Detection of the Plasmodium falciparum Antigen Histidine-Rich Protein 2 in Blood of Pregnant Women: Implications for Diagnosing Placental Malaria
Open accessAbstract
Pregnant women have an increased susceptibility to infection by Plasmodium falciparum. Parasites may be present in the placenta yet not detectable in peripheral blood smears by routine light microscopy. In order to determine how frequently misdiagnosis occurs, peripheral blood and placental samples were collected from 1,077 Cameroonian women at the time of giving birth and examined for the presence of malarial parasites by using light microscopy. Results showed that 20.1% of the women who had placental malaria were peripheral blood smear negative. Thus, malarial infection was not detected by microscopic examination of peripheral blood smears from approximately one out of five malaria-infected women. Since P. falciparum parasites secrete histidine-rich protein 2 (HRP-2), we sought to determine if detecting HRP-2 in either peripheral plasma or whole blood might be used to diagnose the presence of parasites "hidden" in the placenta. Samples of peripheral plasma from 127 women with different levels of placental malarial infection were assayed by HRP-2-specific enzyme-linked immunosorbent assay. HRP-2 was detected in 88% of the women with placental malaria who tested negative by blood smear. Additionally, whole blood was obtained from 181 women and tested for HRP-2 with a rapid, chromatographic strip test (ICT). The ICT test accurately detected malarial infection in 89.1% of P. falciparum-infected women. Furthermore, 94% of women with malaria were accurately diagnosed by using a combination of microscopy and the ICT test. Thus, detection of HRP-2 in conjunction with microscopy should improve diagnosis of malaria in pregnant women.
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Pregnancy poses a unique challenge for falciparum malaria diagnosis because parasites sequester in the placenta and circulating parasitaemia is very low and therefore undetectable by peripheral blood smear microscopy or rapid diagnostic test.
“Pregnancy poses a unique challenge for falciparum malaria diagnosis, as parasites sequester in the placenta and the circulating parasitaemia is very low and therefore undetectable by peripheral blood smear microscopy or rapid diagnostic test [7–10].”
From Intermittent preventive treatment with Sulphadoxine-Pyrimethamine (IPTp-SP) is associated with protection against sub-microscopic P. falciparum infection in pregnant women during the low transmission dry season in southwestern Cameroon: A Semi - longitudinal study (2022) · cites this paper as [8]
Previous studies in Cameroon and other malaria endemic settings have reported similarly large proportions of asymptomatic/sub-microscopic individuals using molecular diagnostic methods compared to RDT or microscopy.
“Previous studies in Cameroon [8] and other malaria endemic settings have also reported similarly large proportions of asymptomatic/sub-microscopic individuals using molecular diagnostic methods compared to affordable tools such as RDT or microscopy [29]”
From Intermittent preventive treatment with Sulphadoxine-Pyrimethamine (IPTp-SP) is associated with protection against sub-microscopic P. falciparum infection in pregnant women during the low transmission dry season in southwestern Cameroon: A Semi - longitudinal study (2022) · cites this paper as [8]
This suggests an improvement of immune protection during subsequent pregnancies, limiting P. falciparum not only to low parasite densities but even to submicroscopic levels.
“This suggests an improvement of immune protection during subsequent pregnancies, limiting P. falciparum not only to low parasite densities but even to submicroscopic levels [8].”
From Intermittent preventive treatment with Sulphadoxine-Pyrimethamine (IPTp-SP) is associated with protection against sub-microscopic P. falciparum infection in pregnant women during the low transmission dry season in southwestern Cameroon: A Semi - longitudinal study (2022) · cites this paper as [8]
Even under optimal conditions, a large proportion of pregnancy malaria cases are missed by peripheral blood microscopy, which calls into question the use of peripheral blood smear as a reference for pregnancy malaria diagnosis.
“Even under optimal conditions, a large proportion of PM cases are missed by peripheral blood microscopy ([13] and Table 1), which calls into question the use of peripheral BS as a reference for PM diagnosis.”
From Diagnosing malaria in pregnancy: An update (2012) · cites this paper as [13]
In studies using both peripheral and placental blood microscopy as references, RDT sensitivity was lower when compared with placental blood microscopy.
