First Malaria vaccine expected to be approved by WHO
July 24, 2015 5:30 AM   Subscribe

Thanks, Big Pharma!

There were an estimated 627 000 malaria deaths worldwide in 2012 (uncertainty interval, 473 000–789 000).

Of the estimated deaths, most occur in sub-Saharan Africa (90%) and in children under 5 years of age (77%).

The good an affordable vaccine could do is almost impossible to comprehend.
posted by Drinky Die at 5:39 AM on July 24, 2015 [16 favorites]

posted by Going To Maine at 5:41 AM on July 24, 2015 [3 favorites]

The obvious immediate benefits are great (more than half a million dead every year, and many more ill.), but it's even bigger than that. Malaria helps to keep you poor.
posted by pracowity at 6:15 AM on July 24, 2015 [1 favorite]

Malaria researcher here, and I think it's important not to elide this part of the the Guardian article:
The latest results, published in the Lancet medical journal in April, showed that the vaccine works better in children from the age of five months than in younger babies. This means it cannot be added to the routine infant vaccination schedule. Another drawback is that it is a multi-dose vaccine, and its effect wanes over time so a booster shot is needed.
In the Lancet article cited in this news piece, they report a substantial loss to follow up among participants in the study. These are people who volunteered to take part, so might be assumed to be more interested than the average person, and they still lost contact with about 1/4 of their sample. It looks like 1/3 of the initial sample was either lost to follow up or had the vaccine administered in some off-protocol way. It is difficult to ensure children receive their standard childhood vaccines in the parts of Africa where malaria is most serious - that is, rural, poor areas. This is an off-schedule partially effective vaccine that requires multiple boosters for maximum efficacy. This is not a silver bullet.

While I welcome the introduction of an effective vaccine for malaria, this vaccine is not necessarily an unalloyed good. Even good patient education cannot fully get around the fact that this is a partially effective vaccine requiring multiple booster shots. This could have a couple of negative repercussions - not using other malaria prevention methods, mistrust of clinical medicine as their children develop malaria anyway, delays in identifying malaria cases because of vaccination status. Add to that effects of mass early childhood vaccination on the distribution of disease in a population - for example, we might be finding older kids getting more malaria than they used to, because they weren't adequately exposed to build up their adaptive immune response to malaria, which may or may not have serious clinical implications.

If you hang out with malaria researchers long enough, you will hear variations on the word 'complex.' There are complex interactions between ecology, economics, human behavior, mosquito behavior, the parasite's response to drugs and the human and mosquito immune systems, and so on.

The TLDR version is that this vaccine will probably save some lives, while almost certainly being less effective in regular use than in the studies and possibly having some adverse effects on other aspects of malaria control because malaria is complex and this vaccine is only partially effective. I am hopeful for the best outcome, while being aware of the challenges of malaria control even in a post-vaccine environment.
posted by palindromic at 6:36 AM on July 24, 2015 [94 favorites]

Palindromic--thanks for the substantial and objective input. Do you see any other promising developments re: managing malaria in the next 5 +/- years.
posted by rmhsinc at 6:47 AM on July 24, 2015 [1 favorite]

A couple of months ago, I randomly ended up on a shuttle bus to the Jasper Skytram with a biomed researcher who said he put his pro bono work into malaria research. I started babbling at him about how impossible malaria seemed to deal with - like the way it has a couple of dozen different surface proteins that it keeps swapping out as soon as the immune system recognizes them - and he said, "You should really look into the latest research, because there's been a huge amount of progress in just the last five years."

Sounds like this is the fruit of some of that research. Very exciting!
posted by clawsoon at 7:01 AM on July 24, 2015 [1 favorite]

palindromic, thank you. Does anyone know which varieties of malaria this vaccine is effective against? (If it is all, wow, given the fact that there are five different species that we're targeting here.)

Also, (this aimed at palindromic or other researchers) having recently read Sonia Shah's The Fever, could you say whether her statistics about the lack of proper use of distributed mosquito nets and the growing resistance of mosquitoes to the pesticides in them is as alarming as it seems?

