Question of the Month - Dengue Fever

Classic dengue and its more lethal form, dengue hemorrhagic fever (DHF), now circle the world with endemic illness and continuing threats of epidemics. With 2.5 billion people at risk and estimated cases in the tens of millions, dengue is considered to be the second most important mosquito-borne disease in the world (surpassed only by malaria).

This month's question is on dengue. The EHP Information Center received a request to provide sources that provide information on recent dengue outbreaks. An information service on emerging diseases, PROMED, tracks this type of information. A link to PROMED is provided below as well as links to Fact Sheets and other online documents.

Information Sources on Dengue

Fact Sheets/OnlineReports
Recent Outbreaks     

Fact Sheets/Online Reports

Dengue Fever: An Environmental Plague for the New Millenium, by R.W. Lennox and A.A. Arata. EHP Capsule Report No. 2. 1999. (393KB)

Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control, by WHO. 2nd edition. 1997.

Dengue and DHF Prevention and Control - WHO

Frequently Asked Questions about Dengue and DHF, by D.J. Gubler/CDC (See Diseases section)

Recent Outbreaks - Indonesia

(For further information on recent dengue outbreaks, see the web site: PROMED

3 Mar 2000
From: M. Cosgriff ; [email protected]
Source: Jakarta Post, 3 Mar 2000

Hospital officials warned on Thursday that a severe outbreak of dengue could strike the city, with many recently admitted patients in the advanced hemorrhagic stage of the disease. Most patients were in an advanced stage of viral infection. In some cases, the patients were hemorrhaging when they were admitted to the hospital.

A hospital spokesperson said she dismissed speculation that dengue was becoming a more serious problem because of public ignorance about symptoms of the disease. "People are now more conscientious while dealing with dengue, mostly after experiencing a dengue fever outbreak in 1998. People now rush for medical treatment even though it is just a light fever," she said.

Another spokesperson said five to six dengue fever patients were admitted to his hospital every day. "When the outbreak was at its peak in 1998, the number could reach 15 patients a day." He said there were 15,000 dengue cases that year, with 133 fatalities. The city administration previously warned of the possibility of a dengue fever outbreak this year as seven people had died of the disease as of March 1. Data at the city's health agency show there were 1,309 cases through March 1.



A Selected Bibliography on Dengue

Rev Soc Bras Med Trop 1999 Jul-Aug;32(4):357-62

[An evaluation of municipal actions in the control of dengue vectors in the region of Sao Jose do Rio Preto, Sao Paulo, 1989 to 1995].

Chiaravalloti Neto F, da Costa AI, Moura MS, Soares MR, Pereira FC, Battigaglia M, Aragao FJ

Superintendencia de Controle de Endemias, Sao Jose do Rio Preto, Sao Carlos. [email protected]

The aim of this study was to determine the coverage of municipal activities in terms of the control of Aedes aegypti and/or Aedes albopictus by routine house-to-house visits and by emergency activity, carried out between 1989 and 1995 in the area of Sao Jose do Rio Preto, Sao Paulo State, and to evaluate the cross-correlation between them and the Breteau index (BI). For towns with up to 50,000 real estate properties, the joint coverage by routine and emergency activities was mostly appropriate and the routine activities showed a negative cross-correlation with the BI. For the county seat (more than 50,000 real estate properties), the coverage provided by the above activities was not correlated with the BI. In general, the coverage was inversely proportional to town size. Emergency activities did not show a correlation with the BI in any town size range, proving to be ineffective.

Am J Trop Med Hyg 1999 Dec;61(6):994-1000

Detection and genetic relationship of dengue virus sequences in seventeen-year-old paraffin-embedded samples from Cuba.

Sariol CA, Pelegrino JL, Martinez A, Arteaga E, Kouri G, Guzman MG

Department of Virology, Pan American Health Organization/World Health Organization Collaborating Center for Viral Diseases, Havana, Cuba.

This study describes the use of the reverse transcriptase-polymerase chain reaction (RT-PCR) to generate dengue 2 amplicons from paraffin-embedded autopsy tissues collected in Cuba 17 years ago. The presumptive diagnoses had been made only by clinical evolution without serologic confirmation. This study confirms once again that dengue 2 virus was directly associated with the fatal cases in children and illustrates the potential of the RT-PCR for retrospective diagnosis of dengue cases 17 years after death. A close similarity in the genomic sequences of the dengue 2 RNA detected in tissue samples from fatal cases and those dengue 2 Cuban strains that had been previously investigated confirms the appropriate genomic classification of the etiologic agent associated with the 1981 dengue hemorrhagic fever Cuban epidemic

J Am Mosq Control Assoc 1999 Dec;15(4):475-8
Aedes albopictus from Albania: a potential vector of dengue viruses.

