Immune-compromised Patients Research Articles

P181 Mucor in the land of the liver: a case report

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM Introduction and ObjectivesMucormycosis is a rare, highly lethal opportunistic fungal infection affecting immune-compromised patients. It accounts for about 2% of invasive fungal infections occurring within 1 year after solid organ transplantation. Among renal recipients, Rhinocerebral is the commonest manifestation and Rhizopus species is the most frequent pathogen.The objectives are:To report a case of Hepatic mucormycosis in a renal transplant recipient.To resolve the dilemma in identification of Mucorale species detected on microscopy but culture negative.MethodA 29-year-old male patient was admitted with severe abdominal pain on day 28 post-live related renal transplantation. Patient was hypertensive, on oral steroids for idiopathic thrombocytopenic purpura, chronic kidney disease with venous thromboembolism-presumed chronic interstitial nephritis, and maintained on hemodialysis for the last 1 year. Post-transplant he was on triple immunosuppressants.Initial ultrasound of abdomen and transplant doppler were normal. CT of abdomen in view of worsening hypotension and non-resolving abdominal pain, revealed hepatomegaly with multiple discrete, coalescing hypodense areas in both lobes of liver with minimal subcapsular extension. Initial cultures included interventional radiology-guided liver aspirate and blood culture. Patient was started on antibiotics and antifungals. Patient continued to deteriorate and a repeat abdominal CT revealed an increase in liver size and rupture of liver abscess. Sample collected on pigtail catheter insertion was also sent for culture.ResultsThe pus aspirate was received for bacterial and fungal culture. Aerobic bacterial culture yielded Klebsiella species. Examination with KOH Calcofluor revealed broad aseptate fungal hyphae. However, fungal culture did not yield any growth. Pain resistant (PDR) Klebsiella species was isolated from blood culture. Pigtail catheter sample also yielded the same. Aseptate fungal hyphae were observed in the pigtail catheter sample also. The team decided on conservative management and patient was started on intravenous amphotericin B deoxycholate(50 mg/day), tigecycline, and meropenem. Immunosuppressants were withheld. The clinical course worsened and the patient succumbed to illness after 18 days of antifungal therapy. The pus sample was then sent to the referral center PGIMER for PCR and sequencing where it was identified as Lichtheimia species.ConclusionMucormycosis is an increasingly emerging invasive fungal infection especially in immune-compromised patients, including solid organ transplant recipients. Though uncommon it is frequently a fatal mycosis in transplant patients. Hepatic mucormycosis in renal transplant recipients has been reported in three patients so far. None are due to Lichtheimia species. The diagnosis of hepatic mucormycosis was confirmed as microscopy was positive in two successive samples. Our patient also had bacteremia with PDR Klebsiella.Diagnosis is challenging and often delayed, as the clinical presentation is non-specific. Although mucormycosis in a renal transplant recipient is rare, a high index of suspicion and critical microscopic examination is warranted for early initiation of specific therapy which includes liposomal amphotericin B and surgery. Often cultures yield no growth and gene sequencing proves to be efficient and time-saving. This probably is the way ahead, especially for culture-negative samples to establish the etiological diagnosis.

P256 A rare case of co-infection with Nigrospora oryzae with mucormycosis in an immunocompromised post-COVID patient

