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During the past decade, the global public health community has been challenged by the emergence and rapid worldwide spread of novel influenza strains, severe acute respiratory syndrome, chikungunya virus, drug-resistant tuberculosis, and other conditions and pathogens. Modern transportation and increased tourism, business travel, and immigration contributed to dissemination of these high-impact pathogens. The effectiveness of interventions such as airport screening, travel restrictions, and other community mitigation measures remains uncertain. However, human migration has occurred for centuries and will continue, despite the threats posed by microbes.

Human mobility has always been associated with the spread of infection, and mobility of nonimmigrant visitors and temporary residents to the United States is increasing, from approximately 12 million in 1987 to approximately 37 million in 2007. Lack of information about the health status of these populations upon arrival and their need for and use of medical services in the United States hinders development of public health policy, education, and provision of adequate clinical care. After these issues and needs are clarified, intervention programs should be developed to increase access and decrease the disparities of care experienced by these populations.

A fundamental role of the veterinary profession is the protection of human health through wholesome food and control of diseases of animal origin, especially zoonoses. Therefore, training of veterinary students worldwide needs to face the new challenges posed by emerging infections, both from wildlife and domestic animals, as well as risks from bio/agroterrorism. New courses emphasising recognition, response, recovery and prevention must be developed to respond to natural or intentionally induced emerging diseases and zoonoses. Training programmes in applied epidemiology, zoonoses and foreign animal diseases are crucial for the development of a strong workforce to deal with microbial threats. Students should learn the reporting pathways for reportable diseases in their countries or states. Knowledge of the principles of ecology and ecosystems should be acquired during pre-veterinary studies. Elective classes on wildlife diseases, emphasising wildlife zoonotic diseases, should be offered during the veterinary curriculum, as well as a course on risk communication, since veterinarians are frequently in the position of having to convey complex information under adverse circumstances.

Yellow fever (YF) vaccine has been used for prevention of YF since 1937 with over 500 million doses administered. However, rare reports of severe adverse events following vaccination have raised concerns about the vaccine's safety. We reviewed reports of adverse events following YF vaccination reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) from 2000 to 2006. We used estimates of age and sex distribution of administered doses obtained from a 2006 survey of authorized vaccine providers to calculate age- and sex-specific reporting rates of all serious adverse events (SAE), anaphylaxis, YF vaccine-associated neurotropic disease, and YF vaccine-associated viscerotropic disease. Reporting rates of SAEs were substantially higher in males and in persons aged > or =60 years. These findings reinforce the generally acceptable safety profile of YF vaccine, but highlight the importance of physician and traveler education regarding the risks and benefits of YF vaccination, particularly for travelers > or =60 years of age. Vaccination should be limited to persons traveling to areas where the risk of YF is expected to exceed the risk of serious adverse events after vaccination, or if not medically contraindicated, where national regulations require proof of vaccination to prevent introduction of YF.

Exposure to animals can provide many benefits during the growth and development of children. However, there are potential risks associated with animal exposures, including exposure to nontraditional pets in the home and animals in public settings. Educational materials, regulations, and guidelines have been developed to minimize these risks. Pediatricians, veterinarians, and other health care professionals can provide advice on selection of appropriate pets as well as prevention of disease transmission from nontraditional pets and when children contact animals in public settings.

Selected data collected for travelers to China from 1998 through November 2007 by the GeoSentinel Surveillance Network were used to provide an evidence base for prioritizing recommendations for Olympic and other future travelers to China. Respiratory illness and injuries were common among patients seen during their travel; acute diarrhea and dog bites were common among those seen after travel. Tropical and parasitic diseases were rare. Pre-travel consultation for China travelers should be individualized according to these findings.

The articles on rabies and Marburg virus featured in this month's Emerging Infectious Diseases (EID) zoonoses issue illustrate common themes. Both discuss zoonotic diseases with serious health implications for humans, and both have a common reservoir, the bat. These articles, and the excitement generated by this year's recognition of World Rabies Day on September 8, also described in this issue, remind us how globalization has had an impact on the worldwide animal trade. This worldwide movement of animals has increased the potential for the translocation of zoonotic diseases, which pose serious risks to human and animal health.

