Plasmodium falciparum hrp2 and hrp3 gene deletion status in Africa and South America by highly sensitive and specific digital PCR

Detalhes bibliográficos
Autor(a) principal: Vera-Arias, Claudia A.
Data de Publicação: 2021
Outros Autores: Holzschuh, Aurel, Oduma, Colins O., Badu, Kingsley, Abdul-Hakim, Mutala, Yukich, Joshua, Hetzel, Manuel W., Fakih, Bakar S., Ali, Abdullah, Ferreira, Marcelo U., Ladeia-Andrade, Simone, Sáenz, Fabián E., Afrane, Yaw, Zemene, Endalew, Yewhalaw, Delenasaw, Kazura, James W., Yan, Guiyun, Koepfli, Cristian
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/49069
Resumo: University of Notre Dame. Notre Dame, IN, USA.
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spelling Vera-Arias, Claudia A.Holzschuh, AurelOduma, Colins O.Badu, KingsleyAbdul-Hakim, MutalaYukich, JoshuaHetzel, Manuel W.Fakih, Bakar S.Ali, AbdullahFerreira, Marcelo U.Ladeia-Andrade, SimoneSáenz, Fabián E.Afrane, YawZemene, EndalewYewhalaw, DelenasawKazura, James W.Yan, GuiyunKoepfli, Cristian2021-09-14T10:26:03Z2021-09-14T10:26:03Z2021VERA-ARIAS, Claudia A. et al. Plasmodium falciparum hrp2 and hrp3 gene deletion status in Africa and South America by highly sensitive and specific digital PCR. medRxiv Preprint, p. 1-5, June 2021.https://www.arca.fiocruz.br/handle/icict/4906910.1101/2021.06.01.21258117engMedRxiv preprintPlasmodium falciparum hrp2Plasmodium falciparum hrp3Status de exclusão do geneÁfricaAmérica do SulPCR digital altamente sensível e específicoPlasmodium falciparum hrp2Plasmodium falciparum hrp3Gene deletion statusÁfricaSouth AmericaHighly sensitive and specific digital PCRPlasmodium falciparum hrp2 and hrp3 gene deletion status in Africa and South America by highly sensitive and specific digital PCRinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversity of Notre Dame. Notre Dame, IN, USA.University of Notre Dame. Notre Dame, IN, USA / Swiss Tropical and Public Health Institute, Switzerland.Kenya Medical Research Institute-Centre for Global Health Research. Kisumu, Kenya / Department of Biochemistry and Molecular Biology, Egerton University, Nakuru, Kenya.Kwame Nkrumah University of Science and Technology. Ghana.Kwame Nkrumah University of Science and Technology. Ghana.Tulane University. USA.Swiss Tropical and Public Health Institute, Switzerland / University of Basel. Basel, Switzerland.Swiss Tropical and Public Health Institute, Switzerland / University of Basel. Basel, Switzerland / Ifakara Health Institute, Dar es Salaam, United Republic of Tanzania.Zanzibar Malaria Elimination Programme,. Zanzibar, United Republic of TanzaniaUniversidade de São Paulo. São Paulo, SP, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.Centro de Investigación para la Salud en América Latina, Facultad de Ciencias Exactas y Naturales. Pontificia Universidad Católica del Ecuador, Quito, Ecuador.Department of Medical Microbiology, University of Ghana Medical School, Accra, Ghana.Tropical and Infectious Diseases Research Center, Jimma University. Ethiopia.Tropical and Infectious Diseases Research Center, Jimma University. Ethiopia.Case Western Reserve University. Cleveland, USA.Program in Public Health, University of California. Irvine, CA 92617, USA.University of Notre Dame. Notre Dame, IN, USA.Background: The most commonly used Plasmodium falciparum rapid diagnostic tests target the Histidine-Rich Proteins 2 and 3 (HRP2, HRP3). An increasing number of countries report parasites that carry hrp2 and/or hrp3 gene deletions, resulting in false negative test results. Molecular surveillance of hrp2 and hrp3 deletions is crucial but adequate protocols have been lacking. Methods and Findings: We have developed novel assays for deletion typing based on droplet digital PCR (ddPCR), targeting hrp2 exon1, hrp2 exon 2, and hrp3. In the ddPCR assay, hrp2 or hrp3 and a control gene were quantified with very high accuracy in a single tube. The theoretical limit of detection of the ddPCR assay was 0.33 parasites/uL, and thus well suited for typing of low-density asymptomatic infections. The deletion was reliably detected in mixed infections with wild-type and hrp2-deleted parasites when the proportion of parasites carrying the deletion was >40%. For a side-by-side comparison with the conventional nested PCR (nPCR) assay, 248 samples from asymptomatic individuals from western Kenya were screened in triplicate by ddPCR and nPCR. No deletions were observed by ddPCR, while by nPCR no band for hrp2 was observed in 8% of samples. The ddPCR assay was applied to screen 830 samples from six countries in Africa and South America. No or very few deletions were observed in Kenya (n=241). Zanzibar/Tanzania (n=91), and Ghana (n=223). In southwestern Ethiopia, 1/47 (2.1%) samples carried hrp2 deletion, and 35/47 (74.5%) hrp3 deletions. In Brazil, 87/187 (46.5%) samples carried hrp2 deletions, and 116/187 (62%) hrp3 deletions. In Ecuador, no hrp2 deletions were observed, but 22/41 (53.7%) samples carried hrp3 deletions. Conclusions: Compared to nPCR, the ddPCR assay minimizes the risk of false-negative results (i.e. hrp2 deletion observed when the sample is wild type), increases sensitivity, and greatly reduces the number of reactions that need to be run. Pronounced differences in the prevalence of deletion were observed among sites, with more hrp3 than hrp2 deletions.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/49069/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALSimoneL_Andrade_etal_IOC_2021.pdfSimoneL_Andrade_etal_IOC_2021.pdfapplication/pdf1614349https://www.arca.fiocruz.br/bitstream/icict/49069/2/SimoneL_Andrade_etal_IOC_2021.pdf076f7695fe7bceaef15e773bab96f42aMD52TEXTSimoneL_Andrade_etal_IOC_2021.pdf.txtSimoneL_Andrade_etal_IOC_2021.pdf.txtExtracted texttext/plain66680https://www.arca.fiocruz.br/bitstream/icict/49069/3/SimoneL_Andrade_etal_IOC_2021.pdf.txtb11dd6f40f75533956154a05e29fc7acMD53icict/490692021-09-17 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dc.title.pt_BR.fl_str_mv Plasmodium falciparum hrp2 and hrp3 gene deletion status in Africa and South America by highly sensitive and specific digital PCR
title Plasmodium falciparum hrp2 and hrp3 gene deletion status in Africa and South America by highly sensitive and specific digital PCR
spellingShingle Plasmodium falciparum hrp2 and hrp3 gene deletion status in Africa and South America by highly sensitive and specific digital PCR
Vera-Arias, Claudia A.
