Deletions of pfhrp2 and pfhrp3 genes were uncommon in rapid diagnostic test-negative Plasmodium falciparum isolates from Uganda
Abstract Background Rapid diagnostic tests (RDTs) play a key role in malaria case management. The most widely used RDT identifies Plasmodium falciparum based on immunochromatographic recognition of P. falciparum histidine-rich protein 2 (PfHRP2). Deletion of the paralogous pfhrp2 and pfhrp3 genes le...
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ftdoajarticles:oai:doaj.org/article:f47ea82463444c419018d31e5abc4629 2023-05-15T15:18:28+02:00 Deletions of pfhrp2 and pfhrp3 genes were uncommon in rapid diagnostic test-negative Plasmodium falciparum isolates from Uganda Sam L. Nsobya Andrew Walakira Elizabeth Namirembe Moses Kiggundu Joaniter I. Nankabirwa Emmanuel Ruhamyankaka Emmanuel Arinaitwe Melissa D. Conrad Moses R. Kamya Grant Dorsey Philip J. Rosenthal 2021-01-01T00:00:00Z https://doi.org/10.1186/s12936-020-03547-4 https://doaj.org/article/f47ea82463444c419018d31e5abc4629 EN eng BMC https://doi.org/10.1186/s12936-020-03547-4 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-020-03547-4 1475-2875 https://doaj.org/article/f47ea82463444c419018d31e5abc4629 Malaria Journal, Vol 20, Iss 1, Pp 1-6 (2021) pfhrp2 pfhrp3 Plasmodium falciparum HRP2 Rapid diagnostic test Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2021 ftdoajarticles https://doi.org/10.1186/s12936-020-03547-4 2022-12-31T10:53:56Z Abstract Background Rapid diagnostic tests (RDTs) play a key role in malaria case management. The most widely used RDT identifies Plasmodium falciparum based on immunochromatographic recognition of P. falciparum histidine-rich protein 2 (PfHRP2). Deletion of the paralogous pfhrp2 and pfhrp3 genes leads to false-negative PfHRP2-based RDTs, and has been reported in P. falciparum infections from South America and Africa. However, identification of pfhrp2/pfhrp3 deletions has usually been based only on failure to amplify these genes using PCR, without confirmation based on PfHRP2 protein expression, and understanding of the true prevalence of deletions is incomplete. Methods Deletions of pfhrp2/pfhrp3 in blood samples were investigated from cross-sectional surveys in 2012-13 in three regions of varied malaria transmission intensity in Uganda. Samples with positive Giemsa-stained thick blood smears, but negative PfHRP2-based RDTs were evaluated by PCR amplification of conserved subunit ribosomal DNA for Plasmodium species, PCR amplification of pfhrp2 and pfhrp3 genes to identify deletions, and bead-based immunoassays for expression of PfHRP2. Results Of 3516 samples collected in cross-sectional surveys, 1493 (42.5%) had positive blood smears, of which 96 (6.4%) were RDT-negative. Of these 96 RDT-negative samples, P. falciparum DNA was identified by PCR in 56 (58%) and only non-falciparum plasmodial DNA in 40 (42%). In all 56 P. falciparum-positive samples there was a failure to amplify pfhrp2 or pfhrp3: in 25 (45%) pfhrp2 was not amplified, in 39 (70%) pfhrp3 was not amplified, and in 19 (34%) neither gene was amplified. For the 39 P. falciparum-positive, RDT-negative samples available for analysis of protein expression, PfHRP2 was not identified by immunoassay in only four samples (10.3%); these four samples all had failure to amplify both pfhrp2 and pfhrp3 by PCR. Thus, only four of 96 (4.2%) smear-positive, RDT-negative samples had P. falciparum infections with deletion of pfhrp2 and pfhrp3 confirmed by failure to ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 20 1 |
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English |
topic |
pfhrp2 pfhrp3 Plasmodium falciparum HRP2 Rapid diagnostic test Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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pfhrp2 pfhrp3 Plasmodium falciparum HRP2 Rapid diagnostic test Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Sam L. Nsobya Andrew Walakira Elizabeth Namirembe Moses Kiggundu Joaniter I. Nankabirwa Emmanuel Ruhamyankaka Emmanuel Arinaitwe Melissa D. Conrad Moses R. Kamya Grant Dorsey Philip J. Rosenthal Deletions of pfhrp2 and pfhrp3 genes were uncommon in rapid diagnostic test-negative Plasmodium falciparum isolates from Uganda |
