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bioRxiv2019

Comparison of antihypertensive drug classes for dementia prevention

IntroductionThere is evidence that hypertension in midlife can increase the risk of Alzheimers disease and vascular dementia in late life. In addition, some treatments for hypertension have been proposed to have cognitive benefits, independent of their effect on hypertension. Consequently, there is potential to repurpose treatments for hypertension for dementia. This study systematically compared seven antihypertensive drug classes for this purpose, using data on over 849,000 patients from the Clinical Practice Research Datalink.\n\nMethodsTreatments for hypertension were assessed in an instrumental variable (IV) analysis to address potential confounding and reverse causation. Physicians prescribing preference was used as a categorical instrument, defined by the physicians last seven prescriptions. Participants were new antihypertensive users between 1996-2016, aged 40 and over.\n\nFindingsWe analysed 849,378 patients with total follow up of 5,497,266 patient-years. Beta-adrenoceptor blockers and vasodilator antihypertensives were found to confer small protective effects - for example, vasodilator antihypertensives resulted in 27 (95% CI: 17 to 38; p=4.4e-7) fewer cases of any dementia per 1000 treated compared with diuretics.\n\nInterpretationWe found small differences in antihypertensive drug class effects on risk of dementia outcomes. However, we show the magnitude of the differences between drug classes is smaller than previously reported. Future research should look to implement other causal analysis methods to address biases in conventional observational research with the ultimate aim of triangulating the evidence concerning this hypothesis.\n\nFundingThis work was supported by the Perros Trust and the Integrative Epidemiology Unit. The Integrative Epidemiology Unit is supported by the Medical Research Council and the University of Bristol [grant number MC_UU_00011/1, MC_UU_00011/3].\n\nRESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSA recent systematic review and meta-analysis has collated the evidence for treating hypertension to prevent dementia. Seven comparable observational studies were identified that used either case-control designs with logistic regression or cohort designs with survival analysis. These studies suggested that some classes, such as angiotensin-II receptor blockers, may prevent dementia. However, conventional observational analyses, such as these, can be subject to confounding and reverse causation.\n\nAdded value of this studyWe have provided new evidence about the potential effects of antihypertensives on risk of dementia through the novel application of instrumental variable analysis to this research question and have shown that the magnitude of the differences between drug classes is smaller than many observational studies have previously reported.\n\nImplications of all the available evidenceFurther research is needed to triangulate this evidence with other sources and to understand the inconsistencies between the studies conducted to date. Ultimately, this will inform the prioritization of antihypertensive drug classes for dementia prevention.

