Disentangling the causes of mumps reemergence in the United States.

Over the past two decades, multiple countries with high vaccine coverage have experienced resurgent outbreaks of mumps. Worryingly, in these countries, a high proportion of cases have been among those who have completed the recommended vaccination schedule, raising alarm about the effectiveness of existing vaccines. Two putative mechanisms of vaccine failure have been proposed as driving observed trends: 1) gradual waning of vaccine-derived immunity (necessitating additional booster doses) and 2) the introduction of novel viral genotypes capable of evading vaccinal immunity. Focusing on the United States, we conduct statistical likelihood-based hypothesis testing using a mechanistic transmission model on age-structured epidemiological, demographic, and vaccine uptake time series data. We find that the data are most consistent with the waning hypothesis and estimate that 32.8% (32%, 33.5%) of individuals lose vaccine-derived immunity by age 18 y. Furthermore, we show using our transmission model how waning vaccine immunity reproduces qualitative and quantitatively consistent features of epidemiological data, namely 1) the shift in mumps incidence toward older individuals, 2) the recent recurrence of mumps outbreaks, and 3) the high proportion of mumps cases among previously vaccinated individuals.

Genomic testing identifies monogenic causes in patients with very early-onset inflammatory bowel disease: a multicenter survey in an Iranian cohort.

Patients with very early-onset inflammatory bowel disease (VEO-IBD) may present because of underlying monogenic inborn errors of immunity (IEI). Strong differences have been observed in the causes of monogenic IBD among ethnic populations. This multicenter study was carried out on 16 Iranian patients with VEO-IBD. We reviewed clinical and basic immunologic evaluation including flow cytometry and immunoglobulin levels. All patients underwent clinical whole exome sequencing (WES). Sixteen patients (8 females and 8 males) with a median age of 43.5 months were enrolled. The median age at the onset of symptoms was 4 months. Most patients (12, 75%) had consanguineous parents. Chronic non-bloody diarrhea (13, 81.3%) and perianal diseases including perianal abscess (6, 37.5%), anal fissure (6, 37.5%), or anal fistula (2, 12.5%) were the most common manifestations. WES identified a spectrum of genetic variants in 13 patients (81.3%): IL10RB (6, 37.5%), MVK (3, 18.8%), and CASP8, SLC35C1, G6PC3, and IKBKB in 1 patient, respectively. In 3 patients (18.7%), no variant was identified. Flow cytometry identified a spectrum of abnormalities that helped to assess the evidence of genetic diagnosis. At the end of the survey, 3 (18.8%) patients were deceased. This high rate of monogenic defects with a broad spectrum of genes reiterates the importance of investigating IEI in patients with infantile-onset IBD.

Changes in lipid profile and glucose metabolism following administration of bupropion alone or in combination with naltrexone: A systematic review and meta-regression analysis.

BACKGROUND: Considering the conflicting effects of bupropion on parameters related to metabolic syndrome including glucose metabolism and lipid profile, in this meta-analysis study, we investigated the effects of this drug alone or in combination with naltrexone on glucose metabolism and lipid profile. METHODS: Scopus, PubMed/Medline, Web of Science and Embase databases were searched using standard keywords to identify all controlled trials investigating effects of bupropion alone and combined with naltrexone on the glucose and lipid profile. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model. RESULTS: Twelve studies with 5152 participants' were included in this article. The pooled findings showed that bupropion alone or in combination with naltrexone would significantly reduce glucose (weighted mean difference (WMD): -2.25 mg/dL, 95% confidence interval (CI): -4.10, -0.40), insulin (WMD: -4.06 µU/mL, 95% CI: -6.09, -2.03), homeostatic model assessment for insulin resistance (HOMA-IR) (WMD: -0.58, 95% CI: -0.98, -0.19), triglyceride (TG) (WMD: -11.78 mg/dL, 95% CI: -14.48 to -9.08) and increase high-density lipoprotein (HDL) (WMD: 2.68 mg/dL, 95% CI: 2.13 to 3.24). A Greater reduction in glucose levels was observed with duration >26 weeks. Dose of bupropion intake ≤360 mg and intervention for more than 26 weeks decreased insulin level significantly. With regard to lipid profile, reduction of triglycerides is more significant with dose of bupropion greater than 360 mg and a shorter intervention length equal to 26 weeks. CONCLUSIONS: The addition of combination therapies such as bupropion and naltrexone to lifestyle modification can significantly improve glucose metabolism and some lipid parameters.

