Relationship between transmission intensity and incidence of dengue hemorrhagic fever in Thailand

Background

Dengue is the most prevalent mosquito-borne virus, and potentially fatal dengue hemorrhagic fever (DHF) occurs mainly in secondary infections. It recently was hypothesized that, due to the presence of cross-immunity, the relationship between the incidence of DHF and transmission intensity may be negative at areas of intense transmission. We tested this hypothesis empirically, using vector abundance as a surrogate of transmission intensity.

Methodology/Principal Findings

House Index (HI), which is defined as the percentage of households infested with vector larvae/pupae, was obtained from surveys conducted on one million houses in Thailand, between 2002 and 2004. First, the utility of HI as a surrogate of transmission intensity was confirmed because HI was correlated negatively with mean age of DHF in the population. Next, the relationship between DHF incidence and HI was investigated. DHF incidence increased only up to an HI of about 30, but declined thereafter. Reduction of HI from the currently maximal level to 30 would increase the incidence by more than 40%. Simulations, which implemented a recently proposed model for cross-immunity, generated results that resembled actual epidemiological data. It was predicted that cross-immunity generates a wide variation in incidence, thereby obscuring the relationship between incidence and transmission intensity. The relationship would become obvious only if data collected over a long duration (e.g., >10 years) was averaged.

Conclusion

The negative relationship between DHF incidence and dengue transmission intensity implies that in regions of intense transmission, insufficient reduction of vector abundance may increase long-term DHF incidence. Further studies of a duration much longer than the present study, are warranted.     

Controlling Dengue with Vaccines in Thailand

Background

Dengue is a mosquito-borne infectious disease that constitutes a growing global threat with the habitat expansion of its vectors Aedes aegyti and A. albopictus and increasing urbanization. With no effective treatment and limited success of vector control, dengue vaccines constitute the best control measure for the foreseeable future. With four interacting dengue serotypes, the development of an effective vaccine has been a challenge. Several dengue vaccine candidates are currently being tested in clinical trials. Before the widespread introduction of a new dengue vaccine, one needs to consider how best to use limited supplies of vaccine given the complex dengue transmission dynamics and the immunological interaction among the four dengue serotypes.

Methodology/Principal Findings

We developed an individual-level (including both humans and mosquitoes), stochastic simulation model for dengue transmission and control in a semi-rural area in Thailand. We calibrated the model to dengue serotype-specific infection, illness and hospitalization data from Thailand. Our simulations show that a realistic roll-out plan, starting with young children then covering progressively older individuals in following seasons, could reduce local transmission of dengue to low levels. Simulations indicate that this strategy could avert about 7,700 uncomplicated dengue fever cases and 220 dengue hospitalizations per 100,000 people at risk over a ten-year period.

Conclusions/Significance

Vaccination will have an important role in controlling dengue. According to our modeling results, children should be prioritized to receive vaccine, but adults will also need to be vaccinated if one wants to reduce community-wide dengue transmission to low levels.     

Dengue and dengue haemorrhagic fever: Indian perspective

The relationship of this country with dengue has been long and intense. The first recorded epidemic of clinically dengue-like illness occurred at Madras in 1780 and the dengue virus was isolated for the first time almost simultaneously in Japan and Calcutta in 1943–1944. After the first virologically proved epidemic of dengue fever along the East Coast of India in 1963–1964, it spread to allover the country. The first full-blown epidemic of the severe form of the illness, the dengue haemorrhagic fever/dengue shock syndrome occurred in North India in 1996. Aedes aegypti is the vector for transmission of the disease. Vaccines or antiviral drugs are not available for dengue viruses; the only effective way to prevent epidemic degure fever/dengue haemorrhagic fever (DF/DHF) is to control the mosquito vector, Aedes aegypti and prevent its bite. This country has few virus laboratories and some of them have done excellent work in the area of molecular epidemiology, immunopathology and vaccine development. Selected work done in this country on the problems of dengue is presented here.     

Etiological relation between Korean hemorrhagic fever and epidemic hemorrhagic fever in Japan.

The first case of epidemic hemorrhagic fever in Japan was seen in Osaka in 1960. The etiologic agent of this disease has not yet been isolated, but a close etiologic relation between Korean hemorrhagic fever and epidemic hemorrhagic fever in Japan has been suspected because of similarities in the clinical and pathological pictures of the two diseases. This relation has now been confirmed serologically by demonstrating specific immunofluorescent antibodies to Korean hemorrhagic fever virus in 19 of 20 sera obtained from subjects 7 to 17 years after an acute attack of epidemic hemorrhagic fever.     

