Infection-induced Changes Research Articles

The behaviour of infected guppies depends on social context, parasite tolerance and host sex

How infected hosts behave critically affects both their fitness and the transmission, and thus fitness, of their parasites. Understanding host–parasite coevolution therefore requires understanding the factors affecting infected host behaviour. This can usefully be decomposed into the current behavioural expression level and any infection-induced changes in that expression: each of these may have different implications for host and parasite fitness. For example, from the perspective of socially transmitted parasites, the more contacts infected hosts make with susceptible conspecifics, the better, regardless of their pre-infection contact behaviour. For social hosts, however, minimizing infection-induced changes to fitness-enhancing behaviours (‘behavioural tolerance’) may reduce the risk of social exclusion and its associated costs. Here, we tested how the presence of conspecifics (‘social context’) affects the behaviour and behavioural tolerance of guppies, Poecilia reticulata, infected with the socially transmitted ectoparasite Gyrodactylus turnbulli. In the absence of a stimulus shoal of three females, males that lost the most mass over the course of infection (i.e. had lowest tissue-specific tolerance) were significantly less active, whereas in the presence of the shoal, male activity levels were high and not correlated with tissue-specific tolerance. Females were consistently active, regardless of their tissue-specific tolerance or social context. Behavioural tolerance, quantified as the per-parasite change in activity level, also differed between the sexes in the absence of the shoal: among females, behavioural tolerance was negatively correlated with tissue-specific tolerance, whereas in males the correlation was strikingly positive. In the presence of the shoal, however, tolerance components were not correlated in either sex. Overall, these sex differences in behaviour and behavioural tolerance indicate that females are highly competent at transmitting this parasite, and that males can conceal their disease when in the presence of females. Our results contribute to the growing literature on factors affecting variation between infected hosts, which fundamentally affects epidemiological predictions.

The regulatory strategy of proteins in the mouse kidney during Babesia microti infection

Babesia is a protozoan that mainly parasitizes mammalian red blood cells. It causes damage to multiple organs of the host, even threatening the life of the host when the infection is severe. This study found that the mouse kidney was injured after Babesia infection, leading to changes such as ischaemia and an abnormal morphology of renal and epithelial cells. Serum tests showed that indices reflecting renal abnormalities (including serum creatinine, uric acid, and bilirubin) appeared to be abnormal. To further explore the molecular mechanism underlying kidney injury and self-healing in infected hosts, we employed a data-independent acquisition (DIA) proteomics method to investigate large-scale B. microti infection-induced changes in protein expression and phosphorylation in mouse kidneys. This study identified and analysed the reasons for the obvious changes in kidney injury-related proteins, repair-related proteins, immune-related proteins, and lipid metabolism-related proteins. The results provide a strong theoretical basis for effective treatments of the kidney disease caused by Babesia infection.

Clinical Profile and Short-Term Outcome of SARS-CoV-2-Infected Neonates from a Government Medical College in West Bengal, India.

IntroductionSevere acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has led to a terrifying global pandemic. The presentations in neonates are varied with less case severity compared to adults.AimTo describe the clinical and laboratory features and outcomes of neonates admitted with SARS-CoV-2 infection during the second surge of COVID-19 pandemic in a Government Medical College, West Bengal, India.Materials and MethodsIt is a hospital-based observational cross-sectional study conducted in the newborn unit of Burdwan Medical College and Hospital between 1 April 2021 and 31 July 2021 including all SARS-CoV-2 Real time RT-PCR (Reverse transcriptase polymerase chain reaction) positive neonates. The demographic, clinical and laboratory characteristics of all the neonates and their outcomes were documented and analysed.ResultsTwenty-two neonates were found to be SARS-CoV-2 RT-PCR positive out of which 9 (40.9%) were found to be asymptomatic and 6 (27.27%) required neonatal intensive care unit admissions. Among the symptomatic neonates, most common presentations were respiratory distress (40.9%) and gastrointestinal manifestations (40.9%). Eight (36.36%) neonates required respiratory support. Three (13.6%) neonates had pneumonia of which one had right middle lobe collapse. Laboratory parameters were nonspecific except for the two (9%) cases of multisystem inflammatory syndrome in neonates. High-resolution computed tomography findings in two cases were suggestive of SARS-CoV-2 infection-induced changes. Two (9%) neonates died of which one was likely due to SARS-CoV-2 infection.ConclusionNeonates with SARS-CoV-2 infection are mostly asymptomatic. However, clinicians must be vigilant as atypical presentations such as consolidation, collapse, meningitis or multisystem inflammatory syndrome may occur.

