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-
1.
 World Health Organization , 2019. Malaria. Diagnostic Testing 2019 [cited 2019 15.11.2019]. Available at: https://www.who.int/malaria/areas/diagnosis/en/.
-
2.
  Schindler T et al.2019. Molecular monitoring of the diversity of human pathogenic malaria species in blood donations on Bioko Island, Equatorial Guinea. Malar J 18: 9.
-
3.
  Oboh MA et al.2018. Molecular identification of Plasmodium species responsible for malaria reveals Plasmodium vivax isolates in Duffy negative individuals from southwestern Nigeria. Malar J 17: 439.
-
4.
  Baker J et al.2010. Global sequence variation in the histidine-rich proteins 2 and 3 of Plasmodium falciparum: implications for the performance of malaria rapid diagnostic tests. Malar J 9: 129.
-
5.
  Deme AB et al.2014. Analysis of pfhrp2 genetic diversity in Senegal and implications for use of rapid diagnostic tests. Malar J 13: 34.
-
6.
  Addai-Mensah O et al.2020. Plasmodium falciparum histidine-rich protein 2 diversity in Ghana. Malar J 19: 256.
-
7.
  Lee N et al.2006. Effect of sequence variation in Plasmodium falciparum histidine-rich protein 2 on binding of specific monoclonal antibodies: implications for rapid diagnostic tests for malaria. J Clin Microbiol 44: 2773–2778.
-
8.
  Nderu D et al.2019. Genetic diversity and population structure of Plasmodium falciparum in Kenyan–Ugandan border areas. Trop Med Int Health 24: 647–656.
-
9.
  Amoah LE et al.2020. Contribution of P. falciparum parasites with Pfhrp 2 gene deletions to false negative PfHRP 2 based malaria RDT results in Ghana: a nationwide study of symptomatic malaria patients. PLoS One 15: e0238749.
-
10.
 World Health Organization and UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases , 2015. Microscopy for the Detection, Identification and Quantification of Malaria Parasites on Stained Thick and Thin Blood Films in Research Settings (Version 1.0): Procedure: Methods Manual. Geneva, Switzerland: WHO. Available at: https://apps.who.int/iris/handle/10665/163782.
-
11.
  Boonma P et al.2007. Comparison of three molecular methods for the detection and speciation of Plasmodium vivax and Plasmodium falciparum. Malar J 6: 124.
-
12.
  Berzosa P et al.2020. First evidence of the deletion in the pfhrp2 and pfhrp3 genes in Plasmodium falciparum from Equatorial Guinea. Malar J 19: 99.
-
13.
  Adjah J, Fiadzoe B, Ayanful-Torgby R, Amoah LE , 2018. Seasonal variations in Plasmodium falciparum genetic diversity and multiplicity of infection in asymptomatic children living in southern Ghana. BMC Infect Dis 18: 432.
-
14.
  Ayanful-Torgby R, Oppong A, Abankwa J, Acquah F, Williamson KC, Amoah LE , 2016. Plasmodium falciparum genotype and gametocyte prevalence in children with uncomplicated malaria in coastal Ghana. Malar J 15: 592.
-
15.
  Katoh K, Misawa K, Kuma K, Miyata T , 2002. MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Res 30: 3059–3066.
-
16.
  Abukari Z et al.2019. The diversity, multiplicity of infection and population structure of P. falciparum parasites circulating in asymptomatic carriers living in high and low malaria transmission settings of Ghana. Genes (Basel) 2019: 10.
-
17.
  Alemayehu GS et al.2021. Genetic variation of Plasmodium falciparum histidine-rich protein 2 and 3 in Assosa zone, Ethiopia: its impact on the performance of malaria rapid diagnostic tests. Malar J 20: 394.
-
18.
Nderu D, Kimani F, Thiong’o K, Karanja E, Akinyi M, Too E, Chege W, Nambati E, Meyer CG, Velavan TP, 2019. Plasmodium falciparum histidine-rich protein (PfHRP2 and 3) diversity in western and coastal Kenya. Sci Rep 9: 1709.
-
19.
  Deme AB et al.2014. Analysis of pfhrp2 genetic diversity in Senegal and implications for use of rapid diagnostic tests. Malar J 13: 34.
-
20.
  Gendrot M, Fawaz R, Dormoi J, Madamet M, Pradines B , 2019. Genetic diversity and deletion of Plasmodium falciparum histidine-rich protein 2 and 3: a threat to diagnosis of P. falciparum malaria. Clin Microbiol Infect 25: 580–585.
