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Syphilis is an STD (sexually transmitted disease) caused by a bacterium called Treponema pallidum, which most common symptom is a painless ulcer on the genitals.
In the era before antibiotics, syphilis was a chronic, prolonged, painful and, in advanced stages, assailed all systems of the body, being very greatly feared and stigmatized. As stated in the introduction of this text, syphilis is caused by a bacterium called Treponema pallidum. In advanced stages of disease, syphilis can be transmitted by kissing and even by touch if there are lesions on the skin or mouth (the symptoms explained below). The transmission of syphilis by blood transfusion is very rare as Treponema pallidum does not survive more than 48 hours in stored blood. There is also congenital syphilis that is acquired by the fetus when the mother is infected by Treponema pallidum during pregnancy.
The disease is divided into three stages, called primary syphilis, secondary syphilis and tertiary syphilis.
The lesion of primary syphilis is a papule (a small, raised, solid pimple or swelling on the skin) on the genitals; in a few hours it turns into a painless ulcer. In some cases ulcer can arise in the mouth or pharynx, if the transmission has been given via the oral sex. The ulcer of syphilis is called chancre, and after 3 to 6 weeks it disappears even without treatment, leading to a false impression of a spontaneous cure. Secondary syphilis Some weeks or months after the disappearance of the chancre, syphilis returns, now spread throughout the body. The lesions on the soles of the feet, palms and oral mucosa are characteristic, but the skin eruptions can occur anywhere on the body. Another typical lesion of secondary syphilis is called condylomalata, a wet lesion, resembling a large wart, which usually appears near where there was injury to the chancre in primary syphilis.
There are cases, however, that secondary syphilis presents few symptoms, so that the patient does not give much importance to the frame.
Just as occurs in primary syphilis, the symptoms of secondary syphilis resolve spontaneously without treatment. Treponema pallidum In primary syphilis, the chancre appears when as yet there was time for the body to produce antibodies to Treponema pallidum, so blood tests are usually negative at this stage. The diagnosis of secondary syphilis, tertiary, or primary, as in later phases, is done by two serological tests: VDRL and FTA-ABS (or TPHA).
As the VDRL may be positive in several diseases other than syphilis, such as lupus, liver disease, mononucleosis, leprosy, smallpox, rheumatoid arthritis, etc.
Penicillin allergic patients can be treated with doxycycline (100mg 2x, daily for 14 days) or azithromycin (2 g, a single dose), but they are not as effective as penicillin. In some cases, such as contaminated with syphilis in pregnant women, may be given a treatment for allergy desensitization of the patient so that it can be treated with penicillin. These photos are the main way I realized what I had, as I thought back to the presentations on the females back after the second time we had sex that night. In immunocompromised individuals, disseminated MAC infection is generally treated with clarithromycin, ethambutol, and rifabutin. Clarithromycin is a macrolide antibiotic with broad activity against many gram-positive and gram-negative bacteria as well as NTM. Treatment of mycobacterial infections requires multiple-drug regimens that often exert significant side effects with the potential to limit tolerability. Syphilis, a chronic systemic infection caused by Treponema pallidum subspecies pallidum, is usually sexually transmitted and is characterized by episodes of active disease interrupted by periods of latency. The Spirochaetales include four genera that are pathogenic for humans and for a variety of other animals: Leptospira species, which cause leptospirosis (Chap.
With the advent of penicillin therapy, the total number of cases of syphilis reported annually in the United States declined significantly to a low of 31,575 cases in 2000—a 95% decrease from 1943—with <6000 reported cases of infectious primary and secondary syphilis (the latter being a better indicator of disease activity than total syphilis cases). The populations at highest risk for acquiring syphilis have changed over time, with outbreaks among MSM in the pre-HIV era of the late 1970s and early 1980s as well as at present. The incidence of congenital syphilis roughly parallels that of infectious syphilis in women. One-third to one-half of individuals named as sexual contacts of persons with infectious syphilis become infected.
Syphilis remains a significant health problem globally; the number of new infections is estimated at 11 million per year. The primary lesion appears at the site of inoculation, usually persists for 4–6 weeks, and then heals spontaneously.
The generalized parenchymal, constitutional, and mucocutaneous manifestations of secondary syphilis usually appear ?6–8 weeks after the chancre heals, although primary and secondary manifestations may overlap.
