scholarly journals Myeloperoxidase and Other Markers of Neutrophil Activation Associate With Malaria and Malaria/HIV Coinfection in the Human Placenta

2021 ◽  
Vol 12 ◽  
Author(s):  
Demba Sarr ◽  
Lilian J. Oliveira ◽  
Brittany N. Russ ◽  
Simon O. Owino ◽  
Joab D. Middii ◽  
...  
Keyword(s):  
Parasite Density ◽  
Peripheral Blood ◽  
Placental Malaria ◽  
Placental Tissue ◽  
Hiv Infections ◽  
Neutrophil Activation ◽  
Hiv Coinfection ◽  
Placental Blood ◽  
Infant Birth ◽  
The Impact

IntroductionPlacental malaria (PM) is characterized by accumulation of inflammatory leukocytes in the placenta, leading to poor pregnancy outcomes. Understanding of the underlying mechanisms remains incomplete. Neutrophils respond to malaria parasites by phagocytosis, generation of oxidants, and externalization of Neutrophil Extracellular Traps (NETs). NETs drive inflammation in malaria but evidence of NETosis in PM has not been reported. Neutrophil activity in the placenta has not been directly investigated in the context of PM and PM/HIV-co-infection.MethodsUsing peripheral and placental plasma samples and placental tissue collected from Kenyan women at risk for malaria and HIV infections, we assessed granulocyte levels across all gravidities and markers of neutrophil activation, including NET formation, in primi- and secundigravid women, by ELISA, western blot, immunohistochemistry and immunofluorescence.ResultsReduced peripheral blood granulocyte numbers are observed with PM and PM/HIV co-infection in association with increasing parasite density and placental leukocyte hemozoin accumulation. In contrast, placental granulocyte levels are unchanged across infection groups, resulting in enhanced placental: peripheral count ratios with PM. Within individuals, PM- women have reduced granulocyte counts in placental relative to peripheral blood; in contrast, PM stabilizes these relative counts, with HIV coinfection tending to elevate placental counts relative to the periphery. In placental blood, indicators of neutrophil activation, myeloperoxidase (MPO) and proteinase 3 (PRTN3), are significantly elevated with PM and, more profoundly, with PM/HIV co-infection, in association with placental parasite density and hemozoin-bearing leukocyte accumulation. Another neutrophil marker, matrix metalloproteinase (MMP9), together with MPO and PRTN3, is elevated with self-reported fever. None of these factors, including the neutrophil chemoattractant, CXCL8, differs in relation to infant birth weight or gestational age. CXCL8 and MPO levels in the peripheral blood do not differ with infection status nor associate with birth outcomes. Indicators of NETosis in the placental plasma do not vary with infection, and while structures consistent with NETs are observed in placental tissue, the results do not support an association with PM.ConclusionsGranulocyte levels are differentially regulated in the peripheral and placental blood in the presence and absence of PM. PM, both with and without pre-existing HIV infection, enhances neutrophil activation in the placenta. The impact of local neutrophil activation on placental function and maternal and fetal health remains unclear. Additional investigations exploring how neutrophil activation and NETosis participate in the pathogenesis of malaria in pregnant women are needed.

scholarly journals The Impact of Gravidity, Symptomatology and Timing of Infection on Placental Malaria

2020 ◽  
Author(s):  
Erin E Tran ◽  
Morgan Cheeks ◽  
Abel Kakuru ◽  
Mary K Muhindo ◽  
Paul Natureeba ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Blood Smear ◽  
Placental Malaria ◽  
Fold Increase ◽  
Preventive Therapy ◽  
Malaria Parasites ◽  
Increased Risk ◽  
Placental Blood ◽  
The Impact ◽  
The Relationship

