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Dengue fever (IPA: ['deŋgeɪ]) and dengue hemorrhagic fever (DHF) are acute febrile diseases, found in the tropics, with a geographical spread similar to malaria. Caused by one of four closely related virus serotypes of the genus Flavivirus, family Flaviviridae, each serotype is sufficiently different that there is no cross-protection and epidemics caused by multiple serotypes (hyperendemicity) can occur. Dengue is transmitted to humans by the mosquito Aedes aegypti (rarely Aedes albopictus).
Signs and Symptoms
This infectious disease is manifested by a sudden onset of fever, with severe headache, muscle and joint pains (myalgias and arthralgiasbreak-bone fever or bonecrusher disease) and rashes; the dengue rash is characteristically bright red petechia and usually appears first on the lower limbs and the chest - in some patients, it spreads to cover most of the body. There may also be gastritis with some combination of associated abdominal pain, nausea, vomiting or diarrhea.
Some cases develop much milder symptoms, which can, when no rash is present, be misdiagnosed as a flu or other viral infection. Thus, travelers from tropical areas may inadvertently pass on dengue in their home countries, having not being properly diagnosed at the height of their illness. Patients with dengue can only pass on the infection through mosquitoes or blood products while they are still febrile.
The classic dengue fever lasts about six to seven days, with a smaller peak of fever at the trailing end of the fever (the so-called "biphasic pattern"). Clinically, the platelet count will drop until the patient's temperature is normal.
Cases of DHF also shows higher fever, haemorrhagic phenomena, thrombocytopenia and haemoconcentration. A small proportion of cases leads to dengue shock syndrome (DSS) which has a high mortality rate.
Diagnosis
The diagnosis of dengue is usually made clinically. The classic picture is high fever with no localising source of infection, a petechial rash with thrombocytopenia and relative leukopenia.
There exists a WHO definition of dengue haemorrhagic fever that has been in use since 1975; all four criteria must be fulfilled:
Treatment
The mainstay of treatment is supportive therapy. The patient is encouraged to keep up oral intake, especially of oral fluids. If the patient is unable to maintain oral intake, supplementation with intravenous fluids may be necessary to prevent dehydration and significant hemoconcentration. A platelet transfusion is rarely indicated if the platelet level drops significantly or if there is significant bleeding. But the transfusion is recommendable on platelet count falling below 20,000 without hemorrhage / bleeding or approx 50,000 with hemorrhage/bleeding. Internal bleeding indicated by dark color of stools, other bleedings indicated at surface as red rashes all over or most of the body parts.
Epidemiology
World-wide dengue distribution, 2005
World-wide dengue distribution, 2000
The first epidemics occurred almost simultaneously, in Asia, Africa, and North America in the 1780s. The disease was identified and named in 1779. A global pandemic began in Southeast Asia in the 1950s and by 1975 DHF had become a leading cause of death among children in many countries in that region. Epidemic dengue has become more common since the 1980s - by the late 1990s, dengue was the most important mosquito-borne disease affecting humans after malaria, there being around 40 million cases of dengue fever and several hundred thousand cases of dengue hemorrhagic fever each year. In February 2002 there was a serious outbreak in Rio de Janeiro, affecting around one million people but only killing sixteen.
Significant outbreaks of dengue fever tend to occur every five or six years. There tend to remain large numbers of susceptible people in the population despite previous outbreaks because there are four different strains of the dengue virus and because of new susceptible individuals entering the target population, either through childbirth or immigration.
There is significant evidence, originally suggested by S.B. Halstead in the 1970s, that dengue hemorrhagic fever is more likely to occur in patients who have secondary infections by serotypes different from the primary infection. This is due to a process known as antibody-dependent enhancement (ADE), which allows for increased uptake and virion replication during a secondary infection with a different strain. Through an immunological phenomena, known as original antigenic sin, the immune system is not able to adequately respond to the stronger infection, and the secondary infection becomes far more serious.[1]
In Singapore, there are about 4,000-5,000 reported cases of dengue fever or dengue haemorrhagic fever every year. In the year 2003, there were 6 deaths from dengue shock syndrome. It is believed that the reported cases of dengue are an underrepresentation of all the cases of dengue as it would ignore subclinical cases and cases where the patient did not present for medical treatment. With proper medical treatment, the mortality rate for dengue can therefore be brought down to less than 1 in 1000.
