Questions for Benjamin Ho

Learn more about my research In December, 2007, Benjamin Ho answered visitors questions about malaria vaccines.

Your Comments, Thoughts, Questions, Ideas

Joe's picture
Joe says:

What inspired you to pursue a career in medicine?

posted on Fri, 12/21/2007 - 11:54pm
Benjamin Ho's picture
Benjamin Ho says:

Hello, Joe, and Hello Science Buzz readers!

I’ve always enjoyed learning about science, since it is always around us. As an undergraduate at Carleton College I dove right in, taking courses in pretty much every scientific discipline, from Analytical Chemistry to Ecosystems Ecology. I was even able to study abroad in Australia and New Zealand on a Marine Biology program. Eventually I found that I really enjoyed learning about the mechanics of the human body, through courses like Biochemistry, Immunology, and Physiology. I followed these interests up after college by joining a lab at the National Institutes of Health that was doing some great cancer biology work (to put it generally).

It was an experience outside of school and the lab that really got me interested in medicine as a career. I was lucky enough to snag a volunteer position at the Washington Free Clinic, a community health center in Washington’s Mount Pleasant neighborhood that offered medical services to a lower-income population. The patients who came to the clinic were often uninsured, and most did not speak English as their primary language. The medical director of the clinic, Dr. Laura Martin, was one of the most incredible people I have ever met. She was fluent in Spanish, and you could tell her patients left the clinic with much more than medical advice. When things get tough and you add on medical problems to living in a new country, paying bills you can’t afford to pay, and living without heath insurance, having a place to go to where people understand your problems and are willing to help can be a godsend. I was inspired, and came to the realization that practicing medicine would be my way to put my background in science to use and make a real difference in a few lives.

posted on Sun, 12/30/2007 - 12:29am
Junior V. Knight's picture
Junior V. Knight says:

Dear (Future) Dr. Ho,
First off, I would like to thank you for your contribution to the greater good of humanity. I understand that malaria is typically "transmitted," if you will, via Mo-ski-toes. Considering the high population of Mo-ski-toes in the fine state of Minnesota, how likely is it that I, a resident of the fine state of Minnesota, will get malaria? In your field work, what did you do to prevent becoming infected with malaria? I assume you must be on some sort of strenuous weight-lifting regime to build-up your natural defenses against malaria, am I right? --J.V.K.

posted on Wed, 12/26/2007 - 12:27pm
Benjamin Ho's picture
Benjamin Ho says:

To answer your question, we should first take a look at how malaria is transmitted. Malaria is caused by four different species of a protozoan parasite called Plasmodium: P. falciparum, P. ovale, P. malariae, and P. vivax. But you are correct – these parasites are carried by mosquitoes. We scientists would say that mosquitoes serve as a “vector” for malaria.

The insect that we joke about as the “state bird of Minnesota” is actually more diverse than you probably think. There are thousands of species of mosquitoes; of these, only several hundred are vectors for malaria. The ones we are interested in regarding malaria belong to the genus Anopheles. Anopheles mosquitoes can be found all over the world – check out this map of their distribution: http://www.cdc.gov/Malaria/biology/mosquito/map.htm. If you really want to steer clear of malaria, move to a desert, to Canada, or to Siberia, where numbers of Anopheles mosquitoes are low. But you can see that there are Anopheles mosquitoes in the United States.

We refer to areas that have high incidences of a disease as being “endemic” to that disease. Since Plasmodium spends part of its life cycle in human blood, it can be picked up by another Anopheles mosquito and brought over to another person. This keeps the cycle of infection high. Plasmodium also needs relatively warm weather to reproduce. So if we in Minnesota have both the mosquitoes and the climate (in at least a few months of the year), why don’t we have malaria?

Since we are fortunate in this country to have well-developed public health programs, malaria was eliminated in the United States in the 1940’s. In other places, however, the combination of climate, rainfall, and access to medicine may provide ideal conditions for malaria to flourish. Indeed, malaria can exist in the United States, but in most cases the disease is “imported;” that is, introduced by a person who had contracted the parasite while traveling in a malaria endemic area. Rest assured, as a resident of Minnesota your chances of getting malaria are very slim!

For those who have the money and resources, there are many methods to avoid malaria while in an endemic area. The easiest is to avoid mosquitoes. While I was abroad, I treated all of my clothing with an insecticide called permethrin. I also slept under a bed-net at night. With a little money, there are also medications you can take that will help prevent malaria, if you happen to get bitten by a vector. Medicines that prevent illnesses are “prophylactic” for that disease. I took a drug called malarone once a day as malaria prophylaxis. Others may take mefloquine once a week but may experience interesting dreams after taking the drug. Chloroquine, hydrochloroquine, doxycycline, and atovaquone/proguanil are other prophylactic treatments.

