Dengue hemorrhagic fever in infants: research opportunities ignored

The age distribution of cases of dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) in infants under the age of 1 year are reported from Bangkok, Thailand, and for the first time for Ho Chi Minh City, Vietnam; Yangon, Myanmar; and Surabaya, Indonesia. The four dengue viruses were isolated from Thai infants, all of whom were having a primary dengue infection. Progress studying the immunologically distinct infant DHF/DSS has been limited; most contemporary research has centered on DHF/DSS accompanying secondary dengue infections. In designing research results obtained in studies on a congruent animal model, feline infectious peritonitis virus (FIPV) infections of kittens born to FIPV-immune queens should be considered. Research challenges presented by infant DHF/DSS are discussed.     

Environmental factors and incidence of dengue fever and dengue haemorrhagic fever in an urban area, Southern Thailand

Using the enumeration district (ED) block level this study looked at the incidence of dengue fever and dengue haemorrhagic fever (DF/DHF) within the Songkhla municipality in Thailand. Each of the 146 blocks in this area were considered as study units and surveyed for their environmental characteristics. A total of 287 cases of DH/DHF occurring in the year 1998 were selected for this study and the location of their homes mapped. Clustering analysis showed point clustering of the homes (P<0.0001) which was probably due to high density habitation, without any actual prevalence of case clustering. There was no evidence of clustering of the ED blocks with an incidence of DF/DHF (P=0.32). DF/DHF incidence for each block was strongly associated with the percentages of shop-houses, brick-made houses and houses with poor garbage disposal (all P<0.01). DF/DHF control should be emphasized for the areas which have a predominance of these housing types.     

Assessment of body fluid compartment volumes by multifrequency bioelectrical impedance spectroscopy in children with dengue

Dengue haemorrhagic fever (DHF), the most severe form of illness following infection with a dengue virus, is characterized by plasma leakage and a period of increased microvascular permeability. Monitoring of plasma volume and body fluid compartment shifts is an integral part of the clinical management of DHF, and is crucial to the performance of clinical research studies on DHF pathogenesis. Multifrequency bioelectrical impedance spectroscopy (BIS) was assessed as a non-invasive method to monitor body fluid compartment shifts in children participating in a prospective, hospital-based, study of dengue virus infections in Thailand. Over the 48 h surrounding defervescence, the extracellular water/intracellular water ratio (ECW/ICW) rose in children with dengue virus infections and correlated with increasing disease severity [DHF > intermediate dengue fever (DF)/DHF > DF]. Plasma leakage remained within the ECW compartment and was not directly measured by multifrequency BIS. Expansion of the ECW space in DHF appeared to be primarily due to diminished renal water clearance. During the course of dengue illness, multifrequency BIS did not improve on serial haematocrit and bodyweight determinations for monitoring plasma volume contraction and ECW expansion, respectively.     

Changing epidemiology of dengue hemorrhagic fever in Thailand

Dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) are reportable diseases, the third most common causes for hospitalization of children in Thailand. Data collected from the Ministry of Public Health were analysed for trends. Rates of DHF increased in Thailand until 1987 when the largest epidemic ever, 325/100000 population, was recorded. Whereas the disease used to be confined to large cities, the rate is now higher in rural (102.2 per 100000) than urban areas (95.4 per 100000 in 1997). The age of highest incidence has increased, and the age group most severely affected is now those 5-9 years old (679/100000 in 1997). The case fatality rate has decreased with improved treatment and is now only 0.28%.     

Geographical gradient of mean age of dengue haemorrhagic fever patients in northern Thailand

Dengue haemorrhagic fever (DHF) is caused by dengue virus transmitted by Aedes mosquitoes; mean age of patients varies temporally and geographically. Variability in age of patients may be due to differences in transmission intensity or demographic structure. To compare these two hypotheses, the mean age of DHF patients from 90 districts in northern Thailand (1994-1996, 2002-2004) was regressed against (i) Aedes abundance or (ii) demographic variables (birthrate, average age) of the district. We also developed software to quantify direction and strength of geographical gradients of these variables. We found that, after adjusting for socioeconomics, climate, spatial autocorrelation, the mean age of patients was correlated only with Aedes abundance. The geographical gradient of mean age of patients originated from entomological, climate, and socioeconomic gradients. Vector abundance was a stronger determinant of mean age of patients than demographic variables, in northern Thailand.     

