The efficacy of vaccine when time since exposure is prolonged (more than 1 week from onset of illness in the index case) is unknown, but is likely to be significantly lower than human normal immunoglobulin (HNIG). We estimated the number of additional secondary cases that may occur through giving vaccine instead of HNIG to contacts of cases of hepatitis A who are identified more than 1 week after onset in the index case. This was calculated for different levels of vaccine efficacy, assuming HNIG efficacy to be 80–90%. The number of households that need to be treated to prevent one secondary case was calculated using estimates of secondary attack ratios (AR). If more than 1 week has elapsed from onset of illness in the index case, for an average household size of 2·3 people, a vaccine efficacy of 50% and an AR of 10–25%, 8–26 households would need to be treated with vaccine before one additional secondary case would be observed. As UK public health professionals manage around one hepatitis A case per month, it would take from 8 months to over 2 years for them to observe one additional case amongst contacts using vaccine rather than HNIG. It is unlikely that an average practitioner would notice if vaccine were 30% less effective than HNIG. Public health practice and advice to patients and contacts should be based on evidence as well as experience.

One of the most pressing issues in facing emerging and re-emerging respiratory infections is how to bring them under control with current public health measures. Approaches such as the Wells–Riley equation, competing-risks model, and Von Foerster equation are used to prioritize control-measure efforts. Here we formulate how to integrate those three different types of functional relationship to construct easy-to-use and easy-to-interpret critical-control lines that help determine optimally the intervention strategies for containing airborne infections. We show that a combination of assigned effective public health interventions and enhanced engineering control measures would have a high probability for containing airborne infection. We suggest that integrated analysis to enhance modelling the impact of potential control measures against airborne infections presents an opportunity to assess risks and benefits. We demonstrate the approach with examples of optimal control measures to prioritize respiratory infections of severe acute respiratory syndrome (SARS), influenza, measles, and chickenpox.

We report a large foodborne outbreak due to group A streptococci (GAS), which caused acute tonsillo-pharyngitis in 200–250 patrons of a company canteen in Copenhagen, Denmark, in June 2006. A retrospective cohort study of canteen users showed that consumption of cold pasta was associated with an increased risk of illness (attack rate 68%, risk ratio 4·1, P<0·0001). Indistinguishable GAS strains (emm89, T-type 3/13/B3264) were cultured from three cases and a cook, who had prepared the pasta. To our knowledge, pasta has previously only twice been incriminated as the source of a GAS outbreak. Only six foodborne GAS outbreaks have been reported in Europe since 1970, four of them in Sweden or Denmark. This geographical clustering suggests that foodborne GAS outbreaks are probably under-recognized elsewhere.

There are only 10 contemporary, population-based studies of typhoid fever that evaluate disease incidence using blood culture for confirmation of cases. Reported incidence ranged from 13 to 976/100 000 persons per year. These studies are likely to have been done preferentially in high- incidence sites which makes generalization of data difficult. Only five of these studies reported mortality. Of these the median (range) mortality was 0% (0–1·8%). Since study conditions usually involved enhanced clinical management of patients and the studies were not designed to evaluate mortality as an outcome, their usefulness for generalizing case-fatality rates is uncertain. No contemporary population-based studies reported rates of complications. Hospital-based typhoid fever studies reported median (range) complication rates of 2·8% (0·6–4·9%) for intestinal perforation and case-fatality rates of 2·0% (0–14·8%). Rates of complications other than intestinal perforation were not reported in contemporary hospital-based studies. Hospital-based studies capture information on the most severe illnesses among persons who have access to health-care services limiting their generalizability. Only two studies have informed the current understanding of typhoid fever age distribution curves. Extrapolation from population-based studies suggests that most typhoid fever occurs among young children in Asia. To reduce gaps in the current understanding of typhoid fever incidence, complications, and case-fatality rate, large population-based studies using blood culture confirmation of cases are needed in representative sites, especially in low and medium human development index countries outside Asia.