While exercise is great for controlling diabetes and hypertension and a bunch of other bad things, I wouldn’t count on it for preventing malaria!

References:
www.cdc.gov
www.who.org

posted on Sun, 12/30/2007 - 1:27am
Tony's picture
Tony says:

If there are medications that can treat malaria, I would think that finding a vaccine would be that much easier. Since you are still searching for a cure, this obviously isn't true. What makes it so hard to find a vaccine? Is the main challenge to find something that doesn't actually make you sick?

posted on Thu, 12/27/2007 - 3:17pm
Benjamin Ho's picture
Benjamin Ho says:

Hi Tony. I should first clarify that I am not personally developing a vaccine to malaria. I do hope that what I discover in terms of the human response to malaria will help build a body of knowledge that will eventually lead to a vaccine, but I’m happy to leave that work for more well-funded colleagues.

You’re right, developing vaccines to any disease can be tricky business. Vaccines are typically small bits of an infectious agent, or the full infectious agent – usually bacteria or virus – that has been killed with heat. When these harmless agents are injected into your body, your immune system will take care of them as they do for any other immunogenic agent. To put it very briefly, certain cells known collectively as “antigen presenting cells” will ingest the foreign particles (known generally as “antigens”) and present them on their surfaces to other cells called B cells and T cells. B cells produce antibodies – these are molecules that will stick to the antigen that started this whole process, and help identify the antigen so that other cells can pick them up and get rid of them. Lucky for you, B cells have a “memory.” That is, your body keeps a population of cells that responds to an antigen so that if you are ever infected with that agent again, you can respond much more quickly than you did the first time. In other words, you have been “immunized.”

Some bugs, however, have come up with clever ways to avoid detection. In particular, some mutate so frequently that they easily become tolerant to vaccines or medications. This has been the case with HIV and influenza. It takes a lot of really smart people to figure out how we can target these disease-causing agents, and I assure you they are all working very hard!

The research done in laboratories, however, is only the first challenge to developing a vaccine. After coming up with an idea and having success in experimental models, one must consider the efficacy in humans, the cost to developing the vaccine, the ease of mass production, the ease of mass distribution… the list is probably much greater than this. Most countries have a very strict series of stages a drug must pass before being available to the public, and in the end only a very few actually make it to the market.

As for malaria, researchers are following up on some very promising leads. When a mosquito injects the malaria parasite into a human host, it is in a stage of life called the sporozoite stage. During this stage of life, the parasite expresses a protein called the circumsporozoite protein. A group from Mozambique has had success using this protein, joined to the hepatitis B surface antigen, in a vaccine called the RTS,S/AS02A vaccine. Just as I described above, the body sees this piece of the malaria parasite and makes antibody to it, so that when a real infection comes it has cells ready to respond to it quickly. Currently this vaccine is in the early stages of clinical trials, and the group published their findings in 2005 in The Lancet, and most recently in Tropical Medicine and International Health, and Vaccine. Check it out!

References:
www.nature.com
Macete, E., Aponte, J. J., Guinovart, C., Sacarlal, J., Ofori-Anyinam, O., Mandomando, I., Espasa, M., Bevilacqua, C., Leach, A., Dubois, M. C., Heppner, D. G., Tello, L., Milman, J., Cohen, J., Dubovsky, F., Tornieporth, N., Thompson, R., and Alonso, P. L. Safety and immunogenicity of the RTS,S/AS02A candidate malaria vaccine in children aged 1-4 in Mozambique. Trop Med and Int Health. 12 (2007): 37-46.

posted on Sun, 12/30/2007 - 1:28am
Anonymous's picture
Anonymous says:

What country has the worst malaria problem and why is it the worst there?

posted on Sat, 12/29/2007 - 3:19pm
Benjamin Ho's picture
Benjamin Ho says:

Malaria hits Sub-Saharan Africa the hardest. Unfortunately, the malaria parasite, Plasmodium, and the mosquito that carries it, Anopheles, do not pay attention to borders, so the disease is pretty bad all across this region. Malaria also hits South and Central America, Asia, and the Pacific. Go to this website to see a really cool Malaria Risk Map: http://www.cdc.gov/malaria/risk_map/

I briefly mentioned some of the factors that favor malaria transmission a few questions earlier. Temperature is an important factor – you will not find malaria in cold climates. Moisture is another important factor, since it is necessary for the vectors to reproduce.

But one of the main reasons why malaria flourishes in some places and does not in others is the public health infrastructure and availability of medicines. As I briefly described above, the parasites that cause malaria spend part of their life-cycle in the bloodstream. At this point, they may be picked up by other mosquitoes and brought over to other people. If there are Anophelese mosquitoes and other people suffering from malaria in your neighborhood, you may very well get it with a simple bite of a mosquito.