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectiveA rare case of co-infection of Nigrospora oryzae with mucormycosis in an immunocompromised post-COVID patient.MethodsA 41-year-old male diabetic patient, with sub-optimal glycemic control, contracted COVID-19 infection and was managed with high-dose steroids. A month after recovery from COVID-19 infection, he developed severe headache with sudden onset right-sided facial swelling. A contrast-enhanced magnetic resonance imaging was done which was suggestive of infective/inflammatory rhinosinusitis with intracranial extension with a possibility of fungal etiology. Functional endoscopic sinus surgery was performed and tissue was sent for microbiological processing. On KOH mount, broad pauciseptate fungal hyphae were seen. Fungal growth was obtained on SDA at 25°C and 37°C within 4 days of inoculation. It was confirmed as Rhizopus arrhizus both phenotypically as well as by MALDI-TOF. Patient was put on antifungal therapy in form of Inj liposomal Amphotericin B 500 mg/d. However, patient had persistent headache, vomiting, and low-grade fever post-procedure. A repeat CE-MRI was performed which was suggestive of necrotic brain tumor/abscess and was planned for frontal lobe abscess drainage. Pus was inoculated on routine mycological media. On KOH mount, broad pauciseptate hyphae along with narrow septate hyphae were seen. Fungal growth was obtained on SDA at 25°C within 5 days of inoculation, which on LPCB were identified as Nigrospora spp. The identity of the isolate was confirmed by Next generation sequencing as Nigrospora oryzae. Post-2 weeks of treatment and strict glycemic control, patient started improving. The headache and swelling subsided. He was further started on oral hypoglycemic agents and discharged and was asked to follow up after a month.ResultsCOVID-19 epidemic that emerged by the end of 2019 has been associated with a huge number of deaths globally. Acute invasive fungal rhino-sinusitis is a potentially fatal infection in immune-compromised patients post COVID-19. Various studies reveal that invasive fungal infections have been the leading cause of death in 25%-73.7% of patients. Among these invasive fungal infections, Mucor spp. were detected in 77.8% patient, Aspergillus fumigatus in 30.6% while 8.3% showed mixed infection with both the fungi. Along with the established pathogenicity of Mucorales in causing invasive fungal infection, other fungal co-infections are also being observed. These invasive fungal infections in an immune-compromised host carry a high mortality and morbidity rate (18%-80%). Therefore, early diagnosis, followed by aggressive medical care, surgical debridement, and control of underlying diseases is of utmost importance.ConclusionAcute invasive fungal rhinosinusitis saw a spurt in incidence during the widespread COVID-19 pandemic.Diagnosis of invasive fungal infection is based on the clinical setting and characteristic presentation, supported by radiological and microbiological evidence. Prompt diagnosis and treatment are the need of the hour.

Regulation of Conidiogenesis in Aspergillus flavus.

Aspergillus flavus is a representative fungal species in the Aspergillus section Flavi and has been used as a model system to gain insights into fungal development and toxin production. A. flavus has several adverse effects on humans, including the production of the most carcinogenic mycotoxin aflatoxins and causing aspergillosis in immune-compromised patients. In addition, A. flavus infection of crops results in economic losses due to yield loss and aflatoxin contamination. A. flavus is a saprophytic fungus that disperses in the ecosystem mainly by producing asexual spores (conidia), which also provide long-term survival in the harsh environmental conditions. Conidia are composed of the rodlet layer, cell wall, and melanin and are produced from an asexual specialized structure called the conidiophore. The production of conidiophores is tightly regulated by various regulators, including the central regulatory cascade composed of BrlA-AbaA-WetA, the fungi-specific velvet regulators, upstream regulators, and developmental repressors. In this review, we summarize the findings of a series of recent studies related to asexual development in A. flavus and provide insights for a better understanding of other fungal species in the section Flavi.

Achromobacter species, an emerging cause of bacteremia in tertiary healthcare facilities in Egypt

During our laboratory routine, we detected Gram-negative, motile, aerobic, oxidase- and catalase-positive, lactose non-fermenting bacilli during microbial isolation from blood cultures of immune compromised patients. Our study investigates this phenomenon. Blood culture results from 1000 samples were taken during febrile attacks in immune compromised patients in adult intensive care units (AICUs), pediatric and neonatal intensive care units (PICUs and NICUs, respectively), liver and kidney departments, and oncology and hematology departments in a tertiary healthcare facility in Cairo, Egypt. The blood cultures were processed in the microbiology laboratory and incubated in an automated system. An automated system was also used to identify the species in positive cultures and perform antimicrobial susceptibility testing. Achromobacter sp. were identified and isolated according to their morphological and biochemical characteristics. Of one thousand blood cultures performed, 310 were positive (Gram-negative: 195, 63%; Gram-positive: 105, 34%; fungi: 10, 3%). Of these positive cultures, 16 (5.2%) were positive for Achromobacter sp., the most common being Achromobacter xylosoxidans (15/16, 93.75%), while A. dentrificans was identified in one case (6.25%). Among those affected, 37.5% were patients with hematological malignancies, 6.25% had organ transplants, 56.5% were in the ICUs (25% were in AICU, 18.8% in the PICU, and 12.5% in the NICU). Achromobacter sp. were resistant to cefepime, aminoglycosides, and fluoroquinolones. Central venous catheter infection occurred in 13 (81.25%) cases. Our findings open discussion concerning Achromobacter sp. as an opportunistic pathogen in immune compromised patients and contribute to the development of future treatment approaches.

