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BACKGROUND: Enterotoxigenic E. coli (ETEC) is a principal cause of diarrhea in travelers, deployed military personnel, and children living in low to middle-income countries. ETEC expresses a variety of virulence factors including colonization factors (CF) that facilitate adherence to the intestinal mucosa. We assessed the protective efficacy of a tip-localized subunit of CF antigen I (CFA/I), CfaE, delivered intradermally with the mutant E. coli heat-labile enterotoxin, LTR192G, in a controlled human infection model (CHIM). METHODS: Three cohorts of healthy adult subjects were enrolled and given three doses of 25 µg CfaE + 100 ng LTR192G vaccine intradermally at 3-week intervals. Approximately 28 days after the last vaccination, vaccinated and unvaccinated subjects were admitted as inpatients and challenged with approximately 2 × 107 cfu of CFA/I+ ETEC strain H10407 following an overnight fast. Subjects were assessed for moderate-to-severe diarrhea for 5 days post-challenge. RESULTS: A total of 52 volunteers received all three vaccinations; 41 vaccinated and 43 unvaccinated subjects were challenged and assessed for moderate-to-severe diarrhea. Naïve attack rates varied from 45.5% to 64.7% across the cohorts yielding an overall efficacy estimate of 27.8% (95% confidence intervals: -7.5-51.6%). In addition to reducing moderate-severe diarrhea rates, the vaccine significantly reduced loose stool output and overall ETEC disease severity. CONCLUSIONS: This is the first study to demonstrate protection against ETEC challenge after intradermal vaccination with an ETEC adhesin. Further examination of the challenge methodology is necessary to address the variability in naïve attack rate observed among the three cohorts in the present study.
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IMPORTANCE: The travelers' gut microbiome is potentially assaulted by acute and chronic perturbations (e.g., diarrhea, antibiotic use, and different environments). Prior studies of the impact of travel and travelers' diarrhea (TD) on the microbiome have not directly compared antibiotic regimens, and studies of different antibiotic regimens have not considered travelers' microbiomes. This gap is important to be addressed as the use of antibiotics to treat or prevent TD-even in moderate to severe cases or in regions with high infectious disease burden-is controversial based on the concerns for unintended consequences to the gut microbiome and antimicrobial resistance (AMR) emergence. Our study addresses this by evaluating the impact of defined antibiotic regimens (single-dose treatment or daily prophylaxis) on the gut microbiome and resistomes of deployed servicemembers, using samples collected during clinical trials. Our findings indicate that the antibiotic treatment regimens that were studied generally do not lead to adverse effects on the gut microbiome and resistome and identify the relative risks associated with prophylaxis. These results can be used to inform therapeutic guidelines for the prevention and treatment of TD and make progress toward using microbiome information in personalized medical care.
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Diarreia , Microbioma Gastrointestinal , Humanos , Diarreia/prevenção & controle , Viagem , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Resistência Microbiana a MedicamentosRESUMO
INTRODUCTION: Enterotoxigenic E. coli (ETEC) is a leading cause of diarrhea in travelers as well as for children living in low- to middle-income countries. ETEC adhere to intestinal epithelium via colonization factors (CFs). CFA/I, a common CF, is composed of a polymeric stalk and a tip-localized minor adhesive subunit, CfaE. Vaccine delivery by the transcutaneous immunization of dscCfaE was safe but was poorly immunogenic in a phase 1 trial when administered to volunteers with LTR(192G) and mLT. To potentially enhance the immunogenicity of CfaE while still delivering via a cutaneous route, we evaluated the safety and immunogenicity of two CfaE constructs administered intradermally (ID) with or without mLT. METHODS: CfaE was evaluated as a donor strand-complemented construct (dscCfaE) and as a chimeric construct (Chimera) in which dscCfaE replaces the A1 domain of the cholera toxin A subunit and assembles non-covalently with the pentamer of heat-labile toxin B (LTB). Subjects received three ID vaccinations three weeks apart with either dscCfaE (1, 5, and 25 µg) or Chimera (2.6 and 12.9 µg) with and without 0.1 µg of mLT. Subjects were monitored for local and systemic adverse events. Immunogenicity was evaluated by serum and antibody-secreting cell (ASC) responses. RESULTS: The vaccine was well-tolerated with predominantly mild and moderate local vaccine site reactions characterized by erythema, induration and post-inflammatory hyperpigmentation. High rates of serologic and ASC responses were seen across study groups with the most robust responses observed in subjects receiving 25 µg of dscCfaE with 0.1 mcg of LT(R192G). CONCLUSION: Both ETEC adhesin vaccine prototypes were safe and immunogenic when co-administered with mLT by the ID route. The observed immune responses induced with the high dose of dscCfaE and mLT warrant further assessment in a controlled human infection model.
