African Journal of Parasitology Research

ISSN 2756-3391

African Journal of Parasitology Research | Vol. 14, No. 8, August 2026 | pp. 637–644

DOI: 10.46882/AJPR/140637

Article Type: Full Length Research Paper

Title: Genomic monitoring of Plasmodium falciparum hrp2 and hrp3 gene deletions among symptomatic patients in the western regions of Madagascar

Names of Authors: Rado H. Rakotomalala¹, Fitiavana N. Andrianarivelo¹, Lucia R. Ramananjanahary²

Authors’ Affiliations: ¹Institut Pasteur de Madagascar, Malariology Unit, Antananarivo, Madagascar. ²Ministère de la Santé Publique, Direction de la Lutte contre les Maladies Transmissibles, Antananarivo, Madagascar.

Abstract: The emergence of Plasmodium falciparum parasites lacking the histidine-rich protein 2 (pfhrp2) and histidine-rich protein 3 (pfhrp3) genes threatens rapid malaria diagnostics. This surveillance program evaluated the prevalence of these genetic deletions among 680 symptomatic malaria patients presenting at health facilities in western Madagascar. Patients were tested using HRP2-based rapid diagnostic tests alongside Giemsa-stained reference microscopy. Discordant samples (microscopy-positive but rapid diagnostic test-negative) were analyzed using multiplex PCR to confirm pfhrp2 and pfhrp3 status. Genotyping confirmed that 6.4 percent (n = 44) of true Plasmodium falciparum infections lacked the pfhrp2 gene, while dual deletions of both pfhrp2 and pfhrp3 occurred in 2.1 percent (n = 14) of isolates. Patients infected with deleted strains showed high geometric mean parasite densities (3400 parasites per microliter). Logistic regression revealed that the frequency of these gene deletions was significantly higher in remote coastal areas with historical over-reliance on single-target HRP2 rapid diagnostic tests (odds ratio = 3.14, 95 percent confidence interval [1.62 to 6.08]). This molecular proof of diagnostic-evading parasites across western Madagascar highlights the urgent need to replace single-target rapid tests with combination rapid diagnostic tests that detect alternative antigens like parasite lactate dehydrogenase.

Keywords: Plasmodium falciparum, pfhrp2 deletion, Diagnostic evasion, Rapid diagnostic tests, Surveillance, Madagascar

Manuscript Timeline: Received: 18 May 2026; Revised: 20 June 2026; Accepted: 18 July 2026; Published: 14 August 2026