Syphilis


yphilis is a sexually transmitted disease caused by the spirochetal bacteria Treponema pallidum subspecies pallidum. The primary route of transmission of syphilis is through sexual contact however it may also be transmitted from mother to fetus during pregnancy or at birth resulting in congenital syphilis.
The signs and symptoms of syphilis vary depending on which of the four stages it presents in (primary, secondary, latent, and tertiary). The primary stage typically presents with a singlechancre, secondary syphilis with a diffuse rash, latent with little to no symptoms, and tertiary with gummas, neurological, or cardiac symptoms. Diagnosis is usually via blood tests. It can be effectively treated with antibiotics, specifically intramuscular penicillin G.
Syphilis is believed to have infected 12 million people worldwide in 1999 with greater than 90% of cases in the developing world. Rates of infection have increased during the 2000s in many countries.

Contents

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Signs and symptoms

Syphilis can present in one of four different stages: primary, secondary, latent, and tertiary.[1] It may also occur congenitally.[2] It has been referred to as the “great imitator of skin diseases" due to its varied presentations.[1]

Primary

Chancres on the penile shaft due to a primary syphilitic infection
Primary syphilis is typically acquired via direct sexual contact with the infectious lesions of another person .[3] Approximately 3–90 days after the initial exposure (average 21 days) a skin lesion appears at the point of contact called a chancre.[1] This is classically (40% of the time) a single firm, painless, non-itchy skin ulceration with a clean base and sharp borders between 0.3 and 3 cm in size.[1] Occasionally multiple lesions may be present.[1] Lesions outside of the genitals may be painful.[1] Lymph node enlargement frequently (80%) occurs around the area of infection.[1] The lesion may persist for 3 to 6 weeks without treatment.[1]

Secondary

Secondary syphilis occurs approximately 4 to 10 weeks after the primary infection.[1] There are many different manifestations of secondary disease. There may be a symmetrical reddish-pink non-itchy rash on the trunk and extremities including the palms and soles.[1][4] The rash may become maculopapular or pustular.[1] On mucous membranes it may form flat, broad, whitish, wart-like lesions known as condyloma latum.[1] All of these lesions are infectious harboring bacteria.[1] Other symptoms may include fever, sore throat, malaise, weight loss, hair loss, andheadache.[1] Rare manifestations include hepatitis, kidney disease, arthritis, periostitis, optic neuritis, uveitis, and interstitial keratitis.[1][5] The acute symptoms usually resolve after 3 to 6 weeks.[5]
Reddish papules and nodules over much of the body due to secondary syphilis

Latent

Latent syphilis is defined as having serologic proof of infection without signs or symptoms of disease.[3] It is further described as either early (less than 1 yr after secondary syphilis) or late (more than 1 year after secondary syphilis).[5] Early latent syphilis may have relapses of symptoms.[5] Late latent syphilis is asymptomatic and not as contagious as early latent syphilis.[5]

Tertiary

Model of the head of a patient with tertiary syphilis.
Tertiary syphilis may occur approximately 3 to 15 years after the initial infection and may be divided into three different forms: late neurosyphilis (6.5%), cardiovascular syphilis (10%) and gummatous syphilis (15%).[1][5] Without treatment a third of people develop tertiary disease.[5] People with tertiary syphilis are not infectious.[1]
Gummatous
Gummatous syphilis or late benign syphilis usually occurs 1–46 years after the initial infection, with an average of 15 years.[1] This stage is characterized by the formation of chronic gummas, which are soft, tumor-like balls of inflammation which may vary considerably in size.[1] They typically affect the skin, bone, and liver, but can occur anywhere.[1]
Late neurosyphilis
Neurosyphilis refers to an infection involving the central nervous system. It may occur early being either asymptomatic or in the form of syphilitic meningitis or late as meningovascular syphilis, general paresis or tabes dorsalis.[1] Late neurosyphilis typically occurs 4 to 25 years after the initial infection.[1] Meningovascular syphilis typically presents with apathy and seizure, general paresis with dementia and tabes dorsalis is associated with poor balance and lightning pains in the lower extremities.[1]
Cardiovascular
Cardiovascular syphilis usually occurs 10–30 years after the initial infection.[1] The most common complications is syphilitic aortitis which may result in aneurysm formation.[1]

Congenital

Congenital syphilis may occur during pregnancy or during the birth process.[6] Most infants (2/3) are born without symptoms.[6] Common symptoms that then develop over the first couple years of life include: hepatosplenomegaly (70%), rash (70%), fever (40%), neurosyphylis (20%), pneumonitis (20%).[6] If untreated late congenital syphilis may occur in 40% including: saddle nose deformation, Higoumenakis sign, saber shin, or Clutton's joints among others.[6]