The course of untreated syphilis was studied retrospectively in a group of nearly 2000 patients with primary or secondary disease diagnosed clinically (the Oslo Study, 1891–1951) and was assessed prospectively in 431 African-American men with seropositive latent syphilis of ?3 years’ duration (the notorious Tuskegee Study, 1932–1972). The Tuskegee Study showed that the death rate among untreated African-American men with syphilis (25–50 years old) was 17% higher than the rate among uninfected subjects and that 30% of all deaths were attributable to cardiovascular or, to a lesser extent, CNS syphilis. In warm, moist, intertriginous areas (commonly the perianal region, vulva, and scrotum), papules can enlarge to produce broad, moist, pink or gray-white, highly infectious lesions (condylomata lata; see Fig.
Constitutional signs and symptoms that may accompany or precede secondary syphilis include sore throat (15–30%), fever (5–8%), weight loss (2–20%), malaise (25%), anorexia (2–10%), headache (10%), and meningismus (5%). Less common complications of secondary syphilis include hepatitis, nephropathy, gastrointestinal involvement (hypertrophic gastritis, patchy proctitis, or a rectosigmoid mass), arthritis, and periostitis. Meningeal syphilis may present as headache, nausea, vomiting, neck stiffness, cranial nerve involvement, seizures, and changes in mental status. Meningovascular syphilis reflects meningitis together with inflammatory vasculitis of small, medium, or large vessels. Routine serologic testing in early pregnancy is considered cost-effective in virtually all populations, even in areas with a low prenatal prevalence of syphilis.
Late congenital syphilis (untreated after 2 years of age) is subclinical in 60% of cases; the clinical spectrum in the remainder of cases may include interstitial keratitis (which occurs at 5–25 years of age), eighth-nerve deafness, and recurrent arthropathy. Classic stigmata include Hutchinson’s teeth (centrally notched, widely spaced, peg-shaped upper central incisors), “mulberry” molars (sixth-year molars with multiple, poorly developed cusps), saddle nose, and saber shins. The most widely used nontreponemal antibody tests for syphilis are the RPR and VDRL tests, which measure IgG and IgM directed against a cardiolipin-lecithin-cholesterol antigen complex. Both nontreponemal and treponemal tests may be nonreactive in early primary syphilis, although treponemal tests are slightly more sensitive (85–90%) during this stage than nontreponemal tests (?80%). Source: Adapted from the 2010 Sexually Transmitted Diseases Treatment Guidelines from the Centers for Disease Control and Prevention. Persons with newly diagnosed HIV infection should be tested for syphilis; conversely, all patients with newly diagnosed syphilis should be tested for HIV infection. The CDC’s 2010 guidelines for the treatment of syphilis are summarized in Table 206-2 and are discussed below. The use of antibiotics other than penicillin G for the treatment of neurosyphilis has not been studied, although very limited data suggest that ceftriaxone may be used.
Whether or not they are infected, newborn infants of mothers with reactive serologic tests may themselves have reactive tests because of transplacental transfer of maternal IgG antibody. In 2012, the results of studies conducted in Ghana and Papua New Guinea showed that a single dose of oral azithromycin provides the same treatment results as a single injection of benzathine penicillin.
It is said that a€?yaws begins where the road endsa€?, implying it is prevalent among populations living in remote, rural areas with no access to health care. Large-scale treatment of populations in affected communities will interrupt transmission and lead to eradication of the disease.
During treatment campaigns, it is important for health workers to examine people and their close contacts for other symptoms associated with yaws. In the past, children would cry because of the painful injection with benzathine penicillin. Almost 75% of people affected are children under 15 years, although peak incidence occurs in children between the ages 6a€“10. All images on this page may be downloaded and used, provided credit is given to WHO and photographers as mentioned with individual photos. Transmission occurs in the vast majority of cases, by sexual contact and happens by the penetration of bacteria through microscopic wounds or abrasions in the mucosa of the vagina or penis.
Syphilis in pregnant women can cause miscarriage, premature birth, fetal death and malformations.
In women, this injury may go unnoticed, since it is small (on average 1 cm in diameter), painless and usually stay hidden among the pubic hair or inside the vagina. Thus, syphilis is a disease initially painless, it often tends to go unnoticed and seems to disappear spontaneously after some time. About 20% of patients with secondary syphilis do not consider their symptoms bothersome enough to seek medical help. Laboratory confirmation can be made after collecting material from the ulcer for direct visualization of the bacteria under a microscope.
Your window period is shorter, and may be positive already after a few days after the appearance of the chancre.
The values of the VDRL after curing fall progressively, becoming negative after some years.
The criterion of cure of syphilis is the disappearance of symptoms and a fall of 4 degrees in antibody levels. The FTA-ABS does not mean to control treatment, because, as already explained, it is not negative after cure. I was getting ready to mount her the third time but from behind rather than on top and saw the conda latum on her butt and the lesions on her back. Only a minority of these environmental organisms, which are found in soil and water, are important human pathogens.
