Wednesday, December 10, 2008

Tuesday's Big News - Almost

The big news yesterday, before Gov. Blog was arrested, was the report of the success of a new malaria vaccine.
The studies, published online Monday in the New England Journal of Medicine, were reported at a New Orleans meeting of tropical medicine researchers and were hailed as a significant breakthroughin the fight against one of the most intractable and deadly infectious diseases.
The paper, if you are interested in reading the actual results, is here.

Let's look at the headline of this report in FP Passport. The headline claims "New malaria vaccine more than 50 percent effective". Ok, so what does "effective" mean? Most vaccines that we get provide what is often called sterile immunity. They prevent occurence of a disease. For example, get vaccinated against the polio or measles virus and you most likely will never become infected with polio or measles.

This malaria vaccine does not provide sterile immunity. It is best described as an anti-disease vaccine. You still become infected, but with fewer parasite-infected red blood cells. This means you might suffer less severe symptoms of malaria. Also, a lower parasite burden may allow for a more effective immune response against the remaining parasites.

So why doesn't the new vaccine (it was actually designed in the late 1980's) provide sterile immunity? It's because of the malaria parasite's life cycle.

Parasites injected into the bloodstream of a host (you) rapidly penetrate liver cells - they become intracellular. The vaccine, RTS, S (with an adjuvant), specifically targets the mosquito-injected stage of the parasite called a sporozoite. The sporozoite is free in the blood for just minutes before they penetrate liver cells. So two types of immunity are necessary. Antibodies can bind to the sporozoites while they are free in the blood and prevent them from penetrating the liver. If no sporozoites reach the liver - you have no malaria and thus sterile immunity. The RTS, S vaccine obviously does not prevent sporozoites from penetrating the liver because vaccinated individuals.

Once the liver cells become infected, a type of immunity called "cell-mediated" immunity is required. Especially needed is a type of T lymphocyte that can kill parasite-infected cells - a CD8+ cytotoxic cell.

A single liver cell infected with a single malaria sporozoite results in hundreds to thousands of merozoite stages that burst out of the liver cell and infect red blood cells.

The RTS, S vaccine induces no immunity to these blood cell stages.

The paper actually reports that "clinical malaria" developed in 32 of 402 RTS, S vaccinated children compared with 66 of 407 children that did not receive the RTS, S vaccine. This is nothing to sneeze at. But how do the researchers define "clinical malaria"?

The primary end point was a clinical episode of malaria, defined as an axillary temperature of 37.5 (degrees C) or higher with a Plasmodium falciparum density or more than 2500 parasites per microliter. The presence of any faciparum parasitemia density with a temperature of 37.5 (degrees C) was a secondary end point.
50% effective means that about half of the vaccinated children did not show signs of a researcher defined "clinical malaria"

This is good for the children that were protected from a more severe case of malaria. This vaccine is likely to save the lives of many children. However, it's unlikely to have any significant effect on reducing the levels of malaria worldwide.

1 comment:

Sara said...

I was just speaking with Kevin about this since his boss & others from their lab were involved in this - pretty cool!!