The gut microbiome regulates a number of homeostatic mechanisms in the healthy host including immune function and gut barrier protection. Loss of normal gut microbial structure and function has been ...associated with diseases as diverse as Clostridioides difficile infection, asthma, and epilepsy. Recent evidence has also demonstrated a link between the gut microbiome and sepsis. In this review, we focus on three key areas of the interaction between the gut microbiome and sepsis. First, prior to sepsis onset, gut microbiome alteration increases sepsis susceptibility through several mechanisms, including (a) allowing for expansion of pathogenic intestinal bacteria, (b) priming the immune system for a robust pro-inflammatory response, and (c) decreasing production of beneficial microbial products such as short-chain fatty acids. Second, once sepsis is established, gut microbiome disruption worsens and increases susceptibility to end-organ dysfunction. Third, there is limited evidence that microbiome-based therapeutics, including probiotics and selective digestive decontamination, may decrease sepsis risk and improve sepsis outcomes in select patient populations, but concerns about safety have limited uptake. Case reports of a different microbiome-based therapy, fecal microbiota transplantation, have shown correlation with gut microbial structure restoration and decreased inflammatory response, but these results require further validation. While much of the evidence linking the gut microbiome and sepsis has been established in pre-clinical studies, clinical evidence is lacking in many areas. To address this, we outline a potential research agenda for further investigating the interaction between the gut microbiome and sepsis.
In this report, Ebola virus was cultured from aqueous humor 14 weeks after disease onset and 9 weeks after resolution of viremia, a finding that indicates the potential for delayed clearance of the ...virus from immune-privileged sites.
The current outbreak of EVD is believed to have begun in December 2013.
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As of April 26, 2015, a total of 26,312 cases of EVD (including 10,899 deaths) had been reported in six countries in West Africa (i.e., Sierra Leone, Liberia, Guinea, Mali, Nigeria, and Senegal), the United States, the United Kingdom, and Spain.
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The outbreak has also resulted in the largest number of EVD survivors in history.
Among survivors of EVD, late complications that include ocular disease can develop during convalescence.
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However, few systematic studies have been conducted on post-EVD sequelae, so the incidence and clinical manifestations of . . .
Most reverse transcription PCR protocols for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) include 2-3 targets for detection. We developed a triplex, real-time reverse transcription ...PCR for SARS-CoV-2 that maintained clinical performance compared with singleplex assays. This protocol could streamline detection and decrease reagent use during current high SARS-CoV-2 testing demands.
The COVID-19 pandemic has changed the way we practice medicine and lead our lives. In addition to pulmonary symptoms; COVID-19 as a syndrome has multisystemic involvement including frequent ...gastrointestinal symptoms such as diarrhea. Due to microbiome alterations with COVID-19 and frequent antibiotic exposure, COVID-19 can be complicated by
infection. Co-infection with these two can be associated with a high risk of complications. Infection control measures in hospitals is enhanced due to the COVID-19 pandemic which in turn appears to reduce the incidence of hospital-acquired infections such as
infection. Another implication of COVID-19 and its potential transmissibility by stool is microbiome-based therapies. Potential stool donors should be screened COVID-19 symptoms and be tested for COVID-19.
The utility of rapid antigen testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is measured within the context for which it is applied; diagnostic accuracy must be considered in ...determining if rapid antigen testing is appropriate for the clinical situation. In this issue of the Journal of Clinical Microbiology, J. N. Kanji, D. T. Proctor, W. Stokes, B. M. Berenger, et al. (J Clin Microbiol 59:e01411-21, 2021, https://doi.org/10.1128/JCM.01411-21) evaluate two rapid antigen tests that demonstrate high false-positive rates in asymptomatic health care workers. The assays may not be useful in situations where there is a shortage of staff, such as health care settings, since isolation would occur unnecessarily for these employees.
This study examines the feasibility of rapidly training and fit testing health care workers to use elastomeric half-mask respirators (EHMRs), widely used in construction and manufacturing, as an ...alternative to N95 respirators during periods of shortage.
Background. Patients with recurrent Clostridium difficile infection (CDI) have a > 60% risk of relapse, as conventional therapies do not address the underlying gastrointestinal dysbiosis. This ...exploratory study evaluated the safety and efficacy of bacterial spores for preventing recurrent CDI. Methods. Stool specimens from healthy donors were treated with ethanol to eliminate pathogens. The resulting spores were fractionated and encapsulated for oral delivery as SER-109. Following their response to standard-of-care antibiotics, patients in cohort 1 were treated with SER-109 on 2 consecutive days (geometric mean dose, 1.7 × 10⁹ spores), and those in cohort 2 were treated on 1 day (geometric mean dose, 1.1 × 10⁸ spores). The primary efficacy end point was absence of C. difficile-positive diarrhea during an 8-week follow-up period. Microbiome alterations were assessed. Results. Thirty patients (median age, 66.5 years; 67% female) were enrolled, and 26 (86.7%) met the primary efficacy end point. Three patients with early, self-limiting C. difficile-positive diarrhea did not require antibiotics and tested negative for C. difficile at 8 weeks; thus, 96.7% (29 of 30) achieved clinical resolution. In parallel, gut microbiota rapidly diversified, with durable engraftment of spores and no outgrowth of non-spore-forming bacteria found after SER-109 treatment. Adverse events included mild diarrhea, abdominal pain, and nausea. Conclusions. SER-109 successfully prevented CDI and had a favorable safety profile, supporting a novel microbiome-based intervention as a potential therapy for recurrent CDI.
Because of the well-established therapeutic benefit of boosting antitumor responses through blockade of the T cell inhibitory receptor PD-1, it has been proposed that PD-1 blockade could also be ...useful in infectious disease settings, including
(Mtb) infection. However, in preclinical models, Mtb-infected PD-1
mice mount exaggerated T
1 responses that drive lethal immunopathology. Multiple cases of tuberculosis during PD-1 blockade have been observed in patients with cancer, but in humans little is understood about Mtb-specific immune responses during checkpoint blockade-associated tuberculosis. Here, we report two more cases. We describe a patient who succumbed to disseminated tuberculosis after PD-1 blockade for treatment of nasopharyngeal carcinoma, and we examine Mtb-specific immune responses in a patient with Merkel cell carcinoma who developed checkpoint blockade-associated tuberculosis and was successfully treated for the infection. After anti-PD-1 administration, interferon-γ-producing Mtb-specific CD4 T cells became more prevalent in the blood, and a tuberculoma developed a few months thereafter. Mtb-specific T
17 cells, CD8 T cells, regulatory T cells, and antibody abundance did not change before the appearance of the granuloma. These results are consistent with the murine model data and suggest that boosting T
1 function with PD-1 blockade may increase the risk or severity of tuberculosis in humans.
Significance In 2014, Ebola virus became a household term. The ongoing outbreak in West Africa is the largest Ebola virus outbreak ever recorded, with over 20,000 cases and over 8,000 deaths to date. ...Very little is known about the human cellular immune response to Ebola virus infection, and this lack of knowledge has hindered development of effective therapies and vaccines. In this study, we characterize the human immune response to Ebola virus infection in four patients. We define the kinetics of T- and B-cell activation, and determine which viral proteins are targets of the Ebola virus-specific T-cell response in humans.
Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10–50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1–2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients’ discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.
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