9th International Conference on Plasmodium vivax Research (ICPvR) – 2025: Day 3

MESA Correspondents bring you cutting-edge coverage from the ICPvR 2025 “Plasmodium vivax: Science and tools for elimination”.

Session 9 – Diagnostics Unlocked: Omics, Single-Cell & Serological Advancements

Liliana Mancio-Silva (Institut Pasteur, France) discussed the unveiling biology of Plasmodium vivax hypnozoites with single-cell transcriptomics. Mancio-Silva highlighted gaps in understanding the molecular basis of dormancy, the need for better in vitro systems, and the importance of identifying specific biomarkers for hypnozoites. Using micropatterned co-cultures (MPCCs) of human hepatocytes, her team employed single-cell transcriptomics to uncover a 10-gene hypnozoite transcriptional signature. This research revealed that hypnozoites rely on transcriptional and translational repression to maintain dormancy and that proteolytic activity and RNA-binding proteins are essential for this process. Mancio-Silva also noted the role of the hepatocyte circadian rhythm in regulating the permissiveness to infection, suggesting that the timing of infection may influence parasite dormancy. These findings offer new insights into the host-parasite interactions that govern relapse and could lead to novel biomarkers and drug targets to prevent malaria relapse.

Ivo Mueller’s (Walter and Eliza Hall Institute of Medical Research – WEHI, Australia) talk focused on a novel serological approach for Plasmodium vivax testing and treatment, called PvSeroTAT. Muller discussed the challenge of hidden P. vivax infections, which hinder malaria elimination, and the importance of targeting this hidden reservoir. Serological markers can identify both current and past infections, with antibody responses helping to classify individuals with recent exposure. Mueller highlighted antigen genetic diversity’s limited impact on classification and antigen expression optimization for better efficacy. PvSeroTAT, a novel intervention, reduces overtreatment and resource use compared to mass drug administration (MDA). The strategy significantly impacts low transmission settings, reducing the risk of recurrent P. vivax infections by 53%. Seropositive individuals were found to be 7.5 times more likely to experience recurrence, while untreated seropositive individuals had a 19-fold higher likelihood of relapse. The approach includes risk stratification to target interventions effectively, alongside monitoring and evaluating ongoing malaria elimination programs.

Erica Pasini (Biomedical Primate Research Center, Netherlands) presented a study aimed at identifying new diagnostic targets for Plasmodium vivax hypnozoites. The study compared P. cynomolgi (a hypnozoite-forming parasite) and P. knowlesi (a non-hypnozoite-forming parasite) using optimized liver-stage cultures for metabolomics analysis. The study detected 567-653 metabolites in P. cynomolgi cultures and 513 metabolites in P. knowlesi. Nineteen hypnozoite-related metabolites were detected, and pathway analysis confirmed their relevance. The next step involves down-titrating P. cynomolgi infection in rhesus monkeys, collecting serum samples at different time points, and applying a sensitivity-based metabolomics approach to validate these metabolites for developing a rapid diagnostic test for hypnozoite infection in P. vivax.

Zach Popkin-Hall (University of North Carolina, United States) presented a study on high-throughput genotyping of Plasmodium vivax in the Peruvian Amazon using molecular inversion probes (MIPs). The study designed four MIP panels targeting geographically differentiating single nucleotide polymorphisms (SNPs), rare and common neutral SNPs, and genes of biological interest, including erythrocyte invasion ligands and antimalarial resistance orthologs. The panels were applied to 866 P. vivax infections, successfully genotyping 685 samples. Key findings included the identification of clonal transmission networks, copy number variation in key proteins, mutations in antimalarial resistance genes, and balancing selection in potential vaccine targets. Popkin-Hall emphasized the study’s importance, showing that MIPs can comprehensively assess genomic epidemiology in P. vivax, offering valuable insights for malaria control and vaccine development. 

Session 10 – Climate Change & Malaria: An Emerging Threat

Michael White (Institut Pasteur, France) delivered a comprehensive talk on mathematical modelling for measuring radical cure efficacy in Plasmodium vivax malaria. White explained that different perspectives influence efficacy measurements: biologists focus on hypnozoite clearance, clinical trial lists assess recurrence reduction, modellers estimate relapse rate reduction, and patients seek symptom resolution. White emphasized that transmission intensity affects efficacy estimates and highlighted challenges in distinguishing relapses from reinfections. He outlined three approaches to address this: relocating patients to areas without reinfection, genotyping recurrent infections, and applying mathematical models to clinical trial data. Using Bayesian statistical methods, White’s team analyzed data from Ethiopia, demonstrating that adherence to primaquine (PQ) and higher doses significantly improve radical cure effectiveness. White stressed the need for operational studies, including cluster randomized trials like PvSTATEM, to evaluate population-level impacts. White concluded by advocating for safe, widespread PQ use with G6PD testing to reduce malaria transmission and support elimination efforts, offering valuable insights into future strategy.

Isabel Byrne (London School of Hygiene and Tropical Medicine – LSHTM, UK) presented research on the spatial heterogeneity of Plasmodium vivax and its implications for randomized controlled trials (RCTs), using the PvSTATEM study as a case example. Byrne emphasized the influence of climate change on malaria transmission, noting P. vivax‘s broader environmental range due to temperature and elevation sensitivity. Byrne explained that cluster randomized trials (cRCTs), while the gold standard for population-level intervention evaluation, often fail to account for environmental and spatial factors during randomization. Her team applied geostatistical simulations using household PCR prevalence data from Ethiopia and Madagascar to assess spatial heterogeneity’s impact. Byrne demonstrated that vegetation and elevation significantly influenced malaria prevalence, with spatial models outperforming non-spatial approaches, and emphasized the need to consider environmental factors when interpreting trial results. Byrne explained that the study simulates environmental conditions to test randomization strategies and improve interventions, highlighting the need to consider climate-driven shifts in malaria transmission for effective control and elimination.

Sagar Pandhare (Indian Institute of Technology Bombay – IIT Bombay, India) presented a study on modeling malaria trends in Dhalai, Tripura, India, using climate data. Three approaches were explored for analyzing temporal patterns: additive decomposition, holt-winters exponential smoothing, and seasonal local regression; finding that seasonal regression provided the most accurate forecasts. The findings revealed that malaria cases peak during the monsoon, with major outbreaks in 2014 and high cases in 2018-2019. Ridge regression identified temperature, normalized difference vegetation index (NDVI), and humidity as key factors influencing malaria trends. Pandhare emphasized the importance of continuous monitoring and predictive modeling to enhance malaria control and facilitate early prevention strategies.

Closing remarks

The 9th International Conference on Plasmodium vivax Research 2025 (ICPvR 2025) successfully concluded in Ocean Spray, Puducherry on February 14, 2025, after three days of impactful discussions and research presentations. The feedback received from the delegates indicated that the Conference was rich in scientific content with ample opportunities for cross-talks and networking between groups working in different domains.  The closing ceremony recognized leading malaria researchers, oral sessions and poster participants, and key contributors, with awards presented for best turbo talks and poster presentations, along with special acknowledgments for young and distinguished researchers. Dr. Manju Rahi, Director, Indian Council of Medical Research–Vector Control Research Centre (ICMR-VCRC) and Convenor of ICPvR 2025 expressed gratitude to the international and national scientific committees, sponsors (BMGF and ANRF) and organizing teams from ICMR-VCRC for their support and thanked all participants for their contributions. The conference officially concluded with the announcement of ICPvR 2027, which will be held in Peru, continuing efforts toward malaria elimination. With renewed enthusiasm, participants bid farewell, looking forward to future collaborations and advancements in malaria research.