Treatment of these mycobacteria is complex and should be undertaken with input from experienced clinicians. This drug is active against MAC organisms and many other NTM species, inhibiting protein synthesis by binding to the 50S mycobacterial ribosomal subunit.
Although technically an azalide and not a macrolide, it works similarly to macrolides, inhibiting protein synthesis through binding to the 50S ribosomal subunit. The prolonged duration of treatment has vastly improved results over those obtained in past decades, but drugs and regimens that will shorten treatment duration and limit adverse drug effects and interactions are needed. After an incubation period averaging 2–6 weeks, a primary lesion appears—often associated with regional lymphadenopathy—that resolves without treatment. Since 2000, the number of cases of primary and secondary syphilis has more than doubled, with more than 14,000 cases reported in 2012 (Fig.
It is speculated that recent increases in syphilis and other sexually transmitted infections in MSM may be due to unprotected sex between persons who are HIV concordant and to disinhibition caused by highly effective antiretroviral therapies. In 2011, 360 cases in infants <1 year of age were reported, for a decline of 20% since 2008.
Many have already developed manifestations of syphilis when they are first seen, and ?30% of asymptomatic contacts examined within 30 days of exposure actually have incubating infection and will later develop infectious syphilis if not treated.
The regions that are most affected include sub-Saharan Africa, South America, China, and Southeast Asia. Histopathologic examination shows perivascular infiltration, chiefly by CD4+ and CD8+ T lymphocytes, plasma cells, and macrophages, with capillary endothelial proliferation and subsequent obliteration of small blood vessels. In contrast, some patients may enter the latent stage without ever recognizing secondary lesions. In the Oslo Study, 24% of patients developed relapsing secondary lesions within 4 years, and 28% eventually developed one or more manifestations of tertiary syphilis. Anatomic evidence of aortitis was found in 40–60% of autopsied subjects with syphilis (vs 15% of control subjects), whereas CNS syphilis was found in only 4%. The clinical appearance depends on the number of treponemes inoculated and on the immunologic status of the patient. The healing primary chancre may still be present in ?15% of cases, and the stages may overlap more frequently in persons with concurrent HIV infection. Acute meningitis occurs in only 1–2% of cases, but CSF cell and protein concentrations are increased in up to 40% of cases, and viable T.
Ocular findings associated with secondary syphilis include pupillary abnormalities and optic neuritis as well as the classic iritis or uveitis.
The diagnosis is often suspected on the basis of a history of primary or secondary lesions, a history of exposure to syphilis, or the delivery of an infant with congenital syphilis. CNS syphilis represents a continuum encompassing early invasion (usually within the first weeks or months of infection), months to years of asymptomatic involvement, and, in some cases, development of early or late neurologic manifestations. CSF abnormalities are demonstrated in up to 40% of cases of primary or secondary syphilis and in 25% of cases of latent syphilis.
The most common presentation is a stroke syndrome involving the middle cerebral artery of a relatively young adult.
Tabes dorsalis is a late manifestation of syphilis that presents as symptoms and signs of demyelination of the posterior columns, dorsal roots, and dorsal root ganglia. Early syphilitic aortitis becomes evident soon after secondary lesions subside, and treponemes that trigger the development of gummas may have seeded the tissue years earlier. Histologic examination shows a granulomatous inflammation, with a central area of necrosis due to endarteritis obliterans.
Low-tech point-of-care tests have been developed and are being widely implemented to facilitate antenatal testing in resource-poor settings.


Both are reactive in persons with any treponemal infection, including yaws, pinta, and endemic syphilis. The RPR test is easier to perform and uses unheated serum or plasma; it is the test of choice for rapid serologic diagnosis in a clinical setting.
Among patients being screened for syphilis because of risk factors, clinical suspicion, or history of exposure, ?1% of reactive tests are falsely positive.
When a low-prevalence population for syphilis is screened, the number of false-positive reactions may outnumber true positives, leading to unnecessary treatment. Elevated CSF cell counts and protein concentrations are not specific for neurosyphilis and may be confounded by HIV co-infection. There is evidence that syphilis and other genital ulcer diseases are important risk factors for acquisition and transmission of HIV infection. Preventive treatment is also recommended for individuals who have been exposed to infectious syphilis within the previous 3 months. These regimens appear to be effective in early syphilis but have not been tested for late or late latent syphilis, and compliance may be problematic.
