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

Dengue Dynamics in Binh Thuan Province, Southern Vietnam: Periodicity, Synchronicity and Climate Variability

Dengue has become a major international public health problem due to increasing geographic distribution and a transition from epidemic transmission with long inter-epidemic intervals to endemic transmission with seasonal fluctuation. Seasonal and multi-annual cycles in dengue incidence vary over time and space. We performed wavelet analyses on time series of monthly notified dengue cases in Binh Thuan province, southern Vietnam, from January 1994 to June 2009. We observed a continuous annual mode of oscillation with a non-stationary 2–3-year multi-annual cycle. We used phase differences to describe the spatio-temporal patterns which suggest that the seasonal wave of infection was either synchronous with all districts or moving away from Phan Thiet district, while the multi-annual wave of infection was moving towards Phan Thiet district. We also found a strong non-stationary association between ENSO indices and climate variables with dengue incidence. We provided insight in dengue population transmission dynamics over the past 14.5 years. Further studies on an extensive time series dataset are needed to test the hypothesis that epidemics emanate from larger cities in southern Vietnam

Targeting vaccinations for the licensed dengue vaccine: considerations for serosurvey design

Background The CYD-TDV vaccine was unusual in that the recommended target population for vaccination was originally defined not only by age, but also by transmission setting as defined by seroprevalence. WHO originally recommended countries consider vaccination against dengue with CYD-TDV vaccine in geographic settings only where prior infection with any dengue serotype, as measured by seroprevalence, was >170% in the target age group. Vaccine was not recommended in settings where seroprevalence was <50%. Test-and-vaccinate strategies suggested following new analysis by Sanofi will still require age-stratified seroprevalence surveys to optimise age-group targeting. Here we address considerations for serosurvey design in the context of vaccination program planning. Methods To explore how the design of seroprevalence surveys affects estimates of transmission intensity, 100 age-specific seroprevalence surveys were simulated using a beta-binomial distribution and a simple catalytic model for different combinations of age-range, survey size, transmission setting, and test sensitivity/specificity. We then used a Metropolis-Hastings Markov Chain Monte-Carlo algorithm to estimate the force of infection from each simulated dataset. Results Sampling from a wide age-range led to more accurate estimates than merely increasing sample size in a narrow age-range. This finding was consistent across all transmission settings. The optimum test sensitivity and specificity given an imperfect test differed by setting with high sensitivity being important in high transmission settings and high specificity important in low transmission settings. Conclusions When assessing vaccination suitability by seroprevalence surveys, countries should ensure an appropriate age-range is sampled, considering epidemiological evidence about the local burden of disease

The prevalence of obesity and the knowledge, attitude and practice of healthy lifestyle among the adult population in Kampung Banyuk, Kampung Kerto and Kampung Langup

Background Obesity has become a great public health concern and prevent!ive measures need to be done. Objective The objective of this research is to determine the prevalence ofobesity and their knowledge, attitude and practices (KAP) towards a healthy lifestyle among the residents in Kampung Banyok, Kampung Kerto and Kampung Langup. Methods A cross-sectional study was done among 126 randomly selected villagers aged 18 years and above from the three selected villages. They were interviewed based on a questionnaire and their body mass index (BMI) was calculated. Results It was found that more than half of the respondents are obese. Among the respondents, for the healthy lifestyle component, the level of good KAP is 69.2%, 46.8% and 60.3% respectively. As for obesity component, the level of good KAP is 60.3%, 54% and 54.8% respectively. Among the obese respondents, the level of knowledge and attitude on healthy lifestyle and obesity is better. Obese respondents have better obesity preventive practice while the non-obese respondents have better practice on healthy lifestyle. The only significant correlation noted was between knowledge and practice on obesity albeit a negative one. Conclusion The level of knowledge and attitude and practice on healthy lifestyle among the obese respondents are encouraged but more effort in the preventive practice ofobesity shou1d be done to reduce the prevalence.

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Visual Health and its Relationship with Screen Time among School Children: A Cross-Sectional Study in Sarawak, Malaysia

Objective: This study intended to determine visual health of the school children and investigate its relationship with screen time. Methods: This was a school-based cross-sectional study using multistage cluster sampling. A self-reported and interviewer-administered questionnaire were used to compile screen time information. Children presenting visual acuity was evaluated with Snellen chart and non-cycloplegic refraction was performed to those acuities worse than 6/12. Data analysis was performed using SPSS version 22. A p-value ≤0.05 with 95% CI was considered as statistically significant. Results: About 87% children had normal or near normal visual acuity and 13% had visual impairment. The prevalence of refractive error was 22.8%.  Astigmatism was the most prevailing type of refractive error, 10%. The children spent on average of 13.82 hours per week on screen time. Television is the most popular electronic devices. Boy spent more time on gaming consoles than girl. There was no statistically significant relationship between refractive error and screen time (p=0.581). Conclusion: The prevalence of refractive error among school children was 23%. The children spent nearly 14 hours per week on screen time. There was no statistically significant relationship between refractive error and screen time. Periodical children vision screening is paramount for early detection of vision impairment and provide possible intervention