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Zecchin B, Marco DN, Nouvellet P, et al., 2019, Genetic and spatial characterization of the red fox (Vulpes vulpes) population in the area stretching between the Eastern and Dinaric Alps and its relationship with rabies and canine distemper dynamics, PLoS ONE, Vol: 14, ISSN: 1932-6203
Information on the population dynamics of a reservoir species have been increasingly adopted to understand and eventually predict the dispersal patterns of infectious diseases throughout an area. Although potentially relevant, to date there are no studies which have investigated the genetic structure of the red fox population in relation to infectious disease dynamics. Therefore, we genetically and spatially characterised the red fox population in the area stretching between the Eastern and Dinaric Alps, which has been affected by both distemper and rabies at different time intervals. Red foxes collected from north-eastern Italy, Austria, Slovenia and Croatia between 2006–2012, were studied using a set of 21 microsatellite markers. We confirmed a weak genetic differentiation within the fox population using Bayesian clustering analyses, and we were able to differentiate the fox population into geographically segregated groups. Our finding might be due to the presence of geographical barriers that have likely influenced the distribution of the fox population, limiting in turn gene flow and spread of infectious diseases. Focusing on the Italian red fox population, we observed interesting variations in the prevalence of both diseases among distinct fox clusters, with the previously identified Italy 1 and Italy 2 rabies as well as distemper viruses preferentially affecting different sub-groups identified in the study. Knowledge of the regional-scale population structure can improve understanding of the epidemiology and spread of diseases. Our study paves the way for an integrated approach for disease control coupling pathogen, host and environmental data to inform targeted control programs in the future.
Forna A, Nouvellet P, Dorigatti I, et al., 2019, Case fatality ratio estimates for the 2013-2016 West African Ebola epidemic: application of Boosted Regression Trees for imputation, Publisher: ELSEVIER SCI LTD, Pages: 128-128, ISSN: 1201-9712
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Suwannahitatorn P, Webster J, Riley S, et al., 2019, Uncooked fish consumption among those at risk of Opisthorchis viverrini infection in central Thailand, PLoS ONE, Vol: 14, Pages: 1-13, ISSN: 1932-6203
In contrast to northern and northeastern Thailand, central Thailand was believed not to be endemic for Opisthorchis viverrini (OV). Fieldwork conducted in a rural area of central Thailand revealed that the prevalence and incidence were relatively high compared with regional average data. We hypothesized that the behavioural-psycho-social background of the study population might play an important role in the high burden of the infection. As a result, a qualitative study was conducted to highlight potential social determinants of the infection dynamics to gain greater understanding of the risk behaviours and their contexts. A qualitative study using focus group discussion and in-depth interviews was conducted in Na-ngam Village, Chachoengsao Province from 2012–14. Framework analysis was used to explore associations between infection and thematic content. Social influence showed a strong impact on infection dynamics of OV infection. Our results revealed that Koi pla (chopped raw fish salad) remains a popular dish in the community, as the dish itself represents northeastern culture. The cultural norm had been transferred from ancestors to their descendants. Some elders complained that discontinuing the consumption of Koi pla went against old traditions with respect to cultural norms and socialization. In contrast, modern education teaches about hygiene including OV infection risks, and accordingly teenagers and young adults were reported to modify their lifestyles including their eating habits. Children are a potential key to pass knowledge to their parents and school-based education programs can serve as a practical hub for knowledge dissemination. However, health education alone might not lead to behavioural change in other age groups. Therefore, more efforts are needed to support the transformation.