Asymptomatic neurosyphilis may relapse as symptomatic disease after treatment with benzathine penicillin, and the risk of relapse may be higher in HIV-infected patients.
In patients with penicillin allergy demonstrated by skin testing, desensitization and treatment with penicillin are recommended. In the untreated pregnant patient with presumed syphilis, expeditious treatment appropriate to the stage of the disease is essential.
If the patient has a documented penicillin allergy, desensitization and penicillin therapy should be undertaken according to the CDC’s 2010 guidelines.
For asymptomatic infants born to women treated adequately with penicillin during the first or second trimester of pregnancy, monthly quantitative nontreponemal tests may be performed to monitor for appropriate reduction in antibody titers. Reaching some endemic communities to provide treatment can be a daunting task, involving walking very long distances. A new point-of-care syphilis test (DPPA® Syphilis Screen & Confirm Assay) is being evaluated for use in yaws eradication campaigns. Trained volunteers can administer the injections to affected populations without the need for qualified health personnel and nurses.
It is estimated that the risk of contagion in each unprotected sexual intercourse with an infected partner is approximately 30%.
However, there are cases where this interval may be as short as three days or as long as three months. No other symptoms associated with lesions of primary syphilis, the patient has a maximum increase in the groin lymph nodes (buboes).
The problem is that the disappearance of the chancre does not mean healing , however, the bacterium is now multiplied and silently spreads body. Also common are fever, malaise, loss of appetite, joint pain, hair loss, eye lesions and enlarged lymph nodes diffusely throughout the body.
This test is not always necessary, since the genital ulcers of syphilis are well characterized.
So if the test is done one or two days after the appearance of the lesion of syphilis, the VDRL test can give false negative. In immunocompetent hosts, MAC species are most often found in conjunction with underlying significant lung disease, such as chronic obstructive pulmonary disease or bronchiectasis. NTM resistance to macrolides is probably caused by overexpression of the gene ermB, with consequent methylation of the binding site. Resistance to azithromycin is almost always associated with complete cross-resistance to clarithromycin.
The secondary stage, associated with generalized mucocutaneous lesions and generalized lymphadenopathy, is followed by a latent period of subclinical infection lasting years or decades. This spirochete possesses severely limited metabolic capabilities, lacking the genes required for de novo synthesis of most amino acids, nucleotides, and lipids. Less common modes of transmission include nonsexual personal contact, infection in utero, blood transfusion, and organ transplantation. The syphilis epidemic that peaked in 1990 predominantly affected African-American heterosexual men and women and occurred largely in urban areas, where infectious syphilis was correlated with the exchange of sex for crack cocaine. The case definition for congenital syphilis was broadened in 1989 and now includes all live or stillborn infants delivered to women with untreated or inadequately treated syphilis. Thus, identification and treatment of all recently exposed sexual contacts continue to be important aspects of syphilis control. During the past decade, the incidence rate in China has increased by approximately eightfold, and higher rates of infectious syphilis have been reported among MSM in many European countries.
The cellular infiltration displays a TH1-type cytokine profile consistent with the activation of macrophages.
The histopathologic features of secondary maculopapular skin lesions include hyperkeratosis of the epidermis, capillary proliferation with endothelial swelling in the superficial dermis, dermal papillae with transmigration of polymorphonuclear leukocytes, and—in the deeper dermis—perivascular infiltration by CD8+ T lymphocytes, CD4+ T lymphocytes, macrophages, and plasma cells.
Asymptomatic CNS involvement, however, is still demonstrable in up to 40% of persons with early syphilis and 25% of patients with late latent syphilis, and cases of general paresis and tabes dorsalis are being reported from China.
Cardiovascular syphilis, including aortitis, was detected in 10% of patients; 7% of patients developed symptomatic neurosyphilis, and 16% developed benign tertiary gummatous syphilis. A large inoculum produces a dark-field-positive ulcerative lesion in nonimmune volunteers but may produce a small dark-field-negative papule, an asymptomatic but seropositive latent infection, or no response at all in some individuals with a history of syphilis. The skin rash consists of macular, papular, papulosquamous, and occasionally pustular syphilides; often more than one form is present simultaneously. Superficial mucosal erosions (mucous patches) occur in 10–15% of patients and commonly involve the oral or genital mucosa (see Fig. The diagnosis of ocular syphilis is often considered in affected patients only after they fail to respond to steroid therapy. A previous negative serologic test or a history of lesions or exposure may help establish the duration of latent infection, which is an important factor in the selection of appropriate therapy. The onset of symptoms usually occurs <1 year after infection for meningeal syphilis, up to 10 years after infection for meningovascular syphilis, at ?20 years for general paresis, and at 25–30 years for tabes dorsalis. Patients presenting with uveitis, iritis, or hearing loss often have meningeal syphilis, but these clinical findings can also be seen in patients with normal CSF. However, unlike the usual thrombotic or embolic stroke syndrome of sudden onset, meningovascular syphilis often becomes manifest after a subacute encephalitic prodrome (with headaches, vertigo, insomnia, and psychological abnormalities), which is followed by a gradually progressive vascular syndrome. Cardiovascular involvement results in uncomplicated aortitis, aortic regurgitation, saccular aneurysm (usually of the ascending aorta), or coronary ostial stenosis. This timing suggests that the pathogenesis of congenital syphilis, like that of adult syphilis, depends on the host immune response rather than on a direct toxic effect of T.
