Neurosyphilis: a series of 178 cases at the 3rd-level hospital of Marrakesh (Morocco).

Neurosyphilis (NS) is an infection of the central nervous system (CNS), caused by Treponema pallidum. Up to 4-10% of patients with untreated syphilis may develop NS which still constitutes a health challenge. The aim of this study is to analyze epidemiological, clinical, paraclinical, therapeutic, and progression profiles of NS in the south of Morocco. Authors analyzed retrospectively 178 files of patients with neurosyphilis, collected in the Neurology Department of Marrakesh over 25 years from January 1994 to March 2019. In our study, the mean age was 46 years (17-75 years). The number of males was dominant (87.6%). The most common presentation was meningoencephalitis. Four cases were atypical (late congenital syphilis, amyotrophic lateral sclerosis, neurosyphilis associated with neuro-Behcet's disease, and acute polyradiculoneuropathy). All patients had positive TPHA and VDRL serologies in blood; CSF-TPHA was positive in all patients, and CSF-VDRL was positive in 64.0% of patients. CT scan and brain MRI showed cortical atrophy in the majority of cases. One hundred seventy-seven patients were treated with intravenous injection of aqueous penicillin G. Neurosyphilis is still a significant medical problem in developing countries, and its occurrence in HIV infection is the reason for a growing number of new cases in developed countries. Given the frequent atypical manifestations of the disease, screening for neurosyphilis should be considered in all patients with neurological or psychiatric symptoms.

Unusual erythematous plaque with white scales, a case of acquired syphilis in a child and literature review.

BACKGROUND: Syphilis in children is uncommon with the mode of infection for this rare condition likely being congenital or acquired. While most acquired cases of syphilis in children result from sexual abuse, children can also be infected with syphilis through kissing, breastfeeding, sharing of daily necessities or pre-chewed food. Here, we report a case of acquired secondary syphilis in a child due to consumption of pre-chewed-food and provide a review of the literature on the characteristics of acquired syphilis in preschool children. CASE PRESENTATION: A 3-year-old girl presented with erythematous plaques and scales on her head, neck, and thighs as well as flat red papules with a moist, well circumscribed surface covered with a grayish-white film. The grandmother who cared for the girl was in the habit of pre-chewing food before giving it to the girl. The child and grandmother tested positive for RPR. The girl, who was not sexually abused, was diagnosed with acquired secondary syphilis, resulting from the transmission of pre-chewed food from her grandmother. CONCLUSIONS: Our case report and literature review reveal that close contact among family members can result in the transmission of syphilis. We recommend that pre-chewing food should be discouraged by caregivers when caring for their children to avoid disease transmission.

Phase II trial evaluating the clinical efficacy of cefixime for treatment of active syphilis in non-pregnant women in Brazil (CeBra).

BACKGROUND: Syphilis is a sexually and vertically transmitted infection caused by the bacteria Treponema pallidum for which there are few proven alternatives to penicillin for treatment. For pregnant women infected with syphilis, penicillin is the only WHO-recommended treatment that will treat the mother and cross the placenta to treat the unborn infant and prevent congenital syphilis. Recent shortages, national level stockouts as well as other barriers to penicillin use call for the urgent identification of alternative therapies to treat pregnant women infected with syphilis. METHODS: This prospective, randomized, non-comparative trial will enroll non-pregnant women aged 18 years and older with active syphilis, defined as a positive rapid treponemal and a positive non-treponemal RPR test with titer ≥1:16. Women will be a, domized in a 2:1 ratio to receive the oral third generation cephalosporin cefixime at a dose of 400 mg two times per day for 10 days (n = 140) or benzathine penicillin G 2.4 million units intramuscularly based on the stage of syphilis infection (n = 70). RPR titers will be collected at enrolment, and at three, six, and nine months following treatment. Participants experiencing a 4-fold (2 titer) decline by 6 months will be considered as having an adequate or curative treatment response. DISCUSSION: Demonstration of efficacy of cefixime in the treatment of active syphilis in this Phase 2 trial among non-pregnant women will inform a proposed randomized controlled trial to evaluate cefixime as an alternative treatment for pregnant women with active syphilis to evaluate prevention of congenital syphilis. TRIAL REGISTRATION: Trial identifier: www.Clinicaltrials.gov, NCT03752112. Registration Date: November 22, 2018.

Molecular Typing and Macrolide Resistance Analyses of Treponema pallidum in Heterosexuals and Men Who Have Sex with Men in Japan, 2017.

