Local immune response to larvae of Rhipicephalus microplus in Santa Gertrudis cattle.

This study investigated the local immune response at larval attachment sites in Santa Gertrudis cattle with low and high levels of tick resistance. Skin samples with tick larvae attached were collected from Santa Gertrudis cattle at the end of a period of 25 weekly infestations, when the animals manifested highly divergent tick-resistant phenotypes. There was a tendency for more CD3+ , CD4+ , CD8+ , CD25+ , γδ T cells and neutrophils to concentrate at larval tick attachment site in susceptible cattle than in resistant cattle but the differences were significant only for γδ T cells and CD4+ cells. Most of the cattle developed intra-epidermal vesicles at the larval attachment site but the predominant cell within or around the vesicles was the neutrophil in susceptible animals and eosinophil in the resistant animals. The monoclonal antibodies (mAbs) specific for CD45 and CD45 RO antigens reacted with skin leucocytes from a higher number of susceptible cattle than resistant cattle. Our data suggest that some of the cellular responses mounted at larval attachment site are not involved in tick protection. The mAbs specific for CD45 and CD45 RO directly, or a test for CD45 genotype might be developed as markers of tick susceptibility or resistance.

Peripheral cellular and humoral responses to infestation with the cattle tick Rhipicephalus microplus in Santa Gertrudis cattle.

Resistance to cattle tick infestation in single-host ticks is primarily manifested against the larval stage and results in the immature tick failing to attach successfully and obtain a meal. This study was conducted to identify immune responses that characterize the tick-resistant phenotype in cattle. Thirty-five tick-naïve Santa Gertrudis heifers were used in this study, thirty of which were artificially infested for thirteen weeks with tick larvae while five animals remained at a tick-free quarantine property to serve as a control group. Following thirteen weeks of tick infestation, the animals in this trial exhibited highly divergent tick-resistant phenotypes. Blood samples collected throughout the trial were used to measure peripheral immune parameters: haematology, the percentage of cellular subsets comprising the peripheral blood mononuclear cell (PBMC) population, tick-specific IgG1 and IgG2 antibody titres, IgG1 avidity for tick antigens and the ability of PBMC to recognize and proliferate in response to stimulation with tick antigens in vitro. The tick-susceptible cattle developed significantly higher tick-specific IgG1 antibody titres compared to the tick-resistant animals. These results suggest that the heightened antibody response either does not play a role in resistance or might contribute to increased susceptibility to infestation.

Low-dose aspirin use does not diminish the immune response to monovalent H1N1 influenza vaccine in older adults.

Non-steroidal anti-inflammatory drugs (NSAIDs) may inhibit antibody production by peripheral blood mononuclear cells; one consequence of this could be decreased effectiveness of vaccines in NSAID users. Because many older adults use low-dose aspirin for primary or secondary prevention of coronary events, any inhibitory effect of aspirin on vaccine immune response could reduce the benefits of vaccination programmes in older adults. We tested whether immune response to vaccination differed between users vs. non-users of low-dose aspirin, using data from four randomized trials of monovalent 2009 pandemic influenza A(H1N1) vaccine. Geometric mean haemagglutination inhibition antibody titres were not significantly lower in low-dose aspirin users compared to non-users. Our results provide reassurance that influenza vaccination effectiveness is probably not reduced in older adults taking chronic low-dose aspirin.

Using winter 2009-2010 to assess the accuracy of methods which estimate influenza-related morbidity and mortality.

We used the winter of 2009-2010, which had minimal influenza circulation due to the earlier 2009 influenza A(H1N1) pandemic, to test the accuracy of ecological trend methods used to estimate influenza-related deaths and hospitalizations. We aggregated weekly counts of person-time, all-cause deaths, and hospitalizations for pneumonia/influenza and respiratory/circulatory conditions from seven healthcare systems. We predicted the incidence of the outcomes during the winter of 2009-2010 using three different methods: a cyclic (Serfling) regression model, a cyclic regression model with viral circulation data (virological regression), and an autoregressive, integrated moving average model with viral circulation data (ARIMAX). We compared predicted non-influenza incidence with actual winter incidence. All three models generally displayed high accuracy, with prediction errors for death ranging from -5% to -2%. For hospitalizations, errors ranged from -10% to -2% for pneumonia/influenza and from -3% to 0% for respiratory/circulatory. The Serfling and virological models consistently outperformed the ARIMAX model. The three methods tested could predict incidence of non-influenza deaths and hospitalizations during a winter with negligible influenza circulation. However, meaningful mis-estimation of the burden of influenza can still result with outcomes for which the contribution of influenza is low, such as all-cause mortality.

