Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum subspecies pallidum.[3] The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, and tertiary).[1] The primary stage classically presents with a single chancre (a firm, painless, non-itchy skin ulceration usually between 1 cm and 2 cm in diameter) though there may be multiple sores.[1] In secondary syphilis, a diffuse rash occurs, which frequently involves the palms of the hands and soles of the feet.[1] There may also be sores in the mouth or vagina.[1] In latent syphilis, which can last for years, there are few or no symptoms.[1] In tertiary syphilis, there are gummas (soft, non-cancerous growths), neurological problems, or heart symptoms.[2] Syphilis has been known asthe great imitatoras it may cause symptoms similar to many other diseases.[1][2]

Syphilis is most commonly spread through sexual activity.[1] It may also be transmitted from mother to baby during pregnancy or at birth, resulting in congenital syphilis.[1][6] Other diseases caused by Treponema bacteria include yaws (تي. pallidum subspecies pertenue), pinta (تي. carateum), and nonvenereal endemic syphilis (تي. pallidum subspecies endemicum).[2] These three diseases are not typically sexually transmitted.[7] Diagnosis is usually made by using blood tests; the bacteria can also be detected using dark field microscopy.[1] The Centers for Disease Control and Prevention (U.S.) recommend all pregnant women be tested.[1]

The risk of sexual transmission of syphilis can be reduced by using a latex or polyurethane condom.[1] Syphilis can be effectively treated with antibiotics.[3] The preferred antibiotic for most cases is benzathine benzylpenicillin injected into a muscle.[3] In those who have a severe penicillin allergy, doxycycline or tetracycline may be used.[3] In those with neurosyphilis, intravenous benzylpenicillin or ceftriaxone is recommended.[3] During treatment people may develop fever, headache, and muscle pains, a reaction known as Jarisch–Herxheimer.[3]

في 2015, حول 45.4 million people were infected with syphilis,[4] with six million new cases.[8] During 2015, it caused about 107,000 deaths, لأسفل من 202,000 في 1990.[5][9] After decreasing dramatically with the availability of penicillin in the 1940s, rates of infection have increased since the turn of the millennium in many countries, often in combination with human immunodeficiency virus (HIV).[2][10] This is believed to be partly due to increased promiscuity, prostitution, decreasing use of condoms and unsafe sexual practices among men who have sex with men.[11][12][13]

العلامات والأعراض

Syphilis canpresent in one of four different stages: primary, secondary, latent, and tertiary,[2] and may also occurcongenitally.[14] It was referred to asthe great imitatorbySir William Osler due to its varied presentations.[2][15][16]

Primary

Primarychancre of syphilis at the site of infection on the penis

Primary syphilis is typically acquired by direct sexual contact with the infectious lesions of another person.[17] Approximately 2–6 weeks after contact (with a range of 10–90 days) a skin lesion, called achancre, appears at the site and this contains infectious spirochetes.[18][19] This is classically(40% من الوقت) a single, firm, painless, non-itchyskin ulceration with a clean base and sharp borders approximately 0.3–3.0 cm in size.[2] The lesion may take on almost any form.[20] In the classic form, it evolves from amacule to apapule and finally to anerosion أوulcer.[20] Occasionally, multiple lesions may be present (~40%),[2] with multiple lesions being more common when coinfected with HIV.[20] Lesions may be painful or tender (30%), and they may occur in places other than the genitals (2–7%).[20] The most common location in women is thecervix (44%), الpenis in heterosexual men (99%), وanally وrectally فيmen who have sex with men (34%).[20] Lymph node enlargement frequently(80%) occurs around the area of infection,[2] occurring seven to 10 days after chancre formation.[20] الlesion may persist for three to six weeks if left untreated.[2]

Secondary

Typical presentation of secondary syphilis with a rash on the palms of the handsReddishpapules وnodules over much of the body due to secondary syphilis

