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An Update on Malaria Rapid Diagnostic Tests

  • Tropical, Travel and Emerging Infections (L Chen and A Boggild, Section Editors)
  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Modern advances in malaria rapid diagnostic test (RDT) technology have increased demand for low-cost, easy-to-use assays in areas endemic for malaria. Substantial developments in diagnostic sensitivity and specificity, improvements in non-falciparum RDTs, and novel biotechnological innovations are gradually aligning the performance of RDTs with reference-level diagnostics including PCR and expert microscopy gold standards.

Recent Findings

Trends have emerged in recent malaria RDT literature: (1) improvements in the sensitivity and specificity of RDTs for Plasmodium falciparum diagnosis, making them comparable to expert microscopic examination; (2) reduced false-positive and false-negative reactions with novel antibody development; (3) improved sensitivity and specificity capabilities of Plasmodium vivax-specific RDTs; (4) developing RDTs for co-endemic mixed infection differentiation; (5) significant improvements of RDTs for Plasmodium knowlesi; (6) a global push towards assessing and confronting the growing concerns of widespread pfhrp2 gene deletions; and (7) original innovation in loop-mediated isothermal amplification (LAMP) biotechnological RDT-like platforms that demonstrate promising performance characteristics for P. falciparum, P. vivax, and P. knowlesi infections.

Summary

The past 5 years have been characterized by increasing demand for malaria RDTs, translating into meaningful improvements in performance and novel biotechnological innovation. Future work should facilitate the development of improved RDT platforms for Plasmodium ovale, P. knowlesi, and Plasmodium malariae, and surmount the issue of pfhrp2 gene deletions, while maintaining comparable performance to both PCR and expert microscopy reference standards.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. World Health Organization (WHO). World malaria report 2017 [Internet]. Geneva: World Health Organization; 2017. [cited 2018 Mar 4]. Available from: http://apps.who.int/iris/bitstream/10665/259492/1/9789241565523-eng.pdf?ua=1.

    Book  Google Scholar 

  2. Committee to Advise on Tropical Medicine and Travel (CATMAT). Canadian recommendations for the prevention and treatment of malaria [Internet]. Ottawa: Public Health Agency of Canada; 2014. [cited 2018 Mar 4]. Available from: http://publications.gc.ca/collections/collection_2014/aspc-phac/HP40-102-2014-eng.pdf.

    Google Scholar 

  3. World Health Organization (WHO). Guidelines for the treatment of malaria [Internet]. third ed. Geneva: World Health Organization; 2015. [cited 2018 Mar 4]. Available from: http://apps.who.int/iris/bitstream/10665/162441/1/9789241549127_eng.pdf?ua=1&ua=1.

    Google Scholar 

  4. Maltha J, Gillet P, Jacobs JJ. Malaria rapid diagnostic tests in endemic settings. Clin Microbiol Infect. 2013;19(5):399–407. https://doi.org/10.1111/1469-0691.

    Article  CAS  PubMed  Google Scholar 

  5. Maltha J, Gillet P, Jacobs JJ. Malaria rapid diagnostic tests in travel medicine. Clin Microbiol Infect. 2013;19(5):408–15. https://doi.org/10.1111/1469-0691.

    Article  CAS  PubMed  Google Scholar 

  6. World Health Organization (WHO). Malaria rapid diagnostic test performance: summary results of WHO product testing of malaria RDTs: round 1-7 (2008–2016) [Internet]. Geneva: World Health Organization; 2017. [cited 2018 Mar 4]. Available from: http://apps.who.int/iris/bitstream/10665/258597/1/9789241512916-eng.pdf?ua=1.

    Google Scholar 

  7. Yegorov S, Galiwango RM, Ssemaganda A, Muwanga M, Wesonga I, Miiro G, et al. Low prevalence of laboratory-confirmed malaria in clinically diagnosed adult women from the Wakiso district of Uganda. Malar J. 2016;15(1):555. https://doi.org/10.1186/s12936-016-1604-z.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Center for Disease Control and Prevention. Malaria [Internet]. Atlanta: Center for Disease Control and Prevention; 2015. [cited 2018 Mar 23]. Available from: https://www.cdc.gov/malaria/about/disease.html.

