
We now have an effective vaccine for Malaria - sethbannon
http://www.reuters.com/article/2011/10/18/us-malaria-vaccine-scientist-idUSTRE79H59220111018
======
carbocation
This was a Phase 3 clinical trial published today in the New England Journal
of Medicine: <http://www.nejm.org/doi/full/10.1056/NEJMoa1102287>

Not home yet or I'd likely have more to say.

 _Home now. Reading the article. First thoughts:_

* This is a vaccine for P. falciparum, which is the nasty form that you really don't want. Good.

* Funding comes from GSK and the Bill and Melinda Gates Foundation

* These are interim results, looking at the older kids (5mo and up) in a 2-prong study (the younger kids haven't all hit the 12mo-duration milestone needed per protocol so this largely ignores them so far with more to come later). Caution. (Because there was no clear rationale given for why this is being reported now, in pieces.)

* Treated kids had higher incidence of meningitis. Caution.

* Treated kids had higher risk of febrile seizures. Caution.

* Generally, few deaths, so these kids seem to be well looked-after in this trial. Appropriate.

So far, so good. Interested to see the final Phase 3 results and to see how
this holds up in Phase 4/postmarketing.

~~~
Thrymr
From my reading of the results, efficacy is only 35-55%. Does that seem low?
Or is that good at this stage of a trial?

~~~
carbocation
Phase 3 is basically the definitive clinical trial. Phase 4 is essentially
keeping track of what happens after your drug comes onto market. Once all of
the results are in, that paper will likely become the definitive paper on this
particular drug (again, it's a bit weird that they did this prelim analysis
without a clearly stated reason). So Phase 3 is the real deal in terms of
winning approval to market the drug.

Regarding efficacy, it is definitely low compared to many modern vaccines
which are in the 90+ range. But my understanding is that this is much higher
than previous malaria vaccines. If the numbers are really true, then they
could possibly save hundreds of thousands of lives per year despite the
relatively low efficacy. And it should be a first foothold in terms of making
immunologic progress against Plasmodium.

------
keecham
As someone who worked in the development world for a year, I can honestly say
that if this vaccine pans out, it would be the biggest development in recent
history and would change the livelihoods of so many individuals and families.

If this doesn't deserve a Nobel I'm not sure what does. Bravo Joe Cohen.

~~~
seven_stones
The real trick is that the existing cultures themselves will have to quickly
reconfigure so that this doesn't simply shift the problem laterally.

For example, initiatives to dig wells in various African countries have turned
out to result in _other_ problems. Some nomadic cultures began staying put,
and then they started overusing all the _other_ resources. The scarcity of
water was a control in itself, limiting how long groups stayed in a given
area. Removal of that control has led to desertification of areas surrounding
the wells. And it also brought disparate groups into contact with each other
for longer periods of time, which led to more disease outbreaks. Nomadic
groups had fewer and briefer encounters with others before, limiting the
spread of disease from one group to another.

Another example is the grave humanitarian crisis in Somalia. Hundreds of
thousands of people are expected to starve to death in the next few months.
Due to raging conflicts, humanitarian aid cannot be effectively distributed.

However, even if the crisis could temporarily be averted, the problem with
food aid is it undermines any possibility of local production. Farmers can't
compete with free food dumped on the market, so they stop farming. Not being
self-sufficient, now you're looking at not only providing aid, but _ever-
increasing_ aid as the population grows, which means if you stop for any
reason -- including civil war flaring up again -- now even _more_ people die:
the ones you saved, and the children they have had in the interim.

See
[http://www.spiegel.de/international/spiegel/0,1518,363663,00...](http://www.spiegel.de/international/spiegel/0,1518,363663,00.html)

Cultures with high child mortality compensate by having high numbers of
children. Once you get rid of the main causes of child mortality, you have to
either stop having so many kids, or dramatically increase food production.
Otherwise curing Malaria can result later in all the problems that accompany a
lack of resources: _bigger_ famines, _increased_ civil strife and warfare.

~~~
masklinn
> Once you get rid of the main causes of child mortality, you have to either
> stop having so many kids, or dramatically increase food production.
> Otherwise curing Malaria can result later in all the problems that accompany
> a lack of resources: bigger famines, increased civil strife and warfare.

Much as what happened in Europe, this tends to self-regulate over a few
generations: high natality is a requirement in high-death and low-income
situations, where you need many children to have some survive (and help you in
old age), and children are hands that can work and provide wealth.

