“Millions of children’s lives could be saved by a new vaccine shown to halve the risk of malaria in the first large-scale trial across seven African countries,” reported The Guardian. The newspaper goes on to say that the long-awaited results of the largest-ever malaria vaccine study, involving 15,460 babies and small children, showed that it could massively reduce the impact of the malaria.
The study reported the results of an initial analysis of a large trial of a malaria vaccine, called RTS,S/AS01. The trial found that after one year, the vaccine reduced the number of episodes of clinical malaria by about 50%, and the number of cases of severe malaria by about 35%. However, there was some evidence that the vaccine’s efficiency was reduced during the follow-up period.
There were a similar number of side effects in children who received the malaria vaccine as in children who received the control vaccine, but there were more cases of meningitis and seizure in the group that received the malaria vaccine.
The results of this trial suggest that this vaccine could be an important tool in the control of malaria. However, the results of longer-term follow-up are required to determine how long the vaccine protects against malaria and to monitor side effects. More will be known when the results of the next phase of the trial are released in 2014.
The Guardian reported that the World Health Organization (WHO) has said that if the results are satisfactory, it will ‘recommend its use and the vaccine may begin to be rolled out as early as 2015, but it will need to be used in conjunction with all the other existing tools of malaria prevention, such as bed nets and insecticide spraying on the inside of homes’.
Where did the story come from?
The study was carried out by the RTS,S Clinical Trials Partnership that included researchers from African research centres (in Gabon, Mozambique, Tanzania, Burkina Faso, Kenya, Ghana, Malawi); the University of Tübingen, Germany, and from GlaxoSmithKline and the PATH Malaria Vaccine Initiative. It was funded by GlaxoSmithKline and the PATH Malaria Vaccine Initiative, which received a grant from the Bill and Melinda Gates Foundation.
The study was published in the peer reviewed journal The New England Journal of Medicine .
One of the sponsors of this trial was GlaxoSmithKline Biologicals, which both developed and manufactures the vaccine.
This story was accurately covered by The Guardian and by several other newspapers. The Guardian provided useful background and context to the study using quotes from the study authors and Bill Gates.
What kind of research was this?
This was a blinded, randomised controlled trial. The aim of the trial was to determine how effective and how safe a possible malaria vaccine, called RTS,S/AS01, is in a large sample of children in Africa. The vaccine had been studied extensively before in laboratory studies and in smaller groups of people.
This is the most appropriate study design to answer this question. However, this study only reported the preliminary results of the trial, and long-term effectiveness and safety results are not due to be released until 2014.
What did the research involve?
The trial enrolled 15,460 children in two age categories: babies 6 to 12 weeks of age and children 5 to 17 months of age. The children in both age categories were randomly allocated to one of three groups. The vaccine is designed to be given in three doses, one month apart. One group received all three doses of the vaccine, a second received all three doses of the vaccine with a booster after 18 months, and a control group received either a rabies vaccine or meningitis vaccine.
The rabies vaccine was given to the children aged 5 to 17 months and the meningitis vaccine (meningococcal serogroup C conjugate) vaccine was given to babies 6 to 12 weeks of age.
As children with malaria are sometimes not taken for medical treatment, or do not seek it, the researchers encouraged participants and their families to seek care for any illness. They recorded the incidence of:
- clinical malaria: defined as an illness in a child who had a temperature of 37.5C or more and more than 5000 P.falciparum parasites per cubic millimetre of blood
- severe malaria: clinical malaria plus one or more markers of disease severity and without diagnosis of a co-morbidity
- side effects
They also took blood samples and determined the levels of antibodies against malaria that were present in the children’s blood.
This study only reported the initial results of the trial in the 5 to 17-month age group (the efficacy against clinical malaria after 12 months in the first 6,000 children enrolled). Equivalent data for the 6 to 12-week age group is not yet available, but the researchers did report the results of some interim analyses of the vaccines efficacy against severe cases of malaria in this age group.
What were the basic results?
In the 5 to 17-month age group, 2,830 children received all three doses of the malaria vaccine (with or without the booster) and 1,466 received the control vaccine.