Molecular networking in infectious disease models.

Small molecule metabolites are the product of many enzymatic reactions. Metabolomics thus opens a window into enzyme activity and function, integrating effects at the post-translational, proteome, transcriptome and genome level. In addition, small molecules can themselves regulate enzyme activity, expression and function both via substrate availability mechanisms and through allosteric regulation. Metabolites are therefore at the nexus of infectious diseases, regulating nutrient availability to the pathogen, immune responses, tropism, and host disease tolerance and resilience. Analysis of metabolomics data is however complex, particularly in terms of metabolite annotation. An emerging valuable approach to extend metabolite annotations beyond existing compound libraries and to identify infection-induced chemical changes is molecular networking. In this chapter, we discuss the applications of molecular networking in the context of infectious diseases specifically, with a focus on considerations relevant to these biological systems.

Profiling SARS-CoV-2 Infection by High-Throughput Shotgun Proteomics.

A comprehensive cartography of viral and host proteins expressed during the different stages of SARS-CoV-2 infection is key to decipher the molecular mechanisms of pathogenesis. For the most detailed analysis, proteins should be first purified and then proteolyzed with trypsin in the presence of detergents. The resulting peptide mixtures are resolved by reverse phase ultrahigh pressure liquid chromatography and then identified by a high-resolution tandem mass spectrometer. The thousands of spectra acquired for each fraction can then be assigned to peptide sequences using a relevant protein sequence database, comprising viral and host proteins and potential contaminants from the growth medium or from the operator. The peptides are evidencing proteins and their intensities are used to infer the abundance of their corresponding proteins. Data analysis allows for highlighting the viral and host proteins dynamics. Here, we describe the sample preparation method adapted to profile SARS-CoV-2 -infected cell models, the shotgun proteomics pipeline to record experimental data, and the workflow for data interpretation to analyze infection-induced proteomic changes in a time-resolved manner.

Persistent coxsackievirus B1 infection triggers extensive changes in the transcriptome of human pancreatic ductal cells

SummaryEnteroviruses, particularly the group B coxsackieviruses (CVBs), have been associated with the development of type 1 diabetes. Several CVB serotypes establish chronic infections in human cells in vivo and in vitro. However, the mechanisms leading to enterovirus persistency and, possibly, beta cell autoimmunity are not fully understood. We established a carrier-state-type persistent infection model in human pancreatic cell line PANC-1 using two distinct CVB1 strains and profiled the infection-induced changes in cellular transcriptome. In the current study, we observed clear changes in the gene expression of factors associated with the pancreatic microenvironment, the secretory pathway, and lysosomal biogenesis during persistent CVB1 infections. Moreover, we found that the antiviral response pathways were activated differently by the two CVB1 strains. Overall, our study reveals extensive transcriptional responses in persistently CVB1-infected pancreatic cells with strong opposite but also common changes between the two strains.

Pre-Symptomatic Detection of Viral Infection in Tobacco Leaves Using PAM Fluorometry

Chlorophyll fluorescence imaging was used to study potato virus X (PVX) infection of Nicotiana benthamiana. Infection-induced changes in chlorophyll fluorescence parameters (quantum yield of photosystem II photochemistry (ΦPSII) and non-photochemical fluorescence quenching (NPQ)) in the non-inoculated leaf were recorded and compared with the spatial distribution of the virus detected by the fluorescence of GFP associated with the virus. We determined infection-related changes at different points of the light-induced chlorophyll fluorescence kinetics and at different days after inoculation. A slight change in the light-adapted steady-state values of ΦPSII and NPQ was observed in the infected area of the non-inoculated leaf. In contrast to the steady-state parameters, the dynamics of ΦPSII and NPQ caused by the dark–light transition in healthy and infected areas differed significantly starting from the second day after the detection of the virus in a non-inoculated leaf. The coefficients of correlation between chlorophyll fluorescence parameters and virus localization were 0.67 for ΦPSII and 0.76 for NPQ. In general, the results demonstrate the possibility of reliable pre-symptomatic detection of the spread of a viral infection using chlorophyll fluorescence imaging.