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BACKGROUND: Inflammatory bowel diseases (IBD) incidence and prevalence in Latin America have experienced a significant shift in the last decades. There is paucity of IBD epidemiologic data in Argentina. AIM: To determine the incidence and prevalence of IBD between 2018 and 2022 of a population from the city of Buenos Aires. MATERIALS AND METHODS: From January 1st, 2018 to December 31st, 2022, the total population of two healthcare insurances were studied. 'Possible' IBD cases were identified using the following information sources: IBD-unit patient databases; electronic medical record; central laboratory electronic database; histopathology electronic database; pharmacy electronic database. Age-adjusted incidence and prevalence rates for Crohn's disease (CD), ulcerative colitis (UC) and IBD were estimated based on the number of patients compared with the at-risk population and expressed per 100,000 subjects. Trends in IBD incidence and prevalence were estimated as annual percentage changes; we used Poisson regression modeling to calculate significance in these trends over time. RESULTS: Information source analysis rendered 172 possible cases, of which 82 cases of IBD were finally confirmed: 27.16% were CD and 72.84% were UC. Mean age-standardized incidence across the study period for IBD, CD and UC was 11.93 (11.28-12.55), 2.88 (2.65-3.07) and 9.05 (8.83-9.2) respectively. Point prevalence on December 31st, 2022 for IBD, UC and CD was 134 (95%CI 132.3-135.6), 98 (96.95-99.52) and 36 (35.69-36.4) respectively. CONCLUSIONS: We found an incidence and prevalence of IBD in a population from Buenos Aires higher than those previously published in epidemiological studies in Argentina.
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Shigella species cause severe disease among travelers to, and children living in, endemic countries. Although significant efforts have been made to improve sanitation, increased antibiotic resistance and other factors suggest an effective vaccine is a critical need. Artificial Invaplex (InvaplexAR) is a subunit vaccine approach complexing Shigella LPS with invasion plasmid antigens. In pre-clinical studies, the InvaplexAR vaccine demonstrated increased immunogenicity as compared to the first generation product and was subsequently manufactured under cGMP for clinical testing in a first-in-human Phase 1 study. The primary objective of this study was the safety of S. flexneri 2a InvaplexAR given by intranasal (IN) immunization (without adjuvant) in a single-center, open-label, dose-escalating Phase 1 trial and secondarily to assess immunogenicity to identify a dose of InvaplexAR for subsequent clinical evaluations. Subjects received three IN immunizations of InvaplexAR, two weeks apart, in increasing dose cohorts (10 µg, 50 µg, 250 µg, and 500 µg). Adverse events were monitored using symptom surveillance, memory aids, and targeted physical exams. Samples were collected throughout the study to investigate vaccine-induced systemic and mucosal immune responses. There were no adverse events that met vaccination-stopping criteria. The majority (96%) of vaccine-related adverse events were mild in severity (most commonly nasal congestion, rhinorrhea, and post-nasal drip). Vaccination with InvaplexAR induced anti-LPS serum IgG responses and anti-Invaplex IgA and IgG antibody secreting cell (ASC) responses at vaccine doses ≥250 µg. Additionally, mucosal immune responses and functional antibody responses were seen from the serum bactericidal assay measurements. Notably, the responder rates and the kinetics of ASCs and antibody lymphocyte secretion (ALS) were similar, suggesting that either assay may be employed to identify IgG and IgA secreting cells. Further studies with InvaplexAR will evaluate alternative immunization routes, vaccination schedules and formulations to further optimize immunogenicity. (Clinical Trial Registry Number NCT02445963).