“In studies that used both peripheral and placental blood microscopy as references, RDT sensitivity was lower when compared with placenta blood microscopy [10,13,18].”
From Diagnosing malaria in pregnancy: An update (2012) · cites this paper as [13]
When performed on peripheral blood for pregnancy malaria diagnosis, RDT-HRP2 sensitivity is more than 90% compared with peripheral blood smear and 80-95% compared with placental blood smear, with specificity between 61 and 94%.
“When performed on peripheral blood samples for PM diagnoses, RDT-HRP2 sensitivity was more than 90% when compared with peripheral BS, and 80–95% when compared with placental BS, with specificity between 61 and 94% [13–16].”
From Diagnosing malaria in pregnancy: An update (2012) · cites this paper as [13]
Among studies of malaria in pregnancy, RDT met the WHO threshold (90% specificity at 95% sensitivity) in only one study.
“However, among PM studies, RDT met this standard in only one study [13].”
From Diagnosing malaria in pregnancy: An update (2012) · cites this paper as [13]
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Cites
Snounou, G., Viriyakosol, S., Zhu, X. P., Jarra, W., Pinheiro, L., do Rosario, V. E., Thaithong, S., & Brown, K. N. (1993) · Molecular and Biochemical Parasitology · doi:10.1016/0166-6851(93)90077-b · Cited by 1,591 · see citing works
Snounou, G., Viriyakosol, S., Jarra, W., Thaithong, S., & Brown, K. N. (1993) · Molecular and Biochemical Parasitology · doi:10.1016/0166-6851(93)90050-8 · Cited by 906 · see citing works
An analysis of malaria in pregnancy in Africa.
Brabin, B. J. (1983) · PubMed · Cited by 785 · see citing works
Epidemiology, Malaria and Pregnancy
McGregor, I. A. (1984) · The American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.1984.33.517 · Cited by 452 · cited 1× · see citing works
“As a result, high numbers of trophozoite and schizont stage parasites may be found in the placenta (4, 13).”
BackgroundMalaria during pregnancy: A priority area of malaria research and control
Menéndez, C. (1995) · Parasitology Today · doi:10.1016/0169-4758(95)80151-0 · Cited by 322 · see citing works
Fried, M., Muga, R., Misore, A. O., & Duffy, P. E. (1998) · PubMed · Cited by 321 · see citing works
Howard, R. J., Uni, S., Aikawa, M., et al. (1986) · The Journal of Cell Biology · doi:10.1083/jcb.103.4.1269 · Cited by 321 · see citing works
Beadle, C., Long, G. W., McElroy, P. D., Hoffman, S. L., Long, G. W., Weiss, W., Maret, S., & Oloo, A. J. (1994) · The Lancet · doi:10.1016/s0140-6736(94)91520-2 · Cited by 317 · see citing works
Use and limitations of light microscopy for diagnosing malaria at the primary health care level.
(1988) · Europe PMC (PubMed Central) · Cited by 281 · see citing works
Fried, M., Muga, R. O., Misore, A. O., & Duffy, P. E. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.5.2523 · Cited by 262 · see citing works
Placental pathologic changes in malaria. A histologic and ultrastructural study.
