BackgroundEfficient and reliable surveillance and notification systems are vital for monitoring public health and disease outbreaks. However, most surveillance and notification systems are affected by a degree of underestimation (UE) and therefore uncertainty surrounds the 'true’ incidence of disease affecting morbidity and mortality rates. Surveillance systems fail to capture cases at two distinct levels of the surveillance pyramid: from the community since not all cases seek healthcare (under-ascertainment), and at the healthcare-level, representing a failure to adequately report symptomatic cases that have sought medical advice (underreporting). There are several methods to estimate the extent of under-ascertainment and underreporting.MethodsWithin the context of the ECDC-funded Burden of Communicable Diseases in Europe (BCoDE)-project, an extensive literature review was conducted to identify studies that estimate ascertainment or reporting rates for salmonellosis and campylobacteriosis in European Union Member States (MS) plus European Free Trade Area (EFTA) countries Iceland, Norway and Switzerland and four other OECD countries (USA, Canada, Australia and Japan). Multiplication factors (MFs), a measure of the magnitude of underestimation, were taken directly from the literature or derived (where the proportion of underestimated, under-ascertained, or underreported cases was known) and compared for the two pathogens.ResultsMFs varied between and within diseases and countries, representing a need to carefully select the most appropriate MFs and methods for calculating them. The most appropriate MFs are often disease-, country-, age-, and sex-specific.ConclusionsWhen routine data are used to make decisions on resource allocation or to estimate epidemiological parameters in populations, it becomes important to understand when, where and to what extent these data represent the true picture of disease, and in some instances (such as priority setting) it is necessary to adjust for underestimation. MFs can be used to adjust notification and surveillance data to provide more realistic estimates of incidence.

High-dose alkylating agents and ovarian radiotherapy at any dose are associated with POI. Patients at the highest risk should be offered fertility preservation whenever feasible. POI contributes to poor general health outcomes in childhood cancer survivors; further studies are needed to investigate the role of sex hormone replacement in improving such outcomes.

Purpose Childhood cancer survivors are at increased risk of subsequent neoplasms (SNs), but the germline genetic contribution is largely unknown. We assessed the contribution of pathogenic/likely pathogenic (P/LP) mutations in cancer predisposition genes to their SN risk. Patients and Methods Whole-genome sequencing (30-fold) was performed on samples from childhood cancer survivors who were ≥ 5 years since initial cancer diagnosis and participants in the St Jude Lifetime Cohort Study, a retrospective hospital-based study with prospective clinical follow-up. Germline mutations in 60 genes known to be associated with autosomal dominant cancer predisposition syndromes with moderate to high penetrance were classified by their pathogenicity according to the American College of Medical Genetics and Genomics guidelines. Relative rates (RRs) and 95% CIs of SN occurrence by mutation status were estimated using multivariable piecewise exponential regression stratified by radiation exposure. Results Participants were 3,006 survivors (53% male; median age, 35.8 years [range, 7.1 to 69.8 years]; 56% received radiotherapy), 1,120 SNs were diagnosed among 439 survivors (14.6%), and 175 P/LP mutations were identified in 5.8% (95% CI, 5.0% to 6.7%) of survivors. Mutations were associated with significantly increased rates of breast cancer (RR, 13.9; 95% CI, 6.0 to 32.2) and sarcoma (RR, 10.6; 95% CI, 4.3 to 26.3) among irradiated survivors and with increased rates of developing any SN (RR, 4.7; 95% CI, 2.4 to 9.3), breast cancer (RR, 7.7; 95% CI, 2.4 to 24.4), nonmelanoma skin cancer (RR, 11.0; 95% CI, 2.9 to 41.4), and two or more histologically distinct SNs (RR, 18.6; 95% CI, 3.5 to 99.3) among nonirradiated survivors. Conclusion The findings support referral of all survivors for genetic counseling for potential clinical genetic testing, which should be prioritized for nonirradiated survivors with any SN and for those with breast cancer or sarcoma in the field of prior irradiation.

