Severe Infectious Disease Research Articles

The association of high Vancomycin trough concentration with acute kidney injury during combination therapy of Piperacillin/Tazobactam and Vancomycin

BackgroundCo-administration of Piperacillin/Tazobactam (PIPC/TAZ) and Vancomycin (VCM) as an antibiotic therapy for severe infectious diseases increases the risk of nephrotoxicity. We retrospectively investigated the utility of monitoring VCM trough concentration in early stage of developing acute kidney injury (AKI) on this combination therapy. MethodsWe enrolled all infectious disease patients who were managed with concurrent PIPC/TAZ and VCM. The record of dosage and the administration interval of each antibiotic and its clinical parameters, as well as the VCM trough concentrations, blood culture for bacteria, and serum creatinine values, were collected. VCM trough concentration was measured during the initial 48–72 h of VCM administration. Nephrotoxicity was evaluated as the degree of AKI. ResultsA total of 47 patients fulfilling the criteria were registered, and AKI developed in 10 patients. There was no statistical difference between the AKI and non-AKI groups with regard to age, height, weight, basal creatinine level, body surface area, body mass index, PIPC/TAZ dose, VCM dose, gender, artificial management, and death within around 30 days. The VCM trough level was increased significantly in the AKI group (mean [standard deviation {SD}]: 25.9 [7.8] μg/mL) compared to that in the non-AKI group (mean [SD]: 15.7 [6.9] μg/mL) (p = 0.003). During the clinical course, renal function returned to normal levels in three out of four AKI stage 2 patients, whereas only partial recovery was achieved in all AKI stage 3 patients. ConclusionsA high VCM trough concentration may have an influence on the occurrence of AKI during combination therapy of PIPC/TAZ and VCM. Careful monitoring of VCM trough concentration will be required to prevent AKI progression.

A Comparison of Regional Brain Volumes in Older Adults With and Without History of COVID-19: Региональные объемы мозга у пожилых людей с наличием и отсутствием COVID-19 в анамнезе.

Recent studies have shown that SARS-CoV-2 can have neuropsychiatric consequences and has the ability to penetrate the blood-brain barrier. If SARS-CoV-2 has a specific route of entry into the brain, it may leave imprints in the form of specific changes in brain morphology. Older individuals are most vulnerable to the neuropsychiatric COVID-19 complications. This study aims to compare regional brain volumes in older adults individuals with and without COVID-19 history (COVID+ and COVID-, respectively). Individuals over 65 years old who applied for treatment to the Memory Clinic (Mental-Health Clinic No. 1 named after N.A. Alexeev, Moscow, Russia) were assessed between October 2020 and April 2021. Their COVID-19 history was determined by the self-report and COVID-19 certificate. Individuals with severe neuropsychiatric or acute or severe chronic somatic or infectious disease and those taking medications potentially affecting cognitive functioning were excluded. All participants underwent MRI examinations followed by image segmentation and morphometric quantitative analysis. Regional brain volumes were compared in COVID+ and COVID- people. 207 participants were included in the study. The COVID+ group consisted of 24 participants. The comparison between groups revealed statistically significant differences in left amygdala area (median 1199.3 mm3 in COVID+ vs. 1263.7 mm3 in COVID-) and right postcentral gyrus volumes (median 8055.5 mm3 in COVID+ vs. 8434.0 mm3 in COVID-). Then case-control analysis was performed in individuals matched for gender, age and common somatic causes of structural brain changes (hypertension and/or diabetes mellitus type 2) for 22 subjects in each group. Statistically significant differences in regional brain volumes between groups were absent. We did not find strong evidence for any regional brain volumes changes in people older than 65 years with a history of COVID-19 in comparison to those without history of COVID-19. Though, given study limitations, these results cannot be generalized to other people who recovered from COVID-19.

Seroprevalence Investigation of Classic Swine Fever Virus Before, During, and After African Swine Fever Virus Outbreak in Some Provinces of China from 2017 to 2021.

