Conceptually, vaccines are very simple things– Dummy viruses/bacteria/pathogen that train your immune system how to fight the real viruses/bacteria/pathogen. All the benefits of being sick (training your B- and/or T-cells how to fight the pathogen) without actually having to get sick.

Nice.

In practice, however, things are infinitely more difficult. Sometimes we use dead viruses. Sometimes we use crippled viruses. Sometimes we dont need to use whole viruses at all– little chunks of the virus are fine. Sometimes we just need chunks of the virus, but we keep them dressed up in hollow membranes.

We have no idea what will work on the front end.

And sometimes none of the approaches that worked for other pathogens, works for the new target. HIV-1 is a prime example. TB is another. And, so is malaria.

The WHO estimates that malaria infects 225 million, and kills 781,000 people each year. 92% of those who die of malaria are African children. To put this number in perspective, in 2009 malaria killed more African children than heart disease killed US adults. What if someone suddenly discovered a way to decrease the burden of heart disease by half? Well, today we hear of an intervention that has the potential to achieve a feat of a similar scale in Africa: a malaria vaccine.

Ideally, we want a vaccine like HPV, which is virtually 100% effective at stopping HPV cervical cancers. But we are to the point in HIV-1, TB, malaria (Im sure some Im forgetting) where we will totally take 50% efficacy. Hell, 30% would be a win. Because when you are dealing with millions of infections and in the case of malaria, ~800K deaths, 50% is a lot of suffering averted. A lot of saved lives.

So scientists are rightly pumped about the results of a recent malarial vaccine trial in African kids (the ones most likely to die from malarial infections):

During 12 months of follow-up in the first 6000 children in the older age category, the incidence of the first or only episode of clinical malaria meeting the primary case definition was 0.44 per person-year in the RTS,S/AS01 group and 0.83 per person-year in the control group, resulting in a vaccine efficacy of 55.8% (97.5% confidence interval [CI], 50.6 to 60.4).

Evaluation of the proportionality of the hazard assumption showed that vaccine efficacy was not constant over time (P<0.001 by Schoenfeld residuals) (Table 9 in the Supplementary Appendix), with vaccine efficacy higher at the beginning than at the end of the follow-up period.

At least one episode of severe malaria that met the primary case definition occurred in 57 of 2830 children (2.0%) in the RTS,S/AS01 group and in 56 of 1466 children (3.8%) in the control group, for a vaccine efficacy of 47.3% (95% CI, 22.4 to 64.2).

Vaccine efficacy against severe malaria in the pooled age categories was 34.8% (95% CI, 16.2 to 49.2).

In the older age category, serious adverse events were reported in 1048 of 5949 children (17.6%; 95% CI, 16.7 to 18.6) in the RTS,S/AS01 group and in 642 of 2974 children (21.6%; 95% CI, 20.1 to 23.1) in the control group (Table 3Table 3Serious Adverse Events after the First Dose of a Study Vaccine in the Intention-to-Treat Population, According to Age Category.).

Similar proportions of children died in each study group.

At least one serious adverse event that was considered to be related to a study vaccine occurred in 11 children in the older age category: 10 of 5949 children in the RTS,S/AS01 group reported 12 events (7 seizures, 3 episodes of pyrexia, 1 episode of myositis, and 1 injection-site reaction) and 1 of 2974 children in the control group reported 1 event (seizure).

Summary– So far, this vaccine works the best we have ever seen of any malaria vaccine. Even though both study and control groups had similar bed-net use, the number of kids who got malaria in the malaria vaccine group (the older kids, who were enrolled first, thus their data is available now) was less than half of what was seen in the control group.

Drawbacks– The protection waned with time, and seizures might be a side-effect in a small percentage of kids.

If this is literally the best we can do, I wouldnt turn my nose up at this vaccine if I had a baby somewhere where malaria was endemic. But I dont think this vaccine is the best we can do– its a really great starting off point. From this vaccine, we can explore how to make it better. Make it 100%, like HPV.

Good on you, malaria folks. I really hope this works out.

Comments

  1. #1 cthellis
    October 19, 2011

    But… won’t this just cause MORE incidents of autism? Or–even worse–MALARIAL autism! WON’T SOMEBODY THING OF THE CHILDRANS??!

