Evaluation of PCR-based surveillance as a Prognostic Tool in malaria

Authors

DOI:

https://doi.org/10.5281/zenodo.22811672

Keywords:

malaria, polymerase chain reaction, molecular surveillance, parasitemia, diagnostic sensitivity

Abstract

Graphical abstract

Background: Light microscopy and antigen-based rapid diagnostic tests remain the mainstay of malaria diagnosis, but both carry a detection floor of roughly 50-200 parasites/microliter and miss a substantial fraction of infections that polymerase chain reaction (PCR) based methods can resolve [1,2].

Objective: This review synthesizes the published evidence on PCR-based detection and quantification of Plasmodium species as a surveillance tool, and on whether PCR-derived parasite load carries prognostic value for disease severity.

Methods: We synthesized assay-development and validation studies, field comparisons of microscopy, rapid diagnostic tests and PCR, systematic reviews of submicroscopic infection, and clinical studies relating parasite DNA load to malaria severity, as a narrative synthesis of the 1993-2018 diagnostics literature.

Findings: PCR consistently recovers infections missed by microscopy and rapid tests, with microscopy-detected Plasmodium vivax prevalence averaging 67% lower than PCR-detected prevalence in a 40-study review [8]; plasma parasite DNA concentration was approximately 40-fold and 10-fold higher in severe than uncomplicated falciparum malaria among African children and Asian adults respectively [13]; and submicroscopic carriage becomes proportionally more important as transmission intensity falls [15,16].

Conclusions: PCR-based methods function both as a more sensitive surveillance tool than microscopy or rapid diagnostic testing and, through quantitative parasite load, as a prognostic marker for severe malaria, though infrastructure and cost barriers still limit routine use outside reference and research settings [20,22].

References

Wongsrichanalai, C., Barcus, M.J., Muth, S., Sutamihardja, A., Wernsdorfer, W.H. (2007) A review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT). American Journal of Tropical Medicine and Hygiene, 77(6 Suppl): 119-127. DOI: 10.4269/ajtmh.2007.77.119

Moody, A. (2002) Rapid diagnostic tests for malaria parasites. Clinical Microbiology Reviews, 15(1): 66-78. DOI: 10.1128/cmr.15.1.66-78.2002

Murray, C.K., Gasser, R.A., Magill, A.J., Miller, R.S. (2008) Update on rapid diagnostic testing for malaria. Clinical Microbiology Reviews, 21(1): 97-110. DOI: 10.1128/cmr.00035-07

Cheng, Q., Gatton, M.L., Barnwell, J., Chiodini, P., McCarthy, J., Bell, D., et al. (2014) Plasmodium falciparum parasites lacking histidine-rich protein 2 and 3: a review and recommendations for accurate reporting. Malaria Journal, 13: 283. DOI: 10.1186/1475-2875-13-283

Snounou, G., Viriyakosol, S., Jarra, W., Thaithong, S., Brown, K.N. (1993) Identification of the four human malaria parasite species in field samples by the polymerase chain reaction and detection of a high prevalence of mixed infections. Molecular and Biochemical Parasitology, 58(2): 283-292. DOI: 10.1016/0166-6851(93)90050-8

Snounou, G., Viriyakosol, S., Zhu, X.P., Jarra, W., Pinheiro, L., do Rosario, V.E., et al. (1993) High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction. Molecular and Biochemical Parasitology, 61(2): 315-320. DOI: 10.1016/0166-6851(93)90077-B

Berzosa, P., de Lucio, A., Romay-Barja, M., Herrador, Z., González, V., García, L., et al. (2018) Comparison of three diagnostic methods (microscopy, RDT, and PCR) for the detection of malaria parasites in representative samples from Equatorial Guinea. Malaria Journal, 17: 333. DOI: 10.1186/s12936-018-2481-4

Moreira, C.M., Abo-Shehada, M., Price, R.N., Fowkes, F.J.I. (2015) A systematic review of sub-microscopic Plasmodium vivax infection. Malaria Journal, 14: 360. DOI: 10.1186/s12936-015-0884-z

Coleman, R.E., Sattabongkot, J., Promstaporm, S., Maneechai, N., Tippayachai, B., Kengluecha, A., et al. (2006) Comparison of PCR and microscopy for the detection of asymptomatic malaria in a Plasmodium falciparum/vivax endemic area in Thailand. Malaria Journal, 5: 121. DOI:

1186/1475-2875-5-121 10. Rosanas-Urgell, A., Mueller, D., Betuela, I., Barnadas, C., Iga, J., Zimmerman, P.A., et al. (2010) Comparison of diagnostic methods for the detection and quantification of the four sympatric Plasmodium species in field samples from Papua New Guinea. Malaria Journal, 9: 361. DOI: 10.1186/1475-2875-9-361

