Recent advances and new challenges on malaria
The recent introduction of vaccines has not yet closed the door on malaria, a disease that killed more than 600,000 people in 2022.
Malaria: 250 million people infected in 2022
During vacations, the desire to travel is strong. But often extraordinary places, from the naturalistic, artistic, cultural and human point of view, pose some extra risks to our health. Especially when massive is the presence of mosquitoes.
Malaria is still a major challenge for health systems worldwide. Malaria is present in large parts of Africa, the Indian subcontinent, South East Asia, Latin America and parts of Central America. 40% of the world's population lives in areas where malaria is endemic. According to the World Health Organisation (WHO), almost 250 million people were infected in 2022 and more than 600,000 people, mainly children under five years of age, died from the disease.
Most infections occur in sub-Saharan Africa. Despite considerable and continuing progress in controlling the infection, recent years have seen not only a plateau in progress, but also a reversal of the trend, with malaria cases increasing again.
Malaria is caused by the Plasmodium parasite, transmitted by infected female Anopheles mosquitoes. There are several Plasmodium species that infect humans: P. falciparum is the most deadly. P. vivax, which causes relapsing malaria, is more widespread geographically, especially in Asia and South America.
Symptomatology consists of fever, chills and flu-like symptoms. This condition can evolve into severe malaria, leading to complications such as organ failure, anaemia and death. Although many individuals in endemic regions develop some degree of immunity, this is not long-lasting and offers limited protection against the more severe forms of the disease.
Malaria vaccines
In recent years, malaria vaccines have been developed that give hope for better infection control in the future. In 2021, WHO first recommended a malaria vaccine, RTS,S/AS01 (RTS,S or Mosquirix), after an extensive trial in sub-Saharan Africa. More recently, in 2023, the R21/Matrix-M vaccine, which showed a higher efficacy rate in clinical trials, was pre-qualified by the WHO. These vaccines target Plasmodium falciparum in its liver stage, preventing the parasite from reaching the bloodstream and thus reducing the severity of the disease.
Although both vaccines have shown promising results, the fight against malaria is not yet over due to several problems, including different levels of efficacy in different populations and the need for multi-dose programmes. Moreover, current vaccines do not provide complete protection, so there is concern that they may not be able to completely prevent transmission of the disease. According to some studies, the spread of partially effective vaccines may increase the virulence of the pathogen. This raises doubts about their long-term effectiveness.
Malaria vaccines with whole sporozoites
Malaria vaccines with whole sporozoites (WSpz) are based on the administration of Plasmodium sporozoites, the infectious liver forms of malaria parasites, as immunising agents. To prevent the development of the symptomatic blood stage of infection after inoculation of the vaccine, the parasites can be attenuated by irradiation (radiation-attenuated sporozoites, RAS) or genetic modification (genetically attenuated parasites, GAP), or be administered under the prophylactic coverage of a drug such as chloroquine, which specifically targets the erythrocytic stages of the parasite.
These WSpz vaccines have shown variable efficacy, influenced by factors such as previous exposure to malaria, immune status and age. In particular, the PfSPZ vaccine, which uses radiation-attenuated Plasmodium falciparum sporozoites, has shown great promise in clinical trials. A study published in “Nature” in 2024 showed that the vaccine provides protection against malaria even in malaria-endemic regions.
The development of genetically modified Plasmodium parasites, such as the transgenic Plasmodium berghei expressing antigens of P. vivax, further increases the prospects of a dual-species vaccine offering protection against both major malaria parasites.
Treatment approaches
The treatment of malaria has evolved significantly over the years. Artemisinin-based combination therapies (ACTs) remain the gold standard for the treatment of P. falciparum malaria. These therapies combine artemisinin derivatives with other antimalarial drugs to increase efficacy and prevent resistance. For severe malaria, intravenous artesunate is the most suitable treatment, although quinine can be used as an alternative.
Despite the efficacy of ACTs, challenges such as drug resistance, particularly in Southeast Asia, pose a significant threat to future treatment options. The emergence of resistance highlights the need for continued monitoring and development of new antimalarial drugs.
The future of prevention and control
While the introduction of vaccines is an important step forward, their dissemination will require overcoming operational challenges such as supply chain issues, population acceptance of the vaccine, and the need for robust health systems. In addition, continued research into new vaccines and treatments, as well as strategies to combat drug resistance, will be critical to ensuring that malaria remains preventable and treatable.
Prevention strategies are essential in malaria endemic areas. The use of insecticide-treated mosquito nets (ITNs) and indoor residual spraying (IRS) of all homes in malaria endemic districts have significantly reduced malaria transmission. Chemoprevention strategies, such as seasonal malaria chemoprevention (SMC) in children, have also proven effective in areas with high transmission rates. Integrating malaria vaccines with these existing interventions is critical to maximize the impact of malaria control programs. Research is ongoing on optimal delivery strategies for these vaccines, either through routine immunization or targeted campaigns.
As climate change accelerates, the geographic distribution of malaria may change, requiring adaptation strategies for prevention and treatment in new areas. Continued investment in malaria research, combined with strong political and financial commitment, will be critical to mitigating the spread of the disease as much as possible.
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