Secondary syphilis occurs approximately four to ten weeks after the primary infection.[2] While secondary disease is known for the many different ways it can manifest, symptoms most commonly involve theskinmucous membranes, وlymph nodes.[21] There may be a symmetrical, reddish-pink, non-itchyrash on the trunk and extremities, including the palms and soles.[2][22] The rash may becomemaculopapular أوpustular.[2] It may form flat, broad, whitish, wart-like lesions on mucous membranes, known ascondyloma latum.[2] All of these lesions harbor bacteria and are infectious.[2] Other symptoms may includefeversore throatmalaiseweight losshair loss, وheadache.[2] Rare manifestations includeliver inflammationkidney diseasejoint inflammationperiostitisinflammation of the optic nerveuveitis, وinterstitial keratitis.[2][23] The acute symptoms usually resolve after three to six weeks;[23] حول 25% of people may present with a recurrence of secondary symptoms.[21][24] Many people who present with secondary syphilis (40–85% of women, 20–65% of men) do not report previously having had the classical chancre of primary syphilis.[21]

Latent

Latent syphilis is defined as havingserologic proof of infection without symptoms of disease.[17] It develops after secondary syphilis and is divided into early latent and late latent stages.[25] Early latent syphilis is defined by theWorld Health Organization as less than 2 years after original infection.[25] Early latent syphilis is infectious as up to 25% of people can develop a recurrent secondary infection (during which spirochetes are actively replicating and are infectious).[25] Two years after the original infection the person will enter late latent syphilis and is not as infectious as the early phase.[23][26] The latent phase of syphilis can last many years after which, without treatment, approximately 15-40% of people can develop tertiary syphilis.[27]

Tertiary

Model of a head of a person with tertiary (gummatous) syphilisMusée de l’Homme, Paris

Tertiary syphilis may occur approximately 3 إلى 15 years after the initial infection, and may be divided into three different forms: gummatous syphilis (15%), lateneurosyphilis (6.5%), and cardiovascular syphilis (10%).[2][23] Without treatment, a third of infected people develop tertiary disease.[23] People with tertiary syphilis are not infectious.[2]

Gummatous syphilis or latebenign syphilis usually occurs 1 to 46 years after the initial infection, with an average of 15 years.[2] This stage is characterized by the formation of chronicgummas, which are soft, tumor-like balls of inflammation which may vary considerably in size.[2] They typically affect the skin, bone, and liver, but can occur anywhere.[2]

Cardiovascular syphilis usually occurs 10–30 years after the initial infection.[2] The most common complication issyphilitic aortitis, which may result inaortic aneurysm formation.[2]

Neurosyphilis refers to an infection involving thecentral nervous system. Involvement of the central nervous system in syphilis (either asymptomatic or symptomatic) can occur at any stage of the infection.[19] It may occur early, being either asymptomatic or in the form of syphiliticmeningitis, or late as meningovascular syphilisgeneral paresis, أوtabes dorsalis.[2]

Meningovascular syphilis involves inflammation of the small and medium arteries of the central nervous system. It can present between 1–10 years after the initial infection. Meningovascular syphilis is characterized by stroke, cranial nerve palsis andspinal cord inflammation.[28] Late symptomatic neurosyphilis can develop decades after the original infection and includes 2 types; general paresis and tabes dorsalis. General paresis presents with dementia, personality changes, أوهام, seizures, psychosis and depression.[28] Tabes dorsalis is characterized by gait instability, sharp pains in the trunk and limbs, impaired positional sensation of the limbs as well as having a positiveRomberg’s sign.[28] Both tabes dorsalis and general paresis may present withArgyll Robertson pupil which are pupils that constrict when the person focuses on near objects (accommodation reflex) but do not constrict when exposed to bright light (pupillary reflex).