Capture–recapture analysis has been used to evaluate infectious disease surveillance. Violation of the underlying assumptions can jeopardize the validity of the capture–recapture estimates and a tool is needed for cross-validation. We re-examined 19 datasets of log-linear model capture–recapture studies on infectious disease incidence using three truncated models for incomplete count data as alternative population estimators. The truncated models yield comparable estimates to independent log-linear capture–recapture models and to parsimonious log-linear models when the number of patients is limited, or the ratio between patients registered once and twice is between 0·5 and 1·5. Compared to saturated log-linear models the truncated models produce considerably lower and often more plausible estimates. We conclude that for estimating infectious disease incidence independent and parsimonious three-source log-linear capture–recapture models are preferable but truncated models can be used as a heuristic tool to identify possible failure in log-linear models, especially when saturated log-linear models are selected.

Notified cases of dengue infections in Singapore reached historical highs in 2004 (9459 cases) and 2005 (13 817 cases) and the reason for such an increase is still to be established. We apply a mathematical model for dengue infection that takes into account the seasonal variation in incidence, characteristic of dengue fever, and which mimics the 2004–2005 epidemics in Singapore. We simulated a set of possible control strategies and confirmed the intuitive belief that killing adult mosquitoes is the most effective strategy to control an ongoing epidemic. On the other hand, the control of immature forms was very efficient in preventing the resurgence of dengue epidemics. Since the control of immature forms allows the reduction of adulticide, it seems that the best strategy is to combine both adulticide and larvicide control measures during an outbreak, followed by the maintenance of larvicide methods after the epidemic has subsided. In addition, the model showed that the mixed strategy of adulticide and larvicide methods introduced by the government seems to be very effective in reducing the number of cases in the first weeks after the start of control.

The aim of this study was to describe the epidemiological and clinical features of tuberculous meningitis in the province of Castellon, Spain. Retrospective analysis was done of all cases attended during the last 15 years. The following groups of variables were assessed: sociodemographic data, medical antecedents, clinical presentation, imaging study results, analyses, cerebrospinal fluid microbiology, treatment, and outcome. Twenty-nine cases were included. Median of age of patients was 34 years, and 17 (59%) were males. HIV infection was present in 15 cases (52%), fever, the most common symptom, occurred in 27 (93%), nuchal rigidity was noted in only 16 (55%), and syndrome of inappropriate ADH secretion (SIADH) occurred in 13 cases (45%). Chest radiograph was abnormal in 15 cases (52%). Anaemia was found in 22 subjects (76%), hypoalbuminaemia in 18 (62%) and hyponatraemia in 15 (52%). Macroscopic aspect of cerebrospinal fluid was normal in 17 cases (65%). Acid-fast stain was positive in only one case (4%). Two patients presented resistance to anti-tuberculous medications. Twelve patients (41%) died and eight (28%) presented sequelae. An association was found between death as outcome and presence of SIADH and lower level of serum cholesterol. Tuberculous meningitis is a rare and frequently difficult to recognize disease, which results in significant morbidity and mortality. We found an association of mortality with SIADH and lower level of serum cholesterol.

In 1999 the Enhanced Tuberculosis Surveillance (ETS) system was introduced in the United Kingdom to strengthen surveillance of tuberculosis (TB). The aim of this study was to assess the use of record-linkage and capture–recapture methodology for estimating the completeness of TB reporting in England between 1999 and 2002. Due to the size of the TB data sources sophisticated record-linkage software was required and the proportion of false-positive cases among unlinked hospital-derived TB records was estimated through a population mixture model. This study showed that record-linkage of TB data sources and cross-validation with additional TB-related datasets improved data quality as well as case ascertainment. Since the introduction of ETS observed completeness of notification in England has increased and the results were consistent with expected levels of under-notification. Completeness of notification estimated by a log-linear capture–recapture model was highly inconsistent with prior estimates and the validity of this methodology was further examined.

In 18 weeks, Health Protection Scotland (HPS) deployed a syndromic surveillance system to early-detect natural or intentional disease outbreaks during the G8 Summit 2005 at Gleneagles, Scotland. The system integrated clinical and non-clinical datasets. Clinical datasets included Accident & Emergency (A&E) syndromes, and General Practice (GPs) codes grouped into syndromes. Non-clinical data included telephone calls to a nurse helpline, laboratory test orders, and hotel staff absenteeism. A cumulative sum-based detection algorithm and a log-linear regression model identified signals in the data. The system had a fax-based track for real-time identification of unusual presentations. Ninety-five signals were triggered by the detection algorithms and four forms were faxed to HPS. Thirteen signals were investigated. The system successfully complemented a traditional surveillance system in identifying a small cluster of gastroenteritis among the police force and triggered interventions to prevent further cases.

