Approaches to the evaluation of outbreak detection methods

BACKGROUND: An increasing number of methods are being developed for the early detection of infectious disease outbreaks which could be naturally occurring or as a result of bioterrorism; however, no standardised framework for examining the usefulness of various outbreak detection methods exists. To promote comparability between studies, it is essential that standardised methods are developed for the evaluation of outbreak detection methods. METHODS: This analysis aims to review approaches used to evaluate outbreak detection methods and provide a conceptual framework upon which recommendations for standardised evaluation methods can be based. We reviewed the recently published literature for reports which evaluated methods for the detection of infectious disease outbreaks in public health surveillance data. Evaluation methods identified in the recent literature were categorised according to the presence of common features to provide a conceptual basis within which to understand current approaches to evaluation. RESULTS: There was considerable variation in the approaches used for the evaluation of methods for the detection of outbreaks in public health surveillance data, and appeared to be no single approach of choice. Four main approaches were used to evaluate performance, and these were labelled the Descriptive, Derived, Epidemiological and Simulation approaches. Based on the approaches identified, we propose a basic framework for evaluation and recommend the use of multiple approaches to evaluation to enable a comprehensive and contextualised description of outbreak detection performance. CONCLUSION: The varied nature of performance evaluation demonstrated in this review supports the need for further development of evaluation methods to improve comparability between studies. Our findings indicate that no single approach can fulfil all evaluation requirements. We propose that the cornerstone approaches to evaluation identified provide key contributions to support internal and external validity and comparability of study findings, and suggest these be incorporated into future recommendations for performance assessment

Sentinel surveillance system for early outbreak detection in Madagascar

<p>Abstract</p> <p>Background</p> <p>Following the outbreak of chikungunya in the Indian Ocean, the Ministry of Health directed the necessary development of an early outbreak detection system. A disease surveillance team including the Institut Pasteur in Madagascar (IPM) was organized to establish a sentinel syndromic-based surveillance system. The system, which was set up in March 2007, transmits patient data on a daily basis from the various voluntary general practitioners throughout the six provinces of the country to the IPM. We describe the challenges and steps involved in developing a sentinel surveillance system and the well-timed information it provides for improving public health decision-making.</p> <p>Methods</p> <p>Surveillance was based on data collected from sentinel general practitioners (SGP). The SGPs report the sex, age, visit date and time, and symptoms of each new patient weekly, using forms addressed to the management team. However, the system is original in that SGPs also report data at least once a day, from Monday to Friday (number of fever cases, rapid test confirmed malaria, influenza, arboviral syndromes or diarrhoeal disease), by cellular telephone (encrypted message SMS). Information can also be validated by the management team, by mobile phone. This data transmission costs 120 ariary per day, less than US$1 per month.</p> <p>Results</p> <p>In 2008, the sentinel surveillance system included 13 health centers, and identified 5 outbreaks. Of the 218,849 visits to SGPs, 12.2% were related to fever syndromes. Of these 26,669 fever cases, 12.3% were related to Dengue-like fever, 11.1% to Influenza-like illness and 9.7% to malaria cases confirmed by a specific rapid diagnostic test.</p> <p>Conclusion</p> <p>The sentinel surveillance system represents the first nationwide real-time-like surveillance system ever established in Madagascar. Our findings should encourage other African countries to develop their own syndromic surveillance systems.</p> <p>Prompt detection of an outbreak of infectious disease may lead to control measures that limit its impact and help prevent future outbreaks.</p

Modeling emergency department visit patterns for infectious disease complaints: results and application to disease surveillance

BACKGROUND: Concern over bio-terrorism has led to recognition that traditional public health surveillance for specific conditions is unlikely to provide timely indication of some disease outbreaks, either naturally occurring or induced by a bioweapon. In non-traditional surveillance, the use of health care resources are monitored in "near real" time for the first signs of an outbreak, such as increases in emergency department (ED) visits for respiratory, gastrointestinal or neurological chief complaints (CC). METHODS: We collected ED CCs from 2/1/94 – 5/31/02 as a training set. A first-order model was developed for each of seven CC categories by accounting for long-term, day-of-week, and seasonal effects. We assessed predictive performance on subsequent data from 6/1/02 – 5/31/03, compared CC counts to predictions and confidence limits, and identified anomalies (simulated and real). RESULTS: Each CC category exhibited significant day-of-week differences. For most categories, counts peaked on Monday. There were seasonal cycles in both respiratory and undifferentiated infection complaints and the season-to-season variability in peak date was summarized using a hierarchical model. For example, the average peak date for respiratory complaints was January 22, with a season-to-season standard deviation of 12 days. This season-to-season variation makes it challenging to predict respiratory CCs so we focused our effort and discussion on prediction performance for this difficult category. Total ED visits increased over the study period by 4%, but respiratory complaints decreased by roughly 20%, illustrating that long-term averages in the data set need not reflect future behavior in data subsets. CONCLUSION: We found that ED CCs provided timely indicators for outbreaks. Our approach led to successful identification of a respiratory outbreak one-to-two weeks in advance of reports from the state-wide sentinel flu surveillance and of a reported increase in positive laboratory test results