Eneanya OA, Fronterre C, Anagbogu I, et al., 2019, MAPPING THE PRE-CONTROL PREVALENCE OF LYMPHATIC FILARIASIS ACROSS NIGERIA, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 557-558, ISSN: 0002-9637
Hay JA, Nouvellet P, Donnelly CA, et al., 2018, Potential inconsistencies in Zika surveillance data and our understanding of risk during pregnancy, PLoS Neglected Tropical Diseases, Vol: 12, ISSN: 1935-2727
BackgroundA significant increase in microcephaly incidence was reported in Northeast Brazil at the end of 2015, which has since been attributed to an epidemic of Zika virus (ZIKV) infections earlier that year. Further incidence of congenital Zika syndrome (CZS) was expected following waves of ZIKV infection throughout Latin America; however, only modest increases in microcephaly and CZS incidence have since been observed. The quantitative relationship between ZIKV infection, gestational age and congenital outcome remains poorly understood.Methodology/Principle findingsWe characterised the gestational-age-varying risk of microcephaly given ZIKV infection using publicly available incidence data from multiple locations in Brazil and Colombia. We found that the relative timings and shapes of ZIKV infection and microcephaly incidence curves suggested different gestational risk profiles for different locations, varying in both the duration and magnitude of gestational risk. Data from Northeast Brazil suggested a narrow window of risk during the first trimester, whereas data from Colombia suggested persistent risk throughout pregnancy. We then used the model to estimate which combination of behavioural and reporting changes would have been sufficient to explain the absence of a second microcephaly incidence wave in Bahia, Brazil; a population for which we had two years of data. We found that a 18.9-fold increase in ZIKV infection reporting rate was consistent with observed patterns.ConclusionsOur study illustrates how surveillance data may be used in principle to answer key questions in the absence of directed epidemiological studies. However, in this case, we suggest that currently available surveillance data are insufficient to accurately estimate the gestational-age-varying risk of microcephaly from ZIKV infection. The methods used here may be of use in future outbreaks and may help to inform improved surveillance and interpretation in countries yet to experience an out
Rawaf S, 2018, Erratum: Department of error., The Lancet, Vol: 392, Pages: 2170-2170, ISSN: 0140-6736
[This corrects the article DOI: 10.1016/S0140-6736(18)32203-7.].
Roth GA, Abate D, Abate KH, et al., 2018, Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017, The Lancet, Vol: 392, Pages: 1736-1788, ISSN: 0140-6736
BackgroundGlobal development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017.MethodsThe causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries—Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised.FindingsAt the broadest grouping of causes of death (Level 1), non-communicable diseases (NCDs) comprised the greatest f
Dicker D, Nguyen G, Abate D, et al., 2018, Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017, The Lancet, Vol: 392, Pages: 1684-1735, ISSN: 0140-6736
BackgroundAssessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally.MethodsThe GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different compone
Eneanya OA, Cano J, Dorigatti I, et al., 2018, Environmental suitability for lymphatic filariasis in Nigeria, Parasites & Vectors, Vol: 11, ISSN: 1756-3305
BackgroundLymphatic filariasis (LF) is a mosquito-borne parasitic disease and a major cause of disability worldwide. It is one of the neglected tropical diseases identified by the World Health Organization for elimination as a public health problem by 2020. Maps displaying disease distribution are helpful tools to identify high-risk areas and target scarce control resources.MethodsWe used pre-intervention site-level occurrence data from 1192 survey sites collected during extensive mapping surveys by the Nigeria Ministry of Health. Using an ensemble of machine learning modelling algorithms (generalised boosted models and random forest), we mapped the ecological niche of LF at a spatial resolution of 1 km2. By overlaying gridded estimates of population density, we estimated the human population living in LF risk areas on a 100 × 100 m scale.ResultsOur maps demonstrate that there is a heterogeneous distribution of LF risk areas across Nigeria, with large portions of northern Nigeria having more environmentally suitable conditions for the occurrence of LF. Here we estimated that approximately 110 million individuals live in areas at risk of LF transmission.ConclusionsMachine learning and ensemble modelling are powerful tools to map disease risk and are known to yield more accurate predictive models with less uncertainty than single models. The resulting map provides a geographical framework to target control efforts and assess its potential impacts.