Abstract Background : Placental malaria is associated with increased risk of adverse perinatal outcomes. While primigravidity has been reported as a risk factor for placental malaria, little is known regarding the relationship between gravidity, symptomatology and timing of Plasmodium falciparum infection and the development of placental malaria. Methods : Our aim was to investigate the relationship between the development of placental malaria and gravidity, timing of infection, and presence of symptoms. This is a secondary analysis of data from a double-blind randomized control trial of intermittent preventive therapy during pregnancy in Uganda. Women were enrolled from 12 to 20 weeks gestation and followed through delivery. Exposure to malaria parasites was defined as symptomatic (fever with positive blood smear) or asymptomatic (based on molecular detection of parasitemia done routinely every 4 weeks). The primary outcome was placental malaria diagnosed by histopathology, placental blood smear, and/or placental blood loop-mediated isothermal amplification. We performed subgroup analysis based on the presence of symptomatic malaria, gravidity, and timing of infection. Results : Of the 228 patients with documented maternal infection with malaria parasites during pregnancy, 101 (44.3%) had placental malaria. Primigravidity was strongly associated with placental malaria (aOR 8.90, 95% CI 4.34-18.2, p<0.001), and each episode of malaria was associated with over a 2-fold increase in placental malaria (aOR 2.35, 95% CI 1.69-3.26, p<0.001). Among multigravid women, the odds of placental malaria increased by 14% with each advancing week of gestation at first documented infection (aOR 1.14, 95% CI 1.02-1.27, p=0.02). When stratified by the presence of symptoms, primigravidity was only associated with placental malaria in asymptomatic women, who had a 12-fold increase in the odds of placental malaria (aOR 12.19, 95% CI 5.23-28.43, p<0.001). Conclusions : Total number of Plasmodium falciparum infections in pregnancy is a significant predictor of placental malaria. The importance of timing of infection on the development of placental malaria varies based on gravidity. In primigravidas, earlier asymptomatic infections were associated with placental malaria, whereas in multigravidas, parasitemias detected later in gestation were associated with placental malaria. Earlier initiation of an effective intermittent preventive therapy may help to prevent placental malaria and improve birth outcomes, particularly in primigravid women.

scholarly journals The impact of gravidity, symptomatology and timing of infection on placental malaria

2020 ◽  
Author(s):  
Erin E Tran ◽  
Morgan Cheeks ◽  
Abel Kakuru ◽  
Mary K Muhindo ◽  
Paul Natureeba ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Blood Smear ◽  
Placental Malaria ◽  
Fold Increase ◽  
Preventive Therapy ◽  
Malaria Parasites ◽  
Increased Risk ◽  
Placental Blood ◽  
The Impact ◽  
The Relationship

Abstract Background Placental malaria is associated with increased risk of adverse perinatal outcomes. While primigravidity has been reported as a risk factor for placental malaria, little is known regarding the relationship between gravidity, symptomatology and timing of Plasmodium falciparum infection and the development of placental malaria. Methods The aim of this study was to investigate the relationship between the development of placental malaria and gravidity, timing of infection, and presence of symptoms. This is a secondary analysis of data from a double-blind randomized control trial of intermittent preventive therapy during pregnancy in Uganda. Women were enrolled from 12 to 20 weeks gestation and followed through delivery. Exposure to malaria parasites was defined as symptomatic (fever with positive blood smear) or asymptomatic (based on molecular detection of parasitemia done routinely every 4 weeks). The primary outcome was placental malaria diagnosed by histopathology, placental blood smear, and/or placental blood loop-mediated isothermal amplification. Multivariate analyses were performed using logistic regression models. Subgroup analysis was performed based on the presence of symptomatic malaria, gravidity, and timing of infection. Results Of the 228 patients with documented maternal infection with malaria parasites during pregnancy, 101 (44.3%) had placental malaria. Primigravidity was strongly associated with placental malaria (aOR 8.90, 95% CI 4.34-18.2, p<0.001), and each episode of malaria was associated with over a 2-fold increase in placental malaria (aOR 2.35, 95% CI 1.69-3.26, p<0.001). Among multigravid women, the odds of placental malaria increased by 14% with each advancing week of gestation at first documented infection (aOR 1.14, 95% CI 1.02-1.27, p=0.02). When stratified by the presence of symptoms, primigravidity was only associated with placental malaria in asymptomatic women, who had a 12-fold increase in the odds of placental malaria (aOR 12.19, 95% CI 5.23-28.43, p<0.001). Conclusions Total number of Plasmodium falciparum infections in pregnancy is a significant predictor of placental malaria. The importance of timing of infection on the development of placental malaria varies based on gravidity. In primigravidas, earlier asymptomatic infections were more frequently identified in those with placental malaria, whereas in multigravidas, parasitemias detected later in gestation were associated with placental malaria. Earlier initiation of an effective intermittent preventive therapy may help to prevent placental malaria and improve birth outcomes, particularly in primigravid women.