epidemiology↗

bioRxiv2019

Emergence of the Zika virus Asian lineage in Angola

Research In ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed without language restrictions using the keywords Zika and Africa for papers published to October 2018. We also checked available Situation Report publications from WHO for evidence of Zika virus (ZIKV) or congenital Zika disease in Africa. ZIKV African lineage has been detected within Africa since the mid 20th century, yet evidence for spread of the ZIKV Asian lineage within Africa is limited. Two countries in Africa (Cabo Verde and Angola) have reported ZIKV cases that are believed to be caused by a newly introduced Asian lineage virus. Sequence data are critical for confirming and understanding the spread of ZIKV Asian lineage within Africa, but these data are currently limited to a single 193bp fragment of the ZIKV NS1 gene from Angola. In addition, whilst epidemiological data on ZIKV and suspected microcephaly cases have been reported in detail from Cabo Verde, data from Angola are extremely limited.\n\nAdded value of this studyWe provide a detailed report of detected ZIKV acute cases and suspected microcephaly cases in Angola. We sequence ZIKV genomes from three acutely infected cases. These represent the first three Asian lineage genomes available from Africa, one of which was acquired from a baby with confirmed microcephaly. Analysis of these sequences suggests that ZIKV may have been introduced to Angola between July 2015 and June 2016, after which it likely circulated for at least one year. This provides the first genetic confirmation of autochthonous ZIKV Asian lineage transmission within Africa. We suggest that the virus was more likely introduced to Angola directly from Brazil, rather than from Cabo Verde. Our analyses from Angola, only the second African country to report presence of the Asian virus lineage, therefore improve our understanding of the extent and clinical impact of ZIKV Asian lineage in the continent.\n\nImplications of all the available evidenceThe circulation of ZIKV Asian lineage within parts of sub-Saharan Africa is concerning given the potential for continued viral spread across much of the continent. Available evidence suggests that ZIKV has circulated and caused cases of microcephaly in Cabo Verde and in Angola. Detecting additional ZIKV transmission using only clinical data on suspected microcephaly or clusters of mild illness may be challenging in countries where systems for reporting birth defects are limited and infectious disease burden is high. Further spread of the ZIKV Asian lineage would likely not be detected unless molecular surveillance systems for ZIKV are implemented to routinely monitor ZIKV transmission in Africa. Implementation of such a surveillance system is especially important in countries that are linked by high human mobility to areas that have experienced recent or ongoing outbreaks of ZIKV.\n\nAbstractO_ST_ABSBackgroundC_ST_ABSZika virus (ZIKV) infections and suspected microcephaly cases have been recently reported in Angola, but no data are available on the origins, epidemiology, and diversity of the virus.\n\nMethodsSerum samples from 54 suspected ZIKV cases, 76 suspected microcephaly cases, and 24 mothers of infants with suspected microcephaly were received by the Angolan Ministry of Health. Computed tomographic brain imaging and serological assays (PRNT) were conducted on one microcephalic infant. All sera were tested for ZIKV by RT-qPCR. 349 samples from HIV+ patients and 336 samples from patients suspected of chikungunya virus or dengue virus infection were also tested. Portable sequencing was used to generate Angolan ZIKV genome sequences, including from a ZIKV+ neonate with microcephaly born in Portugal to an Angolan resident. Genetic and mobility data were analysed to investigate the date of introduction and geographic origin of ZIKV in Angola.\n\nFindingsFour autochthonous cases were ZIKV positive via RT-qPCR, with all positive samples collected between December 2016 and June 2017. Viral genomes were generated for two of these cases, and from the neonate with microcephaly identified in Portugal. Genetic analyses and other data indicate that ZIKV was introduced to Angola from Brazil between July 2015 and June 2016. This introduction likely initiated local ZIKV circulation in Angola that continued until June 2017. The scanned microcephaly case showed brain abnormalities consistent with congenital Zika syndrome and serological evidence for maternal ZIKV infection.\n\nInterpretationOur analyses confirm the autochthonous transmission of the ZIKV Asian lineage in continental Africa. Conducting ZIKV surveillance throughout Africa is critical in the light of presented evidence for autochthonous ZIKV transmission in Angola, and associated microcephaly cases.\n\nFundingRoyal Society, Wellcome Trust, CNPq, CAPES, ERC, Oxford Martin School, Global Challenges Research Fund, Africa Oxford, and John Fell Fund.

epidemiology↗

bioRxiv2019

Determinants of the population health distribution, or why are risk factor-body mass index associations larger at the upper end of the BMI distribution?

Most epidemiological studies examine how risk factors relate to average difference in outcomes (linear regression) or odds a binary outcome (logistic regression); they do not explicitly examine whether risk factors are associated differentially across the distribution of the health outcome investigated. This paper documents a phenomenon found repeatedly in the minority of epidemiological studies which do this (via quantile regression) -associations between a range of established risk factors and body mass index (BMI) are progressively stronger in the upper ends of the BMI distribution. In this paper, we document this finding and provide illustrative evidence of it in a single dataset (the 1958 British birth cohort study). Associations of low childhood socioeconomic position, high maternal weight, low childhood general cognition and adult physical inactivity with higher BMI are larger at the upper end of the BMI distribution, on both absolute and relative scales. For example, effect estimates for socioeconomic position and childhood cognition were around three times larger at the 90th compared with 10th quantile, while effect estimates for physical inactivity were increasingly larger from the 50th-90th quantiles, yet null at lower quantiles. We provide potential explanations for these findings and discuss possible research and policy implications. We conclude by stating that tools such as quantile regression may be useful to better understand how risk factors relate to the distribution of health -particularly so in obesity research given conventional reliance on cut-points -yet for other outcomes in addition given the continuous nature of population health.

epidemiology↗

bioRxiv2019

When does spatial diversification usefully maximise the durability of crop disease resistance?

1Maximising the durability of crop disease resistance genes in the face of pathogen evolution is a major challenge in modern agricultural epidemiology. Spatial diversification in the deployment of resistance genes, where susceptible and resistant fields are more closely intermixed, is predicted to drive lower epidemic intensities over evolutionary timescales. This is due to an increase in the strength of dilution effects, caused by pathogen inoculum challenging host tissue to which it is not well-specialised. The factors that interact with and determine the magnitude of this spatial effect are not currently well understood however, leading to uncertainty over the pathosystems where such a strategy is most likely to be cost-effective. We model the effect on landscape scale disease dynamics of spatial heterogeneity in the arrangement of fields planted with either susceptible or resistant cultivars, and the way in which this effect depends on the parameters governing the pathosystem of interest. Our multi-season semi-discrete epidemiological model tracks spatial spread of wild-type and resistance breaking pathogen strains, and incorporates a localised reservoir of inoculum, as well as the effects of within and between field transmission. The pathogen dispersal characteristics, any fitness cost(s) of the resistance breaking trait, the efficacy of host resistance, and the length of the timeframe of interest, all influence the strength of the spatial diversification effect. These interactions, which are often complex and non-linear in nature, produce substantial variation in the predicted yield gain from the use of a spatial diversification strategy. This in turn allows us to make general predictions of the types of system for which spatial diversification is most likely to be cost-effective, paving the way for potential economic modelling and pathosystem specific evaluation. These results highlight the importance of studying the effect of genetics on landscape scale spatial dynamics within host-pathogen disease systems.

