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Low, N.

Publications and source records attributed to Low, N..

13 recordsLinked to original sources

Ensemble of deep learning language models to support the creation of living systematic reviews for the COVID-19 literature: a retrospective study

BackgroundThe COVID-19 pandemic has led to an unprecedented amount of scientific publications, growing at a pace never seen before. Multiple living systematic reviews have been developed to assist professionals with up-to-date and trustworthy health information, but it is increasingly challenging for systematic reviewers to keep up with the evidence in electronic databases. We aimed to investigate deep learning-based machine learning algorithms to classify COVID-19 related publications to help scale-up the epidemiological curation process. MethodsIn this retrospective study, five different pre-trained deep learning-based language models were fine-tuned on a dataset of 6,365 publications manually classified into two classes, three subclasses and 22 sub-subclasses relevant for epidemiological triage purposes. In a k-fold cross-validation setting, each standalone model was assessed on a classification task and compared against an ensemble, which takes the standalone model predictions as input and uses different strategies to infer the optimal article class. A ranking task was also considered, in which the model outputs a ranked list of sub-subclasses associated with the article. ResultsThe ensemble model significantly outperformed the standalone classifiers, achieving a F1-score of 89.2 at the class level of the classification task. The difference between the standalone and ensemble models increases at the sub-subclass level, where the ensemble reaches a micro F1-score of 70% against 67% for the best performing standalone model. For the ranking task, the ensemble obtained the highest recall@3, with a performance of 89%. Using an unanimity voting rule, the ensemble can provide predictions with higher confidence on a subset of the data, achieving detection of original papers with a F1-score up to 97% on a subset of 80% of the collection instead of 93% on the whole dataset. ConclusionThis study shows the potential of using deep learning language models to perform triage of COVID-19 references efficiently and support epidemiological curation and review. The ensemble consistently and significantly outperforms any standalone model. Fine-tuning the voting strategy thresholds is an interesting alternative to annotate a subset with higher predictive confidence.

bioinformatics↗

The next Zika virus outbreak will affect young women of reproductive age disproportionately: mathematical modeling study

The 2015-2017 epidemics of Zika virus (ZIKV) in the Americas caused widespread protective immunity. The timing and burden of the next Zika virus outbreak remains unclear. We used an agent-based model to simulate the dynamics of age-specific immunity to ZIKV, and predict the future age-specific risk using data from Managua, Nicaragua. We also investigated the potential impact of a ZIKV vaccine. Assuming lifelong immunity, the risk of a ZIKV outbreak will remain low until 2035 and rise above 50% in 2047. The imbalance in age-specific immunity implies that people in the 15-29 age range will be at highest risk of infection during the next ZIKV outbreak, increasing the expected number of congenital abnormalities. ZIKV vaccine development and licensure are urgent to attain the maximum benefit in reducing the population-level risk of infection and the risk of adverse congenital outcomes. This urgency increases if immunity is not lifelong.

epidemiology↗

The rise and fall of the new variant of Chlamydia trachomatis in Sweden: mathematical modelling study

