Malaria is one of humanity’s oldest infectious diseases. The history of malaria stretches from ancient civilizations to modern molecular epidemiology, and its distribution has changed dramatically over time.
Today, malaria remains a major global health problem. In 2024, an estimated 282 million people developed malaria and approximately 610,000 died across 80 countries. About 95% of both cases and deaths occurred in the WHO African Region.
Malaria in Ancient Period
Plasmodium antigens have been detected in Egyptian remains dating to approximately 3200 BC and 1304 BC. Ancient descriptions of periodic fevers and enlarged spleens from several civilizations are also consistent with malaria.
In ancient India, writings from the Vedic period (approximately 1500–800 BC) described malaria-like illness. The disease was reportedly referred to as the “king of diseases.”
Chinese medical writings provide another early record. The Nei Chin, traditionally dated to around 270 BC, described tertian and quartan fevers and associated them with splenic enlargement features compatible with malaria.
Greek writers also described illnesses resembling malaria. References to recurring fever can be found in the works of Homer, Hippocrates, Aristotle, Plato and Sophocles.
Malaria and the Roman World
Malaria became deeply established in the Mediterranean region during antiquity.
Historical evidence suggests that malaria reached Italy during the first century AD, probably through movements of people and trade from North Africa and the eastern Mediterranean.
The Roman Campagna, surrounding Rome, remained notorious for malaria for centuries.
History of Malaria in the Europe
For centuries, malaria occurred throughout large parts of Europe. It was particularly associated with wetlands, river valleys, agricultural areas and marshes where Anopheles mosquitoes could reproduce.
Malaria subsequently moved northward into parts of Europe and was historically present as far north as England and Denmark.
Malaria reaches the Americas
There is no convincing historical evidence for malaria in the Americas before European exploration. European colonists introduced P. vivax and P. malariae, while African slave trading subsequently introduced P. falciparum.
By approximately 1750, P. vivax and P. falciparum were established across extensive areas ranging from tropical Latin America through the Mississippi Valley and into New England.
Discovery of parasite by Laveran: 1880
French army physician Charles Louis Alphonse Laveran examined the blood of a malaria patient in Algeria. On 20 October 1880, he observed unusual pigmented bodies in red blood cells that he recognized as the organism responsible for malaria.
Laveran subsequently examined blood from 192 malaria patients and observed pigment-containing crescent forms in 148 patients.
His discovery established that malaria was caused by a parasite, not by poisonous swamp air. Laveran was awarded the 1907 Nobel Prize in Physiology or Medicine for his discovery of protozoa as the cause of diseases.
Further work by Camillo Golgi demonstrated that rupture of malaria parasites from red blood cells corresponded with the periodic fevers characteristic of malaria. P. vivax and P. malariae were associated with approximately 48-hour and 72-hour cycles, respectively.
The mosquito connection and human transmission cycle: 1897-1898
On 20 August 1897, now commemorated as World Mosquito Day, British physician Ronald Ross discovered pigmented malaria parasites developing inside an Anopheles mosquito that had fed on infected blood.
Ross received the 1902 Nobel Prize in Physiology or Medicine for his work on malaria.
Italian scientists including Giovanni Battista Grassi, Amico Bignami, Giuseppe Bastianelli, Angelo Celli, Camillo Golgi and Ettore Marchiafava subsequently demonstrated that human malaria was transmitted by Anopheles mosquitoes.
Parasite → human host → mosquito vector → human host
Malaria and the Panama Canal
Once mosquitoes were recognized as vectors, malaria control increasingly focused on reducing mosquito populations and preventing mosquito–human contact.
During construction of the Panama Canal, malaria and yellow fever posed major threats to workers.
Under William C. Gorgas, sanitation programmes included drainage, larval control, screening and other measures. These interventions greatly reduced malaria and virtually eliminated yellow fever during the canal construction period.
Quinine changes malaria treatment: 17th-19th centuries
During the 17th century, Jesuit missionaries helped introduce cinchona bark to Europe, where it became an important treatment for intermittent fevers. In 1820, French chemists Pierre Joseph Pelletier and Joseph Bienaimé Caventou isolated quinine from cinchona bark.
Quinine subsequently became the principal antimalarial drug for more than a century.
World War II accelerated malaria research. Pamaquine was developed in the 1920s, while quinacrine became important during World War II. Chloroquine subsequently emerged as one of the most important antimalarial drugs of the twentieth century.
DDT and the Era of malaria eradication
The development of DDT dramatically changed malaria control.
DDT could be applied to the interior walls of houses, killing mosquitoes that rested on treated surfaces.