-
21.
  Li P et al.2015. Genetic diversity of Plasmodium falciparum histidine-rich protein 2 in the China-Myanmar border area. Acta Trop 152: 26–31.
-
22.
  Willie N, Zimmerman PA, Mehlotra RK , 2018. Plasmodium falciparum histidine-rich protein 2 gene variation in a malaria-endemic area of Papua New Guinea. Am J Trop Med Hyg 99: 697–703.
-
23.
  Golassa L, Messele A, Amambua-Ngwa A, Swedberg G , 2020. High prevalence and extended deletions in Plasmodium falciparum hrp2/3 genomic loci in Ethiopia. PLoS One 15: e0241807.
-
24.
  Atroosh WM et al.2015. Genetic variation of pfhrp2 in Plasmodium falciparum isolates from Yemen and the performance of HRP2-based malaria rapid diagnostic test. Parasit Vectors 8: 388.
-
25.
  Kumar N, Sharma S , 2012. Fragment size polymorphism in Plasmodium falciparum histidine rich proteins among Indian population is a cause for concern in rapid diagnosis of malaria. Indian J Med Microbiol 30: 488–489.
-
26.
  Thomson R et al.2019. pfhrp2 and pfhrp3 gene deletions that affect malaria rapid diagnostic tests for Plasmodium falciparum: analysis of archived blood samples from 3 African countries. J Infect Dis 220: 1444–1452.
| Past two years | Past Year | Past 30 Days | |
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Nationwide Surveillance of Pfhrp2 Exon 2 Diversity in Plasmodium falciparum Circulating in Symptomatic Malaria Patients Living in Ghana
Dorcas G. Bredu
Dorcas G. Bredu
Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana;
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George K. Ahadzi
George K. Ahadzi
Department of Microbiology and Immunology, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana;
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Dickson Donu
Dickson Donu
Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana;
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Nana Y. Peprah
Nana Y. Peprah
National Malaria Control Program, Ghana Health Services, Accra, Ghana;
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Alexander Asamoah
Alexander Asamoah
National Malaria Control Program, Ghana Health Services, Accra, Ghana;
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George A. Asumah
George A. Asumah
National Malaria Control Program, Ghana Health Services, Accra, Ghana;
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Benjamin Abuaku
Benjamin Abuaku
Department of Epidemiology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana;
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Kwame K. Asare
Kwame K. Asare
Department of Biomedical Science, School of Allied Health Sciences, College of Allied Health Sciences, University of Cape Coast, Cape Coast, Ghana;
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Dorcas Obiri-Yeboah
Dorcas Obiri-Yeboah
Department of Microbiology and Immunology, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana;
Directorate of Research, Innovation and Consultancy, University of Cape Coast, Cape Coast, Ghana;
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Directorate of Research, Innovation and Consultancy, University of Cape Coast, Cape Coast, Ghana;
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Colby T. Ford
Colby T. Ford
Department of Biological Sciences, University of North Carolina, Charlotte, North Carolina;
School of Data Science, University of North Carolina, Charlotte, North Carolina
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School of Data Science, University of North Carolina, Charlotte, North Carolina
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Eugenia Lo
Eugenia Lo
Department of Bioinformatics and Genomics, University of North Carolina, Charlotte, North Carolina;
School of Data Science, University of North Carolina, Charlotte, North Carolina
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School of Data Science, University of North Carolina, Charlotte, North Carolina
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Keziah L. Malm
Keziah L. Malm
National Malaria Control Program, Ghana Health Services, Accra, Ghana;
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Linda E. Amoah
Linda E. Amoah
Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana;
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ABSTRACT.
