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

Determinants of Inapparent and Symptomatic Dengue Infection in a Prospective Study of Primary School Children in Kamphaeng Phet, Thailand

Dengue viruses are a major cause of illness and hospitalizations in tropical and subtropical regions of the world. Severe dengue illness can cause prolonged hospitalization and in some cases death in both children and adults. The majority of dengue infections however are inapparent, producing little clinical illness. Little is known about the epidemiology or factors that determine the incidence of inapparent infection. We describe in a study of school children in Northern Thailand the changing nature of symptomatic and inapparent dengue infection. We demonstrate that the proportion of inapparent dengue infection varies widely among schools during a year and within schools during subsequent years. Important factors that determine this variation are the amount of dengue infection in a given and previous year. Our findings provide an important insight in the virus-host interaction that determines dengue severity, how severe a dengue epidemic may be in a given year, and important clues on how a dengue vaccine may be effective

HER2 therapy. HER2 (ERBB2): functional diversity from structurally conserved building blocks

EGFR-type receptor tyrosine kinases achieve a broad spectrum of cellular responses by utilizing a set of structurally conserved building blocks. Based on available crystal structures and biochemical information, significant new insights have emerged into modes of receptor control, its deregulation in cancer, and the nuances that differentiate the four human receptors. This review gives an overview of current models of the control of receptor activity with a special emphasis on HER2 and HER3

Empirical Models of Transitions between Coral Reef States: Effects of Region, Protection, and Environmental Change

There has been substantial recent change in coral reef communities. To date, most analyses have focussed on static patterns or changes in single variables such as coral cover. However, little is known about how community-level changes occur at large spatial scales. Here, we develop Markov models of annual changes in coral and macroalgal cover in the Caribbean and Great Barrier Reef (GBR) regions

BSRS-5 (5-item Brief Symptom Rating Scale) scores affect every aspect of quality of life measured by WHOQOL-BREF in healthy workers

This study aims to evaluate and quantify the possible effect of psychological symptoms on healthy workers' quality of life (QOL). The workers were recruited from a factory in south Taiwan. We assessed their psychological symptoms with a 5-item brief symptom rating scale (BSRS-5) and measured the QOL using the Taiwanese version of the World Health Organization Quality of Life (WHOQOL)-BREF. Multiple linear regression analysis was conducted to explore the association between the two tools after control of confounding by other predictors. A total of 1,080 workers , who attended a physical examination, completed questionnaires and informed consent forms. Scores on the BSRS-5 significantly predicted scores in each domain and items of the WHOQOL-BREF. The magnitude of psychological domain score seemed to be affected the most; every 1 point increase in BSRS-5 was associated with a 0.39 raw score (equivalent to 2. 44 percentile) decrease in QOL. The sleep facet of WHOQOL appeared to have the highest association, followed by items of negative feelings, energy, and concentration. The BSRS-5 score is predictive for scores of all four domains and 26 items of the Taiwanese version of the WHOQOL-BREF for regular factory workers

Preexisting Japanese Encephalitis Virus Neutralizing Antibodies and Increased Symptomatic Dengue Illness in a School-Based Cohort in Thailand

Dengue viruses (DENVs) and Japanese encephalitis virus (JEV) have significant cross-reactivity in serological assays, but the possible clinical implications of this remain poorly understood. Interactions between these flaviviruses are potentially important for public health because wild-type JEV continues to co-circulate with DENV in Southeast Asia, the area with the highest burden of DENV illness, and JEV vaccination coverage in this region is high. In this study, we examined how preexisting JEV neutralizing antibodies (NAbs) influenced the clinical severity of subsequent DENV infection using data from a prospective school-based cohort study in Thailand that captured a wide range of clinical severities, including asymptomatic, non-hospitalized, and hospitalized DENV infections. We found that the prior existence of JEV NAbs was associated with an increased occurrence of symptomatic versus asymptomatic DENV infection. This association was most notable in DENV-naives, in whom the presence of JEV NAbs was also associated with an illness of longer duration. These findings suggest that the issue of heterologous flavivirus immunity and DENV infection merits renewed attention and interest and that DENV vaccine developers might incorporate detailed assessments of preexisting immunity to non-DENV flaviviruses and histories of vaccination against non-DENV flaviviruses in evaluating DENV vaccine safety and efficacy