Direct and macrophage stimulation mediated effects of active, inactive, and cell-free supernatant forms of Akkermansia muciniphila and Faecalibacterium duncaniae on hepcidin gene expression in HepG2 cells.

Hepcidin is a crucial regulator of iron homeostasis with protective effects on liver fibrosis. Additionally, gut microbiota can also affect liver fibrosis and iron metabolism. Although the hepatoprotective potential of Akkermansia muciniphila and Faecalibacterium duncaniae, formerly known as F. prausnitzii, has been reported, however, their effects on hepcidin expression remain unknown. We investigated the direct and macrophage stimulation-mediated effects of active, heat-inactivated, and cell-free supernatant (CFS) forms of A. muciniphila and F. duncaniae on hepcidin expression in HepG2 cells by RT-qPCR analysis. Following stimulation of phorbol-12-myristate-13-acetate (PMA) -differentiated THP-1 cells with A. muciniphila and F. duncaniae, IL-6 concentration was assessed via ELISA. Additionally, the resulting supernatant was treated with HepG2 cells to evaluate the effect of macrophage stimulation on hepcidin gene expression. The expression of genes mediating iron absorption and export was also examined in HepG2 and Caco-2 cells via RT-qPCR. All forms of F. duncaniae increased hepcidin expression while active and heat-inactivated/CFS forms of A. muciniphila upregulated and downregulated its expression, respectively. Active, heat-inactivated, and CFS forms of A. muciniphila and F. duncaniae upregulated hepcidin expression, consistent with the elevation of IL-6 released from THP-1-stimulated cells as a macrophage stimulation effect in HepG2 cells. A. muciniphila and F. duncaniae in active, inactive, and CFS forms altered the expression of hepatocyte and intestinal iron-mediated absorption /exporter genes, namely dcytb and dmt1, and fpn in HepG2 and Caco-2 cells, respectively. In conclusion, A. muciniphila and F. duncaniae affect not only directly but also through macrophage stimulation the expression of hepcidin gene in HepG2 cells. These findings underscore the potential of A. muciniphila and F. duncaniae as a potential therapeutic target for liver fibrosis by modulating hepcidin and intestinal and hepatocyte iron metabolism mediated gene expression.

Charting the spatial dynamics of early SARS-CoV-2 transmission in Washington state.

The spread of SARS-CoV-2 has been geographically uneven. To understand the drivers of this spatial variation in SARS-CoV-2 transmission, in particular the role of stochasticity, we used the early stages of the SARS-CoV-2 invasion in Washington state as a case study. We analysed spatially-resolved COVID-19 epidemiological data using two distinct statistical analyses. The first analysis involved using hierarchical clustering on the matrix of correlations between county-level case report time series to identify geographical patterns in the spread of SARS-CoV-2 across the state. In the second analysis, we used a stochastic transmission model to perform likelihood-based inference on hospitalised cases from five counties in the Puget Sound region. Our clustering analysis identifies five distinct clusters and clear spatial patterning. Four of the clusters correspond to different geographical regions, with the final cluster spanning the state. Our inferential analysis suggests that a high degree of connectivity across the region is necessary for the model to explain the rapid inter-county spread observed early in the pandemic. In addition, our approach allows us to quantify the impact of stochastic events in determining the subsequent epidemic. We find that atypically rapid transmission during January and February 2020 is necessary to explain the observed epidemic trajectories in King and Snohomish counties, demonstrating a persisting impact of stochastic events. Our results highlight the limited utility of epidemiological measures calculated over broad spatial scales. Furthermore, our results make clear the challenges with predicting epidemic spread within spatially extensive metropolitan areas, and indicate the need for high-resolution mobility and epidemiological data.

The effect of orlistat in the treatment of non-alcoholic fatty liver in adolescents with overweight and obese.

