Viral Commensalism in Humans?

Valentine, Fred

doi:10.1086/588705

Cited by 17 publications

(10 citation statements)

References 25 publications

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“…Based on the role of IL-4 in immune regulation, it can be surmised that variations in IL-4 production may have detrimental effects on the immune system and could, therefore, initiate an abnormal inflammatory response, resulting in AE development after smallpox vaccination [33,91]. Thus, several studies have analyzed the effects of IL-4 production on immune response post smallpox vaccination.…”

Section: Cytokine Secretion Post Smallpox Vaccinationmentioning

confidence: 99%

“…Based on the results of these studies, it is probable that SNPs in the IL4 gene initiate the production of functionally different IL-4 proteins, or alter its bio-availability, resulting in an overstimulation or under-stimulation of the inflammatory response, leading to abnormal responses to smallpox vaccination [91]. …”

Section: Cytokine Secretion Post Smallpox Vaccinationmentioning

confidence: 99%

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Cytokine Production Associated with Smallpox Vaccine Responses

et al. 2014

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Smallpox was eradicated 34 years ago due to the success of the smallpox vaccine; yet, the vaccine continues to be studied because of its importance in responding to potential biological warfare and the adverse events associated with current smallpox vaccines. Interindividual variations in vaccine response are observed and are, in part, due to genetic variation. In some cases, these varying responses lead to adverse events, which occur at a relatively high rate for the smallpox vaccine compared with other vaccines. Here, we aim to summarize the cytokine responses associated with smallpox vaccine response to date. Along with a description of each of these cytokines, we describe the genetic and adverse event data associated with cytokine responses to smallpox vaccination.

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Section: Cytokine Secretion Post Smallpox Vaccinationmentioning

confidence: 99%

Section: Cytokine Secretion Post Smallpox Vaccinationmentioning

confidence: 99%

Cytokine Production Associated with Smallpox Vaccine Responses

et al. 2014

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“…On average, 0.5% of previously healthy, young individuals and 2.5% of elderly or immunocompromised patients that contract IAV have bacterial coinfections; however, during times of influenza pandemic these numbers climb even higher and in the 1918 influenza virus pandemic up to 6.1% of all patients with IAV were thought to have secondary bacterial infections ( 20 ). In 1918, prior to the use of antibiotics, autopsies confirmed the presence of bacteria in up to 95% of fatalities ( 3 , 21 ). In the 2009 pandemic between 18 and 34% of IAV patients in the ICU had a bacterial coinfection and up to 55% of fatalities were associated with bacterial coinfection ( 21 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

“…In 1918, prior to the use of antibiotics, autopsies confirmed the presence of bacteria in up to 95% of fatalities ( 3 , 21 ). In the 2009 pandemic between 18 and 34% of IAV patients in the ICU had a bacterial coinfection and up to 55% of fatalities were associated with bacterial coinfection ( 21 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

Coinfection With Influenza A Virus and Klebsiella oxytoca: An Underrecognized Impact on Host Resistance and Tolerance to Pulmonary Infections

et al. 2018

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Pneumonia is a world health problem and a leading cause of death, particularly affecting children and the elderly (1, 2). Bacterial pneumonia following infection with influenza A virus (IAV) is associated with increased morbidity and mortality but the mechanisms behind this phenomenon are not yet well-defined (3). Host resistance and tolerance are two processes essential for host survival during infection. Resistance is the host's ability to clear a pathogen while tolerance is the host's ability to overcome the impact of the pathogen as well as the host response to infection (4–8). Some studies have shown that IAV infection suppresses the immune response, leading to overwhelming bacterial loads (9–13). Other studies have shown that some IAV/bacterial coinfections cause alterations in tolerance mechanisms such as tissue resilience (14–16). In a recent analysis of nasopharyngeal swabs from patients hospitalized during the 2013–2014 influenza season, we have found that a significant proportion of IAV-infected patients were also colonized with Klebsiella oxytoca, a gram-negative bacteria known to be an opportunistic pathogen in a variety of diseases (17). Mice that were infected with K. oxytoca following IAV infection demonstrated decreased survival and significant weight loss when compared to mice infected with either single pathogen. Using this model, we found that IAV/K. oxytoca coinfection of the lung is characterized by an exaggerated inflammatory immune response. We observed early inflammatory cytokine and chemokine production, which in turn resulted in massive infiltration of neutrophils and inflammatory monocytes. Despite this swift response, the pulmonary pathogen burden in coinfected mice was similar to singly-infected animals, albeit with a slight delay in bacterial clearance. In addition, during coinfection we observed a shift in pulmonary macrophages toward an inflammatory and away from a tissue reparative phenotype. Interestingly, there was only a small increase in tissue damage in coinfected lungs as compared to either single infection. Our results indicate that during pulmonary coinfection a combination of seemingly modest defects in both host resistance and tolerance may act synergistically to cause worsened outcomes for the host. Given the prevalence of K. oxytoca detected in human IAV patients, these dysfunctional tolerance and resistance mechanisms may play an important role in the response of patients to IAV.