The XXth century dengue pandemic: need for surveillance and research.

By the last decade of the XXth century Aedes aegypti and the 4 dengue viruses had spread to nearly all countries of the tropical world. Some 2 billion persons live in dengue-endemic areas with tens of millions infected annually. Dengue pandemics were also documented in the XVIIIth and XIXth centuries; they were contained by organized anti-Aedes aegypti campaigns and urban improvements. The XXth century dengue pandemic has brought with it the simultaneous circulation of multiple serotypes and in its aftermath, endemic dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). Nearly 3 million children have been hospitalized with this syndrome in the past 3 decades, mainly in South-East Asia. Recent outbreaks of DHF/DSS in the Pacific Islands, China, India, Sri Lanka, Cuba and Venezuela are indicators of the high intensity and rapid spread of dengue transmission. The magnitude of the XXth century dengue pandemic requires urgent improvements in early warning surveillance by WHO Member States and the development of the capacity to study underlying mechanisms of the disease. A key research question is why does DHF/DSS not occur with all second dengue infections? Two answers have been suggested: (1) a human resistance gene. Data from the 1981 DHF/DSS epidemic in Cuba have demonstrated the existence in blacks of a resistance gene. The effect of such a gene in reducing disease susceptibility of American and African blacks requires more study. (2) The existence of dengue "biotypes". Some, but not all biotypes may cause DHF/DSS during a second dengue infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Different clinical and laboratory manifestations between dengue haemorrhagic fever and dengue fever with bleeding tendency

The incidence of dengue fever (DF) is estimated to have increased 30-fold in the past 50 years. The incidence of dengue haemorrhagic fever (DHF), a life-threatening complication of DF, is also increasing. The need for better classification of the severity of dengue infections has been proposed in order to clarify different entities of dengue infections. We defined a class of patients with DF with bleeding tendency (DF w/B) to differentiate further the varying pathogenesis among DF, DF w/B and DHF. In a hospital-based study in Taiwan, we compared clinical features, biochemistry and immune mediators among patients with DHF, DF w/B and DF. Results showed that DF w/B patients, similar to DHF patients, had a higher rate of secondary dengue infection (P<0.001) as well as higher IL-10 (P=0.023) and lower IFNgamma (P=0.009) levels than DF patients. In contrast, DHF patients had significantly higher soluble vascular cell adhesion molecule 1 levels than DF w/B patients (P=0.038) and DF patients (P<0.001). This study provides new insight into the different immune mechanisms of DF, DF w/B and DHF. DF involves a Th1 reaction and DF w/B involves an altered Th2 reaction, whereas DHF involves an altered Th2 reaction and augmented vascular insult.     

Studies on the life budget of Aedes aegypti in Wat Samphaya, Bangkok, Thailand

For a complete understanding of the epidemiology of a vector-borne disease, a knowledge of the bionomics of the vector is needed. The development of Aedes aegypti was studied in Wat Samphaya, Bangkok, Thailand, where work on the adult biology had been carried out the previous year (1966-67). Particular attention was given to the variation in the numbers of immature stages of the mosquito in relation to the known seasonal incidence of dengue haemorrhagic fever. Of the three types of water container in the Wat, water jars were the main source of adults, flower pot plates were less important, and the contribution of ant traps was insignificant.     

Serological and virological features of dengue fever and dengue haemorrhagic fever in Thailand from 1999 to 2002

Serological and virological features of dengue fever (DF) and dengue haemorrhagic fever (DHF) in Thailand were analysed in 2715 patients from 1999 to 2002. The illness was caused by DEN-1 in 45%, DEN-2 in 32%, DEN-3 in 18% and DEN-4 in 5% of patients. Almost all of the DHF cases caused by DEN-2 and DEN-4 were in secondary infection, while approximately 20% of the DHF cases caused by DEN-1 and DEN-3 were in primary infection. Male:female ratio and age distribution were not different among four serotypes in primary and secondary infections. These results indicate that DEN-1 and DEN-3 induce DHF in both primary and secondary infections, and suggest that DEN-2 and DEN-4 in Thailand are less likely to cause DHF in primary infections.     

