6 ms·

Dengue fever vaccine proves 100% effective in human trials

120 points by runesoerensen 11y ago

mibrah 11y ago
YEAHHHHHH BOIIIIIIIIII
ghaff 11y ago
Seems like a big deal. Dengue is different (and more problematic) than a lot of diseases in that if you've had Dengue even mildly or at least not severely, you're actually far more at risk for serious effects the next time if it's a different one of the four varieties of the disease. The article suggests that the trials so far protect against that effect as well. [EDIT: As pak notes elsewhere, this trial apparently didn't test against all four varieties although there was some evidence it might protect against multiple.]
pak 11y ago
While I am of course a huge fan of NIAID and vaccine development against dengue, and I believe that a vaccine that works against dengue will probably be found within our lifetimes and prevent millions of hospitalizations (EDIT: not deaths, sorry) per year, this is a classic example of a downstream news report editorializing the headline and misrepresenting the implications of the original article. The whole challenge in creating a dengue vaccine is that it has to protect against all four serotypes (called a tetravalent vaccine). Incomplete protection against one of the serotypes could potentially lead to an even worse infection if you are infected, through a process called antibody dependent enhancement: https://en.wikipedia.org/wiki/Antibody-dependent_enhancement https://en.wikipedia.org/wiki/Antibody-dependent_enhancement This is why vaccine development against dengue has been so painstakingly slow. The candidates in this trial were only challenged with one serotype, DENV-2. Therefore, we have no way to know if the tetravalence of the vaccine actually achieved efficacy against all four serotypes (although promisingly, antibodies against all serotypes were seen in 92% of the patients). The sample size is also quite small (N = ~20). This is why the original article states its impact conservatively as "This model may serve as an early check for dengue vaccine candidates, limiting the risk of conducting large unsuccessful trials" and furthermore "the true efficacy of TV003 can only be established by performing a phase 3 trial in endemic areas." Here's how you write a more honest headline and summary for lay people: http://www.cnn.com/2016/03/16/health/dengue-vaccine-effective/index.html http://www.cnn.com/2016/03/16/health/dengue-vaccine-effectiv... I don't intend to detract from the achievement here, but I don't like when headlines oversimplify the implications of a clinical trial. It sets unrealistic expectations and decreases the public's trust in proper vaccine research. Disclaimer: I am doing research with a lab that studies dengue virus, and we have collaborators that are working on a commercial vaccine.
- ekianjo 11y ago
  > vaccine that works against dengue will probably be found within our lifetimes and prevent millions of deaths Are you sure about "millions of deaths" ? Dengue fever fatality rate is lower than 1%. I'm not saying this is not a grave disease, but it's hardly something that kills as much as many other viruses out there.
  - pak 11y ago
    You're right, I meant hospitalizations; I goofed.
- runesoerensen 11y ago
  > This is why the original article states its impact conservatively as "This model may serve as an early check for dengue vaccine candidates, limiting the risk of conducting large unsuccessful trials" You're obviously much more familiar with this subject, but doesn't the quote from the original article refer to the testing model itself (i.e. "dengue human challenge model"), rather than the efficacy of the actual vaccine? > this is a classic example of a downstream news report editorializing the headline and misrepresenting the implications of the original article. To be fair, it doesn't seem like Wired has editorialized/misrepresented at least the headline much relative to the original article ("The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model" vs "Dengue fever vaccine proves 100% effective in human trials"). > I believe that a vaccine that works against dengue will probably be found within our lifetimes and prevent millions of deaths per year I tried finding estimates of infections and deaths per year, but didn't find any that are close to millions/year. Do you have a source for that? The closest I got was from the CDC/WHO: The World Health Organization (WHO) estimates that 50 to 100 million infections occur yearly, including 500,000 DHF cases and 22,000 deaths, mostly among children. [0] [0] http://www.cdc.gov/dengue/epidemiology/ http://www.cdc.gov/dengue/epidemiology/
  - pak 11y ago
    > doesn't the quote from the original article refer to the testing model itself Yes, it does, precisely because the trial is about a human challenge model that uses an attenuated virus. It may or may not be representative of efficacy against natural infections by wildtype viruses, hence the second statement by the authors that "the true efficacy of TV003 can only be established by performing a phase 3 trial in endemic areas." > it doesn't seem like Wired has editorialized/misrepresented at least the headline much relative to the original article I believe the inclusion of "in a human challenge model" in the original title is quite significant to its interpretation, but it's precisely the kind of detail that would get overlooked by people unfamiliar with vaccine trials. A researcher in the field would know that human challenge models may or may not be representative of protection against natural infections, but the Wired title ignores that distinction and instead sows confusion by saying the vaccine simply "proves 100% effective". > millions/year You're right, I meant hospitalizations; sorry about that. Dengue hemorrhagic fever is a life-threatening condition that warrants hospitalization, and dengue fever in more vulnerable patients also can result in hospitalization.
