MyEClinic
MyEClinic
Health Dictionary Find a Doctor

Dengue fever

This page is about clinical aspects of the disease.  For microbiologic aspects of the causative organism(s), see Dengue virus.

For patient information, click here.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

Synonyms and keywords: Dengue, Bonecrusher disease, Breakbone fever

Overview

Overview


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Dengue fever (Template:IPA2) and dengue hemorrhagic fever (DHF) are acute febrile diseases, found in the tropics and Africa, with a geographical spread similar to malaria.[1] One major difference, however, is that malaria is often eradicated in major cities, whereas dengue is often found in urban areas of developed tropical nations, like Singapore. 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 Aedes aegypti (rarely Aedes albopictus) mosquito, which feeds during the day[2].

Historical Perspective

Outbreaks resembling dengue fever have been reported throughout history.[3] The first definitive case report dates from 1789 and is attributed to Benjamin Rush, who coined the term “breakbone fever” (because of the symptoms of myalgia and arthralgia). The disease was named Dengue in 1779. The viral etiology and the transmission by mosquitoes were only deciphered in the 20th century. Population movements during World War II spread the disease globally.

Classification

Current WHO guideline classifies dengue into non-severe and severe disease depending on whether there is severe plasma leakage, severe bleeding, or severe organ impairment. For practical purposes, non-severe cases can be further divided into two subgroups: those with warning signs and those without them. Patients with suspected dengue should be triaged and managed accordingly.[4]

Pathophysiology

Aedes aegypti is the principal mosquito vector of dengue fever viruses and is closely associated with humans and their dwellings. The Dengue fever virus also inhibits the human immune response.[5][6]

Causes

Dengue fever is caused by one of four different but related Dengue fever viruses. Aedes aegypti is the principal mosquito vector of dengue fever viruses.[7]

Differentiating Ebola from other Diseases

Dengue fever must be differentiated from other diseases that prevent with flu like symptoms fever, retro-orbital headache, fatigue, joint aches or arthralgias (joint aches), myalgias (muscle aches), nausea/vomiting, and lymphadenopathy (swollen lymph nodes). Diseases with similar symptoms include influenza, measles, rubella, malaria, Zika virus, and Yellow fever.[8]

Epidemiology and Demographics

Dengue is endemic throughout the tropics and subtropics and is a leading cause of febrile illness among travelers returning from the Caribbean, South America, and South and Southeast Asia, according to an analysis of data collected by the GeoSentinel Surveillance Network. Dengue occurs in more than 100 countries worldwide, including Puerto Rico, the US Virgin Islands, and US-affiliated Pacific Islands. Sporadic outbreaks with local transmission have occurred in Florida, Hawaii, and along the Texas-Mexico border. There are 40 million cases worldwide each year.

Risk Factors

Living or traveling to a region of the world where the infection is endemic is a risk factor for the disease. The presence of water-holding containers in and around the home needed for the mosquito’s to complete their development sustains the reservoir for disease and is a risk factor. Risk factors for severe disease include being a neonate or young child, female sex, high body mass index, viral load, genetic polymorphisms and previous infection with DENV-1 if the patient contracts DENV-2 or DENV-3. Diabetes and asthma are risk factors for fatal disease.[9]

Natural History

Dengue fever generally lasts a week or more, and can rarely be complicated by bleeding, febrile convulsions and coma. The prognosis is good. Dengue fever can be life-threatening in people with chronic diseases such as diabetes and asthma.

Diagnosis

History and Symptoms

Dengue virus infection has a wide spectrum of clinical manifestations, ranging from asymptomic infection, to symptoms of non-severe disease (such as flu-like symptoms, fever, retro-orbital headache, fatigue, arthralgia, myalgia, nausea, vomiting, or lymphadenopathy), and to severe complications including signs of plasma leakage (such as pleural effusion or ascites), hemorrhagic tendencies (such as petechiae, ecchymoses, purpura, easy bruising at venipuncture sites, mucosal bleeding, gastrointestinal bleeding, hematemesis, or melena), and organ failure associated with shock.[4]

Physical Examination

The typical signs of Dengue Fever include a high fever with no localizing source of infection on physical examination. Occasionally petechia are present. The physical examination in Dengue fever should be directed toward identifying warning signs that the patient has or may develop severe disease warranting in-hospital observation and/or intensive treatment. These warning signs include tachycardia, postural hypotension, a narrow pulse pressure (<20 mm Hg) and / or frank hypotension could indicate intravascular volume depletion due to either dehydration or capillary leak; petechia, lethargy, restlessness, mucosal bleeding, pleural effusion, ascites, hepatomegaly, abdominal tenderness and pedal edema.[7]

Laboratory Findings

The earliest abnormality in the complete blood count is decreased white cell count (leukopenia), which usually occurs during the febrile phase and should alert the physician to a high probability of dengue. The platelet count usually begins to drop when the temperature is returning to normal and is followed by findings indicative of plasma leakage such as elevated hematocrit level and hypoproteinemia. However, the extent of hemoconcentration may be affected by dilutional effect from excessive fluid administration or significant hemorrhage from the gastrointestinal tract and the white cell count may increase as a result of stress response. Serology and virology tests are used to confirm the diagnosis of dengue virus infection.

Other Diagnostic Studies

Treatment

Medical Therapy

Currently, no effective antiviral agents are available to treat symptomatic dengue virus infection, and management remains supportive with emphasis on judicious fluid administration with oral rehydration solution or intravenous fluids. Acetyl-salicylic (aspirin) derivatives and other non-steroidal anti-inflammatory drugs should be avoided because of their potential to increase the risk of bleeding. Patients who have no complications and are able to tolerate oral fluids may be managed at home or as an outpatient. Development of any warning signs (See Group B or C below) suggests the need for intravenous fluid therapy and hospitalization. If the condition progresses to the Dengue shock syndrome, restoration of plasma volume with fluid boluses and/or blood transfusion is required to maintain adequate tissue perfusion.

Primary Prevention

There is no vaccine for Dengue fever, and the primary mode of preventing disease is through mosquito control and elimination of the reservoir of disease. Personal prevention consists of the use of mosquito nets, repellents containing NNDB or DEET, covering exposed skin, use of DEET-impregnated bednets, and avoiding endemic areas.[7]

Future or Investigational Therapies

References

  1. ↑ “CDC – Yellow Book: [4] Dengue Fever – CDC Traveler’s Health”. Retrieved 2007-05-20.
  2. ↑ “Dengue Fever – Information Sheet” – World Health Organization
  3. ↑ Gubler D (1998). “Dengue and dengue hemorrhagic fever”. Clin Microbiol Rev. 11 (3): 480–96. PMID 9665979.
  4. ↑ 4.0 4.1 “Dengue haemorrhagic fever: diagnosis, treatment, prevention and control” (PDF).
  5. ↑ Diamond MS (2009). “Mechanisms of evasion of the type I interferon antiviral response by flaviviruses”. J Interferon Cytokine Res. 29 (9): 521–30. doi:10.1089/jir.2009.0069. PMID 19694536.
  6. ↑ Jones M, Davidson A, Hibbert L, Gruenwald P, Schlaak J, Ball S; et al. (2005). “Dengue virus inhibits alpha interferon signaling by reducing STAT2 expression”. J Virol. 79 (9): 5414–20. doi:10.1128/JVI.79.9.5414-5420.2005. PMC 1082737. PMID 15827155.
  7. ↑ 7.0 7.1 7.2 “Dengue: guidelines for diagnosis, treatment, prevention and control” (PDF).
  8. ↑ Staples, J. Erin; Breiman, Robert F.; Powers, Ann M. (2009). “Chikungunya Fever: An Epidemiological Review of a Re‐Emerging Infectious Disease”. Clinical Infectious Diseases. 49 (6): 942–948. doi:10.1086/605496. ISSN 1058-4838.
  9. ↑ “WHO: Dengue guidelines for diagnosis, treatment, prevention and control: new edition”.
Historical Perspective

Historical Perspective

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Outbreaks resembling dengue fever have been reported throughout history.[1] The first definitive case report dates from 1789 and is attributed to Benjamin Rush, who coined the term “breakbone fever” (because of the symptoms of myalgia and arthralgia). The disease was named Dengue in 1779. The viral etiology and the transmission by mosquitoes were only deciphered in the 20th century. Population movements during World War II spread the disease globally.