As mortality decreases you need less children as they'll pretty much all
survive, and as wealth increases you _want_ less children because raising them
to your society's standards gets more expensive and there's a much bigger
investment in each child.

Of course there will be 2-3 generations with high natality and low mortality,
and an explosion of younger generations (likely leading to a few revolutions).
But there's little you can do about that in the short term.

~~~
hessenwolf
Yes - see Germany, Italy, Singapore and Japan for high life expectancy and low
birth rate. Interestingly, children also become less affordable, as opposed to
just less financially necessary.

~~~
masklinn
Yep, noted that at the end of the second paragraph (might not have been clear
enough)

~~~
hessenwolf
Oh, no, you were really clear. I just did not read that paragraph. Oops...

------
Sniffnoy
So can anyone explain just why malaria was so hard to vaccinate against by
existing methods in the first place?

~~~
teej
There's a lot of complexity here I'm going to attempt to simplify. Apologies
in advance if I glossed over any important details.

It all starts with what Malaria has evolved to do. The lifecycle of malaria
requires both a mosquito and a human. It gets into a female mosquito, hangs
out in her gut until she bites a human, jumps into the human and hangs out
there for a while mucking about, and then jumps back to a different mosquito.

If malaria straight-up killed its host, it wouldn't transmit itself on to the
next one. This means malaria must be really good at two things: keeping its
host walking around and going undetected for as long as possible. It has lots
of tricks it uses to stay under the radar. This all makes sense because the
longer it can stay in the host, the more likely it'll get picked up by
something else. Think of malaria like a spy that's infiltrated your
population. You know one of your civilians is killing the others, but you
can't figure out who.

It's also important to know HOW vaccinations work. There are four golden
strategies used today:

\- Put a dead bugger in the body.

\- Put a neutered bugger in the body.

\- Put the bugger's coat (a virus-like particle) in the body.

\- Put the bugger's perfume (a protein marker) in the body.

All four of these strategies work the same way. Your body recognizes an
intruder and teaches itself how to eliminate the threat.

We've established that malaria is good at going undetected. This renders the
first two strategies ineffective. Even if we did introduce dead/neutered
malaria into the body, the body will still have a hard time finding it when
real Malaria enters the system.

We can't use the third strategy because Malaria isn't a virus. That leaves us
with only one option: a perfume (subunit) vaccine.

A subunit vaccine is a vaccine where you take the perfume of a bugger and give
it to the body saying "Anything that smells like this, you should probably
deal with". These are difficult vaccines to put together. Proteins, like
perfume, are a carefully constructed thing and are hard to perfectly
replicate. Plus, given their complex nature, the body can get confused and
build ineffective defenses since it's only given a protein to work with.

On top of all this, the malaria bugger goes through three different stages of
its life while in the human body. If you target it late stage, you'll prevent
further transmission but the human could still die. You want to target it
early stage, preventing transmission AND protecting the human from symptoms.
Unfortunately, your body only has 5 minutes from being bitten to to find the
bugger and kick its ass before he effectively vanishes from sight.

So where does that leave us? We have a spy entering our country. We are
already doing everything we can to destroy his transit before he enters our
borders (spraying with DEET to kill mosquitos). We need to catch him before he
masquerades as a citizen, otherwise we will never find him. So our only option
is to look for signs of a spy and ruthlessly eliminate anything that fits the
bill.

That's what RTS,S/AS01 does. In the 80s we were able to produce a protein from
the malaria sporozoite (the first stage inside the human body) to get a small
level of immunity in humans. The problem since then has been ramping up the
immune response. The body needs to act fast (within 5 minutes of being
infected) and with extreme prejudice (wiping out the sporozoites) off of very
little training (a single sporozoite protein). Vetting this vaccination is
also tricky, since it requires human field testing in Africa.

In other words, this vaccine is the culmination of 50 years of dedication,
research, and hard work. It's also a miracle of modern science. Most
importantly, it will save a LOT of human lives.

~~~
todsul
Many thanks for the explanation. You sound like a teacher; I feel like I've
really learned something this morning.

Quick question: is there an issue with resistance when it comes to
vaccinations? I understand the problem with creating better combative
medicines is working out how to attack the critters before they produce
resistance. Either way, it sounds like a profound breakthrough for affected
countries.

