ResearchPad - pediatric-infections https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Successful improvement of antibiotic prescribing at Primary Care in Andalusia following the implementation of an antimicrobial guide through multifaceted interventions: An interrupted time-series analysis]]> https://www.researchpad.co/article/elastic_article_14725 Most effective strategies designed to improve antimicrobial prescribing have multiple approaches. We assessed the impact of the implementation of a rigorous antimicrobial guide and subsequent multifaceted interventions aimed at improving antimicrobial use in Primary Care.MethodsA quasi-experimental study was designed. Interventions aimed at achieving a good implementation of the guide consisted of the development of electronic decision support tools, local training meetings, regional workshops, conferences, targets for rates of antibiotic prescribing linked to financial incentives, feedback on antibiotic prescribing, and the implementation of a structured educational antimicrobial stewardship program. Interventions started in 2011, and continued until 2018. Outcomes: rates of antibiotics use, calculated into defined daily doses per 1,000 inhabitants-day (DID). An interrupted time-series analysis was conducted. The study ran from January 2004 until December 2018.ResultsOverall annual antibiotic prescribing rates showed increasing trends in the pre-intervention period. Interventions were followed by significant changes on trends with a decline over time in antibiotic prescribing. Overall antibiotic rates dropped by 28% in the Aljarafe Area and 22% in Andalusia between 2011 and 2018, at rates of -0.90 DID per year (95%CI:-1.05 to -0.75) in Aljarafe, and -0.78 DID (95%CI:-0.95 to -0.60) in Andalusia. Reductions occurred at the expense of the strong decline of penicillins use (33% in Aljarafe, 25% in Andalusia), and more precisely, amoxicillin clavulanate, whose prescription plummeted by around 50%. Quinolones rates decreased before interventions, and continued to decline following interventions with more pronounced downward trends. Decreasing cephalosporins trends continued to decline, at a lesser extent, following interventions in Andalusia. Trends of macrolides rates went from a downward trend to an upward trend from 2011 to 2018.ConclusionsMultifaceted interventions following the delivering of a rigorous antimicrobial guide, maintained in long-term, with strong institutional support, could led to sustained reductions in antibiotic prescribing in Primary Care. ]]> <![CDATA[Safety of tunneled central venous catheters in pediatric hematopoietic stem cell recipients with severe primary immunodeficiency diseases]]> https://www.researchpad.co/article/elastic_article_14693 Tunneled central venous catheters (TCVCs) provide prolonged intravenous access for pediatric patients with severe primary immunodeficiency disease (PID) undergoing hematopoietic stem cell transplantation (HSCT). However, little is known about the epidemiology and clinical significance of TCVC-related morbidity in this particular patient group. We conducted the retrospective analysis of patients with severe PID who received percutaneous landmark-guided TCVC implantation prior to HSCT. We analyzed 92 consecutive TCVC implantations in 69 patients (median [interquartile range] age 3.0 [0–11] years) with severe combined immune deficiency (n = 39, 42.4%), chronic granulomatous disease (n = 17, 18.4%), and other rare PID syndromes (n = 36, 39.2%). The median length of TCVC observation was 144.1 (85.5–194.6) days with a total of 14,040 catheter days at risk (cdr). The overall rate of adverse events during catheter insertion was 17.4% (n = 16) and 25.0% during catheter dwell period (n = 23, catheter risk [CR] per 1000 cdr = 1.64). The most common complication was TCVC-related infection with an overall prevalence of 9.8% (n = 9, CR = 0.64), followed by late dislocation (n = 6, 6.5%, CR = 0.43), early dislocation (n = 4, 4.3%) and catheter dysfunction (n = 4, 4.3%, CR = 0.28). TCVCs are safe in children with severe PID undergoing HSCT with relatively low rates of TCVC-related infection.

