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Fads and Epidemics in Infectious Disease: Syphilis, Lyme and Bartonella Laura J

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Fads and Epidemics in Infectious Disease: Syphilis, Lyme and Bartonella Laura J Fads and Epidemics in Infectious Disease: Syphilis, Lyme and Bartonella Laura J. Balcer, M.D. Philadelphia, PA Objectives preantibiotic era estimated that syphilis would infect as At the conclusion of this program, participants will be able many as 10% of Americans during their lifetimes.1 to With the development of antibiotics (particularly 1. Identify the neuro-ophthalmologic and ocular manifes- penicillin) and the institution of public health measures to tations of syphilis, Lyme disease, and Bartonella control the spread of disease, incidence rates of primary henselae infection. and secondary infection reduced dramatically, reaching a 2. Apply current techniques for the diagnosis and treat- nadir in 2000 when only 5979 cases were reported in the ment of syphilis, Lyme disease, and Bartonella U.S.1 Since that time, overall incidence rates have again henselae infection with neurologic or ocular involve- increased, with marked variation with respect to geo- ment. graphic, racial, and other demographic factors. Epidemio- 3. Discuss important aspects of the epidemiology and logic studies have also suggested that syphilis increases pathogenesis of syphilis, Lyme disease, and Bartonella susceptibility to human immunodeficiency virus (HIV) henselae infection. infection, and increases the likelihood that patients with both syphilis and HIV will transmit HIV infection.1 To CME Questions control increases in the incidence of primary and second- 1. Which of the following neuro-ophthalmologic manifes- ary syphilis, the U.S. Centers for Disease Control and tations may occur in patients with syphilis, Lyme Prevention (CDC) have launched a National Plan to disease, or Bartonella henselae infection (i.e., which Eliminate Syphilis, with the goal of reducing the annual are common to all three disorders)? number of cases to 1,000 (incidence rate of 0.4/100,000/ a. Dementia year) by 2005.2 b. Optic nerve dysfunction c. Uveitis II. Review of Clinical and Neuro-Ophthalmologic d. Both b and c Features Both the congenital and acquired forms of syphilis may be 2. Adult patients with Lyme disease and ocular or neuro- divided into disease stages. Congenital syphilis includes an logic involvement should receive which of the following early stage that develops before age 2 and resembles the treatments (assuming no allergies to medications)? secondary stage of acquired syphilis, and a late stage that a. Ceftriaxone 2 g IV once/day for 14-28 days corresponds to tertiary syphilis in acquired cases.2 b. Ceftriaxone 1 g IV once/day for 14-28 days Children with early congenital syphilis develop mucocuta- c. Doxycycline 100 mg orally twice daily for 14-21 neous lesions, periostitis, and osteochondritis within days several weeks after birth.2 The most common ocular d. Ceftriaxone 2g IV once/day for 3 months manifestations of this stage include uveitis, chorioretinitis, and retinal vasculitis (salt-and-pepper retinal pigmentary 3. Which of the following are indications for performing a mottling (Table 1).2 Untreated early congenital syphilis lumbar puncture in patients with syphilis? progresses to the late stage, characterized by bony and a. Neurologic or ocular signs and symptoms are dental abnormalities. Interstitial keratitis develops in present children with late congenital syphilis, most commonly b. Patient is HIV positive between the ages of 5 and 20 years (Table 1).2 c. RPR titer is 1:32 or higher Acquired syphilis includes four stages: primary, second- d. All of the above ary, latent (including early and late phases), and tertiary syphilis. Patients with primary syphilis develop a skin Syphilis lesion (chancre) at the site of inoculation with Treponema I. Definition and Epidemiology pallidum; this manifestation occurs within 2-6 weeks 1, 2 Syphilis is an infectious disease caused by the spirochete, following exposure. The chancre is generally painless Treponema pallidum.1, 2 In a manner similar to Lyme and may go unnoticed, although regional lymphadenopathy disease (see below), acquired syphilis infection is charac- may also accompany this stage of infection. terized by a series of overlapping stages, including In untreated patients, secondary syphilis develops primary, secondary, latent, and tertiary disease.1 Infants approximately 4-10 weeks after the appearance of the 1 may also acquire congenital syphilis through maternal- chancre. A diffuse rash develops in >90% of patients, 1 fetal transmission. Syphilis is transmitted through contact and is a presenting manifestation in 70%. The rash of with infectious lesions or body fluids. Studies from the secondary syphilis, while initially macular in nature, may 97 become maculopapular or