~~~
toyg
Most diseases on the same scale as malaria were effectively wiped out by
vaccination, because social pressure to get rid of them was tremendously high.
The same would probably apply with malaria: vaccination programs would be so
immediate and massive to give it very little chance of mutating quick enough
to maintain the current (massive) level of infection. Even a reduction of 70
or 80% would make an incredible difference.

The only real problem will be price. GSK will want a lot of money, and most
malaria-affected countries are poor. Chances are that the "developed world"
will have to step in and sponsor vaccination programs to the tune of billions,
making (mostly African and South-Asian) countries even more dependent on them
that they are now. Some of them had just managed to get rid of old debts, and
now they'll have to make new ones. I expect the debate on pharmaceutical
patents will flare up again.

But it'll all be worth it.

------
jfb
I'd like to recommend (without endorsing the opinions therein) this contrarian
article I read about malaria, poverty, and Western attitudes towards Africa:

<http://www.guernicamag.com/features/2273/pogue_1_15_11>

I found it fascinating, as someone with the intent of (eventually) studying
disease ecology, in particular, that of malaria in West Africa. It's a
thoughtful and well argued essay, but not in the end entirely convincing to
me. But it deserves to be more widely distributed, I think.

PS: Thanks to Instapaper, which made retrieving this article a matter of
seconds. Interesting how one's expectations of the rate of information
retrieval have evolved, speaking as a 40-yr old who well remembers waiting
around weeks at times for books or journals to be delivered to the Reg.

~~~
ianb
I think there's something very patronizing and morally inconsistent about the
kind of argument that is described in that article. Underlying its argument is
a belief that the lives of all the people who die aren't important, that these
deaths are somehow the proper and natural balance. In some ways it may echo
the cultures themselves; when life is precarious and lost for no outward
reason (such as by a disease like malaria) then individual life loses some of
its meaning, people value not only each other but even themselves less.

Medically there's a tone of what-doesn't-kill-you-makes-you-stronger, which is
kind of bullshit. Malaria might not kill native adults very often, but it is
not harmless.

And economically, the argument is similarly patronizing. After going on about
the native immunity many people have, it then talks about how economic
disruption is causing migrations, leading to people (not just whites) who
don't have the immunity to be exposed. The response: people should stay in
their place. That the prerequisite for solving any problem is to revert to
traditional structures and strengthen those structures (the same basic
argument is made about poverty and many other African problems). The idea that
Africans may in fact wish to have control of their own personal destiny is
disregarded -- that if conditions were better, if economic forces were less
manipulative, people might _still_ want to migrate, because the drive to
better one's life persists even when life is okay.

~~~
jfb
I don't disagree. But I think the correlation between urbanization and malaria
is one that would be very interesting to analyze, particularly where rural
people are primarily cattle herders (and as such have beef for the _Anopheles_
to feed on).

------
dkasper
Amazing dedication to work on something for 24 years.

~~~
hugh3
Plenty of people working on projects far less interesting and far, far, far
less worthwhile than this for 24 years.

~~~
jQueryIsAwesome
Repetitive mundane task surely can be called "dedication"...

But in medical research have to try new things, adquire new knowledge,
evaluate that new knowledge with all your previous researchs and don't quit
your objective despite of failing for years... so yeah, i think the parent
comment was talking about _that_ kind of dedication.

EDIT: missing word

------
evjan
As somebody who lives in Africa (Ghana), I cannot overstate how important this
could be. I hate malaria on so many levels.

Poor people die from it all the time. Wealthier people mistake it for a cold
and die. It is also about as common as a cold here, so a lot of productivity
is lost. Not to mention the huge amounts of money being spent on health care.

It is not a coincidence that the worst hit countries are the poorest, people
can't afford treatment and the costs for the societies might actually keep
many African countries in poverty.

Not to mention how inconvenient it is to not be able to sit outdoors at night,
making sure your house is sealed off and spraying with poisonous insect
repellants all the time.

------
ajays
This is fantastic news. However, the vaccine won't be in production and
available till 2015. Nearly 1 million people die every year from it; which
means, about 1.5 million lives could be saved if the vaccine were in
production today. I know it can't happen overnight, but still: 4 years?

~~~
sethbannon
Not as much profit in this as in little blue pills, so it simply won't be a
priority for big pharma, unfortunately.