Dengue: emergence as a global public health problem and prospects for control

Dengue causes more illness and death than any other arboviral infection: there are at least 20 million infections in the world each year and several hundred thousand cases of a severe, life-threatening syndrome known as dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). In recent years, the geographical range of dengue has extended and DHF/DSS is occurring in new areas and with increased incidence. The reasons for the resurgence are complex, but parallel demographic changes and reduced efforts towards disease control. Control of dengue currently depends on controlling its mosquito vector. However, development of a vaccine offers greater hope in the long-term. The dengue group of flaviviruses is unique in that it comprises 4 distinct serotypes which have the potential to cause sequential infections with increased severity. It is reasoned, therefore, that any vaccine should induce solid immunity to all 4 serotypes. Knowledge regarding dengue immunity and pathogenesis is rapidly advancing and it is reasonable to believe that this information can be used to devise a safe and efficacious vaccine for dengue, but it seems unlikely that this will become available in the near future.     

Spatial and temporal circulation of dengue virus serotypes: a prospective study of primary school children in Kamphaeng Phet,Thailand

Dengue virus occurs as four distinct serotypes, each of which causes epidemics throughout the tropical and subtropical regions of the world. Few studies have examined co-circulation of multiple dengue virus serotypes in a well-defined cohort population over time and their capacity to produce severe dengue disease. In this paper, the authors report the details and findings of the first 3 years (1998-2000) of an ongoing prospective study of dengue virus transmission and disease severity in a cohort of children in northern Thailand. A total of 108 dengue virus isolates were obtained from 167 acute dengue virus infections; 23% were DEN-1, 35% were DEN-2, 41% were DEN-3, and 1% were DEN-4. Despite the proximity of the schools, there was marked spatial and temporal clustering of transmission of each dengue serotype. Serotype-specific antibody levels prior to the dengue transmission season were not predictive of the incidence of dengue virus infections or the predominant serotype transmitted at individual schools. All dengue serotypes produced severe dengue illness, although DEN-3 produced more severe symptoms than the other dengue serotypes. The authors' findings emphasize the complexity of dengue serotype-specific virus transmission and severe dengue disease and have important implications for dengue control and vaccine development.     

An information value based analysis of physical and climatic factors affecting dengue fever and dengue haemorrhagic fever incidence

Background  

Vector-borne diseases are the most dreaded worldwide health problems. Although many campaigns against it have been conducted, Dengue Fever (DF) and Dengue Haemorrhagic Fever (DHF) are still the major health problems of Thailand. The reported number of dengue incidences in 1998 for the Thailand was 129,954, of which Sukhothai province alone reported alarming number of 682. It was the second largest epidemic outbreak of dengue after 1987. Government arranges the remedial facilities as and when dengue is reported. But, the best way to control is to prevent it from happening. This will be possible only when knowledge about the relationship of DF/DHF with climatic and physio-environmental agents is discovered. This paper explores empirical relationship of climatic factors rainfall, temperature and humidity with the DF/DHF incidences using multivariate regression analysis. Also, a GIS based methodology is proposed in this paper to explore the influence of physio-environmental factors on dengue incidences. Remotely sensed data provided important data about physical environment and have been used for many vector borne diseases. Information Values (IV) method was utilised to derive influence of various factors in the quantitative terms. Researchers have not applied this type of analysis for dengue earlier. Sukhothai province was selected for the case study as it had high number of dengue cases in 1998 and also due to its diverse physical setting with variety of land use/land cover types.     

Surveillance for an emerging disease: dengue hemorrhagic fever in Puerto Rico, 1988-1997. Puerto Rico Association of Epidemiologists

Surveillance for emerging diseases is critically dependent on four factors: reporting methods, case definition, laboratory diagnosis, and knowledge of the disease among health-care professionals. The dengue hemorrhagic fever (DHF) surveillance system in Puerto Rico collects patient data from three sources: dengue case investigation (DCI) forms sent with diagnostic samples, clinical reports from hospital infection control nurses (ICNs), and hospital records. Recruitment of ICN reporting produced a marked increase in notifications (67 to 294). Hospital records of possible DHF cases showed that tests for ascertaining diagnosis (e.g., blood in stool, serum albumin) were frequently not performed. DCI and ICN reports underestimated severity. After hospital record review, the ratio of total DHF cases to cases detected by surveillance was approximately 3:1, whether using clinical criteria or using clinical and dengue laboratory diagnosis. An important determinant for the low sensitivity (28.4%) and high specificity (96.5%) of the surveillance system was the World Health Organization (WHO) clinical definition for DHF. In spite of such limitations, DHF surveillance data in Puerto Rico provide abundant, reliable information for monitoring disease trends. These methods may be applied to other situations to define the characteristics and incidence trends of emerging infections.     

