Hope for malaria vaccine

A malaria vaccine has been shown to protect African children from infection, the Telegraph reported.

The Guardian said that the vaccine trial had cut "malaria cases among babies by two-thirds" and that this gives "hope of cutting the global death toll of one million a year."

The stories are based on a vaccine trial in babies in Mozambique. This is a well-conducted study showing that the vaccine induces an immune response against malaria in babies.

This aim of this study was to see if the vaccine was safe and well tolerated in babies; which it was. The study was not designed to see how well the study could protect babies from getting malaria, however the findings do suggest that the vaccine can offer 60% protection from infection. The next stage in testing will be larger studies to find conclusive evidence of the vaccine’s effectiveness.

Where did the story come from?

Drs John Aponte, Pedro Alonso and colleagues from the Barcelona Centre for International Health Research. The vaccine was manufactured by GlaxoSmithKline. The work was funded through the PATH Malaria Vaccine Initiative with a grant from the Bill & Melinda Gates Foundation.

The study was published in the peer-reviewed medical journal The Lancet.

What kind of scientific study was this?

This was a randomised controlled trial of a malaria vaccine in 214 babies in Mozambique. The main point of the study was to determine whether the vaccine was safe and well tolerated – i.e. that there were few side effects.

Babies were randomly allocated to receive three doses (delivered as injections into the muscle) of the study vaccine or three doses of hepatitis B vaccine at ages 10, 14, and 18 weeks. The healthcare staff delivering the vaccines did not know which was being given (i.e. they were blinded).

The mothers of the babies had been approached during their pregnancy, given information about the study and counselling and treatment for existing HIV and hepatitis B infection. They had all given their consent to participate. Babies were also given their routine childhood immunisation vaccinations at eight, 12 and 16 weeks of age.

Infants were observed for one hour after receiving their vaccinations to assess any immediate side effects. They also had daily visits by trained field workers for six days after each dose to record any possible side effects. Serious adverse events were recorded throughout the study through a nearby health facility.

The researchers were interested in the babies’ immune response to the vaccines, so they measured antibodies (part of the immune system which fight off infection) to the malaria parasite before the study and at one month and 3.5 months after the babies had received all three doses of the vaccine. They also measured antibodies to hepatitis B before the study and at one month after all three vaccination doses.

New cases of malaria occurring in the 12 weeks after vaccination were recorded both through regular testing of the babies’ blood for the parasite (every fortnight for 12 weeks after the vaccinations were complete) and also by recording cases that came to the health facilities to seek treatment.

What were the results of the study?

The researchers found that there were no significant differences between the malaria and the hepatitis B vaccine groups in the number of babies experiencing side effects and that the side effects did not increase with repeated doses.

They report that during the follow-up period the children, suffered a similar number of “serious” side effects between the groups (31 in the malaria vaccination group and 30 in the hepatitis B vaccination group). None of these side effects were considered to be related to vaccination.

There were four deaths, unrelated to the vaccine programme, with two in each vaccination group, due to septic shock or severe dehydration due to gastroenteritis.

The researchers report that 99% of the babies who had the malaria vaccination had retained antibodies to malaria one month after their third dose while only 4% in the hepatitis B group did. About three months after malaria vaccination, 98% of babies still had antibodies.

In terms of the actual number of malaria infections, 22 of those who received all three doses of the malaria vaccine got malaria, compared to 46 of those who received the hepatitis B vaccination. Results showed that 37.1% of the children vaccinated with the malaria vaccine developed at least one episode of malaria over three months of follow up compared to 77.3% of the children who had not been vaccinated. The researchers determined that the vaccine reduced malaria infection by 62%.

What interpretations did the researchers draw from these results?

The researchers conclude that the RTS,S/AS02D malaria vaccine is safe and well tolerated and is able to induce antibodies to malaria in babies in a rural area of Mozambique.

They declare that these "encouraging data need to be substantiated in phase III trials”. They are encouraged by the results and believe that their findings strengthen the vision that a vaccine that “can partly protect young African children and infants” might help to reduce the malaria disease burden.

What does the NHS Knowledge Service make of this study?

This was a well-conducted study. There are a couple of points to highlight in regard to the interpretation of the study results:

• Importantly, all participants in this study (in both the malaria and the hepatitis B vaccination groups) were also using other vector control methods (e.g. insecticide treated bed nets and insecticide sprays (DDT) in their houses). This study was assessing vaccination as an additional protection to other control methods.
• The study was not designed to assess the effectiveness of the vaccine; it was mainly looking at whether there were significant side effects associated with it. As such, the researchers call for further study in larger trials to corroborate their efficacy findings.
• The main results about effectiveness that the researchers present, are based only on the children who received all three vaccine doses and who had information available during the follow up period. When they analysed all the babies that were enrolled in the study together (those that received none, one, two or three doses), they found that there was no statistically significant effect of vaccination.
• This result puts more emphasis on the need for further, larger studies of the vaccine in infants that are designed to look mainly at efficacy over a longer period of time. These are on their way.

This study adds to the evidence that the RTS,S/AS02D vaccine will be a valuable tool to include in our armoury against malaria.

This was a small and short study conducted in a country where, by the age 7 or 8 months, 74% of infants can expect to have had an episode of malaria and about 2% have died from other infectious disease. This reinforces the importance of supporting research in these settings.

Sir Muir Gray adds...

AIDS gets all the publicity because it is new but tuberculosis and malaria are also still heavy burdens in the region. This research provides good hope that the burden can be lightened.