Impaired peripheral blood T-follicular helper cell function in HIV-infected nonresponders to the 2009 H1N1/09 vaccine.

The generation of Ab-secreting plasma cells depends critically on CD4 T-follicular helper (TFH) cells during the germinal center reaction. Germinal center TFH cells share functional properties with circulating CXCR5(+) CD4 T cells, referred to herein as peripheral TFH (pTFH) cells. Because deficient Ab production and CD4 T-cell loss are recognized features of HIV infection, in the present study, we investigated pTFH cells in 25 HIV-infected patients on antiretroviral therapy. pTFH frequency was equivalent in patients and healthy controls (HCs), and these cells displayed a central memory phenotype. Sixteen patients and 8 HCs in this group were given a single dose of H1N1/09 influenza vaccine during the 2009 H1N1 influenza outbreak. In the vaccine responders (n = 8) and HCs, pTFH cells underwent expansion with increased IL-21 and CXCL13 secretion in H1N1-stimulated PBMC culture supernatants at week 4 (T2). These changes were not seen in vaccine nonresponders (n = 8). In coculture experiments, sorted pTFH cells supported HIN1-stimulated IgG production by autologous B cells only in vaccine responders. At T2, frequencies of pTFH were correlated with memory B cells, serum H1N1 Ab titers, and Ag-induced IL-21 secretion. Characterization of pTFH cells may provide additional insight into cellular determinants of vaccine-induced Ab response, which may have relevance for vaccine design.

Matrix metalloproteinases 2 and 9 as diagnostic markers in the progression to Chagas cardiomyopathy.

BACKGROUND: Infection with the Trypanosoma cruzi parasite is endemic in parts of Central and South America. Approximately 30% of those infected develop Chagas cardiomyopathy, the most common cause of heart failure in this region. No suitable biomarker is available that reflects the evolution of the disease. Although there is substantial evidence of a strong inflammatory reaction following infection that could activate matrix metalloproteinases (MMPs), their role in the development of Chagas cardiomyopathy is unknown. METHODS: A cross-sectional study was conducted in Bucaramanga, Colombia, from 2002 to 2006, including 144 patients at different stages of Chagas disease and 44 control patients. The potential enzyme activities of MMP-2 and MMP-9 in plasma samples were determined by gelatin zymography. Clinical data including T cruzi serology, electrocardiograms, and echocardiograms were recorded for all patients. RESULTS: Densitometric analysis of potential enzyme activities in plasma samples showed a significant increase of 72-kd MMP-2 (P < .001) and 92-kd MMP-9 (P < .001) in T cruzi seropositive patients compared with control subjects. Matrix metalloproteinase 9 showed significantly increased activity in patients with abnormal electrocardiogram (P < .004) and with dilated cardiomyopathy compared (P < .001) with controls. Analysis of the MMP-2 and MMP-9 results in relation to clinical data revealed that abnormal heart relaxation correlated positively with high MMP-2 levels in patients with dilated cardiomyopathy (r = 0.75, P < .01). CONCLUSIONS: Plasma MMP-2 and MMP-9 both appear to be useful biomarkers for detecting the advent and progression of cardiomyopathy in T cruzi-infected individuals.

Upregulation of IL-21 receptor on B cells and IL-21 secretion distinguishes novel 2009 H1N1 vaccine responders from nonresponders among HIV-infected persons on combination antiretroviral therapy.

Mechanisms underlying failure of novel 2009 H1N1 influenza vaccine-induced Ab responses in HIV-infected persons are poorly understood. This study prospectively evaluated 16 HIV-infected patients on combination antiretroviral therapy and eight healthy controls (HC) who received a single 15 µg dose of nonadjuvanted novel 2009 H1N1 influenza vaccine during the 2009 H1N1 epidemic. Peripheral blood was collected at baseline (T0) and at 7 d (T1) and 28 d (T2) postvaccination for evaluation of immune responses. Prevaccination hemagglutination inhibition Ab titer was <1:20 in all except one study participant. At T2, all HC and 8 out of 16 patients (50%) developed a vaccine-induced Ab titer of ≥ 1:40. Vaccine responder (R) and vaccine nonresponder patients were comparable at T0 in age, CD4 counts, virus load, and B cell immunophenotypic characteristics. At T2, HC and R patients developed an expansion of phenotypic and functional memory B cells and ex vivo H1N1-stimulated IgG Ab-secreting cells in an ELISPOT assay. The memory B cell response was preceded by a significant expansion of plasmablasts and spontaneous H1N1-specific Ab-secreting cells at T1. At T2, HC and R patients also exhibited significant increases in serum IL-21 levels and in the frequency and mean fluorescence intensity of IL-21R-expressing B cells, which correlated with serum H1N1 Ab titers. Vaccine nonresponder patients failed to develop the above-described vaccine-induced immunologic responses. The novel association of novel 2009 H1N1 vaccine-induced Ab responses with IL-21/IL-21R upregulation and with development of memory B cells and plasmablasts has implications for future research in vaccine design.

