Are food exposures obtained through commercial market panels representative of the general population? Implications for outbreak investigations

Current methods of control recruitment for case-control studies can be slow (a particular issue for outbreak investigations), resource-intensive and subject to a range of biases. Commercial market panels are a potential source of rapidly recruited controls. Our study evaluated food exposure data from these panel controls, compared with an established reference dataset. Market panel data were collected from two companies using retrospective internet-based surveys; these were compared with reference data from the National Diet and Nutrition Survey (NDNS). We used logistic regression to calculate adjusted odds ratios to compare exposure to each of the 71 food items between the market panel and NDNS participants. We compared 2103 panel controls with 2696 reference participants. Adjusted for socio-demographic factors, exposure to 90% of foods was statistically different between both panels and the reference data. However, these differences were likely to be of limited practical importance for 89% of Panel A foods and 79% of Panel B foods. Market panel food exposures were comparable with reference data for common food exposures but more likely to be different for uncommon exposures. This approach should be considered for outbreak investigation, in conjunction with other considerations such as population at risk, timeliness of response and study resources

Community-onset sepsis and its public health burden : protocol of a systematic review

Background: Sepsis is a life-threatening condition and major contributor of public health and economic burden in the industrialised world. The heterogeneity, absence of more specific definition, and difficulties in accurate diagnosis lead to great variability in the estimates of sepsis incidence. There has been uncertainty regarding the incidence and risk factors attributable to community-onset as opposed to hospital-acquired sepsis. Community-onset sepsis has distinct host characteristics, risk factors, pathogens, and prognosis. A systematic assessment of recent evidence is warranted in light of secular changes in epidemiology, pathogens, and the uncertainties around the incidence and risk factors of community-onset sepsis. This protocol describes a systematic review which aims to synthesise the recent empirical evidence on the incidence and risk factors of community-onset sepsis, severe sepsis, and septic shock in high-income countries. Methods/design: English-language publications of cohort and case-control studies reporting incidence and risk factors of community-onset sepsis will be eligible for inclusion. MEDLINE and Embase databases will be searched from 2002 and onwards. References of relevant publications will be hand-searched. Two reviewers will independently screen titles/abstracts and full texts as well as extract data and appraise the risk of bias of included studies. The data extractions and risk of bias assessments will be cross-checked. Any disagreements will be resolved via consensus. The data on incidence and risk factors of sepsis will be organised and synthesised in text, tables, and forest plots. The evidence will be pooled given sufficient data and degree of similarity across study populations, exposures, and outcomes. The heterogeneity will be assessed through visual inspection of forest plots, Chi-square-based p value, and I (2) statistic. The sources of heterogeneity will be explored via subgroup analysis. Discussion: Timeliness and accuracy of diagnosis of sepsis are both crucial aspects for improving the patient's outcome. The findings of this review will be discussed with a view to better inform future recommendations on improving public-facing campaigns, timely presentation, and diagnosis of sepsis in the community. The review will also discuss gaps in evidence and highlight future research and policy-making avenues for improving public health planning. Systematic review registration: PROSPERO CRD42015023484

Incubation period of typhoidal salmonellosis : a systematic review and meta-analysis of outbreaks and experimental studies occurring over the last century

