Association of Malaria Infection During Pregnancy With Head Circumference of Newborns in the Brazilian Amazon

Dombrowski, Jamille Gregório; Souza, Rodrigo Medeiros de; Lima, Flávia Afonso; Bandeira, Carla Letícia; Murillo, Oscar; Costa, Douglas de Sousa; Peixoto, Erika Paula Machado; Cunha, Marielton dos Passos; Zanotto, Paolo Marinho de Andrade; Bevilacqua, Estela Maris Andrade Forell; Grisotto, Marcos Augusto Grigolin; Lima, Antônio Carlos Pedroso de; Singer, Júlio M.; Campino, Susana; Clark, Taane G.; Epiphânio, Sabrina; Gonçalves, Lígia Antunes; Marinho, Cláudio Romero Farias

doi:10.1001/jamanetworkopen.2019.3300

Cited by 17 publications

(24 citation statements)

References 31 publications

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“…NI pregnant women (n = 59) and women with a positive molecular diagnosis for Pf at the moment of delivery performed by cesarean section (C-section) (active infection) (n = 19) were recruited between 2012 and 2014 from a prospective cohort study conducted at the Hospital da Mulher e da Criança do Juruá in Cruzeiro do Sul, Acre, Brazil (34), an endemic and low transmission area for malaria. After delivery, newborns' anthropometric measurements were recorded, and maternal peripheral and placental blood was collected for direct malaria diagnosis, plasma collection, and evaluation of hematologic parameters.…”

Section: Participants and Specimensmentioning

confidence: 99%

“…After delivery, newborns' anthropometric measurements were recorded, and maternal peripheral and placental blood was collected for direct malaria diagnosis, plasma collection, and evaluation of hematologic parameters. Placentas were weighed, and tissue samples were collected, fixed in 10% buffered formalin, and adequately stored until processing (34). In addition, relevant clinical information including maternal and gestational age and gravidity was recorded through structured questionnaires.…”

Section: Participants and Specimensmentioning

confidence: 99%

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Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes

et al. 2020

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Placental malaria (PM) is associated with severe inflammation leading to abortion, preterm delivery, and intrauterine growth restriction. Innate immunity responses play critical roles, but the mechanisms underlying placental immunopathology are still unclear. Here, we investigated the role of inflammasome activation in PM by scrutinizing human placenta samples from an endemic area and ablating inflammasome components in a PM mouse model. The reduction in birth weight in babies from infected mothers is paralleled by increased placental expression of AIM2 and NLRP3 inflammasomes. Using genetic dissection, we reveal that inflammasome activation pathways are involved in the production and detrimental action of interleukin-1β (IL-1β) in the infected placenta. The IL-1R pharmacological antagonist Anakinra improved pregnancy outcomes by restoring fetal growth and reducing resorption in an experimental model. These findings unveil that IL-1β–mediated signaling is a determinant of PM pathogenesis, suggesting that IL-1R antagonists can improve clinical outcomes of malaria infection in pregnancy.

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Section: Participants and Specimensmentioning

confidence: 99%

Section: Participants and Specimensmentioning

confidence: 99%

Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes

et al. 2020

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“…On the contrary, the Brazilian Amazon basin is an area of unstable transmission that contributes with approximately 42% of malaria cases in the Americas, where falciparum infections during pregnancy are promptly treated [20,21]. Despite the rapid intervention and clearance of systemic infection, placental stress and lesions perpetuate until parturition, which probably dictate the poor gestational outcomes [14,22]. Hence, placental mechanisms of homeostasis like autophagy might be dysregulated due to chronic inflammation and damage caused by P .…”

