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The increased awareness about the harmful effects of excessive use of antibiotics has created an interest in probiotics due to its beneficial effects on gut microbiota. These advantages of probiotics have attracted researchers to find out effects on human metabolism and their role in the treatment of diverse types of diseases or disorders. Additionally, they are clinically used as biocontrol agents in the treatment of mental disorders, anticancer agents and in decreasing the threat of necrotizing enterocolitis in premature infants. In this review, we have focused on various kinds of probiotics and various nondairy substrates for their production. We have also included the importance of probiotics in the treatment of metabolic disorders, type II diabetes and infectious diseases. Furthermore, this review emphasizes applications of probiotics originated from different organisms. Their future health perspectives are discussed to gain insight into their applications.KEY TEACHING POINTSThe global market of probiotics is enormously rising day by day due to its highly beneficial effect on human microbiota.Additionally, these are used as biocontrol agents; mental disorders prevent cancer and decrease the threat of necrotizing enterocolitis (NEC) in premature infants.This review focuses on various kinds of sources of probiotics and various non-dairy substrates for the production of probiotics.The importance of probiotics in the treatment of metabolic disorders, type II diabetes control, cancer and treatment of infectious diseases are also described.It emphasizes diversified probiotics and their applications in various human health aspects and future perspectives.

Objectives: Many secondary care departments receive external advice calls. However, systematic advice-call documentation is uncommon and evidence on call nature and burden infrequent. The Liverpool tropical and infectious disease unit (TIDU) provides specialist advice locally, regionally and nationally. We created and evaluated a recording system to document advice calls received by TIDU., Methods: An electronic advice-call recording system was created for TIDU specialist trainees to document complex, predominantly external calls. Fourteen months of advice calls were summarised, analysed and recommendations for other departments wishing to replicate this system made., Results: Five-hundred and ninety calls regarding 362 patients were documented. Median patient age was 44 years (interquartile range 29-56 years) and 56% were male. Sixty-nine per cent of patients discussed were referred from secondary healthcare, half from emergency or acute medicine departments; 43% of patients were returning travellers; 59% of returning travellers had undifferentiated fever, one-third of whom returned from sub-Saharan Africa; 32% of patients discussed were further reviewed at TIDU. Interim 6-month review showed good user acceptability of the system., Conclusions: Implementing an advice-call recording system was feasible within TIDU. Call and follow-up burden was high with advice regarding fever in returned travellers predominating. Similar systems could improve clinical governance, patient care and service delivery in other secondary care departments., (© Royal College of Physicians 2020. All rights reserved.)

The advent of single-cell research in the recent decade has allowed biological studies at an unprecedented resolution and scale. In particular, single-cell analysis techniques such as Next-Generation Sequencing (NGS) and Fluorescence-Activated Cell Sorting (FACS) have helped show substantial links between cellular heterogeneity and infectious disease progression. The extensive characterization of genomic and phenotypic biomarkers, in addition to host-pathogen interactions at the single-cell level, has resulted in the discovery of previously unknown infection mechanisms as well as potential treatment options. In this article, we review the various single-cell technologies and their applications in the ongoing fight against infectious diseases, as well as discuss the potential opportunities for future development.

Purpose: The Choosing Wisely ® initiative is an international campaign addressing over- and underuse of diagnostic and therapeutic measures in infectious diseases among others. Since 2016, the German Society for Infectious Diseases (DGI) has constantly designed new items in this regard. Here we report the most recent recommendations., Methods: The recommendations of the DGI are part of the "Klug entscheiden" initiative of the German Society of Internal Medicine (DGIM). Topics for the new items were suggested by members of the DGI, checked for scientific evidence and consented within the DGI and the DGIM before publication., Results: The new recommendations are: (1) individuals with immune-suppression, advanced liver cirrhosis or renal insufficiency should receive a dual pneumococcal vaccination. (2) In case of positive blood cultures with Candida spp. thorough diagnostics and treatment should be initiated. (3) In case of suspected meningitis, adult patients should receive dexamethasone and antibiotics immediately after venipuncture for blood cultures and before potential imaging. (4) In case of suspected meningitis a CT scan before lumbar puncture should not be ordered-except for symptoms indicating high CSF pressure or focal brain pathology or in cases of severe immune-suppression. (5) In patients with suspected severe infections, a minimum of two pairs of blood cultures should be drawn using separate venipunctures prior to antibiotic therapy-regardless of body temperature. There is no need of a minimum time interval in between the blood draws., Conclusion: Applying these new Choosing Wisely ® recommendations will increase patient safety and the value of health care.

