Deletion patterns, genetic variability and protein structure of pfhrp2 and pfhrp3: implications for malaria rapid diagnostic test in Amhara region, Ethiopia
Abstract Background Although rapid diagnostic tests (RDTs) play a key role in malaria-control strategies, their efficacy has been threatened by deletion and genetic variability of the genes pfhrp2/3. This study aims to characterize the deletion, genetic patterns and diversity of these genes and thei...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-10-01
|
| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-022-04306-3 |
| _version_ | 1811226579902136320 |
|---|---|
| author | Irene Molina - de la Fuente Mulat Yimar Luz García Vicenta González Arancha Amor Melaku Anegagrie Agustín Benito Javier Martínez Marta Moreno Pedro Berzosa |
| author_facet | Irene Molina - de la Fuente Mulat Yimar Luz García Vicenta González Arancha Amor Melaku Anegagrie Agustín Benito Javier Martínez Marta Moreno Pedro Berzosa |
| author_sort | Irene Molina - de la Fuente |
| collection | DOAJ |
| description | Abstract Background Although rapid diagnostic tests (RDTs) play a key role in malaria-control strategies, their efficacy has been threatened by deletion and genetic variability of the genes pfhrp2/3. This study aims to characterize the deletion, genetic patterns and diversity of these genes and their implication for malaria RDT effectiveness, as well as their genetic evolution in the Amhara region of Ethiopia. Methods The study included 354 isolates from symptomatic patients from the Amhara region of Ethiopia who tested positive by microscopy. Exon 1–2 and exon 2 of genes pfhrp2 and -3 were amplified, and exon 2 was sequenced to analyse the genetic diversity, phylogenetic relationship and epitope availability. Results The deletion frequency in exon 1–2 and exon 2 was 22 and 4.6% for pfhrp2, and 68 and 18% for pfhrp3, respectively. Double deletion frequency for pfhrp2 and pfhrp3 was 1.4%. High genetic diversity, lack of clustering by phylogenetic analysis and evidence of positive selection suggested a diversifying selection for both genes. The amino-acid sequences, classified into different haplotypes, varied widely in terms of frequency of repeats, with novel amino-acid changes. Aminoacidic repetition type 2 and type 7 were the most frequent in all the sequences. The most frequent epitopes among protein sequences were those recognized by MAbs 3A4 and C1-13. Conclusion Deletions and high amino acidic variation in pfhrp2 and pfhrp3 suggest their possible impact on RDT use in the Amhara region, and the high genetic diversity of these genes could be associated with a diversifying selection in Ethiopia. Surveillance of these genes is, therefore, essential to ensure the effectiveness of public health interventions in this region. Graphical Abstract |
| first_indexed | 2024-04-12T09:27:30Z |
| format | Article |
| id | doaj.art-fbe60b845a014ef4aab871b2eda9e413 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-04-12T09:27:30Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-fbe60b845a014ef4aab871b2eda9e4132022-12-22T03:38:27ZengBMCMalaria Journal1475-28752022-10-0121111710.1186/s12936-022-04306-3Deletion patterns, genetic variability and protein structure of pfhrp2 and pfhrp3: implications for malaria rapid diagnostic test in Amhara region, EthiopiaIrene Molina - de la Fuente0Mulat Yimar1Luz García2Vicenta González3Arancha Amor4Melaku Anegagrie5Agustín Benito6Javier Martínez7Marta Moreno8Pedro Berzosa9Department of Biomedicine and Biotechnology, School of Pharmacy, University of AlcaláCollege of Medicine and Health Sciences, Bahir Dar UniversityMalaria and Neglected Diseases Laboratory, National Centre of Tropical Medicine, Institute of Health Carlos IIIMalaria and Neglected Diseases Laboratory, National Centre of Tropical Medicine, Institute of Health Carlos IIIMundo Sano Foundations, Institute of Health Carlos IIIMundo Sano Foundations, Institute of Health Carlos IIIMalaria and Neglected Diseases Laboratory, National Centre of Tropical Medicine, Institute of Health Carlos IIIDepartment of Biomedicine and Biotechnology, School of Pharmacy, University of AlcaláDepartment of Infection Biology, London School of Hygiene and Tropical MedicineMalaria and Neglected Diseases Laboratory, National Centre of Tropical Medicine, Institute of Health Carlos IIIAbstract Background Although rapid diagnostic tests (RDTs) play a key role in malaria-control strategies, their efficacy has been threatened by deletion and genetic variability of the genes pfhrp2/3. This study aims to characterize the deletion, genetic patterns and diversity of these genes and their implication for malaria RDT