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<![CDATA[Risk of infection in the first year of life in preterm children: An Austrian observational study]]> https://www.researchpad.co/article/Ne8c917d2-c06e-4527-bc81-08b9487488ae

Newborns, especially preterm infants, have an immature immune system, which, in combination with the required medical interventions necessary for keeping the neonate alive may lead to an increased risk of infection. Even after reaching stability and adapting to the environment, preterm infants have adverse prognoses regarding infections and long-term outcomes compared to their full-term counterparts. The objective of this study was to research differences in the number and severity of infections between preterm and full-term infants during their first year of life. To answer this question, a monocentric prospective study was conducted in a pediatric practice in Vienna, including 71 full-term infants and 72 preterm infants who were observed during their first year of life regarding occurring infections. In respective samples, there was a significantly higher total number of infections in preterm (mean 6.01 ± 3.90) compared to full-term infants (3.85 ± 1.72) during the observation period of one year. Particularly the count of respiratory and severe infections was considerably higher in preterm infants. Otorhinolaryngeal infections were the most frequent of all types of infections in both groups. The pregnancy period, number of siblings, and length of the postnatal hospital stay, were observed as significantly influencing factors which affected the total number of infections. The group of early term infants (37+0 weeks to 38+6) was not significantly different to late term babies (>39+0). The acquired knowledge about the increased risk of infections should lead to a more extensive care for preterm infants, with the objective of reducing the rates of complications, morbidity and mortality in this vulnerable age group in the future.

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<![CDATA[Resolving "worm wars": An extended comparison review of findings from key economics and epidemiological studies]]> https://www.researchpad.co/article/5c8acc2bd5eed0c48498f08c ]]> <![CDATA[Acute rhinosinusitis among pediatric patients with allergic rhinitis: A nationwide, population-based cohort study]]> https://www.researchpad.co/article/5c6c75e2d5eed0c4843d03bf

Background

While chronic rhinosinusitis is a common complication of allergic rhinitis, the link between acute rhinosinusitis and allergic rhinitis is unclear. The aim of this study was to evaluate the risk of incident acute rhinosinusitis among pediatric patients with allergic rhinitis, using a nationwide, population-based health claims research database.

Methods

Newly diagnosed allergic rhinitis patients aged 5–18 years were identified from the health claim records of the Longitudinal Health Insurance Database 2000 of Taiwan’s National Health Insurance Research Database. A comparison cohort was assembled by randomly selecting patients from the same database with frequency matching by sex, age group, and index year. All patients were followed until a diagnosis of acute rhinosinusitis or the end of the follow-up period. Cox proportional hazards model was used to assess the association between allergic rhinitis and acute rhinosinusitis.

Results

Of the 43,588 pediatric patients included in this study, 55.4% were male and 43.9% were between the ages of 5.0–7.9 years. The risk of acute rhinosinusitis was significantly higher in pediatric patients with allergic rhinitis compared to those without the condition (adjusted hazard ratio = 3.03, 95% confidence interval = 2.89–3.18). Similar hazard ratios were observed between male and female pediatric patients.

Conclusions

This secondary cohort study using a nationwide, population-based health claim data of the Taiwan’s NHIRD showed that allergic rhinitis was significantly associated with a higher risk of acute rhinosinusitis among pediatric patients.

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<![CDATA[EBV miRNA expression profiles in different infection stages: A prospective cohort study]]> https://www.researchpad.co/article/5c6dc9c8d5eed0c48452a18f

The Epstein-Barr virus (EBV) produces different microRNAs (miRNA) with distinct regulatory functions within the infectious cycle. These viral miRNAs regulate the expression of viral and host genes and have been discussed as potential diagnostic markers or even therapeutic targets, provided that the expression profile can be unambiguously correlated to a specific stage of infection or a specific EBV-induced disorder. In this context, miRNA profiling becomes more important since the roles of these miRNAs in the pathogenesis of infections and malignancies are not fully understood. Studies of EBV miRNA expression profiles are sparse and have mainly focused on associated malignancies. This study is the first to examine the miRNA profiles of EBV reactivation and to use a correction step with seronegative patients as a reference. Between 2012 and 2017, we examined the expression profiles of 11 selected EBV miRNAs in 129 whole blood samples from primary infection, reactivation, healthy carriers and EBV seronegative patients. Three of the miRNAs could not be detected in any sample. Other miRNAs showed significantly higher expression levels and prevalence during primary infection than in other stages; miR-BHRF1-1 was the most abundant. The expression profiles from reactivation differed slightly but not significantly from those of healthy carriers, but a specific marker miRNA for each stage could not be identified within the selected EBV miRNA targets.

