Circulating antibodies against Plasmodium falciparum histidine-rich proteins 2 interfere with antigen detection by rapid diagnostic tests

Mei-Fong Ho; Baker, Joanne; Lee, Nelson; Luchavez, Jennifer; Ariey, Frédéric; Nhem, Sina; Oyibo, Wellington; Bell, David; González, Iveth; Chiodini, Peter; Gatton, Michelle L.; Qin Cheng; McCarthy, James S.
December 2014
Malaria Journal;2014, Vol. 13 Issue 1, p108
Academic Journal
Background Rapid diagnostic tests (RDTs) for detection of Plasmodium falciparum infection that target P. falciparum histidine-rich protein 2 (PfHRP2), a protein that circulates in the blood of patients infected with this species of malaria, are widely used to guide case management. Understanding determinants of PfHRP2 availability in circulation is therefore essential to understanding the performance of PfHRP2-detecting RDTs. Methods The possibility that pre-formed host anti-PfHRP2 antibodies may block target antigen detection, thereby causing false negative test results was investigated in this study. Results Anti-PfHRP2 antibodies were detected in 19/75 (25%) of plasma samples collected from patients with acute malaria from Cambodia, Nigeria and the Philippines, as well as in 3/28 (10.7%) asymptomatic Solomon Islands residents. Pre-incubation of plasma samples from subjects with high-titre anti-PfHRP2 antibodies with soluble PfHRP2 blocked the detection of the target antigen on two of the three brands of RDTs tested, leading to false negative results. Pre-incubation of the plasma with intact parasitized erythrocytes resulted in a reduction of band intensity at the highest parasite density, and a reduction of lower detection threshold by ten-fold on all three brands of RDTs tested. Conclusions These observations indicate possible reduced sensitivity for diagnosis of P. falciparum malaria using PfHRP2-detecting RDTs among people with high levels of specific antibodies and low density infection, as well as possible interference with tests configured to detect soluble PfHRP2 in saliva or urine samples. Further investigations are required to assess the impact of pre-formed anti-PfHRP2 antibodies on RDT performance in different transmission settings.


Related Articles

  • Variation in Plasmodium falciparum Histidine-Rich Protein 2 (Pfhrp2) and Plasmodium falciparum Histidine-Rich Protein 3 (Pfhrp3) Gene Deletions in Guyana and Suriname. Akinyi Okoth, Sheila; Abdallah, Joseph F.; Ceron, Nicolas; Adhin, Malti R.; Chandrabose, Javin; Krishnalall, Karanchand; Huber, Curtis S.; Goldman, Ira F.; Macedo de Oliveira, Alexandre; Barnwell, John W.; Udhayakumar, Venkatachalam // PLoS ONE;May2015, Vol. 10 Issue 5, p1 

    Guyana and Suriname have made important progress in reducing the burden of malaria. While both countries use microscopy as the primary tool for clinical diagnosis, malaria rapid diagnostic tests (RDTs) are useful in remote areas of the interior where laboratory support may be limited or...

  • A Murine Model of falciparum-Malaria by In Vivo Selection of Competent Strains in Non-Myelodepleted Mice Engrafted with Human Erythrocytes. Angulo-Barturen, Iñigo; Jiménez-Díaz, María Belén; Mulet, Teresa; Rullas, Joaquín; Herreros, Esperanza; Ferrer, Santiago; Jiménez, Elena; Mendoza, Alfonso; Regadera, Javier; Rosenthal, Philip J.; Bathurst, Ian; Pompliano, David L.; de las Heras, Federico Gómez; Gargallo-Viola, Domingo // PLoS ONE;2008, Vol. 3 Issue 5, p1 

    To counter the global threat caused by Plasmodium falciparum malaria, new drugs and vaccines are urgently needed. However, there are no practical animal models because P. falciparum infects human erythrocytes almost exclusively. Here we describe a reliable falciparum murine model of malaria by...

