Low Prevalence of Plasmodium falciparum Histidine-Rich Protein 2 and 3 Gene Deletions—A Multiregional Study in Central and West Africa

Plasmodium falciparum parasites carrying deletions of histidine-rich protein 2 and 3 genes, pfhrp2 and pfhrp3, respectively, are likely to escape detection via HRP2-based rapid diagnostic tests (RDTs) and, consequently, treatment, posing a major risk to both the health of the infected individual and malaria control efforts. This study assessed the frequency of pfhrp2- and pfhrp3-deleted strains at four different study sites in Central Africa (number of samples analyzed: Gabon N = 534 and the Republic of Congo N = 917) and West Africa (number of samples analyzed: Nigeria N = 466 and Benin N = 120) using a highly sensitive multiplex qPCR. We found low prevalences for pfhrp2 (1%, 0%, 0.03% and 0) and pfhrp3 single deletions (0%, 0%, 0.03% and 0%) at all study sites (Gabon, the Republic of Congo, Nigeria and Benin, respectively). Double-deleted P. falciparum were only found in Nigeria in 1.6% of all internally controlled samples. The results of this pilot investigation do not point towards a high risk for false-negative RDT results due to pfhrp2/pfhrp3 deletions in Central and West African regions. However, as this scenario can change rapidly, continuous monitoring is essential to ensure that RDTs remain a suitable tool for the malaria diagnostic strategy.

• Publication year

  2023

• Venue

  Pathogens

• Publication date

  2023-03-01

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.3390/pathogens12030455PMID 36986377PMCID 10054520
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Prevalence of non-Plasmodium falciparum species in southern districts of Brazzaville in The Republic of the Congo

  2022influential reference
• Fitness costs of pfhrp2 and pfhrp3 deletions underlying diagnostic evasion in malaria parasites

  2022influential reference
• High-throughput Plasmodium falciparum hrp2 and hrp3 gene deletion typing by digital PCR to monitor malaria rapid diagnostic test efficacy

  2022influential reference
• Plasmodium falciparum is evolving to escape malaria rapid diagnostic tests in Ethiopia

  2021cited by this paper
• Plasmodium falciparum Histidine-Rich Protein 2 and 3 Gene Deletions in Strains from Nigeria, Sudan, and South Sudan

  2021cited by this paper
• Detection of high prevalence of Plasmodium falciparum histidine-rich protein 2/3 gene deletions in Assosa zone, Ethiopia: implication for malaria diagnosis

  2021cited by this paper
• Surveillance of

  2021cited by this paper
• Epidemiology of mutant Plasmodium falciparum parasites lacking histidine-rich protein 2/3 genes in Eritrea 2 years after switching from HRP2-based RDTs

  2021cited by this paper
• Contribution of P. falciparum parasites with Pfhrp 2 gene deletions to false negative PfHRP 2 based malaria RDT results in Ghana: A nationwide study of symptomatic malaria patients

  2020cited by this paper
• High prevalence and extended deletions in Plasmodium falciparum hrp2/3 genomic loci in Ethiopia

  2020cited by this paper
• A novel multiplex qPCR assay for detection of Plasmodium falciparum with histidine-rich protein 2 and 3 (pfhrp2 and pfhrp3) deletions in polyclonal infections

  2020cited by this paper
• Characterization of Plasmodium infections among inhabitants of rural areas in Gabon

  2019cited by this paper
• Molecular surveillance of pfhrp2 and pfhrp3 genes deletion in Plasmodium falciparum isolates and the implications for rapid diagnostic tests in Nigeria.

  2019cited by this paper
• A multiplex qPCR approach for detection of pfhrp2 and pfhrp3 gene deletions in multiple strain infections of Plasmodium falciparum

  2019cited by this paper
• Systematic review of the status of pfhrp2 and pfhrp3 gene deletion, approaches and methods used for its estimation and reporting in Plasmodium falciparum populations in Africa: review of published studies 2010–2019

  2019cited by this paper
• Monitoring the threatened utility of malaria rapid diagnostic tests by novel high-throughput detection of Plasmodium falciparum hrp2 and hrp3 deletions: A cross-sectional, diagnostic accuracy study

  2019influential reference
• HRP2: Transforming Malaria Diagnosis, but with Caveats.