Congenital

المقال الرئيسي: Congenital syphilis

Congenital syphilis is that which is transmitted during pregnancy or during birth.[6] Two-thirds of syphilitic infants are born without symptoms.[6] Common symptoms that develop over the first couple of years of life includeenlargement of the liver and spleen (70%), rash (70%), fever (40%), neurosyphilis (20%), وlung inflammation (20%).[6] If untreatedlate congenital syphilis may occur in 40%, بما فيهاsaddle nose deformationHigouménakissignsaber shin, أوClutton’s joints من بين أمور أخرى.[6] Infection during pregnancy is also associated withmiscarriage.[29] The three main dental defects in congenital syphilis areHutchinson’s incisors (screwdriver shaped incisors), Moon’s molars or bud molars, and Fournier’s molars ormulberry molars (molars with abnormal occlusal anatomy resembling amulberry).[30]

سبب

Bacteriology

Histopathology منTreponema pallidumspirochetes using a modifiedSteiner silver stainالمقال الرئيسي: Treponema pallidum

Treponema pallidum subspecies pallidum is a spiral-shapedGram-negative, highly mobile bacterium.[10][20] Three other human diseases are caused by relatedTreponema pallidum subspecies, بما فيهاyaws (subspeciespertenue), pinta (subspeciescarateum) وbejel (subspeciesendemicum).[2] Unlike subspeciespallidum, they do not cause neurological disease.[6] Humans are the only knownnatural reservoir for subspeciespallidum.[14] It is unable to survive more than a few days without ahost.[20] This is due to its small genome (1.14Mbp) failing to encode the metabolic pathways necessary to make most of its macronutrients.[20] It has a slowdoubling time of greater than 30 hours.[20] The bacterium is known for its ability to evade the immune system and its invasiveness.[31]

Transmission

Syphilis is transmitted primarily by sexual contact or duringpregnancy from a mother to her baby; the spirochete is able to pass through intact mucous membranes or compromised skin.[2][14] It is thus transmissible bykissing near a lesion, إلى جانبoralvaginal, وanal sex.[2][32] تقريبا 30% إلى 60% of those exposed to primary or secondary syphilis will get the disease.[23] Itsinfectivity is exemplified by the fact that an individualinoculated with only 57 organisms has a 50% chance of being infected.[20] Most new cases in the United States (60%) occur in men who have sex with men; and in this population 20% of syphilis cases were due to oral sex alone.[2][32] Syphilis can be transmitted byblood products, but the risk is low due to screening ofdonated blood in many countries.[2] The risk of transmission fromsharing needles appears to be limited.[2]

It is not generally possible to contract syphilis through toilet seats, daily activities, hot tubs, or sharing eating utensils or clothing.[33] This is mainly because the bacteria die very quickly outside of the body, making transmission byobjects extremely difficult.[34]

تشخبص

This poster acknowledges the social stigma of syphilis, while urging those who possibly have the disease to be tested (circa 1936).Micrograph of secondary syphilis skin lesions. (A/B) ح&E stain of SS lesions. (C/D) IHC staining reveals abundant spirochetes embedded within a mixed cellular inflammatory infiltrate (shown in the red box) in the papillary dermis. The blue arrow points to a tissue histiocyte and the read arrows to two dermal lymphocytes.[35]

Syphilis is difficult to diagnose clinically during early infection.[20] Confirmation is either viablood tests or direct visual inspection usingdark field microscopy.[2][36] Blood tests are more commonly used, as they are easier to perform.[2] Diagnostic tests are unable to distinguish between the stages of the disease.[37]

Blood tests

Blood tests are divided intonontreponemal and treponemal tests.[20]

Nontreponemal tests are used initially, and includevenereal disease research laboratory (VDRL) وrapid plasma reagin (RPR) tests.False positives on the nontreponemal tests can occur with some viral infections, مثلvaricella (chickenpox) وmeasles. False positives can also occur withسرطان الغدد الليمفاويةtuberculosismalariaendocarditisconnective tissue disease, وpregnancy.[17]

