Editorial
According to WHO’s 2014 World Malaria Report there were an estimated 198 million cases of malaria worldwide in 2013, occurring in around half of the world’s countries. These infections resulted in some 584 000 deaths, principally associated with Plasmodium falciparum infection, of which 90% occurred in equatorial Africa. Most distressingly, malaria mortality is concentrated in children, with about 453 000 deaths of children aged younger than 5 years in 2013, the vast majority in African countries. Infections by Plasmodium vivax and other parasites also cause a very substantial burden of disease. Reducing the heavy burden of malaria, and its damaging effects on the health and prosperity of people in developing countries, is one of the 21st century’s most important health aspirations. Owing to considerable global investment and widespread use of interventions, the point estimate of the number of infections in Africa is believed to have fallen greatly, from about 173 million to 128 million during 2000–13. In addition to pharmacotherapy, of which artemisinin combination therapies are a mainstay, indoor residual spraying with insecticides and provision of insecticidal bednets are preferred preventive strategies. To illustrate the scale of this effort, WHO estimates that 214 million bednets were delivered to African countries affected by malaria in 2014. Yet serious gaps remain. World Malaria Day on April 25, with its theme of Invest in the future, defeat malaria, highlights an annual funding shortfall of US$3·6 billion. In practical terms this means that in 2013, for example, between 56 and 69 million children in Africa with malaria did not receive artemisinin combination therapy. To strengthen efforts in prevention of malaria, vaccine researchers have sought to provide specific and durable protection against P falciparum for children and others. Although this aim has long been frustrated by the complexities of the parasite lifecycle and host immune response, efforts have focused most recently on the pre-erythrocytic stage of infection. In the RTS,S vaccine, epitopes from the parasite circumsporozoite protein have been combined with elements designed to evoke an immune response to prevent hepatocyte infection, and thereby block progression to red blood cells and clinical malaria. To coincide with World Malaria Day, the RTS,S Clinical Trials Partnership reports final www.thelancet.com Vol 385 April 25, 2015
results of a phase 3 trial of the RTS,S/AS01 vaccine, conducted in seven countries in Africa, in a Lancet paper published online. Development of RTS,S has been a unique cooperative endeavour by diverse organisations, including the Bill & Melinda Gates Foundation and GlaxoSmithKline, spanning two decades. In the RTS,S phase 3 trial, groups of children aged 6–12 weeks (n=6537) or 5–17 months (n=8922) were given three doses of the experimental vaccine at months 0, 1, and 2, or a control vaccine, along with a booster or control vaccine at 20 months. Over 48 months, observed protection of children aged 5–17 months against malaria was 36·3% (95% CI 31·8–40·5), or 28·3% (23·3–32·9) without the booster; in children aged 6–12 weeks protection over 38 months was 25·9% (19·9–31·5), or 18·3% (11·7–24·4) without the booster. An apparent excess in cases of meningitis was detected in the groups of children receiving RTS,S vaccine, but the researchers note that these cases could represent chance events occurring at two study sites. As discussed by Vasee Moorthy and Jean-Marie OkwoBele in a Comment accompanying the RTS,S report, apparent protection against malaria by the vaccine is modest in both extent and duration. But, because the vaccine would be used alongside complementary interventions such as bednets, this protection could prove to be very important. Decisions on possible licensing and rollout of RTS,S are expected late in 2015, and will need to take into account all of the evidence on vaccine efficacy and adverse events, in addition to the many practical considerations and costs for vaccination campaigns in developing countries. Other vaccine candidates at earlier stages in development include PfSPZ, a preparation of irradiated whole P falciparum sporozoites given intravenously. Even if the hopes and resources that have been devoted to development of RTS,S and other vaccines are fully realised, malaria will remain a serious problem in countries across Africa, Asia, and South America. Based on the information now available it would be surprising if RTS,S were not to proceed to widespread deployment. The costs and challenges of such an exciting project will be great. However, in the hope that 2015 will be remembered as a turning point in malaria prevention, a vaccine rollout programme deserves our full support. The Lancet
Stephen Morrison/epa/Corbis
Vaccines: a step change in malaria prevention?
