Malaria: The Deadliest Killer Disease Ever Known


By Barry C. Fox, M.D.University of Wisconsin

Malaria is one of the oldest known diseases on Earth. It’s also one of the deadliest killer diseases in the world despite a multitude of global efforts to decrease the mortality rates. And there has been plenty of time to conquer malaria, yet malaria still manages to infect one out of every 21 human beings on the planet and kills nearly one million people every year.

Illustration of infected blood cells with Plasmodium parasite.
Plasmodium parasites cause malaria. They invade blood cells and feed on hemoglobin. (Image: Christoph Burgstedt/Shutterstock)

The Historical Importance of Malaria

On many occasions, malaria has changed the course of human history. For example, malaria may have contributed to the fall of the Roman Empire. The Romans were used to being infected with a non-fatal strain of vivax malaria but later encountered a new mosquito species that brought the much more deadly falciparum malaria form.

In World War II, many battles in the South Pacific, between the U.S. and Japanese armies, were solely for the purpose of securing islands that supported the growth of quinine—the first and most important antimalarial compound at the time. More soldiers were dying in the South Pacific from malaria than from actual combat.

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Ronald Ross’s Malaria Research

A photograph of Sir Ronald Ross.
Sir Ronald Ross discovered that mosquitoes were the transmitters of malaria. (Image: Valérie75/Public domain)

The name ‘malaria’ is derived from Italian mala aria, meaning ‘bad air’. In 1717, a link was suggested between the illness and poisonous swamp gases. It’s fortunate that a British physician in India named Ronald Ross took a keen interest in malaria. In 1894, he headed to Bombay Civil Hospital to assess malaria patients. And he spent two years studying the disease and even contracted the illness himself.

He decided to pay malaria patients to let eight mosquitoes bite them in order to test his theory that mosquitoes were responsible for malaria transmission. After the bites, Ross dissected the mosquitoes. He noticed tiny round cysts that were attached to the mosquito’s stomach wall. 

He realized that the cyst was actually the malaria parasite. Discovering that mosquitoes were the transmitters of malaria was a huge breakthrough. This and other malaria research eventually earned him the 1902 Nobel Prize in Medicine.

The Culprit Responsible for the Spread of Malaria

The Anopheles mosquito species of malaria is the only one of hundreds of mosquitoes that carries the malaria parasite known as Plasmodia. Only the female is responsible for malaria transmission. 

An image of the Anopheles mosquito on a white background.
The Anopheles mosquito carries malaria parasites causing malaria. (Image: Kletr/Shutterstock)

There are five species of plasmodium parasites that affect humans. The most virulent is Plasmodia falciparum, which causes 50 percent of infections and 95 percent of deaths. Plasmodia are so specialized at survival that they have both sexual and asexual forms of reproduction.

When female mosquitoes feed on the blood of an infected human, it absorbs gametocytes—the sexual elements of the parasite—the equivalent to a sperm or egg. The gametocytes combine to form oocytes that burrow into the mosquito’s stomach—the little round cysts Ronald Ross saw.

The growth and division of each oocyte produce thousands of active malaria forms called sporozoites. After a week or two, the oocyte bursts, releasing sporozoites that invade the mosquito’s salivary glands. And the next time the mosquito bites, it releases these sporozoites from its salivary glands into the new human host.

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What Happens after the Mosquito Bite

After the mosquito bite, the parasites move through the bloodstream directly to the liver, where they establish a parasitic stage—taking over the liver cells and replicating thousands of times. But their ultimate destination is not the liver. They break out of the liver cells to attach to and invade the red blood cells of the circulatory system.

The malaria parasites are resilient, and they enhance their multiplication by taking over the red cells and using sexual reproduction to proliferate even further. The immune system is triggered, causing a resetting of the body’s thermostat. 

This causes fever to destroy the invaders, but even though it kills some, most remain. The surviving parasites in the red blood cells are feeding on the hemoglobin as a nutrient source and continuing replication. The red blood cell counts fall, and there is reduced capacity to transport oxygen, which produces fatigue and weakness.

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Various Malaria Species Produce Different Symptoms

At this point, what happens to the individual human is dependent on the species of the malaria parasite causing the infection. If the species is Plasmodium vivax or ovale, they cause mild symptoms and return to the liver. Approximately 72 hours later, they usually produce another wave of parasites that invade the blood. 

Usually, there are two or three waves of blood invasion before they settle into a hibernating state in the liver or the spleen. And they can remain in the liver to enter the blood weeks, months, or occasionally, years later. This 72-hour time cycle is important because victims feel remarkably well in the two days between the three-day parasitic cycle. The fever pattern is actually a major clue to the diagnosis of malaria.

Each time the parasites are released into the blood, there is a loss of oxygen-carrying red blood cells. The liver and spleen also enlarge since these organs act like giant lymph nodes, trapping red blood cell-laden parasites. One of the reasons malaria has survived as a parasitic disease for thousands of years is that P. ovale and vivax usually do not kill the human host. Instead, they act as a reservoir for transmission to others.

Common Questions about Malaria

Q: Who was Ronald Ross? 

Ronald Ross was a British physician who studied malaria patients at Bombay Civil Hospital for two years. He discovered that mosquitoes were the transmitters of malaria and was awarded the 1902 Nobel Prize of Medicine for his research.

Q: What happens after an infected Anopheles mosquito bites a healthy person?

Immediately after the bite, the malaria parasites move through the bloodstream directly to the liver, where they establish a parasitic stage. They replicate thousands of times in the liver and then attach to and invade the red blood cells and feed on hemoglobin.

Q: How many species of Plasmodium parasites are there? 

In general, there are five species of Plasmodium parasites that cause malaria. P. falciparum, P. vivax, and P. ovale are examples of these species. Plasmodia falciparum species causes severe complications and death. P. vivax and P. ovale have milder side effects and usually do not cause death.

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