Number Of Symptomatic Infections Research Articles

Network-augmented compartmental models to track asymptomatic disease spread.

A major challenge in understanding the spread of certain newly emerging viruses is the presence of asymptomatic cases. Their prevalence is hard to measure in the absence of testing tools, and yet the information is critical for tracking disease spread and shaping public health policies. Here, we introduce a framework that combines classic compartmental models with travel networks and we use it to estimate asymptomatic rates. Our platform, traSIR ("tracer"), is an augmented susceptible-infectious-recovered (SIR) model that incorporates multiple locations and the flow of people between them; it has a compartment model for each location and estimates of commuting traffic between compartments. TraSIR models both asymptomatic and symptomatic infections, as well as the dampening effect symptomatic infections have on traffic between locations. We derive analytical formulae to express the asymptomatic rate as a function of other key model parameters. Next, we use simulations to show that empirical data fitting yields excellent agreement with actual asymptomatic rates using only information about the number of symptomatic infections over time and compartments. Finally, we apply our model to COVID-19 data consisting of reported daily infections in the New York metropolitan area and estimate asymptomatic rates of COVID-19 to be ∼34%, which is within the 30-40% interval derived from widespread testing. Overall, our work demonstrates that traSIR is a powerful approach to express viral propagation dynamics over geographical networks and estimate key parameters relevant to virus transmission. No public repository.

Association between infectious exposures in infancy and epigenetic age acceleration in young adulthood in metropolitan Cebu, Philippines.

The drivers of human life expectancy gains over the past 200 years are not well-established, with a potential role for historical reductions in infectious disease. We investigate whether infectious exposures in infancy predict biological aging using DNA methylation-based markers that forecast patterns of morbidity and mortality later in life. N = 1450 participants from the Cebu Longitudinal Health and Nutrition Survey-a prospective birth cohort initiated in 1983-provided complete data for the analyses. Mean chronological age was 20.9 years when venous whole blood samples were drawn for DNA extraction and methylation analysis, with subsequent calculation of three epigenetic age markers: Horvath, GrimAge, and DunedinPACE. Unadjusted and adjusted least squares regression models were evaluated to test the hypothesis that infectious exposures in infancy are associated with epigenetic age. Birth in the dry season, a proxy measure for increased infectious exposure in the first year of life, as well as the number of symptomatic infections in the first year of infancy, predicted lower epigenetic age. Infectious exposures were associated with the distribution of white blood cells in adulthood, which were also associated with measures of epigenetic age. We document negative associations between measures of infectious exposure in infancy and DNA methylation-based measures of aging. Additional research, across a wider range of epidemiological settings, is needed to clarify the role of infectious disease in shaping immunophenotypes and trajectories of biological aging and human life expectancy.

Assessing parameter sensitivity in a university campus COVID-19 model with vaccinations.

From the beginning of the COVID-19 pandemic, universities have experienced unique challenges due to their dual nature as a place of education and residence. Current research has explored non-pharmaceutical approaches to combating COVID-19, including representing in models different categories such as age groups. One key area not currently well represented in models is the effect of pharmaceutical preventative measures, specifically vaccinations, on COVID-19 spread on college campuses. There remain key questions on the sensitivity of COVID-19 infection rates on college campuses to potentially time-varying vaccine immunity. Here we introduce a compartment model that decomposes a campus population into constituent subpopulations and implements vaccinations with time-varying efficacy. We use this model to represent a campus population with both vaccinated and unvaccinated individuals, and we analyze this model using two metrics of interest: maximum isolation population and symptomatic infection. We demonstrate a decrease in symptomatic infections occurs for vaccinated individuals when the frequency of testing for unvaccinated individuals is increased. We find that the number of symptomatic infections is insensitive to the frequency of testing of the unvaccinated subpopulation once about 80% or more of the population is vaccinated. Through a Sobol' global sensitivity analysis, we characterize the sensitivity of modeled infection rates to these uncertain parameters. We find that in order to manage symptomatic infections and the maximum isolation population campuses must minimize contact between infected and uninfected individuals, promote high vaccine protection at the beginning of the semester, and minimize the number of individuals developing symptoms.

