PaperPlayer biorxiv epidemiology

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/674655v1?rss=1

Authors: Becker, D. J., Crowley, D. E., Washburne, A. D., Plowright, R. K.

Abstract:

Sampling reservoir hosts over time and space is critical to detect epizootics, predict spillover, and design interventions. However, because sampling is logistically difficult and expensive, researchers rarely perform spatiotemporal sampling of many reservoir hosts. Bats are reservoirs of many virulent zoonotic pathogens such as filoviruses and henipaviruses, yet the highly mobile nature of these animals has limited optimal sampling of bat populations. To quantify the frequency of temporal sampling and to characterize the geographic scope of bat virus research, we here collated data on filovirus and henipavirus prevalence and seroprevalence in wild bats. We used a phylogenetically controlled meta-analysis to next assess temporal and spatial variation in bat virus detection estimates. Our analysis shows that only one in four bat virus studies report data longitudinally, that sampling efforts cluster geographically (e.g., filovirus data are available across much of Africa and Asia but are absent from Latin America and Oceania), and that sampling designs and reporting practices may affect some viral detection estimates (e.g., filovirus seroprevalence). Within the limited number of longitudinal bat virus studies, we observed high heterogeneity in viral detection estimates that in turn reflected both spatial and temporal variation. This suggests that spatiotemporal sampling designs are essential to understand how zoonotic viruses are maintained and spread within and across wild bat populations, which in turn could help predict and preempt risks of zoonotic viral spillover.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/680140v1?rss=1

Authors: Schindera, C., Weiss, A., Hagenbuch, N., Otth, M., Diesch, T., von der Weid, N., Kuehni, C. E.

Abstract:

BackgroundPhysical activity (PA) can reduce the risk of chronic adverse health conditions in childhood cancer survivors. We examined physical activity and sedentary screen time behavior in a nationwide study in Switzerland.nnProceduresThe Swiss Childhood Cancer Survivor Study sent questionnaires to parents of all Swiss resident [≥]5 year-survivors diagnosed 1995-2010. We assessed physical activity including compulsory school sport, recreational sport, commuting to school, and time spent with screen media in those aged 5-15 years, and compared results to international recommendations.nnResultsWe included 766 survivors with a median age at diagnosis of 2.8 (interquartile range 1.4-5.0) years and a median age at study of 12.5 (10.0-14.3) years. Median PA time was 7.3 (4.8-10.0) hours/week and median screen time 1.4 (0.8-2.0) hours/day. Compulsory school sport hours and walking or cycling to school contributed significantly to total PA. 55% of survivors met PA and 68% screen time recommendations. PA was lower for children living in regions of Switzerland speaking French or Italian compared to German, and for those who had a relapse or musculoskeletal/neurological conditions. Screen time was higher in males, and children with lower parental education and a migration background.nnConclusionsPA and sedentary screen watching were associated with social factors and PA also with clinical risk factors. Structural preventions that afford active commuting to school and sufficient school sport are essential, as is counselling vulnerable survivor groups such as those with musculoskeletal and neurological problems, and those who have had a relapse.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/679316v1?rss=1

Authors: Langdon, R., Richmond, R., Elliott, H., Dudding, T., Kazmi, N., Penfold, C., Ingarfield, K., Ho, K., Bretherick, A., Haley, C., Zeng, Y., Walker, R. M., Pawlita, M., Waterboer, T., Ring, S., Gaunt, T., Smith, G. D., Suderman, M., Thomas, S., Ness, A., Relton, C.