In recent years, syphilis notifications have increased dramatically in Japan. We carried out molecular typing and macrolide resistance analyses of Treponema pallidum subsp. pallidum samples collected from patients at four clinics and a hospital in Tokyo and Osaka prefectures in 2017. The macrolide resistant strain type 14d/f (SS14-like clade) was found in significantly more cases of syphilis among heterosexuals than in those among men who have sex with men (MSM); i.e., 79% (31/39) of the strains from heterosexuals were 14d/f compared to 37% (7/19) of those from MSM (odds ratio [OR], 6.6; 95% confidence interval [CI], 1.7 to 26.7; P = 0.002). In addition, 83% (50/60) of the strains were identified as macrolide resistant with an A2058G mutation in the 23S rRNA gene; 90% (35/39) of the strains from heterosexuals were macrolide resistant compared to 58% (11/19) of those from MSM. The odds of having the resistant mutation were considerably higher in the former (OR, 6.4; 95% CI, 1.3 to 33.5; P = 0.02). Heterosexual women and heterosexual men showed similar distributions, and the association remained the same when restricted to men. The strain type distribution and the prevalence of macrolide resistance differed substantially between syphilis strains from heterosexual cases and from MSM cases, suggesting distinct epidemiologic profiles for the two communities and providing important insight into the dynamics of syphilis in Japan.

Molecular Typing and Macrolide Resistance of Syphilis Cases in Manitoba, Canada, From 2012 to 2016.

BACKGROUND: The province of Manitoba, Canada, with a population of approximately 1.3 million, has been experiencing increased incidence of syphilis cases since 2015. In this study, we examined the detection of Treponema pallidum DNA in 354 clinical samples from 2012 to 2016, and determined molecular types and mutations conferring resistance to azithromycin in the polymerase chain reaction (PCR)-positive samples. METHODS: T. pallidum DNA detection was done by PCR amplification of tpp47, bmp, and polA genes. Syphilis serology results were reviewed for the PCR-positive cases. Molecular typing of syphilis strains was done by analysis of the T, pallidum arp, tpr, and tp0548 gene targets as well as partial sequencing of the 23S rRNA gene for azithromycin resistance. RESULTS: Of the 354 samples tested, 74 individual cases were PCR positive. A result from the treponemal antibody chemiluminescent microparticle immunoassay test was positive in 72 of these cases and that from the Venereal Disease Research Laboratory testing was positive in 66. Mutations conferring resistance to azithromycin were found in all 74 PCR-positive samples. Molecular typing was completed on 57 PCR-positive samples, and 12 molecular types were identified with 14d/g found in 63.2%. Increased strain diversity was observed with 8 molecular types detected in 2016, whereas only 2 to 3 types were found in 2012 to 2014. A patient with 2 episodes of infection 9 months apart caused by different molecular strain types was also identified. CONCLUSIONS: The finding of an increase in genetic diversity in the strains in this study and an increase in macrolide resistance compared with previous Canadian reports highlighted the need for continued surveillance including strain characterization.

A double-edged sword: does highly active antiretroviral therapy contribute to syphilis incidence by impairing immunity to Treponema pallidum?

BACKGROUND AND HYPOTHESIS: Recently, the world has experienced a rapidly escalating outbreak of infectious syphilis primarily affecting men who have sex with men (MSM); many are taking highly active antiretroviral therapy (HAART) for HIV-1 infection. The prevailing hypothesis is that HAART availability and effectiveness have led to the perception among both individuals who are HIV-1 infected and those who are uninfected that HIV-1 transmission has become much less likely, and the effects of HIV-1 infection less deadly. This is expected to result in increased sexual risk-taking, especially unprotected anal intercourse, leading to more non-HIV-1 STDs, including gonorrhoea, chlamydia and syphilis. However, syphilis incidence has increased more rapidly than other STDs. We hypothesise that HAART downregulates the innate and acquired immune responses to Treponema pallidum and that this biological explanation plays an important role in the syphilis epidemic. METHODS: We performed a literature search and developed a mathematical model of HIV-1 and T. pallidum confection in a population with two risk groups with assortative mixing to explore the consequence on syphilis prevalence of HAART-induced changes in behaviour versus HAART-induced biological effects. CONCLUSIONS AND IMPLICATIONS: Since rising syphilis incidence appears to have outpaced gonorrhoea and chlamydia, predominantly affecting HIV-1 positive MSM, behavioural factors alone may be insufficient to explain the unique, sharp increase in syphilis incidence. HAART agents have the potential to alter the innate and acquired immune responses in ways that may enhance susceptibility to T. pallidum. This raises the possibility that therapeutic and preventative HAART may inadvertently increase the incidence of syphilis, a situation that would have significant and global public health implications. We propose that additional studies investigating the interplay between HAART and enhanced T. pallidum susceptibility are needed. If our hypothesis is correct, HAART should be combined with enhanced patient management including frequent monitoring for pathogens such as T. pallidum.