B-cell and T-cell values in peripheral blood in Polish mixed-breed rabbits with addition of blood of meet breeds

2014 ◽  
Vol 17 (3) ◽  
pp. 421-426 ◽  
Author(s):  
B. Tokarz-Deptuła ◽  
P. Niedźwiedzka-Rystwej ◽  
B. Hukowska-Szematowicz ◽  
M. Adamiak ◽  
A. Trzeciak-Ryczek ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Laboratory Animals ◽  
Immunological Parameters ◽  
Four Seasons ◽  
Mixed Breed ◽  
The Impact

Abstract In Poland, rabbit is a highly valued animal, due to dietetic and flavour values of its meat, but above all, rabbits tend to be commonly used laboratory animals. The aim of the study was developing standards for counts of B-cells with CD19+ receptor, T-cells with CD5+ receptor, and their subpopulations, namely T-cells with CD4+, CD8+ and CD25+ receptor in the peripheral blood of mixed-breed Polish rabbits with addition of blood of meet breeds, including the assessment of the impact of four seasons of the year and animal sex on the values of the immunological parameters determined. The results showed that the counts of B- and T-cells and their subpopulations in peripheral blood remain within the following ranges: for CD19+ B-cells: 1.05 - 3.05%, for CD5+ T-cells: 34.00 - 43.07%, CD4+ T-cells: 23.52 - 33.23%, CD8+ T-cells: 12.55 - 17.30%, whereas for CD25+ T-cells: 0.72 - 2.81%. As it comes to the season of the year, it was observed that it principally affects the values of CD25+ T-cells, while in the case of rabbit sex, more changes were found in females.

Assessment of Key Elements in the Innate Immunity System Among Patients with HIV, HCV, and Coinfections of HIV/HCV

2020 ◽  
Vol 18 (3) ◽  
pp. 194-200
Author(s):  
Maryam Moradi ◽  
Alireza Tabibzadeh ◽  
Davod Javanmard ◽  
Saied Ghorbani ◽  
Farah Bokharaei-Salim ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Mononuclear Cells ◽  
Hiv Infections ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Hiv Coinfection ◽  
Tnf Α ◽  
Immunity Genes ◽  
Healthy Control ◽  
Hcv Coinfection

Background: Coinfection of Hepatitis C virus (HCV) with human immunodeficiency virus (HIV) has a higher risk of mortality than HCV or HIV monoinfection. HCV and HIV infections are specified by systemic inflammation, but the inflammation process in HCV/HIV coinfection is much complicated and is not well characterized. Objective: The aim of this study was to analyze the expression of TLR-3, TLR-7, IL-10, IFN-1 (IFN-α, IFN-β), and TNF-α in HIV, HCV and HIV/HCV co-infected patients. Methods: Forty-five patients including HIV group (n=15), HCV group (n=15), HIV/HCV coinfection group (n=15) and healthy control group (n=15) participated. Peripheral blood mononuclear cells (PBMCs) were obtained. PBMC-RNA, HCV and HIV RNA were extracted from all subjects and cDNA was synthesized. The viral load analyzed by reverse transcription-quantitative PCR (RT-qPCR), and the expression levels of IFN-α, IFN-β, TLR-3, TLR-7, TNF, and IL-10 mRNA were quantified in PBMCs. Results: The levels of IFN-I, IL-10, and TNF-α were overexpressed in all patients’ groups (P<0.05), TLR-7 was upregulated in all groups, but this upregulation was not statistically significant (p>0.05). TLR-3 showed a decrease in all patient groups (P<0.05). The statistical analysis demonstrated that TLR-3 has a negative correlation with HIV load, whereas other genes positively correlated with HIV load. In addition, TLR-3, TNF-α, and IFN-I were negatively correlated with HCV load, whereas TLR-7 and IL-10 s were positively correlated with HCV load. Conclusion: Our results showed a significant relationship between the expression level of innate immunity genes and inflammation in HCV, HIV, and HIV/HCV coinfected patients.