Many countries plan to close schools during a future influenza pandemic, although the potential impact is poorly understood. We apply a model of the transmission dynamics of pandemic influenza to consultation, serological and clinical data from the United Kingdom from the 1957 (Asian) influenza pandemic, to estimate the basic reproduction number (R0), the proportion of infected individuals who experience clinical symptoms and the impact of school/nursery closures. The R0 for Asian influenza was about 1·8 and 60–65% of infected individuals were estimated to have experienced clinical symptoms. During a future pandemic, closure of schools/nurseries could reduce the epidemic size only by a very small amount (<10%) if R0 is high (e.g. 2·5 or 3·5), and modest reductions, e.g. 22% might be possible if it is low (1·8) and schools are closed early, depending on assumptions about contact patterns. Further data on contact patterns and their dependence on school closures are needed.

A large outbreak of hepatitis A virus (HAV) infection occurred in 2004 in Campania, a region of southern Italy, with 882 cases reported between 1 January and 1 August. The local public health authorities and the Italian National Institute of Health carried out investigations in order to characterize the agent, identify the source of infection and the route of transmission, and implement appropriate control measures. A web-based reporting system enhanced the flow of information between public health authorities, providing real-time epidemic curves and frequency distributions. The same 1B HAV genotype was found in 90% of sera from a subset of patients with acute disease, suggesting a local common source. A case-control study in the municipality with the highest attack rate showed that raw seafood consumption, in particular if illegally sold in water, was strongly associated with HAV illness. Samples of seafood systematically collected from retailers were found contaminated by HAV.

We undertook a 5-year retrospective study of group A streptococcal (GAS) bacteraemia in Fiji, supplemented by a 9-month detailed retrospective study of β-haemolytic streptococcal (BHS) infections. The all-age incidence of GAS bacteraemia over 5 years was 11·6/100 000. Indigenous Fijians were 4·7 times more likely to present with invasive BHS disease than people of other ethnicities, and 6·4 times more likely than Indo-Fijians. The case-fatality rate for invasive BHS infections was 28%. emm-typing was performed on 23 isolates: 17 different emm-types were found, and the emm-type profile was different from that found in industrialized nations. These data support the contentions that elevated rates of invasive BHS and GAS infections are widespread in developing countries, and that the profile of invasive organisms in these settings reflects a wide diversity of emm-types and a paucity of types typically found in industrialized countries.

Escherichia coli isolates from human blood (n=266) and faecal (n=237) samples were examined for cytotoxic necrotizing factors 1 and 2 (CNF 1 and 2), cytolethal distending toxin (CDT), and putative virulence factors that have been associated with disease conditions in humans and animals. PCR showed that the chromosomally encoded, Rho-activating, CNF1 (68/544, 12·5%) was more common than the transmissible plasmid-borne CNF2 (3/544, 0·6%). The relative risk of having either CNF or CDT toxin genes in blood compared to faecal isolates was 3·88 (95% CI 2·36–6·38). This was highly significant (P<0·0001) and demonstrates the importance of these factors in bloodstream infections. Fifty-one of 65 (78%) E. coli bearing CNF1 and 11 of 21 (52%) of E. coli bearing CDT also carried the pyelonephritis-associated pilus gene, papG. The S fimbrial adhesin gene, sfa, was found in 57 blood (21%) and eight faecal samples (3%). The F17 fimbrial adhesin gene and afimbrial adhesin gene afa did not occur frequently. Haemolysin (hly) was found in all of the isolates tested. Further studies must be designed to identify the clinical significance of these genes and their role in pathogenesis.

In France, surveillance of anti-tuberculosis drug resistance is performed by the Azay-Mycobacteria network, representing 30% of all culture-positive cases. We sought to validate administrative and clinical data gathered by the network in 2004 and to produce corrected resistance rates accounting for the observed misclassification. We reviewed a 10% sample of patients' records diagnosed in 2004 and measured the agreement between controlled data and data collected by the network by using the kappa (κ) statistic. A re-sampling bootstrap-based method was used to investigate the impact of bias found on resistance rates. Most of data collected by the network, such as demographic data, and country of birth had an excellent agreement (κ>0·8) with controlled data. The concordance was good (κ>0·6) for HIV status and tuberculosis site. The only variable slightly discordant with controlled data was prior history of treatment (κ=0·52). However, after correcting crude resistance rates for the observed misclassification, all estimated rates were within confidence intervals based on reported rates. This validation study is in favour of a good quality of data produced by the network, even though corrected rates are slightly different from observed rates. Therefore, data collected through the network may be used for policy making and tuberculosis programme evaluation. However, improvement in data collection regarding prior history of treatment should be considered.

