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Podcast Transcript
Malaria is one of the oldest known infectious diseases, with a history spanning thousands of years. It has shaped human civilization, influenced wars, and driven scientific advancements in medicine and public health.
However, humanity has been making strides against this ancient disease over the last 250 years. We have learned what causes it and how it is transmitted, and we might be close to eradicating it completely.
Learn more about malaria, how it has impacted humanity, and the quest to eliminate it in this episode of Everything Everywhere Daily.
Malaria is one of a small handful of diseases that have majorly impacted humanity.
Some diseases like smallpox have been completely eradicated. Other, such as bubonic plague and cholera still exist, but can be easily treated with modern medicine.
Malaria has a unique history. It has been around probably longer than any other disease that has impacted humanity, and it is still around today. While we are making strides in eradicating the disease, it hasn’t been totally tamed and still takes the lives of hundreds of thousands of people every year.
For most of you listening to this, malaria isn’t something you’ve probably suffered from and not something you probably worry too much about. Nonetheless, it does affect an enormous number of people every year.
Malaria is caused by parasites of the Plasmodium genus of protists, which are transmitted to humans through the bite of infected female Anopheles mosquitoes.
Protists are single-cell eukaryotes, meaning that they have a nucleus in their cell. So, they are not bacteria but also not plants, animals, or fungi.
Malaria has a history that goes back further than any other disease that we know of.
Fossilized mosquitoes trapped in amber, dating back around 100 million years, contain malaria-like parasites.
DNA studies suggest that malaria-causing parasites have co-evolved with humans and primates for at least 30 million years.
Many of the worst diseases that have affected humanity have come from contact with domesticated animals or were passed from person to person. Many of those diseases, like smallpox, were probably seldom seen or were non-existent before the rise of agriculture.
However, because mosquitos transmit malaria, it’s been around forever. It didn’t require a large population for it to spread.
As soon as humans began recording information, there were reports of malaria.
Ancient Sumerian and Egyptian texts describe periodic fevers and enlarged spleens, symptoms characteristic of malaria.
Egyptian mummies from the New Kingdom about 3500 years ago have shown traces of Plasmodium falciparum, the most deadly malaria parasite.
The Atharva Veda, an ancient Hindu scripture, refers to fevers and diseases linked to mosquito-infested swamps.
In China, The Nei Ching, aka The Canon of Medicine, from around 2700 BC describes febrile illnesses similar to malaria.
Malaria likely migrated from Egypt to Rome through trade, military campaigns, and human migration, facilitated by the extensive networks of the Roman Republic and Empire. The Nile River Valley in Egypt was a known hotspot for malaria, particularly due to its warm climate and abundant mosquito breeding grounds. As Rome expanded its influence into North Africa, soldiers, merchants, and slaves carried the parasite with them across the Mediterranean.
The disease found a suitable environment in the marshy areas of Italy, particularly around Rome, where stagnant water provided an ideal breeding ground for Anopheles mosquitoes.
Over time, malaria spread northward into Europe, aided by Roman roads, trade routes, and urbanization, weakening populations and contributing to the decline of the Roman Empire.
During the Middle Ages to the Renaissance, malaria remained endemic across Europe, the Middle East, and Asia.
The disease was known as “Roman fever” due to its association with marshy areas around Rome.
The term “malaria” derives from the Italian phrase mal aria, which means bad air, based on the mistaken belief that miasmas or foul air from swamps caused the disease.
When Europeans went to the Americas, they probably brought malaria. I say probably because mummies found in the New World had malaria antibodies. So, it could be that there was a strain of malaria in the New World, and other, more deadly strains came over in the Columbian Exchange.
Oddly enough, it was in the New World that one of the first major breakthroughs in treating malaria was made.
In the 17th Century, Jesuit missionaries in South America observed that indigenous peoples used cinchona bark to treat fevers.
An extraction made from the Cinchona tree became the first effective treatment for malaria. It was known as Quinine.
Quinine works by interfering with the Plasmodium parasite’s ability to digest hemoglobin inside red blood cells. The malaria parasite consumes hemoglobin as a food source, producing a toxic byproduct called heme, which it normally detoxifies by converting it into an insoluble form called hemozoin.
Quinine disrupts this detoxification process, causing toxic heme to accumulate within the parasite, ultimately leading to its death. Quinine is particularly effective against Plasmodium falciparum, the deadliest malaria strain, and has been used since the 17th century. However, it can cause side effects like tinnitus, nausea, and headaches, and modern treatments have largely replaced quinine in most cases.
Malaria was one of the biggest reasons why most of Africa wasn’t colonized until the 19th century. Europeans who went into the interior of Africa suffered high rates of malaria, which prevented colonization.
Quinine was one of the things that made it possible.
The reason why Europeans had a unique disadvantage was that they didn’t have the genetic adaptations to resist malaria.
Over thousands of years, natural selection has led to the development of several genetic adaptations that provide resistance to malaria, particularly in regions where the disease is endemic. These adaptations affect red blood cells, which the Plasmodium parasite infects, making it harder for the parasite to survive and reproduce.
One of the most common genetic resistances is the Sickle Cell Trait. People with one copy of the sickle cell gene have partial protection against Plasmodium falciparum malaria.
Sickle-shaped red blood cells are less hospitable to the parasite, making it harder for malaria to thrive.
However, inheriting two copies of the gene leads to sickle cell disease, a severe blood disorder.
The late 19th century saw huge advancements in the understanding of malaria and its transmission.
In 1880, Alphonse Laveran, a French army doctor, identified malaria parasites in the blood of infected patients.