HFE gene mutations increase the risk of coronary heart disease in women

The purpose of the present study is to examine HFE gene mutations in relation to newly diagnosed (incident) coronary heart disease (CHD). In a population-based follow-up study of 7,983 individuals aged 55 years and older, we compared the risk of incident CHD between HFE carriers and non-carriers, overall and stratified by sex and smoking status. HFE mutations were significantly associated with an increased risk of incident CHD in women but not in men (hazard ratio [HR] for women = 1.7, 95% confidence interval [CI] 1.2–2.4 versus HR for men = 0.9, 95% CI 0.7–1.2). This increased CHD risk associated with HFE mutations in women was statistically significant in never smokers (HR = 1.8, 95% CI 1.1–2.8) and current smokers (HR = 3.1, 95% CI 1.4–7.1), but not in former smokers (HR = 1.3, 95% CI 0.7–2.4). HFE mutations are associated with increased risk of incident CHD in women

Dengue Infection in Children in Ratchaburi, Thailand: A Cohort Study. II. Clinical Manifestations

Dengue infection is one of the most important diseases transmitted to human by mosquito bite. The disease may be mild or severe. This study reveals the occurrence and clinical features of diseases caused by dengue infection in a 3-year follow-up in school-children aged 3–14 years in Ratchaburi Province, Thailand using an active surveillance for the episodes of fever. Children who had fever were laboratory tested for the evidence of dengue infection and recorded for clinical features. It was found that most of dengue infected patients had headache, anorexia, nausea/vomiting, and muscle ache. About half of the patients had clinical symptoms that closely mimic other diseases, especially respiratory tract infection, and were incorrectly diagnosed by pediatricians. Only 11% of the patients had more a severe disease called “dengue hemorrhagic fever.” This severe disease may be predicted by the presence of anorexia, nausea/vomiting, and abdominal pain after the second day of illness. This study provides better understanding in this disease

Epidemiology of Dengue Virus in Iquitos, Peru 1999 to 2005: Interepidemic and Epidemic Patterns of Transmission

To develop prevention (including vaccines) and control programs for dengue fever, a significant mosquito-borne disease in the tropics, there is an urgent need for comprehensive long term field epidemiological studies. We report results from a study that monitored ∼2,400 school children and some adult family members for dengue infection at 6 month intervals from 1999 to 2005, in the Amazonian city of Iquitos, Peru. At enrollment, ∼80% of the participants had a previous infection with DENV serotypes 1 and 2 or both. During the first 15 months, about 3 new infections for every 100 participants were observed among the study participants. In 2001, DENV-3, a serotype not previously observed in the region, invaded Iquitos in a process characterized by 3 distinct periods: amplification over at least a 5–6 month period, replacement of previously circulating serotypes, and epidemic transmission when incidence peaked. Incidence patterns of new infections were geographically distinct from baseline prevalence rates prior to arrival of DENV-3, but closely mirrored them during the invasion. DENV transmission varied geographically corresponding to elevated mosquito densities. The invasion of a novel serotype is often characterized by 5–6 months of silent transmission before traditional surveillance programs detect the virus. This article sets the stage for subsequent publications on dengue epidemiology

Japanese Encephalitis—A Pathological and Clinical Perspective

Japanese encephalitis (JE) is the leading form of viral encephalitis in Asia. It is caused by the JE virus (JEV), which belongs to the family Flaviviridae. JEV is endemic to many parts of Asia, where periodic outbreaks take hundreds of lives. Despite the catastrophes it causes, JE has remained a tropical disease uncommon in the West. With rapid globalization and climatic shift, JEV has started to emerge in areas where the threat was previously unknown. Scientific evidence predicts that JEV will soon become a global pathogen and cause of worldwide pandemics. Although some research documents JEV pathogenesis and drug discovery, worldwide awareness of the need for extensive research to deal with JE is still lacking. This review focuses on the exigency of developing a worldwide effort to acknowledge the prime importance of performing an extensive study of this thus far neglected tropical viral disease. This review also outlines the pathogenesis, the scientific efforts channeled into develop a therapy, and the outlook for a possible future breakthrough addressing this killer disease