final post on my malaria experience #endmalaria

I went to Oxford and all I got was a lousy parasite infection

 As you could read on this blog, the fourth of July I went to Oxford to join a malaria vaccine trial and got injected with 1,000 P. falciparum infected red blood cells.

At day 10 after the challenge, I was the last one to get diagnosed using the "gold standard": a thick smear of my blood. At that time these parasites had already multiplied (measured by qPCR) to one of the highest numbers in the group: 70,000 parasites per mL blood.
That sounds perhaps like a lot of parasites, but to calculate the parasitemia (percentage of red blood cells infected) you should divide this number by the number of red blood cells in one mL blood, which is actually really a lot:

So, let's make the calculation: 70,000 parasite infected red blood cells in a total of 5 billion red blood cells gives you a parasitemia that could come straight out of the mouth of Tour de France's cyclist Alberto Contador:

Such a low parasitemia (hospitals frequently see patients with more that 5% infected red blood cells) gave me symptoms that already kept me in bed for most of the day... These got even more severe after I started the therapy because when the parasites start dying, the infected red blood cell ruptures (cell lysis) and all the toxic products enter your bloodstream.

The resulting inflammation induces fever, chills, sweating, headaches, fatigue...

So yes, this eventually happened on Tuesday:

But after 60 hours of therapy, I was ready to head back to Belgium... Just in time for Gentse Feesten.

Ghent skyline from CEVAC's research building at sunrise

I'm glad to be cured quickly and that I was able to get a small glimpse of what malaria is.

Malaria is no joke. End malaria now!

I think we have sat around too long. Every minute, a child dies of malaria and many more have to endure the disease, recover, and get infected again..
Malaria is 100% preventable and treatable. Yet, more than 200 million people get malaria each year.


As a scientist working on malaria, I got inspired to work harder by entering this vaccine trial. We should all remember sometimes why we study malaria...

My plan for Plasmodium parasites?

Back to work.

Click here for more info on malaria, the parasite causing the infection, vaccine trial in Oxford.

If you would be interested in joining a clinical malaria challenge you can always check these websites:

Radboud University (Nijmegen, Netherlands)
Jenner Institute (Oxford, UK)

Walter Reed Army Institute of Research (Maryland, USA)

Seattle Biomed (Washington, USA)

malaria update d+9: I got this feeling...

Friday evening: two volunteers get a phone call...

Friday (day 7 after infection) None of the volunteers have any symptoms (yet), but two out of 27 volunteers infected with malaria had a positive blood smear: the researchers were able to see parasites using a microscope, an endpoint of the study.

These two volunteers are now taking their malaria pills and in two days...

How about me?

Saturday evening (day 8 after infection) I got a bit of a headache.. nothing special I guessed, but this morning:

Sunday (day 9 after infection) Woke up feeling a bit tired and still having a headache. If I didn't know better I would think that I had a hangover but there were some clues:

- I know that I am infected with malaria (big spoiler here)

- beer in the UK has hardly any alcohol in it (compared to Belgian beer)


So after having my morning blood sample taken and having some breakfast I went back to bed, like many other party people on a Sunday morning... 

Woke up feeling a bit flu·ish, quite weak, still tired with a headache and some heavy legs. This could still be mistaken for the results of a heavy night or just a bad case of the man flu.


During my afternoon clinic visit I learned that by now 8 out of 27 volunteers have had their malaria infection confirmed using a blood smear.

Since I am having some symptoms I was looking forward to my temperature...

The doctor's reaction was as expected:

At this very moment (Sunday, 8PM) my blood is being analyzed and it will probably be positive for malaria. In a couple of hours I'll also get the phone call and will have to come in to get my therapy. And that's that...

So, is this the disease I was expecting? 

Not completely. I do feel that something is happening, but I am surprised at how unspecific my symptoms are. If I was not aware that I am infected with malaria, I would still be at work now, tomorrow staying at home to recover from a self diagnosed flu... And then it would be already too late for an easy recovery. By the time I would go to a doctor and my blood would be analyzed my symptoms would be so severe that hospitalization is necessary.


I guess this trial is the perfect example of how clinical malaria challenges have evolved: we are able to infect people with a deadly but treatable disease, get significant results on a new vaccine candidate and prevent serious effects on the volunteers' health.

For now, I am going to "enjoy" my malaria a bit with some appropriate youtube clips like this one:

Click here for more info on malaria, the parasite causing the infection, vaccine trial in Oxford.

If you would be interested in joining a clinical malaria challenge you can always check these websites:

Radboud University (Nijmegen, Netherlands)
Jenner Institute (Oxford, UK)

Walter Reed Army Institute of Research (Maryland, USA)

Seattle Biomed (Washington, USA)

Why do we (need you to) join clinical trials?

For most, clinical trials are a necessary evil. 

Almost nobody will voluntarily be the first human guinea pig to test the adverse effects of new drugs, but the sad truth is: we need them...

The results of insufficient thalidomide testing

I don't have to remind you that things can go terribly wrong during a clinical trial, but like all accidents, lessons have been learned, protocols adapted.

If you would like to know more about phase 0 and I drug testing, visit the Ghent University's Drug Research Unit.