Walter, P. R., GARIN, Y. J. F., & Blot, P. (1982) · PubMed · Cited by 253 · see citing works
The rapid manual ParaSight®-F test. A new diagnostic tool for Plasmodium falciparum infection
Shiff, C., Premji, Z. G., & Minjas, J. N. (1993) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(93)90273-s · Cited by 231 · see citing works
Rock, E. P., Marsh, K., Saul, A. J., et al. (1987) · Parasitology · doi:10.1017/s0031182000057681 · Cited by 187 · see citing works
Parra, M., Evans, C. B., & Taylor, D. W. (1991) · Journal of Clinical Microbiology · doi:10.1128/jcm.29.8.1629-1634.1991 · Cited by 173 · see citing works
Self-citationPieroni, P., Mills, C. D., Ohrt, C., Harrington, M. A., & Kain, K. C. (1998) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/s0035-9203(98)90730-1 · Cited by 121 · see citing works
Placental malaria. II. A semi‐quantitative investigation of the pathological features
Bulmer, J. N., Rasheed, F. N., Morrison, L., FRANCIS, N., & Greenwood, B. M. (1993) · Histopathology · doi:10.1111/j.1365-2559.1993.tb00111.x · Cited by 115 · see citing works
Immunochromatographic test for malaria diagnosis
Garcia, M. L., Kirimoama, S., Marlborough, D., Leafasia, J. L., & Rieckmann, K. H. (1996) · The Lancet · doi:10.1016/s0140-6736(96)90700-x · Cited by 106 · see citing works
Yamada, M., Steketee, R. W., Abramowsky, C. R., Kida, M., Wirima, J. J., Heymann, D., Rabbege, J. R., Breman, J. G., & Aikawa, M. (1989) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.1989.41.161 · Cited by 105 · see citing works
The sequestration of Plasmodium falciparum infected erythrocytes in the placenta
Bray, R. S., & Sinden, R. E. (1979) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(79)90028-2 · Cited by 85 · see citing works
Semi-quantitative measurement of Plasmodium falciparum antigen PfHRP2 in blood and plasma
Desakorn, V., Silamut, K., Angus, B., Sahassananda, D., Chotivanich, K., Suntharasamai, P., Simpson, J. A., & White, N. J. (1997) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/s0035-9203(97)90292-3 · Cited by 75 · see citing works
ParaSight-F rapid manual diagnostic test of Plasmodium falciparum infection.
Uguen, C., Rabodonirina, M., Pina, J.-J. D., Vigier, J. P., Martet, G., Maret, M., & Peyron, F. (1995) · Europe PMC (PubMed Central) · Cited by 62 · see citing works
Leopardi, O., Naughten, W., Salvia, L., Colecchia, M., Matteelli, A., Zucchi, A., Shein, A., Muchi, J. A., Carosi, G., & Ghione, M. (1996) · Pathology - Research and Practice · doi:10.1016/s0344-0338(96)80068-9 · Cited by 57 · see citing works
The development and validation of a simple antigen detection ELISA for Plasmodium falciparum malaria
Taylor, D. W., & Voller, A. (1993) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(93)90409-j · Cited by 43 · see citing works
Self-citationSingh, N., Singh, M. P., & Sharma, A. (1997) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.1997.56.188 · Cited by 41 · see citing works
Desowitz, R. S., & Alpers, M. P. (1992) · Annals of Tropical Medicine and Parasitology · doi:10.1080/00034983.1992.11812638 · Cited by 40 · see citing works
Bechem, N. N., Leke, R. F. G., Tietche, F., & Taylor, D. W. (1999) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/s0035-9203(99)90175-x · Cited by 36 · see citing works
Self-citationGaye, O., Diouf, M., Dansokho, E. F., et al. (1998) · Parasite · doi:10.1051/parasite/1998052189 · Cited by 32 · see citing works
WHO Expert Committee on Malaria. Eighteenth report.
(1986) · PubMed · Cited by 27 · see citing works
Field study of an antigen-detection ELISA specific for Plasmodium falciparum malaria
Namsiripongpun, V., Wilde, H., Pamsandang, P., et al. (1993) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(93)90410-r · Cited by 21 · see citing works
Evaluation of a malaria antigen ELISA
