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PubMed1986

Evaluation of febrile patients in Port Sudan, Sudan: isolation of dengue virus.

One hundred consecutive patients admitted to the Port Sudan Hospital with a temperature greater than or equal to 100 degrees F were evaluated. Enteric fever was diagnosed in 19 patients and malaria in 13. Virologic studies identified 21 cases of dengue infection. One dengue 1 and 17 dengue 2 infections were diagnosed by viral isolation. Three untyped dengue infections were identified serologically. The clinical presentation and course of patients infected with dengue virus were most consistent with classic dengue fever. There was no evidence of hemorrhagic phenomena or shock in any of the dengue-infected patients. Both dengue 1 and 2 must be considered causes of acute fever in East Africa.

Adolescent↗
PubMed1997

The first reported outbreak of dengue hemorrhagic fever in Irian Jaya, Indonesia.

During the months of September 1993 through February 1994, an outbreak of hemorrhagic fever occurred in the city of Jayapura, the provincial capital of Irian Jaya, Indonesia. Seventy-two patients (age range = 1-41 years) with suspected dengue hemorrhagic fever (DHF) were enrolled into the outbreak investigation conducted during October-November 1993. The pediatric patient population consisted of 36 individuals ages 1-12 years of age with a similar male to female ratio. From clinical histories obtained from the children diagnosed with DHF (n = 23), the predominant complaints were fever (100%), headache (96.7%), vomiting (47.8%), abdominal pain (39.1%), back/bone pain (39.1%), cough (39.1%), sore throat (21.7%), convulsions (17.4%), and eye pain (13.0%). Clinical findings of the same pediatric patients included a positive tourniquet test result (100%), thrombocytopenia (100%), hemoconcentration (100%), skin petechiae (43.5%), epistaxis (39.1%), and maculopapular rash (26%). All four of the children diagnosed with DHF grade IV had hepatomegaly, pleural effusion, ascites, cold perspiration, and confusion. Serologic data demonstrated that a majority (46 of 70, 68.7%) of the individuals assessed did not have significant levels of IgM specific for dengue viruses at the time of their admission. However, the nine successful dengue virus isolations were only from these serononreactive cases (19.6%). From the other patients assessed, 11.4% had a primary (or first exposure) serologic response to dengue virus antigen (predominantly IgM); 17.1% had a secondary (or subsequent exposure) serologic response to the same dengue antigens (predominantly IgG response) and 5.7% (four adults) had indeterminate serologic data that could not differentiate between reactivity to dengue or Japanese encephalitis virus antigen preparations. Virus culture of blood samples produced nine dengue virus isolates: DEN- 1 (2), DEN-2 (1), and DEN-3 (6). Japanese encephalitis and influenza viruses were not isolated from blood and pharyngeal specimens, respectively, from any of the patients. Thus, this first reported outbreak of DHF in Irian Jaya, Indonesia was found to be attributed to dengue viruses types 1, 2, and 3.

Adolescent↗
PubMed2002

Assessment of dengue risk in relief workers in Puerto Rico after Hurricane Georges, 1998.

Health risk assessment is important in the safe deployment of workers to tropical areas. We monitored dengue incidence in 204 of 222 North American relief workers visiting Puerto Rico after Hurricane Georges and during a dengue epidemic in 1998. We recorded information regarding participants' living conditions and any illness they experienced from arrival to 2 weeks after their departure. Virus isolation, polymerase chain reaction, and serological tests for anti-dengue immunoglobulin (Ig) M and IgG antibodies were used to diagnose dengue infection by means of departure and follow-up serum specimens. Among respondents, 82% (164 of 199) reported mosquito bites, 97% (156 of 161) reported having insect repellent available, and 41% (79 of 195) reported using repellent every day. Twelve participants reported a mild denguelike illness. No participants had laboratory evidence of dengue infection after 1.8 person-years of assessable exposure to areas with dengue transmission (upper 95% confidence limit of 1.67 cases per person-year). The risk of acquiring dengue among relief workers in this study appears low, possibly as a result of protective factors. Travelers to dengue-endemic areas should continue to be advised to protect themselves against mosquito bites.

Adult↗
PubMed2001

Seroepidemiology and active surveillance of dengue fever/dengue haemorrhagic fever in Delhi.

