The history of malaria and quinine

Malaria is caused by a parasite that is carried by several mosquitoes of the genus Anopheles. It is transmitted to humans through the bite of a infected mosquito. The parasite enters the bloodstream and the infected human suffers from intense fever and icy shivering. The spleen becomes painfully enlarged. Once recovered, patients often suffer relapses and seldom regain their original strength. Many die, especially when the parasite reaches the brain, causing cerebral malaria.

References to its unique, periodic fevers are found throughout recorded history beginning as early as 2700 BC in China. Malaria was once the scourge of the Mediterranean and of Rome in particular. Even places as far a field as France, the Netherlands, southern England and Russia were affected by it. Originally an ‘Old World’ disease, it was carried by explorers and settlers into the Americas. Its cure – the quinine found in the bark of the cinchona tree – was discovered in the 17th century in the foothills of the Peruvian Andes, an elevated area where there had never been any malaria.

Nobody quite knows why, but it appears to have abated somewhat in the Middle Ages before flaring up again in the seventeenth and eighteenth centuries. The problem was that the Europeans had no idea what caused malaria. To them it was simply an intermittent fever that took hold of many in the summer months. They simply thought that it was some type of contagion that basically ‘hung about’ in the miasma (i.e. the 'summer mists'). In Rome, where malaria was the most rampant, one was said to catch the fever from the ‘bad air’ (the mal’aria) of the marsh mists.

Malaria causes fevers that recur at approximately three-day intervals (a quartan fever), longer than the two-day (tertian) intervals of the other malarial parasites, hence its alternate names quartan fever and quartan malaria. Malaria – once also variously known as the Roman marsh fever or the intermittent fever – was the ever-present enemy of the Roman Campagna. The Tiber frequently breached its banks in summer and left the countryside covered in stagnating pools of water. Numerous popes, cardinals and ordinary Romans were laid low or killed by malaria; six visiting cardinals died from malaria during the disastrous conclave of 1623. Wealthy citizens would desert the city during the worst of the summer heat, fleeing to the cooler climate of the surrounding hills in an effort to avoid catching the fever. Malaria was only really eradicated in the area in the 1930s when Mussolini had the Pontine marshes drained and the mosquitoes’ breeding grounds in western Italy were finally eliminated.

Malaria was most probably introduced to the New World by the early European explorers and settlers. American settlers then took the disease inland with them as they moved westward. It even found its way into Canada.

[Agostín Salumbrino]

In 1605, the Italian Jesuit Brother Agostín Salumbrino (1561–1642) arrived in Lima, which was then part of the Spanish Viceroyalty of Peru. Salumbrino witnessed how the Incas would take cinchona bark - ground into a powder and drunk in hot water - to stop from shivering when the winter cold had seeped into them. Salumbrino was well acquainted with the symptoms of Roman marsh fever, and the shivering of the locals caused him to think of the shivering phase caused by the fever back home. So he sent a small sample of cinchona bark to Rome in 1631, where it proved to be a cure for the marsh fever. While its effect in treating malaria (and hence malaria-induced shivering) was unrelated to its effect in controlling shivering from cold, it was nevertheless effective for malaria.

In a short time the Jesuits, with the aid of the local Indians, would begin to search for and strip the bark of the cinchona tree in order to send it to the Old World. The Jesuits showed the locals how to strip the bark in vertical pieces so as not to kill the tree. They would plant five new cinchona trees for every one they cut down and they would plant them in the shape of the cross in the hope that God would then bless their growth.

In 1767 the Jesuits were expelled from the Spanish Empire by Carlos III as the latter had grown fearful and jealous of their accrued power and properties. With time the local people would forget the conservational practices taught to them by the Jesuits and the cinchona trees would begin to be overharvested.

[Dutch Indies]

Soon after the discovery every ship traveling from the New World to the Old would carry a consignment of 'Peruvian bark' or Polvo de los Jesuitos ('Jesuits Powder'). Though nobody knew how it worked, its reputation as an effective cure for the intermittent fever soon began to spread throughout Catholic Europe. But the Protestants regarded it with great suspicion. The Reformation and counter-Reformation were in full swing, and many Protestants suspected the so-called remedy to be part of a Popish plot. In addition, the foul taste of the bitter bark led many to think they were being poisoned, and cinchona bark was therefore not widely accepted for a long time.

