Toward the end of WWII, public health efforts, including the use of DDT, led to the elimination of malaria in the United States. Unless we work abroad, malaria is not something US-based trainees encounter much after we learn bugs and drugs. But the rest of the world has not been so fortunate. The WHO estimates that malaria infects 225 million, and kills 781,000 people each year. 92% of those who die of malaria are African children. To put this number in perspective, in 2009 malaria killed more African children than heart disease killed US adults. What if someone suddenly discovered a way to decrease the burden of heart disease by half? Well, today we hear of an intervention that has the potential to achieve a feat of a similar scale in Africa: a malaria vaccine.
This week on NEJM.org, the RTS,S Clinical Trials Partnership presents the first results from its ongoing Phase III trial. This randomized, controlled, double-blind trial enrolled over 15,000 children from 7 African countries to assess the efficacy of a candidate malaria vaccine, otherwise known as RTS,S/AS01. The primary endpoint was vaccine efficacy, at one year, among two groups: 6-12 week-olds and 5-17 month–olds. The efficacy of the vaccine is reported among the older cohort of children, who were among the first 6000 enrolled. The control groups received a comparator vaccine — rabies for the older group and meningogoccal for the younger. A secondary analysis was also performed, looking at the rate of severe malaria among a combined age-group category.
The results are promising. The vaccine was 55.8% effective against clinical malaria among the 5-17 month cohort. Severe malaria was defined as clinical malaria (fever ³ 37.5° C and Plasmodium falciparum parasite density > 5000 parasites/mL), plus at least one additional clinical indicator of disease severity, such as hypotension, acute lung injury, or decreased urine output. The vaccine was 34.8% effective in reducing severe malaria for the combined age-group category. Safety and tolerability were also assessed. Though the authors conclude that the data thus far suggest that the malaria vaccine has a safety profile comparable to that of other pediatric vaccines, there was a slightly higher rate of convulsive seizure in the first week post-malaria vaccine. Given the overall low rate of events, it remains difficult to tell if any true differences in safety exist.
In parsing through this study, and envisioning its potential impact, it is important to remember that more data are forthcoming. Data among the children in the younger cohort will help define the spectrum of safety and efficacy in that key, target population. The possibility of waning vaccine efficacy will be better understood with longer follow-up, which will also help define the impact of the booster vaccine, which is given at 14 months.
“Overall, these data are very encouraging. However, a more complete evaluation- when the entire data set is available in about 2 years- will be important in determining the potential this intervention may have on controlling malaria. Having another tool to deploy in the fight against malaria is an important advance,” comments Dr. Lindsey Baden, NEJM deputy editor.
Of course, the ultimate success of the vaccine will depend not simply on efficacy and safety, but on ongoing public health efforts to make the vaccine widely available and affordable where it is most needed. The good news is that, through the efforts of international organizations, malaria prevention tools such as mosquito nets and indoor spraying are now being used widely. An effective vaccine against malaria would be a welcome addition.