A recent study demonstrated the high cost-effectiveness of using these tests for screening (with subsequent treatment) in sub-Saharan Africa.
Neurosyphilis was present in about one-quarter of untreated patients with late congenital syphilis in the preantibiotic era.
Historically, dark-field microscopy and immunofluorescence antibody staining have been used to identify this spirochete in samples from moist lesions such as chancres or condylomata lata, but these tests are rarely available outside of research laboratories. The VDRL test remains the standard for examining CSF and is superior to the RPR for this purpose. Whereas IgM titers appear to decline after therapy, the presence or absence of specific IgM does not strictly correlate with T. Modern VDRL and RPR tests are highly specific, and false-positive reactions are largely limited to persons with autoimmune conditions or injection drug use. Some manifestations of syphilis may be altered in patients with concurrent HIV infection, and multiple cases of neurologic relapse after standard therapy have been reported in these patients.
The regimens recommended for prevention are the same as those recommended for early syphilis. Both symptomatic and asymptomatic neurosyphilis should be treated with aqueous penicillin (Table 206-2).
Patients should be warned of the risk of a Jarisch-Herxheimer reaction, which may be associated with mild premature contractions but rarely results in premature delivery.
After treatment, a quantitative nontreponemal test should be repeated monthly throughout pregnancy to assess therapeutic efficacy.
Usually, a single skin lesion develops at the point of entry of the bacterium after 2-4 weeks. Your doctor will usually start treatment based only on clinical data, waiting a week or two to confirm the laboratory diagnosis. For patients with nodular or bronchiectatic MAC lung disease, an initial regimen consisting of clarithromycin or azithromycin, rifampin or rifabutin, and ethambutol is given three times per week.
Treatment for disseminated MAC infection in AIDS patients may be lifelong in the absence of immune reconstitution. It is also the second most common cause of NTM pulmonary disease in the United States, where it is most often reported in the southeastern region.
However, in rapidly growing mycobacteria, an inducible erm gene may confer in vivo macrolide resistance to isolates that are susceptible in vitro.
Clarithromycin is used in combination regimens that typically include ethambutol and a rifamycin in order to avoid the development of macrolide resistance.
Azithromycin is well absorbed orally, with good tissue penetration and a prolonged half-life (~48 h). Central nervous system (CNS) involvement may occur early in infection and may be symptomatic or asymptomatic. Endoflagella wind around the cell body in the periplasmic space and are responsible for motility. Approximately 70% of these cases were in men who have sex with men (MSM), 20–70% of whom are co-infected with HIV (depending on geographic location). Phagocytosis of opsonized organisms by activated macrophages ultimately causes their destruction, resulting in spontaneous resolution of the chancre. Treponemes are found in many tissues, including the aqueous humor of the eye and the cerebrospinal fluid (CSF). The factors that contribute to the development and progression of tertiary disease are unknown.
The ethical issues eventually raised by this study, begun in the preantibiotic era but continuing into the early 1970s, had a major influence on the development of current guidelines for human medical experimentation, and the history of the study may still contribute to a reluctance of some African Americans to participate as subjects in clinical research.
The eruption may be very subtle, and 25% of patients with a discernible rash may be unaware that they have dermatologic manifestations.
Early latent syphilis is limited to the first year after infection, whereas late latent syphilis is defined as that of ?1 year’s duration (or of unknown duration). Neurosyphilis is more frequently symptomatic in patients who are co-infected with HIV, particularly in the setting of a low CD4+ T lymphocyte count.
Trophic joint degeneration (Charcot’s joints) and perforating ulceration of the feet can result from loss of pain sensation. In the preantibiotic era, symptomatic cardiovascular complications developed in ?10% of persons with late untreated syphilis.