Feeding performance of juvenile hatchery-reared spotted seatrout Cynoscion nebulosus.

The feeding performance of individual hatchery-reared (HR) and wild juvenile spotted seatrout Cynoscion nebulosus was compared across a series of six 1·5 h feeding exposures over a 3 day period in a controlled experiment. The predation cycle served as a context for discerning feeding performance elements. The experimental design facilitated assessments of the effects of experience, motivation due to hunger or satiation and prey density and encounter frequency. Although feeding success improved significantly across successive trials for both groups of C. nebulosus, wild C. nebulosus successfully captured and consumed significantly more Palaemonetes spp. prey and completed most performance metrics more efficiently than HR C. nebulosus. Total exposure time decreased with experience for both groups of C. nebulosus; however, HR C. nebulosus took longer to complete feeding exposures. Underpinning this difference was the time spent by HR C. nebulosus in non-search mode and for completing various foraging behaviours. Nevertheless, juvenile HR C. nebulosus exhibited sufficient foraging plasticity to switch from a pelleted diet to live novel prey.

Classification algorithms to improve the accuracy of identifying patients hospitalized with community-acquired pneumonia using administrative data.

In epidemiological studies of community-acquired pneumonia (CAP) that utilize administrative data, cases are typically defined by the presence of a pneumonia hospital discharge diagnosis code. However, not all such hospitalizations represent true CAP cases. We identified 3991 hospitalizations during 1997-2005 in a managed care organization, and validated them as CAP or not by reviewing medical records. To improve the accuracy of CAP identification, classification algorithms that incorporated additional administrative information associated with the hospitalization were developed using the classification and regression tree analysis. We found that a pneumonia code designated as the primary discharge diagnosis and duration of hospital stay improved the classification of CAP hospitalizations. Compared to the commonly used method that is based on the presence of a primary discharge diagnosis code of pneumonia alone, these algorithms had higher sensitivity (81-98%) and positive predictive values (82-84%) with only modest decreases in specificity (48-82%) and negative predictive values (75-90%).

Moving Canadian governmental policies beyond a focus on individual lifestyle: some insights from complexity and critical theories.

This paper explores why Canadian government policies, particularly those related to obesity, are 'stuck' at promoting individual lifestyle change. Key concepts within complexity and critical theories are considered a basis for understanding the continued emphasis on lifestyle factors in spite of strong evidence indicating that a change in the environment and conditions of poverty isare needed to tackle obesity. Opportunities to get 'unstuck' from individual-level lifestyle interventions are also suggested by critical concepts found within these two theories, although getting 'unstuck' will also require cross-sectoral collective action. Our discussion focuses on the Canadian context but will undoubtedly be relevant to other countries, where health promoters and others engage in similar struggles for fundamental government policy change.

The effects of salivary gland extracts from Boophilus microplus ticks on mitogen-stimulated bovine lymphocytes.

The effect of salivary gland extract (SGE) from the tick Boophilus microplus was examined in mitogen-stimulated lymphocytes in vitro. SGE was added to lymphocytes of seven cattle together with the mitogens concanavalin A (ConA), phytohaemagglutinin (PHA) and pokeweed mitogen (PWM). Semi-purified B cells from another seven cattle were stimulated with the mitogen lipopolysaccharide (LPS). PHA and ConA stimulated proliferation of lymphocytes to the same extent, but the inhibition due to SGE of Boophilus microplus on the proliferative response stimulated by PHA (39.0% +/- 9.3%) was less than the inhibition of proliferative response stimulated by ConA (75.4% +/- 6.9%). In contrast, SGE of B. microplus stimulated the proliferation of B cells in the presence of LPS in a dose-dependent manner. Enhanced stimulation of B cells by SGE at >4 microg in culture was greater than twice that observed when B cells were stimulated by LPS alone. SGE does not have a direct suppressive effect on bovine B cell proliferation; however, in vivo the effectiveness of B cell responses might be influenced by other immune factors, such as cytokine profiles.

