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[Clinical observation of 15 Thai children with dengue hemorrhagic fever].

Fifteen Thai children, diagnosed with dengue hemorrhagic fever and admitted to the Children's Hospital in Bangkok, were studied. All cases were serologically proved to be secondary dengue infections. The clinical signs and symptoms in the first few days of the acute febrile phase were similar to those observed in cases with classical dengue fever, and included continuously high fever, headache, muscle pain, nausea, vomiting and abdominal pain, etc. In the laboratory findings we noted hypoalbuminemia and mild elevation of the GOT and GPT. The hemogram showed an increasing atypical lymphocyte count during the acute febrile period. Prolongations of the partial thromboplastin time and thrombin time were also found, especially in the severe shock cases. All patients had varying degrees of hepatomegaly and pleural effusion from their chest x-rays accompanied by a rapid increase in the hematocrit of more than 20% and a fall in the platelet count to less than 100000/microliters. During the plasma leakage period the patients easily developed shock, even leading to death, unless adequate fluid supplies were given. This is also the major pathophysiological difference between dengue hemorrhagic fever and classical dengue fever. Although some studies concerning the pathogenesis of dengue hemorrhagic fever have been reported, but the exact mechanisms need further investigation.

Adolescent↗

Dengue serologic survey of schoolchildren in Rio de Janeiro, Brazil, in 1986 and 1987.

Two major epidemic waves of dengue 1 occurred in Rio de Janeiro, Brazil, in 1986 and 1987. This article reports the results of a survey of Rio schoolchildren who were tested serologically for antibodies to dengue 1 before and after the second major epidemic wave. The highest percentages of positive subjects were found in districts with relatively poor socioeconomic conditions and mosquito control problems. It also appears likely that the estimated number of dengue cases occurring in 1986-1987 was substantially below the number that actually occurred. In addition, because of this exposure to dengue 1, Rio de Janeiro now runs the risk of dengue hemorrhagic fever/dengue shock syndrome occurring should another dengue serotype be introduced within the next few years.

Adolescent↗

[Antigen signature analysis of dengue-2 viruses strains in Hainan China].

In this paper, we try to define the extent of antigenic variation between dengue-2 viruses from Hainan province, which had been isolated over a period of 3 years (1985-1987). The dengue-2 viruses were compared with the prototype New Guinea B strain and were subjected to antigen signature analysis. Eight strains of dengue-2 virus were analyzed by three monoclonal antibodies: flavivirus group, subcomplex dengue-2 type-specific reactive epitopes, over a range of antigen concentration. Five out of eight dengue-2 virus strains showed them to be antigenically homogeneous, and the remaining three strains showed them to be heterogeneous. Signature analysis provides a rapid and simple means to different strains derived from different sources, thus permit monitoring changes or introductions of hew dengue virus populations in certain geographic region.

Antibodies, Monoclonal↗

Dengue in Puerto Rico: clinical manifestations and management from 1960's to 1987.

Dengue is a viral disease transmitted by the Aedes aegypti mosquito. It is endemic in Puerto Rico and the Caribbean with periodic epidemics occurring at varying intervals. There are three dengue serotypes present in Puerto Rico, at the present time. The clinical manifestations of dengue in Puerto Rico are presented from a historical perspective. Dengue in Puerto Rico has evolved from a clinically mild illness in the 1960's to a devastating disease with hemorrhagic manifestations in the 1980's and dengue shock syndrome in 1987. The approach to clinical diagnosis and management is presented with emphasis on early recognition, performance of tourniquet test, serial hematocrits and aggressive intravenous fluid replacement with crystalloids of colloids in DSS. The best way to treat dengue is eliminating the vector, therefore, prevention.

Dengue↗

Serological evidence of dengue virus activity in children on the Northern Leeward Islands (Netherlands Antilles).