Purpose: Alcohol dependence is associated with poor prognosis in the intensive care unit (ICU), but it remains uncertain whether moderate alcohol consumption negatively affects the prognosis of critically ill patients admitted with infection., Materials and Methods: In a prospective observational cohort study performed in 478 patients admitted with documented infection, mortality at day 28 in the group of abstainers and nontrauma patients with estimated alcohol consumption lower than 100 g/week was compared with that in non-alcohol-dependent patients with estimated alcohol consumption between 100 and 350 g/week., Results: In 97 patients (20%), alcohol consumption was estimated to be over 100 g/week, and in 391 patients (80%), alcohol consumption was estimated to be 100 g/week or less. The pathogens identified did not significantly differ between the two groups of patients. After adjusted analysis, alcohol consumption between 100 and 350 g/week remained significantly associated with mortality at day 28 (hazard ratio (HR): 1.67; 95% confidence interval (CI): 1.01-2.77; p = .04)., Conclusion: Alcohol consumption between 100 and 350 g/week was independently associated with mortality at day 28. Our results suggest that in critically ill patients admitted with infection, moderate alcohol consumption is associated with a poorer prognosis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: To optimize the focus of future public information campaigns in The Netherlands promoting the uptake of vaccines among adults and children, we quantified the contribution of several attributes to the vaccination decision., Method: We performed a discrete choice experiment (DCE) among Dutch adults including six attributes, i.e. vaccine effectiveness, vaccine-preventable burden of disease (specified in severity and frequency), accessibility of vaccination in terms of co-payment and prescription requirements, frequency of mild side-effects, population-level vaccination coverage and local vaccination coverage among family and friends. Participants answered the DCE from their own perspective ('oneself' group) or with regard to a vaccine decision for their youngest child ('child' group). The data was analysed by means of panel mixed logit models., Results: We included 1547 adult participants (825 'oneself' and 722 'child'). Vaccine effectiveness was the most important attribute in the 'oneself' group, followed by burden of disease (relative importance (RI) 78%) and accessibility (RI 76%). In the 'child' group, burden of disease was most important, but tied closely with vaccine effectiveness (RI 97%). Of less importance was the risk of mild vaccine-related side-effects and both population and local vaccination coverage. Interestingly, participants were more willing to vaccinate when uptake among the population or family and friends was high, indicating that social influence and social norms plays a role., Conclusions: Vaccine effectiveness and disease severity are key attributes in vaccination decision-making for adults making a decision for themselves and for parents who decide for their children. Hence, public information campaigns for both adult and child vaccination should primarily focus on these two attributes. In addition, reinforcing social norms may be considered.

In the present article, the dynamics of a novel combination of ratio-dependent incidence rate and saturated treatment rate in susceptible-infected-recovered disease compartmental model has been presented. The ratio-dependent incidence rate has been incorporated into the model to monitor the situation when ratio of the number of infectives to that of the susceptibles is getting higher. The saturated treatment rate of the infected population has been considered as Holling type II functional, which explains the limitation in treatment availability. From the mathematical analysis of the model, two types of equilibria of the model have been obtained, which are named as disease-free equilibrium (DFE) and endemic equilibrium (EE). The local stability behavior of equilibria has been investigated by the basic reproduction number [Formula: see text], center manifold theory and Routh-Hurwitz criterion. It has been investigated that the DFE is locally asymptotically stable when [Formula: see text], and when [Formula: see text], the DFE exhibits either a forward bifurcation or a backward bifurcation under some conditions. The local stability behavior of the EE has also been analyzed, and some conditions are obtained for the same. Finally, some numerical computations have been performed in support of our theoretical results.

Ongoing social, political and ecological changes in the 21st century have placed more people at risk of life-threatening acute and chronic infections than ever before. The development of new diagnostic, prophylactic, therapeutic and curative strategies is critical to address this burden but is predicated on a detailed understanding of the immensely complex relationship between pathogens and their hosts. Traditional, reductionist approaches to investigate this dynamic often lack the scale and/or scope to faithfully model the dual and co-dependent nature of this relationship, limiting the success of translational efforts. With recent advances in large-scale, quantitative omics methods as well as in integrative analytical strategies, systems biology approaches for the study of infectious disease are quickly forming a new paradigm for how we understand and model host-pathogen relationships for translational applications. Here, we delineate a framework for a systems biology approach to infectious disease in three parts: discovery - the design, collection and analysis of omics data; representation - the iterative modelling, integration and visualization of complex data sets; and application - the interpretation and hypothesis-based inquiry towards translational outcomes.

Background: Since 2014, the migrant population residing in Europe has dramatically increased. Migrants' unmet health needs represent a barrier to integration and should be promptly addressed, without stigma, in order to favour resettlement., Methods: All-cause of admissions in the migrant population at the Infectious Disease Clinic of Policlinico San Martino Hospital in Genoa between 2015 and 2017 were analysed. Patients were classified by duration of residence in Italy according to the Recommendation on Statistics of International Migration, cause of hospitalization, and region of origin. All data were evaluated with SPSS Statistics., Results: Two hundred thirty-five people were admitted, 86 (36.5%) of them residing in Italy for less than 1 year. Except for a significant increase in migrants from Africa, there was no change considering the area of origin, hospitalization reason or by comparing residency in Italy for more or less than 1 year. A considerable number of hospitalizations were related to non-communicable pathologies and latent tuberculosis infection. Residents in Italy for less than 1 year or with active tuberculosis had prolonged hospitalizations, while HIV-infected had shorter hospital stays., Conclusions: No difference in terms of diagnosis were found between migrants with longer or shorter period of residence in Italy. Adequate outpatient services for the management of communicable diseases could significantly reduce the length of hospitalizations in the migrant population.

Within human health research, the remarkable utility of kinase inhibitors as therapeutics has motivated efforts to understand biology at the level of global cellular kinase activity (the kinome). In contrast, the diminished potential for using kinase inhibitors in food animals has dampened efforts to translate this research approach to livestock species. This, in our opinion, was a lost opportunity for livestock researchers given the unique potential of kinome analysis to offer insight into complex biology. To remedy this situation, our lab developed user-friendly, cost-effective approaches for kinome analysis that can be readily incorporated into most research programs but with a specific priority to enable the technology to livestock researchers. These contributions include the development of custom software programs for the creation of species-specific kinome arrays as well as comprehensive deconvolution and analysis of kinome array data. Presented in this review are examples of the application of kinome analysis to highlight the utility of the technology to further our understanding of two key complex biological events of priority to the livestock industry: host immune responses to infectious diseases and animal stress responses. These advances and examples of application aim to provide both mechanisms and motivation for researchers, particularly livestock researchers, to incorporate kinome analysis into their research programs., (Copyright © 2020 Facciuolo, Denomy, Lipsit, Kusalik and Napper.)

