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Abstract Background Gain of function (GOF) mutations in NOD-like receptor family CARD-containing 4 protein (NLRC4) gene induce a wide spectrum of autoinflammatory phenotypes. Currently, we categorize them into four groups: familial cold autoinflammatory syndrome (FCAS)4, autoinflammatory infantile enterocolitis (AIFEC), NLRC4-macrophage associated syndrome (MAS), and neonatal-onset multisystem inflammatory disease (NOMID). The rarity and complexity of the disease necessitate the description of new cases and a reexamination of our understanding of the condition. Case presentations We present three patients with NLRC4-GOF mutations and AIFEC phenotypes. The first patient is an infant girl with periodic fever, seizure, high inflammatory markers, and an episode of macrophage associated syndrome (MAS). History of recurrent fever episodes since childhood was reported in mother and maternal grandmother. A heterozygous mutation was found in CARD domain of NLRC4: c.A91C: p.Asn31His. The second patient is an adolescent boy with periodic fever, diarrhea, aphthous stomatitis, seizure, and central nervous system (CNS) vasculitis. A heterozygous mutation was found in NLRC4 gene: c.1202T > C. p. Val401Ala. The third patient is a child with chronic diarrhea and elevated inflammatory markers. We found a heterozygous mutation in NLRC4 gene: c.390delG: p.S132Afs*21. All mutations have been reported for the first time as NLRC4 mutations associated with autoinflammation. We introduced novel mutations in the CARD domain and between CARD and NBD domain in the first and third cases, respectively. All three children are under remission following treatment. Conclusions NLRC4-GOF mutations can be associated with autoinflammation with diverse symptoms. Given the rarity of the disease and the possibility of new mutations being identified, the existence of a phenotype/genotype correlation has yet to be thoroughly investigated. The variety in manifestations and severity spectrum mandates a variety of treatments. Adalimumab has shown favorable outcomes in our AIFEC cases.

Abstract Background There are conflicting findings regarding the effect of low-carbohydrate diets on obesity-related factors. This study aimed to investigate the effect of a carbohydrate-restricted (CR) diet on changes in anthropometric indicators of adiposity and fat distribution in pediatrics populations. Methods A systematic search was conducted in PubMed/MEDLINE, Web of Science, Scopus, and Embase electronic databases using predefined keywords to identify all randomized controlled trials examining the effects of CR on obesity-related factors. The pooled weighted mean difference (WMD) and 95% confidence intervals (CI) were calculated using a random-effects model. Results Findings from 11 studies demonstrated significant reductions in weight (WMD: -2.31 kg; 95% CI: -4.44, -0.18), BMI (WMD:-1.08 kg/m2; 95% CI: -1.91, -0.26), and fat mass (WMD: -1.43%; 95% CI: -2.43 to -0.43) as well as a significant increase in adiponectin levels (WMD: 0.74 ng/ml; 95% CI: 0.02, 1.47) in the CR diet group compared to the control group. However, no significant effect was observed on BMI z-score (WMD:-0.10; 95% CI: -0.21, 0.01), waist circumference (WMD:-3.03 cm; 95% CI: -6.57, 0.51) or leptin levels (WMD: -0.82 ng/ml; 95% CI: -2.26, 0.61). Stratified analysis rrevealed a greater effect of CR on weight and BMI reduction in interventions ≤ 12 weeks and in very low-carbohydrate diets. Conclusions In conclusion, it appears that CR diet, along with other lifestyle factors, can lead to significant improvements in weight loss on pediatrics with obesity/overweight.

Abstract Background Recent evidence shows the role of sirtuin 1(SIRT1), a family of evolutionarily conserved proteins, as a potential therapeutic target in the prevention and treatment of obesity and metabolic diseases. Some evidence shows the moderating effects of weight loss interventions on this factor. However, the findings are contradictory. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of weight loss interventions on SIRT 1 modulation. Methods For this study, we searched four electronic databases using predefined keywords from inception until March 2024. We includedrandomized controlled trials that evaluated the effect of weight reduction strategies on SIRT1 levels. The random-effects model analysis was used to obtain the pooled weighted mean difference (WMD) and 95% confidence intervals (95% CI). The meta-analysis was conducted using RevMan version 5.3 software and Stata version 12.0. Results Twelve studies with 627 volunteers were included. The pooled findings showed that weight loss interventions have no significant effect on the modulation of SIRT1 compared to the control group (pooled WMD of 0.58 ng/mL; 95% confidence interval [CI] -0.17 to 1.33; p = 0.130). However, subgroup analysis showed that weight loss interventions significantly modulate SIRT1 at metabolic disease (WMD: 1.2 ng/mL, 95% CI: 0.11 to 2.62, I2 = 82.9%). In addition, subgroup findings indicated health status and body mass index (BMI) as sources of high and potential heterogeneity. Conclusions Based on the findings, weight loss therapies in individuals having a metabolic disorder appear to generate a considerable increase in SIRT1 levels.

Abstract Recent evidence shows the beneficial effects of Baltic Sea diet score (BSDS) and healthy Nordic diet index (HNDI) on chronic diseases, however, there is no evidence to investigate them on the risk of non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to investigate the associations between BSDS and HNDI with the risk of NAFLD. In this case–control study, 552 people in good health and 340 people with NAFLD over the age of 18 took part. The evaluation of BSDS and HNDI employed a validated 168-item semi-quantitative food frequency questionnaire (FFQ). Binary logistic regression was used to determine how OBS and NAFLD are related. The mean BSDS and HNDI were 16.00 ± 2.49 and 11.99 ± 2.61, respectively. The final model's confounder adjustment revealed that greater HNDI adherence scores gave protection against the occurrence of NAFLD (odds ratio [OR]: 0.42; 95% confidence interval [CI] 0.18–0.98; P for trend = 0.043). In addition, those with the highest BSDS scores had significantly lower risks of developing NAFLD compared to subjects with the lowest scores (OR = 0.48, 95% CI 0.32–0.89; p for trend = 0.003). Our findings showed that following a healthy Nordic diet can significantly prevent the risk of developing NAFLD, and suggest that the highly nutritious components of the Nordic diet are beneficial for the prevention of NAFLD.