  2. #2 Perplexed
    October 19, 2011

    To be fair there is a TB vaccine and overall it probably manages around 50% efficacy. It’s just a pity that the 50% hides a lot of variation, wherein it works moderately well in Europe and quite badly in more equatorial regions. Obviously a better one would be great for Africa and in terms of overall human benefit, if only research was based on what humanity needed rather than what could be sold to the wealthy nations.

  3. #3 Spence
    October 19, 2011

    Great news that they are making progress on malaria. It takes a terrible toll on some of the poorest parts of the world. Of course there is the non-trivial challenge of organising (and funding) an effective roll out in places where health care infrastructure is almost non-existent.

    Also: I see what you did there :D

  4. #4 mo (one of Abbies's elk)
    October 19, 2011

    Vaccines against eukaryotes? WTF!!!!!!!

  5. #5 boyshealth
    October 19, 2011

    yes it may be something quite important, the vaccine could save many lives. . I am also concerned about the state of small children are exposed to malaria. .

  6. #6 Epinephrine
    October 20, 2011

    Absolutely, 50% is much better than nothing.

    @mo – yup, vaccines against eukaryotes. We’re also seeing vaccines against small molecules (NicVax is one such attempt, though the recent clinical trial data is diappointing), there is work on vaccines against prion diseases (Chronic Wasting Disease in deer is a first target), and other vaccines for misfolded proteins (e.g., vaccine for Amyotrophic Lateral Sclerosis). Very exciting times.

  7. #7 Poodle Stomper
    October 20, 2011

    I’m not allowed to think about the HPV vaccine. Michele Bachmann sez they’re ebil!

  8. #8 Justicar
    October 20, 2011

    This is over my pay grade, but I hope it’s a promising ‘starting’ place for more work on this line.

  9. #9 Schenck
    October 20, 2011

    What’s really crazy is that a lot of people like to argue that “oh, malaria isn’t a big deal, its just a western preoccupation with ‘clearing out the swamps’. For some people work on a malaria vaccine is seen almost like a “neo-imperial” agenda.
    Glad to see progress being made. Worth pointing out that malaria isn’t caused by a virus, but by /Plasmodium/ nematodes, crafty little buggers that they are. They’re effective at avoiding detection.

  10. #10 Levi
    October 20, 2011

    Epinephrine @6 states:
    “there is work on vaccines against prion diseases (Chronic Wasting Disease in deer is a first target), and other vaccines for misfolded proteins (e.g., vaccine for Amyotrophic Lateral Sclerosis). Very exciting times.”

    That sounds quite advanced. Do you have a link or pointer for a public source of information about this research?

  11. #11 msironen
    October 21, 2011

    Well, whatever else one might think about Bill Gates it seems to be mostly his moolah that made this happen:

    The vaccine, known as RTS,S and made by GlaxoSmithKline, has been in development for more than 25 years, initially for the American military and now with most of its support from the Bill and Melinda Gates Foundation.”
    - http://www.nytimes.com/2011/10/19/health/19malaria.html

  12. #12 Epinephrine
    October 21, 2011

    Levi @10
    Sure, there are some press releases concerning some of these efforts on the PREVENT website. There was a presentation on targeting disease specific epitopes related to abnormally folded proteins at the 9th Canadian Immunization Conference.
    http://prevent-cecr.ca/news.php
    http://news.usask.ca/2011/10/05/battling-chronic-wasting-disease-in-elk-and-deer

    All of this is in early stages and could fail, but it’s still exciting.

  13. #13 deetee
    October 23, 2011

    So there is a good chance this vaccine could halve the malaria incidence in kids who get it. That’s good, but there is still a way to go. However, the waning immunity is a concern. In malaria endemic regions, this will merely defer the time kids get malaria, and not avert it. That isn’t too problematic, because the mortality is highest in kids, so this will provide crucial protection for them – a bit like the pertussis story.

    But let’s take an antivax perspective on this one….
    “But look at the serious adverse event rate! 20%!!!”
    “All those kids getting seizures from the vaccine – don’t people know that will cause irreversible brain damage?”

    And once the malaria rates drop, there will be the inevitable:
    “You are more at risk from a vaccine side effect than you are from malaria – don’t touch it!”

    But they will be talking garbage as usual – the risk benefit is clearly favouring giving the vaccine in highly endemic areas. And vaccine trial reported “adverse events” are not side effects from the vaccine – they are any medical problem reported during the trial, whether thought to be due to the vaccine or not. The antivaxers never understand that. In fact the control groups had the same rate of medical problems. They tend to be things kids in Africa are prone to, like malnutrition and pneumonia (see table 3)