Eurosurveillance - Volume 18, Issue 37, 12 September 2013

The test-negative design (TND) is an efficient form of case-control study commonly applied to influenza vaccine effectiveness (VE) estimation. TND validity is predicated on the core assumption that the intervention (vaccine) has no effect on other non-targeted aetiologies resulting in similar illness/disease. Here we verify this core assumption and compare efficacy estimates derived by the TND versus classical per-protocol analysis of four datasets obtained from randomised placebo-controlled clinical trials (RCT) of the live attenuated influenza vaccine (LAIV) in children ≤7 years-old and the elderly ≥60 years-old. We further assess generalisability of the TND approach in two other RCT datasets to evaluate monoclonal antibody in the prevention of respiratory syncytial virus (RSV) hospitalisation. Efficacy estimates and their confidence intervals were virtually identical for per-protocol RCT versus TND analyses of LAIV and also for RSV monoclonal antibody. Neither LAIV nor monoclonal antibodies affected the risk of disease aetiologies that were not specifically targeted by the respective interventions (e.g. other respiratory viruses). This study validates the core assumption of the TND approach for influenza vaccine efficacy estimation and confirms the accuracy and precision of its estimates compared to the gold standard of classic per-protocol RCT analysis of the same data sets. The TND approach is generalisable for other conditions such as RSV for which the core assumption is also met. However, when used in observational studies, the TND, like all designs, still requires assessment for bias and confounding that may exist in the absence of randomised participation and blinded follow-up. .

Saudi Arabia (SA) experienced two large invasive meningococcal disease (IMD) outbreaks during the 2000 and 2001 Hajj pilgrimages. In 2002, polysaccharide quadrivalent ACWY vaccines became mandatory for Mecca and Medina pilgrims/residents older than two years. This study aimed to analyse IMD surveillance data among citizens, residents and pilgrims in SA from 1995 to 2011, focusing on changes before and after the new vaccination policy. For all laboratory-confirmed IMD cases in the national surveillance database from 1995 to 2011, serogroup and age were retrieved. The cases' seasonal distribution as well as the case fatality ratios (CFR) were obtained. For Saudi citizens/residents and Hajj pilgrims, annual rates were calculated using mid-year population estimates. The Student's t-test was used to compare means between the pre-epidemic (1995-1999) and post-epidemic (2002-2011) periods, excluding outbreak years. From 1995 to 2011, laboratories notified 1,103 cases. Between the pre- and post-epidemic periods, mean annual IMD rates decreased from 0.20 (standard deviation (SD): 0.1) to 0.06 cases/100,000 (SD: 0.06; p=0.02), mean numbers of Hajj-related cases from 13 (SD: 9.3) to 2 cases/year (SD: 2.3; p=0.02) and the mean age from 31 (SD: 1.3) to 18 years (SD: 1.4; p<0.01). The CFR in Saudi citizens (10.4) was lower than among foreign pilgrims (28.9) and decreased from 19.3% (SD: 1.8) in the pre-epidemic to 11.4% (SD: 7.0; p=0.04) in the post-epidemic phase. The decrease of annual IMD rates, CFR and Hajj-related cases between the pre- and post- vaccine era suggests a possible positive effect of the mandatory ACWY vaccination for pilgrims/residents in Mecca and Medina. Regular surveillance with an annual data analysis is necessary to monitor trends and circulating serotypes and to implement appropriate public health measures to avoid new IMD epidemics during upcoming Hajj seasons. .

There are an estimated 17 million human diarrhoea cases annually in the United Kingdom. In 2008 and 2009, enteroaggregative E. coli (EAEC) were identified in 1.9% of stools. However, it remains unclear whether there is a causal link between presence of EAEC and disease. This study used bacterial load, the presence of co-infections and demographic data to assess if EAEC was independently associated with intestinal infectious disease. Quantitative real-time PCR data (Ct values) generated directly from stool specimens for several pathogen targets were analysed to identify multiple pathogens, including EAEC, in the stools of cases and healthy controls. Sensitivity and specificity using Ct value (60% and 60%) was not useful for identifying cases or controls, but an independent association between disease and EAEC presence was demonstrated: multivariate logistic regression for EAEC presence (odds ratio: 2.41; 95% confidence interval: 1.78-3.26; p<0.001). The population-attributable fraction was 3.3%. The group of bacteria known as EAEC are associated with gastrointestinal disease in at least half of the cases with EAEC positive stools. We conclude that the current definition of EAEC, by plasmid gene detection, includes true pathogens as well as non-pathogenic variants. .

On 29 May 2013 three European tuberculosis (TB) networks met for the first time to discuss TB prevention, control and care in the World Health Organization (WHO) European Region including the European Union (EU). This meeting, which took place in The Hague, the Netherlands, provided a unique opportunity to discuss progress with the implementation of the Berlin Declaration on TB [1], the European Centre for Disease Prevention and Control (ECDC) Framework Action Plan to fight tuberculosis in the EU [2,3], and the Consolidated Action Plan to prevent and combat multidrug- and extensively drug-resistant tuberculosis (M/XDR-TB) in the WHO European Region [4]. Surveillance focal points, laboratory experts, and National TB Programme Managers (NTPs) exchanged lessons learned and discussed next steps to reach the targets defined in the plans.