Because of the possibility of false positives with nontreponemal tests, confirmation is required with a treponemal test, مثلtreponemal pallidum particle agglutination (TPHA) أوfluorescent treponemal antibody absorption test (FTA-Abs).[2] Treponemal antibody tests usually become positive two to five weeks after the initial infection.[20] Neurosyphilis is diagnosed by finding high numbers ofleukocytes (predominatelylymphocytes) and high protein levels in thecerebrospinal fluid in the setting of a known syphilis infection.[2][17]

Direct testing

Dark field microscopy منserous fluid from a chancre may be used to make an immediate diagnosis.[20] Hospitals do not always have equipment or experienced staff members, and testing must be done within 10 minutes of acquiring the sample.[20] Two other tests can be carried out on a sample from the chancredirect fluorescent antibody (DFA) وpolymerase chain reaction (PCR) tests.[20] DFA usesantibodies tagged withfluorescein, which attach to specific syphilis proteins, while PCR uses techniques to detect the presence of specific syphilisgenes.[20] These tests are not as time-sensitive, as they do not require living bacteria to make the diagnosis.[20]

الوقاية

مصل

اعتبارا من 2018, there is noمصل effective for prevention.[14] Several vaccines based on treponemal proteins reduce lesion development in ananimal model but research continues.[38][39]

Sex

Condom use reduces the likelihood of transmission during sex, but does not completely eliminate the risk.[40] الCenters for Disease Control and Prevention (CDC) states, “Correct and consistent use of latex condoms can reduce the risk of syphilis only when the infected area or site of potential exposure is protected.[41] لكن, a syphilis sore outside of the area covered by a latex condom can still allow transmission, so caution should be exercised even when using a condom.[42]

Abstinence from intimate physical contact with an infected person is effective at reducing the transmission of syphilis. The CDC states, “The surest way to avoid transmission of sexually transmitted diseases, including syphilis, is to abstain from sexual contact or to be in a long-term mutuallymonogamous relationship with a partner who has been tested and is known to be uninfected.[42]

Congenital disease

Portrait of Mr. J. Kay, affected with what is now believed to have been congenital syphilis c. 1820[43]

Congenital syphilis in the newborn can be prevented by screening mothers during early pregnancy and treating those who are infected.[44] الUnited States Preventive Services Task Force (USPSTF) strongly recommends universal screening of all pregnant women,[45] while theWorld Health Organization (من الذى) recommends all women be tested at their first antenatal visit and again in thethird trimester.[46][47] If they are positive, it is recommended their partners also be treated.[46] Congenital syphilis is still common in the developing world, as many women do not receiveantenatal care at all, and the antenatal care others receive does not include screening.[44][48] It still occasionally occurs in the developed world, as those most likely to acquire syphilis are least likely to receive care during pregnancy.[44] Several measures to increase access to testing appear effective at reducing rates of congenital syphilis in low- to middle-income countries.[46] Point-of-care testing to detect syphilis appeared to be reliable although more research is needed to assess its effectiveness and into improving outcomes in mothers and babies.[49]

Screening

The CDC recommends that sexually active men who have sex with men be tested at least yearly.[50] The USPSTF also recommends screening among those at high risk.[51]

Syphilis is anotifiable disease in many countries, including Canada,[52] الEuropean Union,[53] and the United States.[54] This means health care providers are required to notifypublic health authorities, which will then ideally providepartner notification to the person’s partners.[55] Physicians may also encourage patients to send their partners to seek care.[56] Several strategies have been found to improve follow-up for STI testing, including email and text messaging of reminders for appointments.[57]

