Syncytiotrophoblast Degradation and the Pathophysiology of the Malaria-infected Placenta
Open accessAbstract
Malaria is associated with excessive parasitic infection of the placenta and a reduction in neonatal birthweight. This study has investigated placental cell death in women with active and past malarial infection. Term placentae, with and without malarial pathology, were obtained from women in The Gambia. Active and past malaria infections were identified in placental sections and histological examination was used to determine the number of villi, the incidence of apoptosis, syncytial degradation, fibrinoid deposition and the frequency of syncytial knots. Placentae with active malaria infection showed erythrocyte adhesion of infected cells to syncytiotrophoblast, syncytial degradation, increased syncytial knotting and, in rare cases, localized destruction of the villi. Past malarial infection was characterized by syncytiotrophoblast disruption and fibrin-type fibrinoid (FTF) deposition. Perivillous FTF deposition was consistent with increased syncytial lesions and both increased lesions and syncytial knots were associated with birthweight reductions. Active malaria infection produced no alteration in placental apoptosis. The numbers of chorionic villi remained unchanged and infiltration of inflammatory cells, although not measured directly, appeared to be non-pervasive within the infected tissue. These observations establish a direct link between malaria parasitic infection and syncytiotrophoblast damage. The placental rejection of parasite-affected syncytia may invoke structural changes to compensate for inadequate placental exchange. Syncytial destruction could have serious implications; impairing fetal growth and in some rare cases, providing a previously unrecognized pathway to congenital infection.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Haemozoin deposition and haemozoin-loaded macrophages have been implicated in the induction of inflammation in the trophoblast.
“haemozoin deposition and haemozoin-loaded macrophages have implicated in the induction of inflammation in the throphoblast [30,32].”
From Submicroscopic infection of placenta by Plasmodium produces Th1/Th2 cytokine imbalance, inflammation and hypoxia in women from north-west Colombia (2014) · cites this paper as [30]
Early reports on apoptosis in malaria-infected placentas showed no difference in the proportion of apoptotic cells compared with uninfected placentas.
“Early reports on apoptosis in malaria infected placentas showed no difference in the proportion of apoptotic cells when compared to uninfected ones [30].”
From Submicroscopic infection of placenta by Plasmodium produces Th1/Th2 cytokine imbalance, inflammation and hypoxia in women from north-west Colombia (2014) · cites this paper as [30]
Cites
The burden of malaria in pregnancy in malaria-endemic areas
Steketee, R., Nahlen, B., Parise, M., & Menendez, C. (2001) · The American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2001.64.28 · Cited by 1,063 · see citing works
The Impact of Placental Malaria on Gestational Age and Birth Weight
Menendez, C., Ordi, J., Ismail, M. R., Ventura, P. J., Aponte, J. J., Kahigwa, E., Font, F., & Alonso, P. L. (2000) · The Journal of Infectious Diseases · doi:10.1086/315449 · Cited by 467 · see citing works
Placental apoptosis in normal human pregnancy
SMITH, S. C. H., Baker, P. N., & SYMONDS, E. M. (1997) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(97)70438-1 · Cited by 400 · see citing works
Self-citationHung, T., Skepper, J. N., Jones, D. S., & Burton, G. J. (2002) · Circulation Research · doi:10.1161/01.res.0000024411.22110.aa · Cited by 397 · see citing works
Increased placental apoptosis in intrauterine growth restriction
SMITH, S. C. H., Baker, P. N., & SYMONDS, E. M. (1997) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(97)70081-4 · Cited by 374 · see citing works
Self-citationMacara, L., Kingdom, J. C., Kaufmann, P., Kohnen, G., Hair, J., More, I. A. R., Lyall, F., & Greer, I. A. (1996) · Placenta · doi:10.1016/s0143-4004(05)80642-3 · Cited by 352 · see citing works
Placental pathology in malaria: A histological, immunohistochemical, and quantitative study
Ismail, M. R., Ordi, J., Menendez, C., Ventura, P. J., Aponte, J. J., Kahigwa, E., Hirt, R., Cardesa, A., & Alonso, P. L. (2000) · Human Pathology · doi:10.1016/s0046-8177(00)80203-8 · Cited by 328 · see citing works
Malaria 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
Steketee, R. W., Hightower, A. W., Wirima, J. J., Breman, J. G., Heymann, D. L., & Slutsker, L. (1996) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.1996.55.33 · Cited by 303 · see citing works