Where's the beef? The role of cross-contamination in 4 chain restaurant-associated outbreaks of Escherichia coli O157:H7 in the Pacific Northwest.

BACKGROUND: From March through August 1993, outbreaks of Escherichia coli O157:H7 occurred at 4 separate Oregon and Washington steak and salad bar restaurants affiliated with a single national chain. OBJECTIVE: To determine the cause of outbreaks of E coli O157:H7 at 4 chain restaurants. METHODS: Independent case-control studies were performed for each outbreak. Available E coli O157:H7 isolates were subtyped by pulse-field gel electrophoresis and by phage typing. RESULTS: Infection was not associated with beef consumption at any of the restaurants. Implicated foods varied by restaurant but all were items served at the salad bar. Among the salad bar items, no single item was implicated in all outbreaks, and no single item seemed to explain most of the cases at any individual restaurant. Molecular subtyping of bacterial isolates indicated that the first 2 outbreaks, which occurred concurrently, were caused by the same strain, the third outbreak was caused by a unique strain, and the fourth was multiclonal. CONCLUSIONS: Independent events of cross-contamination from beef within the restaurant kitchens, where meats and multiple salad bar items were prepared, were the likely cause of these outbreaks. Meat can be a source of E coli O157:H7 infection even if it is later cooked properly, underscoring the need for meticulous food handling at all stages of preparation.

Association of Chlamydia pneumoniae immunoglobulin A seropositivity and risk of lung cancer.

Chlamydia pneumoniae is a common respiratory pathogen that has also been associated with risk for chronic diseases, including atherosclerotic cardiovascular disease. Two recent studies have reported an association between serological evidence of past infection with the organism and lung cancer. To further evaluate this association, we conducted a case-control study among a subgroup of white male smokers identified for a population-based case-control study of lung cancer in western Washington between 1993 and 1995. Serum specimens obtained at study enrollment from 143 cases and 147 controls were tested for C. pneumoniae IgG, IgM, and IgA antibodies. In multivariate analysis controlling for smoking variables and educational status, IgA antibody titer 216 was independently associated with risk of lung cancer among subjects <60 years of age [odds ratio (OR), 2.67; 95% confidence interval (CI), 1.21-5.89] but not among older subjects (OR, 0.69; 95% CI, 0.34-1.43). Among subjects <60 years of age, there was suggestive evidence of a stronger association among current smokers (OR 4.31; 95% CI, 1.36-13.68) than former smokers (OR 1.50; 95% CI, 0.48-4.75; P for interaction term, 0.26). Additional studies, including prospective serological evaluations, are needed to further assess the possible significance of this association.

Clinical evidence of genomic imprinting in Tourette's syndrome.

Recent genetic studies of Tourette's syndrome (TS) have suggested a sex-specific expression of TS behaviors but not a sex-associated difference in their transmission. In a retrospective study designed to assess the influence of gender of the affected parent on childhood TS phenotype, we compared unmedicated TS subjects with patrilineal (n = 25) or matrilineal (n = 25) inheritance of TS, as determined by family history methodology, with respect to demographic variables, temporal profile of tic evolution, and clinical ratings of tics and associated behaviors, particularly obsessive-compulsive symptoms and attention deficit hyperactivity disorder (ADHD). Maternal transmission of TS was characterized by trends toward greater motor tic complexity and more frequent noninterfering rituals (p < 0.05); paternal transmission was associated with increased vocal tic frequency (p = 0.01), an earlier onset of vocal tics relative to motor tics (p < 0.01), and more prominent ADHD behaviors, including motor restlessness (p < 0.01). These findings are consistent with genomic imprinting in TS. Confirmation of this phenomenon promises not only to advance understanding concerning the genetic link between TS and ADHD but may also help to explain the apparent fit of competing models of genetic transmission in TS.

