Business-centric data solutions for safeguarding animal agriculture in the United States of America.

Business-centric solutions to data-related problems often yield the greatest positive impacts and improvements for private enterprises but are challenging to design and implement at scale within government agencies. The core mission of the Veterinary Services of the United States Department of Agriculture (USDA) Animal Plant Health Inspection Service is to safeguard animal agriculture in the United States of America, and effective data management underpins these efforts. As this agency works to assist data-driven decision-making in animal health management, it continues to use a blend of best practices from Federal Data Strategy initiatives and the International Data Management Association framework. This paper describes three case studies that focus on strategies to improve animal health data collection, integration, reporting and governance for animal health authorities. These strategies have enhanced the way USDA's Veterinary Services execute their mission and core operational activities for prevention, detection and early response to support disease containment and control.

S'agissant des problèmes en lien avec les données, les solutions centrées sur l'activité sont souvent celles qui génèrent le plus d'effets positifs et d'améliorations pour les entreprises du secteur privé, mais elles sont difficiles à concevoir et à mettre en oeuvre à grande échelle au sein des agences gouvernementales. Les Services vétérinaires du Service d'inspection de la santé animale et végétale du département américain de l'Agriculture (USDA) ont pour mission centrale de préserver les productions animales états-uniennes ; une gestion efficace des données vient soutenir cet effort. Dans leur action d'appui aux processus décisionnels de gestion de la santé animale fondés sur les données, ces Services recourent à une combinaison de bonnes pratiques mises en oeuvre aussi bien par les initiatives de la Stratégie fédérale sur les données que dans le cadre de l'Association internationale de gestion des données. Les auteurs décrivent trois études de cas sur des stratégies visant à améliorer la collecte, l'intégration, la notification et la gouvernance des données de santé animale afin de répondre aux besoins des autorités compétentes dans ce domaine. Ces stratégies ont permis aux Services vétérinaires de l'USDA de mieux s'acquitter de leur mission et d'améliorer leurs activités opérationnelles de prévention, de détection et de réaction rapide afin d'endiguer et contrôler les maladies.

Las soluciones eminentemente empresariales a problemas relacionados con los datos deparan con frecuencia los mejores frutos y resultados a la empresa privada, pero son difíciles de diseñar y aplicar a escala dentro de las administraciones públicas. Los Servicios Veterinarios adscritos al Servicio de Inspección Sanitaria de Animales y Plantas del Departamento de Agricultura de los Estados Unidos (USDA) tienen por principal cometido salvaguardar la producción animal estadounidense, labor que pasa en parte por una eficaz gestión de los datos. En su función de apoyo a la adopción de decisiones de gestión zoosanitaria basadas en los datos, este organismo sigue empleando una combinación de prácticas óptimas tomadas de iniciativas de la Estrategia Federal de Datos y de las pautas marcadas por la Asociación Internacional de Gestión de Datos. Los autores presentan y analizan tres ejemplos de estrategias para mejorar la obtención, integración, notificación y administración de datos zoosanitarios para las autoridades del ramo. Estas estrategias han conferido mayor eficacia a los Servicios Veterinarios del USDA en el cumplimiento de su misión y en la ejecución de sus principales actividades operativas de prevención, detección y pronta respuesta para ayudar a contener y combatir enfermedades.

Human papillomavirus antigens and T-cell recognition.

This review will summarize what is known about natural T-cell responses to human papillomavirus infections, including potential mechanisms for their dysregulation which may lead to the development of disease. We will also describe new strategies to enhance human papillomavirus specific T-cell responses following vaccination that are currently in development and recent reports on human vaccine trials with particular regard to the generation of appropriate T-cell responses.

HPV16 E6 oncogene variants in women with cervical intraepithelial neoplasia.