See Perspectives page 1613 See Online/Comment http://dx.doi.org/10.1016/ S0140-6736(15)60767-X See Online/Articles http://dx.doi.org/10.1016/ S0140-6736(15)60721-8
For the 2014 World Malaria Report see http://www.who.int/ malaria/publications/world_ malaria_report_2014/en/ For more on World Malaria Day see http://www.worldmalariaday. org/
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According to WHO’s 2014 World Malaria Report there were an estimated 198 million cases of malaria worldwide in 2013, occurring in around half of the world’s countries. These infections resulted in some 584 000 deaths, principally associated with Plasmodium falciparum infection, of which 90% occurred in equatorial Africa. Most distressingly, malaria mortality is concentrated in children, with about 453 000 deaths of children aged younger than 5 years in 2013, the vast majority in African countries. Infections by Plasmodium vivax and other parasites also cause a very substantial burden of disease. Reducing the heavy burden of malaria, and its damaging effects on the health and prosperity of people in developing countries, is one of the 21st century’s most important health aspirations. Owing to considerable global investment and widespread use of interventions, the point estimate of the number of infections in Africa is believed to have fallen greatly, from about 173 million to 128 million during 2000–13. In addition to pharmacotherapy, of which artemisinin combination therapies are a mainstay, indoor residual spraying with insecticides and provision of insecticidal bednets are preferred preventive strategies. To illustrate the scale of this effort, WHO estimates that 214 million bednets were delivered to African countries affected by malaria in 2014. Yet serious gaps remain. World Malaria Day on April 25, with its theme of Invest in the future, defeat malaria, highlights an annual funding shortfall of US$3·6 billion. In practical terms this means that in 2013, for example, between 56 and 69 million children in Africa with malaria did not receive artemisinin combination therapy. To strengthen efforts in prevention of malaria, vaccine researchers have sought to provide specific and durable protection against P falciparum for children and others. Although this aim has long been frustrated by the complexities of the parasite lifecycle and host immune response, efforts have focused most recently on the pre-erythrocytic stage of infection. In the RTS,S vaccine, epitopes from the parasite circumsporozoite protein have been combined with elements designed to evoke an immune response to prevent hepatocyte infection, and thereby block progression to red blood cells and clinical malaria. To coincide with World Malaria Day, the RTS,S Clinical Trials Partnership reports final www.thelancet.com Vol 385 April 25, 2015
results of a phase 3 trial of the RTS,S/AS01 vaccine, conducted in seven countries in Africa, in a Lancet paper published online. Development of RTS,S has been a unique cooperative endeavour by diverse organisations, including the Bill & Melinda Gates Foundation and GlaxoSmithKline, spanning two decades. In the RTS,S phase 3 trial, groups of children aged 6–12 weeks (n=6537) or 5–17 months (n=8922) were given three doses of the experimental vaccine at months 0, 1, and 2, or a control vaccine, along with a booster or control vaccine at 20 months. Over 48 months, observed protection of children aged 5–17 months against malaria was 36·3% (95% CI 31·8–40·5), or 28·3% (23·3–32·9) without the booster; in children aged 6–12 weeks protection over 38 months was 25·9% (19·9–31·5), or 18·3% (11·7–24·4) without the booster. An apparent excess in cases of meningitis was detected in the groups of children receiving RTS,S vaccine, but the researchers note that these cases could represent chance events occurring at two study sites. As discussed by Vasee Moorthy and Jean-Marie OkwoBele in a Comment accompanying the RTS,S report, apparent protection against malaria by the vaccine is modest in both extent and duration. But, because the vaccine would be used alongside complementary interventions such as bednets, this protection could prove to be very important. Decisions on possible licensing and rollout of RTS,S are expected late in 2015, and will need to take into account all of the evidence on vaccine efficacy and adverse events, in addition to the many practical considerations and costs for vaccination campaigns in developing countries. Other vaccine candidates at earlier stages in development include PfSPZ, a preparation of irradiated whole P falciparum sporozoites given intravenously. Even if the hopes and resources that have been devoted to development of RTS,S and other vaccines are fully realised, malaria will remain a serious problem in countries across Africa, Asia, and South America. Based on the information now available it would be surprising if RTS,S were not to proceed to widespread deployment. The costs and challenges of such an exciting project will be great. However, in the hope that 2015 will be remembered as a turning point in malaria prevention, a vaccine rollout programme deserves our full support. The Lancet
Stephen Morrison/epa/Corbis
Vaccines: a step change in malaria prevention?
See Perspectives page 1613 See Online/Comment http://dx.doi.org/10.1016/ S0140-6736(15)60767-X See Online/Articles http://dx.doi.org/10.1016/ S0140-6736(15)60721-8
For the 2014 World Malaria Report see http://www.who.int/ malaria/publications/world_ malaria_report_2014/en/ For more on World Malaria Day see http://www.worldmalariaday. org/
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