There are of course other clinical trials that don't involve new drugs, for example: developing new vaccines.

My first clinical trial: efficacy of an influenza vaccine against bird flu (H5N1).

In 2006 the pandemic panic was on a high: H5N1 bird flu was going to wipe us out! To test a new vaccine consisting of small parts from the virus (subunits) in low doses (antigen sparing), Ghent University's Center for Vaccinology set up a trial. As a student Biomedical Sciences, I was intrigued by this and joined.

Why? 

• For the 300 euro's? Of course some extra pocket money isn't that bad...
• For science? Experiencing immunology in practice was a bit more interesting than learning all cytotoxins in class..
• To be safe from the H5N1 rapture? I must admit that I really don't like the flu and was happy to get access to a vaccine that was still unavailable to the rest of the population...
• To be able to cuddle birds in the future? No comment..

Was my "sacrifice" useful? Yes!

• The results from this clinical trial were published in one of the highest ranking journals: The Lancet
• I even got mentioned in the acknowledgments:

We thank the National Institute for Biological Standards and Control (Potters Bar, UK) for providing the vaccine virus strain and reference standards; the Centers for Disease Control and Prevention (CDC, Atlanta, USA) for supplying the A/Indonesia/5/2005 strain; the participating clinicians, nurses, and laboratory technicians at the study site and the sponsor’s project staff for their support and contributions throughout the study, in particular Laurence Baufays for study coordination; Catherine Vigano-Wolff for preparation of the study protocol and related study documentation; the study volunteers; Kati Zierenberg, Roger Bernhard, and Elisabeth Neumeier who did the immunological laboratory work; Emmanuel Hanon, W Ripley Ballou, and Roland Saenger for critical reading of the report and very helpful suggestions; Miriam Hynes (independent, UK) for her assistance in preparing the report; and Isabelle Camby (XPePharma SA, Belgium) for coordination. TV is supported by a PhD grant of the Research Foundation-Flanders. This study was supported by GlaxoSmithKline (GSK) Biologicals, Rixensart, Belgium.

• And for me personally: this trial and its results inspired me. Four years later I graduated and joined these researchers for a PhD in malaria vaccine development.

Back to the current trial 

Why do people actually want to get infected with malaria? Even after receiving an informed consent from the study doctor and their own doctor?

For most of the volunteers, it is simple:

You do get a lot of money for this trial, but the trial also asks a lot of time and effort from you

"The amount has been determined before the study and is based on the burden of the clinical trial. Influencing factors of the burden of the clinical trial are e.g. number of blood samples taken, burden of disease, the amount of time the volunteer needs to expend for participation, number of overnight stays, ..."

In this trial, you have a blood sample drawn twice each day, you will probably have some symptoms of malaria, have to stay in town, ...

This is quite a burden, so you'll get a good compensation....

... but it won't make you rich.

So is it wrong to join clinical trials for the money? 

No. People who occasionally join a trial will not have any negative effects on the long term. There are however people who you could call medical prostitutes, who try to make a living out of joining clinical trials. This is of course very bad: the volunteer can have a negative effect from combining different medications that could potentially interact, but more importantly: this is very bad for science! The results can be affected by using the same volunteers each time or that they don't resemble the population anymore (by taking significantly more medications, vaccinations, ... than the average person). In the worst case, development of a promising new therapy is stopped because of wrong results...

To prevent this, there are of course several safeguards: participants are screened in a national database to see if they are currently or very recently enrolled in another trial, the doctor at the trial screens them also to see if they are honest about habits, intentions, ... 

The truth is: we need people who don't mind to make a bit of money by joining trials. 

People should realize that to live in a healthier world, we need volunteers who lend their body to science. If you're a biomedical scientist, you probably know how difficult it is to find volunteers for trials... Of course, you can't join your own studies (ethics, blinding of study results, ...).

However, you can and should join the trials of your peers! 

Don't count on others looking for some extra money, progress starts with you, not only as a scientist, but as a human.

If you would be interested in joining a clinical malaria challenge you can always check these websites:

Radboud University (Nijmegen, Netherlands)

Jenner Institute (Oxford, UK)

Walter Reed Army Institute of Research (Maryland, USA)

Seattle Biomed (Washington, USA)

Living in Belgium and considering joining a vaccine trial?

Centrum voor Vaccinologie (Ghent)

Centre for the Evaluation of Vaccines (Antwerp)

Silent malaria infection: waiting for the storm

First thing people do when they hear I am voluntarily infected with malaria:

Next, the questions start pooring:
"How are you feeling?"
"How is the malaria?"

"Nope, I'm perfectly healthy!"

Recap

Four days ago I was infected with 1,000 malaria infected red blood cells. This is actually a very low dose. If an infected mosquito delivers only one parasite into my skin and it would find its way to my liver, it would grow there during seven days and eventually lead to a blood stage infection with more than 60,000 circulating infected red blood cells. This is still too low to notice, but since malaria parasites (P. falciparum) multiply 10-fold each 48 hours, you'll start noticing that you're infected about 12 days after that itchy mosquito bite.

