The Modern Epidemic of Syphilis Ghanem, Khalil G; Ram, Sanjay; Rice, Peter A
The New England journal of medicine,
02/2020, Letnik:
382, Številka:
9
Journal Article
Approximately 1 in 5 adults in the US had a sexually transmitted infection (STI) in 2018. This review provides an update on the epidemiology, diagnosis, and treatment of gonorrhea, chlamydia, ...syphilis, Mycoplasma genitalium, trichomoniasis, and genital herpes.
From 2015 to 2019, the rates of gonorrhea, chlamydia, and syphilis increased in the US; from 1999 to 2016, while the rates of herpes simplex virus type 1 (HSV-1) and HSV-2 declined. Populations with higher rates of STIs include people younger than 25 years, sexual and gender minorities such as men and transgender women who have sex with men, and racial and ethnic minorities such as Black and Latinx people. Approximately 70% of infections with HSV and trichomoniasis and 53% to 100% of extragenital gonorrhea and chlamydia infections are asymptomatic or associated with few symptoms. STIs are associated with HIV acquisition and transmission and are the leading cause of tubal factor infertility in women. Nucleic acid amplification tests have high sensitivities (86.1%-100%) and specificities (97.1%-100%) for the diagnosis of gonorrhea, chlamydia, M genitalium, trichomoniasis, and symptomatic HSV-1 and HSV-2. Serology remains the recommended method to diagnose syphilis, typically using sequential testing to detect treponemal and nontreponemal (antiphospholipid) antibodies. Ceftriaxone, doxycycline, penicillin, moxifloxacin, and the nitroimidazoles, such as metronidazole, are effective treatments for gonorrhea, chlamydia, syphilis, M genitalium, and trichomoniasis, respectively, but antimicrobial resistance limits oral treatment options for gonorrhea and M genitalium. No cure is available for genital herpes. Effective STI prevention interventions include screening, contact tracing of sexual partners, and promoting effective barrier contraception.
Approximately 1 in 5 adults in the US had an STI in 2018. Rates of gonorrhea, chlamydia, and syphilis in the US have increased, while rates of HSV-1 and HSV-2 have declined. Ceftriaxone, doxycycline, penicillin, moxifloxacin, and the nitroimidazoles are effective treatments for gonorrhea, chlamydia, syphilis, Mycoplasma genitalium, and trichomoniasis, respectively, but antimicrobial resistance limits oral therapies for gonorrhea and Mycoplasma genitalium, and no cure is available for genital herpes.
After reaching a nadir at the turn of the century, syphilis rates in the United States have increased since 2000. Treponema pallidum may disseminate to the central nervous system within hours to days ...after inoculation. In this review, we focus on knowledge gaps and areas of controversy in neurosyphilis epidemiology, diagnosis, and management. Modern estimates of the prevalence of neurosyphilis are hindered by the lack of consistent reporting data and are based on relatively small retrospective cohort studies. The various diagnostic modalities for neurosyphilis have significant limitations. Although several novel biomarkers for neurosyphilis have been evaluated, none to date have found a place in clinical practice. The role of a cerebrospinal fluid examination in patients without neurological symptoms continues to be an area of controversy, whereas the data for the use of antibiotic regimens other than intravenous aqueous or intramuscular procaine penicillin for the treatment of neurosyphilis are limited. As syphilis incidence continues to increase unabated in many countries around the world, it is critical to address these gaps of knowledge.
SUMMARYTreponema pallidum subspecies pallidum, the causative agent of syphilis, disseminates to the central nervous system within days after exposure. Clinical manifestations can occur during any ...stage of the infection, and include asymptomatic neurosyphilis, acute meningeal syphilis, meningovascular syphilis, paretic neurosyphilis, and tabetic neurosyphilis. The majority of cases are reported in HIV-infected patients but the epidemiology of modern neurosyphilis is not well defined because of the paucity of population-based data. Decreasing reports of late neurosyphilis have been countered with increasing reports of early neurologic involvement. This review summarizes the clinical manifestations, diagnosis, and therapy of neurosyphilis, focusing on areas of continued controversy, and highlighting several important questions that remain unanswered. Since 2000, the rates of syphilis continue to increase. Given the effectiveness of penicillin therapy, these trends suggest a failure of prevention. Regrettably, rather than become an infection of historical significance, syphilis in the era of HIV continues to challenge researchers and clinicians.
