From Wikipedia, the free encyclopedia Jump to: navigation, search For other uses, see Dengue fever (disambiguation). Dengue fever Classification and external resources The typical rash seen in dengue fever ICD-10 A90. ICD-9 061 DiseasesDB 3564 MedlinePlus 001374 eMedicine med/528 MeSH C02.782.417.214 Dengue fever (UK: /ˈdɛŋɡeɪ/, US: /ˈdɛŋɡiː/), also known as breakbone fever, is an infectious tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic morbilliform skin rash. In a small proportion of cases the disease develops to the life-threatening dengue hemorrhagic fever (bleeding, low levels of blood platelets and blood plasma leakage) and dengue shock syndrome (circulatory failure). Dengue is transmitted by several species of mosquito within the Aedes genus, principally A. aegypti. The virus has four different types; infection with one type usually gives lifelong immunity to that type, but only short-term immunity to the others. Subsequent infection with a different type is believed to increase the risk of severe complications. As there is no vaccine, prevention is sought by reducing the habitat and the number of mosquitoes and limiting exposure to bites. Treatment of acute dengue is supportive, using either oral or intravenous rehydration for mild or moderate disease, and intravenous fluids and blood transfusion for more severe cases. The incidence of dengue fever has increased dramatically over the last 50 years, with around 50–100 million people infected yearly. Dengue is currently endemic in more than 110 countries. Early descriptions of the condition date from 1779, and its viral cause and the transmission were elucidated in the early 20th century. Dengue has become a worldwide problem since the Second World War. Contents [hide] 1 Signs and symptoms 1.1 Clinical course 1.2 Associated problems 2 Cause 2.1 Virology 2.2 Transmission 2.3 Predisposition 3 Mechanism 3.1 Viral reproduction 3.2 Severe disease 4 Diagnosis 4.1 General 4.2 Classification 4.3 Virology and serology 5 Prevention 6 Management 7 Epidemiology 8 History 8.1 Etymology 8.2 Discovery 9 Research 10 Notes 11 References 12 External links Signs and symptoms Schematic depiction of the symptoms of dengue fever People infected with dengue virus are commonly asymptomatic or only have mild symptoms such as an uncomplicated fever.[1][2] Others have more severe illness, and in a small proportion it is life-threatening.[1] The incubation period (time between exposure and onset of symptoms) ranges from 3–14 days, but most often it is 4–7 days.[3] This means that travellers returning from endemic areas are unlikely to have dengue if fever or other symptoms start more than 14 days after arriving home.[4] Children often experience symptoms similar to those of the common cold and gastroenteritis (vomiting and diarrhea),[5] but are more susceptible to the severe complications.[4] Clinical course The characteristic symptoms of dengue are: a sudden-onset fever, headache (typically behind the eyes), muscle and joint pains, and a rash. The alternative name for dengue, "break-bone fever", comes from the associated muscle and joints pains.[1][6] The course of infection is divided into three phases: febrile, critical, and recovery.[7] The febrile phase involves high fevers, frequently over 40 °C (104 °F) and is associated with generalized pain and a headache; this usually lasts two to seven days.[6][7] Flushed skin and some small red spots called petechiae, which are caused by broken capillaries, may occur at this point,[7] as may some mild bleeding from mucous membranes of the mouth and nose.[4][6] The critical phase, if it occurs, follows the resolution of the high fever and typically lasts one to two days.[7] During this phase there may be significant fluid accumulation in the chest and abdominal cavity due to increased capillary permeability and leakage. This leads to depletion of fluid from the circulation and decreased blood supply to vital organs.[7] During this phase, organ dysfunction and severe bleeding (typically from the gastrointestinal tract) may occur.[4][7] Shock and hemorrhage occur in less than 5% of all cases of dengue,[4] however those who have previously been infected with other serotypes of dengue virus ("secondary infection") have an increased risk.[4][8] The recovery phase occurs next, with resorption of the leaked fluid into the bloodstream.[7] This usually lasts two to three days.[4] The improvement is often striking, but there may be severe itching and a slow heart rate.[4][7] It is during this stage that a fluid overload state may occur, which if it affects the brain may reduce the level of consciousness or cause seizures.[4] Associated problems Dengue may occasionally affect several other body systems.[7] This may be either in isolation or along with the classic dengue symptoms.[5] A decreased level of consciousness occurs in 0.5–6% of severe cases. This may be caused by infection of the brain by the virus or indirectly due to impairment of vital organs, for example, the liver.[5][9] Other neurological disorders have been reported in the context of dengue, such as transverse myelitis and Guillain-Barré syndrome.[5] Infection of the heart and acute liver failure are among the rarer complications of dengue.[4][7] Cause Virology Main article: Dengue virus A TEM micrograph showing dengue virus virions (the cluster of dark dots near the center) Dengue fever virus (DENV) is an RNA virus of the family Flaviviridae; genus Flavivirus. Other members of the same family include yellow fever virus, West Nile virus, St. Louis encephalitis virus, Japanese encephalitis virus, tick-borne encephalitis virus, Kyasanur forest disease virus, and Omsk hemorrhagic fever virus.[9] Most are transmitted by arthropods (mosquitoes or ticks), and are therefore also referred to as arboviruses (arthropod-borne viruses).[9] The dengue virus genome (genetic material) contains about 11,000 nucleotide bases, which code for the three different types of protein molecules that form the virus particle (C, prM and E) and seven other types of protein molecules (NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5) that are only found in infected host cells and are required for replication of the virus.[8][10] There are four strains of the virus, which are called serotypes, and these are referred to as DENV-1, DENV-2, DENV-3 and DENV-4.[2] All four serotypes can cause the full spectrum of disease.[8] Infection with one serotype is believed to produce lifelong immunity to that serotype but only short term protection against the others.[2][6] The severe complications on secondary infection seem to occur particularly if someone previously exposed to serotype DENV-1 then contracts serotype DENV-2 or serotype DENV-3, or if someone previously exposed to type DENV-3 then acquires DENV-2.