Aditi Shenoy received her B.S. in Biomedical Engineering from The George Washington University in 2014 and is currently pursuing her goal of a graduate degree
Dengue virus causes one of the most severe mosquito-borne illnesses in the world. Previously thought as a sporadic disease, in the past fifty years dengue incidence has increased significantly. Now, the virus is endemic in 112 countries in Southeast Asia, South Asia, Far East regions, South America, and Africa. Around 2.5 to 3 billion people predominantly in urban areas of tropical and subtropical regions are considered to be particularly susceptible to infection.
Dengue belongs to the flaviviridae family of viruses that are typically carried by insects and transmitted to humans. The virus likely originated in monkeys and spilled into humans in Africa or Southeast Asia between 100 and 800 years ago. It then established itself in countries around the world during World War II due to the increased transport of cargo. Insects (namely, mosquitoes) are the key transmitter of the virus, which can cause infection by any one of four distinct but closely related subtypes (known as DENV 1 through 4). What’s more, reinfection can lead to dengue hemorrhagic fever (abbreviated DHF) and an equally severe condition known as dengue shock syndrome (DSS), as well as several clinical sequelae.
The symptoms of dengue infection can range from none to a host of diseases: fever, DHF, or DSS. Different viral subtypes lead to varying clinical and epidemiologic profiles: while DENV 2 and DENV 3 tend to cause more severe disease, DENV 4 typically causes a milder illness. As always, many additional factors ultimately play into the severity of disease including immune system strength and whether one has been previously been infected with the virus.
Once someone has been infected with dengue, the incubation period is 7 to 10 days, and initial symptoms are often overlooked as a standard fever. Dengue-induced fever, however, lasts 2 to 7 days and is often accompanied by flushing on the upper body, a severe headache, abdominal discomfort, joint pain, muscle pain, anorexia, or a flat, red rash on the skin.
Recovery from dengue infection takes longer in adults than in children, during which time DHF may occur. According to the World Health Organization, a person developing DHF starts with a fever, with the additional symptoms of bleeding in various body organs, evidence of plasma leakage, and low platelet count. The first stage of progressed DHF begins with a high fever and generalized symptoms. After this stage, the patient either recovers or progresses to the plasma leakage phase, which is identified by a high heart rate and low blood pressure, and sometimes shock (DSS). During this phase, which lasts from 24 to 48 hours, bleeding may occur from any site in the body, though the most common symptoms include vomiting blood, bleeding from the skin, gums, and nose, and from the vagina in females. After this stage, a patient may begin to recover. However, shock can occur in severe cases, and progression to this stage of disease is associated with a high fatality rate (up to 47%).
Severe dengue viral infections can lead to a variety of clinical sequelae including liver failure, brain disease, inflammation of the heart, acute respiratory distress syndrome (ARDS), amnesia, dementia, and manic psychosis. Liver failure is common in all forms of dengue viral diseases, though the extent of liver damage naturally varies with overall severity of infection. For instance, infection with DENV 3 or DENV 4 subtypes typically results in more frequent liver problems than DENV 1 or DENV 2. Regardless of its origin, severe liver failure can lead to death. Brain disease is furthermore reported in 0.5% of patients with DHF, and has a fatality rate of 22%. Mouse studies have shown that this can be the result of direct viral infection of the brain, which can result in conditions like amnesia, dementia, and manic psychosis. Finally, severe heart inflammation has also been associated with dengue infections.
Despite the high number of people who either contract the virus or are at risk of contracting it, there are currently no specific drugs that are effective against dengue. Treatment, which is often inaccessible for the majority of people who suffer from a dengue infection, usually involves ensuring that a patient is kept well-hydrated in addition to supportive care as symptoms progress (such as anti-inflammatory medications to reduce fevers). Early identification of DHF infection also improves outcomes, since it has been shown that death rates are lower in patients who are admitted to hospitals before the onset of DSS.
There has been a lot of research on development of a safe and effective (against all four serotypes) dengue vaccine. The biggest breakthrough in this endeavor occurred last year with the licensing of Sanofi Pasteur’s new Dengvaxia vaccine. According to the company’s clinical trials, the vaccine is almost 60% effective overall, but varies in specific efficacy across different age groups and viral serotypes. As mentioned previously, dengue has a weird pathology that likely contributed to vaccine design being an especially difficult task: whereas most infectious diseases are milder the second time around because the body has developed an immune response, dengue reinfection causes a more severe disease. Almost paradoxically, then, a vaccine could potentially offer more harm than help, acting as a “first case” of the virus. The WHO thus recommends Dengvaxia only in regions of high-burden dengue, where individuals receiving the vaccine have already been exposed to the virus. But doesn’t this just act as a second infection? Dengvaxia is a heavily contested vaccine, with experts still cautioning that the vaccine has potential to cause more harm than good in most places.
To date, the primary method of protection from dengue fever is still the physical prevention of infection. This includes all sorts of mosquito-targeting efforts like bed nets, and behavioral efforts such as avoiding standing or polluted water (where mosquitos tend to breed), avoiding dark areas indoors (where mosquitos nest), and applying mosquito repellants. It goes without saying that dengue disease, an oft-underestimated virus in populations that have never been exposed to it, poses a critical and devastating public health issue in many parts of the world.