A randomized trial to determine whether wearing slippers reduces transfer of bacteriophage MS2 from floors to patients and surfaces in hospital rooms.

In a randomized trial, patients wearing slippers whenever out of bed transferred bacteriophage MS2 from hospital room floors to patients and surfaces significantly less often than controls not provided with slippers. Wearing slippers could provide a simple means to reduce the risk for acquisition of healthcare-associated pathogens from contaminated floors.Registration: ClinicalTrials.gov; NCT04935892.

Innate immune defects correlate with failure of antibody responses to H1N1/09 vaccine in HIV-infected patients.

BACKGROUND: Mechanisms underlying the failure of influenza vaccine-induced antibody responses in HIV-infected persons are poorly understood. OBJECTIVE: To investigate innate immune factors regulating B-cell function in HIV-infected persons and to correlate them with serologic responses to H1N1/09 vaccine. METHODS: We evaluated immunologic characteristics of 17 HIV-infected patients and 8 healthy controls (HCs) at 0, 7, and 28 days (designated T0, T1, and T2) following a single 15-µg dose of nonadjuvanted H1N1/09 influenza vaccine by using flow cytometry, ELISpot, and ELISA. All HCs and 9 patients (53%) seroconverted with >1:40 hemagglutination inhibition antibody titer at T2. RESULTS: In vaccine responders and HCs, serum levels of BAFF (B cell-activating factor) and APRIL (a proliferation-inducing ligand) increased from T0 to T2 in conjunction with increases in frequencies of memory B cells. Concurrently, receptors for these factors showed changes, with increases in expression of TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) and decreases in BAFF receptor in memory B cells. IL-2 secreting cells and IgG antibody-secreting cells increased at T2 in vaccine responders and HCs in ex vivo H1N1 antigen-stimulated cultures. These immunologic responses were not evident at T1 and were deficient in vaccine nonresponder patients at T2. At T0, vaccine nonresponders had lower frequencies of BAFF receptor and TACI-expressing memory B cells than did responders. CONCLUSION: Impaired memory B-cell responses, deficiencies in serum BAFF and APRIL, and alterations in their receptors on B cells were associated with failure of H1N1/09 influenza vaccine responses among virologically controlled HIV-infected patients.

A simulation study to evaluate contamination during reuse of N95 respirators and effectiveness of interventions to reduce contamination.

OBJECTIVE: To assess the potential for contamination of personnel, patients, and the environment during use of contaminated N95 respirators and to compare the effectiveness of interventions to reduce contamination. DESIGN: Simulation study of patient care interactions using N95 respirators contaminated with a higher and lower inocula of the benign virus bacteriophage MS2. METHODS: In total, 12 healthcare personnel performed 3 standardized examinations of mannequins including (1) control with suboptimal respirator handling technique, (2) improved technique with glove change after each N95 contact, and (3) control with 1-minute ultraviolet-C light (UV-C) treatment prior to donning. The order of the examinations was randomized within each subject. The frequencies of contamination were compared among groups. Observations and simulations with fluorescent lotion were used to assess routes of transfer leading to contamination. RESULTS: With suboptimal respirator handling technique, bacteriophage MS2 was frequently transferred to the participants, mannequin, and environmental surfaces and fomites. Improved technique resulted in significantly reduced transfer of MS2 in the higher inoculum simulations (P < .01), whereas UV-C treatment reduced transfer in both the higher- and lower-inoculum simulations (P < .01). Observations and simulations with fluorescent lotion demonstrated multiple potential routes of transfer to participants, mannequin, and surfaces, including both direct contact with the contaminated respirator and indirect contact via contaminated gloves. CONCLUSION: Reuse of contaminated N95 respirators can result in contamination of personnel and the environment even when correct technique is used. Decontamination technologies, such as UV-C, could reduce the risk for transmission.