An arbovirus serologic survey of school children on the Northern Leeward Islands (Saba, St. Eustatius and St. Maarten) using haemagglutination inhibition (HI) detected a high proportion of reactors to dengue types 1,2, and 3. Analysis in relation to age showed an increasing proportion to be positive with increasing age. The results of an all-age survey on St. Eustatius 1970 led to the hypothesis of possible dengue serotype 1 activity on St. Eustatius around 1900, whilst it is thought that dengue type 2 was endemic at other times. In view of the continuous high endemic dengue activity the (re)-appearance of dengue serotype 1 next to type 2 and 3 may be the prelude to the occurrence of the dengue shock syndrome.

Adolescent↗

Changes in dengue and Japanese encephalitis (JE) antibody after JE vaccination.

Serological studies before and after Japanese encephalitis (JE) vaccination were made on subjects of various ethnic groups with or without dengue and/or JE antibodies. In these subjects dengue and JE hemagglutination-inhibition (HI) and neutralization (N) antibodies were measured. Seroconversion to JE was observed in about 45% of the subjects by the HI test and 63% by the N test, whereas seroconversion to dengue with only 4-fold increase in titer after vaccination was detected in 14% by the HI test and in a single case (3%) by the N test. The presence of JE and/or dengue antibody in the prevaccination sera did not significantly influence the seroconversion rates of JE-HI and N-antibodies after vaccination. Moreover the seroconversion rate did not seem to vary markedly in different ethnic groups, although tendencies for subjects from Southeast Asia to have dengue antibodies and Japanese people to have JE antibodies were demonstrated. The presence of dengue N-antibodies in the prevaccination sera did not significantly influence the geometrical mean titer of postvaccination JE-N antibody. Thus the antibody response to JE vaccination was fairly specific to JE, and no marked secondary response was observed.

Adult↗

Framework for application of geographic information system to the monitoring of dengue vectors.

In a successful management program of dengue vectors, not only health education, source reduction or insecticide application should be conducted, but all basic information should also be manipulated properly and efficiently. This information includes the surveys of species, dispersal and dynamics of vectors, as well as the detection of breeding sources, and the records of dengue cases and epidemic periods. Most of the above information expressed as regionalized variables always varies spatially and/or temporally. However, due to the deficiency of topological information, the conventional database management system cannot efficiently analyze those dengue related data. Thus, we have applied the geographic information system (GIS) to the monitoring of dengue vectors. The purpose of this report is to introduce the basic concepts of GIS, to describe the framework of the prototype dengue vector monitoring system which was built using data collected from the Sanmin area, Kaoshiung city, Taiwan, and to indicate the possibility of using this system to manipulate spatially correlated data and support decision making in the control of dengue disease.

Animals↗

A rapid membrane based immunobinding assay for the detection of dengue virus in tissue culture.

A rapid, simple dot immunoassay (DOTIA) was developed and evaluated for the detection of dengue-1 viral antigen in infected Aedes albopictus C6/36 cells. Dengue virus infected cells were solubilize in sodium dodecyl sulfate (SDS) and the lysate was pressure filtered through a hydrophobic polyvinylidene difluoride (PVDF) membrane. Viral antigen retained in the membrane was detected by a dengue-1 type specific monoclonal antibody and a peroxidase-labeled second antibody. Addition of tetramethylbenzidene (TMB) substrate produced a blue-colored precipitate which allowed for quantitation of viral antigen using a portable white light reflectance densitometer. Estimate of viral infectivity in the cell lysates tested by the DOTIA was determined by standard plaque assays and the results indicated an excellent correlation between these two methods. The dot immunoassay detected dengue viral antigen in infected C6/36 cells between days three and eight post-inoculation, depending on the titer of the inoculum. An infectivity titer of at least 10(3) plaque forming units (PFU) per ml was required to detect antigen by the DOTIA. The DOTIA also detected viral antigen in cells inoculated with twelve acute sera from known dengue-1 virus infected patients, thus demonstrating that this technique is useful for the detection and identification of dengue-1 virus from clinical specimens.

