DEAN GOLDRING | Why throwing the kitchen sink has not stopped malaria

Malaria is caused by a very complex organism (parasite) which was found in mosquitoes trapped in resin from 30-million years ago.

The parasite that causes malaria has therefore been around for many years before our own species. Here, I will explore why the parasites that cause malaria are so difficult to beat.

The disease we know as malaria was thought to be caused by breathing “bad air” (mal aria) that emanates from swamps. This was not “fake news” but a lack of understanding and evidence at the time. As you probably know, swamps and stagnant water are excellent breeding sites for mosquitoes that transmit the Plasmodium parasites that cause the disease.

To nourish her developing offspring, the female mosquito needs to feed on blood as an essential rich source of protein and you and I are the local restaurant. Should she have Plasmodium parasites (sporozoites) in her salivary glands, these are injected into the person she is biting along with her saliva and proteins to stop the blood clotting when she sucks up her meal.

The sporozoites she injects very rapidly (30 minutes to three hours) travel to, recognise, and invade liver cells, where they are more difficult for the host’s immune system to detect and fight.

Of the five species of Plasmodium that cause malaria in humans, Plasmodium falciparum is the deadliest. Plasmodium falciparum is responsible for 95% of the deaths caused by malaria, and most of the deaths are in Africa and in young children between five months and five years of age.

P. falciparum parasites take some five to seven days to divide and develop in the liver before emerging as thousands of “merozoites” that each recognise, attach to and enter red blood cells.

Inside a red blood cell, the parasite is hidden from your immune system and again divides and develops to produce 16 to 48 “schizonts” every 48 hours.

As the parasite schizonts burst and break out of red blood cells releasing its waste products your body responds with a high temperature (fever). Only during the red blood cell stage of the parasite’s life do you have the symptoms and feel ill due to malaria.

Some of the parasites in a red blood cell take a different direction, dividing into male and female gametocytes which can be taken up by a feeding mosquito, undergo fertilisation, survive the digestive enzymes in her stomach, find their way through the stomach wall and invade many organs, including her salivary glands.

Being able to live and divide in all these different environments gives an idea of just how complex and adaptable this parasite is.

Ninety-five percent of malaria cases are in Africa, where 1.58-billion people live. There were 292-million cases and 600,000 deaths reported, most of which are in young children living in Africa.

We can learn a lot by looking at some of the numbers involved. The World Health Organisation’s 2025 report suggests that 3.2-billion people are at risk of getting malaria.

Ninety-five percent of malaria cases are in Africa, where 1.58-billion people live. There were 292-million cases and 600,000 deaths reported, most of which are in young children living in Africa.

Here are some other numbers. The population of South Africa is about 63-million people, and the world has 8.3-billion people. The average child with malaria has some 1-trillion malaria parasites in their blood (and yes that is 120 times more than the world population) and in two more days there will be 40 times more parasites.

Your immune system or drugs will have to deal with and kill every one of those parasites. I think you will agree that this is a tough task. Amazingly and happily, many patients do survive malaria.

Drugs have been a very effective way to prevent and treat the disease, but the parasite has found a way to change and survive the drugs we have been using.

The parasite has developed resistance to every drug we have tried: chloroquine, sulphadoxine-purimethamine, mefloquine, piperaquine, amodiaquine, primaquine, atavoquone, quinine, artemisinin, and its derivatives.

These drug-resistant parasites are found in different countries, and they do not need passports to move to a new country, as mozzies, people and planes can do that for them.

There are some promising new drugs in various phases of development that are not yet available.

We need new drugs. The parasite has to have copper, and my students are working on ways to prevent it from getting essential copper.

There are some promising new drugs in various phases of development that are not yet available.

We have a very good diagnostic test (which uses antibodies made in South Africa by the National Bioproducts Institute, Durban) which detects the parasite’s Histidine-rich protein II (HRPII) in a patient’s blood sample.

Unfortunately, many of the parasites in different countries have learnt about the test and so are no longer making the protein, and the test does not detect them. To address this, my students have identified new proteins to diagnose P. falciparum, P. vivax, P. knowlesi and P. malariae malaria, and there are promising diagnostic targets suggested by other laboratories.

We can still diagnose malaria by staining a slide of the patient’s blood and identifying the parasite with a microscope; it just takes a lot longer and requires more training than the HRPII test, which looks for two lines on a test strip (you may have encountered a similar test for Covid-19).

A major breakthrough is that we have two new malaria vaccines RTS,S/AS01 and R21/Matrix-M which aim to prevent sporozoites from getting into the liver. Reports indicate that the RTS,S/AS01 vaccine reduced malaria deaths by 30% in clinical settings and R21/Matrix-M vaccine decreased the number of cases with symptoms by 75%.

The WHO reports that 25 African countries have introduced the vaccines in children from five months to five years old, and the vaccines had 22% reduction in hospitalisations for severe malaria.

These vaccines are very promising. There are other vaccines in the pipeline targeting the red blood cells stage and gametocytes.

I have concentrated on targeting the Plasmodium parasite. If a mozzie does not bite you then you won’t get malaria. Insecticide treated bednets, new insecticides, fiddling with mozzie genetics, mozzie larvae eating fish and mozzie baiting are ways mozzies are being targeted.

I remind you mozzies have been around much longer than we have ...

We saw a huge rise in malaria cases to 64,000 in South Africa after the rains in Limpopo, Mpumulanga, and KwaZulu-Natal in 2000. We had 4,639 cases in 2024. You will be very aware of the recent heavy rains and floods we had earlier this year in Mpumalanga and we hope that we do not see the increase in the number of malaria cases we saw in 2000.

Retired Prof J.P. Dean Goldring has, for the past 40 years, worked on malaria vaccines and cerebral malaria and, more recently, identified novel malaria diagnostic targets for malaria Rapid Diagnostic Tests that detect Plasmodium falciparum, vivax, knowlesi, and ovale parasites.

• He has given 6,470 lectures and taught 7,642 students during his career. Currently, Prof Goldring runs a weekly dissection of scientific journal articles, lab meetings, and workshops on Scaffolding Exegetic Academic Literacy.