Evaluation of a continuously active disinfectant for decontamination of portable medical equipment.

A single spray application of a continuously active disinfectant on portable equipment resulted in significant reductions in aerobic colony counts over 7 days and in recovery of Staphylococcus aureus and enterococci: 3 of 93 cultures (3%) versus 11 of 97 (11%) and 20 of 97 (21%) in quaternary ammonium disinfectant and untreated control groups, respectively.

Inpatient fluoroquinolone use in Veterans' Affairs hospitals is a predictor of Clostridioides difficile infection due to fluoroquinolone-resistant ribotype 027 strains.

BACKGROUND: Reduction in the use of fluoroquinolone antibiotics has been associated with reductions in Clostridioides difficile infections (CDIs) due to fluoroquinolone-resistant strains. OBJECTIVE: To determine whether facility-level fluoroquinolone use predicts healthcare facility-associated (HCFA) CDI due to fluoroquinolone-resistant 027 strains. METHODS: Using a nationwide cohort of hospitalized patients in the Veterans' Affairs Healthcare System, we identified hospitals that categorized >80% of CDI cases as positive or negative for the 027 strain for at least one-quarter of fiscal years 2011-2018. Within these facilities, we used visual summaries and multilevel logistic regression models to assess the association between facility-level fluoroquinolone use and rates of HCFA-CDI due to 027 strains, controlling for time and facility complexity level, and adjusting for correlated outcomes within facilities. RESULTS: Between 2011 and 2018, 55 hospitals met criteria for reporting 027 results, including a total of 5,091 HCFA-CDI cases, with 1,017 infections (20.0%) due to 027 strains. Across these facilities, the use of fluoroquinolones decreased by 52% from 2011 to 2018, with concurrent reductions in the overall HCFA-CDI rate and the proportion of HCFA-CDI cases due to the 027 strain of 13% and 55%, respectively. A multilevel logistic model demonstrated a significant effect of facility-level fluoroquinolone use on the proportion of infections in the facility due to the 027 strain, most noticeably in low-complexity facilities. CONCLUSIONS: Our findings provide support for interventions to reduce use of fluroquinolones as a control measure for CDI, particularly in settings where fluoroquinolone use is high and fluoroquinolone-resistant strains are common causes of infection.

What are the sources of exposure in healthcare personnel with coronavirus disease 2019 infection?

In our facility, 25% of personnel with coronavirus disease 2019 (COVID-19) had a higher-risk exposure to an infected patient or co-worker and 14% reported a higher-risk exposure in the community. All higher-risk exposures to infected patients occurred on non-COVID-19 units, often when there was a delay in diagnosis because COVID-19 was not initially suspected. Higher-risk exposures to co-workers with COVID-19 often involved lapses in compliance with masking in nonpatient care areas such as nursing stations and staff work or break rooms.

Timing and route of contamination of hospitalized patient rooms with healthcare-associated pathogens.

OBJECTIVE: To investigate the timing and routes of contamination of the rooms of patients newly admitted to the hospital. DESIGN: Observational cohort study and simulations of pathogen transfer. SETTING: A Veterans' Affairs hospital. PARTICIPANTS: Patients newly admitted to the hospital with no known carriage of healthcare-associated pathogens. METHODS: Interactions between the participants and personnel or portable equipment were observed, and cultures of high-touch surfaces, floors, bedding, and patients' socks and skin were collected for up to 4 days. Cultures were processed for Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE). Simulations were conducted with bacteriophage MS2 to assess plausibility of transfer from contaminated floors to high-touch surfaces and to assess the effectiveness of wearing slippers in reducing transfer. RESULTS: Environmental cultures became positive for at least 1 pathogen in 10 (59%) of the 17 rooms, with cultures positive for MRSA, C. difficile, and VRE in the rooms of 10 (59%), 2 (12%), and 2 (12%) participants, respectively. For all 14 instances of pathogen detection, the initial site of recovery was the floor followed in a subset of patients by detection on sock bottoms, bedding, and high-touch surfaces. In simulations, wearing slippers over hospital socks dramatically reduced transfer of bacteriophage MS2 from the floor to hands and to high-touch surfaces. CONCLUSIONS: Floors may be an underappreciated source of pathogen dissemination in healthcare facilities. Simple interventions such as having patients wear slippers could potentially reduce the risk for transfer of pathogens from floors to hands and high-touch surfaces.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid contamination of surfaces on a coronavirus disease 2019 (COVID-19) ward and intensive care unit.