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<![CDATA[Carriage and colonization of C. difficile in preterm neonates: A longitudinal prospective study]]> https://www.researchpad.co/article/5c76fe0ed5eed0c484e5b398

Background

Premature neonates (PN) present multiple risk factors for high frequencies and high levels of colonization by C. difficile, yet data is missing about this specific pediatric population. Here, we investigated PN C. difficile carriage and colonization dynamics, analyzed the impact of perinatal determinants on colonization, and characterized the isolates.

Methods

A one year longitudinal monocentric prospective cohort study was performed on 121 PN. C. difficile strains isolated from fecal samples on selective medium were identified and characterized by PCR (tpi housekeeping gene; tcdA and tcdB, and binary toxin genes), capillary gel-based electrophoresis PCR-ribotyping, and Multi-Locus Variable-number tandem-repeat Analysis (MLVA).

Results

Of the 379 samples analyzed, 199 (52%) were C. difficile culture positive with the mean levels of C. difficile colonization decreasing significantly (P = .027) over time. During hospitalization, C. difficile colonization frequency increased up to 61% with 95% of the strains belonging to both non-toxigenic PCR-ribotypes (RTs) FR082 (35%) and 032 (60%). After hospital discharge, if a higher diversity in RTs was observed, RTs FR082 and 032 remained predominant (respectively 40% and 28%). MLVA showed clonal relationship within each FR082 and 032 RTs. Ten toxigenic strains (5%) were isolated, all tcdA+/tcdB+ except for one tcdA-/tcdB+, and all being acquired after hospitalization. At 1 week, the only factors found to be linked with a higher frequency of C. difficile colonization were a higher gestational age (P = 0.006) and a higher birth weight (P = 0.016).

Conclusion

The dynamics of C. difficile colonization in PN followed a specific pattern. C. difficile colonization rapidly occurred after birth with a low diversity of non-toxigenic RTs. After hospitalization, non-toxigenic RTs diversity increased. Sporadic carriage of toxigenic strains was observed after hospitalization.

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<![CDATA[Determining predictors of sepsis at triage among children under 5 years of age in resource-limited settings: A modified Delphi process]]> https://www.researchpad.co/article/5c58d642d5eed0c4840319de

Sepsis is a life-threatening dysfunction of the immune system leading to multiorgan failure that is precipitated by infectious diseases and is a leading cause of death in children under 5 years of age. It is necessary to be able to identify a sick child at risk of developing sepsis at the earliest point of presentation to a healthcare facility so that appropriate care can be provided as soon as possible. Our study objective was to generate a list of consensus-driven predictor variables for the derivation of a prediction model that will be incorporated into a mobile device and operated by low-skilled healthcare workers at triage. By conducting a systematic literature review and examination of global guideline documents, a list of 72 initial candidate predictor variables was generated. A two-round modified Delphi process involving 26 experts from both resource-rich and resource-limited settings, who were also encouraged to suggest new variables, yielded a final list of 45 predictor variables after evaluating each variable based on three domains: predictive potential, measurement reliability, and level of training and resources required. The final list of predictor variables will be used to collect data and contribute to the derivation of a prediction model.

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<![CDATA[Prior dengue virus infection and risk of Zika: A pediatric cohort in Nicaragua]]> https://www.researchpad.co/article/5c50c4a2d5eed0c4845e8aa4

Background

Zika virus (ZIKV) emerged in northeast Brazil in 2015 and spread rapidly across the Americas, in populations that have been largely exposed to dengue virus (DENV). The impact of prior DENV infection on ZIKV infection outcome remains unclear. To study this potential impact, we analyzed the large 2016 Zika epidemic in Managua, Nicaragua, in a pediatric cohort with well-characterized DENV infection histories.