Metabolic Adaptations During Staphylococcus aureus and Candida albicans Co-Infection.

Successful pathogens require metabolic flexibility to adapt to diverse host niches. The presence of co-infecting or commensal microorganisms at a given infection site can further influence the metabolic processes required for a pathogen to cause disease. The Gram-positive bacterium Staphylococcus aureus and the polymorphic fungus Candida albicans are microorganisms that asymptomatically colonize healthy individuals but can also cause superficial infections or severe invasive disease. Due to many shared host niches, S. aureus and C. albicans are frequently co-isolated from mixed fungal-bacterial infections. S. aureus and C. albicans co-infection alters microbial metabolism relative to infection with either organism alone. Metabolic changes during co-infection regulate virulence, such as enhancing toxin production in S. aureus or contributing to morphogenesis and cell wall remodeling in C. albicans. C. albicans and S. aureus also form polymicrobial biofilms, which have greater biomass and reduced susceptibility to antimicrobials relative to mono-microbial biofilms. The S. aureus and C. albicans metabolic programs induced during co-infection impact interactions with host immune cells, resulting in greater microbial survival and immune evasion. Conversely, innate immune cell sensing of S. aureus and C. albicans triggers metabolic changes in the host cells that result in an altered immune response to secondary infections. In this review article, we discuss the metabolic programs that govern host-pathogen interactions during S. aureus and C. albicans co-infection. Understanding C. albicans-S. aureus interactions may highlight more general principles of how polymicrobial interactions, particularly fungal-bacterial interactions, shape the outcome of infectious disease. We focus on how co-infection alters microbial metabolism to enhance virulence and how infection-induced changes to host cell metabolism can impact a secondary infection.

The visual ecology of selective predation: Are unhealthy hosts less stealthy hosts?

Predators can strongly influence disease transmission and evolution, particularly when they prey selectively on infected hosts. Although selective predation has been observed in numerous systems, why predators select infected prey remains poorly understood. Here, we use a mathematical model of predator vision to test a long‐standing hypothesis about the mechanistic basis of selective predation in a Daphnia–microparasite system, which serves as a model for the ecology and evolution of infectious diseases. Bluegill sunfish feed selectively on Daphnia infected by a variety of parasites, particularly in water uncolored by dissolved organic carbon. The leading hypothesis for selective predation in this system is that infection‐induced changes in the transparency of Daphnia render them more visible to bluegill. Rigorously evaluating this hypothesis requires that we quantify the effect of infection on the visibility of prey from the predator's perspective, rather than our own. Using a model of the bluegill visual system, we show that three common parasites, Metschnikowia bicuspidata, Pasteuria ramosa, and Spirobacillus cienkowskii, decrease the transparency of Daphnia, rendering infected Daphnia darker against a background of bright downwelling light. As a result of this increased brightness contrast, bluegill can see infected Daphnia at greater distances than uninfected Daphnia—between 19% and 33% further, depending on the parasite. Pasteuria and Spirobacillus also increase the chromatic contrast of Daphnia. These findings lend support to the hypothesis that selective predation by fish on infected Daphnia could result from the effects of infection on Daphnia's visibility. However, contrary to expectations, the visibility of Daphnia was not strongly impacted by water color in our model. Our work demonstrates that models of animal visual systems can be useful in understanding ecological interactions that impact disease transmission.