Adverse outcomes were reduced, with 64,000 fewer stillbirths, 25,000 fewer neonatal deaths, and up to 25,000 fewer live births of infants with syphilis. Gummatous periostitis occurs at 5–20 years of age and, as in nonvenereal endemic syphilis, tends to cause destructive lesions of the palate and nasal septum.
Sensitive and specific PCR tests have been developed but are not commercially available, although a number of laboratories perform in-house validated PCR testing. Tissue treponemes can be demonstrated more reliably in research laboratories by PCR or by immunofluorescence or immunohistochemical methods using specific monoclonal or polyclonal antibodies to T.
The RPR and VDRL tests are recommended for screening or for quantitation of serum antibody.
After treatment for early syphilis, nontreponemal test titers will generally decline or the tests will become nonreactive, whereas treponemal tests often remain reactive after therapy and are not helpful in determining the infection status of persons with past syphilis. The prevalence of false-positive results increases with advancing age, approaching 10% among persons >70 years old.
The CSF VDRL test is highly specific and, when reactive, is considered diagnostic of neurosyphilis; however, this test is insensitive and may be nonreactive even in cases of symptomatic neurosyphilis.
Lumbar puncture on all asymptomatic patients with untreated syphilis is impractical and unnecessary. Others, on the basis of their own clinical experience, believe that standard therapy—without CSF examination—is sufficient for all cases of early syphilis in HIV-infected patients without neurologic signs or symptoms.
Penicillin G benzathine cures >95% of cases of early syphilis, although clinical relapse can follow treatment, particularly in patients with concurrent HIV infection.
These nonpenicillin regimens have not been carefully evaluated in HIV-infected individuals and should be used with caution.
Administration either of IV aqueous crystalline penicillin G or of IM aqueous procaine penicillin G plus oral probenecid in recommended doses is thought to ensure treponemicidal concentrations of penicillin G in CSF. Treated women whose antibody titers rise by fourfold or whose titers do not decrease by fourfold over a 3-month period should be re-treated. Detection of neonatal IgM antibody may be useful, but no commercially available test is currently recommended. Specific recommendations for the treatment of infants and older children are included in the CDC’s 2010 treatment guidelines. Patients transmitting syphilis are those with the illness during primary or secondary stages, especially if there are active lesions in the sexual organs.


The two major classes of NTM are the slow-growing and rapidly growing species; subcultures of the latter grow within 1 week.
At least 12 months of MAC therapy and 6 months of effective immune reconstitution may be adequate. It is cleared both hepatically and renally; the dosage should be reduced in renal insufficiency. Adverse effects include frequent gastrointestinal intolerance, hepatotoxicity, headache, rash, and rare instances of hypoglycemia. Its mechanism of action against NTM is unknown but may involve inactivation of cell wall synthesis enzymes. The number of primary and secondary cases among women in the United States increased from 2004 to 2008 but has since been declining in conjunction with a decline in congenital syphilis. Cardiovascular syphilis was documented in 35% of men and 22% of women who eventually came to autopsy. 25e-17), whereas in MSM it may be found in the anal canal or rectum, in the mouth, or on the external genitalia. Therefore, syphilis should be considered even in the evaluation of trivial or atypical dark-field-negative genital lesions.
Initial lesions are pale red or pink, nonpruritic, discrete macules distributed on the trunk and proximal extremities; these macules progress to papular lesions that are distributed widely and that frequently involve the palms and soles (Fig. In addition, recent evidence suggests that syphilis infection worsens the cognitive impairment seen in HIV-infected persons and that this effect persists even after treatment for syphilis.
The small, irregular Argyll Robertson pupil, a feature of both tabes dorsalis and paresis, reacts to accommodation but not to light. Common sites include the skin and skeletal system; however, any organ (including the brain) may be involved. The risk of fetal infection during untreated early maternal syphilis is ?75–95%, decreasing to ?35% for maternal syphilis of >2 years’ duration. Neonatal death is usually due to pulmonary hemorrhage, secondary bacterial infection, or severe hepatitis.
The titer reflects disease activity, rising during the evolution of early syphilis, often exceeding 1:32 in secondary syphilis, and declining thereafter without therapy. Moreover, no commercially available IgM test is recommended, even for evaluation of infants with suspected congenital syphilis.
In a patient with a false-positive nontreponemal test, syphilis is excluded by a nonreactive treponemal test. The FTA-ABS test on CSF is reactive far more often than the VDRL test on CSF in all stages of syphilis, but reactivity may reflect passive transfer of serum antibody into the CSF. Because standard therapy with penicillin G benzathine fails to result in treponemicidal drug levels in CSF, however, it is important to identify those persons at higher risk for having or developing neurosyphilis so that appropriate therapy may be given. As described above, RPR titer and CD4+ T cell count can be used to identify patients at higher risk of neurosyphilis for lumbar puncture, although some cases of neurosyphilis will be missed, even when these criteria are used.