scholarly journals Lower peripheral blood Toll-like receptor 3 expression is associated with an unfavorable outcome in severe COVID-19 patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Clara Saad Menezes ◽  
Alicia Dudy Müller Veiga ◽  
Thais Martins de Lima ◽  
Suely Kunimi Kubo Ariga ◽  
Hermes Vieira Barbeiro ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Peripheral Blood ◽  
World Health ◽  
Control Group ◽  
Pyrin Domain ◽  
Peripheral Blood Gene Expression ◽  
Severe Group ◽  
Health Organization ◽  
The Impact

AbstractThe role of innate immunity in COVID-19 is not completely understood. Therefore, this study explored the impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on the expression of Pattern Recognition Receptors (PRRs) in peripheral blood cells and their correlated cytokines. Seventy-nine patients with severe COVID-19 on admission, according to World Health Organization (WHO) classification, were divided into two groups: patients who needed mechanical ventilation and/or deceased (SEVERE, n = 50) and patients who used supplementary oxygen but not mechanical ventilation and survived (MILD, n = 29); a control group (CONTROL, n = 17) was also enrolled. In the peripheral blood, gene expression (mRNA) of Toll-like receptors (TLRs) 3, 4, 7, 8, and 9, retinoic-acid inducible gene I (RIGI), NOD-like receptor family pyrin domain containing 3 (NLRP3), interferon alpha (IFN-α), interferon beta (IFN-β), interferon gamma (IFN-γ), interferon lambda (IFN-λ), pro-interleukin(IL)-1β (pro-IL-1β), and IL-18 was determined on admission, between 5–9 days, and between 10–15 days. Circulating cytokines in plasma were also measured. When compared to the COVID-19 MILD group, the COVID-19 SEVERE group had lower expression of TLR3 and overexpression of TLR4.

scholarly journals Biomarkers for a histological chorioamnionitis diagnosis in pregnant women with or without group B streptococcus infection: a case-control study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jie Ren ◽  
Zhe Qiang ◽  
Yuan-yuan Li ◽  
Jun-na Zhang
Keyword(s):  
Cord Blood ◽  
Pregnant Women ◽  
Peripheral Blood ◽  
Group B Streptococcus ◽  
Diagnostic Value ◽  
Adverse Outcomes ◽  
Intercellular Adhesion Molecule ◽  
Tnf Α ◽  
Group B ◽  
The Impact

Abstract Background Chorioamnionitis may cause serious perinatal and neonatal adverse outcomes, and group B streptococcus (GBS) is one of the most common bacteria isolated from human chorioamnionitis. The present study analyzed the impact of GBS infection and histological chorioamnionitis (HCA) on pregnancy outcomes and the diagnostic value of various biomarkers. Methods Pregnant women were grouped according to GBS infection and HCA detection. Perinatal and neonatal adverse outcomes were recorded with a follow-up period of 6 weeks. The white blood cell count (WBC), neutrophil ratio, and C-reactive protein (CRP) level from peripheral blood and soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 8 (IL-8), and tumor necrosis factor α (TNF-α) levels from cord blood were assessed. Results A total of 371 pregnant women were included. Pregnant women with GBS infection or HCA had a higher risk of pathological jaundice and premature rupture of membranes and higher levels of sICAM-1, IL-8, and TNF-α in umbilical cord blood. Univariate and multivariate regression analysis revealed that sICMA-1, IL-8, TNF-α, WBC, and CRP were significantly related to an increased HCA risk. For all included pregnant women, TNF-α had the largest receiver operating characteristic (ROC) area (area: 0.841; 95% CI: 0.778–0.904) of the biomarkers analyzed. TNF-α still had the largest area under the ROC curve (area: 0.898; 95% CI: 0.814–0.982) for non-GBS-infected pregnant women, who also exhibited a higher neutrophil ratio (area: 0.815; 95% CI: 0.645–0.985) and WBC (area: 0.849; 95% CI: 0.72–0.978), but all biomarkers had lower value in the diagnosis of HCA in GBS-infected pregnant women. Conclusion GBS infection and HCA correlated with several perinatal and neonatal adverse outcomes. TNF-α in cord blood and WBCs in peripheral blood had diagnostic value for HCA in non-GBS-infected pregnant women but not GBS-infected pregnant women.

