Introduction
Dengue viruses (DENV) are arboviruses (i.e., arthropod-borne virus). The dengue viruses are part of the genus Flavivirus of the family Flaviviridae. [1] This family of viruses also includes the yellow fever virus (YFV), the West Nile virus (WNV), the Japanese encephalitis virus (JEV), and the tick-borne encephalitis virus (TBEV). There are four closely related serotypes of the Dengue virus: DENV-1, DENV-2, DENV-3, and DENV-4. [2] Recovery from infection by one serotype will provide permanent immunity against that particular virus, but will only provide “partial and transient protection” against later infections by the other three serotypes. [3] All four serotypes are able to cause the complete range of clinical manifestations that may occur after infection. This range includes asymptomatic infection (where little to no symptoms are present and where it is difficult to clinically distinguish the infection from other viral infections) to dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). DHF and DSS are the most serious forms of the disease. DHF and DSS are mainly found in children under 15 years of age in areas where all four serotypes of DENV are found (called hyperendemic). In eight Southeast Asian countries, DHF and DSS are the principal causes of hospitalization and death of children. [2] The risk for developing dengue hemorrhagic fever or dengue shock syndrome increases with sequential infections from different serotypes of the virus. In one case series it was found that dengue hemorrhagic fever and dengue shock syndrome were “15 to 80 times more likely in secondary infections than in primary infections. [4]
The World Health Organization (WHO) created a classification system to differentiate between dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Although a standardized classification system to identify the severity of dengue virus infections is considered essential to the treatment of the virus as well as to the communication of scientific data, problems with the current World Health Organization classification system have emerged. A study was recently conducted to evaluate the accuracy and usefulness of the WHO system. Researchers found that the classification system is “not accurate in correctly classifying dengue disease severity and it lacks sufficient agreement with clinical practice.” According to this system, dengue hemorrhagic fever is “defined by the presence of fever, a hemorrhagic tendency, thrombocytopenia, and some evidence of plasma leakage due to increased vascular permeability.” More severe cases of DHF are categorized as dengue shock syndrome, which occurs when “circulatory failure is present. [5]
Dengue viruses cannot be transmitted from human to human, but instead require an intermediate vector, which is principally the female Aedes aegypti mosquito (an extremely domesticated mosquito) but also the albopictus mosquito. [6][7] The Aedes aegypti is a day-biting mosquito that breeds in natural or artificial bodies of water. [1] The mosquitoes contract the dengue virus while ingesting the infected blood of humans. After the virus’ incubation of 8 to 10 days, the infected mosquito is able to transmit the virus throughout its lifespan. Infected female mosquitoes are also able to spread the virus to their offspring by way of transovarial transmission (i.e., via the eggs). It is not yet understood how transovarial transmission affects the spread of the virus to humans. The principle “carriers and multipliers” of the dengue virus are humans, with the virus circulating in infected human blood for 2 to 7 days. The mosquito contracts the virus while feeding on human blood during this period. Once the virus is in the human body, it passes to the different glands of the body and then multiplies. The virus then enters the bloodstream. Once the virus enters the blood vessels, they enlarge and leak. The spleen and lymph nodes swell and parts of the liver tissue die. Disseminated intravascular coagulation (DIC) can then occur, which is a process that leads to the risk for hemorrhaging because the chemicals that are needed for blood clotting are depleted. [6] It is thought that some monkeys may play a similar role as humans do in the transmission of the dengue virus. [3]
Before the 1970s, only five countries, found in Southeast Asia, had reported cases of dengue hemorrhagic fever. Now dengue virus infections are endemic in more than 100 countries and infections with dengue viruses are currently the most widespread vector-borne viral disease affecting humans in the world. Along with the increasing numbers of dengue virus infections are large outbreaks of the infection. For example, in 1998 there was a dengue pandemic that occurred in 56 countries resulting in 1.2 million cases of dengue hemorrhagic fever and in 2007, more than 80,000 dengue virus infection cases were reported in Venezuela alone, with more than 6000 reported cases of dengue hemorrhagic fever. [3][8] The increase in dengue virus infections is caused by the geographic spread of all four of the dengue virus serotypes and their vectors, particularly Aedes aegypti. Over the past fifty years, the geographic area of this mosquito vector has greatly expanded. The mosquito is now found in most tropical and subtropical countries, particularly in urban and semi urban areas. The rapid spread of the virus and its vectors is attributable to several factors, including the increase in international air travel and international trade; rapid population growth; migration from rural to urban areas; poor urban infrastructure; increases in solid waste (e.g., used tires); and the breakdown of vector control efforts. [9]
The breeding grounds of Aedes aegypti in Asia and Central and South America are mainly found in artificial containers used for domestic water storage, such as metal drums, concrete tanks, and ceramic pots. Articles that collect rainwater are also prime breeding locations for the Aedes aegypti, such as discarded or abandoned tires and plastic food containers. This mosquito also breeds in natural areas of Africa, including tree holes and gathered leaves that are able to hold rainwater. Aedes albopictus, the secondary dengue virus vector mainly found in Asia, has recently been discovered in the United States, the Caribbean islands, Europe, and Africa. The spread of this vector is primarily caused by the international trade of used tires.