Emerging infectious diseases represent a grave threat to animal and human populations in terms of their impact on global health, agriculture and the economy. Vaccines developed for emerging infections in animals can protect animal health and prevent transmission of zoonotic diseases to humans. Examples in this paper illustrate how industry and public health can collaborate to develop a vaccine to prevent an emerging disease in horses (West Nile virus vaccine), how poultry vaccination can protect animals and prevent transmission to people (avian influenza vaccine), how regulatory changes can pave the way for vaccines that will control the carrier state in animals and thus prevent infection in humans (Bartonella henselae vaccine in cats) and how novel technologies could be applied to vaccinate wildlife reservoir species for rabies. Stemming from the realisation that zoonotic diseases are the predominant source of human emerging infectious diseases, it behoves academic, public health, and animal health agencies to consider creative constructive approaches to combat serious public health challenges. Vaccination of vector/reservoir species, when efficacious vaccines are available, offers significant advantages to combating zoonotic human disease.

From October 1997 through March 1998, three outbreaks of gastrointestinal illness among school children were linked to company A burritos. In September 1998, a similar outbreak occurred in three North Dakota schools following lunches that included company B burritos. We conducted an investigation to determine the source of the North Dakota outbreak, identify other similar outbreaks, characterize the illness, and gather evidence about the cause. The investigation included epidemiologic analyses, environmental investigation, and laboratory analyses. In North Dakota, a case was defined as nausea, headache, abdominal cramps, vomiting, or diarrhea after lunch on 16 September 1998. Case definitions varied in the other states. In North Dakota, 504 students and staff met the case definition; predominant symptoms were nausea (72%), headache (68%), abdominal cramps (54%), vomiting (24%), and diarrhea (16%). The median incubation period was 35 min and median duration of illness was 6 h. Eating burritos was significantly associated with illness (odds ratio, 2.6; 95% confidence interval, 1.6 to 4.2). We identified 16 outbreaks that occurred in seven states from October 1997 through October 1998, affecting more than 1,900 people who ate burritos from two unrelated companies. All tortillas were made with wheat flour, but the fillings differed, suggesting that tortillas contained the etiologic agent. Results of plant inspections, tracebacks, and laboratory investigations were unrevealing. More than two million pounds of burritos were recalled or held from distribution. The short incubation period, symptoms, and laboratory data suggest that these outbreaks were caused by an undetected toxin or an agent not previously associated with this clinical syndrome. Mass psychogenic illness is an unlikely explanation because of the large number of sites where outbreaks occurred over a short period, the similarity of symptoms, the common food item, the lack of publicity, and the link to only two companies. A network of laboratories that can rapidly identify known and screen for unknown agents in food is a critical part of protecting the food supply against natural and intentional contamination.

Purpose: The CDC's Anthrax Vaccine and Antibiotic Availability Program was implemented under an Investigational New Drug (IND) application to provide additional post-exposure prophylaxis for individuals potentially exposed to Bacillus anthracis in the fall of 2001. Participants were provided with two options: (1) 40 additional days of antimicrobial prophylaxis (i.e., ciprofloxacin, doxycycline, or amoxicillin); or (2) 40 additional days of antimicrobial prophylaxis plus three doses of anthrax vaccine adsorbed (AVA)., Methods: Participants were monitored for adverse events (AEs). Participants were asked to complete 2-week AE diaries for 6 weeks post-enrollment, and approximately 2 months after enrollment, active surveillance was conducted through telephone interviews with 1113 (64%) participants., Results: A total of 1727 of approximately 10 000 previously prophylaxed persons enrolled to receive 40 additional days of antibiotics. Of these, 199 opted at enrollment to receive three doses of AVA in addition to the additional 40 days of antibiotic. Overall, 28% of participants reported at least one AE on their diaries. Results varied by surveillance mechanism, the diary data indicated differences in the proportion reporting AEs between participants receiving antibiotic only and participants receiving antibiotic and AVA. However, during the active 2-month telephone follow-up, the rates of AEs reported for both the antibiotic only and antibiotic plus AVA treatment regimens were similar. Additionally, ciprofloxacin and doxycycline had similar AE profiles, with only rigors reported significantly more often among ciprofloxacin recipients., Conclusions: Overall, the rates of AEs experienced by all participants were acceptable given the seriousness of potential B. anthracis exposure.