Nonalcoholic fatty liver disease (NAFLD), which can manifest as nonalcoholic steatohepatitis (NASH) or severe fibrosis, is the most prevalent chronic liver disease in children and adolescents. However, there is no proven cure for it so far. This study was conducted to determine whether adolescents with NAFLD would improve with treatment intervention with orlistat. This study is a randomized controlled trial (RCT). Fifty-three adolescents with overweight/obese as well as with NAFLD randomly allocated to receive orlistat (n = 27) or placebo as control (n = 26) for 12 weeks. In addition, NAFLD activity score, anthropometric factors, biochemical parameters including serum levels of lipid profiles, liver enzyme, and glucose metabolism taken from subjects at baseline and end of the study were investigated. The findings of our article indicated that orlistat improves liver enzymes (alanine transaminase and aspartate transaminase) (P = < 0.001), steatosis score (P = 0.001), NAFLD activity score (P = < 0.001), weight (P = < 0.001), body mass index (BMI) (P = < 0.001), waist circumferences (WC) (P = < 0.001), BMI-Z score (P = < 0.001), glucose metabolism (P = 0.001), total cholesterol (TC) (P = 0.009), low density lipoprotein-cholesterol (LDL) (P = < 0.001), and high density lipoprotein-cholesterol HDL levels (P = 0.014) compared to the control group after adjusting for possible confounders for 12 weeks. However, no significant changes were observed on triglyceride (TG) following intake of orlistat compared to placebo after adjusting for confounders. CONCLUSION: The findings of our study reported that orlistat improved NAFLD-related factors and metabolic syndrome-related factors compared to placebo for 12 weeks. TRIAL REGISTRATION: (Clinical trial registry number: IRCT20220409054467N2, with a registration date of 2022-05-13). WHAT IS KNOWN: • Among the interventions of interest for the management of pediatric NAFLD, we can mention lifestyle and pharmaceutical measures. WHAT IS NEW: • This study was conducted to determine whether adolescents with NAFLD would improve with treatment intervention with orlistat. • The findings of our study reported that orlistat improved NAFLD-related factors and metabolic syndrome-related factors compared to placebo for 12 weeks.

Anomalous influenza seasonality in the United States and the emergence of novel influenza B viruses.

The 2019/2020 influenza season in the United States began earlier than any season since the 2009 H1N1 pandemic, with an increase in influenza-like illnesses observed as early as August. Also noteworthy was the numerical domination of influenza B cases early in this influenza season, in contrast to their typically later peak in the past. Here, we dissect the 2019/2020 influenza season not only with regard to its unusually early activity, but also with regard to the relative dynamics of type A and type B cases. We propose that the recent expansion of a novel influenza B/Victoria clade may be associated with this shift in the composition and kinetics of the influenza season in the United States. We use epidemiological transmission models to explore whether changes in the effective reproduction number or short-term cross-immunity between these viruses can explain the dynamics of influenza A and B seasonality. We find support for an increase in the effective reproduction number of influenza B, rather than support for cross-type immunity-driven dynamics. Our findings have clear implications for optimal vaccination strategies.

Dynamical footprints enable detection of disease emergence.

Developing methods for anticipating the emergence or reemergence of infectious diseases is both important and timely; however, traditional model-based approaches are stymied by uncertainty surrounding the underlying drivers. Here, we demonstrate an operational, mechanism-agnostic detection algorithm for disease (re-)emergence based on early warning signals (EWSs) derived from the theory of critical slowing down. Specifically, we used computer simulations to train a supervised learning algorithm to detect the dynamical footprints of (re-)emergence present in epidemiological data. Our algorithm was then challenged to forecast the slowly manifesting, spatially replicated reemergence of mumps in England in the mid-2000s and pertussis post-1980 in the United States. Our method successfully anticipated mumps reemergence 4 years in advance, during which time mitigation efforts could have been implemented. From 1980 onwards, our model identified resurgent states with increasing accuracy, leading to reliable classification starting in 1992. Additionally, we successfully applied the detection algorithm to 2 vector-transmitted case studies, namely, outbreaks of dengue serotypes in Puerto Rico and a rapidly unfolding outbreak of plague in 2017 in Madagascar. Taken together, these findings illustrate the power of theoretically informed machine learning techniques to develop early warning systems for the (re-)emergence of infectious diseases.

Dissecting recurrent waves of pertussis across the boroughs of London.

