Malaria Elimination: Efforts & Challenges  

Context: The World Health Organisation (WHO) has officially certified Georgia as Malaria-free. Despite decades of global efforts, Malaria still causes over 240 million cases and more than 600,000 deaths annually.

Relevance of the Topic:Prelims: Key facts about Malaria; Malaria vaccines; CRISPR and Gene Drive. 

About Malaria

• About: Life-threatening disease caused by plasmodium parasites transmitted to people through the bites of infected female Anopheles mosquitoes.
• Transmission: Through blood transfusion, organ transplant, shared use of needles or syringes contaminated with blood, because malaria parasite is found in red blood cells of an infected person.
• Types: There are 5 parasite species that cause malaria in humans, and 2 of these species: Plasmodium falciparum and Plasmodium vivax pose the greatest threat.
  • Vivax plasmodium is known to hide in the liver and cause recurrent infections.
• Symptoms: Fever, chills, sweats, headaches, muscle aches, and fatigue. In severe cases, it can lead to complications such as organ failure and death.
• Diagnosis: Through blood tests.
• Antimalarial medications: Chloroquine, artemisinin-based combination therapies (ACTs), but drug resistance is a growing concern.
• Prevention: To control the vector, insecticide-treated bed nets (ITNs) are used by endemic countries.
• Vaccine: RTS,S/AS01 (brand name Mosquirix) and R21/Matrix M.
• Path to malaria eradication:
  • By WHO: Reducing case incidence and mortality rates by 75% in 2025 and 90% in 2030. 
  • By India: Malaria-free by 2027 and to eliminate the disease by 2030.

Malaria parasite’s life-cycle

• An infected Anopheles mosquito bites a human, injecting Plasmodium sporozoites that are highly infective into the bloodstream. 
• These parasites first travel to the liver, invading liver cells and multiplying undetected by the immune system. 
• After this phase, they re-enter the bloodstream, infecting red blood cells and causing malaria’s characteristic fever and chills. 
• The parasite multiplies asexually within RBCs, however, some develop into sexual forms known as gametocytes, which are then taken up by another mosquito when it bites an infected individual. 
• Inside the mosquito, these gametocytes undergo sexual reproduction, maturing into sporozoites that migrate to the mosquito’s salivary glands, making the mosquito infectious to new human hosts. 

Challenges in developing a universal Malaria Vaccine: 

• Deception to evade Immune system: 
  • Plasmodium is a protozoan parasite and eukaryotic organism with multiple stages of development, each featuring different surface antigens. The Malaria parasite masters deception, evading the human immune system.
    • Its greatest strength is antigenic variation, where it frequently changes its surface proteins, making it difficult for immune cells to recognise it and respond.
    • Plasmodium follows an intracellular lifestyle, hiding within the liver and RBCs, shielding itself from immune surveillance. 
  • This ability to evade detection weakens the body’s ability to develop long-lasting immunity, making reinfection common. 
• Adaption and Evolution:
  • Malaria’s life cycle spans multiple stages across two hosts—humans and mosquitoes. So when a vaccine is developed, the parasite’s genetic adaptability enables it to evolve resistance. 
  • When scientists find a way to combat one strain, the parasite alters its proteins and genetic structure to bypass immunity. The adaptability makes it difficult to develop a universal and long-lasting vaccine.

Malaria vaccines

• RTS, S malaria vaccine (brand name Mosquirix) was the first to receive WHO approval for large-scale rollout in endemic regions after 60 years of research.
  • It targets the liver stage of the parasite’s life cycle. However, its efficacy is limited, reducing malaria cases by approximately 36% after four doses over four years in children. 
  • RTS, S requires multiple doses, posing logistical challenges in resource-limited regions.
• Second-generation malaria vaccines:
  • R21/Matrix-M vaccine is one second-generation malaria vaccine which enhances the immune response and has shown 77% efficacy over 12 months. 
  • PfSPZ vaccine is a whole-parasite vaccine that attenuates Plasmodium sporozoites to stimulate immunity against the liver stage of infection. 
  • RH5-based vaccines prevent Plasmodium from invading red blood cells and target the blood stage after symptoms. 
  • Transmission-blocking vaccines aim to halt the spread of malaria by preventing mosquitoes from becoming carriers.

CRISPR and Gene Drive: Global fight for Malaria

• Under normal law of inheritance, a specific trait from an organism has a 50/50 chance to be passed. (Offspring inherit one copy of each gene from each parent, resulting in a random chance of expressing either mother’s version or father’s version)
• Gene Drive is the use of gene-editing techniques to alter the law of inheritance to pass on a particular genetic trait from one generation to the next generation, faster than the normal rate.
  • This is achieved by editing a particular gene in a way that it can copy and paste itself into its corresponding location on the other chromosome, instead of the 50/50 inheritance pattern that occurs naturally. 
  • This copying and pasting occurs during the production of reproductive cells (sperm or egg), resulting in a higher probability that the gene will be passed down to the next generation. 

• CRISPR is being used to edit a gene called ‘doublesex’ in female mosquitoes which are the main transmitters of Malaria. 
• When the female mosquitoes inherit two copies of the disrupted gene, they develop like males and are unable to bite or lay eggs.
• This genetic tweak of double-sex gene follows gene drive inheritance. With this, in 8 generations female mosquitoes are completely eliminated.

Malaria is a neglected tropical disease (i.e, mainly prevalent among impoverished communities in tropical areas). Malaria vaccine research has long suffered from underfunding. Countries risk resurgence of Malaria due to shifting mosquito habitats. 

An effective malaria control strategy will require a combination of more efficient vaccines, mosquito control & improved treatment options.