Classic swine fever is a severe infectious and fatal disease in pigs caused by the classic swine fever virus (CSFV). Surveillance and investigation for CSFV seroprevalence contribute to knowing the immune efficiency of CSFV vaccines and reflect health status of swine herd, especially since the African swine fever virus (ASFV) outbreak in China in 2018. A total of 40,489 pig serum samples with related descriptive variables were obtained from 12 provinces and 2 cities of China from December 2017 to May 2021, covering before, during, and after three periods of ASFV outbreak. Pearson chi-square test and multivariable logistic regression analysis were used to identify impact factors related to variations in CSFV seroprevalence. Total CSFV seroprevalence was 60.40% (95% confidence interval: 59.92-60.88). Seroprevalence and antibody blocking rate mean of CSFV before outbreak of ASFV in China are higher and change gently compared with that after outbreak of ASFV. Serum collected from "summer and autumn," "north, southwest and northwest of China," "pig farm located in hill or mountain," " period before outbreak of ASFV," "PRRSV negative farm," and "replacement gilts, multiparous sows and boars" show high seroprevalence of CSFV. These results show trends in prevalence of CSFV antibody in recent years in China, especially when ASFV entered China. Identified impact factors provide references for improving immune efficiency of CSFV vaccine and benefit for prevention of CSFV.

Combined in-vitro and on-farm evaluation of commercial disinfectants used against Brachyspira\xa0hyodysenteriae

BackgroundSwine dysentery (SD) is a severe infectious disease with a relevant impact on pig production usually caused by Brachyspira hyodysenteriae, although B. hampsonii causes an identical clinical picture. SD control relies on antimicrobials, good management practices and strict biosecurity with cleaning and disinfection as crucial tools to avoid the pathogen transmission. This study evaluates the in-vitro efficacy of an array of commercial disinfectants against a collection of B. hyodysenteriae isolates using broth tests. The efficacy of cleaning and disinfection protocols was also evaluated on two farms with endemic SD using surface swabs collected in emptied pens before and after cleaning and disinfection procedures, using both real-time PCR and bacterial microbiological culture.ResultsMost of the commercial disinfectants evaluated were effective against all B. hyodysenteriae isolates tested, with a reduction of more than 5.00 log10 CFU/mL (bactericidal efficacy of 99.999%). However, some isolates exhibited reduced susceptibility to Virkon-S and Limoseptic disinfectants. The evaluation of cleaning and disinfection protocols on farms with SD outbreaks showed that approximately half the pens tested (n = 25) were positive by real-time PCR after pigs removal (mean B. hyodysenteriae counts 5.72 ± 1.04 log10 CFU/mL) while almost 20% of the pens remained positive after cleaning (n = 7) and disinfection (n = 5) procedures although with significantly lower, mean estimates (4.31 ± 0.43 log10 CFU/mL and 4.01 ± 0.55 log10 CFU/mL, respectively).ConclusionsThese results show the efficacy of disinfectants against B. hyodysenteriae but also stress the need to implement adequately the cleaning and disinfection protocols on pig farms and review and revise their efficiency periodically.

Clinical, Epidemiological and Microbiological Profile of A Potentially Pathogenic Environmental Saprophyte, Burkholderia pseudomallei; at A Tertiary Care Hospital in Coastal India

Melioidosis is a severe systemic infectious disease caused by Burkholderia pseudomallei, a gram-negative bacillus with bipolar staining. It is an environmental saprophyte endemic to Southeast Asia and Northern Australia. The disease can have varying manifestations. This is a retrospective study of the clinical and microbiological profile of culture-proven cases of melioidosis who presented to a tertiary care hospital in Coastal Karnataka between January 2018 and December 2020. The epidemiological, demographic, clinical and laboratory characteristics were studied and analyzed. A total of 27 cases were seen during the study period. All patients were from the western coastal areas of India. Fever was the most common presenting complaint. Analysis of the clinical manifestations showed 11 (40.74%) with bacteremia. Pneumonia was the most common primary clinical presentation with 11 cases (40.74%). 9 (33.3%) patients had an abscess in some part of the body on presentation. Secondary foci were seen in 5 (18.5%) patients. The prominent risk factors seen were history of type 2 diabetes mellitus, age >40 years, alcoholism and smoking. 13 (48.15%) were started with the treatment regimen for melioidosis. Only 8 (29.63%) were prescribed the eradication treatment regimen. One case which was inadequately treated came back with reactivation of melioidosis. Varied clinical presentation of melioidosis makes the specific clinical diagnosis difficult. Due to the high mortality and morbidity rate, early diagnosis and prompt management is warranted, this requires clinical vigilance and an intensive microbiological workup. Lack of adherence to the treatment protocol can lead to reactivation.

Visual analysis of social events and stock market volatility in China and the USA during the pandemic.