[10] Transmission The mosquito Aedes aegypti feeding off a human host Dengue virus is primarily transmitted by Aedes mosquitoes, particularly A. aegypti.[2] These mosquitoes usually live between the latitudes of 35° North and 35° South below an elevation of 1,000 metres (3,300 ft).[2] They bite primarily during the day.[11] Other mosquito species—Aedes albopictus, A. polynesiensis and several A. scutellaris—may also transmit the disease.[2] Humans are the primary host of the virus,[2][9] but it may also circulate in nonhuman primates.[12] An infection may be acquired via a single bite.[13] A mosquito that takes a blood meal from a person infected with dengue fever becomes itself infected with the virus in the cells lining its gut. About 8–10 days later, the virus spreads to other tissues including the mosquito's salivary glands and is subsequently released into its saliva. The virus seems to have no detrimental effect on the mosquito, which remains infected for life. Aedes aegypti prefers to lay its eggs in artificial water containers and tends to live in close proximity to humans, and prefers to feed off people rather than other vertebrates.[14] Dengue may also be transmitted via infected blood products and through organ donation.[15][16] In countries such as Singapore, where dengue is endemic, the risk is estimated to be between 1.6 and 6 per 10,000 transfusions.[17] Vertical transmission (from mother to child) during pregnancy or at birth has been observed.[13] Other person-to-person modes of transmission have been reported, but are very unusual.[6] Predisposition Severe disease is more common in babies and young children, and in contrast to many other infections it is more common in children that are relatively well nourished.[4] Women are more at risk than men.[10] Dengue may be life-threatening in people with chronic diseases such as diabetes and asthma.[10] It is thought that polymorphisms (normal variations) in particular genes may increase the risk of severe dengue complications. Examples include the genes coding for the proteins known as TNFα, mannan-binding lectin,[1] CTLA4, TGFβ,[8] DC-SIGN, and particular forms of human leukocyte antigen.[10] A common genetic abnormality in Africans, known as glucose-6-phosphate dehydrogenase deficiency, appears to increase the risk.[18] Polymorphisms in the genes for the vitamin D receptor and FcγR seem to offer protection.[10] Mechanism When a mosquito carrying DENV bites a person, the virus enters the skin together with the mosquito's saliva. It binds to and enters white blood cells, and reproduces inside the cells while they move throughout the body. The white blood cells respond by producing a number of signalling proteins (such as interferon) that are responsible for many of the symptoms, such as the fever, the flu-like symptoms and the severe pains. In severe infection, the virus production inside the body is greatly increased, and many more organs (such as the liver and the bone marrow) can be affected, and fluid from the bloodstream leaks through the wall of small blood vessels into body cavities. As a result, less blood circulates in the blood vessels, and the blood pressure becomes so low that it cannot supply sufficient blood to vital organs. Furthermore, dysfunction of the bone marrow leads to reduced numbers of platelets, which are necessary for effective blood clotting; this increases the risk of bleeding, the other major complication of dengue.[18] Viral reproduction After entering the skin, DENV binds to Langerhans cells (a population of dendritic cells in the skin that identifies pathogens).[18] The virus enters the cells through binding between viral proteins and membrane proteins on the Langerhans cell, specifically the C-type lectins called DC-SIGN, mannose receptor and CLEC5A.[8] DC-SIGN, a non-specific receptor for foreign material on dendritic cells, seems to be the main one.[10] The dendritic cell moves to the nearest lymph node. Meanwhile, the virus genome is replicated in membrane-bound vesicles on the cell's endoplasmic reticulum, where the cell's protein synthesis apparatus produces new viral proteins, and the viral RNA is copied. Immature virus particles are transported to the Golgi apparatus, the part of the cell where the some of the proteins receive necessary sugar chains (glycoproteins). The now mature new viruses bud on the surface of the infected cell and are released by exocytosis. They are then able enter other white blood cells (such as monocytes and macrophages).[8] The initial reaction of infected cells is to produce the interferon, a cytokine that raises a number of defenses against viral infection through the innate immune system by augmenting the production of a large group of proteins (mediated by the JAK-STAT pathway). Some serotypes of DENV appear to have mechanisms to slow down this process. Interferon also activates the adaptive immune system, which leads to the generation of antibodies against the virus as well as T cells that directly attack any cell infected with the virus.[8] Various antibodies are generated; some bind closely to the viral proteins and target them for phagocytosis (ingestion by specialized cells) and destruction, but some bind the virus less well and appear instead to deliver the virus into a part of the phagocytes where it is not destroyed but is able to replicate further.[8] Severe disease Further information: Antibody-dependent enhancement It is not entirely clear why secondary infection with a different strain of DENV places people at risk of dengue hemorrhagic fever and dengue shock syndrome. The most widely accepted hypothesis is that of antibody-dependent enhancement (ADE). The exact mechanism behind ADE is unclear. It may be caused by poor binding of non-neutralizing antibodies and delivery into the wrong compartment of white blood cells that have ingested the virus for destruction.[8][10] There is a suspicion that ADE is not the only mechanism underlying severe dengue-related complications,[1] and various lines of research have implied a role for T cells and soluble factors (such as cytokines and the complement system).[18] Severe disease is marked by two problems: dysfunction of endothelium (the cells that line blood vessels) and disordered blood clotting.[5] Endothelial dysfunction leads to the leakage of fluid from the blood vessels into the chest and abdominal cavities, while coagulation disorder is responsible for the bleeding complications. Higher levels of virus in the blood and involvement of other organs (such as the bone marrow and the liver) are associated with more severe disease. Cells in the affected organs die, leading to the release of cytokines and activation of both coagulation and fibrinolysis (the opposing systems of blood clotting and clot degradation). These alterations together lead to both endothelial dysfunction and coagulation disorder.