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      A New Framework and Software to Estimate Time-Varying Reproduction Numbers During Epidemics

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          Abstract

          The quantification of transmissibility during epidemics is essential to designing and adjusting public health responses. Transmissibility can be measured by the reproduction number R, the average number of secondary cases caused by an infected individual. Several methods have been proposed to estimate R over the course of an epidemic; however, they are usually difficult to implement for people without a strong background in statistical modeling. Here, we present a ready-to-use tool for estimating R from incidence time series, which is implemented in popular software including Microsoft Excel (Microsoft Corporation, Redmond, Washington). This tool produces novel, statistically robust analytical estimates of R and incorporates uncertainty in the distribution of the serial interval (the time between the onset of symptoms in a primary case and the onset of symptoms in secondary cases). We applied the method to 5 historical outbreaks; the resulting estimates of R are consistent with those presented in the literature. This tool should help epidemiologists quantify temporal changes in the transmission intensity of future epidemics by using surveillance data.

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          Most cited references45

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          Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study

          Summary Background We investigated the temporal progression of the clinical, radiological, and virological changes in a community outbreak of severe acute respiratory syndrome (SARS). Methods We followed up 75 patients for 3 weeks managed with a standard treatment protocol of ribavirin and corticosteroids, and assessed the pattern of clinical disease, viral load, risk factors for poor clinical outcome, and the usefulness of virological diagnostic methods. Findings Fever and pneumonia initially improved but 64 (85%) patients developed recurrent fever after a mean of 8.9 (SD 3.1) days, 55 (73%) had watery diarrhoea after 7.5 (2.3) days, 60 (80%) had radiological worsening after 7.4 (2.2) days, and respiratory symptoms worsened in 34 (45%) after 8.6 (3.0) days. In 34 (45%) patients, improvement of initial pulmonary lesions was associated with appearance of new radiological lesions at other sites. Nine (12%) patients developed spontaneous pneumomediastinum and 15 (20%) developed acute respiratory distress syndrome (ARDS) in week 3. Quantitative reverse-transcriptase (RT) PCR of nasopharyngeal aspirates in 14 patients (four with ARDS) showed peak viral load at day 10, and at day 15 a load lower than at admission. Age and chronic hepatitis B virus infection treated with lamivudine were independent significant risk factors for progression to ARDS (p=0.001). SARS-associated coronavirus in faeces was seen on RT-PCR in 65 (97%) of 67 patients at day 14. The mean time to seroconversion was 20 days. Interpretation The consistent clinical progression, shifting radiological infiltrates, and an inverted V viral-load profile suggest that worsening in week 2 is unrelated to uncontrolled viral replication but may be related to immunopathological damage. Published online May 9, 2003 http://image.thelancet.com/extras/03art4432web.pdf
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            A major outbreak of severe acute respiratory syndrome in Hong Kong.

            There has been an outbreak of the severe acute respiratory syndrome (SARS) worldwide. We report the clinical, laboratory, and radiologic features of 138 cases of suspected SARS during a hospital outbreak in Hong Kong. From March 11 to 25, 2003, all patients with suspected SARS after exposure to an index patient or ward were admitted to the isolation wards of the Prince of Wales Hospital. Their demographic, clinical, laboratory, and radiologic characteristics were analyzed. Clinical end points included the need for intensive care and death. Univariate and multivariate analyses were performed. There were 66 male patients and 72 female patients in this cohort, 69 of whom were health care workers. The most common symptoms included fever (in 100 percent of the patients); chills, rigors, or both (73.2 percent); and myalgia (60.9 percent). Cough and headache were also reported in more than 50 percent of the patients. Other common findings were lymphopenia (in 69.6 percent), thrombocytopenia (44.8 percent), and elevated lactate dehydrogenase and creatine kinase levels (71.0 percent and 32.1 percent, respectively). Peripheral air-space consolidation was commonly observed on thoracic computed tomographic scanning. A total of 32 patients (23.2 percent) were admitted to the intensive care unit; 5 patients died, all of whom had coexisting conditions. In a multivariate analysis, the independent predictors of an adverse outcome were advanced age (odds ratio per decade of life, 1.80; 95 percent confidence interval, 1.16 to 2.81; P=0.009), a high peak lactate dehydrogenase level (odds ratio per 100 U per liter, 2.09; 95 percent confidence interval, 1.28 to 3.42; P=0.003), and an absolute neutrophil count that exceeded the upper limit of the normal range on presentation (odds ratio, 1.60; 95 percent confidence interval, 1.03 to 2.50; P=0.04). SARS is a serious respiratory illness that led to significant morbidity and mortality in our cohort. Copyright 2003 Massachusetts Medical Society
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              Strategies for mitigating an influenza pandemic

              Pandemic flu: talking tactics Numerical models of the epidemiology of a potential flu pandemic show there is no single magic bullet which can control the outbreak, but that a combination of approaches could reduce transmission and save many lives. Border restrictions are unlikely to have much effect and travel restrictions within one country would make very little difference to the spread of a pandemic within that country. The models predict that a pandemic in the United Kingdom would peak within two to three months of the first case, and be over within 4 months. It also shows that vaccines need to be available within two months of the start of a pandemic to have a big effect in reducing infection rates. That means that vaccines would need to be stockpiled in advance to be effective. Supplementary information The online version of this article (doi:10.1038/nature04795) contains supplementary material, which is available to authorized users.
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                Author and article information

                Journal
                Am J Epidemiol
                Am. J. Epidemiol
                aje
                amjepid
                American Journal of Epidemiology
                Oxford University Press
                0002-9262
                1476-6256
                1 November 2013
                15 September 2013
                : 178
                : 9
                : 1505-1512
                Author notes
                [* ]Correspondence to Dr. Anne Cori, Department of Infectious Disease Epidemiology, MRC Centre for Outbreak Analysis and Modelling, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom (e-mail: a.cori@ 123456imperial.ac.uk ).

                Abbreviations: CI, credible interval; SARS, severe acute respiratory syndrome.

                Article
                kwt133
                10.1093/aje/kwt133
                3816335
                24043437
                157faf01-595e-4095-ba54-f276e35161dc
                © The Author 2013. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                History
                : 26 November 2012
                : 23 May 2013
                Categories
                Practice of Epidemiology

                Public health
                incidence,influenza,measles,reproduction number,sars,smallpox,software
                Public health
                incidence, influenza, measles, reproduction number, sars, smallpox, software

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