Cause

Syphilis is caused by the bacteria Treponema pallidum subspecies pallidum, for which humans are the only known natural reservoir.[2] It is transmitted primarily by sexual contact or during pregnancy from a mother to her fetus being able to pass through intact mucus membranes or compromised skin.[1][2] It is thus transmissible by kissing, oral, vaginal, and anal sex.[1] Approximately 30 to 60% of those exposed to primary or secondary syphilis will get the disease.[5] Most (60%) of new cases in the United States occur in men who have sex with men.[1] It can be transmitted via blood products. However, it is tested for in many countries and thus the risk is low.[1] The risk of transmission from sharing needles appears limited.[1] Three other human diseases are caused by related Treponema pallidum including:yaws (subspecies pertenue), pinta (subspecies carateum) and bejel (subspecies endemicum).[1] Unlike subtype pallidum they do not cause neurological disease.[6]

Diagnosis

Poster for testing of syphilis, showing a man and a woman bowing their heads in shame (ca. 1936).
Syphilis may be confirmed either via blood tests or direct visualization using microscopy.[1]Typical diagnosis is with blood tests using nontreponemal and/or treponemal tests.[1]Nontreponemal test are used initially and include venereal disease research laboratory (VDRL) and rapid plasma reagin however as these test occasionally are falsely positive confirmation is required with a treponemal test such as treponemal pallidum particle agglutination (TPHA) orfluorescent treponemal antibody absorption test (FTA-Abs).[1] False positives on the nontreponemal tests can occur with some viral infections such as (varicella and measles), as well as with lymphoma, tuberculosis, malaria, endocarditis, connective tissue disease,pregnancy.[3] Neurosyphilis is diagnosed by finding high numbers of leukocytes (predominatelymphocytes) and high protein levels in the cerebrospinal fluid in the setting of a known syphilis infection.[1][3]

Prevention

As of 2010 there is no vaccine effective for prevention.[2] Abstinence from intimate physical contact with an infected person is effective at reducing the transmission of syphilis, as is the proper use of a latex condom. Condom use, however, does not completely eliminate the risk.[7][8] Syphilis cannot be contracted through toilet seats, daily activities, hot tubs, or sharing eating utensils or clothing.[9]

Treatment

Early infections

The first-choice treatment for uncomplicated syphilis remains a single dose of intramuscular penicillin G.[2] Doxycycline and tetracyclineare alternative choice; however, it cannot be used in pregnant women.[2] Antibiotic resistance has developed to a number of agents including macrolides, clindamycin, and rifampin.[2] Ceftriaxone may be as effective as penicillin based treatment.[1]

Late infections

For neurosyphilis due to the poor penetration of penicillin G into the central nervous system it is recommended that those affected be given large doses of intravenous penicillin for a minimum of 10 days.[1][2] If a person is allergic, ceftriaxone may be used or penicillin desensitization attempted.[1] Other late presentations may be treated with once weekly intramuscular penicillin G for three weeks.[1] If allergic as in the case of early disease doxycycline or tetracycline may be used but for a longer duration.[1] Treatment at this point will limit further progression but has only slight effect on damage which has already occurred.[1]

Jarisch-Herxheimer reaction

One of the potential side effects of treatment is the Jarisch-Herxheimer reaction.[1] It frequently starts within one hour and lasts for 24 hours with symptoms of fever, muscles pains, headache, and tachycardia.[1] It is caused by cytokines released by the immmune system in response to endotoxins released from rupturing syphilis bacteria.[1]

Prognosis

Syphilis increases the risk of HIV transmission by 2 to 5 times and co-infection is common (30-60% in a number of urban centers).[1][2]Untreated it has a mortality of 8% to 58% with a greater death rate in males.[1]

Epidemiology

Age-standardized death from syphilis per 100,000 inhabitants in 2004.[10]
  no data
  <35
  35-70
  70-105
  105-140
  140-175
  175-210
  210-245
  245-280
  280-315
  315-350
  350-500
  >500
Syphilis—Reported Cases by Stage of Infection, United States, 1941–2009
Syphilis is believed to have infected 12 million people in 1999 with greater than 90% of cases in the developing world.[2] It affects between 700,000 and 1.6 million pregnacies a year resulting inspontaneous abortions, stillbirths, and congenital syphilis.[6] In Sub Saharan Africa syphilis contributes to approximately 20% of perinatal deaths.[6]
In the developed world, syphilis infections were in decline until the 1980s and 1990s due to widespread use of antibiotics. Since the year 2000, rates of syphilis have been increasing in the USA, UK, Australia and Europe primarily among men who have sex with men.[2] This is attributed to unsafe sexual practices.[2] Increased rates among heterosexuals have occurred in China and Russia since the 1990s.[2]