Blocking NS3–NS4B interaction inhibits dengue virus in non-human primates

Dengue is a major health threat and the number of symptomatic infections caused by the four dengue serotypes is estimated to be 96 million1 with annually around 10,000 deaths2. However, no antiviral drugs are available for the treatment or prophylaxis of dengue. We recently described the interaction between non-structural proteins NS3 and NS4B as a promising target for the development of pan-serotype dengue virus (DENV) inhibitors3. Here we present JNJ-1802—a highly potent DENV inhibitor that blocks the NS3–NS4B interaction within the viral replication complex. JNJ-1802 exerts picomolar to low nanomolar in vitro antiviral activity, a high barrier to resistance and potent in vivo efficacy in mice against infection with any of the four DENV serotypes. Finally, we demonstrate that the small-molecule inhibitor JNJ-1802 is highly effective against viral infection with DENV-1 or DENV-2 in non-human primates. JNJ-1802 has successfully completed a phase I first-in-human clinical study in healthy volunteers and was found to be safe and well tolerated4. These findings support the further clinical development of JNJ-1802, a first-in-class antiviral agent against dengue, which is now progressing in clinical studies for the prevention and treatment of dengue.

Hospital-Based Quasi-Experimental Study on Hydroxychloroquine Pre-Exposure Prophylaxis for COVID-19 in Healthcare Providers with Its Potential Side-Effects.

Quasi-experimental, controlled, single-center study. The included participants were doctors, nurses, health workers, cleaning staff, and non-healthcare supportive staff. The main outcome was contracting COVID-19 anytime during the period of taking the prophylaxis, confirmed by RT-PCR. A total of 336 participants, without any clinical evidence of COVID-19 and without any known contact with family members, were included in the trial; 230 were assigned to HCQ and 106 declined to take any drug. Among the participants, 43 (18.7%) in the HCQ group and 11 (10.4%) participants in the control group developed COVID-19. For the evaluation of side effects, we evaluated 12-lead ECGs of both groups at the baseline and after 4 weeks to monitor QTc interval. A total of 91% (198 of 217) participants in the prophylaxis group and 92% (11 of 12) in the control group had a QTc < 45o msec, which is within normal limits. Although the number of symptomatic infections in health personnel was lower in the control group, the difference was not statistically significant. However, in the absence of any effective pre-exposure prophylaxis medicine for COVID-19, practicing proper infection prevention and control (IPC) and vaccination is the only way forward.

Vacina COVID-19: quanto valem os Anticorpos?

Introduction Since the appearance of the first cases of COVID-19, the pandemic has shown rapid growth with an impact on a global scale. The ability to generate immunity is a key factor for its control, which is why it has been a topic of exhaustive scientific investigation so far. However, despite the widespread administration of vaccines, several doubts remain as to their immunogenicity. The literature suggests that age, gender, and previous serological status influence the difference in humoral immune response. Seropositivity, young age and female gender seem to have a positive influence on antibody levels in most studies published so far. Objectives The aim of this study is to evaluate the humoral response to the Pfizer-BionNTech vaccine in healthcare professionals at a hospital. Methods Professionals with both positive and negative serology were inoculated with two doses. The influence of age, gender and previous serological status on antibody levels was analyzed over a period of six months. Antibodies were assayed using Abbott’s SARS-CoV-2 IgG chemiluminescence immunoassay (SARS-CoV-2 IgG II Quant®) in four stages: prior to the first vaccine inoculation, as well as on the first, third and sixth month after the second inoculation. The study included an initial sample of 1387 health professionals, but only 391 strictly complied with the 4 stages mentioned above. Of the final sample of 391 collaborators, 341 had negative serology prior to vaccination, and had no history of positive RT-PCR for COVID-19. The remaining 50 had positive serology (>6.8 AU/mL). Results It is observed that there is a more robust response in previously seropositive individuals, having presented a higher quantitative value of IgG, but with a similar behaviour to seronegatives regarding sustainability. Antibodies peaked in the first month, especially in younger subjects, showing a progressive decline in the post-vaccination semester for both groups. In a population where the female sex is predominant, it was this one that had a more robust quantitative response to IgG. Finally, we found a marked decrease in the number of symptomatic infections by COVID-19 after immunization, which is transversal to all the current literature. Conclusion In summary, we conclude that previously infected individuals vaccinated with two doses have the same serological behavior regarding humoral immunity compared to uninfected individuals vaccinated with two doses. This result reinforces that the humoral immunity assay cannot be utilized as a clinical tool for the selection and prioritization of whom to vaccinate. KEYWORDS: SARS-CoV-2; BNT162 Vaccine; Immunity; Occupational Health; COVID 19.

Non-pharmaceutical intervention levels to reduce the COVID-19 attack ratio among children.

