Medical Minute 8-1: Life-Changing Bite: Malaria Takes Limbs

By: Vanessa Welch Email
By: Vanessa Welch Email

Imagine brushing your teeth, fixing your hair or opening a can of pop without your own hands. For Dawn Dubsky, it's a reality not even she was prepared for.

"I never thought I would lose my limbs," said Dawn Dubsky, Lost Four Limbs.

Three years ago, Dawn was studying overseas in Ghana.

When a mosquito bit the back of her leg. Back at home, she went to the ER. Ravaged by the malaria parasite, Dawn woke up a month later -- a quadruple amputee.

"My parents had chosen to amputate my limbs to save my life."

20-thousand travelers are infected with malaria each year. Doctor Mats Wahlgren of the Karolinska Institute in Stockholm, Sweden is working to change that.

"It kills around 1 million people each year, and how many died in 9-11? 3,000. It's more or less the same figure per day that malaria takes away," said Dr. Mats Wahlgren Professor, Karolinska Institute, Stockholm, Sweden.

The parasite penetrates the red blood cells where it produces proteins that clog up the blood vessels -- a potentially deadly situation. The new intravenous drug treatment would prevent that from happening by preventing infected blood cells from binding and releasing blood cells that are already bound.

The breakthrough comes too late for Dawn, but she's not letting that stop her from fighting.

"For some reason, this happened. You have to make the best of it."

She's taking steps to do just that. Her non-profit America Against Malaria is her way of fighting back against a disease that nearly took her life.

For more information on other series produced by Ivanhoe Broadcast News contact John Cherry at (407) 691-1500, jcherry@ivanhoe.com.

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REPORT: MB #3331

BACKGROUND: Malaria is a serious and potentially fatal disease caused by a parasite that commonly infects a specific type of mosquito that feeds on humans. Common symptoms of malaria include high fever, shaking, chills, and flu-like illness. About 1,500 cases of malaria are diagnosed in the United States each year. The majority of these cases happen in travelers and immigrants returning from countries where malaria transmission occurs. This was the case for Dawn Dubsky who, while traveling in Africa, was bitten by a mosquito. Upon returning home to the United States, she went to the emergency room, ravaged by the malaria parasite. Dawn woke up a month later as a quadruple amputee.
(SOURCE: CDC)

PREVALENCE OF MALARIA: About 20,000 travelers are infected with malaria each year. It kills nearly 3,000 people each day and up to 1 million people every year. The parasite penetrates red blood cells where it produces proteins that clog blood vessels. Following the parasitic bite, a period of time passes before the first symptoms start to show. This period can last from seven to 30 days. These long delays between exposure and development of symptoms can result in misdiagnosis or delayed diagnosis because of reduced clinical suspicion by the health care provider.
(SOURCE: CDC)

CURRENT TREATMENTS: Anti-malarial drugs can be prescribed to people traveling to areas where malaria is prevalent. It is important for travelers to see their health care providers well in advance of departure because treatment may begin as early as two weeks before entering the area and continue for a month after leaving the area. The types of anti-malarial medications prescribed will depend on the drug-resistance patterns in the areas to be visited.
(SOURCE: New York Times)

NEW TREATMENT IN THE WORKS: A new intravenous drug treatment is in the works to treat malaria. Researchers from the Karolinska Institute in Sweden are currently studying the therapy. Scientists have been able to treat severe malaria in rats and primates with this new malaria drug, and they hope to replicate the results in humans.
(SOURCE: Karolinska Institute)

FOR MORE INFORMATION, PLEASE CONTACT:
Karolinska Institute Press Office
Stockholm, Sweden
pressinfo@ki.se

The Bill and Melinda Gates Foundation
http://www.gatesfoundation.org

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THE FOLLOWING IS AN IN-DEPTH INTERVIEW WITH THE DOCTOR FROM THE STORY ABOVE:

Dr. Mats Wahlgren, Professor, Dept. of Microbiology, Cell and Tumor Biology, Karolinska Institute, Stockholm, Sweden, talks about a potential new treatment for malaria.

Have you worked with people who have malaria?