علاج او معاملة

Early infections

The first-line treatment for uncomplicated syphilis (primary or secondary stages) remains a single dose ofintramuscular benzathine benzylpenicillin.[58] Doxycycline والتتراسيكلين are alternative choices for those allergic to penicillin; due to the risk ofbirth defects, these are not recommended for pregnant women.[58] Resistance إلىmacrolidesrifampicin, وclindamycin is often present.[14] Ceftriaxone, a third-generationcephalosporin antibiotic, may be as effective as penicillin-based treatment.[2] It is recommended that a treated person avoid sex until the sores are healed.[33]

Late infections

For neurosyphilis, due to the poor penetration of benzathine penicillin into thecentral nervous system, those affected are given large doses ofintravenous penicillin G for a minimum of 10 أيام.[2][14] If a person is allergic to penicillin, ceftriaxone may be used or penicillin desensitization attempted.[2] Other late presentations may be treated with once-weekly intramuscular benzathine penicillin for three weeks.[2] Treatment at this stage solely limits further progression of the disease and has a limited effect on damage which has already occurred.[2] Serologic cure can be measured when the non-treponemal titers decline by a factor of 4 or more in 6–12 months in early syphilis or 12–24 months in late syphilis.[19]

Jarisch–Herxheimer reaction

Jarisch–Herxheimer reaction in a person with syphilis and human immunodeficiency virus[59]

One of the potential side effects of treatment is theJarisch–Herxheimer reaction.[2] It frequently starts within one hour and lasts for 24 ساعات, with symptoms of fever, muscle pains, headache, and afast heart rate.[2] It is caused bycytokines released by the immune system in response tolipoproteins released from rupturing syphilis bacteria.[60]

Pregnancy

Penicillin is an effective treatment for syphilis in pregnancy[61] but there is no agreement on which dose or route of delivery is most effective.[62]

علم الأوبئة

المقال الرئيسي: Epidemiology of syphilisSyphilis deaths per million persons in 2012 0–0 1–1 2–3 4–10 11–19 20–28 29–57 58–138Age-standardizeddisability adjusted life years from syphilis per 100,000 inhabitants in 2004[63]

  no data<35  35–70 70–105 105–140 140–175 175–210  210–245 245–280 280–315 315–350 350–500>500

في 2012, حول 0.5% of adults were infected with syphilis, with 6 million new cases.[8] في 1999, it is believed to have infected 12 million additional people, with greater than 90% of cases in thedeveloping world.[14] It affects between 700,000 and 1.6 million pregnancies a year, resulting inspontaneous abortionsstillbirths, and congenital syphilis.[6] During 2015, it caused about 107,000 deaths, لأسفل من 202,000 في 1990.[5][9] فيsub-Saharan Africa, syphilis contributes to approximately 20% منperinatal deaths.[6] Rates are proportionally higher amongintravenous drug users, those who are infected withHIV, and men who have sex with men.[11][12][13] In the United States about 55,400 people are newly infected each year.[64] In the United States as of 2020, rates of syphilis have increased by more than threefold; في 2018 approximately 86% of all cases of syphilis in the United States were in men.[19] African Americans accounted for almost half of all cases in 2010.[65] اعتبارا من 2014, syphilis infections continue to increase in the United States.[66][67]

Syphilis was very common in Europe during the 18th and 19th centuries.[10] Flaubert found it universal among nineteenth-century Egyptian prostitutes.[68] In the developed world during the early 20th century, infections declined rapidly with the widespread use ofantibiotics, until the 1980s and 1990s.[10] Since 2000, rates of syphilis have been increasing in the US, Canada, the UK, Australia and Europe, primarily among men who have sex with men.[14] Rates of syphilis among US women have remained stable during this time, while rates among UK women have increased, but at a rate less than that of men.[69] Increased rates among heterosexuals have occurred in China and Russia since the 1990s.[14] This has been attributed to unsafe sexual practices, such as sexual promiscuity, prostitution, and decreasing use of barrier protection.[14][69][70]