Abstract:

Smoking status, alcohol consumption and HPV infection (acquired through sexual activity) are the predominant risk factors for oropharyngeal cancer and are thought to alter the prognosis of the disease. Here, we conduct epigenome-wide association studies (EWAS) of these factors and [~]3-year survival using Illumina Methylation EPIC blood DNA methylation profiles from 409 individuals in the Head and Neck 5000 (HN5000) study. CpG site associations below our multiple-testing threshold (PBonferroni < 0.05) with both a prognostic factor and with survival were observed in four gene regions: SPEG (smoking), GFI1 (smoking), PPT2 (smoking), and KHD3CL (alcohol consumption). These were further analysed using 2-step Mendelian randomization to assess whether methylation may be a causal mediator of cancer survival. Evidence for mediation was observed only in the SPEG gene region, showing an association with decreased survival (mortality HR: 1.28, 95% CI: 1.14 to 1.43, P: 2.12x10-05). Replication in data from independent datasets, and from HN5000 participants with longer follow-up times is needed to confirm these findings.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/676882v1?rss=1

Authors: Dutta Gupta, S., Kundu, S., Dhar, B., Das, N., Paul Choudhury, A., Deb, M., Das, A., Das, A., Das, N., Choudhury, B., Varghese, A. C., Kar, K. K., Choudhury, Y., Ghosh, S. K.

Abstract:

BackgroundIn India, the potential risk factors influencing female infertility are not well-characterized. Hence, this study was initially aimed to determine the multi-factor risk-predictive models for the infertile females from different Indian ethnics. Afterwards, when treatment was performed for correcting the abnormal demographic and clinical parameters obtained from our initial findings, some of the patients were observed to be treatment-non-responsive. This further recommended assessing the expression pattern of GDF9 and BMP15 mRNAs in those unexplained infertile females.nnMethodologyThis study included 470 Primary, 209 Secondary infertile and 419 age-matched Healthy females, where baseline demographic and clinicopathological factors were assessed. Additionally, from the treatment-non-responsive patients, laparoscopy and trans-vaginal ultrasound-guided collection of ovarian follicular fluid were done for studying the expression pattern of GDF9 and BMP15 mRNAs using q-PCR.nnPrincipal FindingsMid-education level, no contraception usage and duration of infertility for >2 years were the critical risk factors for female infertility (OR>>1; p<0.05), whereas elevated platelet count showed ~10-fold more risk of having secondary infertility and high ESR showed 3.33-fold increased threat of primary infertility. Besides, abnormal MCV, LH/FSH ratio, mild-anaemia and hypothyroidism were the best risk-predictive multi-factor model. After correcting these abnormal clinical factors, 6.8% of the patients were treatment-non-responsive, where elevated ESR, hypothyroidism and anaemia remained uncorrected. Interestingly, in those unexplained cases, GDF9 and BMP15 mRNAs were significantly down-regulated (2-4 fold) irrespective of age groups. Additionally, for predicting female infertility, the cut-off for the expression level of GDF9 and BMP15 mRNAs were estimated -2.09 and -2.75, respectively, with a relatively high sensitivity ([≥]62.5%) and specificity (75%).nnConclusionsGDF9 and BMP15 mRNAs may be considered as molecular markers for predicting female infertility. Their down-regulation along with hypothyroidism and anaemia probably led to the treatment-non-responsiveness, thus, those patients may be advised to assisted reproductive technology with supplementation of exogenous GDF9 and/or BMP15.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/674663v1?rss=1

Authors: Lydeamore, M., Campbell, P. T., Price, D. J., Wu, Y., Marcato, A. J., Cuningham, W., Carapetis, J. R., Andrews, R. M., McDonald, M. I., McVernon, J., Tong, S. Y. C., McCaw, J. M.

