The self-controlled case-series method was originally developed to investigate potential associations between vaccines and adverse events, and is now commonly used for this purpose. This study reviews applications of the method to vaccine safety investigations in the period 1995–2010. In total, 40 studies were reviewed. The application of the self-controlled case-series method in these studies is critically examined, with particular reference to the definition of observation and risk periods, control of confounders, assumptions and potential biases, methodological and presentation issues, power and sample size, and software. Comparisons with other study designs undertaken in the papers reviewed are also highlighted. Some recommendations are presented, with the emphasis on promoting good practice.

In order to analyse the impact of vaccination against cytomegalovirus (CMV) on congenital infection incidence using current vaccines tested in phase II clinical trials, we simulated different scenarios by mathematical modelling, departing from the current vaccine characteristics, varying age at vaccination, immunity waning, vaccine efficacy and mixing patterns. Our results indicated that the optimal age for a single vaccination interval is from 2 to 6 months if there is no immunity waning. Congenital infection may increase if vaccine-induced immunity wanes before 20 years. Congenital disease should increase further when the mixing pattern includes transmission among children with a short duration of protection vaccine. Thus, the best vaccination strategy is a combined schedule: before age 1 year plus a second dose at 10–11 years. For CMV vaccines with low efficacy, such as the current ones, universal vaccination against CMV should be considered for infants and teenagers.

The A(H1N1) influenza pandemic has been a challenge for public health surveillance systems in all countries. An objective evaluation has not been conducted, as yet, of the performance of those systems during the pandemic. This paper presents an algorithm based on Benford's Law and the mortality ratio in order to evaluate the quality of the data and the sensitivity of surveillance systems. It analyses records of confirmed cases reported to the Pan American Health Organization by its 35 member countries between epidemiological weeks 13 and 47 in 2009. Seventeen countries did not fulfil Benford's Law, and mortality exceeded the regional average in 40% of the countries. The results suggest uneven performance by surveillance systems in the different countries, with the most frequent problem being low diagnostic coverage. Benford's Law proved to be a useful tool for the evaluation of a public health surveillance system's performance.

Optimal antiretroviral strategies for HIV-infected patients still need to be established. To this end a decision tree including different antiretroviral strategies that could be adopted for HIV-infected patients was built. A 10-year follow-up was simulated by using transitional probabilities estimated from a large cohort using a time-homogeneous Markov model. The desired outcome was for patients to maintain a CD4 cell count of >500 cells/mm3 without experiencing AIDS or death. For patients with a baseline HIV viral load ⩾5 log10 copies/ml, boosted protease inhibitor-based immediate highly active antiretroviral therapy (HAART) allowed them to spend 12% more time with CD4 ⩾500/mm3 than did delayed HAART (6·40 vs. 5·69 and 5·57 vs. 4·90 years for baseline CD4 ⩾500 and 350–499/mm3, respectively). In patients with a baseline HIV viral load ⩽3·5 log10 copies/ml, delayed HAART performed better than immediate HAART (6·43 vs. 6·26 and 5·95 vs. 5·18 for baseline CD4 ⩾500 and 350–499/mm3, respectively). Immediate HAART is beneficial in patients with a baseline HIV viral load ⩾5 log10 copies/ml, whereas deferred HAART appears to be the best option for patients with CD4 ⩾350/mm3 and baseline HIV viral load <3·5 log10 copies/ml.

Mobility is associated with HIV due to more risky sexual behaviour of mobile groups such as travellers and migrants. Limited participation of such groups may reduce the effectiveness of HIV interventions disproportionally. The established STDSIM model, which simulates transmission and control of HIV and STD, was extended to simulate mobility patterns based on data from Tanzania. We explored the impact of non-participation of mobile groups (travellers and recent migrants) on the effectiveness of two interventions: condom promotion and health education aiming at partner reduction. If mobile groups do not participate, the effectiveness of both interventions could be reduced by 40%. The impact of targeting travellers with a combined HIV campaign is close to that of a general population intervention. In conclusion, it is important to account for possible non-participation of migrants and travellers. If non-participation is substantial, impact of interventions can be greatly improved by actively approaching these people.

The AEGISS (Ascertainment and Enhancement of Disease Surveillance and Statistics) project uses spatio-temporal statistical methods to identify anomalies in the incidence of gastrointestinal infections in the UK. The focus of this paper is the modelling of temporal variation in incidence using data from the Southampton area in southern England. We identified and fitted a hierarchical stochastic model for the time series of daily incident cases to enable probabilistic prediction of temporal variation in risk, and demonstrated the resulting gains in predictive accuracy by comparison with a conventional analysis based on an over-dispersed Poisson log-linear regression model. We used Bayesian methods of inference in order to incorporate parameter uncertainty in our predictive inference of risk. Incorporation of our model in the overall spatio-temporal model, will contribute to the accurate and timely prediction of unusually high food-poisoning incidence, and thus to the identification and prevention of future outbreaks.