protomyth 11y ago
So, we know people get Dengue fever and what it does to people. Why do you still need the placebo group in a study like this? I'm having a hard time seeing the morality of such a choice when we already have plenty of data on Dengue fever.
- bobbles 11y ago
  "The purpose of the placebo group is to account for the placebo effect, that is, effects from treatment that do not depend on the treatment itself" https://en.wikipedia.org/wiki/Placebo-controlled_study https://en.wikipedia.org/wiki/Placebo-controlled_study
  - protomyth 11y ago
    Yeah, I know the purpose, but I'm really still having a tough time seeing any actual justification when we know how bad a diseases is. I cannot think of a reason it is worth it. I worked in clinical trials briefly (9 months) and still think its a level of cruel that borders on inhuman. "I'm sorry, we know the disease / condition kills, but we gave your loved one sugar pills".
    - ekianjo 11y ago
      The dengue fever does not kill most of the time. It makes you paralyzed with high fever for one to two weeks, but usually it does not kill you, unless you are already old and weak. I'm pretty sure that the recruitment for the clinical trial can ensure that only healthy people with appropriate constitution would not die from dengue fever.
      - protomyth 11y ago
        Don't we actually have enough data on the dengue fever to tell exactly what will happen to the control group? I don't think this is an actual unknown anymore.
        11y ago
imjk 11y ago
Wow this is great news. I was the type of person to not even give thought to these types of diseases, thinking they only applied to poorer populations in less-developed nations. When I went to a destination wedding in Jamaica two years ago, I laughed at all my friends who I thought were being excessively paranoid in constantly applying bug spray for fear of mosquito born viruses. You can imagine what happened next: I was infected with one of those viruses - Chikungunya more specifically - and it was one of the worst year and a half experiences of my life. I've just recently completely gotten over it, but man has the experience changed my outlook on these kids of things.
- ghaff 11y ago
  I caught Dengue in Bali a couple years ago. In retrospect I wasn't as careful about mosquitos as I should have been because I hadn't really noticed any. Fortunately it was "mild" in that I "only" spiked a 104 degree or so fever and was out flat for a week. (And had my doctor send me to the ER after I got some blood work done.) I was OK after a few weeks but now I'm rather paranoid about the (increasing) number of places where the disease can happen. I do like to travel and I'd really like to be able to get a vaccine (although I expect it will be a while) given the risk of re-exposure to a different variety.
  - tjbiddle 11y ago
    I've been living in Bali for the past year; the past couple months I've had multiple friends come down with Dengue - It's not fun!
randomdrake 11y ago
It's hard to understand what it's like to live in fear of mosquitos. Having lived in tropical areas where this is prevalent, and having suffered from dengue, this is incredible news. The people who are most affected by this are those who don't have resources to repel these tiny, common insects. They also don't have resources to properly treat this incredibly agonizing, and sometimes fatal, disease. Lasers, sprays, genetics, and everything else under the sun has been proposed to control mosquitos. Something that controls the thing they spread, which causes so much suffering, is much more exciting.
- bitwize 11y ago
  Mosquitoes spread so many nasty things -- starting with dengue and malaria -- that controlling the insects themselves is a worthwhile endeavor also.
erkkie 11y ago
It's worth to note this is one of a couple of promising vaccines, one of them is already approved in a couple of countries, as of December 2015: https://en.wikipedia.org/wiki/Dengue_vaccine#CYD https://en.wikipedia.org/wiki/Dengue_vaccine#CYD . Not "100% efficient" but nothing really is, nor is that really needed, it's not a boolean thing but a continuum and having any kind of antibody response is better than none; it reduces the chances of more severe disease at least, if not prevent disease all-together.
nonbel 11y ago
Whats with Figure 1? It looks like they didn't remove/replace template text: Lost to follow up (give reasons)... Discontinued intervention (give reasons) Is this normal or does it indicate a problem with the peer review at this journal?
bitwize 11y ago
Wow, that's "screw the control group, give everyone the treatment because it would be inhumane not to" levels of efficacy.