Background Salmonella Typhi is a human pathogen that causes typhoid fever. It is a major cause of morbidity and mortality in developing countries and is responsible for several outbreaks in developed countries. Studying certain parameters of the pathogen, such as the incubation period, provides a better understanding of its pathophysiology and its characteristics within a population. Outbreak investigations and human experimental studies provide an avenue to study these relevant parameters. Methods In this study, the authors have undertaken a systematic review of outbreak investigation reports and experimental studies, extracted reported data, tested for heterogeneity, identified subgroups of studies with limited evidence of heterogeneity between them and identified factors that may contribute to the distribution of incubation period. Following identification of relevant studies, we extracted both raw and summary incubation data. We tested for heterogeneity by deriving the value of I2 and conducting a KS-test to compare the distribution between studies. We performed a linear regression analysis to identify the factors associated with incubation period and using the resulting p-values from the KS-test, we conducted a hierarchical cluster analysis to classify studies with limited evidence of heterogeneity into subgroups. Results We identified thirteen studies to be included in the review and extracted raw incubation period data from eleven. The value of I2 was 84% and the proportion of KS test p-values that were less than 0.05 was 63.6% indicating high heterogeneity not due to chance. We identified vaccine history and attack rates as factors that may be associated with incubation period, although these were not significant in the multivariable analysis (p-value: 0.1). From the hierarchical clustering analysis, we classified the studies into five subgroups. The mean incubation period of the subgroups ranged from 9.7 days to 21.2 days. Outbreaks reporting cases with previous vaccination history were clustered in a single subgroup and reported the longest incubation period. Conclusions We identified attack rate and previous vaccination as possible associating factors, however further work involving analyses of individual patient data and developing mathematical models is needed to confirm these as well as examine additional factors that have not been included in our study

Within-host mathematical modelling of the incubation period of Salmonella Typhi

Mechanistic mathematical models are often employed to understand the dynamics of infectious diseases within a population or within a host. They provide estimates that may not be otherwise available. We have developed a within-host mathematical model in order to understand how the pathophysiology of Salmonella Typhi contributes to its incubation period. The model describes the process of infection from ingestion to the onset of clinical illness using a set of ordinary differential equations. The model was parametrized using estimated values from human and mouse experimental studies and the incubation period was estimated as 9.6 days. A sensitivity analysis was also conducted to identify the parameters that most affect the derived incubation period. The migration of bacteria to the caecal lymph node was observed as a major bottle neck for infection. The sensitivity analysis indicated the growth rate of bacteria in late phase systemic infection and the net population of bacteria in the colon as parameters that most influence the incubation period. We have shown in this study how mathematical models aid in the understanding of biological processes and can be used in estimating parameters of infectious diseases

Taste and safety : is the exceptional cuisine offered by high end restaurants paralleled by high standards of food safety?

Introduction: Restaurant guides such as the Good Food Guide Top 50 create a hierarchy focussing on taste and sophistication. Safety is not explicitly included. We used restaurant associated outbreaks to assess evidence for safety. Methods: All foodborne disease outbreaks in England reported to the national database from 2000 to 2014 were used to compare the Top 50 restaurants (2015) to other registered food businesses using the Public Health England (PHE) outbreak database. Health Protection Teams were also contacted to identify any outbreaks not reported to the national database. Among Good Food Guide Top 50 restaurants, regression analysis estimated the association between outbreak occurrence and position on the list. Results: Four outbreaks were reported to the PHE national outbreak database among the Top 50 giving a rate 39 times higher (95% CI 14.5–103.2) than other registered food businesses. Eight outbreaks among the 44 English restaurants in the Top 50 were identified by direct contact with local Health Protection Teams. For every ten places higher ranked, Top 50 restaurants were 66% more likely to have an outbreak (Odds Ratio 1.66, 95% CI 0.89–3.13). Discussion: Top 50 restaurants were substantially more likely to have had reported outbreaks from 2000-2014 than other food premises, and there was a trend for higher rating position to be associated with higher probability of reported outbreaks. Our findings, that eating at some of these restaurants may pose an increased risk to health compared to other dining out, raises the question of whether food guides should consider aspects of food safety alongside the clearly important complementary focus on taste and other aspects of the dining experience

A systematic review of source attribution of human campylobacteriosis using multilocus sequence typing

This work was supported by the United Kingdom Food Standards Agency [grant number FS101013]; the Wellcome Trust [grant numbers 087622 to M.C.J.M., 072782MA to N.D.M.]; and National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Gastrointestinal Infections at the University of Oxford in partnership with Public Health England (PHE). The views expressed are those of the author(s) and not necessarily those of the FSA, NHS, the NIHR, the Department of Health or Public Health England.Peer reviewedPublisher PD