Influence of family history on clinical expression of Tourette's syndrome.

OBJECTIVE: To determine the influence of family history on clinical expression of Tourette's syndrome (TS). BACKGROUND: Recent studies have suggested that clinical expression of TS is similar among sporadic (SP) and familial patients but may be influenced by bilineal (BIL) transmission of tics or obsessive-compulsive behavior (OCB) in high-density pedigrees. METHODS: The authors used family history methodology, supported by direct examination of affected relatives in 73% of familial patients, to determine the frequency of SP TS, and of unilineal (UNL) and BIL transmission of tics or OCB in 111 consecutively ascertained juvenile TS patients. For individuals in each group, severity of tics, attention deficit hyperactivity disorder (ADHD), and OCB were assessed at presentation and after a mean follow-up interval of 2.6 years, using the Tourette's Syndrome Global Scale and the Clinical Global Impression scales. The phenomenology of OCB was evaluated using the symptom checklist of the Children's Yale-Brown Obsessive Compulsive Scale. RESULTS: The authors documented BIL transmission of tics in seven patients (6%). Patient age and sex were similar for the SP (n = 21; 19%), UNL (n = 66; 59%), and BIL (n = 24; 22%) groups, as was ADHD and tic severity at presentation and follow-up. Severity of OCB differed significantly between groups, with moderate to severe OCB affecting 5% of SP, 12% of UNL, and 37% of BIL patients at presentation (p = 0.007), and 5% of SP, 17% of UNL, and 54% of BIL patients at follow-up (p = 0.0001). Relative to UNL or SP patients, BIL patients were more likely to exhibit self-injurious behaviors (p = 0.0005). CONCLUSIONS: OCB is less prominent in SP than in familial TS, perhaps reflecting a more restricted pathophysiology in this subgroup. Although BIL transmission of tics is relatively infrequent in consecutive TS pedigrees, cotransmission of OCB from an otherwise unaffected parent is common and significantly influences development of OCB and self-injurious behaviors, but not tics, in offspring. Genetic heterogeneity, epigenetic factors, and gene-environment interactions may play a more important role than genetic dosage effects in determining tic severity in TS.

A comparison of the immunosuppressive effects of salivary gland extracts from two laboratory strains of Boophilus microplus.

This study addresses three questions related to the immune response of cattle to tick salivary gland extracts. Firstly, is there a difference in the inhibition of proliferation of Concanavalin A (ConA) stimulated bovine lymphocytes induced by salivary gland extracts of the N and Y strains of Boophilus microplus? Second, is there a difference in the development rate of the Y and N tick strains? Third, does the host affect the inhibitory effect of salivary gland extract on the proliferation of ConA stimulated lymphocytes from the two tick strains? Salivary gland extract of the Y strain inhibited in vitro proliferation of lymphocytes stimulated by ConA significantly more than that of the N strain, when each strain was raised on different animals. A difference in the development rate was observed between the tick strains when raised on the same animal, with female ticks of the Y strain developing faster and reaching a greater fully engorged weight than ticks of the N strain. The difference in their rate of development did not appear to contribute to a difference in inhibitory effects of the salivary gland extracts and there was no difference between the inhibitory effects of salivary gland extracts from both strains. However, when Y strain ticks were raised on different animals, there was a significant difference in the inhibition of lymphocyte proliferation between the two salivary gland extracts. Therefore, it was concluded that there is no difference between the inhibitory effects of the two tick strains and that the host has an influence on salivary gland extract composition of B. microplus and its inhibitive properties.

Elevated anti-parasitic activity in peripheral blood monocytes and neutrophils of cattle infected with Babesia bovis.

