Last Updated: 30/10/2025

Serological markers of recent exposure as surrogate biomarkers of hypnozoite carriage: A proof-of-concept study in Indonesian soldiers (SERO-HYPNOZOITE)

Objectives

The primary objective of the study is to validate a serodiagnostic test for recent infection with P. vivax as an indication of the high probability of hypnozoite carriage. The study employs soldier volunteers returning to a malaria-free base on Java after months of exposure in malarious eastern Indonesia; serodiagnostic screening upon return with months of follow-up to ascertain hypnozoite carriage status at enrollment and screening.

Also, to identify by post-hoc analysis a combination of five antigens providing >90% sensitivity and >80% specificity for the identification of soldiers proven to have been carrying hypnozoites versus confirmed to have been free of the same.

Principal Investigators / Focal Persons

J. Kevin Baird

Partner Investigators

Rintis Noviyanti

Rationale and Abstract

The prognosis for uncomplicated acute malaria caused by any of the plasmodial species is excellent, with prompt diagnosis and effective treatment. When P. vivax malaria goes undiagnosed and untreated, it often progresses to complicated and threatening disease syndromes that may end in death. Confirmatory diagnosis of P. vivax malaria is almost always made by microscopic examination of Giemsa-stained thick and or thin blood films. Rapid diagnostic tests are available but generally have poor sensitivity for P. vivax malaria. PCR diagnostics are also available, and most of these tests are much more sensitive than microscopy but also far more expensive and require specialized skills and laboratory equipment.

All current diagnostic tests are based on directly detecting parasites or parasite antigens in the blood of a patient suffering an acute febrile illness. There is no test or tool known to be practical in making a diagnosis of latent P. vivax malaria. The hypnozoites in the liver are effectively out of the reach of direct diagnosis. A systematic review and meta-analysis of studies conducted all across the vivax-endemic globe showed that >80% of clinical attacks by this species originated as activated latency rather than mosquito bites. It is, therefore, very important to be able to identify and treat silent and invisible carriers of hepatic hypnozoites.

Study Design

This cohort study screened and enrolled soldiers returning from moderately endemic malaria areas in Papua to East Java (battalion 1 at Surabaya from Dec 4, 2018, to Jun 21, 2019, and battalion 2 at Malang from Jan 13, 2022, to Jul 11, 2022). Ethics approval was obtained from the local ethics committee (EIREC No. 123, dated Oct 18, 2018, and EIREC No. 171 dated Dec 31, 2021).

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