UKC

Malaria vaccine - 75% efficacy

Imagine doing a job where you might save 450,000 lives per year.

"Nearly every minute, a child under five dies of malaria. Many of these deaths are preventable and treatable. In 2021, there were 247 million malaria cases globally that led to 619,000 deaths in total. Of these deaths, 77 per cent were children under 5 years of age."

https://data.unicef.org/topic/child-health/malaria/

https://www.ox.ac.uk/news/2023-10-02-oxford-r21matrix-m-malaria-vaccine-rec...

Do we know yet what 75% efficacy means in this case?

Is it 75% less likely to lead to a fatality or is it 75% less likely to get the disease?

If the latter then it could be even more game changing as this would likely lead to an even greater reduction in fatalities and could reduce the amount of infected mosquitoes.

I'm not sure if other animals can be infected by varieties of malaria that can infect humans, but if not, then a vaccine could break the life cycle just enough.

It means the same as it always has. Reduction in disease rates within a controlled study compared to a non-vaccinated cohort.

But it does not follow that this leads to a reduction in transmission, and neither this nor the previous malaria vaccine have been found to reduce transmission. 

The latter rather than the former. My wholly amateur and superficial interpretation is the case fatality rate is about 0.0025 so it's about four hundred times easier to detect reduction in infections than reduction in fatalities. 

add to that the doses will cost as little as $2 to $4.

I don't have to - I work on Malaria amongst other things! Admittedly, however, I had no involvement in this particular vaccine.

Vaccines for malaria and other protozoan parasites are particularly difficult because the parasites are eukaryotic organisms. That means that their fundamental biology is very similar to ours, so it's much harder to create vaccines or drug treatments that don't have adverse effects than it is for bacterial and viral pathogens. These vaccines that have been becoming available for malaria over the last few years really are something special.

To answer some of the questions:

1. 75% efficacy means 75% less likely to get the disease. Malaria is actually very treatable in most cases - the majority of fatalities occur because patients in endemic countries often don't have the time or resources to go to healthcare clinics for every fever. However, the economical burden of treatment is high. Reducing infection rates is much more effective in the grand scheme of things than reducing fatality.
2. The vaccine, is likely to reduce transmission in that humans who aren't infected can't pass it on to mosquitos. However, it has not yet been shown to have a large impact on transmission dynamics. This is because the lifecycle of malaria is very complicated with multiple different lifecycle stages in multiple hosts (mammals and mosquitos). It's almost impossible to make a vaccine or drug that can target all the life stages, and to do this effectively you would need to treat mosquitos as well as mammalian hosts (although we have tried finding drug targets that would theoretically allow this: https://pubmed.ncbi.nlm.nih.gov/31467193/ (PDF freely available from https://eprints.gla.ac.uk/194352/). In comparison, the lifecycles of most bacteria and viruses are much simpler.
3. This vaccine targets a life stage called the sporozoites. This is the life stage that is transmitted from mosquito to human when a mosquito take a blood-meal. Only 10-100 individual sporozoites are required to establish an infection, so this is a good time for the immune system to attack. After this, the parasite replicates itself very quickly, so it's much more difficult for the immune system to get on top of it.

The other really cool thing about this is that although the vaccine is currently produced by the Serum Institute for India, they have arranged a technology transfer deal enabling the vaccine to be produced in Accra, Ghana. This is likely to avoid some of the political problems that have hampered effective roll out of other vaccines in parts of Africa previously.

Very informative, thanks!

Your point 1 hit me when I was last in Nigeria. One of my colleagues developed a malarial fever. I asked him what he was going to do. 'Nothing - we live with it'. This was a fairly senior scientist at a major University. Brought home the reality of it and this was a relatively well off part of the community.

This is true - however it's a bigger problem for children. Teenagers and adults living in endemic areas build up a degree of immunity, so the consequences of malaria are much less severe for them if they are healthy otherwise. Fatalities are much more prevalent in young children, significantly decreasing with age. So, many adults do just live with it regardless of access to healthcare provision, but most would make an effort to get young children to a clinic if they can.

If an otherwise healthy adult has a severe case of malaria, it's often after they've lived abroad for a protracted period. Tourists are generally clued up on the fact that they need to take anti-malarials when they visit an endemic area. However immunity does wane after a year or two without exposure. Anti-malarials are often not advertised to African returnees, and it often doesn't occur to them to ask because they've successfully lived with malaria in the past. I work with quite a few African scientists - it's not uncommon to receive an email after they've returned home saying "oh, so THATS why Europeans take anti-malarials!".

Isn’t the parasite one of the most crazy bits of biology on the planet?  I briefly worked on something imaging related for a malaria person and learning about it blew my mind.  Endosymbiotic organelles that are an “endosymbyote within a lost endosymbyote”.  Very different mitochondrial interactions.  

Like slime molds and polyps like the by-the-wind-sailor it makes me wonder what other paths could have, or yet will be, taken to build macroscopic lifeforms. The potential isn’t so obvious with the malaria parasite but it does so many things different and with a lot of cellular scale smarts.

Christ on a bike you have to hunt around to find something negative to say about a fantastic piece of news and science?

I don't think the data is out on transmission, no?  So where does your second point even come from?

Jesus it frustrates me that people are dedicating their lives to solving these problems and folk then swallow misinformation or come up with their cup 90% empty.

(Yes, I've brought new medicines to market and worn the ingratitude first hand)

Any ingratitude you are perceiving is entirely in your own mind. You are misreading my post. If it seemed terse it was because of montyjohn's previous rants against the developers of the covid vaccines where he had assumed that a good efficacy rate meant that transmission would be stopped, and when this false assumption wasn't borne out he decided that this meant the researchers were fundamentally dishonest.

He asked a question about transmission (seemingly based on the same false assumption that led him to berate the covid researchers), an answer was in about the second paragraph of the news article that I had read (Reuters, I think), so I gave an answer to his question.

They are pretty cool. And, you're correct - the apicoplast is the result of a secondary endosymbiotic event and appears to be the result of a cyanobacterium which was engulfed by a eukaryotic cell to form a photosynthetic algae (debate in the field over whether this was a red or green algae), which was in turn engulfed by a heterotrophic eukaryote. Amongst other things, the apicoplast has retained the membranes from both endosymbiotic event, so it has a double bi-lipid layer.

However, for really crazy biology, look at kinetoplastids. Trypanosoma brucei (African Sleeping Sickness) is a good example. These diverged much earlier than the Apicomplexa (the lineage malaria belongs in) and are really crazy. Probably my favourite weird lineage!

Although these only appear to have had one endosymbiosis event, they still have very divergent mitochondrial-like organelles. Other weirdnesses include:

• They do polycystronic transcription. This means that they can't control the transcriptional level of individual genes - everything is transcribed at the same level all the time. It's kind of like the whole genome is one big operon. Most of their regulation is by means of targeted degradation of mRNAs
• None of their genes have introns - except two which have introns in every organism in the lineage. There isn't really a good hypothesis for why these two introns are conserved.
• The genes encoded in the kinetoplast genome are cryptically encoded. They need to undergo extensive RNA editing before they can be translated. In addition to the primary kinetoplast genome, the kinetoplast also contains a secondary genome encoding guide RNAs to provide templates for this process
• They exhibit mosaic aneuploidy, duplicating entire chromosomes or segments thereof readily and somewhat randomly.
• They appear to duplicate parts of their genome outside of S-phase.

That's interesting. Must read up on it. My favourite beastie, a eukaryotic pathogen in the SAR group, shares a weird subset of genes with even weirder relatives that have hydrogenosomes. Still trying to work out how on earth that happened. Keep up the good work!