Malaria’s new frontlines

Malaria control in India has entered a decisive phase, powered by vaccine breakthroughs and innovation. Yet, persistent tribal hotspots and policy gaps challenge the 2030 elimination goal.

Relevance : GS 2(Health , Governance)

India’s Progress & Persistent Challenges

Achievements:

• >80% reduction in malaria burden between 2015–2023.
• National ambition: Elimination of malaria by 2030.

Persisting Hotspots:

• Tribal districts still highly affected:
  • Lawngtlai (Mizoram): 56+ cases/1000 people.
  • Narayanpur (Chhattisgarh): 22+ cases/1000 people.
• Mixed infections: In Jharkhand, 20% of cases involve both P. falciparum & P. vivax.
• Asymptomatic carriers: Silent transmission even in low-incidence zones.

 Malaria Parasites in India

• P. falciparum (Africa-dominant): More lethal.
• P. vivax (Asia-dominant): Dormant liver stage → late relapses.
• P. cynomolgi (monkey malaria): Crucial research model for P. vivax, but underutilized in India.

First-Generation Vaccines

1. RTS,S (Mosquirix)

• Approved in 2021.
• Protection: ~55% initially, wanes in 18 months.
• Requires 4 doses.

2. R21/Matrix-M (Oxford–Serum Institute)

• WHO-approved in 2023.
• Up to 77% efficacy in Phase 3.
• Low-cost, fewer doses, room-temperature stable → ideal for India.

Limitations of Current Vaccines

• Target only one life stage (pre-erythrocytic).
• Vulnerable to reinfection and continued transmission.
• Need for multi-stage or whole-parasite strategies.

Next-Gen Vaccine Approaches

A. Whole-Parasite Vaccines

• PfSPZ (Sanaria):
  • Uses radiation-weakened sporozoites.
  • 96% antibody response, up to 79% protection after 3 doses.
• PfSPZ-LARC2:
  • Modified version with potential for single-dose use.
  • Targeted use in outbreaks/migrant populations.

B. Blood-Stage Vaccines

• PfRH5:
  • Blocks red blood cell invasion.
  • Strain-transcending protection.
  • Promising Phase 1a/2b trials in UK, Gambia, Burkina Faso.

C. Transmission-Blocking Vaccines (TBVs)

• Pfs230D1 (Mali):
  • Blocks fertilization in mosquito gut.
  • 78% reduction in transmission (Phase 2).
• India’s TBV candidate – AdFalciVax:
  • Combines PfCSP + Pfs230/Pfs48/45.
  • Completed preclinical testing in 2025.
  • Mice: >90% protection with long immune memory (4+ months).
  • Room temp stable (9 months) → ideal for rural India.
• P. vivax TBV (Pvs230D1M):
  • First human trial in Thailand: up to 96% transmission reduction.

Immune Boosting & Novel Platforms

Protein-Based Innovations

• Ferritin nanoparticle + CpG adjuvant:
  • Cut liver-stage parasite burden by 95% in mice.
• PfCSP–MIP3α fusion:
  • Enhances antibody + T-cell response.
  • Reduced infection by 88% in mice.

mRNA-Based Platforms

• Pfs25-mRNA (CureVac + NIH):
  • Complete transmission block in mice.
  • Antibodies lasted 6+ months after 2 doses.
• BNT165e (BioNTech):
  • Blood-stage mRNA candidate.
  • Trial paused by FDA in 2025.

Parasite Evasion & Immune Engineering

• RIFIN proteins bind to LILRB1 receptors, silencing immune cells.
• Antibody D1D2.v-IgG (India):
  • Binds RIFIN 110x stronger than natural receptor.
  • Restores immune response in lab tests.

Vector Control Innovations

CRISPR Gene Drives

• Fertility-suppressing drives:
  • Eliminated entire Anopheles gambiae colonies in lab within a year.
• FREP1 gene edit:
  • Blocks parasite growth inside mosquito.
  • Spread to 90% of lab mosquitoes in 10 generations.

Smart Mosquito Designs

• Engineered to die early if infected → self-limiting transmission.
• Prevents ecological disruption by preserving uninfected mosquito populations.

Institutional & Policy Gaps

Key Challenges:

• Lack of:
  • Trained doctors,
  • Surveillance for resistance, and
  • Robust vector control systems.
• India’s P. vivax research underutilised due to:
  • Restricted monkey access, outdated priorities.

Steps Ahead:

• ICMR Expression of Interest (2025):
  • For industrial partners to co-develop AdFalciVax.
• Critical needs:
  • GMP-grade production, immune biomarkers, and efficacy benchmarking vs RTS,S & R21.

Takeaways