The next big problem was finding a way of producing plentiful, affordable and easily accessible quinine. The cinchona tree grew across northern South America, within the Spanish Empire. If you wanted to travel in Spanish territory, you had to obtain the permission of the King, who was determined that Spain should be the sole benefactor of the intellectual and financial rewards of the cinchona tree. Inadequate quinine supplies would hamper the efforts of explorers, missionaries, settlers, scientists and armies the world over. To be a missionary was a courageous thing – for centuries malaria felled them in their droves, in both Africa and Asia. The exploration of West Africa was only really made possible after the use of quinine as a prophylactic became common in the mid-19th century. Before that, West Africa had been known as “the white man’s grave”.

The Panama Canal was begun in 1881 by the French Compagnie Universelle du Canal Interocéanique. At that time, supplies of quinine were irregular and expensive the world over. The managers of the Compagnie thus considered it more economically viable to replace dead workers with fresh ones, rather than provide the current workers with adequate quinine doses. The incessant downpours in Panama meant that thousands were affected by malaria. Additionally, the legs of hospital beds were placed in water-filled glass bowls in order to prevent ants from reaching the patients, but in so doing those who went into hospital for reasons other than malaria were sure to contract the disease whilst there. Under French administration of the canal, which lasted eight years, more than 20,000 workers died from malaria or yellow fever.

When the Americans took over construction of the canal in 1903, thorough efforts were made to eradicate the area of malaria and adequate quinine supplies for all workers was a priority. Quinine was given as a prophylactic and those who did not take their daily dosage were punished.

In the mid-1900s the British, Dutch and French were all extremely eager to get their hands on cinchona tree seeds so they might grow their own trees. As already mentioned, the cinchona trees were far less numerous than they had once been, and so there was a sense of urgency to the matter. A German-born Dutch botanist, Justus Carl Hasskarl (1811-1894), triggered the rush to smuggle cinchona seeds out of South America when he disguised himself as a German businessman in an attempt to obtain seeds that he would then take to Bandoeng on the island of Java in the Dutch East Indies. Britain eventually managed to lay hold of some cinchona seeds, which they planted in India. But the Dutch were by far the most successful: by the 1930s their Java plantations were producing 97% of the world’s quinine supply.

It was only in the 19th century that scientists started to understand the disease. The first milestone came in 1880 when the Frenchman Charles-Alphonse Laveran, working in Algeria and using what was essentially a magnifying glass, caught sight of the parasite that causes malaria in the human bloodstream. In the last days of the 19th century, whilst working out of a shed in India, Major Ronald ‘Mosquito’ Ross discovered through his dissections that the mosquito is responsible for transmitting malaria. For his efforts he was awarded the Nobel Peace Prize in 1902.

The need to grow more cinchona trees and/or develop synthetic substitutes became painfully apparent during the Second World War. Soldiers were fighting in malarious regions in West Africa, Sicily, the eastern Mediterranean, Singapore, China and the south-west Pacific. In the Pacific countries, malaria took a bigger toll than combat. For the Allied powers, the German occupation of Holland in 1940 was disastrous, as the latter seized control of the quinine headquarters in Amsterdam, with its essential machinery and supplies. Furthermore, the Japanese then took control of Java and its plantations of cinchona. The Japanese kept the Axis powers supplied with quinine, but the Allies were left high and dry. The Americans began growing their own cinchona forests in Costa Rica, but not in time to help with the war effort. The Allies’ only supply of quinine came from the eastern Congo, where plantations had been grown from cinchona seeds that also had been smuggled out of Bolivia and brought there in 1933 by Prince Leopold. It is the Congo that today has the largest cinchona forest in the world.

Quinine frequently has undesirable side effects, such as vomiting, headaches and tinnitus. The synthetic and much-hailed alternative chloroquine eradicated these. But the malarial parasite eventually mutated and chloroquine became ineffective. Other drugs have since been placed on the market, but none of them have proved as effective as the natural quinine found in the bark of the cinchona tree, to which the parasite appears to have developed no immunity.

Malaria is today primarily a disease of the tropics. In 2015, about 3.2 billion people – almost half of the world’s population – are at risk of malaria. According to the latest estimates, there were 214 million cases of malaria in 2015 and 438,000 deaths.