The efficacy of penicillin against syphilis remains undiminished after 60 years of use, and there is no evidence of penicillin resistance in T. However, responses to therapy for cardiovascular syphilis are not dramatic because aortic aneurysm and aortic regurgitation cannot be reversed by antibiotics. If compliance and follow-up cannot be ensured, penicillin-allergic HIV-infected persons with late latent or late syphilis should be desensitized and treated with penicillin. The clinical response to penicillin therapy for meningeal syphilis is dramatic, but treatment of neurosyphilis with existing parenchymal damage may only arrest disease progression. Although not 100% effective, the condom is still the best method for preventing sexual transmission of syphilis. The growth characteristics of NTM have diagnostic, therapeutic, and prognostic implications. Clarithromycin is a substrate for and inhibits cytochrome 3A4 and should not be administered with cisapride, pimozide, or terfenadine because cardiac arrhythmias may occur.
Clarithromycin is contraindicated during pregnancy because of its teratogenicity in animal models. Azithromycin is used in combination with other agents to avoid the development of resistance. The organism contains numerous compensatory genes predicted to encode transporters of amino acids, carbohydrates, and lipids.
Surveillance of the number of new cases of primary and secondary syphilis has revealed multiple 7- to 10-year cycles, which may be attributed to herd immunity in at-risk populations, changing sexual behaviors, and changes in control efforts. Clinical hepatitis and immune complex–induced glomerulonephritis are relatively rare but recognized manifestations of secondary syphilis; liver function tests may yield abnormal results in up to one-quarter of patients with early syphilis. In general, serious late complications were nearly twice as common among men as among women. The genital lesions that most commonly must be differentiated from those of primary syphilis include those caused by herpes simplex virus infection (Chap.
Hepatic involvement is common in syphilis; although it is usually asymptomatic, up to 25% of patients may have abnormal liver function tests. Linear calcification of the ascending aorta on chest x-ray films suggests asymptomatic syphilitic aortitis, as arteriosclerosis seldom produces this sign.
Gummas of the skin produce indolent, painless, indurated nodular or ulcerative lesions that may resemble other chronic granulomatous conditions, including tuberculosis, sarcoidosis, leprosy, and deep fungal infections. Adequate treatment of the woman before the 16th week of pregnancy should prevent fetal damage, and treatment before the third trimester should adequately treat the infected fetus. Where the prevalence of syphilis is high or when the patient is at high risk of reinfection, serologic testing should be repeated in the third trimester and at delivery.
When used to confirm positive nontreponemal test results, treponemal tests have a very high positive predictive value for diagnosis of syphilis. A nonreactive FTA-ABS test on CSF, however, may be used to rule out asymptomatic neurosyphilis. Therapy appropriate for neurosyphilis should be given if there is any evidence of CNS infection.
The rate of growth can provide useful preliminary information within a specific clinical context, in that growth within 2–3 weeks is much more likely to indicate an NTM than M.
For prophylaxis against disseminated MAC infection in immunocompromised individuals, a dose of 1200 mg once per week is given. The half-life of cefoxitin is ~1 h, with primarily renal clearance that requires adjustment in renal insufficiency. In addition, genome analyses and other studies have revealed the existence of a 12-member gene family (tpr) that bears similarities to variable outer-membrane antigens of other spirochetes. The median incubation period in humans (?21 days) suggests an average inoculum of 500–1000 infectious organisms for naturally acquired disease; the incubation period rarely exceeds 6 weeks. 25e-18 and 25e-19) Rarely, severe necrotic lesions (lues maligna) may appear; they are more commonly reported in HIV-infected individuals. Moreover, syphilis has been transmitted through blood transfusion or organ donation from patients with latent syphilis. Although the prognostic implications of these findings in early syphilis are uncertain, it may be appropriate to conclude that even patients with early syphilis who have such findings do indeed have asymptomatic neurosyphilis and should be treated for neurosyphilis; such treatment is particularly important in patients with concurrent HIV infection. Untreated maternal infection may result in a rate of fetal loss of up to 40% (with stillbirth more common than abortion because of the late onset of fetal pathology), prematurity, neonatal death, or nonfatal congenital syphilis.
