Prospects and Pitfalls of Pregnancy-Associated Malaria Vaccination Based on the Natural Immune Response to Plasmodium falciparum VAR2CSA-Expressing Parasites

Table 2

Maternal and foetal outcomes of pregnancy-associated malaria.

	Effect	Possible pathogenesis	Transmission	Likely protection	References
MOTHER	Anaemia	Severe malaria: erythrocyte destruction	BOTH	Maternal IgG	[133, 135, 162]
		IL-10: immunosuppression, affects RBC progenitor cells, reduces available iron concentrations in plasma			[209–211]
		TNF-α: inflicts oxidative stress on RBC membranes, suppresses erythropoiesis secondary to local inflammation	BOTH	Maternal IgG?	[212, 213]
		Non-PAM causes of anaemia: iron deficiency, nutrient deficiency, HIV infection, hookworm infestation			[192, 214, 215]
					Gestational hypertension	Impaired trophoblast invasion, cytokine release	BOTH?		[216]
	FOETUS	Preterm delivery	Maternal anaemia	LOW	T cell memory?	[133, 212]
		Acute parasitaemia
		TNF-α: associated with acutely high parasitaemia
		IL-10: contributes to anaemia
	Spontaneous abortion	TNF-α: necrosis of implanted foetus	LOW		[138, 196, 217]
		IFN-γ increases risk of uterine contraction, activates NK cells that induce abortion
	Low birth weight, IUGR	TNF-α: chronic parasitaemia, damages local placental tissue leading to impaired maternal-foetal exchange	HIGH	Maternal IgG	[133–135, 140]
		Second trimester infection
INFANT	Congenital malaria	Passage of parasites	?	Maternal IgG	[205]
	↓ ability to clear parasites	T cell priming: CD4^+CD25^+ regulatory T cells induced, secrete IL-10, suppresses IFN-γ	?	Maternal IgG	[205]