epidemiology↗

bioRxiv2019

Spatial distribution of Salmonella enterica in poultry shed environments observed by intensive longitudinal environmental sampling

During a series of epidemiological studies to investigate the transmission of salmonellae within poultry environments, intensive longitudinal sampling within caged sheds revealed that both the number and location of sample collection within this environment were important to ensure the best chance of detecting Salmonella spp. Multiple serovars of Salmonella enterica subspecies enterica were detected in each shed; 5% of all samples contained more than one serovar. Samples collected on the north side of the shed (OR = 1.77, 95% CI [1.17, 2.68]), on the sheltered side of the shed (OR = 1.90, 95% CI [1.26, 2.89]) and during winter (OR = 48.41, 95%CI [23.56, 104.19]) were more likely to be positive for salmonellae. The distribution of salmonellae within a shed was not homogenous, as differences were identified in the within-shed distribution of Salmonella enterica subspecies enterica serovar Typhimurium ({chi}2 (27, 1,538) = 54.4, P < 0.001), and Salmonella enterica subspecies enterica serovar Infantis ({chi}2 (27, 1,538) = 79.8, P < 0.0001). The difference in sample prevalence by serovar and spatial location within a shed indicates that there are important shed micro-environmental factors that influence survival and/or distribution of salmonellae. These factors should be taken into consideration when undertaking environmental surveillance for salmonellae in flocks housed in caged sheds. IMPORTANCERoutine epidemiological surveillance for salmonellae in poultry relies initially on environmental sampling. Our study confirmed that the sampling methodology conducted within a poultry environment is a non-trivial part of sampling design. The spatial locations of sample collection within a shed revealed differences in both the sample prevalence and serovar of salmonellae detected.

epidemiology↗

bioRxiv2019

Significant temporal shifts on clonal and plasmid backgrounds of Enterobacteriaceae producing acquired AmpC in Portuguese clinical settings

OBJECTIVESTo provide detailed molecular data on clinical acquired AmpC (qAmpC)-producing Enterobacteriaceae from two different periods (2002-2008 and 2010-2013) in order to clarify the contribution of clonal and plasmid genetic platforms for the current epidemiological scenario concerning extended-spectrum beta-lactams resistance. METHODSWe analysed 1246 Enterobacteriaceae non-susceptible to third-generation cephalosporins from 2 hospitals and 1 community laboratory between 2010 and 2013. Bacterial identification, antibiotic susceptibility, identification of qAmpC and plasmid-mediated quinolone resistance genes, clonal (PFGE, MLST) and plasmid (S1-/I-CeuI-PFGE, replicon typing, hybridization) analysis were performed by standard methods. WGS was performed in two ST11-K. pneumoniae isolates harbouring DHA-1. RESULTSThe occurrence of qAmpC was lower (2.6%) than that observed in a previous survey (7.4%), and varied slightly over time. Isolates produced DHA-1 (53%), CMY-2 (44%) or DHA-6 (3%), but significant epidemiological changes were observed in the two surveys. While DHA-1 persisted in different institutions by selection of a worldwide epidemic IncR plasmid in a ST11 harbouring KL105, CMY-2 rates increased over time linked to IncI1 plasmids (instead of IncK or IncA/C2) in multiple E. coli clones. CONCLUSIONSThe higher frequency of DHA-1 qAmpC in these species contrasts with the scenario of most European countries. Furthermore, the different genetic backgrounds associated with either ESBL or qAmpC in our country might have contributed to their differential expansion.

epidemiology↗

bioRxiv2019

Spatiotemporal analysis of human rabies exposure in Colombia during ten years: A challenge for implementing social inclusion in its surveillance and prevention

