediately available, an effective oral ACT can be given as an interim measure.

The growing challenge of malaria drug resistance

Malarial parasites are getting smarter, and that spells bad news for all of us. Just like bacteria and fungi can become resistant to antibiotics, malaria parasites are increasingly surviving our best antimalarial drugs.

Chloroquine is already ineffective against P. falciparum in many regions.

Additionally, the WHO is very concerned about confirmed partial artemisinin resistance in Eritrea, Rwanda, Uganda, and the United Republic of Tanzania, with such resistance also suspected in Ethiopia, Namibia, Sudan, and Zambia. 

This is especially alarming because artemisinin-based drugs have been our gold standard for treating deadly malaria for years. When these treatments start failing, patients get sicker for longer, more people die, and doctors have to fall back on older, less effective medicines. 

With the African continent carrying 95% of the world’s malaria burden, the spread of drug resistance there could undo decades of progress and turn a treatable disease back into a mass killer.

Continuous surveillance and research into new drugs are vital to stay ahead of the parasite.

Prevention is a cornerstone of malaria control, involving a multi-pronged approach.

Traditional methods: Avoiding mosquito bites

The simplest form of prevention is to avoid being bitten by Anopheles mosquitoes, which primarily bite between dusk and dawn. 

Key strategies include:

• Sleeping under long-lasting insecticidal nets (LLINs)
• Using an insect repellent containing DEET
• Wearing long-sleeved shirts and trousers
• Indoor residual spraying (IRS), where insecticides are applied to the inside walls of homes

Prophylaxis: Medication for travelers

For travelers visiting malaria-endemic regions, chemoprophylaxis is highly effective in preventing malaria. 

This involves taking antimalarial drugs, such as atovaquone-proguanil, doxycycline, or mefloquine, before, during, and after the trip to prevent the disease.

A new era: Malaria vaccines

For decades, a highly effective malaria vaccine was an elusive goal. But recent breakthroughs have changed the landscape of malaria prevention.

• RTS, S/AS01 (Mosquirix): In 2021, the WHO recommended the widespread use of the RTS, S vaccine for children in sub-Saharan Africa. In large-scale clinical trials, the vaccine was shown to reduce clinical malaria cases by about 36% in young children over four years
• R21/Matrix-M: In 2023, a second vaccine, R21/Matrix-M, also received a WHO recommendation. It has shown high efficacy of up to 77% in trials and is expected to significantly increase the supply of malaria vaccines available

These vaccines represent a historic achievement and are a powerful new tool to be used with existing preventive measures to protect the most vulnerable and at-risk groups.

Outbreak monitoring saves lives

Beyond individual protection, cutting-edge disease surveillance and outbreak monitoring systems are critical for staying ahead of malaria. 

Real-time data tracking helps health authorities spot unusual patterns in cases, identify emerging hotspots, and deploy rapid response teams before small outbreaks become major epidemics. 

In our interconnected world, the difference between containing malaria and watching it spread often comes down to how quickly we can detect and respond to the first warning signs.

Malaria remains a formidable public health challenge, but the story of our fight against it is one of remarkable scientific progress and resilience. From understanding its “bad air” origins to deploying groundbreaking vaccines, we have developed an impressive arsenal of tools.

However, challenges like drug resistance and climate change, which can expand mosquito habitats, mean that we cannot afford to be complacent. Continued investment in research, surveillance, and equitable access to prevention and treatment is essential to continue reducing the global burden of this ancient disease and move toward the ultimate goal of eradication.

1. What are the first signs of malaria? 

The first signs of malaria are typically flu-like and can include fever, headache, chills, muscle aches, and fatigue. These symptoms usually begin 10 to 15 days after being bitten by an infected mosquito.

2. Can malaria be cured?

Yes, malaria is a curable disease. With prompt diagnosis and the correct antimalarial medication, the parasites can be cleared from the body. However, if left untreated, especially infections with Plasmodium falciparum, it can become severe and fatal.

3. How is malaria transmitted?

Malaria is transmitted to people through the bites of infected female Anopheles mosquitoes. It is not contagious and cannot be spread through casual contact from person to person. In rare cases, it can be transmitted through blood transfusions or from a mother to her fetus.

4. What is the main cause of malaria?

The main cause of malaria is a single-celled parasite from the Plasmodium genus. Five different species of this parasite can infect humans, with Plasmodium falciparum (P. falciparum) being the most common and deadliest to humans.

GIDEON is one of the most well-known and comprehensive global databases for infectious diseases. Data is refreshed daily, and the GIDEON API allows medical professionals and researchers access to a continuous stream of data. Whether your research involves quantifying data, learning about specific microbes, or testing out differential diagnosis tools– GIDEON has you covered with a program that has met standards for accessibility excellence.

Learn more about infectious diseases on the GIDEON platform.

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