Treponema pallidum Strain Types and Association with Macrolide Resistance in Sydney, Australia: New TP0548 Gene Types Identified.

Strain typing of Treponema pallidum, using the three-target enhanced classification scheme, was performed with 191 samples obtained between 2004 and 2011 in Sydney, Australia. The most common strain type was 14d/g (92/191 samples [48%]). Two new TP0548 gene types were detected (m and n). Strain type was associated with macrolide resistance and possible acquisition outside Australia.

Comparison of serological responses to single-dose azithromycin (2 g) versus benzathine penicillin G in the treatment of early syphilis in HIV-infected patients in an area of low prevalence of macrolide-resistant Treponema pallidum infection.

OBJECTIVES: Effectiveness of single-dose azithromycin (2 g) in the treatment of early syphilis among HIV-infected patients has rarely been evaluated in the era of combination ART. METHODS: Consecutive HIV-infected patients with early syphilis, who received 2 g single-dose azithromycin or 2.4 MU benzathine penicillin G, between 2007 and 2014, were prospectively observed. Genotypic resistance to macrolides was determined in Treponema pallidum isolates identified from clinical specimens using PCR assays. Rapid plasma reagin (RPR) titres were determined at baseline and every 3 months after treatment. Primary outcome was a decline of RPR titre by ≥4-fold at 12 months after treatment. RESULTS: During the study period, 162 HIV-infected patients with early syphilis received benzathine penicillin G and 237 patients received azithromycin. At 12 months follow-up, the serological response rate for penicillin and azithromycin groups was 61.1% and 56.5% (P = 0.41), respectively; respective response rate was 61.1% and 65.9% (P = 0.49) if we only included patients infected with T. pallidum not harbouring macrolide resistance in the azithromycin group. In multivariate analysis, RPR titres ≥1:32 (OR 2.56; 95% CI 1.55-4.21) and prior syphilis (OR 0.54; 95% CI 0.35-0.81) were predictors of serological response. Most common adverse effects of azithromycin included diarrhoea (52.7%), nausea (22.4%), abdominal pain (18.6%), bloating (17.7%) and lassitude/somnolence (27.4%). CONCLUSIONS: In the setting of a low prevalence of macrolide-resistant T. pallidum, 2 g single-dose azithromycin achieved a similar serological response to benzathine penicillin G in HIV-infected patients with early syphilis. Major adverse effects of azithromycin were gastrointestinal symptoms and lassitude/somnolence.

Treponema pallidum pallidum Genotypes and Macrolide Resistance Status in Syphilitic Lesions among Patients at 2 Sexually Transmitted Infection Clinics in Lima, Peru.

We report the circulating genotypes and the frequency of macrolide-resistance patterns among Treponema pallidum pallidum DNA isolated from syphilitic lesions from patients who attended 2 sexual health clinics in Lima, Peru. We implemented and used a molecular typing scheme to describe local T. pallidum pallidum strains. Among 14 specimens, subtype 14d/f was the most prevalent strain in 7 fully typed T. pallidum DNA specimens obtained from men who have sex with men and transgender women presenting with chancre-like lesions. No macrolide-resistance mutations were found in T. pallidum DNA from 10 lesions.

First Report of the 23S rRNA Gene A2058G Point Mutation Associated With Macrolide Resistance in Treponema pallidum From Syphilis Patients in Cuba.

This study aimed to assess the presence of macrolide-resistant Treponema pallidum subtypes in Havana, Cuba. Samples from 41 syphilis patients were tested for T. pallidum 23S rRNA gene mutations. Twenty-five patients (61%) harbored T. pallidum with the A2058G mutation, which was present in all 8 subtypes that were identified. The A2059G mutation was not detected.

Molecular Subtyping and Surveillance of Resistance Genes In Treponema pallidum DNA From Patients With Secondary and Latent Syphilis in Hunan, China.