papulosquamous if left un- treponemal tests in up to 1% of patients.1 The serum treated, affecting the hands and soles of the feet in RPR and VDRL, while useful for screening purposes, addition to other areas.1 Secondary syphilis represents may be negative in patients with neurosyphilis. While it dissemination of infection, and is associated with ophthal- was once taught that treponemal test results remained mologic, neurologic, renal, gastrointestinal, and hepatic positive throughout the lifetimes of patients following disease, as well as constitutional symptoms.1, 2 While the primary infection, a recent study of 857 patients demon- most common ocular manifestation of secondary syphilis strated persistently positive MHA-TP and FTA-ABS is uveitis, this stage also overlaps with early neurosyphilis results in only 87% and 76% of patients, respectively, (a consequence of primary or secondary stages), charac- after a first episode of primary syphilis.1 terized by meningitis, cranial neuropathies, optic neuropa- As recommended by CDC criteria, a lumbar puncture thies (optic neuritis and perineuritis) and meningovascular should be performed in patients with syphilis and any one disease (Table 1).3 Signs and symptoms of secondary of the following features: 1) neurologic or ocular symp- syphilis generally resolve even without treatment, although toms or signs; 2) late latent syphilis or syphilis of unknown recurrences are common (25%).1 The early latent and duration in a patient with HIV; 3) active tertiary syphilis late latent stages of syphilis have been defined by the (i.e., iritis, gumma, aortitis); or 4) treatment failure for CDC as asymptomatic infection during the first year non-neurologic/ocular syphilis.1 Some authors suggest that following initial infection (early latent) or during the period a lumbar puncture should be performed in any patient thereafter (late latent).1 with HIV and syphilis, since these patients, and those with At least 30% of patients with untreated syphilis RPR titers of 1:32 or higher, are at greater risk for central develop late manifestations (tertiary syphilis) between 1 nervous system (CNS) involvement.1 and 50 years following infection.1 Uveitis is again the The interpretation of cerebrospinal fluid (CSF) results most common ocular finding, occurring in 2.5-5% of in patients with syphilis is complicated by the fact that patients who progress to this stage.2 Manifestations of many patients with syphilis also have HIV infection, late neurosyphilis may include meningitis, occlusive which may itself cause a pleocytosis or elevated protein menigovasculitis, cortical atrophy with dementia (general levels.1 CSF VDRL establishes the diagnosis of neuro- paresis), degeneration of the posterior columns (tabes syphilis if the result is positive, but such testing is only 30- dorsalis), and optic atrophy.2, 3 Cardiovascular disease is 70% sensitive.1 CSF FTA-ABS testing, however, is highly also a frequent manifestation of tertiary syphilis. Table 1 sensitive, and a negative result suggests strongly against highlights the most common ocular and neuro-ophthalmo- neurosyphilis.1 Treatment for neurosyphilis (see below) logic manifestations of syphilis, including all stages of should be considered in all patients with syphilis and with disease.1-6 CSF pleocytosis (>5 white blood cells/mm3) or elevated CSF protein level (>45 mg/dL). III. Diagnosis of Syphilis Since Treponema pallidum cannot be cultured, and IV. Treatment and Prevention darkfield examination and direct fluorescent antibody Treatment recommendations for all stages of syphilis, stains from mucocutaneous lesions are insensitive, non- including patients with ocular and neurologic disease, have treponemal serologic tests (rapid plasma regain [RPR] been published by the CDC,1, 2 and are outlined in Table 2. and venereal disease research laboratory [VDRL]) and Parenteral penicillin G is the preferred treatment for all confirmatory treponemal specific tests (T. pallidum stages of syphilis.2 The recommended dose, duration, particle agglutination [TPPA], microhemagluttin assay for preparation, and route of administration (i.e., intravenous Treponema pallidum [MHA-TP], and fluorescent [IV] vs. intramuscular [IM] vs. oral [for doxycycline]) for treponemal antibodies [FTA-ABS]) are the laboratory treatment depend upon the stage of disease, the presence tests of choice for patients with suspected syphilis.1 The of neurologic/ocular involvement, and other host factors. sensitivity of non-treponemal tests ranges from 78-86% in All patients with syphilis should receive clinical follow- primary syphilis, is approximately 100% at the secondary up with serologic testing at 6 and 12 months following stage, and decreases to 95% in latent disease. False- treatment (testing at 3, 9, and 24 months for HIV+ positive non-treponemal serologic tests (RPR titers <1:8 in
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