The antiparallel loops in gal DNA

Interactions between proteins bound to distant sites along a DNA molecule require bending and twisting deformations in the intervening DNA. In certain systems, the sterically allowed protein–DNA and protein–protein interactions are hypothesized to produce loops with distinct geometries that may also be thermodynamically and biologically distinct. For example, theoretical models of Gal repressor/HU-mediated DNA-looping suggest that the antiparallel DNA loops, A1 and A2, are thermodynamically quite different. They are also biologically different, since in experiments using DNA molecules engineered to form only one of the two loops, the A2 loop failed to repress in vitro transcription. Surprisingly, single molecule measurements show that both loop trajectories form and that they appear to be quite similar energetically and kinetically

Early Detection of Tuberculosis Outbreaks among the San Francisco Homeless: Trade-Offs Between Spatial Resolution and Temporal Scale

BACKGROUND: San Francisco has the highest rate of tuberculosis (TB) in the U.S. with recurrent outbreaks among the homeless and marginally housed. It has been shown for syndromic data that when exact geographic coordinates of individual patients are used as the spatial base for outbreak detection, higher detection rates and accuracy are achieved compared to when data are aggregated into administrative regions such as zip codes and census tracts. We examine the effect of varying the spatial resolution in the TB data within the San Francisco homeless population on detection sensitivity, timeliness, and the amount of historical data needed to achieve better performance measures. METHODS AND FINDINGS: We apply a variation of space-time permutation scan statistic to the TB data in which a patient's location is either represented by its exact coordinates or by the centroid of its census tract. We show that the detection sensitivity and timeliness of the method generally improve when exact locations are used to identify real TB outbreaks. When outbreaks are simulated, while the detection timeliness is consistently improved when exact coordinates are used, the detection sensitivity varies depending on the size of the spatial scanning window and the number of tracts in which cases are simulated. Finally, we show that when exact locations are used, smaller amount of historical data is required for training the model. CONCLUSION: Systematic characterization of the spatio-temporal distribution of TB cases can widely benefit real time surveillance and guide public health investigations of TB outbreaks as to what level of spatial resolution results in improved detection sensitivity and timeliness. Trading higher spatial resolution for better performance is ultimately a tradeoff between maintaining patient confidentiality and improving public health when sharing data. Understanding such tradeoffs is critical to managing the complex interplay between public policy and public health. This study is a step forward in this direction

Development of Trypanosoma cruzi in vitro assays to identify compounds suitable for progression in Chagas’ disease drug discovery

Chagas' disease is responsible for significant mortality and morbidity in Latin America. Current treatments display variable efficacy and have adverse side effects, hence more effective, better tolerated drugs are needed. However, recent efforts have proved unsuccessful with failure of the ergosterol biosynthesis inhibitor posaconazole in phase II clinical trials despite promising in vitro and in vivo studies. The lack of translation between laboratory experiments and clinical outcome is a major issue for further drug discovery efforts. Our goal was to identify cell-based assays that could differentiate current nitro-aromatic drugs nifurtimox and benznidazole from posaconazole. Using a panel of T. cruzi strains including the six major lineages (TcI-VI), we found that strain PAH179 (TcV) was markedly less susceptible to posaconazole in vitro. Determination of parasite doubling and cycling times as well as EdU labelling experiments all indicate that this lack of sensitivity is due to the slow doubling and cycling time of strain PAH179. This is in accordance with ergosterol biosynthesis inhibition by posaconazole leading to critically low ergosterol levels only after multiple rounds of division, and is further supported by the lack of effect of posaconazole on the non-replicative trypomastigote form. A washout experiment with prolonged posaconazole treatment showed that, even for more rapidly replicating strains, this compound cannot clear all parasites, indicative of a heterogeneous parasite population in vitro and potentially the presence of quiescent parasites. Benznidazole in contrast was able to kill all parasites. The work presented here shows clear differentiation between the nitro-aromatic drugs and posaconazole in several assays, and suggests that in vitro there may be clinically relevant heterogeneity in the parasite population that can be revealed in long-term washout experiments. Based on these findings we have adjusted our in vitro screening cascade so that only the most promising compounds are progressed to in vivo experiments