Pertussis has resurfaced in the UK, with incidence levels not seen since the 1980s. While the fundamental causes of this resurgence remain the subject of much conjecture, the study of historical patterns of pathogen diffusion can be illuminating. Here, we examined time series of pertussis incidence in the boroughs of Greater London from 1982 to 2013 to document the spatial epidemiology of this bacterial infection and to identify the potential drivers of its percolation. The incidence of pertussis over this period is characterized by 3 distinct stages: a period exhibiting declining trends with 4-year inter-epidemic cycles from 1982 to 1994, followed by a deep trough until 2006 and the subsequent resurgence. We observed systematic temporal trends in the age distribution of cases and the fade-out profile of pertussis coincident with increasing national vaccine coverage from 1982 to 1990. To quantify the hierarchy of epidemic phases across the boroughs of London, we used the Hilbert transform. We report a consistent pattern of spatial organization from 1982 to the early 1990s, with some boroughs consistently leading epidemic waves and others routinely lagging. To determine the potential drivers of these geographic patterns, a comprehensive parallel database of borough-specific features was compiled, comprising of demographic, movement and socio-economic factors that were used in statistical analyses to predict epidemic phase relationships among boroughs. Specifically, we used a combination of a feed-forward neural network (FFNN), and SHapley Additive exPlanations (SHAP) values to quantify the contribution of each covariate to model predictions. Our analyses identified a number of predictors of a borough's historical epidemic phase, specifically the age composition of households, the number of agricultural and skilled manual workers, latitude, the population of public transport commuters and high-occupancy households. Univariate regression analysis of the 2012 epidemic identified the ratio of cumulative unvaccinated children to the total population and population of Pakistan-born population to have moderate positive and negative association, respectively, with the timing of epidemic. In addition to providing a comprehensive overview of contemporary pertussis transmission in a large metropolitan population, this study has identified the characteristics that determine the spatial spread of this bacterium across the boroughs of London.

The role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in the diagnosis and severity of inflammatory bowel disease in children.

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are simple and inexpensive inflammatory biomarkers that reflect systemic inflammation based on complete blood count values. In this study, we investigate the role of these biomarkers in the diagnosis and severity of pediatric inflammatory bowel disease (IBD). We analyzed 73 pediatric patients with IBD with a retrospective study design who underwent measurement of fecal calprotectin (FC) and endoscopy and 67 age- and sex-matched healthy controls. NLR and PLR were compared between the patients and healthy controls. We also plotted the ROC diagrams separately for markers to obtain the optimal point and a suitable cutoff point. We enrolled 73 pediatric patients less than 18 years of age with IBD, 40 subjects with UC and 33 with CD and 67 healthy subjects as control group with median age of 9.00 ± 4.61 in all subjects. Furthermore, the mean score of PCDAI or PUCAI in the all subjects was 19.26 ± 16.31. In the ROC curve, the optimal cutoff value for NLR and PLR for detecting IBD was 2.04 (sensitivity 82.1%; specificity 82.9%) and 103 (sensitivity 67.9%; specificity 71.4%). Also, the optimal cutoff values for NLR and PLR for differentiating IBD severity (remission vs. active disease) were 2.94 (sensitivity 77.8%; specificity 50.0%) and 157 (sensitivity 88.9%; specificity 54.5%), respectively. CONCLUSION: Our findings indicate the role of easy and non-invasive markers such as NLR and PLR in order to diagnose the disease in the initial examinations as well as the severity of the disease. WHAT IS KNOWN: • NLR and PLR are simple and inexpensive inflammatory biomarkers that reflect systemic inflammation based on complete blood count values. WHAT IS NEW: • In this study, we investigate the role of these biomarkers in the diagnosis and severity of pediatric IBD. • Our findings indicate the role of NLR and PLR in order to diagnose the disease in the initial examinations as well as the severity of the disease.

Effect of helicobacter pylori infection eradication on serum level of anti-tissue transglutaminase in children with celiac disease.

BACKGROUND: Evidence shows the increase of anti-tissue transglutaminase (tTG) levels in various conditions, including infectious agents, independently of celiac disease (CD). The aim of this study was to investigate the effect of helicobacter pylori (H.pylori) infection eradication on serum level of tTG in children with CD. METHODS: This study was conducted on children aged 2 to 18 who referred to reference hospitals for diagnosis of CD. After upper endoscopy and biopsy to confirm CD and H.pylori infection, the children were divided into three groups (including group one: 16 CD patients with positive H. pylori; group two: 16 non-CD patients with positive H. pylori; and group three: 56 CD patients with negative H. pylori), respectively. The tTG level in study groups were compared after the eradication of H.pylori. RESULTS: The mean age of the subjects in the group one, two, and three was 9.7 ± 3.33, 11.8 ± 3.14, and 7.6 ± 3.32 years, respectively. Our results showed that in group one, mean tTG increased after eradication of H.pylori infection, however, these changes were not significant (182.43 vs. 157.18, P = 0.121). In the second group, although unlike the first group, mean tTG decreased after eradication of the infection, but still these changes were not significant (9.56 vs. 22.18, P = 0.449). Furthermore, at the baseline level, the mean tTG in the group three was closer to the mean tTG in the first group. CONCLUSION: Our findings showed that the eradication of H.pylori infection does not have a significant effect on tTG levels in children with and without CD.

