Epidemiology of Pathogens Listed as Potential Bioterrorism Agents, the Netherlands, 2009‒2019.

We provide incidences (cases/10 million persons) in the Netherlands during 2009-2019 for pathogens listed as potential bioterrorism agents. We included pathogens from the highest categories of the European Medicines Agency or the US Centers for Disease Control and Prevention. Notifiable diseases and recently published data were used to calculate the average annual incidence. Coxiella burnetii had the highest incidence because of a Q fever epidemic during 2007-2010. Incidence then decreased to 10.8 cases/. Pathogens with an incidence >1 were Brucella spp. (2.5 cases), Francisella tularensis (1.3 cases), and Burkholderia pseudomallei (1.1 cases). Pathogens with an incidence <1 were hemorrhagic fever viruses (0.3 cases), Clostridium botulinum (0.2 cases), and Bacillus anthracis (0.1 cases). Variola major and Yersinia pestis were absent. The generally low incidences make it unlikely that ill-meaning persons can isolate these pathogens from natural sources in the Netherlands. However, the pathogens are stored in laboratories, underscoring the need for biosecurity measures.

Oral fluid: Non-invasive alternative for parvovirus B19 diagnosis?

BACKGROUND: Infections with parvovirus B19 (B19V) have been associated with a wide range of disease manifestations of which erythema infectiosum (fifth disease) in children is most common. Clinical signs following infection of children with B19V can be similar to measles and rubella. Laboratory detection of B19V infections is based on detection of B19V-specific IgM antibodies by enzyme immunoassay (IgM-EIA) and/or B19V DNA by quantitative PCR (qPCR) on blood samples. The need for invasive sampling can be a barrier for public health diagnostics. OBJECTIVES: To evaluate the use of a dual target B19V-qPCR directed against the NS1 and VP2 of B19V on oral fluid samples as a non-invasive alternative for laboratory diagnosis of B19V infections in children below 12 years of age with exanthema. STUDY DESIGN: Oral fluid and serum samples were collected from 116 children with exanthema. All serum samples were tested by IgM-EIA/IgG-EIA, while all oral fluid and 56 serum samples were tested by B19V-qPCR. RESULTS: B19V-specific IgM antibodies were detected in 25 of 116 children in the study. B19V DNA was detected in oral fluid in 17 of the 25 children who were IgM positive, as well as two children who were IgM-equivocal or negative. The child with the equivocal IgM had a high quantity of B19V DNA in oral fluid (7 log IU/ml), compatible with an acute B19V infection. The IgM-negative child was IgG-positive and 4 log IU/ml B19V DNA was detected in the oral fluid sample, suggesting an acute infection and a falsely negative IgM. Sample size calculations indicated that oral fluid samples for qPCR should be collected from 2 to 3 children during outbreaks of exanthema to achieve similar sensitivity as IgM-EIA for one child (≥0.9) to confirm or exclude B19V. CONCLUSIONS: Results indicate that oral fluid samples are a suitable public health alternative for detection of B19V infections, potentially lowering the barriers for sampling.

Characteristics of orphan drug applications that fail to achieve marketing approval in the USA.

The US Orphan Drug Act has fostered the development of drugs for patients with rare diseases by granting 'orphan designations', although several orphan drugs for which a marketing application has been submitted to the FDA have failed to obtain approval. This study identified the clinical trial design, the level of experience of the sponsor and the level of interaction with the FDA to be associated with non-approval. Sponsors, therefore, should engage in dialogue with the FDA and thoughtfully design pivotal clinical trials in accordance with FDA guidance documents.

Annual influenza vaccination in community-dwelling elderly individuals and the risk of lower respiratory tract infections or pneumonia.

BACKGROUND: Influenza vaccination has been associated with a reduction in the number of hospitalizations for respiratory conditions in elderly persons over the period from 1996 to 2002. Little is known, however, about the effect of influenza vaccination on the whole range of severity of respiratory tract infections. METHODS: We investigated the effect of annual influenza vaccination on the occurrence of lower respiratory tract infections (LRTIs) in community-dwelling elderly individuals. From 1996 to 2002, we performed a population-based cohort study, using the computerized Integrated Primary Care Information database in the Netherlands, of community-dwelling subjects who were 65 years or older on January 1 of the year of study entry. For each year, the individual cumulative exposure to influenza vaccination since study entry was computed. We compared the risk of LRTI after a first vaccination or revaccination with the risk for no vaccination using a time-varying multivariate Cox proportional hazard model, adjusted for age, sex, smoking, and underlying disease. RESULTS: In the study population of 26 071 subjects, 3412 developed LRTIs during follow-up. During the influenza epidemic periods, a first vaccination did not reduce risk for LRTI. In the total population, the hazard ratio following a first vaccination was 0.86 (95% confidence interval [CI], 0.71 to 1.05); in the population without or with comorbidity, these ratios were 0.90 (95% CI, 0.56 to 1.45) and 0.83 (95% CI, 0.66 to 1.04), respectively. During epidemic periods, revaccination reduced risk of LRTI by 33% (95% CI, 8% to 52%) in individuals without comorbidity. In individuals with comorbidity, the risk reduction of 5% was nonsignificant (95% CI, -10% to 18%). CONCLUSION: In this study, annual influenza revaccination was associated with a reduction in LRTI in community-dwelling elderly individuals.

Influenza vaccination in community-dwelling elderly: impact on mortality and influenza-associated morbidity.

BACKGROUND: Influenza-related morbidity and mortality have been extensively studied with hospital and reimbursement data. However, little is known about the effectiveness of the annual vaccination programs in generally healthy community-dwelling elderly. The objective of our study was to investigate the effectiveness of influenza vaccination in community-dwelling elderly during the 1996 to 1997 influenza epidemic. METHODS: We performed a population-based cohort study using the computerized Integrated Primary Care Information database in the Netherlands. Subjects who were 65 years and older in 1996 with a permanent status in a practice in the source population were considered eligible for study participation. Two cohorts were defined on the basis of vaccination status. We estimated and compared all-cause mortality, pneumonia, and clinical influenza infection rates between the cohorts. RESULTS: Influenza vaccination was associated with a significant reduction of morbidity and mortality in vaccinated elderly (relative risk [RR], 0.72; 95% confidence interval [CI], 0.60-0.87). Influenza infections decreased significantly in the vaccinated population (RR, 0.48; 95% CI, 0.26-0.91). Mortality was reduced significantly in elderly with comorbidity (RR, 0.67; 95% CI, 0.48-0.94). The risk reduction for pneumonia was nonsignificant (RR, 0.77; 95% CI, 0.55-1.07) but was temporally related to the peak influenza activity. CONCLUSIONS: In this study, influenza vaccination was associated with decreased mortality and influenza infections in community-dwelling elderly. Our results indicate that, in a season of mild influenza activity and good antigenic match between vaccine strains and circulating strains, influenza vaccination reduced mortality in the vaccinated population. Our data support an annual vaccination strategy for all community-dwelling elderly.