Methods and findings

Symptomatic ZIKV infections (Zika cases) were identified by real-time reverse transcription PCR and serology in a community-based cohort study that follows approximately 3,700 children aged 2–14 years old. Annual blood samples were used to identify clinically inapparent ZIKV infections using a novel, well-characterized serological assay. Multivariable Poisson regression was used to examine the relation between prior DENV infection and incidence of symptomatic and inapparent ZIKV infection. The generalized-growth method was used to estimate the effective reproduction number. From January 1, 2016, to February 28, 2017, 560 symptomatic ZIKV infections and 1,356 total ZIKV infections (symptomatic and inapparent) were identified, for an overall incidence of 14.0 symptomatic infections (95% CI: 12.9, 15.2) and 36.5 total infections (95% CI: 34.7, 38.6) per 100 person-years. Effective reproduction number estimates ranged from 3.3 to 3.4, depending on the ascending wave period. Incidence of symptomatic and total ZIKV infections was higher in females and older children. Analysis of the effect of prior DENV infection was performed on 3,027 participants with documented DENV infection histories, of which 743 (24.5%) had experienced at least 1 prior DENV infection during cohort follow-up. Prior DENV infection was inversely associated with risk of symptomatic ZIKV infection in the total cohort population (incidence rate ratio [IRR]: 0.63; 95% CI: 0.48, 0.81; p < 0.005) and with risk of symptomatic presentation given ZIKV infection (IRR: 0.62; 95% CI: 0.44, 0.86) when adjusted for age, sex, and recent DENV infection (1–2 years before ZIKV infection). Recent DENV infection was significantly associated with decreased risk of symptomatic ZIKV infection when adjusted for age and sex, but not when adjusted for prior DENV infection. Prior or recent DENV infection did not affect the rate of total ZIKV infections. Our findings are limited to a pediatric population and constrained by the epidemiology of the site.

Conclusions

These findings support that prior DENV infection may protect individuals from symptomatic Zika. More research is needed to address the possible immunological mechanism(s) of cross-protection between ZIKV and DENV and whether DENV immunity also modulates other ZIKV infection outcomes such as neurological or congenital syndromes.

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<![CDATA[Regional variations in serotype distribution and vaccination status in children under six years of age with invasive pneumococcal disease in Germany]]> https://www.researchpad.co/article/5c3fa564d5eed0c484ca3c8d

Overview

The protective effect of infant pneumococcal conjugate vaccine (PCV) recommendation can be seen in Germany as a whole and in smaller regional groups. Comparisons between population-normalized geographic regions of Germany show different serotype distributions after program implementation, particularly in non-vaccine serotypes. The prior distinct differences in serotype distribution in children between the former East and former West German federal states have vanished. Children under six remain a vulnerable group, but the occurrence of vaccine-type (VT) invasive pneumococcal disease (IPD) in children correctly vaccinated (using a three-dose primary series plus one booster dose) with PCV13 was low (9 out of 374 cases, 2.4%). However, only 18.4% of children in Germany with IPD were correctly vaccinated with PCV13 according to the recommended schedule. Continued surveillance and better schedule adherence are essential to definitively establish the most effective PCV administration schedule.

Vaccination effects

For all PCV products used in Germany (PCV7, PCV10, and PCV13), vaccination status was the most common statistically significant predictor of infection with a particular serotype: Unvaccinated children old enough to have received at least one dose of vaccine in the PCV7 group had significantly higher odds (OR: 6.84, 95%CI: 2.66–22.06, adjusted for per capita income and residence in the northeastern federal states) of contracting VT IPD. In the PCV10 group, VT IPD had an OR of 4.52 (95% CI: 1.60–15.62, adjusted for year of infection, median household size, and residence in the southern federal states) in unvaccinated children, and in the PCV13 group, unvaccinated children continued to have higher odds (OR: 6.21, 95%CI: 3.45–11.36, adjusted for year of infection, age of child, per capita income, residence in the southern federal states, and percentage of children using public daycare) of getting vaccine-type IPD. Being unvaccinated was the most frequent significant indicator for infection with vaccine-type serotypes for each analysis group, while geographic groupings showed more limited potential to predict serotype of infection in early childhood IPD in Germany.

