Social Contact Networks and Disease Eradicability under Voluntary Vaccination

Certain theories suggest that it should be difficult or impossible to eradicate a vaccine-preventable disease under voluntary vaccination: Herd immunity implies that the individual incentive to vaccinate disappears at high coverage levels. Historically, there have been examples of declining coverage for vaccines, such as MMR vaccine and whole-cell pertussis vaccine, that are consistent with this theory. On the other hand, smallpox was globally eradicated by 1980 despite voluntary vaccination policies in many jurisdictions. Previous modeling studies of the interplay between disease dynamics and individual vaccinating behavior have assumed that infection is transmitted in a homogeneously mixing population. By comparison, here we simulate transmission of a vaccine-preventable SEIR infection through a random, static contact network. Individuals choose whether to vaccinate based on infection risks from neighbors, and based on vaccine risks. When neighborhood size is small, rational vaccinating behavior results in rapid containment of the infection through voluntary ring vaccination. As neighborhood size increases (while the average force of infection is held constant), a threshold is reached beyond which the infection can break through partially vaccinated rings, percolating through the whole population and resulting in considerable epidemic final sizes and a large number vaccinated. The former outcome represents convergence between individually and socially optimal outcomes, whereas the latter represents their divergence, as observed in most models of individual vaccinating behavior that assume homogeneous mixing. Similar effects are observed in an extended model using smallpox-specific natural history and transmissibility assumptions. This work illustrates the significant qualitative differences between behavior–infection dynamics in discrete contact-structured populations versus continuous unstructured populations. This work also shows how disease eradicability in populations where voluntary vaccination is the primary control mechanism may depend partly on whether the disease is transmissible only to a few close social contacts or to a larger subset of the population

Erratic Flu Vaccination Emerges from Short-Sighted Behavior in Contact Networks

The effectiveness of seasonal influenza vaccination programs depends on individual-level compliance. Perceptions about risks associated with infection and vaccination can strongly influence vaccination decisions and thus the ultimate course of an epidemic. Here we investigate the interplay between contact patterns, influenza-related behavior, and disease dynamics by incorporating game theory into network models. When individuals make decisions based on past epidemics, we find that individuals with many contacts vaccinate, whereas individuals with few contacts do not. However, the threshold number of contacts above which to vaccinate is highly dependent on the overall network structure of the population and has the potential to oscillate more wildly than has been observed empirically. When we increase the number of prior seasons that individuals recall when making vaccination decisions, behavior and thus disease dynamics become less variable. For some networks, we also find that higher flu transmission rates may, counterintuitively, lead to lower (vaccine-mediated) disease prevalence. Our work demonstrates that rich and complex dynamics can result from the interaction between infectious diseases, human contact patterns, and behavior

Chemical warfare between leafcutter ant symbionts and a co-evolved pathogen

Acromyrmex leafcutter ants form a mutually beneficial symbiosis with the fungus Leucoagaricus gongylophorus and with Pseudonocardia bacteria. Both are vertically transmitted and actively maintained by the ants. The fungus garden is manured with freshly cut leaves and provides the sole food for the ant larvae, while Pseudonocardia cultures are reared on the ant-cuticle and make antifungal metabolites to help protect the cultivar against disease. If left unchecked, specialized parasitic Escovopsis fungi can overrun the fungus-garden and lead to colony collapse. We report that Escovopsis upregulates the production of two specialized metabolites when it infects the cultivar. These compounds inhibit Pseudonocardia and one, shearinine D, also reduces worker behavioral defences and is ultimately lethal when it accumulates in ant tissues. Our results are consistent with an active evolutionary arms race between Pseudonocardia and Escovopsis, which modifies both bacterial and behavioral defences such that colony collapse is unavoidable once Escovopsis infections escalate

Expression of the VEGF and angiopoietin genes in endometrial atypical hyperplasia and endometrial cancer

