Persistence in epidemic metapopulations: quantifying the rescue effects for measles, mumps, rubella and whooping cough

Metapopulation rescue effects are thought to be key to the persistence of many acute immunizing infections. Yet the enhancement of persistence through spatial coupling has not been previously quantified. Here we estimate the metapopulation rescue effects for four childhood infections using global WHO reported incidence data by comparing persistence on island countries vs all other countries, while controlling for key variables such as vaccine cover, birth rates and economic development. The relative risk of extinction on islands is significantly higher, and approximately double the risk of extinction in mainland countries. Furthermore, as may be expected, infections with longer infectious periods tend to have the strongest metapopulation rescue effects. Our results quantitate the notion that demography and local community size controls disease persistence

Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups

IntroductionWhile complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.MethodsWe therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome.ResultsWe show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID.ConclusionIn conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted

Relative risks of extinction on an island.

<p>The probability of extinction for island countries divided by the probability of extinction for non-island countries for 4 childhood infections relative to extinction on the mainland; showing only a fraction of the distribution for mumps for clarity. The proportion of migrants and HDI are set to the median across all countries (–3.52 and 0.67 respectively), and the population size of unvaccinated children is set to 1e5. Median values are 1.92 (1.04–3.37) for rubella, 1.51 (1.07–2.16) for measles, 10.26 (4.06–25.29) for mumps, and 2.27 (1.57,3.32) for pertussis; brackets indicate 2.5% and 97.5% quantiles from prediction made across 2000 samples from the estimated multivariate normal distribution of the parameters.</p

Predicted probability of extinction.

<p>The x axis is population size for four childhood infections and the y axis is probability of extinction for island nations (red) and mainland nations (black) and showing upper and lower standard errors, taken at the median log proportion of resident migrants (an index of connectivity of –3.52) and median human development index (0.67). Parameters underlying these predictions are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074696#pone-0074696-t001" target="_blank">Table 1</a>.</p

Weighted linear regression linking log size of the unvaccinated population and proportion of years for which no cases were reported; followed by the same but taking the size of the number of unvaccinated births as the covariate; corresponding estimates of the CCS, obtained as the point at which the fitted line intersects with zero are shown in Fig. 2.

<p>Weighted linear regression linking log size of the unvaccinated population and proportion of years for which no cases were reported; followed by the same but taking the size of the number of unvaccinated births as the covariate; corresponding estimates of the CCS, obtained as the point at which the fitted line intersects with zero are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074696#pone-0074696-g002" target="_blank">Fig. 2</a>.</p

Estimates of the Critical Community Size.

<p>a) Estimates of the distribution of the population size at which no years with no cases are expected based on linear regressions described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074696#pone-0074696-t001" target="_blank">Table 1</a> and shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074696#pone-0074696-g001" target="_blank">Fig. 1</a> for the total unvaccinated population and for unvaccinated births; here encompassing parameter uncertainty; b) Violin plots showing the distribution of sizes of the unvaccinated populations for which no years with no cases were recorded for each of the infections (p₀ = 0 indicates no zeros in the time-series, and therefore points along the y = 0 line in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074696#pone-0074696-g001" target="_blank">Fig. 1</a>); vertical dotted lines indicated previous estimates of the CCS for each of the infections, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074696#pone-0074696-g001" target="_blank">Fig. 1</a> for a description.</p

Why do stroke survivors not receive recommended amounts of active therapy? Findings from the ReAcT study, a mixed-methods case-study evaluation in eight stroke units

Objective:To identify why the National Clinical Guideline recommendation of 45 minutes of each appropriate therapy daily is not met in many English stroke units.Design:Mixed-methods case-study evaluation, including modified process mapping, non-participant observations of service organisation and therapy delivery, documentary analysis and semi-structured interviews.Setting:Eight stroke units in four English regions.Subjects:Seventy-seven patients with stroke, 53 carers and 197 stroke unit staff were observed; 49 patients, 50 carers and 131 staff participants were interviewed.Results:Over 1000 hours of non-participant observations and 433 patient-specific therapy observations were undertaken. The most significant factor influencing amount and frequency of therapy provided was the time therapists routinely spent, individually and collectively, in information exchange. Patient factors, including fatigue and tolerance influenced therapists’ decisions about frequency and intensity, typically resulting in adaptation of therapy rather than no provision. Limited use of individual patient therapy timetables was evident. Therapist staffing levels were associated with differences in therapy provision but were not the main determinant of intensity and frequency. Few therapists demonstrated understanding of the evidence underpinning recommendations for increased therapy frequency and intensity. Units delivering more therapy had undertaken patient-focused reorganisation of therapists’ working practices, enabling them to provide therapy consistent with guideline recommendations.Conclusion:Time spent in information exchange impacted on therapy provision in stroke units. Reorganisation of therapists’ work improved alignment with guidelines

Supplementary_file_I – Supplemental material for Why do stroke survivors not receive recommended amounts of active therapy? Findings from the ReAcT study, a mixed-methods case-study evaluation in eight stroke units

<p>Supplemental material, Supplementary_file_I for Why do stroke survivors not receive recommended amounts of active therapy? Findings from the ReAcT study, a mixed-methods case-study evaluation in eight stroke units by David J Clarke, Louisa-Jane Burton, Sarah F Tyson, Helen Rodgers, Avril Drummond, Rebecca Palmer, Alex Hoffman, Matthew Prescott, Pippa Tyrrell, Lianne Brkic, Katie Grenfell and Anne Forster in Clinical Rehabilitation</p

Transmission of Equine Influenza Virus during an outbreak is characterized by frequent mixed infections and loose transmission bottlenecks

The ability of influenza A viruses (IAVs) to cross species barriers and evade host immunity is a major public health concern. Studies on the phylodynamics of IAVs across different scales - from the individual to the population - are essential for devising effective measures to predict, prevent or contain influenza emergence. Understanding how IAVs spread and evolve during outbreaks is critical for the management of epidemics. Reconstructing the transmission network during a single outbreak by sampling viral genetic data in time and space can generate insights about these processes. Here, we obtained intra-host viral sequence data from horses infected with equine influenza virus (EIV) to reconstruct the spread of EIV during a large outbreak. To this end, we analyzed within-host viral populations from sequences covering 90% of the infected yards. By combining gene sequence analyses with epidemiological data, we inferred a plausible transmission network, in turn enabling the comparison of transmission patterns during the course of the outbreak and revealing important epidemiological features that were not apparent using either approach alone. The EIV populations displayed high levels of genetic diversity, and in many cases we observed distinct viral populations containing a dominant variant and a number of related minor variants that were transmitted between infectious horses. In addition, we found evidence of frequent mixed infections and loose transmission bottlenecks in these naturally occurring populations. These frequent mixed infections likely influence the size of epidemics