Doomed to Develop Dengue?

Pediatric Blogs

As part of my preparation to return to Nicaragua I recently spent several hours reading about Dengue Fever. I'm glad I did.

Dengue fever is common in Nicaragua. Fortunately up to 50% of infections are not symptomatic. However, for those who do develop Dengue Fever, the symptoms are severe. The infection is sometimes called Breakbone Fever because of the severe bone pain with the infections. The bone pain is thought to be due to destruction of white blood cells and platelet precursors in the bone marrow. 

The infection is caused by one of four serotypes of the Dengue virus and individuals who live in endemic regions will be infected by multiple strains over their lifetime. 

The mosquito that transmits the virus bites by day so mosquito nets are of limited use. Only takes one bite. I have been bitten by lots of mosquitos in dengue endemic areas of the world, so the chances are good that I have had an asymptomatic infection. 

The really bad news about dengue is that a small percent develop Dengue Hemorrhagic Fever and Shock Syndrome. This happens when an individual is infected with a new strain. The risk of Dengue Hemorrhagic Fever increases as the duration of time between infections increases. So, if I experienced an asymptomatic infection in the past, perhaps in Asia, Africa, South America, or the Middle East, and I am infected with a different strain on a trip to Nicaragua, I could be in trouble. 

An immunization has not been developed. There is no anti-viral medication available. The only treatment is supportive care with hydration, blood pressure support with pressors, platelets and plasma for bleeding, and so on. All modern (read not available in Nicaragua) ICU therapies.

So, prevention is important. I will be much more careful with DEET application with this trip.  

For the medical professionals who would like to learn more, I made notes on Dengue Fever from my reading, and the notes follow below. 

The WHO ranks Dengue Fever as the most common mosquito-borne viral disease in the world. In the last 50 years, the incidence of dengue has increased 30-fold.  In 2007, the Pan American Health Organization (PAHO) reported the highest number of dengue fever and dengue hemorrhagic fever cases (918,495) in the Americas since 1985.  Each year Dengue results in an estimated 22,000 deaths, mainly in children.

Dengue is caused by infection with 1 of 4 serotypes of dengue virus. Genetic studies suggest that the serotypes evolved from a common ancestor in primate populations approximately 1000 years ago and emerged into a human urban transmission cycle 500 years ago in either Asia or Africa.

Infection with one dengue serotype confers lifelong immunity only to that serotype. Antibody prevalence increases with age, and most adults are immune.

Dengue is transmitted by mosquitoes of the genus Aedes, which breed around dwellings in small amounts of stagnant water such as those found in old tires or other small containers.

In the Americas, dengue epidemics were rare post World War II because mosquitoes were eradicated with coordinated vector-control efforts. Systematic spraying was halted in the early 1970s because of environmental concerns. By the 1990s, A aegypti mosquitoes repopulated Central and South America.

Female Aedes mosquitoes are daytime feeders. Humans are their preferred hosts, with ankles and the back of the neck being the preferred sites. The mosquito inflicts an innocuous bite and is easily disturbed during a blood meal, causing them to move on to finish a meal on another individual, making them efficient vectors. Not uncommonly, entire families develop infection within a 24- to 36-hour period, presumably from the bites of a single infected mosquito.

Mosquitoes acquire the virus when they feed on a carrier of the virus. Persons with dengue viruses in their blood can transmit the viruses to the mosquito 1 day before the onset of the febrile period. The patient can remain infectious for the next 6-7 days. The mosquito can transmit dengue if it immediately bites another host. In addition, transmission occurs after 8-12 days of viral replication in the mosquito's salivary glands (extrinsic incubation period).  The mosquito remains infected for the remainder of its life. The life span of A aegypti is usually 21 days but ranges from 15 to 65 days. The virus does not adversely affect the mosquito.

Once inoculated into a human host, dengue has an incubation period of 3-14 days (average 4-7 days) during which viral replication takes place in target dendritic cells of the reticuloendothelial system, such as dendritic cells, hepatocytes, and endothelial cells, and the process results in the production of immune mediators.

Infection with the virus is asymptomatic in 50 to 90% of individuals.

Data from the 1997 Cuban epidemic suggest that for every clinically apparent case of dengue fever, 13.9 cases of dengue infection went unrecognized because of absent or minimal symptoms of a non-specific febrile illness.

