
Dengue fever vaccine proves 100% effective in human trials - runesoerensen
http://www.wired.co.uk/news/archive/2016-03/17/dengue-vaccine-human-trial-complete-protection
======
pak
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-effectiv...](http://www.cnn.com/2016/03/16/health/dengue-vaccine-
effective/index.html)

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.

~~~
runesoerensen
> 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
> 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.

~~~
runesoerensen
Alright thanks for clarifying!

------
ghaff
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.]

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

------
erkkie
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.

------
protomyth
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
"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
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".

~~~
wbl
"I'm sorry, we gave your loved one a treatment that's actually harmful,
because we didn't compare to the right group".

~~~
protomyth
They were doing a study and were going to give it out. I just don't believe
that we don't already have the dataset of the control group.

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