120 points by runesoerensen 11y ago

YEAHHHHHH BOIIIIIIIIII

ghaff 11y ago

Seems like a big deal. Dengue is different (and more problematic) than a lot of diseases in that if you've had Dengue even mildly or at least not severely, you're actually far more at risk for serious effects the next time if it's a different one of the four varieties of the disease. The article suggests that the trials so far protect against that effect as well. [EDIT: As pak notes elsewhere, this trial apparently didn't test against all four varieties although there was some evidence it might protect against multiple.]

pak 11y ago

While I am of course a huge fan of NIAID and vaccine development against dengue, and I believe that a vaccine that works against dengue will probably be found within our lifetimes and prevent millions of hospitalizations (EDIT: not deaths, sorry) per year, this is a classic example of a downstream news report editorializing the headline and misrepresenting the implications of the original article. The whole challenge in creating a dengue vaccine is that it has to protect against all four serotypes (called a tetravalent vaccine). Incomplete protection against one of the serotypes could potentially lead to an even worse infection if you are infected, through a process called antibody dependent enhancement: https://en.wikipedia.org/wiki/Antibody-dependent_enhancement https://en.wikipedia.org/wiki/Antibody-dependent_enhancement This is why vaccine development against dengue has been so painstakingly slow. The candidates in this trial were only challenged with one serotype, DENV-2. Therefore, we have no way to know if the tetravalence of the vaccine actually achieved efficacy against all four serotypes (although promisingly, antibodies against all serotypes were seen in 92% of the patients). The sample size is also quite small (N = ~20). This is why the original article states its impact conservatively as "This model may serve as an early check for dengue vaccine candidates, limiting the risk of conducting large unsuccessful trials" and furthermore "the true efficacy of TV003 can only be established by performing a phase 3 trial in endemic areas." Here's how you write a more honest headline and summary for lay people: http://www.cnn.com/2016/03/16/health/dengue-vaccine-effective/index.html http://www.cnn.com/2016/03/16/health/dengue-vaccine-effectiv... I don't intend to detract from the achievement here, but I don't like when headlines oversimplify the implications of a clinical trial. It sets unrealistic expectations and decreases the public's trust in proper vaccine research. Disclaimer: I am doing research with a lab that studies dengue virus, and we have collaborators that are working on a commercial vaccine.

ekianjo 11y ago
> vaccine that works against dengue will probably be found within our lifetimes and prevent millions of deaths Are you sure about "millions of deaths" ? Dengue fever fatality rate is lower than 1%. I'm not saying this is not a grave disease, but it's hardly something that kills as much as many other viruses out there.
- pak 11y ago
  You're right, I meant hospitalizations; I goofed.
runesoerensen 11y ago
> This is why the original article states its impact conservatively as "This model may serve as an early check for dengue vaccine candidates, limiting the risk of conducting large unsuccessful trials" You're obviously much more familiar with this subject, but doesn't the quote from the original article refer to the testing model itself (i.e. "dengue human challenge model"), rather than the efficacy of the actual vaccine? > this is a classic example of a downstream news report editorializing the headline and misrepresenting the implications of the original article. To be fair, it doesn't seem like Wired has editorialized/misrepresented at least the headline much relative to the original article ("The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model" vs "Dengue fever vaccine proves 100% effective in human trials"). > I believe that a vaccine that works against dengue will probably be found within our lifetimes and prevent millions of deaths per year I tried finding estimates of infections and deaths per year, but didn't find any that are close to millions/year. Do you have a source for that? The closest I got was from the CDC/WHO: The World Health Organization (WHO) estimates that 50 to 100 million infections occur yearly, including 500,000 DHF cases and 22,000 deaths, mostly among children. [0] [0] http://www.cdc.gov/dengue/epidemiology/ http://www.cdc.gov/dengue/epidemiology/
- pak 11y ago
  > doesn't the quote from the original article refer to the testing model itself Yes, it does, precisely because the trial is about a human challenge model that uses an attenuated virus. It may or may not be representative of efficacy against natural infections by wildtype viruses, hence the second statement by the authors that "the true efficacy of TV003 can only be established by performing a phase 3 trial in endemic areas." > it doesn't seem like Wired has editorialized/misrepresented at least the headline much relative to the original article I believe the inclusion of "in a human challenge model" in the original title is quite significant to its interpretation, but it's precisely the kind of detail that would get overlooked by people unfamiliar with vaccine trials. A researcher in the field would know that human challenge models may or may not be representative of protection against natural infections, but the Wired title ignores that distinction and instead sows confusion by saying the vaccine simply "proves 100% effective". > millions/year You're right, I meant hospitalizations; sorry about that. Dengue hemorrhagic fever is a life-threatening condition that warrants hospitalization, and dengue fever in more vulnerable patients also can result in hospitalization.