Classic dengue fever is defined by the Pan American Health Organization (PAHO) as an acute febrile illness of 2-7 days duration associated with 2 or more of the following - severe headache, pain behind the eyes, severe muscle pain, joint pain, characteristic rash, hemorrhagic manifestations, low white blood cell count.

Many patients experience a prodrome of chills, red mottling of the skin, and facial flushing (a sensitive and specific indicator of dengue fever). The prodrome might last for 2-3 days. The illness presents with the rapid onset of high fever. The fever lasts 2-7 days and might reach 41°C. In addition to the symptoms and signs above, the patient might have weakness, vomiting, sore throat, or altered taste sensation. The severity of the pain led to the term breakbone fever. The rash is a centrifugal, maculopapular or macular confluent rash over the face, thorax, and flexor surfaces, with islands of skin sparing. The rash typically begins on day 3 and persists 2-3 days. Fever typically resolves with the cessation of viremia.

Leukopenia and thrombocytopenia are common findings in dengue fever and might be caused by direct destructive actions of the virus on bone marrow precursor cells. The resulting active viral replication and cellular destruction in the bone marrow might be the cause the severe bone pain. Approximately one third of patients with dengue fever have mild hemorrhagic symptoms, including petechiae, gingival bleeding, and a positive tourniquet test.

Dengue fever is typically a self-limiting disease with a mortality rate of less then 1%. Supportive care with analgesics, fluid replacement, and bed rest is usually sufficient. Acetaminophen can be used to treat fever and relieve other symptoms. Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids should not be used.

A small percentage of persons who were previously infected by a dengue serotype develop bleeding and endothelial leakage after infection with another serotype. The severity of secondary dengue infections appears to intensify with longer intervals between infections. When an individual is infected with another serotype, non-neutralizing antibodies recognize the dengue virus but do not neutralize or inhibit virus replication. Instead, the virus and antibody form an antigen-antibody complex. This complex is recognized by receptors on macrophages, which then internalize the immune complex and allow the virus to replicate unchecked. This phenomenon is called antibody-dependent enhancement. The affected macrophages release vasoactive mediators that increase vascular permeability.

Patients with dengue fever are at risk for development of dengue hemorrhagic fever or dengue shock syndrome at approximately the time of defervescence. Abdominal pain in conjunction with restlessness, change in mental status, hypothermia, and a drop in the platelet count presages the development of dengue hemorrhagic fever. Of patients with dengue hemorrhagic fever, 90% are younger than 15 years. In persons with dengue hemorrhagic fever, the fever reappears, as a biphasic or "saddleback" fever curve. Along with this biphasic fever, patients with dengue hemorrhagic fever have more obvious hemorrhagic manifestations and plasma leakage.  The critical feature of dengue hemorrhagic fever is plasma leakage. Plasma leakage is caused by increased capillary permeability. Bleeding is caused by capillary fragility and thrombocytopenia. Dengue shock syndrome is essentially dengue hemorrhagic fever with progression into circulatory failure, with ensuing hypotension, and, ultimately, shock and death. Death can occur within 8-24 hours after onset of signs of circulatory failure. The most common clinical findings with impending shock include hypothermia, abdominal pain, vomiting, and restlessness. Dengue hemorrhagic fever has a mortality rate of 2-5% when treated and up to 50% when not treated. Worldwide, children younger than 15 years constitute 90% of dengue hemorrhagic patients

No specific antiviral medication is available to treat dengue infections. Single-dose methylprednisolone showed no mortality benefit in the treatment of dengue shock syndrome in a prospective, randomized, double-blind, placebo-controlled trial.

The only way to prevent dengue virus acquisition is to avoid being bitten by a mosquito.  Susceptible individuals should wear N,N-diethyl-3-methylbenzamide (DEET)–containing mosquito repellant and protective clothing, preferably impregnated with permethrin insecticide.  They should choose well-screened or air-conditioned places.  Mosquito netting is of limited benefit, since the mosquitos bite by day.  Larval habitats (stagnant water) should be eliminated or treated with larvacides.  Indoor sprays should be considered to eliminate mosquitos. Community-based vector control programs include vectoricidal agents and biological control agents.