scholarly journals 1028 Sleep and Enteric Disease: Sleep Now for Less Diarrhea Later

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A390-A391
Author(s):  
J Mantua ◽  
R L Gutierrez ◽  
S D Isidean ◽  
A N Alaca ◽  
K J Testa ◽  
...  
Keyword(s):  
Research Program ◽  
Sleep Time ◽  
Human Infection ◽  
Enterotoxigenic Escherichia Coli ◽  
Infection Model ◽  
Enteric Disease ◽  
Us Army ◽  
Medicine Research ◽  
Severe Diarrhea ◽  
The Us

Abstract Introduction The bi-directional relationship between sleep and immune function is well-established. Sufficient sleep supports immune health and can increase vaccine efficacy. Conversely, sickness can disturb sleep quality, which can delay recovery and waking functioning. However, the bidirectional relationship between sleep and infectious diarrhea, the leading infectious disease threat to deployed military populations, has not been studied. We assessed the bi-directional relationship between sleep and enteric disease utilizing data from a recently-completed controlled human infection model (CHIM) with enterotoxigenic Escherichia coli (ETEC). Methods During a CHIM to assess the efficacy of an immunoprophylactic targeting ETEC (NCT03040687), we measured sleep via actigraphy over an 8-day inpatient period. Participants ingested prophylaxis 3 times/day during days -2 and -1 and ingested ETEC on day 0. The primary outcome was moderate-severe diarrhea following the ETEC challenge. We hypothesized better sleep pre-challenge would reduce risk of disease after the challenge (assessed using linear regression). We also hypothesized total sleep time (TST) and sleep efficiency (SE) after the challenge would be lower/poorer than baseline (assessed using paired t-test). Results Among 59 participants (aged 34.4±8.1yrs, 64% female), longer TST the night preceding ETEC challenge was associated with lower total diarrhea volume (B=-3.13,p=.001). SE was slightly but significantly poorer after the challenge (78 vs. 76%; t(55)=2.2,p=.03), but there was no significant change in TST, potentially due to low TST pre-challenge (316 vs. 329 minutes; p=0.12). Conclusion These results - in aggregation with previous work on sleep and vaccines - suggest military sleep regulations should be put in place to increase sleep prior to traveling to an area of responsibility with high risk for enteric disease. These minor behavioral changes could provide lasting benefits to readiness of military servicemembers. Support This work was supported by Joint Warfighter Medical Research Program (JWMRP) and the Military Operational Medicine Research Program (MOMRP). The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Army or of the US Department of Defense. This abstract has been approved for public release with unlimited distribution.

scholarly journals Consensus Report on Shigella Controlled Human Infection Model: Clinical Endpoints

2019 ◽  
Vol 69 (Supplement_8) ◽  
pp. S591-S595 ◽  
Author(s):  
Calman A MacLennan ◽  
Mark S Riddle ◽  
Wilbur H Chen ◽  
Kawsar R Talaat ◽  
Varsha Jain ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Working Group ◽  
Shigella Flexneri ◽  
The United States ◽  
Human Infection ◽  
Watery Diarrhea ◽  
Infection Model ◽  
Antibiotic Administration ◽  
Severe Diarrhea ◽  
Clinical Endpoints

Abstract The Shigella controlled human infection model (CHIM) is valuable for assessing candidate Shigella vaccine efficacy and potentially accelerating regulatory approval. The Shigella CHIM is currently being conducted at 3 sites in the United States using Shigella flexneri 2a strain 2457T and Shigella sonnei strain 53G. Shigellosis can present variably as watery diarrhea alone or with dysentery, and can be accompanied by manifestations including fever, abdominal cramps, tenesmus, and malaise. For comparability, it is important to harmonize the primary clinical endpoint. An expert working group was convened on 2 February 2018 to review clinical data from Shigella CHIM studies performed to date and to develop a consensus primary endpoint. The consensus endpoint enabled “shigellosis” to present as severe diarrhea or moderate diarrhea or dysentery. The latter 2 criteria are met when concurrent with fever of 38.0°C and/or vomiting, and/or a constitutional/enteric symptom graded at least as “moderate” severity. The use of a blinded independent committee to adjudicate the primary endpoint by subject was also regarded as important. As safety of volunteers in challenge studies is of paramount importance and treatment timing can affect primary outcomes, a standard for early antibiotic administration was established as follows: (1) when the primary endpoint is met; (2) if a fever of ≥39.0°C develops; or (3) if the study physician deems it appropriate. Otherwise, antibiotics are given at 120 hours postinfectious challenge. The working group agreed on objective and subjective symptoms to be solicited, and standardized methods for assessing subject-reported severity of symptoms.