Controlling malaria seems easy on paper. You can avoid mosquitoes by using bed-nets and spraying households with insecticides. You can also kill the parasite once it infects humans by using a variety of medications. But all of these measures cost money, and unfortunately much of the world does not have it. If your family cannot afford bed nets, or you never learned that mosquitoes transmit malaria, if you cannot afford to go to the hospital, or the hospital you go to does not have medicine, or you don’t even live close enough to a hospital or clinic to receive medical care, diseases like malaria will continue to thrive.

posted on Sun, 12/30/2007 - 12:46am
courty's picture
courty says:

what type of virus is malaria???

posted on Sun, 12/30/2007 - 3:54pm
Benjamin Ho's picture
Benjamin Ho says:

Actually, malaria is caused by a protozoan, not a virus. Protozoa are single-celled organisms that are considered eukaryotes – that is, they exhibit all the characteristics of more complex organisms like plants and animals, but they are just a single cell. Viruses are very different creatures… if we can even call them that! Viruses aren’t really living things – essentially they are packets of genetic material encapsulated in a sort of shell, which oftentimes resembles the outside of a human cell. Because they can identify human cells, viruses invade them, use their replication machinery to make copies of their own genetic material, then bud off, ready to infect more cells.

With that background, malaria is caused by four species of the genus Plasmodium: Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium falciparum. Each causes slightly different symptoms, but P. falciparum is the only one that can cause more severe symptoms such as anemia and cerebral malaria.

posted on Fri, 01/18/2008 - 2:45pm
Anonymous's picture
Anonymous says:

In the material titled "Taking aim at a killer" on display at the exhibit, you mention that you are looking for patients who have a particular antibody who have "recovered from malaria the best." Do you find these patients are within a particular racial group or spread more randomly among people of many origins?

posted on Sun, 01/06/2008 - 3:39pm
Benjamin Ho's picture
Benjamin Ho says:

I am not aware of any ethnic differences in antibody response to malaria, although it would definitely be worth a literature search.

Previous work done in our lab has found differences in antibody response between adults and children, however. What this means, we don’t exactly know. The more one is exposed to malaria, the better the body becomes at fighting off the infection. Also, younger patients are at a higher risk of developing more severe symptoms – the most severe is something called cerebral malaria, in which the infection actually goes to the brain. Perhaps the differential antibody response between adults and children have to do with the increasing ability of the immune system in fighting off infection with age? It is an interesting question to ponder.

Your question brings up another interesting issue with malaria: its relationship with Sickle Cell Anemia. Sickle Cell Anemia is a serious blood disorder caused by a mutation in the hemoglobin gene. The abnormal hemoglobin, a molecule found in red blood cells used to transport oxygen through the body, causes the red blood cells to take an abnormal “sickled” shape. Sickle Cell Anemia is autosomal recessive – if you have two copies of the abnormal hemoglobin gene you will express the trait (which is eventually lethal); if you have only one, you are considered a carrier. Carriers, however, are protected against malaria. Individuals of African descent are more likely than others to carry the sickle cell trait: 0.2% of all African Americans have Sickle Cell Anemia, whereas 8% are carriers, and therefore protected against malaria.

www.ncbi.nlm.nih.gov

posted on Fri, 01/18/2008 - 3:25pm
Anonymous Paul's picture
Anonymous Paul says:

Ben,
What is the probability of a poluted river (like the Anacostia) infecting the surrounding land based community?

posted on Wed, 01/09/2008 - 7:34am
Benjamin Ho's picture
Benjamin Ho says:

Hi Anonymous Paul,

Yes, I know this river! Very polluted indeed. For those of you who are unfamiliar, the Anacostia drains a watershed in Prince George’s County, Maryland, and joins the Potomac River at Haine’s Point in Washington DC.

One of the many sources of pollution that is destroying the Anacostia is storm run-off from DC’s outdated water system. Many older cities have systems that use the same pipes for storm run-off and sewage. After a rain, these pipes become overwhelmed and the water – and sewage – is discharged into natural waterways. I’ve read that there are 17 discharge sites on the Anacostia.

You’ll find all kinds of bugs in sewage – E. coli, Enterobacter, Klebsiella, Citrobacter to name a few. A healthy individual will do a good job at fighting off infection if they happen to contact one of these bugs – some of them, in fact, are natural inhabitants of our gut. But if for any reason you happen to come in contact with a lot, or if you happen to have a gap in your immune system at the time, these bugs can definitely make you sick. Depending on where they land, these guys can cause diarrhea, pneumonia, ear infections, or more seriously, meningitis or septicemia (an infection of the blood stream).

The best way to stay healthy around polluted water is to stay clear of the water! Don’t swim in it, and definitely don’t drink the water (that one’s a no-brainer). Basic sanitation habits are very important – after being on or near the river, make sure to wash your hands well. And try not to huli in the Anacostia! I don’t have any numbers as far as probabilities, but if you take these basic precautions you should be ok.