[18] Diagnosis General Warning signs[19] Abdominal pain Ongoing vomiting Liver enlargement Mucosal bleeding High hematocrit with low platelets Lethargy The diagnosis of dengue is typically made clinically, on the basis of reported symptoms and physical examination; this applies especially in endemic areas.[1] Early disease can however be difficult to differentiate from other viral infections.[4] A probable diagnosis is based on the findings of fever plus two of the following: nausea and vomiting, rash, generalized pains, low white blood cell count, positive tourniquet test, or any warning sign (see table) in someone who lives in an endemic area.[19] Warning signs typically occur before the onset of severe dengue.[7] The tourniquet test, which is particularly useful in settings where no laboratory investigations are readily available, involves the application of a blood pressure cuff for five minutes, followed by the counting of any petechial hemorrhages; a higher number makes a diagnosis of dengue more likely.[7] It may be difficult to distinguish dengue fever and chikungunya, a similar viral infection that shares many symptoms and occurs in similar parts of the world to dengue.[6] Often, investigations are performed to exclude other conditions that cause similar symptoms, such as malaria, leptospirosis, typhoid fever, and meningococcal disease.[4] The earliest change detectable on laboratory investigations is a low white blood cell count, which may then be followed by low platelets and metabolic acidosis.[4] In severe disease, plasma leakage may result in hemoconcentration (as indicated by a rising hematocrit) and hypoalbuminemia.[4] Pleural effusions or ascites may be detected by physical examination when large,[4] but the demonstration of fluid on ultrasound may assist in the early identification of dengue shock syndrome.[1][4] The use of ultrasound is limited by lack of availability in many settings.[1] Classification The World Health Organization's 2009 classification divides dengue fever into two groups: uncomplicated and severe.[1][19] This replaces the 1997 WHO classification, which needed to be simplified as it had been found to be too restrictive, but the older classification is still widely used.[19] The 1997 classification divided dengue into undifferentiated fever, dengue fever, and dengue hemorrhagic fever.[4][20] Dengue hemorrhagic fever was subdivided further into four grades (grade I–IV). Grade I is the presence only of easy bruising or a positive "tourniquet test" (see below) in someone with fever, grade II is the presence of spontaneous bleeding into the skin and elsewhere, grade III is the clinical evidence of shock, and grade IV is shock so severe that blood pressure and pulse cannot be detected.[20] Grades III and IV are referred to as "dengue shock syndrome".[19][20] Virology and serology Dengue fever may also be diagnosed by microbiological laboratory testing.[19] This can be done by virus isolation in cell cultures, nucleic acid detection by PCR, viral antigen detection or specific antibodies (serology).[10][21] Virus isolation and nucleic acid detection are more accurate than antigen detection, but these tests are not widely available due to their greater cost.[21] All tests may be negative in the early stages of the disease.[4][10] Apart from serology, laboratory tests are only of diagnostic value during the acute phase of the illness. Tests for dengue virus-specific antibodies, types IgG and IgM, can be useful in confirming a diagnosis in the later stages of the infection. Both IgG and IgM are produced after 5–7 days. The highest levels (titres) of IgM are detected following a primary infection, but IgM is also produced in secondary and tertiary infections. The IgM becomes undetectable 30–90 days after a primary infection, but earlier following re-infections. IgG, by contrast, remains detectable for over 60 years and, in the absence of symptoms, is a useful indicator of past infection. After a primary infection the IgG reaches peak levels in the blood after 14–21 days. In subsequent re-infections, levels peak earlier and the titres are usually higher. Both IgG and IgM provide protective immunity to the infecting serotype of the virus. In the laboratory test the IgG and the IgM antibodies can cross-react with other flaviviruses, such as yellow fever virus, which can make the interpretation of the serology difficult.[6][10][22] The detection of IgG alone is not considered diagnostic unless blood samples are collected 14 days apart and a greater than fourfold increase in levels of specific IgG is detected. In a person with symptoms, the detection of IgM is considered diagnostic.[22] Prevention A 1920s photograph of efforts to disperse standing water and thus decrease mosquito populations There are currently no approved vaccines for the dengue virus.[1] Prevention thus depends on control of and protection from the bites of the mosquito that transmits it.[11][23] The World Health Organization recommends an Integrated Vector Control program consisting of five elements: (1) Advocacy, social mobilization and legislation to ensure that public health bodies and communities are strengthened, (2) collaboration between the health and other sectors (public and private), (3) an integrated approach to disease control to maximize use of resources, (4) evidence-based decision making to ensure any interventions are targeted appropriately and (5) capacity-building to ensure an adequate response to the local situation.[11] The primary method of controlling A. aegypti is by eliminating its habitats.[11] This may be done by emptying containers of water or by adding insecticides or biological control agents to these areas.[11] Reducing open collections of water through environmental modification is the preferred method of control, given the concerns of negative health effect from insecticides and greater logistical difficulties with control agents.[11] People may prevent mosquito bites by wearing clothing that fully covers the skin and/or the application of insect repellent (DEET being the most effective).[13] Management There are no specific treatments for the dengue fever virus.[1] Treatment depends on the symptoms, varying from oral rehydration therapy at home with close follow-up, to hospital admission with administration of intravenous fluids and/or blood transfusion.[24] A decision for hospital admission is typically based on the presence of the "warning signs" listed in the table above, especially in those with preexisting health conditions.[4] Intravenous hydration is usually only needed for one or two days.[24] The rate of fluid administration is titrated to a urinary output of 0.5–1 mL/kg/hr, stable vital signs and normalization of hematocrit.