Population-based estimates of acute gastrointestinal and foodborne illness in Barbados: a retrospective cross-sectional study.

The aim of this study was to determine the burden and impact of acute gastroenteritis (AGE) and foodborne diseases (FBDs) in Barbados through a retrospective, cross-sectional population survey and laboratory study in August 2010-August 2011. Face-to-face interviews were conducted with one person from each of 1,710 randomly-selected households. Of these, 1,433 (84%) interviews were completed. A total of 70 respondents reported having experienced AGE in the 28 days prior to the interview, representing a prevalence of 4.9% and an annual incidence rate of 0.652 episodes per person-year. Age (p = 0.01132), season (p = 0.00343), and income (p < 0.005) were statistically associated with the occurrence of AGE in the population. Norovirus was the leading foodborne pathogen causing AGE-related illness. An estimated 44,270 cases of AGE were found to occur during the period of the study and, for every case of AGE detected by surveillance, an additional 204 cases occurred in the community. Economic costs of AGE ranged from BD$ 9.5 million to 16.5 million (US$ 4.25-8.25) annually. This study demonstrated that the public-health burden and impact of AGE and FBD in Barbados were high and provided the necessary baseline information to guide targeted interventions.

Response to the challenges of pandemic H1N1 in a small island state: the Barbadian experience.

BACKGROUND: Having been overwhelmed by the complexity of the response needed for the severe acute respiratory syndrome (SARS) epidemic, public health professionals in the small island state of Barbados put various measures in place to improve its response in the event of a pandemic METHODS: Data for this study was collected using Barbados' National Influenza Surveillance System, which was revitalized in 2007. It is comprised of ten sentinel sites which send weekly notifications of acute respiratory illness (ARI) and severe acute respiratory illness (SARI) to the Office of the National Epidemiologist. During the 2009 H1N1 pandemic, meetings of the National Pandemic Planning Committee and the Technical Command Committee were convened. The pharmaceutical and non-pharmaceutical interventions (NPIs) implemented as a result of these meetings form the basis of the results presented in this paper. RESULTS: On June 3, 2009, Barbados reported its first case of 2009 H1N1. From June until October 2009, there were 155 laboratory confirmed cases of 2009 H1N1, with one additional case occurring in January 2010. For the outbreak period (June-October 2009), the surveillance team received reports of 2,483 ARI cases, compared to 412 cases for the same period in 2008. The total hospitalization rate due to SARIs for the year 2009 was 90.1 per 100,000 people, as compared to 7.3 per 100,000 people for 2008. Barbados' pandemic response was characterized by a strong surveillance system combining active and passive surveillance, good risk communication strategy, a strengthened public and private sector partnership, and effective regional and international collaborations. Community restriction strategies such as school and workplace closures and cancellation of group events were not utilized as public health measures to delay the spread of the virus. Some health care facilities struggled with providing adequate isolation facilities. CONCLUSIONS: The number of confirmed cases was small but the significant surge in ARI and SARI cases indicate that the impact of the virus on the island was moderate. As a result of 2009 H1N1, virological surveillance has improved significantly and local, regional and international partnerships have been strengthened.

Protein aggregation during overexpression limited by peptide extensions with large net negative charge.

Folding of the human coxsackie and adenovirus receptor immunoglobulin (Ig) variable-type domain (CAR D1) during overexpression in the Escherichia coli cytoplasm was shown previously to be partially rescued by fusion to a 22-residue C-terminal peptide. Here, peptide sequence features required for solubilization and folding of CAR D1 and similar Ig variable-type domains from two other human membrane proteins were investigated. Peptide extensions with net negative charge > -6 fully solubilized CAR D1, and approximately half of the peptide-solubilized protein was correctly folded. The Ig variable-type domains from human A33 antigen and myelin P-zero proteins were only partially solubilized by peptide extensions with net charge of -12, however, and only the solubilized P-zero domain appeared to fold correctly whereas the A33 domain formed soluble microaggregates of misfolded protein. Our results suggest a model where the large net charge of peptide extensions increases electrostatic repulsion between nascent polypeptides. The resulting decrease in aggregation rate can enable some polypeptides to fold spontaneously into their native protein conformations. Analysis of the solubility and folding status of sets of structurally homologous proteins, such as the Ig variable-type domains described here, during overexpression could provide insights into how amino acid and gene sequences influence the efficiency of spontaneous protein folding.

Biodistribution of radioiodinated adenovirus fiber protein knob domain after intravenous injection in mice.

The knob domains from the fiber proteins of adenovirus serotypes 2 and 12 were labeled with radioiodine and then injected into the bloodstreams of mice. Knob proteins with functional binding sites for the coxsackie and adenovirus receptor (CAR) were cleared rapidly from the circulation, with radioactivity appearing predominantly in the stomach, while knob mutants unable to bind to CAR remained in the blood circulation for a prolonged period. The clearance of radiolabeled wild-type knob from the blood was slowed by coinjecting an excess of unlabeled wild-type knob protein. An earlier study showed that (99m)Tc-labeled knob protein with intact CAR-binding activity also cleared rapidly from the blood circulation of mice, with radioactivity accumulating predominantly in the liver (K. R. Zinn et al., Gene Ther. 5:798-808, 1998). Together these results suggest that rapid clearance of knob protein from the blood results from specific binding to CAR in the liver and that the bound knob then enters a degradative pathway. The elevated levels of radioiodine in the stomach observed in our experiments are consistent with deiodination of labeled knob by dehalogenases in hepatocyte microsomes and uptake of the resultant free radioiodine by Na/I symporters in the gastric mucosa. Although CAR has been shown to localize in tight junctions of polarized epithelial cells, where it functions in intercellular adhesion, the results of our study suggest that a subset of CAR molecules in the liver is highly accessible to ligands in the blood and able to rapidly deliver bound ligand to an intracellular degradative compartment.

Hantavirus pulmonary syndrome-associated hantaviruses contain conserved and functional ITAM signaling elements.

Hantaviruses infect human endothelial and immune cells, causing two human diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). We have identified key signaling elements termed immunoreceptor tyrosine-based activation motifs (ITAMs) within the G1 cytoplasmic tail of all HPS-causing hantaviruses. ITAMs direct receptor signaling within immune and endothelial cells and the presence of ITAMs in all HPS-causing hantaviruses provides a means for altering normal cellular responses which maintain vascular integrity. The NY-1 G1 ITAM was shown to coprecipitate a complex of phosphoproteins from cells, and the G1 ITAM is a substrate for the Src family kinase Fyn. The hantavirus ITAM coprecipitated Lyn, Syk, and ZAP-70 kinases from T or B cells, while mutagenesis of the ITAM abolished these interactions. In addition, G1 ITAM tyrosines directed intracellular interactions with Syk by mammalian two-hybrid analysis. These findings demonstrate that G1 ITAMs bind key cellular kinases that regulate immune and endothelial cell functions. There is currently no means for establishing the role of the G1 ITAM in hantavirus pathogenesis. However, the conservation of G1 ITAMs in all HPS-causing hantaviruses and the role of these signaling elements in immune and endothelial cells suggest that functional G1 ITAMs are likely to dysregulate normal immune and endothelial cell responses and contribute to hantavirus pathogenesis.