Currently, the only prevention and control method available to combat dengue virus infections is vector control. Vector control is put into practice by the use of chemical applications and environmental management methods. Insecticidal applications on larval habitats (especially in household environments, such as water storage containers) does prevent vector breeding for many weeks, however the insecticide needs to be periodically reapplied. Biological vector control methods include using copepods (small crustaceans) and small, mosquito-eating fish, which have been successful. Environmental management practices include implementing proper solid waste removal and better water storage practices (e.g., covering containers to prevent vector breeding). These vector control components are often implemented through community-based programs. A recent study reviewed and evaluated community-based dengue control programs and found that multifaceted vector control programs are more effective than single interventions alone and that cooperation among many groups (e.g., local health services, vector control organizations, civil authorities, and community members) is essential for the successful reduction in Aedes aegypti. The review also found that in the existing research, it is unknown whether community-based dengue vector control programs coupled with biological and chemical control methods actually reduces dengue virus transmission. [10]
Statistic
- Two fifths of the world’s population (approximately 2.5 billion people) are currently at risk for infection with a dengue virus.
- Globally, there are approximately 50 million dengue infections each year.
- Dengue is endemic in more than 100 countries in Africa, South and Central America, the Caribbean, the Eastern Mediterranean, Southeast Asia, and the Western Pacific, with Southeast Asia and the Western Pacific being the most severely affected.
- Approximately 500,000 individuals who have dengue hemorrhagic fever are hospitalized every year, with fatalities reaching approximately 2.5% of those infected with DHF.
- Dengue hemorrhagic fever fatality rates can reach more than 20% when not treated.
- In 2007, more than 890,000 cases of dengue virus infections were reported in the Americas, 26,000 of which were reported cases of dengue hemorrhagic fever.
- Children make up approximately 95% of the cases of dengue hemorrhagic fever.
- Approximately 25,000 to 50,000 deaths from dengue infections occur every year. [3][11]
Signs and Symptoms
The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.
Most dengue virus infections are either asymptomatic or occur with only mild symptoms. Classic dengue fever has an incubation period from 3 to 14 days, with an average of 4 to 7 days. Symptoms of DF include a sudden high fever with chills, headache, pain behind the eyes, red eyes, myalgias, flushing of the face, anorexia, abdominal pain, nausea, lower back pain, enlarged lymph nodes, and pain in legs and joints. Rash is also a common symptom with DF and has been reported to occur in more than 80% of cases in some studies. The rash is most often found on the trunk of the body, the insides of the extremities, and on the palms of the hands and soles of the feet. Dengue fever generally occurs in milder forms in young children as compared with older children and adults. Typical laboratory abnormalities that are found in classic dengue virus infections include leukopenia, thrombocytopenia, and a rise in serum transaminases. The “dengue triad” is the term given to the distinctive combination of fever, headache, and rash that accompany dengue fever. [2][6]
In dengue hemorrhagic fever and dengue shock syndrome, the first symptoms to occur are fever and headache. Individuals develop a cough, followed by petechiae, which is a type of rash with tiny purple spots. The developing petechiae are actually areas where the blood is leaking out of the blood vessels. When the bleeding gets worse, large bruises appear. Severe abdominal pain may also occur. Patients may begin to vomit what appears to be coffee grounds, but is actually a sign of abdominal bleeding. When the blood vessels become increasingly damaged, they leak at a higher rate, dilate, and cause decreasing blood flow to bodily tissues. This decrease in blood flow puts the body in a state called shock, causing damage to organs because the lack of blood deprives the organs of needed oxygen. [6]
Treatment Options
Conventional
There is currently no treatment available for dengue fever. Medications may be given to treat the symptoms of the virus, such as to lower fevers and manage pain. For dengue hemorrhagic fever, maintaining an individual’s “circulating fluid volume” is the main aspect of care. When patients who have DHF are cared for by medical staff experienced with this form of the disease, a substantial decrease in mortality rates occurs, from more than 20% down to less than 1%.