We coupled the Wells–Riley equation and the susceptible–exposed–infected–recovery (SEIR) model to quantify the impact of the combination of indoor air-based control measures of enhanced ventilation and respiratory masking in containing pandemic influenza within an elementary school. We integrated indoor environmental factors of a real elementary school and aetiological characteristics of influenza to estimate the age-specific risk of infection (P) and basic reproduction number (R0). We combined the enhanced ventilation rates of 0·5, 1, 1·5, and 2/h and respiratory masking with 60%, 70%, 80%, and 95% efficacies, respectively, to predict the reducing level of R0. We also took into account the critical vaccination coverage rate among schoolchildren. Age-specific P and R0 were estimated respectively to be 0·29 and 16·90; 0·56 and 16·11; 0·59 and 12·88; 0·64 and 16·09; and 0·07 and 2·80 for five age groups 4–6, 7–8, 9–10, 11–12, and 25–45 years, indicating pre-schoolchildren have the highest transmission potential. We conclude that our integrated approach, employing the mechanism of transmission of indoor respiratory infection, population-dynamic transmission model, and the impact of infectious control programmes, is a powerful tool for risk profiling prediction of pandemic influenza among schoolchildren.

A retrospective, cross-sectional telephone survey (n=2090) was conducted in Ontario, Canada, between May 2005 and April 2006, to determine the burden of acute gastrointestinal illness in the population. The 4-week prevalence was 8·56% (95% CI 7·36–9·76); in households with more than one resident, 35% of cases reported someone else in their household had similar symptoms at the same time. The annual adjusted incidence rate was 1·17 (95% CI 0·99–1·35) episodes per person-year, with higher rates in females, rural residents, and in the winter and spring. Health care was sought by 22% of cases, of which 33% were asked to provide a stool sample. Interestingly, 2·2% of cases who did not visit a health-care provider reported self-administering antibiotics. Overall, acute gastrointestinal illness appears to pose a significant burden in the Ontario population. Further research into the specific aetiologies and risk factors is now needed to better target intervention strategies.

The aim of this study was to investigate the burden of disease associated with gastroenteric viruses (rotavirus, norovirus, sapovirus, astrovirus and enteric adenovirus) using structured surveillance of children aged <6 years in the community. Faecal samples were collected between 2000 and 2003 from 685 children with symptoms of gastroenteritis. The children comprised three groups; 223 in the structured surveillance cohort, 203 in a community cohort and 259 in a cohort of hospitalized children. All samples were tested for the presence of viral pathogens using molecular methods. Questionnaires were sent to the parents/carers of the children recruited to the structured surveillance cohort in order to collect data that would allow an estimation of the severity of illness by means of the Vesikari score, and of the cost associated with gastrointestinal disease in this age group. A viral aetiological agent was detected in 53·5% of samples tested. Rotavirus was the most common pathogen found in all three cohorts followed by norovirus and enteric adenoviruses. Multiple viruses were found in 8% of the samples, and commonly involved rotavirus and any other virus. G1P[8] was the most commonly detected rotavirus strain and there was no significant difference in the distribution of rotavirus genotypes among the three cohorts. Analysis of the questionnaires indicated that rotavirus infections were likely to be more severe than any other virus infection, and children from whom a viral pathogen was identified were more likely to require rehydration therapy.

While oral polio vaccine (OPV) has been shown to be safe and effective, it has been observed that it can circulate within a susceptible population and revert to a virulent form. Inactivated polio vaccine (IPV) confers protection from paralytic disease, but provides limited protection against infection. It is possible, then, that an IPV-immunized population, when exposed to OPV, could sustain undetected circulation of vaccine-derived poliovirus. This study examines the possibility of polio vaccine virus circulating within the United States (highly IPV-immunized) population that borders Mexico (OPV-immunized). A total of 653 stool and 20 sewage samples collected on the US side of the border were tested for the presence of poliovirus. All samples were found to be negative. These results suggest that the risk of circulating vaccine-derived poliovirus is low in fully immunized IPV-using populations in developed countries that border OPV-using populations.