Сифилис: сатылары, белгілері және диагностикасы

Sexually transmitted infection

Syphilis can present in one of four different stages: primary, secondary, latent, and tertiary, and may also occur congenitally. It was referred to as "the great imitator" by Sir William Osler due to its varied presentations.

Primary syphilis is typically acquired by direct sexual contact with the infectious lesions of another person. Approximately 2–6 weeks after contact (with a range of 10–90 days) a skin lesion, called a chancre, appears at the site and this contains infectious spirochetes. This is classically (40% of the time) a single, firm, painless, non itchy skin ulceration with a clean base and sharp borders approximately 0.3–3.0 cm in size. Occasionally, multiple lesions may be present (~40%), The rash may become maculopapular or pustular. 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.

Latent syphilis is defined as having serologic proof of infection without symptoms of disease. 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). The latent phase of syphilis can last many years after which, without treatment, approximately 15 40% of people can develop tertiary syphilis.

Tertiary syphilis may occur approximately 3 to 15 years after the initial infection and may be divided into three different forms: gummatous syphilis (15%), late neurosyphilis (6.5%), and cardiovascular syphilis (10%). 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, delusions, seizures, psychosis and depression. The three main dental defects in congenital syphilis are Hutchinson's incisors (screwdriver shaped incisors), Moon's molars or bud molars, and Fournier's molars or mulberry molars (molars with abnormal occlusal anatomy resembling a mulberry).

Treponema pallidum subspecies pallidum is a spiral shaped, Gram negative, highly mobile bacterium. It is unable to survive more than a few days without a host.

Syphilis is transmitted primarily by sexual contact or during pregnancy from a mother to her baby; the spirochete is able to pass through intact mucous membranes or compromised skin. Approximately 30% to 60% of those exposed to primary or secondary syphilis will get the disease. Its infectivity is exemplified by the fact that an individual inoculated with only 57 organisms has a 50% chance of being infected. Syphilis can be transmitted by blood products, but the risk is low due to screening of donated blood in many countries. This is mainly because the bacteria die very quickly outside of the body, making transmission by objects extremely difficult.

Syphilis is difficult to diagnose clinically during early infection. Blood tests are more commonly used, as they are easier to perform.

Blood tests are divided into nontreponemal and treponemal tests. Neurosyphilis is diagnosed by finding high numbers of leukocytes (predominately lymphocytes) and high protein levels in the cerebrospinal fluid in the setting of a known syphilis infection.

Condom use reduces the likelihood of transmission during sex, but does not eliminate the risk. The Centers 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. However, 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."

Congenital syphilis in the newborn can be prevented by screening mothers during early pregnancy and treating those who are infected. The United States Preventive Services Task Force (USPSTF) strongly recommends universal screening of all pregnant women, while the World Health Organization (WHO) recommends all women be tested at their first antenatal visit and again in the third trimester. If they are positive, it is recommended their partners also be treated. It still occasionally occurs in the developed world, as those most likely to acquire syphilis are least likely to receive care during pregnancy. 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.

The CDC recommends that sexually active men who have sex with men be tested at least yearly. The USPSTF also recommends screening among those at high risk. Syphilis is a notifiable disease in many countries, including Canada, the European Union, and the United States. This means health care providers are required to notify public health authorities, which will then ideally provide partner notification to the person's partners. Physicians may also encourage patients to send their partners to seek care. Several strategies have been found to improve follow up for STI testing, including email and text messaging of reminders for appointments.

As a form of chemotherapy, elemental mercury had been used to treat skin diseases in Europe as early as 1363. As syphilis spread, preparations of mercury were among the first medicines used to combat it. Mercury is in fact highly anti microbial: by the 16th century it was sometimes found to be sufficient to halt development of the disease when applied to ulcers as an inunction or when inhaled as a suffumigation. It was also treated by ingestion of mercury compounds. Once the disease had gained a strong foothold, however, the amounts and forms of mercury necessary to control its development exceeded the human body's ability to tolerate it, and the treatment became worse and more lethal than the disease. Nevertheless, medically directed mercury poisoning became widespread through the 17th, 18th, and 19th centuries in Europe, North America, and India. Mercury salts such as mercury (II) chloride were still in prominent medical use as late as 1916, and considered effective and worthwhile treatments.

The first line treatment for uncomplicated syphilis (primary or secondary stages) remains a single dose of intramuscular benzathine benzylpenicillin. Doxycycline and tetracycline are alternative choices for those allergic to penicillin; due to the risk of birth defects, these are not recommended for pregnant women. Resistance to macrolides, rifampicin, and clindamycin is often present.

For neurosyphilis, due to the poor penetration of benzathine penicillin into the central nervous system, those affected are given large doses of intravenous penicillin G for a minimum of 10 days.]] One of the potential side effects of treatment is the Jarisch–Herxheimer reaction.

