Advancements in Malaria Prevention and Vaccination
Malaria is a life-threatening disease caused by Plasmodium parasites transmitted through infected mosquitoes. It disproportionately affects vulnerable populations in 91 countries, particularly in Africa. Malaria is associated with poverty and hinders economic development.
It is an emergency in endemic countries. Anopheles mosquitoes spread the parasites, with Plasmodium falciparum causing the majority of severe cases. Environmental and socioeconomic factors affect transmission rates. Symptoms include fever, headache, chills, and vomiting. Malaria can lead to anaemia and fatal illness if untreated. It also contributes to child mortality and neurological complications.
Current Strategies for Malaria Prevention
Existing strategies to prevent malaria transmission are based on the reduction of infection rates, either to zero or to a level that will decrease clinical cases, mortality, or transmission. Among the preventive tools available today, two of the most successful are insecticide-treated nets and indoor residual spraying. Insecticide-treated nets, which are malleable netting materials with a pyrethroid insecticide incorporated within them, can protect people from mosquito bites when sleeping.
They can reduce the number of mosquitoes that bite as well as impact mosquito feeding and death. On the other hand, indoor residual spraying involves applying insecticides to the interior walls of housing, resting shelters, or animal shelters. This practice is effective for controlling the mosquito population that transmits the parasite if a high percentage of spray coverage is sustained by the intervention.
Public health campaigns, involving community engagement and education, have also shown value in keeping mosquitoes farther from houses. Another environmental practice, such as habitat manipulation or management, can decrease vector reproduction by making human-made breeding sites unavailable or irregular for malaria-transmitting mosquitoes.
Practically, genetically modified mosquitoes that have a late expression of dominant lethal genes by lineage, an endosymbiotic bacteria, or a Wolbachia strain have the potential to decrease vectorial capacity, thereby significantly reducing malaria transmission. Where vectorial capacities are high, it is also recommended that people at risk of malaria take preventive medicines.
Preventive strategies that are evidenced to work and are in routine use include intermittent preventive treatment for pregnant women and infants, increasing the doses of antimalarial treatments for individuals to block infections in pregnant women and babies, and pre-exposure prophylaxis with medicines and vaccines for all populations at risk.
Development of Malaria Vaccines
Much research has gone into understanding the host response to malaria to guide therapeutic strategies. This includes efforts related to the development of a vaccine to prevent infection, as it has been a long-established strategy for other infectious diseases. Malaria vaccines primarily aim to prevent the blood-stage infection or at least kill the parasite promptly upon infection.
Although an effective vaccine could eliminate asymptomatic and symptomatic infections, primarily through herd immunity as seen with vaccination against measles, it is unlikely that a vaccine will completely block transmission.
Several malaria vaccine candidates have been developed, but one in particular has advanced to the furthest stage of clinical development. The most advanced vaccine targets the CSP protein of P. falciparum, expressed on the sporozoites as they enter the human bloodstream. At the time of the first pilot implementation evaluation of the vaccine, more than two crore doses of the vaccine had been administered to young children. During the Phase III trial, immunization with the vaccine reduced malaria by 28% in children aged 5–17 months and by 18% in infants 6–12 weeks old; up to four in 10 cases were prevented. The efficacy did decline over time, and a booster dose was administered to the children through this project.
There is a need for vaccine strategies that induce a long-lasting and protective immune response in young children living in malaria-endemic areas. Opportunities exist to enhance vaccine design through better application of technologies that generate genetic information and inform novel research efforts that aim to better characterize the immune response needed to prevent and rapidly clear liver-blood stage parasites. Public and private partnerships have been critical to malaria vaccine development.
A multi-donor-supported vaccine portfolio has been aligned with global partners to accelerate the development of the first-generation malaria vaccine and develop projects for the next generation of malaria vaccines. In addition, collaboration with relevant countries and partners has engaged stakeholders, addressed program requirements, increased public awareness, and managed issues related to the demand, use, access, and equity of the vaccine in the first pilot implementation program. Such initiatives have facilitated the effective use of complementary funding while ensuring a diverse portfolio of candidates that can trigger contributions on both cost and risk to government funders and also reduce timeline delays arising from technical hurdles.
These combined efforts have provided funding to address multiple co-funded opportunities and landscape preparation activities which are key to ensuring that the future vaccine can be developed. The close collaboration and coordination between key players targeting differently conceived vaccines ensure that the roadmap for malaria vaccine development will provide efficient and targeted guidance. These projects pave the way to accelerate the publication of independently generated vaccines developed in the first decade of the 21st century, particularly in the event of emerging drug resistance.
Challenges and Future Directions in Malaria Prevention and Vaccination
Resistance against anti-malarial drugs and insecticides represents the most important challenge to sustaining the successes of current control and elimination programs. Currently, available chemopreventive and clinical drugs rely on only a few classes, and a single class of insecticide is used for long-lasting insecticide-treated nets and indoor residual spraying worldwide.
Given historical experiences, it seems obvious that slowly decreasing drug and insecticide efficacies or other forms of assumption failure will result. Limited access to healthcare is one of the cornerstones of malaria transmission. The chances of being well-protected from the disease in high-income countries are minimal, but a person living in a low-income country is far more likely to contract malaria.
Given that a significant portion of infections are actively managed, it is reasonable to assume that some causes for morbidity and mortality are linked to the variations of healthcare systems and personal healthcare behaviours seen across different geographic regions. Unfortunately, only a fraction of the basic healthcare needs are being met; funding for healthcare in low-income settings per capita is disproportionately low compared with spending on healthcare in high-income countries.
To sustain malaria control and ultimately eliminate the disease, new ways of managing malaria vectors and controlling Plasmodium transmission need to be harnessed. Global changes such as climate change are increasingly recognized as important components of the puzzle, and the identification of local solutions is also crucial to slow down and reverse the global march of malaria. Integration of new technologies into broader control programs is essential, requiring further research and collaboration among stakeholders to ensure efficient investments and to generate a system that is sustainable in the long term.
The goals and recent progress in vaccine development or scenarios targeting partial protection, transmission-blocking vaccines, the potential closing of the vaccine, the necessity for novel vaccines, and recent developments are all good examples of useful scenarios that can be used. Full malaria eradication or World Health Organization targets for malaria is unlikely to occur without a global commitment and the ability to make substantial investments to find alternative, sustainable means to control or eliminate malaria.
