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.

Validation of serum cytokines as potential biomarkers in acute dengue infection

Objectives: Serum IL-10, Macrophage inhibitory factor (MIF) and interferons have been found to be associated with fatal dengue. We set out to investigate the possibility of using these cytokine as biomarkers to predict severe dengue. Methods: Serum IL-10 levels were determined by quantitative ELISA in 215 adult patients with confirmed acute dengue infection (ADI). Serum IFNα and IFNγ levels were done in 79 patients. Serial recording of clinical features and laboratory investigations were done to determine clinical disease severity. Results: 33 (17.46%) patients were classified as severe dengue (SD). Serum IL-10 levels were significantly higher (p=0.0034) in patients with SD (median= 121.9, range= 24.98 to 3271 pg/ml) when compared to those with non SD (median= 78.28, range= 7.18 to 1343 pg/ml). In the 29 patients with paired serum samples, serum IL-10 levels rose in all 6 patients with SD whereas in 20/23 patients with non SD, serum IL-10 levels fell in the critical phase.  Although serum MIF values were higher in patients with SD (mean 70774, SD± 59874 pg/ml) when compared to those with non SD (mean 45362, SD± 26891 pg/ml), this was not statistically significant. The IFNγ levels were significantly higher (p=0.038) in patients with shock (median= 77.55, range= 18.21 to 468.4 pg/ml) when compared to those who did not develop shock (median= 35.25, range= 4.050 to 733.1 pg/ml). Conclusion: Serum IL-10 levels appear to be associated with SD. It would be crucial to investigate the possible role of this cytokine in the pathogenesis of SD

The impact of the demographic transition on dengue in Thailand: Insights from a statistical analysis and mathematical modeling

Background: An increase in the average age of dengue hemorrhagic fever (DHF) cases has been reported in Thailand. The cause of this increase is not known. Possible explanations include a reduction in transmission due to declining mosquito populations, declining contact between human and mosquito, and changes in reporting. We propose that a demographic shift toward lower birth and death rates has reduced dengue transmission and lengthened the interval between large epidemics. Methods and Findings: Using data from each of the 72 provinces of Thailand, we looked for associations between force of infection (a measure of hazard, defined as the rate per capita at which susceptible individuals become infected) and demographic and climactic variables. We estimated the force of infection from the age distribution of cases from 1985 to 2005. We find that the force of infection has declined by 2% each year since a peak in the late 1970s and early 1980s. Contrary to recent findings suggesting that the incidence of DHF has increased in Thailand, we find a small but statistically significant decline in DHF incidence since 1985 in a majority of provinces. The strongest predictor of the change in force of infection and the mean force of infection is the median age of the population. Using mathematical simulations of dengue transmission we show that a reduced birth rate and a shift in the population's age structure can explain the shift in the age distribution of cases, reduction of the force of infection, and increase in the periodicity of multiannual oscillations of DHF incidence in the absence of other changes. Conclusions: Lower birth and death rates decrease the flow of susceptible individuals into the population and increase the longevity of immune individuals. The increase in the proportion of the population that is immune increases the likelihood that an infectious mosquito will feed on an immune individual, reducing the force of infection. Though the force of infection has decreased by half, we find that the critical vaccination fraction has not changed significantly, declining from an average of 85% to 80%. Clinical guidelines should consider the impact of continued increases in the age of dengue cases in Thailand. Countries in the region lagging behind Thailand in the demographic transition may experience the same increase as their population ages. The impact of demographic changes on the force of infection has been hypothesized for other diseases, but, to our knowledge, this is the first observation of this phenomenon

HLA Class I and Class II Associations in Dengue Viral Infections in a Sri Lankan Population

BACKGROUND: HLA class I and class II alleles have been shown to be associated with the development of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) in different populations. However, the majority of studies have been based on limited numbers of patients. In this study we aimed to investigate the HLA-class I and class II alleles that are positively and negatively associated with the development of DSS in a cohort of patients with DHF and also the alleles associated with development of DHF during primary dengue infections in a Sri Lankan population. METHODOLOGY/PRINCIPAL FINDINGS: The allele frequencies of HLA class I and class II alleles were compared in 110 patients with DHF and 119 individuals from the population who had never reported a symptomatic dengue infection at the time of recruitment. We found that HLA-A*31 (corrected P = 0.01) and DRB1*08 (corrected P = 0.009) were associated with susceptibility to DSS when infected with the dengue virus, during secondary dengue infection. The frequency of DRB1*08 allele was 28.7 times higher than in the normal population in patients with DSS. HLA-A*31 allele was increased 16.6 fold in DHF who developed shock when compared to those who did not develop shock. A*24 (corrected P = 0.03) and DRB1*12 (corrected P = 0.041) were strongly associated with the development of DHF during primary dengue infection. CONCLUSIONS/SIGNIFICANCE: These data suggest that certain HLA alleles confer susceptibility/protection to severe dengue infections. As T cell epitope recognition depend on the HLA type of an individual, it would be now important to investigate how epitope specific T cells associate with primary and secondary dengue infections and in severe dengue infections