    Google Scholar 

  9. Thompson CA, Boggild AK. Five things to know about: rapid diagnostic tests for imported malaria. CMAJ. 2014;186:E557. https://doi.org/10.1503/cmaj.131794.

    Article  PubMed  PubMed Central  Google Scholar 

  10. World Health Organization (WHO). Recommended selection criteria for procurement of malaria rapid diagnostic tests [Internet]. Geneva: World Health Organization; 2018. [cited 2018 Mar 4]. Available from: http://apps.who.int/iris/bitstream/10665/259870/1/WHO-CDS-GMP-2018.01-eng.pdf?ua=1.

    Google Scholar 

  11. • Abba K, Kirkham AJ, Olliaro PL, Deeks JJ, Donegan S, Garner P, et al. Rapid diagnostic tests for diagnosing uncomplicated non-falciparum or Plasmodium vivax malaria in endemic countries. Cochrane Database Syst Rev. 2014;12:CD011431. https://doi.org/10.1002/14651858.CD011431 A comprehensive systematic review outlining the efficacy of malaria RDTs specifically for non- falciparum / P. vivax forms of the disease.

    Article  Google Scholar 

  12. • Grigg MJ, William T, Barber BE, Parameswaran U, Bird E, Piera K, et al. Combining parasite lactate dehydrogenase-based and histidine-rich protein 2-based rapid tests to improve specificity for diagnosis of malaria due to Plasmodium knowlesi and other Plasmodium species in Sabah, Malaysia. J Clin Microbiol. 2014;52(6):2053–60. https://doi.org/10.1128/JCM.00181-14 An analysis of 323 PCR-confirmed malaria patients that showed improvements in performance when LDH and HRP2-based RDTs were used in combination.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Francis B, Gonzalo X, Duggineni S, Thomas JM, NicFhogartaigh C, Babiker ZO. Epidemiology and clinical features of imported malaria in East London. J Travel Med. 2016;23(6):1. https://doi.org/10.1093/jtm/taw060.

    Article  Google Scholar 

  14. • Phuong M, Lau R, Ralevski F, Boggild AK. Survival analysis of diagnostic assays in Plasmodium falciparum malaria. Malar J. 2015;14(350):1–6. https://doi.org/10.1186/s12936-015-0882-1 A survival analysis between RDT, qPCR and microscopic diagnostics for clinically relevant asexual parasitemia in post-treatment specimens, highlighting that microscopy remains the only reliable method that can ascertain between asexual parasitemia and prolonged clearance of antigen.

    Article  Google Scholar 

  15. Lau R, Phuong M, Ralevski F, Boggild AK. Correlating quantitative real-time PCR to rapid diagnostic test and RNA transcript expression in isolated gametocytemia and asexual parasitemia of Plasmodium falciparum malaria. Trop Dis Travel Med Vaccines. 2015;1:8. https://doi.org/10.1186/s40794-015-0008-3.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Tiono AB, Ouédraogo A, Diarra A, Coulibaly S, Soulama I, Konaté AT, et al. Lessons learned from the use of HRP-2 based rapid diagnostic test in community-wide screening and treatment of asymptomatic carriers of Plasmodium falciparum in Burkina Faso. Malar J. 2014;13:30. https://doi.org/10.1186/1475-2875-13-30.

    Article  PubMed  PubMed Central  Google Scholar 

  17. • Kang K, Dzakah E, Li W, Xie M, Luo X, Liu H. Novel monoclonal antibodies against Plasmodium falciparum histidine-rich protein 2: development and application in rapid diagnostic tests of malaria in hyperendemic regions of China and Myanmar. BMC Microbiol. 2015;15(98). https://doi.org/10.1186/s12866-015-0429-1 Production and testing of novel monoclonal RDT antibodies to P. falciparum HRP-2 exon II immunogenic sites demonstrate high sensitivity and specificity.

