A QUESTION FROM OUR READERS
Q. Angela from Winter Park, FL, has a follow-up question: “How does infection with a second dengue serotype place me at higher risk for a severe case of dengue?”
A. As discussed last week, Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) are the two most severe and sometimes fatal manifestations of dengue infection.
The most common of these is DHF. During the acute phase of infection, DHF is characterized by the sudden onset of a fever lasting two to seven days with various virus-like symptoms, including rash, joint pain, headache, and sore throat. As the fever subsides and the patient enters the chronic phase of infection, really bad things begin to happen. The characteristic manifestations of DHF appear as plasma leakage (hence the “hemorrhagic” in DHF) from the skin, nose, ears, mouth, and GI tract. Plasma leakage is accompanied by circulatory failure and shock at about the same time that body temperature normalizes.
The secondary-infection hypothesis of DHF and DSS proposes that individuals experiencing infection with a second dengue serotype have a higher risk of developing severe illness. For example, if your first infection was DEN-1 and your second is DEN-3, you run a greater risk of developing DHF or DSS.
A possible explanation for the onset of severe dengue infection is that the preexisting heterologous dengue antibody from the first infection (e.g., DEN-1) recognizes antigens (virus particles) from the second infection (e.g., DEN-3) and forms an antigen-antibody complex (DEN-3 antigen-DEN-1 antibody). The complex binds to leukocyte (especially macrophages) plasma membranes and is absorbed by the macrophage but not neutralized and destroyed. The virus part of the antigen-antibody complex then begins to replicate inside the macrophage.
The previous dengue infection initiates a cellular process known as antibody-dependent enhancement (ADE) that increases the infectivity and replication rate of the dengue virus in the macrophages. ADE is believed to produce viral particles with increased vascular permeability, resulting in hemorrhage and shock in patients experiencing a second dengue infection with a new serotype.
It is important to note that not all patients infected by a second dengue serotype suffer DHF or DSS. A host of secondary factors, including age (young and old) and co-morbidities (cancer or compromised immune systems), may render individuals more susceptible to severe infection. If infected with dengue, it is good for you to know the serotype and also important for you to know what serotypes are currently circulating in areas where you live or visit.
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