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

In 2012, about 0.5% of adults were infected with syphilis, with 6 million new cases. African Americans accounted for almost half of all cases in 2010. As of 2014, syphilis infections continue to increase in the United States. In the United States as of 2020, rates of syphilis have increased by more than threefold; in 2018 approximately 86% of all cases of syphilis in the United States were in men. Syphilis was very common in Europe during the 18th and 19th centuries. In the developed world during the early 20th century, infections declined rapidly with the widespread use of antibiotics, until the 1980s and 1990s. Increased rates among heterosexuals have occurred in China and Russia since the 1990s. Left untreated, it has a mortality rate of 8% to 58%, with a greater death rate among males.

Paleopathologists have known for decades that syphilis was present in the Americas before European contact. The situation in Europe and Afro Eurasia has been murkier and caused considerable debate. According to the Columbian theory, syphilis was brought to Spain by the men who sailed with Christopher Columbus in 1492 and spread from there, with a serious epidemic in Naples beginning as early as 1495. Contemporaries believed the disease sprang from American roots, and in the 16th century physicians wrote extensively about the new disease inflicted on them by the returning explorers. Most evidence supports the Columbian origin hypothesis. However, beginning in the 1960s, examples of probable treponematosis—the parent disease of syphilis, bejel, and yaws—in skeletal remains shifted the opinion of some towards a "pre Columbian" origin. When living conditions changed with urbanization, elite social groups began to practice basic hygiene and started to separate themselves from other social tiers. Consequently, treponematosis was driven out of the age group in which it had become endemic. It then began to appear in adults as syphilis. Because they had never been exposed as children, they were not able to fend off serious illness. Spreading the disease via sexual contact also led to victims being infected with a massive bacterial load from open sores on the genitalia. Adults in higher socioeconomic groups then became very sick with painful and debilitating symptoms lasting for decades. Often, they died of the disease, as did their children who were infected with congenital syphilis. The difference between rural and urban populations was first noted by Ellis Herndon Hudson, a clinician who published extensively about the prevalence of treponematosis, including syphilis, in times past. The importance of bacterial load was first noted by the physician Ernest Grin in 1952 in his study of syphilis in Bosnia. The most compelling evidence for the validity of the pre Columbian hypothesis is the presence of syphilitic like damage to bones and teeth in medieval skeletal remains. While the absolute number of cases is not large, new ones are continually discovered, most recently in 2015. At least fifteen cases of acquired treponematosis based on evidence from bones, and six examples of congenital treponematosis based on evidence from teeth, are now widely accepted. In several of the twenty one cases the evidence may also indicate syphilis. In 2020, a group of leading paleopathologists concluded that enough evidence had been collected to prove that treponemal disease, almost certainly including syphilis, had existed in Europe prior to the voyages of Columbus. There is an outstanding issue, however. Damaged teeth and bones may seem to hold proof of pre Columbian syphilis, but there is a possibility that they point to an endemic form of treponemal disease instead. As syphilis, bejel, and yaws vary considerably in mortality rates and the level of human disgust they elicit, it is important to know which one is under discussion in any given case, but it remains difficult for paleopathologists to distinguish among them. (The fourth of the treponemal diseases is pinta, a skin disease and therefore unrecoverable through paleopathology.) Ancient DNA (aDNA) holds the answer, because just as only aDNA suffices to distinguish between syphilis and other diseases that produce similar symptoms in the body, it alone can differentiate spirochetes that are 99.8 percent identical with absolute accuracy. Progress on uncovering the historical extent of syndromes through aDNA remains slow, however, because the spirochete responsible for treponematosis is rare in skeletal remains and fragile, making it notoriously difficult to recover and analyze. Precise dating to the medieval period is not yet possible but work by Kettu Majander et al. uncovering the presence of several different kinds of treponematosis at the beginning of the early modern period argues against its recent introduction from elsewhere. Therefore, they argue, treponematosis — possibly including syphilis — almost certainly existed in medieval Europe. Despite significant progress in tracing the presence of syphilis in past historic periods, definitive findings from paleopathology and aDNA studies are still lacking for the medieval period. Evidence from art is therefore helpful in settling the issue. Research by Marylynn Salmon has demonstrated that deformities in medieval subjects can be identified by comparing them to those of modern victims of syphilis in medical drawings and photographs. One of the most typical deformities, for example, is a collapsed nasal bridge called saddle nose. Salmon discovered that it appeared often in medieval illuminations, especially among the men tormenting Christ in scenes of the crucifixion. The association of saddle nose with men perceived to be so evil they would kill the son of God indicates the artists were thinking of syphilis, which is typically transmitted through sexual intercourse with promiscuous partners, a mortal sin in medieval times. One illuminator goes so far as to show a flagellant with an exposed penis, red at the tip as though infected with a syphilitic sore. Others show the deformed teeth associated with congenital syphilis—Hutchinson's incisors—or the eye deformity ptosis that often appears in victims of the disease. It remains mysterious why the authors of medieval medical treatises so uniformly refrained from describing syphilis or commenting on its existence in the population. Many may have confused it with other diseases such as leprosy (Hansen's disease) or elephantiasis. The great variety of symptoms of treponematosis, the different ages at which the various diseases appear, and its widely divergent outcomes depending on climate and culture, would have added greatly to the confusion of medical practitioners, as indeed they did right down to the middle of the 20th century. In addition, evidence indicates that some writers on disease feared the political implications of discussing a condition more fatal to elites than to commoners. Historian Jon Arrizabalaga has investigated this question for Castile with startling results revealing an effort to hide its association with elites. The first written records of an outbreak of syphilis in Europe occurred in 1495 in Naples, Italy, during a French invasion (Italian War of 1494–98). The disease reached London in 1497 and was recorded at St Batholomew's Hospital as infected 10 out of the 20 patients. In 1530, the pastoral name "syphilis" (the name of a character) was first used by the Italian physician and poet Girolamo Fracastoro as the title of his Latin poem in dactylic hexameter Syphilis sive morbus gallicus (Syphilis or The French Disease) describing the ravages of the disease in Italy. In Great Britain it was also called the "Great Pox". In the 16th through 19th centuries, syphilis was one of the largest public health burdens in prevalence, symptoms, and disability, although records of its true prevalence were generally not kept because of the fearsome and sordid status of sexually transmitted infections in those centuries. At the time the causative agent was unknown but it was well known that it was spread sexually and also often from mother to child. Its association with sex, especially sexual promiscuity and prostitution, 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 its pathogenesis 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 to neurosyphilis with tabes dorsalis. Mercury compounds and isolation were commonly used, with treatments often worse than the disease. The first effective treatment for syphilis was arsphenamine, discovered by Sahachiro Hata in 1909, during a survey of hundreds of newly synthesized organic arsenical compounds led by Paul Ehrlich. It was manufactured and marketed from 1910 under the trade name Salvarsan by Hoechst AG. This organoarsenic compound was the first modern chemotherapeutic agent. During the 20th century, as both microbiology and pharmacology advanced greatly, syphilis, like many other infectious diseases, became more of a manageable burden than a scary and disfiguring mystery, at least in developed countries among those people who could afford to pay for timely diagnosis and treatment. Penicillin was discovered in 1928, and effectiveness of treatment with penicillin was confirmed in trials in 1943,

