Rapid diagnostic tests failing to detect infections by Plasmodium falciparum encoding pfhrp2 and pfhrp3 genes in a non-endemic setting View Full Text


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Article Info

DATE

2020-05-11

AUTHORS

Grégoire Pasquier, Vincent Azoury, Milène Sasso, Laëtitia Laroche, Emmanuelle Varlet-Marie, Sandrine Houzé, Laurence Lachaud, Patrick Bastien, Yvon Sterkers, Maude F. Leveque

ABSTRACT

BackgroundRapid diagnostic tests (RDTs) detecting the histidine-rich protein 2 (PfHRP2) have a central position for the management of Plasmodium falciparum infections. Yet, variable detection of certain targeted motifs, low parasitaemia, but also deletion of pfhrp2 gene or its homologue pfhrp3, may result in false-negative RDT leading to misdiagnosis and delayed treatment. This study aimed at investigating the prevalence, and understanding the possible causes, of P. falciparum RDT-negative infections at Montpellier Academic Hospital, France.MethodsThe prevalence of falsely-negative RDT results reported before and after the introduction of a loop-mediated isothermal amplification (LAMP) assay, as part as the malaria screening strategy in January 2017, was analysed. Negative P. falciparum RDT infections were screened for pfhrp2 or pfhrp3 deletion; and exons 2 were sequenced to show a putative genetic diversity impairing PfHRP2 detection.ResultsThe overall prevalence of P. falciparum negative RDTs from January 2006 to December 2018 was low (3/446). Whereas no cases were reported from 2006 to 2016 (0/373), period during which the malaria diagnostic screen was based on microscopy and RDT, prevalence increased up to 4.1% (3/73) between 2017 and 2018, when molecular detection was implemented for primary screening. Neither pfhrp2/3 deletion nor major variation in the frequency of repetitive epitopes could explain these false-negative RDT results.ConclusionThis paper demonstrates the presence of pfhrp2 and pfhrp3 genes in three P. falciparum RDT-negative infections and reviews the possible reasons for non-detection of HRP2/3 antigens in a non-endemic setting. It highlights the emergence of falsely negative rapid diagnostic tests in a non-endemic setting and draws attention on the risk of missing malaria cases with low parasitaemia infections using the RDT plus microscopy-based strategy currently recommended by French authorities. The relevance of a novel diagnostic scheme based upon a LAMP assay is discussed. More... »

PAGES

179

References to SciGraph publications

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  • Identifiers

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    http://scigraph.springernature.com/pub.10.1186/s12936-020-03251-3

    DOI

    http://dx.doi.org/10.1186/s12936-020-03251-3

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/32393251


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    27 schema:description BackgroundRapid diagnostic tests (RDTs) detecting the histidine-rich protein 2 (PfHRP2) have a central position for the management of Plasmodium falciparum infections. Yet, variable detection of certain targeted motifs, low parasitaemia, but also deletion of pfhrp2 gene or its homologue pfhrp3, may result in false-negative RDT leading to misdiagnosis and delayed treatment. This study aimed at investigating the prevalence, and understanding the possible causes, of P. falciparum RDT-negative infections at Montpellier Academic Hospital, France.MethodsThe prevalence of falsely-negative RDT results reported before and after the introduction of a loop-mediated isothermal amplification (LAMP) assay, as part as the malaria screening strategy in January 2017, was analysed. Negative P. falciparum RDT infections were screened for pfhrp2 or pfhrp3 deletion; and exons 2 were sequenced to show a putative genetic diversity impairing PfHRP2 detection.ResultsThe overall prevalence of P. falciparum negative RDTs from January 2006 to December 2018 was low (3/446). Whereas no cases were reported from 2006 to 2016 (0/373), period during which the malaria diagnostic screen was based on microscopy and RDT, prevalence increased up to 4.1% (3/73) between 2017 and 2018, when molecular detection was implemented for primary screening. Neither pfhrp2/3 deletion nor major variation in the frequency of repetitive epitopes could explain these false-negative RDT results.ConclusionThis paper demonstrates the presence of pfhrp2 and pfhrp3 genes in three P. falciparum RDT-negative infections and reviews the possible reasons for non-detection of HRP2/3 antigens in a non-endemic setting. It highlights the emergence of falsely negative rapid diagnostic tests in a non-endemic setting and draws attention on the risk of missing malaria cases with low parasitaemia infections using the RDT plus microscopy-based strategy currently recommended by French authorities. The relevance of a novel diagnostic scheme based upon a LAMP assay is discussed.
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    34 France
    35 French authorities
    36 MethodsThe prevalence
    37 PfHRP2 detection
    38 Plasmodium falciparum
    39 Plasmodium falciparum infection
    40 RDT
    41 RDT results
    42 academic hospital
    43 amplification
    44 antigen
    45 attention
    46 authorities
    47 cases
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    49 central position
    50 deletion
    51 detection
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    55 diversity
    56 emergence
    57 epitopes
    58 exon 2
    59 falciparum
    60 falciparum infection
    61 false-negative RDT results
    62 frequency
    63 genes
    64 genetic diversity
    65 histidine-rich protein 2
    66 hospital
    67 infection
    68 introduction
    69 isothermal amplification
    70 loop-mediated isothermal amplification
    71 low parasitaemia
    72 low-parasitaemia infections
    73 major variations
    74 malaria
    75 malaria cases
    76 management
    77 microscopy
    78 misdiagnosis
    79 molecular detection
    80 motif
    81 negative RDT
    82 negative RDT results
    83 negative rapid diagnostic test
    84 non-endemic setting
    85 novel diagnostic scheme
    86 overall prevalence
    87 paper
    88 parasitaemia
    89 part
    90 period
    91 pfhrp2
    92 pfhrp2 gene
    93 pfhrp2/3 deletions
    94 pfhrp3
    95 pfhrp3 deletions
    96 pfhrp3 genes
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    100 presence
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    102 prevalence
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    104 protein 2
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