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BACKGROUND: Acute diarrhea is the most frequent diagnosis among ill travelers. Sleep loss may weaken the body's defense against pathogens and increase susceptibility to infection. The relationship between sleep and infectious diarrhea has not been studied and was assessed utilizing data from a controlled human infection model (CHIM) for enterotoxigenic Escherichia coli (ETEC). METHODS: During a CHIM assessing the efficacy of an immunoprophylactic targeting ETEC against moderate-to-severe diarrhea (MSD) following challenge, we measured sleep via actigraphy over an 8-day inpatient period. We hypothesized better sleep pre-challenge would predict illness symptomatology following challenge. RESULTS: Among 57 participants (aged 34.4 ± 8.1 years, 64% male), there was no relationship between sleep metrics and incidence of MSD. However, longer total sleep time the night preceding ETEC challenge was associated with lower maximum 24 h diarrhea volume (B = -1.80, p = 0.01) and total diarrhea volume (B = -2.45, p = 0.01). CONCLUSIONS: This novel study showed that shorter sleep duration predicted diarrhea severity over the course of an ETEC infection. Future work should experimentally manipulate sleep to further clarify its impact on diarrhea-related outcomes for ETEC and other important enteric pathogens.
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Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Masculino , Humanos , Feminino , Anticorpos Antibacterianos , Diarreia/prevenção & controle , Infecções por Escherichia coli/prevenção & controle , SonoRESUMO
BACKGROUND: To date, no real-world data are available to describe cefiderocol use in carbapenem-resistant Acinetobacter baumannii (CRAB) meningitis. Furthermore, cefiderocol pharmacokinetic (PK) data to support CNS penetration in human subjects are limited. These gaps pose a significant concern for clinicians who are faced with treating such infections when considering cefiderocol use. OBJECTIVES: To describe cefiderocol CSF and plasma PK and pharmacodynamic (PD) data from two different dosing regimens [2â g IV q6h (regimen 1) and 2â g IV q8h (regimen 2)] during treatment of CRAB meningitis. PATIENTS AND METHODS: A 61-year-old woman with CRAB meningitis was treated with cefiderocol and intraventricular gentamicin. Steady-state plasma and CSF cefiderocol concentrations were evaluated on Day 19 (regimen 1) and Day 24 (regimen 2) during the cefiderocol treatment course. RESULTS: CSF AUC was 146.49 and 118.28â mg·h/L, as determined by the linear-log trapezoidal method for regimens 1 and 2, respectively. Penetration into CSF estimated as the AUCCSF/AUCfree plasma ratio was 68% and 60% for regimens 1 and 2, respectively. Estimated free plasma and CSF concentrations exceeded the MIC of the isolate for 100% of the dosing interval. Microbiological and clinical cure were achieved, and no cefiderocol-associated adverse effects were observed. CONCLUSIONS: Cefiderocol, when given as 2â g q8h and 2â g q6h, attained CSF concentrations that exceeded the organism-specific MIC and the CLSI susceptible breakpoint (≤4â mg/L) for 100% of the dosing interval.
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Acinetobacter baumannii , Meningite , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Cefalosporinas/uso terapêutico , Feminino , Gentamicinas , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , CefiderocolRESUMO
Objetivo: determinar el perfil de la mortalidad por COVID-19 en el municipio de El Alto en la gestión 2020. Metodología: El presente trabajo de investigación es un estudio con enfoque cuantitativo, retrospectivo, descriptivo y de corte transversal, porque recopila la información de las defunciones producidas por COVID-19 en el municipio de El Alto en la gestión 2020. Para este fin se logró tener acceso a la información de 448 personas fallecidas. Resultados: Se realizo el cálculo de las tasas de mortalidad general y especifica. Para el análisis de los datos estadísticos se utilizó gráficas y tablas de frecuencia en el siguiente detalle distribución de los casos de mortalidad por COVID-19 por edad, esperanza de vida al nacer; índice de masculinidad, para todas las variables sociodemográficas y la distribución de los casos de defunción hospitalaria. Conclusiones: La investigación permitió inventariar 448 defunciones por COVID-19 en la gestión 2020, las mismas que fueron registradas en el sistema de Administración de hechos vitales S.I.A.H.V. que es la herramienta orientada al registro, análisis y distribución de la tendencia de la mortalidad en Bolivia.
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COVID-19RESUMO
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.
