Uninfected Control Group Research Articles

Sexual Development in Perinatally HIV-Infected Young People: A Systematic Review and Explorative Study.

Similar to other young people with a chronic health condition, perinatally HIV-infected (PHIV) adolescents may have an impacted sexual development. This paper aims to compare sexual milestones of PHIV to HIV uninfected peers, through a systematic review (SR) and explorative study. We performed a systematic search in 4 electronic databases (Medline, Embase, Web of Science, and Scopus), according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Last search in all databases was performed in May 2021. We included studies that reported on quantitative data of any of the main outcomes and compared PHIV to HIV uninfected control groups. Main outcomes were defined as the occurrence and/or debut age of sexual milestones (falling in love, having been in a romantic relationship, masturbation, kissing, non-genital caressing (feeling or petting, touching), genital caressing (fingering, handjob), giving or receiving oral sex, and penetrative sex (vaginal or anal). We excluded case reports, audits, guidelines, editorials, abstracts, studies that reported on behaviorally infected HIV patients, studies that did not include an HIV uninfected control group and studies that could not be translated to English or Dutch. We used the Agency for Health Care Research and Quality (AHRQ) Checklist for quality assessment. We performed qualitative synthesis of the data. In the explorative study, we compared sexual milestones of PHIV and HIV uninfected controls matched for age, sex, ethnicity and educational level, using a subset of questions of a validated questionnaire. We included eighteen studies in the SR, describing outcomes of an estimated 1,963 participants. Seventeen studies compared the occurrence and/or debut age of intercourse in PHIV and HIV uninfected controls and 4 studies reported on any of the other sexual milestones. The majority of studies found no difference in occurrence (12 of 16 studies) or debut age (6 of 8 studies) of intercourse in PHIV compared to controls. Two of 4 studies reporting on any of the other milestones found no significant differences between PHIV and HIV uninfected controls. In the explorative study, we included ten PHIV participants and 16 HIV uninfected, matched controls. PHIV tended to report a later debut age of sexual milestones than controls (not significant). The SR includes only a small number of studies and few studies report on non-penetrative milestones. The explorative study adds to this review by including non-penetrative milestones and comparing PHIV to HIV-uninfected, well-matched controls. However, the sample size was small. PHIV seem to engage in sexual activities and achieve sexual milestones at a similar rate as their HIV uninfected peers, with a tendency of a later start in well treated PHIV. The review was registered in the PROSPERO database (CRD42021252103) and funded by AIDSfonds. AIDSfonds had no role in the study design or interpretations of this study. ter Haar AM, Fieten A, Van den Hof M, et al. Sexual Development in Perinatally HIV-Infected Young People: A Systematic Review and Explorative Study. Sex Med 2022;10:100578.

Comparative pathogenicity of drug-resistant and drug-sensitive Trypanosoma brucei and Trypanosoma congolense infections in Nigerian local dogs.

Animal trypanosomosis is an important endemic and wasting disease in sub-Saharan Africa. Its control relies on chemotherapy, and resistance to trypanocides has been widely reported. The pathogenicity of drug-resistant canine trypanosomes is not clear with scanty information available. Thus, this study assessed the comparative pathogenicity of drug-resistant and drug-sensitive Trypanosoma brucei and Trypanosoma congolense infections in dogs. Twenty Nigerian local dogs were used and were randomly assigned into five groups (A-E) of four dogs each. Group A served as the uninfected-control group, while groups B and C were infected with 106 drug-sensitive T. congolense and T. brucei. Groups D and E were infected with 106 multidrug-resistant T. congolense and T. brucei, respectively. The pre-patent period (PPP), clinical signs, level of parasitaemia (LOP), rectal temperature, body weight, packed cell volume (PCV), red blood cell count (RBC), haemoglobin concentration (HbC), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), total leucocyte count (TLC) and survivability were assessed. Groups D and E had longer (p < 0.05) mean PPP than groups B and C. Also, group E dogs had lower (p < 0.05) mean LOP, longer (p < 0.05) mean survivability, and higher (p < 0.05) mean body weight, PCV, HbC and RBC than group C dogs. The clinical signs were very severe in group C dogs, compared to group E dogs. However, these parameters did not differ statistically between groups B and D. Thus, multidrug-resistant T. brucei was of lower pathogenicity than drug-sensitive T. brucei, while multidrug-resistant and drug-sensitive T. congolense had comparable pathogenicity following infection in dogs.