Left untreated, it has a mortality rate of 8% إلى 58%, with a greater death rate among males.[2] The symptoms of syphilis have become less severe over the 19th and 20th centuries, in part due to widespread availability of effective treatment, and partly due tovirulence of the bacteria.[21] With early treatment, few complications result.[20] Syphilis increases the risk of HIV transmission by two to five times, and coinfection is common (30–60% in some urban centers).[2][14] In 2015,Cuba became the first country to eliminate mother-to-child transmission of syphilis.[71]

تاريخ

المقال الرئيسي: History of syphilisPortrait ofGerard de Lairesse byRembrandt van Rijn, circa 1665–67, oil on canvas. De Lairesse, himself a painter and art theorist, had congenital syphilis that deformed his face and eventually blinded him.[72]

The origin of syphilis is disputed.[2] Syphilis was present in the Americas before European contact,[73] and it may have been carried from the Americas to Europe by the returning crewmen fromChristopher Columbus‘s voyage to theAmericas, or it may have existed in Europe previously but gone unrecognized until shortly after Columbus’s return.[37][74] These are theColumbian وpre-Columbian hypotheses, على التوالى, with theColumbian hypothesis better supported by the evidence.[37][75][76] لكن, findings fromphylogenetic science suggest that is, in fact, أNew World disease.[77]

The first written records of an outbreak of syphilis in Europe occurred in 1494 أو 1495 فيNaples, إيطاليا, during a French invasion (Italian War of 1494–98).[10][37] Since it was claimed to have been spread by French troops, it was initially called theFrench diseaseby the people of Naples.[78] في 1530, the pastoral namesyphilis” (the name of a character) was first used by the Italian physician and poetGirolamo Fracastoro as the title of hisLatin poem indactylic hexameter describing the ravages of the disease in Italy.[79][80] It was also called theGreat Pox”.[81][82]

In the 16th through 19th centuries, syphilis was one of the largest public health burdens inprevalence, symptoms, and disability,[83]:208–209[84] although records of its true prevalence were generally not kept because of the fearsome and sordid status ofsexually transmitted diseases in those centuries.[83]:208–209 According to a 2020 study, أكثر من 20% of individual in the age range 15–34 years in late 18th century London were treated for syphilis.[85] At the time thecausative agent was unknown but it was well known that it was spread sexually and also often from mother to child. Its association with sex, especiallysexual promiscuity وprostitution, made it an object of fear and revulsion and a taboo. The magnitude of its morbidity and mortality in those centuries reflected that, unlike today, there was no adequate understanding of itspathogenesis and no truly effective treatments. Its damage was caused not so much by great sickness or death early in the course of the disease but rather by its gruesome effects decades after infection as it progressed toneurosyphilis معtabes dorsalisMercury compounds and isolation were commonly used, with treatments often worse than the disease.[81]

The causative organismTreponema pallidum, was first identified byFritz Schaudinn وErich Hoffmann, في 1905.[86] The first effective treatment for syphilis wasArsphenamine, discovered bySahachiro Hata في 1909, during a survey of hundreds of newly synthesized organicarsenical compounds led byPaul Ehrlich. It was manufactured and marketed from 1910 under the trade nameSalvarsan byHoechst AG.[87] هذهorganoarsenic compound was the first modernchemotherapeutic agent.

During the 20th century, as bothmicrobiology وعلم العقاقير advanced greatly, syphilis, like many other infectious diseases, became more of a manageable burden than a scary and disfiguring mystery, at least indeveloped countries among those people who could afford to pay for timely diagnosis and treatment. Penicillin was discovered in 1928, and effectiveness of treatment withpenicillin was confirmed in trials in 1943,[81] at which time it became the main treatment.[88]

Many famous historical figures, بما فيهاFranz SchubertArthur SchopenhauerÉdouard Manet,[10] Charles Baudelaire,[89] وGuy de Maupassant are believed to have had the disease.[90] Friedrich Nietzsche was long believed to have gone mad as a result oftertiary syphilis, but that diagnosis has recently come into question.[91]

