Epidemic dengue transmission in southern Sumatra, Indonesia

An outbreak of dengue fever (DF), dengue haemorrhagic fever (DHF), and dengue shock syndrome (DSS) in the city of Palembang, south Sumatra, Indonesia was investigated to (i) validate epidemic occurrence, (ii) confirm dengue virus aetiology and associated serotype(s), (iii) provide a demonstrable measure of community impact, and (iv) identify causative relationship (if any) with climatic El Ni?o Southern Oscillation (ENSO) influences. Trend analysis based on a 6-year retrospective review of hospital records demonstrates a 3-fold increase in clinical cases for the outbreak period (January-April 1998), relative to historical records. In the 2 hospitals surveyed, the monthly mean number of outbreak-related dengue cases over 4 months was 833 (range 650-995 cases/month); the mean monthly value for the previous 72 months was 107 (range 14-779 cases/month). An apparent trend in epidemic transmission was observed, evolving from a 5-year cyclic phenomenon to an annual occurrence, often indistinguishable from one year to the next. The proportional distribution of clinical outbreak cases into DF, DHF and DSS diagnostic categories was 24%, 66%, and 10%, respectively. The population aged 10-19 years accounted for the largest (35%) proportion of hospitalized DHF cases, followed by children aged 5-9 years (25%) and children aged 4 years (16%). Serum samples obtained during acute illness from 221 hospitalized patients were examined using serology, RT-PCR, and virus isolation in cell culture: 59% of samples had laboratory evidence of a dengue infection. All 4 dengue virus serotypes (DEN 1-4) were identified in epidemic circulation, with DEN 3 predominating (43%). DEN 1 was the principal serotype associated with less severe dengue illness, suggesting that virulence may be, in part, a function of infecting serotype. The climatic influence of ENSO on rainfall and temperature in the months leading up to and during the outbreak was dramatic, and is likely to contribute to favourable outbreak conditions.     

Assessment of body fluid compartment volumes by multifrequency bioelectrical impedance spectroscopy in children with dengue

Dengue haemorrhagic fever (DHF), the most severe form of illness following infection with a dengue virus, is characterized by plasma leakage and a period of increased microvascular permeability. Monitoring of plasma volume and body fluid compartment shifts is an integral part of the clinical management of DHF, and is crucial to the performance of clinical research studies on DHF pathogenesis. Multifrequency bioelectrical impedance spectroscopy (BIS) was assessed as a non-invasive method to monitor body fluid compartment shifts in children participating in a prospective, hospital-based, study of dengue virus infections in Thailand. Over the 48 h surrounding defervescence, the extracellular water/intracellular water ratio (ECW/ICW) rose in children with dengue virus infections and correlated with increasing disease severity [DHF > intermediate dengue fever (DF)/DHF > DF]. Plasma leakage remained within the ECW compartment and was not directly measured by multifrequency BIS. Expansion of the ECW space in DHF appeared to be primarily due to diminished renal water clearance. During the course of dengue illness, multifrequency BIS did not improve on serial haematocrit and bodyweight determinations for monitoring plasma volume contraction and ECW expansion, respectively.     

Plasma levels of tumour necrosis factor alpha and transforming growth factor beta-1 in children with dengue 2 virus infection in French Polynesia.

The pathogenesis of dengue haemorrhagic fever (DHF) is not well understood. In the absence of predictive clinical or biological criteria, the management of DHF patients remains difficult. The role played by cytokines in the occurrence of DHF has been suggested by several authors. In this study, we determined the plasma levels of tumour necrosis factor alpha (TNF alpha) and transforming growth factor beta-1 (TGF beta-1) in 52 children with laboratory-confirmed dengue virus infection admitted to hospital during the recent dengue 2 outbreak in French Polynesia. Thirty-three children were classified as having dengue fever (DF) and 19 as DHF. The plasma of both DF and DHF patients contained similar levels of TNF alpha. By contrast, plasma obtained from children with DHF had significantly higher levels of TGF beta-1 than plasma from children with DF, especially from days 1 to 3 after the onset of fever.     

