In vitro bioassessment of the immunomodulatory activity of Saccharomyces cerevisiae components using bovine macrophages and Mycobacterium avium ssp. paratuberculosis.

The yeast Saccharomyces cerevisiae and its components are used for the prevention and treatment of enteric disease in different species; therefore, they may also be useful for preventing Johne's disease, a chronic inflammatory bowel disease of ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP). The objective of this study was to identify potential immunomodulatory S. cerevisiae components using a bovine macrophage cell line (BOMAC). The BOMAC phagocytic activity, reactive oxygen species production, and immune-related gene (IL6, IL10, IL12p40, IL13, IL23), transforming growth factor ß, ARG1, CASP1, and inducible nitric oxide synthase expression were investigated when BOMAC were cocultured with cell wall components from 4 different strains (A, B, C, and D) and 2 forms of dead yeast from strain A. The BOMAC phagocytosis of mCherry-labeled MAP was concentration-dependently attenuated when BOMAC were cocultured with yeast components for 6 h. Each yeast derivative also induced a concentration-dependent increase in BOMAC reactive oxygen species production after a 6-h exposure. In addition, BOMAC mRNA expression of the immune-related genes was investigated after 6 and 24 h of exposure to yeast components. All yeast components were found to regulate the immunomodulatory genes of BOMAC; however, the response varied among components and over time. The in vitro bioassessment studies reported here suggest that dead yeast and its cell wall components may be useful for modulating macrophage function before or during MAP infection.

Risk factors for tick exposure in suburban settings in the Northeastern United States.

Prevention of tick-borne diseases requires an understanding of when and where exposure to ticks is most likely. We used an epidemiologic approach to define these parameters for residents of a Lyme-endemic region. Two persons in each of 500 Connecticut households were asked to complete a log each night for one week during June, 2013. Participants recorded their whereabouts in 15min increments (indoors, outdoors in their yard, outdoors on others' private property, or outdoors in public spaces) and noted each day whether they found a tick on themselves. Demographic and household information was also collected. Logs were completed for 934 participants in 471 households yielding 51,895 time-place observations. Median participant age was 49 years (range 2-91 years); 52% were female. Ninety-one participants (9.8%) reported finding a tick during the week, with slightly higher rates among females and minors. Household factors positively associated with finding a tick included having indoor/outdoor pets (odds ratio (OR)=1.7; 95% confidence interval (CI): 1.1-2.9), the presence of a bird feeder in the yard (OR=1.9; CI:1.2-3.2), and presence of an outdoor dining area (OR=2.2; CI:1.1-4.3). Individual factors associated with finding a tick on a given day were bathing or showering (OR=3.7; CI:1.3-10.3) and hours spent in one's own yard (OR=1.2, CI:1.1-1.3). Nineteen participants found ticks on multiple days, more than expected assuming independence (p<0.001). Participants who found ticks on multiple days did not spend more time outdoors but were significantly more likely to be male than those finding ticks on a single day (p<0.03). Our findings suggest that most tick exposures in the study area occurred on private property controlled by the respective homeowner. Interventions that target private yards are a logical focus for prevention efforts.

Cat scratch disease: U.S. clinicians' experience and knowledge.

Cat scratch disease (CSD) is a zoonotic infection caused primarily by the bacterium Bartonella henselae. An estimated 12,000 outpatients and 500 inpatients are diagnosed with CSD annually, yet little is known regarding clinician experience with and treatment of CSD in the United States. Questions assessing clinical burden, treatment and prevention of CSD were posed to 3,011 primary care providers (family practitioners, internists, paediatricians and nurse practitioners) during 2014-2015 as part of the annual nationwide DocStyles survey. Among the clinicians surveyed, 37.2% indicated that they had diagnosed at least one patient with CSD in the prior year. Clinicians in the Pacific and Southern regions were more likely to have diagnosed CSD, as were clinicians who saw paediatric patients, regardless of specialty. When presented with a question regarding treatment of uncomplicated CSD, only 12.5% of clinicians chose the recommended treatment option of analgesics and monitoring, while 71.4% selected antibiotics and 13.4% selected lymph node aspiration. In a scenario concerning CSD prevention in immunosuppressed patients, 80.6% of clinicians chose some form of precaution, but less than one-third chose the recommended option of counseling patients to treat their cats for fleas and avoid rough play with their cats. Results from this study indicate that a substantial proportion of U.S. clinicians have diagnosed CSD within the past year. Although published guidelines exist for treatment and prevention of CSD, these findings suggest that knowledge gaps remain. Therefore, targeted educational efforts about CSD may benefit primary care providers.

