So we start with the life cycle.

We all know it starts with a mosquito. If you are bitten by an infected female anopheles mosquito they inject 15 to 20 sporozoites into your blood. They don’t make you sick. The sporozoites don’t last long in the blood and they are never seen. They are taken into liver cells. There they multiply, they keep dividing until there are about 50,000 merozoites in each shizont. By the way I don’t know how to pronounce shizont. Is it shy or pronounced like the Japanese dog a shitzu?

From now on everything I say is about falciparum. The other species in Uganda which are P. Vivax and P. Malariae are different. If you’re interested google it.

Falciparum Malaria

With falciparum after 5 days the shizonts rupture. 20 shizonts releasing 50,000 merozoites each, means up to one million parasites in your blood: unless you were bitten by 2 mosquitoes. Or 5. Most of them will find a suitable red cell to live in and starts to eat it, which is why it’s called a trophozoite. So on day 5 after your night in Murchison you now have malaria in your blood. You have no symptoms: the million trophozoites live quietly in your red cells eating, growing and dividing into usually 16 baby parasites then rupture after 2 days. The new clone of merozoites are released into the plasma, along with all the excreta, bits of dead red cell and haemoglobin that are highly toxic to all our organs particularly the kidneys. It’s those toxins released from the ruptured red cells that make us sick rather than the parasite itself. So it’s possible that a small child or an adult bitten by more than one infected anopheles might just have enough toxins to cause a brief fever 7 days after being bitten. The rest of us are blissfully unaware. Once again about 10 to 15 of these merozoites will find a new red cell, so you now have 10 to 15 million red cells infected. They still don’t do anything except quietly grow and most people will still feel well. But the process is inexorable. 2 days later, day 9 after the bite, those 15 million cells rupture, 10 x as much toxins are released, and a child might have some symptoms of malaria: fever, headaches, vomiting etc. Then once again the numbers jump by x 10 and there are now 100 to 200 million red cells with a new trophozoite growing inside.

Sounds a lot but adults have 25 trillion red cells, so only 1 or 2 cells in 250,000 have a parasite, you won’t be feeling sick yet and you won’t find parasites under the microscope. The rapid diagnostic tests reliably pick up 1 parasite in 25,000 cells so 2 days later, on day 11, you’ve got there. The rapid test is strong positive, and with another x 10 cells parasitised it’s now possible to find them under the microscope. You have mild malaria. If you’re treated you will be fine. If not you’re going to have very severe malaria with multi organ failure in 2 days.

But something else is going on.

Those trophozoites are not infectious to the mosquito. A stomach full of trophozoites is just a meal. Tourists: you are not a danger to the mosquito population, and cannot spread malaria. Now have another look at the diagram and you’ll see that some of the trophozoites don’t divide into 16 clone babies. Instead a few form male and female gametes. They alone are infectious to the mosquitoes. They hatch out in the mosquitoes stomach, do what boys and girls do, and have babies. That’s where the sporozoites that infect us come from. The tourist cannot infect mosquitoes because he is sick with malaria. For him there are only 2 possible outcomes. He is either treated or dead. And mosquitoes don’t bite dead people. So that means no infected mosquitoes, no transmission and no more malaria.

The textbook picture I have described is what happens when someone gets malaria for the first time or after a long time. They either get treated on day 11 or 12, or wait until day 13 and are so sick they go into intensive care, or found dead on day 16.

Research around Murchison showed the average schoolboy in Nakwach is bitten by an infected anopheles 5 times a night. So for him every day is day 11 and he should have the classic progression multiplied by 5. Yet he’s out there playing football or messing about on his mobile phone.

The answer is immunity.

Immunity starts its protection in the first 20 minutes, destroying most of the sporozoites before they even get to the liver. Immunity in the liver reduces the load. Immunity in the blood devours merozoites before they get into a red cell. His large spleen eats the infected red cells. He has induced metabolic pathways that neutralise the toxins so they don’t make him unwell and don’t harm his kidneys. And the immunity puts pressure on the trophozoites to turn into gametocytes rather than dividing into merozoites. And they produce plenty of gametocytes. Every day a few parasites evade the immunity, and multiply enough to form gametocytes. The numbers build, because gametocytes circulate for months These infect the mosquitoes and make malaria endemic. But do you see the point? Malaria can only exist if the general population is immune, don’t get sick and don’t get treatment and instead produce gametocytes.