Background: Machine learning (ML) is a growing field in medicine. This narrative review describes the current body of literature on ML for clinical decision support in infectious diseases (ID)., Objectives: We aim to inform clinicians about the use of ML for diagnosis, classification, outcome prediction and antimicrobial management in ID., Sources: References for this review were identified through searches of MEDLINE/PubMed, EMBASE, Google Scholar, biorXiv, ACM Digital Library, arXiV and IEEE Xplore Digital Library up to July 2019., Content: We found 60 unique ML-clinical decision support systems (ML-CDSS) aiming to assist ID clinicians. Overall, 37 (62%) focused on bacterial infections, 10 (17%) on viral infections, nine (15%) on tuberculosis and four (7%) on any kind of infection. Among them, 20 (33%) addressed the diagnosis of infection, 18 (30%) the prediction, early detection or stratification of sepsis, 13 (22%) the prediction of treatment response, four (7%) the prediction of antibiotic resistance, three (5%) the choice of antibiotic regimen and two (3%) the choice of a combination antiretroviral therapy. The ML-CDSS were developed for intensive care units (n = 24, 40%), ID consultation (n = 15, 25%), medical or surgical wards (n = 13, 20%), emergency department (n = 4, 7%), primary care (n = 3, 5%) and antimicrobial stewardship (n = 1, 2%). Fifty-three ML-CDSS (88%) were developed using data from high-income countries and seven (12%) with data from low- and middle-income countries (LMIC). The evaluation of ML-CDSS was limited to measures of performance (e.g. sensitivity, specificity) for 57 ML-CDSS (95%) and included data in clinical practice for three (5%)., Implications: Considering comprehensive patient data from socioeconomically diverse healthcare settings, including primary care and LMICs, may improve the ability of ML-CDSS to suggest decisions adapted to various clinical contexts. Currents gaps identified in the evaluation of ML-CDSS must also be addressed in order to know the potential impact of such tools for clinicians and patients., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Hospitalization is a common adverse event in people with heart failure and reduced ejection fraction, yet is often not primarily due to decompensated heart failure (HF). We investigated the long-term prognosis following infection-related hospitalization., Methods: We conducted a prospective observational cohort study of 711 people with heart failure and reduced ejection fraction recruited from 4 specialist HF clinics in the United Kingdom. All hospitalization episodes (n=1568) were recorded and categorized as primarily due to decompensated HF, other cardiovascular disease, infection-related, or other noncardiovascular disease. Survival was determined after the first hospitalization., Results: During 2900 patient-years of follow-up, there were a total of 14 686 hospital days. At least one hospitalization occurred in 467 people (66%); 25% of first hospitalizations were primarily due to infection and these were not associated with typical signs including tachycardia and pyrexia. Compared with other categories of hospitalization, infection-related was associated with older age, lower serum albumin, higher blood neutrophil counts, and greater prevalence of chronic obstructive pulmonary disease at recruitment. Median survival after first infection-related hospitalization was 18.6 months, comparable to that after first decompensated HF hospitalization, even after age-sex adjustment. The burden of all-cause rehospitalization was comparable irrespective of the category of first hospitalization, but infection more commonly caused re-hospitalization after index infection hospitalization., Conclusions: Infection is a common driver of hospitalization in heart failure and reduced ejection fraction and often presents without classical signs. It is associated with high mortality rates, comparable to decompensated HF, and a major burden of rehospitalization caused by recurrent episodes of infection.

Prevalence of infectious diseases is substantially higher among patients with substance use disorders (SUD). Factors associated with drug use including sharing needles and injecting supplies, presence of contaminants in drugs and drug use related paraphernalia, risky behaviors associated with drug use, immune suppression secondary to chronic drug use, poverty and homelessness all increase the risk of infections. Persons with SUD have low rates of health care utilization and may miss opportunities for early diagnosis and care of infectious complications of substance use. When infectious diseases are comorbid with drug use, they are associated with substantial morbidity and mortality and result in significant healthcare costs. Patients with SUD may be rescued from an overdose, detoxified or treated for a SUD but facilities and clinicians are often reluctant to assume responsibility for evaluation and treatment of concurrent infectious or medical diseases. Increased screening for these disorders, utilizing vaccinations and other preventative strategies including clean supplies and safe injecting sites and providing comprehensive substance use and infectious disease treatment have the potential to significantly improve patient related outcomes and enhance public health. In this paper we review the prevalence of various common infectious diseases among persons who use drugs, their clinical presentation, mode of transmission, screening and diagnosis. We detail some of the common mechanisms by which persons who use drugs are at increased risk of contracting infections. We also discuss preventive and treatment strategies for infectious diseases occurring in the context of SUD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Infectious intestinal disease affects 25% of the UK population annually; 1 in 50 affected people consult health professionals about their illness., Aims: We tested if anticipated treatment-seeking decisions for suspected infectious intestinal disease could be related to emotional response, tolerance of symptoms, or beliefs about the consequential benefits and harms of seeking treatment (or not)., Methods: Questionnaire survey of adults living in the UK with statistical analysis of responses. A vignette was presented about a hypothetical gastrointestinal illness. People stated their emotional reactions, expected actions in response and beliefs about possible benefits or harms from seeking treatment (or not getting treatment). Multinomial regression looked for predictors of anticipated behaviour., Results: People were inclined to consult a GP when they believed that seeking treatment would be beneficial and that its absence would be harmful. Seeking treatment was less anticipated if the condition was expected to improve quickly. Respondents were also more likely to consult if they strongly disliked fever or headache, and/or if the illness made them feel anxious or angry. Treatment-seeking (or lack of it) was not linked to harms from treatment-seeking, other specific symptoms and emotional responses., Conclusion: It was possible to link anticipated treatment-seeking behaviour to specific factors: expected prognosis, perceived benefits of seeking treatment, some emotions and some specific symptoms., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

