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Germ warfare: in a drawn-out battle, scientists do whatever it takes to try to defeat a deadly disease.

Stefan Kappe sits in a protected area shut off from the rest of his lab at Seattle BioMed. There he breeds what he calls "the most dangerous animal in the world." Is it a great white shark? Or maybe a tiger? No, it's a creature that goes mostly unnoticed until it bites--the mosquito. This tiny terror spreads agents that cause disease, including malaria. "There is no other animal in the world that kills [as] many people," says Kappe.

Every year, mosquitoes transmit malaria to between 300 million and 500 million people in tropical areas (see map, below, right). Victims experience fever, chills, vomiting, and in severe cases, convulsions and coma. More than a million infected people die each year, primarily children. For decades, scientists have tried--and failed--to create a vaccine to wipe out malaria. Now they hope that new vaccine strategies will finally outmaneuver the killer.


Like a scrimmage designed to prepare a sports team for a real game, a vaccine trains the body's disease-fighting immune system to tackle the real enemy. "We want to fake out the immune system to give it a hint of what an infection would be like, and to prepare the immune system to be ready in the event that," you are infected," says Theresa Britschgi, BioQuest science education director at Seattle BioMed. Most vaccines contain either part of an illness-causing microbe or a weakened form of it that can't cause disease. The immune system produces molecules called antibodies and various soils of blood cells to fight the intruder. That way, if the real threat appears, the immune system recognizes it and already has a defense in place.

But the culprit that causes malaria--a single-celled parasite, or organism that depends on another organism to exist--masks its identity to fool the immune system. It enters a human through the bite of an infected mosquito, and then stays undercover by changing form several times during its life cycle (see diagram, p. 10). "It's kind of a shape shifter," says Kappe, who is a parasitologist.


The forms that enter humans--called sporozoites--ride the bloodstream to the liver, where they multiply thousands of times. They exit the liver as merozoites, which invade red blood cells and trigger malaria symptoms. A vaccine called RTS,S is designed to beat the parasites before they can make their move. Joe Cohen a molecular biologist with pharmaceutical company GlaxoSmithKline and co-inventor of the vaccine, says, "RTS,S trains the body's immune system to recognize and attack the malaria parasite at an early stage in its infectious cycle in [humans]."

RTS,S contains pieces of sporozoites, which prepare the immune system to attack this parasite form. "This prevents the parasite from either invading the liver or from maturing and multiplying in it so that the parasite cannot form merozoites, re-enter the bloodstream, infect red blood cells, and cause malaria symptoms," says Cohen.


In tests, RTS,S prevents malaria in about 50 percent of people, and it decreases malaria symptoms in many others. That would prevent millions of cases of severe malaria and save hundreds of thousands of lives every year. The problem: The 50 percent who do get malaria would still carry the parasite. When an uninfected mosquito bites a human carrier, the mosquito gets infected, and in turn infects the next person it bites. Some researchers suggest a surprising strategy to prevent this.


The idea: Vaccinate mosquitoes! "We can immunize the mosquitoes through the humans," says Rhoel Dinglasan, a molecular biologist at the Johns Hopkins Malaria Research Institute in Baltimore, Maryland. Humans would receive a vaccine that negatively affects gametocytes--a malaria parasite in the stage of its life cycle during which it moves from humans to mosquitoes. Dinglasan explains, "The humans will make the antibodies and the appropriate immune response to the vaccine, and then once a mosquito takes a blood meal from a human who's vaccinated, it takes up all of the antibodies and immune cells."

Inside the mosquito, the human-made antibodies would block the gametocytes, so they would die without morphing into another form. And voila: The protected mosquito wouldn't spread malaria. If such a transmission-blocking vaccine works, it could pair with a vaccine like RTS,S to knock the parasite from circulation.




Kappe's lab is also working on a vaccine that contains the entire parasite rather than pieces of it. This vaccine would teach the human immune system to spot all the parasite's components, so it can't hide by shifting form.

However, if the vaccine were to contain healthy parasites, it could give people malaria. "To avoid that, we are cutting out genes (units of hereditary material) from the parasite that are important for the parasite to develop in the liver," says Kappe. This weakened parasite travels to the liver, where it unknowingly alerts the human's immune system. "But it cannot start to grow and then burst out into the bloodstream and cause infection," he says.

