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PubMed1998

Dengue: a review.

Millions of dengue cases occur worldwide each year. Most recently, an outbreak occurred in Texas. Though usually a nonspecific febrile illness that resolves with supportive therapy, the clinical spectrum ranges from asymptomatic to severe hemorrhage and sudden fatal shock. The potential exists for the introduction of dengue virus into other parts of the United States, and for secondary transmission in areas with vector mosquitoes, because of increased travel to and from regions of the Americas where dengue is endemic. The discovery of Aedes (Ae) albopictus strains adapted to temperate conditions makes this threat much greater. With global warming, a more rapid distribution of the Aedes species may occur, moving northward, encompassing larger population centers and leading to increased vectorborne diseases. Control of dengue currently requires control of the principal vector mosquitoes. Vaccine development continues, but at present the only way to avoid dengue in an area where it is endemic or epidemic is to use repellents and mosquito barriers. Lifesaving intervention and management of a patient with dengue and its complications depend upon a complete history, to include travel and physical examination with a high level of suspicion. Physicians and other health care providers should learn to recognize this disease. Once a person is infected, the key to survival is early diagnosis and appropriate treatment for the severe, life-threatening complications of dengue hemorrhagic fever and dengue shock syndrome.

Aedes↗
PubMed1998

Incidence of dengue fever in relation to climatic factors in Ludhiana, Punjab.

An outbreak of dengue fever occurred in Ludhiana in 1996 and 1997. A total of 505 patients who attended the hospital attached to Dayanand Medical College, Ludhiana were clinically diagnosed to have dengue fever. Of these, 460 cases were noticed between October and December 1996 while during 1997 only 45 dengue fever cases were observed. Serological examination using dengue IgG and IgM blot was performed with single serum samples of 189 patients. Of these, 129 serum samples were detected positive for anti dengue antibodies. Twenty eight patients died in the dengue epidemic, 12 of whom suffered from dengue haemorrhagic fever (DHF) and six with dengue shock syndrome (DSS). Male patients outnumbered the female patients. Seasonal and cyclic pattern of the disease incidence was observed.

Adolescent↗
PubMedDate not supplied

Dengue activity in Puerto Rico during an interepidemic period (1995-1997).

From 1995 to 1997 dengue was reported in Puerto Rico at an average annual rate of 1.75/1,000 population, compared to 6.73 in 1994, an epidemic year. Dengue virus serotypes 1 (DEN-1), -2, and -4 were isolated each year, with DEN-2 predominating in 1995 and 1996, and DEN-4 in 1997. From 1995 through 1997 incidence was highest (0.61-0.77/1,000) in persons under 30 years of age; males and females were equally affected. Among positive cases, 28.3% to 37.9% were hospitalized; 28.9% to 35.2% had hemorrhagic manifestations; at least 1.1% to 1.6% fulfilled the criteria for dengue hemorrhagic fever/dengue shock syndrome; and 0.2% to 0.3% died. Neither hurricane preparations (1995) nor widespread floods (1996) seem to have affected dengue incidence. Most municipalities with the highest laboratory-diagnosed dengue rates in 1995 were in the eastern foothills of the central mountains, an area relatively spared by the 1994 epidemic. In the next two years, at least half of the municipalities with the highest laboratory-diagnosed dengue rates were in the west. The most intense municipal outbreak of this period (DEN-2, Villalba, 1995, rate of 11.67/1,000) is described to highlight the importance of local conditions and epidemiologic history in determining the risk of dengue.

Adolescent↗
PubMed1999

Impaired T cell proliferation in acute dengue infection.