[4] Invasive medical procedures such as nasogastric intubation, intramuscular injections and arterial punctures are avoided, in view of the bleeding risk.[4] Acetaminophen may be used for fever and discomfort while NSAIDs such as ibuprofen and aspirin are avoided as they might aggravate the risk of bleeding.[24] Blood transfusion is initiated early in patients presenting with unstable vital signs in the face of a decreasing hematocrit, rather than waiting for the hemoglobin concentration to decrease to some predetermined "transfusion trigger" level.[25] Packed red blood cells or whole blood are recommended, while platelets and fresh frozen plasma are usually not.[25] During the recovery phase intravenous fluids are discontinued to prevent a state of fluid overload.[4] If fluid overload occurs and vital signs are stable, stopping further fluid may be all that is needed.[25] If a person is outside of the critical phase, a loop diuretic such as furosemide may be used to eliminate excess fluid from the circulation.[25] Epidemiology See also: Dengue fever outbreaks Dengue distribution in 2006. Red: Epidemic dengue and Ae. aegypti Aqua: Just Ae. aegypti. Most people with dengue recover without any ongoing problems.[19] The mortality is 1–5% without treatment,[4] and less than 1% with adequate treatment.[19] Severe disease carries a mortality of 26%.[4] Dengue is believed to infect 50 to 100 million people worldwide a year with half a million life-threatening infections requiring hospitalization,[1] resulting in approximately 12,500–25,000 deaths.[5][26] The burden of disease from dengue is estimated to be similar to other childhood and tropical diseases, such as tuberculosis, at 1600 disability-adjusted life years per million population.[10] It is the most common viral disease transmitted by arthropods.[8] As a tropical disease it is deemed only second in importance to malaria.[4] It is endemic in more than 110 countries.[4] The World Health Organization counts dengue as one of sixteen neglected tropical diseases.[27] The incidence of dengue increased 30 fold between 1960 and 2010.[28] This increase is believed to be due to a combination of urbanization, population growth, increased international travel, and global warming.[1] The geographical distribution is around the equator with 70% of the total 2.5 billion people living in endemic areas from Asia and the Pacific.[28] In the United States, the rate of dengue infection among those who return from an endemic area with a fever is 2.9–8.0%,[13] and it is the second most common infection after malaria to be diagnosed in this group.[6] Until 2003, dengue was classified as a potential bioterrorism agent, but subsequent reports removed this classification as it was deemed too difficult to transfer and only caused hemorrhagic fever in a relatively small proportion of people.[29] History Etymology The origins of the word "dengue" are not clear, but one theory is that it is derived from the Swahili phrase Ka-dinga pepo, which describes the disease as being caused by an evil spirit.[30] The Swahili word dinga may possibly have its origin in the Spanish word dengue, meaning fastidious or careful, which would describe the gait of a person suffering the bone pain of dengue fever.[31] However, it is possible that the use of the Spanish word derived from the similar-sounding Swahili.[30] Slaves in the West Indies having contracted dengue were said to have the posture and gait of a dandy, and the disease was known as "dandy fever".[32][33] The term "break-bone fever" was first applied by physician and Founding Father Benjamin Rush, in a 1789 report of the 1780 epidemic in Philadelphia. In the report he uses primarily the more formal term "bilious remitting fever".[29][34] The term dengue fever came into general use only after 1828.[33] Other historical terms include "breakheart fever" and "la dengue".[33] Terms for severe disease include "infectious thrombocytopenic purpura" and "Philippine", "Thai", or "Singapore hemorrhagic fever".[33] Discovery The first record of a case of probable dengue fever is in a Chinese medical encyclopedia from the Jin Dynasty (265–420 AD) which referred to a "water poison" associated with flying insects.[30][35] There have been descriptions of epidemics in the 17th century, but the most plausible early reports of dengue epidemics are from 1779 and 1780, when an epidemic swept Asia, Africa and North America.[35] From that time until 1940, epidemics were infrequent.[35] In 1906, transmission by the Aedes mosquitoes was confirmed, and in 1907 dengue was the second disease (after yellow fever) that was shown to be caused by a virus.[36] Further investigations by John Burton Cleland and Joseph Franklin Siler completed the basic understanding of dengue transmission.[36] The marked rise of spread of dengue during and after the Second World War has been attributed to ecologic disruption. The same trends also led to the spread of different serotypes of the disease to different areas, and the emergence of dengue hemorrhagic fever, which was first reported in the Philippines in 1953. In the 1970s, it became a major cause of child mortality. Around the same time it emerged in the Pacific and the Americas.[35] Dengue hemorrhagic fever and dengue shock syndrome were first noted in Middle and Southern America in 1981, as DENV-2 was contracted by people who had previously been infected with DENV-1 several years earlier.[9] Research Current research efforts to prevent and treat dengue have included different means of vector control,[37] vaccine development, and antiviral drugs.[23] With regards to vector control, a number of novel methods have been used to reduce mosquito numbers with some success including the placement of the fish Poecilia reticulata or copepods in standing water to eat the mosquito larva.[37] There are ongoing programs working on a dengue vaccine to cover all four serotypes.[23] One of the concerns is that a vaccine may increase the risk of severe disease through antibody-dependent enhancement.[38] The ideal vaccine is safe, effective after one or two injections, covers all serotypes, does not contribute to ADE, is easily transported and stored, and is both affordable and cost-effective.[38] A number of vaccines are currently undergoing testing.[10][29][38] It is hoped that the first products will be commercially available by 2015.[23] Apart from attempts to control the spread of the Aedes mosquito and work to develop a vaccine against dengue, there are ongoing efforts to develop antiviral drugs that might be used to treat attacks of dengue fever and prevent severe complications.[39][40] Discovery of the structure of the viral proteins may aid the development of effective drugs.