Huppertz, B., Kingdom, J. C., Caniggia, I., Desoyé, G., Black, S., Korr, H., & Kaufmann, P. (2003) · Placenta · doi:10.1053/plac.2002.0903 · Cited by 288 · see citing works
Increased placental apoptosis in pregnancies complicated by preeclampsia
Leung, D. N., Smith, S. C., To, K. F., Sahota, D. S., & Baker, P. N. (2001) · American Journal of Obstetrics and Gynecology · doi:10.1067/mob.2001.112906 · Cited by 281 · see citing works
Self-citationMassive chronic intervillositis of the placenta associated with malaria infection
Ordi, J., Ismail, M. R., Ventura, P. J., Kahigwa, E., Hirt, R., Cardesa, A., Alonso, P. L., & Menendez, C. (1998) · The American Journal of Surgical Pathology · doi:10.1097/00000478-199808000-00011 · Cited by 265 · see citing works
Placental malaria. I. Pathological classification
BULMER, J. N., RASHEED, F. N., FRANCIS, N., MORRISON, L., & GREENWOOD, B. M. (1993) · Histopathology · doi:10.1111/j.1365-2559.1993.tb00110.x · Cited by 222 · see citing works
Self-citationMoormann, A. M., Sullivan, A. D., Rochford, R. A., Chensue, S. W., Bock, P. J., Nyirenda, T. E., & Meshnick, S. R. (1999) · The Journal of Infectious Diseases · doi:10.1086/315135 · Cited by 208 · see citing works
The pathogenesis of pre-eclampsia
Redman, C. W. G., & Sargent, I. L. (2001) · Gynécologie Obstétrique & Fertilité · doi:10.1016/s1297-9589(01)00180-1 · Cited by 169 · see citing works
Rogerson, S. J., Brown, H. C., Pollina, E., Abrams, E. T., Tadesse, E., Lema, V. M., & Molyneux, M. E. (2003) · Infection and Immunity · doi:10.1128/iai.71.1.267-270.2003 · Cited by 163 · see citing works
Nelson, D. M., Crouch, E. C., Curran, E. M., & Farmer, D. R. (1990) · Europe PMC (PubMed Central) · Cited by 133 · see citing works
Impaired uteroplacental blood flow in pregnancies complicated by falciparum malaria
Dorman, E. K., Shulman, C. E., Kingdom, J. C., Bulmer, J. N., Mwendwa, J. M., Peshu, N. M., & Marsh, K. (2002) · Ultrasound in Obstetrics and Gynecology · doi:10.1046/j.0960-7692.2001.00545.x · Cited by 133 · see citing works
Self-citationPlacental 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
Self-citationYamada, 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
Apoptosis in the placenta of pregnancies complicated with IUGR
Erel, C. T., Dane, B., Calay, Z., et al. (2001) · International Journal of Gynecology & Obstetrics · doi:10.1016/s0020-7292(01)00373-3 · Cited by 91 · see citing works
Malaria and anaemia in pregnant women in urban Zanzibar, Tanzania
Matteelli, A., Donato, F., Shein, A., Muchi, J. A., Leopardi, O., Astori, L., & Carosi, G. (1994) · Annals of Tropical Medicine and Parasitology · doi:10.1080/00034983.1994.11812894 · Cited by 91 · see citing works
The vascular endothelium in normal pregnancy and pre-eclampsia
Lyall, F. (1996) · Reviews of Reproduction · doi:10.1530/ror.0.0010107 · Cited by 89 · see citing works
Matteelli, A., Caligaris, S., Castelli, F., & Carosi, G. (1997) · Annals of Tropical Medicine and Parasitology · doi:10.1080/00034989760563 · Cited by 87 · see citing works
Mayhew, T. M., & Barker, B. L. (2001) · Placenta · doi:10.1053/plac.2001.0700 · Cited by 79 · see citing works
Crocker, I. P., Barratt, S. L., Kaur, M., & Baker, P. N. (2001) · Placenta · doi:10.1053/plac.2001.0733 · Cited by 73 · see citing works
Self-citationOkoko, B. J., Ota, M. O. C., Yamuah, L. K., Idiong, D., Mkpanam, S. N., Avieka, A., BANYA, W. A. S., & Osinusi, K. (2002) · PubMed · Cited by 72 · see citing works
Relationships between maternal malaria and malarial immune responses in mothers and neonates
Rasheed, F. N., Bulmer, J. N., de Francisco, A., Jawla, M., Jakobsen, P., Jepson, A., & Greenwood, B. M. (1995) · Parasite Immunology · doi:10.1111/j.1365-3024.1995.tb00960.x · Cited by 72 · see citing works
Self-citationMalaria associated pre-eclampsia in Senegal
Sartelet, H., Rogier, C., Milko-Sartelet, I., Angel, G., & Michel, G. (1996) · The Lancet · doi:10.1016/s0140-6736(96)90321-9 · Cited by 69 · see citing works
Parasite adhesion and immune evasion in placental malaria
Beeson, J. G., Reeder, J. C., Rogerson, S. J., & Brown, G. V. (2001) · Trends in Parasitology · doi:10.1016/s1471-4922(01)01917-1 · Cited by 68 · see citing works
Placental apoptosis is increased in post‐term pregnancies
SMITH, S. C. H., & Baker, P. N. (1999) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1999.tb08410.x · Cited by 66 · see citing works
Self-citationThe endocrinology of pre‐eclampsia
Page, N. (2002) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2002.01626.x · Cited by 56 · see citing works
Mechanisms of maternofetal exchange across the human placenta
Sibley, C. P., Birdsey, T. J., Brownbill, P., et al. (1998) · Biochemical Society Transactions · doi:10.1042/bst0260086 · Cited by 49 · see citing works
How many paraffin blocks are necessary to detect villitis?