Will Culling White-Tailed Deer Prevent Lyme Disease?

White-tailed deer play an important role in the ecology of Lyme disease. In the United States, where the incidence and geographic range of Lyme disease continue to increase, reduction of white-tailed deer populations has been proposed as a means of preventing human illness. The effectiveness of this politically sensitive prevention method is poorly understood. We summarize and evaluate available evidence regarding the effect of deer reduction on vector tick abundance and human disease incidence. Elimination of deer from islands and other isolated settings can have a substantial impact on the reproduction of blacklegged ticks, while reduction short of complete elimination has yielded mixed results. To date, most studies have been conducted in ecologic situations that are not representative to the vast majority of areas with high human Lyme disease risk. Robust evidence linking deer control to reduced human Lyme disease risk is lacking. Currently, there is insufficient evidence to recommend deer population reduction as a Lyme disease prevention measure, except in specific ecologic circumstances.

Tick Bite Prophylaxis: Results From a 2012 Survey of Healthcare Providers.

In a recent national survey, over 30% of healthcare providers (HCPs) reported prescribing tick bite prophylaxis in the previous year. To clarify provider practices, we surveyed HCPs to determine how frequently and for what reasons they prescribed tick bite prophylaxis. We included four questions regarding tick bite prophylaxis in the DocStyles 2012 survey, a computer-administered questionnaire of 2205 US primary care physicians, paediatricians and nurse practitioners. Responses in 14 states with high Lyme disease incidence (high LDI) were compared with responses from other states (low LDI). Overall, 56.4% of 1485 providers reported prescribing tick bite prophylaxis at least once in the previous year, including 73.9% of HCPs in high LDI and 48.2% in low LDI states. The reasons given were 'to prevent Lyme disease' (76.9%), 'patients request it' (40.4%) and 'to prevent other tickborne diseases' (29.4%). Among HCPs who provided prophylaxis, 45.2% did so despite feeling that it was not indicated. Given a hypothetical scenario involving a patient with an attached tick, 38.1% of HCPs from high LDI states and 15.1% from low LDI states would prescribe a single dose of doxycycline; 19.0% from high LDI states and 27.5% from low LDI states would prescribe a full course of doxycycline. HCPs prescribe tick bite prophylaxis frequently in areas where Lyme disease is rare and for tickborne diseases for which it has not been shown effective. HCPs may be unaware of current tick bite prophylaxis guidelines or find them difficult to implement. More information is needed regarding the efficacy of tick bite prophylaxis for diseases other than Lyme disease.

Transmission dynamics of primary pneumonic plague in the USA.

Plague is thought to have killed millions during three catastrophic pandemics. Primary pneumonic plague, the most severe form of the disease, is transmissible from person-to-person and has the potential for propagating epidemics. Efforts to quantify its transmission potential have relied on published data from large outbreaks, an approach that artificially inflates the basic reproductive number (R(0)) and skews the distribution of individual infectiousness. Using data for all primary pneumonic plague cases reported in the USA from 1900 to 2009, we determined that the majority of cases will fail to transmit, even in the absence of antimicrobial treatment or prophylaxis. Nevertheless, potential for sustained outbreaks still exists due to superspreading events. These findings challenge current concepts regarding primary pneumonic plague transmission.

Salmonella infections associated with mung bean sprouts: epidemiological and environmental investigations.