The aims of the present study were to carry out surveillance for dengue virus infection in adults with short-duration fever, and serological study of dengue virus infection in persons without fever. Patients were divided into two groups. Group 1 included patients above 12 years of age with fever of 2-12 days duration without any apparent cause. Of these, patients who presented with fever for 2-5 days were included for virus isolation (group 1a) while those who presented within 6-12 days of the onset of fever were included for the dengue-specific IgM serology (group 1b). Group 2 included a sample of population belonging to all age groups but without pyrexia and blood was collected for dengue-specific IgG serology. Twenty-six patients were enrolled in group 1a over a period of 4 months (September to December, 1997). Of these, DEN1 was isolated in 5 cases. Group 1b included 182 patients, out of which 34 (18.68%) were positive for dengue-specific IgM antibodies. Significantly, all the positive cases were detected during the months of September to November. Retro-orbital pain was present in a significantly more number of IgM-positive cases as compared to IgM-negative cases. Group 2 included 125 cases without fever. The overall positivity for dengue-specific IgG antibodies was 77.6%, with the highest positivity of 100% in the age group of 31-40 years. It was concluded that dengue virus infection is endemic in and around Delhi with peak incidence between September and Novemver. The prevalent serotype during September and December 1997 was DEN1. Since previous epidemic of DHF was due to DEN2 type, isolation of DEN1 serotype indicates changes of another epidemic of DHF due to DEN1 serotype. The stresses the urgent need for implementation of measures to control the transmission of dengue infection.

Adult↗
PubMed2001

Comparative evaluation of various commercial assays for diagnosis of dengue fever.

Dengue fever (DF) is endemic in India and dengue hemorrhagic fever (DHF) has been reported with increasing frequency in the last decade. We evaluated three commercial assays for detection of antibodies to dengue virus, to assess their performance in a diagnostic laboratory. Sera from 58 patients collected during a febrile outbreak in New Delhi in 1997 were studied. The methods evaluated were MRL Diagnostic Dengue Fever Virus IgM Capture ELISA, Pan Bio Dengue Duo IgM and IgG Capture ELISA and Pan Bio Rapid Immunochromatographic test. The MRL ELISA correctly identified 97.8% (43 of 44) of samples as dengue positive while the Pan Bio Duo ELISA and Pan Bio RIT identified 95.45% (42 of 44). The sensitivities of both Pan Bio Duo ELISA and Pan Bio RIT for primary dengue and secondary dengue were 100% and 93.54% respectively. The specificity of three assays were MRL IgM ELISA 100%, Pan Bio Duo ELISA 92.8% and Pan Bio RIT 85.7%.

Dengue↗
PubMedDate not supplied

[Laboratory diagnosis and symptoms of dengue, during an outbreak in the Ribeirão Preto region, SP, Brazil].

A dengue type 1 outbreak started in the Ribeirao Preto Region, North of Sao Paulo State, Brazil, in November of 1990. About 3500 dengue cases were confirmed by blood tests until February of 1991. The Virus Research Unit of The Faculty of Medicine of Ribeirao Preto-Sao Paulo State University, studied 502 dengue suspect cases. The serologic diagnosis of dengue type 1 was confirmed by haemagglutination inhibition test (HAI) in 19% of the cases. Diagnosis was done later by using an enzyme immuno assay on infected cultured cells (EIA-ICC) which discriminated IgG and IgM dengue, antibodies. EIA-ICC was less sensitive (89%) but more effective than HAI. EIA-ICC is a simple technique. It dispenses a second serum sample for diagnosis and it can be completed in about 5 hours. Dengue virus was isolated from the blood of 21 patients by inoculation in culture of mosquito C6/36 cells. The isolated virus were identified by indirect immunofluorescent test, by using an antisera pool to the flavivirus family and dengue type specific monoclonal antibodies. The dengue most frequent symptoms in 71 patients were observed: fever (90%), myalgias (57%) and arthralgias (41%).

Adolescent↗
PubMed1992

Detection and differentiation of dengue-1 from Japanese encephalitis virus infections by ABC MAC-ELISA.

