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Diagnostic Tools of Malaria During Pregnancy

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Encyclopedia of Malaria

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Synonyms

Hemozoin, malaria pigment; qPCR, quantitative PCR, real-time PCR

Definitions

Malaria during pregnancy is associated with maternal and fetal morbidity and mortality through maternal anemia, low birth weight (LBW), and premature delivery. Thus, diagnostic, treatment, and prevention of malaria during pregnancy is a public health priority, particularly in sub-Saharan Africa.

Pregnant women are highly susceptible to malaria. They are most commonly infected with Plasmodium falciparum, especially in Africa, but P. vivax infections are of great importance to pregnant women in both Latin America and Asia. In this chapter, we will discuss the various options for diagnosing malaria during pregnancy.

Pregnancy poses specific challenges for the diagnosis of malaria, as P. falciparum parasites may be present in the placenta yet absent or not detectable in peripheral blood (Uneke 2008). This phenomenon is due to the accumulation of infected erythrocytes in the intervillous spaces of the...

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References

  • Adegnika AA, Verweij JJ, Agnandji ST, Chai SK, Breitling LP, Ramharter M, Frolich M, Issifou S, Kremsner PG, Yazdanbakhsh M. Microscopic and sub-microscopic Plasmodium falciparum infection, but not inflammation caused by infection, is associated with low birth weight. Am J Trop Med Hyg. 2006;75(5):798–803.

    CAS  PubMed  Google Scholar 

  • Alemayehu S, Feghali KC, Cowden J, Komisar J, Ockenhouse CF, Kamau E. Comparative evaluation of published real-time PCR assays for the detection of malaria following MIQE guidelines. Malar J. 2013;12:277.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Arango E, Maestre A, Carmona-Fonseca J. Effect of submicroscopic or polyclonal Plasmodium falciparum infection on mother and gestation product: systematic review. Rev Bras Epidemiol. 2010;13(3):373–86.

    Article  PubMed  Google Scholar 

  • Ataide R, Mayor A, Rogerson SJ. Malaria, primigravidae, and antibodies: knowledge gained and future perspectives. Trends Parasitol. 2014;30(2):85–94.

    Article  PubMed  Google Scholar 

  • Baltzell KA, Shakely D, Hsiang M, Kemere J, Ali AS, Bjorkman A, Martensson A, Omar R, Elfving K, Msellem M, Aydin-Schmidt B, Rosenthal PJ, Greenhouse B. Prevalence of PCR detectable malaria infection among febrile patients with a negative Plasmodium falciparum specific rapid diagnostic test in Zanzibar. Am J Trop Med Hyg. 2013;88(2):289–91.

    Article  PubMed Central  PubMed  Google Scholar 

  • Bell D, Wongsrichanalai C, Barnwell JW. Ensuring quality and access for malaria diagnosis: how can it be achieved? Nat Rev Microbiol. 2006;4 Suppl 9:S7–20.

    Article  PubMed  Google Scholar 

  • Bostrom S, Ibitokou S, Oesterholt M, Schmiegelow C, Persson JO, Minja D, Lusingu J, Lemnge M, Fievet N, Deloron P, Luty AJ, Troye-Blomberg M. Biomarkers of Plasmodium falciparum infection during pregnancy in women living in northeastern Tanzania. PLoS One. 2012;7(11):e48763.

    Article  PubMed Central  PubMed  Google Scholar 

  • Bulmer JN, Rasheed FN, Francis N, Morrison L, Greenwood BM. Placental malaria. I. Pathological classification. Histopathology. 1993a;22(3):211–8.

    Article  CAS  PubMed  Google Scholar 

  • Bulmer JN, Rasheed FN, Morrison L, Francis N, Greenwood BM. Placental malaria. II. A semi-quantitative investigation of the pathological features. Histopathology. 1993b;22(3):219–25.

    Article  CAS  PubMed  Google Scholar 

  • Carvalho BO, Matsuda JS, Luz SL, Martinez-Espinosa FE, Leite JA, Franzin F, Orlandi PP, Gregoracci GB, Lacerda MV, Nogueira PA, Costa FT. Gestational malaria associated to Plasmodium vivax and Plasmodium falciparum placental mixed-infection followed by foetal loss: a case report from an unstable transmission area in Brazil. Malar J. 2011;10:178.