Dengue and dengue haemorrhagic fever: implications of host genetics

Little is known of the role of human leucocyte antigen (HLA) alleles or non-HLA alleles in determining resistance, susceptibility or the severity of acute viral infections. Dengue fever (DF) and dengue haemorrhagic fever (DHF) are suitable models for immunogenetic studies, yet only superficial efforts have been made to study dengue disease to date. DF and DHF can be caused by both primary and secondary infection by any of the four serotypes of the dengue virus. Differences in host susceptibility to infectious disease and disease severity cannot be attributed solely to the virus virulence. Variations in immune response, often associated with polymorphism in the human genome, can now be detected. Data on the influence of human genes in DF and DHF are discussed here in relation to (1) associations between HLA polymorphism and dengue disease susceptibility or resistance, (2) protective alleles influencing progression to severe disease, (3) alleles restricting CD4(+) and CD8(+) T lymphocytes, and (4) non-HLA genetic factors that may contribute to DHF evolution. Recent discoveries regarding genetic associations in other viral infections may provide clues to understanding the development of end-stage complications in dengue disease. The scanty positive data presented here indicate a need for detailed genetic studies in different ethnic groups in different countries during the acute phase of DF and DHF on a larger number of patients.     

Crimean-Congo hemorrhagic fever: An overview

Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic viral infection that is a serious threat to humans. The disease is widely distributed in Africa, Asia, and Europe and has developed into a serious public health concern. Humans become infected through the bites of ticks, by contact with a patient with CCHF, or by contact with blood or tissues from viremic livestock. Microvascular instability and impaired hemostasis are the hallmarks of the infection. Infection in human begins with nonspecific febrile symptoms, but may progress to a serious hemorrhagic syndrome with high mortality rates. Enzyme-linked immunoassay (ELISA) and polymerase chain reaction (PCR) are the most used and specific tests for the diagnosis. The mainstay of treatment is supportive. Although definitive studies are not available, ribavirin is suggested to be effective especially at the earlier phase of the infection. Uses of universal protective measures are the best way to avoid the infection. In this review, all aspects of CCHF are overviewed in light of the current literature.     

Dengue viral infections; pathogenesis and epidemiology

Dengue viral infections affect up to 100 million individuals per year. Dengue haemorrhagic fever is a clinical form of disease characterised by intravascular fluid loss. There has been a marked increase in the incidence of this form of the disease over the last few decades, associated with significant mortality, particularly in the paediatric population. A number of theories relating to the pathogenesis of dengue haemorrhagic fever exist that have evolved from the analysis of the epidemiology of this disease. Virological and immunopathological factors are both important but the exact mechanisms for the disease are unknown.     

Climate-based models for understanding and forecasting dengue epidemics

Background

Dengue dynamics are driven by complex interactions between human-hosts, mosquito-vectors and viruses that are influenced by environmental and climatic factors. The objectives of this study were to analyze and model the relationships between climate, Aedes aegypti vectors and dengue outbreaks in Noumea (New Caledonia), and to provide an early warning system.

Methodology/Principal Findings

Epidemiological and meteorological data were analyzed from 1971 to 2010 in Noumea. Entomological surveillance indices were available from March 2000 to December 2009. During epidemic years, the distribution of dengue cases was highly seasonal. The epidemic peak (March–April) lagged the warmest temperature by 1–2 months and was in phase with maximum precipitations, relative humidity and entomological indices. Significant inter-annual correlations were observed between the risk of outbreak and summertime temperature, precipitations or relative humidity but not ENSO. Climate-based multivariate non-linear models were developed to estimate the yearly risk of dengue outbreak in Noumea. The best explicative meteorological variables were the number of days with maximal temperature exceeding 32°C during January–February–March and the number of days with maximal relative humidity exceeding 95% during January. The best predictive variables were the maximal temperature in December and maximal relative humidity during October–November–December of the previous year. For a probability of dengue outbreak above 65% in leave-one-out cross validation, the explicative model predicted 94% of the epidemic years and 79% of the non epidemic years, and the predictive model 79% and 65%, respectively.

Conclusions/Significance

The epidemic dynamics of dengue in Noumea were essentially driven by climate during the last forty years. Specific conditions based on maximal temperature and relative humidity thresholds were determinant in outbreaks occurrence. Their persistence was also crucial. An operational model that will enable health authorities to anticipate the outbreak risk was successfully developed. Similar models may be developed to improve dengue management in other countries.     

The feasibility of forecasting influenza epidemics in Cuba.

A large influenza epidemic took place in Havana during the winter of 1988. The epidemiologic surveillance unit of the Pedro Kourí Institute of Tropical Medicine detected the beginning of the epidemic wave. The Rvachev-Baroyan mathematical model of the geographic spread of an epidemic was used to forecast this epidemic under routine conditions of the public health system. The expected number of individuals who would attend outpatient services, because of influenza-like illness, was calculated and communicated to the health authorities within enough time to permit the introduction of available control measures. The approximate date of the epidemic peak, the daily expected number of individuals attending medical services, and the approximate time of the end of the epidemic wave were estimated. The prediction error was 12%. The model was sufficiently accurate to warrant its use as a practical forecasting tool in the Cuban public health system.     