BACKGROUND: Over the past decade, the incidence of syphilis and widespread macrolide resistance in its etiological agent, Treponema pallidum subsp. pallidum, have become a major health concern across countries, including China. Regional trends in subtypes and antibiotic resistance can be monitored effectively by molecular surveillance programs. In this study, whole blood samples were used to assess circulating T. pallidum strains collected from various regions of Hunan, China, between 2013 and 2015. METHODS: Traditional polymerase chain reaction, targeting polA, tpp47, bmp, and tp0319 genes, was used as preliminary screening assay. About 455 polymerase chain reaction-positive specimens were obtained from 2253 whole blood samples of patients with secondary or latent syphilis. Molecular subtyping was performed using a Centers for Disease Control and Prevention-based typing method combined with an analysis of the variable region of tp0548 gene. Resistance to macrolides was analyzed by examining point mutations in 23S rRNA, and the presence of the G1058C point mutation within 16S rRNA associated with decreased susceptibility to doxycycline was assessed. RESULTS: Circulating T. pallidum strains were resolved into 32 subtypes, among which subtype 14d/f was predominant. A2059G mutation in 23S rRNA, and the G1058C mutation in 16S rRNA was absent, but the prevalence of A2058G mutation in 23S rRNA was 97.5%. CONCLUSIONS: We found that it is possible to use whole blood to evaluate molecular subtypes and monitor antibiotic resistance in circulating T. pallidum strains, especially when chancres are absent. High frequency of macrolide-resistant T. pallidum indicates that macrolide antibiotics, such as azithromycin, should be avoided as a treatment option for syphilis in Hunan, China.

Syphilis: An Old Disease With Present-Day Implications.

Syphilis continues to be a burden on the public health system. While men who have sex with men and HIV-infected individuals are the most affected populations, syphilis rates have also increased in reproductive-aged women, resulting in concurrent increases in congenital syphilis. Prompt diagnosis and treatment are requisite components of syphilis control.

Syphilis treatment in the presence of HIV: the debate goes on.

PURPOSE OF REVIEW: Benzathine Penicillin G has been used to treat syphilis for over 50 years; however, the precise regimen of penicillin for treatment of syphilis in HIV-positive individuals remains a hot topic of debate. Although international guidelines recommend the same treatment for syphilis, regardless of HIV status, there are inconsistencies in prescribing practices among clinicians. RECENT FINDINGS: Two previous systematic reviews have found limited evidence for enhanced treatment of syphilis in the presence of HIV. However, a growing body of literature indicates that the rate of asymptomatic neurosyphilis may be higher in HIV, and that syphilis infection is associated with poorer long-term neurocognitive outcomes. A number of retrospective studies propose that serological response may be slower, or serological failure may be higher, among HIV-positive individuals, but these studies are limited by high loss to follow-up, high reinfection rates and a focus on serological rather than clinical response. Beyond penicillin, some evidence suggests equivalence of macrolides, cephalosporins and doxycycline, although macrolide resistance is an increasing concern. SUMMARY: Until a prospective, randomized study is conducted, inconsistency with treatment will continue. We offer a pragmatic approach to recognizing patients who may require further investigation or neuropenetrative antibiotic treatment.

Yaws.

INTRODUCTION: Yaws, caused by Treponema pallidum ssp. pertenue, is endemic in parts of West Africa, Southeast Asia and the Pacific. The WHO has launched a campaign based on mass treatment with azithromycin, to eradicate yaws by 2020. SOURCES OF DATA: We reviewed published data, surveillance data and data presented at yaws eradication meetings. AREAS OF AGREEMENT: Azithromycin is now the preferred agent for treating yaws. Point-of-care tests have demonstrated their value in yaws. AREAS OF CONTROVERSY: There is limited data from 76 countries, which previously reported yaws. Different doses of azithromycin are used in community mass treatment for yaws and trachoma. GROWING POINTS: Yaws eradication appears an achievable goal. The programme will require considerable support from partners across health and development sectors. AREAS TIMELY FOR DEVELOPING RESEARCH: Studies to complete baseline mapping, integrate diagnostic tests into surveillance and assess the impact of community mass treatment with azithromycin are ongoing.

[Macrolide resistance in Treponema pallidum subsp. pallidum in the Czech Republic and in other countries]. / Rezistence puvodce syfilis, Treponema pallidum subsp. pallidum, k makrolidovým antibiotikum v Ceské republice a ve svete.

Treponema pallidum subsp. pallidum (TPA) is the causative agent of the sexually transmitted disease syphilis. In the Czech Republic, several hundred cases of syphilis are reported annually; e.g. in 2012, 696 syphilis cases were documented. In the last decades, an increasing prevalence of macrolide resistant TPA strains harboring A2058G or A2059G mutations in the 23S rRNA gene has been reported. Macrolides were used (and rarely are still being used) in the Czech Republic for the treatment of syphilis in patients allergic to penicillin. While 37% of TPA strains were resistant to macrolides between 2004 and 2010, this rate increased to 67% between 2011-2013. High prevalence of A2058G or A2059G mutations and increasing rates of macrolide resistant TPA strains have also been documented in other developed countries. Therefore, macrolides should not be used in the treatment of syphilis.