Fertility Control and the Welfare of Free-Roaming Horses and Burros on U.S. Public Lands: The Need for an Ethical Framing.

To be effective and publicly acceptable, management of free-roaming horses and burros in the United States and elsewhere needs a consistent ethical framing of the animals and the land they occupy. In the U.S., the two laws that largely govern wild horse and burro management, the 1971 Wild Free-Roaming Horse and Burro Act and the 1976 Federal Land Policy and Management Act ("FLPMA"), rest on conflicting foundations, the former based on an ethic of care and the latter on largely utilitarian principles. These conflicts specifically fuel debates over the selection of appropriate fertility control agents for horse and burro management. Because land-use and management decisions are largely controlled by the FLPMA, and because the ethical treatment of animals is typically considered under conditions established by their use, both the larger debate about equids and land management and the specific debate about fertility control are dominated by cost/benefit calculations and avoid broader ethical considerations. In our view, the long-term health and ethical treatment of free-roaming horses and burros, the lands they occupy, and the wildlife and people they share it with will require the replacement of the resource-use model with a more holistic, care-based approach.

Structural study of L-ascorbic acid 2-phosphate magnesium, a raw material in cell and tissue therapy.

L-ascorbic acid 2-phosphate magnesium (APMg) salt is a vitamin C derivative frequently used as a raw material in cell and tissue therapy. APMg is not only used as a replacement of the unstable ascorbate, but also shows additional cell-biological functionalities. However, its unknown structural characteristics hamper the mechanistic elucidation of its biological role. Therefore, different techniques were applied for APMg structure characterization. Firstly, the stoichiometric composition was characterized by its solvent, ligand and magnesium content. No crystals of APMg could be obtained; however, a single crystal of APNa, the sodium salt of l-ascorbic acid 2-phosphate, was successfully obtained and its crystal structure was elucidated. FT-IR was applied to further clarify the structure of solid APMg. Finally, the structure of APMg in aqueous solution was explored by potentiometric titration as well as FT-IR.

Zwitterionic-hydrophilic interaction liquid chromatography for l-ascorbic acid 2-phosphate magnesium, a raw material in cell therapy.

l-ascorbic acid 2-phosphate magnesium (APMg) salt is a vitamin C derivative frequently used in cell culture media for research purposes. It is also used as a raw material in the GMP-manufacturing of gene-, cell- and tissue advanced therapy medicinal products (ATMPs). However, quality methods are currently lacking. Therefore, a LC method was developed, based on hydrophilic interaction (HILIC)-ion exchange (IE) mixed-mode liquid chromatography. The final method consisted of an isocratic system with 15 mM KH2PO4 buffer (pH 2.5 with HCl) acetonitrile (30:70, v/v) mobile phase on a zwitterionic HILIC column, containing an hydrophilic ligand embedded cation-exchange functionality and a surface anion-exchange group. A flow rate of 0.4 mL/min and UV detection at 240 nm was applied. The assay method of APMg was validated, obtaining adequate linearity (R2 = 0.999), precision (RSD of 0.49%) and accuracy (overall recovery of 100.4%). The developed method was successfully applied on five currently marketed products from different suppliers, showing different related substance impurity profiles. Using atomic absorption spectroscopy (AAS), magnesium was found to be bound on the stationary phase, requiring a strong mobile phase to rinse the column. Finally, related impurities were identified using MS/MS and high resolution MS, and found to be ascorbic acid as well as ethyl derivatives, which was further confirmed by NMR.

Outbreaks caused by sprouts, United States, 1998-2010: lessons learned and solutions needed.