Transmission dynamics reveal the impracticality of COVID-19 herd immunity strategies.

The rapid growth rate of COVID-19 continues to threaten to overwhelm healthcare systems in multiple countries. In response, severely affected countries have had to impose a range of public health strategies achieved via nonpharmaceutical interventions. Broadly, these strategies have fallen into two categories: 1) "mitigation," which aims to achieve herd immunity by allowing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus to spread through the population while mitigating disease burden, and 2) "suppression," aiming to drastically reduce SARS-CoV-2 transmission rates and halt endogenous transmission in the target population. Using an age-structured transmission model, parameterized to simulate SARS-CoV-2 transmission in the United Kingdom, we assessed the long-term prospects of success using both of these approaches. We simulated a range of different nonpharmaceutical intervention scenarios incorporating social distancing applied to differing age groups. Our modeling confirmed that suppression of SARS-CoV-2 transmission is possible with plausible levels of social distancing over a period of months, consistent with observed trends. Notably, our modeling did not support achieving herd immunity as a practical objective, requiring an unlikely balancing of multiple poorly defined forces. Specifically, we found that 1) social distancing must initially reduce the transmission rate to within a narrow range, 2) to compensate for susceptible depletion, the extent of social distancing must be adaptive over time in a precise yet unfeasible way, and 3) social distancing must be maintained for an extended period to ensure the healthcare system is not overwhelmed.

Esophageal Stents for the Management of Benign Esophageal Strictures in Children and Adolescents: A Systematic Review of Observational Studies.

Little is known about the efficacy and safety of esophageal stents for the management of esophageal strictures in children and adolescents. A systematic review was performed to assess the efficacy and safety of esophageal stents for the management of benign esophageal strictures in children and adolescents. Observational studies related to the examination of esophageal stents in pediatrics were extracted using the original databases by December 2021. We found 18 retrospective and prospective studies with a total of 340 children and adolescents. Overall, our findings show that different therapeutic modalities based on esophageal stents were offered to children and adolescents for various indications, in which most studies reported successful cases, although ineffective claims cannot be ignored. Fully covered self-expandable metal stent, self-expandable metal stent, and silastic esophageal stent were the stent types most used, although different materials and prototypes were reported as well. The number of stents used per patient and the duration of the stenting therapy varied widely (ranging from 1 to 584 days). Such treatments were not standardized because of different factors, such as different tolerance to complications in subjects aged 1 month and 16 years, frequent stent migration requiring removal followed or not by its replacement, different guides provided by each stent manufacturer, and successful healing of esophageal lesions. Different esophageal stents may be a reasonable therapeutic approach for the management of benign esophageal strictures in children and adolescents. We believe that esophagus-sparing methods like stents represent a promising alternative or adjunctive treatment to be considered in pediatrics.

Overcoming Waning Immunity in Pertussis Vaccines: Workshop of the National Institute of Allergy and Infectious Diseases.

Despite high vaccine coverage in many parts of the world, pertussis is resurging in a number of areas in which acellular vaccines are the primary vaccine administered to infants and young children. This is attributed in part to the suboptimal and short-lived immunity elicited by acellular pertussis vaccines and to their inability to prevent nasal colonization and transmission of the etiologic agent Bordetella pertussis In response to this escalating public health concern, the National Institute of Allergy and Infectious Diseases held the workshop "Overcoming Waning Immunity in Pertussis Vaccines" in September 2019 to identify issues and possible solutions for the defects in immunity stimulated by acellular pertussis vaccines. Discussions covered aspects of the current problem, gaps in knowledge and possible paths forward. This review summarizes presentations and discussions of some of the key points that were raised by the workshop.