Following World War II, DDT and chloroquine created optimism that malaria might be eliminated globally.
Global Malaria Eradication Programme: 1955
In 1955, WHO launched the Global Malaria Eradication Programme (GMEP). It represented the first major coordinated attempt to eradicate a disease globally.
The strategy relied heavily on:
- indoor residual spraying;
- DDT;
- surveillance;
- rapid diagnosis;
- treatment;
- interruption of transmission.
The programme achieved substantial success in several regions.
However, global eradication proved much more difficult than anticipated.
Why eradication failed
Malaria transmission was influenced by far more than mosquitoes and parasites.
The disease was strongly associated with:
- poverty;
- agricultural practices;
- environmental change;
- inadequate housing;
- migration;
- war;
- political instability;
- weak health systems.
These factors made sustained elimination difficult, particularly in sub-Saharan Africa. Packard’s historical analysis emphasizes that malaria became a distinctly “tropical” disease partly because of the interaction between ecology, economic development, poverty and political conditions.
Resistance created another major problem.
Chloroquine resistance
The first well-established chloroquine-resistant P. falciparum infections appeared in:
- Thailand–Cambodia border: ~1957
- Venezuela/Colombia: ~1960
- Papua New Guinea: mid-1970s
Resistance subsequently spread to Africa, where chloroquine-resistant P. falciparum was documented by 1978 in travellers returning from Kenya and Tanzania.
The discovery of malaria parasites in the liver
In 1948, researchers Henry Shortt and Cyril Garnham identified the previously unknown tissue stage of malaria parasites in the liver. This discovery explained how parasites could develop in the liver before entering the bloodstream.
Later, in 1982, Wojciech Krotoski and colleagues conclusively demonstrated dormant liver stages, known as hypnozoites, in P. vivax and P. ovale. This discovery helped explain why P. vivax infections can relapse months after the original infection.
Artemisinin: A new era of treatment
Another major chapter in malaria history came from China. Artemisinin was derived from Artemisia annua, or sweet wormwood.
Chinese scientists isolated the active antimalarial compound in 1972. The traditional use of A. annua for fever dates back much further; a Chinese medical text associated with Ge Hong in AD 340 described its use for chills and fever.
Artemisinin and its derivatives rapidly became important treatments for P. falciparum malaria. Today, artemisinin-based combination therapies (ACTs) are central to malaria treatment in many endemic countries.
Malaria and the origins of CDC
In 1942, the U.S. established the Malaria Control in War Areas (MCWA) programme to protect military personnel and control malaria around military installations.
On 1 July 1946, the Communicable Disease Center, the predecessor of today’s CDC, was established. Its early work was heavily focused on malaria control.
The National Malaria Eradication Program began on 1 July 1947 and involved 13 southeastern states.
The programme used:
- DDT;
- drainage;
- mosquito-breeding-site reduction;
- insecticide spraying;
- surveillance.
The numbers changed rapidly:
| Year | Reported malaria cases |
| 1947 | 15,000 |
| 1950 | 2,000 |
| 1951 | Malaria considered eliminated |
By the end of 1949, more than 4.65 million houses had been treated with DDT. WHO subsequently certified the United States as malaria-free in 1970.
Malaria in Africa
Africa has historically carried the greatest malaria burden.
Several factors make malaria transmission particularly efficient in sub-Saharan Africa, including highly competent Anopheles vectors, climatic conditions favorable to parasite development, and socioeconomic and health-system factors.
The genetic relationship between malaria and human populations is also striking.
The sickle-cell trait provides partial protection against severe P. falciparum malaria. As a result, the HbS allele has been maintained at relatively high frequencies in some malaria-endemic populations despite the severe disease caused by homozygous sickle-cell disease.
In some African populations, approximately 20% of people have historically been reported to carry one copy of the abnormal haemoglobin-S gene.
This is a classic example of natural selection driven by infectious disease.
Malaria vaccines
WHO recommends the use of malaria vaccines in children living in areas with moderate-to-high P. falciparum transmission.
The first malaria vaccine, RTS,S/AS01, received WHO recommendation in 2021.
A second vaccine, R21/Matrix-M, was recommended by WHO in 2023.
Present Scenario of Malaria
According to WHO estimates for 2024:
- 282 million malaria cases occurred globally.
- 610,000 people died.
- Malaria transmission occurred in 80 countries.
- Approximately 265 million cases occurred in the WHO African Region.
- Approximately 579,000 deaths occurred in the African Region.
- Children under 5 accounted for approximately 75% of malaria deaths in Africa.