After a series of outbreaks associated with sprouts in the mid-1990s, the U.S. Food and Drug Administration (FDA) published guidelines in 1999 for sprouts producers to reduce the risk of contamination. The recommendations included treating seeds with an antimicrobial agent such as calcium hypochlorite solution and testing spent irrigation water for pathogens. From 1998 through 2010, 33 outbreaks from seed and bean sprouts were documented in the United States, affecting 1330 reported persons. Twenty-eight outbreaks were caused by Salmonella, four by Shiga toxin-producing Escherichia coli, and one by Listeria. In 15 of the 18 outbreaks with information available, growers had not followed key FDA guidelines. In three outbreaks, however, the implicated sprouts were produced by firms that appeared to have implemented key FDA guidelines. Although seed chlorination, if consistently applied, reduces pathogen burden on sprouts, it does not eliminate the risk of human infection. Further seed and sprouts disinfection technologies, some recently developed, will be needed to enhance sprouts safety and reduce human disease. Improved seed production practices could also decrease pathogen burden but, because seeds are a globally distributed commodity, will require international cooperation.

Surveillance for foodborne disease outbreaks - United States, 1998-2008.

PROBLEM/CONDITION: Foodborne diseases cause an estimated 48 million illnesses each year in the United States, including 9.4 million caused by known pathogens. Foodborne disease outbreak surveillance provides valuable insights into the agents and foods that cause illness and the settings in which transmission occurs. CDC maintains a surveillance program for collection and periodic reporting of data on the occurrence and causes of foodborne disease outbreaks in the United States. This surveillance system is the primary source of national data describing the numbers of illnesses, hospitalizations, and deaths; etiologic agents; implicated foods; contributing factors; and settings of food preparation and consumption associated with recognized foodborne disease outbreaks in the United States. REPORTING PERIOD: 1998-2008. DESCRIPTION OF THE SYSTEM: The Foodborne Disease Outbreak Surveillance System collects data on foodborne disease outbreaks, defined as the occurrence of two or more cases of a similar illness resulting from the ingestion of a common food. Public health agencies in all 50 states, the District of Columbia, U.S. territories, and Freely Associated States have primary responsibility for identifying and investigating outbreaks and use a standard form to report outbreaks voluntarily to CDC. During 1998-2008, reporting was made through the electronic Foodborne Outbreak Reporting System (eFORS). RESULTS: During 1998-2008, CDC received reports of 13,405 foodborne disease outbreaks, which resulted in 273,120 reported cases of illness, 9,109 hospitalizations, and 200 deaths. Of the 7,998 outbreaks with a known etiology, 3,633 (45%) were caused by viruses, 3,613 (45%) were caused by bacteria, 685 (5%) were caused by chemical and toxic agents, and 67 (1%) were caused by parasites. Among the 7,724 (58%) outbreaks with an implicated food or contaminated ingredient reported, 3,264 (42%) could be assigned to one of 17 predefined commodity categories: fish, crustaceans, mollusks, dairy, eggs, beef, game, pork, poultry, grains/beans, oils/sugars, fruits/nuts, fungi, leafy vegetables, root vegetables, sprouts, and vegetables from a vine or stalk. The commodities implicated most commonly were poultry (18.9%; 95% confidence interval [CI] = 17.4-20.3) and fish (18.6%; CI = 17.2-20), followed by beef (11.9%; CI = 10.8-13.1). The pathogen-commodity pairs most commonly responsible for outbreaks were scombroid toxin/histamine and fish (317 outbreaks), ciguatoxin and fish (172 outbreaks), Salmonella and poultry (145 outbreaks), and norovirus and leafy vegetables (141 outbreaks). The pathogen-commodity pairs most commonly responsible for outbreak-related illnesses were norovirus and leafy vegetables (4,011 illnesses), Clostridium perfringens and poultry (3,452 illnesses), Salmonella and vine-stalk vegetables (3,216 illnesses), and Clostridium perfringens and beef (2,963 illnesses). Compared with the first 2 years of the study (1998-1999), the percentage of outbreaks associated with leafy vegetables and dairy increased substantially during 2006-2008, while the percentage of outbreaks associated with eggs decreased. INTERPRETATION: Outbreak reporting rates and implicated foods varied by state and year, respectively; analysis of surveillance data for this 11-year period provides important information regarding changes in sources of illness over time. A substantial percentage of foodborne disease outbreaks were associated with poultry, fish, and beef, whereas many outbreak-related illnesses were associated with poultry, leafy vegetables, beef, and fruits/nuts. The percentage of outbreaks associated with leafy vegetables and dairy increased during the surveillance period, while the percentage associated with eggs decreased. PUBLIC HEALTH ACTIONS: Outbreak surveillance data highlight the etiologic agents, foods, and settings involved most often in foodborne disease outbreaks and can help to identify food commodities and preparation settings in which interventions might be most effective. Analysis of data collected over several years of surveillance provides a means to assess changes in the food commodities associated most frequently with outbreaks that might occur following improvements in food safety or changes in consumption patterns or food preparation practices. Prevention of foodborne disease depends on targeted interventions at appropriate points from food production to food preparation. Efforts to reduce foodborne illness should focus on the pathogens and food commodities causing the most outbreaks and outbreak-associated illnesses, including beef, poultry, fish, and produce.