Dorigatti I, Donnelly C, Laydon D, et al., 2018, Refined efficacy estimates of the Sanofi Pasteur dengue vaccine CYD-TDV using machine learning, Nature Communications, Vol: 9, ISSN: 2041-1723
CYD-TDV is the first licensed dengue vaccine for individuals 9–45 (or 60) years of age. Using 12% of the subjects enroled in phase-2b and phase-3 trials for which baseline serostatus was measured, the vaccine-induced protection against virologically confirmed dengue during active surveillance (0–25 months) was found to vary with prior exposure to dengue. Because age and dengue exposure are highly correlated in endemic settings, refined insight into how efficacy varies by serostatus and age is essential to understand the increased risk of hospitalisation observed among vaccinated individuals during the long-term follow-up and to develop safe and effective vaccination strategies. Here we apply machine learning to impute the baseline serostatus for subjects with post-dose 3 titres but missing baseline serostatus. We find evidence for age dependence in efficacy independent of serostatus and estimate that among 9–16 year olds, CYD-TDV is protective against serotypes 1, 3 and 4 regardless of baseline serostatus.
Anders K, Cutcher Z, Kleinschmidt I, et al., 2018, Cluster randomized test-negative design (CR-TND) trials: a novel and efficient method to assess the efficacy of community level dengue interventions, American Journal of Epidemiology, Vol: 187, Pages: 2021-2028, ISSN: 1476-6256
Cluster randomized trials are the gold standard for assessing efficacy of community-level interventions, such as vector control strategies against dengue. We describe a novel cluster randomized trial methodology with a test-negative design, which offers advantages over traditional approaches. It utilizes outcome-based sampling of patients presenting with a syndrome consistent with the disease of interest, who are subsequently classified as test-positive cases or test-negative controls on the basis of diagnostic testing. We use simulations of a cluster trial to demonstrate validity of efficacy estimates under the test-negative approach. This demonstrates that, provided study arms are balanced for both test-negative and test-positive illness at baseline and that other test-negative design assumptions are met, the efficacy estimates closely match true efficacy. We also briefly discuss analytical considerations for an odds ratio-based effect estimate arising from clustered data, and outline potential approaches to analysis. We conclude that application of the test-negative design to certain cluster randomized trials could increase their efficiency and ease of implementation.
Moraga P, Dorigatti I, Kamvar Z, et al., 2018, epiflows : an R package for risk assessment of travel- related spread of disease [version 1; referees: 2 approved with reservations], F1000Research, Vol: 7, ISSN: 2046-1402
As international travel increases worldwide, new surveillance tools are needed to help identify locations where diseases are most likely to be spread and prevention measures need to be implemented. In this paper we present epiflows, an R package for risk assessment of travel-related spread of disease. epiflows produces estimates of the expected number of symptomatic and/or asymptomatic infections that could be introduced to other locations from the source of infection. Estimates (average and confidence intervals) of the number of infections introduced elsewhere are obtained by integrating data on the cumulative number of cases reported, population movement, length of stay and information on the distributions of the incubation and infectious periods of the disease. The package also provides tools for geocoding and visualization. We illustrate the use of epiflows by assessing the risk of travel-related spread of yellow fever cases in Southeast Brazil in December 2016 to May 2017.
