scholarly journals Characterising antibody kinetics from multiple influenza infection and vaccination events in ferrets

2018 ◽  
Author(s):  
James A. Hay ◽  
Karen Laurie ◽  
Michael White ◽  
Steven Riley
Keyword(s):  
Mathematical Models ◽  
Influenza Infection ◽  
Haemagglutination Inhibition ◽  
Significant Proportion ◽  
Parameter Estimates ◽  
Human Populations ◽  
Human Antibody ◽  
Short Term ◽  
Immunological Mechanisms ◽  
Antibody Kinetics

AbstractThe strength and breadth of an individual’s antibody repertoire are important predictors of their response to influenza infection or vaccination. Although progress has been made in understanding qualitatively how repeated exposures shape the antibody mediated immune response, quantitative understanding remains limited. We developed a set of mathematical models describing short-term antibody kinetics following influenza infection or vaccination and fit them to haemagglutination inhibition (HI) titres from 5 groups of ferrets which were exposed to different combinations of trivalent inactivated influenza vaccine (TIV with or without adjuvant), A/H3N2 priming inoculation and post-vaccination A/H1N1 inoculation. We fit models with various immunological mechanisms that have been empirically observed but are yet to be included in mathematical models of antibody landscapes, including titre ceiling effects, antigenic seniority and exposure-type specific cross reactivity. Based on the parameter estimates of the best supported models, we describe a number of key immunological features. We found quantifiable differences in the degree of homologous and cross-reactive antibody boosting elicited by different exposure types. Infection and adjuvanted vaccination generally resulted in strong, broadly reactive responses whereas unadjuvanted vaccination resulted in a weak, narrow response. We found that the order of exposure mattered: priming with A/H3N2 improved subsequent vaccine response, and the second dose of adjuvanted vaccination resulted in substantially greater antibody boosting than the first. Either antigenic seniority or a titre ceiling effect were included in the two best fitting models, suggesting that a mechanism describing diminishing antibody boosting with repeated exposures improved the predictive power of the model. Although there was considerable uncertainty in our estimates of antibody waning parameters, our results suggest that both short and long term waning were present and would be identifiable with a larger set of experiments. These results highlight the potential use of repeat exposure animal models in revealing short-term, strain-specific immune dynamics of influenza.Author summaryDespite most individuals having some preexisting immunity from past influenza infections and vaccinations, a significant proportion of the human population is infected with influenza each year. Predicting how an individual’s antibody profile will change following exposure is therefore useful for evaluating which populations are at greatest risk and how effective vaccination strategies might be. However, interpretation of antibody data from humans is complicated by immunological interactions between all previous, unobserved exposures in an individual’s life. We developed a mathematical model to describe short-term antibody kinetics that are important in building an individual’s immune profile but are difficult to observe in human populations. We validated this model using antibody data from ferrets with known, varied infection and vaccination histories. We were able to quantify the independent contributions of various exposures and immunological mechanisms in generating observed antibody titres. These results suggest that data from experimental systems may be included in models of human antibody dynamics, which may improve predictions of vaccination strategy effectiveness and how population susceptibility changes over time.

scholarly journals Development of the reproduction number from coronavirus SARS-CoV-2 case data in Germany and implications for political measures

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Sahamoddin Khailaie ◽  
Tanmay Mitra ◽  
Arnab Bandyopadhyay ◽  
Marta Schips ◽  
Pietro Mascheroni ◽  
...  
Keyword(s):  
Structural Changes ◽  
Reproduction Number ◽  
National Level ◽  
Transmission Dynamics ◽  
Federal State ◽  
Parameter Estimates ◽  
Time Varying ◽  
Short Term ◽  
Robert Koch Institute ◽  
Federal States

