Laura Riggall explains the most important breakthrough in the disease’s history
Malaria is a leading cause of human morbidity and mortality. Despite huge progress in tackling the disease, there are still 212 million new cases of malaria and 430,000 malaria-related deaths worldwide each year according to the World Health Organisation (WHO). Most cases (80%) and deaths (90%) were in sub-Saharan African.
However, over three billion individuals across 108 countries are at risk. Babies, young children and pregnant women are particularly susceptible to the disease. Not only does malaria cost lives, it accounts for huge economical deficits and contributes to the poverty cycle in many resource-limited countries.
Malaria is caused by the infectious Plasmodium parasite. Female Anopheles mosquitoes deposit parasite sporozoites into the skin of a human host whilst searching for blood. Sporozoites infect liver cells, and divide to become merozoites, which infect red blood cells once mature. Merozoites in turn develop into gametocytes, which are ingested by a mosquito collecting blood. Gametocytes mature in the mosquito’s gut to become sporozoites, and transmission to a human host repeats the cycle. Although five Plasmodium species are known to infect humans, P. falciparum is one of the most devastating forms.
Following the discovery of malaria transmission by mosquitoes in the late nineteenth century, efforts towards its eradication began. Means to treat and control malaria include the use of insecticidal nets to reduce transmission risk, but these lack effectiveness. A vaccine could offer a highly effective form of intervention, but challenges have hindered development.
For a start, the parasite’s transmission is incredibly complex. Several strains of the parasite have also arisen through evolution to overcome immune responses against it. Nevertheless, continued efforts over two decades, at a cost of £500 million to sponsors and donors, have enabled the development of the World’s first vaccine against a parasitic disease: RTS,S.
RTS,S, known by its trade name Mosquirix, uses antibodies to target proteins presented by sporozoites (such as the circumsporozoite protein of P. falciparum) to enhance the immune system and help prevent the parasite from infecting the liver. Mosquirix is also engineered using a hepatitis B viral protein and a chemical adjuvant to further boost the immune response for enhanced effectiveness.
Recently, the WHO announced that Mosquirix would be piloted in three African countries, Ghana, Kenya and Malawi, from 2018, and will be tested on more than 750,000 children aged between five and 17 months. Around half will be administered the vaccine in order to compare the real-world effectiveness of the jab. In this age group, four doses have been shown to prevent nearly four in ten cases of malaria. The vaccine also cuts the most severe cases by a third, and reduces the number of children needing hospital treatment.
Ghana, Kenya and Malawi were chosen for the pilot as they have comparatively high rates of malaria, as well as programmes already in place to tackle the disease. In turn, these countries will choose how to run the pilots, and in which regions. In particular, high-risk areas will likely receive priority, as these will allow experts to determine how beneficial the use of the vaccine is.
However, in clinical trials Mosquirix only proved partially effective, and the vaccine needs to be administered in a four-dose schedule: once a month for three months and then a fourth dose 18 months later. Whilst this was achieved in highly regulated clinical trials, it is uncertain whether the protective effect of Mosquirix can be replicated where access to healthcare is limited in the World’s poorest areas.
Nevertheless, Mosquirix presents an exciting step towards the eradication of malaria, and could save many lives. The pilots have also obtained large amounts of funding from a variety of organisations, further emphasising the importance of the vaccine; Mosquirix has been developed by GlaxoSmithkline (GSK) in partnership with the non-profit PATH Malaria Vaccine Initiative and the Bill & Melinda Gates Foundation.
Interestingly, Mosquirix somewhat dispels the criticism large pharmaceutical companies have rightly received for restricting access to medicines. Understandably, the cost of R&D needs to be recouped in order to promote future innovation. Mosquirix is, however, no longer patent protected. Whilst GSK will never gain return on investment, the company is bound by an ethical obligation to promote access to healthcare, ranking number 1 in the Access to Medicines Index, and will likely provide the vaccine at cost price to those in need.
Overall, Mosquirix is the most advanced candidate vaccine against malaria to date, and finally presents great hope against one of the World’s most devastating diseases.
Image credit: Pexels
You can read more in the latest edition of Pi Magazine (Issue 719, The Editor’s Edition)