To formulate the optimal strategy of combatting bacterial biofilms, in this review we update current knowledge on the growing problem of biofilm formation and its resistance to antibiotics which has spurred the search for new strategies to deal with this complication. Based on recent findings, the role of bacteriophages in the prevention and elimination of biofilm-related infections has been emphasized. In vitro, ex vivo and in vivo biofilm treatment models with single bacteriophages or phage cocktails have been compared. A combined use of bacteriophages with antibiotics in vitro or in vivo confirms earlier reports of the synergistic effect of these agents in improving biofilm removal. Furthermore, studies on the application of phage-derived lysins in vitro, ex vivo or in vivo against biofilm-related infections are encouraging. The strategy of combined use of phage and antibiotics seems to be different from using lysins and antibiotics. These findings suggest that phages and lysins alone or in combination with antibiotics may be an efficient weapon against biofilm formation in vivo and ex vivo, which could be useful in formulating novel strategies to combat bacterial infections. Those findings proved to be relevant in the prevention and destruction of biofilms occurring during urinary tract infections, orthopedic implant-related infections, periodontal and peri-implant infections. In conclusion, it appears that most efficient strategy of eliminating biofilms involves phages or lysins in combination with antibiotics, but the optimal scheme of their administration requires further studies.

Background: Conflict has played a role in the large-scale deterioration of health systems in low-income and middle-income countries (LMICs) and increased risk of infections and outbreaks. This systematic review aimed to synthesise the literature on mechanisms of delivery for a range of infectious disease-related interventions provided to conflict-affected women, children and adolescents., Methods: We searched Medline, Embase, CINAHL and PsychINFO databases for literature published in English from January 1990 to March 2018. Eligible publications reported on conflict-affected neonates, children, adolescents or women in LMICs who received an infectious disease intervention. We extracted and synthesised information on delivery characteristics, including delivery site and personnel involved, as well as barriers and facilitators, and we tabulated reported intervention coverage and effectiveness data., Results: A majority of the 194 eligible publications reported on intervention delivery in sub-Saharan Africa. Vaccines for measles and polio were the most commonly reported interventions, followed by malaria treatment. Over two-thirds of reported interventions were delivered in camp settings for displaced families. The use of clinics as a delivery site was reported across all intervention types, but outreach and community-based delivery were also reported for many interventions. Key barriers to service delivery included restricted access to target populations; conversely, adopting social mobilisation strategies and collaborating with community figures were reported as facilitating intervention delivery. Few publications reported on intervention coverage, mostly reporting variable coverage for vaccines, and fewer reported on intervention effectiveness, mostly for malaria treatment regimens., Conclusions: Despite an increased focus on health outcomes in humanitarian crises, our review highlights important gaps in the literature on intervention delivery among specific subpopulations and geographies. This indicates a need for more rigorous research and reporting on effective strategies for delivering infectious disease interventions in different conflict contexts., Prospero Registration Number: CRD42019125221., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: Studies on healthcare-seeking behaviour usually adopted a patient care perspective, or restricted to specific disease conditions. However, pre-diagnosis symptoms may be more relevant to healthcare-seeking behaviour from a patient perspective. We described healthcare-seeking behaviours by specific symptoms related to respiratory and gastrointestinal-related infections., Methods: We conducted a longitudinal population-based telephone survey in Hong Kong. We collected data on healthcare-seeking behaviour specific to symptoms of respiratory and gastrointestinal-related infections and also associated demographic factors. We performed descriptive analyses and estimated the proportion of participants who sought medical consultation, types of services utilized and duration from symptom onset to healthcare seeking, by different age groups. Post-stratification was used to compensate non-response and multiple imputation to handle missing and right-censored data., Results: We recruited 2564 participants who reported a total of 4370 illness episodes and 7914 symptoms. Fatigue was the most frequently reported symptom, followed by headache and runny nose, with 30-day incidence rate of 9.1, 7.7, and 7.7% respectively. 78% of the participants who had fever sought medical consultation, followed by those with rash (60%) and shortness of breath (58%). Older adults (aged ≥55y) who had symptoms including fever, sore throat, and headache had a significantly higher consultation rate comparing to the other age groups. The 30-day incidence rates of influenza-like illness (ILI) and acute respiratory illness (ARI) were 0.8 and 7.2% respectively, and the consultation rates among these participants were 91 and 64%. Private general practitioner clinics was the main service utilized by participants for most of the symptoms considered, especially those related to acute illness such as fever, diarrhoea and vomiting. Chinese medicine clinics were mostly likely to be visited by participants with low back pain, myalgia and fatigue. Among participants who have sought medical services, most were within 3 days of symptom onset., Conclusions: Healthcare-seeking behaviour were different by symptoms and age. Characterization of these patterns provides crucial parameters for estimating the full burden of common infectious diseases from facility-based surveillance system, for planning and allocation of healthcare resources.