History

Alternative names

The name "syphilis" was coined by the Italian physician and poet Girolamo Fracastoro in hisepic noted poem, written in Latin, titled Syphilis sive morbus gallicus (Latin for "Syphilis or TheFrench Disease") in 1530. The protagonist of the poem is a shepherd named Syphilus (perhaps a variant spelling of Sipylus, a character in Ovid's Metamorphoses). Syphilus is presented as the first man to contract the disease, sent by the god Apollo as punishment for the defiance that Syphilus and his followers had shown him.[not in citation given] From this character Fracastoro derived a new name for the disease, which he also used in his medical text De Contagionibus ("On Contagious Diseases").[11]
Until that time, as Fracastoro notes,[not in citation given] syphilis had been called the "French disease" in Italy, Poland and Germany, and the "Italian disease" in France. In addition, theDutch called it the "Spanish disease", the Russians called it the "Polish disease", the Turkscalled it the "Christian disease" or "Frank disease" (frengi) and the Tahitians called it the "British disease". These "national" names are due to the disease often being spread by foreign sailors and soldiers during their frequent sexual contact with local prostitutes.[citation needed]
During the 16th century, it was called "great pox" in order to distinguish it from smallpox. In its early stages, the great pox produced a rash similar to smallpox (also known asvariola).[citation needed] However, the name is misleading, as smallpox was a far more deadly disease. The terms "Lues"[12] (or Lues venerea, Latin for "venereal plague") and "Cupid's disease"[13] have also been used to refer to syphilis. In Scotland, syphilis was referred to as theGrandgore. The ulcers suffered by British soldiers in Portugal were termed "The Black Lion".[14]

Origins

The exact origin of syphilis is unknown.[1] Three theories have been proposed. It is generally agreed upon by historians and anthropologists that syphilis was present among the indigenous peoples of the Americas before Europeans traveled to and from the New World. However, whether strains of syphilis were present in the entire world for millennia, or if the disease was confined to the Americas in the pre-Columbian era, is debated.[citation needed]
  • In 79 CE the Roman town of Pompeii was destroyed by a volcanic eruption. The entombed remains of the population provide insights into their health as many infectious diseases leave marks in tooth enamel. The remains of one pair of twins show what are almost certainly the signs of congenital syphilis.[15]
  • The "pre-Columbian theory" holds that syphilis was present in Europe before the discovery of the Americas by Europeans. Some scholars during the 18th and 19th centuries believed its symptoms were described by Hippocrates in Classical Greece in itsvenereal/tertiary form.[16] There are other suspected syphilis findings for pre-contact Europe, including at a 13–14th century Augustinianfriary in the northeastern English port of Kingston upon Hull. This city's maritime history, with its continual arrival of sailors from distant places, is thought to have been a key factor in the transmission of syphilis.[17] Carbon-dated skeletons of monks who lived in the friary showed bone lesions that supporters say are typical of venereal syphilis, although this is disputed by critics of this theory. Skeletons in pre-Columbus Pompeii and Metaponto in Italy with damage similar to that caused by congenital syphilis have also been found,[18][19]although the interpretation of this evidence has been disputed.[20] Douglas Owsley, a physical anthropologist at the Smithsonian Institution, and other supporters of this idea say that many medieval European cases of leprosy, colloquially called lepra, were actually cases of syphilis. Although folklore claimed that syphilis was unknown in Europe until the return of the diseased sailors of the Columbian voyages,
    ... syphilis probably cannot be "blamed"—as it often is—on any geographical area or specific race. The evidence suggests that the disease existed in both hemispheres from prehistoric times. It is only coincidental with the Columbus expeditions that the syphilis previously thought of as "lepra" flared into virulence at the end of the fifteenth century.[21]
    Lobdell and Owsley wrote that a European writer who recorded an outbreak of "lepra" in 1303 was "clearly describing syphilis."[21]
  • The "Columbian Exchange theory" holds that syphilis was a New World disease brought back by Columbus and Martin Alonso Pinzon. They cite documentary evidence linking crewmen of Columbus's voyages to the Naples syphilis outbreak of 1494.[22][not in citation given]This theory is supported by genetic studies of venereal syphilis and related bacteria, which found a disease intermediate between yawsand syphilis in Guyana, South America.[23][24]
  • Finally, historian Alfred Crosby suggests both theories are partly correct in a "combination theory". Crosby says that the bacterium that causes syphilis belongs to the same phylogenetic family as the bacteria that cause yaws and several other diseases. Despite the tradition of assigning the homeland of yaws to sub-Saharan Africa, Crosby notes that there is no unequivocal evidence of any related disease having been present in pre-Columbian Europe, Africa, or Asia.
Crosby writes, "It is not impossible that the organisms causing treponematosis arrived from America in the 1490s...and evolved into both venereal and non-venereal syphilis and yaws."[25] However, Crosby considers it more likely that a highly contagious ancestral species of the bacteria moved with early human ancestors across the land bridge of the Bering Straits many thousands of years ago without dying out in the original source population. He hypothesizes that "the differing ecological conditions produced different types of treponematosisand, in time, closely related but different diseases."[25]