There are currently no vaccinations available for the treatment of dengue viruses; however two vaccine candidates are in development that have advanced to human evaluation in endemic countries. There are also several possible vaccines currently in earlier development stages. [3] [6]
Nutritional Supplementation
Herbal Supplementation
There are many cultures that use traditional herbal remedies to treat the symptoms of dengue fever. However, there is no clinical evidence to support the use of these remedies. A limited listing of these traditional herbal remedies may be found below:
Ayurvedic Herbs
Punarnava has been used in the Ayurvedic system of medicine for thousands of years. Extracts can be taken from the whole plant or just the root. Most commonly, Punarnava is used to treat gastrointestinal [14] and hepatic disorders. [15] The leaves from Punarnava are traditionally used to treat dyspepsia, enlarged spleen, and general abdominal discomfort. [16] The whole plant is used in treatment of biliousness, jaundice, internal inflammation and constipation. [16] [17] In addition to its use in the gastrointestinal system, Punarnava has been used in asthma, congestion. It also has been used as a blood purifier, cardiotonic and a treatment for anemia. Ayurvedic medicine also qualifies Punarnava as useful in treatment of leucorrhoea, anascara, and as an antidote to snake venom. Its rasa (taste) has been classified as madhura (sweet), titka (bitter), and kasaya (astringent). Punarnava pacifies the kapha and vata doshas, stimulates the pitta dosha and has a generally warming effect on the body.
Tulsi is used in traditional Ayurvedic medicine for upper respiratory disorders. The leaves provide substantial expectorant and cough suppressant characteristics. Often just the juice of the leaf or an infusion such as tea is useful in cough and bronchitis. Additionally, O. sanctum can be used to treat diarrhea, dysentery and dyspepsia. Tulsi pacifies the vata and kapha doshas while having a stimulating effect on the pitta dosha. Its rasa (taste) is characterized as being katu (pungent) and titka (bitter). [17] [18]
South/Central America Herbs
In South America, Una de gato has a history of use that dates back to over 2000 years. In Peru, indigenous tribes used this herb as a treatment for rheumatic complaints and inflammation. It was also used by various indigenous peoples to treat asthma, urinary tract infections, gastric ulcers, diabetes and as an internal detoxification agent. [19] Large doses were used in Peru as a contraceptive, a practice that had unwanted side effects as large doses over extended periods of time may result in sterility.
Other uses include dysentery, gonorrhea, menstrual irregularity, wounds, gastric ulcers, dysentery, fever, bone pain, cirrhosis and diabetes. [19] [20]
Essential Oils
The World Health Organizations recommends various Essential Oils as insect repellants against the mosquitoes that carry this disease. These oils include neem, lemongrass, lemon-scented eucalyptus.
Clinical Notes
The arbovirus that causes dengue fever is one of only a few types of arboviruses that is able to be isolated from blood serum; this is because the dengue virus stays longer in the bloodstream than other arboviruses do. [6] The laboratory diagnosis of dengue virus infection is usually performed by virus isolation in tissue culture, “serodiagnosis by detection of IgM/IgG antibodies, or molecular detection by the demonstration of viral RNA by RT-PCR.” A significant challenge to diagnosis is the time it takes for definitive results. For example, diagnosis by IgM antibody detection is only possible after 5 to 7 days of illness. There are tests available that claim diagnostic results after a day of illness; however they are expensive tests that are not feasible for use in developing countries. [1]
References
- P. Bharaj, H.S. Chahar, A. Pandey. Concurrent infections by all four dengue virus serotypes during an outbreak of dengue in 2006 in Delhi, India. Virol J 2008; 5:1. doi: 10.1186/1743-422X-5-1.
