Blockade of caspase cascade overcomes malaria-associated acute respiratory distress syndrome in mice.

Malaria is an enormous burden on global health that caused 409,000 deaths in 2019. Severe malaria can manifest in the lungs, an illness known as acute respiratory distress syndrome (ARDS). Not much is known about the development of malaria-associated ARDS (MA-ARDS), especially regarding cell death in the lungs.

Longitudinal Analysis of Antibody Responses to the mRNA BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis: A 6-Month Follow-Up.

Patients on hemodialysis (HD) are at higher risk for COVID-19, overall are poor responders to vaccines, and were prioritized in the Portuguese vaccination campaign. This work aimed at evaluating in HD patients the immunogenicity of BTN162b2 after the two doses induction phase, the persistence of specific antibodies along time, and factors predicting these outcomes. We performed a prospective, 6-month long longitudinal cohort analysis of 156 HD patients scheduled to receive BTN162b2.

Adverse pregnancy outcomes are associated with Plasmodium vivax malaria in a prospective cohort of women from the Brazilian Amazon.

Background: Malaria in Brazil represents one of the highest percentages of Latin America cases, where approximately 84% of infections are attributed to Plasmodium (P.) vivax. Despite the high incidence, many aspects of gestational malaria resulting from P.

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

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.

Plasmodium falciparum infection dysregulates placental autophagy.

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.

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

Importance: Malaria during pregnancy is associated with adverse events for the fetus and newborn, but the association of malaria during pregnancy with the head circumference of the newborn is unclear.

Objective: To investigate the association of malaria during pregnancy with fetal head growth.

Design, Setting, And Participants: Two cohort studies were conducted at the general maternity hospital of Cruzeiro do Sul (Acre, Brazil) in the Amazonian region.

Fetal-Derived MyD88 Signaling Contributes to Poor Pregnancy Outcomes During Gestational Malaria.

Placental malaria (PM) remains a severe public health problem in areas of high malaria transmission. Despite the efforts to prevent infection poor outcomes in endemic areas, there is still a considerable number of preterm births and newborns with low birth weight resulting from PM. Although local inflammation triggered in response to malaria is considered crucial in inducing placental damage, little is known about the differential influence of maternal and fetal immune responses to the disease progression.

Malaria during pregnancy and newborn outcome in an unstable transmission area in Brazil: A population-based record linkage study.

Background: Malaria in pregnancy (MiP) is one of the major causes of mortality and morbidity in tropical regions, causing maternal anemia, intrauterine growth retardation, preterm birth, and low birth weight (LBW). The integration of the information systems on pregnancy and malaria could prove to be a useful method of improved decision making for better maternal-child health.

Methods: A population-based observational study acquired information retrospectively from all live births that occurred between 2006 and 2014 in Cruzeiro do Sul (Acre, Brazil).

Publisher Correction: TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria.

Malaria-associate pregnancy has a significant impact on infant morbidity and mortality. The detrimental effects of malaria infection during pregnancy have been shown to correlate with immune activation in the placental tissue. Herein we sought to evaluate the effect of Toll-like receptors (TLRs) activation on placental malaria (PM) development by using the Plasmodium berghei NK65 infection model.

G6PD deficiency alleles in a malaria-endemic region in the Western Brazilian Amazon.

Background: Plasmodium vivax parasites are the predominant cause of malaria infections in the Brazilian Amazon. Infected individuals are treated with primaquine, which can induce haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals and may lead to severe and fatal complications. This X-linked disorder is distributed globally and is caused by allelic variants with a geographical distribution that closely reflects populations exposed historically to endemic malaria.

HGF Secreted by Activated Kupffer Cells Induces Apoptosis of -Infected Hepatocytes.

Malaria liver stage infection is an obligatory parasite development step and represents a population bottleneck in infections, providing an advantageous target for blocking parasite cycle progression. Parasite development inside hepatocytes implies a gross cellular insult evoking innate host responses to counteract intra-hepatocytic infection. Using primary hepatocyte cultures, we investigated the role of Kupffer cell-derived hepatocyte growth factor (HGF) in malaria liver stage infection.

Emerging Plasmodium vivax resistance to chloroquine in South America: an overview.

The global emergence of Plasmodium vivax strains resistant to chloroquine (CQ) since the late 1980s is complicating the current international efforts for malaria control and elimination. Furthermore, CQ-resistant vivax malaria has already reached an alarming prevalence in Indonesia, East Timor and Papua New Guinea. More recently, in vivo studies have documented CQ-resistant P.

Modeling malaria infection and immunity against variant surface antigens in Príncipe Island, West Africa.