Donnelly CA, Garske T, 2018, How deadly is Ebola?, Biomedical Science Journal for teens
The Ebola Outbreak Epidemiology Team, Bhatia S, Cori A, et al., 2018, Outbreak of Ebola virus disease in the Democratic Republic of the Congo, April–May, 2018: an epidemiological study, The Lancet, Vol: 392, Pages: 213-221, ISSN: 0140-6736
BackgroundOn May 8, 2018, the Government of the Democratic Republic of the Congo reported an outbreak of Ebola virus disease in Équateur Province in the northwest of the country. The remoteness of most affected communities and the involvement of an urban centre connected to the capital city and neighbouring countries makes this outbreak the most complex and high risk ever experienced by the Democratic Republic of the Congo. We provide early epidemiological information arising from the ongoing investigation of this outbreak.MethodsWe classified cases as suspected, probable, or confirmed using national case definitions of the Democratic Republic of the Congo Ministère de la Santé Publique. We investigated all cases to obtain demographic characteristics, determine possible exposures, describe signs and symptoms, and identify contacts to be followed up for 21 days. We also estimated the reproduction number and projected number of cases for the 4-week period from May 25, to June 21, 2018.FindingsAs of May 30, 2018, 50 cases (37 confirmed, 13 probable) of Zaire ebolavirus were reported in the Democratic Republic of the Congo. 21 (42%) were reported in Bikoro, 25 (50%) in Iboko, and four (8%) in Wangata health zones. Wangata is part of Mbandaka, the urban capital of Équateur Province, which is connected to major national and international transport routes. By May 30, 2018, 25 deaths from Ebola virus disease had been reported, with a case fatality ratio of 56% (95% CI 39–72) after adjustment for censoring. This case fatality ratio is consistent with estimates for the 2014–16 west African Ebola virus disease epidemic (p=0·427). The median age of people with confirmed or probable infection was 40 years (range 8–80) and 30 (60%) were male. The most commonly reported signs and symptoms in people with confirmed or probable Ebola virus disease were fever (40 [95%] of 42 cases), intense general fatigue (37 [90%] of 41 cases), an
Donnelly CA, Boyd I, Campbell P, et al., 2018, Four principles for synthesizing evidence, NATURE, Vol: 558, Pages: 361-364, ISSN: 0028-0836
Calder M, Craig C, Culley D, et al., 2018, Computational modelling for decision-making: where, why, what, who and how, Royal Society Open Science, Vol: 5, ISSN: 2054-5703
In order to deal with an increasingly complex world, we need ever more sophisticated computational models that can help us make decisions wisely and understand the potential consequences of choices. But creating a model requires far more than just raw data and technical skills: it requires a close collaboration between model commissioners, developers, users and reviewers. Good modelling requires its users and commissioners to understand more about the whole process, including the different kinds of purpose a model can have and the different technical bases. This paper offers a guide to the process of commissioning, developing and deploying models across a wide range of domains from public policy to science and engineering. It provides two checklists to help potential modellers, commissioners and users ensure they have considered the most significant factors that will determine success. We conclude there is a need to reinforce modelling as a discipline, so that misconstruction is less likely; to increase understanding of modelling in all domains, so that the misuse of models is reduced; and to bring commissioners closer to modelling, so that the results are more useful.
Radhakrishnan S, Tamim Vanak A, Nouvellet P, et al., 2018, A question of accessibility: modelling the effects of demography and accessibility for vaccination on elimination of rabies in free-ranging dog populations in India., 16th conference on Ecology and Evolution of Infectious Diseases
A key strategy for achieving the WHO global target of zero human dog-mediated rabies deaths by 2030 is massrabies vaccination of free-ranging dog populations, the primary rabies reservoir in endemic nations. AlthoughIndia accounts for the highest burden of dog-mediated human rabies deaths, very little is known about freerangingdog ecology, demography, ownership or accessibility for vaccination. Experience from mass sterilisationcampaigns in the state of Kerala suggests that a significant proportion of free-ranging dogs are difficult to accessfor capture or handling, raising concerns about the feasibility of achieving the WHO-recommended 70%vaccination coverage for rabies elimination. This study reports results from mathematical models of rabiestransmission and control that are being built to inform fieldwork in India. The effects of varying demography,accessibility for vaccination and duration of immunity on rabies persistence and prospects for elimination will bepresented, and potential strategies for expanding coverage discussed.
