Rapid Fire Presentation 8th International Conference on Plasmodium vivax Research 2022

Assessment of IgG3 as a Serological Exposure Marker for Plasmodium vivax Malaria in Moderate Endemic Areas  (#318)

Yanie Tayipto 1 2 , Jason Rosado 3 , Dionicia Gamboa 4 , Herbert Opi 5 , James Beeson 5 , Leanne Robinson 5 , Ivo Mueller 1 2 , Rhea Longley 1 2
  1. Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
  2. Medical Biology, University of Melbourne, Melbourne, Victoria, Australia
  3. Unité Malaria: Parasites et Hôtes, Département Parasites et Insectes Vecteurs, Institut Pasteur, Paris, France
  4. Laboratorio ICEMR-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru
  5. Burnet Institute, Melbourne, Victoria, Australia

A more sensitive surveillance tool is needed to accelerate the elimination of Plasmodium vivax. P. vivax infections result in low parasitemia, which may not be detected using parasite detection tools. To address this challenge, our laboratory has developed an 8-antigen panel that detects total IgG as serological markers of P. vivax exposure within the prior 9 months. These markers have been validated for use in low endemic areas. In moderate-high endemic areas, there is evidence that total IgG is more long-lived, causing less optimal performance of these markers, so antibodies that are more short-lived may be better markers in moderate endemic areas. Using a multiplex assay, antibody kinetics of total IgG, IgG1, IgG3, and IgM against 29 P. vivax antigens were measured over 36 weeks following asymptomatic P. vivax infection in Papua New Guinean children (n=33). IgG3 declined faster to background than total IgG, IgG1 and IgM. Based on these kinetics, IgG3 performance were then assessed in classifying recent exposure in a cohort of Peruvian individuals (n=590). The highest sensitivity and specificity of IgG3 tested was 70% in classifying recent P. vivax infections in the prior 9 months, while total IgG reached higher sensitivity and specificity, around 80%. To understand the acquisition and decay of IgG3 in this cohort, relevant epidemiological factors were explored using a regression model. IgG3 levels were associated with age, living in a higher endemic area, and having three or more blood stage P. vivax infections within the last 13 months. The accuracy of serological markers is affected by the acquisition of antibody and not just the longevity, and our results suggest high levels of exposure are required for a sufficient IgG3 response.

  1. Longley RJ, White MT, Takashima E, Brewster J, Morita M, Harbers M, Obadia T, Robinson LJ, Matsuura F, Liu ZSJ et al. (2020) Development and validation of serological markers for detecting recent Plasmodium vivax infection. Nat Med. 26(5):741-749.
  2. Rosado J, White MT, Longley RJ, Lacerda M, Monteiro W, Brewster J, Sattabongkot J, Guzman-Guzman M, Llanos-Cuentas A, Vinetz JM et al. (2021) Heterogeneity in response to serological exposure markers of recent Plasmodium vivax infections in contrasting epidemiological contexts. PLOS Neglected Tropical Diseases. 15(2):e0009165.