Voller, A., Bidwell, D. E., & Chiodini, P. L. (1994) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(94)90289-5 · Cited by 9 · see citing works
Pellagra considered from the point of view of a disease of insufficient nutrition
Sandwith, F. M. (1915) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/s0035-9203(15)90035-4 · Cited by 5 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [28]Wellems T E, Rock E P, Maloy W L, Taylor D W, Howard R J. Histidine-rich proteins in Plasmodium falciparum: an update and perspective. UCLA Symp Mol Cell Biol New Ser. 1986;42:47–58. [Google Scholar]
Cited by
Sorted by citations
Point-of-Care Diagnostics for Global Health
Yager, P., Domingo, G. J., & Gerdes, J. (2008) · Annual Review of Biomedical Engineering · doi:10.1146/annurev.bioeng.10.061807.160524 · Cited by 1,076 · see citing works
TER KUILE, F. O., TERLOUW, D. J., PHILLIPS-HOWARD, P. A., HAWLEY, W. A., FRIEDMAN, J. F., KARIUKI, S. K., SHI, Y. P., KOLCZAK, M. S., LAL, A. A., VULULE, J. M., et al. (2003) · The American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2003.68.50 · Cited by 204 · see citing works
Fried, M., & Duffy, P. E. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a025551 · Cited by 202 · see citing works
Evaluation of rapid diagnostic tests: malaria
Bell, D., & Peeling, R. W. (2006) · Nature Reviews Microbiology · doi:10.1038/nrmicro1524 · Cited by 170 · see citing works
Kattenberg, J. H., Ochodo, E. A., Boer, K. R., Schallig, H. D., Mens, P. F., & Leeflang, M. M. (2011) · Malaria Journal · doi:10.1186/1475-2875-10-321 · Cited by 138 · see citing works
Rogerson, S. J., Mkundika, P., & Kanjala, M. K. (2003) · Journal of Clinical Microbiology · doi:10.1128/jcm.41.4.1370-1374.2003 · Cited by 113 · see citing works
Tagbor, H., Bruce, J., Agbo, M., Greenwood, B., & Chandramohan, D. (2010) · PLoS ONE · doi:10.1371/journal.pone.0014425 · Cited by 113 · see citing works
Diagnosis of Placental Malaria
Mockenhaupt, F. P., Ulmen, U., von Gaertner, C., Bedu-Addo, G., & Bienzle, U. (2002) · Journal of Clinical Microbiology · doi:10.1128/jcm.40.1.306-308.2002 · Cited by 108 · see citing works
Submicroscopic <i>Plasmodium falciparum</i> infections in pregnancy in Ghana
Mockenhaupt, F. P., Rong, B., Till, H., Eggelte, T. A., Beck, S., Gyasi‐Sarpong, C., Thompson, W. N. A., & Bienzle, U. (2000) · Tropical Medicine & International Health · doi:10.1046/j.1365-3156.2000.00532.x · Cited by 105 · see citing works
Mayor, A., Moro, L., Aguilar, R., Bardají, A., Cisteró, P., Serra-Casas, E., Sigaúque, B., Alonso, P. L., Ordi, J., & Menéndez, C. (2012) · Clinical Infectious Diseases · doi:10.1093/cid/cis236 · Cited by 92 · see citing works
Detection and clinical manifestation of placental malaria in southern Ghana
Mockenhaupt, F. P., Bedu-Addo, G., von Gaertner, C., Boyé, R., Fricke, K., Hannibal, I., Karakaya, F., Schaller, M., Ulmen, U., Acquah, P. A., et al. (2006) · Malaria Journal · doi:10.1186/1475-2875-5-119 · Cited by 81 · see citing works
Diagnosing malaria in pregnancy: An update
Fried, M., Muehlenbachs, A., & Duffy, P. E. (2012) · Expert Review of Anti-infective Therapy · doi:10.1586/eri.12.98 · Cited by 80 · see citing works
EVALUATION OF A MALARIA RAPID DIAGNOSTIC TEST FOR ASSESSING THE BURDEN OF MALARIA DURING PREGNANCY
SINGER, L. M., NEWMAN, R. D., DIARRA, A., MORAN, A. C., HUBER, C. S., STENNIES, G., SIRIMA, S. B., KONATE, A., YAMEOGO, M., SAWADOGO, R., et al. (2004) · The American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2004.70.481 · Cited by 77 · see citing works
SUGUITAN, A. L., CADIGAN, T. J., NGUYEN, T. A., ZHOU, A., LEKE, R. J. I., METENOU, S., THUITA, L., MEGNEKOU, R., FOGAKO, J., LEKE, R. G. F., et al. (2003) · The American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2003.69.574 · Cited by 72 · see citing works