History of Epidemics

The first epidemics occurred almost simultaneously in Asia, Africa, and North America in the 1780s. A global pandemic began in Southeast Asia in the 1950s and by 1975 Dengue Hemorrhagic Fever (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. There was a serious outbreak in Rio de Janeiro in February, 2002 affecting around one million people and killing sixteen.

Etymology

The disease was named Dengue in 1779. The origins of the word “Dengue” are not clear, but one theory is that it is derived from the Swahili phrase “Ka-dinga pepo”, which describes the disease as being caused by an evil spirit.[2] The Swahili word “dinga” may possibly have its origin in the Spanish word “dengue” (fastidious or careful), describing the gait of a person suffering dengue fever,[3] or, alternatively, the Spanish word may derive from the Swahili.[4]

References

  1. ↑ Gubler D (1998). “Dengue and dengue hemorrhagic fever”. Clin Microbiol Rev. 11 (3): 480–96. PMID 9665979.
  2. ↑ Chemical and Biological Warfare Agents
  3. ↑ Etymonline entry
  4. ↑ “etomologia: dengue” (PDF). Emerging Infectious Diseases. 12 (6): 893. 2006.
Classification

Classification

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alonso Alvarado, M.D. [2]

Overview

Current WHO guideline classifies dengue into non-severe and severe disease depending on whether there is severe plasma leakage, severe bleeding, or severe organ impairment. For practical purposes, non-severe cases can be further divided into two subgroups: those with warning signs and those without them. Patients with suspected dengue should be triaged and managed accordingly.

Classification

1997 WHO Classification

Historically, symptomatic dengue virus infections were classified as dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. The case definitions were found too difficult to apply in resource-limited settings and too specific, as it failed to identify a substantial proportion of severe dengue cases, including cases of hepatic failure and encephalitis.

The tables below describe the 1997 WHO dengue case classification:[1]

Dengue Fever
Probable Dengue Fever
❑ An acute febrile illness
PLUS
❑ Two or more of the following manifestations:
   ❑ Headache
   ❑ Retro-orbital pain
   ❑ Myalgia
   ❑ Arthralgia
   ❑ Rash
   ❑ Hemorrhagic manifestations
   ❑ Leukopenia
PLUS
❑ Supportive serology
   ❑ A reciprocal hemagglutination-inhibition antibody titre ≥1280
   ❑ A comparable IgG enzyme-linked immunosorbent assay (ELISA) titer
   ❑ A positive IgM test on a late acute or convalescent-phase serum specimen
Confirmed Dengue Fever
❑ A case confirmed by laboratory criteria
   ❑ Isolation of the dengue virus from serum or autopsy samples
   ❑ Demonstration of a fourfold or greater change in reciprocal IgG or IgM antibody titers to one or more dengue virus antigens in paired serum samples
   ❑ Demonstration of dengue virus antigen in autopsy tissue, serum or cerebrospinal fluid (CSF) samples by immunohistochemistry, immunofluorescence or ELISA
   ❑ Detection of dengue virus genomic sequences in autopsy tissue serum or CSF samples by polymerase chain reaction (PCR)
Reportable Dengue Fever
❑ Any probable or confirmed case should be reported
Dengue Hemorrhagic Fever & Dengue Shock Syndrome
Dengue Hemorrhagic Fever (DHF)
❑ Fever, or history of acute fever, lasting 2–7 days, occasionally biphasic
PLUS
❑ Hemorrhagic tendencies, evidenced by at least one of the following:
   ❑ A positive tourniquet test†
   ❑ Petechiae, ecchymoses, or purpura
   ❑ Bleeding from the mucosa, gastrointestinal tract, injection sites or other locations
   ❑ Hematemesis or melena
PLUS
❑ Thrombocytopenia (100,000 cells per mm3 or less)
PLUS
❑ Evidence of plasma leakage due to increased vascular permeability, manifested by at least one of the following:
   ❑ A rise in the hematocrit equal to or greater than 20% above average for age, sex and population
   ❑ A drop in the hematocrit following volume-replacement treatment equal to or greater than 20% of baseline
   ❑ Signs of plasma leakage such as pleural effusion, ascites and hypoproteinemia
Dengue Shock Syndrome (DSS)
❑ All of the above four criteria for DHF must be present
PLUS
❑ Evidence of circulatory failure manifested by:
   ❑ Rapid and weak pulse AND narrow pulse pressure
❑ OR manifested by:
   ❑ Hypotension for age AND cold, clammy skin and restlessness

   † The tourniquet test is performed by inflating a blood pressure cuff on the upper arm to a point midway between the systolic and diastolic pressures for 5 minutes. A test is considered positive when 20 or more petechiae per 2.5 cm (1 inch) square are observed. The test may be negative or mildly positive during the phase of profound shock. It usually becomes positive, sometimes strongly positive, if the test is conducted after recovery from shock.

2009 WHO Classification

A newer classification published by WHO in 2009 categorizes the disease into probable dengue or laboratory-confirmed dengue (with or without warning signs) and severe dengue (encompassing severe plasma leakage, severe bleeding, and severe organ involvement). However, it has been criticized as overly inclusive for several reasons:[2]

  • It allows several different ways to qualify for severe dengue.
  • Nonspecific warning signs are used as diagnostic criteria.
  • Severity determination is dependent on individual judgment due to the lack of explicit clinical criteria for establishing severe dengue.

