Predictability in a highly stochastic system: final size of measles epidemics in small populations.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.A standard assumption in the modelling of epidemic dynamics is that the population of interest is well mixed, and that no clusters of metapopulations exist. The well-known and oft-used SIR model, arguably the most important compartmental model in theoretical epidemiology, assumes that the disease being modelled is strongly immunizing, directly transmitted and has a well-defined period of infection, in addition to these population mixing assumptions. Childhood infections, such as measles, are prime examples of diseases that fit the SIR-like mechanism. These infections have been well studied for many systems with large, well-mixed populations with endemic infection. Here, we consider a setting where populations are small and isolated. The dynamics of infection are driven by stochastic extinction-recolonization events, producing large, sudden and short-lived epidemics before rapidly dying out from a lack of susceptible hosts. Using a TSIR model, we fit prevaccination measles incidence and demographic data in Bornholm, the Faroe Islands and four districts of Iceland, between 1901 and 1965. The datasets for each of these countries suffer from different levels of data heterogeneity and sparsity. We explore the potential for prediction of this model: given historical incidence data and up-to-date demographic information, and knowing that a new epidemic has just begun, can we predict how large it will be? We show that, despite a lack of significant seasonality in the incidence of measles cases, and potentially severe heterogeneity at the population level, we are able to estimate the size of upcoming epidemics, conditioned on the first time step, to within reasonable confidence. Our results have potential implications for possible control measures for the early stages of new epidemics in small populations.US Department of Homeland Security HSHQDC-12-C-00058 Eunice Kennedy Shriver National Institute of Child Health and Human Development 5R24HD047879 National Institutes of Health 5T32HD007163 Bill and Melinda Gates Foundation RAPIDD program of the Science and Technology Directorate, Department of Homeland Security Fogarty International Center, National Institutes of Healt

Stress related disorders and subsequent risk of life threatening infections: population based sibling controlled cohort study.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadOBJECTIVE: To assess whether severe psychiatric reactions to trauma and other adversities are associated with subsequent risk of life threatening infections. DESIGN: Population and sibling matched cohort study. SETTING: Swedish population. PARTICIPANTS: 144 919 individuals with stress related disorders (post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reactions) identified from 1987 to 2013 compared with 184 612 full siblings of individuals with a diagnosed stress related disorder and 1 449 190 matched individuals without such a diagnosis from the general population. MAIN OUTCOME MEASURES: A first inpatient or outpatient visit with a primary diagnosis of severe infections with high mortality rates (ie, sepsis, endocarditis, and meningitis or other central nervous system infections) from the Swedish National Patient Register, and deaths from these infections or infections of any origin from the Cause of Death Register. After controlling for multiple confounders, Cox models were used to estimate hazard ratios of these life threatening infections. RESULTS: The average age at diagnosis of a stress related disorder was 37 years (55 541, 38.3% men). During a mean follow-up of eight years, the incidence of life threatening infections per 1000 person years was 2.9 in individuals with a stress related disorder, 1.7 in siblings without a diagnosis, and 1.3 in matched individuals without a diagnosis. Compared with full siblings without a diagnosis of a stress related disorder, individuals with such a diagnosis were at increased risk of life threatening infections (hazard ratio for any stress related disorder was 1.47 (95% confidence intervals1.37 to 1.58) and for PTSD was 1.92 (1.46 to 2.52)). Corresponding estimates in the population based analysis were similar (1.58 (1.51 to 1.65) for any stress related disorder, P=0.09 for difference between sibling and population based comparison, and 1.95 (1.66 to 2.28) for PTSD, P=0.92 for difference). Stress related disorders were associated with all studied life threatening infections, with the highest relative risk observed for meningitis (sibling based analysis 1.63 (1.23 to 2.16)) and endocarditis (1.57 (1.08 to 2.30)). Younger age at diagnosis of a stress related disorder and the presence of psychiatric comorbidity, especially substance use disorders, were associated with higher hazard ratios, whereas use of selective serotonin reuptake inhibitors in the first year after diagnosis of a stress related disorder was associated with attenuated hazard ratios. CONCLUSION: In the Swedish population, stress related disorders were associated with a subsequent risk of life threatening infections, after controlling for familial background and physical or psychiatric comorbidities.Grant of Excellence, Icelandic Research Fund European Research Council (ERC) Karolinska Institutet Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) West China Hospital, Sichuan University (1.3.5 Project for Disciplines of Excellence

The evolution of cellular deficiency in GATA2 mutation.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageConstitutive heterozygous GATA2 mutation is associated with deafness, lymphedema, mononuclear cytopenias, infection, myelodysplasia (MDS), and acute myeloid leukemia. In this study, we describe a cross-sectional analysis of 24 patients and 6 relatives with 14 different frameshift or substitution mutations of GATA2. A pattern of dendritic cell, monocyte, B, and natural killer (NK) lymphoid deficiency (DCML deficiency) with elevated Fms-like tyrosine kinase 3 ligand (Flt3L) was observed in all 20 patients phenotyped, including patients with Emberger syndrome, monocytopenia with Mycobacterium avium complex (MonoMAC), and MDS. Four unaffected relatives had a normal phenotype indicating that cellular deficiency may evolve over time or is incompletely penetrant, while 2 developed subclinical cytopenias or elevated Flt3L. Patients with GATA2 mutation maintained higher hemoglobin, neutrophils, and platelets and were younger than controls with acquired MDS and wild-type GATA2. Frameshift mutations were associated with earlier age of clinical presentation than substitution mutations. Elevated Flt3L, loss of bone marrow progenitors, and clonal myelopoiesis were early signs of disease evolution. Clinical progression was associated with increasingly elevated Flt3L, depletion of transitional B cells, CD56(bright) NK cells, naïve T cells, and accumulation of terminally differentiated NK and CD8(+) memory T cells. These studies provide a framework for clinical and laboratory monitoring of patients with GATA2 mutation and may inform therapeutic decision-making.Lymphoma and Leukaemia Research British Society of Hematology Bright Red George Walker Trust Wellcome Trus

Physical and cognitive impact following SARS-CoV-2 infection in a large population-based case-control study

© 2023. The Author(s).BACKGROUND: Persistent symptoms are common after SARS-CoV-2 infection but correlation with objective measures is unclear. METHODS: We invited all 3098 adults who tested SARS-CoV-2 positive in Iceland before October 2020 to the deCODE Health Study. We compared multiple symptoms and physical measures between 1706 Icelanders with confirmed prior infection (cases) who participated, and 619 contemporary and 13,779 historical controls. Cases participated in the study 5-18 months after infection. RESULTS: Here we report that 41 of 88 symptoms are associated with prior infection, most significantly disturbed smell and taste, memory disturbance, and dyspnea. Measured objectively, cases had poorer smell and taste results, less grip strength, and poorer memory recall. Differences in grip strength and memory recall were small. No other objective measure associated with prior infection including heart rate, blood pressure, postural orthostatic tachycardia, oxygen saturation, exercise tolerance, hearing, and traditional inflammatory, cardiac, liver, and kidney blood biomarkers. There was no evidence of more anxiety or depression among cases. We estimate the prevalence of long Covid to be 7% at a median of 8 months after infection. CONCLUSIONS: We confirm that diverse symptoms are common months after SARS-CoV-2 infection but find few differences between cases and controls in objective parameters measured. These discrepancies between symptoms and physical measures suggest a more complicated contribution to symptoms related to prior infection than is captured with conventional tests. Traditional clinical assessment is not expected to be particularly informative in relating symptoms to a past SARS-CoV-2 infection.Peer reviewe