Dengue haemorrhagic fever in children: ten years of clinical experience

In Bucaramanga, Colombia, dengue haemorrhagic fever (DHF) has become endemo-epidemic since 1992. A cross-sectional study covering a period of 10 years (February, 1992 to February, 2002) was undertaken in children under 13 years of age hospitalized at the University Hospital. Observations were recorded on the clinical features, laboratory tests and the natural development of the disease. A total of 763 patients were examined, of whom 617 were classified as having DHF according to the WHO criteria (9.1% Grade I, 61.5% Grade II, 21.7% Grade III and 7.5% Grade IV). One hundred forty six patients could not be classified. The highest incidence took place in 1997, 1998 and 2001. Seventy four per cent of patients came from the metropolitan area of Bucaramanga; 48% were males; 0.3%, newborns; 11.8%, infants; 23%, pre-school children, and 64.9%, school children. The most important clinical features were fever and haemorrhagic manifestations (100%); vomiting (60%); abdominal pain (57%); headache (50%); osteomyalgia (40.8%); hepatomegaly (33%), and macular rash (29%). Among the haemorrhagic manifestations we found petechiae (56%); positive tourniquet test (35%); gastrointestinal bleeding (34%), and epistaxis (32%). Serous effusion was found in 17.7% of cases. Alarm signs of shock were found in 29%. Fifty two per cent had leucopenia and 37.3% atypic lymphocytes. Among other unusual manifestations were hepatitis, encephalopathy, alithiasic cholecystitis, acute renal failure, haemophagocytic syndrome and coinfections. Of the 617 cases, 12 died (1.5%).     

Q fever epidemiology and pathogenesis

The lungs are a port of entry and primary infectious focus of Coxiella burnetii, the obligate intracellular contagium of the worldwide zoonosis Q fever. The infectious process and immune response are characterised by studies in cell culture and animal systems. Following endocytosis, replication exclusively occurs in the phagolysosome. Several potential virulence factors are described.     

Coagulation abnormalities in Dengue fever infection: A systematic review and meta-analysis

BackgroundCoagulation mechanisms are reported to be affected in dengue illness and evidenced by prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT). The main aim of this systematic review and meta-analysis is to determine the magnitude of coagulation abnormalities among patients with dengue fever infection.MethodThis systematic review and meta-analysis were conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The Joana Brigg’s Institute (JBI) critical appraisal checklist was used for quality appraisal. STATA version 11 software was used for meta-analysis. The magnitude of coagulation abnormalities among dengue fever patients was determined by using a random-effects model. Subgroup and sensitivity analysis were performed to investigate the possible source of heterogeneity. Egger weighted regression tests were used to check the presence of publication bias among the included articles.ResultForty-two studies with a total of 12,221 dengue fever patients were eligible for meta-analysis in this study. Of which 22, 15, and 26 studies were used to determine the magnitude of prolonged APTT, PT, and thrombocytopenia, respectively. The magnitude of prolonged APTT and PT among patients with dengue fever infection were 42.91% (95% CI: 30.95, 54.87) I² = 99.1% and 16.48% (95% CI: 10.95, 22.01) I² = 97.0%, respectively. Besides, the magnitude of thrombocytopenia among dengue fever patients was 70.29% (95% CI: 62.69, 77.89) I² = 99.3%. The magnitude of prolonged APTT in children and adults was 51.21% (95% CI: 24.54, 77.89) and 44.89% (95% CI: 28.32, 61.45), respectively. Similarly, the overall magnitude of prolonged PT in children and adults were 13.40% (95% CI: 6.09, 20.71) and 18.73% (95% CI: 7.49, 29.96), respectively.ConclusionThe result of this study showed that there is a high magnitude of prolonged APTT and PT in dengue fever patients. Therefore, screening and early correction of coagulation abnormalities may be helpful to reduce further complications in those patients.     

Molecular epidemiology of rabies in Thailand.

For the purpose of making clear the dynamics of rabies viruses that are prevalent among dogs in Asia, especially Thailand, nucleoprotein (N) genes of isolates derived from Thailand were partially sequenced, and a phylogenetic analysis was performed on the basis of the sequencing data. Firstly, all 27 isolates from Thailand belonged to one group that was distantly related to an isolate from China and was separated into at least six lineages. On the other hand, the isolate from Japan was related to viruses from the Arctic. Secondly, in order to analyze the diversity of the N gene more conveniently, restriction fragment length polymorphism (RFLP) analysis was performed on the N gene of 27 isolates from Thailand. The RFLP analysis could distinguish the lineages of each isolate, and the lineages of additional 34 isolates were deduced by this method. On examination of the geographical distribution of the six lineages, based on the results of phylogenetic and RFLP analyses, it was clear that infection cycles of the rabies virus in Thailand have tended to be maintained endemically.