Reports of increasing false-negative HRP2-based rapid diagnostic test results across Africa require constant monitoring of factors associated with these false-negative outcomes, as failure of this diagnostic tool will have severe consequences on malaria treatment and control programs. This study characterized the extent of genetic diversity in the Plasmodium falciparum histidine-rich protein 2 (Pfhrp2) gene in P. falciparum isolates from symptomatic malaria patients across the regions of Ghana. Exon 2 of Pfhrp2 was amplified from gDNA using polymerase chain reaction. All Pfhrp2-negative samples were subjected to Pf18S rRNA and Pfmsp2 gene amplifications. The amplified Pfhrp2 exon 2 fragments from clonal samples were sent for commercial Sanger sequencing. The type and number of PfHRP2 repeats, classified based on repeat types previously reported, were estimated from the sequence data and compared among geographical regions. About 81% (2,333/2,890) of the original microscopy positive dried blood spot (DBS) samples were available and used in this study. The Pfhrp2 exon 2 amplification was successful in 98.5% (2,297/2,333) of the tested samples, with band size ranging from 400 bp to 1,050 bp. A total of 13 out of the 24 previously reported repeat types were identified among the samples, with three samples lacking both type 2 and type 7 repeat motifs. This study suggested that the genetic diversity of Pfhrp2 exon 2 identified in P. falciparum circulating in symptomatic malaria patients in Ghana is unlikely to influence the sensitivity and specificity of HRP2 RDT-based diagnosis.
- Supplemental Materials (PDF 662 KB)
Author Notes
Financial support: This work was funded by the Global Fund through the Ghana National Malaria Control Program.
Disclosure: Approval of the study was obtained from the Institutional Review Board (IRB) of the Noguchi Memorial Institute for Medical Research (NMIMR).
Disclaimer: All data generated or analyzed during this study are included in the manuscript and its supplementary files.
Authors’ addresses: Dorcas G. Bredu, Dickson Donu, and Linda E. Amoah, Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana, E-mails: gyamahdorcas11@gmail.com, ddonu100@gmail.com, and lamoah@ug.edu.gh. George K. Ahadzi, Department of Microbiology and Immunology, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana, E-mail: george.ahadzi@stu.ucc.edu.gh. Nana Y. Peprah, Alexander Asamoah, George A. Asumah, and Keziah L. Malm, National Malaria Control Program, Accra, Ghana, E-mails: naya_pep@yahoo.com, lexislea@yahoo.com, georgeaduasumah@yahoo.com, and keziah.malm@ghsmail.org. Benjamin Abuaku, Department of Epidemiology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana, E-mail: babuaku@noguchi.ug.edu.gh. Kwame K. Asare, Department of Biomedical Science, School of Allied Health Sciences, College of Allied Health Sciences, University of Cape Coast, Cape Coast, Ghana, E-mail: kwamsare@hotmail.com. Dorcas Obiri-Yeboah, Department of Microbiology and Immunology, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana, and Directorate of Research, Innovation and Consultancy, University of Cape Coast, Cape Coast, Ghana, E-mail: dobiri-yeboah@ucc.edu.gh. Colby T. Ford, Department of Bioinformatics and Genomics, University of North Carolina, Charlotte, NC, and Department of Biological Sciences, University of North Carolina, Charlotte, NC, E-mail: cford38@uncc.edu. Eugenia Lo, Department of Biological Sciences, University of North Carolina, Charlotte, NC, and School of Data Science, University of North Carolina, Charlotte, NC, E-mail: eugenia.lo@uncc.edu.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
 World Health Organization , 2019. Malaria. Diagnostic Testing 2019 [cited 2019 15.11.2019]. Available at: https://www.who.int/malaria/areas/diagnosis/en/.
-
2.
  Schindler T et al.2019. Molecular monitoring of the diversity of human pathogenic malaria species in blood donations on Bioko Island, Equatorial Guinea. Malar J 18: 9.
-
3.
  Oboh MA et al.2018. Molecular identification of Plasmodium species responsible for malaria reveals Plasmodium vivax isolates in Duffy negative individuals from southwestern Nigeria. Malar J 17: 439.
-
4.
  Baker J et al.2010. Global sequence variation in the histidine-rich proteins 2 and 3 of Plasmodium falciparum: implications for the performance of malaria rapid diagnostic tests. Malar J 9: 129.
-
5.
  Deme AB et al.2014. Analysis of pfhrp2 genetic diversity in Senegal and implications for use of rapid diagnostic tests. Malar J 13: 34.
-
6.
  Addai-Mensah O et al.2020. Plasmodium falciparum histidine-rich protein 2 diversity in Ghana. Malar J 19: 256.
-
7.
  Lee N et al.2006. Effect of sequence variation in Plasmodium falciparum histidine-rich protein 2 on binding of specific monoclonal antibodies: implications for rapid diagnostic tests for malaria. J Clin Microbiol 44: 2773–2778.
-
8.
  Nderu D et al.2019. Genetic diversity and population structure of Plasmodium falciparum in Kenyan–Ugandan border areas. Trop Med Int Health 24: 647–656.
-
9.
