Recrudescent Plasmodium berghei from Pregnant Mice Displays Enhanced Binding to the Placenta and Induces Protection in Multigravida

Pregnancy-associated malaria (PAM) is associated with placenta pathology and poor pregnancy outcome but the mechanisms that control the malaria parasite expansion in pregnancy are still poorly understood and not amenable for study in human subjects. Here, we used a set of new tools to re-visit an experimental mouse model of pregnancy-induced malaria recrudescence, BALB/c with chronic Plasmodium berghei infection. During pregnancy 60% of the pre-exposed primiparous females showed pregnancy-induced malaria recrudescence and we demonstrated that the recrudescent P. berghei show an unexpected enhancement of the adherence to placenta tissue sections with a marked specificity for CSA. Furthermore, we showed that the intensity of parasitemia in primigravida was quantitatively correlated with the degree of thickening of the placental tissue and up-regulation of inflammation-related genes such as IL10. We also confirmed that the incidence of pregnancy-induced recrudescence, the intensity of the parasitemia peak and the impact on the pregnancy outcome decreased gradually from the first to the third pregnancy. Interestingly, placenta pathology and fetal impairment were also observed at low frequency among non-recrudescent females. Together, the data raise the hypothesis that recrudescent P. berghei displays selected specificity for the placenta tissue enabling on one hand, the triggering of the pathological process underlying PAM and on the other hand, the induction of PAM protection mechanisms that are revealed in subsequent pregnancies. Thus, by exploiting P. berghei pregnancy-induced recrudescence, this experimental system offers a mouse model to study the susceptibility to PAM and the mechanisms of disease protection in multigravida

Pregnancy Outcome and Placenta Pathology in Plasmodium berghei ANKA Infected Mice Reproduce the Pathogenesis of Severe Malaria in Pregnant Women

Pregnancy-associated malaria (PAM) is expressed in a range of clinical complications that include increased disease severity in pregnant women, decreased fetal viability, intra-uterine growth retardation, low birth weight and infant mortality. The physiopathology of malaria in pregnancy is difficult to scrutinize and attempts were made in the past to use animal models for pregnancy malaria studies. Here, we describe a comprehensive mouse experimental model that recapitulates many of the pathological and clinical features typical of human severe malaria in pregnancy. We used P. berghei ANKA-GFP infection during pregnancy to evoke a prominent inflammatory response in the placenta that entails CD11b mononuclear infiltration, up-regulation of MIP-1 alpha chemokine and is associated with marked reduction of placental vascular spaces. Placenta pathology was associated with decreased fetal viability, intra-uterine growth retardation, gross post-natal growth impairment and increased disease severity in pregnant females. Moreover, we provide evidence that CSA and HA, known to mediate P. falciparum adhesion to human placenta, are also involved in mouse placental malaria infection. We propose that reduction of maternal blood flow in the placenta is a key pathogenic factor in murine pregnancy malaria and we hypothesize that exacerbated innate inflammatory responses to Plasmodium infected red blood cells trigger severe placenta pathology. This experimental model provides an opportunity to identify cell and molecular components of severe PAM pathogenesis and to investigate the inflammatory response that leads to the observed fetal and placental blood circulation abnormalities

Adaptação da técnica de Paul-Bunnell-Davidsohn a micrométodo

After doing a revision about infectious mononucleosis and its methods of diagnosis, the author presents a micromethod adapted from the Paul-Bunnell-Davidsohn reaaction. Because it is easily and quicklyperformed, the micromethodis particularly useful for epidemiological studies.info:eu-repo/semantics/publishedVersio

Adaptation de la technique de Paul-Bunnell-Davidsohn a la micromethode

info:eu-repo/semantics/publishedVersio

A propósito do isolamento do antigénio carcino-embrionário (CEA)

Fazendo parte de uma linha de investigação que visa o estudo de alguns antigénios tumorais, foram preparados extractos semipurificados de tumores do colon e recto, com vista ao isolamento do antigénio carcino-embrionário (CEA). Através de técnicas de imunoprecipitação e utilizando imuno-soros de Coelho, foi pesquisado o CEA e alguns antigénios semelhantes na fracção percloro-solúvel do extracto. Ensaios análogos foram realizados para identificação de proteínas plasmáticas possivelmente existentes nessa fracção. Apresentam-se os resultados obtidos e comparam-se com os de outros autores.info:eu-repo/semantics/publishedVersio

Doseamento do antigénio carcino-embrionário (CEA) em neoplasias colo-rectais: seu valor no prognóstico e evolução da doença

info:eu-repo/semantics/publishedVersio

Pregnancy outcome obtained at caesarean section on G18 after <i>Plasmodium berghei</i> infection during pregnancy^(a)

(a)<p>BALB/c mothers were infected G13 with <i>P.berghei</i> by IV injection of 10⁶ iRBC.</p>(b)<p>Pregnants sacrificed at G18.</p>(c)<p>Average values.</p>(d)<p>Student's <i>t</i> test.</p

Effect of <i>Plasmodium berghei</i> infection during pregnancy on reproductive outcome and fetus development ^(a)

(a)<p>BALB/c mothers were infected on G13 with <i>P.berghei</i> by IV injection of 10⁶ iRBC and were allowed to give birth at term.</p>(b)<p>Average values.</p>(c)<p>Number of unsuccessful pregnancies (mother dead pregnant/preterm delivery or abortion).</p>(d)<p>Student's <i>t</i> test.</p

<i> P. berghei-</i>GFP infection impairs pregnancy outcome and fetus development.

<p>(A) Representative uterus at G18 from BALB/c pregnant females, uninfected (upper) and infected on G13 with <i>P. berghei-</i>GFP by IV injection of 10⁶ iRBC (bottom). The arrowheads indicate abortions. (B) Fetus from uninfected (left) and from infected mother (right). In detail, mouse placenta from an uninfected (C) and infected mother (D). Lack of blood circulation is noticeable in the placenta, paws and tail in panel (D). Scale bar represents 1 cm in A–B and 0.5 cm in C–D.</p

Increased disease susceptibility in pregnant BALB/c mice infected with <i>P. berghei-</i>GFP.

<p>BALB/c pregnant females were infected on G13 by IV injection of 10⁶ iRBC and non-pregnant females were simultaneously infected. The plots represent cumulative results of three independent experiments in a total of 32 pregnant and 16 non-pregnant females. (A) Parasitemia curves where data points represent mean±SE. From day 3 post-infection onwards parasitemia was significantly higher in pregnant females (<i>P-</i>value<0.05). (B) Survival curves up to 10 days after infection show that survival time of pregnant female mice are significantly lower than in controls (<i>P</i>-value<0.0001). It should be noted that non-pregnant females died at a later stage with hyperparasitemia.</p