PSXV-21 Transcriptome Analysis of Chicken Reveals the Impact of Herpesvirus of Turkeys on Bursa RNA Expression in Marek’s Disease Virus Infections

Abstract Marek’s disease virus (MDV) is an oncogenic herpesvirus that causes various clinical syndromes in chicken. MDV early infection induces a transient immunosuppression and harbored in B cells of the bursa during the cytolysis phase of its replication cycle. One of the most commonly used commercial vaccines is Herpesvirus of Turkeys (HVT), which is a nonpathogenic virus of domestic turkey and may influence the expression of RNA. The aim of this study is to characterize the regulation of bursa gene in MDV infections and the impact of HVT vaccination on RNA expression in MDV-infected chickens. We used RNA-seq on the bursa samples to compare the transcriptome differences among MDV-infected chickens, HVT-infected chickens, co-infected chickens and uninfected control groups at 4, 7, 14 and 21 days post infection. Meanwhile, we also compared the expression at three different time points to examine alterations in the expression pattern. The result of differential gene expression showed that 14 days post infection might be the point in time when HVT worked. At false discovery (FDR) &amp;lt; 0.05 and fold change (FC) ≥2, we found 745, 218 and 76 genes in MDV-infected chickens, HVT-infected chickens and co-infected chickens respectively as differentially expressed compared with control group and 713 genes between MDV-infected chickens and co-infected chickens at 14 dpi. KEGG and GO enrichment analysis showed that these genes were highly enriched for Lysosome, immune response, inflammatory response, plasma membrane and so on. Overall, these findings help to better understand host-pathogen interaction in the bursa and elucidate the mechanism how HVT contribute to resist MDV. Further investigation of the roles of these candidate genes and signaling pathways in the regulation of MDV-HVT interaction may lead new directions for the development of drugs or cultivation of highly MDV resistant chickens.

Klotho Expression in Aging and Disease

Klotho is a regulatory anti‐aging protein that is significantly expressed in the choroid plexus, plays an important role in regulating the immune response in the CNS, and diminishes with age. It is known that a decline of klotho expression has been linked to significant neuroinflammation, oxidative damage in the neural parenchyma, and decline in neurocognitive functions. As the choroid plexus is a known reservoir for latent Human Immunodeficiency Virus (HIV) infection, the relationship between HIV and klotho expression could be a cause of the neurocognitive dysfunction that accompanies HIV infections. The objective of this project was to observe levels of klotho expression in the choroid plexus in a Simian Immunodeficiency Virus (SIV) model of HIV infection, as well as to determine a pattern of age‐related decline in klotho expression. To carry out the study, Choroid plexus samples of Rhesus macaques of various ages and SIV‐infection status were studied. The tissues were stained using immunohistochemistry for polyclonal klotho, structural proteins (vimentin), and nuclei (DAPI), and imaged at varying magnifications of 4x, 10x, and 40x. The images obtained were then analyzed using the fluorescent imaging software Fiji. The epithelial cells of the choroid plexus were measured for their fluorescence intensity to measure their relative klotho expression levels. Although klotho expression was varied in the uninfected Rhesus macaques, there was an overall decreasing trend with the advancement of age. In SIV‐infected Rhesus macaques, the choroid plexus had significantly less klotho expression than the uninfected control group regardless of age (p=0.01). Analysis of the uninfected data shows that there was a decreasing pattern of klotho expression in Rhesus macaques. The variability of klotho levels in the uninfected individuals can be attributed to genetic variations between individuals. However, SIV infection significantly reduced klotho expression in the choroid plexus in comparison to uninfected individuals. This decrease in klotho expression was regardless of age. The exact mechanism in which SIV diminishes klotho expression is unknown and additional studies are warranted to examine this phenomenon.

Immunopathogenesis of the Canadian Delmarva (DMV/1639) infectious bronchitis virus (IBV): Impact on the reproductive tract in layers

IBV infection may lead to reduced egg production and poor egg quality in layer flocks. The DMV/1639 strain was recently identified as one of the most dominant IBV variants isolated from Canadian layer flocks with egg production problems. The current study aimed to investigate the immunopathogenesis of the Canadian DMV/1639 strain in laying chickens. Specific-pathogen-free (SPF) layers were infected at the peak of lay (29 weeks; n = 10) with an uninfected control group (n = 10). Egg production in the infected group dropped to 40% by the fifth day post-infection (dpi). Five birds from the infected and the control groups were euthanized at 5 and 10 dpi. Ovarian regression and shortened oviduct with marked histopathological changes were observed in the infected group at 10 dpi. An increase in the IBV viral load in reproductive tissues was accompanied by a significant recruitment (p < 0.05) of KUL01+ macrophages and CD4+ and CD8+ T cell subsets at 10 dpi. Additionally, anti-IBV antibody response was detected in serum and locally in the reproductive tract washes of the infected group. Overall, our findings contribute to the understanding of the pathogenicity of the Canadian DMV/1639 strain and the subsequent host responses in the reproductive tract of chickens.

