Malaria was a well-studied disease in the West until the middle of the 20^th century. Until that time the disorder was still endemic in North America and large parts of Europe. It was a significant impediment for the European nations during the colonial period. Malaria also played a large part in the wars of the 19^th and 20^th centuries. For many years it had been known that people who died of malaria had large amounts of black pigment in their liver, kidneys, spleen and bone marrow. Yet the cause of this disorder long remained a riddle. In 1880 the French army doctor Charles Louis Alphonse Laveran discovered malaria parasites in fresh blood from a chronic malaria patient in the coastal town of Bone (Annaba), Algeria. He also observed exflagellation (see below), which normally only takes place in the stomach of the mosquito. The names which were given to the microscopic organisms were "Laverania falcipara" and "Oscillaria malariae". At that time there were as yet no staining techniques, and microscopes were quite primitive with a limited magnification. In 1884 the German Ernst Karl Abbe, together with Carl Zeiss, developed the oil immersion lens and a few years later the optical condenser, which allowed a greater magnification and clearer, sharper views. The Russian Dimitri Romanowsky developed a staining method based on methylene blue. The findings of Laveran could now be verified by others. Laveran received the Nobel prize in 1907.

The study of dyes led to the development of various techniques for staining bacterial preparations and histological sections. Romanovsky stains are based on a mixture of basic dyes (positively charged) such as methylene blue, and anionic dyes (negatively charged), such as eosin. The positively charged dye will bind to negative structures (nucleic acids, ribosomes), and the negative dye will attach to positively charged structures (many cytoplasmic proteins). The specific mixtures, techniques and variants were named after those who developed them, e.g. Giemsa, Wright, May-Grünwald.

The transmission of malaria had for long been a mystery. One of the researchers was the Briton Sir Ronald Ross. He left for India with a personal mission to prove transmission via insects. In 1897, after three years of hard work, he demonstrated the parasites in mosquitoes which had bitten patients. Later he also demonstrated the transmission of avian malaria via mosquitoes (Plasmodium relictum transmitted from one sparrow to another via Culex fatigans). He was able to describe the complete development of the parasite in the mosquito and also demonstrated that transmission took place via the bite of the mosquito (and not via the presence of dead mosquitoes in drinking water, as his mentor Patrick Manson had initially thought). For this he received the Nobel prize in 1902. Subsequently the Italian Giovanni Battista Grassi and Patrick Manson confirmed that human malaria could be transmitted by Anopheles mosquitoes by carrying out extensive experiments in Italy and by allowing Manson’s own son to be bitten by Anopheles mosquitoes which had fed on a patient with P. vivax malaria.