    Article  PubMed Central  PubMed  Google Scholar 

  • Cheng Z, Sun X, Yang Y, Wang H, Zheng Z. A novel, sensitive assay for high-throughput molecular detection of plasmodia for active screening of malaria for elimination. J Clin Microbiol. 2013;51(1):125–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Conroy AL, Liles WC, Molyneux ME, Rogerson SJ, Kain KC. Performance characteristics of combinations of host biomarkers to identify women with occult placental malaria: a case–control study from Malawi. PLoS One. 2011;6(12):e28540.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Conroy AL, McDonald CR, Kain KC. Malaria in pregnancy: diagnosing infection and identifying fetal risk. Expert Rev Anti Infect Ther. 2012;10(11):1331–42.

    Article  CAS  PubMed  Google Scholar 

  • De Monbrison F, Gerome P, Chaulet JF, Wallon M, Picot S, Peyron F. Comparative diagnostic performance of two commercial rapid tests for malaria in a non-endemic area. Eur J Clin Microbiol Infect Dis. 2004;23(10):784–6.

    Article  PubMed  Google Scholar 

  • Dondorp AM, Desakorn V, Pongtavornpinyo W, Sahassananda D, Silamut K, Chotivanich K, Newton PN, Pitisuttithum P, Smithyman AM, White NJ, Day NP. Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2. PLoS Med. 2005;2(8):e204.

    Article  PubMed Central  PubMed  Google Scholar 

  • Farrugia C, Cabaret O, Botterel F, Bories C, Foulet F, Costa JM, Bretagne S. Cytochrome b gene quantitative PCR for diagnosing Plasmodium falciparum infection in travelers. J Clin Microbiol. 2011;49(6):2191–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fried M, Duffy PE. Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science. 1996;272(5267):1502–4.

    Article  CAS  PubMed  Google Scholar 

  • Fried M, Muehlenbachs A, Duffy PE. Diagnosing malaria in pregnancy: an update. Expert Rev Anti Infect Ther. 2012;10(10):1177–87.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fu S, Qu G, Guo S, Ma L, Zhang N, Zhang S, Gao S, Shen Z. Applications of loop-mediated isothermal DNA amplification. Appl Biochem Biotechnol. 2011;163(7):845–50.

    Article  CAS  PubMed  Google Scholar 

  • Hanscheid T, Pinto BG, Cristino JM, Grobusch MP. Malaria diagnosis with the haematology analyser Cell-Dyn 3500: what does the instrument detect? Clin Lab Haematol. 2000;22(5):259–61.

    Article  CAS  PubMed  Google Scholar 

  • Hanscheid T, Egan TJ, Grobusch MP. Haemozoin: from melatonin pigment to drug target, diagnostic tool, and immune modulator. Lancet Infect Dis. 2007;7(10):675–85.

    Article  CAS  PubMed  Google Scholar 

  • Hanscheid T, Langin M, Codices V, Luty AJ, Adegnika AA, Kremsner PG, Grobusch MP. Automated detection of haemozoin-containing monocytes for the diagnosis of malaria in microscopically negative cases during pregnancy. Acta Trop. 2009;109(3):245–6.

    Article  PubMed  Google Scholar 

  • Hsiang MS, Lin M, Dokomajilar C, Kemere J, Pilcher CD, Dorsey G, Greenhouse B. PCR-based pooling of dried blood spots for detection of malaria parasites: optimization and application to a cohort of Ugandan children. J Clin Microbiol. 2010;48(10):3539–43.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ismail MR, Ordi J, Menendez C, Ventura PJ, Aponte JJ, Kahigwa E, Hirt R, Cardesa A, Alonso PL. Placental pathology in malaria: a histological, immunohistochemical, and quantitative study. Hum Pathol. 2000;31(1):85–93.

    Article  CAS  PubMed  Google Scholar 

  • Kattenberg JH, Ochodo EA, Boer KR, Schallig HD, Mens PF, Leeflang MM. Systematic review and meta-analysis: rapid diagnostic tests versus placental histology, microscopy and PCR for malaria in pregnant women. Malar J. 2011;10(1):321.

    Article  PubMed Central  PubMed  Google Scholar 

  • Koita OA, Doumbo OK, Ouattara A, Tall LK, Konare A, Diakite M, Diallo M, Sagara I, Masinde GL, Doumbo SN, Dolo A, Tounkara A, Traore I, Krogstad DJ. False-negative rapid diagnostic tests for malaria and deletion of the histidine-rich repeat region of the hrp2 gene. Am J Trop Med Hyg. 2012;86(2):194–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kumar N, Pande V, Bhatt RM, Shah NK, Mishra N, Srivastava B, Valecha N, Anvikar AR. Genetic deletion of HRP2 and HRP3 in Indian Plasmodium falciparum population and false negative malaria rapid diagnostic test. Acta Trop. 2013;125(1):119–21.