  18. Hailu T, Kebede T. Assessing the performance of CareStart malaria Pf/Pv combo test against thick blood film in the diagnosis of malaria in Northwest Ethiopia. Am J Trop Med Hyg. 2014;90(6):1109–12. https://doi.org/10.4269/ajtmh.13-0607.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kim J-Y, Ji S-Y, Goo Y-K, Na B-K, Pyo H-J, Lee H-N, et al. Comparison of rapid diagnostic tests for the detection of Plasmodium vivax malaria in South Korea. PLoS One. 2013;8(5):e64353. https://doi.org/10.1371/journal.pone.0064353.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hawkes M, Conroy AL, Opoka RO, Namasopo S, Liles WC, John CC, et al. Use of a three-band HRP2/pLDH combination rapid diagnostic test increases diagnostic specificity for falciparum malaria in Ugandan children. Malar J. 2014;13:43. https://doi.org/10.1186/1475-2875-13-43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. • Ehtesham R, Fazaeli A, Raeisi A, Keshavarz H, Heidari A. Detection of mixed-species infections of Plasmodium falciparum and Plasmodium vivax by nested PCR and rapid diagnostic tests in southeastern Iran. Am J Trop Med Hyg. 2015;93(1):181–5. https://doi.org/10.4269/ajtmh.14-0650 The study demonstrates the usefulness of RDTs in differentiating between mixed-species infections especially in areas where chloroquine resistance is elevated.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Dzakah EE, Kang K, Ni C, Tang S, Wang J, Wang J. Comparative performance of aldolase and lactate dehydrogenase rapid diagnostic tests in Plasmodium vivax detection. Malar J. 2014;13(372):272. https://doi.org/10.1186/1475-2875-13-272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. • Wurtz N, Fall B, Bui K, Pascual A, Fall M, Camara C, et al. Pfhrp2 and pfhrp3 polymorphisms in Plasmodium falciparum isolates from Dakar, Senegal: impact on rapid malaria diagnostic tests. Malar J. 2013;12(34). https://doi.org/10.1186/1475-2875-12-34 A report illustrating the inaccuracy and inability of RDTs to detect malaria in parasites with high pfhrp2 and pfhrp3 polymorphisms.

    Article  CAS  Google Scholar 

  24. • Ota-Sullivan K, Blecker-Shelly DL. Use of the rapid BinaxNOW malaria test in a 24-hour laboratory associated with accurate detection and decreased malaria testing turnaround times in a pediatric setting where malaria is not endemic. J Clin Microbiol. 2013;51(5):1567–9. https://doi.org/10.1128/JCM.00293-13 RDT proves to be significantly useful in non-endemic pediatric populations, especially at reducing turnaround time.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Mouatcho JC, Goldring JP. Malaria rapid diagnostic tests: challenges and prospects. J Med Microbiol. 2013;62:1491–505. https://doi.org/10.1099/jmm.0.052506-0.

    Article  CAS  PubMed  Google Scholar 

  26. Tanizaki R, Kato Y, Iwagami M, Kutsuna S, Ujiie M, Takeshita N, et al. Performance of rapid diagnostic tests for Plasmodium ovale malaria in Japanese Travellers. Trop Med Health. 2014;42(4):149–53. https://doi.org/10.2149/tmh.2014-07.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Foster D, Cox-Singh J, Mohamad DSA, Krishna S, Chin PP, Singh B. Evaluation of three rapid diagnostic tests for the detection of human infections with Plasmodium knowlesi. Malar J. 2013;13(60). https://doi.org/10.1186/1475-2875-13-60.