High resolution proteomics of Aedes aegypti salivary glands infected with either dengue, Zika or chikungunya viruses identify new virus specific and broad antiviral factors

Arboviruses such as dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses infect close to half a billion people per year, and are primarily transmitted through Aedes aegypti bites. Infection-induced changes in mosquito salivary glands (SG) influence transmission by inducing antiviral immunity, which restricts virus replication in the vector, and by altering saliva composition, which influences skin infection. Here, we profiled SG proteome responses to DENV serotype 2 (DENV2), ZIKV and CHIKV infections by using high-resolution isobaric-tagged quantitative proteomics. We identified 218 proteins with putative functions in immunity, blood-feeding or related to the cellular machinery. We observed that 58, 27 and 29 proteins were regulated by DENV2, ZIKV and CHIKV infections, respectively. While the regulation patterns were mostly virus-specific, we separately depleted four uncharacterized proteins that were upregulated by all three viral infections to determine their effects on these viral infections. Our study suggests that gamma-interferon responsive lysosomal thiol-like (GILT-like) has an anti-ZIKV effect, adenosine deaminase (ADA) has an anti-CHIKV effect, salivary gland surface protein 1 (SGS1) has a pro-ZIKV effect and salivary gland broad-spectrum antiviral protein (SGBAP) has an antiviral effect against all three viruses. The comprehensive description of SG responses to three global pathogenic viruses and the identification of new restriction factors improves our understanding of the molecular mechanisms influencing transmission.

Metabolomic Characterization of Cerebrospinal Fluid from Intracranial Bacterial Infection Pediatric Patients: A Pilot Study.

Intracranial bacterial infection remains a major cause of morbidity and mortality in neurosurgical cases. Metabolomic profiling of cerebrospinal fluid (CSF) holds great promise to gain insights into the pathogenesis of central neural system (CNS) bacterial infections. In this pilot study, we analyzed the metabolites in CSF of CNS infection patients and controls in a pseudo-targeted manner, aiming at elucidating the metabolic dysregulation in response to postoperative intracranial bacterial infection of pediatric cases. Untargeted analysis uncovered 597 metabolites, and screened out 206 differential metabolites in case of infection. Targeted verification and pathway analysis filtered out the glycolysis, amino acids metabolism and purine metabolism pathways as potential pathological pathways. These perturbed pathways are involved in the infection-induced oxidative stress and immune response. Characterization of the infection-induced metabolic changes can provide robust biomarkers of CNS bacterial infection for clinical diagnosis, novel pathways for pathological investigation, and new targets for treatment.

Sars-Cov-2 Infection Promotes Endothelial Dysfunction and Thrombosis in a Mouse Model of COVID-19

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most infected individuals are asymptomatic or show only mild symptoms, but 20% of infected individuals become severely ill resulting in a 2-5% mortality rate for severe infections. Men, the elderly and patients with comorbidities (such as cardiovascular disease, hypertension, diabetes, and obesity) are more likely to develop severe disease. Clinical features characterizing severe COVID-19 cases include inflammation and thrombosis, but the molecular mechanisms underlying these processes remain elusive. K18 hACE2 transgenic mice express the SARSCoV-2 receptor human angiotensin-converting enzyme 2 (hACE2) under the control of the human cytokeratin 18 (K18) promoter. K18 hACE2 mice express hACE2 in airway epithelial cells and are susceptible to SARS-CoV-1 and SARS-CoV-2 infections. At the dose of 10 5 PFU/mouse, all SARS-CoV-2-infected K18 hACE2 mice rapidly lose weight and succumb to viral infection by 5-6 days post infection. Morbidity and mortality correlated with SARS-CoV-2 replication in the nasal turbinates and lungs. Notably, susceptibility was highly associated with a local and systemic cytokine/chemokine storm. SARS-CoV-2 infection in K18 hACE2 mice recapitulates many of the pathological findings observed in human patients offering a reliable animal model for the study of SARS-CoV-2 pathogenesis. Infection with a lower viral dose (10 4 and 2.5x10 3 PFU/mouse) prolongs the symptomatic phase of the infection, postponing time of death up to 16 days post infection (mortality rate at 10 4 PFU: ~40% in females, 100% in males; mortality rate at 2.5x10 3 PFU: ~30% in females, ~55% in males). At these lower viral doses, K18 hACE2 mouse males exhibited both increased susceptibility to the SARS-CoV-2 infection and more severe disease. Male mice showed increased mortality associated with an increase in weight loss and decrease in body temperature. Disease characteristics showed striking similarities with reported human COVID-19 cases, including severely reduced O 2 saturation. The pathogenesis of severe COVID-19 cases involves both virus-induced cell damage and secondary tissue damage due to a vicious cycle of dysregulated - hyperactive coagulation and inflammatory pathways that present as “a cytokine storm”, endothelial dysfunction, and “immunothrombosis”. Analysis of murine plasma analytes from infected mice revealed additional pathogenetic features resembling SARS-CoV-2 infection in humans. High circulating D-dimer levels are now considered a main predictor of poor outcome of SARS-CoV-2 infection. Notably, we also observed a progressive increase of circulating D-dimer levels in the plasma of K18 hACE2 infected mice peaking at day 7 post infection, suggestive of a hypercoagulable state. Moreover, similar to humans, the increase in soluble thrombomodulin plasma concentration and its correlation with disease severity was indicative of endothelial activation and dysfunction in K18 hACE2 infected mice. SARS-CoV-2 infection-induced changes of coagulation and endothelial activation in mice resulted in a biphasic alteration of endothelial permeability where an initial increase in vascular permeability, peaking at day 5 post infection, was followed by a sudden decrease in Evan's blue dye extravasation in the lung parenchyma and characterized by the appearance of areas of hemorrhagic infarction indicative of thrombotic events. Altogether, our results identify the K18 hACE2 transgenic mouse as an important small animal model to study the molecular mechanisms involved in the derangement of the finely tuned interaction between the immune and coagulation systems associated with severe cases of SARS-CoV-2 infections. DisclosuresMosnier: Hematherix: Membership on an entity's Board of Directors or advisory committees; Coagulant Therapeutics: Research Funding.