Prevention
There is no commercially available vaccine for the dengue flavivirus. However, one of the many ongoing vaccine development programs is the Pediatric Dengue Vaccine Initiative (PDVI) which was set up in 2003 with the aim of accelerating the development and introduction of dengue vaccine(s) that are affordable and accessible to poor children in endemic countries.
Thai researchers, in phase III testing, have planned to test a dengue fever vaccine on 3,000-5,000 human volunteers within the next three years after having successfully conducted tests on animals and a small group of human volunteers.[2]
A field technician looking for larvae in standing water containers during the 1965 Aedes Aegypti eradication program in Miami, Florida. In the 1960s, a major effort was made to eradicate the principal urban vector mosquito of dengue and yellow fever viruses, A. aegypti, from southeast United States.
Courtesy: Centers for Disease Control and Prevention Publich Health Image Library
Primary prevention of dengue mainly resides in eliminating or reducing the mosquito vector for dengue. Public spraying for mosquitoes is the most important aspect of this vector. Application of larvicides such as Abatestanding water is more effective in the long term control of mosquitoes. Initiatives to eradicate pools of standing water (such as in flowerpots) have proven useful in controlling mosquito-borne diseases. Promising new techniques have been recently reported from Oxford University on rendering the Aedes mosquito pest sterile.
Personal prevention consists of the use of mosquito nets, repellents, cover exposed skin, use DEET-impregnated bednets, and avoiding endemic areas. This is also important for malaria prevention.
Potential antiviral approaches
In cell culture experiments Morpholino antisense oligos have shown specific activity against Dengue virus.[3]
In 2002 the Swiss pharma company Novartis and the Singapore Economic Development board created the Novartis Institute for Tropical Diseases (NITD). NITD is a public-private partnership that researches neglected tropical disease. NITD's dengue unit is researching anti-viral drug discovery to treat or prevent dengue fever.
In 2006, a group of Argentine scientists directed by Andrea Gamarnik discovered the molecular replication mechanism of the virus, which could be attacked by disruption the polymerase's work
Signs and Symptoms
This infectious disease is manifested by a sudden onset of fever, with severe headache, muscle and joint pains (myalgias and arthralgiasbreak-bone fever or bonecrusher disease) and rashes; the dengue rash is characteristically bright red petechia and usually appears first on the lower limbs and the chest - in some patients, it spreads to cover most of the body. There may also be gastritis with some combination of associated abdominal pain, nausea, vomiting or diarrhea.
Some cases develop much milder symptoms, which can, when no rash is present, be misdiagnosed as a flu or other viral infection. Thus, travelers from tropical areas may inadvertently pass on dengue in their home countries, having not being properly diagnosed at the height of their illness. Patients with dengue can only pass on the infection through mosquitoes or blood products while they are still febrile.
The classic dengue fever lasts about six to seven days, with a smaller peak of fever at the trailing end of the fever (the so-called "biphasic pattern"). Clinically, the platelet count will drop until the patient's temperature is normal.
Cases of DHF also shows higher fever, haemorrhagic phenomena, thrombocytopenia and haemoconcentration. A small proportion of cases leads to dengue shock syndrome (DSS) which has a high mortality rate.
Diagnosis
The diagnosis of dengue is usually made clinically. The classic picture is high fever with no localising source of infection, a petechial rash with thrombocytopenia and relative leukopenia.
There exists a WHO definition of dengue haemorrhagic fever that has been in use since 1975; all four criteria must be fulfilled:
- Fever
- Haemorrhagic tendency (positive tourniquet test, spontaneous bruising, bleeding from mucosa, gingiva, injection sites, etc.; vomiting blood, or bloody diarrheahematocrit more than 20% higher than expected, or drop in haematocrit of 20% or more from baseline following IV fluid, pleural effusion, ascites, hypoproteinaemia)
- Weak rapid pulse,
- Narrow pulse pressure (less than 20 mm Hg)
- Hypotension for age;
- Cold, clammy skin and restlessness.