We investigated an outbreak of Salmonella Enteritidis (SE) infections linked to raw mung bean sprouts in 2000 with two case-control studies and reviewed six similar outbreaks that occurred in 2000-2002. All outbreaks were due to unusual phage types (PT) of SE and occurred in the United States (PT 33, 1, and 913), Canada (PT 11b and 913), and The Netherlands (PT 4b). PT 33 was in the spent irrigation water and a drain from one sprout grower. None of the growers disinfected seeds at recommended concentrations. Only two growers tested spent irrigation water; neither discarded the implicated seed lots after receiving a report of Salmonella contamination. We found no difference in the growth of SE and Salmonella Newport on mung beans. Mung bean sprout growers should disinfect seeds, test spent irrigation water, and discontinue the use of implicated seed lots when pathogens are found. Laboratories should report confirmed positive Salmonella results from sprout growers to public health authorities.

Dog-associated risk factors for human plague.

Plague is a rare but often fatal zoonosis endemic to the western United States. Previous studies have identified contact with pets as a potential risk factor for infection. We conducted a matched case-control study to better define the risks associated with pets at both the household and individual levels. Using a written questionnaire, we surveyed nine surviving plague patients, 12 household members of these patients, and 30 age- and neighbourhood-matched controls about household and individual exposures. Overall, 79% of households had at least one dog, 59% had at least one cat and 33% used flea control, with no significant differences between case and control households. Four (44%) case households reported having a sick dog versus no (0%) control households [matched odds ratio, (mOR) 18.5, 95% confidence interval (CI) 2.3-infinity], and four (44%) patients reported sleeping in the same bed with a pet dog versus three (10%) controls (mOR 5.7, 95% CI 1.0-31.6). Within case households with multiple members, two (40%) of five patients slept with their dogs versus none (0%) of 12 healthy family members (P=0.13). The exposures to cats were not significant. Sleeping in the same bed as a pet dog remained significantly associated with infection in a multivariate logistic regression model (P=0.046). Our findings suggest that dogs may facilitate the transfer of fleas into the home and that activities with close extended contacts with dogs may increase the risk of plague infection.

Bacterial and fungal meningitis in patients with cancer.

OBJECTIVE: To analyze cases of bacterial and fungal meningitis in patients with cancer. METHODS: Retrospective chart review from 1993 to 2004 was performed of patients with cancer at our institution who had positive CSF bacterial or fungal culture. RESULTS: We identified 312 positive CSF cultures representing 175 unique presentations. Ninety-six cultures were deemed contaminants, leaving 79 cultures for analysis in 77 patients; 78% had prior neurosurgery. Organisms included 68% gram-positive cocci, 10% gram-positive bacilli, 14% gram-negative bacilli, 7% Cryptococcus, and 1% C. albicans. None had N. meningitidis or H. influenza. Two patients each had S. pneumoniae or L. monocytogenes. Five percent of presentations demonstrated the triad of fever, nuchal rigidity, and mental status changes. Seventy-five percent of presentations demonstrated CSF pleocytosis (> or = 10). Median CSF WBC count was 74 cells/mm(3). CSF protein was elevated and glucose was depressed in 71%. In neutropenic patients (n = 6), 4 had 0 to 1 CSF WBC/mm(3), and 2 had normal CSF. VP shunt infections were more likely to present with mental status changes. Thirty day mortality was 13%. CONCLUSIONS: Patients with cancer do not manifest symptoms of meningitis as often as patients without cancer and display a very different set of CSF organisms compared to a general population. The CSF inflammatory response is muted in patients with cancer with meningitis. Most patients with cancer with meningitis have had prior neurosurgery. Additionally, the organisms causing meningitis in the cancer population have shifted over time, with a decline in the organisms which typically infect immunocompromised hosts and an increase in gram-positive infections.

Risk factors for sporadic Shiga toxin-producing Escherichia coli O157 infections in FoodNet sites, 1999-2000.