Blood samples taken this morning

In my case? Let's do the math:

1,000 parasites (inside a red blood cell) were injected in a volume of 5 liters of blood (me!). Today, four days and two multiplication rounds later, this should amount to a number of 100,000 infected red blood cells, or 20 infected red blood cells per mL or 1 infected red blood cell per 250 million(!) healthy red blood cells.

Still a really low number right? Actually, this is still too low to detect my infection using a microscope... But it should be just near the detection limit of current qPCR techniques.

Quantitative Polymerase Chain Reaction

I'm not going to get too technical, but to explain this technique quickly: it is possible to detect the genetic material of malaria parasites by specifically amplifying a small part of its DNA or RNA (chain reaction) until there is so much of it that you can visualize and quantify it using fluorescent molecules.

That's the technical part, the lab technician analyzing my blood sample should get something like this on her/his screen in a couple of hours:

What's next?

The waiting game.

Each morning and evening a blood sample is taken for analysis (microscopy and qPCR). I expected this to be quite annoying, but until now it went very easy. I'm lucky to be in the caring hands of an expert team of doctors and nurses!

The researchers from Jenner Institute expect us (controls) to start noticing the first malaria symptoms on day 7 to 9. Around that time the number of parasites will be high enough to start seeing them under the microscope. And that will be the (scientific) endpoint of this clinical trial...

For me, it will only be the beginning of the end. From the moment I receive therapy (pictured above), the infected red blood cells will be killed which causes more inflammation and actually a worsening of symptoms. 

For now though.. I am enjoying my time in the beautiful city of Oxford.

Click here for more info on malaria, the parasite causing the infection, vaccine trial in Oxford.

If you would be interested in joining a clinical malaria challenge you can always check these websites:

Radboud University (Nijmegen, Netherlands)
Jenner Institute (Oxford, UK)

Walter Reed Army Institute of Research (Maryland, USA)

Seattle Biomed (Washington, USA)

Clinical trial: infecting yourself with malaria (deliberately)

As a malaria researcher, you often wonder what it would be like to have a malaria infection.  At least, I do. It is a topic you work on every day, but being safe in Europe your chance of getting infected is zero, even when travelling to an endemic region we have the luxury of prophylactic pills to prevent an infection. People living in these regions don’t.

But I’m in luck! I have the chance to experience a malaria infection in the controlled environment of the University of Oxford during a clinical trial to test the efficacy of a vaccine.

Malaria kills.

Malaria is an infectious disease that is spread by the bite of an infected mosquito. It causes high fever, chills, flu-like symptoms, and severe anemia. Malaria is especially dangerous for pregnant women and young children who are experiencing the disease for the first time. Each year, 250 million people are infected and almost one million die.

Current treatments are inefficient and resistance against drugs is rising. 

These depressing facts indicate that the need for an effective vaccine is very high.

Several research groups across the world are developing vaccines against the parasite causing malaria (Plasmodium falciparum). Eventually, these vaccines should be tested in a clinical trial.

Human experimental malaria infections are carried out under strictly controlled laboratory and clinical conditions. During a trial, volunteers are exposed to either the bites of laboratory-reared infected mosquitoes or injected with infected blood.

These studies are very important since they provide early information on vaccine efficacy.

When you tell people you’re enrolled in a malaria challenge trial, their first reaction is: “You’re nuts!!”

People associate malaria of course with:

But since this is a trial, the researchers will actually stop the infection with an effective treatment from the moment it is detected, so the symptoms should be very low or none (hopefully).

The big challenge with these studies is actually the intense follow-up with blood sampling twice daily.

So I will likely look more like this at the end:

Note: this is a picture from a heroin addict, taking a few blood samples doesn't make your arm look this shitty...

Infection day

A group of 25 people is sitting here since 8 AM waiting to get a malaria shot. Some do it to help the cause, others do it for the adventure, but most are attracted by the large compensation you receive at the end (4 digit number). Of course, it would be really difficult to find volunteers for these studies without compensating them (and doing these studies on prisoners is illegal now).
Some people look scared, is it actually a good idea to get infected with such a deadly disease? Others didn't show up: second thoughts, family issues,...
The doctors try to prevent most worries by giving you all possible information during the intake conversation (a month before the start) and you are allowed to leave the study at any moment.


In a moment, my guinea pig colleagues and me will be injected with 5mL of infected blood through a catheter that was inserted in our veins.

After the infection we wait for an hour during which we get a little survival package consisting of medication and... a card!

Next we will have to… wait. The infected red blood cells are diluted in my blood and will start to multiply until their numbers are high enough to be detected using a microscope. After this, the trial is done and I get a standard treatment to kill all the parasites and can go home.

The scientists will then analyze all the blood samples from vaccine recipients and controls (my group). The most important result will be visible to all of us: 

Will the vaccine prevent or delay the clinical symptoms?

Click here for more info on malaria, the parasite causing the infection, vaccine trial in Oxford.

If you would be interested in joining a clinical malaria challenge you can always check these websites:

Radboud University (Nijmegen, Netherlands)
Jenner Institute (Oxford, UK)

Walter Reed Army Institute of Research (Maryland, USA)

Seattle Biomed (Washington, USA)