Woodroffe R, Donnelly CA, 2018, European badgers and the control of bovine tuberculosis in the United Kingdom, Biology and Conservation of Musteloids, Pages: 410-419, ISBN: 9780198759812
The European badger has become infamous because of its incompletely understood role in the spread of bovive tuberculosis to cattle, despite in actuality being directly implicated in only 5.7% of herd breakdowns. Randomised Badger culling trial data suggest that badger culling could make only a limited contribution to TB eradication in Britain. Surviving badgers in both proactive and reactive culling areas immigrate into the surrounding area, which generally worsens the rate of cattle herd breakdowns by around 25% in these areas. While badger vaccination appears promising as a potential TB control tool, there is not yet sufficient evidence to judge its effectiveness. Free shooting of badgers has proven less effective than hoped, failing to reach cull targets. Furthermore, instances of badger suffering have been reported. Consequently, controlling TB through badger management remains technically, ethically and politically challenging and alternative approaches directed at cattle are likely to be more effective.
Charniga K, Cucunuba Z, Mercado M, et al., 2018, SPATIAL AND TEMPORAL SPREAD OF ZIKA AND CHIKUNGUNYA VIRUSES IN COLOMBIA, A GRAVITY-MODEL BASED APPROACH, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 305-305, ISSN: 0002-9637
Eneanya O, Cano J, Garske T, et al., 2018, ENVIRONMENTAL SUITABILITY FOR LYMPHATIC FILARIASIS IN NIGERIA, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 391-391, ISSN: 0002-9637
Clements MN, Donnelly CA, Fenwick A, et al., 2017, Interpreting ambiguous 'trace' results in Schistosoma mansoni CCA tests: estimating sensitivity and specificity of ambiguous results with no gold standard, PLoS Neglected Tropical Diseases, Vol: 11, ISSN: 1935-2727
BackgroundThe development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results.Methodology/Principle findingsWe show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d’Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population.Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries.ConclusionsIncorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence.
Pinsent A, Qureshi U, Donnelly C, et al., 2017, THE INCUBATION PERIOD OF MALARIA AMONGST TRAVELERS RETURNING TO THE UK, 65th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 311-311, ISSN: 0002-9637
Wang H, Abajobir A, Abate KH, et al., 2017, Global, regional, and national under-5 mortality, adultmortality, age-specific mortality, and life expectancy,1970–2016: a systematic analysis for the Global Burden ofDisease Study 2016, The Lancet, Vol: 390, Pages: 1084-1150, ISSN: 0140-6736
BackgroundDetailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016.MethodsWe have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15–60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to
Brunton LA, Donnelly CA, O'Connor H, et al., 2017, Assessing the effects of the first 2 years of industry-led badger culling in England on the incidence of bovine tuberculosis in cattle in 2013–2015, Ecology and Evolution, Vol: 7, Pages: 7213-7230, ISSN: 2045-7758
Culling badgers to control the transmission of bovine tuberculosis (TB) between this wildlife reservoir and cattle has been widely debated. Industry-led culling began in Somerset and Gloucestershire between August and November 2013 to reduce local badger populations. Industry-led culling is not designed to be a randomised and controlled trial of the impact of culling on cattle incidence. Nevertheless, it is important to monitor the effects of the culling and, taking the study limitations into account, perform a cautious evaluation of the impacts. A standardised method for selecting areas matched to culling areas in factors found to affect cattle TB risk has been developed to evaluate the impact of badger culling on cattle TB incidence. The association between cattle TB incidence and badger culling in the first two years has been assessed. Descriptive analyses without controlling for confounding showed no association between culling and TB incidence for Somerset, or for either of the buffer areas for the first two years since culling began. A weak association was observed in Gloucestershire for Year 1 only. Multivariable analysis adjusting for confounding factors showed that reductions in TB incidence were associated with culling in the first two years in both the Somerset and Gloucestershire intervention areas when compared to areas with no culling (IRR: 0.79, 95%CI: 0.72-0.87, p<0.001 and IRR: 0.42, 95%CI: 0.34-0.51, p<0.001 respectively). An increase in incidence was associated with culling in the 2 km buffer surrounding the Somerset intervention area (IRR: 1.38, 95%CI: 1.09-1.75, p=0.008), but not in Gloucestershire (IRR: 0.91, 95%CI: 0.77-1.07, p=0.243). As only two intervention areas with two years’ of data are available for analysis, and the biological cause-effect relationship behind the statistical associations is difficult to determine, it would be unwise to use the
Dorigatti I, Hamlet A, Aguas R, et al., 2017, International risk of yellow fever spread from the ongoing outbreak in Brazil, December 2016 to May 2017, EUROSURVEILLANCE, Vol: 22, Pages: 1-4, ISSN: 1560-7917
States in south-eastern Brazil were recently affected by the largest Yellow Fever (YF) outbreak seen in a decade in Latin America. Here we provide a quantitative assessment of the risk of travel-related international spread of YF indicating that the United States, Argentina, Uruguay, Spain, Italy and Germany may have received at least one travel-related YF case capable of seeding local transmission. Mitigating the risk of imported YF cases seeding local transmission requires heightened surveillance globally.