Human papillomaviruses (HPVs) are strongly associated with the development of high grade cervical intraepithelial neoplasia (CIN) and cervical carcinoma, with between 40-80% of patients with cervical carcinoma being attributed to a single HPV type, HPV16 depending on the methods used and geographical location of the particular study [van den Brule et al., 1996]. An HPV16 E6 variant has been described which is strongly associated with high grade CIN [Ellis et al., 1997] and with the human leukocyte antigen (HLA)-B7 genotype in women with cervical carcinoma where HLA-B7 positive patients were demonstrated to have a significantly poorer clinical outcome [Ellis et al., 1995]. To determine whether this HPV16 E6 variant might play a significant role in the pathogenesis of cervical disease, 174 HPV16 positive women were selected from those attending the colposcopy clinics of Guy's and St Thomas' Hospital Trust following polymerase chain reaction (PCR) amplification of HPV16 L1 or E5 DNAs from cervical brush swabs or fixed biopsy tissue. HPV16 E6 DNA was amplified by PCR and the variant sequence was identified by Msp 1 restriction enzyme digestion, as the nucleotide substitution creates an additional unique Msp 1 site. The study group comprised 29 normal controls, 7 women with borderline cytology, 123 women with cervical dysplasia and 12 women with cervical cancer. 101/174 (58%) of these women had amplifiable E6 DNA and restriction enzyme digestion was performed on 95 of these. The variant E6 sequence was identified in 3/95 (3%) individuals, two of whom had normal histology and one had a CIN II lesion. Wild type E6 sequence was identified in the remaining 92/95 (97%) individuals. These data suggest that this particular E6 variant does not play a major role in the pathogenesis of HPV16 related cervical disease in women living in the South London area.

Serological and T-helper cell responses to human papillomavirus type 16 L1 in women with cervical dysplasia or cervical carcinoma and in healthy controls.

In a cross-sectional study we have investigated serological and T-helper (Th) cell responses to human papillomavirus type 16 (HPV-16) L1 in women with HPV-16 related diseases and related them to cervical histology and HPV DNA status. Using a virus-like particle (VLP) based ELISA to detect antibodies to the HPV-16 L1 capsid protein, 45% (33/73) of women with cervical dysplasia, 40% (2/5) of women with cervical cancer, 36% (4/11) of healthy adult female controls and 6% (2/35) of healthy children were found to be seropositive. Amongst women with cervical dysplasia, the highest levels of seropositivity were found in those who were HPV-16 DNA positive (60%, 15/25) or positive for any of the "high-risk' HPV types, 16/18/33 (58%, 18/31), when compared with those with HPV type "X' (25%, 5/20) or with healthy children (6%, 2/35; P < 0.05 for all comparisons). There was a trend for women with cervical dysplasia to show an increased level of seropositivity with increasing grade of lesion. There was no direct correlation found between seropositivity and Th cell responses in all groups studied. However, a combined analysis of each individual's Th and B cell responses suggests that a Th1 pattern of response is predominant amongst healthy adult controls (80% of responders) but reduced in women with cervical dysplasia (55% of responders). A trend towards a decrease in Th1 type responses was also noted with increasing grade of dysplastic lesion. These findings provide further evidence for the importance of the Th response in the control of genital HPV infections.

Proliferative T cell responses to the human papillomavirus type 16 E7 protein in women with cervical dysplasia and cervical carcinoma and in healthy individuals.

The levels of proliferative T cell responses to peptides representing the human papillomavirus type 16 (HPV-16) E7 protein have been measured using short-term T cell lines derived from peripheral blood of healthy women and those with cervical dysplasias and carcinoma of the cervix. In healthy individuals 47 percent (7/15) responded predominantly to the N- and C-terminal regions of the protein and 6/7 responders were to a single peptide between amino acids 80-94. In comparison 29 percent (9/31) of women with cervical dysplasia responded to HPV-16 E7, with a significantly reduced response to both the N- and C-terminal regions (P = 0.03 and 0.038, respectively). A higher proportion of responders was found in patients with high grade lesions (56 percent, 5/9) versus those with atypical or low grade histology (20 percent, 4/20) and the response to a single peptide between amino acids 75-94 was also increased in this patient group (P = 0.044). This may be a reflection of higher levels of current or previous exposure to HPV-16 in patients with high grade lesions. Correlation of T cell responses with HPV DNA type (detected by PCR of cervical biopsy tissue) showed that 3/9 (33 percent) HPV-16 DNA-positive individuals responded. This suggests that E7 may not be the dominant target of the immune response or that the response to E7 is down-regulated in these patients. In addition 4/18 (22 percent) HPV-16 DNA-negative individuals responded, suggesting that their T cells may have been primed by previous exposure to HPV-16 or that a cross-reactive response was detected. Proliferative T cell responses to both HPV-16 E7 and L1 were reduced in women with cervical carcinoma in comparison to those with cervical dysplasia and healthy controls. The observed down-regulation of responses to HPV-16 E7 in women with cervical dysplasia and cervical carcinoma may reflect an altered functional balance between subsets of T helper cells in HPV-16 infections.

