Placental malaria pathogenesis — DTM&H MCQ

Instant feedback + full explanation. One question, done properly.

HardMalariaPlacental malaria pathogenesisDTM&H

A 32-year-old pregnant woman at 36 weeks in Tanzania develops preterm labour, fever, and is found to have P. falciparum parasitaemia of 3%. She delivers a low-birth-weight infant. Histological examination of the placenta shows parasitised erythrocytes in the intervillous spaces. What adhesin mediates placental sequestration?

Educational content. Not a substitute for clinical judgement or local policy.

Reveal the answer and explanation

Correct answer: C — PfEMP1 (VAR2CSA) binding to chondroitin sulphate A

The correct answer is C, PfEMP1 (VAR2CSA) binding to chondroitin sulphate A. Placental malaria is caused by a distinct parasite subpopulation that expresses the VAR2CSA variant of PfEMP1 on the infected erythrocyte surface, which binds specifically to low-sulphated chondroitin sulphate A expressed on syncytiotrophoblast in the intervillous space, unlike the ICAM-1 or CD36 binding used for sequestration in other vascular beds. This tissue-specific adhesin-receptor pairing explains why parasitised erythrocytes accumulate in the placenta rather than being cleared by the spleen, producing the intervillous parasitaemia, maternal fever, preterm labour, and low birth weight described in the stem. Primigravid women have not yet developed protective anti-VAR2CSA antibodies, so they suffer the highest burden of placental sequestration and its fetal consequences, which is why VAR2CSA is the lead target for placental malaria vaccine development. Why the other options are wrong: D. PfEMP1 binding to ICAM-1: ICAM-1 mediates cerebral sequestration (cytoadherence in brain microvasculature), not placental sequestration, so it does not explain the intervillous finding. A. CSP binding to hepatocyte receptors: circumsporozoite protein mediates sporozoite invasion of hepatocytes during the pre-erythrocytic liver stage, a completely different life cycle step unrelated to erythrocyte sequestration in pregnancy. B. MSP-1 binding to red cell receptors: merozoite surface protein 1 is involved in merozoite attachment and invasion of erythrocytes during the blood stage, not in cytoadherence of infected cells to placental tissue. E. TRAP binding to salivary gland cells: thrombospondin-related anonymous protein mediates sporozoite motility and hepatocyte invasion after mosquito salivary gland release, not placental adhesion. Key point: Placental sequestration is uniquely mediated by VAR2CSA-expressing PfEMP1 binding chondroitin sulphate A on syncytiotrophoblast, distinguishing it from ICAM-1/CD36-mediated sequestration elsewhere in the body.

Reference: RCOG Green-top Guideline No. 54b, The Diagnosis and Treatment of Malaria in Pregnancy (2010, reaffirmed), https://www.rcog.org.uk/media/rfrerkjz/gtg_54b.pdf