Aedes↗

Protocol for out-patient management of dengue illness in young adults.

A prospective study on the practicality of an out-patient management protocol for dengue infection in adults was carried out during a 2-month period. Doctors were requested to follow the protocol and assessment was done on the patients' outcome, the admission rate, and the compliance to the protocol by doctors and patients. One hundred and sixty-two patients (mean age 27.3 years) were clinically diagnosed to have dengue illness. Among them, 82.7% had dengue fever (DF); 13.0% had dengue haemorrhagic fever (DHF) and 4.3% had dengue shock syndrome (DSS). Dengue aetiology was confirmed in 69.4% of the DF group and 85.7% of the DHF and DSS groups. There were no deaths among the 162 patients. The admission rate was 43.8%. A high compliance rate of 86.4% by the doctors and a low patient default rate of 16.4% showed that the protocol was practical.

Adolescent↗

[The risk of dengue transmission: a space for stratification].

The emergence of dengue fever as a public health problem in the Americas is increasing. Its rapid spread in the region and the geographical dissemination of dengue infection has not been followed by a corresponding input of financial, human and technical resources necessary to control dengue fever epidemics. This situation compelled to the analysis of dengue transmission in Mexico with the objective of designing a strategy of dengue fever surveillance based on the stratification of transmission risks taking into account geographical variables like climate, rain precipitation, mean annual temperature and altitude, as well as socio-demographical variables like population density and socio-economic level. This strategy will permit the efficient use of the scant resources available for control, although the impact of dengue transmission is yet to be evaluated.

Adolescent↗

Genetic differentiation of Aedes aegypti, the vector of dengue virus in French Polynesia.

In recent years the incidence of dengue fever epidemics has increased and transmission has tended to be established over a geographically expanding area, including French Polynesia. An increase in air transportation contributes to the diffusion of the dengue virus from Southeast Asia, a region considered to be a hyperendemic dengue zone, to the Pacific region. Presently, little is known about the role of the vector (Aedes aegypti) in the diffusion of the dengue fever virus. A study on the genetic structure of vector populations was conducted using allozyme polymorphism. This study showed a low level of genetic exchange between mosquito populations on different islands. It is concluded that the occurrence of dengue hemorrhagic fever in French Polynesia during the last few years was likely due to the dispersal of the dengue virus via viremic people rather than via infected vectors.

Aedes↗

[Aedes aegypti in French Guiana. Some aspects of history, general ecology and vertical transmission of the dengue virus].

Aedes aegypti is suspected to be present in the country since the late 18th century, and was responsible of urban yellow fever epidemics in the last century. This mosquito was identified for the first time in French Guiana in 1902. More recently, in 1940, an eradication campaign started and Aedes aegypti was eradicated between 1950 and 1963, date of the reinfestation. During the past 30 years, some dengue outbreaks occurred every 2 to 6 years, and the first dengue haemorrhagic fever epidemic spread over the country in 1992. Actually, Ae. aegypti is distributed almost all inhabited areas of French Guiana: in the towns, villages, smaller human settlements, and was also found in a wild area. The most frequent Ae. aegypti breeding-sources are the outside discarded small containers, other less frequent breeding-sites are the outside flower pots and the outside big containers. The type of breeding-source significantly influences the duration of larval and pupal development. In French Guiana, Ae. aegypti is the only vector of dengue. The vertical transmission of dengue viruses under field conditions was demonstrated. Dengue is thus endemic in the country and has almost the same distribution as Ae. aegypti, with most probably the same possibilities of extension. Ae. aegypti can be considered not only as vector and an amplificator of dengue in French Guiana, but also as a reservoir, even if occasional.

Aedes↗

[Re-emergence of dengue in Panama].