An IgM antibody capture enzyme linked immunosorbent assay using avidin biotin complex system (ABC MAC-ELISA) was established for the detection and differentiation of dengue-1 and Japanese encephalitis virus infections. The cut-off value of MAC-ELISA was based on the mean value of optical density at 490 nm of seven negative human sera carried along in each assay multiplied by 2.1. The specificity of MAC-ELISA tested on 200 healthy enrolled male serum was 99.5% and 98.0% for dengue-1 and Japanese encephalitis IgM, respectively. Two hundred and sixty-six acute or followed-up dengue serum specimens which were identified to possess dengue-1 virus by virus isolation technique using C6/36 cell line and monoclonal antibody immunofluorescent assay (IFA) were tested by MAC-ELISA for IgM antibodies to dengue-1 and Japanese encephalitis virus infection. The positivity of IgM antibody for serum collected from day 1 to day 7 after onset of the disease was 0.0%, 0.0%, 7.6% 14.2%, 25.0%, and 77.7% by each consecutive day, correspondingly, for those collected from day 8 to two month was 96.7% overall. By comparison the P/N value of dengue-1 IgM to JE IgM, 98.5% and 96.8% of the dengue-1 and Japanese encephalitis suspected serum specimens could be distinguished from each other, respectively. MAC-ELISA is a convenient, rapid, sensitive and specific method for the detection and differentiation of dengue-1 from Japanese encephalitis virus infections.

Antibodies, Viral↗
PubMed2005

Laboratory diagnosis of dengue virus infection: current and future perspectives in clinical diagnosis and public health.

Since no protective vaccine or specific treatments are available for dengue fever/dengue hemorrhagic fever (DHF), accurate diagnosis is critical for the early initiation of specific preventive health measures to curtail epidemic spread and reduce economic losses. Commonly used diagnosis methods for confirming dengue infection involve virus isolation, detection of virus antigen or RNA in plasma or serum or tissues, and the presence of dengue virus-specific antibodies in serum and other body fluids. Recently, several techniques have been developed for rapid laboratory diagnosis of dengue virus, including centrifugation amplification to enhance virus isolation rate, the flow cytometry method for early detection of cultured virus, detecting viral nucleic acid e.g., by nested reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative RT-PCR, nucleic acid sequence-based amplification, and real-time PCR, detecting free viral non-structure antigens, anti-dengue virus immunoglobulin M (IgM) or IgG antibodies by enzyme-linked immunosorbent assay, and differentiation of primary versus secondary dengue virus infection. Newly established methods must be standardized to maintain high quality laboratory performance. Laboratory diagnostics must be tailored to a specific laboratory environment, the objectives of clinical needs and the availability of clinical specimens. Speed and accuracy of diagnosis must be balanced against test cost and availability. Future challenges in the study of dengue and DHF include the application of modern techniques, such as nucleic acid chips, protein chips and new biomarkers to avoid cross-reactivity among different serotypes of dengue viruses and other flaviviruses, plus development of internationally standardized guidelines to improve quality assurance of these advanced laboratory tests.

Antibodies, Viral↗
PubMed2005

[Hepatic alterations in patients with dengue].

Clinical features of Dengue are very variable due to multiple alterations induced by the virus in the organism. Increased levels of transaminases similar to those produced by the Hepatitis virus have been reported in patients with Dengue from hiperendemic zones in Asia. The objectives of this study were to determine alterations in the liver tests in patients with Dengue and to relate them to the disease, clinically and serologically. Clinical history, hemathological tests serum transaminases (ALT y AST) and bilirubin assays were performed in 62 patients with clinical and serological diagnosis of Dengue. According to clinical features 38.7% of the patients with classical (CD) and hemorrhagic (DHF) forms of Dengue reffered abdominal pain and 2 patients with DHF had ictericia and hepatomegaly. Laboratory test findings showed leucopenia in 72.5% in both forms of Dengue and of patients with DHF severe thrombocytopenia (< 50.000 platelets x mm3), long PT and PPT in 70.9%, 23.0% and 42.3%, respectively. Transaminase values five fold higher than the normal values (p < 0.005) were observed in 36.8% and 74.4% of patients with CD and DHF respectively; AST was predominant in both groups. Our results suggest liver damage during the course of Dengue. A differential diagnosis has to be done between the hepatic involvement of Dengue cases and others viral diseases with hepatic disfunctions.