Abstract:

Prevalence of impetigo (skin sores) remains high in remote Australian Aboriginal communities, Fiji, and other areas of socio-economic disadvantage. Skin sore infections, driven primarily in these settings by Group A Streptococcus (GAS) contribute substantially to the disease burden in these areas. Despite this, estimates for the force of infection, infectious period and basic reproductive ratio -- all necessary for the construction of dynamic transmission models -- have not been obtained. By utilising three datasets each containing longitudinal infection information on individuals, we estimate each of these epidemiologically important parameters. With an eye to future study design, we also quantify the optimal sampling intervals for obtaining information about these parameters. We verify the estimation method through a simulation estimation study, and test each dataset to ensure suitability to the estimation method. We find that the force of infection differs by population prevalence, and the infectious period is estimated to be between 12 and 20 days. We also find that optimal sampling interval depends on setting, with an optimal sampling interval between 9 and 11 days in a high prevalence setting, and 21 and 27 days for a lower prevalence setting. These estimates unlock future model-based investigations on the transmission dynamics of GAS and skin sores.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/672808v1?rss=1

Authors: Wu, Z., Chen, I.

Abstract:

SO_SCPLOWUMMARYC_SCPLOWOptimal prevention and treatment strategies for a disease of multiple causes must be informed by the population distribution of causes among cases, or cause-specific case fraction (CSCFs) which may further depend on explanatory variables. However, the true causes are often not observed, motivating the use of non-gold-standard diagnostic tests that provide indirect etiologic evidence. Based on case-control multivariate binary data, this paper proposes a novel and unified modeling framework for estimating CSCF functions, closing the existing methodological gap in disease etiology research. With a novel shrinkage prior to encourage parsimonious approximation to a multivariate binary distribution given covariates, the model leverages critical control data for valid probabilistic cause assignment for cases. We derive an efficient Markov chain Monte Carlo algorithm for flexible posterior inference. We illustrate the inference of CSCF functions using extensive simulations and show that the proposed model produces less biased estimates and more valid inference of the overall CSCFs than an analysis that omits covariates. A regression analysis of pediatric pneumonia data reveals the dependence of CSCFs upon season, age, HIV status and disease severity.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/674887v1?rss=1

Authors: Marchi, J., Lassig, M., Mora, T., Walczak, A. M.

Abstract:

Viruses evolve in the background of host immune systems that exert selective pressure and drive viral evolutionary trajectories. This interaction leads to different evolutionary patterns in antigenic space. Examples observed in nature include the effectively one-dimensional escape characteristic of influenza A and the prolonged coexistence of lineages in influenza B. Here we use an evolutionary model for viruses in the presence of immune host systems with finite memory to delineate parameter regimes of these patterns in a in two-dimensional antigenic space. We find that for small effective mutation rates and mutation jump ranges, a single lineage is the only stable solution. Large effective mutation rates combined with large mutational jumps in antigenic space lead to multiple stably co-existing lineages over prolonged evolutionary periods. These results combined with observations from data constrain the parameter regimes for the adaptation of viruses, including influenza.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/670612v1?rss=1

Authors: Krijkamp, E., Alarid-Escudero, F., Enns, E., Pechlivanoglou, P., Hunink, M., Jalal, H.

Abstract:

Cost-effectiveness analyses often rely on cohort state-transition models (cSTMs). The cohort trace is the primary outcome of cSTMs, which captures the proportion of the cohort in each health state over time (state occupancy). However, the cohort trace is an aggregated measure that does not capture the information about the specific transitions among the health states (transition dynamics). In practice, these transition dynamics are crucial in many applications, such as incorporating transition rewards or computing various epidemiological outcomes that could be used for model calibration and validation (e.g. disease incidence and lifetime risk). In this manuscript we propose modifying the transitional cSTMs cohort trace computation to compute and store cSTMs dynamics that capture both state occupancy and transition dynamics. This approach produces a multidimensional matrix from which both the state occupancy and the transition dynamics can be recovered. We highlight the advantages and potential applications of this approach with an example coded in R to facilitate the implementation of our method.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/674572v1?rss=1

Authors: Laneri, K., Cabella, B., Prado, P. I., Coutinho, R. M., Kraenkel, R. A.

