Efficacy of a heterologous vaccine and adjuvant in ferrets challenged with influenza virus H5N1.

BACKGROUND: In 1997, highly pathogenic avian influenza (HPAI) viruses caused outbreaks of disease in domestic poultry markets in Hong Kong. The virus has also been detected in infected poultry in Europe and Africa. OBJECTIVE: The objective of this study was to determine the efficacy of a heterologous vaccine administered with and without the aluminum hydroxide adjuvant in ferrets challenged with HPAI (A/Vietnam/1203/04). METHODS: Animals in four of the five groups were vaccinated twice 21 days apart, with two doses of a heterologous monovalent subvirion vaccine with or without an aluminum hydroxide adjuvant and challenged with a lethal target dose of A/Vietnam/1203/04. RESULTS: All animals vaccinated with the heterologous vaccine in combination with the aluminum hydroxide adjuvant survived a lethal challenge of A/Vietnam/1203/04. Four of the eight animals vaccinated with 30 µg of the vaccine without the adjuvant survived, while two of the eight animals vaccinated with 15 µg of the vaccine without the adjuvant survived. None of the unvaccinated control animals survived challenge. Additionally, changes in virus recovered from nasal washes and post-mortem tissues and serology suggest vaccine efficacy. CONCLUSIONS: Altogether, the data suggest that the heterologous vaccine in combination with the aluminum hydroxide adjuvant offers maximum protection against challenge with A/Vietnam/1203/04 when compared to the unvaccinated control animals or animals vaccinated without any adjuvant.

The Northwest's Hot Topics in Preparedness forum: a novel distance-learning collaborative.

The Northwest Center for Public Health Practice at the University of Washington hosts a training forum, called Hot Topics in Preparedness, that is delivered via a synchronous, Web conferencing system. These monthly, 1-hour sessions focus on key topics related to emergency preparedness for public health professionals and their emergency response partners in the Northwest region. This distance learning series was conceived and implemented as a regional collaborative, overseen by an advisory board representing state, local, and tribal health agencies. Results of session evaluations, challenges, and lessons learned from the first year of the Hot Topics in Preparedness forum are reported. Web conferencing is a popular, convenient, and effective strategy for delivering training in the rapidly changing field of preparedness across a large geographic region.

Levofloxacin treatment of active tuberculosis and the risk of adverse events.

BACKGROUND: Fluoroquinolones are commonly used in the treatment of tuberculosis (TB) for drug-sensitive patients who are intolerant to first-line antituberculous agents or who are infected with drug-resistant organisms. Despite increasing use of these agents, there is little information on their tolerance outside of clinical trial settings. OBJECTIVES: To compare overall rate of major adverse events associated with levofloxacin-containing regimen to standard therapy. METHODS: Cases (levofloxacin-containing regimen) were matched by age and sex to their control subjects (standard first-line TB drugs). Eligible patients were identified from the provincial TB database from 2001 to 2004. Drug safety was assessed by evaluation of the nature of the adverse event, the likelihood of association with the study medications, and severity. Only major side effects, that is, those who had a severe or moderate adverse event that was categorized to be definitely, probably, or possibly related to the TB medications, were considered for the analysis. RESULTS: During the 3-year study period, 102 patients received levofloxacin, and 358 patients received first-line agents for treatment of active TB. There were no significant differences between the two groups except for indication (82% of patients in the levofloxacin group had an antecedent adverse event to first-line TB drugs, whereas 18% received levofloxacin because of resistance) and concurrent use of first-line drugs (majority of patients in the levofloxacin arm were not receiving concurrent isoniazid or rifampin). The rate of any major adverse event was almost half among those using levofloxacin as among those on standard therapies (rate ratio, 0.60; 95% confidence interval [CI], 0.44 to 0.82). After adjustment for the differences in exposure of concomitant medications, the rate of any major adverse event was similar between the levofloxacin and control arms (adjusted rate ratio, 0.83; 95% CI, 0.66 to 1.03). Furthermore, there was no difference between the levofloxacin and control arms with respect to CNS (adjusted rate ratio, 0.94; 95% CI, 0.61 to 1.43), GI tract (adjusted rate ratio, 0.81; 95% CI, 0.58 to 1.13), skin (adjusted rate ratio, 0.65; 95% CI, 0.38 to 1.10), or musculoskeletal (MSK) [adjusted rate ratio, 0.87; 95% CI, 0.48 to 1.60] related adverse events when adjusted for concomitant drugs. The results of the secondary analysis for the rate of major adverse events within the first 100 days were similar to the primary analysis. The time to the first major adverse event was similar between the levofloxacin group and the control group (adjusted hazards ratio, 1.01; 95% CI, 0.76 to 1.34). CONCLUSIONS: Concomitant use of a levofloxacin-containing regimen resulted in a similar rate of adverse events compared with conventional first-line regimens when used for treatment of active TB, despite a history of adverse events.