Vazeille-Falcoz M, Adhami J, Mousson L, Rodhain F

Unite d'Ecologie des Systemes Vectoriels, Institut Pasteur, Paris, France.

Aedes albopictus collected in Durazzo, the main port of Albania, were tested for oral susceptibility to dengue type 2 virus and their infection rates were compared to those of an Aedes aegypti strain (Paea) and another strain of Ae. albopictus (Tananarive). Infection rates for the Albanian Ae. albopictus were dose dependent, ranging from 38.9 +/- 13.6% to 85.1% with the titer of the meal increasing from 10 x 8.1 to 10 x 9.1 50% mosquito infectious doses (MID50)/ml. The percentage of infected females was lower for the Ae. albopictus Durazzo strain than for the Ae. aegypti Paea strain: 38.9 +/- 13.6% compared with 92.4 +/- 4.9% for a meal of 10 x 8.1 MID50/ml, respectively. However, the difference was less when the titer of the meal was increased: 85.1% compared with 100% for a meal of 10 x 9.1 MID50/ml, respectively. The infection rate was also lower for the Durazzo strain than for the Tananarive strain of Ae. albopictus. The degree of viral replication in infected females was not significantly different in the 3 strains tested and we were able to demonstrate the ability of females from the Durazzo strain to transmit the virus in the course of a blood meal. Our results lead us to conclude that Ae. albopictus from Albania could serve as a vector for dengue virus.

Trop Med Int Health 1999 Nov;4(11):765-73

Dengue: an evaluation of dengue severity in French Polynesia based on an analysis of 403 laboratory-confirmed cases.

Murgue B, Deparis X, Chungue E, Cassar O, Roche C

Unite de Virologie, Institut Territorial de Recherches de Medicales Louis Malarde, Papeete, Tahiti, French Polynesia.

We conducted a retrospective study of 403 laboratory-confirmed dengue cases hospitalized in Tahiti between August 1989 and March 1997. According to standard WHO criteria, 337 of these cases were dengue fever (DF) and 64 were dengue haemorrhagic fever (DHF). Of the 10 fatal cases, 6 were DF and 4 were DHF. As an alternative, we used a correspondence analysis procedure to define dengue severity based on basic clinical and biological criteria for which we assigned a severity score, and then selected the 50 most severe cases from this analysis. Of the latter, 17 patients had been classified as DF and 33 as DHF by the WHO criteria. From this analysis, haemorrhages and decreased platelets counts associated with hepatic disorders are the main criteria associated with the severe dengue cases. Thus in our study population, the WHO classification does not account for the overall severity of dengue; hepatic failure should be considered as a specific severe form of dengue since plasma leakage, which is the pathophysiological hallmark of DHF, is only one of the pathogenic mechanisms leading to severity.

West Indian Med J 1999 Sep;48(3):115-7

Childhood dengue shock syndrome in Trinidad.

Teelucksingh S, Lutchman G, Udit A, Pooransingh S

Dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) is a major cause of hospitalisation and mortality among children in South East Asia. We now report, for the first time, the occurrence of DHF/DSS in Trinidadian children. The presence of vomiting, abdominal pain and hepatomegaly in the setting of a dengue epidemic should alert clinicians to the possibility of DHF/DSS. Timely diagnosis and aggressive supportive treatment are essential for a successful outcome. Source reduction, vector control and community participation are also necessary to avert the South East Asian scenario from emerging in the Caribbean.

Cad Saude Publica 1999 Jul-Sep;15(3):477-86
[Distribution of Aedes aegypti and dengue in the State of Maranhao, Brazil].

Rebelo JM, Costa JM, Silva FS, Pereira YN, da Silva JM

Nucleo de Patologia Tropical e Medicina Social, Departamento de Patologia, Universidade Federal do Maranhao, Praca Madre Deus 2, Sao Luis, MA, 65025-560, Brasil.