Acute pancreatitis in 60 Iranian children: do pediatricians follow the new guidelines in diagnosis and management of acute pancreatitis?

BACKGROUND: The incidence of acute pancreatitis in children is increasing, but causes and diagnostic and therapeutic methods are various in different centers. The aim of this study was to investigate the common causes and routine diagnostic and therapeutic methods of acute pancreatitis in children in a pediatric gastrointestinal referral center and its accordance with existing guidelines. METHODS: In this retrospective, cross-sectional study, a total of 60 children with a diagnosis of acute pancreatitis, were studied. RESULTS: The most common causes of acute pancreatitis were systemic and metabolic diseases and medications. CT scan was performed for 36% of patients, but 31% of patients, for whom a CT scan was performed had no clear indication of CT scan. Only half of the patients received fluid 1.5 times their maintenance in the first 24 h. Antibiotic therapy was performed for 48% of patients but medical indications for antibiotic treatment were found in only 34% of cases. During the COVID-19 pandemic, the relative incidence of acute pancreatitis was increased. CONCLUSIONS: In children with systemic and metabolic disease and using anticonvulsant drugs, it is important to consider the incidence of this disease. In clinical education, the risks of radiation due to unnecessary CT scans and inappropriate prescription of antibiotics need to be emphasized. More research should be done to study the association between COVID-19 and acute pancreatitis.

Serum matrix metalloproteinase-7 levels in infants with cholestasis and biliary atresia.

BACKGROUND: The aim of this study was to evaluate the serum level of matrix metalloproteinase 7 (MMP7) in infants with cholestasis and the diagnostic values of this biomarker to differentiate biliary atresia (BA) from other causes of cholestasis. METHODS: This multi-center study is conducted during 2 years in Mofid children's hospital and Children's Medical Center, Pediatrics Center of Excellence Tehran, Iran. 54 infants with cholestasis were enrolled in this study with a control group consists of 41 healthy infants with the same age. Serum samples were taken from all these patients to assess serum levels of MMP7, Gamma-glutamyl Transferase (GGT). For each biomarker, we calculated the sensitivity and specificity and other statistical characteristics. RESULTS: There were 89 subjects, 22 patients with BA, 32 patients with non-BA cholestasis and 41 subjects as control group. The mean serum MMP7 levels in BA, non-BA cholestasis and control group was 15.91 ng/ml ± 6.64, 4.73 ng/ml ± 2.59 and 0.49 ng/ml ± 0.33, respectively. The best cut-off point is calculated 7.8 ng/ml for MMP7 and 434.5 U/L for GGT. The area under curve (AUC) for these two markers are 0.988 ± 0.008 and 0.854 ± 0.052, respectively. The sensitivity and specificity of MMP7 to differentiate biliary atresia from nonbiliary atresia cholestasis in our study was 95.5% and 94.5%, respectively. The sensitivity and specificity of GGT was 77.3% and 77.8%, respectively. These results show that the MMP7 has more sensitivity and specificity in differentiation. CONCLUSION: MMP7 demonstrated good accuracy to differentiate biliary atresia from other causes of cholestasis.

Five approaches to the suppression of SARS-CoV-2 without intensive social distancing.

Initial efforts to mitigate transmission of SARS-CoV-2 relied on intensive social distancing measures such as school and workplace closures, shelter-in-place orders and prohibitions on the gathering of people. Other non-pharmaceutical interventions for suppressing transmission include active case finding, contact tracing, quarantine, immunity or health certification, and a wide range of personal protective measures. Here we investigate the potential effectiveness of these alternative approaches to suppression. We introduce a conceptual framework represented by two mathematical models that differ in strategy. We find both strategies may be effective, although both require extensive testing and work within a relatively narrow range of conditions. Generalized protective measures such as wearing face masks, improved hygiene and local reductions in density are found to significantly increase the effectiveness of targeted interventions.

Detecting critical slowing down in high-dimensional epidemiological systems.