topic_facet |
pfhrp2 pfhrp3 Plasmodium falciparum HRP2 Rapid diagnostic test Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Rapid diagnostic tests (RDTs) play a key role in malaria case management. The most widely used RDT identifies Plasmodium falciparum based on immunochromatographic recognition of P. falciparum histidine-rich protein 2 (PfHRP2). Deletion of the paralogous pfhrp2 and pfhrp3 genes leads to false-negative PfHRP2-based RDTs, and has been reported in P. falciparum infections from South America and Africa. However, identification of pfhrp2/pfhrp3 deletions has usually been based only on failure to amplify these genes using PCR, without confirmation based on PfHRP2 protein expression, and understanding of the true prevalence of deletions is incomplete. Methods Deletions of pfhrp2/pfhrp3 in blood samples were investigated from cross-sectional surveys in 2012-13 in three regions of varied malaria transmission intensity in Uganda. Samples with positive Giemsa-stained thick blood smears, but negative PfHRP2-based RDTs were evaluated by PCR amplification of conserved subunit ribosomal DNA for Plasmodium species, PCR amplification of pfhrp2 and pfhrp3 genes to identify deletions, and bead-based immunoassays for expression of PfHRP2. Results Of 3516 samples collected in cross-sectional surveys, 1493 (42.5%) had positive blood smears, of which 96 (6.4%) were RDT-negative. Of these 96 RDT-negative samples, P. falciparum DNA was identified by PCR in 56 (58%) and only non-falciparum plasmodial DNA in 40 (42%). In all 56 P. falciparum-positive samples there was a failure to amplify pfhrp2 or pfhrp3: in 25 (45%) pfhrp2 was not amplified, in 39 (70%) pfhrp3 was not amplified, and in 19 (34%) neither gene was amplified. For the 39 P. falciparum-positive, RDT-negative samples available for analysis of protein expression, PfHRP2 was not identified by immunoassay in only four samples (10.3%); these four samples all had failure to amplify both pfhrp2 and pfhrp3 by PCR. Thus, only four of 96 (4.2%) smear-positive, RDT-negative samples had P. falciparum infections with deletion of pfhrp2 and pfhrp3 confirmed by failure to ... |
format |
Article in Journal/Newspaper |
author |
Sam L. Nsobya Andrew Walakira Elizabeth Namirembe Moses Kiggundu Joaniter I. Nankabirwa Emmanuel Ruhamyankaka Emmanuel Arinaitwe Melissa D. Conrad Moses R. Kamya Grant Dorsey Philip J. Rosenthal |
author_facet |
Sam L. Nsobya Andrew Walakira Elizabeth Namirembe Moses Kiggundu Joaniter I. Nankabirwa Emmanuel Ruhamyankaka Emmanuel Arinaitwe Melissa D. Conrad Moses R. Kamya Grant Dorsey Philip J. Rosenthal |
author_sort |
Sam L. Nsobya |
title |
Deletions of pfhrp2 and pfhrp3 genes were uncommon in rapid diagnostic test-negative Plasmodium falciparum isolates from Uganda |
title_short |
Deletions of pfhrp2 and pfhrp3 genes were uncommon in rapid diagnostic test-negative Plasmodium falciparum isolates from Uganda |
title_full |
Deletions of pfhrp2 and pfhrp3 genes were uncommon in rapid diagnostic test-negative Plasmodium falciparum isolates from Uganda |
title_fullStr |
Deletions of pfhrp2 and pfhrp3 genes were uncommon in rapid diagnostic test-negative Plasmodium falciparum isolates from Uganda |
title_full_unstemmed |
Deletions of pfhrp2 and pfhrp3 genes were uncommon in rapid diagnostic test-negative Plasmodium falciparum isolates from Uganda |
title_sort |
deletions of pfhrp2 and pfhrp3 genes were uncommon in rapid diagnostic test-negative plasmodium falciparum isolates from uganda |
publisher |
BMC |
publishDate |
2021 |
url |
https://doi.org/10.1186/s12936-020-03547-4 https://doaj.org/article/f47ea82463444c419018d31e5abc4629 |
geographic |
Arctic |
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Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 20, Iss 1, Pp 1-6 (2021) |
op_relation |
https://doi.org/10.1186/s12936-020-03547-4 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-020-03547-4 1475-2875 https://doaj.org/article/f47ea82463444c419018d31e5abc4629 |
op_doi |
https://doi.org/10.1186/s12936-020-03547-4 |
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Malaria Journal |
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