Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions among patients enrolled at 100 health facilities throughout Tanzania: February to July 2021
Abstract Plasmodium falciparum with the histidine rich protein 2 gene (pfhrp2) deleted from its genome can escape diagnosis by HRP2-based rapid diagnostic tests (HRP2-RDTs). The World Health Organization (WHO) recommends switching to a non-HRP2 RDT for P. falciparum clinical case diagnosis when pfhr...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-04-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-58455-3 |
| _version_ | 1797209443226615808 |
|---|---|
| author | Eric Rogier Nastassia Battle Catherine Bakari Misago D. Seth Douglas Nace Camelia Herman Achut Barakoti Rashid A. Madebe Celine I. Mandara Beatus M. Lyimo David J. Giesbrecht Zachary R. Popkin-Hall Filbert Francis Daniel Mbwambo Issa Garimo Sijenunu Aaron Abdallah Lusasi Fabrizio Molteni Ritha Njau Jane A. Cunningham Samwel Lazaro Ally Mohamed Jonathan J. Juliano Jeffrey A. Bailey Venkatachalam Udhayakumar Deus S. Ishengoma |
| author_facet | Eric Rogier Nastassia Battle Catherine Bakari Misago D. Seth Douglas Nace Camelia Herman Achut Barakoti Rashid A. Madebe Celine I. Mandara Beatus M. Lyimo David J. Giesbrecht Zachary R. Popkin-Hall Filbert Francis Daniel Mbwambo Issa Garimo Sijenunu Aaron Abdallah Lusasi Fabrizio Molteni Ritha Njau Jane A. Cunningham Samwel Lazaro Ally Mohamed Jonathan J. Juliano Jeffrey A. Bailey Venkatachalam Udhayakumar Deus S. Ishengoma |
| author_sort | Eric Rogier |
| collection | DOAJ |
| description | Abstract Plasmodium falciparum with the histidine rich protein 2 gene (pfhrp2) deleted from its genome can escape diagnosis by HRP2-based rapid diagnostic tests (HRP2-RDTs). The World Health Organization (WHO) recommends switching to a non-HRP2 RDT for P. falciparum clinical case diagnosis when pfhrp2 deletion prevalence causes ≥ 5% of RDTs to return false negative results. Tanzania is a country of heterogenous P. falciparum transmission, with some regions approaching elimination and others at varying levels of control. In concordance with the current recommended WHO pfhrp2 deletion surveillance strategy, 100 health facilities encompassing 10 regions of Tanzania enrolled malaria-suspected patients between February and July 2021. Of 7863 persons of all ages enrolled and providing RDT result and blood sample, 3777 (48.0%) were positive by the national RDT testing for Plasmodium lactate dehydrogenase (pLDH) and/or HRP2. A second RDT testing specifically for the P. falciparum LDH (Pf-pLDH) antigen found 95 persons (2.5% of all RDT positives) were positive, though negative by the national RDT for HRP2, and were selected for pfhrp2 and pfhrp3 (pfhrp2/3) genotyping. Multiplex antigen detection by laboratory bead assay found 135/7847 (1.7%) of all blood samples positive for Plasmodium antigens but very low or no HRP2, and these were selected for genotyping as well. Of the samples selected for genotyping based on RDT or laboratory multiplex result, 158 were P. falciparum DNA positive, and 140 had sufficient DNA to be genotyped for pfhrp2/3. Most of these (125/140) were found to be pfhrp2+/pfhrp3+, with smaller numbers deleted for only pfhrp2 (n = 9) or only pfhrp3 (n = 6). No dual pfhrp2/3 deleted parasites were observed. This survey found that parasites with these gene deletions are rare in Tanzania, and estimated that 0.24% (95% confidence interval: 0.08% to 0.39%) of false-negative HRP2-RDTs for symptomatic persons were due to pfhrp2 deletions in this 2021 Tanzania survey. These data provide evidence for HRP2-based diagnostics as currently accurate for P. falciparum diagnosis in Tanzania. |
| first_indexed | 2024-04-24T09:54:47Z |
| format | Article |
| id | doaj.art-d92f31d7cdc04d58bd7d693c2fc892ca |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T09:54:47Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d92f31d7cdc04d58bd7d693c2fc892ca2024-04-14T11:13:11ZengNature PortfolioScientific Reports2045-23222024-04-0114111010.1038/s41598-024-58455-3Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions among patients enrolled at 100 health facilities throughout Tanzania: February to July 2021Eric Rogier0Nastassia Battle1Catherine Bakari2Misago D. Seth3Douglas Nace4Camelia Herman5Achut Barakoti6Rashid A. Madebe7Celine I. Mandara8Beatus M. Lyimo9David J. Giesbrecht10Zachary R. Popkin-Hall11Filbert Francis12Daniel Mbwambo13Issa Garimo14Sijenunu Aaron15Abdallah Lusasi16Fabrizio Molteni17Ritha Njau18Jane A. Cunningham19Samwel Lazaro20Ally Mohamed21Jonathan J. Juliano22Jeffrey A. Bailey23Venkatachalam Udhayakumar24Deus S. Ishengoma25Malaria Branch, Centers for Disease Control and PreventionCDC FoundationNational Institute for Medical ResearchNational Institute for Medical ResearchMalaria Branch, Centers for Disease Control and PreventionMalaria Branch, Centers for Disease Control and PreventionMalaria Branch, Centers for Disease Control and PreventionNational Institute for Medical ResearchNational Institute for Medical ResearchNational Institute for Medical ResearchBrown UniversityUniversity of North CarolinaNational Institute for Medical ResearchNational Malaria Control ProgrammeNational Malaria Control ProgrammeNational Malaria Control ProgrammeNational Malaria Control ProgrammeSwiss Tropical Public Health InstituteWorld Health Organization, Country OfficeWorld Health Organization, HeadquartersNational Malaria Control ProgrammeNational Malaria Control ProgrammeUniversity of North CarolinaBrown UniversityMalaria Branch, Centers for Disease Control and PreventionNational Institute for Medical ResearchAbstract Plasmodium falciparum with the histidine rich protein 2 gene (pfhrp2) deleted from its genome can escape diagnosis by HRP2-based rapid diagnostic tests (HRP2-RDTs). The