Decreased proliferative responses to mitogens and recall Ags have been observed in PBMC obtained during several acute human viral infections. To determine whether cell-mediated responses are altered during acute dengue infection, we examined the proliferative responses of PBMC from children enrolled in a prospective study of dengue infections in Thailand. All responses of PBMC during acute illness were compared with the same patients' PBMC obtained at least 6 mo after their infection. Proliferative responses to PHA, anti-CD3, tetanus toxoid, and dengue Ags were decreased significantly in PBMC obtained during the acute infection. The proliferative responses to PHA were restored by the addition of gamma-irradiated autologous convalescent or allogeneic PBMC. Cell contact with the irradiated PBMC was necessary to restore proliferation. Non-T cells from the acute PBMC of dengue patients did not support proliferation of T cells from control donors in response to PHA, but T cells from the PBMC of patients with acute dengue proliferated if accessory cells from a control donor were present. Addition of anti-CD28 Abs restored anti-CD3-induced proliferation of the PBMC of some patients. The percentage of monocytes was reduced in the acute sample of PBMC of the dengue patients. Addition of IL-2 or IL-7, but not IL-4 or IL-12, also restored proliferation of acute PBMC stimulated with anti-CD3. The results demonstrate that both quantitative and qualitative defects in the accessory cell population during acute dengue illness result in a depression of in vitro T cell proliferation.

Acute Disease↗
PubMed2003

Dengue fever in the Western Hemisphere.

Dengue virus, an arthropod-borne viral agent, causes two distinct diseases: classic dengue fever (DF) and dengue hemorrhagic fever (DHF). There are four dengue virus serotypes: DEN-1, DEN-2, DEN-3, and DEN-4. Although infection with dengue stimulates immunologic response to a serotype, there is no cross-immunity conferred. Hence, a person can potentially be infected with each serotype during his or her lifetime. An infected female Aedes mosquito transmits the virus from person to person while feeding. The disease, now endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, Southeast Asia, and Western Pacific, is spreading to new areas and causing explosive outbreaks. Because of the major impact on lives and local economies epidemics produce, rapid detection of dengue infection has become an important public health research issue. Recently developed serological procedures to detect dengue infections have shown great potential for field use.

Aedes↗
PubMed2004

Imported Dengue fever presenting with febrile diarrhoea: report of two cases.

Dengue fever is a significant health problem in most tropical regions and increasingly observed among travelers returning from tropical countries. Clinical presentation might not be typical in patients from non-endemic areas. We report 2 patients returning from South-East Asia with proven Dengue-virus infection initially presenting with "febrile diarrhea" followed by hemorrhagic skin lesions during hospitalization. Blood and stool examination remained negative for bacteria, parasites and plasmodia. Dengue fever was suspected early, mainly due to the typical course of the complete blood cell count with thrombocytopenia (19 x 10(9)/L and 86 x 10(9)/L) and leucopenia (3 x 10(9)/L and 1.8 x 10(9)/L). Both patients had a benign clinical course, which still required intensive care monitoring. Platelet inhibitors and NSAIDs should be stopped when Dengue infection (Dengue fever and Dengue hemorrhagic fever) is suspected in order to minimalize the risk of bleeding. Although presentation of the disease might not always be typical, Dengue infection has to be considered early in the course of disease by taking an in-depth history and profound physical examination.

Adult↗
PubMed2005

Is dengue severity related to nutritional status?

A retrospective review of dengue patients admitted to Queen Sirikit National Institute of Child Health (previously known as Children's Hospital) from 1995 to 1999 revealed 4,532 confirmed cases of dengue infection; 80.9% were dengue hemorrhagic fever (DHF) and 19.1% were dengue fever cases (DF). Among the DHF patients; 30.6% had shock. The majority of them, 66.6%, had a normal nutritional status, while 9.3% were malnourished and 24.2% had obesity as classified by weight for age. Compared with control patients with other diagnoses (excluding HIV/AIDS patients), malnourished children had a lower risk of contracting dengue infection (odds ratio = 0.48, 95% Cl = 0.39-0.60, p = 0.000) while obese children had a greater risk of infection with dengue viruses (odds ratio = 1.96, 95% Cl = 1.55-2.5, p = 0.000). The clinical signs, symptoms and laboratory findings of dengue were almost the same among the 3 groups of malnourished, normal, and obese patients. The minor differences observed were that in obese children liver enlargement was found less often; maculopapular/convalescence rash and elevations of alanine aminotransferase were found more often. Malnourished patients had a higher risk of developing shock (37.8%) than normal (29.9%) and obese patients (30.2%) (p = 0.000). Obese patients had more unusual presentations: encephalopathy (1.3%) and associated infections (4.8%), than normal (0.5% and 2.7%) and malnourished patients (1.2% and 3.1%). Complications of fluid overload were found more in obese patients (6.5%) compared to normal (3.2%) and malnourished patients (2.1%) (p = 0.000). The case-fatality rates (CFR) in malnourished patients and obese patients were 0.5% and 0.4%, respectively, while in normal patients the CFR was 0.07%. Under and over nutrition DHF patients had either a greater risk of shock or unusual presentations and complications, which can lead to severe disease or complications and probably a higher CFR.