Section: Introductionmentioning

confidence: 99%

Plasmodium falciparum infection dysregulates placental autophagy

et al. 2019

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Plasmodium (P.) falciparum malaria during pregnancy has been frequently associated with severe consequences such as maternal anemia, abortion, premature birth, and reduced birth weight. Placental damage promotes disruption of the local homeostasis; though, the mechanisms underlying these events are still to be elucidated. Autophagy is a fundamental homeostatic mechanism in the natural course of pregnancy by which cells self-recycle in order to survive in stressful environments. Placentas from non-infected and P. falciparum-infected women during pregnancy were selected from a previous prospective cohort study conducted in the Brazilian Amazon (Acre, Brazil). Newborns from infected women experienced reduced birth weight (P = 0.0098) and placental immunopathology markers such as monocyte infiltrate (P < 0.0001) and IL-10 production (P = 0.0122). The placentas were evaluated for autophagy-related molecules. As a result, we observed reduced mRNA levels of ULK1 (P = 0.0255), BECN1 (P = 0.0019), and MAP1LC3B (P = 0.0086) genes in placentas from P. falciparum-infected, which was more striking in those diagnosed with placental malaria. Despite the protein levels of these genes followed the same pattern, the observed reduction was not statistically significant in placentas from P. falciparum-infected women. Nevertheless, our data suggest that chronic placental immunopathology due to P. falciparum infection leads to autophagy dysregulation, which might impair local homeostasis during malaria in pregnancy that may result in poor pregnancy outcomes.

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“…The early symptoms demonstrated by infected newborns are fever, anemia, and low birth weight. Other signs and symptoms include jaundice, regurgitation, loose stools, poor diet [ 114 , 115 ] and, in addition, microcephaly and brain damage [ 116 ]. Vertical transmission possibly occurs through the sequestration of infected maternal erythrocytes in the placenta intervillous space.…”

Section: Malaria: Congenital Malaria Is Defined When the Parasite mentioning

confidence: 99%

Lights and Shadows of TORCH Infection Proteomics

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Palmisano

et al. 2020

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Congenital abnormalities cause serious fetal consequences. The term TORCH is used to designate the most common perinatal infections, where: (T) refers to toxoplasmosis, (O) means "others" and includes syphilis, varicella-zoster, parvovirus B19, zika virus (ZIKV), and malaria among others, (R) refers to rubella, (C) relates to cytomegalovirus infection, and (H) to herpes simplex virus infections. Among the main abnormalities identified in neonates exposed to congenital infections are central nervous system (CNS) damage, microcephaly, hearing loss, and ophthalmological impairment, all requiring regular follow-up to monitor its progression. Protein changes such as mutations, post-translational modifications, abundance, structure, and function may indicate a pathological condition before the onset of the first symptoms, allowing early diagnosis and understanding of a particular disease or infection. The term “proteomics” is defined as the science that studies the proteome, which consists of the total protein content of a cell, tissue or organism in a given space and time, including post-translational modifications (PTMs) and interactions between proteins. Currently, quantitative bottom-up proteomic strategies allow rapid and high throughput characterization of complex biological mixtures. Investigating proteome modulation during host–pathogen interaction helps in elucidating the mechanisms of infection and in predicting disease progression. This “molecular battle” between host and pathogen is a key to identify drug targets and diagnostic markers. Here, we conducted a survey on proteomic techniques applied to congenital diseases classified in the terminology “TORCH”, including toxoplasmosis, ZIKV, malaria, syphilis, human immunodeficiency virus (HIV), herpes simplex virus (HSV) and human cytomegalovirus (HCVM). We have highlighted proteins and/or protein complexes actively involved in the infection. Most of the proteomic studies reported have been performed in cell line models, and the evaluation of tissues (brain, muscle, and placenta) and biofluids (plasma, serum and urine) in animal models is still underexplored. Moreover, there are a plethora of studies focusing on the pathogen or the host without considering the triad mother-fetus-pathogen as a dynamic and interconnected system.

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Association of Malaria Infection During Pregnancy With Head Circumference of Newborns in the Brazilian Amazon

Cited by 17 publications

References 31 publications

Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes

Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes

Plasmodium falciparum infection dysregulates placental autophagy

Lights and Shadows of TORCH Infection Proteomics

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