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Interações Hospedeiro-Patógeno , Pacientes Internados , HumanosRESUMO
BACKGROUND: Travellers' diarrhoea (TD) is the most common travel-related illness with an estimated 10 million people afflicted annually. Outcome measures to assess the efficacy of primary and secondary TD interventions were historically based on diarrhoea frequency with ≥1 associated gastrointestinal symptom. Furthermore, efficacy determination is often made on the presence or absence of TD, rather than on TD illness severity. Current severity classifications are based on subjective consideration of impact of illness on activity. We sought to develop a standardized scoring system to characterize TD severity to potentially apply as a secondary outcome in future field studies. METHODS: Data on multiple signs and symptoms were obtained from a previously published multisite TD treatment trial conducted by the US Department of Defense (TrEAT TD). Correlation, regression and multiple correspondence analyses were performed to assess impact on activity and a TD severity score was established. RESULTS: Numerous signs and symptoms were associated with impaired function, with malaise and nausea most strongly associated [odds ratio (OR) 5.9-44.3, P < 0.0001 and OR 2.8-37.1, P < 0.0001, respectively). Based on co-varying symptomatology, a TD severity score accounting for diarrhoea frequency in addition to several signs and symptoms was a better predictor of negative impact on function than any single sign/symptom (X2 = 127.16, P < 0.001). Additionally, there was a significant difference (P < 0.0001) in the mean TD severity score between those with acute watery diarrhoea (3.9 ± 1.9) and those with dysentery or acute febrile illness (6.2 ± 2.0). CONCLUSIONS: The newly developed disease severity score better predicted a negative impact on activity due to TD than did any single sign or symptom. Incorporating multiple parameters into the TD severity score better captures illness severity and moves the field towards current recommendations for TD management by considering symptoms with high functional impact. Further validation of this score is needed in non-military travellers and other settings.
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Disenteria , Vacinas , Diarreia/tratamento farmacológico , Humanos , Índice de Gravidade de Doença , Viagem , Doença Relacionada a Viagens , Vacinas/uso terapêuticoRESUMO
The controlled human infection model (CHIM) for enterotoxigenic Escherichia coli (ETEC) has been instrumental in defining ETEC as a causative agent of acute watery diarrhea, providing insights into disease pathogenesis and resistance to illness, and enabling preliminary efficacy evaluations for numerous products including vaccines, immunoprophylactics, and drugs. Over a dozen strains have been evaluated to date, with a spectrum of clinical signs and symptoms that appear to replicate the clinical illness seen with naturally occurring ETEC. Recent advancements in the ETEC CHIM have enhanced the characterization of clinical, immunological, and microbiological outcomes. It is anticipated that omics-based technologies applied to ETEC CHIMs will continue to broaden our understanding of host-pathogen interactions and facilitate the development of primary and secondary prevention strategies.
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INTRODUCTION: Enterotoxigenic Escherichia coli (ETEC) is a common cause of infectious diarrhoea and a leading cause of morbidity and mortality in children living in resource-limited settings. It is also the leading cause of travellers' diarrhoea among civilian and military travellers. Its dual importance in global public health and travel medicine highlights the need for an effective vaccine. ETEC express colonization factors (CFs) that mediate adherence to the small intestine. An epidemiologically prevalent CF is coli surface antigen 6 (CS6). We assessed the safety and immunogenicity of a CS6-targeted candidate vaccine, CssBA, co-administered intramuscularly with the double-mutant heat-labile enterotoxin, dmLT [LT(R192G/L211A)]. METHODS: This was an open-label trial. Fifty subjects received three intramuscular injections (Days 1, 22 and 43) of CssBA alone (5 µg), dmLT alone (0.1 µg) or CssBA (5, 15, 45 µg) + dmLT (0.1 and 0.5 µg). Subjects were actively monitored for adverse events for 28 days following the third vaccination. Antibody responses (IgG and IgA) were characterized in the serum and from lymphocyte supernatants (ALS) to CS6 and the native ETEC heat labile enterotoxin, LT. RESULTS: Across all dose cohorts, the vaccine was safe and well-tolerated with no vaccine-related severe or serious adverse events. Among vaccine-related adverse events, a majority (98%) were mild with 79% being short-lived vaccine site reactions. Robust antibody responses were induced in a dose-dependent manner with a clear dmLT adjuvant effect. Response rates in subjects receiving 45 µg CssBA and 0.5 µg dmLT ranged from 50 to 100% across assays. CONCLUSION: This is the first study to demonstrate the safety and immunogenicity of CssBA and/or dmLT administered intramuscularly. Co-administration of the two components induced robust immune responses to CS6 and LT, paving the way for future studies to evaluate the efficacy of this vaccine target and development of a multivalent, subunit ETEC vaccine.
