Effect of emergency FMD vaccine antigen payload on protection, sub-clinical infection and persistence following direct contact challenge of cattle.

Previous work, in sheep vaccinated with emergency foot-and-mouth disease (FMD) vaccine, indicated the benefit of increasing the antigen payload in inhibiting local virus replication and consequently persistence following an indirect aerosol challenge with a virus homologous to the vaccine strain. The work presented here investigates this possibility further using cattle and a more severe semi-heterologous direct contact challenge. The quantitative dynamics of virus replication and excretion in both vaccinated and non-vaccinated cattle following challenge are examined. Two experiments were carried out each involving 20 vaccinated and 5 non-vaccinated cattle. An O(1) Manisa vaccine (18 PD(50)) was used for the first, previously reported experiment [Cox SJ, Voyce C, Parida S, Reid SM, Hamblin PA, Paton DJ, et al. Protection against direct contact challenge following emergency FMD vaccination of cattle and the effect on virus excretion from the oropharynx. Vaccine 2005;23:1106-13]. The same vaccine was used for the second experiment described in this paper except the antigen payload was increased 10-fold per bovine dose, resulting in significantly higher FMD virus neutralising antibody titres prior to challenge. Twenty-one days post-vaccination the cattle received a 5-day direct contact challenge with FMD virus from five further non-vaccinated cattle infected 24h earlier with O UKG 34/2001. All vaccinated cattle regardless of antigen payload were protected against clinical disease. Sub-clinical oropharyngeal infection was detected in animals from both experiments but the level of virus replication shortly after direct contact challenge was significantly reduced in vaccinated animals. Cattle immunised with the 10-fold antigen payload cleared the virus more readily and consequently at 28 days post-challenge fewer animals were persistently infected compared to the single strength vaccine. Following a severe challenge, the results from both experiments show that use of emergency vaccine can prevent or decrease local virus replication and thereby dramatically reduce the amount of virus released into the environment, particularly during the early post-exposure period. Additionally, increasing the antigen payload of the vaccine may reduce sub-clinical infection, leading to fewer persistently infected virus carrier animals.

Protection against direct-contact challenge following emergency FMD vaccination of cattle and the effect on virus excretion from the oropharynx.

The ability of emergency foot-and-mouth disease (FMD) vaccine to protect cattle from a heterologous direct-contact challenge and the effect on virus excretion from the oropharynx were examined. An oil adjuvant O1 Manisa FMD vaccine protected 20 cattle from clinical disease following 5 days of direct-contact exposure to five infected cattle at 21 days post vaccination. The donor cattle had been infected by tongue inoculation with a different FMD virus of the same serotype (O UKG 2001). Protection from clinical disease did not prevent localised sub-clinical infection at the oropharynx in most animals, although quantitative reverse transcriptase polymerase chain reaction (RT-PCR) showed that the level of virus replication shortly after direct-contact challenge was greatly reduced in vaccinated animals. Nevertheless, 45% of the vaccinated cattle became persistently infected with 10(3)-10(6) RNA copies per millilitre of oropharyngeal fluid at 28 days post challenge. However, since live virus could not be readily isolated, the risk of these animals transmitting disease was probably very low. The findings show that even after an extremely severe challenge, use of an emergency vaccine will prevent or reduce local virus replication and thereby dramatically reduce the amount of virus released into the environment in the all-important early post-exposure period. These data should help to model the dynamics of virus transmission in future outbreaks of disease where vaccination is considered.

Evidence that high potency foot-and-mouth disease vaccine inhibits local virus replication and prevents the "carrier" state in sheep.

The ability of a single administration of a high, medium and low potency foot-and-mouth disease (FMD) vaccine to decrease or inhibit local virus replication and excretion in the oropharynx of sheep following aerosol challenge with homologous live virus 14 days later was examined. Unvaccinated sheep showed signs of clinical FMD, whereas all of the vaccinated sheep, regardless of antigen payload, were protected against clinical disease and development of viraemia. Virological and serological results confirmed that there had been no local virus replication in the oropharynx of sheep from the high potency vaccine group in contrast to moderate or substantial virus replication in the oropharynx of the low potency vaccinated or unvaccinated sheep respectively. The vaccines showed no evidence of promoting a local mucosal antibody response at the time of virus challenge, but were capable of stimulating a systemic gamma interferon response, the level of which was related to the antigen payload. This suggests that the systemic gamma interferon response could be a useful indicator of the ability of a FMD vaccine to elicit a sterile immunity and indicates that further work is warranted to investigate the role of systemic gamma interferon in this immunity. This is the first experiment to clearly show that high potency, high payload, FMD vaccines are capable of inhibiting local virus replication and consequently persistence and the carrier state in this target species.

