Pfhrp2 and pfhrp3 polymorphisms in Plasmodium falciparum isolates from Dakar, Senegal: impact on rapid malaria diagnostic tests

Nathalie Wurtz 1, 2 Bécaye Fall 3 Kim Bui 1, 2 Aurélie Pascual 1, 2, 4 Mansour Fall 5 Cheikhou Camara 6 Bakary Diatta 5 Khadidiatou Ba Fall 7 Pape Saliou Mbaye 8 Yaya Diémé 3 Raymond Bercion 3 Boubacar Wade 9 Sébastien Briolant 1, 2 Bruno Pradines 1, 2, 3, 4, *
* Auteur correspondant
1 Unité de Parasitologie
2 URMITE - Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes
3 Laboratoire d'étude de la chimiosensibilité du paludisme
4 Unité de Parasitologie
5 Service de Réanimation Médicale
6 Service des Urgences
7 Service de Pathologie Infectieuse
8 Département de Médecine Interne et Spécialités Médicales de Pathologie Tropicale
9 Chefferie
Abstract : Background
An accurate diagnosis is essential for the rapid and appropriate treatment of malaria. The accuracy of the histidine-rich protein 2 (PfHRP2)-based rapid diagnostic test (RDT) Palutop+4® was assessed here. One possible factor contributing to the failure to detect malaria by this test is the diversity of the parasite PfHRP2 antigens.
Methods
PfHRP2 detection with the Palutop+4® RDT was carried out. The pfhrp2 and pfhrp3 genes were amplified and sequenced from 136 isolates of Plasmodium falciparum that were collected in Dakar, Senegal from 2009 to 2011. The DNA sequences were determined and statistical analyses of the variation observed between these two genes were conducted. The potential impact of PfHRP2 and PfHRP3 sequence variation on malaria diagnosis was examined.
Results
Seven P. falciparum isolates (5.9% of the total isolates, regardless of the parasitaemia; 10.7% of the isolates with parasitaemia ≤0.005% or ≤250 parasites/μl) were undetected by the PfHRP2 Palutop+4® RDT. Low parasite density is not sufficient to explain the PfHRP2 detection failure. Three of these seven samples showed pfhrp2 deletion (2.4%). The pfhrp3 gene was deleted in 12.8%. Of the 122 PfHRP2 sequences, 120 unique sequences were identified. Of the 109 PfHRP3 sequences, 64 unique sequences were identified. Using the Baker's regression model, at least 7.4% of the P. falciparum isolates in Dakar were likely to be undetected by PfHRP2 at a parasite density of ≤250 parasites/μl (slightly lower than the evaluated prevalence of 10.7%). This predictive prevalence increased significantly between 2009 and 2011 (P = 0.0046).
Conclusion
In the present work, 10.7% of the isolates with a parasitaemia ≤0.005% (≤250 parasites/μl) were undetected by the PfHRP2 Palutop+4® RDT (7.4% by the predictive Baker'model). In addition, all of the parasites with pfhrp2 deletion (2.4% of the total samples) and 2.1% of the parasites with parasitaemia >0.005% and presence of pfhrp2 were not detected by PfHRP2 RDT. PfHRP2 is highly polymorphic in Senegal. Efforts should be made to more accurately determine the prevalence of non-sensitive parasites to pfHRP2.
keyword : Malaria Plasmodium falciparum Diagnosis Rapid diagnostic test Plasmodium falciparum histidine-rich protein 2 Anti-malarial
Type de document :
Article dans une revue
Malaria Journal, BioMed Central, 2013, 12 (1), pp.34. 〈10.1186/1475-2875-12-34〉
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Nathalie Wurtz, Bécaye Fall, Kim Bui, Aurélie Pascual, Mansour Fall, et al.. Pfhrp2 and pfhrp3 polymorphisms in Plasmodium falciparum isolates from Dakar, Senegal: impact on rapid malaria diagnostic tests. Malaria Journal, BioMed Central, 2013, 12 (1), pp.34. 〈10.1186/1475-2875-12-34〉. 〈inserm-00787797〉

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