Dengue

Transmitted mostly by Aedes aegypti. 

Efforts to control A.aegypti populations with the use of insecticides or environmental management methods have not been effective in controlling dengue as a public health problem in most countries.

In a small percentage of patients a potentially lethal forms, dengue hemorrhagic fever and dengue shock syndrome may develop.

More than half the worlds population lives in areas where a mosquito-born disease is endemic.

Denge hemorrhagic fever associated with thrombocytopenia,, bleeding, and capillary leakage that may progress to dengue shock syndrome.

Antibodies to the two surface proteins of the dengue virus, the precursor membrane protein and the envelope protein, can neutralize the virus’ ability to be infectious and confers protection.

The variation in the severity of the disease may be due to cross-stereotypic immune response that a person has, who has had previous infection with dengue and then becomes infected a second, third, or fourth time.

Through a process known as antibody-dependent enhancement, the previous antibodies to the old strain of dengue virus interferes with the immune response to the current infection leading to more viral entries and uptakes that correlate with increased severity of disease.

The envelope protein is the more important antigen target to provide protection.

Self-limited systemic viral infection transmitted by mosquitoes to humans.

A lack of long-term cross immunity occurs because four virus types have antigenic diversity that allows for multiple sequential infections.

The four serotypes of dengue virus are transmitted between humans, the primary reservoir host, by infected female mosquitoes most commonly Aedes egypti and 80s A. Albopictus.

Inadequate water storage containers, rainwater filledcontainers such as tires, pods, and tree holes can become mosquito breeding sites and drive epidemics.

Transovarian transmission from female mosquitoes to their offspring and long distance dispersal or drought resistant 80 eggs in suitable containers facilitate expansion of the virus worldwide.

There has been a expansion of these vectors due to climate change.

Illness that ranges from subclinical to fulminant hemorrhagic disease with shock and death.

50 million cases per year and 500,000 cases of hemorrhagic fever annually in more than 100 countries.

Incidence has increased exponentially over the past decades.

Increased incidence due to increased urbanization, population migrations, demographic changes and travel.

Now endemic in most tropical countries.

Increased incidence, intensity and enlarging geographic areas.

The incidence has increased by a factor of 30 over the past 50 years.

Almost half of the world’s population lives in dengue endemic areas in more than 100 countries worldwide, where approximately 390 million cases are estimated to occur each year.

Endemic process is facilitated by rapid urbanization in Asia and Latin America with increased population density and an abundance of vector breeding sites within crowded urban communities and area surrounding them.

Tends to occur in explosive epidemics and can paralyze communities and even entire nations.

Increasing incidence in the U.S. after being absent for decades.

Most common vector borne viral disease in the world.

Causes an estimated 50-100 million infections and 23,000 deaths worldwide, annually (Gibbons RV).

The process can range from asymptomatic to severe disease with mortality rate of 20%.

Primary vector Aedes aegypti mosquito, which is widely distributed across tropical and subtropical latitudes.

The range of Aedes albopictus, a secondary vector, has expanded globally at a significant rate, and has spread to 36 states and increases the risks of outbreaks.

Global trade, especially from used tires, has increased the dispersal of eggs and immature forms of arboviral vectors into new territories.

Majority of cases occur in the developing world.

Can cause epidemic illness.

About 1200 cases brought in to the U.S. by travelers annually.

Caused by one of four single stranded positive-sensitive RNA viruses.

Flavivirus related to Japanese encephalitis, West Nile and yellow fever viruses.

Caused by four antigenically related viruses, DENV1-4).

Endemic in most tropical and subtropical areas.

In 2007 nearly 1,000,000 cases reported in the Americas alone.

Commonly occurs among US residents returning from travel in endemic areas.

Has an incubation period of 3-14 days.

4 variants of virus, DEN-1, 2, 3 and 4 with infection associated with immunity the individual strains and not to the others.

Infectious virus and virus encoded NS1 are present in blood during the acute phase, and high levels in early viremia and NS1 antigenemia are associated with more severe symptoms.

Infection provides decades of protective immunity against the specific of infecting serotype, but secondary infection with a different serotype increases the risk for severe disease.

NS1 detection is basis of diagnostic testing.

Viruses are maintained in continuous cycles of human-mosquito-human transmission.

Within each dengue virus serotype there are multiple genotypes and infection with one serotype confers long lived serotype specific immunity, but only short-lived cross-immunity between serotypes.

After infection with one variant and subsequent exposure to another serotype associated with increasing disease severity.

There are four different dengue viruses so people can get dengue more than once in their lifetime.

Dengue virus causes suspected disruption in the function of the endothelial glycocalyx layer, the latter functions as a molecular sieve, restricting molecules within plasma according to their size, charge, and shape.

During dengue infections hypoalbuminemia and proteinuria occur reflecting related to a change in filtration characteristics of the glycocalyx.

Dengue virus and NS1 adhere to heparan sulfate structure in the glycocalyx, and increased urinary heparan sulfate excretion is present in children with severe infection (Avirutnan P et al).

Mostly found in cities, but increasingly seen in rural areas.

Spread primarily by Aedes aegypti and Aedes albopictus mosquitoes that become infective 10-12 days after biting a viremic host.

