Seroprevalance of dengue viral infections and serotype specific t cell responses in healthy individuals in Colombo, Sri lanka

Objective: Although dengue viral infections cause dengue haemorrhagic fever and fatalities in some individuals, it is a mild /asymptomatic infection in the majority of infected individuals. Therefore, we set out to determine silent dengue transmission in the community. Methods: 236 healthy individuals aged 5-80 years recruited from community to test the presence of anti-dengue virus(DV)antibodies. Ex vivo and cultured ELISpot assays for serotype specific (SS)DV peptides, DEN3 NS3 and non-dengue viral peptides were done in 47/263 individuals. Cultured ELISpots for SS responses done in 3 individuals < 20 years, in 20 for  20-40years  age and in 24 aged >40years. Results: The seropositivity rates for DV-specific antibodies were 40%,62.5%,100% at 10,20,40 years of age respectively. A significant(p=0.001) and positive correlation observed with  age and DV- seropositivity (Spearman r =0.8365,95%CI 0.55-0.95).  SS T cell responses detected in all seropositive individuals(n=44) but absent in all dengue seronegative (n=3) individuals. SS responses seen in only 1 person of the <20 age group who responded to SS peptides of DEN-2. 3/20(25%), 6/20(40%), 3/20(25%) and 5/20(30%) of individuals between 2-40 years responded to at least one SS peptide of DEN-1, DEN-2, DEN3 and DEN-4 peptides respectively. 12/24(50%), 5/24(33%), 12/24(50%) and 6/24(25%) of individuals aged >40 years responded to at least one SS peptide of DEN-1, DEN-2, DEN-3 and DEN-4 peptides respectively. Conclusions: Seropositivity rates to the DV significantly rises with age, almost 100% at 40 years of age. The SS T cell responses to DEN-1 and DEN-3 SS peptides were more frequent aged >40 years.

Outcome of Home-Based Early Intervention for Autism in Sri Lanka: Follow-Up of a Cohort and Comparison with a Nonintervention Group

This paper presents the outcome of a home-based autism intervention program (HBAIP) in 18- to 40-month-old children newly diagnosed and treatment naïve. Intervention was exclusively implemented at home. Outcome was measured at 3 months and 6 months after intervention and compared with a group of newly diagnosed children with autism who were >40 months at intake but had not received any autism specific clinical management. Aim was also to estimate whether natural development would contribute to gain in skills and compare with the effect of intervention. Five selected parameters of behavior representing social interaction and social communication were used to assess outcome. Results showed a statistically significant improvement between preintervention and postintervention in all the measured parameters. The effect size was large when compared to preintervention and gains were indicated by changes in mean scores and p values within a narrow confidence interval. Highest gains were in first 3 months of postintervention which continued up to 6 months. Although the comparison group was more advanced in the measured skills at intake, they were significantly below the level reached by experimental group at 3 months and 6 months after intervention. This study was registered in the Sri Lanka Clinical Trials Registry (SLCTR/2009/011)

Assessment of outcome of an ADHD treatment program using parent feedback

Background Attention deficit hyperactivity disorder (ADHD) is a common behaviour disorder in children where the associated aggressive tendencies, learning difficulties and poor social skills pose a substantial burden of care on the parents. However, in traditional clinical practice, parental expectation of outcome of treatment is rarely considered. Aims This study prospectively analysed an outpatient treatment programme for children with ADHD, where parents provided feedback on the outcome of treatment. Methods Parents completed structured formats to provide information on presenting complaints, outcome at 3 months and 6 months after commencing treatment and side effects of the drug methylphenidate. Parents also attended psycho-educational and support groups. Results Of the 102 patients, parents reported a positive outcome in the majority. There was significantly better improvement in symptoms of ADHD at 6 months when compared to 3 months of treatment (p<0.005). Also, hyperactivity improved more than attention deficit and impulsiveness at the end of 6 months, though persistence of learning difficulties (50%) and disruptive behaviour were causes for dissatisfaction about treatment. The commonest side effect was poor appetite (49%), though none of the children had identifiable weight loss. Conclusions Close involvement of parents in monitoring outcome of treatment of ADHD helps to focus on aspects of care relevant to them

Enhancing immunity in viral infections, with special emphasis on COVID-19: A review