[40] There are several plausible targets. The first approach is inhibition of the viral RNA-dependent RNA polymerase (coded by NS5), which copies the viral genetic material, with nucleoside analogs. Secondly, it may be possible to develop specific inhibitors of the viral protease (coded by NS3), which splices viral proteins.[41] Finally, it may be possible to develop entry inhibitors, which stop the virus entering cells, or inhibitors of the 5' capping process, which is required for viral replication.[39] Notes ^ a b c d e f g h i j k l m Whitehorn J, Farrar J (2010). "Dengue". Br. Med. Bull. 95: 161–73. doi:10.1093/bmb/ldq019. PMID 20616106. ^ a b c d e f g WHO (2009), pp. 14–16 ^ Gubler (2010), p. 379 ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa Ranjit S, Kissoon N (July 2010). "Dengue hemorrhagic fever and shock syndromes". Pediatr. Crit. Care Med. 12 (1): 90–100. doi:10.1097/PCC.0b013e3181e911a7. PMID 20639791. ^ a b c d e f Varatharaj A (2010). "Encephalitis in the clinical spectrum of dengue infection". Neurol. India 58 (4): 585–91. doi:10.4103/0028-3886.68655. PMID 20739797. ^ a b c d e f g h Chen LH, Wilson ME (October 2010). "Dengue and chikungunya infections in travelers". Curr. Opin. Infect. Dis. 23 (5): 438–44. doi:10.1097/QCO.0b013e32833c1d16. PMID 20581669. ^ a b c d e f g h i j k l WHO (2009), pp. 25–27 ^ a b c d e f g h i j Rodenhuis-Zybert IA, Wilschut J, Smit JM (August 2010). "Dengue virus life cycle: viral and host factors modulating infectivity". Cell. Mol. Life Sci. 67 (16): 2773–86. doi:10.1007/s00018-010-0357-z. PMID 20372965. ^ a b c d e Gould EA, Solomon T (February 2008). "Pathogenic flaviviruses". The Lancet 371 (9611): 500–9. doi:10.1016/S0140-6736(08)60238-X. PMID 18262042. ^ a b c d e f g h i j k l m Guzman MG, Halstead SB, Artsob H, et al. (December 2010). "Dengue: a continuing global threat". Nat. Rev. Microbiol. 8 (12 Suppl): S7–S16. doi:10.1038/nrmicro2460. PMID 21079655. ^ a b c d e f WHO (2009), pp. 59–60 ^ "Vector-Borne Viral Infections". World Health Organization. Retrieved 17 January 2011. ^ a b c d Center for Disease Control and Prevention. "Chapter 5 – Dengue Fever (DF) and Dengue Hemorrhagic Fever (DHF)". 2010 Yellow Book. Retrieved 2010-12-23. ^ Gubler (2010), pp. 377–78 ^ Wilder-Smith A, Chen LH, Massad E, Wilson ME (January 2009). "Threat of dengue to blood safety in dengue-endemic countries". Emerg. Infect. Dis. 15 (1): 8–11. doi:10.3201/eid1501.071097. PMC 2660677. PMID 19116042. ^ Stramer SL, Hollinger FB, Katz LM, et al. (August 2009). "Emerging infectious disease agents and their potential threat to transfusion safety". Transfusion 49 Suppl 2: 1S–29S. doi:10.1111/j.1537-2995.2009.02279.x. PMID 19686562. ^ Teo D, Ng LC, Lam S (April 2009). "Is dengue a threat to the blood supply?". Transfus Med 19 (2): 66–77. doi:10.1111/j.1365-3148.2009.00916.x. PMC 2713854. PMID 19392949. ^ a b c d e Martina BE, Koraka P, Osterhaus AD (October 2009). "Dengue virus pathogenesis: an integrated view". Clin. Microbiol. Rev. 22 (4): 564–81. doi:10.1128/CMR.00035-09. PMC 2772360. PMID 19822889. ^ a b c d e f g h WHO (2009), pp. 10–11 ^ a b c WHO (1997). "Chapter 2: clinical diagnosis". Dengue haemorrhagic fever: diagnosis, treatment, prevention and control (2nd ed.). Geneva: World Health Organization.. pp. 12–23. ISBN 9241545003. ^ a b WHO (2009), pp. 90–95 ^ a b Gubler (2010), p. 380 ^ a b c d WHO (2009), p. 137 ^ a b c WHO (2009), pp. 32–37 ^ a b c d WHO (2009), pp. 40–43 ^ WHO media centre (March 2009). "Dengue and dengue haemorrhagic fever". World Health Organization. Retrieved 2010-12-27. ^ Neglected Tropical Diseases. "Diseases covered by NTD Department". World Health Organization. Retrieved 2010-12-27. ^ a b WHO (2009), p. 3 ^ a b c Barrett AD, Stanberry LR (2009). Vaccines for biodefense and emerging and neglected diseases. San Diego: Academic. pp. 287–323. ISBN 0-12-369408-6. ^ a b c Anonymous (2006). "Etymologia: dengue". Emerg. Infec. Dis. 12 (6): 893. ^ Harper D (2001). "Etymology: dengue". Online Etymology Dictionary. Retrieved 2008-10-05. ^ Anonymous (1998-06-15). "Definition of Dandy fever". MedicineNet.com. Retrieved 2010-12-25. ^ a b c d Halstead SB (2008). Dengue (Tropical Medicine: Science and Practice). River Edge, N.J: Imperial College Press. pp. 1–10. ISBN 1-84816-228-6. ^ Rush AB (1789). "An account of the bilious remitting fever, as it appeared in Philadelphia in the summer and autumn of the year 1780". Medical enquiries and observations. Philadelphia, Pa.: Prichard and Hall. pp. 104–117. ^ a b c d Gubler DJ (July 1998). "Dengue and dengue hemorrhagic fever". Clin. Microbiol. Rev. 11 (3): 480–96. PMC 88892. PMID 9665979. ^ a b Henchal EA, Putnak JR (October 1990). "The dengue viruses". Clin. Microbiol. Rev. 3 (4): 376–96. PMC 358169. PMID 2224837. ^ a b WHO (2009), p. 71 ^ a b c Webster DP, Farrar J, Rowland-Jones S (November 2009). "Progress towards a dengue vaccine". Lancet Infect Dis 9 (11): 678–87. doi:10.1016/S1473-3099(09)70254-3. PMID 19850226. ^ a b Sampath A, Padmanabhan R (January 2009). "Molecular targets for flavivirus drug discovery". Antiviral Res. 81 (1): 6–15. doi:10.1016/j.antiviral.2008.08.004. PMC 2647018. PMID 18796313. ^ a b Noble CG, Chen YL, Dong H, et al. (March 2010). "Strategies for development of Dengue virus inhibitors". Antiviral Res. 85 (3): 450–62. doi:10.1016/j.antiviral.2009.12.011. PMID 20060421. ^ Tomlinson SM, Malmstrom RD, Watowich SJ (June 2009). "New approaches to structure-based discovery of dengue protease inhibitors". Infectious Disorders Drug Targets 9 (3): 327–43. PMID 19519486. References Gubler DJ (2010). "Dengue viruses". In Mahy BWJ, Van Regenmortel MHV. Desk Encyclopedia of Human and Medical Virology. Boston: Academic Press. ISBN 0-12-375147-0. WHO (2009). Dengue Guidelines for Diagnosis, Treatment, Prevention and Control. World Health Organization. ISBN 9241547871. External links Find more about Dengue fever on Wikipedia's sister projects: Definitions from Wiktionary Images and media from Commons Learning resources from Wikiversity News stories from Wikinews Quotations from Wikiquote Source texts from Wikisource Textbooks from Wikibooks Dengue fever at the Open Directory Project "Dengue". WHO. Retrieved 2010-12-24. "Dengue". US Centers for Disease Control and Prevention. Retrieved 2010-12-24. "Dengue fever". UK Health Protection Agency. Retrieved 2010-12-24. 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• Hepatitis A Overview
• Hepatitis A Causes
• Hepatitis A Symptoms
• When to Seek Medical Care
• Hepatitis A Diagnosis
• Hepatitis A Treatment
• Self-Care at Home
• Medical Treatment
• Next Steps
• Follow-up
• Hepatitis A Prevention
• Hepatitis A Prognosis
• Support Groups and Counseling
• For More Information
• Web Links
• Synonyms and Keywords
• Authors and Editors
• Read more on Hepatitis A from Healthwise
• Viewer Comments: Hepatitis A - Symptoms
• Viewer Comments: Hepatitis A