The introduction of a centralized system for recording cattle movements in the UK has provided a framework for network-based models for disease spread. However, there are many types of non-reportable contacts between farms which may play a role in disease spread. The lack of real pathogen data with which to test network models makes it difficult to assess whether reported data adequately captures the risk-potential network between farms and improves the accuracy of disease forecasts. A novel multi-disciplinary approach is described whereby network-based models, built upon reported cattle movements and non-reportable local contacts between study farms, are parameterized using field data on bovine Staphylococcus aureus strains. Reported cattle movements were found to play a role in strain spread between farms, but other contacts via farm visitors were also correlated with strain distribution, suggesting that parameterizing contact networks using cattle-tracing data alone may not adequately capture the disease dynamics.

Most mathematical models of sexually transmitted infections (STIs) assume that infected individuals become susceptible to re-infection immediately after recovery. This paper assesses whether extending the standard model to allow for temporary immunity after recovery improves the correspondence between observed and modelled levels of STI prevalence in South Africa, for gonorrhoea, chlamydial infection and trichomoniasis. Five different models of immunity and symptom resolution were defined, and each model fitted to South African STI prevalence data. The models were compared in terms of Bayes factors, which show that in the case of gonorrhoea and chlamydial infection, models that allow for immunity provide a significantly better fit to STI prevalence data than models that do not allow for immunity. For all three STIs, estimates of the impact of changes in STI treatment and sexual behaviour are significantly lower in models that allow for immunity. Mathematical models that do not allow for immunity could therefore overestimate the effectiveness of STI interventions.

Weekly (August 2003–December 2008) numbers of five common paediatric diseases and the incidence of respiratory viruses were obtained from a children's hospital in Singapore and correlated with climate data using multivariate time-series techniques. Upper respiratory tract infections were positively correlated with the incidences of influenza A, B, respiratory syncytial virus (RSV) and parainfluenza viruses (types 1–3 combined). Lower respiratory tract infections were positively correlated with only the incidence of RSV. Both upper and lower respiratory tract infections were negatively correlated with relative humidity. Asthma admissions were negatively correlated with maximum temperature and positively correlated with the incidence of influenza B and increasing hours of sunshine. Although sporadic cases of adenovirus infection were identified, not enough cases were available for a more detailed analysis. Gastroenteritis and urinary tract infections, included as control diseases, were not correlated significantly with any climate parameters. These correlations are compatible with current understanding of respiratory virus survival under certain climate conditions and may assist the prediction of disease burdens and hospital resource planning in such tropical environments.

Non-pharmaceutical interventions (NPI) such as facemasks and intensified hand hygiene may be effective in preventing influenza infections in households. It may be equally important that household members, especially children, can learn to use, maintain and tolerate these measures. We monitored adherence and tolerability of these NPI within a cluster-randomized trial in households with influenza index patients. We recruited 147 participants in 41 households, 39 (95%) out of 41 index patients were children (aged <14 years). In households assigned to wear facemasks, their use peaked on day 4 after symptom onset of the index patient at 73% and at 65% for children and adults, respectively. Mean daily frequency of hand disinfection in households assigned to intensified hand hygiene measures peaked at 7·7 (day 6) for children and at 10·1 (day 5) for adults. The majority of participants reported no problems with mask wearing. Data suggest that usage of NPI can be taught and that measures are well tolerated by adults and even sick children alike.

Most studies describing high rates of acute respiratory illness in aboriginals have focused on rural or remote communities. Hypothesized causes include socioeconomic deprivation, limited access to healthcare, and a high prevalence of chronic disease. To assess influenza rates in an aboriginal community while accounting for healthcare access, deprivation and chronic disease prevalence, we compared rates of influenza-related outpatient and emergency-department visits in an urban Mohawk reserve (Kahnawá:ke) to rates in neighbouring regions with comparable living conditions and then restricted the analysis to a sub-population with a low chronic disease prevalence, i.e. those aged <20 years. Using medical billing claims from 1996 to 2006 we estimated age-sex standardized rate ratios. The rate in Kahnawá:ke was 58% greater than neighbouring regions and 98% greater in the analysis of those aged <20 years. Despite relatively favourable socioeconomic conditions and healthcare access, rates of influenza-related visits in Kahnawá:ke were elevated, particularly in the younger age groups.

Information about the changing epidemiology of drug-resistant tuberculosis (TB) in hospitals in China over the past decade remains largely unknown. This study examined the susceptibility patterns and trends of drug-resistant TB cases in the 309 Hospital in Beijing, China. Mycobacterium tuberculosis isolates were retrospectively identified, drug susceptibility test (DST) results and clinical data were analysed for the period 1997–2009. Of the 5523 culture-positive TB patients, 47·1% had resistance to any anti-TB drug, 14·8% had mono-resistant TB, 19·8% had poly-resistant TB, 19·4% had multidrug-resistant TB (MDR-TB), and 1·3% had extensively drug-resistant TB (XDR-TB). Drug-resistant TB was significantly associated with age group, residential situation, and TB treatment history (P<0·001). During 1997–2000, the percentage of TB patients with any resistance, mono-resistant TB, poly-resistant TB, MDR-TB and XDR-TB all increased significantly (P<0·001). During 2000–2003, the increasing trends of MDR-TB and XDR-TB cases were reversed. During 2004–2009, the percentage of TB patients with any resistance, mono-resistant TB, poly-resistant TB, MDR-TB and XDR-TB all declined significantly (P<0·001), but the prevalence of MDR-TB and poly-resistant TB cases remained high. Our study provides evidence demonstrating that intensive TB control measures have helped reverse the increasing trends of drug-resistant TB in China, but continuous surveillance of drug-resistant TB and better case management are still needed to further reduce the remaining high prevalence of drug-resistant TB.