Kappe's vaccine is in the testing phase. Eventually, it will be in the form of a shot, but right now, human volunteers get vaccinated by placing an arm over a mosquito-filled container until they are bitten. To test if the vaccine works, the volunteers later will allow malaria-infested mosquitoes to bite them. In case it doesn't work, researchers will have anti-malarial drugs ready to knock out the infection.

Defeating a complex parasite is a long battle. RTS,S, which is much further along than other malaria vaccines, may be available to the public in five years. Researchers are already working on improved versions, with the goal of leaving the killer nowhere to hide.


April 25, 2011, is World Malaria Day--a day to raise awareness of the global effort to control this potentially deadly disease. The latest data show 109 countries, and half the world's population, are still battling malaria.



COMPOUND EYE: A mosquito's eye has thousands of lenses that allow it to see in many directions at once to spot a host.

PALPS: These fleshy appendages help mosquitoes detect chemicals, such as carbon dioxide in a person's breath, from 36 meters (118 feet) away.

ANTENNAE: Tiny hairs on a mosquito's antennae detect sound vibrations, air movement, and odor to track a host.

HUMAN FLESH: Hairs on a person's skin are not usually sensitive enough to detect when a mosquito has landed. The insect also injects chemicals to prevent blood from clotting and reduce pare, which irritate the skin and later cause itching.

PROBOSCIS: A mosquito's long needlelike mouthparts are tipped with sharp stylets that pierce the skin.


The parasite that causes malaria has a very complex life cycle. It goes through more than 10 distinct stages, making it a tough enemy for scientists to fight.


1. MOSQUITO BITES An infected mosquito bites a person, injecting wormlike sporozoites.

2. FROM BLOOD TO LIVER The person's blood carries the sporozoites to the liver, where they invade liver cells.

3. INSIDE LIVER CELLS Sporozoites change into a form called schizonts, which grow and divide into thousands of merozoites. This new form bursts from liver cells into the blood.

4. INSIDE BLOOD CELLS Merozoites multiply in red blood cells. The cells burst and release more parasites, eventually damaging the brain and lungs and causing fever, chills, and anemia.

5. BACK TO MOSQUITO Some merozoites develop into sexually reproductive gametocytes, which pass into mosquitoes that bite infected people. Inside the mosquitoes, the gametocytes combine into an oocyte. This form releases sporozoites and the cycle begins again.

[VIDEO EXTRA] Watch a video about the RTS,S vaccine at:


* What is a parasite? Do you know of any diseases that are caused by a parasite?

* What are the symptoms of malaria?

* What are some methods for fighting diseases like malaria?


* Quinine is an important drug that has been used to treat malaria since the 17th century. It comes from the ground bark of the cinchona tree. Peru's Quechua Indians added the ground bark to water and drank tile tonic to stop shivering from cold temperatures. European explorers brought the tonic back and used it to reduce symptoms of malaria, which is usually accompanied by intense shivers.

* Four Nobel prizes have been awarded for work associated with malaria: to Sin Ronald Ross ill 1909 for discovering the parasite; to Charles Louis Alphonse Laveran in 1907 for finding that it's a protozoa; to Julius Wagner-Jauregg in 1927 for treating people who had become paralyzed front syphillis with malaria; and to Paul Hermann Muller in 1948 for using insecticides to control mosquito-borne diseases.


* The Bill & Melinda Gates Foundation, which was started by Microsoft founder Bill Gates and his wife, has been fighting malaria since 1998. It invests in vaccine research and other programs to prevent the spread of malaria. If you were a billionaire like Bill Gates and wanted to spend your money on a cause like the eradication of malaria, what would the cause be? Explain your choice.


LANGUAGE ARTS/ARTS: April 25, 2011, is World Malaria Day, which is sponsored by the World Health Organization. Use statistics about malaria provided on their Web site to make posters that will raise awareness about World Malaria Day:


You can access these Web links at

* VIDEO EXTRA: Watch a video about the RTS,S vaccine at:

* Learn more about mosquitoes and how they transmit malaria at the CDC's Web site: /biology/mosquitoes/index.html.

* The Seattle Times has a comprehensive Web site about malaria with articles, infographics, interviews, and more at:
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Title Annotation:BIOLOGY: MALARIA
Author:Adams, Jacqueline
Publication:Science World
Geographic Code:1USA
Date:Mar 18, 2011
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