Arts and literature

أنظر أيضا: List of syphilis casesAn early medical illustration of people with syphilis, Vienna, 1498

The earliest known depiction of an individual with syphilis isAlbrecht Dürer‘sSyphilitic Man, a woodcut believed to represent aLandsknecht, a Northern Europeanmercenary.[92] The myth of thefemme fatale أو “poison womenof the 19th century is believed to be partly derived from the devastation of syphilis, with classic examples in literature includingJohn Keats‘ “La Belle Dame sans Merci“.[93][94]

The Flemish artistStradanus designed a print calledPreparation and Use of Guayaco for Treating Syphilis, a scene of a wealthy man receiving treatment for syphilis with the tropical woodguaiacum sometime around 1590.[95]

Tuskegee and Guatemala studies

أنظر أيضا: Tuskegee syphilis experiment وGuatemala syphilis experimentأWork Projects Administration poster about syphilis c. 1940

ال “Tuskegee Study of Untreated Syphilis in the Negro Malewas an infamous, unethical and racistclinical study conducted between 1932 و 1972 by theنحن. Public Health Service.[96][97] Whereas the purpose of this study was to observe thenatural history of untreated syphilis; the African-American men in the study were told they were receiving free treatment forbad bloodfrom the United States government.[98]

The Public Health Service started working on this study in 1932 in collaboration withTuskegee University, أhistorically black college in Alabama. Researchers enrolled 600 poor, African-Americansharecroppers من عندMacon CountyAlabama in the study. Of these men, 399 had contracted syphilis before the study began, و 201 did not have the disease.[97] Medical care, hot meals and free burial insurance were given to those who participated. The men were told that the study would last six months, but in the end it continued for 40 سنوات.[97] After funding for treatment was lost, the study was continued without informing the men that they were only being studied and would not be treated. Facing insufficient participation, the Macon County Health Department nevertheless wrote to subjects to offer them alast chanceto get a special “علاج او معاملة”, which was not a treatment at all, but a spinal tap administered exclusively for diagnostic purposes.[96] None of the men infected were ever told that they had the disease, and none were treated withpenicillin even after the antibiotic had been proven to successfully treat syphilis. According to theCenters for Disease Control, the men were told they were being treated forbad blood—a colloquialism describing various conditions such as fatigueanemia and syphilis—which was a leading cause of death among southern African-American men.[97]

The 40-year study became a textbook example of poormedical ethics because researchers had knowingly withheld treatment withpenicillin and because the subjects had been misled concerning the purposes of the study. The revelation in 1972 of these study failures by awhistleblowerPeter Buxtun, led to major changes in U.S. law and regulation on the protection of participants in clinical studies. Now studies requireinformed consent,[99] communication ofتشخبص, and accurate reporting of test results.[100]Preparation and Use of Guayaco for Treating Syphilis, بعد، بعدماStradanus, 1590

Similar experiments were carried out inGuatemala من عند 1946 إلى 1948. It was done during the administration of American PresidentHarry S. Truman and Guatemalan PresidentJuan José Arévalo with the cooperation of some Guatemalan health ministries and officials.[101] Doctors infected soldiers, prostitutes, prisoners andmental patients with syphilis and othersexually transmitted diseases, without theinformed consent of the subjects, and treated most subjects withantibiotics. The experiment resulted in at least 83 deaths.[102][103] In October 2010, the U.S. formally apologized to Guatemala for the ethical violations that took place. Secretary of StateHillary Clinton and Health and Human Services SecretaryKathleen Sebelius statedAlthough these events occurred more than 64 years ago, we are outraged that such reprehensible research could have occurred under the guise of public health. We deeply regret that it happened, and we apologize to all the individuals who were affected by such abhorrent research practices.[104] The experiments were led by physicianJohn Charles Cutler who also participated in the late stages of the Tuskegee syphilis experiment.[105]


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