The tables below describe the 2009 WHO dengue case classification:[3][4]

Dengue ± Warning Signs
Probable Dengue (live in or travel to dengue endemic area)
❑ Fever
PLUS
❑ Two of the following criteria:
   ❑ Nausea or vomiting
   ❑ Rash
   ❑ Aches and pains
   ❑ Tourniquet test positive†
   ❑ Leukopenia
   ❑ Any warning sign
Warning Signs
❑ Warning signs requiring strict observation and medical intervention:
   ❑ Abdominal pain or tenderness
   ❑ Persistent vomiting
   ❑ Clinical fluid accumulation
   ❑ Mucosal bleed
   ❑ Lethargy, restlessness
   ❑ Liver enlargment >2 cm
   ❑ Increase in hematocrit with rapid decrease in platelet count
Severe Dengue
Severe Plasma Leakage
❑ Severe plasma leakage leading to:
   ❑ Shock (dengue shock syndrome)
   ❑ Fluid accumulation with respiratory disrtess
Severe Bleeding
❑ Severe bleeding as evaluated by clinician:
   ❑ Persistent and/or severe overt bleeding in the presence of unstable hemodynamic status, regardless of the hematocrit level
   ❑ A decrease in hematocrit after fluid resuscitation together with unstable hemodynamic status
   ❑ Refractory shock unresposive to fluid resuscitation of 40–60 ml/kg
   ❑ Hypotensive shock with low/normal hematocrit before fluid resuscitation
   ❑ Persistent or worsening metabolic acidosis ± a well-maintained systolic blood pressure, especially in those with severe abdominal tenderness and distension
Severe Organ Involvement
❑ Severe organ involvement indicated by:
   ❑ Liver: AST or ALT ≥1000 IU/L
   ❑ CNS: impaired consciousness
   ❑ Heart or other organs

   † The tourniquet test is performed by inflating a blood pressure cuff on the upper arm to a point midway between the systolic and diastolic pressures for 5 minutes. A test is considered positive when 20 or more petechiae per 2.5 cm (1 inch) square are observed. The test may be negative or mildly positive during the phase of profound shock. It usually becomes positive, sometimes strongly positive, if the test is conducted after recovery from shock.

Laboratory Tests for Confirmed and Probable Dengue Infection

Definition Method† Interpretation† Sample Characteristics
Confirmed Dengue Infection Viral isolation Virus isolated Serum (collected at 1–5 days of fever) or necropsy tissues
Genome detection Positive RT-PCR or positive real-time RT-PCR
Antigen detection Positive NS1 Ag
Positive immunohistochemical Necropsy tissues
IgM seroconversion From negative IgM to positive IgM in paired sera Acute serum (days 1–5) and convalescent serum (15–21 days after first serum)
IgG seroconversion From negative IgG to positive IgG in paired sera or 4-fold increase IgG levels among paired sera
Probable Dengue Infection Positive IgM Positive IgM Single serum collected after day 5
High IgG levels High IgG levels by ELISA or hemagglutination inhibition assay (≥1280)

   † ELISA = enzyme-linked immunosorbent assay; IgG = immunoglobulin G; IgM = immunoglobulin M; NS1 Ag = non-structural protein 1 antigen; RT-PCR = reverse transcriptase polymerase chain reaction

Referemces

  1. ↑ “Dengue haemorrhagic fever: diagnosis, treatment, prevention and control” (PDF).
  2. ↑ “Infectious Diseases Related To Travel”.
  3. ↑ 3.0 3.1 “Handbook for Clinical Management of dengue” (PDF).
  4. ↑ “Dengue: guidelines for diagnosis, treatment, prevention and control” (PDF).
Pathophysiology

Pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alonso Alvarado, M.D. [2]

Overview

Aedes aegypti is the principal mosquito vector of dengue fever viruses and is closely associated with humans and their dwellings. The Dengue fever virus also inhibits the human immune response.

The Vector is the Aedes aegypti Mosquito

  • Aedes aegypti, the principal mosquito vector of dengue viruses, is an insect closely associated with humans and their dwellings. People not only provide the mosquitoes with blood meals but also water-holding containers in and around the home needed to complete their development.
  • The mosquito lays her eggs on the sides of containers with water and eggs hatch into larvae after a rain or flooding.
  • A larva changes into a pupa in about a week and into a mosquito in two days.

The Pathogen is Dengue fever virus

Dengue fever virus (DENV) is an RNA virus of the family Flaviviridae; genus Flavivirus. Other members of the same genus include yellow fever virus, West Nile virus, St. Louis encephalitis virus, japanese encephalitis virus, tick-borne encephalitis, Kyasanur Forest disease virus, and Omsk hemorrhagic fever virus. Most are transmitted by arthropods (mosquitoes or ticks), and are therefore also referred to as arboviruses (arthropod-borne viruses).

The dengue virus genome contains about 11,000 nucleotide bases, which code for the three different types of protein molecules (C, prM and E) that form the virus particle and seven other types of protein molecules (NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5) that are only found in infected host cells and are required for replication of the virus. There are five strains of the virus, of which the first four are referred to as DENV-1, DENV-2, DENV-3 and DENV-4. The distinctions between the serotypes is based on the their antigenicity.

Transmission

Dengue virus is primarily transmitted by Aedes mosquitoes, particularly A. aegypti. These mosquitoes typically bite during the day, particularly in the early morning and in the evening, but they are able to bite and thus spread infection at any time of day through all the year. Other Aedes species that transmit the disease include A. albopictus, A. polynesiensis and A. scutellaris. Humans are the primary host of the virus, but it also circulates in nonhuman primates. An infection can be acquired via a single bite. A female mosquito that takes a blood meal from a person infected with dengue fever, during the initial 2 to 10 day febrile period, becomes itself infected with the virus in the cells lining its gut. About 8 to 10 days later, the virus spreads to other tissues including the mosquito‘s salivary glands and is subsequently released into its saliva. The virus seems to have no detrimental effect on the mosquito, which remains infected for life. Aedes aegypti prefers to lay its eggs in artificial water containers, to live in close proximity to humans, and to feed on people rather than other vertebrates.

Dengue can also be transmitted via infected blood products and through organ donation and through Vertical transmission. Other person-to-person modes of transmission have also been reported, but are very unusual. The genetic variation in dengue viruses is region specific, suggestive that establishment into new territories is relatively infrequent, despite dengue emerging in new regions in recent decades.

Inhibition of the Human Immune System by the Dengue Fever Virus

Dengue virus inhibits the innate immune response in serval ways as discussed below.[1][2]

Inhibition of interferon signaling by blocking signal transducer [3][4]

  • NS4B: Is a protein associated with the endoplasmic reticulum. It may block the phosphorylation of STAT 1 after induction by interferons type I alpha and beta. The activity of Tyk2 kinase decreases with the dengue virus; then the STAT 1 phosphorylation also decreases. Therefore, the innate immune system response may be blocked. Thus there is no production of ISG. NS2A and NS4A cofactor may also take part in the STAT 1 inhibition.[5]
  • NS5 : Is a protein associated with the inactivation of STAT2 (via the signal transduction of the response to interferon) when it is expressed alone. When NS5 is cleaved with NS4B by a protease (NS2B3) it can degrade STAT2. In fact, after the cleavage of NS5 by the protease, there is an E3 ligase association with STAT2, and the E3 ligase targets STAT2 for the degradation.

Inhibition of the type I interferon response

NS2B3 protease complex is a proteolytic core consisting of the last 40 amino acids of NS2B and the first 180 amino acids of NS3. Cleavage of the NS2B3 precursor activates the protease complex. This protease complex allows the inhibition of the production of type I interferon by reducing the activity of IFN-β promoter: studies have shown that NS2B3 protease complex is involved in inhibiting the phosphorylation of IRF3.[6] A recent study shows that the NS2B3 protease complex inhibits (by cleaving) protein MITA which allows the IRF3 activation.