Different clinical and laboratory manifestations between dengue haemorrhagic fever and dengue fever with bleeding tendency

The incidence of dengue fever (DF) is estimated to have increased 30-fold in the past 50 years. The incidence of dengue haemorrhagic fever (DHF), a life-threatening complication of DF, is also increasing. The need for better classification of the severity of dengue infections has been proposed in order to clarify different entities of dengue infections. We defined a class of patients with DF with bleeding tendency (DF w/B) to differentiate further the varying pathogenesis among DF, DF w/B and DHF. In a hospital-based study in Taiwan, we compared clinical features, biochemistry and immune mediators among patients with DHF, DF w/B and DF. Results showed that DF w/B patients, similar to DHF patients, had a higher rate of secondary dengue infection (P<0.001) as well as higher IL-10 (P=0.023) and lower IFNgamma (P=0.009) levels than DF patients. In contrast, DHF patients had significantly higher soluble vascular cell adhesion molecule 1 levels than DF w/B patients (P=0.038) and DF patients (P<0.001). This study provides new insight into the different immune mechanisms of DF, DF w/B and DHF. DF involves a Th1 reaction and DF w/B involves an altered Th2 reaction, whereas DHF involves an altered Th2 reaction and augmented vascular insult.     

The north Indian dengue outbreak 2006: a retrospective analysis of intensive care unit admissions in a tertiary care hospital

Dengue fever (DF), dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) have emerged as public health problems of international concern. During a dengue outbreak in north India in October 2006, more than 10000 patients presented to hospital with fever. We retrospectively analysed the presenting features, treatment given and the outcome of patients admitted to the Intensive Care Unit (ICU), All India Institute of Medical Sciences (AIIMS): a tertiary care hospital in New Delhi. A total of 72 critically ill patients were referred for admission to the ICU. The common symptoms were fever (100%), myalgia (40%) and gastrointestinal bleed. Menorrhagia and haematuria were seen as the sole presenting features in many females. Treatment consisted of bed rest, oxygen therapy, intensive monitoring, antipyretics, platelet transfusions, hydration and electrolyte correction. On average, six units of platelets were required per patient. The average duration of stay in the ICU was 3 d. There were eight deaths. Adequate hydration and platelet replacement with transfusions, especially apheresis platelets to a target level above 60000 platelets/mm3, were effective means of combating the disease.     

Dengue outbreak in Karachi, Pakistan, 2006: experience at a tertiary care center

This is the first report of the largest epidemic of dengue hemorrhagic fever (DHF) virus infection (2006) with IgM-confirmed cases from Karachi, Pakistan. Medical records of 172 IgM-positive patients were reviewed retrospectively for demographic, clinical and laboratory data. Patients were categorized into dengue fever (DF) and DHF according to the WHO severity grading scale. The mean+/-SD age of the patients was 25.9+/-12.8 years, 55.8% were males and the hemoconcentration was recorded in a small number of patients [10 (7.0%)]. Male gender [odds ratio (OR)=14.7, P=0.003), positive history of vomiting (OR=4.3, P=0.047), thrombocytopenia at presentation (OR=225.2, P<0.001) and monocytosis (OR=5.8, P=0.030) were independently associated with DHF, but not with DF. Five cases (2.9%) had a fatal outcome, with a male-to-female ratio of 1:4. Three were from a pediatric group (<15 years). Pulmonary hemorrhages, disseminated intravascular coagulation and cerebral edema preceded death in these patients. The results have highlighted significant findings, such as adult susceptibility to DHF, pronounced abdominal symptoms and lack of hemoconcentration at time of presentation in the study population. These findings may play an important role in the case definitions of future studies from this part of the world.     

Silent spread of dengue and dengue haemorrhagic fever to Coimbatore and Erode districts in Tamil Nadu, India, 1998: need for effective surveillance to monitor and control the disease

Dengue fever (DF) or dengue haemorrhagic fever (DHF) has not previously been reported in Coimbatore and Erode districts in Tamil Nadu in India. In 1998, 20 hospitalized cases of fever tested positive for dengue virus IgM and/or IgG antibodies. All of them had dengue-compatible illness, and at least four had DHF. Two of them died. Sixteen cases were below 10 years of age. The cases were scattered in 15 distantly located villages and 5 urban localities that had a high Aedes aegypti population. Although the incidence of dengue-like illness has not increased recently, almost 89% (95/107) of samples from healthy persons in the community tested positive for dengue IgG antibodies. The study showed that dengue has been endemic in the area, but was not suspected earlier. A strong laboratory-based surveillance system is essential to monitor and control DF/DHF.     