Garlic (Allium sativum Linnaeus) improved inflammation and reduced cryptosporidiosis burden in immunocompromised mice

Ethnopharmacological relevanceFor thousands of years, garlic (Allium sativum Linnaeus) has been consumed in food and health by numerous civilizations. Cryptosporidium (C.) parvum is an apicomplexan parasite that causes a gastrointestinal disease, with the most common symptoms being watery diarrhea. Although several substances have been tried for its anti-cryptosporidial action, there is no effective treatment for Cryptosporidium disease, especially in immunocompromised individuals. The present study aimed firstly to characterize the bio-active compounds in Allium sativum L. and secondly to evaluate its efficacy as a therapy for cryptosporidiosis especially in immunocompromised mice. Materials and methodsThis was accomplished by evaluating the parasitological and histopathological parameters in the experimentally infected immunocompetent and immunocompromised mice. Also, the cytokine profile during the experimental time was recorded through the measuring of T helper (h)1, Th2 and Th17 cells cytokines. Immunosuppressed mice were given 0.25 μg/g per day of dexamethasone orally, before infection with Cryptosporidium parvum oocysts, for fourteen consecutive days. Starting 10 days post infection (PI), nitazoxanide (100 mg/kg per day) or Allium sativum (50 mg/kg per day) was given orally for fourteen consecutive days. ResultsOur results showed that oocyst shedding, on the 32nd day PI, in immunocompromised infected group treated with Allium sativum (354.11, 99.35% PR) showed a significant decrease when compared to its corresponding group treated with nitazoxanide (4369.14, 92.05% PR). On the 32nd day PI, all cytokines levels have been decreased to levels that were similar to those of their uninfected corresponding control groups; also, the histopathological changes and the loss in animals’ body weight had been improved. Treatment with nitazoxanide did not result in infection clearance or a reduction in the increased cytokines' levels. ConclusionAllium sativum L. displayed high efficacy as a potential therapeutic agent against Cryptosporidium, which supports its traditional usage in parasite diseases.

The TNF-Alpha Inducing Protein is Associated With Gastric Inflammation and Hyperplasia in a Murine Model of Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the human stomach leading to the development of chronic gastritis, peptic ulcers and gastric adenocarcinoma. A combination of host, environment and bacterial virulence factors contribute to disease development. The H. pylori TNFα inducing protein (Tipɑ) is a virulence factor shown to induce multiple pro-inflammatory cytokines in addition to TNFα in vitro. The goal of the present study was to elucidate the role of Tipα in promoting inflammation in vivo and to identify the molecular pathways associated with Tipα associated virulence. Mice were infected with wild-type Sydney strain (SS1) or a tipα mutant (Δtipα) for 1 month and 4 months. We also completed a second 4 months infection including a 1:1 SS1 to Δtipα co-infected group in addition to SS1 and Δtipα infected groups. The expression of TNFα, and KC were significantly higher in the SS1 infected group compared to both uninfected control (naïve) and Δtipα groups. Mice infected with Tipα expressing SS1 induced more severe histological gastritis and developed hyperplasia compared to Δtipα infected mice. Microarray analysis of gastric epithelial cells co-cultured with recombinant Tipα (rTipα) demonstrates up-regulation of the NFκB pathway. This data suggest Tipα plays an important role in H. pylori induced inflammation.

Peripheral lymphocyte subset alteration in patients with COVID-19 having differential clinical manifestations.