Abstract
A panel of experts generated 5 “key questions” in the management of adult syphilis. A systematic literature review was conducted and tables of evidence were constructed to answer these ...questions. Available data suggest no clinical benefit to >1 dose of benzathine penicillin G for early syphilis in human immunodeficiency virus (HIV)–infected patients. While penicillin remains the drug of choice to treat syphilis, doxycycline to treat early and late latent syphilis is an acceptable alternate option if penicillin cannot be used. There are very limited data regarding the impact of additional antibiotic doses on serologic responses in serofast patients and no data on the impact of additional antibiotic courses on long-term clinical outcomes. In patients with isolated ocular or otic signs and symptoms, reactive syphilis serologic results, and confirmed ocular/otic abnormalities at examination, a diagnostic cerebrospinal fluid (CSF) examination is not necessary, because up to 40% and 90% of patients, respectively, would have no CSF abnormalities. Based on the results of 2 studies, repeated CSF examinations are not necessary for HIV-uninfected patients or HIV-infected patients on antiretroviral therapy who exhibit appropriate serologic and clinical responses after treatment for neurosyphilis. Finally, several important gaps were identified and should be a priority for future research.
Abstract
We reviewed the relevant syphilis diagnostic literature to address the following question: what are the performance characteristics, stratified by the stage of syphilis, for nontreponemal ...serologic tests? The database search included key terms related to syphilis and nontreponemal tests from 1960–2017, and for data related to the venereal disease research laboratory test from 1940–1960. Based on this review, we report the sensitivity and specificity for each stage of syphilis (primary, secondary, early latent, late latent, or unknown duration; tertiary as well as neurosyphilis, ocular syphilis, and otic syphilis). We also report on reactive nontreponemal tests in conditions other than syphilis, false negatives, and automated nontreponemal tests. Overall, many studies were limited by their sample size, lack of clearly documented clinical staging, and lack of well-defined gold standards. There is a need to better define the performance characteristics of nontreponemal tests, particularly in the late stages of syphilis, with clinically well-characterized samples. Published data are needed on automated nontreponemal tests. Evidence-based guidelines are needed for optimal prozone titrations. Finally, improved criteria and diagnostics for neurosyphilis (as well as ocular and otic syphilis) are needed.
A panel of experts generated 8 "key questions" in the management of adult syphilis. A systematic literature review was conducted and tables of evidence were constructed to answer these important ...questions. Penicillin is the drug of choice to treat syphilis. Doxycycline to treat early and late latent syphilis is an acceptable alternate option if penicillin cannot be used. There is no added benefit to enhanced antimicrobial therapy when treating human immunodeficiency virus–infected persons with syphilis. If a patient misses a dose of penicillin in a course of weekly therapy for late syphilis, clinical experience suggests that an interval of 10–14 days between doses might be acceptable before restarting the sequence of injections. Pharmacologic considerations suggest that an interval of 7–9 days between doses, if feasible, may be more optimal. Missed doses are not acceptable for pregnant women. A cerebrospinal fluid examination to diagnose neurosyphilis is recommended in persons diagnosed with tertiary syphilis (eg, cardiovascular syphilis or late benign syphilis), persons with neurological signs or symptoms consistent with neurosyphilis, and asymptomatic persons whose serological titers do not decline appropriately following recommended therapy and in whom reinfection is ruled out. Infection and reinfection rates, particularly among men who have sex with men, are high. Frequent serological screening of this population appears to be the most cost-efficient intervention. The Centers for Disease Control and Prevention continues to recommend the use of the traditional rapid plasma reagin–based screening algorithm. The positive predictive value for syphilis associated with an isolated unconfirmed reactive treponemal chemiluminescence assay or enzyme immunoassay is low if the epidemiological risk and clinical probability for syphilis are low. Among pregnant women with serodiscordant serologies (positive treponemal tests and a negative nontreponemal test), the risk of vertical transmission from mother to infant is low. Several important questions regarding the management of syphilis remain unanswered and should be a priority for future research.
State-of-the-Art Review: Neurosyphilis Hamill, Matthew M; Ghanem, Khalil G; Tuddenham, Susan
Clinical infectious diseases,
2024-May-15, 2024-05-15, 20240515, Letnik:
78, Številka:
5
Journal Article
Recenzirano
Odprti dostop
We review key concepts in the diagnosis, treatment, and follow-up of individuals with neurosyphilis. We describe the epidemiology of syphilis in the United States, highlight populations that are ...markedly affected by this infection, and attempt to estimate the burden of neurosyphilis. We describe the cardinal clinical features of early and late (tertiary) neurosyphilis and characterize the clinical significance of asymptomatic neurosyphilis in the antibiotic era. We review the indications for cerebrospinal fluid (CSF) examination and the performance characteristics of different CSF assays including treponemal and lipoidal antibodies, white cell count, and protein concentration. Future biomarkers and the role of imaging are briefly considered. We review preferred and alternative treatments for neurosyphilis and evidence for their use, including evidence for the use of enhanced intramuscular benzathine penicillin G to supplement intravenous penicillin.
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