Pathogenic role of cytokines in COVID-19, its association with contributing co-morbidities and possible therapeutic regimens.

The Covid-19, a threatening pandemic, was originated from China in December 2019 and spread quickly to all over the world. The pathogenesis of coronavirus is linked with the disproportionate response of the immune system. This involves the systemic inflammatory reaction which is characterized by marked pro-inflammatory cytokine release commonly known as cytokine release storm (CRS). The pro inflammatory cytokines are involved in cascade of pulmonary inflammation, hyper coagulation and thrombosis which may be lethal for the individual. That’s why, it is very important to have understanding of pro inflammatory cytokines and their pathological role in SARS-CoV-2. The pathogenesis of Covid is not the same in every individual, it can vary due to the presence of pre-existing comorbidities like suffering from already an inflammatory disease such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), chronic obstructive pulmonary disease (COPD), an immune-compromised patients suffering from Diabetes Mellitus (DM) and Tuberculosis (TB) are more vulnerable morbidity and complications following COVID-19. This review is particularly related to COVID-19 patients having comorbidity of other inflammatory diseases. We have discussed the brief pathogenesis of COVID-19 and cytokines release storm with reference to other co-morbidities including RA, IBD, COPD, DM and TB. The available therapeutic regimens for COVID-19 including cytokine inhibitors, anti-viral, anti-biotic, bronchodilators, JAK- inhibitors, immunomodulators and anti-fibrotic agents have also been discussed briefly. Moreover, newly emerging medicines in the clinical trials have also been discussed which are found to be effective in treating Covid-19.

Directing HIV-1 for degradation by non-target cells, using bi-specific single-chain llama antibodies

While vaccination against HIV-1 has been so far unsuccessful, recently broadly neutralizing antibodies (bNAbs) against HIV-1 envelope glycoprotein were shown to induce long-term suppression in the absence of antiretroviral therapy in patients with antibody-sensitive viral reservoirs. The requirement of neutralizing antibodies indicates that the antibody mediated removal (clearance) of HIV-1 in itself is not efficient enough in these immune compromised patients. Here we present a novel, alternative approach that is independent of a functional immune system to clear HIV-1, by capturing the virus and redirecting it to non-target cells where it is internalized and degraded. We use bispecific antibodies with domains derived from small single chain Llama antibodies (VHHs). These bind with one domain to HIV-1 envelope proteins and with the other domain direct the virus to cells expressing epidermal growth factor receptor (EGFR), a receptor that is ubiquitously expressed in the body. We show that HIV envelope proteins, virus-like particles and HIV-1 viruses (representing HIV-1 subtypes A, B and C) are efficiently recruited to EGFR, internalized and degraded in the lysosomal pathway at low nM concentrations of bispecific VHHs. This directed degradation in non-target cells may provide a clearance platform for the removal of viruses and other unwanted agents from the circulation, including toxins, and may thus provide a novel method for curing.

Class 1,2 Integron Genes Distribution in Pseudomonas aeruginosa Isolated from Clinical Specimens.

Pseudomonas aeruginosa, a Gram-negative human pathogen, P. aeruginosa is lone of the furthermost common hospital pathogens also is a chief concern, particularly in immune-compromised patients. The purpose of this study was to identify phenotypic and genotypic antibiotic resistance in Pseudomonas aeruginosa isolated from wound infection The bacterial isolates (30) were obtained from patients admitted to Mirjan Medical City in Babylon, Iraq (burns, wound unit). was identified biochemically and morphologically, and the isolates were subjected to standard bacteriological culturing processes on blood and MacConkey agar plates for 24-48 hours at 37oC for isolation and purification, Viteck 2 compact system confirmed the isolates and antibacterial sensitivity as well. These findings revealed that P.aeruginosa has a high rate of penicillin resistance, with a resistance rate of (100percent ) isolates. Advanced resistance to cephalosporin antibiotics was also found in resistant isolates of Cefoxitin, Ceftriaxone (75%), Ceftazidime, and cefepime (85%). For carbapenem antibiotics, had a high resistance rate (90percent). Aminoglycosides have variable resistance to Amikacin (60percent), Gentamicin (70 percent), and tobramycine resistant (90%). The findings revealed that all Pseudomonas aeruginosa isolates tested positive for Class 1,2 Integron resistance genes. with positive results (35%) for Int1 and 35% for Int2 (25%). This study found that P.aeruginosa has a high rate of resistance to Penicillins, Cephalosporin, Carbapenem and Aminoglycosides antibiotics.