Background & objectives:The COVID-19 disease profile in Indian patients has been found to be different from the Western world. Changes in lymphocyte compartment have been correlated with disease course, illness severity and clinical outcome. This study was aimed to assess the peripheral lymphocyte phenotype and subset distribution in patients with COVID-19 disease from India with differential clinical manifestations.Methods:Percentages of peripheral lymphocyte subsets were measured by flow cytometry in hospitalized asymptomatic (n=53), mild symptomatic (n=36), moderate and severe (n=30) patients with SARS-CoV-2 infection, recovered individuals (n=40) and uninfected controls (n=56) from Pune, Maharashtra, India.Results:Percentages of CD4+Th cells were significantly high in asymptomatic, mild symptomatic, moderate and severe patients and recovered individuals compared to controls. Percentages of Th memory (CD3+CD4+CD45RO+), Tc memory (CD3+CD8+CD45RO+) and B memory (CD19+CD27+) cells were significantly higher in the recovered group compared to both asymptomatic, mild symptomatic patient and uninfected control groups. NK cell (CD56+CD3-) percentages were comparable among moderate +severe patient and uninfected control groups.Interpretation & conclusions:The observed lower CD4+Th cells in moderate+severe group requiring oxygen support compared to asymptomatic+mild symptomatic group not requiring oxygen support could be indicative of poor prognosis. Higher Th memory, Tc memory and B memory cells in the recovered group compared to mild symptomatic patient groups might be markers of recovery from mild infection; however, it remains to be established if the persistence of any of these cells could be considered as a correlate of protection.

Histopathological and ultrastructural assessment of atovaquone-proguanil hydrochloride combination in chronic murine toxoplasmosis

ABSTRACT Over one billion people worldwide are expected to have Toxoplasma gondii infection with anonymous health problems. Available therapies are ineffective for persistent chronic toxoplasmosis. So, there is an imperative need for effective therapies to eliminate chronic tissue stage. In this study, we aimed to assess the effect of a drug combination of atovaquone and proguanil hydrochloride in the treatment of experimental chronic toxoplasmosis. Fifty Swiss Webster mice were used in the study. Forty mice were infected with Me49 type II cystogenic Toxoplasma gondii strain and allocated into four groups: infected untreated (vehicle-administered), infected and treated with cotrimoxazole (CTX) 370 mg/kg/day, infected and treated with atovaquone (ATV) 100 mg/kg/day, and infected and treated with atovaquone/proguanil (ATV/PROG) 50 mg/kg/day. An additional group of uninfected mice was used as an uninfected control group. Drug treatment was initiated 8 weeks post-infection and continued for two weeks. All mice were sacrificed 12 weeks post-infection. Parasitological and histopathological parameters were assessed. Toxoplasma gondii cysts recovered from brain tissue homogenates of both infected untreated and ATV/PROG-treated groups were examined by scanning electron microscopy. Combined ATV/PROG treatment demonstrated a significant reduction of Toxoplasma gondii cyst count in brain tissue (a reduction rate of 84.87%) compared to untreated group (P < .001). Brain tissues obtained from ATV/PROG treated group showed reduction of inflammatory infiltrate and marked attenuation and deformation of recovered Toxoplasma gondii cysts. We conclude that ATV/PROG drug combination could offer a potential drug therapy for Toxoplasma gondii chronic cystic stage.

Haematological changes in Wistar rats experimentally infected with Trypanosoma congolense and Trypanosoma brucei brucei obtained from North-west Nigeria

This study determined haematological changes in Wistar rats experimentally infected with local strains of Trypanosoma congolense and Trypanosoma brucei brucei. Forty-five Wistar rats between 10 – 12 weeks old weighing between 210 – 240 g were used. The Wistar rats were randomly divided into four groups (A, B, C and D), with the infected groups (B, C and D) having 10 rats each, while the uninfected control group (A) had 15 rats. Group A rats were not infected and served as the control, group B were infected with Trypanosoma congolense, group C were infected with Trypanosoma brucei brucei and group D were co-infected with Trypanosoma congolense and Trypanosoma brucei brucei. Infection was achieved using 0.1mL of blood containing approximately 1 × 103 trypanosomes intraperitoneally into each Wistar rat in the infected groups. Clinical signs were observed. The changes in the blood cells were assayed in the groups post-infection. Duncan’s Least Square Deviation showed significantly (p&lt;0.05) higher parasitaemia in infected groups. However, group D showed a higher significant (p&lt;0.05) difference in parasitaemia when compared to groups B and C. The pattern of mean parasitaemia for the infected groups, revealed a positive correlation with days of post-infection (p&lt;0.05) before the decline. The packed cell volume, total red blood cell count and haemoglobin concentration were significantly (p&lt;0.05) lower in infected groups B, C and D. The total white blood cell count, platelet counts and differential leucocyte count were significantly (p&lt;0.05) lower in infected groups when compared to the uninfected group. These findings suggest that co-infection with Trypanosoma congolense and Trypanosoma brucei brucei obtained from Wurno and Ngaski in Sokoto and Kebbi States respectively produced a more damaging effect on haematological parameters.

Immune gene expression in cyprinid herpesvirus-2 (CyHV-2)-sensitized peripheral blood leukocytes (PBLs) co-cultured with CyHV-2-infected goldfish fin cell line.