Humans have high levels of virus and can infect vector mosquitoes.

Humans and mosquitoes with dengue virus are the only hosts in urban or endemic settings.

In forested areas mosquito borne viruses transmit the virus between nonhuman primates and, rarely from primates to humans.

Virus replicates in the salivary glands of aedes mosquitoes and they can transmit the virus to other humans.

Incubation period generally 4-7 days with a range of 3-14 days, followed by a biphasic illness.

Illness has a wide spectrum of clinical manifestations from asymptomatic to severe.

Most cases of dengue virus infection are asymptomatic.

Approximately 5% of patients with dengue develop severe symptoms, such as persistent vomiting, severe abdominal pain, gastrointestinal, or vaginal bleeding, shortness of breath, low blood pressure, and lethargy.

Clinical manifestation range from mild febrile illness to severe and fatal disease.

Patients typically present with fever, chills, headache, myalgias, nausea vomiting, cough, abdominal pain, lymph node enlargement and a maculopapular rash which lasts 3-7 days.

Diagnosis considered in any patient presenting with fever that has developed within 14 days after a trip to the tropics or subtropics.

Differential diagnosis includes other arboviral infections, rubella, enterovirus infections, adenovirus infections, influenza, malaria, typhoid, malaria, leptospirosis, viral hepatitis, rickettsial diseases, and bacterial sepsis

A period of 2-3 day defervescence may occur following the initial illness and then worsening of symptoms may occur.

Bleeding may occur but not associated frequently associated in dengue hemorrhagic fever.

No carrier state exists.

Maintained in nature by transmission to human by monkeys and mosquitoes that breed in tree holes.

Defervescence of fever marks the disappearance of the virus from the blood.

If an illness arises more than 2 weeks after traveling into an endemic area or symptoms last more than 2 weeks dengue virus is not responsible.

Studies have demonstrated young age, female sex, high body mass index, virus strain and genetic variants of human major histocompatibility complex class I-related sequence B and phospholipase C epsilon 1genes as risk factors for severe disease.

Secondary infections due l to sequential different serotypes, is also a risk factor for severe disease.

Increased risk secondary infection linked to antibody dependent enhancement of virus infection in Fc receptor bearing cells and the generation of large infected cell mass.

Differential diagnosis includes other arboviral infections, rubella, enterovirus infections, adenovirus infections, influenza, malaria, typhoid, malaria, leptospirosis, viral hepatitis, rickettsial diseases, and bacterial sepsis

As this disorder has reemerged, its fatal form, dengue hemorrhagic fever has also increased.

Dengue hemorrhagic fever and dengue shock syndrome are possible sequelae of dengue.

Hemorrhagic fever along with fever consists of bleeding, thrombocytopenia, plasma leakage, ascites, pleural effusions, hypoalbuminemia and hypoproteinemia weakness, abdominal pain, cyanosis, hepatomegaly, diaphoresis and restlessness.

A small number of individuals develop hemorrhagic fever and it is most common in children.

Dengue shock syndrome occurs in up to 20% of children with dengue hemorrhagic fever.

Fatality rate of dengue hemorrhagic fever and dengue shock syndrome can be as high as 20% and 44%, respectively.

Hemorrhagic fever and shock syndrome develop between 3 and 7 days after onset of illness, often with onset of defervescence.

No drug therapy or useful diagnostic tests exist.

Detection of a viral nucleic acid by PCR is confirmatory, with sensitivities approaching 90%.

During the first five days of illness, dengue can be diagnosed by detecting the virus in the blood using a PCR test.

After the fourth day of infection, testing for antibodies in the blood can be used to detect infection with dengue.

Enzyme-linked immunoabsorbent assay (ELISA) to detect serum conversion with IgM antibodies between paired samples commonly used to establish a presumptive diagnosis.

Supportive care with fluids in leak or shock cases, and platelet support in hemorrhagic cases can decrease mortality rates.

Vector control via chemical of biologic targeting of mosquitoes and removal of their breeding sites is the mainstay of prevention, but this approach has failed to stop disease transmission in almost all countries where the process is endemic.

The FDA has approved the first vaccine to prevent dengue disease caused by all dengue virus serotypes (1,2, 3, and 4) for people aged 9 through 16 years who have previously had laboratory-confirmed dengue infection and who live in endemic areas.

The vaccine, Dengvaxia, is a live, attenuated vaccine given in three injections.

The initial dose is followed by two additional injections 6 and 12 months later.

The safety and efficacy of Dengvaxia were demonstrated in three randomized, placebo-controlled studies involving about 35,000 people in dengue-endemic areas, including Puerto Rico, Latin America, and the Asia Pacific region.

The vaccine was roughly 76% effective in preventing symptomatic dengue disease in individuals aged 9 to 16 years old.

Tetravalent Dengue vaccine TAK-003 is efficacious against Dengue in countries in which the disease is endemic.

The uMel strain of Wolbachia infecting A. aegypti mosquitos reduces the incidence of symptomatic dengue.

A single dose of Butantan-DV prevent symptomatic dengue virus – 1 and dengue virus – 2 infections.