Many pathogens use the same immune evasion mechanisms as cancer cells. Patients with chronic infections have elevated levels of checkpoint receptors (e.g., programed cell death 1, PD1) on T cells. Monoclonal antibody (mAb)-based inhibitors to checkpoint receptors have also been shown to enhance T-cell responses in models of chronic infection. Therefore, inhibitors have the potential to act as a vaccine "adjuvant" by facilitating the expansion of vaccine antigen-specific T-cell repertoires. Here, we report the discovery and characterization of a peptide-based class of PD1 checkpoint inhibitors, which have a potent adaptive immunity adjuvant capability for vaccines against infectious diseases. Briefly, after identifying peptides that bind to the recombinant human PD1, we screened for in vitro efficacy in reporter assays and human peripheral blood mononuclear cells (PBMC) readouts. We first found the baseline in vivo performance of the peptides in a standard mouse oncology model that demonstrated equivalent efficacy compared to mAbs against the PD1 checkpoint. Subsequently, two strategies were used to demonstrate the utility of our peptides in infectious disease indications: (1) as a therapeutic in a bacteria-induced lethal sepsis model in which our peptides were found to increase survival with enhanced bacterial clearance and increased macrophage function; and (2) as an adjuvant in combination with a prophylactic malaria vaccine in which our peptides increased T-cell immunogenicity and the protective efficacy of the vaccine. Therefore, our peptides are promising as both a therapeutic agent and a vaccine adjuvant for infectious disease with a potentially safer and more cost-effective target product profile compared to mAbs. These findings are essential for deploying a new immunomodulatory regimen in infectious disease primary and clinical care settings., (Copyright © 2020 Kotraiah, Phares, Browne, Pannucci, Mansour, Noe, Tucker, Christen, Reed, MacKay, Weir, Rajagopalan, Stanford, Chung, Ayala, Huang, Tsuji and Gutierrez.)

Rationale: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are extremely rare but potentially life-threatening disorders. We presented 3 fatal pediatric SJS/TEN cases., Patient Concerns: Our patients had some severe complications such as septic shock, respiratory failure and obliterans bronchiolitis (BO) etc. DIAGNOSIS:: Three patients diagnosed SJS/TEN with clinical symptoms that were triggered by antibiotics, nonsteroidal anti-inflammatory drugs, previous infection, or neoplasms., Interventions: All of them accepted mechanical ventilation, intravenous immunoglobulin (IVIG), blood transfusion, glucocorticoid, and multi-anti-infectious therapy., Outcomes: They all died because of out-of-control severe infections. In Patient 1, he died 6 days after being admitted to the PICU on the 28th day from onset. In Patient 2, he died on the 211th day from the onset of illness during the third time of PICU admission. In Patient 3, she died 12 days after PICU admission on the 87th day from onset., Lessons: We should be aware that mucosal damage occurs on the skin and within the mucosa of visceral organs, leading to the occurrence of bronchiectasia, BO, enterocolitis, acute renal failure, and severe secondary infections. Establish a clinically predictive score that includes severe infection for pediatric patients to evaluate the risk of mortality in children in order to improve poor outcomes.

Micromotors are man-made nano/microscale devices capable of transforming energy into mechanical motion. The accessibility and force offered by micromotors hold great promise to solve complex biomedical challenges. This Review highlights current progress and prospects in the use of nano and micromotors for diagnosis and treatment of infectious diseases and cancer. Motion-based sensing and fluorescence switching detection strategies along with therapeutic approaches based on direct cell capture; killing by direct contact or specific drug delivery to the affected site, will be comprehensively covered. Future challenges to translate the potential of nano/micromotors into practical applications will be described in the conclusions., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Encephalitis causes high morbidity and mortality. An incidence of 4.3 cases of encephalitis/100 000 population has been reported in the UK. We performed a retrospective evaluation of the diagnosis and management of adults admitted to hospital with a clinical diagnosis of encephalitis/meningoencephalitis. Clinical, laboratory and radiological data were collated from electronic records. Thirty-six patients, median age 55 years and 24 (67%) male were included. The aetiology was confirmed over nine months in 25 (69%) of whom 16 were infections (six viral, seven bacterial, two parasitic and one viral and parasitic co-infection); 7 autoimmune; 1 metabolic and 1 neoplastic. Of 24 patients with fever, 15 (63%) had an infection. The median time to computed topography, magnetic resonance imaging and electroencephalography (EEG) was 1, 8 and 3 days respectively. Neuroimaging was abnormal in 25 (69%) and 17 (89%) had abnormal EEGs. Only 19 (53%) received aciclovir treatment. Six (17%) made good recoveries, 16 (44%) had moderate disability, 8 (22%) severe disability and 6 (17%) died. Outcomes were worse for those with an infectious cause. In summary, a diagnosis was made in 69.4% of patients admitted with encephalitis/meningoencephalitis. Autoimmune causes are important to consider at an early stage due to a successful response to treatment. Only 53% of patients received aciclovir on admission. Neuroimaging and EEG studies were delayed. The results of this work resulted in further developing the clinical algorithm for managing these patients.

