Norovirus is the most frequent cause of acute infectious gastroenteritis and it is difficult to control in crowded environments like hospitals and nursing homes. Transmission depends on oral intake of virus deposited in the environment by infectious subjects. Data from volunteer studies indicate that virus concentrations in stool are highly variable, but systematic studies of the time-course of shedding and its individual variation are lacking. This paper quantifies norovirus shedding in a large population of 102 subjects, including asymptomatic shedders, and uses a longitudinal model to generalize shedding patterns. Enhanced surveillance for studies of transmission of norovirus in hospital outbreaks has yielded a considerable number of faecal samples from symptomatic and asymptomatic shedders, both from patients and staff. Norovirus concentrations were determined by real-time PCR. A quantitative dynamic model was fitted to the shedding data, in a multilevel Bayesian framework, to study the time-course of shedding and its variation. The results indicate that shedding in asymptomatic subjects is similar to that in symptomatic infections, both showing considerable variation in peak levels (average 105−109 /g faeces) as well as duration of virus shedding (average 8–60 days). Patients appear to shed higher numbers of virus than staff, for slightly longer durations, but the differences are too small to be significant. Given equal shedding, the greater contribution of symptomatic cases to transmission must be caused by their higher efficiency in spreading these viruses. The results of this study will be helpful for risk studies that need to quantify the deposition of virus in the environment.

As a major foodborne pathogen, Campylobacter is frequently isolated from food sources of animal origin. In contrast, human Campylobacter illness is relatively rare, but has a considerable health burden due to acute enteric illness as well as severe sequelae. To study silent transmission, serum antibodies can be used as biomarkers to estimate seroconversion rates, as a proxy for infection pressure. This novel approach to serology shows that infections are much more common than disease, possibly because most infections remain asymptomatic. This study used antibody titres measured in serum samples collected from healthy subjects selected randomly in the general population from several countries in the European Union (EU). Estimates of seroconversion rates to Campylobacter were calculated for seven countries: Romania, Poland, Italy, France, Finland, Denmark and The Netherlands. Results indicate high infection pressures in all these countries, slightly increasing in Eastern EU countries. Of these countries, the differences in rates of notified illnesses are much greater, with low numbers in France and Poland, possibly indicating lower probability of detection due to differences in the notification systems, but in the latter case it cannot be excluded that more frequent exposure confers better protection due to acquired immunity.

Large outbreaks of Q fever in The Netherlands have provided a unique opportunity for studying longitudinal serum antibody responses in patients. Results are presented of a cohort of 344 patients with acute symptoms of Q fever with three or more serum samples per patient. In all these serum samples IgM and IgG against phase 1 and 2 Coxiella burnetii were measured by an immunofluorescence assay. A mathematical model of the dynamic interaction of serum antibodies and pathogens was used in a mixed model framework to quantitatively analyse responses to C. burnetii infection. Responses show strong heterogeneity, with individual serum antibody responses widely different in magnitude and shape. Features of the response, peak titre and decay rate, are used to characterize the diversity of the observed responses. Binary mixture analysis of IgG peak levels (phases 1 and 2) reveals a class of patients with high IgG peak titres that decay slowly and may represent potential chronic cases. When combining the results of mixture analysis into an odds score, it is concluded that not only high IgG phase 1 may be predictive for chronic Q fever, but also that high IgG phase 2 may aid in detecting such putative chronic cases.

E. coli O157 can be transmitted to humans by three primary (foodborne, environmental, waterborne) and one secondary (person-to-person transmission) pathways. A regression model and quantitative microbiological risk assessments (QMRAs) were applied to determine the relative importance of the primary transmission pathways in NE Scotland. Both approaches indicated that waterborne infection was the least important but it was unclear whether food or the environment was the main source of infection. The QMRAs over-predicted the number of cases by a factor of 30 and this could be because all E. coli O157 strains may not be equally infective and/or the level of infectivity in the dose–response model was too high. The efficacy of potential risk mitigation strategies to reduce human exposure to E. coli O157 using QMRAs was simulated. Risk mitigation strategies focusing on food and environment are likely to have the biggest impact on infection figures.

Trichinella is an important foodborne pathogen causing considerable morbidity and mortality. To prevent human trichinellosis, meat inspection for Trichinella spp. at slaughter is a key instrument. Current testing is based on minimal infectious dose in humans, but a scientific basis for this approach is lacking. To this end, a dose–response model must be developed, allowing translation of exposure into disease burden at the population level. We developed novel methods for dose–response assessment using outbreak data incorporating sexual reproduction of the parasite. A selection of suitable outbreak studies, reporting numbers exposed and infected, as well as estimated doses, was collated from a literature study. Humans appear to be highly susceptible: exposure to low doses (few larvae) is associated with a considerable risk of infection. As a consequence, levels of Trichinella in meat must be low to maintain acceptable health risks.