Dr. Mats Wahlgren: Yes. I have, and I have worked as a doctor for adults for quite some time. I became a Professor of Parasitology in 1993. That is quite some time ago. Before that, I worked as a doctor. I finished my MD in 1979, where I went on to study tropical medicine for some time. After that, I came back and finished my PhD in 1986 on malaria as well. During these years, I worked as a doctor. My wife and I then went to California where we worked on postoperative patients. I came back in 1993, and received my professorship where both my wife and I had a lovely time. I thought that it was great.

I don’t think that a lot of people understand quite the severity of what widespread malaria can cause. I think that a lot of people think that malaria is something found merely in the jungle, however, it is far from that. Can you briefly discuss the severity of it to people listening that don’t have an understanding of the disease?

Dr. Mats Wahlgren: It is much bigger than that. The latest figures show that anywhere from 250 million to 300 million clinical cases are reported annually. Of course, it hits all of the tropical south, however, the most intense of transmissions occurs in Sub-Sahara as well as Africa. You can also find it in Latin America though, in addition to Southeast Asia and Asia for that matter.

Why are you so interested in this?

Dr. Mats Wahlgren: Well, malaria is a disease of the poor’s. It is a very imperative ailment to study because it kills so many people every day. Malaria kills approximately one million people each year. How many people died in 9/11? 3,000 people. It is more or less the same figure per day, which malaria takes away. The 3,000 people that 9/11 took is in due course the same for what malaria takes every day. It is a disease that ultimately hits the poorest of the poor. You find it predominantly in cities that are a part of poor countries. It has a strong gender perspective, in the sense that it can affect pregnant women as well as children. Of course, men often get sick, however, not so often and not so severe. Malaria is a very serious and important disease for the world to combat.

What are the reason for malaria hitting women more often than that of their counterparts?

Dr. Mats Wahlgren: You build immunity, and you protect yourself against the disease when you are a child. It takes nevertheless an exceptionally long time to do so. Ultimately, the girls and boys that are fifteen are immune to the disease in areas where it is endemic.

So, it takes till about fifteen years of age to become immune to the disease?

Dr. Mats Wahlgren: No, it doesn’t. It depends principally on how intense the transmission is. If it is highly endemic, you would be immune by perhaps five years of age. In other areas, it could possibly take up to ten years. Anyhow, women that are pregnant – this tissue that malaria attacks is not pregnant in the man or the woman who is not pregnant for that matter – their placenta is far different from any of the other tissues that are evident throughout our bodies. So, parasites find a new niche and a new place to attack. After pregnancy and after the placenta falls out, if you follow a woman, which has been done (it was performed in a study in Congo) that shows that the parasite actually leaves the body within a week of delivering the child. There is something very particular about the placenta, as well as the context of a pregnancy that makes the parasite like it, and they use that niche.

So, you have been on the front lines and seen the detrimental results that come with contracting the disease?

Dr. Mats Wahlgren: Yes. I have been working quite a bit in Uganda over the past few years as well as other places. Nonetheless, Uganda has been our main site for the reason that Northern Uganda has the highest transmission throughout the world. Kids in these countries get roughly 1,500 infected bites per year, which means that these are some of the intense transmission recorded in the world. That means that each week, you are injected with parasites during your whole childhood. This is tremendous pressure – a tremendous amount of malaria. What is Uganda? It is a place with a lot of turmoil. You remember Lord’s Resistance Army, correct? This is a place that is with immense poverty levels. Malaria seems to hit areas of poverty in addition to political unrest. Another place that you can think of is Burma or Mein Ma for example for the reason that neighboring countries still remain in political unrest and poverty. Thailand almost has no malaria left.

When you venture to these third world countries, what kind of symptoms do these children show that are inflicted with malaria?

Dr. Mats Wahlgren: Malaria is a disease that gives fever, and are characterized by general symptoms. You may see a child that appears to be very sick (difficulties breathing), where this can lead to cerebral malaria and moreover unconsciousness. It is not uncommon to see someone unconscious for the reason that the parasites actually stick in the brain and upset the circulation. Other problems that can stem from malaria include but are not limited to respiratory stress (typical of severe cases) and anemia.

Is malaria a slow progressing disease or does it have an immediate effect on one’s health?

Dr. Mats Wahlgren: Malaria can be chronic or semi chronic, nevertheless, it can be very quick in its progression. You can see a child come in with malaria and think nothing of it. 24 hours later, that same child is in a coma and alas dies from the disease. It is a very traumatic thing, and imperative that we handle the severity of disease as best we can throughout the entire world. You have to have full respect for the disease, because it can lead to death as you can tell.