Self-citationMankhambo, L., Kanjala, M., Rudman, S., Lema, V. M., & Rogerson, S. J. (2002) · Journal of Clinical Microbiology · doi:10.1128/jcm.40.1.155-158.2002 · Cited by 65 · see citing works
Anchang-Kimbi, J. K., Achidi, E. A., Nkegoum, B., Sverremark-Ekström, E., & Troye-Blomberg, M. (2009) · Malaria Journal · doi:10.1186/1475-2875-8-126 · Cited by 65 · see citing works
Kattenberg, J. H., Tahita, C. M., Versteeg, I. A. J., Tinto, H., Traoré‐Coulibaly, M., Schallig, H. D. F. H., & Mens, P. F. (2012) · Tropical Medicine & International Health · doi:10.1111/j.1365-3156.2012.02975.x · Cited by 63 · see citing works
Uneke, C. J. (2008) · Parasitology Research · doi:10.1007/s00436-007-0782-6 · Cited by 53 · see citing works
Conroy, A. L., Liles, W. C., Molyneux, M. E., Rogerson, S. J., & Kain, K. C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028540 · Cited by 46 · see citing works
Thévenon, A. D., Zhou, J. A., Megnekou, R., Ako, S., Leke, R. G. F., & Taylor, D. W. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1002293 · Cited by 44 · see citing works
Self-citationDETECTION OF PLASMODIUM FALCIPARUM IN PREGNANCY BY LASER DESORPTION MASS SPECTROMETRY
NYUNT, M., PISCIOTTA, J., FELDMAN, A. B., THUMA, P., SCHOLL, P. F., DEMIREV, P. A., LIN, J. S., SHI, L., KUMAR, N., & SULLIVAN, D. J. (2005) · The American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2005.73.485 · Cited by 43 · see citing works
Kyabayinze, D. J., Tibenderana, J. K., Nassali, M., Tumwine, L. K., Riches, C., Montague, M., Counihan, H., Hamade, P., Van Geertruyden, J.-P., & Meek, S. (2011) · Malaria Journal · doi:10.1186/1475-2875-10-306 · Cited by 42 · see citing works
Ahmed, R., Levy, E. I., Maratina, S. S., de Jong, J. J., Asih, P. B. S., Rozi, I. E., Hawley, W., Syafruddin, D., & ter Kuile, F. (2015) · Malaria Journal · doi:10.1186/s12936-015-0943-5 · Cited by 38 · see citing works
Ofori, M. F., Staalsoe, T., Bam, V., Lundquist, M., David, K. P., Browne, E. N. L., Akanmori, B. D., & Hviid, L. (2003) · Infection and Immunity · doi:10.1128/iai.71.3.1584-1586.2003 · Cited by 37 · see citing works
Tagbor, H. (2008) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s2809 · Cited by 24 · see citing works
Apinjoh, T. O., Ntui, V. N., Chi, H. F., Moyeh, M. N., Toussi, C. T., Mayaba, J. M., Tangi, L. N., Kwi, P. N., Anchang-Kimbi, J. K., Dionne-Odom, J., et al. (2022) · PLOS ONE · doi:10.1371/journal.pone.0275370 · Cited by 13 · see citing works
- Authors
- Leke, R. F. G., Djokam, R. R., Mbu, R., Leke, R. J., Fogako, J., Megnekou, R., Metenou, S., Sama, G., Zhou, Y., Cadigan, T., Parra, M., & Taylor, D. W.
- Affiliations
- Université de Yaoundé I (CM)
- Georgetown University (US)
- Venue
- Journal of Clinical Microbiology
- Publisher
- American Society for Microbiology
- Published
- 1999-09
- Volume
- 37
- Issue
- 9
- Pages
- 2992-2996
- ISSN
- 0095-1137 (ISSN-L)
- 1098-660X
- PMC
- PMC85431
- OpenAlex
- W2115855731
- Cited by
- 118
- References
- 31
- Citations by year
- 2024: 1 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 3 · 2018: 3 · 2017: 5 · 2016: 2 · 2015: 7 · 2014: 4 · 2013: 5 · 2012: 5
- FWCI
- 5.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Microbiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (UO1 AI 35839, U01AI035839)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Life Sciences › Immunology and Microbiology › Parasitology › Bird parasitology and diseases
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- Plasmodium falciparum, placental malaria, HRP-2, malaria in pregnancy, rapid diagnostic tests, misdiagnosis
- MeSH terms
- Histidine-Rich Glycoprotein, Animals, Antigens, Protozoan, Enzyme-Linked Immunosorbent Assay, Female, Humans, Microscopy, Placenta, Plasmodium falciparum, Pregnancy, Pregnancy Complications, Proteins, Reagent Strips, Malaria, Falciparum, Parasitemia
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