Modeling anticipated changes in numbers of SARS-CoV-2 infections within communities due to immunization campaigns.

Background: As SARS-CoV-2 spread in early 2020, uncertainty about the scope, duration, and impact of the unfolding outbreaks caused numerous countries to interrupt many routine activities, including health services. Because immunization is an essential health service, modeling changes in SARS-CoV-2 infections among communities and health workers due to different vaccination activities was undertaken to understand the risks and to inform approaches to resume services. Methods: Agent-based modeling examined the impact of Supplemental Immunization Activities (SIAs) delivery strategies on SARS-CoV-2 transmission in communities and health workers for six countries capturing various demographic profiles and health system performance: Angola, Ecuador, Lao PDR, Nepal, Pakistan, and Ukraine. Results: Urban, fixed-post SIAs during periods of high SARS-CoV-2 prevalence increased infections within the community by around 28 [range:0-79] per 1000 vaccinations. House-to-house SIAs in mixed urban and rural contexts may import infections into previously naïve communities. Infections are elevated by around 60 [range:0-230] per 1000 vaccinations, but outcomes are sensitive to prevalence in health workers and SIA timing relative to peak. Conclusions: Younger populations experience lower transmission intensity and fewer excess infections per childhood vaccine delivered. Large rural populations have lower transmission intensity but face a greater risk of introduction of SARS-CoV-2 during an SIA.

Corrigendum to "Examination of scenarios introducing rubella vaccine in the Democratic Republic of the Congo" [Vaccine: X 9 (2021) 100127].

[This corrects the article DOI: 10.1016/j.jvacx.2021.100127.].

Examination of scenarios introducing rubella vaccine in the Democratic Republic of the Congo.

BACKGROUND: Rubella vaccine has yet to be introduced into the national immunization schedule of the Democratic Republic of the Congo (DRC); the current burden of congenital rubella syndrome (CRS) is unknown and likely to be high. An important consideration prior to introducing rubella containing vaccine (RCV) is the potential inverse relationship between RCV coverage and CRS incidence. Increasing RCV coverage will also increase in the average age of infection. Cumulative infections across all age groups will decrease, but the number of infections in age groups vulnerable to CRS may increase. METHODS: Rubella transmission dynamics in the DRC were simulated using a stochastic agent-based model of transmission. Input parameter values for known properties, demographic variables, and interventions were fixed; infectivity was inferred from seropositivity profiles in survey data. RESULTS: Our simulations of RCV introduction for the DRC demonstrate that an increase in CRS burden is unlikely. Continued endemic transmission is only plausible when routine immunization coverage is less than 40% and follow-up supplemental immunization activities have poor coverage for decades. CONCLUSION: Increased vaccination coverage tends to increase the annual variability of CRS burden. Simulations examining low vaccination coverage and high mean CRS burden are outbreak prone, with multiple years of reduced burden followed by acute outbreaks. These outcomes contrast simulations with no vaccination coverage and high mean CRS burden, which have more consistent burden from year to year.

Comparison of Coverage-Dependent Binding Energy Models for Mean-Field Microkinetic Rate Predictions.

The binding energies of adsorbates at catalytic surfaces are in general functions of adsorbate coverage, with corresponding consequences for equilibrium surface coverages and reaction rates under relevant conditions. This coverage dependence is commonly incorporated into mean-field microkinetic models by writing adsorption energies as an algebraic function of coverage and parametrizing against density functional theory models. In this work, we compare the performance of three different analytical coverage-dependent forms, including linear and piecewise models and a logarithmic form inspired by Wilson's activity model, against accurate results obtained from a lattice-based cluster expansion (CE) representation of adsorbate interactions combined with a Monte Carlo evaluation of reaction rates. We take as a model system O2 dissociation-limited NO oxidation to NO2 over Pt(111), parametrize all models against the same set of previously reported coverage-dependent NO and O binding energies, and solve kinetic models under the same set of assumptions. Steady-state coverages from the analytical models are similar to each other and the ensemble-averaged CE result, other than the discontinuities in O and NO coverages that appear in the piecewise model. Predicted steady-state rates differ more substantially, reflecting the sensitivity of the O2 dissociation activation energy to coverage-dependent binding energies. The activity model predicts reaction rates reliably at low temperatures and systematically deviates from CE rates at high temperatures, where minority surface sites, having low local coverage around vacant pairs, dominate overall reaction rates. The results highlight the challenges of developing coverage-dependent microkinetic models that are reliable across a range of conditions.

Optimization of frequency and targeting of measles supplemental immunization activities in Nigeria: A cost-effectiveness analysis.

BACKGROUND: Measles causes significant childhood morbidity in Nigeria. Routine immunization (RI) coverage is around 40% country-wide, with very high levels of spatial heterogeneity (3-86%), with supplemental immunization activities (SIAs) at 2-year or 3-year intervals. We investigated cost savings and burden reduction that could be achieved by adjusting the inter-campaign interval by region. METHODS: We modeled 81 scenarios; permuting SIA calendars of every one, two, or three years in each of four regions of Nigeria (North-west, North-central, North-east, and South). We used an agent-based disease transmission model to estimate the number of measles cases and ingredients-based cost models to estimate RI and SIA costs for each scenario over a 10 year period. RESULTS: Decreasing SIAs to every three years in the North-central and South (regions of above national-average RI coverage) while increasing to every year in either the North-east or North-west (regions of below national-average RI coverage) would avert measles cases (0.4 or 1.4 million, respectively), and save vaccination costs (save $19.4 or $5.4 million, respectively), compared to a base-case of national SIAs every two years. Decreasing SIA frequency to every three years in the South while increasing to every year in the just the North-west, or in all Northern regions would prevent more cases (2.1 or 5.0 million, respectively), but would increase vaccination costs (add $3.5 million or $34.6 million, respectively), for $1.65 or $6.99 per case averted, respectively. CONCLUSIONS: Our modeling shows how increasing SIA frequency in Northern regions, where RI is low and birth rates are high, while decreasing frequency in the South of Nigeria would reduce the number of measles cases with relatively little or no increase in vaccination costs. A national vaccination strategy that incorporates regional SIA targeting in contexts with a high level of sub-national variation would lead to improved health outcomes and/or lower costs.