Purpose of Review: Immunocompromised children are a largely under-vaccinated population and are vulnerable to acquiring vaccine-preventable infections (VPIs). A variety of factors contribute to poor vaccine coverage including: severity of underlying illness, sporadic contact with primary care physicians, and lack of awareness among specialty providers regarding vaccination status. In this review, we report recent data regarding incidence of VPIs, new approaches to vaccine use, rates of vaccine coverage, and strategies to optimize vaccine administration in immunocompromised populations., Recent Findings: Pediatric transplant recipients and patients with autoimmune disorders receiving novel biological therapies, represent growing immunocompromised patient populations. VPIs continue to be a concern for such patients. Underlying disease severity may limit efforts to immunize pediatric patients early in their disease process, prior to immunosuppression. Inactive vaccines are safe and immunogenic after the introduction of immunosuppression, but live vaccines are typically contraindicated. Emerging data support the safety and effectiveness of live vaccines in certain immunocompromised individuals. Care providers must remain vigilant in maintaining patients' vaccination status based on current vaccination guidelines, and create a multidisciplinary approach to optimizing vaccination., Summary: Immunocompromised children remain under-vaccinated and vulnerable to VPIs. Optimizing vaccines should be a priority for every provider caring for this population.

A non-smooth epidemic model with piecewise incidence rate dependent on the derivative of the case number is proposed for the transmission dynamics of an infectious disease with media coverage, enhanced vaccination and treatment policy. This is an implicitly defined system, which is converted into an explicit system with three thresholds by employing the properties of the Lambert W function. We first analyze the dynamics of the proposed model for the limiting case, which induces two non-smooth but continuous models. The dynamic analysis of the model demonstrates that either one of the two generalized equilibria or the pseudo-equilibrium is globally asymptotically stable if the disease does not die out. This suggests that the case number can be contained either at an a priori level or at a high/low level, depending on the threshold, which governs whether the enhanced vaccination and treatment policies are implemented. Media coverage cannot help eradicate the disease, but it significantly delays the epidemic peak and lowers the peak case number. Hence, a good threshold policy and continuously updating the awareness of case numbers are required to combat the disease successfully.

Purpose of Review: This review summarizes the current state of school-entry vaccination requirements and related exemption policies in the United States and examines recent changes to these policies., Recent Findings: With recent infectious disease outbreaks in the United States, there has been heightened awareness on unvaccinated individuals, and the state-level policies that allow individuals to be exempted from school-entry vaccination requirements. Between 2015 and 2017, there have been eleven states that have altered their policies regarding school-entry vaccination requirements and related reporting for which no formal evaluations have been published. One policy change during that period, California SB 277, which became law in 2016, reduced the nonmedical exemption and increased the childhood vaccination coverage rate in that state, though with some evidence of exemption replacement through the use of medical exemptions. Through September 2019, five additional state law changes have been enacted., Summary: The large number of heterogeneous changes to state-level policies for school-entry vaccination requirements in recent years need rigorous evaluation to identify best practices for balancing public health authority and parental autonomy while seeking to achieve the highest level of infectious disease prevention for children.

Immune support by micronutrients is historically based on vitamin C deficiency and supplementation in scurvy in early times. It has since been established that the complex, integrated immune system needs multiple specific micronutrients, including vitamins A, D, C, E, B6, and B12, folate, zinc, iron, copper, and selenium, which play vital, often synergistic roles at every stage of the immune response. Adequate amounts are essential to ensure the proper function of physical barriers and immune cells; however, daily micronutrient intakes necessary to support immune function may be higher than current recommended dietary allowances. Certain populations have inadequate dietary micronutrient intakes, and situations with increased requirements (e.g., infection, stress, and pollution) further decrease stores within the body. Several micronutrients may be deficient, and even marginal deficiency may impair immunity. Although contradictory data exist, available evidence indicates that supplementation with multiple micronutrients with immune-supporting roles may modulate immune function and reduce the risk of infection. Micronutrients with the strongest evidence for immune support are vitamins C and D and zinc. Better design of human clinical studies addressing dosage and combinations of micronutrients in different populations are required to substantiate the benefits of micronutrient supplementation against infection., Competing Interests: S.M. and A.P. are employed by Bayer Consumer Care Ltd., a manufacturer of multivitamins. A.F.G. has received funding for conducting research on a product from Bayer Consumer Care Ltd.

Siglec-15 is a member of the Siglec family of glycan-recognition proteins, primarily expressed on a subset of myeloid cells. Siglec-15 has been known to be involved in osteoclast differentiation, and is considered to be a potential therapeutic target for osteoporosis. Recent studies revealed unexpected roles of Siglec-15 in microbial infection and the cancer microenvironment, expanding the potential pathophysiological roles of Siglec-15. Chemical biology has advanced our understanding of the nature of Siglec-15 ligands, but the exact nature of Siglec-15 ligand depends on the biological context, leaving plenty of room for further exploration.