The annual number of episodes of clinical gastroenteritis caused by Campylobacter spp. in The Netherlands is estimated to be 75 000, i.e. once per 200 person life-years. This number is based on extrapolation of culture results from population-based studies. The number of culture-confirmed cases of Campylobacter infection peaks in the first 3 years of life and again between the ages of 20 and 25 years. The seroepidemiology of Campylobacter describes the relationship between age and exposure to Campylobacter and reflects both symptomatic and asymptomatic infections. Using a validated ELISA system, antibodies to Campylobacter were measured in an age-stratified sample (n=456) of the PIENTER serum collection of the Dutch general population. The seroprevalence of Campylobacter IgG antibodies increased with age, reaching almost 100% at age 20 years. Antibody levels steadily increased with age until young adulthood, suggesting repeated exposure to Campylobacter. In conclusion, seroepidemiological data demonstrated repeated exposures to Campylobacter throughout life, most of which do not lead to clinical symptoms. From young adulthood, >95% of the population in The Netherlands had serological evidence for exposure to Campylobacter.

Effective infection control measures during norovirus outbreaks are urgently needed in places where vulnerable individuals gather. In the present study, the effect of a number of measures was investigated in daily practice. Forty-nine Dutch nursing homes were monitored prospectively for norovirus outbreaks during two winter seasons. A total of 37 norovirus outbreaks were registered. Control measures were most effective when implemented within 3 days after onset of disease of the first patient. Measures targeted at reduced transmission between persons, via aerosols, and via contaminated surfaces reduced illness in staff and in residents. Reducing illness in staff results in fewer costs for sick leave and substitution of staff and less disruption in the care of residents. The effect of control measures on outbreak duration was limited. This is the first intervention study examining the effect of control measures. Further research is needed to extend and refine the conclusions.

To gain insight into pertussis disease dynamics, we studied age-specific long-term periodicity and seasonality of pertussis in The Netherlands. Hierarchical time-series models were used to analyse the monthly reported pertussis incidence in January 1996–June 2006 by age group. The incidence of pertussis showed a slightly increasing long-term trend with highest incidence rates seen in 1996, 1999, 2001 and 2004. For all age groups the annual peak incidence was found in August, except for the 13–18 years age group where the peak occurred in November. Monthly trends in adults showed high correlation with trends in age groups 0–4 years (0·94) and 5–12 years (0·92). We found no evidence for a relationship between annual rises in pertussis and the opening of schools. Concurrent annual fluctuations of pertussis incidence in adults and infants suggest frequent transmission within and between these age groups. Studying trends offers insight into transmission dynamics and may facilitate decisions on future vaccination strategies.

The infectivity of pathogenic microorganisms is a key factor in the transmission of an infectious disease in a susceptible population. Microbial infectivity is generally estimated from dose–response studies in human volunteers. This can only be done with mildly pathogenic organisms. Here a hierarchical Beta-Poisson dose–response model is developed utilizing data from human outbreaks. On the lowest level each outbreak is modelled separately and these are then combined at a second level to produce a group dose–response relation. The distribution of foodborne pathogens often shows strong heterogeneity and this is incorporated by introducing an additional parameter to the dose–response model, accounting for the degree of overdispersion relative to Poisson distribution. It was found that heterogeneity considerably influences the shape of the dose–response relationship and increases uncertainty in predicted risk. This uncertainty is greater than previously reported surrogate and outbreak models using a single level of analysis. Monte Carlo parameter samples (α, β of the Beta-Poisson model) can be readily incorporated in risk assessment models built using tools such as S-plus and @ Risk.

To investigate the possible dependence on age of the rate of decline of IgG antibodies to pertussis toxin (IgG-PT) after natural infection with Bordetella pertussis we measured IgG-PT in follow-up sera of 121 patients (age 0–94 years) obtained after 123 episodes of B. pertussis infection. For analysis we applied a dynamic model for the inactivation of B. pertussis by the immune system. There were no significant differences in rise, peak and decline of IgG-PT between different age groups, although there was a tendency for a more rapid increase, a higher peak and a faster decline with increasing age. The IgG-PT cut-off of 100 U/ml for serodiagnosis of pertussis appeared valid in all age groups. A decline of IgG-PT to <10 U/ml was associated with increased risk of re-infection with B. pertussis.

We aimed to provide a quantitative description of decay in pertussis antibody levels to aid in finding a serological estimate of the incidence of pertussis. The serum IgG response against pertussis toxin was studied in a group of clinically diagnosed patients. Individual records consisted of repeated serum IgG measurements at irregular intervals for up to 10 years post diagnosis. These data were analysed with a nonlinear regression model taking into account censoring at upper and lower threshold levels, measurement errors, and individual variation in the shape and magnitude of the immune response. There was considerable variation between individual responses, both in strength (amplitude) and duration (shape). The inverse model relating IgG levels to time from infection (diagnosis) can be applied to cross-sectional IgG data to generate distributions of times from infection, which may be used to calculate infection rates and their variation, in populations sampled for cross-sectional IgG data.