High-dose radiation exposure of cold-stored whole blood does not affect hemostatic function.

Whole blood (WB) transfusion is routinely used to resuscitate severely injured military trauma patients. Blood can be stored refrigerated while still maintaining reasonable function but is susceptible to environmental influences, including radiation exposure. Immune-compromised patients are transfused with irradiated blood to inactivate donor lymphocyte function (25 Gy per Association for the Advancement of Blood and Biotherapies [AARB] standard 5.7.3.2). However, there is limited information on function of WB exposed to high radiation doses. This study aimed to determine if stored irradiated WB still retains function. This will be important if the stored blood supply is exposed to radiation in a combat situation or mass casualty incident when the need for blood will be high. Whole blood collected from healthy donors was irradiated at 0, 25, or 75 Gy and stored at 4°C. Blood cell count, blood gas chemistry, thromboelastometry, platelet aggregation, and reactive oxygen species were measured before irradiation and at 1, 7, and 14 days of storage. Irradiated WB was compared with nonirradiated WB controls. Irradiated WB stored for up to 14 days was not significantly different than nonirradiated WB in most of the parameters measured. Stored blood showed expected changes associated with functional decline at longer storage times, but irradiation did not hasten the decline. There was a significant change in potassium and sodium ion concentrations after irradiation, but the functional relevance is not clear. High-dose irradiation had little effect on stored WB. Although there were changes in plasma sodium and potassium levels, there was little to no effect on hemostasis and blood cell viability. This suggests that stored blood subjected to a radiation event generating at least a dose of 75 Gy is still suitable for transfusion, which could be particularly important in the event of a mass casualty event where a large amount of blood is needed.

Paraprobiotics and Postbiotics of Lactobacillus delbrueckii CIDCA 133 Mitigate 5-FU-Induced Intestinal Inflammation.

Intestinal mucositis is a commonly reported side effect in oncology practice. Probiotics are considered an excellent alternative therapeutic approach to this debilitating condition; however, there are safety questions regarding the viable consumption of probiotics in clinical practice due to the risks of systemic infections, especially in immune-compromised patients. The use of heat-killed or cell-free supernatants derived from probiotic strains has been evaluated to minimize these adverse effects. Thus, this work evaluated the anti-inflammatory properties of paraprobiotics (heat-killed) and postbiotics (cell-free supernatant) of the probiotic Lactobacillus delbrueckii CIDCA 133 strain in a mouse model of 5-Fluorouracil drug-induced mucositis. Administration of paraprobiotics and postbiotics reduced the neutrophil cells infiltrating into the small intestinal mucosa and ameliorated the intestinal epithelium architecture damaged by 5-FU. These ameliorative effects were associated with a downregulation of inflammatory markers (Tlr2, Nfkb1, Il12, Il17a, Il1b, Tnf), and upregulation of immunoregulatory Il10 cytokine and the epithelial barrier markers Ocln, Cldn1, 2, 5, Hp and Muc2. Thus, heat-killed L. delbrueckii CIDCA 133 and supernatants derived from this strain were shown to be effective in reducing 5-FU-induced inflammatory damage, demonstrating them to be an alternative approach to the problems arising from the use of live beneficial microorganisms in clinical practice.