World Health Organization (WHO) recommends switching to a non-HRP2 RDT for P. falciparum clinical case diagnosis when pfhrp2 deletion prevalence causes ≥ 5% of RDTs to return false negative results. Tanzania is a country of heterogenous P. falciparum transmission, with some regions approaching elimination and others at varying levels of control. In concordance with the current recommended WHO pfhrp2 deletion surveillance strategy, 100 health facilities encompassing 10 regions of Tanzania enrolled malaria-suspected patients between February and July 2021. Of 7863 persons of all ages enrolled and providing RDT result and blood sample, 3777 (48.0%) were positive by the national RDT testing for Plasmodium lactate dehydrogenase (pLDH) and/or HRP2. A second RDT testing specifically for the P. falciparum LDH (Pf-pLDH) antigen found 95 persons (2.5% of all RDT positives) were positive, though negative by the national RDT for HRP2, and were selected for pfhrp2 and pfhrp3 (pfhrp2/3) genotyping. Multiplex antigen detection by laboratory bead assay found 135/7847 (1.7%) of all blood samples positive for Plasmodium antigens but very low or no HRP2, and these were selected for genotyping as well. Of the samples selected for genotyping based on RDT or laboratory multiplex result, 158 were P. falciparum DNA positive, and 140 had sufficient DNA to be genotyped for pfhrp2/3. Most of these (125/140) were found to be pfhrp2+/pfhrp3+, with smaller numbers deleted for only pfhrp2 (n = 9) or only pfhrp3 (n = 6). No dual pfhrp2/3 deleted parasites were observed. This survey found that parasites with these gene deletions are rare in Tanzania, and estimated that 0.24% (95% confidence interval: 0.08% to 0.39%) of false-negative HRP2-RDTs for symptomatic persons were due to pfhrp2 deletions in this 2021 Tanzania survey. These data provide evidence for HRP2-based diagnostics as currently accurate for P. falciparum diagnosis in Tanzania.https://doi.org/10.1038/s41598-024-58455-3Plasmodium falciparumTanzaniaRDTpfhrp2pfhrp3Gene deletion |
| spellingShingle | Eric Rogier Nastassia Battle Catherine Bakari Misago D. Seth Douglas Nace Camelia Herman Achut Barakoti Rashid A. Madebe Celine I. Mandara Beatus M. Lyimo David J. Giesbrecht Zachary R. Popkin-Hall Filbert Francis Daniel Mbwambo Issa Garimo Sijenunu Aaron Abdallah Lusasi Fabrizio Molteni Ritha Njau Jane A. Cunningham Samwel Lazaro Ally Mohamed Jonathan J. Juliano Jeffrey A. Bailey Venkatachalam Udhayakumar Deus S. Ishengoma Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions among patients enrolled at 100 health facilities throughout Tanzania: February to July 2021 Scientific Reports Plasmodium falciparum Tanzania RDT pfhrp2 pfhrp3 Gene deletion |
| title | Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions among patients enrolled at 100 health facilities throughout Tanzania: February to July 2021 |
| title_full | Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions among patients enrolled at 100 health facilities throughout Tanzania: February to July 2021 |
| title_fullStr | Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions among patients enrolled at 100 health facilities throughout Tanzania: February to July 2021 |
| title_full_unstemmed | Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions among patients enrolled at 100 health facilities throughout Tanzania: February to July 2021 |
| title_short | Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions among patients enrolled at 100 health facilities throughout Tanzania: February to July 2021 |
| title_sort | plasmodium falciparum pfhrp2 and pfhrp3 gene deletions among patients enrolled at 100 health facilities throughout tanzania february to july 2021 |
| topic | Plasmodium falciparum Tanzania RDT pfhrp2 pfhrp3 Gene deletion |
| url | https://doi.org/10.1038/s41598-024-58455-3 |
| work_keys_str_mv | AT ericrogier plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT nastassiabattle plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT catherinebakari plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT misagodseth plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT douglasnace plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT cameliaherman plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT achutbarakoti plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT rashidamadebe plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT celineimandara plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT beatusmlyimo plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT davidjgiesbrecht plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT zacharyrpopkinhall plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT filbertfrancis plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT danielmbwambo plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT issagarimo plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT sijenunuaaron plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT abdallahlusasi plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT fabriziomolteni plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT rithanjau plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT janeacunningham plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT samwellazaro plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT allymohamed plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT jonathanjjuliano plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT jeffreyabailey plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT venkatachalamudhayakumar plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 AT deussishengoma plasmodiumfalciparumpfhrp2andpfhrp3genedeletionsamongpatientsenrolledat100healthfacilitiesthroughouttanzaniafebruarytojuly2021 |