1921
Volume 99, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

Histidine-rich protein 2 of (PfHRP2) forms the basis of many current malaria rapid diagnostic tests (RDTs). It is concerning that there are parasites that lack part or all of the gene, and thus do not express the PfHRP2 protein; such parasites are not identifiable by PfHRP2-detecting RDTs. Very limited information is available regarding genetic variation in Papua New Guinea (PNG). In the present study, this gene variation was evaluated using 169 samples previously collected from the Wosera area in East Sepik Province of PNG. Molecular diagnosis of these samples showed that 81% were infected, and was present in 91% of those infected samples. One hundred and twenty samples were amplified for exon-2, from which 12 randomly selected amplicons were sequenced, yielding 18 sequences, all of which were unique. Baker repeat type 2 × type 7 numbers ranged from 0 to 108. Epitope mapping analysis revealed that three major epitopes, DAHHAHHA, AHHAADAHHA, and AHHAADAHH, were present in high prevalence and frequencies. These major epitopes have been shown to be recognized by the monoclonal antibodies 3A4 and PTL-3 (DAHHAHHA), C1-13 (AHHAADAHHA), and S2-5 and C2-3 (AHHAADAHH). This study provides further information on the high genetic variation of and its unclear relationship with prediction of RDT detection sensitivity, and identifies major epitopes in this gene from PNG. These results could be relevant and useful to understand the genetic diversity of this gene and the performance of current and future RDTs in this malarious region of the world.