The Controlled Human Infection Model for Enterotoxigenic Escherichia coli

2021 ◽  
Author(s):  
Chad K. Porter ◽  
Kawsar R. Talaat ◽  
Sandra D. Isidean ◽  
Alwine Kardinaal ◽  
Subhra Chakraborty ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Human Infection ◽  
Enterotoxigenic Escherichia Coli ◽  
Infection Model

scholarly journals Consensus Report on Shigella Controlled Human Infection Model: Immunological Assays

2019 ◽  
Vol 69 (Supplement_8) ◽  
pp. S596-S601 ◽  
Author(s):  
Robert W Kaminski ◽  
Marcela F Pasetti ◽  
Ana Older Aguilar ◽  
Kristen A Clarkson ◽  
Sjoerd Rijpkema ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Human Infection ◽  
Health Concern ◽  
Substantial Contribution ◽  
Enzyme Linked Immunosorbent Assay ◽  
Infection Model ◽  
Middle Income ◽  
Severe Diarrhea ◽  
Vaccine Type ◽  
Immunological Assays

Abstract Moderate to severe diarrhea caused by Shigella is a global health concern due to its substantial contribution to morbidity and mortality in children aged <5 years in low- and middle-income countries. Although antibiotic treatment can be effective, emerging antimicrobial resistance, limited access, and cost affirm the role of vaccines as the most attractive countermeasure. Controlled human infection models (CHIMs) represent a valuable tool for assessing vaccine efficacy and potentially accelerating licensure. Currently, immunological analysis during CHIM studies is customized based on vaccine type, regimen, and administration route. Additionally, differences in type of immunoassays and procedures used limit comparisons across studies. In November 2017, an expert working group reviewed Shigella CHIM studies performed to date and developed consensus guidelines on prioritization of immunoassays, specimens, and collection time points. Immunoassays were ranked into 3 tiers, with antibodies to Shigella lipopolysaccharide (LPS) being the highest priority. To facilitate comparisons across clinical studies, a second workshop was conducted in December 2017, which focused on the pathway toward a recognized enzyme-linked immunosorbent assay (ELISA) to determine serum immunoglobulin G titers against Shigella LPS. The consensus of the meeting was to establish a consortium of international institutions with expertise in Shigella immunology that would work with the National Institute for Biological Standards and Control to establish a harmonized ELISA, produce a reference sera, and identify a reliable source of Shigella LPS for global utilization. Herein we describe efforts toward establishing common procedures to advance Shigella vaccine development, support licensure, and ultimately facilitate vaccine deployment and uptake.

scholarly journals Hyperimmune Bovine Colostral Anti-CS17 Antibodies Protect Against Enterotoxigenic Escherichia coli Diarrhea in a Randomized, Doubled-Blind, Placebo-Controlled Human Infection Model

2019 ◽  
Vol 220 (3) ◽  
pp. 505-513 ◽  
Author(s):  
Stephen J Savarino ◽  
Robin McKenzie ◽  
David R Tribble ◽  
Chad K Porter ◽  
Aisling O’Dowd ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Clinical Trials ◽  
Human Infection ◽  
Enterotoxigenic Escherichia Coli ◽  
Watery Diarrhea ◽  
Infection Model ◽  
Significant Protection ◽  
Etec Strain ◽  
Colonization Factors ◽  
To Receive