    Article  Google Scholar 

  28. Grigg MJ, William T, Barber BE, Parameswaran U, Bird E, Piera K, et al. Combining parasite lactate dehydrogenase-based and histidine-rich protein 2-based rapid tests to improve specificity for diagnosis of malaria due to Plasmodium knowlesi and other Plasmodium species in Sabah, Malaysia. J Clin Microbiol. 2014;52(6):2053–60. https://doi.org/10.1128/JCM.00181-14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. • Piera KA, Aziz A, William T, Bell D, Gonzalez IJ, Barber BE, et al. Detection of Plasmodium knowlesi, Plasmodium falciparum and Plasmodium vivax using loop-mediated isothermal amplification (LAMP) in a co-endemic area in Malaysia. Malar J. 2017;16(29). https://doi.org/10.1186/s12936-016-1676-9 Novel LAMP RDT is able to detect P. knowlesi infections with great accuracy, making huge strides in previously unavailable non- falciparum diagnostics.

  30. • Yongkiettrakul S, Jaroenram W, Arunrut N, Chareanchim W, Pannengpetch S, Suebsing R, et al. Application of loop-mediated isothermal amplification assay combined with lateral flow dipstick for detection of Plasmodium falciparum and Plasmodium vivax. Parasitol Int. 2014;63(6):777–84. https://doi.org/10.1016/j.parint.2014.06.004 LAMP in the form of a dipstick proves to be extremely useful in reducing time-to-diagnosis and depicts a 10-fold higher detection limit than PCR.

    Article  CAS  PubMed  Google Scholar 

  31. Kim S, Nhem S, Dourng D, Menard D. Malaria rapid diagnostic test as point-of-care test: study protocol for evaluating the VIKIA malaria Ag Pf/Pan. Malar J. 2015;14:114. https://doi.org/10.1186/s12936-015-0633-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chong C-K, Cho PY, Na B-K, Ahn SK, Kim JS, Lee J-S, et al. Evaluation of the accuracy of the EasyTest malaria Pf/Pan Ag, a rapid diagnostic test, in Uganda. Korean J Parasitol. 2014;52(5):501–5. https://doi.org/10.3347/kjp.2014.52.5.501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Genton B, D’Acremont V. Standby emergency treatment of malaria in travellers (SBET): so be eager to test. J Travel Med. 2017;24(5). https://doi.org/10.1093/jtm/tax032.

  34. Behrens R. Standby emergency treatment of malaria for travellers to low transmission destinations. Does it make sense or save lives? J Travel Med. 2017;24(5). https://doi.org/10.1093/jtm/tax034.

  35. • Alnasser Y, Ferradas C, Clark T, Calderon M, Gurbillon A, Gamboa D, et al. Colorimetric detection of Plasmodium vivax in urine using MSP10 Oligonucleotides and Gold nanoparticles. PLoS Negl Trop Dis. 2016;10:e0005029. https://doi.org/10.1371/journal.pntd.0005029 The report demonstrates a novel gold nanoparticle-based colorimetric diagnostic assay using only urine, with moderate sensitivity and high specificity.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. World Health Organization (WHO). Protocol for estimating the prevalence of pfhrp2/pfhrp3 gene deletions among symptomatic falciparum patients with false-negative RDT results [Internet]. Geneva: World Health Organization; 2018. [cited 2018 Mar 5]. Available from: http://apps.who.int/iris/bitstream/10665/260140/1/WHO-CDS-GMP-2018.03-eng.pdf?ua=1.

    Google Scholar 

  37. World Health Organization and FIND. Malaria RDT product testing: interactive guide [Internet]. Geneva: World Health Organization; 2017. [cited 2018 Mar 23]. Available from: http://www.rdt-interactive-guide.org/.

    Google Scholar 

  38. • Marti H, Stalder C, Gonzalez IJ. Diagnostic accuracy of a LAMP kit for diagnosis of imported malaria in Switzerland. Travel Med Infect Dis. 2015;13:167–71. https://doi.org/10.1016/j.tmaid.2014.12.016 Usage of LAMP in a non-endemic traveler population shows that it has versatile applications with comparable performance results to qPCR.

    Article  PubMed  Google Scholar 

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Correspondence to Andrea K. Boggild.

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Mukkala, A.N., Kwan, J., Lau, R. et al. An Update on Malaria Rapid Diagnostic Tests. Curr Infect Dis Rep 20, 49 (2018). https://doi.org/10.1007/s11908-018-0655-4

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