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Hoze, N.

Publications and source records attributed to Hoze, N..

4 recordsLinked to original sources

Quantifying circulation and antibody cross-reactivity for co-circulating flaviviruses: the case of Usutu and West Nile virus in blackbirds

Serological testing is important for assessing past exposure and immunity, but interpretation can be complicated by antibody cross-reactivity between closely related viruses. We assess this challenge for Usutu virus (USUV) and West Nile virus (WNV), flaviviruses that recently emerged in Europe. We analysed samples from wild blackbirds collected in the Netherlands between 2016-2022. Samples (N=1742) were screened using an NS1-based protein micro-array, with positives confirmed by Focus Reduction Neutralization Tests (FRNT). We jointly estimated seroprevalence and antibody responses by fitting a Bayesian latent-variable model to FRNT values. Estimates of homologous and cross-reactive antibody responses were used to improve interpretation of observed titres for serosurveillance. Estimated seroprevalence varied across time and regions between 4.9% (95%CrI 3.5-6.7) to 18.5% (95%CrI 14.9-22.7) for USUV and between 2.4% (95%CrI 1.3-3.8) to 6.4% (95%CrI 3.9-9.6) for WNV. These were 1.5 (USUV) to 2.4 times (WNV) higher than estimates based on the current threshold-based algorithm. USUV induced a higher antibody response and was more likely to induce a cross-reactive response than WNV. Our classification algorithm informed by these estimates showed high sensitivity (WNV: 0.88, USUV: 0.97) and specificity (both: >0.99). Our results illustrate how quantitative frameworks can improve serological interpretation in settings with co-circulating pathogens.

ecology↗

The analysis of a large dataset of PCR-test results in the community reveals the impact of age, variants and vaccination status on SARS-CoV-2 viral dynamics

The COVID-19 pandemic has shown the value of large-scale community PCR tests for epidemic surveillance, but the viral load measurements they provide have seldom been exploited to reconstruct within-host trajectories. Because these data are collected for diagnostic rather than research purposes, they are characterized by sparse longitudinal follow-up, heterogeneous sampling, and missing metadata, raising uncertainty about their usefulness to reconstruct with-host viral dynamics. We first conducted a simulation study to assess the feasibility of estimating the viral dynamics patterns from such datasets. Across multiple scenarios replicating realistic sampling patterns, we found that peak viral load and clearance time could be estimated with good accuracy, although uncertainty tended to be underestimated. Parameters driving early viral kinetics, e.g. incubation and proliferation time, were mostly estimated with poor precision, as most community tests are conducted after symptom onset, later in infection. We then applied this framework to a large dataset of 322,218 PCR tests associated with symptomatic SARS-CoV-2 infections in France between July 2021 and March 2022, encompassing both Delta-variant circulation and the emergence of first Omicron variants. We quantified the effects of age, vaccination, and variants on viral load trajectories. Age [≥]65 years was consistently associated with longer clearance time, extending the duration of detectable viral load by 2 to 6 days. Vaccination shortened the clearance time by 2 to 4 days but had minimal impact on peak viral load. Infections by Omicron-variants were associated with a lower peak viral load and shorter clearance times compared with pre-Omicron (Delta) infections. Thus, community PCR tests can be leveraged to identify key parameters of viral dynamics. As multiplex PCR testing becomes increasingly widespread, establishing robust frameworks for data collection, sharing, and privacy protection will be essential to support the use of these data. Author SummaryIn this study, we explored whether viral load data collected routinely in community laboratories can help us understand how factors like age, vaccination, and viral variant influence the course of infection. These data, collected for diagnostic purposes rather than research, are large but often incomplete, with most individuals tested only after the time of symptoms onset. We first used simulations to assess whether, despite these limitations, key aspects of viral dynamics can be reliably estimated. We then applied our approach to millions of test results collected in France during periods dominated by Delta and Omicron variants. We found that older age was consistently associated with longer infection duration, while vaccination reduced the time the virus remained detectable without affecting peak viral levels. Omicron infections were generally associated with lower peak viral load and somewhat faster clearance than pre-Omicron infections. Overall, our work demonstrates that community testing data, can provide valuable insights into viral dynamics and help monitor the effects of new variants or interventions. As multiplex tests become more common, facilitating and improving data collection, sharing, and privacy protection will be essential to make the most of these resources in future outbreaks.

systems biology↗

Aggressive or moderate drug therapy for infectious diseases? Trade-offs between different treatment goals at the individual and population levels

Antimicrobial resistance is one of the major public health threats of the 21st century. There is a pressing need to adopt more efficient treatment strategies in order to prevent the emergence and spread of resistant strains. The common approach is to treat patients with high drug doses, both to clear the infection quickly and to reduce the risk of de novo resistance. Recently, several studies have argued that, at least in some cases, low-dose treatments could be more suitable to reduce the within-host emergence of antimicrobial resistance. However, the choice of a drug dose may have consequences at the population level, which has received little attention so far.\n\nHere, we study the influence of the drug dose on resistance and disease management at the host and population levels. We develop a nested two-strain model and unravel trade-offs in treatment benefits between an individual and the community. We use several measures to evaluate the benefits of any dose choice. Two measures focus on the emergence of resistance, at the host level and at the population level. The other two focus on the overall treatment success: the outbreak probability and the disease burden. We find that different measures can suggest different dosing strategies. In particular, we identify situations where low doses minimize the risk of emergence of resistance at the individual level, while high or intermediate doses prove most beneficial to improve the treatment efficiency or even to reduce the risk of resistance in the population.\n\nAuthor summaryThe obvious goals of antimicrobial drug therapy are rapid patient recovery and low disease prevalence in the population. However, achieving these goals is complicated by the rapid evolution and spread of antimicrobial resistance. A sustainable treatment strategy needs to account for the risk of resistance and keep it in check. One parameter of treatment is the drug dosage, which can vary within certain limits. It has been proposed that lower doses may, in some cases, be more suitable than higher doses to reduce the risk of resistance evolution in any one patient. However, if lower doses prolong the period of infectiousness, such a strategy has consequences for the pathogen dynamics of both strains at the population level. Here, we set up a nested model of within-host and between-host dynamics for an acute self-limiting infection. We explore the consequences of drug dosing on several measures of treatment success: the risk of resistance at the individual and population levels and the outbreak probability and the disease burden of an epidemic. Our analysis shows that trade-offs may exist between optimal treatments under these various criteria. The criterion given most weight in the decision process ultimately depends on the disease and population under consideration.

epidemiology↗

Statistical methods for large ensemble of super-resolution stochastic single particle trajectories

Following recent progresses in super-resolution microscopy obtained in the last decade, massive amount of redundant single stochastic trajectories are now available for statistical analysis. Flows of trajectories of molecules or proteins are sampling the cell membrane or its interior at a very high time and space resolution. Several statistical analysis were developed to extract information contained in these data, such as the biophysical parameters of the underlying stochastic motion to reveal the cellular organization. These trajectories can further reveal hidden subcellular organization. We present here the statistical analysis of these trajectories based on the classical Langevin equation, which serves as a model of trajectories. Parametric and non-parametric estimators are constructed by discretizing the stochastic equations and they allow recovering tethering forces, diffusion tensor or membrane organization from measured trajectories, that differ from physical ones by a localization noise. Modeling, data analysis and automatic detection algorithms serve extracting novel biophysical features such as potential wells and other sub-structures, such as rings at an unprecedented spatiotem-poral resolution. It is also possible to reconstruct the surface membrane of a biological cell from the statistics of projected random trajectories.

biophysics↗