Abstract Background SARS-CoV-2 has induced a worldwide pandemic and subsequent non-pharmaceutical interventions (NPIs) to control the spread of the virus. As in many countries, the SARS-CoV-2 pandemic in Germany has led to a consecutive roll-out of different NPIs. As these NPIs have (largely unknown) adverse effects, targeting them precisely and monitoring their effectiveness are essential. We developed a compartmental infection dynamics model with specific features of SARS-CoV-2 that allows daily estimation of a time-varying reproduction number and published this information openly since the beginning of April 2020. Here, we present the transmission dynamics in Germany over time to understand the effect of NPIs and allow adaptive forecasts of the epidemic progression. Methods We used a data-driven estimation of the evolution of the reproduction number for viral spreading in Germany as well as in all its federal states using our model. Using parameter estimates from literature and, alternatively, with parameters derived from a fit to the initial phase of COVID-19 spread in different regions of Italy, the model was optimized to fit data from the Robert Koch Institute. Results The time-varying reproduction number (Rt) in Germany decreased to <1 in early April 2020, 2–3 weeks after the implementation of NPIs. Partial release of NPIs both nationally and on federal state level correlated with moderate increases in Rt until August 2020. Implications of state-specific Rt on other states and on national level are characterized. Retrospective evaluation of the model shows excellent agreement with the data and usage of inpatient facilities well within the healthcare limit. While short-term predictions may work for a few weeks, long-term projections are complicated by unpredictable structural changes. Conclusions The estimated fraction of immunized population by August 2020 warns of a renewed outbreak upon release of measures. A low detection rate prolongs the delay reaching a low case incidence number upon release, showing the importance of an effective testing-quarantine strategy. We show that real-time monitoring of transmission dynamics is important to evaluate the extent of the outbreak, short-term projections for the burden on the healthcare system, and their response to policy changes.

scholarly journals Characterising antibody kinetics from multiple influenza infection and vaccination events in ferrets

2019 ◽  
Vol 15 (8) ◽  
pp. e1007294 ◽  
Author(s):  
James A. Hay ◽  
Karen Laurie ◽  
Michael White ◽  
Steven Riley
Keyword(s):  
Influenza Infection ◽  
Antibody Kinetics

Frequency distribution of Wuchereria bancrofti microfilariae in human populations and its relationships with age and sex

Parasitology ◽  
1990 ◽  
Vol 101 (3) ◽  
pp. 429-434 ◽  
Author(s):  
P. K. Das ◽  
A. Manoharan ◽  
A. Srividya ◽  
B. T. Grenfell ◽  
D. A. P. Bundy ◽  
...  
Keyword(s):  
Frequency Distribution ◽  
Negative Binomial ◽  
Age Distribution ◽  
Indirect Evidence ◽  
Wuchereria Bancrofti ◽  
Parameter Estimates ◽  
Human Populations ◽  
Sampling Errors ◽  
Frequency Distributions ◽  
Age And Sex

SUMMARYThis paper examines the effects of host age and sex on the frequency distribution of Wuchereria bancrofti infections in the human host. Microfilarial counts from a large data base on the epidemiology of bancroftian filariasis in Pondicherry, South India are analysed. Frequency distributions of microfilarial counts divided by age are successfully described by zero-truncated negative binomial distributions, fitted by maximum likelihood. Parameter estimates from the fits indicate a significant trend of decreasing overdispersion with age in the distributions above age 10; this pattern provides indirect evidence for the operation of density-dependent constraints on microfilarial intensity. The analysis also provides estimates of the proportion of mf-positive individuals who are identified as negative due to sampling errors (around 5% of the total negatives). This allows the construction of corrected mf age–prevalence curves, which indicate that the observed prevalence may underestimate the true figures by between 25% and 100%. The age distribution of mf-negative individuals in the population is discussed in terms of current hypotheses about the interaction between disease and infection.

DEVELOPMENT OF MATHEMATICAL MODELS FOR THE SHORT-TERM FORECASTING OF DAILY CONSUMPTION SCHEDULES OF ACTIVE POWER BY MOSCOW

2021 ◽  
Author(s):  
S. А. Vyalkova ◽  
◽  
O. А. Kornykova ◽  
I. I. Nadtoka ◽  
◽  
...  
Keyword(s):  
Mathematical Models ◽  
Active Power ◽  
Short Term ◽  
Daily Consumption ◽  
Short Term Forecasting

Изложены результаты по решению проблемы повышения точности прогнозирования электропотребления. Целью является разработка математических моделей для краткосрочного прогнозирования суточных графиков активной мощности г. Москвы с учетом метеофакторов. Выполнены исследования четырех прогнозных моделей, базирующихся на сингулярном спектральном анализе (SSA), методе наименьших квадратов, тригонометрической интерполяции, нейронных и нечётких нейронных сетях (ННС). Показано, что наименьшую погрешность имеет ННС и гибридная модель на основе MSSA и ННС.

