Plasmodium vivax: The Malaria Parasite with a Few Tricks Up Its Sleeve
It has its own way of doing things.
For starters, P. vivax is rather picky about the red blood cells it invades. While P. falciparum is happy to invade red blood cells at different stages of their development, P. vivax has a preference for reticulocytes; those young, not-quite-fully-mature red blood cells.
And that preference has consequences. Because reticulocytes make up only a small fraction of circulating red blood cells, P. vivax generally doesn't reach the spectacularly high parasitaemias that we can see with P. falciparum.
But once P. vivax gets inside its chosen red cell, it isn't exactly shy about announcing itself.
Look closely at an infected erythrocyte and you can see the famous Schüffner's dots ( little stipplings scattered across the red cell). They are one of those wonderfully useful morphological clues that make a microscopist think, Ah… I know who you are.
And then there is the trophozoite.
Where P. falciparum trophozoites tend to have a rather neat, compact appearance, P. vivax trophozoites can become wonderfully amoeboid. They stretch, twist and occupy the red cell in a way that makes them look almost as though they have forgotten that they are supposed to maintain a particular shape.
The schizont is equally interesting. When it matures, it can contain somewhere around 12–24 merozoites, essentially preparing a small army of offspring for the next round of invasion.
But perhaps the most mischievous trick P. vivax has is one that you won't see in a blood film at all.
After the initial infection, some parasites retreat into the liver and become dormant forms called hypnozoites.
And then they wait.
They can remain hidden for weeks, months or even years before waking up and causing another episode of malaria. So with P. vivax, clearing the parasites from the bloodstream isn't necessarily the end of the story. The parasite may simply have gone somewhere you can't see.
That is why treatment of P. vivax has an extra complication. Drugs such as primaquine or tafenoquine are used for what is called radical cure. The idea being to eliminate not only the parasites circulating in the blood, but also those troublesome dormant liver stages.
There is, however, an important catch.
Before using these drugs, G6PD status needs to be considered, because they can cause potentially serious haemolysis in people with G6PD deficiency.
And then we arrive at one of my favourite contrasts between P. vivax and P. falciparum.
If you've spent time culturing P. falciparum, you might reasonably assume that you can simply take P. vivax, put it into a flask, give it the right medium and gas mixture, and wait for it to grow.
Unfortunately, P. vivax doesn't seem particularly interested in cooperating with that plan.
Continuous in-vitro culture of P. vivax has historically been extremely difficult. Its dependence on reticulocytes is part of the problem, and the parasite has proved remarkably reluctant to behave itself in the laboratory in the way P. falciparum does.
Then there is the genome.
P. vivax has a highly polymorphic genome, and among the genes that attract considerable interest are those involved in the parasite's ability to invade reticulocytes. The Duffy-binding protein (DBP) family is particularly important here. A highly polymorphic genome means P. vivax is genetically diverse. Different parasites can carry quite different versions of many of their genes. Polymorphic does not mean that every parasite has a completely different genome. Most of the genome is conserved; polymorphism refers to the specific regions where sequence variation occurs.
Traditionally, the story was relatively straightforward: P. vivax uses the Duffy antigen, also known as ACKR1, on the surface of red blood cells as an important receptor for invasion.
Except… biology rarely likes simple stories.
We now know that P. vivax infections can occur in people who are Duffy-negative, particularly in Africa. That observation has challenged the traditional idea that the Duffy antigen is an absolute requirement for P. vivax invasion and has opened up a whole new set of questions about how this parasite actually gets into red blood cells.