Goldfish is one of the preferred ornamental fish which is highly susceptible to cyprinid herpesvirus-2 (CyHV-2) infection. The present study aimed to analyse immune gene expression in a co-culture of CyHV-2-sensitized goldfish peripheral blood leukocytes (PBLs) with CyHV-2-infected fantail goldfish fin cell lines (FtGF). Goldfish were sensitized with intraperitoneal TCID50 dose (107.8±0.26/mL) of CyHV-2. After 2 weeks, PBLs were collected and co-cultured with CyHV-2-infected FtGF cells keeping both uninfected FtGF cells and PBL control groups. After 2 days of co-culture, WST-1 assay for cell proliferation was performed at 450 nm during the 2nd, 4th and 6th days of co-culture. The results showed a significant increase (p < 0.05) in cell density in CyHV-2-infected PBL and virus-infected FtGF cells during the 4th day post co-culture which confirmed effector cell generation. Expressions of few immune genes were checked taking RNA samples of CyHV-2-induced PBLs post co-culture with infected FtGF cells along with uninfected FtGF cells as control group at different time periods (2nd, 4th and 6th days) in triplicate. The results indicated increased expression of CD8α, IFNγ, b2m, MHC I, LMP 7, IL-10, IL-12 and GATA3 except Tapasin. From the above study, we concluded that goldfish showed both Th1- and Th2-mediated immune responses to CyHV-2. The current findings support the scope for further vaccine development against CyHV-2 for goldfish.

Muscle strength in young children perinatally infected with HIV who were initiated on antiretroviral therapy early

Background. As children with perinatally acquired HIV (PHIV) are living longer, long-term physical sequelae of the disease are becoming more pertinent. Muscle strength is known to be adversely affected in adults infected with HIV but little is known about the muscle strength of children with PHIV. Objectives. To determine the muscle strength of children perinatally infected with HIV compared with an uninfected control group. Associations between clinical and anthropometric variables and muscle strength were investigated. Methods. In this cross-sectional descriptive study, 175 children who acquired HIV perinatally and 171 children who were HIV-uninfected had their muscle strength assessed by hand-held dynamometry and the ‘make test’. Clinical data were extracted from the children’s clinic files. Height and weight were assessed using a stadiometer and a digital scale, respectively. Children were between the ages of 5 and 11 years of age at assessment. The children living with HIV had all been initiated on antiretroviral treatment (ART) at a young age (mean (standard deviation (SD)) 8.7 (6.7) months) and their disease was well controlled. Results. Despite the children with HIV presenting with significantly lower height, weight and body mass index (BMI) for age z-scores, there was no statistical difference in muscle strength between the two groups. BMI and Tanner staging were associated with muscle strength in both groups. Conclusions. Children who are initiated on ART at an early age and whose disease is well controlled are able to attain near-normal muscle strength. Longitudinal follow-up of these children as they go through puberty is warranted.

Therapeutic effect of Schisandrin A on avian colibacillosis through gut-liver axis

This study evaluated the therapeutic efficacy of Schisandrin A on systemic colibacillosis of chickens. One hundred and eighty, 1-day-old Hailan Brown chickens were divided into 6 groups of 30 chickens each and assigned to the following treatments: 1) uninfected/untreated control; 2) infected Escherichia coli; 3) infected-plus low dose of Schisandrin A therapy (50 mg/kg); 4) infected-plus medium dose of Schisandrin A therapy (100 mg/kg); 5) infected-plus high dose of Schisandrin A therapy (200 mg/kg) and 6) infected-plus antimicrobial therapy (florfenicol). Each group of chickens was placed in cages with a photoperiod of 12 h of light and 12 h of dark. Feed and water for all groups were provided ad libitum for the duration of the study. On d 14, all the chickens except the uninfected control group were intraperitoneally inoculated with a fresh culture of E. coli containing 1 × 108 CFU/mL. The parameters measured included: average daily weight gain (ADG), percent survivability, liver index, serum activity of enzymes (ALT and AST), hepatic and intestinal concentrations of TNF-α, IL-1β, IL-6, IL-8, and LPS, expression of tight junction proteins (occludin, ZO-1, and claudin-1), relative abundance of bacterial species and histopathological changes in hepatic and intestinal tissue. The results showed that the medium and high doses of Schisandrin A ameliorated the detrimental effects of colibacillosis on weight gain. Regarding organ indexes, E. coli infection induced a significant increase in liver index, all the doses of Schisandrin A produced a significant reduction of liver index in comparison to the E. coli infected control. Serum activity of ALT and AST enzymes significantly increased due to E. coli infection, with the exception of the low dose of Schisandrin A for AST enzyme activity, all the Schisandrin A treatments significantly lowered enzyme activity in comparison to the E. coli infected control. Regarding concentrations of inflammatory markers in hepatic and intestinal, E. coli infection caused a significant increase in TNF-α, IL-1β, IL-6, and IL-8, except the lowest dose of Schisandrin A for IL-1β, the rest of the doses tested were able to significantly reduced the concentrations of inflammatory markers. Concentrations of LPS in hepatic and intestinal tissues were significantly increased by E. coli infection, all doses of Schisandrin A significantly reduced the concentration of LPS in hepatic and intestinal tissue. E. coli infection significantly reduced the expression of 2 tight junction proteins (ZO-1 and Claudin-1), the higher doses of Schisandrin A were effective in significantly increasing the expression of these tight junction proteins when compared with the E. coli infected control. Taken together, these results show that Schisandrin A has potential as an alternative therapy for the treatment of colibacillosis in chickens.