To monitor risk factors for illness, we conducted a case-control study of sporadic Shiga toxin-producing Escherichia coli O157 (STEC O157) infections in 1999-2000. Laboratory-confirmed cases of STEC O157 infection were identified through active laboratory surveillance in all or part of seven states. Patients and age-matched controls were interviewed by telephone using a standard questionnaire. Information was collected on demographics, clinical illness, and exposures to food, water, and animals in the 7 days before the patient's illness onset. During the 12-month study, 283 patients and 534 controls were enrolled. STEC O157 infection was associated with eating pink hamburgers, drinking untreated surface water, and contact with cattle. Eating produce was inversely associated with infection. Direct or indirect contact with cattle waste continues to be a leading identified source of sporadic STEC O157 infections.

The joint diabetic-renal clinic in clinical practice: 10 years of data from a District General Hospital.

BACKGROUND: Diabetic nephropathy is the leading cause of end-stage renal failure. Untreated, it causes continuous decline in glomerular function, worsening hypertension and a marked increase in cardiovascular risk. Joint diabetic-renal clinics were established to address these factors and prepare patients for renal replacement therapy. AIM: To determine whether our joint diabetic-renal clinic influenced progression of renal disease, and whether we were able to achieve targets from clinical trials and guidelines in routine practice. DESIGN: Retrospective review. METHODS: We collected data using clinical notes and electronic records for 130 patients attending the clinic over 10 years. RESULTS: Our patients had 62% type 2 and 38% type 1 diabetes. Mean duration of diabetes was 24 years for type 1 and 11 years for type 2 diabetes. At referral, 56% had evidence of vascular disease and 45%, proliferative retinopathy. Baseline median creatinine was 124 micromol/l. Significant improvements were made in systolic BP, diastolic BP and cholesterol (p < 0.001), compared to measurements at presentation. We analysed progression of renal disease by linear regression on 45 patients who had follow-up data for 3 years. Rate of decline of GFR was significantly reduced from 1.09 ml/min/month in the first year to 0.39 ml/min/month in the third year, (p < 0.004). DISCUSSION: Our findings suggest that the rate of deterioration of renal function can be reduced by aggressive management of risk factors. Joint diabetic-renal clinics appear to be useful in achieving targets in routine clinical practice.

Nationwide outbreak of listeriosis due to contaminated meat.

We used molecular subtyping to investigate an outbreak of listeriosis involving residents of 24 US states. We defined a case as infection with Listeria monocytogenes serotype 4b yielding one of several closely related patterns when subtyped by pulsed-field gel electrophoresis. Patients infected with strains yielding different patterns were used as controls. A total of 108 cases were identified with 14 associated deaths and four miscarriages or stillbirths. A case-control study implicated meat frankfurters as the likely source of infection (OR 17.3, 95% CI 2.4-160). The outbreak ended abruptly following a manufacturer-issued recall, and the outbreak strain was later detected in low levels in the recalled product. A second strain was recovered at higher levels but was not associated with human illness. Our findings suggest that L. monocytogenes strains vary widely in virulence and confirm that large outbreaks can occur even when only low levels of contamination are detected in sampled food. Standardized molecular subtyping and coordinated, multi-jurisdiction investigations can greatly facilitate detection and control of listeriosis outbreaks.

Salmonella enterica serotype Javiana infections associated with amphibian contact, Mississippi, 2001.

Salmonella Javiana is a Salmonella serotype that is restricted geographically in the United States to the Southeast. During the summer of 2001, the number of reported S. Javiana infections in Mississippi increased sevenfold. To identify sources of infection, we conducted a case-control study, defining a case as an infection with S. Javiana between August and September in a Mississippi resident. We enrolled 55 cases and 109 controls. Thirty (55%) case patients reported exposure to amphibians, defined as owning, touching, or seeing an amphibian on one's property, compared with 30 (29%) controls (matched odds ratio 2.8, P=0.006). Contact with amphibians and their environments may be a risk factor for human infection with S. Javiana. The geographic pattern of S. Javiana infections in the United States mimics the distribution of certain amphibian species in the Southeast. Public health officials should consider amphibians as potential sources of salmonellosis, and promote hand washing after contact with amphibians.

