Outcome Of Infectious Diseases Research Articles

Systematic analysis of infectious disease outcomes by age shows lowest severity in school-age children

The COVID-19 pandemic has ignited interest in age-specific manifestations of infection but surprisingly little is known about relative severity of infectious disease between the extremes of age. In a systematic analysis we identified 142 datasets with information on severity of disease by age for 32 different infectious diseases, 19 viral and 13 bacterial. For almost all infections, school-age children have the least severe disease, and severity starts to rise long before old age. Indeed, for many infections even young adults have more severe disease than children, and dengue was the only infection that was most severe in school-age children. Together with data on vaccine response in children and young adults, the findings suggest peak immune function is reached around 5–14 years of age. Relative immune senescence may begin much earlier than assumed, before accelerating in older age groups. This has major implications for understanding resilience to infection, optimal vaccine scheduling, and appropriate health protection policies across the life course.

Variation of HLA class I (-A and -C) genes in individuals infected with hepatitis B or hepatitis C virus in Cameroon

The Human Leucocyte Antigens (HLA) work in concert with other immune factors to modulate immunity to viral infections. Extensive variation has been reported in the genetic sequences and functions of classical HLA class I genes in many (mostly Western) populations, and several HLA associations with infectious disease outcomes have been reported. Little is known about their role in the susceptibility or resistance to hepatitis viruses in Central African populations. The aim of this study was to determine variants of two HLA class I genes (HLA-A and -C) in adults infected with hepatitis B (HBV)- or -C (HCV) virus in Cameroon.In this case-control study, a total of 169 unrelated adults comprising 68 HCV-infected, 38 HBV-infected and 63 uninfected (controls) individuals participated. Each consented participant was screened for HBV, HCV, and HIV infections and willingly donated a single blood sample for genomic DNA isolation and some clinical laboratory tests. HLA-A and HLA-C were genotyped using previously described sequence-based techniques (SBT).A total of 54 HLA alleles were identified in the study population (27 HLA-A and 27 HLA-C). HLA-A∗23:01 and HLA-C∗07:01 were the most common alleles with genotype frequencies of 31.4% and 29.3%, respectively. Hepatitis individuals were six times more likely to be HLA-A∗30:01 carriers than uninfected controls (OR = 6.30, p = 0.020 (HBV); OR = 6.21, p = 0.010 (HCV), respectively). Similarly, carriers of HLA-C∗17:01 were over-represented in the HBV-infected compared to the uninfected control group (21.9% vs. 6.4%, respectively) suggesting that this allele could play a role in the susceptibility to HBV infection.These findings demonstrate that carriers of HLA-A∗30:01 were over-represented in the hepatitis group compared to uninfected controls while HLA-C∗17:01 was completely absent in the HCV + group.

Relationship Between the Presence of Infectious Disease and Clinical Outcomes of Patients with Cardiorenal Syndrome Type 1

Relationship Between the Presence of Infectious Disease and Clinical Outcomes of Patients with Cardiorenal Syndrome Type 1

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19.

Fighting infectious diseases, particularly viral infections, is a demanding task for human health. Targeting the pathogens or targeting the host are different strategies, but with an identical purpose, i.e., to curb the pathogen’s spreading and cure the illness. It appears that targeting a host to increase tolerance against pathogens can be of substantial advantage and is a strategy used in evolution. Practically, it has a broader protective spectrum than that of only targeting the specific pathogens, which differ in terms of susceptibility. Methods for host targeting applied in one pandemic can even be effective for upcoming pandemics with different pathogens. This is even more urgent if we consider the possible concomitance of two respiratory diseases with potential multi-organ afflictions such as Coronavirus disease 2019 (COVID-19) and seasonal flu. Melatonin is a molecule that can enhance the host’s tolerance against pathogen invasions. Due to its antioxidant, anti-inflammatory, and immunoregulatory activities, melatonin has the capacity to reduce the severity and mortality of deadly virus infections including COVID-19. Melatonin is synthesized and functions in mitochondria, which play a critical role in viral infections. Not surprisingly, melatonin synthesis can become a target of viral strategies that manipulate the mitochondrial status. For example, a viral infection can switch energy metabolism from respiration to widely anaerobic glycolysis even if plenty of oxygen is available (the Warburg effect) when the host cell cannot generate acetyl-coenzyme A, a metabolite required for melatonin biosynthesis. Under some conditions, including aging, gender, predisposed health conditions, already compromised mitochondria, when exposed to further viral challenges, lose their capacity for producing sufficient amounts of melatonin. This leads to a reduced support of mitochondrial functions and makes these individuals more vulnerable to infectious diseases. Thus, the maintenance of mitochondrial function by melatonin supplementation can be expected to generate beneficial effects on the outcome of viral infectious diseases, particularly COVID-19.