The COVID-19 pandemic is one of the most severe infectious diseases in recent decades, and has had a significant impact on the global economy, and the stock market. Most existing studies on stock market volatility during the pandemic have been conducted from a data science perspective, with statistical analysis and mathematical models often revealing the superficial relationship between Covid and the stock market at the data level. In contrast, few studies have explored the relationship between more specialised aspects of the pandemic. Specifically, the relationship found between major social events and the stock market. In this work, a multi-source, data-based relationship analysis method is proposed, that collects historical data on significant social events and related stock data in China and the USA, to further explore the potential correlation between stock market index fluctuations and the impact of social events by analysing cross-timeline data. The results suggest and offer more evidence that social events do indeed impact equity markets, and that the indices in both China and the USA were also affected more by the epidemic in 2020 than in 2021, and these indices became less affected by the epidemic as it became the world adapted. Moreover, these relationships may also be influenced by a variety of other factors not covered in this study. This research, so far, is in its initial stage, and the methodology is not rigorous and cannot be applied as an individual tool for decision; however, it could potentially serve as a supplementary tool and provide a multi-dimensional basis for stock investors and policymakers to make decisions.

Modelling and stability analysis of ASFV with swill and the virus in the environment.

African swine fever (ASF) is an acute, hemorrhagic and severe infectious disease caused by the African swine fever virus (ASFV), and leads to a serious threat to the pig industry in China. Yet the impact of the virus in the environment and contaminated swill on the ASFV transmission is unclear in China. Then we build the ASFV transmission model with the virus in the environment and swill. We compute the basic reproduction number, and prove that the disease-free equilibrium is globally asymptotically stable when $ R_0 < 1 $ and the unique endemic equilibrium is globally asymptotically stable when $ R_0 > 1 $. Using the public information, parameter values are evaluated. PRCCs and eFAST sensitivity analysis reveal that the release rate of ASFV from asymptomatic and symptomatic infectious pigs and the proportion of pig products from infectious pigs to swill have a significant impact on the ASFV transmission. Our findings suggest that the virus in the environment and contaminated swill contribute to the ASFV transmission. Our results may help animal health to prevent and control the ASFV transmission.

Role and significance of tracheotomy in intensive care units in coronavirus disease 2019-positive patients

Introduction. The role of tracheotomy in the treatment of patients with prolonged intubation in intensive care units is known and confirmed. In light of the global pandemic of severe acute respiratory syndrome coronavirus-2 infection and consequent coronavirus disease 2019, we present our experiences with tracheotomy in infected patients. Material and Methods. A retrospective observational study of patients treated in intensive care units at the Clinical Hospital Center ?Dr. Dragisa Misovic Dedinje? was carried out in the period from March 21, 2020 to May 14, 2020. Results. A total of 970 coronavirus disease 2019-positive patients were treated and out of that number, 116 patients were treated in intensive care units (12%), of which 49 patients (42%) were on non-invasive mechanical ventilation and 67 patients (58%) on intensive mechanical ventilation. The average age of the patients was 59.3 years; the youngest patient was 46, and the oldest 73 years old. Tracheotomy was performed in 24 patients (21%), in 13 males (54.1%) and 11 females (45.9%). The mean time from intubation to tracheotomy was 11.6 days. Of the 24 tracheotomized patients, 12 had a successful decannulation (50%) and were discharged from intensive care units, 6 had a lethal outcome, and 6 patients were in treatment. Discussion. All the patients underwent tracheotomy in the hospital room, because we considered that any transfer and manipulation of these severe patients may lead to worsening of the generally serious condition. Although some guidelines recommend that it would be ideal to know the coronavirus disease 2019 status before any invasive procedure, we believe that this is not necessary, especially considering the clinical picture of patients during the pandemic, as well as computed tomography findings in the lungs. Conclusion. Tracheotomy has an important place in the treatment of patients with severe coronavirus disease 2019 infection since it provides easier maintenance of the airway, and in the recovery phase leads to easier transition of patients from mechanical ventilation to spontaneous breathing. The decision on the day when the tracheotomy will be performed is strictly individual and depends on the general condition of the patient, and the use of thermocautery does not affect the course of treatment and the final outcome.

Epidemiology and laboratory diagnosis of very virulent infectious bursal disease virus in vaccinated chickens in Khartoum, Sudan.