Genome-Wide Differential Expression Profiling of Pulmonary circRNAs Associated With Immune Reaction to Pasteurella multocida in Goats

Pasteurella multocida is a highly versatile pathogen that infects a wide range of animals, including goats, causing pneumonia and hemorrhagic septicemia. Circular RNA (circRNA) is a type of non-coding RNA that plays an important role in regulating cellular metabolism. However, whether and how circRNA is involved in regulating immune responses in the goat lung has not been reported. Thus, this study was designed to examine the function of circRNA in goats infected with Pasteurella multocida. Goats were assigned into one of two groups: an uninfected control group (CK) and an infected group challenged with P. multocida. Compared with the CK group, which remained healthy, the infected goats showed clinical signs of infection, including depression, cough, nasal discharge, and dyspnea, along with elevated body temperature and lesions in the lung. Whole-transcriptome sequencing and small RNA sequencing were then performed using lung samples from goats from each group. A total of 138 circRNA, 56 microRNAs (miRNA), and 2,673 messenger RNA (mRNA) molecules were significantly differentially expressed in the P. multocida-infected group compared with the CK group. Randomly selected differentially expressed circRNA, miRNA, and mRNA molecules (n = 5 per group) were then validated by quantitative reverse-transcriptase polymerase chain reaction analysis. Gene ontology (GO) analysis of the source genes indicated that six immune-related terms were enriched among the differentially expressed cirRNA molecules, including inflammatory response, immune effector process, cell activation involved in immune response, cytokine-mediated signaling pathway, response to endogenous stimulus, and immune response. The corresponding circRNA molecules were then selected for construction of a competitive endogenous RNA network to identify networks that may be involved in the immune response to P. multocida infection. The results indicated that P. multocida HN01 may cause pneumonia and stimulate an immune response in goats via regulation of circRNA expression. This study presents the first comprehensive circRNA profile in response to P. multocida infection in goats, thus, providing a basis for understanding the function of circRNA in the host immune response to P. multocida infection.

Patients Living With HIV Are Less Likely to Receive Appropriate Statin Therapy for Cardiovascular Disease Risk Reduction

Background: Recent studies suggest that statins are underprescribed in patients living with HIV (PLWH) at risk for atherosclerotic cardiovascular disease (ASCVD), but none have assessed if eligible patients receive the correct statin and intensity compared to uninfected controls. Objectives: The primary objective was to determine whether statin-eligible PLWH are less likely to receive appropriate statin therapy compared to patients without HIV. Methods: This retrospective study evaluated statin eligibility and prescribing among patients in both an HIV and internal medicine clinic at an urban, academic medical center from June-September 2018 using the American College of Cardiology/American Heart Association guideline on treating blood cholesterol to reduce ASCVD risk. Patients were assessed for eligibility and actual treatment with appropriate statin therapy. Characteristics of patients appropriately and not appropriately treated were compared with chi-square testing and predictors for receiving appropriate statin therapy were determined with logistic regression. Results: A total of 221/300 study subjects were statin-eligible. Fewer statin-eligible PLWH were receiving the correct statin intensity for their risk benefit group versus the uninfected control group (30.2% vs 67.0%, p < 0.001). In the multivariable logistic regression analysis, PLWH were significantly less likely to receive appropriate statin therapy, while those with polypharmacy were more likely to receive appropriate statin therapy. Conclusion: Our study reveals that PLWH may be at a disadvantage in receiving appropriate statin therapy for ASCVD risk reduction. This is important given the heightened risk for ASCVD in this population, and strategies that address this gap in care should be explored.