Based on reported cases of human rabies exposure to Colombia public health surveillance system between 2007 and 2016 we conducted a spatiotemporal analysis to identify epidemiological scenarios of human rabies exposure by dog, cat, bat or farm animal (n= 666,411 cases). Spatiotemporal analysis, incidence rate, cluster and outlier analysis were conducted for all Colombian cities (n= 1122). The incidence rate of human rabies exposure by dogs and cats showed an increasing trend while aggression by bats and farm animals fluctuated throughout the analyzed period. Human rabies transmitted by cat and bat occurred in Andean and Orinoquia region, where the larger scenario was observed. There, urban scenario showed high risk to human rabies exposure by cat and dog in cities characterized for having the highest human population density and greater economic development. In contrary, rural area where was observed high risk of human rabies exposure by farm animals in workers from agroforestry area (42.7%). exposed to rabies by contact of mucosa or injured skin with saliva infected with rabies virus (74.5%) composed rural scenario. In Inequality scenario, exposure by farm animals showed some outlier cities with high risk principally in Pacific region, where was observed the lowest incidence rates to human rabies exposure in all years studied and the highest poverty rates in Colombia. There, afro-descendant (55%) and indigenous (8.2%) people were mostly affected. High risk of exposure by bat bite was observed in indigenous (98.5%) located in cities of Amazon region with dispersed population (Amazonian scenario). Analysis presented here can encourage surveillance, care and prevention programs to focus both on ethnic, dispersed populations and areas with rabies viral circulation, since each scenario requires different approach strategies. Author SummaryWorldwide, rabies is transmitted by saliva contact contaminated with the rabies virus through a bite, scratching or licking of bat, dog, cat and other mammals. If disease is not treated in time is going to cause death. In Colombia, 14 deaths have been reported due to Classical Rabies Virus (RABV) in the last 10 years, but no spatial analysis has been carried out to determine different geographical risk factors. In this study, we analyzed people who were exposed to RAVB or died between 2007 and 2016, showing a relationship between age group, sex, occupation, ethnicity and illness. Considering these variables were possible to identify four different epidemiological scenarios where high migratory effect of the population takes the animals to areas with high population densities and also detect municipalities with very poor and vulnerable populations, located far from the health centers increasing the risk to die by rabies virus. Another contribution is the location of human rabies exposure in distinctly agricultural or indigenous areas, where exposure is clearly high and worrying.

epidemiology↗

bioRxiv2019

The evolution and phylodynamics of serotype A and SAT2 foot-and-mouth disease viruses in endemic regions of Africa

Foot-and-mouth disease (FMD) is a major livestock disease with direct clinical impacts as well as indirect trade implications. Control through vaccination and stamping-out has successfully reduced or eradicated the disease from Europe and large parts of South America. However, sub-Saharan Africa remains endemically affected with 5/7 serotypes currently known to be circulating across the continent. This has significant implications both locally for livestock production and poverty reduction but also globally as it represents a major reservoir of viruses, which could spark new epidemics in disease free countries or vaccination zones. This paper describes the phylodynamics of serotypes A and SAT2 in Africa including recent isolates from Cameroon in Central Africa. We estimated the most recent common ancestor for serotype A was an East African virus from the 1930s compared to SAT2 which has a much older common ancestor from the early 1700s. Detailed analysis of the different clades shows clearly that different clades are evolving and diffusing across the landscape at different rates with both serotypes having a particularly recent clade that is evolving and spreading more rapidly than other clades within their serotype. However, the lack of detailed sequence data available for Africa seriously limits our understanding of FMD epidemiology across the continent. A comprehensive view of the evolutionary history and dynamics of FMD viruses is essential to understand many basic epidemiological aspects of FMD in Africa such as the scale of persistence and the role of wildlife and thus the opportunities and scale at which vaccination and other controls could be applied. Finally we ask endemic countries to join the OIE/FAO supported regional networks and take advantage of new cheap technologies being rolled out to collect isolates and submit them to the World Reference Laboratory.

epidemiology↗

bioRxiv2019

Accurate forecasts of the effectiveness of interventions against Ebola may require models that account for variations in symptoms during infection

Epidemiological models are routinely used to predict the effects of interventions aimed at reducing the impacts of Ebola epidemics. Most models of interventions targeting symptomatic hosts, such as isolation or treatment, assume that all symptomatic hosts are equally likely to be detected. In other words, following an incubation period, the level of symptoms displayed by an individual host is assumed to remain constant throughout an infection. In reality, however, symptoms vary between different stages of infection. During an Ebola infection, individuals progress from initial non-specific symptoms through to more severe phases of infection. Here we compare predictions of a model in which a constant symptoms level is assumed to those generated by a more epidemiologically realistic model that accounts for varying symptoms during infection. Both models can reproduce observed epidemic data, as we show by fitting the models to data from the ongoing epidemic in the Democratic Republic of Congo and the 2014-16 epidemic in Liberia. However, for both of these epidemics, when interventions are altered identically in the models with and without levels of symptoms that depend on the time since first infection, predictions from the models differ. Our work highlights the need to consider whether or not varying symptoms should be accounted for in models used by decision makers to assess the likely efficacy of Ebola interventions.