ObjectivesA new variant of Chlamydia trachomatis (nvCT) was discovered in Sweden in 2006. The nvCT has a plasmid deletion, which escaped detection by two nucleic acid amplification tests (Abbott/Roche, AR), which were used in 14 of 21 Swedish counties. The objectives of this study were to assess when and where nvCT emerged in Sweden, the proportion of nvCT in each county, and the role of a potential fitness difference between nvCT and co-circulating wild-type strains (wtCT). MethodsWe used a compartmental mathematical model describing the spatial and temporal spread of nvCT and wtCT. We parameterised the model using sexual behaviour data and Swedish spatial and demographic data. We used Bayesian inference to fit the model to surveillance data about reported diagnoses of chlamydia infection in each county and data from four counties that assessed the proportion of nvCT in multiple years. ResultsModel results indicated that nvCT emerged in central Sweden (Dalarna, Gavleborg, Vasternorrland), reaching a proportion of 1% of prevalent CT infections in late 2002 or early 2003. The diagnostic selective advantage enabled rapid spread of nvCT in the presence of high treatment rates. After detection, the proportion of nvCT decreased from 30-70% in AR counties and 5-20% in counties that Becton Dickinson tests, to around 5% in 2015 in all counties. The decrease in nvCT was consistent with an estimated fitness cost of around 5% in transmissibility or 17% reduction in infectious duration. ConclusionsWe reconstructed the course of a natural experiment in which a mutant strain of C. trachomatis spread across Sweden. Our modelling study provides support, for the first time, of a reduced transmissibility or infectious duration of nvCT. This mathematical model improved our understanding of the first nvCT epidemic in Sweden and can be adapted to investigate the impact of future diagnostic escape mutants. Key messagesO_LIThe dynamics of a new variant of Chlamydia trachomatis (nvCT) that escaped testing and treatment in Sweden can be reconstructed using a mathematical transmission model. C_LIO_LIOur study for the first time provides support of a reduced transmissibility or infectious duration of the nvCT in Sweden. C_LIO_LIThis mathematical model improved our understanding of the nvCT epidemic in Sweden and can be adapted to investigate the impact of future diagnostic escape mutants. C_LI

epidemiology↗

Spatial epidemiology of gestational age and birth weight in Switzerland: Census-based linkage study

BackgroundGestational age and birth weight are strong predictors of infant morbidity and mortality. Understanding spatial variation can inform policies to reduce health inequalities. We examined small-area variation in gestational age and birth weight in Switzerland.\n\nMethodsAll singleton live births recorded in the Swiss Live Birth Register 2011 to 2014 were eligible. We deterministically linked the Live Birth Register with census and survey data to create datasets including neonatal and pregnancy-related variables, parental characteristics and geographical variables. We produced maps of 705 areas and fitted linear mixed-effect models to assess to what extent spatial variation was explained by these variables.\n\nResultsWe analysed all 315,177 eligible live births. Area-level averages of gestational age varied between 272-279 days, and between 3138-3467g for birth weight. The fully adjusted models explained 31% and 87% of spatial variation of gestational age and birth weight, respectively. Language region explained most of the variation, with shorter gestational age and lower birth weight in French- and Italian- than in German-speaking areas. Other variables explaining variation were, for gestational age, the level of urbanisation, the parents nationality and missing father. For birth weight, they were gestational age, altitude, born out of wedlock, and parental nationality. In a subset of 69,463 live births with data on parental education, levels of education were only weakly associated with gestational age or birth weight.\n\nConclusionsIn Switzerland, small area variation in birth weight is largely explained, and variation in gestational age partially explained by geocultural, socio-demographic and pregnancy factors.\n\nStrengths and limitations of this studyO_LIThis study was based on a large sample with national coverage, with data on neonatal and pregnancy-related predictors of gestational age and birth weight, and precise spatial data.\nC_LIO_LINo data were available on the mode of delivery, maternal smoking, mothers weight and height or gestational diabetes.\nC_LIO_LIThe fully adjusted model explained about 80% of the regional variation in birth weight and about 40% of the variation in gestational age.\nC_LIO_LILanguage region, a proxy for cultural, social and behavioural factors, was a strong explanatory factor, with lower birth weight and shorter gestation in the French and Italian compared to the German language region.\nC_LIO_LIUnknown father was associated with shorter gestation and lower birth weight, indicating that children not recognised by their fathers may be at higher risk of poor outcomes.\nC_LI

epidemiology↗

Gini coefficients for measuring the distribution of sexually transmitted infections among individuals with different levels of sexual activity