Four dengue virus serotypes found circulating during an outbreak of dengue fever and dengue haemorrhagic fever in Jakarta, Indonesia, during 2004

Periodic outbreaks of dengue have emerged in Indonesia since 1968, with the severity of resulting disease increasing in subsequent years. In early 2004, a purported dengue outbreak erupted across the archipelago, with over 50,000 cases and 603 deaths reported. To confirm the disease aetiology and to provide an epidemiological framework of this epidemic, an investigation was conducted in ten hospitals within the capital city of Jakarta. Clinical and laboratory findings were determined from a cohort of 272 hospitalised patients. Exposure to dengue virus was determined in 180 (66.2%) patients. When clinically assessed, 100 (55.6%) of the 180 patients were classified as having dengue fever (DF), 31 (17.2%) as DF with haemorrhagic manifestations and 49 (27.2%) as dengue haemorrhagic fever (DHF). Evidence from haemagglutination inhibition assays suggested that 33/40 (82.5%) of those with DHF from which laboratory evidence was available suffered from a secondary dengue infection. All four dengue viruses were identified upon viral isolation, with DEN-3 being the most predominant serotype recovered, followed by DEN-4, DEN-2 and DEN-1. In summary, the 2004 outbreak of dengue in Jakarta, Indonesia, was characterised by the circulation of multiple virus serotypes and resulted in a relatively high percentage of a representative population of hospitalised patients developing DHF.     

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

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.     

Serological and virological features of dengue fever and dengue haemorrhagic fever in Thailand from 1999 to 2002

Serological and virological features of dengue fever (DF) and dengue haemorrhagic fever (DHF) in Thailand were analysed in 2715 patients from 1999 to 2002. The illness was caused by DEN-1 in 45%, DEN-2 in 32%, DEN-3 in 18% and DEN-4 in 5% of patients. Almost all of the DHF cases caused by DEN-2 and DEN-4 were in secondary infection, while approximately 20% of the DHF cases caused by DEN-1 and DEN-3 were in primary infection. Male:female ratio and age distribution were not different among four serotypes in primary and secondary infections. These results indicate that DEN-1 and DEN-3 induce DHF in both primary and secondary infections, and suggest that DEN-2 and DEN-4 in Thailand are less likely to cause DHF in primary infections.     

Dengue surveillance in the Pacific Islands

Adequate monitoring of dengue activity can be achieved using a combination of mosquito vector surveillance, fever surveillance, sentinel clinicians and laboratory screening. An apparent increase in fever cases or clinically suspected DF should prompt a careful clinical and laboratory investigation. If an outbreak of dengue is confirmed, health authorities will need to implement emergency community-wide control strategies. Laboratories will quickly feel the burden of clinical monitoring of cases admitted with DHF/DSS. Surveillance can change to clinical case definitions as health workers become familiar with the presenting features of DF and DHF/DSS. Criteria for hospital referral and admission must be well understood. Routine laboratory and sentinel surveillance may resume as the epidemic wanes, and should then continue indefinitely to monitor any resurgence of dengue activity.     

Dengue: a newly emerging viral infection in Andaman and Nicobar Islands, India

Prior to 2009 dengue fever had not been reported in the Andaman and Nicobar archipelago. In 2009, a few patients with dengue fever-like illness were reported, some of whom tested positive for dengue antibodies. In 2010, 516 suspected cases were reported, including some with dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS); 80 (15·5%) were positive for dengue antibodies. DENV RNA was detected in five patients and PCR-based typing showed that three of these belonged to serotype 1 and two to serotype 2. This was confirmed by sequence typing. Two clones of dengue virus, one belonging to serotype 1 and the other to serotype 2 appeared to be circulating in Andaman. Emergence of severe diseases such as DHF and DSS might be due to recent introduction of a more virulent strain or because of the enhancing effect of sub-neutralizing levels of antibodies developed due to prior infections. There is a need to revise the vector-borne disease surveillance system in the islands.     