European outbreak

A medical illustration attributed toAlbrecht Dürer (1496) depicting a person with syphilis. Here, the disease is believed to have astrological causes.
The first well-recorded European outbreak of what is now known as syphilis occurred in 1494 when it broke out among French troops besieging Naples.[26] The French may have caught it via Spanish mercenaries serving King Charles of France in that siege.[21] From this centre, the disease swept across Europe. As Jared Diamond describes it, "[W]hen syphilis was first definitely recorded in Europe in 1495, its pustules often covered the body from the head to the knees, caused flesh to fall from people's faces, and led to death within a few months." The disease then was much more lethal than it is today. Diamond concludes,"[B]y 1546, the disease had evolved into the disease with the symptoms so well known to us today."[27] Theepidemiology of this first syphilis epidemic shows that the disease was either new or a mutated form of an earlier disease.
Researchers concluded that syphilis was carried from the New World to Europe after Columbus' voyages. Many of the crew members who served on this voyage later joined the army of King Charles VIII in his invasion of Italy in 1495 resulting in the spreading of the disease across Europe and as many as 5 million deaths.[28][29] The findings suggested Europeans could have carried the nonvenereal tropical bacteria home, where the organisms may have mutated into a more deadly form in the different conditions and low immunity of the population of Europe.[30]Syphilis was a major killer in Europe during the Renaissance.[31] In his Serpentine Malady(Seville, 1539) Ruy Diaz de Isla estimated that over a million people were infected in Europe.[32]

Historical treatments

There were originally no effective treatments for syphilis. The Spanish priest Francisco Delicadowrote El modo de adoperare el legno de India (Rome, 1525) about the use of Guaiacum in the treatment of syphilis. He himself suffered from syphilis.[citation needed] Nicholas Culpeperrecommended the use of heartsease (wild pansy), an herb with antimicrobial activities.[33][not in citation given] Another common remedy was mercury: the use of which gave rise to the saying "A night in the arms of Venus leads to a lifetime on Mercury".[34] It was administered multiple ways including by mouth,[citation needed] by rubbing it on the skin[citation needed] and by injection.[35][non-primary source needed] One of the more curious methods was fumigation, in which the patient was placed in a closed box with his head sticking out. Mercury was placed in the box and a fire was started under the box that caused the mercury to vaporize. It was a grueling process for the patient and the least effective for delivering mercury to the body.[citation needed] The use of mercury was the earliest known suggested treatment for syphilis.[verification needed] This has been suggested to date back to The Canon of Medicine (1025) by the Persian physician, Ibn Sina (Avicenna).,[36] although this is only possible if syphilis existed in the Old World prior to Columbus (see Origins section). Giorgio Sommariva of Verona is recorded to have used it for this purpose in 1496.[citation needed]
As the disease became better understood, more effective treatments were found. The first antimicrobial to be used for treating disease was the organo-arsenical drug Salvarsan, developed in 1908 by Sahachiro Hata in the laboratory of Nobel prize winner Paul Ehrlich. This group later discovered the related arsenical, Neosalvarsan, which is less toxic. Unfortunately, these drugs were not 100% effective, especially in late disease, and were sometimes unpredictably toxic to patients.[citation needed] It was observed that sometimes patients who developed high fevers were cured of syphilis. Thus, for a brief time malaria was used as treatment for tertiary syphilis because it produced prolonged and high fevers (a form of pyrotherapy). This was considered an acceptable risk because the malaria could later be treated with quinine, which was available at that time.[citation needed] Malaria as a treatment for syphilis was usually reserved for late disease, especially neurosyphilis, and then followed by either Salvarsan or Neosalvarsan as adjuvant therapy. This discovery was championed by Julius Wagner-Jauregg,[37] who won the 1927 Nobel Prize for Medicine for his discovery of the therapeutic value of malaria inoculation in the treatment of neurosyphilis. Later, hyperthermal cabinets (sweat-boxes) were used for the same purpose.[38] These treatments were finally rendered obsolete by the discovery of penicillin, and its widespread manufacture after World War II allowed syphilis to be effectively and reliably cured.[39]