    Article  CAS  PubMed  Google Scholar 

  • Leke RF, Djokam RR, Mbu R, Leke RJ, Fogako J, Megnekou R, Metenou S, Sama G, Zhou Y, Cadigan T, Parra M, Taylor DW. Detection of the Plasmodium falciparum antigen histidine-rich protein 2 in blood of pregnant women: implications for diagnosing placental malaria. J Clin Microbiol. 1999;37(9):2992–6.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Mahajan B, Zheng H, Pham PT, Sedegah MY, Majam VF, Akolkar N, Rios M, Ankrah I, Madjitey P, Amoah G, Addison E, Quakyi IA, Kumar S. Polymerase chain reaction-based tests for pan-species and species-specific detection of human Plasmodium parasites. Transfusion. 2012;52(9):1949–56.

    Article  CAS  PubMed  Google Scholar 

  • Malhotra I, Dent A, Mungai P, Muchiri E, King CL. Real-time quantitative PCR for determining the burden of Plasmodium falciparum parasites during pregnancy and infancy. J Clin Microbiol. 2005;43(8):3630–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Malhotra I, Mungai P, Muchiri E, Kwiek JJ, Meshnick SR, King CL. Umbilical cord-blood infections with Plasmodium falciparum malaria are acquired antenatally in Kenya. J Infect Dis. 2006;194(2):176–83.

    Article  PubMed  Google Scholar 

  • Mankhambo L, Kanjala M, Rudman S, Lema VM, Rogerson SJ. Evaluation of the OptiMAL rapid antigen test and species-specific PCR to detect placental Plasmodium falciparum infection at delivery. J Clin Microbiol. 2002;40(1):155–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mayor A, Serra-Casas E, Bardaji A, Sanz S, Puyol L, Cistero P, Sigauque B, Mandomando I, Aponte JJ, Alonso PL, Menendez C. Sub-microscopic infections and long-term recrudescence of Plasmodium falciparum in Mozambican pregnant women. Malar J. 2009;8:9.

    Article  PubMed Central  PubMed  Google Scholar 

  • Mayor A, Bardaji A, Felger I, King CL, Cistero P, Dobano C, Stanisic DI, Siba P, Wahlgren M, del Portillo H, Mueller I, Menendez C, Ordi J, Rogerson S. Placental infection with Plasmodium vivax: a histopathological and molecular study. J Infect Dis. 2012a;206(12):1904–10.

    Article  CAS  PubMed  Google Scholar 

  • Mayor A, Moro L, Aguilar R, Bardaji A, Cistero P, Serra-Casas E, Sigauque B, Alonso PL, Ordi J, Menendez C. How hidden can malaria be in pregnant women? Diagnosis by microscopy, placental histology, polymerase chain reaction and detection of histidine-rich protein 2 in plasma. Clin Infect Dis. 2012b;54(11):1561–8.

    Article  CAS  PubMed  Google Scholar 

  • Mayxay M, Pukrittayakamee S, Chotivanich K, Looareesuwan S, White NJ. Persistence of Plasmodium falciparum HRP-2 in successfully treated acute falciparum malaria. Trans R Soc Trop Med Hyg. 2001;95(2):179–82.

    Article  CAS  PubMed  Google Scholar 

  • McGready R, Davison BB, Stepniewska K, Cho T, Shee H, Brockman A, Udomsangpetch R, Looareesuwan S, White NJ, Meshnick SR, Nosten F. The effects of Plasmodium falciparum and P. vivax infections on placental histopathology in an area of low malaria transmission. Am J Trop Med Hyg. 2004;70(4):398–407.

    PubMed  Google Scholar 

  • Menendez C, Mayor A. Congenital malaria: the least known consequence of malaria in pregnancy. Semin Fetal Neonatal Med. 2007;12(3):207–13.

    Article  PubMed  Google Scholar 

  • Mockenhaupt FP, Rong B, Till H, Eggelte TA, Beck S, Gyasi-Sarpong C, Thompson WN, Bienzle U. Submicroscopic Plasmodium falciparum infections in pregnancy in Ghana. Trop Med Int Health. 2000;5(3):167–73.

    Article  CAS  PubMed  Google Scholar 

  • Mockenhaupt FP, Ulmen U, von Gaertner C, Bedu-Addo G, Bienzle U. Diagnosis of placental malaria. J Clin Microbiol. 2002;40(1):306–8.