I see this as great news, but given the only partial effectiveness, I wonder what the long term results will be.
posted by Hactar at 7:20 AM on July 24, 2015

The cost will surely come down over time. Even with the barriers, this represents a huge advance. Thanks for posting, it's nice to have some good news.
posted by theora55 at 7:30 AM on July 24, 2015

The actual numbers from the study:
8922 children... were included in the modified intention-to-treat analyses.

From month 0 until study end, compared with 9585 episodes of clinical malaria that met the primary case definition in children in the [control] group, 6616 episodes occurred in the [three dose plus booster] group and 7396 occurred in the [three dose plus comparator vaccine booster] group.

[C]ompared with 171 children who experienced at least one episode of severe malaria in the [control] group, 116 children experienced at least one episode of severe malaria in the [three dose plus booster] group and 169 in the [three dose plus comparator vaccine booster] group.

In children, 1774 cases of clinical malaria were averted per 1000 children in the [three dose plus booster] group and 1363 per 1000 children in the [three dose plus comparator vaccine booster] group.
Sounds like most of the treated children got malaria at least once, but they got it less often than they otherwise would've. And 21 kids in the vaccine groups got meningitis, compared to 1 in the control group.

So, if I'm doing my math right, ~55 cases of severe malaria were prevented and ~20 cases of meningitis were caused by vaccine treatment. For less severe malaria, "1774 cases of clinical malaria were averted per 1000 children," or a reduction of about one-third.
posted by clawsoon at 7:40 AM on July 24, 2015 [2 favorites]

Does anyone know which varieties of malaria this vaccine is effective against?

This vaccine is against Plasmodium falciparum, which is the most common and most deadly species of Plasmodia.

Do you see any other promising developments re: managing malaria in the next 5 +/- years.

I have been watching the development of gametocytocidal agents with interst. Gametocytes are the part of the parasite's life cycle where humans are infectious to mosquitoes - they are relatively rare compared to other human stages, and they don't appear to trigger much of an immune response from infected hosts. That means (and a colleague of mine has shown) that there is a measurable proportion of the population who exhibit no symptoms of malaria, but are contributing to transmission. The goal of gametocytocidal agents is to break transmission, but unfortunately, they don't provide much direct benefit to the person taking them, so you need to make a really good case that the interrupted transmission is a) real and b) at a level where the reduction in malaria burden is greater than the increased risk of taking a drug.

Right now I am working on a study that hopes to link infected mosquitoes with the actual humans they bit. We're hoping to create a network of exposure and infection to identify both the entomological and human behavioral/immunological characteristics that contribute to transmission in different ecological contexts. That way we can say things like 'bed nets work well in these cases, but not in these. Asymptomatic people contributed x% to the transmission burden, etc.' As an infectious disease epidemiologist, I sort of naturally lean toward transmission blocking interventions, rather than clinical case prevention, but ultimately both sides have the same goal: a world with fewer cases and deaths from malaria.

We are also living in a great era to get good data quickly and relatively inexpensively. The explosion of mobile phone ownership is one tool that clinicians and researchers alike are using to help identify and manage cases, to monitor stocks of drugs and nets, and so on. Handheld GPS and satellite imagery allow for more rapid and inexpensive identification of areas that are ecologically most at-risk for outbreaks or sustained high levels of year-round transmission. Rapid diagnostic tests allow clinicians and researchers to identify and treat cases within minutes in rural settings, without requiring microscopy or repeated visits. There has been substantial progress on malaria mortality in the past decade, and I see no reason why that progress should be halted now.

I'd like to think that the most promising development of malaria control is the growing awareness that there needs to be a comprehensive program that involves not just bed nets, not just indoor residual spraying, not just ecological management, not just drugs and vaccines, but a coordinated multi-pronged campaign that is appropriate to local environmental and behavioral/economic conditions.
posted by palindromic at 7:52 AM on July 24, 2015 [18 favorites]


*guitar windmill*

I'll see myself out.
posted by SansPoint at 8:00 AM on July 24, 2015 [1 favorite]

"1774 cases of clinical malaria were averted per 1000 children..."