Child↗
PubMed1995

Indirect immunofluorescence for serological diagnosis of dengue virus infections in Swedish patients.

BACKGROUND: An increasing number of travellers to dengue endemic areas has emphasized the need for an easy and reliable serological test for diagnosis of dengue virus infections. OBJECTIVES: Indirect immunofluorescence (IF) and hemagglutination inhibition (HI) tests were compared for serological diagnosis of dengue fever (DF). STUDY DESIGN: Sera from patients with clinical symptoms compatible with DF and a travel history comprising dengue endemic areas were included in the study. Paired serum samples from 24 patients and single convalescent sera from five patients were investigated by HI and IF. Paired sera from ten patients were investigated by plaque reduction neutralization test (PRNT) in order to confirm the HI/IF results. RESULTS: In twelve of the patients with paired sera a sero-conversion or a significant (4-fold) antibody titer rise was seen with HI as well as with IF. Four patients with stationary HI-titers had significant titer rises when investigated by IF. Stationary or declining HI- and IF-titers were found in the remaining eight patients. The five single sera were antibody-positive by both methods. Investigation by PRNT of paired sera from ten patients confirmed the IF results. A total of 298 serum samples (paired sera or early convalescent samples) were investigated for dengue antibodies by IF. A sero-conversion, significant titer-rise or an IF-titer of 320 was generally seen 7-13 days post onset of disease. During the years 1991-1993 altogether 161 cases of dengue were diagnosed by IF in Swedish patients, a majority of which had travelled to Southeast Asia. CONCLUSION: Antibody detection by indirect IF proved to be at least as reliable as HI for diagnosis of dengue infections in Swedish patients. The specificity of the IF was ensured by testing the sera of ten patients for serotype specific neutralizing dengue antibodies.

Journal Article↗
PubMed1995

Semi-nested PCR using NS3 primers for the detection and typing of dengue viruses in clinical serum specimens.

BACKGROUND: More rapid, specific and sensitive tests for the laboratory diagnosis of dengue virus infections are needed. OBJECTIVE: To develop a semi-nested polymerase chain reaction (PCR) assay based on primers within the NS3 gene for the simultaneous detection and typing of dengue viruses in human sera. STUDY DESIGN: A first round of single-step reverse transcription-polymerase chain reaction (RT-PCR) was carried out with a pair of consensus primers, followed by a second round of semi-nested amplification using the upstream consensus primer and four type-specific down-stream primers. The sensitivity and specificity of the semi-nested PCR assay were determined using plaque- or TCID(50)-titrated virus-infected tissue culture fluid, and total RNA extracted from C6/36 cells infected with dengue and other flaviviruses, respectively. A retrospective study was performed on acute sera from thirteen patients with dengue (confirmed by virus isolation) employing semi-nested PCR in parallel with virus re-isolation and a single-step RT-PCR method for the typing of dengue viruses in human sera. RESULTS: The semi-nested PCR assay could detect up to 1 pfu of dengue virus, but not other flaviviruses. The semi-nested PCR and single-step RT-PCR assays correctly typed dengue viruses in twelve and five sera, respectively, whereas none of the sera was positive by virus re-isolation. CONCLUSIONS: This semi-nested PCR assay is a sensitive and specific tool for the detection and typing of dengue viruses from viremic human sera.