Background:Infectious Bursal Disease (IBD, Gumboro disease) has become more severe than in early outbreaks in the 1980s. The present research aims to study the epidemiology of IBD in Khartoum state and compare some commonly used laboratory techniques for diagnosis.Method:We collected epidemiological data from 30 farms that showed signs suggestive of IBD, estimated the morbidity and mortality rates, and interviewed the owners about the type and the doses of the used vaccines. We collected bursas of Fabricius for virus assays and histopathology. Samples positive in the agar gel immunodiffusion (AGID) test were inoculated onto chicken embryo fibroblast cell culture and embryonated chicken eggs. Twenty-two-day-old chicks were infected experimentally with three selected isolates, and morbidity and mortality rates were compared.Results:The results showed that 70% of outbreaks occurred between 6 and 8 weeks of age, and the mean mortality rate was 51%. Epidemiologic, clinical, gross, and histopathological findings were characteristic of the severe disease caused by the very virulent IBDvirus (vvIBDV). The farms that used intermediate or the intermediate plus vaccines had lowered mortality compared with the farms that used intermediate vaccines. The AGID was found more sensitive than the counter-immuno-electrophoresis (CIEP) since it detected 83.4% of the IBDV antigen in the samples while the CIEP detected 66.7% of the samples. The reverse transcriptase polymerase chain reaction (RT-PCR) was found to be rapid, specific, and was more sensitive detecting 100% of the tested samples. Virus isolation in embryonated eggs and cell culture was not successful.Conclusion:A vvIBDV is responsible for the recent outbreaks of the disease in Sudan, resulting in a mean high mortality rate of 51%, even in vaccinated flocks. The RT-PCR and AGID are the best methods for laboratory confirmation.

Establishment and application of a solid-phase blocking ELISA method for detection of antibodies against classical swine fever virus.

BackgroundClassical swine fever (CSF) is a severe infectious disease of pigs that causes significant economic losses to the swine industry.ObjectivesThis study developed a solid-phase blocking enzyme-linked immunosorbent assay (spbELISA) method for the specific detection of antibodies against the CSF virus (CSFV) in porcine serum samples.MethodsA spbELISA method was developed based on the recombinant E2 expressed in Escherichia coli. The specificity of this established spbELISA method was evaluated using reference serum samples positive for antibodies against other common infectious diseases. The stability and sensitivity were evaluated using an accelerated thermostability test.ResultsThe spbELISA successfully detected the antibody levels in swine vaccinated with the C-strain of CSFV. In addition, the detection ability of spbELISA for CSFV antibodies was compared with that of other commercial ELISA kits and validated using an indirect immunofluorescence assay. The results suggested that the spbELISA provides an alternative, stable, and rapid serological detection method suitable for the large-scale screening of CSFV serum antibodies.ConclusionsThe spbELISA has practical applications in assessing the vaccination status of large pig herds.

Preparation and Biocompatibility Evaluation of Nanoscale Isoniazide-Loaded Mineralized Collagen Implants for Tuberculous Bone and Joint Repair.

Bone and joint tuberculosis is an extremely severe infectious disease that commonly occurs due to the primary infection of a type of mycobacteria, called Mycobacterium tuberculosis. Under the current scenario, there are very limited supplies of bone grafts available for the treatment of deceased bone, including autogenous bone and synthetic biomaterials. The present study aimed to construct a nanoscale isoniazid-loaded mineralized collagen implant, and then to explore its physicochemical properties and to investigate its biocompatibility suitable for bone and joint repair. Using type I collagen as raw material and the principle of biomimetic mineralization for self-assembly of bone tissue, a new drug-loaded mineralized collagen implant was constructed by molecular coprecipitation with isoniazid. Its surface morphology, elemental composition, and porosity were characterized by field emission scanning electron microscope (SEM), X-ray diffraction (XRD), and pycnometer. The performance of the implant was gauged by sustained release and degradation, which were studied using an ultraviolet spectrophotometer and a simulated in vivo environment. The drug loading and encapsulation rates of the implants were (6.25 ± 0.48)% and (54 ± 2.34)%, respectively. The in vitro release time of the scaffold was more than 12 weeks and the degradation performance was excellent. The scaffold was then implanted into mice, and the inflammatory reaction of local tissue was observed by Haemotoxylin and Eosin (H&E) and Masson. The in vivo evaluation in mice showed that the scaffold was biocompatible. Overall, compared with traditional drug loading systems, the isoniazid biomimetic mineralized collagen implant constructed here has better drug release performance, biodegradability, and biocompatibility. This kind of collagen implant may find potential applications in tuberculous bone and joint repair.

