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Malaria is a disease caused by four species of the protozoan Plasmodium and is transmitted by the bites of infected mosquitoes, killing over 2 million people every year. Plasmodium falciparum is the most serious and common cause of the disease. The development of a safe and effective malaria vaccine would be a necessary component of a widespread malaria control strategy. A number of malaria vaccines are currently undergoing intensive research, however, only a few have reached advanced stages of clinical evaluation. Different stages of the complex life cycle of malaria can present a number of potential targets for vaccines. We discuss existing control strategies and the current state of malaria vaccine development against each stage of life cycle. We analyse and compare the most advanced vaccines in clinical development, focusing on their safety, immunogenicity, and clinical efficacy. Having analysed alternative strategies we evaluate which malaria vaccine strategy is the best, and whether a combination of vaccines or alternative strategies is the best way forward.
Malaria is associated with considerable morbidity and mortality worldwide. Malaria is most often transmitted from human to human by the bites of female Anopheles mosquito which is infected with a malaria parasite. The causative agents in humans are four distinct species of Plasmodium protozoa: P.falciparum, P. vivax, P. malariae and P. ovale. Out of these, P.falciparum is responsible for most of the infections and is the most deadly. Malaria has a major effect on social and economic growth, trapping families and communities in a descend of poverty. In many parts of the world, the parasites have developed resistance to a number of antimalarial drugs, and mosquito vectors have developed resistance to insecticide. This has resulted in the re-emergence of malaria. Thus the development of a malaria vaccine is urgently needed for the effective control of malaria. We will discuss why malaria vaccines are required, and the existing control strategies and how effective they are. We explain the life cycle of malaria and how each stages of the cycle can be targeted by vaccines. Having assessed the malaria vaccines being developed, we mainly focus on the vaccines that have reached the advanced phases of clinical trials, by evaluating and comparing their features, functions, safety, immunogenicity, and clinical effectiveness. Ultimately, on the basis of this evaluation, we determine which vaccination strategy is best in terms of offering protection and reducing malaria-related morbidity and mortality, and evaluate whether the combination of vaccines and alternative strategies is the best way forward in controlling malaria.
Why are vaccines needed?
Along with tuberculosis and HIV/AIDS, malaria is thought to be one of the â€˜big threeâ€™ infectious killers in the world today, as it is associated with significant morbidity and mortality. The World Health Organization (WHO) estimates there are 300 to 500 million clinical cases of malaria per year leading to 1.5 to 2.7 million deaths worldwide. Approximately 40% of the world's population are at risk in about 90 countries and areas in Asia, Africa, South and Central America; sub-Saharan Africa being the most affected area. Children under the age of five are most susceptible to malaria and every 30 seconds a child dies from malaria. There are four human malaria strains, but P.falciparum is primarily responsible for ~95% of malaria deaths with a mortality rate of 1 to 3% worldwide. Pregnant women and travellers from malaria-free areas to malaria-endemic areas are also vulnerable to the disease. (WHO, 2009)
Malaria has recently returned to regions where it was believed to have been eradicated and it is a re-emerging disease. This situation may have arisen due the increasing resistance of the malaria parasite to general antimalarial drugs. In addition, many insecticides that were once useful in repelling mosquitoes are now ineffective in many malaria endemic areas because the malaria vector (mosquito) is developing resistance to insecticides. Drug resistance has become one of the greatest challenges in treating malaria. Another factor for the re-emergence of malaria is the migration of refugee populations from non-endemic areas into malaria endemic regions (26). Also, because of environmental changes (e.g. atmospheric carbon accumulation) malaria transmission are now more prevalent. This situation was made worse by weak national control strategies, planning problems, unsuccessful use of resources, and poor health-care facilities (27, 28).
â€œIn Africa today, malaria is understood to be both a disease of poverty and a cause of povertyâ€ (WHO, 2009). Malaria is a major barrier to economic development. Endemic countries with widespread malaria consistently show low economic growth every year compared to those countries free from the disease. About 40% of public health expenditures are provided for the prevention and control of malaria in some endemic areas of Africa. For all these all reasons, the development of a safe, effective malaria vaccine could be promising strategy for reducing the disease burden and save millions of lives. The vaccine strategy could also provide a cost-effective intervention for addition to the existing malaria control strategies.