Epidemiologic studies on Dengue in Santiago de Cuba, 1997

A small, isolated outbreak of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) due to dengue virus type 2 (DEN-2) was documented in Santiago de Cuba on the island of Cuba beginning in January 1997. There were 205 DHF/DSS cases, all in persons older than age 15 years. All but three had evidence of a prior dengue infection, with the only known opportunity being the islandwide dengue virus type 1 (DEN-1) epidemic of 1977-1979. Virtually complete clinical and laboratory surveillance of overt disease was achieved. From December 1997 to January 1998, a random, age-stratified serum sample was obtained from 1,151 persons in 40 residential clusters in Santiago. Sera were tested for DEN-1 and DEN-2 neutralizing antibodies. The prevalence of DEN-2 antibodies in children age 15 years and under, born after the 1981 DEN-2 epidemic, was taken as the 1997 DEN-2 infection rate. This was adjusted slightly to accommodate observed cases, resulting in an estimated infection rate of 4.3%. Dengue fever and DHF/DSS attack rates were calculated from estimated total primary and secondary DEN-2 infections. Only 3% of 13,116 primary infections were overt. The DHF/DSS attack rate for adults of all ages was 420 per 10,000 secondary DEN-2 infections.     

The XXth century dengue pandemic: need for surveillance and research.

By the last decade of the XXth century Aedes aegypti and the 4 dengue viruses had spread to nearly all countries of the tropical world. Some 2 billion persons live in dengue-endemic areas with tens of millions infected annually. Dengue pandemics were also documented in the XVIIIth and XIXth centuries; they were contained by organized anti-Aedes aegypti campaigns and urban improvements. The XXth century dengue pandemic has brought with it the simultaneous circulation of multiple serotypes and in its aftermath, endemic dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). Nearly 3 million children have been hospitalized with this syndrome in the past 3 decades, mainly in South-East Asia. Recent outbreaks of DHF/DSS in the Pacific Islands, China, India, Sri Lanka, Cuba and Venezuela are indicators of the high intensity and rapid spread of dengue transmission. The magnitude of the XXth century dengue pandemic requires urgent improvements in early warning surveillance by WHO Member States and the development of the capacity to study underlying mechanisms of the disease. A key research question is why does DHF/DSS not occur with all second dengue infections? Two answers have been suggested: (1) a human resistance gene. Data from the 1981 DHF/DSS epidemic in Cuba have demonstrated the existence in blacks of a resistance gene. The effect of such a gene in reducing disease susceptibility of American and African blacks requires more study. (2) The existence of dengue "biotypes". Some, but not all biotypes may cause DHF/DSS during a second dengue infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dengue fever--an emerging viral fever in Ludhiana, North India

The present study was undertaken to determine the seroprevalence of dengue fever and dengue haemorrhagic fever (DHF) in patients attending medical clinics or admitted in ICU with febrile signs and symptoms of heamorrhages. 168 (39.4%) out of 426 samples were tested positive for IgM antibodies. Of the 168 positive cases 159 were detected during the months of October and November 2005. Early detection of DHF/DSS can go a long way in managing these patients and to reduce morbidity and mortality specially in DHF and DSS cases.     

Economic impact of dengue and dengue hemorrhagic fever in the State of Zulia, Venezuela, 1997-2003]

OBJECTIVES: To determine the direct and indirect costs of medical care provided to cases of dengue and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) between 1997 and 2003 in Zulia State, Venezuela. METHODS: The total number of patients with dengue and DHF/DSS was obtained from records belonging to the Regional Epidemiology Office of the state of Zulia and from reports of cases that were confirmed in the Virology Section of Dr. Americo Negrette's Clinical Research Institute, Zulia University, Maracaibo, Venezuela, between 1 January 1997 and 31 December 2003. Direct costs included the cost of emergency medical care for all cases and hospital costs for cases with DHF/DSS (cost per bed-day and laboratory expenses). The costs connected to absence from work among patients over 15 years of age and mothers who accompanied their children under 15 years of age comprised the indirect costs, which were adjusted for the proportion of men and women in the labor force. Calculations were based on the minimum yearly wage, and results were given in United States dollars, converted according to each year's average exchange rate. RESULTS: During the study period, 33,857 cases of dengue and DHF/DSS were seen. Of them, 30 251 (89.35%) were cases of dengue, and 3606 (10.65%) were cases of DHF/DSS. Six cases of DHF/DSS died (lethality rate: 0.2 per 100 cases of DHF/DSS). Direct costs were 474,251.70 US dollars; of these costs, 132,042.30 US dollars were spent on emergency medical care and 342,209.40 US dollars on the hospital costs of DHF/DSS cases. Indirect costs were 873,825.84 US dollars and comprised 64.8% of overall expenditures (1 ,48,077.54 US dollars) connected to this disease during the study years. CONCLUSIONS: This is the first study on the economic impact of dengue in the state of Zulia and in Venezuela. In spite of some limitations, results show that dengue is an important public health problem that causes great expense because of temporary absenteeism from work and that undermines regional and national economic development.     