Preparation, characterizations and in vitro evaluation of Econazole-Betamethasone loaded solid lipid nanoparticles (SLNs)

Tremendous increase of fungal infections in hospitalized or immune compromised patients has been reported from the last two decades. These infections are commonly treated using econazole and miconazole that have shorter half-life and produce severe side effects. All such issues can be addressed using targeted drug delivery. We developed SNLs based formulation for the treatment of mycosis. The high pressure homogenization method was employed for formulation followed by characterization, assay for antifungal activity, in vitro drug release and ex vivo permeation. The particle size of Econazole-Betamethasone-loaded SLNs, Econazole-loaded SLNs, Betamethasone-loaded SLNs and Blank SLNs were 377.4±23 nm, 298.7±9 nm, 177.7±15 nm and 113.4±6 nm respectively. The SEM images displayed that droplets are uniform and spherical in shape which ranged from 113.4±6 to 377.4±23 nm. In DSC, the SLNs formulation showed endothermic peak at 185.2 °C±0.9. Drug content of Econazole loaded SLNs was 82±0.1 and its entrapment efficiency was approximately 90.4±0.2. Betamethasone SLNs displayed highest drug content which was 83.5±0.4 while encapsulation efficiency of same formulation was 94.2±0.4. The Econazole and Betamethasone combined SLNs exhibited drug content of 80±0.3 while its encapsulation efficiency was 93.1±0.5. E-SLNs have significantly high drug release (p < 0.05) as compared to other formulation B-SLNs and EB-SLNs.The Econazole loaded formulations displayed antifungal activity with no synergistic or antagonistic effect with each other. Drug permeation from Econazole SLNs, Betamethasone SLNs and combined Econazole and Betamethasone SLNs was 45%, 40% and 38% respectively. Overall, SLN’s are an effective carrier for topical delivery of antifungals agents and that may be helpful in bypassing the serious side effects associated with oral delivery.

General practitioner knowledge gaps regarding live attenuated zoster vaccination of immunocompromised individuals: An ongoing concern?

Live attenuated herpes zoster vaccine (Zostavax [CSL/Merck]) was included on the Australian National Immunisation Program from 1 November 2016 for adults aged 70 years, with a catch-up program for adults aged 71-79 years. The aim of this study was to assess the knowledge of Australian general practitioners (GPs) regarding Zostavax. A national cross-sectional online survey was distributed to GPs by Healthed, a private health education provider. Of 605 GPs, 502 responded to the survey (response rate 83%). Eighty-nine per cent were aware that Zostavax is funded and recommended for adults aged 70-79 years. Approximately 10% incorrectly responded that immunocompromise is not a contraindication to Zostavax, and 8% were unsure. For five clinical scenarios assessing knowledge of Zostavax contraindications, theproportion of correct responses ranged 25-82%. While most GPs surveyed had good knowledge, notable gaps were identified. Further efforts are needed to promote awareness of recommendations, particularly for immunocompromised individuals. The availability of Shingrix, a non-live recombinant subunit zoster vaccine, in the private market provides an alternative, especially for immuncompromised patients.

Gender difference about superficial Fungl infections among immunocompromised patients in Dhi Qar governorate 2021-2022

Superficial fungal infections are caused by many fungi, which can invade various aspects of the human body which effect the skin, hair, and nails, are widely observed in the world. Causative agents are Candida species, dermatophytes, and Malassezia species. This study aims to knowledge gender difference about superficial fungal infections among immune compromised patients in Dhi Qar Governorate. A non-probability (convenience sample) of 500 sample were selected throughout the use of non-probability sampling approach. The study was conducted in six health institutions affiliated to the Dhi Qar Health Department, in addition to the medical clinics in the governorate. A questionnaire as a means for data collection, it consist of four parts include demographic data, diseases that weaken the immune system (Diabetes, cancer, leukemia, genetic blood diseases and kidney failure) , locations of the superficial fungal infection and risk factors. Through questionnaire the, data were collected and analyzed through the application of descriptive and inferential statistical data analysis approach. Most of the study sample aged 44 years, 310 (62%) of them were males, 190(38%) of them were female, about 346(69.2%) of them were from urban residence, about 227(45.4%) of them were not working, most of them were married 309(61.8%).

Perioperative anaesthetic challenges in coronavirus disease associated mucormycosis: A retrospective study

Background & Aim: Mucormycosis is a life-threatening fungal infection that occurs in immune-compromised patients. There were large number of mucormycosis cases reported during COVID pandemic (2019-21) mainly as post COVID sequelae. In the present retrospective study we aimed to evaluate the perioperative challenges faced in the anaesthetic management of Coronavirus disease associated Mucormycosis (CAM) patients who underwent surgery under general anesthesia. Methods: The perioperative records of CAM patients who underwent surgery from May 2021-July 2021 for mucormycosis were reviewed and evaluated in terms of difficult bag mask ventilation, difficult intubation and other intraoperative and post-operative complications. Observation and Results: The incidence of CAM and its associated surgery was significantly more in males than females and the mean age of the patients was 50 years. In 39.8% patients we encountered difficult bag mask ventilation. and in 17.5% patients more than two attempts for intubation were required. Conclusion: Mucormycosis patients posted for surgery may pose various anesthetic challenges especially in airway management and anesthesiologists must be well prepared for it

P1587: IS IT SAFE FOR OUR PATIENTS TO COME OUT?