epidemiology↗

bioRxiv2019

Genetic Susceptibility to Multiple Sclerosis: Interactions between Conserved Extended Haplotypes of the MHC and other Susceptibility Regions

OBJECTIVETo study the accumulation of MS-risk resulting from different combinations of MS-associated conserved-extended-haplotypes of the MHC and three non-MHC risk-loci nearby genes EOMES, ZFP36L1, CLEC16A.\n\nBACKGROUNDDefining \"genetic-susceptibility\" as having a non-zero probability of developing MS, both theoretical considerations and epidemiological observations indicate that only 2.2-4.5% of northern-populations can possibly be \"genetically-susceptible\" to MS. Nevertheless, many haplotypes (both within the MHC and elsewhere) are unequivocally MS-associated and, yet, have population-frequencies of >20%. Such frequency-disparities underscore the complex-interactions that must occur between these \"risk-haplotypes\" and MS-susceptibility.\n\nDESIGN/MEHTODSThe WTCCC dataset was statistically-phased at the MHC and at three other susceptibility-regions. Haplotypes were stratified by their impact on \"MS-risk\". MS-associations for different combinations of \"risk-haplotypes\" were assessed. The appropriateness of both additive and multiplicative risk-accumulation models was determined.\n\nRESULTSCombinations of different \"risk-haplotypes\" produced an MS-risk that was considerably closer to an additive model than a multiplicative model. Nevertheless, neither of these simple probability-models adequately accounted for the accumulation of disease-risk in MS at these four loci.\n\nCONCLUSIONS\"Genetic-susceptibility\" to MS seems to depend upon the exact state at each \"risk-locus\" and upon specific gene-gene combinations across loci. Moreover, \"genetic-susceptibility\" is both rare in the population and, yet, is a necessary condition for MS to develop in any individual. In this sense, MS is a \"genetic\" disease. Nevertheless although, \"genetic-susceptibility\" is a necessary condition for MS to develop, environmental factors (whatever these may be) and stochastic processes are also necessary determinants of whether a \"genetically-susceptible\" individual will actually get MS.\n\nAuthor SummaryDefining a \"genetically-susceptible\" individual to be any person in the population who has any chance of developing multiple sclerosis (MS), we demonstrate that, at a theoretical level and using widely-accepted epidemiological observations, only 2.2-4.5% of individuals in northern populations can possibly be \"genetically susceptible\" to MS. Thus, more than 95.5% of individuals in these populations have no chance of getting MS, regardless of the environmental circumstances that they may experience.\n\nNevertheless, certain \"susceptibility-haplotypes\" (e.g., HLA-DRB1*15:01~DQB1*06:02) have a far greater carrier-frequency than 2.2-4.5%. Consequently, most carriers of these \"susceptibility-haplotypes\" have no chance of getting MS and, therefore, their \"susceptibility\" must arise from some combination of these haplotypes with other \"susceptibility-haplotypes\". By analyzing such combinatorial impacts at four susceptibility-loci, we found significant interactions both within and between the different \"susceptibility-haplotypes\", thereby confirming the relationship between \"genetic-susceptibility\" and specific gene-gene combinations.\n\nThe nature of \"genetic-susceptibility\" developed here is applicable to other complex genetic disorders. Indeed, any disease for which the MZ-twin concordance rate is substantially greater than the life-time risk in the general population, only a small fraction of the population can possibly be in the \"genetically-susceptible\" subset (i.e., have any chance of developing the disease).