The dengue surveillance system in Panama during the 1994 and 1995 epidemics shows the following results: In 1994 we registered 793 dengue cases and a year after 3,083 dengue cases, with three dengue haemorrhagic cases (one death). To estimate the accumulated incidence rates in 1994-1995 period, we consolidated the cases. The highest risk of dengue and the highest dengue haemorrhagic propension were observed in: West Panama (709.49 per 100,000 persons), Los Santos (405.74 per 100,000 persons), Herrera (337.62 per 100,000), Metropolitana (126.98 per 100,000) and San Miguelito (125.10 per 100,000 persons).

Adult↗

[Dengue, arbovirus and migrations in the Indian Ocean].

An arbovirus requires a competent haematophagous arthropod for transmission from one vertebrate to another susceptible host. Air transportations allow quick transfers from place to place and the diffusion of potential vectors or infectious hosts. The merchandise transportation by containers allowed the diffusion of Ae. albopictus from Asia through Africa and America. Emerging arbovirusis may occur in zones where they do not exist. Dengue which originally was located in southeastern Asia, is the most important arbovirusis in the world. The occurrence of dengue haemorrhagic fever (DHF) in Asia and America, mostly in urban areas, increased the global concern about dengue. Likewise, cases of DHF are not reported in Africa and in the Indian Ocean southwestern islands. The principal vector of dengue, Aedes aegypti, was present during the dengue 1 outbreak in Comoros, in 1993. In the other islands, only few specimens of Ae. aegypti are observed, and described mostly as none anthropophilic forms. The role of Ae. albopictus as vector of dengue was suspected and reported during outbreaks in Seychelles and Réunion island in 1977-1978. Yellow fever, present in Africa mostly in restricted areas, is absent in Asia. Japanese encephalitis considered as an emerging disease in India could expand through the islands. Rift valley fever, with periodic epizootics in domestic ungulates in Africa, was described as a new disease in Madagascar in 1990-1991. Crimean-Congo haemorrhagic fever is also present in Madagascar. Humans can be infected by vector bite or by handling infectious animal products. The distribution of other viruses (West Nile, Sindbis, Wesselsbron or Chikungunya) is discussed.

Aedes↗

[Cutaneo-mucous manifestations of dengue].

OBJECTIVES: To describe muco-cutaneous manifestations of dengue fever, assessing their incidence and histopathological aspects. PATIENTS AND METHODS: During a dengue 2 epidemic, occurring in Guadeloupe in 1994, all patients admitted with a confirmed diagnostic of dengue fever were assessed for dermatological changes by 2 clinicians; 5 patients underwent skin biopsy with immuno-fluorescence staining. RESULTS: Among 39 adult inpatients (Sex ratio 1.1, medium age 41 years) none presented a severe form of the disease, whereas 18/39 (46 p. 100) had some muco-cutaneous changes, associating rash (13 cases (33 p. 100)), mucous membranes involvement (7 cases (18 p. 100)), or minor haemorrhages (6 cases (15 p. 100)). The rash appeared macular, discrete, itching, troncular with peripheral extension, rather than maculo-papular (morbiliform) as usually described. Apart from cases which minor haemorrhagic changes, significatively associated with marked thrombocytopenia (medium 37 x 10(9)/1), dengue cases either with or without muco-cutaneous changes had similar clinical (duration, severity) or biological (neutro-lympho-thrombocytopenia, transaminases) features, and evolution. Histological changes appeared non specific (minor lymphocytic dermal vasculitis, non contributive immuno-fluorescence). DISCUSSION: Clinical and histological features of the rash are unspecific and inconstant: they do not allow an easy and accurate diagnosis. Complete clinical, epidemiological (very recent travel in endemic areas) or biological data should be collected, and early virological or later serological confirmation is needed. As well as travel facilities are growing, the dengue area is extending: dengue fever should therefore be considered in every traveller with fever and rash.

Adolescent↗

Autoimmune pathogenesis in dengue virus infection.