The phytonutrient cinnamaldehyde limits intestinal inflammation and enteric parasite infection

Phytonutrients such as cinnamaldehyde (CA) have been studied for their effects on metabolic diseases, but their influence on mucosal inflammation and immunity to enteric infection are not well documented. Here, we show that consumption of CA in mice significantly down-regulates transcriptional pathways connected to inflammation in the small intestine, and alters T-cell populations in mesenteric lymph nodes. During infection with the enteric helminth Heligomosomoides polygyrus, CA treatment attenuated infection-induced changes in biological pathways connected to cell cycle and mitotic activity, and tended to reduce worm burdens. Mechanistically, CA did not appear to exert activity through a prebiotic effect, as CA treatment did not significantly change the composition of the gut microbiota. Instead, in vitro experiments showed that CA directly induced xenobiotic metabolizing pathways in intestinal epithelial cells and suppressed endotoxin-induced inflammatory responses in macrophages. Collectively, our results show that CA down-regulates inflammatory pathways in the intestinal mucosa and can limit the pathological response to enteric infection. These properties appear to be largely independent of the gut microbiota, and instead connected to the ability of CA to induce antioxidant pathways in intestinal cells. Our results encourage further investigation into the use of CA and related phytonutrients as functional food components to promote intestinal health in humans and animals.

Roles of TLR7 in Schistosoma japonicum Infection-Induced Hepatic Pathological Changes in C57BL/6 Mice.

S. japonicum infection can induce granulomatous inflammation in the liver of the host. Granulomatous inflammation limits the spread of infection and plays a role in host protection. Toll-like receptor 7 (TLR7) is an endosomal TLR that recognizes single-stranded RNA (ssRNA). In this study, the role of TLR7 in S. japonicum infection-induced hepatitis was investigated in both normal and TLR7 knockout (KO) C57BL/6 mice. The results indicated that TLR7 KO could aggravate S. japonicum infection-induced damage in the body, with less granuloma formation in the tissue, lower WBCs in blood, and decreased ALT and AST in the serum. Then, the expression of TLR7 was detected in isolated hepatic lymphocytes. The results indicated that the percentage of TLR7+ cells was increased in the infected mice. Hepatic macrophages, DCs, and B cells could express TLR7, and most of the TLR7-expressing cells in the liver of infected mice were macrophages. The percentage of TLR7-expressing macrophages was also increased after infection. Moreover, macrophages, T cells, and B cells showed significant changes in the counts, activation-associated molecule expression, and cytokine secretion between S. japonicum-infected WT and TLR7 KO mice. Altogether, this study indicated that TLR7 could delay the progression of S. japonicum infection-induced hepatitis mainly through macrophages. DCs, B cells, and T cells were involved in the TLR7-mediated immune response.

Concepts to Reveal Parvovirus-Nucleus Interactions.