ObjectivesGini coefficients have been used to describe the distribution of Chlamydia trachomatis (CT) infections among individuals with different levels of sexual activity. The objectives of this study were to investigate Gini coefficients for different sexually transmitted infections (STIs), and to determine how STI control interventions might affect the Gini coefficient over time.\n\nMethodsWe used population-based data for sexually experienced women from two British National Surveys of Sexual Attitudes and Lifestyles (Natsal-2: 1999-2001; Natsal-3: 2010-2012) to calculate Gini coefficients for CT, Mycoplasma genitalium (MG), and human papillomavirus (HPV) types 6, 11, 16 and 18. We applied bootstrap methods to assess uncertainty and to compare Gini coefficients for different STIs. We then used a mathematical model of STI transmission to study how control interventions affect Gini coefficients.\n\nResultsGini coefficients for CT and MG were 0.33 (95% confidence interval (CI): 0.18-0.49) and 0.16 (95% CI: 0.02-0.36), respectively. The relatively small coefficient for MG suggests a longer infectious duration compared with CT. The coefficients for HPV types 6, 11, 16 and 18 ranged from 0.15-0.38. During the decade between Natsal-2 and Natsal-3, the Gini coefficient for CT did not change. The transmission model shows that higher STI treatment rates are expected to reduce prevalence and increase the Gini coefficient of STIs. In contrast, increased condom use reduces STI prevalence but does not affect the Gini coefficient.\n\nConclusionsGini coefficients for STIs can help us to understand the distribution of STIs in the population, according to level of sexual activity, and could be used to inform STI prevention and treatment strategies.\n\nKey messagesO_LIThe Gini coefficient can be used to describe the distribution of STIs in a population, according to different levels of sexual activity.\nC_LIO_LIGini coefficients for Chlamydia trachomatis (CT) and human papillomavirus (HPV) type 18 appear to be higher than for Mycoplasma genitalium and HPV 6, 11 and 16.\nC_LIO_LIMathematical modelling suggests that CT screening interventions should reduce prevalence and increase the Gini coefficient, whilst condom use reduces prevalence without affecting the Gini coefficient.\nC_LIO_LIChanges in Gini coefficients over time could be used to assess the impact of STI prevention and treatment strategies.\nC_LI

epidemiology↗

Mycoplasma genitalium incidence, persistence, concordance between partners and progression: systematic review and meta-analysis

BackgroundMycoplasma genitalium is increasingly seen as an emerging sexually transmitted pathogen, and has been likened to Chlamydia trachomatis, but its natural history is poorly understood. The objectives of this systematic review were to determine M. genitalium incidence, persistence, concordance between sexual partners, and the risk of pelvic inflammatory disease (PID).\n\nMethodsWe searched Medline, EMBASE, LILACS, IndMed and African Index Medicus from 1 January 1981 until 17 March 2018. Two independent researchers screened studies for inclusion and extracted data. We examined results in forest plots, assessed heterogeneity and conducted meta-analysis where appropriate. Risk of bias was assessed for all studies.\n\nResultsWe screened 4634 records and included 17 studies; five (4100 women) reported on incidence, five (636 women) on persistence, 10 (1346 women and men) on concordance and three (5139 women) on PID. Incidence in women in two very highly developed countries was 1.07 per 100 person-years (95% CI, 0.61 to 1.53, I2 0%). Median persistence of M. genitalium was estimated from one to three months in four studies but 15 months in one study. In ten studies measuring M. genitalium infection status in couples, 39-50% of male or female sexual partners of infected participants also had M. genitalium detected. In prospective studies, the incidence of PID was higher in women with M. genitalium than those without (RR 1.68, 95% CI 0.59 to 2.77, I2 0%, 2 studies).\n\nDiscussionBased on findings from this and our linked review of prevalence, concordant M. genitalium might be less common than for C. trachomatis and the age distributions of the infections differ. The synthesised data about prevalence, incidence and persistence of M. genitalium infection are inconsistent. Taken together with evidence about antimicrobial resistance in the two infections, M. genitalium is not the new chlamydia.\n\nRegistration NumbersPROSPERO: CRD42015020420, CRD42015020405\n\nKEY MESSAGESO_LIThere are calls for widespread screening for Mycoplasma genitalium, but the natural history of this emerging sexually transmitted pathogen is poorly understood.\nC_LIO_LIM. genitalium incidence was 1.07 (95% confidence intervals, CI 0.61 to 1.53) per 100-person years in women in highly developed countries, 39-50% of infected individuals had a heterosexual partner with M. genitalium and the risk ratio for pelvic inflammatory disease was 1.68 (95% CI 0.59 to 2.77).\nC_LIO_LIThe duration of untreated M. genitalium infection is probably longer than persistent detection of M. genitalium, as measured in most cohort studies, in which inadvertent treatment cannot be ruled out.\nC_LIO_LIThe results of this systematic review and other evidence sources show important differences in the epidemiology and dynamics of M. genitalium and Chlamydia trachomatis infection.\nC_LI