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<![CDATA[Impact of glucose-6-phosphate dehydrogenase deficiency on dengue infection in Myanmar children]]> https://www.researchpad.co/article/5c3667d8d5eed0c4841a666f

Glucose-6-phosphate dehydrogenase (G6PD) deficiency may affect the clinical presentation of dengue due to the altered redox state in immune cells. We aimed to determine the association between G6PD deficiency and severity of dengue infection in paediatric patients in Myanmar. A cross-sectional study was conducted among paediatric patients aged 2–13 years with dengue in Yankin Children Hospital, Myanmar. One hundred and ninety-six patients positive for dengue infection, as determined via PCR or ELISA, were enrolled. Dengue severity was determined according to the 2009 WHO classification guidelines. Spectrophotometric assays determined G6PD levels. The adjusted median G6PD value of males in the study population was used to define various cut-off points according to the WHO classification guidelines. G6PD genotyping for Mahidol, Kaiping and Mediterranean mutations was performed for 128 out of 196 samples by real-time multiplex PCR. 51 of 196 (26.0%) patients had severe dengue. The prevalence of G6PD phenotype deficiency (< 60% activity) in paediatric patients was 14.8% (29/196), specifically, 13.6% (14/103) in males and 16.2% (15/93) in females. Severe deficiency (< 10% activity) accounted for 7.1% (14/196) of our cohort, occurring 11.7% (12/103) in males and 2.2% (2/93) in females. Among 128 samples genotyped, the G6PD gene mutations were detected in 19.5% (25/128) of patients, with 20.3% (13/ 64) in males and 18.8% (12/64) in females. The G6PD Mahidol mutation was 96.0% (24/25) while the G6PD Kaiping mutation was 4.0% (1/25). Severe dengue was not associated with G6PD enzyme deficiency or presence of the G6PD gene mutation. Thus, no association between G6PD deficiency and dengue severity could be detected.

Trial registration: The study was registered following the WHO International Clinical Trials Registry Platform (WHO-ICTRP) on Thai Clinical Trials Registry (TCTR) website, registration number # TCTR20180720001

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<![CDATA[Iron chelating properties of Eltrombopag: Investigating its role in thalassemia-induced osteoporosis]]> https://www.researchpad.co/article/5c0ed779d5eed0c484f141f9

Chronic blood transfusions are responsible to cause iron overload, which leads to several complications to end organs and osteoporosis. Iron chelation is needed to remove iron excess and to contain bone-mass loss. Deferasirox is the most recent oral iron chelator that prevents transfusion related iron overload complications. Recently Eltrombopag (ELT) iron chelating properties are emerging. ELT is an agonist at Thrombopoietin receptor, used in treatment of thrombocytopenia. We tested ELT and Deferasirox in iron overloaded osteoclasts from thalassemic patients and donors measuring intracellular iron, TRAP expression and osteoclast activity. We confirmed ELT iron chelation capacity also in bone tissue and a synergic effect when used with Deferasirox. Moreover, having demonstrated its effects on osteoclast activity, we suggest for the first time that ELT could ameliorate bone tissue’s health reducing bone mass loss.

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<![CDATA[A pragmatic cluster randomised controlled trial of a tailored intervention to improve the initial management of suspected encephalitis]]> https://www.researchpad.co/article/5c12cf55d5eed0c4849143d0

Objective

To determine whether a tailored multifaceted implementation strategy improves the initial management of patients with suspected encephalitis.

Design

Pragmatic two arm cluster randomised controlled trial.

Setting

Hospitals within the United Kingdom.

Participants

Twenty-four hospitals nested within 12 postgraduate deaneries. Patients were identified retrospectively by searching discharge, microbiology, radiology and pharmacy records and included if they met clinical criteria or had a recorded suspicion of encephalitis.

Intervention

An implementation strategy designed to overcome barriers to change, comprising local action planning, education and training, feedback on performance, a lumbar puncture pack and a range of optional components.

Outcomes

The primary outcome was the proportion of patients with suspected encephalitis undergoing diagnostic lumbar puncture within 12 hours of admission and starting aciclovir treatment within six hours. Secondary outcomes included the proportions of adults and children who had a lumbar puncture, who had appropriate cerebrospinal fluid investigations, and who had appropriate radiological imaging within 24 hours of admission. Data were collected from patient records for 12 months before and 12 months during the intervention period, and analysed blind to allocation.