Proliferative T cell responses to human papillomavirus type 16 L1 peptides in patients with cervical dysplasia.

Human papillomavirus type 16 (HPV-16) can cause genital warts, cervical dysplasias and carcinoma of the cervix. Cell-mediated immunity is thought to be important in protection against the virus and in its elimination, but little is known about the mechanisms involved. In a cross-sectional study we have demonstrated proliferative T cell responses to peptides representing the HPV-16 L1 capsid protein (aa 199-409) in the peripheral blood of 63% of patients (n = 41) with histological evidence of cervical dysplasia and in 45% of healthy age-matched controls (n = 11). This was achieved by generating short-term T cell lines (STLs) from each individual in vitro against a beta-galactosidase-HPV- 16 L1 (aa 199-409) fusion protein for 2 weeks, and then identifying the HPV epitopes they recognized with overlapping synthetic peptides (15-mers) spanning this region in 3 day specificity assays. Histological grading and HPV typing by PCR were performed on patients' cervical biopsies taken at the same clinical visit as the peripheral blood samples. An immunogenic region was identified between aa 311-345 in 73% of patients (18% in controls) who responded to HPV-16 L1 (aa 199-409). The number of responders to this region was significantly higher in patients with HPV-16-positive biopsies when compared to those with HPV-16-negative biopsies (P = 0.006), as was the number of responders to individual peptides 311-325 (NLASSNYFPTPSGSM; p = 0.04) and 321-335 (PSGSMVTSDAQIFNK; P = 0.004) representing this region. The mean level of response to each individual peptide was also higher in the patient group than the controls (P < 0.05). The most significant finding was that all patients with evidence of a current HPV-16 infection responded to one or more L1 peptides (P = 0.0004) and 92% had high grade cervical intraepithelial neoplasia (CIN III). We also found that the CIN III group was more likely to respond to any L1 peptide than either the atypical group (P = 0.04) or the controls (P = 0.05). Data from four individuals showed that the majority of peptide-specific STLs were CD4+ but some CD8+ STLs were also detected.

Epstein-Barr virus infection of HIV-seropositive individuals is transiently suppressed by high-dose acyclovir treatment.

OBJECTIVE: To assess whether oral acyclovir can eliminate persistent Epstein-Barr virus (EBV) infection and thereby prevent EBV-associated lymphoma development in HIV-seropositive homosexual men. METHOD: Persistent EBV infection was examined in a group of 21 HIV-seropositive homosexual men before, during and after treatment with oral acyclovir at a dose of 800 mg every 6 h (10 individuals) or with a placebo (11 individuals). RESULTS: In 13 individuals, EBV was isolated from the oropharynx before and after treatment (seven cases from the acyclovir-treated group and six from the placebo-treated group). A significant reduction in virus isolation occurred during treatment in the acyclovir-treated group, but not in the placebo-treated group. In seven cases in whom EBV shedding was detected before and after treatment, the EBV strain isolated was identical throughout the study, even when acyclovir had abolished detectable shedding for the duration of the treatment. In two other cases more than one strain was detected. On examination of the EBV type present, 89% of a group of 18 patients consistently shed type A virus, 5.5% type B virus and 5.5% showed evidence of co-infection with both virus types. This compares with figures of 100, 0 and 0%, respectively, in a control group of HIV-seronegative individuals. CONCLUSIONS: High-dose acyclovir therapy does not eliminate persistent EBV infection from the oropharynx of healthy HIV-seropositive individuals and therefore would not necessarily prevent lymphoma development. Our results suggest that infection by type B EBV, and co-infections of both A and B type, are more common in HIV-seropositives than HIV-seronegatives.

Aetiology and pathogenesis of non-Hodgkin lymphoma in AIDS.

The AIDS-NHLs constitute a histologically diverse group of tumours. Comparisons with some groups of non-AID-NHLs, including eBL, sBL and large cell lymphoma, have been made and similar pathogenetic mechanisms postulated for such groups. However, the incidence of the different pathological types of NHL in AIDS is not yet clear, and further work is necessary to determine the contribution of factors such as c-myc translocations and the presence of EBV. AIDS-NHLs are clearly a more diverse group of tumours than their non-AIDS counterparts, and this probably reflects the involvement of a whole range of different pathogenetic stimuli that occur in individual AIDS cases.