Dengue and Aedes aegypti are widespread in the State of Maranhao. During 1995, 87 of the 136 of the State's counties, including 176 towns and 480,687 households, were studied, of which 30 counties (34. 4%), 118 towns (67.0%) and 10,357 households (2.1%) were positive for Aedes aegypti. The positive counties are distributed as follow: 3 on Sao Luis Island, 7 in the Amazonia of Maranhao, 12 in the southern zone of the cerrados or savannas, and 5 in the mixed forest/savanna/palm grove zone. One positive county for Ae. aegypti was located in each of the following: alluvial fields, forest/palm grove, and sand dune/shoals areas. The Ae. aegypti-positive household rates were higher in the Amazonia of Maranhao (3.5%) and on Sao Luis Island (2.5%), because they are the most heavily traveled migratory and trade routes between Maranhao and neighboring states and are also the State's main economic centers. Household infestation rates for Ae. aegypti and reported dengue case rates were higher during the rainy season, showing the importance of rain in forming prime breeding sites for Aedes and spreading dengue.

Am J Trop Med Hyg 1999 Sep;61(3):412-9

A prospective seroepidemiologic study on dengue in children four to nine years of age in Yogyakarta, Indonesia I. studies in 1995-1996.

Graham RR, Juffrie M, Tan R, Hayes CG, Laksono I, Ma'roef C, Erlin, Sutaryo, Porter KR, Halstead SB

Naval Medical Research Unit No. 2 (NAMRU-2), Jakarta, Indonesia.

A prospective study on dengue (DEN) viruses was initiated in October 1995 in Gondokusuman kecamatan, Yogyakarta, Indonesia. This report presents data from the first year of the study. The studied cohort included all children 4-9 years of age living in the kecamatan. Blood samples for serology were collected from 1,837 children in October 1995 and again in October 1996. Blood samples for virus isolation and serology were collected from cohort children who were seen in municipal health clinics with febrile syndromes or admitted to hospitals with a provisional diagnosis of dengue hemorrhagic fever. Dengue serotype antibody prevalence and 1995-1996 infection rates were calculated using a single dilution (1:60) 70% plaque reduction endpoint neutralization test. Prevalence of dengue antibody at the beginning of the study was DEN 1 = 12%, DEN 2 = 16%, DEN 3 = 2%, DEN 4 = 4%, and two or more dengue infections = 22%. Total dengue antibody prevalence increased from 38% in 4-year-old children to 69% in 9-year-old children. During the observation period, primary dengue infection rates were DEN 1 = 4.8%, DEN 2 = 7.7%, DEN 3 = 4.2%, and DEN 4 = 3.4%, while two or more dengue infections occurred in 6.7% of the study population. The secondary dengue infection rate was 19.0%. From febrile cases, all four dengue viruses were isolated with DEN 3 predominating. Seven children were hospitalized, including one fatal case with a hospital diagnosis of dengue shock syndrome. Based upon presence of antibody in the initial cohort bleeding and the serologic response both weeks and several months following illness, all had secondary dengue infections. Neutralizing antibody patterns in the initial cohort bleeding and in late convalescent serum samples permitted recognition of dengue infection sequence in five patients: DEN 2-DEN 1 (3), DEN 2-DEN 4 (1), DEN 1-DEN 3 (1), and none in the sequence DEN 1-DEN 2. In the total cohort 6.5% of the observed secondary infections were of the sequence DEN 2-DEN 1, while 4.9% were DEN 1-DEN 2, a highly pathogenic sequence in previous studies. Reduced pathogenic expression of secondary DEN 2 with enhanced pathogenic expression of secondary DEN 1 infections was an unexpected finding. Further studies will be required to understand the respective contributions to pathogenicity of antibody from initial dengue infections versus the biological attributes of the second infecting dengue viruses.

Trans R Soc Trop Med Hyg 1999 May-Jun;93(3):294-8

Dengue haemorrhagic fever in children in the 1996 Delhi epidemic.

Kabra SK, Jain Y, Pandey RM, Madhulika, Singhal T, Tripathi P, Broor S, Seth P, Seth V

Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
[email protected]

An epidemic of dengue haemorrhagic fever (DHF) occurred in Delhi in 1996. A total of 240 children between the age of 4 months to 13 years of either sex, admitted in one hospital, were evaluated. Two hundred and sixteen (90%) children were from Delhi. A clinical diagnosis of dengue fever (DF) was made in 25 (10%), dengue fever with unusual bleeding (DFB) in 22 (9%), DHF in 80 (33%) and dengue shock syndrome (DSS) in 113 (47%) of the children strictly according to the WHO classification. The age peaked at 8 years. There was no association between various grades of severity of illness and age-groups though girls suffered from more severe illness. No association between severity of malnutrition and severity of illness was observed. Tourniquet test was positive in 40% with DF, 18% with DFB, 62% with DHF and 64% with DSS. In DSS haematemesis was present in 55 (49%), epistaxis in 39 (35%), melaena in 27 (24%) and ecchymosis in 34 (30%) patients. Children diagnosed as DFB had haematemesis and epistaxis in 12 (55%) and 10 (45%) respectively. Intravenous fluid requirement was clearly less in DFB patients than in DHF/DSS patients. Unusual clinical features in the form of jaundice were present in 7 (6%), hepatic encephalopathy in 6 (5%) and dengue encephalopathy in 6 (5%) patients. Dengue 2 virus was isolated from 10 of the 50 patients for whom viral culture was done on C6/36 clone of Aedes albopictus cell line. Eighteen patients suffering from DSS died giving an overall case fatality of 7.5%. The mortality rate in DHF/DSS was 9.3%. It is further suggested that DFB is a distinct entity. Most patients could be classified by the WHO classification if a retrospective packed cell volume was used to assess haemoconcentration. We suggest that development of area-specific criteria for diagnosis and management is desirable.

