Identification of Biological Hazards in Produce Consumed in Industrialized Countries: A Review.

Microbial contamination of fresh produce (fresh fruits and vegetables) poses serious public health concerns worldwide. This study was conducted as a comprehensive analysis of biological hazards in the global fresh produce chain. Data about produce-related outbreaks and illness were collected from the annual reports and databases of foodborne outbreak surveillance systems in different regions and countries from 2010 to 2015. The global patterns of and regional differences in documented outbreaks and cases were analyzed, and produce commodities and pathogens of greatest concern were identified. Data on sporadic illnesses were also collected through a comprehensive literature review of case-control studies. We found 988 produce-related outbreaks (with known agents) and 45,723 cases in all regions and countries. The numbers of produce-related outbreaks per million person-years were approximately 0.76, 0.26, 0.25, 0.13, 0.12, and 0.05 in New Zealand, Australia, the United States, the European Union, Canada, and Japan, respectively. The top three food categories and pathogens contributing to produce-related outbreaks were vegetables and nonfruits (i.e., food other than fruits; 27.0%), unspecified vegetables (12.2%), and vegetable row crops (11.7%) and norovirus (42.4%), Salmonella enterica (19.9%), and Staphylococcus aureus (7.9%), respectively. Produce consumption was identified as a protective factor, a risk factor, and either a protective or risk factor for sporadic illnesses in 11, 5, and 5 studies, respectively, among 21 case-control studies. Risks associated with produce consumption in the United States and the European Union have been linked to various factors such as irrigation water, cross-contamination, storage time and temperature abuse, infected food handlers, and unprocessed contaminated ingredients. The results of the current study indicate the complexity of produce products consumed across the globe and the difficulty in tracing illnesses back to specific food ingredients.

Insulin glargine and its two active metabolites: A sensitive (16pM) and robust simultaneous hybrid assay coupling immunoaffinity purification with LC-MS/MS to support biosimilar clinical studies.

MK-1293 is a newly approved follow-on/biosimilar insulin glargine for the treatment of Type 1 and Type 2 diabetics. To support pivotal clinical studies during biosimilar evaluation, a sensitive, specific and robust liquid chromatography and tandem mass spectrometry (LC-MS/MS) assay for the simultaneous quantification of glargine and its two active metabolites, M1 and M2 were developed. Strategies to overcome analytical challenges, so as to optimize assay sensitivity and improve ruggedness, were evolved, resulting in a fully validated LC-MS/MS method with a lower limit of quantification (LLOQ) at 0.1ng/mL (∼16pM, equivalent to ∼2.8µU/mL) for glargine, M1 and M2, respectively, using 0.5mL of human plasma. The assay employed hybrid methodology that combined immunoaffinity purification and reversed-phase chromatography followed by electrospray-MS/MS detection operated under positive ionization mode. Stable-isotope labeled 6[D10]Leu-glargine and 4[D10]Leu-M1 were used as internal standards. With a calibration range from 0.1 to 10ng/mL, the intra-run precision (n=5) and accuracy were <6.21%, and 96.9-102.1%, while the inter-run (n=5/run for 7days) precision and accuracy were <9.55% and 96.5-105.1%, respectively, for all 3 analytes. Matrix effect, recovery, analyte stability, and interferences from control matrix, potential concomitant medications and anti-drug antibody were assessed. The assay was fully automated and has been successfully used in support of biosimilar clinical studies. Greater than 94.3% of incurred sample reanalysis (ISR) results met acceptance criteria, demonstrating the robustness of the assay. The strategic considerations during method development and validation are discussed, and can be applied to quantification of other peptides, especially insulin analogs, in the future.

Largest measles epidemic in North America in a decade--Quebec, Canada, 2011: contribution of susceptibility, serendipity, and superspreading events.

BACKGROUND: The largest measles epidemic in North America in the last decade, occurred in 2011 in Quebec, Canada, where rates of 1- and 2-dose vaccine coverage among children 3 years of age were 95%-97% and 90%, respectively, with 3%-5% unvaccinated. METHODS: Case patients identified through passive surveillance and outbreak investigation were contacted to determine clinical course, vaccination status, and possible source of infection. RESULTS: There were 21 measles importations and 725 cases. A superspreading event triggered by 1 importation resulted in sustained transmission and 678 cases. The overall incidence was 9.1 per 100,000; the highest incidence was in adolescents 12-17 years old (75.6 per 100,000), who comprised 56% of case patients. Among adolescents, 22% had received 2 vaccine doses. Outbreak investigation showed this proportion to have been an underestimate; active case finding identified 130% more cases among 2-dose recipients. Two-dose recipients had milder illness and a significantly lower risk of hospitalization than those who were unvaccinated or single-dose recipients. CONCLUSIONS: A chance superspreading event revealed an overall level of immunity barely above the elimination threshold when unexpected vulnerability in 2-dose recipients was taken into account. Unvaccinated individuals remain the immunization priority, but a better understanding of susceptibility in 2-dose recipients is needed to define effective interventions if elimination is to be achieved.