Viral Load, Clinical Disease Severity and Cellular Immune Responses in Primary Varicella Zoster Virus Infection in Sri Lanka

BACKGROUND: In Sri Lanka, varicella zoster virus (VZV) is typically acquired during adulthood with significant associated disease morbidity and mortality. T cells are believed to be important in the control of VZV replication and in the prevention of reactivation. The relationship between viral load, disease severity and cellular immune responses in primary VZV infection has not been well studied. METHODOLOGY: We used IFNgamma ELISpot assays and MHC class II tetramers based on VZV gE and IE63 epitopes, together with quantitative real time PCR assays to compare the frequency and phenotype of specific T cells with virological and clinical outcomes in 34 adult Sri Lankan individuals with primary VZV infection. PRINCIPAL FINDINGS: Viral loads were found to be significantly higher in patients with moderate to severe infection compared to those with mild infection (p&lt;0.001) and were significantly higher in those over 25 years of age (P&lt;0.01). A significant inverse correlation was seen between the viral loads and the ex vivo IFNgamma ELISpot responses of patients (P&lt;0.001, r = -0.85). VZV-specific CD4+ T cells expressed markers of intermediate differentiation and activation. CONCLUSIONS: Overall, these data show that increased clinical severity in Sri Lankan adults with primary VZV infection associates with higher viral load and reduced viral specific T cell responses

Incidence and effects of Varicella Zoster Virus infection on academic activities of medical undergraduates - a five-year follow-up study from Sri Lanka

<p>Abstract</p> <p>Background</p> <p>The adult population in Sri Lanka is having high level of susceptibility for Varicella Zoster Virus (VZV) infection. Among medical undergraduates, 47% are VZV seronegative. The purpose of the present study was to determine the incidence of VZV infection in medical undergraduates in Sri Lanka, and to describe the effects of VZV infection on their academic activities.</p> <p>Methods</p> <p>A retrospective cohort of medical undergraduates' susceptible for VZV infection was selected from the University of Peradeniya, Sri Lanka. Data on the incidence of VZV infection (Chickenpox) during their undergraduate period was collected using a self-administered structured questionnaire. A second questionnaire was administered to collect data on the details of VZV infection and the impact of it on their academic activities. VZV incidence rate was calculated as the number of infections per 1,000 person years of exposure. Descriptive statistics were used to describe the impact of VZV infection on academic activities.</p> <p>Results</p> <p>Out of the 172 susceptible cohort, 153 medical undergraduates were followed up. 47 students reported VZV infection during the follow up period and 43 of them participated in the study. The cumulative incidence of VZV infection during the period of five and half years of medical training was 30.7%. Incidence density of VZV infection among medical undergraduates in this cohort was 65.1 per 1,000 person years of follow-up. A total of 377 working days were lost by 43 students due to the VZV infection, averaging 8.8 days per undergraduate. Total academic losses for the study cohort were; 205 lectures, 17 practicals, 13 dissection sessions, 11 tutorials, 124 days of clinical training and 107 days of professorial clinical appointments. According to their perception they lost 1,927 study hours due to the illness (Median 50 hours per undergraduate).</p> <p>Conclusions</p> <p>The incidence of VZV infection among Sri Lankan medical undergraduates is very high and the impact of this infection on academic activities causes severe disruption of their undergraduate life. VZV immunization for susceptible new entrant medical undergraduates is recommended.</p

Comparison of cardiovascular risk factors between sri lankans living in kandy and oslo

<p>Abstract</p> <p>Background</p> <p>South Asians living in western countries are known to have unfavourable cardiovascular risk profiles. Studies indicate migrants are worse off when compared to those living in country of origin. The purpose of this study was to compare selected cardiovascular risk factors between migrant Sri Lankans living in Oslo, Norway and Urban dwellers from Kandy, Sri Lanka.</p> <p>Methods</p> <p>Data on non fasting serum lipids, blood pressure, anthropometrics and socio demographics of Sri Lankan Tamils from two almost similar population based cross sectional studies in Oslo, Norway between 2000 and 2002 (1145 participants) and Kandy, Sri Lanka in 2005 (233 participants) were compared. Combined data were analyzed using linear regression analyses.</p> <p>Results</p> <p>Men and women in Oslo had higher HDL cholesterol. Men and women from Kandy had higher Total/HDL cholesterol ratios. Mean waist circumference and body mass index was higher in Oslo. Smoking among men was low (19.2% Oslo, 13.1% Kandy, P = 0.16). None of the women smoked. Mean systolic and diastolic blood pressure was significantly higher in Kandy than in Oslo.</p> <p>Conclusions</p> <p>Our comparison showed unexpected differences in risk factors between Sri Lankan migrants living in Oslo and those living in Kandy Sri Lanka. Sri Lankans in Oslo had favorable lipid profiles and blood pressure levels despite being more obese.</p