~~~
cjy
Really? I'm bet it has to do with further testing. You could give a little bit
of credit to GlaxoSmithKline for working on this for 24 years. This isn't
exactly a good example of "big pharma" greed.

~~~
JVirissimo
If it was indeed made by GlaxoSmithKline, then this is a good example of "big
pharma" greed. Only, in this case, "big pharma" greed might end up saving
millions of lives.

~~~
0x12
That all depends on the price. If the price is reasonable then fine. But
typically big pharma that gets a lock-in on 'life' is anything but reasonable
in their pricing, after all, what's the value of a human life.

The 5% profits over costs is promising, even if it leaves some wiggle room.

------
grannyg00se
I was actually surprised to see no mention of Bill Gates or his foundation.

~~~
rbanffy
They have supported the PATH MVI, but I am not sure how much money they
invested on this compared to what GSK did in the past 24 years.

------
jroseattle
As I get older, I think more and more about my work being impactful on the
lives of others. Not higher performance, better UI, greater convenience or
less cost; rather, something that positively improves the lives of others.

That is really cool for Joe Cohen. Way to go.

------
sciurus
While this vaccine is an important development, there's still a _lot_ of work
to be done. If you'd like to develop free, publicly available tools that help
researchers improve treatments for malaria and other parasites, send a resume
to jobs AT apidb DOT org. We need not only people with bioinformatics
backgrounds but also web developers to help us improve resources like the
malaria genome database, <http://plasmodb.org/>

~~~
jfb
I'm a programmer with an extreme interest in disease ecology (in particular,
that of malaria). Please email me at my profile address and let me know if
there's anything I can do to help.

------
ck2
No, in 2015 they'll have a vaccine.

And they are only taking 5% profit over "costs" which sounds promising.

------
yaix
This could have adverse effects, similar to medication agains HIV/AIDS. People
will get a vaccine and reduce their efforts of protection against Malaria by
mosquito nets and other means. I hope that will not happen.

~~~
mousa
I doubt people will back off of malaria at this point in the past it seems
like once it starts getting under control in a region it keeps going down.
There is a lot of anti-malaria momentum building up with awareness and malaria
education only increasing.

The last few years have been success after success with the Global Fund and
the Gates Foundation pouring in money.

------
mattangriffel
I hope that the discovery of vaccines like this increase in frequency over
time. I'm not sure if that IS the case, but I'd really like it to be so that
one day soon AIDS and Cancer are as benign as Polio.

~~~
sliverstorm
Small note: cancer is not a disease, so it cannot be _vaccinated_ against

~~~
ars
I think you need to clarify that sentence.

Do you mean cancer isn't caused by a pathogen? Because that isn't true for
some cancers, and there are suggestions that all cancers are caused by
viruses.

And cancer vaccines do exist, but they need to be individually created for
each case.

~~~
hugh3
Are there any examples of cancers caused by viruses apart from HPV?

Certainly it can't be true that _all_ cancers are caused by viruses, can it?
For instance, some cancers are caused by radiation.

~~~
ars
There are plenty of examples: <http://en.wikipedia.org/wiki/Oncovirus> and
<http://en.wikipedia.org/wiki/HHV-8>

I guess not all are caused, but perhaps I can rephrase as all can be caused?
It's only suggestions that this is the case, but it's not actually known yet.
I certainly don't know.

This: <http://en.wikipedia.org/wiki/Cancer_Virus#Viral> says that 12% of
cancers are caused by viruses. The true number may be a lot higher since more
viruses are being discovered all the time. But even 12% is a lot if someone
were able to make a vaccine for them.

------
alttag
It sounds like this vaccine should be combined with some of the mosquito
eradication methods highlighted in a recent HN link [1]. One commenter there
("Ox12") pointed to an article in Nature which argues the reduction in
mosquito population would likely not be problematic.

1: <http://news.ycombinator.com/item?id=3043065> 2:
<http://www.nature.com/news/2010/100721/full/466432a.html>

------
dfriedmn
Hard to believe, but hope this turns out to be true. Would represent
meaningful progress for the world.

~~~
sethbannon
Agreed. Clinical trials look very promising!

------
Volpe
effective at reducing malaria incidence by 50%...

Is that what we are calling 'effective vaccine'?