The Impact of Hypertension and Use of Calcium Channel Blockers on Tuberculosis Treatment Outcomes

Hypertension induces systemic inflammation, but its impact on the outcome of infectious diseases like tuberculosis (TB) is unknown. Calcium channel blockers (CCB) improve TB treatment outcomes in preclinical models, but their effect in patients with TB remain unclear. This retrospective cohort study, including all patients > 18 years receiving treatment for culture-confirmed, drug-sensitive TB from 2000 to 2016 at the National Taiwan University Hospital, assessed the association of hypertension and CCB use with all-cause and infection-related mortality during the first 9 months of TB treatment, as well as sputum smear microscopy and sputum culture positivity at 2 and 6 months. Of the 2894 patients, 1052 (36.4%) had hypertension. A multivariable analysis revealed that hypertension was associated with increased mortality due to all causes (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.23-1.99) and infections (HR, 1.87; 95% CI, 1.34-2.6), but there were no statistical differences in microbiological outcomes when stratified based on hypertensive group. Dihydropyridine-CCB (DHP-CCB) use was associated only with reduced all-cause mortality (HR, 0.67; 95% CI, .45-.98) by univariable Cox regression. There were no associations between DHP-CCB use and infection-related mortality (HR, 0.78; 95% CI, .46-1.34) or microbiological outcomes in univariable or multivariable regression analyses. Patients with hypertension have increased all-cause mortality and infection-related mortality during the 9 months following TB treatment initiation. DHP-CCB use may lower all-cause mortality in TB patients with hypertension. The presence of hypertension or the use of CCB did not result in a significant change in microbiological outcomes.

Keeping in Touch with Type-III Secretion System Effectors: Mass Spectrometry-Based Proteomics to Study Effector-Host Protein-Protein Interactions.

Manipulation of host cellular processes by translocated bacterial effectors is key to the success of bacterial pathogens and some symbionts. Therefore, a comprehensive understanding of effectors is of critical importance to understand infection biology. It has become increasingly clear that the identification of host protein targets contributes invaluable knowledge to the characterization of effector function during pathogenesis. Recent advances in mapping protein–protein interaction networks by means of mass spectrometry-based interactomics have enabled the identification of host targets at large-scale. In this review, we highlight mass spectrometry-driven proteomics strategies and recent advances to elucidate type-III secretion system effector–host protein–protein interactions. Furthermore, we highlight approaches for defining spatial and temporal effector–host interactions, and discuss possible avenues for studying natively delivered effectors in the context of infection. Overall, the knowledge gained when unravelling effector complexation with host factors will provide novel opportunities to control infectious disease outcomes.

Travel-related control measures to contain the COVID-19 pandemic: a rapid review.