Results

13 hospitals were randomised to intervention and 11 to control (no intervention), with 266 and 223 patients with suspected encephalitis identified respectively. There was no significant difference in primary outcome between intervention and control hospitals (13.5% and 14.8% respectively, p = 0.619; treatment effect -0.188, 95% confidence interval -0.927 to 0.552), but both had improved compared to pre-intervention (8.5%).

Conclusion

The improvement in both intervention and control arms may reflect overall progress in management of encephalitis through wider awareness and education.

Trial registration

Controlled Trials: ISRCTN06886935.

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<![CDATA[Using risk adjustment to improve the interpretation of global inpatient pediatric antibiotic prescribing]]> https://www.researchpad.co/article/5b4a287d463d7e4513b897f7

Objectives

Assessment of regional pediatric last-resort antibiotic utilization patterns is hampered by potential confounding from population differences. We developed a risk-adjustment model from readily available, internationally used survey data and a simple patient classification to aid such comparisons.

Design

We investigated the association between pediatric conserve antibiotic (pCA) exposure and patient / treatment characteristics derived from global point prevalence surveys of antibiotic prescribing, and developed a risk-adjustment model using multivariable logistic regression. The performance of a simple patient classification of groups with different expected pCA exposure levels was compared to the risk model.

Setting

226 centers in 41 countries across 5 continents.

Participants

Neonatal and pediatric inpatient antibiotic prescriptions for sepsis/bloodstream infection for 1281 patients.

Results

Overall pCA exposure was high (35%), strongly associated with each variable (patient age, ward, underlying disease, community acquisition or nosocomial infection and empiric or targeted treatment), and all were included in the final risk-adjustment model. The model demonstrated good discrimination (c-statistic = 0.83) and calibration (p = 0.38). The simple classification model demonstrated similar discrimination and calibration to the risk model. The crude regional pCA exposure rates ranged from 10.3% (Africa) to 67.4% (Latin America). Risk adjustment substantially reduced the regional variation, the adjusted rates ranging from 17.1% (Africa) to 42.8% (Latin America).

Conclusions

Greater comparability of pCA exposure rates can be achieved by using a few easily collected variables to produce risk-adjusted rates.

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<![CDATA[Scabies and impetigo in Timor-Leste: A school screening study in two districts]]> https://www.researchpad.co/article/5b28b391463d7e126303d2a8

Introduction

Scabies and impetigo are common and important skin conditions which are often neglected in developing countries. Limited data have been published on the prevalence of scabies and impetigo in Timor-Leste. Sequelae including cellulitis, bacteraemia, nephritis, acute rheumatic fever and rheumatic heart disease contribute significantly to the burden of disease.

Methods

School students were recruited from schools in Dili (urban) and Ermera (rural) in Timor-Leste for an epidemiological study in October 2016. A standard questionnaire was used to record demographics, anthropometry and skin examination results. Impetigo and scabies were diagnosed based on clinical examination of exposed surfaces, and clinical photographs were reviewed for correlation by an infectious diseases paediatrician. Prevalence of scabies and impetigo were calculated and binary risk factor associations were described using relative risks and 95% confidence intervals. Adjusted odds ratios were calculated using logistic regression multivariate analysis. Continuous variables were analysed for associations using the Mann-Whitney Rank Sum test.

Results

The study enrolled 1396 students; median age 11 years (interquartile range (IQR) 9–15). The prevalence of scabies was 22.4% (95% CI 20.2–24.7%) and active impetigo 9.7% (95% CI 8.3–11.4%); 68.2% of students had evidence of either active or healed impetigo. Students in Ermera were more likely than those in Dili to have scabies (prevalence 32.0% vs 5.2%, aOR 8.1 (95% CI 5.2–12.4), p<0.01). There was no difference in the prevalence of active impetigo between urban and rural sites. More than a third of participants were moderately or severely underweight. Stunting was markedly more common in the rural district of Ermera.

Conclusion

Scabies and impetigo are common in Timor-Leste, with very high prevalence of scabies in the rural district of Ermera. Improvements in prevention and treatment are needed, with prioritised activities in the rural areas where prevalence is highest.