scholarly journals Screening of Highly Expressed Mycobacterial Genes Identifies Rv3615c as a Useful Differential Diagnostic Antigen for the Mycobacterium tuberculosis Complex

2008 ◽  
Vol 76 (9) ◽  
pp. 3932-3939 ◽  
Author(s):  
Ben Sidders ◽  
Chris Pirson ◽  
Philip J. Hogarth ◽  
R. Glyn Hewinson ◽  
Neil G. Stoker ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Significant Proportion ◽  
Growth Conditions ◽  
Control Measures ◽  
Human Populations ◽  
Infected Cattle ◽  
Ifn Γ ◽  
Mycobacterial Antigens ◽  
And Control ◽  
Differential Antigens

ABSTRACT Tuberculous infections caused by mycobacteria, especially tuberculosis of humans and cattle, are important both clinically and economically. Human populations can be vaccinated with Mycobacterium bovis bacille Calmette-Guérin (BCG), and control measures for cattle involving vaccination are now being actively considered. However, diagnostic tests based on tuberculin cannot distinguish between genuine infection and vaccination with BCG. Therefore, identification of differential diagnostic antigens capable of making this distinction is required, and until now sequence-based approaches have been predominant. Here we explored the link between antigenicity and mRNA expression level, as well as the possibility that we may be able to detect differential antigens by analyzing quantified global transcriptional profiles. We generated a list of 14 candidate antigens that are highly expressed in Mycobacterium tuberculosis and M. bovis under a variety of growth conditions. These candidates were screened in M. bovis-infected and naïve cattle for the ability to stimulate a gamma interferon (IFN-γ) response. We identified one antigen, Rv3615c, which stimulated IFN-γ responses in a significant proportion of M. bovis-infected cattle (11 of 30 cattle [37%] [P < 0.01]) but not in naïve or BCG-vaccinated animals. Importantly, the same antigen stimulated IFN-γ responses in a significant proportion of infected cattle that did not respond to the well-characterized mycobacterial antigens ESAT-6 and CFP-10. Therefore, use of the Rv3615c epitope in combination with previously described differential tests based on ESAT-6 and CFP-10 has the potential to significantly increase diagnostic sensitivity without reducing specificity in BCG-vaccinated populations.

scholarly journals Risks associated with the transportation of hazardous materials on public roads

2018 ◽  
Vol 231 ◽  
pp. 05004
Author(s):  
Eligiusz Mieloszyk ◽  
Anita Milewska
Keyword(s):  
Mathematical Models ◽  
Dynamic Systems ◽  
Negative Impact ◽  
Significant Proportion ◽  
Water Reservoir ◽  
Hazardous Materials ◽  
Road Users ◽  
Distributed Parameters ◽  
Surrounding Environment ◽  
Flow Surface

A significant proportion of the transport of hazardous materials is carried out on public roads. Therefore, the safety of such transport is becoming increasingly important. Every catastrophe involving hazardous materials has a negative impact on direct road users and the surrounding environment, becauses its range is mostly not local. It follows that in the event of such catastrophe, its effects should be minimized. This is possible only when we know the mechanism of spreading effects of a catastrophe involving hazardous materials. Those effects are spread by two basic media: ground (in particular water in the ground) and air. Sometimes those effects are spread by water, while the catastrophe has occurred near a water reservoir or watercourse with a free flow surface. In extreme cases, this can even lead to an ecological disaster. Dynamic systems, especially those with distributed parameters, can be used to describe the mechanism of the disaster's spread. Properties of phenomena accompanying analyzed catastrophes are well reflected in their linear or non-linear mathematical models [1,2], which are analyzed by various operator methods [3].

scholarly journals Animal origins of SARS coronavirus: possible links with the international trade in small carnivores

2004 ◽  
Vol 359 (1447) ◽  
pp. 1107-1114 ◽  
Author(s):  
Diana Bell ◽  
Scott Roberton ◽  
Paul R. Hunter
Keyword(s):  
Significant Proportion ◽  
Interdisciplinary Approach ◽  
Wildlife Trade ◽  
Human Populations ◽  
Sars Coronavirus ◽  
Natural Habitats ◽  
Biodiversity Crisis ◽  
International Borders ◽  
Animal Populations ◽  
International Wildlife Trade