epidemiology↗

Discrepancies between observed data and predictions from mathematical modelling of the impact of screening interventions on Chlamydia trachomatis prevalence

Mathematical modelling studies of C. trachomatis transmission predict that interventions to screen and treat chlamydia infection will reduce prevalence to a greater degree than that observed in empirical population-based studies. We investigated two factors that might explain this discrepancy: partial immunity after natural infection clearance and differential screening coverage according to infection risk. We used four variants of a compartmental model for heterosexual C. trachomatis transmission, parameterized using data from England about sexual behaviour and C. trachomatis testing, diagnosis and prevalence, and Markov Chain Monte Carlo methods for statistical inference. A model in which partial immunity follows natural infection clearance and the proportion of tests done in chlamydia-infected people decreases over time fitted the data best. The model predicts that partial immunity reduced susceptibility to reinfection by 72% (95% Bayesian credible interval 57-86%). The estimated screening rate was 4.6 (2.6-6.5) times higher for infected than for uninfected women in 2000; this decreased to 2.1 (1.4-2.9) in 2011. Other factors not included in the model could have further reduced the expected impact of screening. Future mathematical modelling studies investigating the effects of screening interventions on C. trachomatis transmission should incorporate host immunity and changes over time in the targeting of screening.

epidemiology↗

Oxford Nanopore MinION genome sequencer: performance characteristics, optimised analysis workflow, phylogenetic analysis and prediction of antimicrobial resistance in Neisseria gonorrhoeae

Antimicrobial resistant (AMR) Neisseria gonorrhoeae strains are common and compromise gonorrhoea treatment internationally. Rapid identification and characterisation of AMR gonococcal strains could ensure appropriate and even personalised treatment, and support identification and investigation of gonorrhoea outbreaks in nearly real-time. Whole-genome sequencing is ideal for investigation of the emergence and dissemination of AMR determinants that predict AMR in the gonococcal population and spread of AMR strains in the human population. The novel, rapid and revolutionary long-read sequencer MinION is a small hand-held device that can generate bacterial genomes within one day. However, the accuracy of MinION reads has been suboptimal for many objectives and the MinION has not been evaluated for gonococci. In this first MinION study for gonococci, we show that MinION-derived sequences analysed with existing open-access, web-based sequence analysis tools are not sufficiently accurate to identify key gonococcal AMR determinants. Nevertheless, using an in house-developed CLC Genomics Workbench, we show that ONT-derived sequences can be used for accurate prediction of decreased susceptibility or resistance to recommended therapeutic antimicrobials. We also show that the ONT-derived sequences can be useful for rapid phylogenomic-based molecular epidemiological investigations, and, in hybrid assemblies with Illumina sequences, for producing contiguous assemblies and finished reference genomes.

genomics↗

De novo mutations drive the spread of macrolide resistant Mycoplasma genitalium: mathematical modelling study

BackgroundThe rapid spread of azithromycin resistance in sexually transmitted Mycoplasma genitalium infections is a growing concern. It is not yet clear to what degree macrolide resistance in M. genitalium results from the emergence of de novo mutations or the transmission of resistant strains.\n\nMethodsWe analyzed epidemiological data and developed a compartmental model to investigate the contribution of de novo macrolide resistance mutations to the spread of antimicrobial-resistant M. genitalium. We fitted the model to data from France, Denmark and Sweden and estimated treatment rates of infected individuals and the time point of azithromycin introduction.\n\nResultsWe found a high probability of de novo resistance (12%, 95% CI 8-17%), which is responsible for the observed rapid spread of antimicrobial resistant M. genitalium. The estimated per capita treatment rate in France was lower than in Denmark and Sweden but confidence intervals for the three estimates overlap. The estimated dates of introduction of azithromycin in each country are consistent with published reports.\n\nConclusionsSince de novo resistance is the main driver of macrolide resistance in M. genitalium, blind treatment of urethritis with azithromycin is not recommended. Clinical management strategies for M. genitalium should limit the unnecessary use of macrolides.