Abstract Background The global prevalence of obesity and overweight is a significant concern in the field of public health. However, addressing and combating these conditions pose considerable challenges. Numerous interventional studies have been conducted to assess the possible impact of bupropion on weight reduction. The primary objective of this study was to conduct a comprehensive investigation into the effects of bupropiona alone and in combination with naltrexone on weight, body mass index (BMI), and waist circumferences (WC). Methods A systematic search was conducted in five databases using established keywords. The purpose of this search was to uncover controlled trials that examined the impact of bupropion, either as a standalone intervention or in combination with naltrexone, on weight loss outcomes. The random-effects model analysis was used to provide pooled weighted mean difference and 95% confidence intervals. Results Twenty five studies with 22,165 participants’ were included in this article. The pooled findings showed that bupropion administration has an effect on lowering weight (WMD: -3.67 kg, 95% CI: -4.43 to -2.93) and WC (WMD: -2.98 cm, 95% CI -3.78 to -2.19) in compared with control groups. The analysis also showed that the effects of the present intervention on weight and WC during the intervention are > 26 weeks and ≤ 26 weeks compared to the other group, respectively. In addition, changes in weight loss and WC after receiving bupropion together with naltrexone were more compared to bupropion alone. Conclusions In conclusion, the addition of combination therapies like bupropion and naltrexone to lifestyle modifications including diet would cause significant weight loss.

Abstract Background Overall, there is conflicting evidence regarding the beneficial effects of optimal lifestyle modification, particularly weight loss interventions, with nonalcoholic fatty liver disease (non‐alcoholic fatty liver disease (NAFLD)). Therefore, this study investigated the effects of weight loss interventions on laboratory and clinical parameters in children and adolescents with NAFLD. Methods Original databases (PubMed/MEDLINE, Web of Science, SCOPUS, and Embase) were searched using standard keywords to identify all controlled trials investigating the effects of weight loss interventions among NAFLD children and adolescents. Pooled weighted mean difference and 95% confidence intervals were achieved by random‐effects model analysis. Results Eighteen eligible clinical trials were included in this systematic review and meta‐analysis. The pooled findings showed that especially more intense weight loss interventions significantly reduced the glucose (p = 0.007), insulin (p = 0.002), homeostatic model assessment‐insulin resistance (HOMA‐IR) (p = 0.003), weight (p = 0.025), body mass index (BMI) (p = 0.003), BMI z‐score (p 0.05) following weight loss interventions. Conclusions Weight loss interventions had significant effects on NAFLD‐related parameters including glucose, insulin, HOMA‐IR, weight, BMI, BMI z‐score, WC, TG, and AST.

Abstract A key goal of pertussis control is to protect infants too young to be vaccinated, the age group most vulnerable to this highly contagious respiratory infection. In the last decade, maternal immunization has been deployed in many countries, successfully reducing pertussis in this age group. Because of immunological blunting, however, this strategy may erode the effectiveness of primary vaccination at later ages. Here, we systematically reviewed the literature on the relative risk (RR) of pertussis after primary immunization of infants born to vaccinated vs. unvaccinated mothers. The four studies identified had ≤6 years of follow-up and large statistical uncertainty (meta-analysis weighted mean RR: 0.71, 95% CI: 0.38–1.32). To interpret this evidence, we designed a new mathematical model with explicit blunting mechanisms and evaluated maternal immunization’s short- and long-term impact on pertussis transmission dynamics. We show that transient dynamics can mask blunting for at least a decade after rolling out maternal immunization. Hence, the current epidemiological evidence may be insufficient to rule out modest reductions in the effectiveness of primary vaccination. Irrespective of this potential collateral cost, we predict that maternal immunization will remain effective at protecting unvaccinated newborns, supporting current public health recommendations.

A gluten-free diet (GFD) may have a stronger potential impact on reducing cardiovascular (CV) risk factors, according to research evidence. We investigated the impact of GFD on CV risk variables by doing a systematic review and meta-analysis for this reason. We conducted a thorough database search starting on January 1, 2000, and ending on July 12, 2022. We used random-effects models to pool the data. Totally 19 articles met the eligible criteria and were included. Pooled findings indicated that intervention with GFD has a significantly beneficial effect on high-density lipoprotein (HDL) (WMD: 4.80 mg/dl, 95% CI: 2.09, 7.51, P = 0.001), systolic blood pressure (SBP) (WMD: –2.96 mmHg; 95% CI: –4.11, –1.81, P < 0.001), and C-reactive protein (CRP) (WMD: –0.40, mg/l, 95% CI: –0.67, –0.14, P = 0.002) levels. In celiac patients as well as with an intervention duration of more than 48 weeks, GFD increased TC and HDL compared to non-celiac patients and with an intervention duration lower than 48 weeks, respectively. The results of the present study showed that GFD can have a significant and beneficial effect on HDL, SBP, and CRP.

Cardiovascular disease (CVD) is one of the most important diseases which controlling its related risk factors, such as metabolic and inflammatory biomarkers, is necessary because of the increased mortality risk of that. The aim of our meta-analysis is to reveal the general effect of vitamin K supplementation on its related risk factors. Original databases were searched using standard keywords to identify all randomized clinical trials (RCTs) investigating the effects of vitamin K on CVD. Pooled weighted mean difference (WMD) and 95 % confidence intervals (95 % CI) were achieved by random-model effect analysis for the best estimation of outcomes. The statistical heterogeneity was determined using the Cochran's Q test and I2 statistics. Seventeen studies were included in this systematic review and meta-analysis. The pooled findings showed that vitamin K supplementation can reduce homeostatic model assessment insulin resistance (HOMA-IR) (WMD: −0⋅24, 95 % CI: −0⋅49, −0⋅02, P = 0⋅047) significantly compared to the placebo group. However, no significant effect was observed on other outcomes. Subgroup analysis showed a significant effect of vitamin K2 supplementation compared to vitamin K1 supplementation on HOMA-IR. However, no significant effect was observed on other variables. Also, subgroup analysis showed no potential effect of vitamin K supplementation on any outcome and omitting any articles did not affect the final results. We demonstrated that supplementation with vitamin K has no effect on anthropometrics indexes, CRP, glucose metabolism, and lipid profile factors except HOMA-IR.

Abstract Evidence has also shown that oxidative stress and systemic inflammation, or in other words, disruption of the oxidant and antioxidant balance, can play an important role in the initiation or progression of NAFLD. The purpose of this study was to investigate the associations between the oxidative balance scores (OBS) and the risk of NAFLD. 552 healthy and 340 patients adult over the age of 18 with NAFLD participated in this case–control research. A validated 168-item quantitative food frequency questionnaire (FFQ) and indicators of physical activity, obesity, and smoking status were used to assess OBS score. The connection between OBS and NAFLD was discovered using binary logistic regression. The mean (± SD) age and (body mass index) BMI of the study population was 40.22 ± 9.79 years and 29.06 ± 3.92 kg/m2, respectively. The mean ± SD of OBS was 41.48 ± 5.23. After adjustment for potential confounders, higher scores of adherence to the OBS conferred a protection for the presence of NAFLD (odds ratio [OR]: 0.29; 95% confidence interval [CI]: 0.15–0.49; P for trend

Abstract 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.

Routine vaccination with pertussis vaccines has been successful in driving down pertussis mortality and morbidity globally. Despite high vaccination coverage, countries such as Australia, USA, and UK have experienced increase in pertussis activity over the last few decades. This may be due to local pockets of low vaccination coverage that result in persistence of pertussis in the population and occasionally lead to large outbreaks. The objective of this study was to characterize the association between pertussis vaccination coverage and sociodemographic factors and pertussis incidence at the school district level in King County, Washington, USA. We used monthly pertussis incidence data for all ages reported to the Public Health Seattle and King County between January 1, 2010 and December 31, 2017 to obtain school district level pertussis incidence. We obtained immunization data from the Washington State Immunization Information System to estimate school-district level vaccination coverage as proportion of 19–35 month old children fully vaccinated with ≥4 doses of the Diphtheria-Tetanus-acellular-Pertussis (DTaP) vaccine in a school district. We used two methods to quantify the effects of vaccination coverage on pertussis incidence: an ecological vaccine model and an endemic–epidemic model. Even though the effect of vaccination is modeled differently in the two approaches, both models can be used to estimate the association between vaccination coverage and pertussis incidence. Using the ecological vaccine model, we estimated the vaccine effectiveness of 4 doses of Diphtheria-Tetanus-acellular-Pertussis vaccine to be 83% (95% credible interval: 63%, 95%). In the endemic–epidemic model, under-vaccination was statistically significantly associated with epidemic risk of pertussis (adjusted Relative Risk, aRR: 2.76; 95% confidence interval: 1.44, 16.6). Household size and median income were statistically significantly associated with endemic pertussis risk. The endemic–epidemic model suffers from ecological bias, whereas the ecological vaccine model provides less biased and more interpretable estimates of epidemiological parameters, such as DTaP vaccine effectiveness, for each school district.

Abstract Introduction Fecal calprotectin (FC) is a noninvasive biomarker for assessing the inflammatory status of the gastrointestinal tract. The aim of this study was to determine the association between FC levels and Eosinophilic colitis (EC) before and after treatment in pediatrics. Method In this cross-sectional study, 330 patients with rectorrhagia and FC levels > 200 μg/g were included in the study. Patients were then subjected to colonoscopy, and if 30 or more eosinophils were observed in the pathology of at least two parts of the colon, EC was diagnosed. Of the 330 patients included in the study, 14 patients were diagnosed as EC. Treatment included seven food elimination diet (food allergens) for 3 months. After 3 months, FC levels were repeated and colonoscopy was performed. Results The mean age of the children was 5.9 years. After the elimination diet, the number of eosinophils in all segments of colon significantly decreased (P

BackgroundDespite the fact that obesity and overweight are serious major health problems worldwide, fighting against them is also considered a challenging issue. Several interventional studies have evaluated the potential weight-reduction effect of Tirzepatide. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of subcutaneous Tirzepatide on obesity and overweight.MethodsScopus, PubMed/Medline, Web of Science, Cochrane, and Embase databases were searched using standard keywords to identify all controlled trials investigating the weight loss effects of Tirzepatide. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model analysis for the best estimation of outcomes. The statistical heterogeneity and publication bias were determined using the Cochran’s Q test and I2 statistics and using the funnel plot and Egger’s test, respectively.ResultsTwenty three treatments arm with 7062 participants’ were included in this systematic review and meta‐regression analysis. The pooled findings showed that Tirzepatide vs placebo significantly reduced body weight (weighted mean difference (WMD): -11.34 kg, 95% confidence interval (CI): -12.79 to -9.88, P< 0.001), body mass index (BMI) (WMD: -3.11 kg/m2, 95% CI: -4.36 to -1.86, P< 0.001), and waist circumference (WC) (WMD: -7.24 cm, 95% CI -10.12 to -4.36, P< 0.001). These reductions were even greater, especially with higher doses and duration of Tirzepatide.ConclusionsTirzepatide medication had significant effects on weight management with the reduction of body weight, BMI, and WC. Administration of Tirzepatide can be considered a therapeutic strategy for overweight or obese people.

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.

Abstract 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.

Abstract 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.

Pediatric community-acquired pneumonia (CAP) remains a pressing global health concern, particularly in low-resource settings where diagnosis and treatment rely on empiric, symptoms-based guidelines such as the WHO’s Integrated Management of Childhood Illness (IMCI). This study details the delivery of IMCI-based health care to 1,320 young infants and their mothers in a low-resource urban community in Lusaka, Zambia during 2015. Our Southern Africa Mother Infant Pertussis Study (SAMIPS) prospectively monitored a cohort of mother/infant pairs across infants’ first four months of life, recording symptoms of respiratory infection and antibiotics prescriptions (predominantly penicillins), and tested nasopharyngeal (NP) samples for respiratory syncytial virus (RSV) and Bordetella pertussis. Our retrospective analysis of the SAMIPS cohort found that symptoms and antibiotics use were more common in infants (43% and 15.7%) than in mothers (16.6% and 8%), while RSV and B. pertussis were observed at similar rates in infants (2.7% and 32.5%) and mothers (2% and 35.5%), albeit frequently at very low levels. In infants, we observed strong associations between symptoms, pathogen detection, and antibiotics use. Critically, we demonstrate that non-macrolide antibiotics were commonly prescribed for pertussis infections, some of which persisted across many weeks. We speculate that improved diagnostic specificity and/or clinician education paired with timely, appropriate treatment of pertussis could substantially reduce the burden of this disease while reducing the off-target use of penicillins.

AimVitamin D deficiency is very common among children with IBD. Since there are conflicting results regarding the association of vitamin D with IBD, we conducted this systematic review to confirm the association of vitamin D with IBD.MethodsWe conducted a systematic search in Scopus, Cochrane Library, Web of Science, PubMed, and Google Scholar to find relevant studies. Articles with cross-sectional and case-control designs that reported the association between vitamin D and IBD among children were included.ResultsEventually, 9 studies (with 16 effect sizes) reported the mean and SD or the median and the interquartile range of serum vitamin D levels in both subjects with IBD and control subjects. The random effects meta-analysis revealed that subjects with IBD had −1.159 ng/ml (95% CI: −2.783, 0.464) lower serum vitamin D concentrations compared with their healthy counterparts, but this difference was not significant. A total of 14 studies (with 18 effect sizes) with 2,602 participants provided information for the prevalence of vitamin D deficiency or insufficiency in patients with IBD as 44% (95% CI: 0.34–0.54) with significant heterogeneity noted among studies (p < 0.001; I2 = 97.31%).ConclusionThis systematic and meta-analysis study revealed that vitamin D deficiency was associated with IBD. Longitudinal studies should be conducted in the future to confirm our findings. Large randomized controlled trials assessing the doses of supplementation of vitamin D would provide a better understanding of the association between vitamin D and IBD.

Abstract Early warning tools are crucial for the timely application of intervention strategies and the mitigation of the adverse health, social and economic effects associated with outbreaks of epidemic potential such as COVID-19. This paper introduces, the Epidemic Volatility Index (EVI), a new, conceptually simple, early warning tool for oncoming epidemic waves. EVI is based on the volatility of newly reported cases per unit of time, ideally per day, and issues an early warning when the volatility change rate exceeds a threshold. Data on the daily confirmed cases of COVID-19 are used to demonstrate the use of EVI. Results from the COVID-19 epidemic in Italy and New York State are presented here, based on the number of confirmed cases of COVID-19, from January 22, 2020, until April 13, 2021. Live daily updated predictions for all world countries and each of the United States of America are publicly available online. For Italy, the overall sensitivity for EVI was 0.82 (95% Confidence Intervals: 0.75; 0.89) and the specificity was 0.91 (0.88; 0.94). For New York, the corresponding values were 0.55 (0.47; 0.64) and 0.88 (0.84; 0.91). Consecutive issuance of early warnings is a strong indicator of main epidemic waves in any country or state. EVI’s application to data from the current COVID-19 pandemic revealed a consistent and stable performance in terms of detecting new waves. The application of EVI to other epidemics and syndromic surveillance tasks in combination with existing early warning systems will enhance our ability to act swiftly and thereby enhance containment of outbreaks.

Abstract 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.

Abstract The pandemic of COVID-19 has become one of the greatest threats to human health, causing severe disruptions in the global supply chain, and compromising health care delivery worldwide. Although government authorities sought to contain the spread of SARS-CoV-2, by restricting travel and in-person activities, failure to deploy time-sensitive strategies in ramping-up of critical resource production exacerbated the outbreak. Here, we developed a mathematical model to analyze the effects of the interaction between supply chain disruption and infectious disease dynamics using coupled production and disease networks built on global data. Analysis of the supply chain model suggests that time-sensitive containment strategies could be created to balance objectives in pandemic control and economic losses, leading to a spatiotemporal separation of infection peaks that alleviates the societal impact of the disease. A lean resource allocation strategy can reduce the impact of supply chain shortages from 11.91 to 1.11% in North America. Our model highlights the importance of cross-sectoral coordination and region-wise collaboration to optimally contain a pandemic and provides a framework that could advance the containment and model-based decision making for future pandemics.

BackgroundEvidence suggests the role of changing traditional lifestyle patterns, such as Paleolithic, to the modern lifestyle in the incidence and epidemic of chronic diseases. The purpose of this study was to investigate the associations between the Paleolithic diet (PD) and the Paleolithic-like lifestyle and the risk of non-alcoholic fatty liver disease (NAFLD) among an adult population.Materials and MethodsThis case-control study was carried out among 206 patients with NAFLD and 306 healthy subjects aged >18 years. PD score was evaluated using a validated 168-item quantitative food frequency questionnaire. In addition, to calculate the Paleolithic-like lifestyle score, the components of physical activity, body mass index (BMI), and smoking status of the participants were combined with the score of the PD.ResultsThe mean PD and Paleolithic-like lifestyle scores were 38.11 ± 5.63 and 48.92 ± 6.45, respectively. After adjustment for potential confounders, higher scores of adherence to the PD diet conferred a protection for the presence of NAFLD [odds ratio (OR): 0.53; 95% confidence interval (CI): 0.28–0.98; P for trend = 0.021]. Furthermore, PD and healthy lifestyle habits were negatively associated with NAFLD (OR = 0.42, 95% CI 0.23–0.78; P for trend = 0.007).ConclusionOur data suggest that the PD alone and in combination with lifestyle factors was associated with decreased risk of NAFLD in a significant manner in the overall population. However, prospective studies are needed to further investigate this association.

Abstract 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.

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.

Background: Obesity is a complex disorder influenced by various genetic and environmental factors. It has been shown that gut microbiota, which colonizes gastrointestinal tract, has a substantial role as an environmental factor in the pathophysiology of obesity. Since the composition of gut microbiota alters with regard to different criteria, such as ethnicity, geographical location, diet, lifestyle, age, and gender, we aimed to determine firmicutes/bacteroidetes (F/B) ratio and the abundance of important gut microbiota members, Akkermansia muciniphila, Faecalibacterium prausnitzii, Roseburia, Bifidobacterium, and Prevotella in Iranian obese and normal weight individuals, for the first time. Methods: In this study, 50 normal and 50 obese subjects were recruited and classified based on their BMI into normal weight and obese groups. Stool samples were collected. Following DNA extraction from the samples, quantitative PCR was conducted based on 16s rDNA universal primers. Finally, the correlation between the bacterial abundance and obesity was analyzed by statistical analyses. Results: We observed a significant increase of F/B ratio in the obese group, compared to the normal weight group (p = 0.002). Although A. muciniphila (p = 0.039) and Bifidobacterium (p = 0.049) abundance significantly decreased, the abundance of F. prausnitzii (p = 0.046) significantly elevated with BMI increase in the studied groups. Conclusion: Owing to the importance of the gut microbiota composition in obesity development, determination and targeted restoration of gut microbiota pattern could be valuable in the control and treatment of obesity in certain populations.

Abstract Background Interpretation of abnormalities in liver function tests, especially in asymptomatic children, is a common problem faced by clinicians. Isolated elevation of aspartate aminotransferase may further puzzle physicians. Macro-aspartate aminotransferase (AST) results from complexes AST produces with other plasma components, such as immunoglobulin. To our knowledge, this is the first report on a case of macro-AST-associated incomplete Kawasaki disease (KD). It is to make physicians aware of this benign condition and help to prevent extensive, unnecessary investigations and invasive workups. Case presentation A 16-month old boy with a 7-day history of fever was admitted to our pediatric ward for pyrexia workup. After complete investigations, KD was confirmed by a pediatric rheumatologist. During his admission and serial follow-up tests, an isolated AST elevation was noted. Comprehensive tests were performed and using the polyethylene glycol (PEG) precipitation method, macro-AST was confirmed. The patient has been followed up for 3 years, and so far, the benign nature of this condition has been confirmed. Conclusion Clinicians should consider testing for macro-AST when elevated AST is the only abnormal lab finding. Although an uncommon finding, macro-AST may be seen in both children and adults. There are many reasons for this phenomenon, including resolved acute hepatitis or in some cases, inflammatory bowel disease, hepatic malignancy, monoclonal gammapathy, celiac disease, or KD; however, it may be observed in asymptomatic healthy children as well. Using the PEG precipitation method, a definitive diagnosis can be made. In none of these conditions does macro-AST have any prognostic significance. An appreciation of macro-AST may prevent the need for more invasive investigations to which patients may be unnecessarily subjected. It is important to recognize this condition as benign and assure patients that no specific treatment is required.

Recent pertussis resurgence in numerous countries may be driven by asymptomatic infections. Most pertussis surveillance studies are cross-sectional and cannot distinguish asymptomatic from pre-symptomatic infections. Longitudinal surveillance could overcome this barrier, providing more information about the true burden of pertussis at the population level. Here we analyze 17,442 nasopharyngeal samples from a longitudinal cohort of 1320 Zambian mother/infant pairs. Our analysis has two elements. First, we demonstrate that the full range of IS481 qPCR CT values provides insight into pertussis epidemiology, showing concordance of low and high CT results over time, within mother/infant pairs, and in relation to symptomatology. Second, we exploit these full-range qPCR data to demonstrate a high incidence of asymptomatic pertussis, including among infants. Our results demonstrate a wider burden of pertussis infection than we anticipated in this population, and expose key limitations of threshold-based interpretation of qPCR results in infectious disease surveillance.

Background: Severe acute respiratory syndrome corona virus 2 (SARS- CoV-2) is known as COVID 19 seems to be one of the most contagious and dangerous infection in children and adults. According to first adult studies association of gastrointestinal (GI) symptoms with COVID 19 infection was as high as 79% (1).But later study showed lower association around 18% (2).As the pandemic of COVID 19 is going on, different clinical presentation of disease especially in children are well appeared. In addition atypical presentations may confuse and mislead physician to do different diagnostic procedures and interventions. We report a 6 years and half old boy with diarrhea, abdominal pain with first diagnosis acute abdomen due to acute appendicitis. At last diagnosis of pneumatosis intestinalis due to enterocolitis was confirmed. Case presentation: A 6 years and half old boy with severe abdominal pain admitted in emergency ward. He had history of fever, nine days of diarrhea and recurrent vomiting. The abdominal pain was severe with moderate tenderness in right lower quadrant. He admitted in pediatric surgery ward after surgical consultation for rolling out acute appendicitis. The results of first lab studies were shown leucopenia, lymphopenia and COVID 19 PCR was positive. During admission the cough has increased and abdominal distention has evolved. Vomiting was intractable and feeding was impossible. Pneumatosis intestinalis in ascending colon and dilatation in colon caliber were detected abdominal. Miliary like pattern in lung has reported in chest CT. Stool exam results revealed loss of protein in high amount in spite of normal pancreatic and enterocyte function. The calprotectin was high and implied high inflammation in large intestine. With all above data necrotizing enterocolitis management was started. After 14 days patients had good appetite and feeding slowly introduced. All symptoms resolved with exception of cough. Albumin and other electrolytes remained stable. The patient discharged without morbidity. Conclusion: COVID 19 infection has many different and mysterious presentations. GI manifestations are among important, common presentations. The acute abdomen like presentation with different complications like pneumatosis intestinalis, protein losing enteropathy are not common but knowledge about these presentations assist physician to be aware and make decision accurately.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is responsible for the outbreak of a new viral respiratory infection. It has been demonstrated that the microbiota has a crucial role in establishing immune responses against respiratory infections, which are controlled by a bidirectional cross-talk, known as the “gut-lung axis.” The effects of microbiota on antiviral immune responses, including dendritic cell (DC) function and lymphocyte homing in the gut-lung axis, have been reported in the recent literature. Additionally, the gut microbiota composition affects (and is affected by) the expression of angiotensin-converting enzyme-2 (ACE2), which is the main receptor for SARS-CoV-2 and contributes to regulate inflammation. Several studies demonstrated an altered microbiota composition in patients infected with SARS-CoV-2, compared to healthy individuals. Furthermore, it has been shown that vaccine efficacy against viral respiratory infection is influenced by probiotics pretreatment. Therefore, the importance of the gut microbiota composition in the lung immune system and ACE2 expression could be valuable to provide optimal therapeutic approaches for SARS-CoV-2 and to preserve the symbiotic relationship of the microbiota with the host.

Introduction Reliable information on rates of up-to-date coverage and timely administration of routine childhood immunisations are critical for guiding public health efforts worldwide, yet prospective observation of vaccination programmes within individual communities is rare. Here, we provide a longitudinal analysis of the directly observed administration of a three-dose primary vaccination series to infants in a low-resource community in Lusaka, Zambia.Methods Throughout 2015, we recruited a longitudinal birth cohort of mother/infant pairs (initial enrolment, 1981 pairs; attending, 1497 pairs) from the periurban informal settlement of Chawama compound, located in Lusaka, Zambia. We prospectively monitored the administration of scheduled diphtheria–tetanus–pertussis (DTP) vaccinations across the first 14–18 weeks of life. We analysed study attendance and vaccine coverage, both overall and stratified by age group. We employed Kaplan-Meier analyses to estimate delays in age-appropriate administration of vaccine doses. We also assessed schedule timing violations, including early and compressed dose administration.Results At study completion, first dose (DTP1) rates were high (92.9% of attending), whereas third dose completion (DTP3) rates were far lower (61.9%). Missed vaccinations and study dropout both contributed to the low DTP3 completion rates. DTP1 was administered very late (at or after 10 weeks) to 61 infants (4.1%). DTP1 was administered too early to 64 infants (4.3%), and 77 (5.1%) received consecutive doses below the minimum recommended spacing of 28 days.Conclusions We observe substantial individual variation in the timing of early childhood DTP doses, though following this birth cohort proved challenging. Our results indicate that timely administration of both DTP1 and DTP3 remains a challenge in this community. These directly-observed, individual-based results provide an important counterpoint to more course-grained, survey-based national and province estimates of up-to-date vaccine coverage. This study also highlights the challenges of vaccine hesitancy and suboptimal utilisation of (no-cost) healthcare services in a low-resource urban setting.

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.

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.

Abstract Background Childhood obesity is one of the most serious public health issues of the twenty-first century affecting even low- and middle-income countries. Overweight and obese children are more likely to stay obese into adulthood. Due to the paucity of data on local practices, our study aimed to assess the knowledge and practices of physicians from the Middle East and North Africa region with respect to early-onset obesity. Methods A specific questionnaire investigating the perception and knowledge on early-onset obesity was circulated to healthcare providers (general physicians, pediatricians, pediatric gastroenterologist, neonatologists) practicing in 17 Middle East and North African countries. Results A total of 999/1051 completed forms (95% response) were evaluated. Of all respondents, 28.9% did not consistently use growth charts to monitor growth during every visit and only 25.2% and 46.6% of respondents were aware of the correct cut-off criterion for overweight and obesity, respectively. Of those surveyed, 22.3, 14.0, 36.1, 48.2, and 49.1% of respondents did not consider hypertension, type 2 diabetes, coronary heart disease, fatty liver disease, and decreased life span, respectively, to be a long-term complication of early childhood obesity. Furthermore, only 0.7% of respondents correctly answered all survey questions pertaining to knowledge of early childhood overweight and obesity. Conclusion The survey highlights the low use of growth charts in the evaluation of early childhood growth in Middle East and North Africa region, and demonstrated poor knowledge of healthcare providers on the short- and long-term complications of early-onset obesity. This suggests a need for both continued professional education and development, and implementation of guidelines for the prevention and management of early childhood overweight and obesity.

Emerging and re-emerging pathogens exhibit very complex dynamics, are hard to model and difficult to predict. Their dynamics might appear intractable. However, new statistical approaches-rooted in dynamical systems and the theory of stochastic processes-have yielded insight into the dynamics of emerging and re-emerging pathogens. We argue that these approaches may lead to new methods for predicting epidemics. This perspective views pathogen emergence and re-emergence as a "critical transition," and uses the concept of noisy dynamic bifurcation to understand the relationship between the system observables and the distance to this transition. Because the system dynamics exhibit characteristic fluctuations in response to perturbations for a system in the vicinity of a critical point, we propose this information may be harnessed to develop early warning signals. Specifically, the motion of perturbations slows as the system approaches the transition.

Epidemic transitions are an important feature of infectious disease systems. As the transmissibility of a pathogen increases, the dynamics of disease spread shifts from limited stuttering chains of transmission to potentially large scale outbreaks. One proposed method to anticipate this transition are early-warning signals (EWS), summary statistics which undergo characteristic changes as the transition is approached. Although theoretically predicted, their mathematical basis does not take into account the nature of epidemiological data, which are typically aggregated into periodic case reports and subject to reporting error. The viability of EWS for epidemic transitions therefore remains uncertain. Here we demonstrate that most EWS can predict emergence even when calculated from imperfect data. We quantify performance using the area under the curve (AUC) statistic, a measure of how well an EWS distinguishes between numerical simulations of an emerging disease and one which is stationary. Values of the AUC statistic are compared across a range of different reporting scenarios. We find that different EWS respond to imperfect data differently. The mean, variance and first differenced variance all perform well unless reporting error is highly overdispersed. The autocorrelation, autocovariance and decay time perform well provided that the aggregation period of the data is larger than the serial interval and reporting error is not highly overdispersed. The coefficient of variation, skewness and kurtosis are found to be unreliable indicators of emergence. Overall, we find that seven of ten EWS considered perform well for most realistic reporting scenarios. We conclude that imperfect epidemiological data is not a barrier to using EWS for many potentially emerging diseases.