No safe haven. II: The effects of violence exposure on urban youth.

OBJECTIVES: To examine the moderating effects of gender, grade level, and ethnicity on the associations between violence exposure and adolescents' internalizing symptoms and externalizing behavior and to explore whether such relationships persist over time. METHOD: A survey of adolescents' exposure to violence, internalizing symptoms, and externalizing behavior was administered to 2 cross-sectional samples of 6th, 8th, and 10th graders (N = 2,748 in 1994 and 2,600 in 1996) in an urban school system. Approximately 1,100 adolescents participated in both surveys and served as the longitudinal sample. RESULTS: Structural equation models indicated that violence exposure was closely associated with both externalizing behavior (r = 0.74-0.79) and internalizing symptoms (r = 0.36-0.38). The strength of association was similar across gender and ethnic groups. However, violence exposure was more closely related with internalizing symptoms for younger adolescents than their older counterparts. The longitudinal analysis suggested that exposure to violence reported at time 1 was related to adolescents' internalizing symptoms and externalizing behavior 2 years later. CONCLUSIONS: These results document high levels of violence exposure for urban youths and indicate links to a range of psychiatric symptoms and indicators of poor adjustment. Such findings carry implications for direct clinical work with young people, as well as for program development and public policy.

High-risk sexual behavior among young urban students.

A substantial number of adolescents, including many as young as 11, engage in high-risk sexual behavior. In a 1992 survey of 2,248 urban students in grades 6, 8 and 10, 45% of respondents, including 28% of sixth graders, were sexually active; the majority of sexually experienced students had had two or more partners. Among sexually active respondents, however, the level of condom use at last intercourse was higher than expected (71%). Results of multivariate analyses indicate that students in grades 8 and 10 were significantly more likely than sixth graders to be sexually experienced; males, blacks and socioeconomically disadvantaged students were significantly more likely than their female, white and better-off counterparts to be sexually active. The effects of gender and race interacted in some cases, and race and socioeconomic status had significant independent effects on rates of sexual intercourse. While males and black students reported high levels of sexual activity, they also were more likely than young women and Hispanics to have used condoms at last intercourse.

No safe haven: a study of violence exposure in an urban community.

OBJECTIVE: To examine levels of violence exposure and reports of feeling unsafe in relation to psychological and behavioral characteristics for a general population sample of youths from an urban setting. METHOD: A comprehensive survey of high-risk behaviors, attitudes, indicators of adaptive behavior, and daily involvements was administered to a sample of 2,248 students in the 6th, 8th, and 10th grades in an urban public school system. RESULTS: More than 40% of the youths surveyed reported exposure to a shooting or stabbing in the past year, and 74% reported feeling unsafe in one or more common environmental contexts. Multiple regression analyses indicated significant relationships between violence exposure/feeling unsafe and a set of indicators of psychological and behavioral adaptation and expressed attitudes. CONCLUSIONS: These results attest to the picture of violence as a common fact of inner-city life and to the demand that is placed on urban youths to accommodate in their psychological development to chronic threat and lack of safety.

Involvement in multiple problem behaviors of young urban adolescents.

This paper examines four areas of "problem behavior" (i.e., delinquency, high-risk sexual behavior, school failure, and substance abuse) in a sample of urban sixth and seventh grade students. We report descriptive statistics regarding rates of problem behaviors in each of the four categories and examine their interrelationships. The results suggest that the prevalence of problem behaviors in this sample is substantial. Data show a high degree of co-occurrence among problem behaviors in different areas, although many individuals also exhibit more limited involvement. These results underscore the importance of studying younger adolescents in poor, urban communities who may have different patterns and rates of problem behavior involvement than older youth from other contexts. The data also suggest that efforts to prevent high-risk involvements for youth in poor, urban communities should be broad-ranging and be implemented prior to middle school.

Development and validation of the Parent Health Locus of Control scales.

We describe the development and validation of the Parent Health Locus of Control (PHLOC) scales. Using factor analytic and item analytic methods, 30 items comprising six scales were extracted from a pool of 84 items. The individual scales correspond to beliefs in Child, Divine, Fate, Media, Parental, and Professional Influence over child health. Results were compared for six samples totalling 822 parents. Internal consistency reliabilities were above .70 for all scales with all samples. Test-retest correlations based on a separate sample were all above .60. Validity was assessed by means of a known groups strategy that made use of presumed differences among the six samples studied. The results generally agreed with predicted differences, offering good initial evidence of the validity for the PHLOC scales.