Solution Structure of the BPSL1445 Protein of Burkholderia pseudomallei Reveals the SYLF Domain Three-Dimensional Fold.

The SYLF domain is an evolutionary conserved protein domain with phosphatidylinositol binding ability, whose three-dimensional structure is unknown. Here, we present the solution structure and the dynamics characterization of the SYLF domain of the bacterial BPSL1445 protein. BPSL1445 is a seroreactive antigen and a diagnostic marker of Burkholderia pseudomallei, the etiological agent of melioidosis, a severe infectious disease in the tropics. The BPSL1445 SYLF domain (BPSL1445-SYLF) consists of a β-barrel core, with two flexible loops protruding out of the barrel and three helices packing on its surface. Our structure allows for a more precise definition of the boundaries of the SYLF domain compared to the previously reported one and suggests common ancestry with bacterial EipA domains. We also demonstrate by phosphatidyl-inositol phosphate arrays and nuclear magnetic resonance titrations that BPSL1445-SYLF weakly interacts with phosphoinositides, thus supporting lipid binding abilities of this domain also in prokaryotes.

Review and Thinking on Forensic Pathological Changes of Coronavirus-Infected Diseases.

Since the beginning of this century, three types of coronavirus have widely transmitted and caused severe diseases and deaths, which strongly indicates that severe infectious diseases caused by coronavirus infection are not accidental events. Coronavirus-infected diseases are mainly manifested by respiratory symptoms, with multiple organ dysfunctions. Precisely investigating the pathological process, characteristics and pathogenesis of coronavirus-infected diseases will be beneficial for us to understand clinical manifestations and provide targeted suggestions on prophylaxis and treatment. This paper briefly reviews the pathological findings of three known coronavirus-infected diseases, and attempts to construct the pathological spectrum of coronavirus-infected diseases, aiming to provide reference and thinking for autopsy, histopathological examination and animal infection model study of coronavirus-infected diseases.

Chest Imaging in the Diagnosis and Management of Pulmonary Tuberculosis: The Complementary Role of Thoraci Ultrasound.

Tuberculosis (TB) is a severe infectious disease that still represents a major cause of mortality and morbidity worldwide. For these reasons, clinicians and radiologists should use all the available diagnostic tools in the assessment of the disease in order to provide precise indications about starting an anti-tubercular treatment and reduce risk of TB transmission and complications especially in developing countries where the disease is still endemic. As TB mycobacteria are mainly transmitted through respiratory droplets, the pulmonary parenchyma is usually the first site of infection. As a result, chest imaging plays a central role in the diagnostic process. Thoracic ultrasound (TUS) is a portable, non-invasive, radiation-free, and cost-contained technology which could be easily available in resource-limited settings. This perspective article focuses on the potential role of TUS in the diagnosis and management of patients with pulmonary TB. Unfortunately, there are still insufficient evidence and too contrasting data to judge TUS as an appropriate diagnostic method for the screening of the disease. Despite this, TUS may have a useful role in identifying pleural and anterior pericardial effusions or in the identification of abscesses of the anterior chest wall and paraspinal collections in low- and middle-income settings. In addition, TUS seems to have a milestone role in guiding minimally invasive interventional procedures, such as placement of chest tubes, drainage of loculated collections, thoracentesis and pericardiocentesis, and percutaneous biopsy of subpleural pulmonary consolidations or pleural plaques.

B. , A. , I.S. , A.S. , B.G.

Background. Vaccination is one of the greatest advancements in medicine regarding prevention of severe infectious diseases. The current COVID-19 pandemic placed a tremendous burden on the shoulders of national and international health and governmental authorities, which fueled a common effort to produce a vaccine against this disease. <br />Material and method. The authors performed a prospective quantitative research, based on an on-line questionnaire, regarding the attitude of medical students studying in Romania toward COVID-19 vaccination and the factors that influence their decision. <br />Results. 511 students participated in the survey, both Romanian and foreign students, of which 78.3% agree with COVID-19 vaccination. The following factors influenced positively the decision to accept the vaccine: studying in Romanian language, having acquaintances suffering from COVID-19, taking care of COVID-19 patients, positive attitude towards vaccines in general, trusting the authorities, having a higher level of fear of infection and a lower level of fear of side effects. <br />Conclusions. The results of our study highlighted the factors that influence the attitude of medical students towards vaccination. Given that the future doctors will have a decisive role in consolidating a safer and more certain future of medicine, it is important that these factors are addressed and targeted by the strategic programs to make them understand the importance of immunization of the population against severe infectious diseases.