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References

  1. Parra ME, Evans CB, Taylor DW, , 1991. Identification of Plasmodium falciparum histidine-rich protein 2 in the plasma of humans with malaria. J Clin Microbiol 29: 16291634. [Google Scholar]
  2. Moody A, , 2002. Rapid diagnostic tests for malaria parasites. Clin Microbiol Rev 15: 6678. [Google Scholar]
  3. Genton B, Hii J, Paget S, Alpers MP, , 1996. Rapid manual diagnosis of Plasmodium falciparum malaria using ParaSight-F dipsticks applied to human blood and urine. J Travel Med 3: 172173. [Google Scholar]
  4. Genton B, Paget S, Beck HP, Gibson N, Alpers MP, Hii J, , 1998. Diagnosis of Plasmodium falciparum infection using ParaSight®-F test in blood and urine of Papua New Guinean children. Southeast Asian J Trop Med Public Health 29: 3540. [Google Scholar]
  5. Senn N, Rarau P, Manong D, Salib M, Siba P, Robinson LJ, Reeder J, Rogerson S, Mueller I, Genton B, , 2012. Rapid diagnostic test-based management of malaria: an effectiveness study in Papua New Guinean infants with Plasmodium falciparum and Plasmodium vivax malaria. Clin Infect Dis 54: 644651. [Google Scholar]
  6. Manning L, Laman M, Rosanas-Urgell A, Turlach B, Aipit S, Bona C, Warrell J, Siba P, Mueller I, Davis TM, , 2012. Rapid antigen detection tests for malaria diagnosis in severely ill Papua New Guinean children: a comparative study using Bayesian latent class models. PLoS One 7: e48701. [Google Scholar]
  7. Umbers AJ, 2015. Accuracy of an HRP-2/panLDH rapid diagnostic test to detect peripheral and placental Plasmodium falciparum infection in Papua New Guinean women with anaemia or suspected malaria. Malar J 14: 412. [Google Scholar]
  8. Cheng Q, Gatton ML, Barnwell J, Chiodini P, McCarthy J, Bell D, Cunningham J, , 2014. Plasmodium falciparum parasites lacking histidine-rich protein 2 and 3: a review and recommendations for accurate reporting. Malar J 13: 283. [Google Scholar]
  9. Baker J, 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. [Google Scholar]
  10. Baker J, McCarthy J, Gatton M, Kyle DE, Belizario V, Luchavez J, Bell D, Cheng Q, , 2005. Genetic diversity of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and its effect on the performance of PfHRP2-based rapid diagnostic tests. J Infect Dis 192: 870877. [Google Scholar]
  11. Kumar Bharti P, Singh Chandel H, Krishna S, Nema S, Ahmad A, Udhayakumar V, Singh N, , 2017. Sequence variation in Plasmodium falciparum histidine rich proteins 2 and 3 in Indian isolates: implications for malaria rapid diagnostic test performance. Sci Rep 7: 1308. [Google Scholar]
  12. Willie N, Mehlotra RK, Howes RE, Rakotomanga TA, Ramboarina S, Ratsimbasoa AC, Zimmerman PA, , 2018. Insights into the performance of SD Bioline Malaria Ag P.f/Pan rapid diagnostic test and Plasmodium falciparum histidine-rich protein 2 gene variation in Madagascar. Am J Trop Med Hyg 98: 16831691. [Google Scholar]
  13. Kemp DJ, Thompson JK, Walliker D, Corcoran LM, , 1987. Molecular karyotype of Plasmodium falciparum: conserved linkage groups and expendable histidine-rich protein genes. Proc Natl Acad Sci USA 84: 76727676. [Google Scholar]
  14. Kasehagen LJ, 2006. Changing patterns of Plasmodium blood-stage infections in the Wosera region of Papua New Guinea monitored by light microscopy and high throughput PCR diagnosis. Am J Trop Med Hyg 75: 588596. [Google Scholar]
  15. McNamara DT, Kasehagen LJ, Grimberg BT, Cole-Tobian J, Collins WE, Zimmerman PA, , 2006. Diagnosing infection levels of four human malaria parasite species by a polymerase chain reaction/ligase detection reaction fluorescent microsphere-based assay. Am J Trop Med Hyg 74: 413421. [Google Scholar]
  16. Mariette N, Barnadas C, Bouchier C, Tichit M, Menard D, , 2008. Country-wide assessment of the genetic polymorphism in Plasmodium falciparum and Plasmodium vivax antigens detected with rapid diagnostic tests for malaria. Malar J 7: 219. [Google Scholar]
  17. Walker-Jonah A, Dolan SA, Gwadz RW, Panton LJ, Wellems TE, , 1992. An RFLP map of the Plasmodium falciparum genome, recombination rates and favored linkage groups in a genetic cross. Mol Biochem Parasitol 51: 313320. [Google Scholar]
  18. Lee N, Gatton ML, Pelecanos A, Bubb M, Gonzalez I, Bell D, Cheng Q, McCarthy JS, , 2012. Identification of optimal epitopes for Plasmodium falciparum rapid diagnostic tests that target histidine-rich proteins 2 and 3. J Clin Microbiol 50: 13971405. [Google Scholar]
  19. Mehlotra RK, Kasehagen LJ, Baisor M, Lorry K, Kazura JW, Bockarie MJ, Zimmerman PA, , 2002. Malaria infections are randomly distributed in diverse holoendemic areas of Papua New Guinea. Am J Trop Med Hyg 67: 555562. [Google Scholar]
  20. Mehlotra RK, Lorry K, Kastens W, Miller SM, Alpers MP, Bockarie M, Kazura JW, Zimmerman PA, , 2000. Random distribution of mixed species malaria infections in Papua New Guinea. Am J Trop Med Hyg 62: 225231. [Google Scholar]
  21. Genton B, al-Yaman F, Beck HP, Hii J, Mellor S, Narara A, Gibson N, Smith T, Alpers MP, , 1995. The epidemiology of malaria in the Wosera area, East Sepik Province, Papua New Guinea, in preparation for vaccine trials. I. Malariometric indices and immunity. Ann Trop Med Parasitol 89: 359376. [Google Scholar]
  22. Lee N, Baker J, Andrews KT, Gatton ML, Bell D, Cheng Q, McCarthy J, , 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: 27732778. [Google Scholar]
  23. Fola AA, Harrison GLA, Hazairin MH, Barnadas C, Hetzel MW, Iga J, Siba PM, Mueller I, Barry AE, , 2017. Higher complexity of infection and genetic diversity of Plasmodium vivax than Plasmodium falciparum across all malaria transmission zones of Papua New Guinea. Am J Trop Med Hyg 96: 630641. [Google Scholar]
  24. Lalremruata A, 2017. Species and genotype diversity of Plasmodium in malaria patients from Gabon analysed by next generation sequencing. Malar J 16: 398. [Google Scholar]
  25. Levitt B, Obala A, Langdon S, Corcoran D, O’Meara WP, Taylor SM, , 2017. Overlap extension barcoding for the next generation sequencing and genotyping of Plasmodium falciparum in individual patients in western Kenya. Sci Rep 7: 41108. [Google Scholar]
  26. Golassa L, Enweji N, Erko B, Aseffa A, Swedberg G, , 2013. Detection of a substantial number of sub-microscopic Plasmodium falciparum infections by polymerase chain reaction: a potential threat to malaria control and diagnosis in Ethiopia. Malar J 12: 352. [Google Scholar]
  27. Harris I, 2010. A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands: challenges for malaria diagnostics in an elimination setting. Malar J 9: 254. [Google Scholar]
  28. Tripura R, 2017. Submicroscopic Plasmodium prevalence in relation to malaria incidence in 20 villages in western Cambodia. Malar J 16: 56. [Google Scholar]
  29. Zaw MT, 2017. Asymptomatic and sub-microscopic malaria infection in Kayah State, eastern Myanmar. Malar J 16: 138. [Google Scholar]
  30. Rosewell A, Makita L, Muscatello D, John LN, Bieb S, Hutton R, Ramamurthy S, Shearman P, , 2017. Health information system strengthening and malaria elimination in Papua New Guinea. Malar J 16: 278. [Google Scholar]
  31. Das S, Peck RB, Barney R, Jang IK, Kahn M, Zhu M, Domingo GJ, , 2018. Performance of an ultra-sensitive Plasmodium falciparum HRP2-based rapid diagnostic test with recombinant HRP2, culture parasites, and archived whole blood samples. Malar J 17: 118. [Google Scholar]
  32. Leow CH, Jones M, Cheng Q, Mahler S, McCarthy J, , 2014. Production and characterization of specific monoclonal antibodies binding the Plasmodium falciparum diagnostic biomarker, histidine-rich protein 2. Malar J 13: 277. [Google Scholar]
  33. Ramutton T, 2012. Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria. Malar J 11: 276. [Google Scholar]
  34. Baker J, Gatton ML, Peters J, Ho MF, McCarthy JS, Cheng Q, , 2011. Transcription and expression of Plasmodium falciparum histidine-rich proteins in different stages and strains: implications for rapid diagnostic tests. PLoS One 6: e22593. [Google Scholar]
  35. Beshir KB, Sepulveda N, Bharmal J, Robinson A, Mwanguzi J, Busula AO, de Boer JG, Sutherland C, Cunningham J, Hopkins H, , 2017. Plasmodium falciparum parasites with histidine-rich protein 2 (pfhrp2) and pfhrp3 gene deletions in two endemic regions of Kenya. Sci Rep 7: 14718. [Google Scholar]
  36. Gamboa D, 2010. A large proportion of P. falciparum isolates in the Amazon region of Peru lack pfhrp2 and pfhrp3: implications for malaria rapid diagnostic tests. PLoS One 5: e8091. [Google Scholar]
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  • Received : 15 Feb 2018
  • Accepted : 24 May 2018
  • Published online : 02 Jul 2018

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