Expression of MicroRNA of Macrophages Infected with Attenuated Leishmania major Parasite

Abstract Objective Leishmaniasis has been proposed as one of the neglected vector-borne diseases due to an obligate intracellular parasite of the genus Leishmania. MicroRNAs (miRNAs) with a length of 22-nucleotide are known as the noncoding small RNAs. MiRNAs contribute to many biological and cellular approaches. Therefore, the present study evaluated expressing mmu-miR-721, mmu-miR-294–3p, mmu-miR-155–3p, and mmu-miR-30a in murine macrophages infected with attenuated Leishmania major parasites on 3 days after infection. Methods Attenuated promastigotes have been achieved after 20 passages of Leishmania major parasites. Cell line J774A.1 (murine macrophage) has been used for in vitro experiments. The stationary phase of attenuated L. major promastigotes has been chosen to infect the cells, and then their incubation has been performed with 5% CO2 at 37°C for 3 days. The real-time polymerase chain reaction (PCR) has also been performed with SYBR Green master-mix Kit for measuring the level of mmu-miR-721, mmu-miR-294–3p, mmu-miR-30a, and mmu-miR-155-3p expression. Uninfected macrophages have been considered as a control group. Results Real-time PCR demonstrated overexpression of mmu-miR-155-3p, mmu-miR-294–3p, and, mmu-miR-721 in the infected cells with Leishmania parasites after 3 days. Results showed no statistically significant difference in the mmu-miR-30a expression between infected macrophages and the uninfected control group. Conclusion Our findings suggested the significant contribution of the alterations in the miRNA levels to the regulation of macrophage functions following the creation of intracellular parasites like Leishmania. These data could help to understand better the genes' expression in the host cells in the course of leishmaniasis.

Correlation between some haematological parameters, leukocyte ratios, parasitaemia and their prognostic value in canine trypanosomosis

African trypanosomosis is a disease of high economic importance in animals and humans caused by an apicomplexan haemoparasite of the genus Trypanosoma. Canine trypanosomosis is relatively common in Nigeria because of the high prevalence of the insect vector. The haematology, erythrocyte, and serum sialic acid levels of dogs experimentally infected with Federe strain of Trypanosoma brucei brucei was studied in a total of five (5) 4-month old dogs. Three of the dogs were randomly selected and inoculated subcutaneously with 1 × 106 of T. brucei, while the remaining two dogs served as the uninfected control. The parasitaemia, packed cell volume (PCV), total and differential white blood cell count, erythrocyte surface sialic acid (ESSA) and free serum sialic acid (FSSA) were determined twice a week. The lymphocyte/monocyte ratio (LMR) and neutrophil/lymphocyte ratio (NLR) were calculated. The infected dogs had a significantly lower PCV, total white blood cell count (TWBC), LMR and ESSA compared to the uninfected control group. There was a strong positive correlation between NLR and PCV decrease, moderate negative correlation between LMR and PCV decrease, strong negative correlation between LMR and ESSA changes, and a moderate positive correlation between ESSA changes and parasitaemia. The higher NLR in trypanosome infection associated with decreasing levels of PCV indicates a poor prognosis, and NLR may be a useful tool in estimating trypanosomosis effect on PCV in dogs. Similarly, the moderate negative and strong negative correlations between LMR with decreases in PCV and ESSA respectively indicates poor prognosis in the response to trypanosomosis in dogs. Thus, NLR, LMR and ESSA levels can be used as markers for predicting disease outcome in trypanosome infection in dogs. This is, however, not the case with parasitaemia as the clinico-pathologic effect of trypanosomosis cannot be estimated from the level of parasitaemia alone.

A CONTROLLED CLINICAL STUDY TO EVALUATE A PROPRIETARY NON-INVASIVE SMARTPHONE BASED DIGITAL BIOMARKER TOOL LYFAS® IN ENABLING EARLY DETECTION OF COVID-19 INFECTION AMONG ASYMPTOMATIC INDIVIDUALS