Cori A, Donnelly CA, dorigatti, et al., 2017, Key data for outbreak evaluation: building on the Ebola experience, Philosophical Transactions of the Royal Society B: Biological Sciences, Vol: 372, ISSN: 1471-2970
Following the detection of an infectious disease outbreak, rapid epidemiological assessmentis critical to guidean effectivepublic health response. To understand the transmission dynamics and potential impact of an outbreak, several types of data are necessary. Here we build on experience gained inthe West AfricanEbolaepidemic and prior emerging infectious disease outbreaksto set out a checklist of data needed to: 1) quantify severity and transmissibility;2) characterise heterogeneities in transmission and their determinants;and 3) assess the effectiveness of different interventions.We differentiate data needs into individual-leveldata (e.g. a detailed list of reported cases), exposure data(e.g.identifying where / howcases may have been infected) and populationlevel data (e.g.size/demographicsof the population(s)affected andwhen/where interventions were implemented). A remarkable amount of individual-level and exposuredata was collected during the West African Ebola epidemic, which allowed the assessment of (1) and (2). However,gaps in population-level data (particularly around which interventions were applied whenand where)posed challenges to the assessment of (3).Herewehighlight recurrent data issues, give practical suggestions for addressingthese issues and discuss priorities for improvements in data collection in future outbreaks.
Garske T, Cori A, Ariyarajah A, et al., 2017, Heterogeneities in the case fatality ratio in the West African Ebola outbreak 2013 – 2016, Philosophical Transactions of the Royal Society B: Biological Sciences, Vol: 372, ISSN: 1471-2970
The 2013–2016 Ebola outbreak in West Africa is the largest on record with 28 616 confirmed, probable and suspected cases and 11 310 deaths officially recorded by 10 June 2016, the true burden probably considerably higher. The case fatality ratio (CFR: proportion of cases that are fatal) is a key indicator of disease severity useful for gauging the appropriate public health response and for evaluating treatment benefits, if estimated accurately. We analysed individual-level clinical outcome data from Guinea, Liberia and Sierra Leone officially reported to the World Health Organization. The overall mean CFR was 62.9% (95% CI: 61.9% to 64.0%) among confirmed cases with recorded clinical outcomes. Age was the most important modifier of survival probabilities, but country, stage of the epidemic and whether patients were hospitalized also played roles. We developed a statistical analysis to detect outliers in CFR between districts of residence and treatment centres (TCs), adjusting for known factors influencing survival and identified eight districts and three TCs with a CFR significantly different from the average. From the current dataset, we cannot determine whether the observed variation in CFR seen by district or treatment centre reflects real differences in survival, related to the quality of care or other factors or was caused by differences in reporting practices or case ascertainment.