The innate immune response to bovine Babesia bovis infection in vivo has not previously been established. We used assays measuring phagocytosis and oxidative burst to investigate the immune response because they are indicative of the innate antimicrobial capacity of monocytes and neutrophils. Monocyte and neutrophil phagocytosis is thought to be non-specific in nature and so the phagocytosis of either opsonised Zymosan or Escherichia coli was used to indicate the non-specific phagocytic capacity of monocytes and neutrophils ex vivo. The kinetics of both phagocytic and oxidative burst activity in monocytes and neutrophils were followed twice weekly from pre-inoculation (day 0) through to 31 days after inoculation. Peripheral blood monocytes were found to display a pronounced oxidative burst, but a suppressed capacity to phagocytose during a primary infection. On the other hand, neutrophils exhibited an increased phagocytic capacity and reduced oxidative activity during a primary infection. These findings identified considerable antimicrobial activity evident in peripheral blood monocytes and neutrophils from cattle exposed to B. bovis as a primary exposure. This elevated antimicrobial activity was coincident with the time that parasite numbers peaked in the circulation and occurred prior to parasite clearance. These results suggest that peripheral blood monocytes and neutrophils are active mediators in the innate immune response to a primary B. bovis.

Outbreak of leptospirosis associated with swimming.

Between July 7 and 18, 1991, five boys from a small town in rural Illinois experienced the onset of an acute febrile illness subsequently confirmed as leptospirosis by serologic tests. A cohort study found that swimming in a small swimming hole, Steel Tunnel Pond, was associated with disease (P < 0.01), the attack rate being 28%. Leptospira interrogans serovar grippotyphosa was isolated from urine cultures from two of the case patients and from a culture of Steel Tunnel Pond water. A high seroprevalence for grippotyphosa was found in animals near the pond. Drought conditions had been present in the month before the outbreak, creating an environment in the pond which probably facilitated transmission of the organism from area animals to humans. Although leptospirosis is infrequently reported in humans in the United States, it is endemic in animals and the potential for outbreaks exists, especially when environmental conditions are favorable.

Evaluation of the use of mass chemoprophylaxis during a school outbreak of enzyme type 5 serogroup B meningococcal disease.

BACKGROUND: A vaccine for prevention of serogroup B meningococcal disease is not available in the United States, and indications for the use of mass chemoprophylaxis for control of meningococcal outbreaks are not well-defined. In response to an outbreak of six cases of enzyme type 5 serogroup B meningococcal disease among students at a middle school, we implemented a program of mass rifampin prophylaxis and evaluated the effectiveness of this preventive measure. METHODS: Oropharyngeal cultures were obtained from 351 of the 900 students before prophylaxis; 196 participants were recultured 3 weeks later. Meningococcal isolates were subtyped and tested for rifampin susceptibility, and risk factors for disease or carriage among students were evaluated. RESULTS: No cases occurred after prophylaxis. Before prophylaxis 10% (34 of 351) of students were meningococcal carriers and 3.4% (12 of 351) carried the epidemic strain. After prophylaxis 2.5% (5 of 196) were carriers and 1.0% (2 of 196) carried the epidemic strain. Rifampin was 85% effective in eradicating carriage, and the rate of acquisition of carriage during the 3-week period was low (0.5%). Carriage persisted after prophylaxis in 4 students; 3 of these postprophylaxis isolates were rifampin-resistant. Rifampin resistance thus developed in 12% (3 of 26) of preprophylaxis isolates. Disease/epidemic strain carriage was associated with enrollment in the school band and certain other classes. CONCLUSIONS: These findings suggests that mass chemoprophylaxis may be effective and should be considered for control of school serogroup B meningococcal outbreaks. This approach is less likely to be effective for control of outbreaks affecting larger, less well-defined populations and is associated with the rapid development of antibiotic resistance.

Risk of infection with hepatitis A, B or C, cytomegalovirus, varicella or measles among child care providers.

