Persistence of Plasmodium falciparum HRP2 antigen after effective antimalarial therapy

Abstract

Introduction: Histidine Rich Protein 2 based (HRP2-based) malaria rapid diagnostic tests (mRDTs) have been shown to perform as well as routine light microscopy, however, they are limited by some factors including persistence of HRP2 antigenemia. In this paper we report the evaluation of an HRP2-based mRDT in a prospective study that enrolled children and followed them up for 28 days.

Methods: Children aged below five years, with acute episode of fever/pyrexia,were enrolled. The enrolled participants had expert malaria microscopy and RDT done at enrolment (Day 0), and on days 1, 2, 3, 7, 14, 21, and 28. The malaria RDT test was considered positive when the antigen and control lines were visible  in their respective windows, negative when only the control band was visible and invalid when the control  band was not visible. Faint test lines were considered positive. The RDT results were compared to  those of expert microscopy.

Results: Two hundred and twenty-six children aged 29.2 ± 15.5 months were enrolled. The proportion of children positive by expert malaria microscopy and RDT was 100% and 95.6% respectively. During the 28 day follow up of the children the proportions positive by microscopy and RDT on days 3, 7, 14, and 28  were 1% and 94.6%, 0% and 93.5%, 0% and 91%, and 16.5% and 80.6% respectively. Gender and age dependent analysis of proportion of positive children were similar. Proportion of children with persistence of HRP2 antigen appeared to be lower in those with parasite density below 200/µL, however, this  observation requires further evaluation in larger studies.

Conclusions: the study revealed a high proportion of persistence of HRP2 antigen in the children 28 days  after effective antimalarial therapy. Histidine rich protein 2 based malaria rapid diagnostic tests are not  recommended for monitoring of antimalarial therapies.