Comparisons of the clinical and mycological characteristics of pediatric candidemia

Invasive candidiasis is a severe infectious disease that could lead to mortality in critically ill children. We collected data regarding demographics, underlying diseases, predisposing factors, outcomes for pediatric patients with candidemia at a medical centre in Taiwan from 2011 to 2017. Fifty-eight patients with 60 candidemia episodes were diagnosed. The 3 most common species were Candida albicans (42%), Candida parapsilosis (25%) and Candida tropicalis (23%). C. parapsilosis predominantly infected infants and neonates (median age: 0.8 years, range: 0.1-14.5). Cases with C. tropicalis had significantly higher rates of multidrug resistance (p=0.011) and disseminated candidiasis (p=0.025) compared with other cases. The all-cause mortality rate was 43%, and the candidemia-related mortality rate was 29%. Pediatric sequential organ failure assessment score >8 [adjusted odds ratio (aOR) 66.2, 95% CI 4.03-1088.5] and posaconazole resistance (aOR 33.57, 95% CI 1.61-700.3) were the most significant risk factors associated with candidemia-related mortality, whereas treatment with effective antifungal agents within 48h (aOR 0.07, 95% CI 0.01-0.9) was the only significant protective factor. Candidemia-related mortality was related to azole resistance; therefore, empirical therapy with echinocandin or amphotericin B is recommended pending species and susceptibility results.

Antibiotic sensitivity of Pseudomonas aeruginosa strains isolated from milk of highly productive dairy cows

Pseudomonas aeruginosa is a free-living bacterium that is conditionally pathogenic in natural conditions, but when ingested by an animal can cause severe infectious diseases, depending on the location and stage of infection, increasing the time of convalescence. It is naturally resistant to a number of widely used antibacterial drugs: fluoroquinolones, tetracyclines, chloramphenicol; it is capable of forming a biofilm. The aim of this work was to assess the level of sensitivity of strains isolated from cow's milk to the main groups of antibiotics with clinically significant anti-pseudomonasal activities. The work provides microbiological monitoring data for 2020-2021. During this period, 350 milk samples were taken from Holstinized black-and-white cows of the dairy direction of various lactation ages. All isolates were characterized by generally accepted phenotypic methods, with confirmation of biochemical properties. A number of antibiotics selected in this work comply with the recommendations of EUCAST. Sensitivity testing of the isolated strains was carried out by the disco-diffuse method. Pseudomonas aeruginosa was detected in 69 milk samples, which accounted for 19.7% of the total number of milk samples. Pseudomonas Aeruginosa was isolated as a monoculture in 42.03% of cases, in association with gram (-) bacteria in 20.29% and gram (+) in 37.68%. The percentage of pigmented strains in our work was 98.55% of all isolated strains, and 1.45% of poorly pigmented. During the research work, it was found that more than 90% of the strains were resistant to cefepime, the rest showed partial resistance. Therefore, it can be recommended for use only after a correction for sensitivity to this drug. The aminoglycoside group drugs, amikacin and gentamicin, had the highest activity - over 90% against the isolated Ps.a. strains. The results obtained indicate that the isolated strains of Ps.a. they showed high resistance to representatives of the cephalosporin group, which is also increasing with respect to fluoroquinolones, which is a serious problem in the spread of antibiotic resistance.

African Swine Fever Virus pI215L Negatively Regulates cGAS-STING Signaling Pathway through Recruiting RNF138 to Inhibit K63-Linked Ubiquitination of TBK1.