Hepatitis A Vaccine

What is the hepatitis A vaccine, and who should get one?

There are vaccines that work to prevent infection with hepatitis A virus.

• The vaccines, Havrix and VAQTA, contain no live virus and are very safe. No serious adverse effects have been reported. Some people have some soreness at the injection site for a few days.
• The vaccines are given in a series of 2 shots. The second is given 6-18 months after the first. The shots can be given at the same time as other vaccines.
• Your protection starts about 2-4 weeks after the first shot. The second dose is necessary to ensure long-term protection.
• The vaccines are thought to protect from infection for at least 20 years.
• The vaccines must be given before exposure to the virus. They do not work after exposure.

Not everyone needs to have the hepatitis A vaccines. However, the vaccines are recommended for the following groups:

• People who are likely to be exposed to HAV at work - The only group of workers shown to be at higher risk than the general population is people who work in research laboratories where HAV is stored and handled. Routine vaccination is not recommended for health care workers, food service workers, daycare personnel, and sewage and waste-water workers.
• Individuals visiting developing countries (it must be given at least 4 weeks before the trip)
• Men who have sex with men
• People who use illegal drugs - This group has higher-than-average rates of HAV infection.
• People who are likely to become seriously ill if they are infected with HAV - This includes people with impaired immune systems or chronic liver disease.
• People with blood-clotting disorders who receive clotting factors

Read more in-depth information about the hepatitis A vaccine and who should get one »

Hepatitis A Overview

Hepatitis is a general term that means inflammation of the liver. Inflammation of the liver can result from infection, from exposure to alcohol, certain medications, chemicals, or poisons, or from a disorder of the immune system.