History of diagnosis

Portrait of Gerard de Lairesse byRembrandt van Rijn, ca. 1665–67, oil on canvas. De Lairesse, himself a painter and art theorist, suffered from congenital syphilis that severely deformed his face and eventually blinded him.[40]
In 1905, Schaudinn and Hoffmann discovered Treponema pallidum in tissue of patients with syphilis.[41] One year later, the first effective test for syphilis, the Wassermann test, was developed. Although it had some false positive results, it was a major advance in the detection and prevention of syphilis.[citation needed] By allowing testing before the acute symptoms of the disease had developed, this test allowed the prevention of transmission of syphilis to others, even though it did not provide a cure for those infected. In the 1930s the Hinton test, developed by William Augustus Hinton, and based on flocculation, was shown to have fewer false positivereactions than the Wassermann test.[citation needed] Both of these early tests have been superseded by newer analytical methods.
While working at the Rockefeller University (then called the Rockefeller Institute for Medical Research) in 1913, Hideyo Noguchi, a Japanese scientist, demonstrated the presence of the spirochete Treponema pallidum in the brain of a progressive paralysis patient, proving conclusively that Treponema pallidum was the cause of syphilis.[42][dead link] Prior to Noguchi's discovery, syphilis had been a burden to humanity in many lands. Without its cause being understood, it was sometimes misdiagnosed and often misattributed to damage by political enemies.

Notable cases

Mental illness caused by late-stage syphilis was once a common form of dementia. This was known as the general paresis of the insane. The list below contains a representative listing of famous historical figures diagnosed with or strongly suspected (marked "S") as having had syphilis at some time. Many people who acquired syphilis were treated and recovered; died from it (marked "†").
Many famous historical figures, including Charles VIII of France, Hernán Cortés of Spain, Adolf Hitler, Benito Mussolini, and Ivan the Terrible, were often alleged to have had syphilis or other sexually transmitted infections. Sometimes these allegations were false and formed part of a political whispering campaign. In other instances, retrospective diagnoses of suspected cases have been made in modern times.
Keys: S—suspected case; †—died of syphilis

Society and culture

Art

The artist Jan van der Straet painted a scene of a wealthy man receiving treatment of syphilis with the tropical wood guaiacum sometime around 1580.[50] The title of the work is "Preparation and Use of Guayaco for Treating Syphilis." That the artist chose to include this image in a series of works celebrating the New World indicates how important a "cure" (however ineffective) for syphilis was to the European elite at that time. The richly colored and detailed work depicts four servants preparing the concoction while a physician looks on, hiding something behind his back while the hapless patient drinks.[51]

Literature

Moll dies of syphillis, Hogarth's A Harlot's Progress.
It has been suggested that the main character in Edgar Allan Poe's "The Tell-Tale Heart" may have been infected with neurosyphilis, due to his strange obsessions and apparent insanity.[citation needed] Francisco de Quevedo puns in his Buscón[52] about a nose entre Roma y Francia meaning both "between Rome and France" and "between snub and eaten by the French illness".[clarification needed]
William Hogarth's works frequently show his subject's infection with syphilis. Two examples areA Harlot's Progress and Marriage à-la-mode. In both instances it is used to indicate the moral profligacy of the infected. Some critics have argued that the character of Edward Rochester's first wife, Bertha, in Charlotte Brontë's novel Jane Eyre, suffers from the advanced stages of syphilitic infection, general paralysis of the insane, and point to corroborative evidence within the text to substantiate this view.[53]
In Eça de Queiroz's novel written in 1870, 'The Mystery of the Sintra Road', some of the characters have syphilis, and it plays an important role in the plot of a recent movie adaptation.[54][not in citation given]

Tuskegee study

Main article: Tuskegee syphilis experiment
One of the best-documented US cases of unethical human medical experimentation in the twentieth century was the Tuskegee syphilis study. The study took place in Tuskegee, Alabama, and was supported by the U.S. Public Health Service (PHS) in partnership with theTuskegee Institute.[55] The study began in 1932, when syphilis was a widespread problem and there was no effective treatment or cure. The study was designed to measure the progression of untreated syphilis.
By 1947 penicillin had been validated as an effective cure for syphilis and was becoming widely used by doctors and public health centers to treat the disease. PHS study directors continued the study, denying patients treatment by penicillin, and actively discouraging them from having penicillin administered by other sources. The men were never advised that they had syphilis, nor were they offered a treatment.[citation needed] The study did not end until 1972.