AbstractBackgroundEnterotoxigenic Escherichia coli (ETEC) commonly cause diarrhea in children living in developing countries and in travelers to those regions. ETEC are characterized by colonization factors (CFs) that mediate intestinal adherence. We assessed if bovine colostral IgG (bIgG) antibodies against a CF, CS17, or antibodies against CsbD, the minor tip subunit of CS17, would protect subjects against diarrhea following challenge with a CS17-expressing ETEC strain.MethodsAdult subjects were randomized (1:1:1) to receive oral bIgG against CS17, CsbD, or placebo. Two days prior to challenge, subjects began dosing 3 times daily with the bIgG products (or placebo). On day 3, subjects ingested 5 × 109 cfu ETEC strain LSN03-016011/A in buffer. Subjects were assessed for diarrhea for 120 hours postchallenge.ResultsA total of 36 subjects began oral prophylaxis and 35 were challenged with ETEC. While 50.0% of the placebo recipients had watery diarrhea, none of the subjects receiving anti-CS17 had diarrhea (P = .01). In contrast, diarrhea rates between placebo and anti-CsbD recipients (41.7%) were comparable (P = 1.0).ConclusionsThis is the first study to demonstrate anti-CS17 antibodies provide significant protection against ETEC expressing CS17. More research is needed to better understand why anti-CsbD was not comparably efficacious.Clinical Trials Registration. NCT00524004

A site assessment tool for inpatient controlled human infection models for enteric disease pathogens

2021 ◽  
pp. 174077452110524
Author(s):  
Chad K Porter ◽  
Katherine J Detizio ◽  
Nicole Maier ◽  
Kayla J Testa ◽  
Kawsar R Talaat ◽  
...  
Keyword(s):  
Assessment Tool ◽  
Human Infection ◽  
Infection Model ◽  
Enteric Disease ◽  
Ethical Considerations ◽  
Site Assessment ◽  
Susceptible Host ◽  
Infection Models ◽  
A Site ◽  
Ongoing Evaluation

The use of the controlled human infection model to facilitate product development and to advance understanding of host-pathogen interactions is of increasing interest. While administering a virulent (or infective) organism to a susceptible host necessitates an ongoing evaluation of safety and ethical considerations, a central theme in conducting these studies in a safe and ethical manner that yields actionable data is their conduct in facilities well-suited to address their unique attributes. To that end, we have developed a framework for evaluating potential sites in which to conduct inpatient enteric controlled human infection model to ensure consistency and increase the likelihood of success.

Neuro-Optometric Treatment of Complications from a Cerebellar Astrocytoma

2020 ◽  
pp. 304-312
Keyword(s):  
Visual System ◽  
Common Site ◽  
Us Army ◽  
Cranial Nerve Palsies ◽  
Pilocytic Astrocytomas ◽  
The Us ◽  
Extent Of Damage ◽  
Functional Components ◽  
The Brain

Background: Insult to the brain, whether from trauma or other etiologies, can have a devastating effect on an individual. Symptoms can be many and varied, depending on the location and extent of damage. This presentation can be a challenge to the optometrist charged with treating the sequelae of this event as multiple functional components of the visual system can be affected. Case Report: This paper describes the diagnosis and subsequent ophthalmic management of an acquired brain injury in a 22 year old male on active duty in the US Army. After developing acute neurological symptoms, the patient was diagnosed with a pilocytic astrocytoma of the cerebellum. Emergent neurosurgery to treat the neoplasm resulted in iatrogenic cranial nerve palsies and a hemispheric syndrome. Over the next 18 months, he was managed by a series of providers, including a strabismus surgeon, until presenting to our clinic. Lenses, prism, and in-office and out-of-office neurooptometric rehabilitation therapy were utilized to improve his functioning and make progress towards his goals. Conclusions: Pilocytic astrocytomas are the most common primary brain tumors, and the vast majority are benign with excellent surgical prognosis. Although the most common site is the cerebellum, the visual pathway is also frequently affected. If the eye or visual system is affected, optometrists have the ability to drastically improve quality of life with neuro-optometric rehabilitation.

EDUCATIONAL-TRAINING FACILITIES OF GROUND US FORCES

2019 ◽  
pp. 168-176
Author(s):  
D.B. Izyumov ◽  
E.L. Kondratyuk
Keyword(s):  
United States ◽  
Armed Forces ◽  
The United States ◽  
Educational Training ◽  
Us Army ◽  
The Us ◽  
Level Of Training ◽  
Army Personnel

The article discusses issues related to the development and use of training means and facilities in order to improve the level of training of US Army personnel. An overview of the main simulators used in the US Armed Forces at present is given, and the prospects for the development of the United States in this area are presented.

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