microbiology↗

Exploring variation in human papillomavirus vaccination uptake: multi-level spatial analysis

BackgroundUnderstanding the factors that influence human papillomavirus (HPV) vaccination uptake is critically important to design effective vaccination programmes. In Switzerland, completed HPV vaccination by age 16 years among women ranges from 30 to 79% across 26 cantons (states). Our objective was to identify factors that are associated with the spatial variation in HPV vaccination uptake.\n\nMethods and findingsWe used data from the Swiss National Vaccination Coverage Survey 2009-2016 on HPV vaccination status ([≥]1 dose) of 14-17 year old girls, their municipality of residence and their nationality for 21 of 26 cantons (N=8,965). We examined covariates at municipality level: language, degree of urbanisation, socio-economic position, religious denomination, results of a vote about vaccination laws; and, at cantonal level, availability of school-based vaccination and survey period. We used a series of conditional auto regressive (CAR) models to assess the effects of covariates while accounting for variability between cantons and municipal-level spatial autocorrelation. In the best-fit model, school-based vaccination (adjusted odds ratio, OR: 2.51, 95% credible interval, CI: 1.77-3.56) was associated with increased uptake, while lower acceptance of vaccination laws was associated with lower HPV vaccination uptake (OR 0.61, 95% CI: 0.50-0.73). Overall, the covariates explained 88% of the municipal-level variation in uptake.\n\nConclusionsIn Switzerland, cantons play a prominent role in the variation in HPV vaccination uptake, especially through the provision of school-based vaccination delivery. HPV vaccination uptake is also strongly associated with inhabitants attitudes towards vaccination. To increase uptake, efforts should be made both to mitigate vaccination scepticism and to encourage school-based vaccination.

epidemiology↗

Prevalence of Mycoplasma genitalium in different population groups: systematic review and meta-analysis

BackgroundMycoplasma genitalium is a common cause of non-gonococcal non-chlamydial urethritis and cervicitis. Testing of asymptomatic populations has been proposed, but prevalence rates in asymptomatic populations are not well established. We aimed to estimate the prevalence of M. genitalium in adults in the general population, in clinic-based samples, pregnant women, men who have sex with men (MSM) and female sex workers (FSW).\n\nMethodsWe searched Embase, Medline, IndMED, AIM and LILACS from 1 January 1991 to 12 July 2016 without language restrictions. We included studies with 500 participants or more. We screened and selected studies and extracted data in duplicate. We examined eligible studies in forest plots and conducted random effects meta-analysis to estimate prevalence, if appropriate. Between study heterogeneity was examined using the I2 statistic and meta-regression.\n\nResultsOf 3,316 screened records, 63 were included. In randomly selected samples from the general population, the summary prevalence estimate was 1.3% (95% confidence intervals, CI 1.0 to 1.8%, I2 41.5%, 3 studies) in countries with higher levels of development and 3.9% (95% CI 2.2 to 6.7, I2 89.2%, 3 studies) in countries with lower levels. Prevalence estimates were similar in women and men (p=0.47). In clinic-based samples prevalence estimates were higher, except in asymptomatic patients (0.8%, 95% CI 0.4 to 1.4, I2 0.0%, 3 studies). Summary prevalence estimates were: pregnant women 0.9% (95% CI 0.6 to 1.4%, I2 0%, 4 studies); MSM in the community 3.2% (95% CI 2.1 to 5.1, I2 78.3%, 5 studies); FSW in the community 15.9% (95% CI 13.5 to 18.9, I2 =79.9%, 4 studies).\n\nDiscussionThis systematic review can inform testing guidelines for M. genitalium infection. The low estimated prevalence of M. genitalium in the general population, pregnant women and asymptomatic attenders at clinics does not support expansion of testing to asymptomatic people in these groups.\n\nRegistration Numbers\n\nPROSPERO: CRD42015020420

epidemiology↗

Antibiotic Resistance Detection Is Essential For Gonorrhoea Point-Of-Care Testing: A Mathematical Modelling Study