Journal Article↗
PubMed1997

Dengue: A Literature Review and Case Study of Travelers from the United States, 1986-1994.

Dengue fever is an acute, mosquito-transmitted viral disease characterized by fever, headache, arthralgia, myalgia, rash, nausea, and vomiting. Infections are caused by any of four virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4). The incidence of dengue is increasing in most tropical areas throughout the world (Fig. 1). Although dengue is not endemic in the continental United States, Hawaii, or Alaska, more than 500 laboratory-positive cases of introduced dengue were reported from 1977 through 1994 in U.S. residents who visited dengue-endemic areas throughout the world.1-4 In addition, two competent mosquito vectors (Aedes aegypti and Aedes albopictus) are found in the southeastern United States, and both could possibly transmit an introduced virus. In Hawaii, Ae. albopictus is the dominant mosquito on all islands; Ae. aegypti has only focal distribution on Molokai and the Kona coast of Hawaii. Economic, political, technologic, ecologic, and demographic changes have brought about the emergence of new microbial diseases, as well as an increase in the incidence of previously known infections. The increase in dengue activity in Asia, Africa, and the Americas represents a pandemic that is being facilitated by increased air travel; global urbanization; population growth; greater abundance of disposable, nondegradable containers that can serve as Aedes production sites; and lack of effective mosquito control programs.5,6 This report summarizes information about risk factors for severe disease, recent dengue outbreaks throughout the world, and cases of dengue virus infection in travelers who have been diagnosed on return to the United States.

Journal Article↗
PubMed2001

Activation of coagulation and fibrinolysis during dengue virus infection.

Dengue virus infection can induce mild dengue fever (DF) or severe dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) in human. The pathogenesis of hemorrhage in dengue virus infection is not fully understood. Since hemostasis depends on the balance between coagulation and fibrinolysis, alternation of some coagulation parameters (platelet count and activated partial thromoboplastin time, APTT) as well as fibrinolytic parameters (tissue plasminogen activator, tPA and plasminogen activator inhibitor-1, PAI-1) were compared in 8 DHF/DSS and 17 DF patients. Patients showed thrombocytopenia, APTT prolongation, and tPA increase in the acute stage of disease, indicating activation of coagulation and fibrinolysis. The activation of coagulation and fibrinolysis in DHF/DSS patients was much more severe than DF patients. In the convalescent stage, a rise of PAI-1 level and platelet count with concomitant decline of tPA level and APTT returned to normal in both DHF/DSS and DF patients. Therefore, the activation of coagulation and fibrinolysis during the acute stage of dengue virus infection is offset by the increase of platelet and PAI-1 during convalescent stage. Taken together, these results suggest that the degree of coagulation and fibrinolysis activation induced by dengue virus infection is associated with the disease severity.

Adolescent↗
PubMed2006

Dengue virus infection of human microvascular endothelial cells from different vascular beds promotes both common and specific functional changes.

Dengue shock syndrome (DSS), the major life threatening outcome of severe dengue disease, which occurs in some patients in the course of dengue infection, is the consequence of plasma leakage in the microvascular territories. Data from clinical and in vitro studies suggest that an inadequate immunological response is partly responsible for the pathophysiology of DSS, but few is known concerning the consequences of direct infection of endothelial cells by dengue virus per se. In this study, an attempt was made to study the response of two microvascular human cell lines originating, respectively, from liver and dermis to infection by a dengue type 2 virus, by analyzing the virus-induced modulation of functional markers. It is shown that the two microvascular cell lines exhibit both common and specific behaviors upon infection. In particular, LSEC and HMEC-1 replicate efficiently the low-passage virus and respond to infection by over-producing inflammatory mediators involved in the cross talk with circulating immune cells. However, direct infection modulates differently the cell surface expression of molecules critically involved in the interactions between endothelial and inflammatory cells. ICAM-1 and HLA-I are up regulated as a consequence of infection in LSEC whereas direct infection results in downregulation of ICAM-1 in HMEC-1. The present results show that infection of human microvascular cells by unadapted dengue virus results in both common and specific activation patterns depending likely on the tissue origin of the cells, thus suggesting that endothelia from different territories may contribute differently to the pathophysiological events in the course of dengue infection.