Community-onset sepsis and its public health burden : a systematic review

Background: Sepsis is a life-threatening condition and major contributor to public health and economic burden in the industrialised world. The difficulties in accurate diagnosis lead to great variability in estimates of sepsis incidence. There has been even a greater uncertainty regarding the incidence of and risk factors for community-onset sepsis (COS). We systematically reviewed the recent evidence on the incidence and risk factors of COS in high income countries. Methods: Cohort and case-control studies were eligible for inclusion. Medline and Embase databases were searched from 2002 onwards. References of relevant publications were hand searched. Two reviewers screened titles/abstracts and full-texts independently. One reviewer extracted data and appraised studies which were cross-checked by independent reviewers. Disagreements were resolved via consensus. Odds ratios (ORs) and 95 percent confidence intervals (95% CIs) were ascertained by type of sepsis (non-severe, severe, and septic shock). Results: 10 cohort and 4 case-control studies were included. There was a wide variation in the incidence (# cases per 100,000 per year) of non-severe sepsis (range: 64 - 514), severe sepsis (range: 40 - 455), and septic shock (range: 9 - 31). Heterogeneity precluded statistical pooling. Two cohort and 4 case-control studies reported risk factors for sepsis. In one casecontrol and one cohort study, older age and diabetes were associated with increased risk of sepsis. The same case-control study showed an excess risk for sepsis in participants with clinical conditions (e.g., immunosuppression, lung disease, and peripheral artery disease). In one cohort study, higher risk of sepsis was associated with being a nursing home resident (OR=2.60, 95% CI: 1.20, 5.60) and in the other cohort study with being physically inactive (OR=1.33, 95% CI: 1.13, 1.56) and smoking tobacco (OR=1.85, 95% CI: 1.54, 2.22). The evidence on sex, ethnicity, statin use, and body mass index as risk factors was inconclusive. Conclusions: The lack of a valid standard approach for defining sepsis makes it difficult to determine the true incidence of COS. Differences in case ascertainment contribute to the variation in incidence of COS. The evidence on COS is limited in terms of the number and quality of studies. This review highlights the urgent need for an accurate and standard method for identifying sepsis. Future studies need to improve the methodological shortcomings of previous research in terms of case definition, identification, and surveillance practice

Pneumococcal disease : a systematic review of health utilities, resource use, costs, and economic evaluations of interventions

Background Pneumococcal diseases cause substantial mortality, morbidity, and economic burden. Evidence on data inputs for economic evaluations of interventions targeting pneumococcal disease is critical. Objectives To summarize evidence on resource use, costs, health utilities, and cost-effectiveness for pneumococcal disease and associated interventions to inform future economic analyses. Methods We searched MEDLINE, Embase, Web of Science, CINAHL, PsycINFO, EconLit, and Cochrane databases for peer-reviewed studies in English on pneumococcal disease that reported health utilities using direct or indirect valuation methods, resource use, costs, or cost-effectiveness of intervention programs, and summarized the evidence descriptively. Results We included 383 studies: 9 reporting health utilities, 131 resource use, 160 economic costs of pneumococcal disease, 95 both resource use and costs, and 178 economic evaluations of pneumococcal intervention programs. Health state utility values ranged from 0 to 1 for both meningitis and otitis media and from 0.3 to 0.7 for both pneumonia and sepsis. Hospitalization was shortest for otitis media (range: 0.1-5 days) and longest for sepsis/septicemia (6-48). The main categories of costs reported were drugs, hospitalization, and household or employer costs. Resource use was reported in hospital length of stay and number of contacts with general practitioners. Costs and resource use significantly varied among population ages, disease conditions, and settings. Current vaccination programs for both adults and children, antibiotic use and outreach programs to promote vaccination, early disease detection, and educational programs are cost-effective in most countries. Conclusion This study has generated a comprehensive repository of health economic evidence on pneumococcal disease that can be used to inform future economic evaluations of pneumococcal disease intervention programs