He won the Nobel Prize in Physiology in 1907 for this discovery.
In 1897, British physician Sir Ronald Ross demonstrated that Anopheles mosquitoes transmit the malaria parasite.
This discovery revolutionized malaria control efforts, leading to mosquito eradication campaigns.
In the 20th century, malaria was still a major problem in North America, Europe, Asia, South America, and Africa.
The war on malaria was fought on two fronts. One was the development of treatments for malaria, and the other was the eradication of malaria-carrying mosquitoes.
One of the biggest advances in the treatment of malaria was the discovery of Chloroquine.
Chloroquine was first synthesized in 1934 by German scientist Hans Andersag and his team while working for the Bayer Corporation. Initially, it was dismissed as too toxic and remained largely unutilized. However, during World War II, the search for antimalarial drugs intensified due to quinine shortages, prompting researchers to re-examine chloroquine.
By the 1940s, it was found to be both effective and safe for malaria treatment, leading to its widespread use as the primary antimalarial drug for decades. Unfortunately, by the 1950s through 1970s, Plasmodium falciparum developed resistance to chloroquine.
Several other treatments were developed, but they suffered from resistant strains which quickly developed.
One of the biggest advances was Artemisinin, which was discovered in the 1970s.
Derived from the sweet wormwood plant it was discovered by Chinese scientist Tu Youyou. She won the Nobel Prize in Medicine for her discoveries in 2015.
This became the foundation for artemisinin-based combination therapies, which remain the gold standard for malaria treatment today.
On the mosquito front, the biggest development was the creation of Dichlorodiphenyltrichloroethane, or DDT, in 1939. It became a revolutionary insecticide in the fight against malaria.
During World War II, DDT was used to protect troops from malaria.
Post-war, DDT spraying campaigns were launched globally to eliminate Anopheles mosquito populations.
These efforts were largely disjointed and unorganized until 1955 when the World Health Organization launched the Global Malaria Eradication Program or GMEP.
The program’s goal was nothing less than to eliminate malaria worldwide through massive mosquito control and antimalarial treatment efforts.
The program relied heavily on indoor residual spraying with DDT, draining mosquito breeding sites, and widespread distribution of antimalarial drugs like chloroquine. GMEP saw significant success in North America, Europe, the Caribbean, and parts of Asia and Latin America, where malaria was largely eliminated.
However, it failed in sub-Saharan Africa, where logistical, financial, and environmental challenges, DDT-resistant mosquitoes, and drug-resistant parasites made eradication infeasible.
Despite its successes, the program was ended in 1969 due to funding shortages.
Starting in the 1970s, the overuse of DDT led to mosquito resistance.
Environmental concerns about DDT’s effect on wildlife led to DDT bans in many countries and a shift to alternative pesticides.
Slowly but surely, more and more countries were able to eliminate malaria.
In the late 20th and 21st centuries, strategies changed. The remaining countries where malaria was still prevalent were the ones where it was the hardest to eradicate.
One of the biggest modern techniques to fight malaria has been the adoption of Insecticide-Treated Bed Nets.
Bed nets seem like a rather low-tech solution, and in some ways, it is, but it is also highly effective.
Insecticide-treated bed nets are one of the most effective tools for malaria prevention, designed to protect people from mosquito bites while they sleep. These nets are impregnated with long-lasting insecticides which not only act as a physical barrier but also kill or repel mosquitoes that come into contact with them.
ITNs have been shown to reduce malaria transmission by over 50% and lower child mortality rates in endemic regions. They are especially crucial in sub-Saharan Africa, where malaria transmission is highest.
Perhaps the most promising development in the war on malaria has been the development of malaria vaccines.
The development of malaria vaccines has been a long and challenging process due to the complex lifecycle of the Plasmodium parasite, which allows it to evade the human immune system.
??The Mosquirix vaccine was developed over several decades, with research beginning in the 1980s. It was created by GlaxoSmithKline in collaboration with the PATH Malaria Vaccine Initiative.
The first successful clinical trials were conducted in the early 2000s, and large-scale Phase III trials took place between 2009 and 2014, demonstrating partial efficacy against Plasmodium falciparum. After years of evaluation, the World Health Organization officially endorsed Mosquirix in October 2021, making it the first malaria vaccine approved for widespread use.
Mosquirix had an efficacy of only 40%, which was good but not great.
A more effective alternative emerged with the R21/Matrix-M vaccine, developed by Oxford University and the Serum Institute of India. Approved by WHO in October 2023, this vaccine demonstrated a higher efficacy of around 75% in clinical trials.
Like Mosquirix, it targets the liver stage of the malaria parasite but appears to provide longer-lasting protection. With a production capacity expected to reach 100 million doses per year, R21 is seen as a more scalable and cost-effective solution, and its rollout began in early 2024 in Burkina Faso, Ghana, and Nigeria.
Malaria is still a significant problem in the world.
Currently, malaria causes approximately 600,000 to 620,000 deaths per year, with the vast majority occurring in sub-Saharan Africa, particularly among children under five years old.
There is a belt around the equator where malaria still exists. This includes Southeast Asia, South America, the Middle East, and Sub-Saharan Africa.
However, progress is being made. In 2024, two more countries, Cape Verde and Egypt, were declared malaria-free. That means there were three consecutive years of zero cases in each country.
With these two additions, there are now 44 countries that have been declared malaria free.
Malaria has shaped human history for millennia, influencing civilizations, wars, and scientific advancements. While major progress has been made, the battle against malaria is far from over. New vaccines and global eradication programs finally offer hope for a future that is malaria-free.