epidemiology↗

bioRxiv2019

Human Chrysomya bezziana myiasis: A systematic review

BackgroundMyiasis due to Old World screw-worm fly, Chrysomya bezziana, is an important obligate zoonotic disease in the OIE-list of diseases and is found throughout much of Africa, the Indian subcontinent, southeast and east Asia. C. bezziana myiases cause not only morbidity and death to animals and humans, but also economic losses in the livestock industries. Because of the aggressive and destructive nature of this disease in hosts, we initiated this study to provide a comprehensive understanding of human myiasis caused by C. bezziana.\n\nMethodsWe conducted a systematic search of the databases in English (PubMed, Embase and African Index Medicus) and Chinese (CNKI, Wanfang, and Duxiu), and international government online reports to 6th February, 2019, to identify studies concerning Chrysomya bezziana. Another ten human cases in China and Papua New Guinea that our team had recorded were also included.\n\nResultsWe retrieved 1,048 reports from which 202 studies were ultimately eligible for inclusion in the present descriptive analyses. Since the first human case due to C. bezziana was reported in 1909, we have summarized 291 cases and found that these cases often occurred in poor hygiene, low socio-economic conditions, old age, and underlying diseases including infections, age-related diseases, and noninfectious chronic diseases. But C. bezziana myiasis appears largely neglected as a serious medical or veterinary condition, with human and animal cases only reported in 16 and 24 countries respectively, despite this fly species recorded as present in 44 countries worldwide.\n\nConclusionOur findings indicate that cryptic myiasis cases due to the obligate parasite, C. bezziana, are under-recognized. Through this in-depth study to clarify the knowledge of human C. bezziana myiasis including its etiology, clinical features, diagnosis, treatment, epidemiology, prevention and control, we call for more vigilance and awareness of the disease from governments, health authorities, clinicians, veterinary workers, nursing homes, and also the general public.\n\nAuthor summaryChrysomya bezziana larvae are characterized by feeding aggressively on the living tissues and body fluids of the host. The nightmare-like feelings of patients suffering from this myiasis, severe tissues and bones destruction, even death, and enormous economic loss in the livestock industries have been described in the previous reports. But our findings indicate that C. bezziana myiases still appear to be under-recognized as a serious medical or veterinary condition throughout the world. Both in China and the world at large, it is probable that C. bezziana distribution could be greater than currently reported. For the first time, we have therefore systematically investigated human myiasis caused by C. bezziana. Our study provides an opportunity for clinicians and health authorities to gain a better understanding of this disease from its etiology, pathology, clinical features, diagnosis, treatment, epidemiology, prevention and control. In addition, our findings will hopefully engage governments, health staff, veterinary workers, the elderly homes, and also the general public in efforts to recognize, prevent and control such infestations.

epidemiology↗

bioRxiv2019

Modeling in an oral health study through two statisticalmethods in Uruguay

In epidemiological studies it is common practice to work with binary variables that reflect the presence of certain diseases, which in turn may be associated with another set of variables, that in general are assumed as risk factors of the former. In the field of epidemiological studies referred to oral health, it is common to inquire about the relationship between the presence of some pathologies and certain characteristics of the study participants through generalized linear models (GLM). However, this type of analysis is usually carried out for each variable of interest separately and at no time is a measure obtained that summarizes the status of each participant. The objective was to apply and compare two methodologies; one applying classical approach of explaining each oral disease separately from a set of explanatory variables and another using item response theory (IRT) models (specifically the Rasch model) since they allow the joint analysis of a set of variables obtaining an individual assessment as a by-product, which in this case is interpreted as \"sickness proneness\". On the other hand, the analysis presented here extends the Rasch model including a linear predictor that allows to investigate about the possible effect of several factors on the propensity of the individuals to suffer the different pathologies. Our results found evidence of an effect of gender, insufficient physical activity (IPhA) and age on general proneness to oral diseases.

epidemiology↗

bioRxiv2019

On the Mathematics of Populations

Selection acting on unobserved heterogeneity is a fundamental issue in the mathematics of populations. As recognised in disciplines as diverse as demography [11, 23, 24], ecology [10, 9], evolution [21] and epidemiology [1, 4, 5], in any population, individuals differ in many characteristics and it is essential that researchers understand which of these are under selection and how selection processes operate. Here I describe conceptual and methodological developments in demography and ecology, and discuss the importance of adopting similar approaches in evolution and epidemiology.