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<![CDATA[Post-Discharge Mortality in Children with Severe Malnutrition and Pneumonia in Bangladesh]]> https://www.researchpad.co/article/5989da95ab0ee8fa60ba191e

Background

Post-discharge mortality among children with severe illness in resource-limited settings is under-recognized and there are limited data. We evaluated post-discharge mortality in a recently reported cohort of children with severe malnutrition and pneumonia, and identified characteristics associated with an increased risk of death.

Methods

Young children (<5 years of age) with severe malnutrition (WHO criteria) and radiographic pneumonia on admission to Dhaka Hospital of icddr,b over a 15-month period were managed according to standard protocols. Those discharged were followed-up and survival status at 12 weeks post-discharge was determined. Verbal autopsy was requested from families of those that died.

Results

Of 405 children hospitalized with severe malnutrition and pneumonia, 369 (median age, 10 months) were discharged alive with a follow-up plan. Of these, 32 (8.7%) died in the community within 3 months of discharge: median 22 (IQR 9–35) days from discharge to death. Most deaths were reportedly associated with acute onset of new respiratory or gastrointestinal symptoms. Those that died following discharge were significantly younger (median 6 [IQR 3,12] months) and more severely malnourished, on admission and on discharge, than those that survived. Bivariate analysis found that severe wasting on admission (OR 3.64, 95% CI 1.66–7.97) and age <12 months (OR 2.54, 95% CI 1.1–8.8) were significantly associated with post-discharge death. Of those that died in the community, none had attended a scheduled follow-up and care-seeking from a traditional healer was more common (p<0.001) compared to those who survived.

Conclusion and Significance

Post-discharge mortality was common in Bangladeshi children following inpatient care for severe malnutrition and pneumonia. The underlying contributing factors require a better understanding to inform the potential of interventions that could improve survival.

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<![CDATA[Dissecting the human serum antibody response to secondary dengue virus infections]]> https://www.researchpad.co/article/5989db5cab0ee8fa60be0171

Dengue viruses (DENVs) are mosquito-borne flaviviruses and the causative agents of dengue fever and dengue hemorrhagic fever. As there are four serotypes of DENV (DENV1-4), people can be infected multiple times, each time with a new serotype. Primary infections stimulate antibodies that mainly neutralize the serotype of infection (type-specific), whereas secondary infections stimulate responses that cross-neutralize 2 or more serotypes. Previous studies have demonstrated that neutralizing antibodies induced by primary infections recognize tertiary and quaternary structure epitopes on the viral envelope (E) protein that are unique to each serotype. The goal of the current study was to determine the properties of neutralizing antibodies induced after secondary infection with a different (heterotypic) DENV serotypes. We evaluated whether polyclonal neutralizing antibody responses after secondary infections consist of distinct populations of type-specific antibodies to each serotype encountered or a new population of broadly cross-neutralizing antibodies. We observed two types of responses: in some individuals exposed to secondary infections, DENV neutralization was dominated by cross-reactive antibodies, whereas in other individuals both type-specific and cross-reactive antibodies contributed to neutralization. To better understand the origins of type-specific and cross-reactive neutralizing antibodies, we analyzed sera from individuals with well-documented sequential infections with two DENV serotypes only. These individuals had both type-specific and cross-reactive neutralizing antibodies to the 2 serotypes responsible for infection and only cross-reactive neutralizing antibodies to other serotypes. Collectively, the results demonstrate that the quality of neutralizing (and presumably protective) antibodies are different in individuals depending on the number of previous exposures to different DENV serotypes. We propose a model in which low affinity, cross-reactive antibody secreting B-cell clones induced by primary exposure evolve during each secondary infection to secrete higher affinity and more broadly neutralizing antibodies.

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<![CDATA[Standardising and Assessing Digital Images for Use in Clinical Trials: A Practical, Reproducible Method That Blinds the Assessor to Treatment Allocation]]> https://www.researchpad.co/article/5989d9feab0ee8fa60b731fa

With the increasing availability of high quality digital cameras that are easily operated by the non-professional photographer, the utility of using digital images to assess endpoints in clinical research of skin lesions has growing acceptance. However, rigorous protocols and description of experiences for digital image collection and assessment are not readily available, particularly for research conducted in remote settings. We describe the development and evaluation of a protocol for digital image collection by the non-professional photographer in a remote setting research trial, together with a novel methodology for assessment of clinical outcomes by an expert panel blinded to treatment allocation.

