Evidence map›Paper›PMID 31761619›Full record

ArticleEBioMedicine2019

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.

Andrea Kreidenweiss, Franziska Trauner, Miriam Rodi, Erik Koehne, Jana Held, Lea Wyndorps, Gédéon Prince Manouana, Matthew McCall, Ayola Akim Adegnika, Albert Lalremruata and 3 more

Abstract read
In one paragraph

Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  12. Low Prevalence ofPathogens (Basel, Switzerland) · 2023
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  13. High-throughputeLife · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Andrea KreidenweissInstitute of Tropical Medicine, University Hospital Tübingen, Wilhelmstrasse 27, D-72074 Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, B.P. 242, Lambaréné, Gabon. Electronic address: andrea.kreidenweiss@uni-tuebingen.de.
Franziska TraunerInstitute of Tropical Medicine, University Hospital Tübingen, Wilhelmstrasse 27, D-72074 Tübingen, Germany.
Miriam RodiInstitute of Tropical Medicine, University Hospital Tübingen, Wilhelmstrasse 27, D-72074 Tübingen, Germany.
Erik KoehneInstitute of Tropical Medicine, University Hospital Tübingen, Wilhelmstrasse 27, D-72074 Tübingen, Germany.
Jana HeldInstitute of Tropical Medicine, University Hospital Tübingen, Wilhelmstrasse 27, D-72074 Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, B.P. 242, Lambaréné, Gabon.
Lea WyndorpsInstitute of Tropical Medicine, University Hospital Tübingen, Wilhelmstrasse 27, D-72074 Tübingen, Germany.
Gédéon Prince ManouanaCentre de Recherches Médicales de Lambaréné, B.P. 242, Lambaréné, Gabon.
Matthew McCallCentre de Recherches Médicales de Lambaréné, B.P. 242, Lambaréné, Gabon.
Ayola Akim AdegnikaInstitute of Tropical Medicine, University Hospital Tübingen, Wilhelmstrasse 27, D-72074 Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, B.P. 242, Lambaréné, Gabon; German Center for Infection Research (DZIF), Tübingen, Germany.
Albert LalremruataInstitute of Tropical Medicine, University Hospital Tübingen, Wilhelmstrasse 27, D-72074 Tübingen, Germany.
Peter G KremsnerInstitute of Tropical Medicine, University Hospital Tübingen, Wilhelmstrasse 27, D-72074 Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, B.P. 242, Lambaréné, Gabon; German Center for Infection Research (DZIF), Tübingen, Germany.
Rolf FendelInstitute of Tropical Medicine, University Hospital Tübingen, Wilhelmstrasse 27, D-72074 Tübingen, Germany.
Thaisa Lucas SandriInstitute of Tropical Medicine, University Hospital Tübingen, Wilhelmstrasse 27, D-72074 Tübingen, Germany. Electronic address: thaisa.lucas-sandri@uni-tuebingen.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPlasmodium falciparum deficient for hrp2 and hrp3 genes are a threat to malaria management and elimination, since they escape widely used HRP2-based rapid diagnostic tests and treatment. Hrp2/hrp3 deletions are increasingly reported from all malaria endemic regions but are currently only identified by laborious methodologies.

methodsWe developed a novel hydrolysis probe-based, quantitative, real-time PCR (4plex qPCR) for detection and discrimination of P. falciparum infection (cytb) and hrp2 and hrp3 gene status, and to control assay validity (btub). A cross-sectional, diagnostic accuracy study was performed in Gabon for assay validation and deletion screening.

findingsIn parallel to identification of P. falciparum infection in samples down to 0.05 parasites/µl, the 4plex qPCR enabled specific and valid interrogation of the parasites´s hrp2 and hrp3 genes in one go - even in low parasitemic samples. The assay was precise and robust also when performed in a routine healthcare setting in Gabon. The risk of falsely identifying hrp2 or hrp3 deletion was reduced by 100-fold compared to conventional PCR. Evaluation against microscopy was performed on 200 blood samples collected in Gabon: sensitivity and specificity of 4plex qPCR (cytb) were 100% and 80%, respectively. Stringent testing revealed hrp2 deletion in 2 of 95 P. falciparum positive and validated samples.

interpretationThe novel 4plex qPCR is sensitive, accurate and allows resource-efficient rapid screening. Monitoring and mapping of hrp2/hrp3 deletions is required to identify areas where control strategies may need to be adapted to ensure appropriate patient care and ultimately achieve malaria elimination.

fundingBMBF (03VP00402).

Indexed as

Antigens, ProtozoanCross-Sectional StudiesElectrophoresis, CapillaryHigh-Throughput Screening AssaysHumansMalaria, FalciparumPlasmodium falciparumProtozoan ProteinsReal-Time Polymerase Chain ReactionReproducibility of ResultsSensitivity and SpecificityAntigens, ProtozoanHRP-2 antigen, Plasmodium falciparumHRP3 protein, Plasmodium falciparumProtozoan Proteins

Identifiers

PMID31761619
PMCPMC6921222

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.