Studying the Underlying Event in Drell-Yan and High Transverse Momentum Jet Production at the Tevatron

We study the underlying event in proton-antiproton collisions by examining the behavior of charged particles (transverse momentum pT > 0.5 GeV/c, pseudorapidity |\eta| < 1) produced in association with large transverse momentum jets (~2.2 fb-1) or with Drell-Yan lepton-pairs (~2.7 fb-1) in the Z-boson mass region (70 < M(pair) < 110 GeV/c2) as measured by CDF at 1.96 TeV center-of-mass energy. We use the direction of the lepton-pair (in Drell-Yan production) or the leading jet (in high-pT jet production) in each event to define three regions of \eta-\phi space; toward, away, and transverse, where \phi is the azimuthal scattering angle. For Drell-Yan production (excluding the leptons) both the toward and transverse regions are very sensitive to the underlying event. In high-pT jet production the transverse region is very sensitive to the underlying event and is separated into a MAX and MIN transverse region, which helps separate the hard component (initial and final-state radiation) from the beam-beam remnant and multiple parton interaction components of the scattering. The data are corrected to the particle level to remove detector effects and are then compared with several QCD Monte-Carlo models. The goal of this analysis is to provide data that can be used to test and improve the QCD Monte-Carlo models of the underlying event that are used to simulate hadron-hadron collisions.Comment: Submitted to Phys.Rev.

Measurement of the Dipion Mass Spectrum in X(3872) -> J/Psi Pi+ Pi- Decays

We measure the dipion mass spectrum in X(3872)--> J/Psi Pi+ Pi- decays using 360 pb-1 of pbar-p collisions at 1.96 TeV collected with the CDF II detector. The spectrum is fit with predictions for odd C-parity (3S1, 1P1, and 3DJ) charmonia decaying to J/Psi Pi+ Pi-, as well as even C-parity states in which the pions are from Rho0 decay. The latter case also encompasses exotic interpretations, such as a D0-D*0Bar molecule. Only the 3S1 and J/Psi Rho hypotheses are compatible with our data. Since 3S1 is untenable on other grounds, decay via J/Psi Rho is favored, which implies C=+1 for the X(3872). Models for different J/Psi-Rho angular momenta L are considered. Flexibility in the models, especially the introduction of Rho-Omega interference, enable good descriptions of our data for both L=0 and 1.Comment: 7 pages, 4 figures -- Submitted to Phys. Rev. Let

Epidemiology of severe pediatric adenovirus lower respiratory tract infections in Manitoba, Canada, 1991-2005

<p>Abstract</p> <p>Background</p> <p>Most pediatric adenovirus respiratory infections are mild and indistinguishable from other viral causes. However, in a few children, the disease can be severe and result in substantial morbidity. We describe the epidemiologic, clinical, radiologic features and outcome of adenovirus lower respiratory tract infections (LRTI) in Aboriginal and Non-Aboriginal children in Manitoba, Canada during the years 1991 and 2005.</p> <p>Methods</p> <p>This was a retrospective study of 193 children who presented to the department of pediatrics at Winnipeg Children's Hospital, Manitoba, Canada with LRTI and had a positive respiratory culture for adenovirus. Patients' demographics, clinical and radiologic features and outcomes were collected. Adenovirus serotype distributions and temporal associations were described. Approximate incidence comparisons (detection rates) of adenovirus LRTI among Aboriginal and Non-Aboriginal children were estimated with 95% confidence intervals.</p> <p>Results</p> <p>Adenovirus infections occurred throughout the year with clusters in the fall and winter. Serotypes 1 to 3 were the predominant isolates (two thirds of the cases). The infection was more frequent among Canadian Aboriginals, as illustrated in 2004, where its incidence in children 0-4 years old was 5.6 fold higher in Aboriginals (13.51 vs. 2.39 per 10,000, <it>p </it>< 0.000). There were no significant differences in length of hospitalization and use of ventilator assistance between the two groups (<it>p </it>> 0.185 and <it>p </it>> 0.624, respectively) nor across serotypes (<it>p </it>> 0.10 and <it>p </it>> 0.05, respectively). The disease primarily affected infants (median age, 9.5 months). Most children presented with bronchiolitis or pneumonia, with multi-lobar consolidations on the chest x-ray. Chronic (residual) changes were documented in 16 patients, with eight patients showing bronchiectasis on the chest computerized tomography scan.</p> <p>Conclusions</p> <p>Adenovirus infection is associated with significant respiratory morbidities, especially in young infants. The infection appears to be more frequent in Aboriginal children. These results justify a careful follow-up for children with adenovirus LRTI.</p