Twelve months after the third dose of vaccine in the trial, there were 932 first episodes of malaria in the older age group that had received the malaria vaccine, and 752 first episodes of malaria in the control group. This translated to 0.44 first episodes of malaria per person per year in the group that received the malaria vaccine, and 0.83 first episodes of malaria per person per year in the control group.
The researchers calculated the vaccine’s efficacy, the proportion of cases of malaria that were prevented by vaccinations. They say that in this group the vaccine had 55.8% efficacy (97.5% confidence interval [CI] 50.6 to 60.4). If all episodes of malaria (including repeat episodes) were included, the vaccine efficacy was 55.1% (95% CI 50.5 to 59.3).
The researchers carried out another analysis after 14 months, which included all the older children irrespective of whether they had received the vaccine or not. This group was called the ‘intention to treat’ population, and is the most appropriate way to analyse the data. This analysis showed there were 0.32 first episodes of malaria per person-year in the malaria vaccine group, and 0.55 episodes per person-year in the control group. Therefore, this analysis showed the vaccine to be 50.4% effective (95% CI 45.8 to 54.6).
There was evidence that vaccine efficacy was higher at the beginning than at the end of the follow-up period.
The researchers then analysed the incidence of severe episodes of malaria. For this analysis, they used data from both age groups. Vaccine efficacy against severe malaria was 34.8% (95% CI 16.2 to 69.2) over an average follow-up of 11 months, in a population that received vaccinations and follow-ups in line with the protocol.
There were a similar number of severe adverse events in both groups in the older age category (17.6% for the malaria vaccine group compared with 21.6% in the control group). However, although there were not significant differences in the numbers of adverse effects, meningitis and seizures were reported more frequently in the group that received the malaria vaccine.
Meningitis occurred in 11 of 5,949 children aged 5 to 17 months given the malaria vaccine and 1 of 2,974 children of the same age given the control (rabies) vaccine (relative risk [RR] 5.5, 95% CI 0.7 to 42.6). Seizures occurred 1.04 times per 1,000 vaccinations in the malaria vaccine group compared to 0.57 times per 1,000 vaccinations in the control group (relative risk 1.8, 95% CI 0.6 to 4.9) in the older age category.
How did the researchers interpret the results?
The researchers say that the ‘initial results show that the RTS,S/AS01 vaccine reduced malaria by half in children 5 to 17 months of age during the 12 months after vaccination, and that the vaccine has the potential to have an important effect on the burden of malaria in young children. Additional information on vaccine efficacy among young infants and the duration of protection will be critical to determining how this vaccine could be used most effectively to control malaria.’
In this study, researchers have reported the results of an interim analysis of a large trial of a malaria vaccine, called RTS,S/AS01, carried out in several African countries. The efficacy and safety of the vaccine over 12 months in the first 6,000 children aged 5 to 17 months old who received the vaccine was reported, together with an evaluation of the first 250 cases of severe malaria.
The trial found that the vaccine reduced the number of episodes of clinical malaria by about 50%, and the number of cases of severe malaria by about 35%. There was some evidence that the vaccine reduced in efficiency during the follow-up period. Side effects occurred with a similar frequency in children that had received either the malaria vaccine or the control vaccine.
There were more cases of meningitis and incidences of seizure in the group that received the malaria vaccine, but the difference was not statistically significant.
This was a well-reported and conducted trial and the findings appear to be robust. The researchers say that the vaccine had a high efficacy against severe malaria, although no reduction in the rate of death from malaria or from any cause was observed in the malaria vaccine group. However, only 10 of the 151 reported deaths (6.6%) in the trial were due to malaria and this is comparatively low for this area. Seven of these 10 deaths were confirmed on blood tests to have been caused by malaria. The researchers say this may be because those in the trial had access to the high-quality care provided at study facilities.
The researchers add that the potential of the vaccine to improve health and reduce mortality in people with poorer access to health care is an important reason for further trials.
The results of this trial suggest that this vaccine could be an important tool that could contribute to the control of malaria. However, the results of longer-term follow-up are needed to determine how long the vaccine protects against malaria and to monitor side effects and any reductions in mortality.