BACKGROUND: Employment as a child care provider has been suggested as an indication for hepatitis A virus (HAV) immunization; however, whether this occupational group is at increased risk of HAV infection is not well-defined. METHODS: We obtained sera samples for testing for antibodies to hepatitis A, B and C, cytomegalovirus, varicella and measles from a sample of child care providers in King County, WA, and administered a questionnaire to assess employment characteristics and other potential risk factors for infection. We also compared the anti-HAV seroprevalence among providers with that of subjects in the Third National Health and Nutrition Survey, representative of the US general population. RESULTS: Thirteen percent (48 of 360) of providers were anti-HAV-positive (46% (22 of 47) of foreign born vs. 8% (26 of 313) of US-born (P < 0.001)). In multivariate analysis anti-HAV seropositivity was associated with foreign birth, age, income and Hispanic ethnicity but was not associated with characteristics of employment. Seroprevalence among US-born providers tended to be lower than that among Third National Health and Nutrition Survey subjects of similar age, sex, race and income. Sixty-two percent of providers were seropositive to cytomegalovirus, which was associated with nonwhite race, changing diapers > or = 3 days/week while at work and having a child in the household. Antibody prevalence was 1.4% to hepatitis B core antigen, 0.6% to hepatitis C, 94% to measles and 98% to varicella. CONCLUSIONS: The anti-HAV prevalence among US-born providers was low, and seropositivity was not associated with employment characteristics, indicating that occupational exposure to HAV is uncommon under non-outbreak circumstances.

Prevention of chickenpox in reproductive-age women: cost-effectiveness of routine prenatal screening with postpartum vaccination of susceptibles.

OBJECTIVE: To evaluate economic and clinical outcomes of a program of routine prenatal serotesting for varicella and postpartum vaccination of seronegative women. METHODS: An analytic cost-effectiveness model was constructed to compare the current strategy of no serotesting with 1) selective serotesting of pregnant women without a prior history of chickenpox and 2) serotesting of all pregnant women. In both serotesting strategies, seronegative women were vaccinated postpartum. The model followed a hypothetical cohort of 4 million women over 20 years. Costs and chickenpox disease outcomes during and outside of subsequent pregnancies were considered. The incremental cost-effectiveness (cost per adult chickenpox case prevented) of selective serotesting compared with the current strategy was measured. RESULTS: Compared to no testing, selective serotesting would prevent 43% (48,577 of 112,654) of adult chickenpox cases, save $21.8 million in discounted medical and work loss costs from the societal perspective, and cost $1126 per case prevented from the health payer's perspective (medical costs only). The model was sensitive to varicella seroprevalence and incidence of chickenpox among susceptible women but was relatively insensitive to the cost of serologic testing and vaccination. Compared with selective serotesting, the serotest-all strategy would prevent an additional 15,645 cases, at a societal cost of $7653 per additional case prevented. CONCLUSION: The selective serotesting strategy could prevent nearly half of chickenpox cases among this cohort and is cost-saving from the societal perspective. From the health payer's perspective, it compares favorably with other generally accepted preventive practices. It should be considered for prevention of chickenpox among women of childbearing age.

Phenotypic analysis of bovine leukocyte cell lines infected with Theileria annulata.

Six cell lines that were infected with Theileria annulata were compared for expression of a range of surface molecules. Immunofluorescence staining with the panel of monoclonal antibodies formulated for the Second Workshop was analysed by flow cytometry. Four lines generated from bovine peripheral blood mononuclear cells by exposure to sporozoites in vitro and one line generated in vivo from an infected calf were phenotypically similar. Phenotypic analysis of those lines did not demonstrate a monocyte or B cell origin, but indicated they were not derived from T cells. An uncloned line generated in vivo from an infected calf was CD3+ and gamma/delta TCR+. The results indicate that a wider range of host cell types may be infected in vivo than suspected hitherto and that some of the cells may express an abnormal pattern of surface molecules. Both could have profound consequences for the pathogenesis of T. annulata infection.

Bacterial meningitis.

In recent years, investigators have made significant advances in understanding the pathogenesis of bacterial meningitis, particularly with regard to understanding the cascade of biologic events that cause excessive inflammation within the central nervous system (CNS). Nevertheless, the most important event in the field of bacterial meningitis in the past decade is the dramatic decline in the incidence of Haemophilus influenzae meningitis in children as a result of the widespread use of the conjugated H. influenzae type b vaccine. Currently, the most important clinical challenge in this field is the emergence of the drug-resistant Streptococcus pneumoniae. This problem has significantly complicated initial management of patients with suspected bacterial meningitis. Preliminary data show promise with new conjugated S. pneumoniae vaccines.