DENGUE FEVER
Introduction
● Dengue fever is one of the world’s major emerging infectious diseases. It is now the most common cause of arboviral disease in the world. 2
● It is caused by the dengue virus, an arbovirus that is transmitted by the bite of an infected mosquito.
● Most cases will be self-limiting with good recovery, however occasionally severe disease can occur in the form of dengue hemorrhagic fever and/ or dengue shock syndrome.
Severe disease is more likely with re-exposure to a different serotype. This is thought to be due to immune enhancement in a person with dengue antibodies due to a previous infection that is subsequently infected by a dengue virus of a different serotype.
● It should be considered in the differential diagnosis of fever in a returned traveler within 14 days from tropical regions of the world or from Northern Queensland.
Pathology
Organism
● Dengue virus has four related but distinct serotypes: 1, 2, 3 and 4.
● Dengue virus belongs to the family Flaviviridae (single-stranded, non-segmented RNA viruses), genus flavivirus.
Pathophysiology
● Dengue haemorrhagic fever is believed to be caused by immune enhancement when a person with dengue antibodies due to a previous infection is subsequently infected by a dengue virus of a different serotype. 1
Epidemiology
Dengue virus has been recognized since the latter part of the 18th century as causing epidemics in tropical and subtropical parts throughout the world. Global distribution of dengue fever, 2002, (CDC)
Transmission
● Dengue virus is an arbovirus, (or arthropod-borne virus), ie it is transmitted by the bite of an infected Aedes mosquito.
● Dengue virus is transmitted by mosquitoes of the genus aedes including Aedes aegypti and Aedes albopictus.
Aedes aegypti is found worldwide in the tropics and subtropics, and is the principal vector. It is an efficient vector because it is highly susceptible to dengue virus, feeds preferentially on human blood, is a daytime feeder, has an almost imperceptible bite, and is capable of biting several people in a short period for one blood meal. The mosquito is well adapted to life in urban settings and typically breeds in clean, stagnant water in containers that collect rainwater, such as tires, tin cans, pots, and buckets.
Aedes albopictus, a mosquito common in South East Asia and Papua New Guinea is also an important vector.
● Other Aedes species are involved in the enzootic monkey cycle.
● Note that in countries where dengue currently is not endemic but where a capable vector exists, new autochthonous cycles of infection may be established from infected travelers or immigrants who are coming from areas where the disease is endemic. ● There is no evidence of person to person transmission.
Incubation Period
● The incubation period is usually about three days but may be up to fourteen days.
Reservoir
● Humans are the only vertebrate hosts of the virus. There is a jungle cycle between monkeys and mosquitoes, but this plays no role in human disease.
Period of Communicability
● There is no evidence for person to person transmission.
Susceptibility and Resistance
● Infection with one serotype confers long-term immunity only to that serotype, and therefore persons may be infected up to four times. 2
Clinical Features
Two forms of dengue fever are described, classical dengue (also known as “break bone fever”) and the more severe life threatening form, dengue hemorrhagic fever.
See appendix 1 below for a suggested algorithm for the clinical diagnosis of possible dengue fever.
Classic Dengue Fever (Break Bone Fever)
There is a high sub-clinical rate of milder disease in children compared to adults.
Fatality rate is low.
Clinical features include:
1. Dengue fever classically presents as an acute febrile illness of sudden onset.
2. Fever lasting three to five days
3. Non-specific constitutional symptoms:
These can be extremely debilitating and are usually described as “flu-like”
● Myalgias (particularly backache).
● Arthralgias ● Headache, frontal and retro-orbital pain is common.
● Lethargy/ malaise.
4. GIT upset
● Anorexia, nausea and vomiting.
5. Rash
● A non-specific viral rash may be seen in about 50% of cases. 2
Typical dengue rash with patchy sparing of islands of skin.
6. Convalescence may be prolonged.
Dengue Hemorrhagic Fever
Dengue haemorrhagic fever (DHF) is a severe from of dengue virus infection.
It occurs mainly in children.
In its severest form it may result in shock (dengue shock syndrome), which has a high fatality rate.
The rate of death from dengue haemorrhagic fever without dengue shock syndrome is up to 5%, with the shock syndrome mortality is high without aggressive supportive treatment.
Clinical features include:
1. Abrupt onset of fever
2. Non-specific constitutional symptoms: These can be extremely debilitating and are usually described as “flu-like”
● Myalgias (particularly backache),
● Arthralgias
● Headache, retro-orbital pain is also common.
● Lethargy/ malaise.
4. GIT upset
● Anorexia, nausea and vomiting.
5. Haemorrhagic phenomena
● Haemorrhagic skin lesions, petechiae, purpura.
● Mucosal bleeding, gums, epistaxis or GIT
● Thrombocytopenia. Check for a positive tourniquet test. 2
The tourniquet test is performed by inflating a blood pressure cuff on the upper arm to a point midway between systolic and diastolic blood pressures for five minutes. A test is considered positive when there are 20 or more petechiae per square inch (6.25 cm2) on the forearm.
6. Dengue shock syndrome
● Circulatory collapse and death.
● Of the severe complications hypotension is more common than hemorrhagic complications. Note that hemorrhagic phenomena alone is not considered to constitute DHF, there must also be evidence of capillary leakage (rising hematocrit or circulatory compromise) 2
Investigations
Biochemical
1. FBE
● In particular for thrombocytopenia, (< 100,000/ mm 3) which is very suggestive of dengue fever in the absence of other reason for thrombocytopenia.
● Elevated hematocrit, reflecting hemo-concentration due to increased vascular permeability is also considered very suggestive.
● Leukopenia may be seen.
2. U&Es/ glucose
3. Coagulation profile, including DIC screen.
4. LFTs
● Mild to moderate elevation in liver transaminases may be seen.
Serology
● IgM indicates acute infection. May take up to 5 days after the onset of fever. IgM levels will then remain detectable for 3-6 months.
● IgG merely indicates indeterminate past infection. A rise in titre will generally begin after 7-10 days of the fever. A four fold rise in titre however is only useful retrospectively. IgG will remain detectable for life.
● Note however that, either IgM or IgG positivity may result from cross-reactivity with other flavivirus antibodies (such as West Nile, Yellow fever or Japanese encephalitis) and so the possibility of exposure to other flaviviruses must be considered. Levels may also be elevated due to previous vaccination against flaviviruses.
PCR
● PCR testing is available for blood or CSF samples
Management
1. Supportive treatment: There is no specific treatment for dengue fever.
● Fluid resuscitation is important, especially in cases of dengue hemorrhagic fever.
● Inotropes may be required for cardiogenic shock
● Other supportive measures as clinically indicated.
2. Anti-pyretics:
● Paracetomol may be given. Aspirin and NSAIDs are best avoided due to the potential to aggravate bleeding complications.
3. Monitoring:
● Platelet counts and hematocrit determinations should be carefully monitored to allow prompt recognition of the development of DHF and institution of fluid therapy.
4. FFP and platelets may be required in cases of DIC.
Disposition
● Any patient with suspected dengue fever must be admitted to hospital. This will usually be the case for fever in any returned traveller from regions of the world where serious infectious disease is endemic
● Dengue fever will rarely be diagnosed in the ED and other serious infectious diseases such as malaria or typhoid will also need to be considered in the first instance.
Vaccine
● There is no vaccine currently available for dengue fever, but intensive research continues. Appendix 1
Algorithm for the clinical diagnosis of Dengue in returning travellers. 2 References
1. The Blue Book Website, January 2008.
2. Annelies Wilder-Smith, Dengue in Travelers N Engl J Med 2005; 353:924-32.
3. CDC Website, February 2007.