Monitoring the continued absence of local transmission on border regions of Yunnan Province using novel serological markers of exposure to P. vivax infections

This joint PhD project will be based at the Shanghai Jiao Tong University with a minimum 12 month stay at The University of Melbourne. Please note the deadlines associated with SJTU admission eligibility and requirements.

Project description
Yunnan Province was the last malaria area in China. Given it borders endemic areas in Myanmar and Laos, monitoring of introduced infections is essential to keep it malaria free. We recently developed serological markers that detect recent exposures to P. vivax with high precision. Here, we will transfer this assay to SJTU and confirm its ability to detect foci of local transmission using archival samples collected pre- and post-elimination, before prospectively applying it in ongoing case investigations in Yunnan. This laboratory and epidemiological project aims to confirm the use of serology for confirming the absence of local transmission.

The malaria elimination program in Yunnan offers a unique opportunity to both validate the existing serological markers of exposure for the certification of elimination as well as explore their use in the investigation of cases of malaria re-introduction and suspected local transmission.

Overall aim

Validate the use of serological markers of exposure to P. vivax to document the absence of local transmission in Yunnan.

Objectives

  • Transfer the P. vivax serological marker assay to SJTU/ NIPD
  • Explore the utility of these markers to determine the decrease and eventual absence of local transmission in population in the border region of Yunnan.
  • Develop diagnostic algorithms with improved specificity in elimination settings.
  • Apply the markers to confirm the absence or not of local transmission in case investigation of suspected malaria cases.

Approaches

  • Laboratory assay: Antibodies to our serological marker panel are measured using a highly multiplexed assay using the Luminex MagPIX system, which can measure titres to up to 50 antigens in as little 1ul of plasma or serum. In these assay antigens are bound to magnetic beads, incubated with plasma and labelled with a fluorescent secondary antibody. Bead are the separated on a magnetic array and the fluorescent signal measure using a high-resolution imaging system.
  • Validation in archival samples: For validation, we will identify archival plasma or serum samples from cross- sectional surveys conducted in previously endemic village in the Yunnan-Myanmar border region both pre- and post- elimination, where possible in villages with several surveys conducted over time. Additional pre- /post-elimination sample sets may be available from Central China and Hainan. Such samples will be identified among the sample sets held at the School of Global Health, Chinese Center for Tropical Diseases Research-SJTUSM in Shanghai.
  • Improving diagnostic algorithm: In a first step existing algorithms will be used to classify survey participants as recently exposed or not and the prevalence compared with the prevalence of bloodstage  infections  in  the same surveys as well as the number of reported P. vivax cases in the preceding 12 months as part of routine surveillance activities. In addition, the decay of population antibody titres and prevalence will be related to time since last confirmed locally transmitted malaria cases. Current algorithms are based on random forest classifiers validated on low transmission cohorts in Thailand, Brazil and Solomon Island (Longley, White et al 2020 Nat Med, 26, 741-749). Further algorithms will be developed with higher specificity to differentiate samples from survey conducted per- and at different amounts of time after the last reported locally transmitted cases.
  • Application to case investigation: Once fully validated the assay will be used to test population-based samples collected during investigations of suspected locally transmitted malaria cases occurring in Yunnan border areas and confirm the absence of transmission in local communities.

The project will be complemented by the project Modelling the last mile to elimination: Learning from China’s successes to inform malaria elimination in the Asia-Pacific and the collaboration will ensure a successful completion of the project.

Supervision team:

Professor Xiao-Nong Zhou (Shanghai Jiao Tong University)

Prof Ivo Mueller (The University of Melbourne)

How to apply

If you are interested in this opportunity, read the application guidelines before contacting the lead supervisor.