References

  1. ↑ Diamond MS (2009). “Mechanisms of evasion of the type I interferon antiviral response by flaviviruses”. J Interferon Cytokine Res. 29 (9): 521–30. doi:10.1089/jir.2009.0069. PMID 19694536.
  2. ↑ Jones M, Davidson A, Hibbert L, Gruenwald P, Schlaak J, Ball S; et al. (2005). “Dengue virus inhibits alpha interferon signaling by reducing STAT2 expression”. J Virol. 79 (9): 5414–20. doi:10.1128/JVI.79.9.5414-5420.2005. PMC 1082737. PMID 15827155.
  3. ↑ Ho LJ, Hung LF, Weng CY, Wu WL, Chou P, Lin YL; et al. (2005). “Dengue virus type 2 antagonizes IFN-alpha but not IFN-gamma antiviral effect via down-regulating Tyk2-STAT signaling in the human dendritic cell”. J Immunol. 174 (12): 8163–72. PMID 15944325.
  4. ↑ Ashour J, Laurent-Rolle M, Shi PY, García-Sastre A (2009). “NS5 of dengue virus mediates STAT2 binding and degradation”. J Virol. 83 (11): 5408–18. doi:10.1128/JVI.02188-08. PMC 2681973. PMID 19279106.
  5. ↑ Muñoz-Jordan JL, Sánchez-Burgos GG, Laurent-Rolle M, García-Sastre A (2003). “Inhibition of interferon signaling by dengue virus”. Proc Natl Acad Sci U S A. 100 (24): 14333–8. doi:10.1073/pnas.2335168100. PMC 283592. PMID 14612562.
  6. ↑ Rodriguez-Madoz JR, Belicha-Villanueva A, Bernal-Rubio D, Ashour J, Ayllon J, Fernandez-Sesma A (2010). “Inhibition of the type I interferon response in human dendritic cells by dengue virus infection requires a catalytically active NS2B3 complex”. J Virol. 84 (19): 9760–74. doi:10.1128/JVI.01051-10. PMC 2937777. PMID 20660196.
Causes

Causes

This page is about microbiologic aspects of the organism(s).  For clinical aspects of the disease, see Dengue Fever.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: DENV

Overview

The dengue virus (DENV) in one of five[1] serotypes is the cause of dengue fever. It is a mosquito-borne single positive-stranded RNA virus of the family Flaviviridae; genus Flavivirus.[2][3] All five serotypes can cause the full spectrum of disease.[2]

Its genome is about 11000 bases that codes for three structural proteins, capsid protein C, membrane protein M, envelope protein E; seven nonstructural proteins, NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5; and short non-coding regions on both the 5′ and 3′ ends.[2][4] Further classification of each serotype into genotypes often relates to the region where particular strains are commonly found or were first found.

Evolution

The dengue type 1 virus appears to have evolved in the early 19th century.[5] Based on the analysis of the envelope protein there are at least four genotypes (1 to 4). The rate of nucleotide substitution for this virus has been estimated to be 6.5Template:E per nucleotide per year, a rate similar to other RNA viruses. The American African genotype has been estimated to have evolved between 1907 to 1949. This period includes World War I and II which were associated with considerable movement of populations and environmental disturbance, factors known to promote the evolution of new vector borne viral species.

Life Cycle

Until a few hundred years ago dengue virus was transmitted in sylvatic cycles in Africa and Asia between mosquitoes of the genus Aedes and non-human primates with rare emergences into human populations.[6][7] The global spread of dengue virus, however, has followed its emergence from sylvatic cycles and the primary life cycle now exclusively involves transmission between humans and Aedes mosquitoes.[8] Vertical transmission from mosquito to mosquito has also been observed in some vector species.[9]

Structure

E Protein

The DENV E (envelope) protein, found on the viral surface, is important in the initial attachment of the viral particle to the host cell. Dengue virus is transmitted by a mosquito known as Aedes some time called enfluenga. Several molecules which interact with the viral E protein (ICAM3-grabbing non-integrin),[10] CD209,[11] Rab 5,[12] GRP 78,[13] and The Mannose Receptor [14])have been shown to be important factors mediating attachment and viral entry.[15]

prM/M Protein

The DENV prM (membrane) protein, which is important in the formation and maturation of the viral particle, consists of seven antiparallel β-strands stabilized by three disulfide bonds.[15]

The glycoprotein shell of the mature DENV virion consists of 180 copies each of the E protein and M protein. The immature virion starts out with the E and prM proteins forming 90 heterodimers that give a spiky exterior to the viral particle. This immature viral particle buds into the endoplasmic reticulum and eventually travels via the secretory pathway to the Golgi apparatus. As the virion passes through the trans-Golgi Network (TGN) it is exposed to low pH. This acidic environment causes a conformational change in the E protein which disassociates it from the prM protein and causes it to form E homodimers. These homodimers lie flat against the viral surface giving the maturing virion a smooth appearance. During this maturation pr peptide is cleaved from the M peptide by the host protease, furin. The M protein then acts as a transmembrane protein under the E-protein shell of the mature virion. The pr peptide stays associated with the E protein until the viral particle is released into the extracellular environment. This pr peptide acts like a cap, covering the hydrophobic fusion loop of the E protein until the viral particle has exited the cell.[15]

NS3 Protein

The DENV NS3 is a serine protease, as well as an RNA helicase and RTPase/NTPase. The protease domain consists of six β-strands arranged into two β-barrels formed by residues 1–180 of the protein. The catalytic triad (His-51, Asp-75 and Ser-135), is found between these two β-barrels, and its activity is dependent on the presence of the NS2B cofactor. This cofactor wraps around the NS3 protease domain and becomes part of the active site. The remaining NS3 residues (180–618), form the three subdomains of the DENV helicase. A six-stranded parallel β-sheet surrounded by four α-helices make up subdomains I and II, and subdomain III is composed of 4 α-helices surrounded by three shorter α-helices and two antiparallel β-strands.[15]

NS5 Protein

The DENV NS5 protein is a 900 residue peptide with a methyltransferase domain at its N-terminal end (residues 1–296) and a RNA-dependent RNA polymerase (RdRp) at its C-terminal end (residues 320–900). The methyltransferase domain consists of an α/β/β sandwich flanked by N-and C-terminal subdomains. The DENV RdRp is similar to other RdRps containing palm, finger, and thumb subdomains and a GDD motif for incorporating nucleotides.[15]

Severe Disease

The reason that some people suffer from more severe forms of dengue, such as dengue hemorrhagic fever, is multifactorial. Different strains of viruses interacting with people with different immune backgrounds lead to a complex interaction. Among the possible causes are cross-serotypic immune response, through a mechanism known as antibody-dependent enhancement, which happens when a person who has been previously infected with dengue gets infected for the second, third or fourth time. The previous antibodies to the old strain of dengue virus now interfere with the immune response to the current strain, leading paradoxically to more virus entry and uptake.[16]

Immune System Interaction

In recent years, many studies have shown that flaviviruses, especially dengue virus has the ability to inhibit the innate immune response during the infection.[17][18] Indeed, the dengue virus has many nonstructural proteins that allow the inhibition of various mediators of the innate immune system response. These proteins act on two levels :

Inhibition of Interferon Signaling by Blocking Signal Transducer

NS4B it is a small hydrophobic protein located in association with the endoplasmic reticulum. It may block the phosphorylation of STAT 1 after induction by interferons type I alpha, beta. In fact, the activity of Tyk2 kinase decreases with the dengue virus, so STAT 1 phosphorylation decreases too.[19] Therefore, the innate immune system response may be blocked. Thus there is no production of ISG. NS2A and NS4A cofactor may also take part in the STAT 1 inhibition.[20]

NS5 : the presence of this 105 kDa protein results in inactivation of STAT2 (via the signal transduction of the response to interferon) when it is expressed alone.[21] When NS5 is cleaved with NS4B by a protease (NS2B3) it can degrade STAT2. In fact, after the cleavage of NS5 by the protease, there is an E3 ligase association with STAT2, and the E3 ligase targets STAT2 for the degradation.[22][23]

Inhibition of the Type I Interferon Response

NS2B3 protease complex is a proteolytic core consisting of the last 40 amino acids of NS2B and the first 180 amino acids of NS3. Cleavage of the NS2B3 precursor activates the protease complex.[24] This protease complex allows the inhibition of the production of type I interferon by reducing the activity of IFN-beta promoter: studies have shown that NS2B3 protease complex is involved in inhibiting the phosphorylation of IRF3.[25] A recent study shows that the NS2B3 protease complex inhibits (by cleaving) protein MITA which allows the IRF3 activation.[26]

Vaccine Research

There currently is no human vaccine available. Several vaccines are under development by private and public researchers.[27] Developing a vaccine against the disease is challenging. With five different serotypes of the dengue virus that can cause the disease, the vaccine must immunize against all five types to be effective.[1] Vaccination against only one serotype could possibly lead to severe dengue hemorrhagic shock (DHS) when infected with another serotype due to antibody-dependent enhancement. One vaccine was in phase III trials in 2012 and planning for vaccine usage and effectiveness surveillance had started.[28]

In September 2012, it was announced that one of the vaccines had not done well in clinical trials.[1]

As researchers continue their work, governments should also make efforts in protecting their citizens by providing clean environments to live in, which can be done through developing cleaning teams to keep the cities clean.

References

  1. ↑ 1.0 1.1 1.2 Dennis Normile (25 October 2013). “Surprising New Dengue Virus Throws A Spanner in Disease Control Efforts”. Science. 342: 415. doi:10.1126/science.342.6157.415.
  2. ↑ 2.0 2.1 2.2 Rodenhuis-Zybert IA, Wilschut J, Smit JM (August 2010). “Dengue virus life cycle: viral and host factors modulating infectivity”. Cell. Mol. Life Sci. 67 (16): 2773–86. doi:10.1007/s00018-010-0357-z. PMID 20372965.
  3. ↑ WHO (2009). Dengue Guidelines for Diagnosis, Treatment, Prevention and Control (PDF). World Health Organization. ISBN 92-4-154787-1.
  4. ↑ Hanley, K.A. and Weaver, S.C. (editors) (2010). Frontiers in Dengue Virus Research. Caister Academic Press. ISBN 978-1-904455-50-9.
  5. ↑ Patil JA, Cherian S, Walimbe AM; et al. (August 2011). “Evolutionary dynamics of the American African genotype of dengue type 1 virus in India (1962–2005)”. Infection, Genetics and Evolution. 11 (6): 1443–8. doi:10.1016/j.meegid.2011.05.011. PMID 21632029.
  6. ↑ “Dengue virus”.
  7. ↑ Holmes, EC; Twiddy, SS (May 2003). “The origin, emergence and evolutionary genetics of dengue virus”. Infection, Genetics and Evolution. 3 (1): 19–28. doi:10.1016/s1567-1348(03)00004-2. PMID 12797969.
  8. ↑ Halstead, SB (1988). “Pathogenesis of dengue: challenges to molecular biology”. Science. 239 (4839): 476–481. Bibcode:1988Sci…239..476H. doi:10.1126/science.3277268. PMID 3277268. Retrieved 23 February 2013.
  9. ↑ Haddow, AD (Jun 5, 2013). “First isolation of Aedes flavivirus in the Western Hemisphere and evidence of vertical transmission in the mosquito Aedes (Stegomyia) albopictus (Diptera: Culicidae)”. Virology. 440 (2): 134–9. doi:10.1016/j.virol.2012.12.008. PMID 23582303. Unknown parameter |coauthors= ignored (help)
  10. ↑ Navarro-Sanchez E, Altmeyer R, Amara A; et al. (July 2003). “Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses”. EMBO Reports. 4 (7): 723–8. doi:10.1038/sj.embor.embor866. PMC 1326316. PMID 12783086.
  11. ↑ Tassaneetrithep B, Burgess TH, Granelli-Piperno A; et al. (April 2003). “DC-SIGN (CD209) mediates dengue virus infection of human dendritic cells”. J. Exp. Med. 197 (7): 823–9. doi:10.1084/jem.20021840. PMC 2193896. PMID 12682107.
  12. ↑ Krishnan MN, Sukumaran B, Pal U; et al. (May 2007). “Rab 5 is required for the cellular entry of dengue and West Nile viruses”. J. Virol. 81 (9): 4881–5. doi:10.1128/JVI.02210-06. PMC 1900185. PMID 17301152.
  13. ↑ Jindadamrongwech S, Thepparit C, Smith DR (May 2004). “Identification of GRP 78 (BiP) as a liver cell expressed receptor element for dengue virus serotype 2”. Arch. Virol. 149 (5): 915–27. doi:10.1007/s00705-003-0263-x. PMID 15098107.
  14. ↑ Miller JL, de Wet BJ, deWet BJ; et al. (February 2008). “The mannose receptor mediates dengue virus infection of macrophages”. PLoS Pathog. 4 (2): e17. doi:10.1371/journal.ppat.0040017. PMC 2233670. PMID 18266465.
  15. ↑ 15.0 15.1 15.2 15.3 15.4 Perera R, Kuhn RJ (August 2008). “Structural proteomics of dengue virus”. Current Opinion in Microbiology. 11 (4): 369–77. doi:10.1016/j.mib.2008.06.004. PMC 2581888. PMID 18644250.
  16. ↑ Dejnirattisai W, Jumnainsong A, Onsirisakul N; et al. (May 2010). “Cross-reacting antibodies enhance dengue virus infection in humans”. Science. 328 (5979): 745–8. Bibcode:2010Sci…328..745D. doi:10.1126/science.1185181. PMID 20448183.
  17. ↑ Diamond MS (September 2009). “Mechanisms of evasion of the type I interferon antiviral response by flaviviruses”. J. Interferon Cytokine Res. 29 (9): 521–30. doi:10.1089/jir.2009.0069. PMID 19694536.
  18. ↑ Jones M, Davidson A, Hibbert L; et al. (May 2005). “Dengue virus inhibits alpha interferon signaling by reducing STAT2 expression”. J. Virol. 79 (9): 5414–20. doi:10.1128/JVI.79.9.5414-5420.2005. PMC 1082737. PMID 15827155.
  19. ↑ Ho LJ, Hung LF, Weng CY; et al. (June 2005). “Dengue virus type 2 antagonizes IFN-alpha but not IFN-gamma antiviral effect via down-regulating Tyk2-STAT signaling in the human dendritic cell”. Journal of Immunology. 174 (12): 8163–72. PMID 15944325.
  20. ↑ Muñoz-Jordan JL, Sánchez-Burgos GG, Laurent-Rolle M, García-Sastre A (November 2003). “Inhibition of interferon signaling by dengue virus”. Proc. Natl. Acad. Sci. U.S.A. 100 (24): 14333–8. Bibcode:2003PNAS..10014333M. doi:10.1073/pnas.2335168100. PMC 283592. PMID 14612562.
  21. ↑ Ashour J, Laurent-Rolle M, Shi PY, García-Sastre A (June 2009). “NS5 of dengue virus mediates STAT2 binding and degradation”. J. Virol. 83 (11): 5408–18. doi:10.1128/JVI.02188-08. PMC 2681973. PMID 19279106.
  22. ↑ Mazzon M, Jones M, Davidson A, Chain B, Jacobs M (October 2009). “Dengue virus NS5 inhibits interferon-alpha signaling by blocking signal transducer and activator of transcription 2 phosphorylation”. J. Infect. Dis. 200 (8): 1261–70. doi:10.1086/605847. PMID 19754307.
  23. ↑ Morrison J, Aguirre S, Fernandez-Sesma A (March 2012). “Innate immunity evasion by dengue virus”. Viruses. 4 (3): 397–413. doi:10.3390/v4030397. PMC 3347034. PMID 22590678.
  24. ↑ Yusof R, Clum S, Wetzel M, Murthy HM, Padmanabhan R (April 2000). “Purified NS2B/NS3 serine protease of dengue virus type 2 exhibits cofactor NS2B dependence for cleavage of substrates with dibasic amino acids in vitro”. J. Biol. Chem. 275 (14): 9963–9. doi:10.1074/jbc.275.14.9963. PMID 10744671.
  25. ↑ Rodriguez-Madoz JR, Belicha-Villanueva A, Bernal-Rubio D, Ashour J, Ayllon J, Fernandez-Sesma A (October 2010). “Inhibition of the type I interferon response in human dendritic cells by dengue virus infection requires a catalytically active NS2B3 complex”. J. Virol. 84 (19): 9760–74. doi:10.1128/JVI.01051-10. PMC 2937777. PMID 20660196.
  26. ↑ Yu CY, Chang TH, Liang JJ; et al. (June 2012). Diamond, Michael S, ed. “Dengue virus targets the adaptor protein MITA to subvert host innate immunity”. PLoS Pathog. 8 (6): e1002780. doi:10.1371/journal.ppat.1002780. PMC 3386177. PMID 22761576.
  27. ↑ Vaccine Development, Dengue Vaccine Initiative, November 2012, accessed November 5, 2013
  28. ↑ Preparing for Dengue Vaccine Introduction: Recommendations from the 1st Dengue v2V International Meeting, Joseph Torresi, Roberto Tapia-Conyer, Harold Margolis, PLoS Negl Trop Dis 7(9): e2261. doi:10.1371/journal.pntd.0002261
  29. ↑ 29.0 29.1 29.2 29.3 29.4 “Public Health Image Library (PHIL)”.
Differentiating Dengue fever from other Diseases

Differentiating Dengue fever from other Diseases

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Dengue fever must be differentiated from other diseases that prevent with flu like symptoms fever, retro-orbital headache, fatigue, joint aches or arthralgias (joint aches), myalgias (muscle aches), nausea/vomiting, and lymphadenopathy (swollen lymph nodes). Diseases with similar symptoms include influenza, measles, rubella, malaria, Zika virus, and Yellow fever.

Diseases with Similar Symptoms

Comparison between Chikungunya and Dengue Fever Adapted from Clin Infect Dis. (2009) 49(6):942-948.[1]


Clinical and laboratory findings of chikunguyna and dengue fever
Clinical Findings Chikungunya Dengue Fever
Fever (>102°F or 39°C) +++ ++
Headache ++ ++
Rash ++ +
Arthralgias +++ +/–
Myalgias + ++
Shock — +/–
Bleeding dyscrasias +/– ++
Laboratory Findings
Elevated hematocrit — ++
Leukopenia ++ +++
Neutropenia + +++
Lymphopenia +++ ++
Thrombocytopenia + +++
Mean frequency of symptoms from studies where the two diseases were directly compared among patient seeking care; +++ = 70-100% of patients; ++ = 40-69%; + = 10-39%; +/– = <10%; — = 0%[2][3]

Comparison Between Dengue Virus and Zika Virus

The following table summarizes the distinguishing and common features between Zika fever and Dengue fever:

Dengue Fever Zika Fever
Common Clinical Features Biphasic fever pattern, maculopapular rash, arthralgia, headache, and signs of hemorrhage Fever, maculopapular rash, conjunctivitis, and headache
Hemorrhage Common? Yes No
Symptom Severity May be severe Usually mild
Symptom Duration 2 to 7 days 4 to 7 days
Incubation Period 4 to 10 days 3 to 12 days
Endemicity Americas, Africa, Southeast Asia Americas, Africa, Southeast Asia
Vector Aedes mosquito Aedes mosquito
Laboratory Findings Leucopenia, rising hematocrit (suggestive of impending hemorrhage), thrombocytopenia, elevated liver function tests Leucopenia but normal hematocrit, platelet count, and liver function tests
Diagnosis RT-PCR or ELISA RT-PCR or ELISA
Treatment Supportive care, avoid aspirin and other NSAIDs Supportive care

References

  1. ↑ Staples, J. Erin; Breiman, Robert F.; Powers, Ann M. (2009). “Chikungunya Fever: An Epidemiological Review of a Re‐Emerging Infectious Disease”. Clinical Infectious Diseases. 49 (6): 942–948. doi:10.1086/605496. ISSN 1058-4838.
  2. ↑ S. Nimmannitya, S. B. Halstead, S. N. Cohen & M. R. Margiotta (1969). “Dengue and chikungunya virus infection in man in Thailand, 1962-1964. I. Observations on hospitalized patients with hemorrhagic fever”. The American journal of tropical medicine and hygiene. 18 (6): 954–971. PMID 5355242. Unknown parameter |month= ignored (help)
  3. ↑ Patrick Hochedez, Ana Canestri, Amelie Guihot, Segolene Brichler, Francois Bricaire & Eric Caumes (2008). “Management of travelers with fever and exanthema, notably dengue and chikungunya infections”. The American journal of tropical medicine and hygiene. 78 (5): 710–713. PMID 18458301. Unknown parameter |month= ignored (help)
Epidemiology and Demographics

Epidemiology and Demographics

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]

Overview

Dengue is endemic throughout the tropics and subtropics and is a leading cause of febrile illness among travelers returning from the Caribbean, South America, and South and Southeast Asia, according to an analysis of data collected by the GeoSentinel Surveillance Network. Dengue occurs in more than 100 countries worldwide, including Puerto Rico, the US Virgin Islands, and US-affiliated Pacific Islands. Sporadic outbreaks with local transmission have occurred in Florida, Hawaii, and along the Texas-Mexico border. There are 40 million cases worldwide each year.

Epidemiology and Demographics

Distribution of dengue in the Americas and the Caribbean.
Distribution of dengue in Africa and the Middle East.
Distribution of dengue in Asia and Oceania.

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. One model to explain this process is 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] This process is also known as superinfection (Nowak and May 1994; Levin and Pimentel 1981).

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.

Developed Countries

United States

Nearly all dengue cases reported in the 48 continental states were acquired elsewhere by travelers or immigrants. (Travel Associated Dengue Infections – United States, 2001- 2004 , Imported Dengue – United States, 1999 and 2000 ) Because contact between Aedes and people is infrequent in the continental U.S., these imported cases rarely result in secondary transmission. The last reported continental dengue outbreak was in south Texas in 2005. (Dengue Hemorrhagic Fever – U.S.- Mexico Border, 2005) A small dengue outbreak occurred in Hawaii in 2001.

Most dengue cases in U.S. citizens occur in those inhabitants of Puerto Rico, the U.S. Virgin Islands, Samoa and Guam, which are endemic for the virus. Dengue and DHF have been a particular challenge in Puerto Rico, where outbreaks have been reported since 1915 and large island-wide epidemics have been documented since the late 1960s. The most recent island-wide epidemic occurred in 2007, when more than 10,000 cases were diagnosed. In Puerto Rico, and most of the Caribbean Basin, the principle dengue vector Ae. aegypti is abundant year-round. Dengue transmission in the Puerto Rico follows a seasonal pattern. Low transmission season begins in March and lasts until June, and high transmission begins in August until November.

Asia Pacific

  • Australia: 2006 March 15, 2 confirmed cases at Gordonvale, Cairns, Queensland.
  • China: September 2006, 70 cases since June in Guangzhou,Guangdong.[2]
  • Cook Islands: [3](October 2006-January 2007) 460 cases.
  • Singapore: 2007 more than 4029 cases, 8 deaths at 29 Sept.. 2005 at least 13 deaths. 2004 9460 cases. 2003, 4788 cases.

Developing Countries

Americas

  • Dominican Republic: [4](August – October 2006) 4,968 cases with 44 dead.
  • Puerto Rico: [5](August 2007) 2,343 confirmed cases of dengue.
  • Cuba: Media reports [6][7][8][9] (dated September and October 2006) speculate on an outbreak although there is no official report.

Asia Pacific

  • India: 2006 September, more than 400 cases and 22 deaths were reported due to dengue fever in New Delhi. [10] By October 7, 2006, reports were of 3,331 cases of the mosquito-borne virus and a death toll of 49. [11]
  • Indonesia: 2004 80,000 infected with 800 deaths.
  • Malaysia: January 2005 33,203 cases.
  • Pakistan: 2006 Over 3230 cases, 50 deaths.
    • Karachi 2006 October, the number of infected patients rose to 1836 of which 30 had died.
    • Lahore, 2006 October 23, the disease shifted to Lahore during the holidays with the luggage of some people travelling to their homes to celebrate Eid. The number of infected patients is 400 by October 31, of which 4 had died.
  • Philippines: [12](January – August 2006) 13,468 cases with 167 dead.
  • Thailand: 2005 May, 7200 infected. At least 12 dead.

Outbreaks

2005 dengue outbreak
Country Cases Deaths Date of Information Sources
Cambodia 20,000 38 Sep. [3]
Costa Rica 19,000 1 7 Sep. [4]
India, (West Bengal) 90,000 1,500 Sep. [5]
Indonesia 80,837 1,099 Jan. 2006 [6]
Malaysia 32,950 83 1 Nov. [7]
Martinique 6,000 2 26 Sep. [8]
Philippines 21,537 280 2 Oct. [9]
Singapore 12,700 19 22 Oct. [10]
Sri Lanka 3,000 – 16 Sep. [11]
Thailand 31,000 58 Sep. [12]
Vietnam 20,000 28 4 Oct. [13]
Pakistan 4,800 50 11 Dec 2006. [14]
Total† 232,724 16,673 — —
†For listed countries only. World Health Organization estimates that there may be 50 million cases of dengue infection worldwide each year. [15]

Twenty-four US cases of dengue were reported in 2014 among individuals with travel history to a dengue endemic country in the two weeks prior to onset. Countries of origin were: Bolivia, Brazil (2), Caribbean, Cuba (8), Dominican Republic (4), Guadeloupe, Honduras, Puerto Rico (3), Trinidad, and Venezuela (2). Florida counties reporting cases were: Alachua, Broward (2), Clay, Hillsborough (3), Marion, Miami-Dade (10), Orange, Osceola (3), Pinellas, and Seminole. Four of the cases were reported in non-Florida residents.[13]

During the first months of 2007 over 16,000 cases were reported in Paraguay, of which around 100 have been detected as DHF cases. Ten deaths were reported, including that of a high ranking member of the Ministry of Health. The epidemic was the root of a scandal in the Paraguayan Department of Health, where one official resigned because he had approved the use of expired batches of insecticide to control the mosquito vectors of dengue.[14][15] The disease propagated to Argentina (where it is not considered endemic), and was transmitted in almost all cases by people who recently arrived from Paraguay. In the Brazilian state of Mato Grosso do Sul, which borders on Paraguay, the number of cases in March 2007 was estimated to be more than 45,000.[15] Epidemics in the states of Ceará, Pará, São Paulo, and Rio de Janeiro have taken the Brazilian national tally of cases in 2007 to over 70,000, with upwards of 20 deaths. The proportion of cases registered as DHF is reported to be higher than in previous years.

  • DengueMap: An interactive map of global dengue activity collaboratively developed by CDC and HealthMap.org

References

  1. ↑ Rothman, Alan L. Dengue: defining protective versus pathologic immunity. (Full text-html) J Clin Invest. 2004 April 1; 113(7): 946–951
  2. ↑ China, Dengue Fever Cases Jump, Taipei Times, 29 August, 2006.
  3. ↑ “460 people in Cook Islands affected by Dengue Fever outbreak”. Radio New Zealand International. 15 January, 2007. Retrieved 2007-01-15. Check date values in: |date= (help)
  4. ↑ Batista, L. “Más de 4,968 afectados por dengue” (in Spanish). Diario Libre. Retrieved 2006-10-19. Unknown parameter |coauthors= ignored (help)
  5. ↑ “Dengue fever surging in Puerto Rico”. MSNBC, Telemundo. Aug. 08, 2007. Retrieved 2007-26-09. Check date values in: |accessdate=, |date= (help)
  6. ↑ “Protecting the Revolution”. Strategypage.com. September 17, 2006. Retrieved 2006-10-07.
  7. ↑ Acosta, Dalia (2006-09-12). “War on Mosquitoes Continues During Global Summit”. Inter Press Service. Retrieved 2006-10-07.
  8. ↑ “Cuba wages war on tiny enemy”. Independent Online, South Africa. September 25, 2006. Retrieved 2006-10-07.
  9. ↑ “Cuba waging war against dengue fever”. Miami Herald. October 7, 2006. Retrieved 2006-10-07.
  10. ↑ http://www.iht.com/articles/ap/2006/10/02/asia/AS_GEN_India_Dengue_Outbreak.php International Herald Tribune, Associated Press News, Published: October 2, 2006 & Accessed on: October 2, 2006]
  11. ↑ India says dengue outbreak serious as death toll rises Pratap Chakravarty, news.yahoo.com, 7 October 2006. Retrieved 8 October 2006.
  12. ↑ Santos, Tina (September 10, 2006). “DOH names dengue-hit areas in metropolis”. Philippine Daily Inquirer. Retrieved 2006-10-07.
  13. ↑ [1]
  14. ↑ “Dengue sparks Paraguay emergency”. BBC News. 2 March 2007. Retrieved 2007-06-19.
  15. ↑ 15.0 15.1 “Paraguay dengue official sacked”. BBC News. 6 March 2007. Retrieved 2007-06-19.
Risk Factors

Risk Factors

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Living or traveling to a region of the world where the infection is endemic is a risk factor for the disease. The presence of water-holding containers in and around the home needed for the mosquito’s to complete their development sustains the reservoir for disease and is a risk factor. Risk factors for severe disease include being a neonate or young child, female sex, high body mass index, viral load, genetic polymorphisms and previous infection with DENV-1 if the patient contracts DENV-2 or DENV-3. Diabetes and asthma are risk factors for fatal disease.[1]

Standing Water

The presence of water-holding containers in and around the home needed for the mosquito’s to complete their development sustains the reservoir for disease and is a risk factor.