  • Therapeutic Efficacy of Artemether-Lumefantrine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Northern Ethiopia. Kinfu, Gebremedhin; Gebre-Selassie, Solomon; Fikrie, Nigus // Malaria Research & Treatment;2012, p1 

    Introduction. Multidrug resistance of Plasmodium falciparum is spreading throughout Africa. This has posed major challenges to malaria control in sub-Saharan Africa. Objective. The aim of the study was to evaluate the efficacy of artemether-lumefantrine for the treatment of uncomplicated...

  • Assessment of therapeutic responses to gametocytocidal drugs in Plasmodium falciparum malaria. White, Nicholas J.; Ashley, Elizabeth A.; Recht, Judith; Delves, Michael J.; Ruecker, Andrea; Smithuis, Frank M.; Eziefula, Alice C.; Bousema, Teun; Drakeley, Chris; Chotivanich, Kesinee; Imwong, Mallika; Pukrittayakamee, Sasithon; Prachumsri, Jetsumon; Chu, Cindy; Andolina, Chiara; Bancone, Germana; Hien, Tran T.; Mayxay, Mayfong; Taylor, Walter R. J.; von Seidlein, Lorenz // Malaria Journal;2014, Vol. 13 Issue 1, p186 

    Indirect clinical measures assessing anti-malarial drug transmission-blocking activity in falciparum malaria include measurement of the duration of gametocytaemia, the rate of gametocyte clearance or the area under the gametocytaemia-time curve (AUC). These may provide useful comparative...

  • Taking a Bite Out of Mosquitoes: A New Drug to Block Transmission of Malaria. Durvasula, Ravi // Journal of Infectious Diseases;Jan2014, Vol. 209 Issue 2, p177 

    The author reflects on the development of new drugs and strategies to control the transmission of malaria with reference of the study "Specific inhibitor of PfCDPK4 blocks malaria transmission: Chemical-genetic validation" by K. K. Ojo and colleagues, published within the issue of as of January...

  • Estimation of Recent and Long-Term Malaria Transmission in a Population by Antibody Testing to Multiple Plasmodium falciparum Antigens. Ondigo, Bartholomew N.; Hodges, James S.; Ireland, Kathleen F.; Magak, Ng'wena G.; Lanar, David E.; Dutta, Sheetij; Narum, David L.; Park, Gregory S.; Ofulla, Ayub V.; John, Chandy C. // Journal of Infectious Diseases;Oct2014, Vol. 210 Issue 7, p1123 

    Background. Tools that estimate recent and long-term malaria transmission in a population would be highly useful for malaria elimination programs.Methods. The prevalence of antibodies to 11 Plasmodium falciparum antigens was assessed by cytometric bead assay or enzyme-linked immunosorbent assay...

  • Molecular incidence and clearance of Plasmodium falciparum infection. Krogstad, Donald J.; Koita, Ousmane A.; Diallo, Mouctar; Gerone, John L.; Poudiougou, Belco; Diakité, Mahamadou; Touré, Yéya T. // Malaria Journal;10/22/2015, Vol. 14 Issue 1, p1 

    Background: Although the epidemiology of malaria has been based primarily on microscopy and rapid diagnostic tests, molecular methods are necessary to understand the complexity of natural infection in regions where transmission is intense and simultaneous infection with multiple parasite...

  • Plasmodium falciparum infection-induced changes in erythrocyte membrane proteins. Fontaine, Albin; Bourdon, Stéphanie; Belghazi, Maya; Pophillat, Mathieu; Fourquet, Patrick; Granjeaud, Samuel; Torrentino-Madamet, Marylin; Rogier, Christophe; Fusai, Thierry; Almeras, Lionel // Parasitology Research;Feb2012, Vol. 110 Issue 2, p545 

    Over the past decade, advances in proteomic and mass spectrometry techniques and the sequencing of the Plasmodium falciparum genome have led to an increasing number of studies regarding the parasite proteome. However, these studies have focused principally on parasite protein expression,...

  • Malaria chemoprophylactic regimens for travellers.  // Bulletin of the World Health Organization;1994, Vol. 72 Issue 2, p307 

    The article outlines recommendations of the World Health Organization (WHO) regarding the use of chemoprophylactic anti-malaria regimens among travelers. For areas where Plasmodium vivax is the predominant species, chloroquine is recommended. A combination of chloroquine and proguanil is...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics