Chitosan Nanoparticles for Enhanced Delivery of Sida cordifolia Extract: Formulation, Optimization and Bioactivity Assessment.

In a continuous search for an essential antidiabetic agent, Sida cordifolia hydroalcoholic (SCHA) extract-loaded chitosan nanoparticles (SCHA-CS-NP) were optimized. The Box-Behnken design (BBD Design-Expert software, version 14) with three parameters was used to optimize the nanoparticles after creating them using the ion gelation method. The chitosan and Tween 20 contents and the stirring speed were chosen as the independent variables, and their separate and combined effects on particle size (Y1), polydispersity index (Y2) and entrapment efficiency (Y3) were observed. The optimized formulation showed a particle size of 51 nm, an entrapment efficiency of 84.54% and a polydispersity index of 0.391. Physicochemical characterization, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), a drug release study, an ex vivo permeation study, and an antioxidant study were performed. Confocal laser scanning microscopy (CLSM) images demonstrated that chitosan nanoparticles loaded with rhodamine B-laden SCHA extract had superior penetration compared to the control (rhodamine B solution). Furthermore, compared to conventional ascorbic acid (IC50 = 45 µg/mL), a superior antioxidant activity was discovered for SCHA-CS-NPs (IC50 = 86.45 ± 2.24 µg/mL), while SCHA-CS-NPs also exhibited strong antidiabetic potential (IC50 = 93.71 ± 1.79 µg/mL) compared to standard acarbose (IC50 = 97.25 ± 1.43 µg/mL). The overall results demonstrated that SCHA-CS-NPs are a promising and efficient formulation for oral delivery.

Effectiveness, safety and economic viability of daycare versus usual hospital care management of severe pneumonia with or without malnutrition in children using the existing health system of Bangladesh: a cluster randomised controlled trial.

Background: We aimed to define clinical and cost-effectiveness of a Day Care Approach (DCA) alternative to Usual Care (UC, comparison group) within the Bangladesh health system to manage severe childhood pneumonia. Methods: This was a cluster randomised controlled trial in urban Dhaka and rural Bangladesh between November 1, 2015 and March 23, 2019. Children aged 2-59 months with severe pneumonia with or without malnutrition received DCA or UC. The DCA treatment settings comprised of urban primary health care clinics run by NGO under Dhaka South City Corporation and in rural Union health and family welfare centres under the Ministry of Health and Family welfare Services. The UC treatment settings were hospitals in these respective areas. Primary outcome was treatment failure (persistence of pneumonia symptoms, referral or death). We performed both intention-to-treat and per-protocol analysis for treatment failure. Registered at www.ClinicalTrials.gov, NCT02669654. Findings: In total 3211 children were enrolled, 1739 in DCA and 1472 in UC; primary outcome data were available in 1682 and 1357 in DCA and UC, respectively. Treatment failure rate was 9.6% among children in DCA (167 of 1739) and 13.5% in the UC (198 of 1472) (group difference, -3.9 percentage point; 95% confidence interval (CI), -4.8 to -1.5, p = 0.165). Treatment success within the health care systems [DCA plus referral vs. UC plus referral, 1587/1739 (91.3%) vs. 1283/1472 (87.2%), group difference 4.1 percentage point, 95% CI, 3.7 to 4.1, p = 0.160)] was better in DCA. One child each in UC of both urban and rural sites died within day 6 after admission. Average cost of treatment per child was US$94.2 (95% CI, 92.2 to 96.3) and US$184.8 (95% CI, 178.6 to 190.9) for DCA and UC, respectively. Interpretation: In our population of children with severe pneumonia with or without malnutrition, >90% were successfully treated at Day care Clinics at 50% lower cost. A modest investment to upgrade Day care facilities may provide a cost-effective, accessible alternative to hospital management. Funding: UNICEF, Botnar Foundation, UBS Optimus Foundation, and EAGLE Foundation, Switzerland.

Gradient-Descent Quantum Process Tomography by Learning Kraus Operators.

We perform quantum process tomography (QPT) for both discrete- and continuous-variable quantum systems by learning a process representation using Kraus operators. The Kraus form ensures that the reconstructed process is completely positive. To make the process trace preserving, we use a constrained gradient-descent (GD) approach on the so-called Stiefel manifold during optimization to obtain the Kraus operators. Our ansatz uses a few Kraus operators to avoid direct estimation of large process matrices, e.g., the Choi matrix, for low-rank quantum processes. The GD-QPT matches the performance of both compressed-sensing (CS) and projected least-squares (PLS) QPT in benchmarks with two-qubit random processes, but shines by combining the best features of these two methods. Similar to CS (but unlike PLS), GD-QPT can reconstruct a process from just a small number of random measurements, and similar to PLS (but unlike CS) it also works for larger system sizes, up to at least five qubits. We envisage that the data-driven approach of GD-QPT can become a practical tool that greatly reduces the cost and computational effort for QPT in intermediate-scale quantum systems.

Trends and determinants of organised sports participation in immigrant and Australian children: A nine-year follow-up.

OBJECTIVES: This study aimed to examine trends and determinants of organised sports participation among children of immigrant parents from low-and-middle-income countries, high-income countries, and Australian children. DESIGN: Longitudinal (nine-year follow-up). METHODS: Data were from the birth-cohort of Australian Children aged 6-15 years with follow-up between 2010 and 2018. Organised sports participation was measured using two items about regular participation in team and individual sports. Multilevel logit modelling was used to assess the determinants of organised sports participation across groups. RESULTS: Both team sports participation and individual sports participation increased between 6 and 11 years and declined between 11 and 15 years across the three groups. Children of immigrant parents from low-and-middle-income countries (OR 0.65; 95 % CI 0.57-0.74) and high-income countries (OR 0.82; 95 % CI 0.76-0.89) had lower odds of team sports participation than Australian children. Children of immigrant parents from low-and-middle-income countries had lower odds of team sports participation (OR 0.79; 95 % CI 0.69-0.90) than children of immigrant parents from high-income countries. Female children, high screen time, high psychological difficulties, increased number of siblings and low socio-economic position were identified as determinants of lower team and individual sports participation. CONCLUSIONS: The present study identified evidence of disparities in organised sports participation among children of immigrant parents and Australian children. Multilevel and multicomponent interventions to promote children's organised sports participation should be prioritised, with a focus on children of the female sex, older children, children with lower socioeconomic status, and children with higher screen time and higher psychological difficulties.

Is Fibersol-2 efficacious in reducing duration of watery diarrhea and stool output in children 1-3 years old? A randomized, parallel, double-blinded, placebo-controlled, two arm clinical trial.

BACKGROUND: Fibersol-2 has innumerable beneficial effects on human health. It is a fermentable, non-viscous, water-soluble, indigestible dextrin containing 90% dietary fiber produced from corn starch. We aimed to evaluate whether additional intake of Fibersol-2 along with oral rehydration solution treatment can reduce the duration of watery diarrhea and daily stool output in children 1-3 years as well as recovery of such children within 72 hours, compared to placebo. METHODS: This placebo-controlled double-blinded, randomized parallel two arm trial conducted in Kumudini Women's Medical College Hospital in rural Bangladesh between March and October, 2018 used 5 gm of either Fibersol-2 or placebo dissolved in 50-ml drinking water which was given orally to ninety-two children with watery diarrhea on enrollment twice daily for a period of 7 days. Randomization was done using a randomization table. We randomly allocated 45 (49%) and 47 (51%) children in Fibersol-2 and placebo groups, respectively. Outcome measures were duration of resolution of watery diarrhea, daily stool output and the proportion of children recovered within 72 hours. Primary and safety analyses were by intention to treat. This trial was registered at ClinicalTrials.gov, number NCT03565393. RESULTS: There was no significant difference observed in terms of duration of resolution of diarrhea (adjusted mean difference 8.20, 95% CI -2.74 to 19.15, p = 0.14, adjusted effect size 0.03); the daily stool output (adjusted mean difference 73.57, 95% CI -94.17 to 241.32, p = 0.38, adjusted effect size 0.33) and the proportion of children recovered within 72 hours (adjusted odds ratio 0.49, 95% CI = 0.12 to 1.96, p = 0.31, adjusted risk difference -0.06 (95% CI -0.19 to -0.06), after regression analysis between Fibersol-2 and placebo. CONCLUSION: No beneficial role of Fibersol-2 was observed in diarrheal children aged 1-3 years. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, number NCT03565393. The authors confirmed that all ongoing and related trials for this drug/intervention are registered. https://clinicaltrials.gov/ct2/show/NCT03565393.

Digestive tolerability and acceptability of Fibersol-2 in healthy and diarrheal children 1-3 years old at a rural facility, Bangladesh: Results from a four arm exploratory study.

BACKGROUND: Fibersol-2 has some beneficial effects on human health. We aimed to evaluate the digestive tolerability and acceptability of Fibersol-2 in healthy and diarrheal children, as well as improvement in stool consistencies in young diarrheal children. METHODS: Sixty children of either sex, aged 1-3 years having four groups (healthy children/low dose, healthy children/high dose, children with diarrhea/low dose and children with diarrhea/high dose) were enrolled into this exploratory study between 1st August to 23rd October 2017. Two presumptive doses, low (2.5g) and high (5g), twice daily with 50 ml drinking water for seven days were the interventions. Outcomes were to observe the development of possible abdominal symptoms, such as pain, distension, rumbling, and bloating during the intervention and post-intervention periods in healthy and diarrheal children as well as improvement in stool consistencies in diarrheal children. RESULTS: Among the diarrheal children, the median (IQR) duration of resolution of diarrhea was 3.9 (2.9, 5.1) days vs. 3.5 (2.0, 8.0) days, p = 0.885; in low dose and high dose groups, respectively. Significant difference was observed in terms of abdominal pain (27% vs. 7%, p = 0.038) and distension (40% vs. 0%, p<0.001) in diarrheal children, compared to healthy children during the pre-intervention period. We also observed significant difference in respect of abdominal distension (23% vs. 0%, p = 0.011), rumbling (27% vs. 0%, p = 0.005) and bloating (43% vs. 3%, p = 0.001) in diarrheal children, compared to healthy children during the intervention period. However, no significant difference was observed in relation to abdominal pain (p = 0.347) and distension (p = 0.165) during the pre-intervention period, compared to the intervention period in diarrheal children. Moreover, no significant difference was observed during the post-intervention period for the diarrheal and healthy children. CONCLUSION: Fibersol-2 was found to be well tolerated in healthy and diarrheal children aged 1-3 years. TRIAL REGISTRATION: This study was registered as part of a randomized trial at ClinicalTrials.gov, number NCT03565393. The authors confirmed that all ongoing and related trials for this drug/intervention were registered.

Lifestyle behaviours of immigrant and Australian children: Evidence from a nationally representative sample.

This study aimed to examine the prevalence of physical activity (PA), screen time (ST), sleep, and fruit and vegetable intake of children with low-and-middle-income countries (LMIC) parents, high-income countries (HIC), and Australian children, and whether these behaviours are associated with their immigrant status. Data for this study were from wave 7 of the Birth cohort (B cohort) of the Longitudinal Study of Australian Children. We used generalized estimating equations (GEE) to examine associations between health behaviours and immigrant status. The models were adjusted for a number of covariates. Children with LMIC parents had lower odds of meeting PA and sleep recommendations and higher odds ratio (OR) of meeting fruit and vegetable intake, and ST recommendations than Australian or HIC children. Children with LMIC parents had one-third the odds of meeting the PA recommendations (OR 0.39 [95%CI 0.22-0.70]) than Australian children. No significant differences were observed in lifestyle behaviours among children with HIC parents and Australian children. Lifestyle behaviours of children with LMIC parents differed from those of HIC and Australian children. However, children with HIC parents and Australian children had comparable lifestyle behaviours. Identified disparities in lifestyle behaviours among immigrant children can inform strategies to bring equity in Australian children's lifestyles. Our study underscores the importance of culturally appropriate targeted interventions to promote PA and sleep of children with LMIC parents.

Toxoplasma gondii Infection Is Associated with Low Birth Weight: Findings from an Observational Study among Rural Bangladeshi Women.

Gestational Toxoplasma gondii (T. gondii) infection may cause substantial adverse effects on developing fetuses, newborns and also mothers. This study aims to estimate the seroprevalence of T. gondii among rural Bangladeshi pregnant women and determine the risk of a low birth weight (LBW). We followed a longitudinal design where 208 pregnant women were followed until the birth of their infants. Levels of IgG and IgM of T. gondii were assessed using chemiluminescent immunoassay. Modified Poisson regression was used to estimate crude and adjusted associations and multiple regression analysis was performed to understand the confounding and modifying effects of the variables. Thirty-nine (19%) children were born with LBW, among whom 15 (39%) mothers were positive for T. gondii IgG during pregnancy. After adjusting for several confounders and modifiers, pregnant women with T. gondii IgG or IgM seropositivity were significantly associated with LBW of infants (aRR: 2.00, 95% CI: 1.17-3.42). The strength of this association increased after adjusting for maternal education (aRR: 4.88, 95% CI: 1.74-13.69). The final model had an AROC of 0.84 with a sensitivity of 36% and specificity of 97%. Although causality is yet to be established, the study observed an association between T. gondii infection during pregnancy among rural Bangladeshi women and LBW of newborns.

Anthropometric Indices of Giardia-Infected Under-Five Children Presenting with Moderate-to-Severe Diarrhea and Their Healthy Community Controls: Data from the Global Enteric Multicenter Study.

Among all intestinal parasitosis, giardiasis has been reported to be associated with delayed growth in malnourished children under 5 living in low- and middle-income countries. Relevant data on the nutritional status of children aged 0-59 months presenting with moderate-to-severe diarrhea (MSD) and giardia infection were collected from sentinel health facilities of the Global Enteric Multicenter Study's (GEMS) seven field settings, placed in diverse countries of Sub-Saharan Africa and South Asia between, December 2007 and February 2011. Then, this study analyzed a robust dataset of study participants (n = 22,569). Children having giardiasis with MSD constituted as cases (n = 1786), and those without MSD constituted as controls (n = 3470). Among the seven field sites, symptomatic giardiasis was 15% and 22% in Asian and African sites, respectively, whereas asymptomatic giardia infection (healthy without MSD) in Asian and African sites was 21.7% and 30.7%, respectively. Wasting and underweight were more frequently associated and stunting less often associated with symptomatic giardiasis (for all, p < 0.001). Symptomatic giardiasis had a significant association with worsening of nutritional status in under-five children. Improved socio-economic profile along with proper sanitation and hygienic practices are imperative to enhance child nutritional status, particularly in resource limited settings.

Quantum State Tomography with Conditional Generative Adversarial Networks.

Quantum state tomography (QST) is a challenging task in intermediate-scale quantum devices. Here, we apply conditional generative adversarial networks (CGANs) to QST. In the CGAN framework, two dueling neural networks, a generator and a discriminator, learn multimodal models from data. We augment a CGAN with custom neural-network layers that enable conversion of output from any standard neural network into a physical density matrix. To reconstruct the density matrix, the generator and discriminator networks train each other on data using standard gradient-based methods. We demonstrate that our QST-CGAN reconstructs optical quantum states with high fidelity, using orders of magnitude fewer iterative steps, and less data, than both accelerated projected-gradient-based and iterative maximum-likelihood estimation. We also show that the QST-CGAN can reconstruct a quantum state in a single evaluation of the generator network if it has been pretrained on similar quantum states.

Pathogens Associated With Linear Growth Faltering in Children With Diarrhea and Impact of Antibiotic Treatment: The Global Enteric Multicenter Study.

BACKGROUND: The association between childhood diarrheal disease and linear growth faltering in developing countries is well described. However, the impact attributed to specific pathogens has not been elucidated, nor has the impact of recommended antibiotic treatment. METHODS: The Global Enteric Multicenter Study enrolled children with moderate to severe diarrhea (MSD) seeking healthcare at 7 sites in sub-Saharan Africa and South Asia. At enrollment, we collected stool samples to identify enteropathogens. Length/height was measured at enrollment and follow-up, approximately 60 days later, to calculate change in height-for-age z scores (ΔHAZ). The association of pathogens with ΔHAZ was tested using linear mixed effects regression models. RESULTS: Among 8077 MSD cases analyzed, the proportion with stunting (HAZ below -1) increased from 59% at enrollment to 65% at follow-up (P < .0001). Pathogens significantly associated with linear growth decline included Cryptosporidium (P < .001), typical enteropathogenic Escherichia coli (P = .01), and untreated Shigella (P = .009) among infants (aged 0-11 months) and enterotoxigenic E. coli encoding heat-stable toxin (P < .001) and Cryptosporidium (P = .03) among toddlers (aged 12-23 months). Shigella-infected toddlers given antibiotics had improved linear growth (P = .02). CONCLUSIONS: Linear growth faltering among children aged 0-23 months with MSD is associated with specific pathogens and can be mitigated with targeted treatment strategies, as demonstrated for Shigella.

Epidemiology and genetic characterization of human sapovirus among hospitalized acute diarrhea patients in Bangladesh, 2012-2015.

Human sapovirus, which causes acute gastroenteritis, is not well studied and poorly understood. This study aims to investigate the contribution of sapovirus in diarrhea, their clinical association, and genotypic diversity. Fecal specimens (n = 871) were randomly selected from diarrheal patients who attended International Centre for Diarrhoeal Disease Research, Bangladesh hospital in Dhaka, Bangladesh during January 2012-December 2015 and tested for the presence of sapovirus RNA using real-time polymerase chain reaction. Sapovirus RNA was identified in 2.3% (n = 20) of the samples. Seventy-five percent of the sapovirus positive cases were coinfected with other pathogens, such as rotavirus, norovirus, enterotoxigenic Escherichia coli, adenovirus, Shigella spp., and Vibrio cholerae. A vast genetic diversity was observed among sapovirus with at least seven common genotypes (GI.1, GI.2, GI.7, GII.1, GII.4, GII.6, and GIV), and a new genotype GII.NA1. Some of the GI.1 strains detected were similar to GI.4 in the polymerase region sequence and were confirmed as recombinant strains. Our findings suggest that the overall contribution of sapovirus in hospitalized diarrheal illness is low but highlight enormous genetic diversity.

Global Prevalence of Physical Activity, Sedentary Behaviour, and Sleep of Immigrant Children: a Systematic Review.

BACKGROUND: Although insufficient physical activity (PA), high sedentary behaviour (SB), and inadequate sleep are fairly common among children, little is known about these behaviours in immigrant children. This systematic review examined the prevalence of PA, SB, and sleep among immigrant children aged 5-17 years around the globe. METHODS: Four electronic databases were searched to retrieve the English language peer-reviewed original articles published between 2000 and 2019. Cross-sectional, cohort, or longitudinal studies that reported on the prevalence of PA, SB, or sleep-related outcomes among immigrant children were included. RESULTS: Of 2724 retrieved articles, 55 were selected for full-text screening and 12 met the eligibility criteria. Five studies were based on nationally representative samples. Over half (n = 7; 58%) of the studies assessed only PA, one reported only sleep, three reported both PA and SB, and one reported all three behaviours. Only one study used device-based measure. Assessment of PA and SB varied greatly across the studies with their differing definitions. The prevalence of doing PA ranged from 48 to 72%. Three studies reported an average sedentary time ranging from 1 to 3 h/day. One study reported that 10-13% of immigrant children in the USA had inadequate sleep. All of the studies reviewed were from Western countries with no study from non-Western countries. CONCLUSIONS: Future studies should include all three movement behaviours and use standard assessment tools and definitions. Future research should extend beyond Western countries to non-Western countries with immigrant children.

The Clinical Presentation of Culture-positive and Culture-negative, Quantitative Polymerase Chain Reaction (qPCR)-Attributable Shigellosis in the Global Enteric Multicenter Study and Derivation of a Shigella Severity Score: Implications for Pediatric Shigella Vaccine Trials.

BACKGROUND: Shigella is a leading cause of childhood diarrhea and target for vaccine development. Microbiologic and clinical case definitions are needed for pediatric field vaccine efficacy trials. METHODS: We compared characteristics of moderate to severe diarrhea (MSD) cases in the Global Enteric Multicenter Study (GEMS) between children with culture positive Shigella to those with culture-negative, quantitative polymerase chain reaction (qPCR)-attributable Shigella (defined by an ipaH gene cycle threshold <27.9). Among Shigella MSD cases, we determined risk factors for death and derived a clinical severity score. RESULTS: Compared to culture-positive Shigella MSD cases (n = 745), culture-negative/qPCR-attributable Shigella cases (n = 852) were more likely to be under 12 months, stunted, have a longer duration of diarrhea, and less likely to have high stool frequency or a fever. There was no difference in dehydration, hospitalization, or severe classification from a modified Vesikari score. Twenty-two (1.8%) Shigella MSD cases died within the 14-days after presentation to health facilities, and 59.1% of these deaths were in culture-negative cases. Age <12 months, diarrhea duration prior to presentation, vomiting, stunting, wasting, and hospitalization were associated with mortality. A model-derived score assigned points for dehydration, hospital admission, and longer diarrhea duration but was not significantly better at predicting 14-day mortality than a modified Vesikari score. CONCLUSIONS: A composite severity score consistent with severe disease or dysentery may be a pragmatic clinical endpoint for severe shigellosis in vaccine trials. Reliance on culture for microbiologic confirmation may miss a substantial number of Shigella cases but is currently required to measure serotype specific immunity.

A Retrospective Case-Control Study of the Relationship between the Gut Microbiota, Enteropathy, and Child Growth.

The microbial communities residing in the child gut are thought to play an important role in child growth, although the relationship is not well understood. We examined a cohort of young children from Mirzapur, Bangladesh, prospectively over 18 months. Four fecal markers of environmental enteropathy (EE) (high levels of alpha-1-antitrypsin, calprotectin, myeloperoxidase, and neopterin) were examined and anthropometric measures obtained from a cohort of 68 children. The 16S rRNA gene of bacterial DNA was sequenced from stool samples and used to estimate amplicon sequence variants (ASVs). We age-matched children with poor growth to children with normal growth within 1 month and compared the change in abundance and diversity of ASVs over time. Elevated EE markers and poor linear growth in children were associated with changes in microbial communities in the gut. There were increased amounts of Escherichia/Shigella and Proteobacteria and decreased amounts of Prevotella associated with poorly growing children consistent with the mounting evidence supporting the relationship between intestinal inflammation, child growth, and changes in gut microbiota composition. Future research is needed to investigate this association among young children in low- and middle-income countries.

Pathogen-specific risk of seizure in children with moderate-to-severe diarrhoea: Case control study with follow-up.

OBJECTIVE: To determine the pathogen-specific risk of seizure in under-five children hospitalised with moderate-to-severe diarrhoea (MSD) in rural settings. METHOD: This was a prospective case-control study with follow-up, conducted in a sentinel facility of Global Enteric Multicenter Study in Mirzapur, a rural community of Bangladesh between 2007 and 2010. Children aged 0-59 months who presented with MSD and seizure constituted the cases whereas those who did not have seizure comprised the controls. MSD was defined if the episodes were associated with dehydration or dysentery or required hospitalisation with diarrhoea or dysentery. All enrolled children were followed up at home within 50-90 days of enrolment. A total of 64 cases and 128 randomly selected controls formed the analysable dataset. RESULTS: The result of logistic regression analysis after adjusting for potential confounders revealed that shigellosis (Shigella species, OR = 5.34, 95% CI = 2.37-12.04) particularly S. flexneri (OR = 3.34, 95% CI = 1.48-7.57), S. flexneri 6 (OR = 23.24, 95% CI = 2.79-193.85), S. sonnei (OR = 6.90, 95% CI = 2.34-19.85); norovirus (OR = 6.77, 95% CI = 1.69-27.11), fever (OR = 16.75, 95% CI = 1.81-154.70) and loss of consciousness (OR = 35.25, 95% CI = 1.71-726.20) were the independent risk factors for seizure in MSD children. At enrolment, cases had lower WHZ (P = 0.006) compared to their peers, follow-up anthropometrics showed significant improvement in WHZ (P < 0.001) and WAZ (P < 0.05), whereas deterioration in HAZ (P < 0.001) in both cases and controls. CONCLUSION: Childhood MSD episodes particularly due to Shigella and norovirus are often associated with seizure. Prompt identification and appropriate management of children with shigellosis may reduce occurrence and adverse consequences of seizure linked with MSD.

OBJECTIF: Déterminer le risque spécifique de convulsions chez les enfants de moins de cinq ans hospitalisés pour une diarrhée modérée à sévère (DMS) en milieu rural. MÉTHODE: Il s'agissait d'une étude prospective cas-témoins avec suivi, menée dans un établissement sentinelle de l'Etude Globale Multicentrique Entérique à Mirzapur, une communauté rurale du Bangladesh entre 2007 et 2010. Les enfants âgés de 0 à 59 mois qui se sont présentés avec une DMS et des convulsions constituaient les cas, tandis que ceux qui n'avaient pas des convulsions constituaient les témoins. La DMS a été définie si les épisodes étaient associés à une déshydratation ou à une dysenterie ou nécessitaient une hospitalisation pour diarrhée ou dysenterie. Tous les enfants recrutés ont été suivis à domicile dans les 50 à 90 jours suivant le recrutement. Un total de 64 cas et 128 témoins sélectionnés au hasard ont constitué l'ensemble de données analysables. RÉSULTATS: Le résultat de l'analyse de régression logistique après ajustement des facteurs de confusion potentiels a révélé que la shigellose (espèce Shigella, OR = 5,34 ; IC95%: 2,37-12,04) en particulier S. flexneri (OR = 3,34 ; IC95%: 1,48-7,57), S. flexneri 6 (OR = 23,24 ; IC95%: 2.79-193,85), S. sonnei (OR = 6,90 ; IC95%: 2,34-19,85) ; les norovirus (OR = 6,77 ; IC95%: 1,69-27,11), la fièvre (OR = 16,75 ; IC95%: 1,81-154,70) et la perte de conscience (OR = 35,25 ; IC95%: 1,71-726,20) étaient les facteurs de risque indépendants de convulsions chez les enfants souffrant de DMS. Lors du recrutement, les cas avaient un score Z poids pour la taille (ZPT) plus faible (P = 0,006) que leurs pairs, les anthropométries de suivi ont montré une amélioration significative du ZPT (P < 0,001) et du score Z poids pour l'âge (P < 0,05); tandis que le score Z taille pour l'âge (p < 0,001) s'est détérioré chez cas et chez les témoins. CONCLUSION: Les épisodes de DMS de l'enfance, notamment due à Shigella et aux norovirus, sont souvent associés à des convulsions. L'identification rapide et la prise en charge appropriée des enfants atteints de shigellose peuvent réduire la survenue et les conséquences négatives des crises liées aux DMS.

Diarrhoeal disease and subsequent risk of death in infants and children residing in low-income and middle-income countries: analysis of the GEMS case-control study and 12-month GEMS-1A follow-on study.

BACKGROUND: The Global Enteric Multicenter Study (GEMS) was a 3-year case-control study that measured the burden, aetiology, and consequences of moderate-to-severe diarrhoea (MSD) in children aged 0-59 months. GEMS-1A, a 12-month follow-on study, comprised two parallel case-control studies, one assessing MSD and the other less-severe diarrhoea (LSD). In this report, we analyse the risk of death with each diarrhoea type and the specific pathogens associated with fatal outcomes. METHODS: GEMS was a prospective, age-stratified, matched case-control study done at seven sites in Africa and Asia. Children aged 0-59 months with MSD seeking care at sentinel health centres were recruited along with one to three randomly selected matched community control children without diarrhoea. In the 12-month GEMS-1A follow-on study, children with LSD and matched controls, in addition to children with MSD and matched controls, were recruited at six of the seven sites; only cases of MSD and controls were enrolled at the seventh site. We compared risk of death during the period between enrolment and one follow-up household visit done about 60 days later (range 50-90 days) in children with MSD and LSD and in their respective controls. Approximately 50 pathogens were detected using, as appropriate, classic bacteriology, immunoassays, gel-based PCR and reverse transcriptase PCR, and quantitative real-time PCR (qPCR). Specimens from a subset of GEMS cases and controls were also tested by a TaqMan Array Card that compartmentalised probe-based qPCR for 32 enteropathogens. FINDINGS: 223 (2·0%) of 11 108 children with MSD and 43 (0·3%) of 16 369 matched controls died between study enrolment and the follow-up visit at about 60 days (hazard ratio [HR] 8·16, 95% CI 5·69-11·68, p<0·0001). 12 (0·4%) of 2962 children with LSD and seven (0·2%) of 4074 matched controls died during the follow-up period (HR 2·78, 95% CI 0·95-8·11, p=0·061). Risk of death was lower in children with dysenteric MSD than in children with non-dysenteric MSD (HR 0·20, 95% CI 0·05-0·87, p=0·032), and lower in children with LSD than in those with non-dysenteric MSD (HR 0·29, 0·14-0·59, p=0·0006). In children younger than 24 months with MSD, infection with typical enteropathogenic Escherichia coli, enterotoxigenic E coli encoding heat-stable toxin, enteroaggregative E coli, Shigella spp (non-dysentery cases), Aeromonas spp, Cryptosporidium spp, and Entamoeba histolytica increased risk of death. Of 61 deaths in children aged 12-59 months with non-dysenteric MSD, 31 occurred among 942 children qPCR-positive for Shigella spp and 30 deaths occurred in 1384 qPCR-negative children (HR 2·2, 95% CI 1·2-3·9, p=0·0090), showing that Shigella was strongly associated with increased risk of death. INTERPRETATION: Risk of death is increased following MSD and, to a lesser extent, LSD. Considering there are approximately three times more cases of LSD than MSD in the population, more deaths are expected among children with LSD than in those with MSD. Because the major attributable LSD-associated and MSD-associated pathogens are the same, implementing vaccines and rapid diagnosis and treatment interventions against these major pathogens are rational investments. FUNDING: Bill & Melinda Gates Foundation.

Modelling the ultra-strongly coupled spin-boson model with unphysical modes.

A quantum system weakly coupled to a zero-temperature environment will relax, via spontaneous emission, to its ground-state. However, when the coupling to the environment is ultra-strong the ground-state is expected to become dressed with virtual excitations. This regime is difficult to capture with some traditional methods because of the explosion in the number of Matsubara frequencies, i.e., exponential terms in the free-bath correlation function. To access this regime we generalize both the hierarchical equations of motion and pseudomode methods, taking into account this explosion using only a biexponential fitting function. We compare these methods to the reaction coordinate mapping, which helps show how these sometimes neglected Matsubara terms are important to regulate detailed balance and prevent the unphysical emission of virtual excitations. For the pseudomode method, we present a general proof of validity for the use of superficially unphysical Matsubara-modes, which mirror the mathematical essence of the Matsubara frequencies.

Viral Pathogen-Specific Clinical and Demographic Characteristics of Children with Moderate-to-Severe Diarrhea in Rural Bangladesh.

Diarrheal disease is a leading cause of childhood morbidity and mortality worldwide, but particularly in low-income countries in sub-Saharan Africa and South Asia. The Global Enteric Multicenter Study (GEMS) examined the infectious etiologies as well as associated demographics, socioeconomic markers, health-care-seeking behaviors, and handwashing practices of the households of children with diarrhea and their age- and gender-matched controls in seven countries over a 3-year period (December 2007-December 2010). Stool studies to determine diarrheal etiologies and anthropometry were performed at baseline and at 60-day follow-up visits, along with surveys to record demographics and living conditions of the children. We performed secondary analyses of the GEMS data derived from the Bangladesh portion of the study in children with diarrhea associated with viral enteropathogens and explored pathogen-specific features of disease burden. Rotavirus and norovirus were the most prevalent pathogens (39.3% and 35%, respectively). Disease due to rotavirus and adenovirus was more common in infants than in older children (P < 0.001 and P = 0.001, respectively). Height for age decreased from baseline to follow-up in children with diarrhea associated with rotavirus, norovirus, and adenovirus (P < 0.001). Based on these analyses, preventive measures targeted at rotavirus, norovirus, and adenovirus will be expected to have meaningful clinical impact. Cost of treatment was highest for rotavirus as well, making it an obvious target for intervention. Association of specific viruses with stunting is particularly notable, as stunting is an attributable risk factor for poor cognitive development and future productivity and economic potential.

Relation of childhood diarrheal morbidity with the type of tube well used and associated factors of Shigella sonnei diarrhea in rural Bangladesh site of the Global Enteric Multicenter Study.

BACKGROUND: Diarrheal disease still remains a major public health threat and is often associated with fatal outcome especially in children with shigellosis mostly in developing countries. This study aimed to determine the presence of any associations between drinking shallow tube well (STW) water and childhood shigellosis. A total of 1394 children aged 0-59 months who presented with moderate-to-severe diarrhea (MSD) in Kumudini Women's Medical College and Hospital, Bangladesh, from December 2007 to March 2011 were enrolled into the study. RESULTS: Among the study children, STW users often represented poor families (44% vs. 37%, p = 0.010); less often had household electricity (60% vs. 68%, p = 0.001) and cemented floor material (12% vs. 21%, p < 0.001); washed hand before eating (79% vs. 84%, p = 0.020); and had Shigella sonnei infections (7.8% vs. 13.1, p = 0.002) compared to deep tube well (DTW) water families (in bivariate analysis). After adjusting for covariates, a significant negative association was observed between childhood MSD episodes due to Shigella sonnei infections and the use of STW water (aOR 0.53, 95% CI 0.36, 0.79). CONCLUSIONS: An emergence of less severe Shigella sonnei has replaced relatively more severe Shigella flexneri among the MSD children from DTW-user families. However, more monitoring in terms of disease surveillance for changes in the distribution of Shigella serogroups and serotypes and its upsurges and antimicrobial susceptibility is essential.