Dengue↗
PubMedDate not supplied

Dengue hemorrhagic fever: clinical manifestations and management.

Dengue virus infection may remain asymptomatic or manifest as nonspecific viral infection to life threatening dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). Patients with DHF/DSS have fever, hemorrhagic manifestations along with thrombocytopenia and hemoconcentration. Thrombocytopenia and hemoconcentration are distinguishing features between DHF/DSS and dengue fever (DF). Some patients with dengue fever may have significant bleed and mild thrombocytopenia but no hemoconcentration. These patients are labelled to have dengue fever with unusual bleeds. Laboratory findings in DHF/DSS include rising hematocrit, thrombocytopenia and transformed lymphocytes on peripheral smear. There may be increased transaminases, hyponatremia, transient increase in blood urea nitrogen and creatinine. In severe disease there may be lab evidence of dissemination intravascular coagulation. X-ray film of the chest may show pleural-effusion. Ultrasonogram of abdomen may detect thickened gall bladder wall with hepatomegaly and ascitis. In some patients there may be abnormality in electrocardiogram and echocardiogram. The diagnosis of DHF/DSS is based on typical clinical findings. For confirmation of dengue virus infection viral culture can be done on blood obtained from patients during early phase of illness. In later part of illness antibodies against dengue virus can be demonstrated by various techniques. The treatment of DF is symptomatic. For control of fever nonsteroidal anti-inflammatory drugs should be avoided. DHF/DSS are managed by intravenous fluid infusion with repeated monitoring of vital parameters and packed cell volume (PCV).

Acetaminophen↗
PubMed2001

Phylogenetic analysis of dengue-3 viruses prevalent in Guatemala during 1996-1998.

Dengue is an acute viral disease transmitted by the Aedes aegypti mosquito which is present in most tropical urban areas of the world. There are four antigenically distinct serotypes, designated dengue-1 (DEN-1), dengue-2 (DEN-2), dengue-3 (DEN-3) and dengue-4 virus (DEN-4). In this study, we determined the serotypes of dengue viruses isolated in Guatemala in 1995-1998, and found that DEN-3 viruses appeared in 1995 and became predominant in the following three years. We then sequenced cDNAs from fifteen DEN-3 isolates recovered during 1996-1998. From the nucleic acid sequences and previously determined DEN-3 sequences, a phylogenetic tree was constructed using the neighbor joining method. The tree indicated that all fifteen isolates and other DEN-3 viruses isolated in Sri Lanka, India, Samoa and Mozambique formed subtype III. More than two decades ago, DEN-3 virus was prevalent in the Caribbean, but the isolates obtained at that time belonged to subtype IV. Therefore, we concluded that the 1996-1998 dengue epidemic in Guatemala was caused by DEN-3 strains, imported from a tropical area of Asia or Africa or from a Pacific island.

DNA, Complementary↗
PubMed1981

Infection of young adult mice with dengue virus type 2.

Young adult female mice, five to six weeks old, were injected intraperitoneally with 2.5 x 10(6.3) LD50 of dengue-2 virus, New Guinea C strain. The mice were killed on day 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, and 35 respectively. By means of the immunofluorescent antibody technique, viral antigen appeared as irregular granules in the reticuloendothelial cells of liver, lymph nodes and spleen of infected mice on the first day after inoculation and then diminished. From the fifth to sixth day of infection dengue antigen appeared again as homogeneous staining in the cytoplasm of single or groups of mononuclear cells in the lymphatic sinuses only. Later, by the third week of infection, dengue antigen could be seen in the mononuclear cells located in the marginal zone of lymphoid follicle of the spleen, the pattern of staining changing to bright spherical granules. At the same time, the deposition of immune complexes (composed of dengue antigen, mouse gamma and beta 1C globulin) could be seen in the renal glomeruli of infected mice. Serum antibody to dengue virus was found at low levels, being maximal on the 14th day after infection. Dengue virus was not isolated from the sera or from the infected organs. Granulomatous inflammation developed in lymph nodes and liver of mice infected with dengue virus and in mice inoculated with normal mouse brain suspension. Proliferative glomerular lesion was observed on day 14 after inoculation without definite abnormal urine findings.