The pathogenic mechanisms of dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) caused by dengue virus (DV) infection remain unresolved. Patients with DHF/DSS are characterized by several manifestations, including severe thrombocytopenia, vascular leakage, and hepatomegaly. In addition to the effect of virus load and virus variation, abnormal immune responses of the host after DV infection may also account for the progression of DHF/DSS. Actually, viral autoimmunity is involved in the pathogenesis of numerous viral infections, such as human immunodeficiency virus, human hepatitis C virus, human cytomegalovirus, herpes simplex virus, Epstein- Barr virus, and DV. In this review, we discuss the implications of autoimmunity in dengue pathogenesis. Antibodies directed against DV nonstructural protein 1 (NS1) showed cross-reactivity with human platelets and endothelial cells, which lead to platelet and endothelial cell damage and inflammatory activation. Based on these findings, we hypothesize that anti-DV NS1 is involved in the pathogenesis of DF and DHF/DSS, and this may provide important information in dengue vaccine development.

Antibodies, Viral↗

Molecular evolution of dengue type 2 virus in Thailand.

Dengue is a mosquito-borne viral infection that in recent years has become a major international public health concern. Dengue hemorrhagic fever (DHF), first recognized in Southeast Asia in the 1950s, is today a leading cause of childhood death in many countries. The pathogenesis of this illness is poorly understood, mainly because there are no laboratory or animal models of disease. We have studied the genetic relationships of dengue viruses of serotype 2, one of four antigenically distinct dengue virus groups, to determine if viruses obtained from cases of less severe dengue fever (DF) have distinct evolutionary origins from those obtained from DHF cases. A very large number (73) of virus samples from patients with DF or DHF in two locations in Thailand (Bangkok and Kamphaeng Phet) were compared by sequence analysis of 240 nucleotides from the envelope/nonstructural protein 1 (E/NS1) gene junction of the viral genome. Phylogenetic trees generated with these data have been shown to reflect long-term evolutionary relationships among strains. The results suggest that 1) many different virus variants may circulate simultaneously in Thailand, thus reflecting the quasispecies nature of these RNA viruses, in spite of population immunity; 2) viruses belonging to two previously distinct genotypic groups have been isolated from both DF and DHF cases, supporting the view that they arose from a common progenitor and share the potential to cause severe disease; and 3) viruses associated with the potential to cause DHF segregate into what is now one, large genotypic group and they have evolved independently in Southeast Asia for some time.

Dengue↗

Mechanisms of hemorrhage in dengue without circulatory collapse.

To characterize the molecular basis for the hemostatic defects of dengue infections, a study was conducted in Bangkok, Thailand. Febrile children (n = 68) hospitalized with suspected dengue were enrolled before their clinical syndromes were classified as either dengue fever (DF) or dengue hemorrhagic fever (DHF). Hospital course and outcome were recorded; blood was obtained during the febrile illness (S1), after defervescence (S2), and 1 month after onset of disease (S4). Patients were classified as DF (n = 21) and DHF grades 1, 2, and 3; (DHF1, n = 8; DHF2, n = 30; and DHF3, n = 9). All had marked thrombocytopenia. Bleeding scores were assigned on the basis of bleeding site. Although there was no correlation between bleeding scores and pleural effusion index (a measure of vascular leakage) or bleeding scores and platelet counts, there was a correlation between pleural effusion index and platelet counts. Bleeding scores did not correlate with hemostatic data. Activated partial thromboplastin time was prolonged, with trends toward decreased fibrinogen and increased levels of prothrombin fragment F1.2 in the acute-phase samples. However, no factor level was dramatically decreased. We conclude that most patients with DF or DHF, even without overt hemorrhage, have consumptive coagulopathy. Nevertheless, hemorrhage in dengue without circulatory collapse is most likely due to activation of platelets rather than coagulopathy, which is well compensated. Our data suggest that vascular alteration may be the principal factor involved in the association of thrombocytopenia and hemorrhage with disease severity.

Adolescent↗