Altemani, A., Gonzatti, A. G. R., & Metze, K. (2002) · Placenta · doi:10.1053/plac.2002.0875 · Cited by 34 · see citing works
Watkinson, M., Rushton, D. I., & Lunn, P. G. (1985) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(85)90059-8 · Cited by 28 · see citing works
Development of early uteroplacental circulation.
Jaffe, R. B. (2001) · PubMed · Cited by 20 · see citing works
STRESS, IMMUNE FUNCTION, AND RELATIONSHIP TO PREGNANCY OUTCOME
Gennaro, S., & Fehder, W. P. (1996) · Nursing Clinics of North America · doi:10.1016/s0029-6465(22)00140-2 · Cited by 18 · see citing works
Removal of Acid Hematin-Type Pigments from Sections; Efficacy of Alcoholic Picric Acid Solution
Waldrop, F. S., Puchtler, H., & Terry, M. S. (1969) · Stain Technology · doi:10.3109/10520296909063366 · Cited by 7 · see citing works
Severe Plasmodium falciparum malaria in a non‐immune pregnant woman
Bukman, A., Weinans, M. J. N., & van Loon, A. J. (1997) · International Journal of Gynecology & Obstetrics · doi:10.1016/s0020-7292(97)00205-1 · Cited by 3 · see citing works
Malaria in pregnancy. 2: Physiological effects on the placenta, fetus and neonate.
Jones, E. (2000) · PubMed · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Formation of Syncytial Knots is Increased by Hyperoxia, Hypoxia and Reactive Oxygen Species
Heazell, A. E. P., Moll, S. J., Jones, C. J. P., Baker, P. N., & Crocker, I. P. (2007) · Placenta · doi:10.1016/j.placenta.2006.10.007 · Cited by 204 · see citing works
Self-citationChaikitgosiyakul, S., Rijken, M. J., Muehlenbachs, A., Lee, S. J., Chaisri, U., Viriyavejakul, P., Turner, G. D., Pongponratn, E., Nosten, F., & McGready, R. (2014) · Malaria Journal · doi:10.1186/1475-2875-13-4 · Cited by 66 · see citing works
Placental Hypoxia during Placental Malaria
Boeuf, P., Tan, A., Romagosa, C., Radford, J., Mwapasa, V., Molyneux, M. E., Meshnick, S. R., Hunt, N. H., & Rogerson, S. J. (2008) · The Journal of Infectious Diseases · doi:10.1086/526521 · Cited by 50 · see citing works
Agudelo, O. M., Aristizabal, B. H., Yanow, S. K., Arango, E., Carmona-Fonseca, J., & Maestre, A. (2014) · Malaria Journal · doi:10.1186/1475-2875-13-122 · Cited by 37 · see citing works
Malaria in pregnancy: adverse pregnancy outcomes and the future of prevention
Berhe, A. D., Doritchamou, J. Y. A., & Duffy, P. E. (2023) · Frontiers in Tropical Diseases · doi:10.3389/fitd.2023.1229735 · Cited by 30 · see citing works
- Authors
- Crocker, I. P., Tanner, O. M., Myers, J. E., Bulmer, J. N., Walraven, G., & Baker, P. N.
- Affiliations
- University of Manchester (GB)
- Newcastle University (GB)
- London School of Hygiene & Tropical Medicine (GB)
- Corresponding author
- Crocker, I.P.
- Venue
- Placenta
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 25
- Issue
- 4
- Pages
- 273-282
- ISSN
- 0143-4004 (ISSN-L)
- OpenAlex
- W2100354205
- Cited by
- 92
- References
- 40
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 4 · 2013: 7 · 2012: 7
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Placenta (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Medical Research Council
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- malaria, syncytiotrophoblast, syncytial knots, fibrinoid deposition, placental apoptosis, placental pathology, erythrocyte adhesion, fetal growth
- MeSH terms
- Adolescent, Adult, Chorionic Villi, Female, Fibrin, Gambia, Humans, Malaria, Maternal Age, Pregnancy, Trophoblasts, Pregnancy Complications, Parasitic, Apoptosis, Pregnancy, High-Risk
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