See also

References

  1. ^ 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 ab ac ad ae af ag ah aiaj ak al am an ao ap aq ar as at au Kent ME, Romanelli F (February 2008). "Reexamining syphilis: an update on epidemiology, clinical manifestations, and management". Ann Pharmacother 42(2): 226–36. doi:10.1345/aph.1K086. PMID 18212261.
  2. ^ a b c d e f g h i j k l m Stamm LV (February 2010). "Global challenge of antibiotic-resistant Treponema pallidum".Antimicrob. Agents Chemother. 54 (2): 583–9.doi:10.1128/AAC.01095-09. PMC 2812177.PMID 19805553.
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  5. ^ a b c d e f g h Bhatti MT (2007). "Optic neuropathy from viruses and spirochetes". Int Ophthalmol Clin 47 (4): 37–66, ix.doi:10.1097/IIO.0b013e318157202d. PMID 18049280.
  6. ^ a b c d e f g Woods CR (June 2009). "Congenital syphilis-persisting pestilence". Pediatr. Infect. Dis. J. 28 (6): 536–7.doi:10.1097/INF.0b013e3181ac8a69. PMID 19483520.
  7. ^ Koss CA, Dunne EF, Warner L (July 2009). "A systematic review of epidemiologic studies assessing condom use and risk of syphilis". Sex Transm Dis 36 (7): 401–5.doi:10.1097/OLQ.0b013e3181a396eb. PMID 19455075.
  8. ^ How can Syphilis be Prevented?, Centers for Disease Control and Prevention
  9. ^ Centers for Disease Control (CDC) (05-2004). "STD Facts - Syphilis". Centers for Disease Control. Retrieved 2007-05-30.
  10. ^ "WHO Disease and injury country estimates". World Health Organization. 2004. Retrieved Nov. 11, 2009.
  11. ^ "Syphilis". Online Etymology Dictionary. 2001.
  12. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007).Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0.
  13. ^ Semple, David; Smythe, Robert (2009). Oxford handbook of psychiatry. Oxford, UK: Oxford University Press. p. 160. ISBN 978-0-19-923946-7.
  14. ^ Rudy's List of Archaic Medical Terms (2007-04-27). "B". Antiquus Morbus. Retrieved 2008-04-28.
    Referencing:
    Robley Dunglison (1874). Dunglison's Medical Dictionary – A Dictionary of Medical Science. Philadelphia, USA: Collins.
  15. ^ Beard, Mary (First published 2010- Dec 14). "Pompeii skeletons reveal secrets of Roman family life". BBC Pompeii: Life and Death in a Roman Town will be broadcast on BBC Two at 2100 GMT on Tuesday 14 December.. Retrieved 2010-12-14.
  16. ^ Bollaert, WM (1864), Introduction of Syphilis from the New World, "I will now briefly allude to some historical accounts on this subject, particularly as regards the Old World. In the Aphorisms of Hippo crates, 400 b.c., and in the Sentences of Celsus, 400 years after Hippocrates, as found in Sprengell's translations, in 1708. When Sprengell alludes to his own added Aphorisms " On the French dis-ease," he says, it was just known to former more temperate ages, and, in a note, how far it was known in former ages, he refers to Ecclesiasticus, c. 19, v. 2, 3. Hippocrates, in. ; Epidemics, ill., 41, 74, 59, and i. Be Morbus Mulierum, 127. Galen, lib. iv. ; Meth. c. 5, and lib. i. De Genet:, c. 23 ; lib. iii. Epidemics, sec. 3, com. 25. Pliny His. Nat., lib. 26, c. i. Avicen, lib. 2. Valesius; Rhodius ; Vigo-nius, Lib. de Morb. Gall., c. &c. And that it does not, according to the vulgar opinion, derive its origin from Naples, France, East or West Indies. Josephus, c. xi., p. 108, says, when on the subject of purification, that Moses ordered those who had gonorrhoea should not come into the city."
  17. ^ Keys D (2000-07-24). "English syphilis epidemic pre-dated European outbreaks by 150 years". London: Independent News and Media Limited. Retrieved 2007-09-22.
  18. ^ Henneberg M, Henneberg RJ (1994). "Treponematosis in an Ancient Greek colony of Metaponto, Southern Italy 580-250 BCE". In O Dutour, G Palfi, J Berato, J-P Brun (eds). The Origin of Syphilis in Europe, Before or After 1493?. Toulon-Paris: Centre Archeologique du Var, Editions Errance. pp. 92–98.
  19. ^ Henneberg M, Henneberg RJ (2002). "Reconstructing Medical Knowledge in Ancient Pompeii from the Hard Evidence of Bones and Teeth". In J Renn, G Castagnetti (eds). Homo Faber: Studies on Nature. Technology and Science at the Time of Pompeii,. Rome: "L’ERMA" di Bretschneider. pp. 169–187.
  20. ^ Rose M (January/February 1997). "Origins of Syphilis".Archaeology 50 (1).
  21. ^ a b c Lobdell J, Owsley D (August 1974). "The origin of syphilis".Journal of Sex Research 10 (1): 76–79.doi:10.1080/00224497409550828. (via JSTOR)
  22. ^ Baker, et al.
  23. ^ Debora MacKenzie (15 January 2008). "Columbus blamed for spread of syphilis". NewScientist.