Background: Vaccination against COVID-19 commenced in England in December 2020, most haematology patients iwere included in the first wave as they are identified as extremely vulnerable. A second dose was administered 12 weeks after the initial dose, and booster doses became available in September 2021. Severely immune compromised patients started to be contacted in December 2021 to offer them a fourth dose of vaccine. With the availability of treatments there arose a need for early confirmation of presence or absence of antibodies against COVID-19 and testing for antibody was introduced into routine practice for patients about to commence chemotherapy, or those who had yet to complete the four-dose protocol. On the 1st of March most restrictions imposed during the pandemic were removed, in the expectation that the majority of people would have protective antibodies from vaccination. Aims: Over a period of six months from October 2021 to February 2022 we tested 90 patients attending routine haematology clinics, with a number of conditions, mainly malignancy under follow-up or recieving treatment. We reviewed the results of these tests, to assess degree of protection Methods: Retrospective analysis of all requests for SARS-Cov antibody tests carried out in our patient populations. Results: There were 55 males, and 35 females, with an average age of 65y (range 24-90) The majority attended clinic for management of haematological malignancy (Plasma cell disorders, Chronic Leukaemia, Lymphomas) with a smaller number of patients being managed for congenital or immune conditions. - Diagnosis No detectable antibody Antibody<500 units Antibody > 500 units Plasma cell disorders 1 5 19 25 tests 22 patients CLL 13 8 5 26 tests in 20 patients HL 1 4 6 11 tests in 10 patients DLBCL 3 1 2 6 MPN 1 5 6 LGNHL 3 5 7 15 tests in 13 patients MCL 2 2 CML 3 3 Immune 2 2 4 Haemoglobinopathy 2 2 CMML 1 1 Total 23 29 49 Summary/Conclusion: Despite early availability of vaccines, and delivery of more than two doses to the majority of our patients, only half our patients had significant antibody response, and almost one quarter still had no detectable antibody. Although the number of new cases is reducing, in the vicinity of our hospital there were 483 new cases per 100,000 on the last day of February, and during the six months of this study two fully vaccinated patients with CLL with no detectctable antibody died in hospital with covid-19 pneumonitis. For some haematology patients particulalry those with CLL it is still not safe to come out.

Challenges posed by anti-inflammatory drugs in COVID-19 treatment

COVID-19 pandemic is the major outbreak that has exterminated many lives for past years and still not subsided completely. A number of vaccinations are in trials to eradicate the COVID-19 virus. This study deals with the challenges posed by anti- inflammatory drugs in the treatment of COVID-19.NSAID'S can mask early symptoms such as fever,myalgia in COVID-19 infected patients and can be used as adjunct therapy in severe COVID-19 treatment as they have anti-viral and anti-inflammatory properties. The risk of infection was found to be declined in the patients who had prior aspirin exposure. Indomethacin must be used with caution as it exhibits coronary vasoconstriction effects in patients. Anakinra even at higher doses resulted quite safe in COVID-19, confirming its potential role in selected conditions like immune compromised patients with superinfection, contraindications to other anti-inflammatory drugs. Early management with tocilizumab prevents cytokine strom and mortality. Patients who received Hydroxychloroquine with azithromycin combination had frequent cardiac arrest. No reasons to pause NSAIDs and no evidence of mortality rate dissimilarity between ibuprofen and paracetamol in COVID-19. still paracetamol remains first line. WHO guidelines recommend to avoid corticosteroids in COVID-19 management.

