Over half of the world’s population live where they are at risk of contracting malaria. In areas where malaria is common it is an enormous drain on the economy, imposing massive health care costs and preventing people from going to work. In fact, malaria-ridden regions have a 1.3% lower gross domestic product (GDP) than nearby areas that are not plagued with the disease. Malaria is also deadly. The WHO reports that a child dies every 30 seconds from malaria.
Malaria is caused by protozoan parasites of the genus Plasmodium. Although a handful of Plasmodium species are capable of causing malaria, only one (Plasmodium falciparum) is frequently associated with lethal cases of the disease. The parasite reproduces sexually in Anopheles mosquitoes and lodges itself in the mosquito’s salivary glands after reaching maturity. When the mosquito bites a human, the parasite moves out of the mosquito’s salivary glands and into the human bloodstream.
The most impressive thing about malaria is how it manages to evade the immune system. When a Plasmodium parasite enters the body, its first stop is the liver. Here it invades liver cells and begins multiplying rapidly. The liver cells alert the immune system, but the immune system cannot respond quickly enough. The parasite is too fast. Before the immune system can rally the troops, the parasite makes approximately 40,000 copies of itself, bursts out of the liver cell, and goes in search of its next home: a red blood cell.
Unlike liver cells, red blood cells do not contain genes. Without genes the cells lack the codes and machinery necessary to synthesize proteins which would alert the immune system that it is under attack. This buys the parasite some time, but it still has the spleen to worry about…
Red blood cells (RBCs) are usually very squishy, a necessity when your job requires squeezing through tiny capillaries throughout the body. As RBCs age, they get worn out and lose some of their pliability. When they pass through the spleen, it identifies the aging cells and retires them. The spleen would almost certainly destroy any RBC harboring a Plasmodium because the parasite changes the structure of the cell, making it far more rigid. The parasite needs to make sure that the red blood cell never makes it to the spleen.
To stop the RBC in its tracks, Plasmodium creates hook-like proteins that extend out from the RBC and attach to the blood vessels. While this action saves the parasite from ever encountering the spleen, the proteins alert the immune system to its presence.
Over its evolutionary history, this parasite has managed to exploit the immune system’s need for specificity. The immune system first identifies a foreign body by some telltale protein on a cell’s surface (e.g., the “hook” mentioned earlier). Once this protein has been identified, the immune system builds an army which will focus on attacking only those cells that display the protein they have been built to identify. Should that identifying protein change configuration, then the current army of immune cells will be unable to recognize the intruder. In this case, a new army will need to be readied that is capable of identifying the new protein.
Plasmodium reproduces quickly. It multiplies in one red blood cell and will then burst out in search of new ones. Every few generations, these clever parasites will turn on a different gene that codes for a protein hook with a slightly different configuration. By the time the immune system is capable of recognizing and attacking the parasite, the parasite has switched protein hooks and becomes unrecognizable to the army built to destroy it. In this way, malaria parasites often manage to stay ahead of the human body’s immune response.
There are drugs to prevent malaria and there are drugs to treat malaria, but both are often too expensive for people living in malaria-ridden areas to afford. Additionally, malarial drugs often have nasty side effects. Finding a vaccine would likely save lots of money in the long run and would do much to ease suffering. For many years, vaccine research has proceeded without much luck.
The advent of genetic techniques may now have paved the way for the creation of a vaccine.
The vaccine described in the article mentioned above uses a genetically modified version of the parasite. Scientists identified and knocked out 2 genes that the parasite needs during the stage when it is infecting cells in the liver. This genetic modification means that the parasite can be injected into people without posing any threat. The presence of the parasite gears up the immune system, which creates an army which is ready to attack Plasmodium as soon as it enters the body. This eliminates that lag time that the parasite had been exploiting and gives the immune system the edge that it needs to destroy the parasite before it can cause any real damage.
The vaccine has proved to be 100% effective in animal trials and will hopefully be made available publicly in the near future. If the vaccine is affordable enough to be distributed widely then this should have huge human health and economic impacts. Third world countries that are so often plagued by malaria should save millions in health care costs and should experience increased GDP as a result of the healthier work force. Best of all, millions of lives will be saved in the years after the vaccine becomes available.
If you thought this post was interesting, then I suggest reading Parasite Rex by Carl Zimmer. I got a lot of the information that I presented from this book, and it’s a fun read.