Serological Testing and Treatment for Plasmodium Vivax Malaria: a Trial in Ethiopia and Madagascar

Summary

The resilience of P. vivax to malaria elimination efforts is due to its ability to form dormant liver stages (hypnozoites) that reactivate weeks to months after the initial infection causing recurrent episodes of malaria (relapses) and ongoing parasite transmission. Relapses account for a majority of recurrent infections and clinical cases of P. vivax malaria, and therefore have a significant effect on morbidity at the individual level.

With current technology, it is not possible to directly measure hypnozoite biomarkers. Rather than directly detecting hypnozoites, our team developed an indirect approach by measuring antibodies induced by the primary blood-stage infection. Antibodies to different blood-stage antigens decay at different rates. Measuring antibodies to a carefully selected panel of P. vivax antigens can aid to identify individuals who have been infected within the previous 9 months (approximately the lifespan of hypnozoites).

A serological test based on selected P. vivax antigens can detect recent exposure and predict future relapses. Coupling this test with a safe and efficacious primaquine treatment regimen, results in a population-based intervention to target the hypnozoite reservoir. This intervention is referred to as Plasmodium vivax Serological Testing and Treatment (PvSeroTAT).

PvSTATEM is a cluster randomised trial in Madagascar and Ethiopia. This study will provide insights into the feasibility, acceptability, and efficacy of the PvSeroTAT approach. In this study, individuals, randomised by clusters, will be tested for the presence of serological markers of a recent P. vivax infection, followed by a targeted drug treatment intervention aimed at killing P. vivax hypnozoites.

Conditions

• Malaria Vivax
• Malaria Falciparum
• Plasmodium Vivax
• Plasmodium Falciparum

Interventions

COMBINATION_PRODUCT

PvSeroTAT

Two rounds (month 0 and month 6) of serological screening for antibodies against P. vivax in the blood of all eligible cluster inhabitants. In the clusters in the PvSeroTAT arm, participants with a positive P. vivax serology at baseline or month 6 will be treated with 14 days of primaquine 0.25mg/kg/day (Ethiopia) or 7 days of primaquine 0.5mg/kg/day (Madagascar), and a three-day course of either chloroquine (Ethiopia) or artesunate-amodiaquine (Madagascar)

DIAGNOSTIC_TEST

Control

Two rounds (month 0 and month 6) of serological screening for antibodies against P. vivax in the blood of a subset of eligible cluster inhabitants. Serological status will be assessed at a later stage (months later) and will not lead to treatment of sero-positive individuals.

Sponsors & Collaborators

• Institut Pasteur

  collaborator INDUSTRY

• Institut Pasteur de Madagascar

  collaborator OTHER

• Armauer Hansen Research Institute (AHRI), Ethiopia

  collaborator UNKNOWN

• London School of Hygiene and Tropical Medicine

  lead OTHER

Principal Investigators

• Chris Drakeley · London School of Hygiene and Tropical Medicine

• Michael T White · Institut Pasteur

• Rindra Randremanana · Institut Pasteur de Madagascar

• Fitsum G Tadesse · Armauer Hansen Research Institute

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

12 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-05-12

Primary Completion

2027-04-28

Completion

2027-04-28

Countries

• Ethiopia
• Madagascar

Study Locations