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Toxinas Bacterianas , Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Proteínas de Escherichia coli , Vacinas contra Escherichia coli , Anticorpos Antibacterianos , Criança , Enterotoxinas , Infecções por Escherichia coli/prevenção & controle , Proteínas de Escherichia coli/genética , Vacinas contra Escherichia coli/efeitos adversos , Temperatura Alta , Humanos , Vacinas de Subunidades AntigênicasRESUMO
BACKGROUND: Human challenge models for enterotoxigenic Escherichia coli (ETEC) facilitate vaccine down-selection. The B7A (O148:H28 CS6+LT+ST+) strain is important for vaccine development. We sought to refine the B7A model by identifying a dose and fasting regimen consistently inducing moderate-severe diarrhea. METHODS: An initial cohort of 28 subjects was randomized (1:1:1:1) to receive B7A following an overnight fast at doses of 108 or 109 colony forming units (cfu) or a 90-minute fast at doses of 109 or 1010 cfu. A second cohort included naïve and rechallenged subjects who had moderate-severe diarrhea and were given the target regimen. Immune responses to important ETEC antigens were assessed. RESULTS: Among subjects receiving 108 cfu of B7A, overnight fast, or 109 cfu, 90-minute fast, 42.9% (3/7) had moderate-severe diarrhea. Higher attack rates (71.4%; 5/7) occurred in subjects receiving 109 cfu, overnight fast, or 1010 cfu, 90-minute fast. Upon rechallenge with 109 cfu of B7A, overnight fast, 5/11 (45.5%) had moderate-severe diarrhea; the attack rate among concurrently challenge naïve subjects was 57.9% (11/19). Anti-CS6, O148 LPS and LT responses were modest across all groups. CONCLUSIONS: An overnight fast enabled a reduction in the B7A inoculum dose; however, the attack rate was inconsistent and protection upon rechallenge was minimal.
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Antígenos de Bactérias/análise , Diarreia/etiologia , Escherichia coli Enterotoxigênica/patogenicidade , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/análise , Vacinas contra Escherichia coli , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Carga Bacteriana , Toxinas Bacterianas/imunologia , Ciprofloxacina/uso terapêutico , Diarreia/microbiologia , Diarreia/terapia , Relação Dose-Resposta Imunológica , Escherichia coli Enterotoxigênica/imunologia , Escherichia coli Enterotoxigênica/isolamento & purificação , Enterotoxinas/imunologia , Infecções por Escherichia coli/prevenção & controle , Proteínas de Escherichia coli/imunologia , Jejum , Fezes/microbiologia , Feminino , Hidratação , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lipopolissacarídeos/imunologia , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: The efficacy of public health measures to control the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been well studied in young adults. METHODS: We investigated SARS-CoV-2 infections among U.S. Marine Corps recruits who underwent a 2-week quarantine at home followed by a second supervised 2-week quarantine at a closed college campus that involved mask wearing, social distancing, and daily temperature and symptom monitoring. Study volunteers were tested for SARS-CoV-2 by means of quantitative polymerase-chain-reaction (qPCR) assay of nares swab specimens obtained between the time of arrival and the second day of supervised quarantine and on days 7 and 14. Recruits who did not volunteer for the study underwent qPCR testing only on day 14, at the end of the quarantine period. We performed phylogenetic analysis of viral genomes obtained from infected study volunteers to identify clusters and to assess the epidemiologic features of infections. RESULTS: A total of 1848 recruits volunteered to participate in the study; within 2 days after arrival on campus, 16 (0.9%) tested positive for SARS-CoV-2, 15 of whom were asymptomatic. An additional 35 participants (1.9%) tested positive on day 7 or on day 14. Five of the 51 participants (9.8%) who tested positive at any time had symptoms in the week before a positive qPCR test. Of the recruits who declined to participate in the study, 26 (1.7%) of the 1554 recruits with available qPCR results tested positive on day 14. No SARS-CoV-2 infections were identified through clinical qPCR testing performed as a result of daily symptom monitoring. Analysis of 36 SARS-CoV-2 genomes obtained from 32 participants revealed six transmission clusters among 18 participants. Epidemiologic analysis supported multiple local transmission events, including transmission between roommates and among recruits within the same platoon. CONCLUSIONS: Among Marine Corps recruits, approximately 2% who had previously had negative results for SARS-CoV-2 at the beginning of supervised quarantine, and less than 2% of recruits with unknown previous status, tested positive by day 14. Most recruits who tested positive were asymptomatic, and no infections were detected through daily symptom monitoring. Transmission clusters occurred within platoons. (Funded by the Defense Health Agency and others.).
