Malaria and Pregnancy: Placental Cytokine Expression and Its Relationship to Intrauterine Growth Retardation

Moormann, Ann M.; Sullivan, Amy D.; Rochford, Rosemary; Chensue, Stephen W.; Bock, Paul J.; Nyirenda, Thomas; Meshnick, Steven R.

doi:10.1086/315135

Cited by 187 publications

(162 citation statements)

References 47 publications

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“…In humans, serum levels of IL-8, a potent N chemoattractant and activator (48), increase during severe malaria (49). Interestingly, IL-8 expression was reported only in HZ-laden M in placental malaria (50). Even though no murine homologue has been described for IL-8, this human chemokine most closely resembles murine MIP-2 (51); therefore, HZ-mediated MIP-2 and IL-8 upregulation may have some common biological effects during malaria.…”

Section: Discussionmentioning

confidence: 99%

Hemozoin-Inducible Proinflammatory Events In Vivo: Potential Role in Malaria Infection

Jaramillo

Plante

Ouellet

et al. 2004

The Journal of Immunology

123

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During malaria infection, high levels of proinflammatory molecules (e.g., cytokines, chemokines) correlate with disease severity. Even if their role as activators of the host immune response has been studied, the direct contribution of hemozoin (HZ), a parasite metabolite, to such a strong induction is not fully understood. Previous in vitro studies demonstrated that both Plasmodium falciparum HZ and synthetic HZ (sHZ), β-hematin, induce macrophage/monocyte chemokine and proinflammatory cytokine secretion. In the present study, we investigated the proinflammatory properties of sHZ in vivo. To this end, increasing doses of sHZ were injected either i.v. or into an air pouch generated on the dorsum of BALB/c mice over a 24-h period. Our results showed that sHZ is a strong modulator of leukocyte recruitment and more specifically of neutrophil and monocyte populations. In addition, evaluation of chemokine and cytokine mRNA and protein expression revealed that sHZ induces the expression of chemokines, macrophage-inflammatory protein (MIP)-1α/CCL3, MIP-1β/CCL4, MIP-2/CXCL2, and monocyte chemoattractant protein-1/CCL2; chemokine receptors, CCR1, CCR2, CCR5, CXCR2, and CXCR4; cytokines, IL-1β and IL-6; and myeloid-related proteins, S100A8, S100A9, and S100A8/A9, in the air pouch exudates. Of interest, chemokine and cytokine mRNA up-regulation were also detected in the liver of i.v. sHZ-injected mice. In conclusion, our study demonstrates that sHZ is a potent proinflammatory agent in vivo, which could contribute to the immunopathology related to malaria.

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Section: Discussionmentioning

confidence: 99%

Hemozoin-Inducible Proinflammatory Events In Vivo: Potential Role in Malaria Infection

Jaramillo

Plante

Ouellet

et al. 2004

The Journal of Immunology

123

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“…In The Gambia, placental malaria was also significantly associated with IUGR [31], and in Mangochi, southern Malawi, two studies have shown a significant association between placental malaria and IUGR [21,32]. The exact mechanism leading to IUGR with placental malaria is unclear although placental insufficiency and reduction of oxygen and/or glucose transport to the fetus are likely to play a role.…”

Section: Discussionmentioning

confidence: 99%

Adverse birth outcomes in a malarious area

et al. 2005

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SUMMARYTo determine factors associated with fetal growth, preterm delivery and stillbirth in an area of high malaria transmission in Southern Malawi, a cross-sectional study of pregnant women attending and delivering at two study hospitals was undertaken. A total of 243 (17 . 3 %) babies were preterm and 54 (3 . 7%) stillborn. Intra-uterine growth retardation (IUGR) occurred in 285 (20 . 3 %), of whom 109 (38 . 2%) were low birthweight and 26 (9 . 1%) preterm. Factors associated with IUGR were maternal short stature [adjusted odds ratio (AOR) 1 . 6, 95 % confidence interval (CI) 1 . 0-2 . 5] ; primigravidae (AOR 1 . 9, 95 % CI 1 . 4-2 . 7) ; placental or peripheral malaria at delivery (AOR 1 . 4, 95 % CI 1 . 0-1 . 9) and maternal anaemia at recruitment (Hb <8 g/dl) (AOR 1 . 9, 95% CI 1 . 3-2 . 7). Increasing parasite density in the placenta was associated with both IUGR (P=0 . 008) and prematurity (P=0 . 02). Factors associated with disproportionate fetal growth were maternal malnutrition [mid-upper arm circumference (MUAC) <23 cm, AOR 1 . 9, 95% CI 1 . 0-3 . 7] and primigravidae (AOR 1 . 8, 95% CI 1 . 0-3 . 1). Preterm delivery and stillbirth were associated with <5 antenatal care visits (AOR 2 . 2, 95% CI 1 . 3-3 . 7 and AOR 3 . 1, 95 % CI 1 . 4-7 . 0 respectively) and stillbirth with a positive Venereal Disease Research Laboratory (VDRL) test (AOR 4 . 7, 95 % CI 1 . 5-14 . 8). Interventions to reduce poor pregnancy outcomes must reduce the burden of malaria in pregnancy, improve antenatal care and maternal malnutrition.

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“…Infection of placenta by malaria parasites stimulate production of TNF-α [90][91][92][93] and IFN-γ [92,94], IL-1β [91] and IL-2 [92]. These cytokines induce T cell proliferation and enhance phagocytic activity of macrophages by production of reactive oxygen intermediates and nitric oxide [95].…”

Section: Specific Antimalarial Immunity During Pregnancymentioning

confidence: 99%

Immune responses during gestational malaria: a review of the current knowledge and future trend of research

Maestre

Carmona‐Fonseca

2014

J Infect Dev Ctries

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Women pregnant with their first child are susceptible to severe P. falciparum disease from placental malaria because they lack immunity to placenta-specific cytoadherence proteins. In subsequent pregnancies, as immunity against placental parasites is acquired, there is a reduced risk of adverse effects of malaria on the mother and fetus and asymptomatic parasitaemia is common. In the case of vivax malaria, with increasing reports of severe cases in Asia and South America, the effects of infection by this species during pregnancy remain to be elucidated. This review summarized the main aspects involved in the acquisition of specific antimalarial immune responses during pregnancy with emphasis in research carried out in America and Asia, in order to offer a framework of interpretation for studies on pregnant women with malaria which are recently being produced in these regions. The authors conclude that (1) Effective humoral responses during gestational malaria are mainly directed against variant surface antigens codified by genes of the var2Csa family of P. falciparum; (2) Acquisition of immunity against these variant antigens depends on the degree and intensity of transmission, and the chance increases with age and successive pregnancies; (3) Antibody development is guided by specific cellular immune responses in cases of placental and maternal infection, and (4) The study of the significance of acquisition of specific immunity against both P. falciparum and P. vivax in America, should be performed.

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Malaria and Pregnancy: Placental Cytokine Expression and Its Relationship to Intrauterine Growth Retardation

Cited by 187 publications

References 47 publications

Hemozoin-Inducible Proinflammatory Events In Vivo: Potential Role in Malaria Infection

Hemozoin-Inducible Proinflammatory Events In Vivo: Potential Role in Malaria Infection

Adverse birth outcomes in a malarious area

Immune responses during gestational malaria: a review of the current knowledge and future trend of research

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