Stratification of a hyperendemic city in hemorrhagic dengue]

Any effort to control dengue hemorrhagic fever (DHF) faces a number of challenges. Among these are the great environmental heterogeneity of homes and neighborhoods in urban centers where the primary dengue vector, Aedes aegypti, breeds, as well as shortages of resources and of personnel trained in mosquito control. Adequate epidemiological surveillance could serve as a basis to begin to stratify urban communities and identify the areas in them where control efforts should be focused. In this study we stratified Maracay, Venezuela, a city with hyperendemic dengue hemorrhagic fever, using a geographic information system and analyzing the persistence, incidence, and prevalence of dengue, by means of clinical diagnoses reported from 1993 through 1998. Maracay has around one million inhabitants living in some 349 neighborhoods in the six communities that make up the greater Maracay metropolitan area. During that 1993-1998 period the Maracay area reported 10,576 cases of dengue, 2,593 cases of DHF, and 8 deaths. The incidence of DHF was related to the incidence of dengue, the number of inhabitants in an area, and population density. The spatial pattern of dengue incidence was stable over the years that were studied, and significant, positive relationships were found between pairs of years and the incidence of dengue by neighborhood. The persistence of dengue was related directly to monthly incidence by neighborhood. These spatial patterns helped to divide the city into three strata: 68 neighborhoods without apparent dengue, 226 neighborhoods with low persistence and prevalence, and 55 neighborhoods with high persistence and prevalence. We recommend giving the highest priority for control efforts to these 55 neighborhoods, which make up just 35% of the Maracay urban area but had 70% of all the reported dengue cases.     

Epidemiology of inapparent and symptomatic acute dengue virus infection: a prospective study of primary school children in Kamphaeng Phet,Thailand

Dengue viruses are a major cause of morbidity in tropical and subtropical regions of the world. Knowledge about the epidemiology and host determinants of inapparent and severe dengue virus infections is limited. In this paper, the authors report findings from the first 3 years of a prospective study of dengue virus transmission and disease severity conducted in a cohort of 2,119 elementary school children in northern Thailand. A total of 717,106 person-school days were observed from 1998 to 2000. The incidence of inapparent and of symptomatic dengue virus infection was 4.3% and 3.6% in 1998, 3.2% and 3.3% in 1999, and 1.4% and 0.8% in 2000, respectively. Symptomatic dengue virus infection was responsible for 3.2%, 7.1%, and 1.1% of acute-illness school absences in 1998, 1999, and 2000, respectively. The early symptom complex of acute dengue virus infection is protean and difficult to distinguish from other causes of febrile childhood illnesses. The authors' results illustrate the spatial and temporal diversity of dengue virus infection and the burden of dengue disease in schoolchildren in Thailand. Their findings increase understanding of dengue virus transmission and disease severity in a well-defined cohort population and offer a study design in which to test the efficacy of potential dengue vaccines.     

Dengue hemorrhagic fever--U.S.-Mexico border, 2005

Dengue fever is a mosquito-transmitted disease caused by any of four closely related virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4) of the genus Flavivirus. Infection with one of these serotypes provides lifelong immunity to the infecting serotype only. Therefore, persons can acquire a second dengue infection from a different serotype, and second infections place them at greater risk for dengue hemorrhagic fever (DHF), the more severe form of the disease. DHF is characterized by bleeding manifestations, thrombocytopenia, and increased vascular permeability that can lead to life-threatening shock. In south Texas, near the border with Mexico, sporadic, locally acquired outbreaks of dengue fever have been reported previously; however, on the Texas side of the border, these outbreaks have not included recognized cases of locally acquired DHF in persons native to the area. In July 2005, a case of DHF was reported in a resident of Brownsville, Texas. In August 2005, health authorities in the neighboring state of Tamaulipas, Mexico, reported an ongoing dengue outbreak with 1,251 cases of dengue fever, including 223 cases (17.8%) of DHF. To characterize this dengue outbreak, the Texas Department of State Health Services (TDSHS), Mexican health authorities, and CDC conducted a clinical and epidemiologic investigation. This report summarizes the results of that investigation, which determined that the percentage of DHF cases associated with dengue fever outbreaks at the Texas-Tamaulipas border has increased. Health-care providers along the U.S. border with Mexico should be vigilant for DHF and familiar with its diagnosis and management to reduce the number of severe illnesses and deaths associated with outbreaks of dengue fever.     