Background: Campylobacter causes >1 million infections annually in the United States. Fluoroquinolones (e.g., ciprofloxacin) are used to treat Campylobacter infections in adults. Although human infections with ciprofloxacin-resistant Campylobacter have become increasingly common, the human health consequences of such infections are not well described., Methods: A case-control study of persons with sporadic Campylobacter infection was conducted within 7 FoodNet sites during 1998-1999. The E-test system (AB Biodisk) was used to test for antimicrobial susceptibility to ciprofloxacin; ciprofloxacin resistance was defined as a ciprofloxacin minimum inhibitory concentration of > or =4 microg/mL. We conducted a case-comparison study of interviewed persons who had an isolate tested., Results: Of 858 isolates tested, 94 (11%) were ciprofloxacin resistant. Among 290 persons with Campylobacter infection who did not take antidiarrheal medications, persons with ciprofloxacin-resistant infection had a longer mean duration of diarrhea than did persons with ciprofloxacin-susceptible infection (9 vs. 7 days [P=.04]). This difference was even more pronounced among the 63 persons who did not take antidiarrheal medications or antimicrobial agents (12 vs. 6 days [P=.04]). In a multivariable analysis-of-variance model, the persons with ciprofloxacin-resistant infection had a longer mean duration of diarrhea than did the persons with ciprofloxacin-susceptible infection (P=.01); this effect was independent of foreign travel. The association between ciprofloxacin resistance and prolonged diarrhea is consistent across a variety of analytical approaches., Conclusions: Persons with ciprofloxacin-resistant Campylobacter infection have a longer duration of diarrhea than do persons with ciprofloxacin-susceptible Campylobacter infection. Additional efforts are needed to preserve the efficacy of fluoroquinolones.

An anti-Anthrax Vaccine Adsorbed (anti-AVA) standard human reference serum pool, AVR414, has been prepared, and the total and protective antigen (PA)-specific immunoglobulin G (IgG) were quantified. AVR414 was prepared by plasmapheresis of healthy adults who had received a minimum of four subcutaneous injections of AVA. Mass values (in milligrams per milliliter) for total IgG and IgG subclasses 1 to 4 were determined by radial immunodiffusion. Anti-PA-specific IgG assignment (in micrograms per milliliter) was done by consensus of two complementary approaches: homologous enzyme-linked immunosorbent assay (ELISA) with affinity-purified anti-PA IgG as a calibrator and summation of mean PA-specific IgG subclass concentrations determined by IgG subclass-specific ELISA using the United States National Reference Preparation for Human Serum Proteins as a standard. The total IgG concentration assigned to AVR414 reference serum was 8.33 mg/ml. IgG subclass concentrations were the following: for IgG1, 4.48 mg/ml; for IgG2, 3.35 mg/ml; for IgG3, 0.37 mg/ml; and for IgG4, 0.30 mg/ml. The assigned mass value for total anti-PA-specific IgG was 141.2 microg/ml. Anti-PA-specific IgG subclass concentrations were the following: for IgG1, 79.6 microg/ml; for IgG2, 35.3 microg/ml; for IgG3, 3.2 microg/ml; and for IgG4, 25.3 microg/ml. Human reference serum pool AVR414 will have direct application in the standardization of anthrax serological assays, in reagent qualification, and as a standard for quantification of PA-specific IgG in humans who have been vaccinated with or otherwise exposed to Bacillus anthracis PA.