Int J Infect Dis 1999 Spring;3(3):130-5

Fatal dengue hemorrhagic fever in Cuba, 1997.

Guzman MG, Alvarez M, Rodriguez R, Rosario D, Vazquez S, Vald s L, Cabrera MV, Kouri G

Department of Virology, PAHO/WHO Collaborator Center for Viral Diseases, Tropical Medicine Institute of Havana, Havana, Cuba.

OBJECTIVES: After more than 15 years without dengue activity, a dengue II epidemic was reported in Cuba in 1997. Three thousand and twelve serologically confirmed cases were reported, with 205 dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) cases and 12 fatalities. This report presents the clinical, serologic, and virologic findings in the 12 fatal DHF/DSS cases. METHODS: Serum and necropsy samples were studied by viral isolation in C636 cell line and polymerase chain reaction. Serum samples were tested by IgM capture enzyme-linked immunoassay (ELISA) and ELISA inhibition method (EIM). RESULTS: All 12 cases were classified as DHF/DSS according to the Pan American Health Organization Guidelines for Control and Prevention of Dengue and Dengue Hemorrhagic Fever in the Americas. All patients were older than 15 years. Women were more frequently affected. The symptoms and signs presented by these patients were similar to those previously described in DHF/DSS cases. Clinical deterioration occurred on average at day 3.75. Abdominal pain and persistent vomiting were the earliest and most frequent warning signs. Dengue infection was confirmed in all cases. IgM antibodies were detected in 11 of 12 cases, all of them with a secondary infection. Dengue II virus was detected by viral isolation in 12 samples and by polymerase chain reaction in 17. Virus or RNA was detected in various tissues, including kidney, heart, lung, and brain. CONCLUSION: The clinical, pathologic, and laboratory features of 12 cases of fatal dengue hemorrhagic fever were reviewed. The results obtained demonstrate that adults with a primary dengue infection are at risk of developing the severe disease (DHF) if they are infected with a different serotype.

Emerg Infect Dis 1999 Jul-Aug;5(4):575-8

Dengue reemergence in Argentina.

Aviles G, Rangeon G, Vorndam V, Briones A, Baroni P, Enria D, Sabattini MS

Instituto Nacional de Enfermedades Virales Humanas Dr. J.I. Maiztegui, Administracion Nacional de Laboratorios e Institutos de Salud Dr. C. Malbran, Pergamino, Argentina.

Aedes aegypti, eradicated from Argentina in 1963, has now reinfested the country as far south as Buenos Aires. In 1997, four persons with travel histories to Brazil, Ecuador, or Venezuela had confirmed dengue, and surveillance for indigenous transmission allowed the detection of 19 dengue cases in Salta Province. These cases of dengue are the first in Argentina since 1916 and represent a new southern extension of dengue virus.

Emerg Infect Dis 1999 Jul-Aug;5(4):589-90

The first major outbreak of dengue hemorrhagic fever in Delhi, India.

Dar L, Broor S, Sengupta S, Xess I, Seth P

All India Institute of Medical Sciences, Ansari Nagar, New Delhi.

India An outbreak of dengue hemorrhagic fever/dengue shock syndrome (DHS/DSS) occurred in 1996 in India in and near Delhi. The cause was confirmed as dengue virus type 2, by virus cultivation and indirect immunofluorescence with type-specific monoclonal antibodies. This is the largest such outbreak reported from India, indicating a serious resurgence of dengue virus infection.

Rev Panam Salud Publica 1999 Jul;6(1):16-25

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

Valdes L, Guzman MG, Kouri G, Delgado J, Carbonell I, Cabrera MV, Rosario D, Vazquez S

Centro Provincial de Higiene y Epidemiologia, Santiago de Cuba, Cuba.

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