Mast cells (MCs) bear many receptors that allow them to respond to a variety of exogenous and endogenous stimuli. However, MC function is dual since they can initiate pathological events or protect the host against infectious challenges. The role of MCs in disease will be analyzed in a broad sense, describing cellular and molecular mechanisms related to their involvement in auto-inflammatory diseases, asthma, autoimmune diseases and cancer. On the other hand, their protective role in the course of bacterial, fungal and parasitic infections will also be illustrated. As far as treatment of MC-derived diseases is concerned, allergen immunotherapy as well as other attempts to reduce MC-activation will be outlined according to the recent data. Finally, in agreement with current literature and our own data polyphenols have been demonstrated to attenuate type I allergic reactions and contact dermatitis in response to nickel. The use of polyphenols in these diseases will be discussed also in view of MC involvement., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Observational studies demonstrating reduced rates of infections, necrotizing enterocolitis (NEC), and mortality in preterm infants fed their own mother's milk, as opposed to formula, have prompted endeavors to achieve similar effects with the right choice of food and food additives. In a systematic review of meta-analyses and randomized controlled trials (RCTs), we considered nutritional interventions aimed at reducing the rates of infections, NEC, or mortality in very preterm infants. The overall effects of particular interventions were presented as risk ratios with 95% confidence intervals. In RCTs, pasteurized human donor milk, as opposed to formula, reduced NEC but not infections or mortality. No differences emerged between infants receiving human or bovine milk-based fortifiers. Pooled data of small trials and a recent large RCT suggested that bovine lactoferrin reduced rates of fungal sepsis without impact on other infections, NEC, or mortality. Pooled data of RCTs assessing the use of prebiotic oligosaccharides found reduced infection but not mortality. Enteral L-glutamine (six RCTs) lowered infection rates, and enteral L-arginine (three RCTs) reduced NEC. A meta-analysis sensitivity approach found multiple-strain (but not single-strain) probiotics to be highly effective in reducing NEC and mortality. Thus, selected food components may help to improve outcomes in preterm infants.

Solid organ transplant recipients are at risk for potentially life-threatening infections due to lifelong immunosuppression. Vaccine-preventable infections result in graft injury, morbidity, mortality, and significantly increased medical costs. Unfortunately, the majority of transplant recipients continue to be underimmunized at the time of transplant and thereafter. Given the rising rates of vaccine hesitancy and refusal in the general population, transplant recipients can no longer rely on herd immunity to protect them from vaccine-preventable infections. Novel tools are desperately needed to overcome transplant-specific immunization barriers to improve immunization rates in this high-risk population. Digital health technologies may offer a solution by addressing transplant-specific barriers: specifically, providing accurate information about vaccine safety, efficacy, and timing in the pre- and posttransplant periods; making a complete immunization record universally available and easily accessible; enabling communication between patients and multiple providers; and providing automated vaccine reminders to both patients and providers when vaccines are due using transplant-specific immunization guidelines. Digital health has transformed health care by empowering patients with their own health information and connecting patients, their providers, and public health officials. In doing so, it offers a potential platform to address and overcome the problem of underimmunization in the transplant population., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: The purpose of this study was to examine the attitudes and behaviors of emergency medical technicians (EMTs) and Paramedics when faced with the decision to care for patients with suspected Ebola Virus Disease (EVD) and to illicit suggestions for improvement of infectious disease (ID) preparedness. Methods: A convenience sample of 22 EMT/Paramedics were recruited from an emergency department at one of the designated Ebola centers. Each provider participated in one of three on-site focus groups. Participants answered questions about how they gained their knowledge, felt about caring for EVD patients, made decisions about caring for EVD patients, and suggestions for improvement of ID preparedness. Focus groups were recorded, transcribed, and coded using inductive content analysis. Results: Analysis revealed five prominent themes: reactions to scare, education/training, danger, decision making, and suggestions for future responses. Overall, first responders were excited to be a part of the response to EVD. They were more comfortable caring for EVD patients if they received adequate education and transparency from the administration. This resulted in a decreased perceived danger of the disease and decreased hesitancy when caring for EVD patients. However, those that expressed the most hesitancy also expressed the most emotional distress. Suggestions for improvement of ID preparedness included continuing education, tiered training models, peer training models, collaboration between emergency medical services (EMS) systems, better communication between departments, and the development of an infectious disease response team. Conclusions: Although first responders were excited to be a part of the response to EVD, this did not come without hesitation and emotional distress. Some of these concerns may be mitigated by first providing a clear definition of "duty to care," followed by interventions such as the development of clear and consistent ID preparedness training and interventions that address the emotional distress experienced by these providers.

Objective: In Peru, prisons are spaces with overcrowding, deteriorated infrastructure, poor sanitary conditions and difficult access to medical treatment. The objective of this study is to estimate the burden of disease and access to treatment for different morbidities in the Peruvian inmate population., Methods: An analysis of secondary data of the First National Penitentiary Census (PCNP) 2016 in Peru was carried out. The absolute frequencies and percentages of each self-reported health condition, the presence of a diagnosis of a disease before entering the prison system and access to treatment were obtained., Results: 74,130 inmates were included in the analysis. The most common diseases in prisons are depression (9.6%), anxiety (8.6%), chronic lung disease (8.4%) and arterial hypertension (6.9%). All diseases included, with the exception of hepatitis, have a diagnostic before the incarceration of less than 60%. Access to medical treatment was higher in women than in men and in general, mental health illnesses had low access to medical treatment., Conclusions: Chronic and infectious diseases are frequent in those deprived of liberty, with mental health problems being more prevalent in women. In general, access to treatment is low, especially in men and for mental health illnesses. This situation reflects the need to develop intervention programs that promote health and increase the universality of health care in those deprived of liberty.

The article presents the life and work of dr. Mieczysław Biernacki, a Polish doctor of medicine, freemason, social, economic and political activist unknown to the younger generation of Polish doctors, who was born in 1862, Throughout his life, he actively worked to raise the level of education and health of Lublin's inhabitants. He held managerial positions in numerous associations, economic institutions, local government and political organizations. Above all, he was a doctor who effectively fought against infectious diseases, venereal diseases and tuberculosis. As an editor and publicist, he took the floor by writing on medical, economic and literary subjects. He died in 1948, at the age of eighty-eight.