After remarkable success of vector control campaigns worldwide, concerns about loss of immunity against Plasmodium falciparum due to lack of exposure to the parasite are relevant since an increase of severe cases in less immune individuals is expected. We present a mathematical model to investigate the impact of reducing exposure to the parasite on the immune repertoire against P. falciparum erythrocyte membrane protein 1 (PfEMP1) variants.

TREM2 governs Kupffer cell activation and explains belr1 genetic resistance to malaria liver stage infection.

Plasmodium liver stage infection is a target of interest for the treatment of and vaccination against malaria. Here we used forward genetics to search for mechanisms underlying natural host resistance to infection and identified triggering receptor expressed on myeloid cells 2 (TREM2) and MHC class II molecules as determinants of Plasmodium berghei liver stage infection in mice. Locus belr1 confers resistance to malaria liver stage infection.

IL-12p40 deficiency leads to uncontrolled Trypanosoma cruzi dissemination in the spinal cord resulting in neuronal death and motor dysfunction.

Chagas' disease is a protozoosis caused by Trypanosoma cruzi that frequently shows severe chronic clinical complications of the heart or digestive system. Neurological disorders due to T. cruzi infection are also described in children and immunosuppressed hosts.

Host-mediated regulation of superinfection in malaria.

In regions of high rates of malaria transmission, mosquitoes repeatedly transmit liver-tropic Plasmodium sporozoites to individuals who already have blood-stage parasitemia. This manifests itself in semi-immune children (who have been exposed since birth to Plasmodium infection and as such show low levels of peripheral parasitemia but can still be infected) older than 5 years of age by concurrent carriage of different parasite genotypes at low asymptomatic parasitemias. Superinfection presents an increased risk of hyperparasitemia and death in less immune individuals but counterintuitively is not frequently observed in the young.

The liver plays a major role in clearance and destruction of blood trypomastigotes in Trypanosoma cruzi chronically infected mice.

Intravenous challenge with Trypanosoma cruzi can be used to investigate the process and consequences of blood parasite clearance in experimental Chagas disease. One hour after intravenous challenge of chronically infected mice with 5x10(6) trypomastigotes, the liver constituted a major site of parasite accumulation, as revealed by PCR. Intact parasites and/or parasite remnants were visualized at this time point scattered in the liver parenchyma.

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.

Kinome-wide RNAi screen implicates at least 5 host hepatocyte kinases in Plasmodium sporozoite infection.

Plasmodium sporozoites, the causative agent of malaria, are injected into their vertebrate host through the bite of an infected Anopheles mosquito, homing to the liver where they invade hepatocytes to proliferate and develop into merozoites that, upon reaching the bloodstream, give rise to the clinical phase of infection. To investigate how host cell signal transduction pathways affect hepatocyte infection, we used RNAi to systematically test the entire kinome and associated genes in human Huh7 hepatoma cells for their potential roles during infection by P. berghei sporozoites.

Host scavenger receptor SR-BI plays a dual role in the establishment of malaria parasite liver infection.

An obligatory step of malaria parasite infection is Plasmodium sporozoite invasion of host hepatocytes, and host lipoprotein clearance pathways have been linked to Plasmodium liver infection. By using RNA interference to screen lipoprotein-related host factors, we show here that the class B, type I scavenger receptor (SR-BI) is the strongest regulator of Plasmodium infection among these factors. Inhibition of SR-BI function reduced P.

Genistein-supplemented diet decreases malaria liver infection in mice and constitutes a potential prophylactic strategy.

In tropical regions millions of people still live at risk of malaria infection. Indeed the emergence of resistance to chloroquine and other drugs in use in these areas reinforces the need to implement alternative prophylactic strategies. Genistein is a naturally occurring compound that is widely used as a food supplement and is thought to be effective in countering several pathologies.

Heme oxygenase-1 is an anti-inflammatory host factor that promotes murine plasmodium liver infection.

The clinically silent Plasmodium liver stage is an obligatory step in the establishment of malaria infection and disease. We report here that expression of heme oxygenase-1 (HO-1, encoded by Hmox1) is upregulated in the liver following infection by Plasmodium berghei and Plasmodium yoelii sporozoites. HO-1 overexpression in the liver leads to a proportional increase in parasite liver load, and treatment of mice with carbon monoxide and with biliverdin, each an enzymatic product of HO-1, also increases parasite liver load.

Malaria liver stage susceptibility locus identified on mouse chromosome 17 by congenic mapping.

Host genetic variants are known to confer resistance to Plasmodium blood stage infection and to control malaria severity both in humans and mice. This work describes the genetic mapping of a locus for resistance to liver stage parasite in the mouse. First, we show that decreased susceptibility to the liver stage of Plasmodium berghei in the BALB/c mouse strain is attributable to intra-hepatic factors and impacts on the initial phase of blood stage infection.