Parvoviruses are small single-stranded (ss) DNA viruses, which replicate in the nucleoplasm and affect both the structure and function of the nucleus. The nuclear stage of the parvovirus life cycle starts at the nuclear entry of incoming capsids and culminates in the successful passage of progeny capsids out of the nucleus. In this review, we will present past, current, and future microscopy and biochemical techniques and demonstrate their potential in revealing the dynamics and molecular interactions in the intranuclear processes of parvovirus infection. In particular, a number of advanced techniques will be presented for the detection of infection-induced changes, such as DNA modification and damage, as well as protein–chromatin interactions.

Helicobacter pylori infection-induced changes in the intestinal microbiota of 14-year-old or 15-year-old Japanese adolescents: a cross-sectional study

ObjectiveThe relationship between Helicobacter pylori and the intestinal microbiota has not yet been clearly demonstrated in children and adolescents. The present study aimed at evaluating how H. pylori infection could...

Physiologically Relevant Concentrations of Dolutegravir, Emtricitabine, and Efavirenz Induce Distinct Metabolic Alterations in HeLa Epithelial and BV2 Microglial Cells.

Microglia, the resident brain phagocytes, likely play a key role in human immunodeficiency virus (HIV) infection of the central nervous system (CNS) and subsequent neuropathogenesis; however, the nature of the infection-induced changes that yield damaging CNS effects and the stimuli that provoke microglial activation remains elusive, especially in the current era of using antiretroviral (ARV) drugs for ARV therapy (ART). Altered microglial metabolism can modulate cellular functionality and pathogenicity in neurological disease. While HIV infection itself alters brain energy metabolism, the effect of ARV drugs, particularly those currently used in treatment, on metabolism is understudied. Dolutegravir (DTG) and emtricitabine (FTC) combination, together with tenofovir (TAF or TDF), is one of the recommended first line treatments for HIV. Despite the relatively good tolerability and safety profile of FTC, a nucleoside reverse transcriptase inhibitor, and DTG, an integrase inhibitor, adverse side effects have been reported and highlight a need to understand off-target effects of these medications. We hypothesized that similar to previous ART regimen drugs, DTG and FTC side effects involve mitochondrial dysfunction. To increase detection of ARV-induced mitochondrial effects, highly glycolytic HeLa epithelial cells were forced to rely on oxidative phosphorylation by substituting galactose for glucose in the growth media. We assessed ATP levels, resazurin oxidation-reduction (REDOX), and mitochondrial membrane potential following 24-hour exposure (to approximate effects of one dose equivalent) to DTG, FTC, and efavirenz (EFV, a known mitotoxic ARV drug). Further, since microglia support productive HIV infection, act as latent HIV cellular reservoirs, and when dysfunctional likely contribute to HIV-associated neurocognitive disorders, the experiments were repeated using BV2 microglial cells. In HeLa cells, FTC decreased mitochondrial REDOX activity, while DTG, similar to EFV, impaired both mitochondrial ATP generation and REDOX activity. In contrast to HeLa cells, DTG increased cellular ATP generation and mitochondrial REDOX activity in BV2 cells. Bioenergetic analysis revealed that DTG, FTC, and EFV elevated BV2 cell mitochondrial respiration. DTG and FTC exposure induced distinct mitochondrial functional changes in HeLa and BV2 cells. These findings suggest cell type-specific metabolic changes may contribute to the toxic side effects of these ARV drugs.

Effect of Pre and Post Infection Administration of Zinc and Selenium on some Biochemical indices in Wistar Rats infected with Trypanosoma brucei

