Biology subjects

Althaus, C. L.

Publications and source records attributed to Althaus, C. L..

8 recordsLinked to original sources

bioRxiv2020

Pattern of early human-to-human transmission of Wuhan 2019-nCoV

On December 31, 2019, the World Health Organization was notified about a cluster of pneumonia of unknown aetiology in the city of Wuhan, China. Chinese authorities later identified a new coronavirus (2019-nCoV) as the causative agent of the outbreak. As of January 23, 2020, 655 cases have been confirmed in China and several other countries. Understanding the transmission characteristics and the potential for sustained human-to-human transmission of 2019-nCoV is critically important for coordinating current screening and containment strategies, and determining whether the outbreak constitutes a public health emergency of international concern (PHEIC). We performed stochastic simulations of early outbreak trajectories that are consistent with the epidemiological findings to date. We found the basic reproduction number, R0, to be around 2.2 (90% high density interval 1.4--3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of a similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and the 1918 pandemic influenza. These findings underline the importance of heightened screening, surveillance and control efforts, particularly at airports and other travel hubs, in order to prevent further international spread of 2019-nCoV.

microbiology↗

bioRxiv2019

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↗

bioRxiv2019

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↗

bioRxiv2018

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↗

bioRxiv2018

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↗

bioRxiv2017

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↗

bioRxiv2017

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↗

bioRxiv2017

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↗