As Veterinary Services and animal health organisations attempt to respond to a new era of emerging and re-emerging zoonotic diseases, their ability and skill in forming new strategic partnerships will be paramount. While these new partnerships are likely to include many relationships outside traditional Veterinary Services and animal agriculture, none will become more important than the formation of new animal health and public health partnerships. Episodes of emerging zoonoses are being increasingly recognised around the world and the confluence of people, animals and animal products today is unprecedented. Concurrently, a wide array of complex factors are also converging that will not only ensure the continuous emergence of zoonoses, but are also likely to drive the further increase and expansion of these diseases. This article discusses the need for the creation of more effective and co-operative partnerships in the face of new microbial threats, the complexity of both the formation and expansion of zoonoses, and the collective abilities of both human and animal health services to respond to them. Lessons learned from recent zoonotic epidemics supportthe need for co-ordinated research, interdisciplinary centres, integrated surveillance systems, response systems and infrastructures, and workforce development strategies. While there are some excellent examples of collaborative animal and public health relationships, there is no question that more and stronger partnerships among national and international organisations, both academic and private, will be necessary to meet the future challenges of emerging zoonoses and to manage their profound implications.

A 12-month, population-based, case-control study of Campylobacter infections was conducted at Foodborne Disease Active Surveillance Network surveillance areas during 1998-1999. Of 858 Campylobacter isolates tested for antimicrobial susceptibility to the fluoroquinolone ciprofloxacin, 94 (11%) were resistant. Travel outside of the United States was reported by 27 (42%) of 64 patients with fluoroquinolone-resistant Campylobacter infection and by 51 (9%) of 582 patients with fluoroquinolone-susceptible Campylobacter infection (odds ratio [OR], 7.6; 95% confidence interval [CI], 4.3-13.4). When patients with domestically acquired fluoroquinolone-resistant Campylobacter infection were compared with matched healthy control subjects in a multivariate analysis, those infected were 10 times more likely to have eaten chicken or turkey cooked at a commercial establishment (18 [55%] of 33 case patients vs. 7 [21%] of 33 controls; matched OR, 10.0; 95% CI, 1.3-78). Although travel outside of the United States was associated with fluoroquinolone-resistant Campylobacter infection, most infections among study participants were domestically acquired. This study provides additional evidence that poultry is an important source of domestically acquired fluoroquinolone-resistant Campylobacter infection. Control measures should include efforts to improve food handling in commercial establishments.

On 20 December 2001, the Centers for Disease Control and Prevention (CDC) initiated the Anthrax Vaccine and Antibiotic Availability Program (hereafter, the "Program") under an investigational new drug application with the US Food and Drug Administration. This Program provided options for additional preventive treatment for persons at risk for inhalation anthrax as a result of recent bioterrorism attacks who had concluded or were concluding a 60-day course of antimicrobial prophylaxis. Participants were offered an additional 40 days of antibiotic therapy (with ciprofloxacin, doxycycline, or amoxicillin) or antibiotic therapy plus 3 doses of anthrax vaccine. By 11 February 2002, a total of 5420 persons had received standardized education about the Program and 1727 persons (32%) had enrolled. Twelve participants have been identified as having serious adverse events (SAEs). One SAE, which occurred in a participant with ciprofloxacin-induced allergic interstitial nephritis, was considered to be probably associated with treatment received in the Program. No SAEs were associated with anthrax vaccine. CDC will continue to monitor Program participants during the next 2 years.

Adventure travel is becoming more popular, increasing the likelihood of contact with unusual pathogens. We investigated an outbreak of leptospirosis in "Eco-Challenge" multisport race athletes to determine illness etiology and implement public health measures. Of 304 athletes, we contacted 189 (62%) from the United States and 26 other countries. Eighty (42%) athletes met our case definition. Twenty-nine (36%) case-patients were hospitalized; none died. Logistic regression showed swimming in the Segama River (relative risk [RR]=2.0; 95% confidence interval [CI]=1.3 to 3.1) to be an independent risk factor. Twenty-six (68%) of 38 case-patients tested positive for leptospiral antibodies. Taking doxycycline before or during the race was protective (RR=0.4, 95% CI=0.2 to 1.2) for the 20 athletes who reported using it. Increased adventure travel may lead to more frequent exposure to leptospires, and preexposure chemoprophylaxis for leptospirosis (200 mg oral doxycycline/week) may decrease illness risk. Efforts are needed to inform adventure travel participants of unique infections such as leptospirosis.