  24. ^ Harper KN, Ocampo PS, Steiner BM, et al (2008). "On the origin of the treponematoses: a phylogenetic approach". PLoS Negl Trop Dis 2 (1): e148. doi:10.1371/journal.pntd.0000148.PMC 2217670. PMID 18235852.
  25. ^ a b Crosby, Alfred W.. The Columbian exchange: biological and cultural consequences of 1492. New York: Praeger; 2003. ISBN 0-275-98092-8. p. 146.
  26. ^ Oriel, J.D. (1994). The Scars of Venus: A History of Venereology. London: Springer-Verlag. ISBN 354019844X.
  27. ^ Diamond, Jared (1997). Guns, Germs and Steel. New York: W.W. Norton. pp. 210. ISBN 848306667X.
  28. ^ CBC News Staff (January 2008). "Study traces origins of syphilis in Europe to New World". Retrieved 2008-01-15.
  29. ^ Harper, Kristin, et al. (January 2008). "On the Origin of the Treponematoses: A Phylogenetic Approach". Retrieved 2008-01-21.
  30. ^ "Genetic Study Bolsters Columbus Link to Syphilis", New York Times, January 15, 2008
  31. ^ "Columbus May Have Brought Syphilis to Europe", LiveScience
  32. ^ "Pox and Paranoia in Renaissance Europe". History Today.
  33. ^ Nicholas Culpeper. "A complete herbal".
  34. ^ Hanlon M (7 June 2007). "The magical properties of Mercury, the metal the EU wants to ban". The Daily Mail. Retrieved 2007-08-07.
  35. ^ Thomas James Walker (December 4 1869). "The Treatment of Syphilis by the Hypodermic Injection of the Salts of Mercury". Br Med J. 2 (466): 605–608. doi:10.1136/bmj.2.466.605.PMC 2261112. PMID 20745696.
  36. ^ Ozuah, Philip O. (March 2000). "Mercury poisoning". Current Problems in Pediatrics 30 (3): 91–99 [91].doi:10.1067/mps.2000.104054.
  37. ^ Raju T (2006). "Hot brains: manipulating body heat to save the brain". Pediatrics 117 (2): e320–1. doi:10.1542/peds.2005-1934. PMID 16452338.
  38. ^ Spink, W.W. "Infectious diseases: prevention and treatment in the nineteenth and twentieth centuries" U of Minnesota Press, 1978, p. 316.
  39. ^ Brown, Kevin (2006). The Pox: The Life and Near Death of a Very Social Disease. Stroud: WSutton. pp. 85–111, 185–91.
  40. ^ The Metropolitan Museum of Art Bulletin, Summer 2007, pp. 55–56.
  41. ^ Fritz Richard Schaudinn, Erich Hoffmann: Vorläufiger Bericht über das Vorkommen von Spirochaeten in syphilitischen Krankheitsprodukten und bei Papillomen. Arbeiten aus dem kaiserlichen Gesundheitsamtes (Berlin), vol. 22, pp. 527–534, 1905.
  42. ^ "Noguchi, Hideyo". The Columbia Encyclopedia (Sixth ed.).
  43. ^ Donelson, Linda (1998). Out of Isak Dinesen in Africa. Coulsong. ISBN 0964389398.
  44. ^ "Frederick Delius Biography Sublime Music, Tragic Life".Favorite Classical Composers. Retrieved 2011-05-30.
  45. ^ Lerner V, Finkelstein Y, Witztum E (June 2004). "The enigma of Lenin's (1870–1924) malady". Eur. J. Neurol. 11 (6): 371–6.doi:10.1111/j.1468-1331.2004.00839.x. PMID 15171732.
  46. ^ Tithonus, Pednuad, J.. "Eugen Sandow - Father of Bodybuilding". The Human Marvels. Retrieved 2008-09-17. "At the time of his death in 1925, a cover story was released stating Sandow died prematurely at age 58 of a stroke shortly after pushing his car out of the mud. The actual cause of death was more likely due to complications from syphilis."
  47. ^ Tom Pendergast and Sara Pendergast (2000). St. James encyclopedia of popular culture. St. James Press.ISBN 9781558624047. "... speculates that the strongman's death may have been the result of an aortic aneurysm brought about by syphilis. ..."
  48. ^ Wilson, A. G. (2001). Tolstoy: A Biography. New York: Norton.ISBN 0-393-32122-3.
  49. ^ "Did Hitler Have Syphilis?". Medical News Today. Retrieved 2010-10-02. "An encounter with a Jewish prostitute in Vienna in 1908 may have given Hitler neuro-syphilis and provided the 'deadly logic and blueprint for the Holocaust' as well as giving him a reason to attempt to eliminate the mentally retarded, according to evidence presented at the Royal College of Psychiatrists."
  50. ^ Johannes Stradanus undated brief review of works hosted at the University of York in the United Kingdom. Accessed August 6, 2007.
  51. ^ Jan van der Straet's "Preparation..." at commercial art site. Accessed August 6, 2007.
  52. ^ wikisource:es:Historia de la vida del Buscón: Libro Primero: Capítulo III: continues with [...] porque se le había comido de unas búas de resfriado, que aun no fueron de vicio porque cuestan dinero;: "[...] because it had been eaten by the bubons of a cold, which were not of vice because they cost money;".
  53. ^ See for example: Imlay, Elizabeth. Charlotte Bronte and the Mysteries of Love. p. 47-50.
  54. ^ "O Mist�rio da Estrada de Sintra". Retrieved 2007-08-07.
  55. ^ "U.S. Public Health Service Syphilis Study at Tuskegee".CDC. Retrieved 2010-07-07.