- S.S. Whitehead, J.E. Blaney, A.P. Durbin. Prospects for a dengue virus vaccine. Nat Rev Microbiol 2007; 5(7): 518-528.
- World Health Organization. Dengue and dengue haemorrhagic fever. Fact sheet no. 117, March 2009. Available from: http://www.who.int/mediacentre/factsheets/fs117/en/print.html. [Accessed on December 10, 2009]
- J.R. Stephenson. Understanding dengue pathogenesis: implications for vaccine design. Bulletin of the World Health Organization 2005; 83(4): 308-314.
- T.E. Setiati, A.T.A. Mairuhu, P. Koraka. Dengue disease severity in Indonesian children: an evaluation of the World Health Organization classification system. BMC Infectious Diseases 2007; 7:22 doi: 10.1186/1471-2334-7-22.
- R. Carson-DeWitt. Dengue fever. In: Longe JL, editor. Gale encyclopedia of medicine. vol. 2, 3rd edition. Detroit (MI): Gale Group; 2006. p. 1132-1133.
- O.M. Sessions, N.J. Barrows, J.A. Souza-Neto. Discovery of insect and human dengue virus host factors . Nature 2009; 458(7241): 1047-1050.
- H.M. Thu, K. Lowry, T.T. Myint. Myanmar dengue outbreak associated with displacement of serotypes 2, 3, and 4 by Dengue 1. Emerging Infectious Diseases 2004; 10(4): 593-597.
- World Health Organization. Weekly epidemiological record. March 13, 2009; 84(11/12):85-88. Available from: http://www.who.int/wer. [Accessed on December 10, 2009]
- C. Heintze, M.V. Garrido, A. Kroeger. What do community-based dengue control programmes achieve? A systematic review of published evaluations. Trans R Soc Trop Med Hyg. Apr2007; 101(4):317-325.
- S. Ash. Dengue fever [editorial]. Ocul Immunol Inflamm 2004; 12(4): 251-253.
- H. Loke, D. Bethell, C.X. Phuong, N. Day, N. White, J. Farrar, A. Hill. Susceptibility to dengue hemorrhagic fever in Vietnam: evidence of an association with variation in the vitamin D receptor and Fc gamma receptor IIa genes. Am J Trop Med Hyg. Jul 2002;67(1):102-106.
- P. Klassen, H.K. Biesalski, M. Mazariegos, N.W. Solomons, P. Fürst. Classic dengue fever affects levels of circulating antioxidants. Nutrition. Jun2004;20(6):542-547.
- F. Borrelli, V. Ascione, R. Capasso, A.A. Izzo, E. Fattorusso, O. Taglialatela-Scafati. Spasmolytic effects of nonprenylated rotenoid constituents of Boerhaavia diffusa roots. J Nat Prod. Jun2006;69(6):903-6.
- A.K. Rawat, S. Mehrotra, S.C. Tripathi, U. Shome. Hepatoprotective activity of Boerhaavia diffusa L. roots–a popular Indian ethnomedicine. J Ethnopharmacol. Mar1997;56(1):61-66.
- Society for Parthenium Management (SOPAM). 2004. Available from http://www.hort.purdue.edu/newcrop/CropFactSheets/punanrnava.html. [Accessed on March 25, 2009]
- L.D. Kapoor. CRC Handbook of Ayurvedic Medicinal Plants. Boca Raton, FL: CRC Press; 2001. p136.
- S. Gerson. National Institute of Ayurvedic Medicine. Ocimum sanctum. 1997. Available from http://www.niam.com/corp-web/ocimum.htm. [Accessed on February 16, 2009]
- L. Taylor. The Healing Power of Rainforest Herbs: A Guide to Understanding and Using Herbal Medicinals. New York: Square One Publishers.2005.p344.
- J.A. Duke. Medicinal Plants of Latin America. Boca Raton, FL: Taylor and Francis. 2009. p413