Objective: To determine if a home-based nurse intervention (INT), focusing on parenting education/skills and caregiver emotional support, reduces child behavioral problems and parenting stress in caregivers of in utero drug-exposed children., Design: Randomized clinical trial of a home-based INT., Settings: Two urban hospital newborn nurseries; homes of infants (the term infant is used interchangeably in this study with the term child to denote those from birth to the age of 36 months); and a research clinic in Baltimore, Md., Participants: In utero drug-exposed children and their caregivers (N = 100) were examined when the child was between the ages of 2 and 3 years. Two groups were studied: standard care (SC) (n = 51) and INT (n = 49)., Intervention: A home nurse INT consisting of 16 home visits from birth to the age of 18 months to provide caregivers with emotional support and parenting education and to provide health monitoring for the infant., Main Outcome Measures: Scores on the Child Behavior Checklist and the Parenting Stress Index., Results: Significantly more drug-exposed children in the SC group earned t scores indicative of significant emotional or behavioral problems than did children in the INT group on the Child Behavior Checklist Total (16 [31%] vs 7 [14%]; P =.04), Externalizing (19 [37%] vs 8 [16%]; P =.02), and Internalizing (14 [27%] vs. 6 [12%]; P =.05) scales and on the anxiety-depression subscale (16 [31%] vs. 5 [10%]; P =.009). There was a trend (P =.06) in more caregivers of children in the SC group reporting higher parenting distress than caregivers of children in the INT group., Conclusions: In utero drug-exposed children receiving a home-based nurse INT had significantly fewer behavioral problems than did in utero drug-exposed children receiving SC (P =.04). Furthermore, those caregivers receiving the home-based INT reported a trend toward lower total parenting distress compared with caregivers of children who received SC with no home visits.

In the present paper, we report on the properties of sphingolipid-enriched domains of rat cerebellar granule cells in culture at different stages of neuronal development. The major lipid components of these domains were glycerophospholipids and cholesterol. Glycerophospholipids were 45-75% and cholesterol 15-45% of total lipids of the domains. This corresponded to 5-17% of total cell glycerophospholipids and 15-45% of total cell cholesterol. Phosphatidylcholine, mainly dipalmitoylphosphatidylcholine, was 66-85% of all the glycerophospholipids associated with these domains. Consequently, the palmitoyl residue was significantly enriched in the domains. The surface occupied by these structures increased during development. 40-70% of cell sphingolipids segregated in sphingolipid-enriched membrane domains, with the maximum ganglioside density in fully differentiated neurons. A high content of ceramide was found in the domains of aging neurons. Then, the sphingolipid/glycerophospholipid molar ratio was more than doubled during the initial stage of development, whereas the cholesterol/glycerophospholipid molar ratio gradually decreased during in vitro differentiation. Phosphorylated phosphoinositides, which were scant in the domains of undifferentiated cells, dramatically increased during differentiation and aging in culture. Proteins were minor components of the domains (0.1-2.8% of all domain components). Phosphotyrosine-containing proteins were selectively recovered in the sphingolipid-enriched domain. Among these, Src family protein-tyrosine kinases, known to participate to the process of neuronal differentiation, were associated with the sphingolipid-enriched domains in a way specific for the type of kinase and for the developmental stage of the cell. Proteins belonging to other signaling pathways, such as phosphoinositide 3-kinase and its downstream target, Akt, were not associated with the domains.

Historically, veterinary medicine has made its greatest contributions in the public sector and in settings other than direct care of the individual patient. So why are so many of us unaware of our profession's achievements in this arena? My introduction to veterinary preventive medicine and public health was through military service. My obligation to serve a two-year doctor draft in the United States Air Force became an adventure for my family and me, rather than an unwelcome intrusion on my ultimate desire to return to private clinical practice. The operative words are private and clinical. Why was I unaware of the opportunities available to those of us educated in this discipline sometimes referred to as comparative medicine?