Hepatitis A refers to liver inflammation caused by infection with the hepatitis A virus (HAV). HAV is one of several viruses that can cause hepatitis and is one of the 3 most common hepatitis viruses in the United States. The other 2 are hepatitis B and hepatitis C.

Unlike hepatitis B and hepatitis C, hepatitis A does not cause chronic (ongoing, long-term) disease. Although the liver does become inflamed and swollen, it heals completely in most people without any long-term damage. Once you have had hepatitis A, you develop lifelong immunity and cannot get the disease again.

Because of the way it is spread, the hepatitis A virus tends to occur in epidemics and outbreaks. As many as 1 in 3 people in the United States have antibody to HAV, meaning they have been exposed to the virus, but most do not become ill. The number of cases of hepatitis A in the United States varies among different communities and has not been affected significantly by the introduction of the hepatitis A vaccine since the early 1990s.

Hepatitis A Causes

• The hepatitis A virus is found in the stools (feces) of people with hepatitis A. It is transmitted when a person puts something in his or her mouth that has been contaminated with the feces of an affected person. This is referred to as fecal-oral transmission.
  
  
  • If food or drinking water becomes contaminated with stool from an infected person (usually because of inadequate hand washing or poor sanitary conditions), the virus can quickly spread to anyone who drinks or swallows the contaminated food or water.
    
  • The virus can also be spread by eating raw or undercooked shellfish collected from water that has been contaminated by sewage.
    
  • The hepatitis A virus can be transmitted through blood transfusions, although this is extremely rare.
• People who are infected can start spreading the infection about 1 week after their own exposure. People who do not have symptoms can still spread the virus. Infection with HAV is known to occur throughout the world.
  
• The risk of infection is greatest in developing countries with poor sanitation or poor personal hygiene standards.
  
• Infection rates are also higher in areas where direct fecal-oral transmission is likely to occur, such as daycare centers, prisons, and mental institutions. 
• People at increased risk for hepatitis A infection
  
  
  • Household contacts of people infected with HAV
    
  • Sexual partners of people infected with HAV
    
  • International travelers, especially to developing countries
    
  • Military personnel stationed abroad, especially in developing countries
    
  • Men who have sex with other men
    
  • Users of illegal drugs (injected or non-injected)
    
  • People who may come into contact with HAV at work
• Workers in professions such as health care, food preparation, and sewage and waste water management are not at greater risk of infection than the general public. 
• People who live or work in close quarters, such as dormitories, prisons, and residential facilities, or work in or attend daycare facilities are at increased risk only if strict personal hygiene measures are not observed.

  Hepatitis A Symptoms

  Many people with HAV infection have no symptoms at all. Sometimes symptoms are so mild that they go unnoticed. Older people are more likely to have symptoms than children. People who do not have symptoms can still spread the virus.
  • Symptoms of hepatitis A usually develop between 2 and 6 weeks after infection. The symptoms are usually not too severe and go away on their own, over time. The most common symptoms are as follows:
    • Nausea
    • Vomiting
    • Diarrhea, especially in children
    • Low-grade fever
    • Loss of appetite
    • Rash
    • Tiredness, fatigue
    • Jaundice - A yellow discoloration of the skin and the whites of the eyes
    • Urine is dark brownish in color, like cola or strong tea.
    • Pain in area of liver - On the right side of the abdomen, just under the rib cage
  • If the vomiting is severe, dehydration may occur. The symptoms of dehydration include the following:
    • Feeling weak, tired, or "blah"
    • Feeling confused or unable to concentrate
    • Rapid heartbeat
    • Headache
    • Urinating less frequently than usual
    • Irritability
  • Symptoms usually last less than two months, although they may last as long as nine months. About 15% of people infected with hepatitis A have symptoms that come and go for 6-9 months.
  • Hepatitis does not occur simply from being near someone who has the disease at work or at school.

    When to Seek Medical Care

    The health care provider should be called if any of the following symptoms occur:
    • Nausea and vomiting that does not improve within 1-2 days
    • Yellow skin or eyes
    • Dark colored urine
    • Pain in the belly (abdomen)
    The following situations also warrant a call to the health care provider:
    • You have symptoms and think that you might have been exposed to someone with hepatitis.
    • You have other medical problems and think that you might have hepatitis.
    • You have had close contact with someone diagnosed with hepatitis.
    If you cannot reach your health care provider, or if you have any of the following, go to theemergency department.
    • Vomiting and inability to keep down any liquids
    • Severe pain or high fever
    • Confusion, delirium, or difficulty awakening

      Hepatitis A Diagnosis

      Your health care provider will ask you questions about your illness. You will be asked about your symptoms and about any possible exposures to hepatitis.
      If your health care provider determines that you may be at risk for contracting hepatitis, you will have blood drawn.
      • The blood will be tested to determine how well your liver is functioning.
      • A test will be done for antibody to hepatitis A. The test will show whether you have been exposed recently to HAV.
      • Your blood probably will be tested for the hepatitis B and hepatitis C viruses as well.
      If you have had a large amount of vomiting or have not been able to take in liquids, your bloodelectrolytes may be out of balance. Your blood chemistry may be tested to check this.