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<![CDATA[Physicians, Primary Caregivers and Topical Repellent: All Under-Utilised Resources in Stopping Dengue Virus Transmission in Affected Households]]> https://www.researchpad.co/article/5989daffab0ee8fa60bc6155

Background

Primary health care facilities frequently manage dengue cases on an ambulatory basis for the duration of the patient’s illness. There is a great opportunity for specific messaging, aimed to reduce dengue virus (DENV) transmission in and around the home, to be directly targeted toward this high-risk ambulatory patient group, as part of an integrated approach to dengue management. The extent however, to which physicians understand, and can themselves effectively communicate strategies to stop focal DENV transmission around an ambulatory dengue case is unknown; the matter of patient comprehension and recollection then ensues. In addition, the effectiveness of N,N-diethyl-3-methylbenzamide (DEET)-based insect repellent in protecting dengue patients from Aedes aegypti mosquitoes’ bites has not been investigated.

Methodology

A knowledge, attitude and practice (KAP) survey, focusing on the mechanisms of DENV transmission and prevention, was performed using semi-structured questionnaires. This survey was targeted towards the patients and family members providing supportive care, and physicians routinely involved in dengue patient management in Southern Vietnam. An additional clinical observational study was conducted to measure the efficacy of a widely-used 13% DEET-based insect repellent to repel Ae. aegypti mosquitoes from the forearms of dengue cases and matched healthy controls.

Principal Findings

Among both the physician (n = 50) and patient (n = 49) groups there were several respondents lacking a coherent understanding of DENV transmission, leading to some inappropriate attitudes and inadequate acute preventive practices in the household. The application of insect repellent to protect patients and their relatives from mosquito bites was frequently recommended by majority of physicians (78%) participating in the survey. Nevertheless, our tested topical application of 13% DEET conferred only ~1hr median protection time from Ae. aegypti landing. This is notably shorter than that advertised on the manufacturer’s label. No differences in landing time between febrile dengue cases or matched healthy controls (n = 19 experiments) were observed.

Conclusion/Significance

Our study identifies missed opportunities for primary care physicians to improve public health through communication of strategies that could prevent focal dengue transmission in and around a case household. We advocate better access to more efficient communication methods for physicians and auxilliary health workers, supporting to educate those at high risk of DENV transmission. Our empirical testing of a widely-available 13% DEET-based repellent was limited in its protective efficacy against Ae. aegypti mosquito bites, and therefore DENV transmission, suggesting more frequent application is necessary to be beneficial.

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<![CDATA[A novel recombinant variant of latent membrane protein 1 from Epstein Barr virus in Argentina denotes phylogeographical association]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdc0d8

Epstein Barr virus (EBV) infection in Argentina occurs at an early age and occasionally develops infectious mononucleosis (IM). EBV is also related with lymphomas. LMP1, the viral oncoprotein is polymorphic and is used to define viral variants.

Aim

To study LMP1 variants distribution among children with EBV+ malignant and benign conditions as well as in healthy carriers.

Methods

Oral secretions and blood cells from 31 children with IM, and biopsies from 14 EBV+ reactive lymphoid hyperplasia and 33 EBV+ lymphomas were included. LMP1 was amplified by nested PCR and sequenced. Phylogenetic reconstructions were made under Maximun Likelihood, Bayesian and coalescent algorithms.

Results

Six clades were defined (China1, China2, Med-, Alaskan, B95.8 and Argentine). Argentine variants, the most prevalent (46%), harbored 3 distinctive mutations and were a recombination between Raji and China1. Despite no pathology or compartment associations were observed for LMP1, the Argentine clade showed a phylogeographic association with our region. LMP1 estimated evolution rate was 8.591x10-5s/s/y and the estimated tMRCA for Raji and Argentine was 136ybp.

Conclusions

An LMP1 Argentine clade was defined. LMP1 evolutionary rate was higher than expected for herpesviruses. The tMRCA for Raji and the Argentine agrees with African immigration and could explain the recombinant nature of the Argentine variant.

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