  Amoah LE et al.2020. Contribution of P. falciparum parasites with Pfhrp 2 gene deletions to false negative PfHRP 2 based malaria RDT results in Ghana: a nationwide study of symptomatic malaria patients. PLoS One 15: e0238749.
-
10.
 World Health Organization and UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases , 2015. Microscopy for the Detection, Identification and Quantification of Malaria Parasites on Stained Thick and Thin Blood Films in Research Settings (Version 1.0): Procedure: Methods Manual. Geneva, Switzerland: WHO. Available at: https://apps.who.int/iris/handle/10665/163782.
-
11.
  Boonma P et al.2007. Comparison of three molecular methods for the detection and speciation of Plasmodium vivax and Plasmodium falciparum. Malar J 6: 124.
-
12.
  Berzosa P et al.2020. First evidence of the deletion in the pfhrp2 and pfhrp3 genes in Plasmodium falciparum from Equatorial Guinea. Malar J 19: 99.
-
13.
  Adjah J, Fiadzoe B, Ayanful-Torgby R, Amoah LE , 2018. Seasonal variations in Plasmodium falciparum genetic diversity and multiplicity of infection in asymptomatic children living in southern Ghana. BMC Infect Dis 18: 432.
-
14.
  Ayanful-Torgby R, Oppong A, Abankwa J, Acquah F, Williamson KC, Amoah LE , 2016. Plasmodium falciparum genotype and gametocyte prevalence in children with uncomplicated malaria in coastal Ghana. Malar J 15: 592.
-
15.
  Katoh K, Misawa K, Kuma K, Miyata T , 2002. MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Res 30: 3059–3066.
-
16.
  Abukari Z et al.2019. The diversity, multiplicity of infection and population structure of P. falciparum parasites circulating in asymptomatic carriers living in high and low malaria transmission settings of Ghana. Genes (Basel) 2019: 10.
-
17.
  Alemayehu GS et al.2021. Genetic variation of Plasmodium falciparum histidine-rich protein 2 and 3 in Assosa zone, Ethiopia: its impact on the performance of malaria rapid diagnostic tests. Malar J 20: 394.
-
18.
Nderu D, Kimani F, Thiong’o K, Karanja E, Akinyi M, Too E, Chege W, Nambati E, Meyer CG, Velavan TP, 2019. Plasmodium falciparum histidine-rich protein (PfHRP2 and 3) diversity in western and coastal Kenya. Sci Rep 9: 1709.
-
19.
  Deme AB et al.2014. Analysis of pfhrp2 genetic diversity in Senegal and implications for use of rapid diagnostic tests. Malar J 13: 34.
-
20.
  Gendrot M, Fawaz R, Dormoi J, Madamet M, Pradines B , 2019. Genetic diversity and deletion of Plasmodium falciparum histidine-rich protein 2 and 3: a threat to diagnosis of P. falciparum malaria. Clin Microbiol Infect 25: 580–585.
-
21.
  Li P et al.2015. Genetic diversity of Plasmodium falciparum histidine-rich protein 2 in the China-Myanmar border area. Acta Trop 152: 26–31.
-
22.
  Willie N, Zimmerman PA, Mehlotra RK , 2018. Plasmodium falciparum histidine-rich protein 2 gene variation in a malaria-endemic area of Papua New Guinea. Am J Trop Med Hyg 99: 697–703.
-
23.
  Golassa L, Messele A, Amambua-Ngwa A, Swedberg G , 2020. High prevalence and extended deletions in Plasmodium falciparum hrp2/3 genomic loci in Ethiopia. PLoS One 15: e0241807.
-
24.
  Atroosh WM et al.2015. Genetic variation of pfhrp2 in Plasmodium falciparum isolates from Yemen and the performance of HRP2-based malaria rapid diagnostic test. Parasit Vectors 8: 388.
-
25.
  Kumar N, Sharma S , 2012. Fragment size polymorphism in Plasmodium falciparum histidine rich proteins among Indian population is a cause for concern in rapid diagnosis of malaria. Indian J Med Microbiol 30: 488–489.
-
26.
  Thomson R et al.2019. pfhrp2 and pfhrp3 gene deletions that affect malaria rapid diagnostic tests for Plasmodium falciparum: analysis of archived blood samples from 3 African countries. J Infect Dis 220: 1444–1452.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 1459 | 296 | 31 |
| Full Text Views | 158 | 51 | 0 |
| PDF Downloads | 134 | 14 | 0 |