Background In late 2019, first cases of coronavirus disease 2019, or COVID‐19, caused by the novel coronavirus SARS‐CoV‐2, were reported in Wuhan, China. Subsequently COVID‐19 spread rapidly around the world. To contain the ensuing pandemic, numerous countries have implemented control measures related to international travel, including border closures, partial travel restrictions, entry or exit screening, and quarantine of travellers. Objectives To assess the effectiveness of travel‐related control measures during the COVID‐19 pandemic on infectious disease and screening‐related outcomes. Search methods We searched MEDLINE, Embase and COVID‐19‐specific databases, including the WHO Global Database on COVID‐19 Research, the Cochrane COVID‐19 Study Register, and the CDC COVID‐19 Research Database on 26 June 2020. We also conducted backward‐citation searches with existing reviews. Selection criteria We considered experimental, quasi‐experimental, observational and modelling studies assessing the effects of travel‐related control measures affecting human travel across national borders during the COVID‐19 pandemic. We also included studies concerned with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) as indirect evidence. Primary outcomes were cases avoided, cases detected and a shift in epidemic development due to the measures. Secondary outcomes were other infectious disease transmission outcomes, healthcare utilisation, resource requirements and adverse effects if identified in studies assessing at least one primary outcome. Data collection and analysis One review author screened titles and abstracts; all excluded abstracts were screened in duplicate. Two review authors independently screened full texts. One review author extracted data, assessed risk of bias and appraised study quality. At least one additional review author checked for correctness of all data reported in the 'Risk of bias' assessment, quality appraisal and data synthesis. For assessing the risk of bias and quality of included studies, we used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool for observational studies concerned with screening, ROBINS‐I for observational ecological studies and a bespoke tool for modelling studies. We synthesised findings narratively. One review author assessed certainty of evidence with GRADE, and the review author team discussed ratings. Main results We included 40 records reporting on 36 unique studies. We found 17 modelling studies, 7 observational screening studies and one observational ecological study on COVID‐19, four modelling and six observational studies on SARS, and one modelling study on SARS and MERS, covering a variety of settings and epidemic stages. Most studies compared travel‐related control measures against a counterfactual scenario in which the intervention measure was not implemented. However, some modelling studies described additional comparator scenarios, such as different levels of travel restrictions, or a combination of measures. There were concerns with the quality of many modelling studies and the risk of bias of observational studies. Many modelling studies used potentially inappropriate assumptions about the structure and input parameters of models, and failed to adequately assess uncertainty. Concerns with observational screening studies commonly related to the reference test and the flow of the screening process.

Immunometabolism and HIV-1 pathogenesis: food for thought.

Antiretroviral therapies efficiently block HIV-1 replication but need to be maintained for life. Moreover, chronic inflammation is a hallmark of HIV-1 infection that persists despite treatment. There is, therefore, an urgent need to better understand the mechanisms driving HIV-1 pathogenesis and to identify new targets for therapeutic intervention. In the past few years, the decisive role of cellular metabolism in the fate and activity of immune cells has been uncovered, as well as its impact on the outcome of infectious diseases. Emerging evidence suggests that immunometabolism has a key role in HIV-1 pathogenesis. The metabolic pathways of CD4+ T cells and macrophages determine their susceptibility to infection, the persistence ofinfected cells and the establishment of latency. Immunometabolism also shapes immune responses against HIV-1, and cell metabolic products are key drivers of inflammation during infection. In this Review, we summarize current knowledge of the links between HIV-1 infection and immunometabolism, and we discuss the potential opportunities and challenges for therapeutic interventions.

Extracellular Vesicle-Related Thrombosis in Viral Infection.

Although the outcomes of viral infectious diseases are remarkably varied, most infections cause acute diseases after a short period. Novel coronavirus disease 2019, which recently spread worldwide, is no exception. Extracellular vesicles (EVs) are small circulating membrane-enclosed entities shed from the cell surface in response to cell activation or apoptosis. EVs transport various kinds of bioactive molecules between cells, including functional RNAs, such as viral RNAs and proteins. Therefore, when EVs are at high levels, changes in cell activation, inflammation, angioplasty and transportation suggest that EVs are associated with various diseases. Clinical research on EVs includes studies on the coagulatory system. In particular, abnormal enhancement of the coagulatory system through EVs can cause thrombosis. In this review, we address the functions of EVs, thrombosis, and their involvement in viral infection.

Elevated body mass index is associated with an increased risk of infectious disease admissions and mortality: a mendelian randomization study

ObjectiveThe effect of body mass index (BMI) on the risk of infectious diseases admissions and mortality is unclear and is difficult to study given the risks of confounding variables. MethodsWe used genome-wide association studies (GWASs) with mendelian randomization (MR) to obtain causal inference of BMI on the following infectious diseases outcomes: hospital admissions for pneumonia, sepsis, urinary tract infections, skin and soft tissue infections (SSTIs) or all-cause infections. For patients with pneumonia and sepsis, we also analysed their 28-day and 90-day mortalities. The UK Biobank (UKB) cohort (n > 500 000) provided data for GWASs on infectious diseases. The GIANT consortium (n = 681 265) GWAS was used to identify single-nucleotide polymorphisms (SNPs) associated with BMI. ResultsGenetically increased BMI, by one standard deviation, was associated with higher rates of admission due to all infectious disease. The effect was most important for SSTIs (OR: 1.11, 95%CI: 1.09, 1.12). Increasing BMI by one standard deviation was associated with higher pneumonia mortality, especially at 28 days (OR: 1.03, 95%CI: 1.01, 1.05). BMI was not clearly associated with sepsis mortality, although interpretation of the results was limited by a small sample size. There were consistent findings in sensitivity analysis performed by removing highly pleiotropic SNPs and multivariate MR including type-2 diabetes mellitus, estimated glomerular filtration rate, high-density lipoprotein, educational attainment, and a history of smoking. ConclusionsIncreased BMI was associated with increased risk of admission for infectious disease and mortality. While the pathophysiology behind this phenomenon remains unknown, increasing BMI may influence immune dysregulation.