    Article  PubMed Central  PubMed  Google Scholar 

  • Mockenhaupt FP, Bedu-Addo G, von Gaertner C, Boye R, Fricke K, Hannibal I, Karakaya F, Schaller M, Ulmen U, Acquah PA, Dietz E, Eggelte TA, Bienzle U. Detection and clinical manifestation of placental malaria in southern Ghana. Malar J. 2006;5:119.

    Article  PubMed Central  PubMed  Google Scholar 

  • Mohammed AH, Salih MM, Elhassan EM, Mohmmed AA, Elzaki SE, El-Sayed BB, Adam I. Submicroscopic Plasmodium falciparum malaria and low birth weight in an area of unstable malaria transmission in Central Sudan. Malar J. 2013;12(1):172.

    Article  PubMed Central  PubMed  Google Scholar 

  • Moody A. Rapid diagnostic tests for malaria parasites. Clin Microbiol Rev. 2002;15(1):66–78.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Newman RD, Hailemariam A, Jimma D, Degifie A, Kebede D, Rietveld AE, Nahlen BL, Barnwell JW, Steketee RW, Parise ME. Burden of malaria during pregnancy in areas of stable and unstable transmission in Ethiopia during a nonepidemic year. J Infect Dis. 2003;187(11):1765–72.

    Article  PubMed  Google Scholar 

  • Nyunt M, Pisciotta J, Feldman AB, Thuma P, Scholl PF, Demirev PA, Lin JS, Shi L, Kumar N, Sullivan Jr DJ. Detection of Plasmodium falciparum in pregnancy by laser desorption mass spectrometry. Am J Trop Med Hyg. 2005;73(3):485–90.

    CAS  PubMed  Google Scholar 

  • Ohrt C, Purnomo, Sutamihardja MA, Tang D, Kain KC. Impact of microscopy error on estimates of protective efficacy in malaria-prevention trials. J Infect Dis. 2002;186(4):540–6.

    Article  PubMed  Google Scholar 

  • Ordi J, Ismail MR, Ventura PJ, Kahigwa E, Hirt R, Cardesa A, Alonso PL, Menendez C. Massive chronic intervillositis of the placenta associated with malaria infection. Am J Surg Pathol. 1998;22(8):1006–11.

    Article  CAS  PubMed  Google Scholar 

  • Parekh FK, Davison BB, Gamboa D, Hernandez J, Branch OH. Placental histopathologic changes associated with subclinical malaria infection and its impact on the fetal environment. Am J Trop Med Hyg. 2010;83(5):973–80.

    Article  PubMed Central  PubMed  Google Scholar 

  • Parra ME, Evans CB, Taylor DW. Identification of Plasmodium falciparum histidine-rich protein 2 in the plasma of humans with malaria. J Clin Microbiol. 1991;29(8):1629–34.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Patel JC, Oberstaller J, Xayavong M, Narayanan J, DeBarry JD, Srinivasamoorthy G, Villegas L, Escalante AA, DaSilva A, Peterson DS, Barnwell JW, Kissinger JC, Udhayakumar V, Lucchi NW. Real-time loop-mediated isothermal amplification (RealAmp) for the species-specific identification of Plasmodium vivax. PLoS One. 2013;8(1):e54986.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Piper R, Lebras J, Wentworth L, Hunt-Cooke A, Houze S, Chiodini P, Makler M. Immunocapture diagnostic assays for malaria using Plasmodium lactate dehydrogenase (pLDH). Am J Trop Med Hyg. 1999;60(1):109–18.

    CAS  PubMed  Google Scholar 

  • Polley SD, Gonzalez IJ, Mohamed D, Daly R, Bowers K, Watson J, Mewse E, Armstrong M, Gray C, Perkins MD, Bell D, Kanda H, Tomita N, Kubota Y, Mori Y, Chiodini PL, Sutherland CJ. Clinical evaluation of a loop-mediated amplification kit for diagnosis of imported malaria. J Infect Dis. 2013;208(4):637–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rantala AM, Taylor SM, Trottman PA, Luntamo M, Mbewe B, Maleta K, Kulmala T, Ashorn P, Meshnick SR. Comparison of real-time PCR and microscopy for malaria parasite detection in Malawian pregnant women. Malar J. 2010;9:269.

    Article  PubMed Central  PubMed  Google Scholar 

  • Rogerson SJ, Mkundika P, Kanjala MK. Diagnosis of Plasmodium falciparum malaria at delivery: comparison of blood film preparation methods and of blood films with histology. J Clin Microbiol. 2003;41(4):1370–4.