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“…Alternatively, or in addition, the impact of altered cytokine profiles on the cardiopulmonary system may influence the severity of HFMD [ 6 ]. In small studies, the severity of EV71 infection has been associated with altered concentrations of a number of different cytokines, including TNF∝, INFγ, IL6, and IL13, in blood and cerebrospinal fluid (CSF), with evidence that cytokine levels correlate with the degree of injury to the brainstem and spinal ganglia [ 7 ]. Moreover, in a number of animal studies of neurogenic hypertension, associations have been demonstrated between inflammatory cytokine levels and enhanced vasomotor and cardiac sympathetic drive [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Intravenous magnesium sulfate for the management of severe hand, foot, and mouth disease with autonomic nervous system dysregulation in Vietnamese children: study protocol for a randomized controlled trial

Qui

Khanh

Trieu

et al. 2016

Trials

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BackgroundOver the last 15 years, hand, foot, and mouth disease (HFMD) has emerged as a major public health burden across the Asia-Pacific region. A small proportion of HFMD patients, typically those infected with enterovirus 71 (EV71), develop brainstem encephalitis with autonomic nervous system (ANS) dysregulation and may progress rapidly to cardiopulmonary failure and death. Although milrinone has been reported to control hypertension and support myocardial function in two small studies, in practice, a number of children still deteriorate despite this treatment. Magnesium sulfate (MgSO4) is a cheap, safe, and readily available medication that is effective in managing tetanus-associated ANS dysregulation and has shown promise when used empirically in EV71-confirmed severe HFMD cases.Methods/DesignWe describe the protocol for a randomized, placebo-controlled, double-blind trial of intravenous MgSO4 in Vietnamese children diagnosed clinically with HFMD plus ANS dysregulation with systemic hypertension. A loading dose of MgSO4 or identical placebo is given over 20 min followed by a maintenance infusion for 72 h according to response, aiming for Mg levels two to three times the normal level in the treatment arm. The primary endpoint is a composite of disease progression within 72 h defined as follows: development of pre-specified blood pressure criteria necessitating the addition of milrinone, the need for ventilation, shock, or death. Secondary endpoints comprise these parameters singly, plus other clinical endpoints including the following: requirement for other inotropic agents; duration of hospitalization; presence of neurological sequelae at discharge in survivors; and neurodevelopmental status assessed 6 months after discharge. The number and severity of adverse events observed in the two treatment arms will also be compared. Based on preliminary data from a case series, and allowing for some losses, 190 patients (95 in each arm) will allow detection of a 50 % reduction in disease progression with 90 % power at a two-sided 5 % significance level.DiscussionGiven the large numbers of HFMD cases currently being seen in hospitals in Asia, if MgSO4 is shown to be effective in controlling ANS dysregulation and preventing severe HFMD complications, this finding would be important to pediatric care throughout the region.Trial registrationClinicalTrials.gov Identifier: NCT01940250 (Registered 22 August 2013).Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1215-6) contains supplementary material, which is available to authorized users.

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Viral Commensalism in Humans?

Cited by 17 publications

References 25 publications

Cytokine Production Associated with Smallpox Vaccine Responses

Cytokine Production Associated with Smallpox Vaccine Responses

Coinfection With Influenza A Virus and Klebsiella oxytoca: An Underrecognized Impact on Host Resistance and Tolerance to Pulmonary Infections

Intravenous magnesium sulfate for the management of severe hand, foot, and mouth disease with autonomic nervous system dysregulation in Vietnamese children: study protocol for a randomized controlled trial

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