Geographic Risk Factors

People who live in or travel to high-risk areas including:

  • Indonesian archipelago into northeastern Australia
  • South and Central America
  • Southeast Asia
  • Sub-Saharan Africa

Risk Factors for Secondary Infection

Although there is no commercially available vaccine for Dengue fever, it is notable that infection with one serotype is thought to produce lifelong immunity to that type, but only short term protection against the other three. Unfortunately, the risk of severe disease from secondary infection actually increases if someone previously exposed to serotype DENV-1 contracts serotype DENV-2 or DENV-3, or if someone previously exposed to DENV-3 acquires DENV-2.

Risk Factors for Severe Disease

Severe disease is more common in babies and young children,[2] and in contrast to many other infections it is more common in children that are relatively well nourished. Other risk factors for severe disease include female sex, high body mass index, and viral load.[3] While each serotype can cause the full spectrum of disease, virus strain is a risk factor. Infection with one serotype is thought to produce lifelong immunity to that type, but only short term protection against the other three. The risk of severe disease from secondary infection increases if someone previously exposed to serotype DENV-1 contracts serotype DENV-2 or DENV-3, or if someone previously exposed to DENV-3 acquires DENV-2.[4] Dengue can be life-threatening in people with chronic diseases such as diabetes[5] and asthma.[6][7]

Polymorphisms in particular genes have been linked with an increased risk of severe dengue complications. Examples include the genes coding for the proteins known as TNF-α, mannan-binding lectin, CTLA-4, TGF-β, DC-SIGN, PLCE1, and particular forms of human leukocyte antigen from gene variations of HLA-B. A common genetic abnormality in Africans, known as glucose-6-phosphate dehydrogenase deficiency, appears to increase the risk. Polymorphisms in the genes for the vitamin D receptorand FcγR seem to offer protection against severe disease in secondary dengue infection.

References

  1. ↑ “WHO: Dengue guidelines for diagnosis, treatment, prevention and control: new edition”.
  2. ↑ De Rivera IL, Parham L, Murillo W, Moncada W, Vazquez S (2008). “Humoral immune response of dengue hemorrhagic fever cases in children from Tegucigalpa, Honduras”. Am J Trop Med Hyg. 79 (2): 262–6. PMID 18689634.
  3. ↑ Huy NT, Van Giang T, Thuy DH, Kikuchi M, Hien TT, Zamora J; et al. (2013). “Factors associated with dengue shock syndrome: a systematic review and meta-analysis”. PLoS Negl Trop Dis. 7 (9): e2412. doi:10.1371/journal.pntd.0002412. PMC 3784477. PMID 24086778.
  4. ↑ Guzmán MG, Alvarez M, Rodríguez R, Rosario D, Vázquez S, Vald s L; et al. (1999). “Fatal dengue hemorrhagic fever in Cuba, 1997”. Int J Infect Dis. 3 (3): 130–5. PMID 10460923.
  5. ↑ Limonta D, Torres G, Capó V, Guzmán MG (2008). “Apoptosis, vascular leakage and increased risk of severe dengue in a type 2 diabetes mellitus patient”. Diab Vasc Dis Res. 5 (3): 213–4. doi:10.3132/dvdr.2008.034. PMID 18777495.
  6. ↑ González D, Castro OE, Kourí G, Perez J, Martinez E, Vazquez S; et al. (2005). “Classical dengue hemorrhagic fever resulting from two dengue infections spaced 20 years or more apart: Havana, Dengue 3 epidemic, 2001-2002”. Int J Infect Dis. 9 (5): 280–5. doi:10.1016/j.ijid.2004.07.012. PMID 16023878.
  7. ↑ Figueiredo MA, Rodrigues LC, Barreto ML, Lima JW, Costa MC, Morato V; et al. (2010). “Allergies and diabetes as risk factors for dengue hemorrhagic fever: results of a case control study”. PLoS Negl Trop Dis. 4 (6): e699. doi:10.1371/journal.pntd.0000699. PMC 2879373. PMID 20532230.
Natural History, Complications and Prognosis

Natural History, Complications and Prognosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Dengue fever generally lasts a week or more, and can rarely be complicated by bleeding, febrile convulsions and coma. The prognosis is good. Dengue fever can be life-threatening in people with chronic diseases such as diabetes and asthma.

Natural History

  • Dengue fever generally lasts about six to seven days, with a smaller peak of fever at the trailing end of the fever (the so-called “biphasic pattern”). The platelet count will drop until the patient’s temperature is normal.[1]

Complications

Possible complications of Dengue fever include:[2]

Prognosis

Although uncomfortable, dengue fever is generally not deadly.[1]. Mortality rates between 0% and 5.4% have been reported.[5][6] Dengue fever can be life-threatening in people with chronic diseases such as diabetes and asthma.

References

  1. ↑ 1.0 1.1 “Dengue: guidelines for diagnosis, treatment, prevention and control” (PDF).
  2. ↑ Halstead SB (2007). “Dengue”. Lancet. 370 (9599): 1644–52. doi:10.1016/S0140-6736(07)61687-0. PMID 17993365.
  3. ↑ Wang CC, Liu SF, Liao SC, Lee IK, Liu JW, Lin AS; et al. (2007). “Acute respiratory failure in adult patients with dengue virus infection”. Am J Trop Med Hyg. 77 (1): 151–8. PMID 17620647.
  4. ↑ Puccioni-Sohler M, Orsini M, Soares CN (2012). “Dengue: a new challenge for neurology”. Neurol Int. 4 (3): e15. doi:10.4081/ni.2012.e15. PMC 3555217. PMID 23355928.
  5. ↑ Guzmán MG, Kourí G (2002). “Dengue: an update”. Lancet Infect Dis. 2 (1): 33–42. PMID 11892494.
  6. ↑ Ong A, Sandar M, Chen MI, Sin LY (2007). “Fatal dengue hemorrhagic fever in adults during a dengue epidemic in Singapore”. Int J Infect Dis. 11 (3): 263–7. doi:10.1016/j.ijid.2006.02.012. PMID 16899384.
Diagnosis

Diagnosis

History and Symptoms | Physical Examination | Laboratory Findings | Other Imaging Findings | Other Diagnostic Studies

Treatment

Treatment

Medical Therapy | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies

Case Studies

Case Studies

Case #1

See Also

See Also

External links

Looking for the patient version?

Back to the patient-friendly article

Imprint

Privacy Policy

Terms and Conditions

© 2026 MyEClinic – IFTM Institut für Telematik in der Medizin GmbH