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Malaria Diaries, part 2

Now that you've had a little time with elimination, eradication, and those horrible images of foot-long guinea worms coming out of someone's leg, let's talk about why malaria is so much harder to beat.

**And let me remind you I am still not a scientist or any sort of malaria expert. Everything I'm sharing is based on what I'm learning every single day as an interested and curious onlooker.

Comparing guinea worm disease to malaria is an apples to oranges comparison, but I wanted to start out slowly for what should be fairly apparent reasons in a moment. Malaria is just not that simple. Consider:

  • Malaria is condition in humans (and monkeys and higher primates) caused by an infection by a protozoan parasite. The most common is Plasmodium falciparum, but P. vivax, P. ovale, P. malariae and P. knowlesi. All cause malaria, some more lethal than others. Oh yeah, each are slightly different from the other, and are found all over the world.
    This means that we're not dealing with one little worm, but with a raft of them doing different things in different locations.
  • Plasmodium has two natural hosts: mosquitoes and humans. Generally speaking, the parasite is passed back and forth between these two species.
    It's not impossible to rid us of mosquitoes, but it requires substantial capital and political will. In fact, malaria was all over the southeastern US up until the early 1950s. What changed? Post-WWII economics, coupled with infrastructure improvement and scientific progress.
  • A person can get malaria over and over again in their lifetime, never developing full immunity.
    So the symptoms get more bearable, assuming you're not dealing with the more lethal strain.
  • Malaria's biggest impact is on children, as they have much less robust immune systems. Any compromise to the immune system (including chronic malnourishment) makes beating malaria during those early years that much more difficult.
    Populations in Sub-Saharan Africa are exposed to so many diseases (there's even a class of diseases called neglected tropical diseases), compromised immune systems are a given.
  • Some strains of Plasmodium never leave the human host. They hide in the spleen and liver during specific biological phases of the parasite, a process called sequestration. When they're hiding, there's virtually no evidence malaria's present.
    How do you beat something you can't find?
  • Currently, transmissibility levels of malaria are unknown.
    That means we don't  know how little malaria must be in the blood to not transmit to a mosquito.
  • Some strains of Plasmodium are starting to show antibiotic-resistance.
    Antibiotic resistance is often the result of incomplete antibiotic treatment cycles, meaning folks start antibiotics and don't always complete them. There are economic and social factors at play here, not just biological.

We used to think of cancer as a single disease, but now we understand there are differences because of environment, genetics, and behavior. I don't think I'm going too far to suggest that beating malaria is akin to beating cancer. Malaria is a highly complex disease that will require significant advances in vaccine development, vector control, diagnostics, antibiotics, and population health.

In an earlier post, I said that I'm working with folks trying to understand the biological complexities of malaria. Let me get specific.

In order to eliminate (and eventually eradicate) malaria, we first need to recognize it so we can treat it. This is where diagnostics come in. Typically, malaria is diagnosed in the field by a health practitioner, usually through a clinical exam, and then verified by a blood draw and microscopy. Microscopy tests are expensive, requiring transport of blood from patient to lab (considering the reach of malaria in infrastructure-poor parts of Africa), and are dependent on finding actual parasites in the blood.

About 15 years ago, Rapid Diagnostic Tests (RDTs) were introduced, and these allowed diagnosis in-the-field by a finger-prick's amount of blood. There are two kinds of RDT-style tests many folks have probably seen: EPT (Early Pregnancy Test, which produces a simple +/- result) and glucose strips (which take a measurement of blood glucose in a finger-prick's worth of blood). Malaria RDTs are like the EPT test - they indicate if a person is +/- for malaria. 

Malaria RDTs are based on detection of HRP2 antigens in the blood, the tell-tale sign that the parasite has been there. They don't tell you how much malaria is in a person's system, they just tell you if the person is +/-. For a test to declare a person positive, the test strip will attract enough HRP2 to make it change color. Any less? Not positive. But what happens if the disease was there at some point during an acute infection, but now the parasite levels are low? Would the person test positive or negative? Likely negative. But technically a mosquito could bite a person with really low parasitemia (translated in as HRP2 levels) and still get some of those parasites back - and restart the cycle again. Any progress you thought you'd made toward elimination could be walked back by someone harboring malaria who doesn't even know it.

I'm a member of a team trying to improve the sensitivity of RDTs. While I am restricted from sharing scientific results here (manuscripts forthcoming), let's just say that there are a couple of key issues we need to address in order to make a dent:

  1. RDTs need lower levels of detection (LOD), meaning they need to see a person as positive, even if they're not showing clinical signs of an acute infection. How do we get there?
  2. Once we lower the LOD, how many more people will me miss?
  3. We don't know how low a person's parasitemia level must be in order to declare them malaria-free. Is it a single parasite (protozoa) in the blood? Is it a certain number of picograms of HRP2?
  4. Similarly, we don't know what impacts transmissibility - will someone with a fantastically low HRP2 level still transmit something of use to a mosquito?
  5. What's the absolute lowest level of HRP2 or parasites measurable by any method?

Let me sum this up. Malaria is a giant universe of complex biological challenges, from the protozoa to the mosquito, with all of its biology to humans, and everything the environment adds to that picture. We're working on something that's 1 trillionth the size of a gram, and we don't even know if this is the right approach. I wish I could see elimination on the horizon, but everything I learn opens a new nesting box of unknowns. That's the scientific method at work, after all. 

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