Neurocognitive functioning in MDR-TB patients with and without HIV in KwaZulu-Natal, South Africa.

Optimising medication adherence is one of the essential factors in reversing the tide of a TB-HIV syndemic in sub-Saharan Africa, especially South Africa. Impairment in key neurocognitive domains may impair patients' ability to maintain adherence to treatment, but the level of cognition and its relationship to HIV status has not been examined in individuals with drug-resistant TB. We therefore investigated performance on several key neurocognitive domains in relationship to HIV status in a multidrug-resistant tuberculosis patients (MDR-TB) sample. We enrolled microbiologically confirmed MDR-TB inpatients at a TB-specialist referral hospital in KwaZulu-Natal province, South Africa. We collected cross-sectional data on sociodemographic, clinical and neurocognitive function (e.g. attention, memory, executive functioning, language fluency, visual-spatial, eye-hand coordination). For the primary analysis, we excluded participants with major depressive episode/substance use disorder (MDE/SUD). We fitted adjusted Poisson regression models to explore the association between HIV and neurocognitive function. We enrolled 200 people with MDR-TB; 33 had MDE/SUD, and data of 167 were analysed (151 HIV+, 16 HIV-). The mean age of participants was 34.2years; the majority were female (83%), and 53% had not completed secondary school. There was evidence of impaired neurocognitive functioning across all domains in both HIV+/- study participants. Based on the regression analyses, individuals with co-infection (MDR-TB/HIV+), as well as those who had longer duration of hospital stays experienced significantly lower cognitive performance in several domains. Poor cognitive performance was significantly related to older age and lower educational attainment. The presence of major depression or substance use disorders did not influence the significance of the findings. Adults with MDR-TB have significant neurocognitive impairment, especially if HIV positive. An integrated approach is necessary in the management of MDR-TB as cognitive health influences the ability to adhere to chronic treatment, clinical outcomes and functionality.

Heterogeneous SIR Models, the Spread of Infectious Diseases and the Theoretical Paths for the Efficacy of Lockdowns, Mass Testing and Vaccination

This paper uses Heterogeneous SIR Models to predict the evolution of infection diseases in the presence of heterogeneity in the susceptible population. For illustration purposes, the simulation parameters chosen are in line with those observed for the SARS-CoV-2 pandemic. The paper shows that heterogeneity of susceptibility might play an important role in influencing health outcomes of infectious diseases. In particular, lockdowns or measures dividing the population into essential and non-essential workers might positively affect health outcomes due to increased heterogeneity in the infection rates of the different segments of the population – an effect not predicted by the standard SIR Model. Heterogeneous SIR Models also help us think about efficient ways of designing testing and vaccination programs.

Risk of Acute Kidney Injury in Combat-Injured Patients Associated With Concomitant Vancomycin and Extended-Spectrum β-Lactam Antibiotic Use.