protomyth 11y ago

So, we know people get Dengue fever and what it does to people. Why do you still need the placebo group in a study like this? I'm having a hard time seeing the morality of such a choice when we already have plenty of data on Dengue fever.

bobbles 11y ago
"The purpose of the placebo group is to account for the placebo effect, that is, effects from treatment that do not depend on the treatment itself" https://en.wikipedia.org/wiki/Placebo-controlled_study https://en.wikipedia.org/wiki/Placebo-controlled_study
- protomyth 11y ago
  Yeah, I know the purpose, but I'm really still having a tough time seeing any actual justification when we know how bad a diseases is. I cannot think of a reason it is worth it. I worked in clinical trials briefly (9 months) and still think its a level of cruel that borders on inhuman. "I'm sorry, we know the disease / condition kills, but we gave your loved one sugar pills".
  - ekianjo 11y ago
    The dengue fever does not kill most of the time. It makes you paralyzed with high fever for one to two weeks, but usually it does not kill you, unless you are already old and weak. I'm pretty sure that the recruitment for the clinical trial can ensure that only healthy people with appropriate constitution would not die from dengue fever.
    - protomyth 11y ago
      Don't we actually have enough data on the dengue fever to tell exactly what will happen to the control group? I don't think this is an actual unknown anymore.
      - 11y ago

imjk 11y ago

Wow this is great news. I was the type of person to not even give thought to these types of diseases, thinking they only applied to poorer populations in less-developed nations. When I went to a destination wedding in Jamaica two years ago, I laughed at all my friends who I thought were being excessively paranoid in constantly applying bug spray for fear of mosquito born viruses. You can imagine what happened next: I was infected with one of those viruses - Chikungunya more specifically - and it was one of the worst year and a half experiences of my life. I've just recently completely gotten over it, but man has the experience changed my outlook on these kids of things.

ghaff 11y ago
I caught Dengue in Bali a couple years ago. In retrospect I wasn't as careful about mosquitos as I should have been because I hadn't really noticed any. Fortunately it was "mild" in that I "only" spiked a 104 degree or so fever and was out flat for a week. (And had my doctor send me to the ER after I got some blood work done.) I was OK after a few weeks but now I'm rather paranoid about the (increasing) number of places where the disease can happen. I do like to travel and I'd really like to be able to get a vaccine (although I expect it will be a while) given the risk of re-exposure to a different variety.
- tjbiddle 11y ago
  I've been living in Bali for the past year; the past couple months I've had multiple friends come down with Dengue - It's not fun!

randomdrake 11y ago

It's hard to understand what it's like to live in fear of mosquitos. Having lived in tropical areas where this is prevalent, and having suffered from dengue, this is incredible news. The people who are most affected by this are those who don't have resources to repel these tiny, common insects. They also don't have resources to properly treat this incredibly agonizing, and sometimes fatal, disease. Lasers, sprays, genetics, and everything else under the sun has been proposed to control mosquitos. Something that controls the thing they spread, which causes so much suffering, is much more exciting.

bitwize 11y ago
Mosquitoes spread so many nasty things -- starting with dengue and malaria -- that controlling the insects themselves is a worthwhile endeavor also.

erkkie 11y ago

It's worth to note this is one of a couple of promising vaccines, one of them is already approved in a couple of countries, as of December 2015: https://en.wikipedia.org/wiki/Dengue_vaccine#CYD https://en.wikipedia.org/wiki/Dengue_vaccine#CYD . Not "100% efficient" but nothing really is, nor is that really needed, it's not a boolean thing but a continuum and having any kind of antibody response is better than none; it reduces the chances of more severe disease at least, if not prevent disease all-together.

nonbel 11y ago

Whats with Figure 1? It looks like they didn't remove/replace template text: Lost to follow up (give reasons)... Discontinued intervention (give reasons) Is this normal or does it indicate a problem with the peer review at this journal?

bitwize 11y ago

Wow, that's "screw the control group, give everyone the treatment because it would be inhumane not to" levels of efficacy.