On coronavirus disease 2019 (COVID-19) wards, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid was frequently detected on high-touch surfaces, floors, and socks inside patient rooms. Contamination of floors and shoes was common outside patient rooms on the COVID-19 wards but decreased after improvements in floor cleaning and disinfection were implemented.

Effectiveness of foam disinfectants in reducing sink-drain gram-negative bacterial colonization.

BACKGROUND: Sink drainage systems are not amenable to standard methods of cleaning and disinfection. Disinfectants applied as a foam might enhance efficacy of drain decontamination due to greater persistence and increased penetration into sites harboring microorganisms. OBJECTIVE: To examine the efficacy and persistence of foam-based products in reducing sink drain colonization with gram-negative bacilli. METHODS: During a 5-month period, different methods for sink drain disinfection in patient rooms were evaluated in a hospital and its affiliated long-term care facility. We compared the efficacy of a single treatment with 4 different foam products in reducing the burden of gram-negative bacilli in the sink drain to a depth of 2.4 cm (1 inch) below the strainer. For the most effective product, the effectiveness of foam versus liquid-pouring applications, and the effectiveness of repeated foam treatments were evaluated. RESULTS: A foam product containing 3.13% hydrogen peroxide and 0.05% peracetic acid was significantly more effective than the other 3 foam products. In comparison to pouring the hydrogen peroxide and peracetic acid disinfectant, the foam application resulted in significantly reduced recovery of gram-negative bacilli on days 1, 2, and 3 after treatment with a return to baseline by day 7. With repeated treatments every 3 days, a progressive decrease in the bacterial load recovered from sink drains was achieved. CONCLUSIONS: An easy-to-use foaming application of a hydrogen peroxide- and peracetic acid-based disinfectant suppressed sink-drain colonization for at least 3 days. Intermittent application of the foaming disinfectant could potentially reduce the risk for dissemination of pathogens from sink drains.

Impact of Reduced Fluoroquinolone Use on Clostridioides difficile Infections Resulting From the Fluoroquinolone-Resistant Ribotype 027 Strain in a Veterans Affairs Medical Center.

BACKGROUND: Fluoroquinolone restriction has been proposed as a control measure for Clostridioides difficile infection (CDI) outbreaks associated with fluoroquinolone-resistant ribotype 027 strains. However, relatively few reports of fluoroquinolone restriction interventions have evaluated the impact on C. difficile strain types and fluoroquinolone resistance. METHODS: In a hospital and affiliated long-term care facility (LTCF), antimicrobial stewardship and environmental cleaning interventions were implemented between 2009 and 2018, and C. difficile isolates during this period (~20 per year) were ribotyped and tested for fluoroquinolone resistance by moxifloxacin minimum inhibitory concentrations (MICs). Pearson's correlation coefficient was used to assess the association between use of fluoroquinolones and the percentage of CDI cases due to the 027 strain over time. RESULTS: Between 2009 and 2018, prescribing of fluoroquinolones to inpatients decreased by 43%, coinciding with significant reductions in the healthcare-associated CDI rates in the hospital and LTCF and a decline in the percentage of C. difficile isolates that were ribotype 027 from 70% to 10%. Ninety-five percent of ribotype 027 and 6% of non-027 isolates were moxifloxacin resistant. Hospital fluoroquinolone use was strongly correlated with the incidence of hospital-associated CDI (r = 0.79, 95% confidence interval, 0.31-0.95), but LTCF fluoroquinolone use was not correlated with LTCF-associated CDI (r = 0.29, 95% confidence interval, -0.43-0.77). During the study period, there were statistically significant downward trends in the use of penicillins, intravenous vancomycin, carbapenems, and clindamycin. CONCLUSION: Our results provide support for fluoroquinolone restriction as a control measure for CDI outbreaks due to fluoroquinolone-resistant 027 strains, but also highlight the need for randomized trials as factors such as reduction in other antibiotic classes and improved cleaning may also impact CDI rates.