scholarly journals Consequences of COVID-19 crisis for persons with HIV: the impact of social determinants of health

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kristie C. Waterfield ◽  
Gulzar H. Shah ◽  
Gina D. Etheredge ◽  
Osaremhen Ikhile
Keyword(s):  
Public Health ◽  
Health Care ◽  
Clinical Care ◽  
Hiv Infections ◽  
People Living With Hiv ◽  
Negative Consequences ◽  
Persons Who Inject Drugs ◽  
Persons Living With Hiv ◽  
Living With Hiv ◽  
The Impact

Abstract Background With the indiscriminate spread of COVID-19 globally, many populations are experiencing negative consequences such as job loss, food insecurity, and inability to manage existing medical conditions and maintain preventive measures such as social distancing and personal preventative equipment. Some of the most disadvantaged in the COVID-19 era are people living with HIV/AIDS and other autoimmune diseases. Discussion As the number of new HIV infections decrease globally, many subpopulations remain at high risk of infection due to lack of or limited access to prevention services, as well as clinical care and treatment. For persons living with HIV or at higher risk of contracting HIV, including persons who inject drugs or men that have sex with men, the risk of COVID-19 infection increases if they have certain comorbidities, are older than 60 years of age, and are homeless, orphaned, or vulnerable children. The risk of COVID-19 is also more significant for those that live in Low- and Middle-Income Countries, rural, and/or poverty-stricken areas. An additional concern for those living the HIV is the double stigma that may arise if they also test positive for COVID-19. As public health and health care workers try to tackle the needs of the populations that they serve, they are beginning to realize the need for a change in the infrastructure that will include more efficient partnerships between public health, health care, and HIV programs. Conclusion Persons living with HIV that also have other underlying comorbidities are a great disadvantage from the negative consequences of COVID-19. For those that may test positive for both HIV and COVID-19, the increased psychosocial burdens stemming from stress and isolation, as well as, experiencing additional barriers that inhibit access to care, may cause them to become more disenfranchised. Thus, it becomes very important during the current pandemic for these challenges and barriers to be addressed so that these persons living with HIV can maintain continuity of care, as well as, their social and mental support systems.

scholarly journals Towards Transabdominal Functional Photoacoustic Imaging of the Placenta: Improvement in Imaging Depth Through Optimization of Light Delivery

2021 ◽  
Author(s):  
Kristie Huda ◽  
Kenneth F. Swan ◽  
Cecilia T. Gambala ◽  
Gabriella C. Pridjian ◽  
Carolyn L. Bayer
Keyword(s):  
Delivery System ◽  
Light Propagation ◽  
Ex Vivo ◽  
Photoacoustic Imaging ◽  
Incidence Angle ◽  
Incident Angle ◽  
Placental Tissue ◽  
Light Delivery ◽  
Imaging Depth ◽  
The Impact

AbstractFunctional photoacoustic imaging of the placenta could provide an innovative tool to diagnose preeclampsia, monitor fetal growth restriction, and determine the developmental impacts of gestational diabetes. However, transabdominal photoacoustic imaging is limited in imaging depth due to the tissue’s scattering and absorption of light. The aim of this paper was to investigate the impact of geometry and wavelength on transabdominal light delivery. Our methods included the development of a multilayer model of the abdominal tissue and simulation of the light propagation using Monte Carlo methods. A bifurcated light source with varying incident angle of light, distance between light beams, and beam area was simulated to analyze the effect of light delivery geometry on the fluence distribution at depth. The impact of wavelength and the effects of variable thicknesses of adipose tissue and muscle were also studied. Our results showed that the beam area plays a major role in improving the delivery of light to deep tissue, in comparison to light incidence angle or distance between the bifurcated fibers. Longer wavelengths, with incident fluence at the maximum permissible exposure limit, also increases fluence within deeper tissue. We validated our simulations using a commercially available light delivery system and ex vivo human placental tissue. Additionally, we compared our optimized light delivery to a commercially available light delivery system, and conclude that our optimized geometry could improve imaging depth more than 1.6×, bringing the imaging depth to within the needed range for transabdominal imaging of the human placenta.

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