Aims: The effect of pre and post-infection administration of zinc and selenium on Trypanosoma brucei brucei infection in wistar rats on some biochemical parameters were investigated.
 Study Design: The study was designed to evaluate the effect of pre and post infection administration of zinc and selenium on Trypanosoma brucei brucei infection in wistar rats.
 Place and Duration of Study: The study was conducted at the Nigerian Institute for Trypanosomiasis Research (NITR), Kaduna and Department of Biochemistry, Ahmadu Bello University (ABU), Zaria, between January 2014 to March 2014.
 Methodology: Fifty four (54) wistar rats were divided into nine groups of six (6) rats each. Groups III-IX were infected intraperitoneally with 1x103parasite load. Animals in group III were infected but untreated while the infected/treated groups received prophylactic (IV, V and VI) and therapeutic (VII, VIII and IX) treatment with zinc and selenium 50mg/kg and 10mg/kg body weight respectively.
 Results: Results obtained showed that serum alkaline phosphatase (ALP), alanine amino transferase (ALT) and aspartate amino transferase (AST) activities in the infected-untreated control group were significantly different (P<0.05) and higher as compared to infected treated and normal control. Similarly, the two minerals significantly decreased (P<0.05) the levels of Urea and Creatinine in the infected treated when compared to the infected untreated rats, with the exception of creatinine value of the post-infected treated with selenium where there was no significant (P>0.05) decrease. On the other hand, a significant (P<0.05) increase in serum levels of total Protein, albumin and total bilirubin and no significant (P>0.05) difference in direct bilirubin was recorded in infected treated group compared to infected untreated and normal control.
 Conclusion: It was concluded that administration of zinc and selenium ameliorate the infection-induced biochemical changes in tissues and organs associated with Trypanosoma brucei brucei infection in Wistar rats.

The most important biomarker associated with coagulation and inflammation among COVID-19 patients.

Coronavirus disease 2019 (COVID-19) induced by SARS-Cov-2 can be related to coagulopathy. Also, the infection-induced inflammatory changes are found in patients with disseminated intravascular coagulopathy (DIC). The lack of previous immunity to COVID-19 has caused infection of a large number of patients worldwide and unpredictability regarding the management of the complications that appear in the course of this viral illness. Lungs are the most important target organ of the SARS-COV-2. In COVID-19 patients, acute lung injury leads to respiratory failure. However, multiorgan failure can also occur in these patients. The primary coagulopathy of COVID-19 is marked by a considerable elevation of D-dimer, ferritin, and fibrinogen degradation products. In comparison, abnormalities in platelet count, prothrombin time, and partial thromboplastin time are partly uncommon in initial presentations. Inflammatory biomarkers including CRP, LDH, and IL-6 are significantly elevated in the early stages of the disease. In this regard, inflammation-associated biomarkers and coagulation test screening, including the assessment of IL-6, CRP, LDH, D-dimer, platelet count, PT&PTT time, ferritin, and fibrinogen levels are suggested for detecting infection by this virus. Overall, COVID-19-associated coagulopathy should be managed like other patients with critical conditions, and supportive care and thromboembolic prophylaxis should be used for severe patients.

Targeted Transcriptomic Analysis of C57BL/6 and BALB/c Mice During Progressive Chronic Toxoplasma gondii Infection Reveals Changes in Host and Parasite Gene Expression Relating to Neuropathology and Resolution.

Toxoplasma gondii is a resilient parasite that infects a multitude of warm-blooded hosts and results in a lifelong chronic infection requiring continuous responses by the host. Chronic infection is characterized by a balanced immune response and neuropathology that are driven by changes in gene expression. Previous research pertaining to these processes has been conducted in various mouse models, and much knowledge of infection-induced gene expression changes has been acquired through the use of high throughput sequencing techniques in different mouse strains and post-mortem human studies. However, lack of infection time course data poses a prominent missing link in the understanding of chronic infection, and there is still much that is unknown regarding changes in genes specifically relating to neuropathology and resulting repair mechanisms as infection progresses throughout the different stages of chronicity. In this paper, we present a targeted approach to gene expression analysis during T. gondii infection through the use of NanoString nCounter gene expression assays. Wild type C57BL/6 and BALB/c background mice were infected, and transcriptional changes in the brain were evaluated at 14, 28, and 56 days post infection. Results demonstrate a dramatic shift in both previously demonstrated and novel gene expression relating to neuropathology and resolution in C57BL/6 mice. In addition, comparison between BALB/c and C57BL/6 mice demonstrate initial differences in gene expression that evolve over the course of infection and indicate decreased neuropathology and enhanced repair in BALB/c mice. In conclusion, these studies provide a targeted approach to gene expression analysis in the brain during infection and provide elaboration on previously identified transcriptional changes and also offer insights into further understanding the complexities of chronic T. gondii infection.