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

Developing sero-diagnostic tests to facilitate Plasmodium vivax Serological Test-and-Treat approaches: modelling the balance between public health impact and overtreatment (#320)

Thomas Obadia 1 , Narimane Nekkab 2 , Leanne Robinson 3 , Chris Drakeley 4 , Michael T White 1 , Ivo Mueller 3
  1. Institut Pasteur, Paris, PARIS, France
  2. Swiss Tropical and Public Health Institute, Basel
  3. Walter and Eliza Hall Institute of Medical Research, Melbourne
  4. London School of Hygiene and Tropical Medicine, London

Eliminating Plasmodium vivax will require targeting the hidden liver-stage reservoir of hypnozoites. This necessitates new interventions balancing the benefit of reducing vivax transmission against the risk of over-treating some individuals with drugs which may induce haemolysis. By measuring antibodies to a panel of vivax antigens, a strategy of serological-testing-and-treatment (PvSeroTAT) can identify individuals with recent blood-stage infections who are likely to carry hypnozoites and target them for radical cure.

Methods

PvSeroTAT can identify likely hypnozoite carriers with ~80% sensitivity and specificity. Diagnostic test sensitivities and specificities ranging 50–100% were incorporated into a mathematical model of vivax transmission to explore how they affect the risks and benefits of PvSeroTAT strategies involving hypnozoiticidal regimens. Risk was measured as the rate of overtreatment and benefit as reduction of community-level vivax transmission.

Results

PvSeroTAT was substantially more effective than bloodstage mass screen and treat strategies and only marginally less than mass drug administration. The key characteristic determining of the benefit of PvSeroTAT strategies is diagnostic sensitivity, with higher values leading to more hypnozoite carriers effectively treated and greater reductions in transmission. The key determinant of risk is diagnostic specificity: higher specificity ensures that a lower proportion of uninfected individuals are unnecessarily treated with primaquine. Increased treatment efficacy and adherence can partially compensate for lower test performance. Multiple rounds of PvSeroTAT with a lower performing test may lead to similar or higher reductions in vivax transmission than fewer rounds with a higher performing test.

Conclusions

PvSeroTAT is predicted to be a safe and efficacious option for targeting the hypnozoite reservoir towards vivax elimination. P. vivax sero-diagnostic tests should aim for both high performance and ease of use in the field. The target product profiles informing such development should thus reflect the trade-offs between impact, overtreatment and ease of programmatic implementation.