Non-cholera Vibrio infections are an important public health problem. Non-cholera Vibrio species usually cause sporadic infections, often in coastal states, and have also caused several recent nationwide outbreaks of gastroenteritis in the United States. We report a survey of laboratory stool culturing practices for Vibrio among randomly selected clinical laboratories in Gulf Coast states (Alabama, Florida, Louisiana, Mississippi, and Texas). Interviews conducted with the microbiology supervisors of 201 clinical laboratories found that 164 (82%) received stool specimens for culture. Of these, 102 (62%) of 164 processed stool specimens on site, and 20 (20%) of these 102 laboratories cultured all stool specimens for Vibrio, indicating that at least 34,463 (22%) of 152, 797 stool specimens were cultured for Vibrio. This survey suggests that despite an increased incidence of non-cholera Vibrio infections in Gulf Coast states, a low percentage of clinical laboratories routinely screen all stool specimens, and fewer than 25% of stool specimens collected are routinely screened for non-cholera Vibrio.

Src family kinases play a relevant role in the development and differentiation of neuronal cells. They are abundant in sphingolipid-enriched membrane domains of many cell types, and these domains are hypothesized to function in bringing together molecules important to signal transduction. We studied the association of Src family tyrosine kinases and their negative regulatory kinase, Csk, with sphingolipids in sphingolipid-enriched domains of rat cerebellar granule cells differentiated in culture. We find that c-Src, Lyn and Csk are enriched in the sphingolipid-enriched fraction prepared from these cells. Coimmunoprecipitation experiments show that these and sphingolipids are part of the same domain. Cross-linking experiments with a photoactivable, radioactive GD1b derivative show that c-Src and Lyn, which are anchored to the membrane via a myristoyl chain, associate directly with GD1b. Csk, which is not inserted in the hydrophobic core of the membrane, is not photolabeled by this ganglioside. These results suggest that lipid-lipid, lipid-protein, and protein-protein interactions cooperate to maintain domain structure. We hypothesize that such interactions might play a role in the process of neuronal differentiation.

In order to investigate the functional similarities of the high affinity receptor for IgE (Fc epsilon RI) and the T cell receptor for antigen, we have developed a high efficiency polyethylene glycol-mediated fusion method to make somatic hybrids between cells from a mast cell line (RBL-2H3) and cells from T lymphoma cell lines (Jurkat and HPB-ALL). Using flow cytometry to select for the heterologously fused cells, we demonstrated that aggregation of the T cell receptor results in the efficient secretion of [3H]5-hydroxytryptamine from RBL cell-derived granules. In addition, both receptors mediate Ca2+ mobilization in the hybrid cells that is insensitive to inhibition by the protein kinase C activator phorbol-12-myristoyl-13-acetate (PMA). In contrast, Ca2+ mobilization caused by aggregation of Fc epsilon RI in the parent RBL cells is completely inhibited by PMA. The results indicate that these two different receptors for foreign antigen can substitute for each other to trigger responses in the hybrid cells that are unique to each cell type. The methodology employed has general utility for studying signal transduction mediated by mammalian cell surface receptors.

The nerve growth factor (NGF) receptor, solubilized with Triton X-100 detergent, has been purified from human melanoma cell line A875. Purification to near-homogeneity was achieved by chromatography on wheat germ agglutinin-agarose, followed by immunoaffinity chromatography on Sepharose columns coupled with anti-NGF receptor monoclonal antibody (MAb). The purified receptor, a 75,000-dalton protein, retains the capacity to bind NGF as well as anti-receptor MAbs. Final purification was achieved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The sequence of amino acid residues at the amino terminus has been determined. Possible sequence homology between the NGF receptor and several other proteins is discussed. Using the purified receptor as immunogen, new MAbs to the NGF receptor have been produced. The NGF receptor was visualized by immunoperoxidase staining in tissue sections of dorsal root ganglia from monkeys.