The parasite causing malaria, Plasmodium spp., was discovered in 1880 by Sir Charles Louis Alphonse Laveran. Soon after its discovery followed the vector responsible for the transmission of the parasite, when Sir Ronald Ross managed to incriminate mosquitoes in the transmission of malaria, particularly avian malaria.
Subsequently, an Italian group of scientists described the human malaria between the years 1898 and 1900. Recent studies have demonstrated the possibility of malaria being one of the world’s oldest diseases based on the malaria antigen detected in an Egyptian remains dating from 3200-1304 BC. Moreover, the Indian writings of the Vedic period (1500-800 BC) referred to malaria as the “King of diseases” based on the severity, distribution, and the long-surviving status of the disease.
According to the NCBI (2004), 150 to 300 million lives have been lost to malaria in the 20th century, which only counted for 2-5% of the deaths. To date, malaria’s chief sufferers are the poor of sub-Saharan Africa, Asia, the Amazon basin, and other tropical regions. Approximately 40% of the world’s population still live with malaria. Malaria has been infecting and killing people for centuries, yet the first malaria vaccine was only approved by the World Health Organisation (WHO) in October 2021.
Prohibited vaccine production
The search for a vaccine against Plasmodium spp. has been under development since the 1960s as a means to mitigate the negative impact of malaria on the health and economic status of more than 36 African countries affected by the disease. However, the efforts put into developing a malaria vaccine have yielded no tangible product. This was attributed to several obstacles encountered during the process, hence most of the developed vaccines could not go beyond phase 1 testing. Obstacles and challenges faced by malaria vaccine developers included:
Plasmodium parasites have a complex life cycle and there is a poor understanding of the complex immune response to malaria infection. Effective vaccine production requires a total understanding of the complete life cycles, the different cell types produced by the parasite in the host as well as the immunological response of the host to each cell type.
Moreover, the parasites are also genetically complex, producing thousands of potential antigens. Plasmodium parasites make use of an antigenic variation mechanism to evade the host’s immune response and therefore, establish the chronic stage of infections in the host. With this process, the parasites actively modify the expression of variant surface proteins, Plasmodium falciparum erythrocyte membrane protein 1 or PfEMP1 (proteins present on the membrane surface of the infected cells), to remain invisible to the adaptive immune system. According to El-Moamly and El-Sweify (2023), Plasmodium parasites’ genetic make-up consists of 5 400 coding. Antigenic variation allows the parasites to periodically express a different surface antigen to the immune system, therefore evading the clearance of a specific antibody. This variation can happen 5 400 times which results in the exhaustion of the immune system.
Lastly, unlike the diseases for which we currently have effective vaccines, exposure to malaria parasites does not confer lifelong protection. Acquired immunity only partially protects against future disease, mainly due to genetic diversity, pathophysiological complexity and parasite evasion mechanisms employed by the parasite to remain undetected by the host’s immunity.
Main types of vaccine candidates
Three types of vaccine candidates have been intensively investigated. The pre-erythrocytic (anti-infection) vaccines to prevent infection of the liver cells by the sporozoites and the red blood cells by the merozoites from the liver. Secondly, the blood-stage vaccines to clear parasitemia and prevent clinical disease in the infected red blood cells. And lastly, the transmission-blocking vaccines to prevent infection by mosquitoes and interrupt malaria transmission in populations.
Vaccine options for preventing Plasmodium infection
There are currently two vaccines developed for the prevention of malaria or Plasmodium infection, RTS,S (trade name MosquirixTM) created in 1987 and approved in October 2021, and R21, that is currently undergoing Phase III clinical trials. The commercialisation of the RTS,S vaccine is considered the biggest achievement in the medical field after years of development. The efficacy of RTS,S granted the opportunity for the development of a better vaccine, the R21. According to Dzi (2023), four doses of RTS,S resulted in a 39% reduction of cases of uncomplicated malaria, and 30% reduction was reported in severe cases, whilst the R21 resulted in 75% reduction in the following a three-dose series. Nonetheless, the WHO has advised against the replacement of RTS,S with R21 but instead suggested that the two options can complement each other. Moreover, they both induce a compatible immune response.
Both RTS,S and R21 form part of the pre-erythrocytic (anti-infection) option. Mosquitoes inject few sporozoites (0-100) during a single blood meal before multiplying, which makes this stage the ideal target stage for vaccine production. Moreover, the skin of the host possesses effective means for the reduction of the injected sporozoites, therefore reducing chances of liver cell infection by 50%.
Countries start rolling out vaccines
African countries with heavy annual burdens of malaria such as Ghana, Mali, Burkina Faso, Nigeria, Kenya and Malawi already started vaccine roll-out with the RTS,S vaccine from 2021. Ghana’s Food and Drug Authority has assessed the progress of the R21 vaccine trial and reached a decision to approve it for use in children aged 5-36 months who are at a greater risk of the infection. According to Joi (2023), the results for phase III trial of R21 from 4 800 children in Burkina Faso, Kenya, Mali and Tanzania are expected to be published soon.
South Africa and malaria
Malaria in South Africa dates back to 1837 and 1838 with epidemics and outbreaks recorded in Durban (1905) where 44 people died; Gordonia, Kenhart and Upington (1906) which resulted from the flooding of the Orange River, and a localised outbreak in Durban (1918), which is presumed to have been initiated by a group of Indians returning from East Africa. This signals the possibility of outbreaks and/or epidemic in South Africa, if relevant preventive measures are not taken into account. Furthermore, global warming has the potential to exacerbate the current malaria conditions in the country. Anopheles mosquitoes develop optimally between 17-35°C, warmer temperatures will present various challenges such as faster mosquito development, increased bites, invasion of new locations and the faster spread of the vector-borne diseases. On the contrary, higher temperatures may result in the change of the malaria season in the country because summer seasons will be too high for the survival of the mosquitoes, while winter could end up warm enough to cater for the breeding and development of the Anopheles mosquito. Furthermore, South Africa is currently experiencing a La Niña cycle which provides perfect conditions for the survival of the mosquitoes.
In conclusion, the successful development of the two vaccines is the greatest breakthrough in the malaria field after a considerable number of attempts without any results. Nonetheless, the presence of vaccines does not suggest that the traditional methods should be disregarded. Case management, epidemiology, distribution, vector control, prophylaxis or preventive treatment and consistent surveillance of the disease should continue.
Opinion article by Dr Nthatisi Molefe-Nyembe, Lecturer: Department of Zoology and Entomology, University of the Free State.