Emergence of salsa and guacamole as frequent vehicles of foodborne disease outbreaks in the United States, 1973-2008.

Fresh salsa and guacamole often contain diced raw produce, are often made in large batches, and are often poorly refrigerated, which may make them prone to contamination that can cause foodborne illness. The safety of salsa and guacamole is increasingly important as these foods gain popularity. Since 1973, local, state, and territorial health departments have voluntarily reported foodborne disease outbreaks to the Centers for Disease Control and Prevention's Foodborne Disease Outbreak Surveillance System (FDOSS) using a standard reporting form. FDOSS used paper-based reporting for 1973-1997 and switched to electronic reporting for 1998-2008. We reviewed all reports of outbreaks during 1973-2008 in which salsa or guacamole was reported as a vehicle. We found 136 outbreaks in which salsa or guacamole was reported as a possible vehicle, which resulted in 5,658 illnesses. Of these 136 salsa- or guacamole-associated (SGA) outbreaks additional possible food vehicles were reported for 33 (24%) outbreaks. There were no SGA outbreaks reported before 1984. Among reported outbreaks, most were caused by norovirus (24%), nontyphoidal Salmonella (19%), and Shigella (7%). Eighty-four percent of outbreaks were caused by foods prepared in restaurants or delis; of these, 19% reported ill foodworkers, and 29% reported improper storage as possible contributing factors. Among all foodborne disease outbreaks with a reported food vehicle during 1984-1997, 26 (0.9%) of 2,966 outbreaks were SGA, and during 1998-2008, 110 (1.4%) of 7,738 outbreaks were SGA. The number of reported foodborne disease outbreaks attributable to salsa or guacamole increased in the United States from 1984 to 2008, especially in later years, and especially in restaurants. Fresh salsa and guacamole require careful preparation and storage. Focused prevention strategies should reduce the risk of illness and ensure that these foods are enjoyed safely.

Trends in health worker performance after implementing the Integrated Management of Childhood Illness strategy in Benin.

OBJECTIVE: Training health workers to use Integrated Management of Childhood Illness (IMCI) guidelines can improve care for ill children in outpatient settings in developing countries. However, even after IMCI training, important performance gaps exist. One potential reason is that the effect of training can rapidly wane. Our aim was to determine if the performance of IMCI-trained health workers deteriorated over 3 years. METHODS: We studied two departments in Benin. First, we performed a record review of 32 IMCI-trained health workers during the first year of IMCI implementation (2001-2002). Second, we analysed data from cross-sectional health facility surveys from 2001 to 2004 that represented the entire study area. Primary outcomes were the proportion of children under 5 years old with potentially life-threatening illnesses who received either recommended or adequate treatment, and among all children, an index of overall guideline adherence. Secondary outcomes reflected the treatment of individual diseases. Outcomes were calculated monthly, and time trends were evaluated with regression modelling. RESULTS: The record review included 9393 consultations, and the surveys included 411 consultations performed by 105 health workers. For both data sources, performance trends were essentially flat for nearly all outcomes. Absolute levels of performance revealed substantial performance gaps. CONCLUSIONS: We found no evidence that performance declined over 3 years after IMCI training. However, important performance gaps found immediately after IMCI training persisted and should be addressed.