Multidrug-resistant infections complicating combat-related trauma necessitate the use of broad-spectrum antimicrobials. Recent literature posits an association between vancomycin (VANC) and piperacillin-tazobactam (VPT) combination therapy and acute kidney injury (AKI). We examined whether therapy with VPT was associated with an increased risk of AKI compared to VANC and other broad-spectrum β-lactam antibiotics (VBL) following combat-related injuries. Patients within the Trauma Infectious Disease Outcomes Study (TIDOS) who received ≥48 hours concomitant VPT or VBL started within 24 hours of each other were assessed. Exclusion criteria were receipt of renal replacement therapy and baseline creatinine >1.5 mg/dL. Acute kidney injury was defined by meeting any of the Risk, Injury, Failure, Loss, End Stage Renal Disease (RIFLE), AKIN, or VANC consensus guidelines criteria 3 to 7 days after therapy initiation. Variables significantly associated with AKI were used in inverse probability treatment weighting to perform univariate and subsequent logistic regression multivariate modeling to determine significant risk factors for AKI. Sixty-one patients who received VPT and 207 who received VBL were included. Both groups had a median age of 24 years and initial median creatinine of 0.7 mg/dL. The VBL patients were more likely to have sustained blast injuries (P = .001) and received nephrotoxic agents (amphotericin [P = .002] and aminoglycosides [P < .001]). In the VBL group, AKI incidence was 9.7% compared to 13.1% in the VPT group (P = .438). Multivariate analysis identified a relative risk of 1.727 (95% CI: 1.027-2.765) for AKI associated with VPT exposure. Acute kidney injury severity generally met RIFLE Risk criteria and was 1 day in duration. Only 1 patient had persistent renal dysfunction 30 days after therapy completion. In this young and previously healthy, severely ill combat-injured population, VPT was associated with nearly twice the risk of AKI compared to VBL. Nevertheless, AKI was of low severity, short duration, and had high rates of renal recovery.

NcRI: a manually curated database for experimentally validated non-coding RNAs in inflammation

BackgroundInflammation has been considered to be central to the onset, progression, and outcome of infectious diseases, especially as one of the hallmarks of cancer. Non-coding RNAs (ncRNAs), such as miRNAs and lncRNAs, have emerged as vital regulators in control of immune and inflammatory processes, and also play important roles in the inflammatory disease and immunotherapy.ResultsIn this study, we presented a database ncRI, which documented experimentally verified ncRNAs in inflammatory diseases, from published articles. Each entry contained the detailed information about ncRNA name, inflammatory diseases, mechanism, experimental techniques (e.g., microarray, RNA-seq, qRT-PCR), experimental samples (cell line and/or tissue), expression patterns of ncRNA (up-regulated or down-regulated), reference information (PubMed ID, year of publication, title of paper) and so on. Collectively, ncRI recorded 11,166 entries that include 1976 miRNAs, 1377 lncRNAs and 107 other ncRNAs across 3 species (human, mouse, and rat) from more than 2000 articles. All these data are free for users to search, browse and download.ConclusionIn summary, the presented database ncRI provides a relatively comprehensive credible repository about ncRNAs and their roles in inflammatory diseases, and will be helpful for research on immunotherapy. The ncRI is now freely available to all users at http://www.jianglab.cn/ncRI/.

Use of antimicrobials in obstetric practice – A narrative review

Improvement of the outcome of infectious diseases by early and appropriate antimicrobial therapy is of paramount importance in any clinical discipline. Special considerations need to be given for the use of antimicrobial agents in obstetric practice, as it relates to the safety of both the mother and the fetus. However, their use and misuse are associated with significantly increasing antibiotic resistance. The objective of this review was to provide a useful overview for the practicing obstetrician, of current recommendations for the use of antibiotics in common situations related to pregnancy and the postpartum period,

Gender differences in community-acquired pneumonia

Community-acquired pneumonia (CAP) is the most common type of lower respiratory tract infection and a major cause of morbidity and mortality in adults worldwide. Sex and gender play an active role in the incidence and outcomes of major infectious diseases, including CAP. Some studies have reported higher male susceptibility to pulmonary infections and higher risk of death due to sepsis, but others have found the opposite effect. Biological differences (e.g. hormonal cycles and cellular immune- mediated responses) together with cultural, behavioral and socio-economic differences are important determinants of the course and outcome of CAP. Identify gender differences in CAP can guide patient's prognostication and management. The purpose of this review is to provide the available literature evidences about gender's influence on the clinical course of CAP in order to optimize the assessment, monitoring and treatment of this disease and to reduce its negative outcomes.

Linking administrative data sets of inpatient infectious diseases diagnoses in far North Queensland: a cohort profile

PurposeTo design a linked hospital database using administrative and clinical information to describe associations that predict infectious diseases outcomes, including long-term mortality.ParticipantsA retrospective cohort of Townsville Hospital inpatients discharged with...