In 2009, the European Centre for Disease Prevention and Control initiated the ‘Burden of Communicable Diseases in Europe (BCoDE)’ project to generate evidence-based and comparable burden-of-disease estimates of infectious diseases in Europe. The burden-of-disease metric used was the Disability-Adjusted Life Year (DALY), composed of years of life lost due to premature death (YLL) and due to disability (YLD). To better represent infectious diseases, a pathogen-based approach was used linking incident cases to sequelae through outcome trees. Health outcomes were included if an evidence-based causal relationship between infection and outcome was established. Life expectancy and disability weights were taken from the Global Burden of Disease Study and alternative studies. Disease progression parameters were based on literature. Country-specific incidence was based on surveillance data corrected for underestimation. Non-typhoidal Salmonella spp. and Campylobacter spp. were used for illustration. Using the incidence- and pathogen-based DALY approach the total burden for Salmonella spp. and Campylobacter spp. was estimated at 730 DALYs and at 1,780 DALYs per year in the Netherlands (average of 2005–2007). Sequelae accounted for 56% and 82% of the total burden of Salmonella spp. and Campylobacter spp., respectively. The incidence- and pathogen-based DALY methodology allows in the case of infectious diseases a more comprehensive calculation of the disease burden as subsequent sequelae are fully taken into account. Not considering subsequent sequelae would strongly underestimate the burden of infectious diseases. Estimates can be used to support prioritisation and comparison of infectious diseases and other health conditions, both within a country and between countries.

BackgroundThe recent outbreak of Q fever in the Netherlands between 2007 and 2009 is the largest recorded Q fever outbreak. Exposure to Coxiella burnetii may cause Q fever but the size of the population exposed during the outbreak remained uncertain as little is known of the infectivity of this pathogen. The quantification of the infectiousness and the corresponding response is necessary for assessing the risk to the population.MethodsA human challenge study was published in the 1950s but this study quantified the dose of C. burnetii in relative units. Data from a concurrent guinea pig challenge study were combined with a recent study in which guinea pigs were challenged with a similar aerosol route to quantify human exposure. Concentration estimates for C. burnetii are made jointly with estimates of the dose response parameters in a hierarchical Bayesian framework.ResultsThe dose for 50% infection (InfD50%) in human subjects is 1.18 bacteria (95% credible interval (CI) 0.76-40.2). The dose for 50% illness (IllD50) in challenged humans is 5.58 (95%CI 0.89-89.0) bacteria. The probability of a single viable C. burnetii causing infection in humans is 0.44 (95%CI 0.044-0.59) and for illness 0.12 (95%CI 0.0006-0.55).ConclusionsTo our knowledge this is the first human dose–response model for C. burnetii. The estimated dose response relation demonstrates high infectivity in humans. In many published papers the proportion of infected individuals developing illness is reported to be 40%. Our model shows that the proportion of symptomatic infections may vary with the exposure dose. This implies that presence of these bacteria in the environment, even in small numbers, poses a serious health risk to the population.

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Setting priorities in the field of infectious diseases requires evidence-based and robust baseline estimates of disease burden. Therefore, the European Centre for Disease Prevention and Control initiated the Burden of Communicable Diseases in Europe (BCoDE) project. The project uses an incidence- and pathogen-based approach to measure the impact of both acute illness and sequelae of infectious diseases expressed in disability-adjusted life years (DALYs). This study presents first estimates of disease burden for four pathogens in Germany. The number of reported incident cases adjusted for underestimation served as model input. For the study period 2005-2007, the average disease burden was estimated at 33 116 DALYs/year for influenza virus, 19 115 DALYs/year for Salmonella spp., 8708 DALYs/year for hepatitis B virus and 740 DALYs/year for measles virus. This methodology highlights the importance of sequelae, particularly for hepatitis B and salmonellosis, because if omitted, the burden would have been underestimated by 98% and 56%, respectively.

In 2009 two notable outbreaks, Q fever and the novel influenza A(H1N1)pdm09, occurred in The Netherlands. Using a composite health measure, disability-adjusted life years (DALYs), the outbreaks were quantified and compared. DALYs were calculated using standardized methodology incorporating age- and sex-stratified data in a disease progression model; years lost due to disability and years of life lost were computed by outcome. Nationally, influenza A(H1N1)pdm09 caused more DALYs (24 484) than Q fever (5797). However, Q fever was 8·28 times more severe [497 DALYs/1000 symptomatic cases (DP1SC)] than A(H1N1)pdm09 (60 DP1SC). The A(H1N1)pdm09 burden is largely due to mortality while the Q fever burden is due primarily to long-term sequelae. Intervention prioritization for influenza should support patients in a critical condition while for Q fever it should target immediate containment and support for patients with long-term sequelae. Burden estimates provide guidance for focusing intervention options during outbreaks of infectious diseases.