Big infectious diseases do harm to the whole society, and it is highly crucial to control them on time. The major purpose of this article is to theoretically demonstrate that the Chinese government's intervention in large-scale infectious diseases is successful and efficient. Two potential strategies were considered: strategy 1 was infectious disease without government intervention, and strategy 2 was infectious disease with government intervention. By evolution model, this article illustrates the efficiency of big infectious disease reimbursement policy in China. Without government reimbursement, this article finds that high expenditures accelerate the disease infection. The number of infected persons decreases under big infectious disease reimbursement policy in China. The higher the treatment costs, the more important the government intervention. Big infectious disease reimbursement policy in China can serve as an efficient example to cope with big infectious diseases.

Background: Despite known gender-specific differences in terms of prevalence, transmission and exposure to neglected tropical diseases (NTDs), there is limited discussion of the influence of gender in NTD programmes and interventions. There is a paucity of research on how gender interacts with NTD service provision and uptake. This study, part of broader implementation research in Ethiopia, applied a gender lens to health seeking for five NTDs: lymphatic filariasis, podoconiosis, schistosomiasis, soil-transmitted helminth infection and trachoma., Methodology/principal Findings: The study was conducted in a district of the Southern Nations, Nationalities, and Peoples' Region of Ethiopia where the five NTDs are prevalent. A qualitative methodology was adopted to explore participants' perspectives and experiences. Data generation methods included 20 interviews and four focus group discussions. Community members, volunteer Health Development Army leaders, Health Extension Workers and a range of health workers at the health post, health centre and hospital level (n = 59) were purposively sampled. Interviews and focus group discussions were audio recorded, transcribed verbatim into English then analysed through open coding, drawing on constant comparative methods. Gender related factors affected care seeking for NTDs and were described as reasons for not seeking care, delayed care seeking and treating NTDs with natural remedies. Women faced additional challenges in seeking health care due to gender inequalities and power dynamics in their domestic partnerships. Participants recommended raising community awareness about NTDs, however this remains problematic due to gender and social norms around appropriate discourse with members of the opposite gender., Conclusions/significance: The findings from this study provide crucial insights into how gender interacts with accessing health services, at different levels of the health system. If we are committed to leaving no one behind and achieving universal health coverage, it is essential to address gender disparities to access and utilisation of interventions delivered by national NTD programmes., Competing Interests: The authors have declared that no competing interests exist.

Development of therapeutic antibodies for treating infectious diseases is more recent than for cancer and inflammatory diseases. To date, seven antibodies have been approved worldwide and only five in France. Medical indications are so far limited to the prophylaxis of bronchiolitis caused by respiratory syncytial virus (RSV), treatment of multidrug-resistant HIV disease, exposure to rabies and anthrax pulmonary disease, prevention of diarrhea recurrence due to Clostridium difficile, and atypical hemolytic uremic syndrome caused by Escherichia coli. In a near future, new technologies would allow accelerating the development of anti-infectious monoclonal antibodies to improve the anti-bacterial and anti-viral therapeutic arsenal., (© 2019 médecine/sciences – Inserm.)

Monoclonal antibodies have revolutionized the treatment of many diseases, but their clinical effectiveness remains limited in some cases. Associations of antibodies binding to the same target (homo-combination) or to several different targets (hetero-combination), thereby mimicking a polyclonal humoral immune response, have demonstrated a therapeutic improvement in pre-clinical and clinical trials, mainly in the field of oncology and infectious diseases. The combinations increase the efficacy of the biological responses and override resistance mechanisms observed with antibody monotherapy. The most common method of formulating and administering antibody combinations is a separate formulation, with sequential injection of each antibody as individual drug substance. Alternatively, combined formulations are developed where the separately-produced antibodies are mixed before administration or produced simultaneously by a single cell line, or a mixture of cell lines as a polyclonal master cell bank. The regulation, the toxicity and the injection sequence of these oligoclonal antibody-based mixtures remain points to be clarified and optimized for a better therapeutic effect., (© 2019 médecine/sciences – Inserm.)

The gene editing tool CRISPR-Cas has become the foundation for developing numerous molecular systems used in research and, increasingly, in medical practice. In particular, Cas proteins devoid of nucleolytic activity (dead Cas proteins; dCas) can be used to deliver functional cargo to programmed sites in the genome. In this review, we describe current CRISPR systems used for developing different dCas-based molecular approaches and summarize their most significant applications. We conclude with comments on the state-of-art in the CRISPR field and future directions.

Infectious diseases are still a significant cause of morbidity and mortality worldwide. Despite the progress in drug development, the occurrence of microbial resistance is still a significant concern. Alternative therapeutic strategies are required for non-responding or relapsing patients. Chimeric antigen receptor (CAR) T cells has revolutionized cancer immunotherapy, providing a potential therapeutic option for patients who are unresponsive to standard treatments. Recently two CAR T cell therapies, Yescarta® (Kite Pharma/Gilead) and Kymriah® (Novartis) were approved by the FDA for the treatments of certain types of non-Hodgkin lymphoma and B-cell precursor acute lymphoblastic leukemia, respectively. The success of adoptive CAR T cell therapy for cancer has inspired researchers to develop CARs for the treatment of infectious diseases. Here, we review the main achievements in CAR T cell therapy targeting viral infections, including Human Immunodeficiency Virus, Hepatitis C Virus, Hepatitis B Virus, Human Cytomegalovirus, and opportunistic fungal infections such as invasive aspergillosis., (Copyright © 2019 Seif, Einsele and Löffler.)