      Hepatitis A Treatment

      There are no specific medicines to cure infection with hepatitis A. Most people require no treatment except to relieve symptoms.
      If you have been exposed to someone who is infected with HAV, there is a treatment that may prevent you from becoming infected. It is called immune globulin and is more likely to be effective when given within 2 weeks of exposure.

      Self-Care at Home

      The following measures can help you feel better while you are having symptoms.
      • Take it easy; curtail your normal activities and spend time resting at home.
      • Drink plenty of clear fluids to prevent dehydration.
      • Avoid medicines and substances that can cause harm to the liver such asacetaminophen (Tylenol) and preparations that contain acetaminophen.
      • Avoid alcoholic beverages, as these can worsen the effects of HAV on the liver.
      • Avoid prolonged, vigorous exercise until symptoms start to improve.
      Call your health care provider if symptoms worsen or a new symptom appears.
      Be very careful about personal hygiene to avoid fecal-oral transmission to other members of the household.

      Medical Treatment

      • If you are dehydrated, your doctor may prescribe IV fluid to help you feel better.
        
      • If you are experiencing significant nausea and vomiting, you will receive medicines to control these symptoms.
        
      • People whose symptoms are well controlled can be cared for at home.
        
      • If dehydration or other symptoms are severe or if you are extremely confused or difficult to arouse, then you may need to stay in the hospital.

        Next Steps

        Follow-up

        Follow the recommendations of your health care provider.
        • Take it easy; get plenty of rest.
        • Drink plenty of clear fluids.
        • Avoid alcoholic beverages.
        • Avoid medicines such as acetaminophen (Tylenol) that can be harmful to the liver.
        • Avoid prolonged or vigorous physical exercise until your symptoms improve.
        • Call your health care provider if symptoms worsen or a new symptom appears.

          Hepatitis A Prevention

          If you have hepatitis A, strict personal hygiene and hand washing help prevent transmission of HAV to others.
          
          • Wash your hands thoroughly every time you use the bathroom, before touching or preparing food, and before touching others. Wash carefully with soap and warm water and dry thoroughly.
            
          • Contaminated surfaces should be cleaned with household bleach to kill the virus.
            
          • Heat food or water to 185°F or 85°C to kill the virus.
          If you are not infected with HAV, you can protect yourself from becoming infected.
          
          
          • Wash your hands carefully with soap and warm water several times a day, including every time you use the bathroom, every time you change a diaper, and before preparing food.
            
          • Do not eat raw or undercooked seafood or shellfish such as oysters from areas of questionable sanitation (just about everywhere).
            
          • Travelers to developing countries should not drink untreated water or beverages with ice in them. Fruits and vegetables should not be eaten unless cooked or peeled.
          There are vaccines that work to prevent infection with HAV.
          
          
          • The vaccines, Havrix and VAQTA, contain no live virus and are very safe. No serious adverse effects have been reported. Some people have some soreness at the injection site for a few days.
            
          • The vaccines are given in a series of 2 shots. The second is given 6-18 months after the first. The shots can be given at the same time as other vaccines.
            
          • Your protection starts about 2-4 weeks after the first shot. The second dose is necessary to ensure long-term protection.
            
          • The vaccines are thought to protect from infection for at least 20 years.
            
          • The vaccines must be given before exposure to the virus. They do not work after exposure.
          Not everyone needs to have the hepatitis A vaccines. However, the vaccines are recommended for the following groups:
          
          
          • All children older than 2 years who live in communities where the number of HAV infections is unusually high or where there are periodic outbreaks of hepatitis A (The vaccines are not recommended for children younger than 2 years because they are not as effective.)
            
          • People who are likely to be exposed to HAV at work - The only group of workers shown to be at higher risk than the general population is people who work in research laboratories where HAV is stored and handled. Routinevaccination is not recommended for health care workers, food service workers, daycare personnel, and sewage and waste-water workers.
            
          • Travelers to developing countries (it must be given at least 4 weeks before travel)
            
          • Men who have sex with men
            
          • People who use illegal drugs - This group has higher-than-average rates of HAV infection.
            
          • People who are likely to become seriously ill if they are infected with HAV - This includes people with impaired immune systems or chronic liver disease.
            
          • People with blood-clotting disorders who receive clotting factors
          If you have never had hepatitis A and are exposed to the virus, call your health care provider immediately. There is a treatment that may prevent you from becoming infected. It is called hepatitis B immune globulin (BayHep B, Nabi-HB).
          
          
          • Immune globulin is a preparation of antibodies that can fight the virus in the body.
            
          • It is given as a one-time shot (injection).
            
          • It must be given within 2 weeks after exposure for maximum protection.
            
          • Immune globulin can be safely given to children younger than 2 years.
            
          • Immune globulin can be given during pregnancy and breastfeeding.
            
          • Immune globulin can provide short-term protection against infection if given before exposure. This protection lasts no longer than 3 months.
          If you have had hepatitis A confirmed by a blood test, you cannot get it again. You should continue to practice preventive measures, however, to prevent transmission of other infections.

          Hepatitis A Prognosis

          Hepatitis A symptoms are usually mild and go away on their own.
          • Rarely will you develop complications such as relapsing hepatitis or liver failure.
          • With relapsing hepatitis, symptoms improve, but then return.
          • Death from hepatitis A is rare.
          • The elderly, the very young, and people with advanced chronic liver diseases such as from hepatitis C are at greatest risk for complications from hepatitis A.