Abdominal Pain↗
PubMed2005

[Analysis on clinical and epidemiological characteristics of 1032 patients with Dengue fever in Guangzhou].

OBJECTIVE: To analyze the clinical and epidemiological characteristics of Dengue fever (DF) during the Dengue-1 epidemic in Guangzhou. METHODS: Clinical and epidemiological data of 1032 patients with DF from May 2002 to November 2003 were retrospectively analyzed. Dengue virus were isolated by cell culture and typed by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Age of the patients ranged from 55 days to 91 years old (average 34.7 +/- 13.2 years) with sex ratio 1.03:1. Incubation period ranged from 2 to 12 days with mean periods of 5.3 +/- 2.4 days. Most (45.0%) cases appeared in September and the epidemic last from July to November. Dengue outbreak had involved 675 cases in 26 common places. The common manifestations were seen as fever (100%), headache (90.9%), myalgia (68.4%), bone soreness (48.8%), fatigue (79.3%), skin rash (60.1%), positive tourniquet test (45.3%), leukopenia (63.3%) and thrombocytopenia (60.8%), respectively. Dengue virus was isolated from serum of 19 out of 54 patients' and identified as Dengue virus type 1. DNA sequence analyzes on rates of nucleotide homology were 97%, 97% and 98% compared with those of Dengue virus type 1 strain of DF outbreak in Cambodia, in 1997 and 1999 in China. CONCLUSION: The epidemic of DF in Guangzhou in 2002/2003 was caused by Dengue virus type-1 with most patients showing classic type of the disease. Date suggested that change can happen from non-endemic to hypoendemic regions in Guangdong province.

Adolescent↗
PubMed2006

Diagnostic methods for detection & isolation of dengue viruses from vector mosquitoes.

Dengue is a deadly mosquito-borne infection warranting urgent attention for its containment particularly in the tropical and subtropical countries. In the absence of a vaccine or any specific drug for its treatment, an early diagnosis is considered indispensable to prevent any casualty. Detection of viruses in human sera particularly in endemic areas is cumbersome, difficult and also not desirable. Therefore, as an alternative approach, detection of the dengue virus antigen in mosquitoes has provided a reliable tool to (i) comprehend the types of viruses circulating in nature; and (ii) help in designing vector-specific control strategies. A mélange of diagnostic techniques are currently available with some advantages or disadvantages. Traditionally, cell cultures and suckling mice have been employed for virus isolations. While the virus isolation method in baby mice is time consuming, slow and expensive, the mosquito cell cultures offer a good degree of specificity. Mosquito inoculation techniques have been reported for detection and propagation of flaviviruses. Though this technique is sensitive for routine virological confirmation of dengue fever, it requires large number of infected mosquitoes, besides being time consuming. Insect bioassays (Toxo-IFA) are generally cumbersome requiring special facilities and are not suitable for large-scale epidemiological surveillance. ELISA has been shown to be a rapid and sensitive alternative to insect bioassays for monitoring arboviruses in wild populations. Reverse transcriptase polymerase chain reaction (RT-PCR) is a recent molecular diagnostic technology used for detecting virus infections in mosquitoes, which gives rapid results but is expensive and prone to contamination. This review describes the development of various techniques involved in detection and isolation of dengue viruses in mosquitoes. Definite diagnosis of the impending dengue epidemic can be made using ELISA for virological surveillance system on dengue virus antigen in the mosquito vectors. Therefore, ELISA offers a potential tool and a convenient system for quickly screening large number of samples up to the serotype level which can be employed effectively and efficiently for large scale dengue surveillance programmes on wild caught mosquito vectors. ELISA positive samples can be screened further by Toxo-IFA system for virus isolation. On the other hand, techniques like mosquitoes cell culture, mosquito inoculation (Toxo-IFA) and RT-PCR techniques can be employed for dengue virus amplification.

Aedes↗
PubMedDate not supplied

Some clinical and epidemiological observations on virologically confirmed dengue hemorrhagic fever.