Are nutrition-induced epigenetic changes the link between socioeconomic pathology and cardiovascular diseases?

The prevalence of cardiovascular diseases (CVD) and diabetes mellitus type 2 (DM 2) is decreasing in developed countries despite the increase in the percentage of subjects with obesity and other well-recognized cardiovascular risk factors. In contrast, the recent transition of the economic model experienced by developing countries, characterized by the adoption of a Western lifestyle, that we have named "socioeconomic pathology," has led to an increase in the burden of CVD. It has been demonstrated that conventional cardiovascular risk factors in developed and developing countries are the same. Why then does the population of developing countries currently have a higher incidence of CVD than that of developed countries if they share the same risk factors? We have proposed the existence of a higher susceptibility to the development of systemic inflammation at low levels of abdominal obesity in the population of developing countries and the consequent endothelial dysfunction, insulin resistance, DM 2, and CVD. In contrast, an important percentage of obese people living in developed countries have a healthy phenotype and low risk of developing CVD and DM 2. Human epidemiologic studies and experimental dietary interventions in animal models have provided considerable evidence to suggest that nutritional imbalance and metabolic disturbances early in life may later have a persistent effect on an adult's health that may even be transmitted to the next generations. Epigenetic changes dependent on nutrition could be key in this evolutionary health behavior, acting as a buffering system, permitting the adaptation to environmental conditions by silencing or increasing the expression of certain genes.

Hyperinsulinemia is a predictor of new cardiovascular events in Colombian patients with a first myocardial infarction.

BACKGROUND: Acute Myocardial Infarction (AMI) is one of the main causes of mortality and disability in Colombia. The factors associated to a new event in surviving subjects to a first AMI in our population have not yet been fully identified. METHODS: Two hundred and ninety five surviving subjects to a first AMI (58.8±12.6 years) were included in a prospective cohort study between 2000 and 2006. Lipid profile, glycemia and plasma insulin levels were measured. Deaths of cardiovascular origin, a new AMI, unstable angina, heart failure, stroke, new myocardial revascularization or angioplasty were considered new cardiovascular events. RESULTS: The study included 61 (20.6%) women and 234 (79.4%) men. The mean follow up time was 50±30 months with a 38.9% incidence of new events. Fifty five patients (18.6%) were diabetic. Bi-varied analysis identified as risk factors for a new cardiovascular event the presence of: hypertension, anterior descending coronary artery stenosis, intrahospital cardiac failure, age over 55, low income, lack of education, Killip III-IV, heart rate over 76 bpm, pulse pressure over 80 mmHg, total cholesterol over 200 mg/dl and insulin over 10 IU/ml. After logistic regression analysis, the log values of insulin remained as the only significant predictor for new cardiovascular events. CONCLUSIONS: Hyperinsulinism was the most important factor associated to the occurrence of new cardiovascular events in Colombian patients with AMI, which emphasizes the pivotal role of insulin resistance in the physiopathologic mechanisms of atherosclerosis, especially in undeveloped countries.

A controlled, randomized-blinded clinical trial to assess the efficacy of a nitric oxide releasing patch in the treatment of cutaneous leishmaniasis by Leishmania (V.) panamensis.

A topical nanofiber nitric oxide (NO) releasing patch ( approximately 3.5 mumol NO/cm(2)/day for 20 days, NOP) was compared with intramuscular meglumine antimoniate (Glucantime, 20 mg/kg/day for 20 days) for the treatment of cutaneous leishmaniasis (CL) caused by Leishmania (V.) panamensis in Santander and Tolima, Colombia. A double-blind, randomized, placebo-controlled, clinical trial was conducted to determine whether the NOP is as effective as Glucantime for the treatment of CL. Patients were randomly assigned to Glucantime and placebo patches or NOP and placebo of Glucantime. The cure rates after a 3-month follow-up were 94.8% for the group that received Glucantime compared with 37.1% in the NOP group. Despite the lower efficacy of the NOP versus Glucantime, a significantly lower frequency of non-serious adverse events and a reduced variation in serum markers were observed in patients treated with NOP. Treatment of CL with NOP resulted in a lower effectiveness compared with Glucantime; however, the low frequency of adverse events and the facility of topic administration justify the development of new generations of NOP systems for the treatment of CL.