The parasite that causes malaria resides in red blood cells. That is why doctors in the past drained infected blood and replaced it with donor blood. Whether these so‑called 'exchange transfusions' actually improved survival was never convincingly demonstrated. They have since fallen out of use because of the lack of proven benefit and the advent of fast, more effective antimalarial drugs.
In malaria, parasites infect red blood cells. 'The more mature malaria parasites cause those red blood cells to adhere to the vessel wall. This leads to blockage of small blood vessels, and that is one of the main reasons malaria makes you so ill', explains internal medicine specialist Quirijn de Mast of Radboudumc. 'That is why doctors, even into the current century, sometimes replaced infected blood with donor blood.'
Health benefit
These exchange transfusions were mainly used in people with a high parasite load, sometimes with more than ten percent of red blood cells infected, or in severe complications such as cerebral malaria. 'But various studies on these transfusions have never shown a convincing health benefit', says De Mast. 'At the same time, the method carried risks, such as transfusion reactions and clotting problems.'
Doctors could exchange blood in different ways. In the simplest form, a patient received two IV lines: on one side a doctor drew blood using a large syringe, while on the other side donor blood was administered. In some cases, a large proportion of the total blood volume was replaced. Later, apheresis was used, an apparatus that removes red blood cells, after which plasma and other components are returned and red blood cells are replaced.
Sweet wormwood
'That exchange transfusions fell out of favor has several reasons. In addition to the lack of evidence for clinical benefit, we also gained new drugs that suppress parasite numbers more quickly and reliably. Resistance to several older drugs, such as chloroquine, made the search for better therapy more urgent', says De Mast. 'The world had to look for something new. Researchers then came upon a substance called artemisinin. It came from the plant Artemisia annua, sweet wormwood. That substance turned out to be by far the most effective against malaria.'
'Artemisinin and related compounds cause a rapid decline in the number of parasites in the blood. In addition, they act quickly against multiple blood stages of the parasite, unlike other drugs that only target the more mature parasite', De Mast explains. 'With the arrival of this therapy—and the absence of convincing evidence for their effectiveness—exchange transfusions fell out of use.'
Nobel Prize
The substance was, in a sense, rediscovered, as the Chinese had been using the plant for centuries to treat fever-related illnesses. Its effect against malaria also became apparent during the Vietnam War. De Mast explains: 'The North Vietnamese then had difficulty obtaining antimalarial drugs. Mao Zedong came to their aid. In 1967, he brought together Chinese scientists with the assignment: come up with a new medicine against malaria.'
They succeeded. In the early 1970s, researcher Youyou Tu and her colleagues isolated an active compound that caused a rapid reduction in parasites. The group initially shared this important discovery mainly within China, and international recognition was slow to follow. As a result, it was not until around the turn of the century that artemisinin triggered a worldwide revolution in the treatment of malaria. In 2015, Tu ultimately received a Nobel Prize for her contribution to this breakthrough.
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Annemarie Eek
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