This study is a part of a one year prospective study on dengue hemorrhagic fever (DHF) carried out in the Department of Pediatrics, Sumber Waras Hospital in West Jakarta. Viral isolation and serologic analysis for DHF were done by Namru-2 in Jakarta. The subjects were 151 virologically confirmed DHF Patients admitted to the Department of Pediatrics during the period of September 1987-June 1988, consisting of 82 boys and 69 girls of 6 months-15 years old. The predominant age group was 5 to 9 years, representing 49.7% subjects. Dengue virus was isolated from sera during the first 8 days of illness and in 139 (42.1%) during the first 5 days of illness. Dengue virus type 1, 2, 3 and 4 were isolated from 16.6%, 13.2%, 69.5% and 0.7% subjects, respectively. The clinical manifestations revealed no striking differences between dengue 3 and others except for thrombocytopenia and shock. High fever, hemoconcentration and thrombocytopenia on admission was observed in 30.5%, 8.6% and 8.6% of subjects, respectively. Dengue shock syndrome (DSS) were observed in 23 (15.2%) with 3 (2%) fatal cases. Dengue virus serotype 3 was observed in 20 out of 23 DSS cases (86.9%) and all fatal cases were associated with dengue type 2. This study revealed that dengue 3 is the predominant virus circulating during recent epidemics and is associated with more severe clinical manifestation and with a higher incidence rate of living area.

Adolescent↗
PubMed1986

[Pathogenesis of hemorrhagic dengue: critical discussion of current hypotheses].

The major hypotheses which have been advanced to explain the pathogenesis of "dengue hemorrhagic fever" are reviewed. Because of the difficulty in applying the definition of "dengue hemorrhagic fever" proposed by the World Health Organization, most of the discussion deals only with the most severe form of dengue, "dengue shock syndrome", which may or may not be a subset of "dengue hemorrhagic fever". It is not clear if it is the virus or the host that plays the predominant role in the pathogenesis of the dengue shock syndrome. More specifically, there is considerable difference of opinion as to whether or not a prior dengue infection with a heterologous dengue serotype constitutes a risk factor for the development of the syndrome. The evidence cited in favor of the latter concept is discussed from a critical point of view.

Dengue↗
PubMed1979

Epidemic dengue hemorrhagic fever in rural Indonesia. I. Virological and epidemiological studies.

Virological studies were carried out during an epidemic of dengue hemorrhagic fever in Central Java, Indonesia in 1976. Dengue virus was isolated from the acute sera of 45 of 69 patients (65%). The isolation rate was higher in primary than secondary cases. Dengue 3 was the predominant serotype being transmitted (27 isolates), but both dengue 1 (8 isolates) and dengue 4 (10 isolates) were also being transmitted. A composite picture of magnitude and duration of viremia showed that many patients were circulating over 10(8) MID50 per milliliter dengue 3 virus for the first 3 days of illness and that viremia persisted for 5-6 days in some persons. If all shock cases were considered, there was no relationship between dengue serotype and severity of disease. All three confirmed fatal cases, however, were associated with dengue type 3 infections.

Antibodies, Viral↗
PubMed1995

Augmented inflammatory cytokines in primary dengue infection progressing to shock.

Dengue fever (DF) which is caused by four serotypes of dengue virus may in some cases progress into a life threatening situation of dengue haemorrhage fever (DHF) and dengue shock syndrome (DSS). It has been suggested that sequential infection with different dengue virus serotypes predisposes the patient towards DHF/DSS. We report here a primary dengue infection in a 10-year-old boy progressing from DF to DSS while under clinical observation. The report provides unequivocal evidence for the development of DSS in primary dengue infection caused by virus serotype 4. The close relationship between sequential changes in the levels of tumour necrosis factor (TNF), Interleukin 1 and 6 (IL-1 and IL-6) in the serum, to the clinical progression of the disease from DF to DHF/DSS and then to full recovery implicates a pathogenetic role for the inflammatory cytokines. The child also manifested clinical features consistent with Reye's syndrome and this suggests a common pathogenetic origin for DSS and the Reye-like syndrome induced by dengue virus.

Child↗
PubMed1997

Dengue haemorrhagic fever/dengue shock syndrome. An unwelcome arrival in Trinidad.