Influences of Land-Use Dynamics and Surface Water Systems Interactions on Water-Related Infectious Diseases—A Systematic Review

Human interactions with surface water systems, through land-use dynamics, can influence the transmission of infectious water-related diseases. As a result, the aim of our study was to explore and examine the state of scientific evidence on the influences of these interactions on water-related infectious disease outcomes from a global perspective. A systematic review was conducted, using 54 peer-reviewed research articles published between 1995 and August 2019. The study revealed that there has been an increase in the number of publications since 2009; however, few of these publications (n = 6) made explicit linkages to the topic. It was found that urban and agricultural land-use changes had relatively high adverse impacts on water quality, due to high concentrations of fecal matter, heavy metals, and nutrients in surface water systems. Water systems were found as the common “vehicle” for infectious disease transmission, which in turn had linkages to sanitation and hygiene conditions. The study found explicit linkages between human–surface water interaction patterns and the transmission of water-based disease. However, weak and complex linkages were found between land-use change and the transmission of water-borne disease, due to multiple pathways and the dynamics of the other determinants of the disease. Therefore, further research studies, using interdisciplinary and transdisciplinary approaches to investigate and enhance a deeper understanding of these complexities and linkages among land use, surface water quality, and water-related infectious diseases, is crucial in developing integrated measures for sustainable water quality monitoring and diseases prevention.

Selective reconstitution of IFN‑γ gene function in Ncr1+ NK cells is sufficient to control systemic vaccinia virus infection

IFN-γ is an enigmatic cytokine that shows direct anti-viral effects, confers upregulation of MHC-II and other components relevant for antigen presentation, and that adjusts the composition and balance of complex cytokine responses. It is produced during immune responses by innate as well as adaptive immune cells and can critically affect the course and outcome of infectious diseases, autoimmunity, and cancer. To selectively analyze the function of innate immune cell-derived IFN-γ, we generated conditional IFN-γOFF mice, in which endogenous IFN-γ expression is disrupted by a loxP flanked gene trap cassette inserted into the first intron of the IFN-γ gene. IFN-γOFF mice were intercrossed with Ncr1-Cre or CD4-Cre mice that express Cre mainly in NK cells (IFN-γNcr1-ON mice) or T cells (IFN-γCD4-ON mice), respectively. Rosa26RFP reporter mice intercrossed with Ncr1-Cre mice showed selective RFP expression in more than 80% of the NK cells, while upon intercrossing with CD4-Cre mice abundant RFP expression was detected in T cells, but also to a minor extent in other immune cell subsets. Previous studies showed that IFN-γ expression is needed to promote survival of vaccinia virus (VACV) infection. Interestingly, during VACV infection of wild type and IFN-γCD4-ON mice two waves of serum IFN-γ were induced that peaked on day 1 and day 3/4 after infection. Similarly, VACV infected IFN-γNcr1-ON mice mounted two waves of IFN-γ responses, of which the first one was moderately and the second one profoundly reduced when compared with WT mice. Furthermore, IFN-γNcr1-ON as well as IFN-γCD4-ON mice survived VACV infection, whereas IFN-γOFF mice did not. As expected, ex vivo analysis of splenocytes derived from VACV infected IFN-γNcr1-ON mice showed IFN-γ expression in NK cells, but not T cells, whereas IFN-γOFF mice showed IFN-γ expression neither in NK cells nor T cells. VACV infected IFN-γNcr1-ON mice mounted normal cytokine responses, restored neutrophil accumulation, and showed normal myeloid cell distribution in blood and spleen. Additionally, in these mice normal MHC-II expression was detected on peripheral macrophages, whereas IFN-γOFF mice did not show MHC-II expression on such cells. In conclusion, upon VACV infection Ncr1 positive cells including NK cells mount two waves of early IFN-γ responses that are sufficient to promote the induction of protective anti-viral immunity.

Microbiota in viral infection and disease in humans and farm animals.

The influence of the microbiota on viral infection susceptibility and disease outcome is undisputable although varies among viruses. The purpose of understanding the interactions between microbiota, virus, and host is to identify practical, effective, and safe approaches that target microbiota for the prevention and treatment of viral diseases in humans and animals, as currently there are few effective and reliable antiviral therapies available. The initial step for achieving this goal is to gather clinical evidences, focusing on the viral pathogens—from human and animal studies—that have already been shown to interact with microbiota. The subsequent step is to identify mechanisms, through experimental evidences, to support the development of translational applications that target microbiota. In this chapter, we review evidences of virus infections altering microbiota and of microbiota enhancing or suppressing infectivity, altering host susceptibility to certain viral diseases, and influencing vaccine immunogenicity in humans and farm animals.