Neonatal congenital syphilis must be differentiated from other generalized congenital infections, including rubella, cytomegalovirus or herpes simplex virus infection, and toxoplasmosis, as well as from erythroblastosis fetalis. VDRL titers do not correspond directly to RPR titers, and sequential quantitative testing (as for response to therapy) must employ a single test. The utility of measuring CXCL13 in CSF to distinguish between neurosyphilis and HIV-related CSF abnormalities has been demonstrated. Serologic testing after treatment is important for all patients with syphilis, particularly for those also infected with HIV. Rifampin lowers clarithromycin levels; conversely, rifampin levels are increased by clarithromycin. Adverse effects are uncommon but include gastrointestinal manifestations, rash, eosinophilia, fever, and neutropenia. One member, TprK, has discrete variable (V) regions that undergo antigenic variation during infection, providing a mechanism for immune evasion. The paradoxical appearance of secondary manifestations despite high titers of antibody (including immobilizing antibody) to T.
Consequently, primary syphilis goes unrecognized in women and homosexual men more often than in heterosexual men. Involvement of the hair follicles may result in patchy alopecia of the scalp hair, eyebrows, or beard in up to 5% of cases. Renal involvement usually results from immune complex deposition and produces proteinuria associated with an acute nephrotic syndrome. Before the advent of penicillin, the risk of development of clinical neurosyphilis in untreated asymptomatic persons was roughly proportional to the intensity of CSF changes, with the overall cumulative probability of progression to clinical neurosyphilis ?20% in the first 10 years but increasing with time. Among infants born alive, only fulminant congenital syphilis is clinically apparent at birth, and these babies have a very poor prognosis.
As will be discussed (see “Evaluation for Neurosyphilis,” below), the RPR titer may be useful in determining which patients will benefit from CSF examination. Large-scale prospective studies have now provided evidence-based guidelines for determining which syphilis patients may benefit most from CSF examination for evidence of neurosyphilis. When NTM do grow from cultures, colonization should be distinguished from active disease in order to optimize the risk and benefit of prolonged treatment with multiple medications.
Like those of primary syphilis, the manifestations of the secondary stage resolve spontaneously, usually within 1–6 months. It is now apparent, however, that the more sensitive treponemal antibody tests rarely, if ever, become nonreactive without treatment. Most experts agree that neurosyphilis is more common in HIV-infected persons, while immunocompetent patients with untreated latent syphilis and normal CSF probably run a very low risk of subsequent neurosyphilis. Treponemal tests are likely to remain reactive even after adequate treatment and cannot differentiate past from current T. Until recently, the subspecies were distinguished primarily by the clinical syndromes they produce. Secondary lesions generally subside within 2–6 weeks, and the infection enters the latent stage, which is detectable only by serologic testing. Regional (usually inguinal) lymphadenopathy accompanies the primary syphilitic lesion, appearing within 1 week of lesion onset.
Although progression to clinically evident late syphilis is very rare today, the occurrence of spontaneous cure is in doubt. In several recent studies, neurosyphilis was associated with a rapid plasma reagin (RPR) titer of ?1:32, regardless of clinical stage or HIV infection status. Isolation of NTM from blood or from an infected-appearing extrapulmonary site, such as soft tissue or bone, is usually indicative of disseminated or local NTM infection (Chap. Researchers have now identified molecular signatures that can differentiate the three subspecies of T.
In the preantibiotic era, up to 25% of untreated patients experienced at least one generalized or localized mucocutaneous relapse, usually during the first year.
Therefore, identification and examination of sexual contacts are most important for patients with syphilis of <1 year’s duration. Inguinal lymphadenopathy is bilateral and may occur with anal as well as with external genital chancres. Macrolide resistance mutations have been identified in nearly all samples reported from some regions of China. The chancre generally heals within 4–6 weeks (range, 2–12 weeks), but lymphadenopathy may persist for months. In contrast, a study based in Madagascar documented the equivalence of benzathine penicillin and azithromycin for treatment of early syphilis, although a sample from one azithromycin clinical failure in that study showed the presence of a 23S rRNA resistance mutation. Side effects of the regimens employed are common, and intermittent therapy is often used to mitigate these adverse events. A more recent survey from South Africa showed a very low (1%) frequency of known 23s rRNA resistance mutations. Treatment regimens depend on the NTM species, the extent or type of disease, and—to some degree—drug susceptibility test results. In short, the prevalence of resistant strains varies widely by geographic location, and routine treatment of syphilis with azithromycin is not recommended.
The nodular bronchiectatic form of MAC infection is generally treated three times per week, whereas fibrocavitary or disseminated MAC infection is treated daily.
In all cases, careful follow-up of any patient treated for syphilis with azithromycin must be ensured.




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