Angiogenesis is critical for the growth and metastasis of endometrial cancer and is therefore an important therapeutic target. Vascular endothelial growth factor-A (VEGF-A) is a key molecule in angiogenesis, but the identification of related molecules and the angiopoietins suggests a more complex picture. We investigated the presence of transcripts for VEGF-A, VEGF-B, VEGF-C, VEGF-D, Angiopoietin-1 and Angiopoietin-2 in benign endometrium, atypical complex hyperplasia (ACH) and endometrioid endometrial carcinoma using in situ hybridisation. We confirmed the presence of VEGF-A mRNA in the epithelial cells of cancers examined (13 out of 13), but not in benign endometrium or ACH. We also demonstrate, using quantitative polymerase chain reaction, that levels of VEGF-B mRNA are significantly lower in endometrial cancer than benign endometrium. We conclude that loss of VEGF-B may contribute to the development of endometrial carcinoma by modulating availability of receptors for VEGF-A

Antiangiogenic agents in the treatment of recurrent or newly diagnosed glioblastoma: Analysis of single-agent and combined modality approaches

Surgical resection followed by radiotherapy and temozolomide in newly diagnosed glioblastoma can prolong survival, but it is not curative. For patients with disease progression after frontline therapy, there is no standard of care, although further surgery, chemotherapy, and radiotherapy may be used. Antiangiogenic therapies may be appropriate for treating glioblastomas because angiogenesis is critical to tumor growth. In a large, noncomparative phase II trial, bevacizumab was evaluated alone and with irinotecan in patients with recurrent glioblastoma; combination treatment was associated with an estimated 6-month progression-free survival (PFS) rate of 50.3%, a median overall survival of 8.9 months, and a response rate of 37.8%. Single-agent bevacizumab also exceeded the predetermined threshold of activity for salvage chemotherapy (6-month PFS rate, 15%), achieving a 6-month PFS rate of 42.6% (p < 0.0001). On the basis of these results and those from another phase II trial, the US Food and Drug Administration granted accelerated approval of single-agent bevacizumab for the treatment of glioblastoma that has progressed following prior therapy. Potential antiangiogenic agents-such as cilengitide and XL184-also show evidence of single-agent activity in recurrent glioblastoma. Moreover, the use of antiangiogenic agents with radiation at disease progression may improve the therapeutic ratio of single-modality approaches. Overall, these agents appear to be well tolerated, with adverse event profiles similar to those reported in studies of other solid tumors. Further research is needed to determine the role of antiangiogenic therapy in frontline treatment and to identify the optimal schedule and partnering agents for use in combination therapy

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

The SocialVidStim: a video database of positive and negative social evaluation stimuli for use in social cognitive neuroscience paradigms

This paper describes the SocialVidStim-a database of video stimuli available to the scientific community depicting positive and negative social evaluative and neutral statements. The SocialVidStim comprises 53 diverse individuals reflecting the demographic makeup of the USA, ranging from 9 to 41 years old, saying 20-60 positive and 20-60 negative social evaluative statements (e.g. 'You are a very trustworthy/annoying person'), and 20-60 neutral statements (e.g. 'The sky is blue'), totaling 5793 videos post-production. The SocialVidStim are designed for use in behavioral and functional magetic resonance imaging paradigms, across developmental stages, in diverse populations. This study describes stimuli development and reports initial validity and reliability data on a subset videos (N = 1890) depicting individuals aged 18-41 years. Raters perceive videos as expected: positive videos elicit positively valenced ratings, negative videos elicit negatively valenced ratings and neutral videos are rated as neutral. Test-retest reliability data demonstrate intraclass correlations in the good-to-excellent range for negative and positive videos and the moderate range for neutral videos. We also report small effects on valence and arousal that should be considered during stimuli selection, including match between rater and actor sex and actor believability. The SocialVidStim is a resource for researchers and we offer suggestions for using the SocialVidStim in future research