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Teste para COVID-19 , COVID-19/transmissão , Transmissão de Doença Infecciosa/estatística & dados numéricos , Militares , Quarentena , SARS-CoV-2/isolamento & purificação , Infecções Assintomáticas , COVID-19/diagnóstico , COVID-19/epidemiologia , Genoma Viral , Humanos , Masculino , Filogenia , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , SARS-CoV-2/genética , South Carolina/epidemiologia , Sequenciamento Completo do Genoma , Adulto JovemRESUMO
Enterotoxigenic Escherichia coli (ETEC) is a leading cause of diarrhea among travelers and pediatric populations worldwide. The tip-localized adhesin of colonization factor antigen (CFA)/I fimbriae was engineered as a donor strand complemented variant (dscCfaE) and delivered via transcutaneous immunization. Preclinical vaccine testing demonstrated safety, immunogenicity and efficacy. A series of open-label dose-escalating phase 1 studies evaluated a 3-dose (days 0, 21, 42) regimen via a transcutaneous skin patch. A total of forty-six subjects were enrolled into one of four vaccine dose levels (10, 50, 250, or 1250 µg) co-administered with single-mutant heat-labile enterotoxin (LTR(192G)). At the 50 µg dose level, ten subjects received the dscCfaE vaccine without LT(R192G). The vaccine was well tolerated with mild local vaccine site reactions characterized by an erythematous papular rash and pruritus, which were less frequent and reactive in the group not receiving LT(R192G). The frequency of responses to dscCfaE were moderate, whereas anti-toxin responses (serum IgA/IgG) ranged from 75 to 100% across groups that received LT(R192G). Antigen-specific antibody-secreting cell responses were elicited at all dose levels, but were generally low. Follow-on studies will optimize construct and route of delivery and assess efficacy in an ETEC challenge study.
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Toxinas Bacterianas , Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Proteínas de Escherichia coli , Vacinas contra Escherichia coli , Anticorpos Antibacterianos , Toxinas Bacterianas/genética , Criança , Enterotoxinas/genética , Infecções por Escherichia coli/prevenção & controle , Proteínas de Escherichia coli/genética , Temperatura Alta , Humanos , Imunoglobulina A , MutaçãoRESUMO
Travelers' diarrhea (TD) has historically been common among deployed military personnel and remains a leading infectious disease threat to this population. The risk factors, work performance, and illness associated with TD among British active duty service members exercising at British Army Training Unit Kenya (BATUK) were assessed. Members of the British Army who were finishing a 6-week combined arms training exercise in Nanyuki, Kenya, completed routine public health surveillance questionnaires. Survey data included information on demographics, rank, risk factors, illness characteristics, and impact on work performance. Among 1,227 survey respondents, 21.9% (n=269) reported having diarrhea, with an estimated 824 days of total missed work and 1,215 days of work underperformance. The majority of cases (54.6%) had multiple diarrheal episodes. One quarter (24.9%) of the respondents with TD sought medical care and 19.7% were bedded down because of their illness. There were no statistically significant differences between the TD and no TD groups on the demographic characteristics examined. The strongest risk factor for diarrhea was having a colleague with diarrhea (adjusted odds ratio=51.78; 95% confidence interval: 29.44-91.06). TD had a notable impact on duty status and operational capability. Efforts are needed to improve BATUK's participant education on the importance of diarrheal disease prevention and management.