Many famous historical figures, including Franz Schubert, Arthur Schopenhauer, Édouard Manet, and Guy de Maupassant are believed to have had the disease. Friedrich Nietzsche was long believed to have gone mad as a result of tertiary syphilis, but that diagnosis has recently come into question.

The earliest known depiction of an individual with syphilis is Albrecht Dürer's Syphilitic Man (1496), a woodcut believed to represent a Landsknecht, a Northern European mercenary. The myth of the femme fatale or "poison women" of the 19th century is believed to be partly derived from the devastation of syphilis, with classic examples in literature including John Keats' "La Belle Dame sans Merci". The Flemish artist Stradanus designed a print called Preparation and Use of Guayaco for Treating Syphilis, a scene of a wealthy man receiving treatment for syphilis with the tropical wood guaiacum sometime around 1590.

The "Tuskegee Study of Untreated Syphilis in the Negro Male" was an infamous, unethical and racist clinical study conducted between 1932 and 1972 by the U. S. Public Health Service. Whereas the purpose of this study was to observe the natural history of untreated syphilis; the African American men in the study were told they were receiving free treatment for "bad blood" from the United States government. The Public Health Service started working on this study in 1932 in collaboration with Tuskegee University, a historically black college in Alabama. Researchers enrolled 600 poor, African American sharecroppers from Macon County, Alabama in the study. Of these men, 399 had contracted syphilis before the study began, and 201 did not have the disease. communication of diagnosis, and accurate reporting of test results. Similar experiments were carried out in Guatemala from 1946 to 1948. It was done during the administration of American President Harry S. Truman and Guatemalan President Juan José Arévalo with the cooperation of some Guatemalan health ministries and officials. Doctors infected soldiers, prostitutes, prisoners and mental patients with syphilis and other sexually transmitted infections, without the informed consent of the subjects and treated most subjects with antibiotics. The experiment resulted in at least 83 deaths. In October 2010, the U. S. formally apologized to Guatemala for the ethical violations that took place. Secretary of State Hillary Clinton and Health and Human Services Secretary Kathleen Sebelius stated "Although 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." The experiments were led by physician John Charles Cutler who also participated in the late stages of the Tuskegee syphilis experiment.

It was first called grande verole or the "great pox" by the French. Other historical names have included "button scurvy", sibbens, frenga and dichuchwa, among others. Since it was a disgraceful disease, the disease was known in several countries by the name of their neighbouring, often hostile country. The English, the Germans, and the Italians called it "the French disease", while the French referred to it as the "Neapolitan disease". The Dutch called it the "Spanish/Castilian disease". To the Turks it was known as the "Christian disease", whilst in India, the Hindus and Muslims named the disease after each other.