  2019cited by this paper
• High proportions of pfhrp2 gene deletion and performance of HRP2-based rapid diagnostic test in Plasmodium falciparum field isolates of Odisha

  2018cited by this paper
• Modelling the drivers of the spread of Plasmodium falciparum hrp2 gene deletions in sub-Saharan Africa

  2017influential reference
• Performance of pfHRP2 versus pLDH antigen rapid diagnostic tests for the detection of Plasmodium falciparum: a systematic review and meta-analysis

  2017cited by this paper
• Pfhrp2-Deleted Plasmodium falciparum Parasites in the Democratic Republic of the Congo: A National Cross-sectional Survey

  2016influential reference
• False-negative RDT results and implications of new reports of P . falciparum histidine-rich protein 2 / 3 gene deletions

  2016cited by this paper
• Plasmodium falciparum histidine rich protein-2 diversity and the implications for PfHRP 2: based malaria rapid diagnostic tests in Ghana

  2016cited by this paper
• Limit of blank and limit of detection of Plasmodium falciparum thick blood smear microscopy in a routine setting in Central Africa

  2014cited by this paper
• False-negative rapid diagnostic tests for malaria and deletion of the histidine-rich repeat region of the hrp2 gene.

  2012cited by this paper
• A Large Proportion of P. falciparum Isolates in the Amazon Region of Peru Lack pfhrp2 and pfhrp3: Implications for Malaria Rapid Diagnostic Tests

  2010cited by this paper
• Effect of Sequence Variation in Plasmodium falciparum Histidine- Rich Protein 2 on Binding of Specific Monoclonal Antibodies: Implications for Rapid Diagnostic Tests for Malaria

  2006cited by this paper
• Improved real-time RT-PCR method for high-throughput measurements using second derivative calculation and double correction.

  2005cited by this paper
• Neutralization of toxic heme by Plasmodium falciparum histidine-rich protein 2.

  2003cited by this paper
• Endotoxin‐neutralizing effects of histidine‐rich peptides

  2003cited by this paper
• Quantification on the LightCycler

  2001cited by this paper
• Rapid Cycle Real-Time PCR

  2001cited by this paper
• Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa.

  1995cited by this paper
• The measurement of observer agreement for categorical data.

  1977cited by this paper
• Measuring nominal scale agreement among many raters.

  1971cited by this paper

• Field performance of the SD Bioline Malaria Ag P.f. rapid diagnostic test among children under five in Nigeria: insights from the 2021 Malaria Indicator Survey

  2026influential citation
• Prevalence of Plasmodium falciparum parasites with pfhrp2 exon 2 gene deletion in symptomatic malaria patients across Ghana in 2021

  2025cites this paper
• Genomic Deletion of PfHRP2 and PfHRP3 in Plasmodium falciparum Strains, Ethiopia, 2009

  2025cites this paper
• No evidence of molecular markers of piperaquine resistance in southeastern Nigeria

  2025cites this paper
• Analysis of pfhrp2 and pfhrp3 gene deletions, and the structure and variability of PfHRP2 and PfHRP3 proteins: implications for the performance of malaria rapid diagnostic tests in Cubal, Angola

  2025influential citation
• Intracellular Parasitic Infections Caused by Plasmodium falciparum, Leishmania spp., Toxoplasma gondii, Echinococcus multilocularis, Among Key Pathogens: Global Burden, Transmission Dynamics, and Vaccine Advances—A Narrative Review with Contextual Insights from Armenia

  2025influential citation
• Real-time PCR for malaria diagnosis and identification of Plasmodium species in febrile patients in Cubal, Angola

  2024cites this paper
• Extensive low-density Plasmodium falciparum reservoir in the island of Príncipe, an isolated malaria pre-elimination setting.

  2024cites this paper
• Comparative Evaluation of Microscopy, Rapid Diagnostic Tests, and Polymerase Chain Reaction (PCR) for Malaria Diagnosis in Nigerian Children

  2024cites this paper
• Evaluating Malaria Rapid Diagnostic Tests and Microscopy for Detecting Plasmodium Infection and Status of Plasmodium falciparum Histidine-Rich Protein 2/3 Gene Deletions in Southeastern Nigeria.

  2024cites this paper
• Comparison of SD Bioline Malaria Ag Pf/Pan and Acro Malaria P.f./P.v./Pan with Microscopy and Real Time PCR for the Diagnosis of Human Plasmodium Species

  2024cites this paper
• Malaria diagnosis challenges and pfhrp2 and pfhrp3 gene deletions using pregnant women as sentinel population in Nanoro region, Burkina Faso

  2024cites this paper
• Polymorphism analysis of drug resistance markers in Plasmodium falciparum isolates from Benin.

  2023cites this paper
• Promising Effects of Duck

  year unknowncites this paper