African swine fever is a severe animal infectious disease caused by African swine fever virus (ASFV), and the morbidity and mortality associated with virulent ASFV isolates are as high as 100%. Previous studies showed that the ability of ASFV to antagonize IFN production is closely related to its pathogenicity. Here, we report that ASFV HLJ/18 infection induced low levels of type I IFN and inhibited cGMP-AMP-induced type I IFN production in porcine alveolar macrophages that were isolated from specific pathogen-free Landrace piglets. Subsequently, an unbiased screen was performed to screen the ASFV genes with inhibitory effects on the type I IFN production. ASFV pI215L, a viral E2 ubiquitin-conjugating enzyme, was identified as one of the strongest inhibitory effectors on the production of type I IFN. Knockdown of pI215L expression inhibited ASFV replication and enhanced IFN-β production. However, inhibition of type I IFN production by pI215L was independent of its E2 enzyme activity. Furthermore, we found that pI215L inhibited type I IFN production and K63-linked polyubiquitination of TANK-binding kinase 1 through pI215L-binding RING finger protein 138 (RNF138). ASFV pI215L enhanced the interaction between RNF138 and RNF128 and promoted RNF138 to degrade RNF128, which resulted in reduced K63-linked polyubiquitination of TANK-binding kinase 1 and type І IFN production. Taken together, our findings reveal a novel immune escape mechanism of ASFV, which provides a clue to the design and development of an immune-sensitive attenuated live vaccine.

Etiology and outcome of febrile children coming from the tropics

IntroductionInternational travelers have grown significantly over last years, as well as imported diseases from tropical areas. Information in pediatric population is scarce. We describe demographic and clinical characteristics of febrile children coming from the tropics. MethodsRetrospective review of patients under 18 years old, presenting at a tertiary hospital and surrounding primary health care centers between July 2002 and July 2018 with a stay in a tropical region during the previous year. Patients were selected from microbiological charts of thick smears for malaria or dengue serologies. Results188 patients were studied: 52.7% were born in Spain with a median age of 3.0 years old (IQR 1.5–8.0). Main regions of stay were Sub-Saharan Africa (54.8%) and Latin America (29.8%), mostly for visiting their friends and relatives (56.3%), followed by recent arrival migrants (32.4%). Only 34% of travelers attended pre-travel consultation. More than 80% of these febrile children attended directly the Emergency Room. The most frequent diagnoses were febrile syndrome without source (56.4%), respiratory condition (15.4%) and acute diarrhea (11.7%). Around a half (52.1%) were managed as outpatients, but 46.2% were hospitalized and 7.4% were admitted to Intensive Care Unit. No specific diagnosis was achieved in 24% of cases. However, 29.7% were diagnosed with malaria. ConclusionChildren with fever coming from tropical areas were at risk of severe infectious diseases. Malaria was diagnosed in one out of four and 7% required admission in PICU. This information emphasizes the need of reinforcing training about tropical diseases among first line physicians.

Increased soluble programed cell death-ligand 1 is associated with acute coronary syndrome

BackgroundProgrammed cell death (PD)-1 and its ligand (PD-L1) plays crucial roles in T-cell tolerance as immune checkpoint. Previous studies reported that increased serum levels of soluble PD-L1 (sPD-L1) reflect myocardial and vascular inflammation. However, little is known about the clinical relationship between sPD-L1 and acute coronary syndrome (ACS). We investigated the relation of sPD-L1 and ACS. MethodsWe prospectively measured serum levels of sPD-L1 using a commercially available enzyme-linked immunosorbent assay kit in patients with coronary artery disease (CAD) and continuous non-CAD admitted to Kumamoto University Hospital between December 2017 and June 2019. All malignant diseases, patients who underwent hemodialysis, active collagen diseases, and severe infectious diseases were excluded. ResultsTotally, 446 CAD patients [ACS, n = 124; chronic coronary syndrome (CCS), n = 322] and 24 non-CAD patients were analyzed. The levels of sPD-L1 were significantly higher in patients with ACS than those both with non-CAD and CCS {ACS, 188.7 (111.0–260.8) pg/mL, p < 0.001 vs. non-CAD [83.5 (70.8–130.4) pg/mL]; and p = 0.009 vs. CCS [144.2 (94.8–215.5) pg/mL], respectively}. Univariate logistic regression analysis identified that sPD-L1 was significantly associated with ACS [odds ratio (OR): 1.459, 95% confidence interval (CI): 1.198–1.778, p < 0.001]. Multivariable logistic regression analysis with nine significant factors identified from the univariate analysis revealed that sPD-L1 was significantly and independently associated with ACS (OR: 1.561, 95% CI: 1.215–2.006, p < 0.001). ConclusionsThis is the first clinical study to demonstrate the increased level of sPD-L1 in patients with CAD, and the significant association with ACS.