effectiveness, as well as their genetic evolution in the Amhara region of Ethiopia. Methods The study included 354 isolates from symptomatic patients from the Amhara region of Ethiopia who tested positive by microscopy. Exon 1–2 and exon 2 of genes pfhrp2 and -3 were amplified, and exon 2 was sequenced to analyse the genetic diversity, phylogenetic relationship and epitope availability. Results The deletion frequency in exon 1–2 and exon 2 was 22 and 4.6% for pfhrp2, and 68 and 18% for pfhrp3, respectively. Double deletion frequency for pfhrp2 and pfhrp3 was 1.4%. High genetic diversity, lack of clustering by phylogenetic analysis and evidence of positive selection suggested a diversifying selection for both genes. The amino-acid sequences, classified into different haplotypes, varied widely in terms of frequency of repeats, with novel amino-acid changes. Aminoacidic repetition type 2 and type 7 were the most frequent in all the sequences. The most frequent epitopes among protein sequences were those recognized by MAbs 3A4 and C1-13. Conclusion Deletions and high amino acidic variation in pfhrp2 and pfhrp3 suggest their possible impact on RDT use in the Amhara region, and the high genetic diversity of these genes could be associated with a diversifying selection in Ethiopia. Surveillance of these genes is, therefore, essential to ensure the effectiveness of public health interventions in this region. Graphical Abstracthttps://doi.org/10.1186/s12936-022-04306-3MalariaEthiopiaPlasmodium falciparumpfhrp2Rapid diagnostic testDeletions |
| spellingShingle | Irene Molina - de la Fuente Mulat Yimar Luz García Vicenta González Arancha Amor Melaku Anegagrie Agustín Benito Javier Martínez Marta Moreno Pedro Berzosa Deletion patterns, genetic variability and protein structure of pfhrp2 and pfhrp3: implications for malaria rapid diagnostic test in Amhara region, Ethiopia Malaria Journal Malaria Ethiopia Plasmodium falciparum pfhrp2 Rapid diagnostic test Deletions |
| title | Deletion patterns, genetic variability and protein structure of pfhrp2 and pfhrp3: implications for malaria rapid diagnostic test in Amhara region, Ethiopia |
| title_full | Deletion patterns, genetic variability and protein structure of pfhrp2 and pfhrp3: implications for malaria rapid diagnostic test in Amhara region, Ethiopia |
| title_fullStr | Deletion patterns, genetic variability and protein structure of pfhrp2 and pfhrp3: implications for malaria rapid diagnostic test in Amhara region, Ethiopia |
| title_full_unstemmed | Deletion patterns, genetic variability and protein structure of pfhrp2 and pfhrp3: implications for malaria rapid diagnostic test in Amhara region, Ethiopia |
| title_short | Deletion patterns, genetic variability and protein structure of pfhrp2 and pfhrp3: implications for malaria rapid diagnostic test in Amhara region, Ethiopia |
| title_sort | deletion patterns genetic variability and protein structure of pfhrp2 and pfhrp3 implications for malaria rapid diagnostic test in amhara region ethiopia |
| topic | Malaria Ethiopia Plasmodium falciparum pfhrp2 Rapid diagnostic test Deletions |
| url | https://doi.org/10.1186/s12936-022-04306-3 |
| work_keys_str_mv | AT irenemolinadelafuente deletionpatternsgeneticvariabilityandproteinstructureofpfhrp2andpfhrp3implicationsformalariarapiddiagnostictestinamhararegionethiopia AT mulatyimar deletionpatternsgeneticvariabilityandproteinstructureofpfhrp2andpfhrp3implicationsformalariarapiddiagnostictestinamhararegionethiopia AT luzgarcia deletionpatternsgeneticvariabilityandproteinstructureofpfhrp2andpfhrp3implicationsformalariarapiddiagnostictestinamhararegionethiopia AT vicentagonzalez deletionpatternsgeneticvariabilityandproteinstructureofpfhrp2andpfhrp3implicationsformalariarapiddiagnostictestinamhararegionethiopia AT aranchaamor deletionpatternsgeneticvariabilityandproteinstructureofpfhrp2andpfhrp3implicationsformalariarapiddiagnostictestinamhararegionethiopia AT melakuanegagrie deletionpatternsgeneticvariabilityandproteinstructureofpfhrp2andpfhrp3implicationsformalariarapiddiagnostictestinamhararegionethiopia AT agustinbenito deletionpatternsgeneticvariabilityandproteinstructureofpfhrp2andpfhrp3implicationsformalariarapiddiagnostictestinamhararegionethiopia AT javiermartinez deletionpatternsgeneticvariabilityandproteinstructureofpfhrp2andpfhrp3implicationsformalariarapiddiagnostictestinamhararegionethiopia AT martamoreno deletionpatternsgeneticvariabilityandproteinstructureofpfhrp2andpfhrp3implicationsformalariarapiddiagnostictestinamhararegionethiopia AT pedroberzosa deletionpatternsgeneticvariabilityandproteinstructureofpfhrp2andpfhrp3implicationsformalariarapiddiagnostictestinamhararegionethiopia |