Singh, B., Kim Sung, L., Matusop, A., Radhakrishnan, A., Shamsul, S.S.G., Cox-Singh, J., et al. (2004) A large focus of naturally acquired Plasmodium knowlesi infections in human beings. Lancet, 363(9414): 1017-1024. DOI: 10.1016/S0140-6736(04)15836-4

Cox-Singh, J., Davis, T.M.E., Lee, K.S., Shamsul, S.S.G., Matusop, A., Ratnam, S., et al. (2008) Plasmodium knowlesi malaria in humans is widely distributed and potentially life threatening. Clinical Infectious Diseases, 46(2): 165-171. DOI: 10.1086/524888

Imwong, M., Woodrow, C.J., Hendriksen, I.C.E., Veenemans, J., Verhoef, H., Faiz, M.A., et al. (2015) Plasma concentration of parasite DNA as a measure of disease severity in falciparum malaria. Journal of Infectious Diseases, 211(7): 1128-1133. DOI: 10.1093/infdis/jiu590

Dondorp, A.M., Desakorn, V., Pongtavornpinyo, W., Sahassananda, D., Silamut, K., Chotivanich, K., et al. (2005) Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2. PLoS Medicine, 2(8): e204. DOI: 10.1371/journal.pmed.0020204

Okell, L.C., Ghani, A.C., Lyons, E., Drakeley, C.J. (2009) Submicroscopic infection in Plasmodium falciparum-endemic populations: a systematic review and meta-analysis. Journal of Infectious Diseases, 200(10): 1509-1517. DOI: 10.1086/644781

Okell, L.C., Bousema, T., Griffin, J.T., Ouédraogo, A.L., Ghani, A.C., Drakeley, C.J. (2012) Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nature Communications, 3: 1237. DOI: 10.1038/ncomms2241

Perandin, F., Manca, N., Calderaro, A., Piccolo, G., Galati, L., Ricci, L., et al. (2004) Development of a real-time PCR assay for detection of Plasmodium falciparum, Plasmodium vivax, and Plasmodium ovale for routine clinical diagnosis. Journal of Clinical Microbiology, 42(3): 1214-1219. DOI: 10.1128/jcm.42.3.1214-1219.2004

Mangold, K.A., Manson, R.U., Koay, E.S., Stephens, L., Regner, M., Thomson, R.B., et al. (2005) Real-time PCR for detection and identification of Plasmodium spp. Journal of Clinical Microbiology, 43(5): 2435-2440. DOI: 10.1128/jcm.43.5.2435-2440.2005

Imwong, M., Hanchana, S., Malleret, B., Rénia, L., Day, N.P.J., Dondorp, A., et al. (2014) High-throughput ultrasensitive molecular techniques for quantifying low-density malaria parasitemias. Journal of Clinical Microbiology, 52(9): 3303-3309. DOI: 10.1128/jcm.01057-14

Hofmann, N., Mwingira, F., Shekalaghe, S., Robinson, L.J., Mueller, I., Felger, I. (2015) Ultra-sensitive detection of Plasmodium falciparum by amplification of multi-copy subtelomeric targets. PLoS Medicine, 12(3): e1001788. DOI: 10.1371/journal.pmed.1001788

Steenkeste, N., Incardona, S., Chy, S., Duval, L., Ekala, M.T., Lim, P., et al. (2009) Towards high-throughput molecular detection of Plasmodium: new approaches and molecular markers. Malaria Journal, 8: 86. DOI: 10.1186/1475-2875-8-86

McMorrow, M.L., Aidoo, M., Kachur, S.P. (2011) Malaria rapid diagnostic tests in elimination settings-can they find the last parasite? Clinical Microbiology and Infection, 17(11): 1624-1631. DOI: 10.1111/j.1469-0691.2011.03639.x

Slater, H.C., Ross, A., Ouédraogo, A.L., White, L.J., Nguon, C., Walker, P.G.T., et al. (2015) Assessing the impact of next-generation rapid diagnostic tests on Plasmodium falciparum malaria elimination strategies. Nature, 528(7580): S94-S101. DOI: 10.1038/nature16040

Tangpukdee, N., Duangdee, C., Wilairatana, P., Krudsood, S. (2009) Malaria diagnosis: a brief review. Korean Journal of Parasitology, 47(2): 93-102. DOI: 10.3347/kjp.2009.47.2.93

Graphical abstract

Published

2020-01-04

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Articles