Antibiotic resistance is threatening to make gonorrhoea untreatable. Point-of-care (POC) tests that detect resistance promise individually tailored treatment, but might lead to more treatment and higher levels of resistance. We investigate the impact of POC tests on antibiotic-resistant gonorrhoea. We used data about the prevalence and incidence of gonorrhoea in men who have sex with men (MSM) and heterosexual men and women (HMW) to calibrate a mathematical gonorrhoea transmission model. With this model, we simulated four clinical pathways for the diagnosis and treatment of gonorrhoea: POC test with (POC + R) and without (POC - R) resistance detection, culture, and nucleic acid amplification tests (NAATs). We calculated the proportion of resistant infections, cases averted after 5 years, and compared how fast resistant infections spread in the populations. The proportion of resistant infections after 30 years is lowest for POC + R (median MSM: 0.18%, HMW: 0.12%), and increases for culture (MSM: 1.19%, HWM: 0.13%), NAAT (MSM: 100%, HMW: 99.27%), and POC - R (MSM: 100%, HMW: 99.73%). NAAT leads to 36 366 (median MSM) and 1 228 (median HMW) observed cases after 5 years. When compared with NAAT, POC + R results in most cases averted after 5 years (median MSM: 3 353, HMW: 118 per 100 000 persons). POC tests that detect resistance with intermediate sensitivity slow down resistance spread more than NAAT. POC tests with very high sensitivity for the detection of resistance are needed to slow down resistance spread more than using culture. POC with high sensitivity to detect antibiotic resistance can keep gonorrhoea treatable longer than culture or NAAT. POC tests without reliable resistance detection should not be introduced because they can accelerate the spread of antibiotic-resistant gonorrhoea.

epidemiology↗

Modeling the consequences of regional heterogeneity in human papillomavirus (HPV) vaccination uptake on transmission in Switzerland

BackgroundCompleted human papillomavirus (HPV) vaccination by age 16 years among women in Switzerland ranges from 17 to 75% across 26 cantons. The consequences of regional heterogeneity in vaccination coverage on transmission and prevalence of HPV-16 are unclear.\n\nMethodsWe developed a deterministic, population-based model that describes HPV-16 transmission among young adults within and between the 26 cantons of Switzerland. We parameterized the model using sexual behavior data from Switzerland and data from the Swiss National Vaccination Coverage Survey. First, we investigated the general consequences of heterogeneity in vaccination uptake between two sub-populations. We then compared the predicted prevalence of HPV-16 after the introduction of heterogeneous HPV vaccination uptake in all of Switzerland with homogeneous vaccination at an uptake that is identical to the national average (52%).\n\nResultsHPV-16 prevalence in women is 3.34% when vaccination is introduced and begins to diverge across cantons, ranging from 0.14 to 1.09% after 15 years of vaccination. After the same time period, overall prevalence of HPV-16 in Switzerland is only marginally higher (0.55 %) with heterogeneous vaccination uptake than with homogeneous uptake (0.49%). Assuming inter-cantonal sexual mixing, cantons with low vaccination uptake benefit from a reduction in prevalence at the expense of cantons with high vaccination uptake.\n\nConclusionsRegional variations in uptake diminish the overall effect of vaccination on HPV-16 prevalence in Switzerland, although the effect size is small. Cantonal efforts towards HPV-prevalence reduction by increasing vaccination uptake are impaired by cantons with low vaccination uptake. Harmonization of cantonal vaccination programs would reduce inter-cantonal differences in HPV-16 prevalence.

epidemiology↗