National outbreak of Salmonella serotype saintpaul infections: importance of Texas restaurant investigations in implicating jalapeño peppers.

BACKGROUND: In May 2008, PulseNet detected a multistate outbreak of Salmonella enterica serotype Saintpaul infections. Initial investigations identified an epidemiologic association between illness and consumption of raw tomatoes, yet cases continued. In mid-June, we investigated two clusters of outbreak strain infections in Texas among patrons of Restaurant A and two establishments of Restaurant Chain B to determine the outbreak's source. METHODOLOGY/PRINCIPAL FINDINGS: We conducted independent case-control studies of Restaurant A and B patrons. Patients were matched to well controls by meal date. We conducted restaurant environmental investigations and traced the origin of implicated products. Forty-seven case-patients and 40 controls were enrolled in the Restaurant A study. Thirty case-patients and 31 controls were enrolled in the Restaurant Chain B study. In both studies, illness was independently associated with only one menu item, fresh salsa (Restaurant A: matched odds ratio [mOR], 37; 95% confidence interval [CI], 7.2-386; Restaurant B: mOR, 13; 95% CI 1.3-infinity). The only ingredient in common between the two salsas was raw jalapeño peppers. Cultures of jalapeño peppers collected from an importer that supplied Restaurant Chain B and serrano peppers and irrigation water from a Mexican farm that supplied that importer with jalapeño and serrano peppers grew the outbreak strain. CONCLUSIONS/SIGNIFICANCE: Jalapeño peppers, contaminated before arrival at the restaurants and served in uncooked fresh salsas, were the source of these infections. Our investigations, critical in understanding the broader multistate outbreak, exemplify an effective approach to investigating large foodborne outbreaks. Additional measures are needed to reduce produce contamination.

Anti-folate drug resistance in Africa: meta-analysis of reported dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutant genotype frequencies in African Plasmodium falciparum parasite populations.

BACKGROUND: Mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes of Plasmodium falciparum are associated with resistance to anti-folate drugs, most notably sulphadoxine-pyrimethamine (SP). Molecular studies document the prevalence of these mutations in parasite populations across the African continent. However, there is no systematic review examining the collective epidemiological significance of these studies. This meta-analysis attempts to: 1) summarize genotype frequency data that are critical for molecular surveillance of anti-folate resistance and 2) identify the specific challenges facing the development of future molecular databases. METHODS: This review consists of 220 studies published prior to 2009 that report the frequency of select dhfr and dhps mutations in 31 African countries. Maps were created to summarize the location and prevalence of the highly resistant dhfr triple mutant (N51I, C59R, S108N) genotype and dhps double mutant (A437G and K540E) genotype in Africa. A hierarchical mixed effects logistic regression was used to examine the influence of various factors on reported mutant genotype frequency. These factors include: year and location of study, age and clinical status of sampled population, and reporting conventions for mixed genotype data. RESULTS: A database consisting of dhfr and dhps mutant genotype frequencies from all African studies that met selection criteria was created for this analysis. The map illustrates particularly high prevalence of both the dhfr triple and dhps double mutant genotypes along the Kenya-Tanzania border and Malawi. The regression model shows a statistically significant increase in the prevalence of both the dhfr triple and dhps double mutant genotypes in Africa. CONCLUSION: Increasing prevalence of the dhfr triple mutant and dhps double mutant genotypes in Africa are consistent with the loss of efficacy of SP for treatment of clinical malaria in most parts of this continent. Continued assessment of the effectiveness of SP for the treatment of clinical malaria and intermittent preventive treatment in pregnancy is needed. The creation of a centralized resistance data network, such as the one proposed by the WorldWide Antimalarial Resistance Network (WWARN), will become a valuable resource for planning timely actions to combat drug resistant malaria.