Background and aims Balanced nutrition which can help in maintaining immunity is essential for prevention and management of viral infections. While data regarding nutrition in coronavirus infection (COVID-19) are not available, in this review, we aimed to evaluate evidence from previous clinical trials that studied nutrition-based interventions for viral diseases (with special emphasis on respiratory infections), and summarise our observations.Methods A systematic search strategy was employed using keywords to search the literature in 3 key medical databases: PubMed®, Web of Science® and SciVerse Scopus®. Studies were considered eligible if they were controlled trials in humans, measuring immunological parameters, on viral and respiratory infections. Clinical trials on vitamins, minerals, nutraceuticals and probiotics were included.Results A total of 640 records were identified initially and 22 studies were included from other sources. After excluding duplicates and articles that did not meet the inclusion criteria, 43 studies were obtained (vitamins: 13; minerals: 8; nutraceuticals: 18 and probiotics: 4). Among vitamins, A and D showed a potential benefit, especially in deficient populations. Among trace elements, selenium and zinc have also shown favourable immune-modulatory effects in viral respiratory infections. Several nutraceuticals and probiotics may also have some role in enhancing immune functions. Micronutrients may be beneficial in nutritionally depleted elderly population.Conclusions We summaries possible benefits of some vitamins, trace elements, nutraceuticals and probiotics in viral infections. Nutrition principles based on these data could be useful in possible prevention and management of COVID-1

Development and validation of an assay for detection of Japanese encephalitis virus specific antibody responses.

IntroductionAlthough immune responses to the Japanese Encephalitis virus (JEV), and the dengue viruses (DENV) have a potential to modulate the immune responses to each other, this has been poorly investigated. Therefore, we developed an ELISA to identify JEV specific, DENV non cross-reactive antibody responses by identifying JEV specific, highly conserved regions of the virus and proceeded to investigate if the presence of JEV specific antibodies associate with dengue disease severity.Methodology and results22 JEV specific peptides were identified from highly conserved regions of the virus and the immunogenicity and specificity of these peptides were assessed in individuals who were non-immune to JEV and DENV (JEV-DENV-, N = 30), those who were only immune to the JEV and not DENV (JEV+DENV-, N = 30), those who were only immune to DENV(JEV-DENV+, N = 30) and in those who were immune to both viruses (JEV+DENV+, N = 30). 7/22 peptides were found to be highly immunogenic and specific and these 7 peptides were used as a pool to further evaluate JEV-specific responses. All 30/30 JEV+DENV- and 30/30 JEV+DENV+ individuals, and only 3/30 (10%) JEV-DENV+ individuals responded to this pool. We further evaluated this pool of 7 peptides in patients following primary and secondary dengue infection during the convalescent period and found that the JEV-specific peptides, were unlikely to cross react with DENV IgG antibodies. We further compared this in-house ELISA developed with the peptide pool with an existing commercial JEV IgG assay to identify JEV-specific IgG following vaccination, and our in-house ELISA was found to be more sensitive. We then proceeded to investigate if the presence of JEV-specific antibodies were associated with dengue disease severity, and we found that those who had past severe dengue (n = 175) were significantly more likely (pConclusionsAs our data show that this assay is highly sensitive and specific for detection of JEV-specific antibody responses, it would be an important tool to determine how JEV seropositivity modulate dengue immunity and disease severity when undertaking dengue vaccine trials

Urinary leukotrienes and histamine in patients with varying severity of acute dengue.

BackgroundVascular leak is a hallmark of severe dengue, and high leukotriene levels have been observed in dengue mouse models, suggesting a role in disease pathogenesis. We sought to explore their role in acute dengue, by assessing levels of urinary LTE4 and urinary histamine in patients with varying severity of acute dengue.MethodsUrinary LTE4, histamine and creatinine were measured by a quantitative ELISA, in healthy individuals (n = 19), patients with dengue fever (DF = 72) and dengue haemorrhagic fever DHF (n = 48). The kinetics of LTE4 and histamine and diurnal variations were assessed in a subset of patients.ResultsUrinary LTE4 levels were significantly higher (p = 0.004) in patients who proceed to develop DHF when compared to patients with DF during early illness (≤ 4 days) and during the critical phase (p = 0.02), which continued to rise in patients who developed DHF during the course of illness. However, LTE4 is unlikely to be a good biomarker as ROCs gave an AUC value of 0.67 (95% CI 0.57 and 0.76), which was nevertheless significant (p = 0.002). Urinary LTE4 levels did not associate with the degree of viraemia, infecting virus serotype and was not different in those with primary vs secondary dengue. Urinary histamine levels were significantly high in patients with acute dengue although no difference was observed between patients with DF and DHF and again did not associate with the viraemia. Interestingly, LTE4, histamine and the viral loads showed a marked diurnal variation in both patients with DF and DHF.ConclusionsOur data suggest that LTE4 could play a role in disease pathogenesis and since there are safe and effective cysteinyl leukotriene receptor blockers, it would be important to assess their efficacy in reducing dengue disease severity

Predicted conformational epitopes of C protein.

<p>Predicted conformational epitopes of C protein.</p