Something I'm not understanding about how the numbers are presented here. Are they calculating multiple instances of malaria per child?
posted by destro at 8:25 AM on July 24, 2015

The study covered 48 months, and children in malaria endemic areas often get >1 case per year, so yes, there are multiple occurrences of incident malaria per child.
posted by palindromic at 8:42 AM on July 24, 2015 [2 favorites]

Another thing I am interested in with these vaccines is their long-term effectiveness. For example, we already know that people living in malaria endemic areas develop a clinical immunity to malaria symptoms as a result of repeated infection in early life. How does vaccination affect the development of this clinical immunity? Is there an increased of clinical malaria among older children and adults resulting from lack of repeated infection in early childhood? It is obviously too early to answer these questions, but another potential complication of administering a vaccine that does not induce sterilizing immunity.

We see a similar dynamic playing out here in the States with pertussis, where people thought that the vaccine was like the disease, in that each conferred more or less lifelong immunity. What appears to actually be the case is that the disease only seemed to confer lifelong immunity because clinical immunity was boosted by repeated exposure to pertussis in the population. Now that pertussis is rare in the population, we can see that the immunity induced both by vaccination and infection is not sterilizing, so now people are investigating whether and how often adult boosters are needed to keep pertussis from re-emerging in adult populations. Also similar to malaria is that adult pertussis is a bit of a nuisance at worst (chronic nagging cough), but childhood pertussis is potentially lethal. This means clinically immune adults are still contributing to transmission even though they are not considered an at-risk population for the disease.
posted by palindromic at 8:50 AM on July 24, 2015 [9 favorites]

How does vaccination affect the development of this clinical immunity?

Effectively interrupting transmission would likewise affect this immunity too though, no? The trade-off for both vaccine and epidemiological prevention of infection in young children would both be increased risk of more severe adult infection if exposed.
posted by Panjandrum at 1:55 PM on July 24, 2015

Palindromic's very pertinent caveats aside, this is a great thing. Our understanding and control of malaria is developing very rapidly right now, and twenty years hence we may look back on the introduction of this vaccine as the point in time when malaria turned from an endemic global scourge, the killingest disease on the face of the planet, to "just" another nasty infectious disease.

Lyme, dengue, rickettsia, etc. are all crappy diseases that can and do kill people. Malaria, however, is a neverending plague of biblical proportions. If you haven't spent time in a part of the world where it is a problem, it is almost impossible to understand how bad it is. Every single person I met in central Africa had had it more than once, and every single person I met knew someone, usually a child, who had died from it. This is a devastating disease that affects billions of people, and it never stops. If something this deadly got loose in the U.S. for even a week, the news media would panic, a state of emergency would be declared, and people would be talking about it for a generation. In much of the world, it is just a part of everyday life.

A vaccine, even an imperfect one, is a game-changer. Just as importantly, this vaccine is just the beginning. The global community has been quietly bending its collective will toward solving this problem for some time now, and we are making huge strides. We are learning a tremendous amount about the epidemiology of malaria, which is helping us develop new public health strategies to break the cycle of transmission. We have Coartem, a treatment which is relatively cheap and simple enough that it can be deployed effectively by minimally-trained persons. And now we have our first vaccine, in many ways the holy grail of malaria management. No, it's not an ideal vaccine. But we are certainly not stopping now, and better ones will surely come along. We are on the verge of conquering this thing, and doing so will improve the world in ways most of us cannot even imagine. This may not be the end of the struggle, but it is a huge milestone and a huge symbolic victory. The first malaria vaccine. I never quite believed I'd see it.
posted by Anticipation Of A New Lover's Arrival, The at 3:14 PM on July 24, 2015 [5 favorites]

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