Dawkins MS, Roberts SJ, Cain RJ, et al., 2017, Early warning of footpad dermatitis and hockburn in broiler chicken flocks using optical flow, bodyweight and water consumption, VETERINARY RECORD, Vol: 180, ISSN: 0042-4900
Footpad dermatitis and hockburn are serious welfare and economic issues for the production of broiler (meat) chickens. The authors here describe the use of an inexpensive camera system that monitors the movements of broiler flocks throughout their lives and suggest that it is possible to predict, even in young birds, the cross-sectional prevalence at slaughter of footpad dermatitis and hockburn before external signs are visible. The skew and kurtosis calculated from the authors’ camera-based optical flow system had considerably more power to predict these outcomes in the 50 flocks reported here than water consumption, bodyweight or mortality and therefore have the potential to inform improved flock management through giving farmers early warning of welfare issues. Further trials are underway to establish the generality of the results.
Nouvellet P, Cori A, Garske T, et al., 2017, A simple approach to measure transmissibility and forecast incidence, Epidemics, Vol: 22, Pages: 29-35, ISSN: 1755-4365
Outbreaks of novel pathogens such as SARS, pandemic influenza and Ebola require substantial investments in reactive interventions, with consequent implementation plans sometimes revised on a weekly basis. Therefore, short-term forecasts of incidence are often of high priority. In light of the recent Ebola epidemic in West Africa, a forecasting exercise was convened by a network of infectious disease modellers. The challenge was to forecast unseen “future” simulated data for four different scenarios at five different time points. In a similar method to that used during the recent Ebola epidemic, we estimated current levels of transmissibility, over variable time-windows chosen in an ad hoc way. Current estimated transmissibility was then used to forecast near-future incidence. We performed well within the challenge and often produced accurate forecasts. A retrospective analysis showed that our subjective method for deciding on the window of time with which to estimate transmissibility often resulted in the optimal choice. However, when near-future trends deviated substantially from exponential patterns, the accuracy of our forecasts was reduced. This exercise highlights the urgent need for infectious disease modellers to develop more robust descriptions of processes – other than the widespread depletion of susceptible individuals – that produce non-exponential patterns of incidence.
Anderson R, Farrell S, Turner H, et al., 2017, Assessing the interruption of the transmission of human helminths with mass drug administration alone: optimizing the design of cluster randomized trials, PARASITES & VECTORS, Vol: 10, ISSN: 1756-3305
Background:A method is outlined for the use of an individual-based stochastic model of parasite transmission dynamics to assess different designs for a cluster randomized trial in which mass drug administration (MDA) is employed in attempts to eliminate the transmission of soil-transmitted helminths (STH) in defined geographic locations. The hypothesis to be tested is: Can MDA alone interrupt the transmission of STH species in defined settings? Clustering is at a village level and the choice of clusters of villages is stratified by transmission intensity (low, medium and high) and parasite species mix (either Ascaris, Trichuris or hookworm dominant).Results:The methodological approach first uses an age-structured deterministic model to predict the MDA coverage required for treating pre-school aged children (Pre-SAC), school aged children (SAC) and adults (Adults) to eliminate transmission (crossing the breakpoint in transmission created by sexual mating in dioecious helminths) with 3 rounds of annual MDA. Stochastic individual-based models are then used to calculate the positive and negative predictive values (PPV and NPV, respectively, for observing elimination or the bounce back of infection) for a defined prevalence of infection 2 years post the cessation of MDA. For the arm only involving the treatment of Pre-SAC and SAC, the failure rate is predicted to be very high (particularly for hookworm-infected villages) unless transmission intensity is very low (R0, or the effective reproductive number R, just above unity in value).Conclusions:The calculations are designed to consider various trial arms and stratifications; namely, community-based treatment and Pre-SAC and SAC only treatment (the two arms of the trial), different STH transmission settings of low, medium and high, and different STH species mixes. Results are considered in the light of the complications introduced by the choice of statistic to define success or failure, varying adherence to treatment, mig
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