Coronavirus disease 2019 (COVID-19), is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the increasing number of individuals infected with COVID-19, there is a growing need for easy, dependable, accurate, scalable, and cost-effective tools. These tools should serve the purpose of population screening/surveillance, diagnosis, and prognosis. Unlike the other pandemics in the past, the current viral infection presents itself with long incubation period up to 14days. This situation is challenging because it results in an extremely high proportion of asymptomatic individuals (up to 80% and more). These individuals in turn contribute to high risk of transmission among the vulnerable population with coexisting diseases and the aged. Currently, the real time PCR test and serology is being largely employed only in symptomatic individuals. Therefore, there is a need for a dependable additional test to identify the asymptomatic individuals, to qualify them for the conrmatory rtPCR and/or serology tests. To meet these the above requirement, we decided to repurpose and test our proprietary non-invasive smartphone-based health screening mobile application Lyfas. The validated parameters captured from Lyfas were found to be inherent indicators of several cardiorespiratory, cardiovascular, autonomic nervous system, hematology and biochemistry anomalies. Apparently, these anomalies were also found and reported as early indicators of COVID-19 infection. Therefore, by means of rationale selection of these parameters, we derived a unique LYFAS_COVID_SCORE to enable detection and prioritize conrmatory testing for asymptomatic individuals. A controlled clinical study was conducted in 25(n=25) subjects to prove the hypothesis and establish the difference in LYFAS_COVID_SCORE between an infected and non-infected group of individuals. The LYFAS_COVID_SCORE derived out of this clinical study was found to be different between the two groups. The positive infected test group had a signicantly high(p=.00012) median score of 19.8(range 9.9 to 22.1) compared to 6.9(range 2.2 to 7.8) that of the healthy uninfected control group. The accuracy, sensitivity and the specicity of the study was found to be 92%, 93.2% and 90% respectively. The result of this study is therefore an evidence to use Lyfas as a potential tool in the identication, screening, and surveillance of asymptomatic individuals. The ndings from the study deserves to be extended to a large population conrmatory clinical study to add proof and value to the tool.

SYNERGY BETWEEN BETA-1, 3-GLUCAN AND PRAZIQUANTEL IN THE TREATMENT OF EXPERIMENTAL CHRONIC SCHISTOSOMIASIS MANSONI

Praziquantel can develop resistance and cannot counteract schistosomiasis pathology. β-glucanwas used as an immunomodulator for innate and acquired immunity. This study evaluated theeffects of β-glucan either alone or with PZQ on chronic Schistosoma mansoni infection. Micewere divided into five groups: uninfected control, infected untreated, PZQ treated, β-glucantreated and combined treatment groups. Treatment started at the end of 8th week P.I. Parasitological,histopathological, immunohistochemical (α-SMA) studies and biochemical assays (Myeloperoxidaseactivity, NO, TNF-α, INF-γ, IL-13 & hydroxyproline) in liver tissues were done.Combination of β-glucan and PZQ therapy resulted in significant decrease in adults count, hepaticegg loads, granuloma number and diameter as well as significant improvement of hepaticpathology and reduction of hepatic fibrosis.

Persistence of monocyte activation under treatment in people followed since acute HIV-1 infection relative to participants at high or low risk of HIV infection.

BackgroundInterpretation of the increase in certain inflammatory markers in virally suppressed HIV-infected individuals must rely on an appropriate uninfected control group well characterized for non-HIV-related factors that contribute to chronic inflammation, e.g. smoking, alcohol consumption, or being overweight. We compared the inflammatory profiles of HIV-infected participants under long-term antiretroviral therapy (ART) with those of two HIV-uninfected groups with contrasting health behaviours.MethodsWe studied 150 HIV-infected participants (42 women, 108 men) under long-term ART (median, 6 years) followed in the ANRS PRIMO cohort since acute/early HIV-1 infection (AHI) diagnosis. Sex and age-matched controls were sampled from i) the ANRS IPERGAY pre-exposure prophylaxis trial among men at high risk for HIV infection and with high frequencies of non-HIV factors of inflammation ii) the ANRS COHVAC cohort of volunteers in vaccine trials with a low-risk profile for HIV infection. We measured the plasma levels of ten inflammatory markers.FindingsAfter adjusting for smoking, alcohol use and body mass index, both HIV-infected men and women had higher levels of sCD14, sCD163, sTNFRII and I-FABP than their high-risk IPERGAY and low-risk COHVAC counterparts. Hierarchical clustering showed a subset of 15 PRIMO participants to have an inflammatory profile similar to that of most HIV-negative participants. These participants already had favourable markers at AHI diagnosis.InterpretationLong-term ART, even when initiated at a low level of immunodeficiency, fails to normalize monocyte/macrophage activation and gut epithelial dysfunction. Persistent inflammation under treatment may be related to an increased inflammatory profile since AHI.FundingANRS and Paris-Saclay University.