Circulating antibodies against Plasmodium falciparum histidine-rich proteins 2 interfere with antigen detection by rapid diagnostic tests
Tóm tắt
Rapid diagnostic tests (RDTs) for detection of Plasmodium falciparum infection that target P. falciparum histidine-rich protein 2 (PfHRP2), a protein that circulates in the blood of patients infected with this species of malaria, are widely used to guide case management. Understanding determinants of PfHRP2 availability in circulation is therefore essential to understanding the performance of PfHRP2-detecting RDTs. The possibility that pre-formed host anti-PfHRP2 antibodies may block target antigen detection, thereby causing false negative test results was investigated in this study. Anti-PfHRP2 antibodies were detected in 19/75 (25%) of plasma samples collected from patients with acute malaria from Cambodia, Nigeria and the Philippines, as well as in 3/28 (10.7%) asymptomatic Solomon Islands residents. Pre-incubation of plasma samples from subjects with high-titre anti-PfHRP2 antibodies with soluble PfHRP2 blocked the detection of the target antigen on two of the three brands of RDTs tested, leading to false negative results. Pre-incubation of the plasma with intact parasitized erythrocytes resulted in a reduction of band intensity at the highest parasite density, and a reduction of lower detection threshold by ten-fold on all three brands of RDTs tested. These observations indicate possible reduced sensitivity for diagnosis of P. falciparum malaria using PfHRP2-detecting RDTs among people with high levels of specific antibodies and low density infection, as well as possible interference with tests configured to detect soluble PfHRP2 in saliva or urine samples. Further investigations are required to assess the impact of pre-formed anti-PfHRP2 antibodies on RDT performance in different transmission settings.
Tài liệu tham khảo
WHO: Guidelines for the Treatment of Malaria. 2010, Geneva: World Health Organization, 2
WHO: World Malaria Report 2013. 2013, Geneva: World Health Organization
Stow NW, Torrens JK, Walker J: An assessment of the accuracy of clinical diagnosis, local microscopy and a rapid immunochromatographic card test in comparison with expert microscopy in the diagnosis of malaria in rural Kenya. Trans R Soc Trop Med Hyg. 1999, 93: 519-520. 10.1016/S0035-9203(99)90359-0.
Wongsrichanalai C: Rapid diagnostic techniques for malaria control. Trends Parasitol. 2001, 17: 307-309. 10.1016/S1471-4922(01)01925-0.
Endeshaw T, Gebre T, Ngondi J, Graves PM, Shargie EB, Ejigsemahu Y, Ayele B, Yohannes G, Teferi T, Messele A, Zerihun M, Genet A, Mosher AW, Emerson PM, Richards FO: Evaluation of light microscopy and rapid diagnostic test for the detection of malaria under operational field conditions: a household survey in Ethiopia. Malar J. 2008, 7: 118-10.1186/1475-2875-7-118.
van den Broek I, Hill O, Gordillo F, Angarita B, Hamade P, Counihan H, Guthmann JP: Evaluation of three rapid tests for diagnosis of P. falciparum and P. vivax malaria in Colombia. Am J Trop Med Hyg. 2006, 75: 1209-1215.
Rakotonirina H, Barnadas C, Raherijafy R, Andrianantenaina H, Ratsimbasoa A, Randrianasolo L, Jahevitra M, Andriantsoanirina V, Menard D: Accuracy and reliability of malaria diagnostic techniques for guiding febrile outpatient treatment in malaria-endemic countries. Am J Trop Med Hyg. 2008, 78: 217-221.
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: 119-127.
Birku Y, Welday D, Ayele D, Shepherd A: Rapid diagnosis of severe malaria based on the detection of Pf-Hrp-2 antigen. Ethiop Med J. 1999, 37: 173-179.
Gamboa D, Ho MF, Bendezu J, Torres K, Chiodini PL, Barnwell JW, Incardona S, Perkins M, Bell D, McCarthy J, Cheng Q: 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. 2010, 5: e8091-10.1371/journal.pone.0008091.
Baker J, Gatton ML, Peters J, Ho M-F, McCarthy JS: Transcription and expression of Plasmodium falciparum histidine-rich proteins in different stages and strains: implications for rapid diagnostic tests. PLoS One. 2011, 6: e22593-10.1371/journal.pone.0022593.
Gillet P, Mori M, Van Esbroeck M, Van den Ende J, Jacobs J: Assessment of the prozone effect in malaria rapid diagnostic tests. Malar J. 2009, 8: 271-10.1186/1475-2875-8-271.
Luchavez J, Baker J, Alcantara S, Belizario V, Cheng Q, McCarthy JS, Bell D: Laboratory demonstration of a prozone-like effect in HRP2-detecting malaria rapid diagnostic tests: implications for clinical management. Malar J. 2011, 10: 286-10.1186/1475-2875-10-286.
Chiodini PL, Bowers K, Jorgensen P, Barnwell JW, Grady KK, Luchavez J, Moody AH, Cenizal A, Bell D: The heat stability of Plasmodium lactate dehydrogenase-based and histidine-rich protein 2-based malaria rapid diagnostic tests. Trans R Soc Trop Med Hyg. 2007, 101: 331-337. 10.1016/j.trstmh.2006.09.007.