The attack ratio in a subpopulation is defined as the total number of infections over the total number of individuals in this subpopulation. Using a methodology based on an age-stratified transmission dynamics model, we estimated the attack ratio of COVID-19 among children (individuals 0–11 years) when a large proportion of individuals eligible for vaccination (age 12 and above) are vaccinated to contain the epidemic among this subpopulation, or the effective herd immunity (with additional physical distancing measures). We describe the relationship between the attack ratio among children, the time to remove infected individuals from the transmission chain and the children-to-children daily contact rate while considering the increased transmissibility of virus variants (using the Delta variant as an example). We illustrate the generality and applicability of the methodology established by performing an analysis of the attack ratio of COVID-19 among children in the population of Canada and in its province of Ontario. The clinical attack ratio, defined as the number of symptomatic infections over the total population, can be informed from the attack ratio and both can be reduced substantially via a combination of reduced social mixing and rapid testing and isolation of the children.

Early childhood infections and body mass index in adolescence.

The incidence of childhood overweight and obesity is rising. It is hypothesized that infections in early childhood are associated with being overweight. This study investigated the association between the number of symptomatic infections or antibiotic prescriptions in the first 3 years of life and body mass index (BMI) in adolescence. The current study is part of the Prevention and Incidence of Asthma and Mite Allergy population-based birth cohort study. Weight and height were measured by trained research staff at ages 12 and 16 years. The 3015 active participants at age 18 years were asked for informed consent for general practitioner (GP) data collection and 1519 gave written informed consent. Studied exposures include (1) GP-diagnosed infections, (2) antibiotic prescriptions, and (3) parent-reported infections in the first 3 years of life. Generalized estimating equation analysis was used to determine the association between each of these exposures and BMI z-score. Exposure data and BMI measurement in adolescence were available for 622 participants. The frequencies of GP-diagnosed infections and antibiotic prescriptions were not associated with BMI z-score in adolescence with estimates being 0.14 (95% CI -0.09-0.37) and 0.10 (95% CI -0.14-0.34) for the highest exposure categories, respectively. Having ≥6 parent-reported infections up to age 3 years was associated with a 0.23 (95% CI 0.01-0.44) higher BMI z-score compared to <2 parent-reported infections. For all infectious disease measures an increase in BMI z-score for the highest childhood exposure to infectious disease was observed, although only statistically significant for parent-reported infections. These results do not show an evident link with infection severity, but suggest a possible cumulative effect of repeated symptomatic infections on overweight development.

Cost-effectiveness of pertussis booster vaccination in the Netherlands

The aim of the current study is to estimate the epidemiological and economical consequences of several extended pertussis booster vaccination strategies and to explore the impact of parameters surrounded by large uncertainty on the cost-effectiveness.We developed an age structured transmission dynamic model to evaluate the impact of programs targeting (i) adolescents or adults using a single booster dose, (ii) a combination of adolescent and adult vaccination, and (iii) an every 10 years booster dose.The base case analysis, that is a single adolescent booster administered at the age of 12 years, resulted in a reduction of pertussis infections. However, due to an increase in the number of symptomatic infections in adults, the benefits in terms of QALYs gained and costs saved in children were partly offset. Despite these negative indirect effects in the adult population, administering an additional booster dose could still be considered cost effective with an ICER of €4200 per QALY gained. Combining an adolescent booster dose at the age of 10 (most cost-effective age for a single adolescent booster dose) with an adult (18–30 years) booster dose always resulted in favorable ICERs (<€10,000/QALY). Finally the every 10 year booster dose resulted in an ICER of €16,900 per QALY. The impact of different assumptions regarding the disease epidemiology, disease-related parameters, and vaccination program-related issues was limited.To conclude, we show that extended pertussis booster vaccination strategies are likely to be considered as cost-effective.

Methenamine-hippurate and bacteriuria in the geriatric patient with a catheter.

Oral treatment with methenamine-hippurate (MH) in patients with an indwelling catheter has been found to reduce the need of frequent catheter exchange and the number of symptomatic infections. Bacteriuria, however, persists during MH treatment. The hypothesis that the therapeutic effect is due to a reduction in the number of bacteria, or a change in the pattern of strains was tested in a crossover study (2 x 6 weeks). MH treatment, 1 g twice daily, was compared to control periods in 52 patients. The majority of quantitative and qualitative bacterial cultures at 2-week intervals yielded 2--4 strains. Of the bacterial isolates, 50% were found on 4--6 occasions out of 6 possible. MH treatment had no significant influence on the pattern of various strains. A 30% decrease in the mean total bacterial count during MH treatment did not reach statistical significance (p approximately 0.07). It is suggested that prevention of catheter complications during MH treatment may be due to a physiochemical action on salt formation rather than a direct antibacterial effect.