Modeling the hepatitis A epidemiological transition in Thailand

BackgroundIn most low- and middle-income countries, hepatitis A virus (HAV) is shifting or expected to shift from high endemicity to intermediate or low endemicity. A decreased risk of HAV infection will cause an increase in the average age at infection and will therefore increase the proportion of infections that results in severe disease. Mathematical models can provide insights into the factors contributing to this epidemiological transition.MethodsAn MSLIR compartmental dynamic transmission model stratified by age and setting (rural and urban) was developed and calibrated with demographic, environmental, and epidemiological data from Thailand. HAV transmission was modeled as a function of urbanization and access to clean drinking water. The model was used to project various epidemiological measures.ResultsThe age at midpoint of population immunity remains considerably younger in rural areas than in urban areas. The mean age of symptomatic hepatitis A infection in Thailand has shifted from childhood toward early adulthood in rural areas and is transitioning from early adulthood toward middle adulthood in urban areas. The model showed a significant decrease in incidence rates of total and symptomatic infections in rural and urban settings in Thailand over the past several decades as water access has increased, although the overall incidence rate of symptomatic HAV is projected to slightly increase in the coming decades.ConclusionsModeling the relationship between water, urbanization, and HAV endemicity is a novel approach in the estimation of HAV epidemiological trends and future projections. This approach provides insights about the shifting HAV epidemiology and could be used to evaluate the public health impact of vaccination and other interventions in a diversity of settings.     

Epidemiology of dengue and hemorrhagic dengue in Santiago, Cuba 1997]

A dengue epidemic that Cuba reported in 1997 registered more than 500,000 cases of dengue fever produced by viral serotype 1. In 1981, there was an epidemic of dengue hemorrhagic fever produced by serotype 2 of the virus. This time 344,203 clinical cases were reported, 10,312 of which were severe cases of hemorrhagic fever that led to 158 fatalities (101 of them among children). The reintroduction of dengue, and specifically of dengue viral serotype 2 (Jamaica genotype), was quickly detected in January 1997 through an active surveillance system with laboratory confirmation of cases in the municipality of Santiago de Cuba, in the province of the same name. The main epidemiological features of this outbreak are reported in this paper. A total of 3,012 cases were reported and serologically confirmed. These included 205 cases classified as dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), 12 of which were case fatalities (all among adults). Secondary infection with dengue virus was one of the most important risk factors for DHF/DSS. Ninety-eight percent of the DHF/DSS cases and 92% of the fatal cases had contracted a secondary infection. It was the first time dengue hemorrhagic fever was documented as a secondary infection 16 to 20 years after initial infection. Belonging to the white racial group was another important risk factor for DHF/DSS, as had been observed during the 1981 epidemic. During the most recent epidemic it was demonstrated that the so called "fever alert" is not useful for early detection of an epidemic. Measures taken by the country's public health officials prevented spread of the epidemic to other municipalities plagued by Aedes aegypti.     

Dengue fever epidemic potential as projected by general circulation models of global climate change.

Climate factors influence the transmission of dengue fever, the world's most widespread vector-borne virus. We examined the potential added risk posed by global climate change on dengue transmission using computer-based simulation analysis to link temperature output from three climate general circulation models (GCMs) to a dengue vectorial capacity equation. Our outcome measure, epidemic potential, is the reciprocal of the critical mosquito density threshold of the vectorial capacity equation. An increase in epidemic potential indicates that a smaller number of mosquitoes can maintain a state of endemicity of disease where dengue virus is introduced. Baseline climate data for comparison are from 1931 to 1980. Among the three GCMs, the average projected temperature elevation was 1.16 degrees C, expected by the year 2050. All three GCMs projected a temperature-related increase in potential seasonal transmission in five selected cities, as well as an increase in global epidemic potential, with the largest area change occurring in temperate regions. For regions already at risk, the aggregate epidemic potential across the three scenarios rose on average between 31 and 47% (range, 24-74%). If climate change occurs, as many climatologists believe, this will increase the epidemic potential of dengue-carrying mosquitoes, given viral introduction and susceptible human populations. Our risk assessment suggests that increased incidence may first occur in regions bordering endemic zones in latitude or altitude. Endemic locations may be at higher risk from hemorrhagic dengue if transmission intensity increases.