It's a major achievement, but if this is 'effective vaccine' then we already
have an 'effective cure' to a number of cancers as well. A bit link baity.

~~~
zmanian
The thing to remember about malaria is that is an infectious disease.

In order to have a malaria epidemic, Alice needs to be bitten by a malaria
carrying mosquito. Alice needs to become ill and have a large number of
juvenile parasites in her blood. She then needs to be bitten by another
mosquito. This parasites becomes adults in the mosquito's gut and the mosquito
then needs to bite Bob and infect him.

A vaccine that reduces the chances of an infected individual becoming ill
effectively reduces the reproduction rate of malaria.

In a vaccinated area, one would expect to see reductions in the number of
infected people during the high season by potentially an order of magnitude.

~~~
wisty
Malaria can survive in cattle, not just humans. Mosquitoes bite infected cows
(which don't necessarily have symptoms), then bite humans. It's not like most
infections diseases, which can be entirely eradicated just by vaccinating a
critical number of people.

~~~
jfb
This is one of the reasons that malaria incidence goes down as the number of
cattle being raised goes up. _Anopheles_ is happy to take a blood meal from a
beef rather than a human.

~~~
FrojoS
Do you have a source for this? I find this weird. Wouldn't more food for
Anopheles increase their population and hence the risk for humans to get
bitten?

~~~
mekoka
It's been observed that the anophele does prefer cattle. I just dug this
though <http://www.malariajournal.com/content/6/1/100>

------
dpollak2020
made me happy.

------
chernevik
It sounds great but I don't think Africa needs an autism epidemic right now.

~~~
chernevik
Attention Humor-Impaired Downvoters:

This is a sarcastic reference to anti-measles vaccine activists.

That is all.

~~~
burgerbrain
We got it. It's just not funny.

~~~
chernevik
There's no arguing about taste.

But I seriously don't want anyone imagining I think vaccines cause autism.

------
aidenn0
Now we just need there to be a vaccine scare in africa so that malaria mutates
and the vaccine is ineffective again

------
dewiz
Vaccine have dangers (not just risks), I can't welcome this news, I only see a
new "product". I would be much happier if a cure was found.

<http://vran.org> <http://educate-yourself.org>

------
aymeric
I saw this article and I thought: less people who die = more people on the
planet.

Isn't overpopulation the biggest challenge we are facing right now?

Who is working on this problem?

(if someone I care about was ill from Malaria, I would be happy to be able to
cure that person, but my belief about overpopulation remains)

~~~
Spyro7
Overpopulation is a hard problem. There are complex socioeconomic reasons for
why some countries have higher fertility rates than others. This is a heavily
studied topic in health economics, but I am unwell right now and do not feel
like digging through research papers. Instead, I will point you to a wikipedia
article that talks about one (popular with economists) take on overpopulation:

<http://en.wikipedia.org/wiki/Demographic_transition>

Sorry for the wikipedia link, but it is not a half bad article on the subject
and it was easy to find. Basically, this theory suggests that increased income
per capita is correlated with a decrease in a country's fertility rate.

There are arguments on both sides regarding the flow of causality, but if you
wanted to know what was being done to address the challenge of overpopulation
then that article above is a good starting point for your own inquiries.

(Also, just as a side note, it is probably the case that you were down-voted
for being off-topic and not due to some overwhelming sentimentality. Maybe if
you want to talk about overpopulation you should have written a blog post and
posted it up, I bet that would have probably got a much better reception.)

~~~
wisty
You can subtract death rate from birth rate, and the world looks screwed. For
China, this is (13.1 - 7.1) per 1000. For India, it's (21.76 - 6.23) per 1000.
So for the world's middle class, that's about 2% population growth per year.
Yikes.

But the you realize, that China and India have very few really old people. Now
that they have decent medical treatment, the older Chinese and Indians live
longer, pushing the population up. But they aren't having any babies, so in
the long term we might not be growing like lemmings.

So you look at the fertility rate:

[http://en.wikipedia.org/wiki/List_of_countries_and_territori...](http://en.wikipedia.org/wiki/List_of_countries_and_territories_by_fertility_rate)

For China, it's 1.54, and it's 2.6 for India. Anything under 2 (plus a bit for
the ones who don't reach fertility) means a declining population, in the long
term.

~~~
nknight
And then you leap from the frying pan into the fire: Too many old people
relative to the number of young people.

As far as I can tell, "health" isn't keeping up with "life", so we _are_
screwed, just the other way around.

But now we also have to divine the state of robotics and AI, say 100 years
out, and my brain begins to strangle itself.