Is malaria something that is commonly found throughout Sweden?

Dr. Mats Wahlgren: No much. We have had imported cases. We had a prevalence of malaria, although that was a long time ago. Today, we have perhaps one hundred imported cases reported annually.

How do you currently test for malaria?

Dr. Mats Wahlgren: You take a small blood sample via a finger prick, where you will then stain it and observe it under a microscope in a effort to determine whether there are or aren’t parasites evident. We still diagnose malaria the same way we did almost one hundred years ago.

Are you currently looking for novel ways to help test for malaria more efficiently?

Dr. Mats Wahlgren: Yes. There has been the development of innovative diagnostic tests that include a dipstick (a band on a small stick), however, it is not an exceptionally responsive tool, but rather an imperative one for following population. My work has not been primarily in the diagnostic field of malaria, but how a child will come down with malaria. We are currently investigating what it is that is in malaria that causes a child to become so sick. With that information, we are trying to develop a drug that helps reverse it. We started a company a couple of years back, where we have developed a drug that is going to be tested in Burma as well as in Thailand.

How exactly will this drug be able to reverse the damage inflicted upon the child by the parasites?

Dr. Mats Wahlgren: This is not prophylactic. This is more like a treatment. You would have a drug that targets and kills the parasites that would be taken when someone is not well. Then, you would add something on that would resolve, because the parasites often stick and clog the vessels when you have a severe case of malaria. These are especially gluey parasites – they express a glueyness, which blocks the blood flow for these children. What this drug will do is aid in clearing those tubes once the parasites have been destroyed, and help reestablish blood flow to areas of the brain, which are critical for our being, as well as the lungs, as well as other crucial places that need to function properly to maintain one’s being.

Would this treatment be administered to these children intravenously?

Yes. It would be given to patients through an intravenous infusions for a few minutes over a period of a few days. It is the same phenomenon as that of if you have a pregnant woman with malaria – the parasites tend to stick and create abundant problems. Of course, the whole body reacts to the accumulation of parasites in different ways, one of which is the immune system.

Could this become in a sense a vaccine for those in third world countries?

Dr. Mats Wahlgren: No. It wouldn’t be a vaccine, because you think of vaccine like that of a prophylactic. Of course they could be therapeutic vaccines as well, but I would say that these would not be considered a vaccine, because this is the part which the parasite in which the parasite uses to connect to the body. So we are using what is commonly referred to as the receptor. With this drug, we would disrupt the injection and the parasite would go away. It sticks to the blood in the fine microcirculation in an effort to avoid being killed in the spleen. The parasite changes the red cell when it is infected so much, so it would be flushed and recognized by the spleen, and in due course be killed there. The parasite likes to stick somewhere else where the immune system isn’t so present. So, the receptor is the drug actually, and if I was to construct a vaccine, I was use the parasite part in order to mount an immune response to the parasite’s glue. The ‘glue vaccine’ is what you could call it.

How many parasites are present in the body when it is infected with malaria?

Dr. Mats Wahlgren: Too many. It can be up to billions though. It really depends on how many infected red blood cells there are. We have around 109 red cells that are infected. If half of them are infected, and we have approximately four to five liters of blood, the parasite level is absolutely enormous. It is inside our blood. It is inside of our immune system much like that of HIV. So the parasite is inside of the blood as well as the immune system.

When will you commence your study?

Dr. Mats Wahlgren: We have already done a phase I study in England some years ago. We have all of the papers cleared in addition to ethical clearance to perform in various places, so this is going to be very soon. I estimate that maybe after summer – two to three months even. I have been following these leads for an extended period of time, and found that these in-vitro tubes could destroy or distract the infection, which has been tested in rats and monkeys over the past fifteen years. Finally. It is also scary though if it doesn’t work. That is something that I shouldn’t say, but things may not be as they are in a test tube when we get out there and start.

What if it does work?

Dr. Mats Wahlgren: If it does it would be wonderful. We have very good indication that it should work, because we have tested this on monkeys and have received optimal results. It should work. This could save millions of lives and be exceptionally important to the survival of 300,000 people a day around the world. This is something that I think would be very important if it works.


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