The incidence of whooping cough in the US has been rising slowly since the 1970s, but the pace of this has accelerated sharply since acellular pertussis vaccines replaced the earlier whole cell vaccines in the late 1990s. A similar trend occurred in many other countries, including the UK, Canada, Australia, Ireland, and Spain, following the switch to acellular vaccines. The key question is why. Two leading theories (short duration of protective immunologic persistence and evolutionary shifts in the pathogen to evade the vaccine) explain some but not all of these shifts, suggesting that other factors may also be important. In this synthesis, we argue that sterilizing mucosal immunity that blocks or abbreviates the duration of nasopharyngeal carriage of Bordetella pertussis and impedes person-to-person transmission (including between asymptomatically infected individuals) is a critical factor in this dynamic. Moreover, we argue that the ability to induce such mucosal immunity is fundamentally what distinguishes whole cell and acellular pertussis vaccines and may be pivotal to understanding much of the resurgence of this disease in many countries that adopted acellular vaccines. Additionally, we offer the hypothesis that observed herd effects generated by acellular vaccines may reflect a modification of disease presentation leading to reduced potential for transmission by those already infected, as opposed to inducing resistance to infection among those who have been exposed.

Background. Eosinophilic esophagitis is an inflammatory condition where there is a dense infiltration of eosinophils typically exceeding fifteen cells per high power field. Familial Mediterranean fever is an autosomal recessive disorder characterized by brief, acute, and self-limited episodes of fever and polyserositis that recur at irregular intervals. Case Presentation. A three-year-and-nine-month-old Iranian girl was admitted to our center. The patient’s parents complained of a history of abdominal pain, poor appetite, and poor weight gain from 1.5 years ago and episodes of food impaction after starting solid foods. Eosinophilic esophagitis was diagnosed based on histology. Because of continuing abdominal pain after treatment of eosinophilic esophagitis, the episodic nature of disease, and the presence of fever with pain, screening for familial Mediterranean fever mutation was performed and the patient was found to be heterozygote for Mediterranean fever. Conclusion. We have reported a case of eosinophilic esophagitis coexisting with familial Mediterranean fever which has not been described previously.

Controlling Ebola outbreaks and planning an effective response to future emerging diseases are enhanced by understanding the role of geography in transmission. Here we show how epidemic expansion may be predicted by evaluating the relative probability of alternative epidemic paths. We compared multiple candidate models to characterize the spatial network over which the 2013–2015 West Africa epidemic of Ebola virus spread and estimate the effects of geographical covariates on transmission during peak spread. The best model was a generalized gravity model where the probability of transmission between locations depended on distance, population density and international border closures between Guinea, Liberia and Sierra Leone and neighbouring countries. This model out-performed alternative models based on diffusive spread, the force of infection, mobility estimated from cell phone records and other hypothesized patterns of spread. These findings highlight the importance of integrated geography to epidemic expansion and may contribute to identifying both the most vulnerable unaffected areas and locations of maximum intervention value.

Sustained and coordinated vaccination efforts have brought polio eradication within reach. Anticipating the eradication of wild poliovirus (WPV) and the subsequent challenges in preventing its re-emergence, we look to the past to identify why polio rose to epidemic levels in the mid-20th century, and how WPV persisted over large geographic scales. We analyzed an extensive epidemiological dataset, spanning the 1930s to the 1950s and spatially replicated across each state in the United States, to glean insight into the drivers of polio's historical expansion and the ecological mode of its persistence prior to vaccine introduction. We document a latitudinal gradient in polio's seasonality. Additionally, we fitted and validated mechanistic transmission models to data from each US state independently. The fitted models revealed that: (1) polio persistence was the product of a dynamic mosaic of source and sink populations; (2) geographic heterogeneity of seasonal transmission conditions account for the latitudinal structure of polio epidemics; (3) contrary to the prevailing "disease of development" hypothesis, our analyses demonstrate that polio's historical expansion was straightforwardly explained by demographic trends rather than improvements in sanitation and hygiene; and (4) the absence of clinical disease is not a reliable indicator of polio transmission, because widespread polio transmission was likely in the multiyear absence of clinical disease. As the world edges closer to global polio eradication and continues the strategic withdrawal of the Oral Polio Vaccine (OPV), the regular identification of, and rapid response to, these silent chains of transmission is of the utmost importance.

A 46 year old man was transfused ten units of packed red blood cells during subtotal colectomy after intraoperative point-of-care testing values demonstrated hemoglobin values less than seven grams per deciliter (g/dL). A post-operative hemoglobin analyzed in a standard hematologic laboratory revealed a hemoglobin value of 27.8 g/dL. He underwent emergent red blood cell depletion therapy which decreased his hemoglobin to 7.5 g/dL. The physiologic consequences of iatrogenic polycythemia caused by massive transfusion during major abdominal surgery must take into account the fluid shifts that interplay between the osmotic load, viscosity of blood, and postoperative third spacing of fluid. Treatment of acute iatrogenic polycythemia can be effectively accomplished by red blood cell depletion therapy. However, fluid shifts caused by massive transfusion followed by rapid red cell depletion produce a unique physiologic state that is without a well-described algorithm for management.

Avian influenza viruses (AIVs) have been pivotal to the origination of human pandemic strains. Despite their scientific and public health significance, however, there remains much to be understood about the ecology and evolution of AIVs in wild birds, where major pools of genetic diversity are generated and maintained. Here, we present comparative phylodynamic analyses of human and AIVs in North America, demonstrating (i) significantly higher standing genetic diversity and (ii) phylogenetic trees with a weaker signature of immune escape in AIVs than in human viruses. To explain these differences, we performed statistical analyses to quantify the relative contribution of several potential explanations. We found that HA genetic diversity in avian viruses is determined by a combination of factors, predominantly subtype-specific differences in host immune selective pressure and the ecology of transmission (in particular, the durability of subtypes in aquatic environments). Extending this analysis using a computational model demonstrated that virus durability may lead to long-term, indirect chains of transmission that, when coupled with a short host lifespan, can generate and maintain the observed high levels of genetic diversity. Further evidence in support of this novel finding was found by demonstrating an association between subtype-specific environmental durability and predicted phylogenetic signatures: genetic diversity, variation in phylogenetic tree branch lengths, and tree height. The conclusion that environmental transmission plays an important role in the evolutionary biology of avian influenza viruses-a manifestation of the "storage effect"-highlights the potentially unpredictable impact of wildlife reservoirs for future human pandemics and the need for improved understanding of the natural ecology of these viruses.