Agreement between gastrointestinal panel testing and standard microbiology methods for detecting pathogens in suspected infectious gastroenteritis : test evaluation and meta-analysis in the absence of a reference standard

Objective: Multiplex gastrointestinal pathogen panel (GPP) tests simultaneously identify bacterial, viral and parasitic pathogens from the stool samples of patients with suspected infectious gastroenteritis presenting in hospital or the community. We undertook a systematic review to compare the accuracy of GPP tests with standard microbiology techniques. Review methods: Searches in Medline, Embase, Web of Science and the Cochrane library were undertaken from inception to January 2016. Eligible studies compared GPP tests with standard microbiology techniques in patients with suspected gastroenteritis. Quality assessment of included studies used tailored QUADAS-2. In the absence of a reference standard we analysed test performance taking GPP tests and standard microbiology techniques in turn as the benchmark test, using random effects meta-analysis of proportions. Results: No study provided an adequate reference standard with which to compare the test accuracy of GPP and conventional tests. Ten studies informed a meta-analysis of positive and negative agreement. Positive agreement across all pathogens was 0.93 (95% CI 0.90 to 0.96) when conventional methods were the benchmark and 0.68 (95% CI: 0.58 to 0.77) when GPP provided the benchmark. Negative agreement was high in both instances due to the high proportion of negative cases. GPP testing produced a greater number of pathogen-positive findings than conventional testing. It is unclear whether these additional ‘positives’ are clinically important. Conclusions: GPP testing has the potential to simplify testing and accelerate reporting when compared to conventional microbiology methods. However the impact of GPP testing upon the management, treatment and outcome of patients is poorly understood and further studies are needed to evaluate the health economic impact of GPP testing compared with standard methods

Comparing interferon-gamma release assays with tuberculin skin test for identifying latent tuberculosis infection that progresses to active tuberculosis : systematic review and meta-analysis

Background Timely and accurate identification of people with latent tuberculosis infection (LTBI) is important for controlling Mycobacterium tuberculosis (TB). There is no gold standard for diagnosis of LTBI. Screening tests such as interferon gamma release assays (IGRAs) and tuberculin skin test (TST) provide indirect and imperfect information. This systematic review compared two types of IGRAs QuantiFERON®-TB Gold In-Tube test (QFT-GIT) and T-SPOT.TB with TST for identification of LTBI by predicting progression to a diagnosis of active TB in three subgroups: children, immunocompromised people, and those recently arrived from countries with high TB burden. Methods Cohort studies were eligible for inclusion. We searched MEDLINE, EMBASE, the Cochrane Library and other databases from December 2009 to June 2015. One reviewer screened studies, extracted data, and assessed risk of bias with cross checking by a second reviewer. Strength of association between test results and incidence of TB was summarised using cumulative incidence ratios (CIRs with 95% CIs). Summary effect measures: the ratio of CIRs (R-CIR) with 95% CIs. R-CIRs, were pooled using a random-effects model. Heterogeneity was assessed using Chi-squared and I2 statistics. Results Seventeen studies, mostly of moderate or high risk of bias (five in children, 10 in immunocompromised people, and two in those recently arrived) were included. In children, while in two studies, there was no significant difference between QFT-GIT and TST (≥5 mm) (pooled R-CIR = 1.11, 95% CI: 0.71, 1.74), two other studies showed QFT-GIT to outperform TST (≥10 mm) in identifying LTBI. In immunocompromised people, IGRA (T-SPOT.TB) was not significant different from TST (≥10 mm) for identifying LTBI, (pooled R-CIR = 1.01, 95% CI: 0.65, 1.58). The forest plot of two studies in recently arrived people from countries with high TB burden demonstrated inconsistent findings (high heterogeneity; I2 = 92%). Conclusions Prospective studies comparing IGRA testing against TST on the progression from LTBI to TB were sparse, and these results should be interpreted with caution due to uncertainty, risk of bias, and unexplained heterogeneity. Population-based studies with adequate sample size and follow-up are required to adequately compare the performance of IGRA with TST in people at high risk of TB