The search for animal host origins of severe acute respiratory syndrome (SARS) coronavirus has so far remained focused on wildlife markets, restaurants and farms within China. A significant proportion of this wildlife enters China through an expanding regional network of illegal, international wildlife trade. We present the case for extending the search for ancestral coronaviruses and their hosts across international borders into countries such as Vietnam and Lao People's Democratic Republic, where the same guilds of species are found on sale in similar wildlife markets or food outlets. The three species that have so far been implicated, a viverrid, a mustelid and a canid, are part of a large suite of small carnivores distributed across this region currently overexploited by this international wildlife trade. A major lesson from SARS is that the underlying roots of newly emergent zoonotic diseases may lie in the parallel biodiversity crisis of massive species loss as a result of overexploitation of wild animal populations and the destruction of their natural habitats by increasing human populations. To address these dual threats to the long–term future of biodiversity, including man, requires a less anthropocentric and more interdisciplinary approach to problems that require the combined research expertise of ecologists, conservation biologists, veterinarians, epidemiologists, virologists, as well as human health professionals.

scholarly journals Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients With Inflammatory Bowel Disease: Results From the Eneida Registry

2019 ◽  
Author(s):  
María José Casanova ◽  
María Chaparro ◽  
Miguel Mínguez ◽  
Elena Ricart ◽  
Carlos Taxonera ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Combination Therapy ◽  
Adverse Events ◽  
Bowel Disease ◽  
Tumor Necrosis ◽  
Significant Proportion ◽  
Short Term ◽  
Loss Of Response ◽  
Inflammatory Bowel ◽  
Necrosis Factor

Abstract Background The effectiveness of the switch to another anti–tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8–3; P < 0.0001) and ulcerative colitis vs Crohn’s disease (HR, 1.6; 95% CI, 1.1–2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.

scholarly journals The use of the haemagglutination-inhibition test in epidemiological influenza-virus studies

1949 ◽  
Vol 47 (4) ◽  
pp. 396-397 ◽  
Author(s):  
Hendrik L. Wolff
Keyword(s):  
Influenza Virus ◽  
Influenza Infection ◽  
Haemagglutination Inhibition ◽  
Inhibition Test ◽  
Haemagglutination Inhibition Test

The importance of the haemagglutination-inhibition test does not need to be stressed. It is a fact that the inhibition titre of a single serum has no constant value, but may vary in repeated estimations. This may be due to the use of different virus or erythrocyte suspensions or to differences in environmental circumstances, such as temperature. Duplicate tests carried out at the same time and with the same materials yield identical results. This makes it necessary to compare a serum obtained during convalescence from the same case. The ratio between the two titres shows whether an influenza infection has taken place or not. Although it is commonly accepted that a titre rising by two twofold dilutions (a fourfold rise) is significant, some workers will accept even a twofold rise (Sartwill & Long, 1948; Rasmussen, Stoles & Smadel, 1948). Such observations have been made on pairs of sera taken from the same indicidual with not more than a 5-week interval between them.

Physiological temperature response and embryonic mortality in stressed swine

1975 ◽  
Vol 229 (6) ◽  
pp. 1471-1475 ◽  
Author(s):  
DE Wildt ◽  
GD Riegle ◽  
WR Dukelow
Keyword(s):  
Thermal Environment ◽  
Physiological Responses ◽  
Significant Proportion ◽  
Temperature Response ◽  
Reproductive Function ◽  
Embryonic Mortality ◽  
Delayed Effect ◽  
Short Term ◽  
Embryo Survival ◽  
Early Gestation

Physiological responses and some aspects of reproductive function were examined in mated female pigs subjected to a short-term heat stress during two intervals of early gestation. Trial 1 control and treated animals experienced temperatures of 24.0 and 40.2 degrees C, respectively, from days 2 through 13 of pregnancy. Trial 2 control and treated pigs were exposed to 23.3 and 40.4 degrees C, respectively, from days 14 through 25 of pregnancy. Both high thermal exposures caused significant increases (P less than 0.05) in rectal temperature. At body temperatures of 41.1 degrees C or above, animals became more active and behavioral patterns erratic. Stressed pigs in both trials exhibited adaptation to the short-term high thermal environment as treatment days progressed. Embryonic mortality in the stressed animals in trial 1 was greater than in controls, with the animals in the former group retaining a normal size litter or losing the entire litter by day of slaughter. A significant proportion (P less than 0.01) of litters from stressed animals contained degenerating fetuses at day 42 of gestation, suggesting a continuous or delayed effect of thermal stress on embryo survival.

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