This is the first report of dengue haemorrhagic fever and dengue shock syndrome in Trinidad. Dengue infection was confirmed serologically or by viral isolation in five patients, aged 15 to 53 years, who presented with fever, thrombocytopenia and haemoconcentration. Three patients developed dengue shock syndrome, which was fatal; although there was no haemorrhagic tendency among these patients, bleeding occurred shortly before death in one of them. Two patients who had dengue haemorrhagic fever survived. The co-circulation of dengue virus serotypes 1, 2, and 4 in the Caribbean facilitates the development of dengue shock syndrome (DSS) or dengue haemorrhagic fever (DHF). Clinicians should therefore be aware of their clinical features, laboratory diagnosis and clinical management. Appropriate public health interventions and improved surveillance should be implemented to reduce the risk of DHF/DSS associated mortality in Trinidad and Tobago.

Adolescent↗
PubMed1995

Rapid and sensitive streptavidin-biotin amplified fluorogenic enzyme-linked immunosorbent-assay for direct detection and identification of dengue viral antigens in serum.

Each of the four serotypes of dengue viruses is responsible for a spectrum of illnesses that range from nonspecific febrile syndrome with good prognosis to dengue haemorrhagic fever or dengue shock syndrome. Definite diagnosis of dengue is provided by the detection of virus in acute-phase sera of patients. Virus isolation can be accomplished with mosquito cell lines or mosquito inoculations. However, these methods are time consuming and labour intensive. The reverse-transcriptase polymerase chain reaction (RT-PCR) provides a potential means of rapid diagnosis but requires specialised facilities and equipment and is expensive. Therefore a rapid, simple, sensitive, and economical method for direct detection of viral antigens in viraemic sera is needed for clinical and epidemiological investigations. An amplified fluorogenic enzyme-linked immunosorbent assay (F-ELISA) is described for the detection and identification of dengue-3 viruses in serum specimens. This assay utilizes biotinylated mouse IgG antibody directed against dengue antigens captured by anti-dengue monoclonal antibody coated onto polystyrene microplate wells. It takes advantage of the high affinity of biotin for the multivalent binding sites of streptavidin-labelled beta-galactosidase, and combines the amplification effect of biotin-streptavidin interaction with the high sensitivity of fluorogenic detection methods. Following optimisation of the procedure by reducing non-specific binding of proteins and enhancing the specific binding of antigens, F-ELISA was tested on 259 sera submitted routinely to our laboratory for confirmation of dengue diagnosis. The sensitivity of the F-ELISA was 90%, the specificity was 99% and the agreement rate was 98% between F-ELISA and virus isolation results.

Animals↗
PubMed2005

Nitric oxide radical suppresses replication of wild-type dengue 2 viruses in vitro.

Nitric oxide is well accepted as one of the defenses for inhibiting viral dissemination. Macrophages and cells in the macrophage lineage are professional nitric oxide producers which sub-serve as target for dengue virus. The interaction between nitric oxide and dengue virus in such target cell is unknown. In this report, the impact of nitric oxide on infectious dengue virus serotype 2 production and RNA replication was investigated in vitro. Primary isolates of dengue virus serotype 2 from dengue patients were replicated in mouse neuroblastoma cells in the presence of an exogenous nitric oxide donor, s-nitroso-N-acethylpennicillamine, SNAP, at the concentration of 50 or 75 or 100 microM. Nitric oxide inhibited viral replication in a dose and a multiplicity of infection dependent manner. Nitric oxide from 50 and 75 microM SNAP delayed and suppressed replication of dengue virus isolates while higher concentration of nitric oxide, 100 microM SNAP, completely inhibited production of infectious particles up to 36 hr study. Twenty-four out of forty tested isolates, 60%, were susceptible to 50 microM SNAP inhibitory effect. The mechanism of inhibition was investigated at the level of RNA synthesis and was found that RNA production was suppressed which correlated to production of the infectious particles. Down-regulation of the RNA synthesis resulted in reduction of protein synthesis which was detected by lower level of NS1 protein synthesis using immunoblotting. In conclusion, nitric oxide from exogenous nitric oxide donor down regulated replication of dengue virus serotype 2 isolates from dengue patients. The suppression was clearly shown at the level of viral RNA and protein synthesis resulting in reduction of viral progenies production. This phenomenon implies that nitric oxide may serve as a defense which diminishes viral load in patients.

Animals↗