Plasmodium falciparum hrp2
Plasmodium falciparum hrp3
Status de exclusão do gene
África
América do Sul
PCR digital altamente sensível e específico
Plasmodium falciparum hrp2
Plasmodium falciparum hrp3
Gene deletion status
África
South America
Highly sensitive and specific digital PCR
title_short Plasmodium falciparum hrp2 and hrp3 gene deletion status in Africa and South America by highly sensitive and specific digital PCR
title_full Plasmodium falciparum hrp2 and hrp3 gene deletion status in Africa and South America by highly sensitive and specific digital PCR
title_fullStr Plasmodium falciparum hrp2 and hrp3 gene deletion status in Africa and South America by highly sensitive and specific digital PCR
title_full_unstemmed Plasmodium falciparum hrp2 and hrp3 gene deletion status in Africa and South America by highly sensitive and specific digital PCR
title_sort Plasmodium falciparum hrp2 and hrp3 gene deletion status in Africa and South America by highly sensitive and specific digital PCR
author Vera-Arias, Claudia A.
author_facet Vera-Arias, Claudia A.
Holzschuh, Aurel
Oduma, Colins O.
Badu, Kingsley
Abdul-Hakim, Mutala
Yukich, Joshua
Hetzel, Manuel W.
Fakih, Bakar S.
Ali, Abdullah
Ferreira, Marcelo U.
Ladeia-Andrade, Simone
Sáenz, Fabián E.
Afrane, Yaw
Zemene, Endalew
Yewhalaw, Delenasaw
Kazura, James W.
Yan, Guiyun
Koepfli, Cristian
author_role author
author2 Holzschuh, Aurel
Oduma, Colins O.
Badu, Kingsley
Abdul-Hakim, Mutala
Yukich, Joshua
Hetzel, Manuel W.
Fakih, Bakar S.
Ali, Abdullah
Ferreira, Marcelo U.
Ladeia-Andrade, Simone
Sáenz, Fabián E.
Afrane, Yaw
Zemene, Endalew
Yewhalaw, Delenasaw
Kazura, James W.
Yan, Guiyun
Koepfli, Cristian
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Vera-Arias, Claudia A.
Holzschuh, Aurel
Oduma, Colins O.
Badu, Kingsley
Abdul-Hakim, Mutala
Yukich, Joshua
Hetzel, Manuel W.
Fakih, Bakar S.
Ali, Abdullah
Ferreira, Marcelo U.
Ladeia-Andrade, Simone
Sáenz, Fabián E.
Afrane, Yaw
Zemene, Endalew
Yewhalaw, Delenasaw
Kazura, James W.
Yan, Guiyun
Koepfli, Cristian
dc.subject.other.pt_BR.fl_str_mv Plasmodium falciparum hrp2
Plasmodium falciparum hrp3
Status de exclusão do gene
África
América do Sul
PCR digital altamente sensível e específico
topic Plasmodium falciparum hrp2
Plasmodium falciparum hrp3
Status de exclusão do gene
África
América do Sul
PCR digital altamente sensível e específico
Plasmodium falciparum hrp2
Plasmodium falciparum hrp3
Gene deletion status
África
South America
Highly sensitive and specific digital PCR
dc.subject.en.pt_BR.fl_str_mv Plasmodium falciparum hrp2
Plasmodium falciparum hrp3
Gene deletion status
África
South America
Highly sensitive and specific digital PCR
description University of Notre Dame. Notre Dame, IN, USA.
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-09-14T10:26:03Z
dc.date.available.fl_str_mv 2021-09-14T10:26:03Z
dc.date.issued.fl_str_mv 2021
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv VERA-ARIAS, Claudia A. et al. Plasmodium falciparum hrp2 and hrp3 gene deletion status in Africa and South America by highly sensitive and specific digital PCR. medRxiv Preprint, p. 1-5, June 2021.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/49069
dc.identifier.doi.pt_BR.fl_str_mv 10.1101/2021.06.01.21258117
identifier_str_mv VERA-ARIAS, Claudia A. et al. Plasmodium falciparum hrp2 and hrp3 gene deletion status in Africa and South America by highly sensitive and specific digital PCR. medRxiv Preprint, p. 1-5, June 2021.
10.1101/2021.06.01.21258117
url https://www.arca.fiocruz.br/handle/icict/49069
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MedRxiv preprint
publisher.none.fl_str_mv MedRxiv preprint
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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