A survey of 788 pigs from 120 farms was conducted to determine the within-farm prevalence of pathogenic Yersinia enterocolitica and a questionnaire of management conditions was mailed to the farms afterwards. A univariate statistical analysis with carriage and shedding as outcomes was conducted with random-effects logistic regression with farm as a clustering factor. Variables with a P value <0·15 were included into the respective multivariate random-effects logistic regression model. The use of municipal water was discovered to be a protective factor against carriage and faecal shedding of the pathogen. Organic production and buying feed from a certain feed manufacturer were also protective against total carriage. Tonsillar carriage, a different feed manufacturer, fasting pigs before transport to the slaughterhouse, higher-level farm health classification, and snout contacts between pigs were risk factors for faecal shedding. We concluded that differences in management can explain different prevalences of Y. enterocolitica between farms.

During Easter 2009, almost 200 people resident in a small Swedish village fell ill with gastrointestinal symptoms. We conducted a retrospective cohort study and a molecular investigation in order to identify the source of the outbreak. Residents living in households connected to the public water network were at an increased risk of developing disease (relative risk 4·80, 95% confidence interval 1·68–13·73) compared to those with no connection to the public network. Norovirus genotype GI.3 was identified in stool samples from six patients and in a sample from the public water network. Contamination of one of the wells supplying the public water network was thought to be the source of the outbreak. This is a description of a norovirus outbreak linked to a municipal drinking-water supply in Sweden. Information from epidemiological and molecular investigations is of utmost importance to guide outbreak control measures and to prevent future outbreaks.

In March 2008, the Health Protection Agency in England conducted a retrospective case-control study to investigate the cause of 179 cases of the newly recognized, fully antimicrobial-sensitive Salmonella Typhimurium PT U320. Forty-three symptomatic laboratory-confirmed case-patients and 84 asymptomatic location-matched controls were interviewed by telephone about exposures in the 3 days prior to illness or interview. Multivariate logistic analysis indicated consumption of pre-packaged egg sandwiches (odds ratio 3·29, 95% confidence interval 1·19–9·09) was independently associated with illness. Eight of the 15 case-patients who consumed egg sandwiches did so from retail chain A (53·3%) whereas none of the eight controls consumed similar sandwiches (χ2=7·20, P⩽0·01). A review of the pre-packaged egg sandwich ingredients suggested this outbreak was probably caused by exposure to an ingredient common to pre-packaged sandwiches and prepared salads but we established a definitive epidemiological link with only the former. Short shelf-life, product diversity and investigation lag hinder epidemiological investigations of such popular products, providing continued challenges for food safety enforcement of freshly prepared produce.

Within Europe, Ireland has one of the highest reported infection rates with the diarrhoeal protozoan pathogen Cryptosporidium. In this study 249 Cryptosporidium parvum isolates collected from Irish patients between 2000 and 2009 were subtyped by sequence analysis of the GP60 locus. A subsample of 127 isolates was also typed at the MS1 and ML1 loci. GP60 subtype IIaA18G3R1 was the predominant subtype in every year and every season throughout the country. Over the 10-year period there was no evidence that host immunity to the predominant subtype caused a shift in its prevalence. Length frequency distributions of the GP60 TCA/TCG repeats compiled from published data, showed distinct patterns for countries with predominantly zoonotic or anthroponotic transmission cycles, respectively. Although considered to be mostly affected by zoonotic cryptosporidiosis, the GP60 fragment length of Irish C. parvum isolates mirrored that of countries with predominantly human-to-human transmission, indicating more complex routes of infection between livestock and humans. Due to their homogeneity, ML1 and MS1 were not considered useful loci for subtyping C. parvum strains in Ireland.

On 13 November 2009, the authorities of Flemish Brabant, Belgium, received an alert concerning a potential outbreak of Shigella sonnei at a public institution. A study was conducted to assess the extent, discover the source and to implement further measures. We performed a matched case-control study to test an association between shigellosis and canteen-food consumption. Water samples and food handlers' faecal samples were tested. The reference laboratory characterized the retrospectively collected Shigella specimens. We found 52 cases distributed over space (25/35 departments) and time (2 months). We found a matched odds ratio of 3·84 (95% confidence interval 1·02–14·44) for canteen-food consumption. A food handler had travelled to Morocco shortly before detection of the first laboratory-confirmed case. Water samples and food handlers' faecal samples tested negative for Shigella. Confirmed cases presented PFGE profiles, highly similar to archived isolates from Morocco. Foodborne transmission associated with the canteen was strongly suspected.