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Diarreia/epidemiologia , Militares/estatística & dados numéricos , Adulto , Estudos de Casos e Controles , Estudos Transversais , Diarreia/fisiopatologia , Feminino , Humanos , Quênia , Masculino , Inquéritos e Questionários , Reino Unido/epidemiologia , Adulto JovemRESUMO
Travelers' diarrhea (TD) is the most prevalent illness encountered by deployed military personnel and has a major impact on military operations, from reduced job performance to lost duty days. Frequently, the etiology of TD is unknown and, with underreporting of cases, it is difficult to accurately assess its impact. An increasing number of ailments include an altered or aberrant gut microbiome. To better understand the relationships between long-term deployments and TD, we studied military personnel during two nine-month deployment cycles in 2015-2016 to Honduras. To collect data on the prevalence of diarrhea and impact on duty, a total of 1173 personnel completed questionnaires at the end of their deployment. 56.7% reported reduced performance and 21.1% reported lost duty days. We conducted a passive surveillance study of all cases of diarrhea reporting to the medical unit with 152 total cases and a similar pattern of etiology. Enteroaggregative E. coli (EAEC, 52/152), enterotoxigenic E. coli (ETEC, 50/152), and enteropathogenic E. coli (EPEC, 35/152) were the most prevalent pathogens detected. An active longitudinal surveillance of 67 subjects also identified diarrheagenic E. coli as the primary etiology (7/16 EPEC, 7/16 EAEC, and 6/16 ETEC). Eleven subjects were recruited into a nested longitudinal substudy to examine gut microbiome changes associated with deployment. A 16S rRNA amplicon survey of fecal samples showed differentially abundant baseline taxa for subjects who contracted TD versus those who did not, as well as detection of taxa positively associated with self-reported gastrointestinal distress. Disrupted microbiota was also qualitatively observable for weeks preceding and following the incidents of TD. These findings illustrate the complex etiology of diarrhea amongst military personnel in deployed settings and its impacts on job performance. Potential factors of resistance or susceptibility can provide a foundation for future clinical trials to evaluate prevention and treatment strategies.
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Diarreia/epidemiologia , Disenteria/epidemiologia , Escherichia coli Enteropatogênica/isolamento & purificação , Infecções por Escherichia coli/epidemiologia , Adulto , Diarreia/genética , Diarreia/microbiologia , Disenteria/genética , Disenteria/microbiologia , Disenteria/patologia , Escherichia coli Enteropatogênica/genética , Escherichia coli Enteropatogênica/patogenicidade , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Honduras/epidemiologia , Humanos , Masculino , Militares , RNA Ribossômico 16S/genética , Fatores de Risco , Viagem , Doença Relacionada a ViagensRESUMO
BACKGROUND: Trials assessing the safety of novel vaccine candidates are essential in the evaluation and development of candidate vaccines. Immunogenicity and dose-sparing features of vaccination approaches which target skin and associated tissues have garnered increased interest; for enteric vaccines, cutaneous vaccination has been of particular interest. Cutaneous vaccine site reactions are among the most common and visible vaccine related adverse events (AEs) when skin routes are used. Regulatory guidelines governing classification of severity focus on functional impact but are insufficient to characterize a spectrum of skin reaction and allow for comparisons of routes, doses and products with similar local cutaneous AEs. OBJECTIVES: Our group developed a grading scale to evaluate and compare cutaneous vaccine site reactions ahead of early-phase clinical trials of intradermal (ID) and transcutaneous immunization (TCI) with enterotoxigenic E.coli (ETEC) vaccine candidates (adhesin-based vaccine co-administered with LTR192G). We reviewed existing methods for characterizing the appearance and severity of local vaccine site reactions following TCI and ID vaccination and devised a standardized vaccine site appearance grading scale (VSAGS) for use in the clinical development of novel ETEC vaccine candidates which focused on pathophysiologic manifestation of skin findings. RESULTS: Available data from published reports revealed erythematous papules and pruritus were the most common local AEs associated with TCI. Frequency of reactions varied notably across studies as did TCI vaccination methodologies and products. ID vaccination commonly results in erythema and induration at the vaccine site as well as pigmentation changes. There was no published methodology to characterize the spectrum of dermatologic findings. CONCLUSION: ID and TCI vaccination are associated with a largely predictable range of cutaneous AEs. A grading scale focused on the appearance of cutaneous changes was useful in comparing cutaneous AEs. A standardized grading scale will facilitate documentation and comparison of cutaneous AEs.