epidemiology↗

bioRxiv2019

A Bayesian Monte Carlo approach for predicting the spread of infectious diseases

In this paper, a simple yet interpretable, probabilistic model is proposed for the prediction of reported case counts of infectious diseases. A spatio-temporal kernel is derived from training data to capture the typical interaction effects of reported infections across time and space, which provides insight into the dynamics of the spread of infectious diseases. Testing the model on a one-week-ahead prediction task for campylobacteriosis and rotavirus infections across Germany, as well as Lyme borreliosis across the federal state of Bavaria, shows that the proposed model performs on-par with the state-of-the-art hhh4 model. However, it provides a full posterior distribution over parameters in addition to model predictions, which aides in the assessment of the model. The employed Bayesian Monte Carlo regression framework is easily extensible and allows for incorporating prior domain knowledge, which makes it suitable for use on limited, yet complex datasets as often encountered in epidemiology.\n\nAuthor summaryWhy was this study done?\n\nO_LIStatistical modeling is invaluable to public-health policy as it helps understand and anticipate the dynamics of the spread of infectious diseases. The available training data is often limited and reported with a low spatial and temporal resolution. This poses a challenge and makes it particularly important to incorporate domain knowledge and prior assumptions to guide the modeling process.\nC_LIO_LIIn order to evaluate the trustworthiness and reliability of a models predictions, it is crucial to be able to interpret the model and quantify the model uncertainty.\nC_LIO_LITo address this, we develop an interpretable model that uses Bayesian inference (rather than commonly used maximum likelihood estimation) and provides a probability distribution over inferred parameters.\nC_LI\n\nWhat did the researchers do and find?\n\nO_LIWe develop and test a single probabilistic model that learns to predict the number of weekly case counts for three different diseases (campylobacteriosis, rotaviral enteritis and Lyme borreliosis) at the county level one week ahead of time.\nC_LIO_LIWe employ a Bayesian Monte Carlo regression approach that provides an estimate of the full probability distribution over inferred parameters as well as model predictions.\nC_LIO_LIThe model learns an interpretable spatio-temporal kernel that captures typical interactions between infection cases of the tested diseases.\nC_LIO_LIThe predictive performance of our model compares favorably with a contemporary reference model for all diseases tested.\nC_LI\n\nWhat do these findings mean?\n\nO_LIInterpretable predictive models can be applied to surveillance data to gain insights into the dynamics of infectious diseases.\nC_LIO_LIProbabilistic modeling approaches provide a suitable framework for many challenges of working with epidemiological data.\nC_LI

epidemiology↗

bioRxiv2019

Demonstration of different entity of appendicitis and related causes of disease through study of cluster/outbreak: Systematic Review and Meta Analysis.

ObjectiveTo demonstrate different entities of appendicitis and causal association between microbiota and different types of appendicitis through studying cluster/outbreak, and providing guidance to find new cluster/outbreak of appendicitis and the epidemiological evidences of infectious etiology of appendicitis.\n\nData SourcesPubMed, Embase, CNKI, WanFang, VIP, CBM from their establishment to Jan, 2019, and the references lists from retrieved reports.\n\nStudy EligibilityReports on cluster/outbreak of appendicitis and reports of case series occurring in cluster/outbreak worldwide according to CDCs definition of cluster/outbreak.\n\nData Extraction and SynthesisTwo researchers independently assessed report quality and extracted data according to Moose. We used random effect model for meta-analysis by Meta-Analyst {beta}3.13 software. Study-level assessment was conducted according to investigation methods introduced by Reingold and outcome-level assessment by GRADE system. We selected outcome measures before data collection began.\n\nResultsWe included 10 clusters/outbreaks of appendicitis from China and USA with total 626 patients. We demonstrated two entities, type 1 appendicitis (455 patients) and type 2 appendicitis (151patients). 20 patients left were unclassified type. For type 1 appendicitis, Natural history showed progression from a non-perforated appendicitis to perforated appendicitis as described traditionally. More than 88% of patients had elevated body temperature, WBC and neutrophil percentage. For type 2 appendicitis, natural history showed that only a few patients developed into phlegmonous appendicitis (6.9%,) or acute gangrenous appendicitis (1.4%) and no perforation or periappendicular abscess. More than 78% of patients had normal body temperature, WBC and NP. The patients time of type 1 appendicitis is shorter than that of type 2 appendicitis. Type 2 appendicitis had different histological features from type 1 appendicitis and was associated with fusobacteria. 9 of 10 cluster/outbreak occurred in group living unity such as school and camps, and many of them showed features of infectious diseases. The bodies of evidence were high quality in Meta analysis.\n\nConclusionCluster/outbreak of appendicitis is more often than expected worldwide and occurred in group living unity. Sporadic perforated appendicitis and non-perforated appendicitis may be not two different entities, but different stages of a same entity, which is inconsistent with modern classification of appendicitis. Type 2 appendicitis is a new entities. Studying cluster/outbreak is a new method in finding of new entity and causal association between microbiota and different types of appendicitis. Epidemiological evidence supported infectious etiology of appendicitis.