Myanmar dengue outbreak associated with displacement of serotypes 2, 3, and 4 by dengue 1

In 2001, Myanmar (Burma) had its largest outbreak of dengue-15,361 reported cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), including 192 deaths. That year, 95% of dengue viruses isolated from patients were serotype 1 viruses belonging to two lineages that had diverged from an earlier, now extinct, lineage sometime before 1998. The ratio of DHF to DSS cases in 2001 was not significantly different from that in 2000, when 1,816 cases of DHF/DSS were reported and dengue 1 also was the most frequently isolated serotype. However, the 2001 ratio was significantly higher than that in 1998 (also an outbreak year) and in 1999, when all four serotypes were detected and serotypes 1, 2, and 3 were recovered in similar numbers. The large number of clinical cases in 2001 may have been due, in part, to a preponderance of infections with dengue 1 viruses.     

Dengue haemorrhagic fever/dengue shock syndrome: lessons from the Cuban epidemic, 1981

Dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) is one of the principal causes of hospitalization and death among children in several south-east Asian countries. Also, in the Region of the Americas, there has been an increase in the frequency of dengue fever epidemics and in the number of cases of DHF/DSS. In 1981 an epidemic of dengue haemorrhagic fever occurred in Cuba and this suggests that there is a high risk that such epidemics could recur in the region. The article summarizes the main clinical, virological, and epidemiological data obtained during the outbreak, some of which are reported for the first time.     

Why dengue haemorrhagic fever in Cuba? 1. Individual risk factors for dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS)

During the dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) epidemic in Cuba in 1981, we identified some individual risk factors for the development of the severe clinical picture or for the fatal outcome of the disease. The percentage of secondary infection in 3 groups of patients with DHF/DSS was between 95 and 98.3 and it is concluded that secondary infection is an important, but not the only, condition for the development of DHF/DSS. An analysis of these 3 groups of patients and a fourth group of fatal cases showed that chronic diseases such as bronchial asthma, diabetes mellitus and sickle cell anaemia were additional risk factors contributing significantly to the development of DHF/DSS. The study also revealed that race was an individual risk factor, since DHF/DSS was more prevalent in white than in black persons.     

Clinical observations on virologically confirmed fatal dengue infections in Jakarta, Indonesia

Thirty virologically confirmed cases of dengue infection with a fatal outcome were studied clinically in Jakarta, Indonesia, from 1975 to 1978. All 4 dengue virus serotypes were isolated from fatal cases, but dengue type 3 was responsible for 21 (70%) of these isolates, compared to only 47% of isolates from all cases of dengue infection. The majority (60%) of these 30 cases were males in the 5-9-year age group. Nonspecific signs and symptoms in the fatal cases were no different from those in patients who survived dengue infection, but 70% of the patients with fatal outcome had one or more signs of encephalitis, primarily convulsions and somnolence; 3 of them developed spastic tetraparesis before death and 2 died of an illness clinically compatible with viral encephalitis. Other unexpected observations were that only 63% of the patients had classical dengue shock syndrome with haemoconcentration, thrombocytopenia and shock. A high percentage (80%) had gastrointestinal haemorrhage, and in 9 patients (30%) this was severe enough to cause shock and death. In these 9 cases, the gastrointestinal haemorrhage and haematemesis began before the onset of shock and there was no evidence of haemoconcentration or pleural effusion at any time during hospitalization. According to certain widely accepted criteria, these patients would not be diagnosed as dengue haemorrhagic fever (DHF). But as they made up nearly one-third of the confirmed fatal dengue infections in this study and had massive gastrointestinal haemorrhages with thrombocytopenia, the definition of DHF should be changed to include this type of patient. It is proposed that the disease should be more realistically classified as dengue fever with or without haemorrhage and dengue shock syndrome.