Implementation and applications of EMOD, an individual-based multi-disease modeling platform.

Individual-based models provide modularity and structural flexibility necessary for modeling of infectious diseases at the within-host and population levels, but are challenging to implement. Levels of complexity can exceed the capacity and timescales for students and trainees in most academic institutions. Here we describe the process and advantages of a multi-disease framework approach developed with formal software support. The epidemiological modeling software, EMOD, has undergone a decade of software development. It is structured so that a majority of code is shared across disease modeling including malaria, HIV, tuberculosis, dengue, polio and typhoid. In additional to implementation efficiency, the sharing increases code usage and testing. The freely available codebase also includes hundreds of regression tests, scientific feature tests and component tests to help verify functionality and avoid inadvertent changes to functionality during future development. Here we describe the levels of detail, flexible configurability and modularity enabled by EMOD and the role of software development principles and processes in its development.

Middle ear adenoma with neuroendocrine differentiation : A pediatric case report.

BACKGROUND: Middle ear adenoma with neuroendocrine differentiation (MEA-ND), also known as carcinoid tumor of the middle ear, is an extremely rare neoplasm, especially when located within the tympanic cavity. To the best of our knowledge, this represents the first pediatric case of a MEA-ND described in Europe. Excluding the present case, only three other pediatric cases of this disease have been published globally. CASE REPORT: We report on a 15-year-old female patient who presented with conductive hearing loss of the right ear. A tympanogram was flat. Ear microscopy revealed bulging of the right posterior superior tympanic quadrant. Computed tomography depicted an opacification of the middle ear and mastoid air cells without evidence of bone erosion. Paracentesis was performed assuming a serous otitis media. Since there was no liquid found the patient underwent an atticoantrotomy and mastoidectomy as therapy for cholesteatoma. Histologic examination revealed a highly differentiated neuroendocrine tumor. Immunohistochemical evaluation showed strong positivity for synaptophysin. On the basis of these results, the patient underwent a middle ear revision surgery. After 15 months, magnetic resonance imaging and octreotide scans suggested disease recurrence, prompting a second surgical revision. The histologic examination confirmed a recurrence of only 1 mm, but postoperative imaging still showed pathological diffuse enhancement. Eight years after the initial diagnosis there has been no evidence of recurrence or metastasis. CONCLUSION: In our opinion a pathological radiological result is insufficient to identify recurrent or residual disease within the tympanic cavity.

Method for modeling transport of particles in realistic porous networks: application to the computation of NMR flow propagators.

We model the transport of particles present in a fluid steadily flowing through a porous medium. The porous medium is described by a representative three-dimensional network. The particles are subjected to advection by the flow and to thermal diffusion. We propose to calculate their trajectories with the continuous time random walk framework. This enables us to efficiently sample disordered networks with realistic topology. The method proposed in this paper is general and can be adapted to model dispersion of tracers. It is applied here to simulate the measurement of the flow propagator [Formula: see text] which is defined as the ensemble density distribution of tracer displacements [Formula: see text], in a given time interval delta t. It can be extracted from pulsed magnetic field gradient spin echo NMR experiments carried out on porous media while fluid is flowing. Preliminary numerical results show good qualitative agreement with experiments.

Facilitating the Furrowed Brow: An Unobtrusive Test of the Facial Feedback Hypothesis Applied to Unpleasant Affect.

We examined the hypothesis that muscle contractions in the face influence subjective emotional experience. Previously, researchers have been critical of experiments designed to test this facial feedback hypothesis, particularly in terms of methodological problems that may lead to demand characteristics. In an effort to surmount these methodological problems Strack, Martin, and Stepper (1988) developed an experimental procedure whereby subjects were induced to contract facial muscles involved in the production of an emotional pattern, without being asked to actually simulate an emotion. Specifically, subjects were required to hold a pen in their teeth, which unobtrusively creates a contraction of the zygomaticus major muscles, the muscles involved in the production of a human smile. This manipulation minimises the likelihood that subjects are able to interpret their zygomaticus contractions as representing a particular emotion, thereby preventing subjects from determining the purpose of the experiment. Strack et al. (1988) found support for the facial feedback hypothesis applied to pleasant affect, in that subjects in the pen-in-teeth condition rated humorous cartoons as being funnier than subjects in the control condition (in which zygomaticus contractions were inhibited). The present study represents an extension of this nonobtrusive methodology to an investigation of the facial feedback of unpleasant affect. Consistent with the Strack et al. procedure, we wanted to have subjects furrow their brow without actually instructing them to do so and without asking them to produce any emotional facial pattern at all. This was achieved by attaching two golf tees to the subject's brow region (just above the inside comer of each eye) and then instructing them to touch the tips of the golf tees together as part of a "divided-attention" experiment. Touching the tips of the golf tees together could only be achieved by a contraction of the corrugator supercilii muscles, the muscles involved in the production of a sad emotional facial pattern. Subjects reported significantly more sadness in response to aversive photographs while touching the tips of the golf tees together than under conditions which inhibited corrugator contractions. These results provide evidence, using a new and unobtrusive manipulation, that facial feedback operates for unpleasant affect to a degree similar to that previously found for pleasant affect.