epidemiology↗

bioRxiv2019

Seasonal influenza: Modelling approaches to capture immunity propagation

Seasonal influenza poses serious problems for global public health, being a significant contributor to morbidity and mortality. In England, there has been a long-standing national vaccination programme, with vaccination of at-risk groups and children offering partial protection against infection. Transmission models have been a fundamental component of analysis, informing the efficient use of limited resources. However, these models generally treat each season and each strain circulating within that season in isolation. Here, we amalgamate multiple data sources to calibrate a susceptible-latent-infected-recovered type transmission model for seasonal influenza, incorporating the four main strains and mechanisms linking prior season epidemiological out-comes to immunity at the beginning of the following season. Data pertaining to nine influenza seasons, starting with the 2009/10 season, informed our estimates for epidemiological processes, virological sample positivity, vaccine uptake and efficacy attributes, and general practitioner influenza-like-illness consultations as reported by the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). We performed parameter inference via approximate Bayesian computation to assess strain transmissibility, dependence of present season influenza immunity on prior protection, and variability in the influenza case ascertainment across seasons. This produced reasonable agreement between model and data on the annual strain composition. Parameter fits indicated that the propagation of immunity from one season to the next is weaker if vaccine derived, compared to natural immunity from infection. Projecting the dynamics forward in time suggests that while historic immunity plays an important role in determining annual strain composition, the variability in vaccine efficacy hampers our ability to make long-term predictions.

epidemiology↗

bioRxiv2019

Comparison of two individual-based models for simulating HIV epidemics in a population with HSV-2 using as case study Yaounde-Cameroon, 1989-1998

Model comparisons have been widely used to guide intervention strategies to control infectious diseases. Agreement between different models is crucial for providing robust evidence for policy-makers because differences in model properties can influence their predictions. In this study, we compared models generated with two individual-based model simulators for HIV epidemiology in a population with HSV-2. For each model simulator, we constructed four models, starting from a simplified model and stepwise including more model complexity. For the resulting eight models, the predictions of the impact of behavioural interventions on the HIV epidemic in Yaounde (Cameroon) were compared. The results show that differences in model assumptions and model complexity can influence the size of the predicted impact of the intervention, as well as the predicted qualitative behaviour of the HIV epidemic after the intervention. Moreover, two models that agree in their predictions of the HIV epidemic in absence of an intervention can have different outputs when predicting the impact of interventions. These findings highlight the importance of making more data available for the calibration and validation of epidemiological models.

epidemiology↗

bioRxiv2019

Chikungunya Outbreak in Bangladesh (2017): Clinical and hematological findings

A massive outbreak of Chikungunya occurred in Bangladesh during the period of April-September, 2017 and over two million people were at risk of getting infected by the virus. A prospective cohort of viremic patients was constituted and analyzed to define the clinical, hematological and long-term aspects of this outbreak. A 35-day long comprehensive survey was conducted in two major, neighboring cities, Dhaka and Mymensingh. One-hundred and eighty-seven clinically proven Chikungunya cases were enrolled in the cross-sectional cohort study. Additionally, a smaller group of 48 Chikungunya patients was monitored for post-infection effects for 12 months. Clinical data revealed that a combination of fever and arthralgia (oligoarthralgia and/or polyarthralgia) was the cardinal hallmark (97.9% of cases) of the infection. Hematological analysis showed that, irrespective of age groups, hemoglobin level significantly decreased and erythrocyte sedimentation rate remarkably increased in Chikungunya confirmed patients. However, the majority of the patients had a normal range of whole WBC and platelet counts; RBC counts for mid aged (40 - 60 years) and senior (61+ years) patients (especially in the females) were beyond the reference values. The post-infection study revealed that children had an early recovery from the infection compared to the adults. Moreover, post-infection weakness, successive relapse of arthralgic pain and memory problems were the most significant aftereffects, which had an impact on daily activities of patients. This study represents a comprehensive overview of clinical and epidemiological features of the 2017 outbreak of Chikungunya in Bangladesh as well as its chronic outcomes till the 12th month. It provides insights into the natural history of this disease which may help to improve management of the Chikungunya patients.\n\nAuthor summeryThe clinical profile, epidemiology and the economic impacts during the acute phase of Chikungunya infection has been studied quite rigorously. However, studies regarding the hematological features and chronic consequences are very limited. In this study, a dataset of 187 clinically proven chikungunya patients were analyzed for the clinical and hematological features at acute phase of the infection. Additionally, the long-term consequences till month 12 after the infection were studied for a smaller group of 48 patients. Clinical data revealed that a combination of fever and joint pain (arthralgia) was the cardinal hallmark in the acute phase of the infection. Hematological analysis showed that, hemoglobin levels of the patients were significantly reduced and erythrocyte sedimentation rate increased remarkably. Also, RBC counts for mid-aged and older patients were beyond the reference values. The post-infection consequence study unveiled that children recovered better from the infection compared to the adults. Further, post-infection weakness, successive relapse of joint pain and memory problems were the most significant aftereffects. Overall, the infection had moderate to severe impact on daily activities of the respondents. This study provides insights into the clinical and hematological aspects of Chikungunya infection during the acute phase as well as describes an account for its chronic outcomes which puts forward to the knowledge for clinicians and epidemiologists regarding the infection diversity and to help improved patient management.

epidemiology↗