Abstract:

In this work we analyze potential environmental drivers of malaria cases in Northwestern Argentina. We inspect causal links between malaria and climatic variables by means of the convergent cross mapping technique, which provides a causality criterion from the theory of dynamic systems. Analysis is based on 12 years of weekly malaria P. vivax cases in Tartagal, Salta, Argentina--at the southern fringe of malaria incidence in the Americas--together with humidity and temperature time-series spanning the same period. Our results show that there are causal links between malaria cases and both maximum temperature, with a delay of five weeks, and minimum temperature, with delays of zero and twenty two weeks. Humidity is also a driver of malaria cases, with thirteen weeks delay between cause and effect. Furthermore we also determined the sign and strength of the effects. Temperature has always a positive non-linear effect on cases, with maximum temperature effects more pronounced above 25{degrees} C and minimum above 17{degrees} C, while effects of humidity are more intricate: maximum humidity above 85% has a negative effect, whereas minimum humidity has a positive effect on cases. These results might be signaling processes operating at short (below 5 weeks) and long (over 12 weeks) time delays, corresponding to effects related to parasite cycle and mosquito population dynamics respectively. The non-linearities found for the strength of the effect of temperature on malaria cases make warmer areas more prone to higher increases in the disease incidence. Moreover, our results indicate that an increase of extreme weather events could enhance the risks of malaria spreading and re-emergence beyond the current distribution. Both situations, warmer climate and increase of extreme events, will be remarkably increased by the end of the century in this hot spot of climate change.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/674689v1?rss=1

Authors: Howell, S., German, D., Bender, A., Phan, F., Mukundan, S., Perez-Alday, E., Rogovoy, N., Haq, K., Yang, K., Wirth, A., Jensen, K., Tereshchenko, L. G.

Abstract:

BackgroundSex is a well-recognized risk factor for sudden cardiac death (SCD). Sex differences in electrophysiological (EP) substrate of SCD are known. However, it remains unknown whether sex can modify an association of EP substrate with SCD.nnMethodsParticipants from the Atherosclerosis Risk in Communities study with analyzable ECGs (n=14,725; age, 54.2{+/-}5.8 yrs; 55% female, 74% white) were included. EP substrate was characterized by traditional 12-lead ECG (heart rate, QRS, QTc, Cornell voltage), spatial ventricular gradient (SVG) and sum absolute QRST integral (SAI QRST) metrics. Two competing outcomes were adjudicated SCD and nonSCD. Interaction of ECG metrics with sex was studied in Cox proportional hazards and Fine-Gray competing risk models. Relative hazard ratio (RHR) and relative sub-hazard ratio (RSHR) with a 95% confidence interval for SCD and nonSCD risk for women relative to men were calculated. Model 1 was adjusted for prevalent cardiovascular disease (CVD) and risk factors. Time-updated model 2 was additionally adjusted for incident non-fatal CVD.nnResultsOver a median follow-up of 24.4 years, there were 530 SCDs (incidence 1.72 (1.58-1.88)/1000 person-years) and 2,178 nonSCDs (incidence 7.09; (6.80-7.39)/ 1000 person-years). Women experienced a greater than men risk of SCD associated with Cornell voltage (RHR 1.18(1.06-1.32); P=0.003), SAI QRST (RHR 1.16(1.04-1.30); P=0.007), area SVG magnitude (RHR 1.24(1.05-1.45); P=0.009), and peak SVG magnitude (RHR 1.22(1.04-1.44); P=0.018), independently from incident CVD. Greater risk of SCD for women than men associated with QRS duration (RHR 1.24(1.07-1.44); P=0.004) and QTc (RSHR 1.15(1.02-1.30); P=0.025) was explained by incident CVD. Furthermore, women had greater odds of SCD associated with heart rate (RSHR 1.19(1.01-1.40); P=0.036), independently of incident CVD.nnConclusionsSex modifies an association of EP substrate with SCD. In women, global EP substrate is associated with up to 27% greater risk of SCD than in men. Development of sex-specific risk scores of SCD is necessary. Further studies of mechanisms behind sex differences in EP substrate of SCD are warranted.

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