By Dr Ananya Mandal, MD
Malaria has been known to mankind for thousands of years. Around 7,000-12,000 years ago with increase in temperatures in Africa, rise in humidity creating new water sources and the start of agriculture in the Middle East and North East Africa there were several water bodies and pools of water. This led to a favorable climate and area for breeding and transmission of malaria parasites and its carrier, the mosquito.
Human resistance to malaria
The spread and vulnerability to malaria can be traced by the evolution of the G6PD, thalassaemia and sickle cell mutations. These in their carrier state, give humans resistance to malaria.
The most-studied influence of the malaria parasite upon the human genome is a hereditary blood disease called the sickle-cell disease. Those affected even partially have substantial protection against malaria.
In sickle-cell disease, there is a mutation in the ''HBB'' gene, which encodes the beta-globin subunit of haemoglobin. This leads to a change from hydrophilic to a hydrophobic amino acid in the RBC leading to deformity of RBCs into a "sickle" shape. Such deformed cells are cleared rapidly from the blood, mainly in the spleen, for destruction and recycling.
In the merozoite stage of its life cycle, the malaria parasite lives inside red blood cells. If there are both sickle and normal haemoglobin in blood the merozoites are more likely to be likely to become deformed and be destroyed before the daughter parasites emerge.
Thalassaemias are another form of haemoglobin mutations found in the human genome associated with malaria. Studies in Sardinia and Papua New Guinea have found that the gene frequency of β-thalassaemias is related to the level of malaria episodes in a population. Those with malaria have a 50% decreased chance of getting clinical malaria.
The Duffy antigens are antigens expressed on red blood cells and other cells in the body acting as a chemokine receptors. These are encoded by the Fy genes (Fya, Fyb, Fyc etc.). Plasmodium vivax malaria uses the Duffy antigen to enter blood cells. The genotype is very rare in European, Asian and American populations, but is found in almost all of the indigenous population of West and Central Africa. This gene form offers a protection against P. vivax infection.
Other genotypes that are associated with malaria risk include Glucose-6-phosphate dehydrogenase (G6PD) deficiency. A genetic deficiency in this enzyme results in increased protection against severe malaria. HLA-B53 antigen is also associated with low risk of severe malaria.
Malaria is thought to have spread with the army of Alexander the Great. It was described first by the Chinese in the Nei Ching (the Canon of Medicine) in 2700 BC and then they also described, the use of the qing hoa plant (annual or sweet wormwood) for fever in 340 AD.
Where does the term malaria come from?
The term malaria is derived from the Italian term “mal” or bad and “aria” or air. It meant foul or bad air as people initially noted that by shuttering up the houses and not going out in the evening reduced the risk from the gases of the swamp and risk of malaria.
It was in South America, where the effects of the bark of the Cinchona tree (containing quinine) were found to be effective in treatment of malaria. A legend describes cinchona taking its name from the countess of Chinchon, wife of a Peruvian viceroy who was cured of fever in 1658.
Cinchona was included in the British Pharmacopoeia in 1677, and later became known as 'Jesuit's powder' or 'Jesuit's bark' from those who first used it. The Dutch travellers brought seeds of the tree from Bolivia and successfully grew this in their Indonesian colonies. They had a monopoly on the supply.
Discovery of the protozoan parasite
Alphonse Laveran, a French military physician, discovered the protozoan parasite in 1880, whilst working in Algeria. He was lauded with the Nobel Prize for this in 1907. Grassi and Filetti, Italian researchers named Plasmodium vivax, and Plasmodium malariae in 1890, and an American, Welch, named Plasmodium falciparum in 1897. Stephens named the last of the four, P. ovale, in 1922. It was Sir Ronald Ross, an officer in the Indian Medical Service who discovered the transmission of malaria by mosquito from bird to bird in 1897 in Calcutta, India, earning the Nobel Prize in 1902.
Discovery of chloroquine
Chloroquine was discovered in 1934 by the German Hans Andersag. Chloroquine was not recognised as an effective and safe antimalarial until 1946. It was in 1944 that quinine was synthesized chemically for the first time.
At present studies are on to develop effective antimalarial vaccines, development of new antimalarial drugs for prevention and treatment of malaria. The Malaria Genome Project is hoped to provide new targets for both drugs and vaccines.
Reviewed by April Cashin-Garbutt, BA Hons (Cantab)