Further reading

  • Parascandola, John. Sex, Sin, and Science: A History of Syphilis in America (Praeger, 2008) 195 pp. ISBN: 978-0-275-99430-3 excerpt and text search
  • Shmaefsky, Brian, Hilary Babcock and David L. Heymann. Syphilis (Deadly Diseases & Epidemics) (2009)
  • Stein, Claudia. Negotiating the French Pox in Early Modern Germany (2009)

External links

Find more about Syphilis 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

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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. [hide]v · d · eZoonotic viral diseases (A80–B34, 042–079) Arthropod/ (arbovirus) Mosquito Bunyaviridae Arbovirus encephalitis: La Crosse encephalitis (LCV) · California encephalitis (CEV) Viral hemorrhagic fever: Rift Valley fever (RVFV) Flaviviridae Arbovirus encephalitis: Japanese encephalitis (JEV) · Australian encephalitis (MVEV, KUNV) · St. Louis encephalitis (SLEV) · West Nile fever (WNV) Viral hemorrhagic fever: Dengue fever (DV) other: Yellow fever (YFV) · Zika fever Togaviridae Arbovirus encephalitis: Eastern equine encephalomyelitis (EEEV) · Western equine encephalomyelitis (WEEV) · Venezuelan equine encephalomyelitis (VEEV) other: Chikungunya (CV) · O'Nyong-nyong fever (OV) · Ross River fever (RRV) Tick Bunyaviridae Viral hemorrhagic fever: Crimean-Congo hemorrhagic fever (CCHFV) Flaviviridae Arbovirus encephalitis: Tick-borne encephalitis (TBEV) · Powassan encephalitis (PV) · Deer tick virus encephalitis (DTV) Viral hemorrhagic fever: Omsk hemorrhagic fever (OHFV) · Kyasanur forest disease (KFDV/Alkhurma virus)) · Langat virus (LGTV) Reoviridae Colorado tick fever (CTFV) Mammal Rodent (Robovirus) Arenaviridae Viral hemorrhagic fever: Lassa fever (LV) · Venezuelan hemorrhagic fever (Guanarito virus) · Argentine hemorrhagic fever (Junin virus) · Bolivian hemorrhagic fever (Machupo virus) · Lujo virus Bunyaviridae Puumala virus · Andes virus · Sin Nombre virus · Hantavirus (HV) Bat Filoviridae VHF: Ebola hemorrhagic fever · Marburg hemorrhagic fever Rhabdoviridae Australian bat lyssavirus · Mokola virus · Duvenhage virus · Lagos bat virus · Chandipura virus(sandfly) Bornaviridae Menangle · Henipavirus · Borna disease (Borna disease virus) Multiple Rhabdoviridae Rabies (RV) M: VIR virs(prot)/clss cutn/syst (hppv/hiva, infl/zost/zoon)/epon drugJ(dnaa, rnaa, rtva, vacc) Retrieved from "http://en.wikipedia.org/wiki/Dengue_fever"

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