Sharps injury reduction using Sharpsmart--a reusable sharps management system.

Sharps containers are associated with 11-13% of total sharps injuries (SI) yet have received little attention as a means of SI reduction. A newly developed reusable sharps containment system (Sharpsmart) was trialed in eight hospitals in three countries. The system was associated with an 86.8% reduction of container-related SI (CRSI) (P=0.012), a 25.7% reduction in non-CRSI (P=0.003), and a 32.6% reduction in total SI (P=0.002) compared with historical data. The study concludes that the Sharpsmart system is an effective engineered control in reducing SI.

Chlamydia trachomatis in the endometrium: can surgical pathologists identify plasma cells?

Chlamydia trachomatis infection is the most common bacterial sexually transmitted disease. The authors examined the relation between chronic endometritis, which they term plasma cell endometritis (PCE), and chlamydial infection using plasmid-based polymerase chain reaction (PCR) and immunohistochemical staining (IHC) of paraffin-embedded endometrial sections. C. trachomatis infection was detected in 5 (24%) of 21 cases of PCE and in 1 (4%) of histologically normal endometrium. The diagnosis of chronic endometritis (with plasma cells confirmed by methyl green pyronin staining) was correctly made in 74% of the cases originally diagnosed as PCE and in 23% of control cases originally diagnosed as normal. The authors conclude that the histopathologic finding of plasma cells in endometrial samples should encourage further examination for chlamydial infection.

Multistate outbreak of Norwalk-like virus gastroenteritis associated with a common caterer.

In February 2000, an outbreak of gastroenteritis occurred among employees of a car dealership in New York. The same meal was also supplied to 52 dealerships nationwide, and 13 states reported illness at dealerships where the banquet was served. A retrospective cohort study was conducted to identify risk factors associated with the illness. Stool samples were collected to detect Norwalk-like virus, and sera were drawn and tested for immunoglobulin A antibodies to the outbreak strain. By univariate analysis, illness was significantly associated with consumption of any of four salads served at the banquet (relative risk = 3.8, 95% confidence interval: 2.5, 5.6). Norwalk-like virus was detected by reverse transcription-polymerase chain reaction assay in 32 of 59 stool samples from eight states. Nucleotide sequences of a 213-base pair fragment from 16 stool specimens collected from cases in eight states were identical, confirming a common source outbreak. Two of 15 workers at caterer A had elevated immunoglobulin A titers to an antigenically related Norwalk-like virus strain. This study highlights the value of molecular techniques to complement classic epidemiologic methods in outbreak investigations and underscores the critical role of food handlers in the spread of foodborne disease associated with Norwalk-like virus.

neptune, a Krüppel-like transcription factor that participates in primitive erythropoiesis in Xenopus.

The specification of the erythroid lineage from hematopoietic stem cells requires the expression and activity of lineage-specific transcription factors. One transcription factor family that has several members involved in hematopoiesis is the Krüppel-like factor (KLF) family [1]. For example, erythroid KLF (EKLF) regulates beta-globin expression during erythroid differentiation [2-6]. KLFs share a highly conserved zinc finger-based DNA binding domain (DBD) that mediates binding to CACCC-box and GC-rich sites, both of which are frequently found in the promoters of hematopoietic genes. Here, we identified a novel Xenopus KLF gene, neptune, which is highly expressed in the ventral blood island (VBI), cranial ganglia, and hatching and cement glands. neptune expression is induced in response to components of the BMP-4 signaling pathway in injected animal cap explants. Similar to its family member, EKLF, Neptune can bind CACCC-box and GC-rich DNA elements. We show that Neptune cooperates with the hematopoietic transcription factor XGATA-1 to enhance globin induction in animal cap explants. A fusion protein comprised of Neptune's DBD and the Drosophila engrailed repressor domain suppresses the induction of globin in ventral marginal zones and in animal caps. These studies demonstrate that Neptune is a positive regulator of primitive erythropoiesis in Xenopus.