English

Pseudomonas aeruginosa causes infections in humans, particularly immune-compromised patients with cystic fibrosis, severe burns, and HIV, resulting in high morbidity and mortality. The pathogenic bacteria, P.&nbsp;aeruginosa, produces virulence factors regulated by the mechanism called quorum sensing system. The aim of this study was to assess the anti-quorum sensing activity of Ageratum conyzoides extracts. Chloroform fraction from hydro-methanolic extract at the sub-inhibitory concentration of 100 &micro;g/mL reduced quorum sensing virulence factors production such as pyocyanin, elastases, and rhamnolipids in P. aeruginosa PAO1 after 8 and 18 h monitoring. Moreover, a significant inhibition in HSL-mediated violacein production on C. violaceum CV026 was recorded after 24 and 48 h monitoring without affecting the bacterial growth. The chloroform fraction was rich in polyphenols and triterpenes, and was found to interact with QS receptors. The regulatory genes (rhlR and lasR) and downstream genes [EC3]&nbsp;(RhlA and lasB) were the most affected, while synthase genes (lasI and rhlI) were the least affected. High-performance liquid chromatography with diode-array detection (HPLC-DAD) analysis allowed the identification and quantification of some compounds such as gallic acid, vanillic acid, ellagic acid, sinapic acid, and quercetin. Caffeic acid, rutin, and kaempferol were detected in trace amounts. The presence of these phytochemicals could be responsible for the observed anti-quorum activity. The present study is probably the first attempt to investigate the anti-QS potential of A. conyzoides against P. aeruginosa. These data provide additional scientific evidence to justify the wide use of A. conyzoides in traditional medicine in Burkina Faso. Key words: Ageratum conyzoides, Chromobacterium violaceum, Pseudomonas aeruginosa, quorum sensing.

Complexities of JC Polyomavirus Receptor-Dependent and -Independent Mechanisms of Infection.

JC polyomavirus (JCPyV) is a small non-enveloped virus that establishes lifelong, persistent infection in most of the adult population. Immune-competent patients are generally asymptomatic, but immune-compromised and immune-suppressed patients are at risk for the neurodegenerative disease progressive multifocal leukoencephalopathy (PML). Studies with purified JCPyV found it undergoes receptor-dependent infectious entry requiring both lactoseries tetrasaccharide C (LSTc) attachment and 5-hydroxytryptamine type 2 entry receptors. Subsequent work discovered the major targets of JCPyV infection in the central nervous system (oligodendrocytes and astrocytes) do not express the required attachment receptor at detectable levels, virus could not bind these cells in tissue sections, and viral quasi-species harboring recurrent mutations in the binding pocket for attachment. While several research groups found evidence JCPyV can use novel receptors for infection, it was also discovered that extracellular vesicles (EVs) can mediate receptor independent JCPyV infection. Recent work also found JCPyV associated EVs include both exosomes and secretory autophagosomes. EVs effectively present a means of immune evasion and increased tissue tropism that complicates viral studies and anti-viral therapeutics. This review focuses on JCPyV infection mechanisms and EV associated and outlines key areas of study necessary to understand the interplay between virus and extracellular vesicles.

Molecular Detection of VEB and OXA-23 Resistance Gene in Pseudomonas Aeruginosa Isolates at Dr. Wahidin Sudirohusodo Hospital Makassar

Pseudomonas aeruginosa is a common gram-negative pathogen in nosocomial infections in immune-compromised patients. It exhibits high rates of intrinsic resistance to many classes of antibiotics, especially beta-lactam antibiotics. Production of extended-spectrum beta-lactamase (ESBL) and genes belonging to the carbapenem-hydrolyzing class D subgroup β-lactamases (CHDL) are a problem for increasing antibiotic resistance worldwide. This study aimed to identify P. aeruginosa containing the VEB and OXA-23 genes. Eighty-five clinical isolates of P. aeruginosa from various clinical samples were identified and tested for antimicrobial susceptibility using VITEK 2 compact. VEB and OXA-23 genes were detected using the Polymerase Chain Reaction (PCR) method. The PCR results revealed that 13 (15.3%) of P. aeruginosa isolates were positive OXA-23 gene, but no isolate positive for the VEB gene in P. aeruginosa isolates. The study results demonstrated the spread of the OXA-23 gene in P. aeruginosa isolates at Dr. Wahidin Sudirohusodo Hospital Makassar.

Prospective Medicinal Plants and Their Phytochemicals Shielding Autoimmune and Cancer Patients Against the SARS-CoV-2 Pandemic: A Special Focus on Matcha.