Despite medical advances, the emergence and re-emergence of infectious diseases continue to pose a public health threat. Low-dimensional epidemiological models predict that epidemic transitions are preceded by the phenomenon of critical slowing down (CSD). This has raised the possibility of anticipating disease (re-)emergence using CSD-based early-warning signals (EWS), which are statistical moments estimated from time series data. For EWS to be useful at detecting future (re-)emergence, CSD needs to be a generic (model-independent) feature of epidemiological dynamics irrespective of system complexity. Currently, it is unclear whether the predictions of CSD-derived from simple, low-dimensional systems-pertain to real systems, which are high-dimensional. To assess the generality of CSD, we carried out a simulation study of a hierarchy of models, with increasing structural complexity and dimensionality, for a measles-like infectious disease. Our five models included: i) a nonseasonal homogeneous Susceptible-Exposed-Infectious-Recovered (SEIR) model, ii) a homogeneous SEIR model with seasonality in transmission, iii) an age-structured SEIR model, iv) a multiplex network-based model (Mplex) and v) an agent-based simulator (FRED). All models were parameterised to have a herd-immunity immunization threshold of around 90% coverage, and underwent a linear decrease in vaccine uptake, from 92% to 70% over 15 years. We found evidence of CSD prior to disease re-emergence in all models. We also evaluated the performance of seven EWS: the autocorrelation, coefficient of variation, index of dispersion, kurtosis, mean, skewness, variance. Performance was scored using the Area Under the ROC Curve (AUC) statistic. The best performing EWS were the mean and variance, with AUC > 0.75 one year before the estimated transition time. These two, along with the autocorrelation and index of dispersion, are promising candidate EWS for detecting disease emergence.

Blood lead concentrations among pediatric patients with abdominal pain: a prospective cross-sectional study.

BACKGROUND: Lead exposure is one of the most menacing of environmental exposures, particularly in children. Children are more susceptible to the effects of lead which manifest in many organ systems, including interference with mental and motor development. Lead poisoning can cause colicky abdominal pain. In this study, the authors sought to evaluate the prevalence of elevated blood lead level (BLL) and its contributing factors among pediatric patients presenting with abdominal pain. An epidemic of lead poisoning in adults was previously uncovered, and thus a concern for pediatric lead poisoning was raised. METHODS: Pediatric patients presenting to two pediatric clinics in Tehran with abdominal pain were eligible for enrollment in a descriptive prospective cross-sectional study. A predesigned questionnaire was filled for each patient by their consenting parents. The questionnaire queried demographic information, environmental, social, and other relevant parameters for lead exposure. After completion of the questionnaire, biometrics were obtained, and a blood sample was taken from each patient for measurement of BLL and complete blood count. RESULTS: A total of 187 patients were enrolled in the study. Of them, almost 20% had BLL ≥ 5 µg/dL. Univariate analysis showed that age (p = 0.002, OR 3.194, CI 95% 1.504-6.783), weight (p = 0.009, OR 2.817, CI 95% 1.266-6.269), height (p = 0.003, OR 3.155, CI 95% 1.443-6.899), and playing with both plastic and cotton toys (p = 0.03, OR 2.796, CI 95% 1.072-7.295) were significant predictors of high BLLs. Maternal level of education correlated with blood lead concentrations (p = 0.048, OR 2.524, CI 95% 1.006-6.331). CONCLUSIONS: A clinically significant number of cases of abdominal pain may have high BLLs. Specific attention should be paid to children presenting with abdominal pain, especially due to the detrimental effects of lead on their mental and motor development.

The emerging epidemic of inflammatory bowel disease in Asia and Iran by 2035: A modeling study.

BACKGROUND: The projection studies are imperative to satisfy demands for health care systems and proper response to the public health problems such as inflammatory bowel disease (IBD). METHODS: To accomplish this, we established an illness-death model based on available data to project the future prevalence of IBD in Asia, Iran in particular, separately from 2017 to 2035. We applied two deterministic and stochastic approaches. RESULTS: In 2035, as compared to 2020, we expected a 2.5-fold rise in prevalence for Iran with 69 thousand cases, a 2.3-fold increment for North Africa and the Middle East with 220 thousand cases, quadrupling of the prevalence for India with 2.2 million cases, a 1.5-fold increase for East Asia region with 4.5 million cases, and a 1.6-fold elevation in prevalence for high-income Asia-Pacific and Southeast Asia regions with 183 and 199 thousand cases respectively. CONCLUSIONS: Our results showed an emerging epidemic for the prevalence of IBD in Asia regions and/or countries. Hence, we suggest the need for immediate action to control this increasing trend in Asia and Iran. However, we were virtually unable to use information about age groups, gender, and other factors influencing the evolution of IBD in our model due to lack of access to reliable data.