Treatment
The mainstay of treatment is supportive therapy. The patient is encouraged to keep up oral intake, especially of oral fluids. If the patient is unable to maintain oral intake, supplementation with intravenous fluids may be necessary to prevent dehydration and significant hemoconcentration. A platelet transfusion is rarely indicated if the platelet level drops significantly or if there is significant bleeding. But the transfusion is recommendable on platelet count falling below 20,000 without hemorrhage / bleeding or approx 50,000 with hemorrhage/bleeding. Internal bleeding indicated by dark color of stools, other bleedings indicated at surface as red rashes all over or most of the body parts.
Epidemiology
World-wide dengue distribution, 2005
World-wide dengue distribution, 2000
The first epidemics occurred almost simultaneously, in Asia, Africa, and North America in the 1780s. The disease was identified and named in 1779. A global pandemic began in Southeast Asia in the 1950s and by 1975 DHF had become a leading cause of death among children in many countries in that region. Epidemic dengue has become more common since the 1980s - by the late 1990s, dengue was the most important mosquito-borne disease affecting humans after malaria, there being around 40 million cases of dengue fever and several hundred thousand cases of dengue hemorrhagic fever each year. In February 2002 there was a serious outbreak in Rio de Janeiro, affecting around one million people but only killing sixteen.
Significant outbreaks of dengue fever tend to occur every five or six years. There tend to remain large numbers of susceptible people in the population despite previous outbreaks because there are four different strains of the dengue virus and because of new susceptible individuals entering the target population, either through childbirth or immigration.
There is significant evidence, originally suggested by S.B. Halstead in the 1970s, that dengue hemorrhagic fever is more likely to occur in patients who have secondary infections by serotypes different from the primary infection. This is due to a process known as antibody-dependent enhancement (ADE), which allows for increased uptake and virion replication during a secondary infection with a different strain. Through an immunological phenomena, known as original antigenic sin, the immune system is not able to adequately respond to the stronger infection, and the secondary infection becomes far more serious.[1]
In Singapore, there are about 4,000-5,000 reported cases of dengue fever or dengue haemorrhagic fever every year. In the year 2003, there were 6 deaths from dengue shock syndrome. It is believed that the reported cases of dengue are an underrepresentation of all the cases of dengue as it would ignore subclinical cases and cases where the patient did not present for medical treatment. With proper medical treatment, the mortality rate for dengue can therefore be brought down to less than 1 in 1000.
Prevention
There is no commercially available vaccine for the dengue flavivirus. However, one of the many ongoing vaccine development programs is the Pediatric Dengue Vaccine Initiative (PDVI) which was set up in 2003 with the aim of accelerating the development and introduction of dengue vaccine(s) that are affordable and accessible to poor children in endemic countries.
Thai researchers, in phase III testing, have planned to test a dengue fever vaccine on 3,000-5,000 human volunteers within the next three years after having successfully conducted tests on animals and a small group of human volunteers.[2]
A field technician looking for larvae in standing water containers during the 1965 Aedes Aegypti eradication program in Miami, Florida. In the 1960s, a major effort was made to eradicate the principal urban vector mosquito of dengue and yellow fever viruses, A. aegypti, from southeast United States.
Courtesy: Centers for Disease Control and Prevention Publich Health Image Library
Primary prevention of dengue mainly resides in eliminating or reducing the mosquito vector for dengue. Public spraying for mosquitoes is the most important aspect of this vector. Application of larvicides such as Abatestanding water is more effective in the long term control of mosquitoes. Initiatives to eradicate pools of standing water (such as in flowerpots) have proven useful in controlling mosquito-borne diseases. Promising new techniques have been recently reported from Oxford University on rendering the Aedes mosquito pest sterile.
Personal prevention consists of the use of mosquito nets, repellents, cover exposed skin, use DEET-impregnated bednets, and avoiding endemic areas. This is also important for malaria prevention.
Potential antiviral approaches
In cell culture experiments Morpholino antisense oligos have shown specific activity against Dengue virus.[3]
In 2002 the Swiss pharma company Novartis and the Singapore Economic Development board created the Novartis Institute for Tropical Diseases (NITD). NITD is a public-private partnership that researches neglected tropical disease. NITD's dengue unit is researching anti-viral drug discovery to treat or prevent dengue fever.
In 2006, a group of Argentine scientists directed by Andrea Gamarnik discovered the molecular replication mechanism of the virus, which could be attacked by disruption the polymerase's work
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