I once knew a guy who paddled a canoe on the Anacostia River just a few days after having a minor skin surgery on his back. Thankfully, nothing serious happened to him – he must have either had a great immune system, or had a good seal on the duct tape he was using to cover the wound. I do remember, however, that the incision took a long time to heal and had a pretty nasty looking scab on it for a while. This may be a bunch of handwaving, but that incision was probably the site of some major immunology. If I was this guy’s doctor, I would have definitely given him an earful!

posted on Fri, 01/18/2008 - 2:48pm
a tall friend's picture
a tall friend says:

now that you're near the end of your med school career (kind of), how do you feel about the decision?

posted on Wed, 01/09/2008 - 11:04pm
Benjamin Ho's picture
Benjamin Ho says:

Hello, tall friend!
Medical school has definitely been a difficult experience. It feels a lot like running a marathon – but every day. And with minimal amounts of sleep in between marathons. There’s always new information being thrown at you, and having that information solid in your head by exam time takes a lot of work.
That said, I consider myself extremely lucky to be where I am. Having the opportunity to follow what I believe is my “calling” is something that I am really grateful for.

posted on Fri, 01/18/2008 - 2:48pm
Joyce's picture
Joyce says:

As a high school counselor, I have many students who aspire to "become a doctor". What advice would you have for those high school students who are interested in entering the field of medicine?

posted on Sat, 01/12/2008 - 10:30pm
Benjamin Ho's picture
Benjamin Ho says:

Aloha, Joyce!
It’s great that your kids are aspiring to become doctors. You must have some smart ones!

My biggest piece of advice to your students would be to make sure medicine is what they really want to do. I think the best way to figure this out is to volunteer. They can inquire at hospitals, clinics, the Red Cross, nursing homes, or any other place where they can see health care professionals work amongst each other and with patients. Here, they will discover whether they would be comfortable working with people (all kinds of people) on a daily basis, and also hopefully get a glimpse into how doctors and nurses carry out their jobs.

Also, if they have the right connections, it would be great if they could shadow a physician. This is often a pretty big favor to ask since doctors are very busy and having an extra body in an exam room can be a lot to ask for. But if your kids have family friends or college alumni who are willing to help, shadowing can be an invaluable experience.

This may sound unrelated, but looking back on things I would tell aspiring physicians keep up with their foreign languages. Physicians who are fluent in Spanish, or here in Minneapolis, Hmong or Somali, can reach out to many more patients than us uni-linguals.

My final piece of advice is the same as my first piece of advice – make sure it’s what they want to do! A career in medicine will demand a lot of sacrifices. They’ll want to be 150% sure that really want a life in medicine before investing the time and money getting into it.

posted on Fri, 01/18/2008 - 2:49pm
Anonymous's picture
Anonymous says:

What is your favorite thing about what it is you are doing?

posted on Fri, 01/18/2008 - 2:37pm
Benjamin Ho's picture
Benjamin Ho says:

In medical school, I like the feeling that my knowledge and skills are gradually coming together, so that I can start to think and function like a doctor. In my laboratory research, I like the fact that the information we are gathering is coming straight from humans. I find it a bit more satisfying than doing work on laboratory animals or cultured cell lines, because we know what we find is actually true for humans.

posted on Tue, 02/12/2008 - 5:27pm
Anonymous's picture
Anonymous says:

How long is a person with malaria infectious after getting the sickness themselves?

posted on Thu, 01/24/2008 - 6:44pm
Benjamin Ho's picture
Benjamin Ho says:

This is a difficult question to answer – to be honest I don’t really know. If a person has any amount of the parasite in their blood, and happen to be in an area where they may be bitten by an Anopheles mosquito, then the disease can spread. It can take the human body up to 2 weeks or longer to establish an immune response that can control the organisms in the blood. Malaria parasites, however, spend part of their life-cycles hidden in liver cells and red blood cells. So it can take a long time for the body to completely clear the parasite. In fact, some people are exposed to so much malaria that they become chronically parasitemic – that is, they never really get rid of the parasite. If the parasite happens to be floating in the bloodstream at the time of a bite, there is always a chance that a mosquito can pick it up and bring it to someone else.

posted on Tue, 02/12/2008 - 5:25pm
Anonymous's picture
Anonymous says:

Are there varients of malaria that are becoming resistant to treatments?

posted on Thu, 01/24/2008 - 6:45pm
Benjamin Ho's picture
Benjamin Ho says:

Great question. Yes, chloroquine-resistant P. falciparum and P. vivax are known to exist. Any time you treat an infection heavily with one agent, you apply a significant amount of selective pressure that will naturally lead to the development of resistance. Fortunately, there are many other treatments for malaria – if one drug happens to be ineffective, it is easy to try another.

posted on Tue, 02/12/2008 - 5:26pm