Animals↗
PubMed1985

Antibody-capture ELISA for detection of immunoglobulin M antibodies in sera from Japanese encephalitis and dengue hemorrhagic fever patients.

Immunoglobulin M (IgM) antibody titers in paired sera from 19 encephalitis and 44 dengue hemorrhagic fever (DHF) patients in Thailand and 42 Japanese encephalitis (JE) patients in Japan were measured by the antibody capture ELISA and applied to distinguish JE virus infection from dengue virus infection. Titer distribution and the ratio of the titers against JE and dengue antigens led to the following diagnostic criteria. The specimens can be considered as positive with JE when IgM-ELISA titer showed over 200 against JE and 4-fold or more higher than titers against any types of dengue antigens. The specimens can be considered as positive with dengue infection when IgM ELISA titer showed over 200 against one of the 4 types of dengue antigens and 4-fold or more higher than against JE antigen. Based on these criteria, 41 of 42 patients in Japan and 11 of 19 encephalitis patients in Thailand could be diagnosed as having JE virus infection while 2 of 19 encephalitis patients in Thailand and 26 of 44 DHF patients in Thailand could be diagnosed as having dengue virus infections.

Antibodies, Viral↗
PubMed2004

Dengue virus infection in travellers returning to Berlin, Germany: clinical, laboratory, and diagnostic aspects.

BACKGROUND: Dengue is a mosquito-borne viral infection endemic throughout the tropics and subtropics. The global prevalence of dengue has grown dramatically in recent years and it has been recognized as a potential hazard to tourists. OBJECTIVE: In this study, we analyzed the epidemiology, clinical manifestations, laboratory features and serological/virological results in a series of German travellers returning to Berlin with acute dengue virus infection. STUDY DESIGN: Laboratory-confirmed dengue virus infections among German travellers returning to Berlin were studied retrospectively during the period of 1993-2001. Seventy-one patients tested positive for dengue fever and were included in this study. RESULTS: The majority of patients (77.5%) contracted the disease in South Central and South East Asia. The most important clinical characteristics were fever and prostration (100%), headache, predominantly frontal or retroorbital (86%), arthralgia (79%), morbilliform rash (66%) and myalgia (48%). The most meaningful laboratory results were: marked leucopenia (72%), thrombocytopenia (70-89%), hyponatremia (41%) and increased hepatic enzymes ALAT (41%), ASAT (45%) and LDH (62%). Dengue virus infection was diagnosed by means of a matching clinico-epidemiological history and positivity of specific serology and/or virus isolation. Hemorrhagic phenomena appeared in 10 of the 71 patients (14%), out of which one was diagnosed with DHF according to WHO criteria. All patients recovered fully. CONCLUSION: Pretravel advice should be given to all travellers to dengue-endemic areas. DF must be included in the differential diagnosis of patients returning febrile from tropical areas.

Adolescent↗
PubMed2004

Dengue diagnosis, advances and challenges.

Dengue diagnosis was one of the topics discussed at the symposium 'The Global Threat of Dengue - Desperately Seeking Solutions' organized during the 10th International Congress of Infectious Diseases held in Singapore in 2002. In this paper, a review is presented focusing on the main advances, problems and challenges of dengue diagnosis.IgM capture ELISA, virus isolation in mosquito cell lines and live mosquitoes, dengue specific monoclonal antibodies and PCR have all represented major advances in dengue diagnosis. However, an appropriate rapid, early and accessible diagnostic method useful both for epidemiological surveillance and clinical diagnosis is still needed. Also, tools that suggest a prognosis allowing for better management are also needed. Finally, laboratory infrastructure, technical expertise and research capacity must be improved in endemic countries in order to positively influence dengue surveillance, clinical case management and the development of new approaches to dengue control.

Animals↗