Avian influenza viruses (AIVs) are considered a threat for their potential to seed human influenza pandemics. Despite their acknowledged importance, there are significant unknowns regarding AIV transmission dynamics in their natural hosts, wild birds. Of particular interest is the difference in subtype dynamics between human and bird populations-in human populations, typically only two or three subtypes cocirculate, while avian populations are capable of simultaneously hosting a multitude of subtypes. One species in particular-ruddy turnstones (Arenaria interpres)--has been found to harbour a very wide range of AIV subtypes, which could make them a key player in the spread of new subtypes in wild bird populations. Very little is known about the mechanisms that drive subtype dynamics in this species, and here we address this gap in our knowledge. Taking advantage of two independent sources of data collected from ruddy turnstones in Delaware Bay, USA, we examine patterns of subtype diversity and dominance at this site. We compare these patterns to those produced by a stochastic, multi-strain transmission model to investigate possible mechanisms that are parsimonious with the observed subtype dynamics. We find, in agreement with earlier experimental work, that subtype differences are unnecessary to replicate the observed dynamics, and that neutrality alone is sufficient. We also evaluate the role of subtype cross-immunity and find that it is not necessary to generate patterns consistent with observations. This work offers new insights into the mechanisms behind subtype diversity and dominance in a species that has the potential to be a key player in AIV dynamics in wild bird populations.

Successful replication within an infected host and successful transmission between hosts are key to the continued spread of most pathogens. Competing selection pressures exerted at these different scales can lead to evolutionary trade-offs between the determinants of fitness within and between hosts. Here, we examine such a trade-off in the context of influenza A viruses and the differential pressures exerted by temperature-dependent virus persistence. For a panel of avian influenza A virus strains, we find evidence for a trade-off between the persistence at high versus low temperatures. Combining a within-host model of influenza infection dynamics with a between-host transmission model, we study how such a trade-off affects virus fitness on the host population level. We show that conclusions regarding overall fitness are affected by the type of link assumed between the within- and between-host levels and the main route of transmission (direct or environmental). The relative importance of virulence and immune response mediated virus clearance are also found to influence the fitness impacts of virus persistence at low versus high temperatures. Based on our results, we predict that if transmission occurs mainly directly and scales linearly with virus load, and virulence or immune responses are negligible, the evolutionary pressure for influenza viruses to evolve toward good persistence at high within-host temperatures dominates. For all other scenarios, influenza viruses with good environmental persistence at low temperatures seem to be favored.

There is growing interest in understanding the nature and consequences of interactions among infectious agents. Pathogen interactions can be operational at different scales, either within a co-infected host or in host populations where they co-circulate, and can be either cooperative or competitive. The detection of interactions among pathogens has typically involved the study of synchrony in the oscillations of the protagonists, but as we show here, phase association provides an unreliable dynamical fingerprint for this task. We assess the capacity of a likelihood-based inference framework to accurately detect and quantify the presence and nature of pathogen interactions on the basis of realistic amounts and kinds of simulated data. We show that when epidemiological and demographic processes are well understood, noisy time series data can contain sufficient information to allow correct inference of interactions in multi-pathogen systems. The inference power is dependent on the strength and time-course of the underlying mechanism: stronger and longer-lasting interactions are more easily and more precisely quantified. We examine the limitations of our approach to stochastic temporal variation, under-reporting, and over-aggregation of data. We propose that likelihood shows promise as a basis for detection and quantification of the effects of pathogen interactions and the determination of their (competitive or cooperative) nature on the basis of population-level time-series data.

Pejman Rohani discusses a new study that examined the dynamic relationship between climate variables and dengue incidence in Thailand, Mexico, and Puerto Rico.

Case notifications of pertussis have shown an increase in a number of countries with high rates of routine pediatric immunization. This has led to significant public health concerns over a possible pertussis re-emergence. A leading proposed explanation for the observed increase in incidence is the loss of immunity to pertussis, which is known to occur after both natural infection and vaccination. Little is known, however, about the typical duration of immunity and its epidemiological implications. Here, we analyze a simple mathematical model, exploring specifically the inter-epidemic period and fade-out frequency. These predictions are then contrasted with detailed incidence data for England and Wales. We find model output to be most sensitive to assumptions concerning naturally acquired immunity, which allows us to estimate the average duration of immunity. Our results support a period of natural immunity that is, on average, long-lasting (at least 30 years) but inherently variable.

Avian influenza virus (AIV) persists in North American wild waterfowl, exhibiting major outbreaks every 2-4 years. Attempts to explain the patterns of periodicity and persistence using simple direct transmission models are unsuccessful. Motivated by empirical evidence, we examine the contribution of an overlooked AIV transmission mode: environmental transmission. It is known that infectious birds shed large concentrations of virions in the environment, where virions may persist for a long time. We thus propose that, in addition to direct fecal/oral transmission, birds may become infected by ingesting virions that have long persisted in the environment. We design a new host-pathogen model that combines within-season transmission dynamics, between-season migration and reproduction, and environmental variation. Analysis of the model yields three major results. First, environmental transmission provides a persistence mechanism within small communities where epidemics cannot be sustained by direct transmission only (i.e., communities smaller than the critical community size). Second, environmental transmission offers a parsimonious explanation of the 2-4 year periodicity of avian influenza epidemics. Third, very low levels of environmental transmission (i.e., few cases per year) are sufficient for avian influenza to persist in populations where it would otherwise vanish.