    Article  PubMed Central  PubMed  Google Scholar 

  • Rogerson SJ, Mwapasa V, Meshnick SR. Malaria in pregnancy: linking immunity and pathogenesis to prevention. Am J Trop Med Hyg. 2007;77 Suppl 6:14–22.

    PubMed  Google Scholar 

  • Romagosa C, Menendez C, Ismail MR, Quinto L, Ferrer B, Alonso PL, Ordi J. Polarisation microscopy increases the sensitivity of hemozoin and Plasmodium detection in the histological assessment of placental malaria. Acta Trop. 2004;90(3):277–84.

    Article  PubMed  Google Scholar 

  • Singer LM, Newman RD, Diarra A, Moran AC, Huber CS, Stennies G, Sirima SB, Konate A, Yameogo M, Sawadogo R, Barnwell JW, Parise ME. Evaluation of a malaria rapid diagnostic test for assessing the burden of malaria during pregnancy. Am J Trop Med Hyg. 2004;70(5):481–5.

    PubMed  Google Scholar 

  • Singh N, Saxena A, Valecha N. Field evaluation of the ICT malaria P.f/P.v immunochromatographic test for diagnosis of Plasmodium falciparum and P.vivax infection in forest villages of Chhindwara, central India. Trop Med Int Health. 2000;5(11):765–70.

    Article  CAS  PubMed  Google Scholar 

  • Smith LA, Jones C, Adjei RO, Antwi GD, Afrah NA, Greenwood B, Chandramohan D, Tagbor H, Webster J. Intermittent screening and treatment versus intermittent preventive treatment of malaria in pregnancy: user acceptability. Malar J. 2010;9:18.

    Article  PubMed Central  PubMed  Google Scholar 

  • Snounou G, Viriyakosol S, Jarra W, Thaithong S, Brown KN. 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. Mol Biochem Parasitol. 1993a;58(2):283–92.

    Article  CAS  PubMed  Google Scholar 

  • Snounou G, Viriyakosol S, Zhu XP, Jarra W, Pinheiro L, do Rosario VE, Thaithong S, Brown KN. High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction. Mol Biochem Parasitol. 1993b;61(2):315–20.

    Article  CAS  PubMed  Google Scholar 

  • Tagbor H, Bruce J, Agbo M, Greenwood B, Chandramohan D. Intermittent screening and treatment versus intermittent preventive treatment of malaria in pregnancy: a randomised controlled non-inferiority trial. PLoS One. 2010;5(12):e14425.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Taylor SM, Juliano JJ, Trottman PA, Griffin JB, Landis SH, Kitsa P, Tshefu AK, Meshnick SR. High-throughput pooling and real-time PCR-based strategy for malaria detection. J Clin Microbiol. 2010;48(2):512–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Thevenon AD, Zhou JA, Megnekou R, Ako S, Leke RG, Taylor DW. Elevated levels of soluble TNF receptors 1 and 2 correlate with Plasmodium falciparum parasitemia in pregnant women: potential markers for malaria-associated inflammation. J Immunol. 2010;185(11):7115–22.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Uneke CJ. Diagnosis of Plasmodium falciparum malaria in pregnancy in sub-Saharan Africa: the challenges and public health implications. Parasitol Res. 2008;102(3):333–42.

    Article  CAS  PubMed  Google Scholar 

  • Wongsrichanalai C, Barcus MJ, Muth S, Sutamihardja A, Wernsdorfer WH. A review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT). Am J Trop Med Hyg. 2007;77 Suppl 6:119–27.

    PubMed  Google Scholar 

  • Zheng Z, Luo Y, McMaster GK. Sensitive and quantitative measurement of gene expression directly from a small amount of whole blood. Clin Chem. 2006;52(7):1294–302.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain

    Alfredo Mayor

  2. Centro De Investigação Em Saúde Da Manhiça (CISM), Maputo, Mozambique

    Alfredo Mayor

  3. Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, 27599, USA

    Steven R. Meshnick

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  1. Alfredo Mayor
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  2. Steven R. Meshnick
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Correspondence to Alfredo Mayor .

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Editors and Affiliations

  1. Heswall, United Kingdom

    Marcel Hommel

  2. Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany

    Peter G. Kremsner

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Mayor, A., Meshnick, S.R. (2015). Diagnostic Tools of Malaria During Pregnancy. In: Hommel, M., Kremsner, P. (eds) Encyclopedia of Malaria. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8757-9_68-1

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