BackgroundBeing “positive” has been one of the most frustrating words anyone could hear since the end of 2019. This word had been overused globally due to the high infectious nature of SARS-CoV-2. All citizens are at risk of being infected with SARS-CoV-2, but a red warning sign has been directed towards cancer and immune-compromised patients in particular. These groups of patients are not only more prone to catch the virus but also more predisposed to its deadly consequences, something that urged the research community to seek other effective and safe solutions that could be used as a protective measurement for cancer and autoimmune patients during the pandemic.AimThe authors aimed to turn the spotlight on specific herbal remedies that showed potential anticancer activity, immuno-modulatory roles, and promising anti-SARS-CoV-2 actions.MethodologyTo attain the purpose of the review, the research was conducted at the States National Library of Medicine (PubMed). To search databases, the descriptors used were as follows: “COVID-19”/”SARS-CoV-2”, “Herbal Drugs”, “Autoimmune diseases”, “Rheumatoid Arthritis”, “Asthma”, “Multiple Sclerosis”, “Systemic Lupus Erythematosus” “Nutraceuticals”, “Matcha”, “EGCG”, “Quercetin”, “Cancer”, and key molecular pathways.ResultsThis manuscript reviewed most of the herbal drugs that showed a triple action concerning anticancer, immunomodulation, and anti-SARS-CoV-2 activities. Special attention was directed towards “matcha” as a novel potential protective and therapeutic agent for cancer and immunocompromised patients during the SARS-CoV-2 pandemic.ConclusionThis review sheds light on the pivotal role of “matcha” as a tri-acting herbal tea having a potent antitumorigenic effect, immunomodulatory role, and proven anti-SARS-CoV-2 activity, thus providing a powerful shield for high-risk patients such as cancer and autoimmune patients during the pandemic.

Systemic White Blood Cell Count as a Biomarker for Malignant Cerebral Edema in Large Vessel Ischemic MCA Stroke

ObjectivesLarge middle cerebral artery (MCA) strokes remain a major cause for mortality and morbidity all over the world, and therefore early identification of patients with the highest risk for malignant cerebral edema is crucial for early intervention. Neutrophils to lymphocytes ratio (NLR) and peripheral total white blood cell (WBC) count are inflammatory markers done routinely for all patients, and this study evaluated the use of NLR and elevated white blood cell count within the first 24 h of MCA ischemic stroke onset, with the absence of significant hemorrhagic transformation, to predict malignant cerebral edema. Materials and methodsA total of 156 patients with large MCA strokes were included. We collected demographic, clinical, radiological data, and NLR and WBCs within the first 24 h from admission.We excluded patients who had any underlying infections diagnosed 7 days before or within 72 h after admission. We used a body temp of 38 C or more, abnormal CXR or abnormal urine analysis within the first 72 h to exclude patients with possible infections.We excluded immune-compromised patients and patients on steroid therapy. We compared the NLR and WBC count in patients who developed malignant cerebral edema versus the patients who did not. NLR > 3.5 and < 3.5 was used for comparison. We then conducted multivariate logistic regression models to explore the relationship between cerebral edema, WBCs and NLR count simultaneously. ResultsNLR, WBC, radiological involvement of more than 50% of MCA territory infarction on presentation, hyperdense MCA sign, and NIH stroke scale were all significantly higher in patients with malignant cerebral edema within the first 24 h. Using univariate logistic regression, NLR performs better than WBC when predicting the occurrence of malignant cerebral edema (AUC = 0.74 vs. 0.62). However, NIH stroke scale scores, and radiological involvement of more than 50% of MCA territory infarction on the first 24 h of presentation on CT scan both showed better discriminative performance for malignant cerebral edema than NLR (AUC = 0.84 and 0.76, respectively). When combined, NLR > 3.5 paired with the NIH stroke scale score had the best predictive performance (AUC = 0.87). ConclusionNLR > 3.5 can be used for early prognostication in patients with large vessel MCA ischemic strokes with no significant hemorrhagic transformation within the first 24 h regardless if they had reperfusion therapy or not. Combining NLR of > 3.5 in addition to high NIHSS provided the best predictive model in our study. Further studies are needed to further develop the best predictive model in diverse populations.