A Novel Histological Grading Scheme for Placental Malaria Applied in Areas of High and Low Malaria Transmission
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BACKGROUND: Plasmodium falciparum-infected erythrocytes sequester in the placenta and elicit an inflammatory response that is harmful to both fetus and mother. Histologic measurements during placental malaria might provide surrogate end points for interventional trials, but existing histologic schemes capture limited complexity and are not consistently used among study sites. METHODS: Using frozen-section histologic evaluation in Tanzania (high-transmission area), we established a novel grading scheme to separately quantify inflammation and pigment deposition during placental malaria (n = 102). To generalize this method, formalin-fixed, paraffin-embedded placental samples from Karen women in Thailand (low-transmission area) were selected from among women with documented antenatal parasitemia who were near term (n = 18). RESULTS: In the Tanzanian cohort, the inflammation and pigment-deposition scores were independently associated with birth weight, and the inflammation score was associated with chemokine levels. In the smaller cohort from Thailand, both inflammation and pigment scores were associated with birth weight, and the pigment score had an inverse trend with the number of antenatal clinic visits. CONCLUSIONS: This semiquantitative pathological grading scheme is simple to implement and captures information that is associated with outcomes in Asia and Africa; therefore, it should facilitate the comparison and standardization of results among clinical trials across areas of differing endemicity.
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Because a single infection during pregnancy contributes to poor pregnancy outcomes, submicroscopic infections among primigravid women may indicate an earlier patent infection causing low birthweight, which would also be reflected by increased pigment deposition.
“Because a single infection during pregnancy contributes to poor pregnancy outcomes [2], submicroscopic infections among primigravid women may indicate an earlier patent infection causing LBW, which would also be reflected by increased pigment deposition (calculated as the percentage of fields containing pigment in intervillous fibrin) [54].”
From Diagnosing malaria in pregnancy: An update (2012) · cites this paper as [54]
Hemozoin can persist for months following treatment of a documented infection, and the extent of hemozoin deposition is thought to correlate with cumulative exposure, with levels associated with gravidity, degree of parasitemia at treatment and reinfection before delivery.
“Hemozoin can persist for months in women following treatment of a documented infection [58], and the extent of hemozoin deposition is thought to correlate with cumulative exposure [54] such that levels have been associated with gravidity, the degree of parasitemia at the time of treatment and reinfection before delivery [57].”
From Diagnosing malaria in pregnancy: An update (2012) · cites this paper as [54]
In anticipation of future interventional trials, the authors developed a grading scheme that used either frozen or formalin-fixed paraffin-embedded tissues and incorporated semiquantitative scoring of inflammation and hemozoin deposition, and found both measures are independently associated with clinical outcomes.
“In anticipation of future interventional trials, we developed a grading scheme that used either frozen or FFPE tissues and incorporated semiquantitative scoring of inflammation and hemozoin deposition, and found both measures are independently associated with clinical outcomes [54].”
From Diagnosing malaria in pregnancy: An update (2012) · cites this paper as [54]
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Self-citation
- Authors
- Muehlenbachs, A., Fried, M., McGready, R., Harrington, W. E., Mutabingwa, T. K., Nosten, F., & Duffy, P. E.
- Affiliations
- Center for Infectious Disease Research (US)
- Churchill Hospital (GB)
- Corresponding author
- Duffy, Patrick E.
- ORCID
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-11-15
- Volume
- 202
- Issue
- 10
- Pages
- 1608-1616
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC3006170
- OpenAlex
- W2110164177
- Cited by
- 100
- References
- 34
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 6 · 2021: 7 · 2020: 20 · 2019: 7 · 2018: 6 · 2017: 6 · 2016: 5 · 2015: 4 · 2014: 5 · 2013: 9 · 2012: 6
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Wellcome Trust
- National Institute of Allergy and Infectious Diseases (R01AI052059, R01AI52059)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Global Maternal and Child Health
- Keywords
- placental malaria, Plasmodium falciparum, placental inflammation, birth weight, chemokines, malaria transmission intensity, surrogate endpoints, frozen section histology, Karen women
- MeSH terms
- Erythrocytes, Female, Humans, Placenta, Placenta Diseases, Plasmodium falciparum, Pregnancy, Tanzania, Thailand, Cohort Studies, Pregnancy Complications, Parasitic, Malaria, Falciparum
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