Lee N, Gatton ML, Pelecanos A, Bubb M, Gonzalez I, Bell D, Cheng Q, McCarthy JS: Identification of optimal epitopes for Plasmodium falciparum rapid diagnostic tests that target histidine-rich proteins 2 and 3. J Clin Microbiol. 2012, 50: 1397-1405. 10.1128/JCM.06533-11.
WHO: Malaria Rapid Diagnostic Test Performance. Results of WHO Product Testing of Malaria RDTs: Round 4. 2012, Geneva, Switzerland: World Health Organization
Howard RJ, Uni S, Aikawa M, Aley SB, Leech JH, Lew AM, Wellems TE, Rener J, Taylor DW: Secretion of a malarial histidine-rich protein (Pf HRP II) from Plasmodium falciparum-infected erythrocytes. J Cell Biol. 1986, 103: 1269-1277. 10.1083/jcb.103.4.1269.
Desakorn V, Dondorp AM, Silamut K, Pongtavornpinyo W, Sahassananda D, Chotivanich K, Pitisuttithum P, Smithyman AM, Day NP, White NJ: Stage-dependent production and release of histidine-rich protein 2 by Plasmodium falciparum. Trans R Soc Trop Med Hyg. 2005, 99: 517-524. 10.1016/j.trstmh.2004.11.014.
Mayxay M, Pukrittayakamee S, Chotivanich K, Looarecsuwan S, White N: Persistence of Plasmodium falciparum HRP-2 in successfully treated acute falciparum malaria. Trans R Soc Trop Med Hyg. 2001, 95: 179-182. 10.1016/S0035-9203(01)90156-7.
Tjitra E, Suprianto S, Dyer ME, Currie BJ, Anstey NM: Detection of histidine rich protein 2 and panmalarial ICT Malaria Pf/Pv test antigens after chloroquine treatment of uncomplicated falciparum malaria does not reliably predict treatment outcome in eastern Indonesia. Am J Trop Med Hyg. 2001, 65: 593-598.
Noedl H, Wernsdorfer WH, Miller RS, Wongsrichanalai C: Histidine-rich protein II: a novel approach to malaria drug sensitivity testing. Antimicrob Agents Chemother. 2002, 46: 1658-1664. 10.1128/AAC.46.6.1658-1664.2002.
Biswas S, Tomar D, Rao DN: Investigation of the kinetics of histidine-rich protein 2 and of the antibody responses to this antigen, in a group of malaria patients from India. Ann Trop Med Parasitol. 2005, 99: 553-562. 10.1179/136485905X51463.
Johnson BC, Swanson AM: Milk Serum Proteins. I. A quantitative Biuret test for milk serum proteins. J Dairy Sci. 1952, 35: 823-828. 10.3168/jds.S0022-0302(52)93762-4.
WHO: Malaria Rapid Diagnostic Tests Performance : Results of WHO Product Testing of Malaria RDTs: Round 1 (2008). 2009, Geneva: World Health Organization
WHO: Malaria Rapid Diagnostic Test Performance Results of WHO Product Testing of Malaria RDTs: Round 2 (2009). 2010, Geneva: World Health Organization
WHO-TDR-FIND: Methods Manual for Laboratory Quality Control Testing of Malaria Rapid Diagnostic Test, Version 6. 2010, Geneva: World Health Organization
Rzepczyk CM, Hale K, Woodroffe N, Bobogare A, Csurhes P, Ishii A, Ferrante A: Humoral immune responses of Solomon Islanders to the merozoite surface antigen 2 of Plasmodium falciparum show pronounced skewing towards antibodies of the immunoglobulin G3 subclass. Infect Immun. 1997, 65: 1098-1100.
Trager W, Jensen JB: Human malaria parasites in continuous culture. Science. 1976, 193: 673-675. 10.1126/science.781840.
Lambros C, Vanderberg JP: Synchronization of Plasmodium falciparum erythrocytic stages in culture. J Parasitol. 1979, 65: 418-420. 10.2307/3280287.
Nishanian P, Huskins KR, Stehn S, Detels R, Fahey JL: A simple method for improved assay demonstrates that HIV p24 antigen is present as immune complexes in most sera from HIV-infected individuals. J Infect Dis. 1990, 162: 21-28. 10.1093/infdis/162.1.21.
Schupbach J, Flepp M, Pontelli D, Tomasik Z, Luthy R, Boni J: Heat-mediated immune complex dissociation and enzyme-linked immunosorbent assay signal amplification render p24 antigen detection in plasma as sensitive as HIV-1 RNA detection by polymerase chain reaction. AIDS. 1996, 10: 1085-1090.
Wilson NO, Adjei AA, Anderson W, Baidoo S, Stiles JK: Detection of Plasmodium falciparum histidine-rich protein II in saliva of malaria patients. Am J Trop Med Hyg. 2008, 78: 733-735.
Genton B, Paget S, Beck HP, Gibson N, Alpers MP, Hii J: Diagnosis of Plasmodium falciparum infection using ParaSight(R)-F test in blood and urine of Papua New Guinean children. Southeast Asian J Trop Med Public Health. 1998, 29: 35-40.