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Background. Syphilis infection may potentiate transmission of human immunodeficiency virus (HIV). We sought to determine the extent to which HIV acquisition was associated with syphilis infection within an HIV preexposure prophylaxis (PrEP) trial and whether emtricitabine/tenofovir (FTC/TDF) modified that association. Methods. The Preexposure Prophylaxis Initiative (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily FTC/TDF or placebo. Syphilis prevalence at screening and incidence during follow-up were measured. Hazard ratios for the effect of incident syphilis on HIV acquisition were calculated. The effect of FTC/TDF on incident syphilis and HIV acquisition was assessed. Results. Of 2499 individuals, 360 (14.4%) had a positive rapid plasma reagin test at screening; 333 (92.5%) had a positive confirmatory test, which did not differ between the arms (FTC/TDF vs placebo, P = .81). The overall syphilis incidence during the trial was 7.3 cases per 100 person-years. There was no difference in syphilis incidence between the study arms (7.8 cases per 100 person-years for FTC/TDF vs 6.8 cases per 100 person-years for placebo, P = .304). HIV incidence varied by incident syphilis (2.8 cases per 100 person-years for no syphilis vs 8.0 cases per 100 person-years for incident syphilis), reflecting a hazard ratio of 2.6 (95% confidence interval, 1.6–4.4; P < .001). There was no evidence for interaction between randomization to the FTC/TDF arm and incident syphilis on HIV incidence. Conclusions. In HIV-seronegative MSM, syphilis infection was associated with HIV acquisition in this PrEP trial; a syphilis diagnosis should prompt providers to offer PrEP unless otherwise contraindicated.

Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and cytomegalovirus (CMV) may lead to adverse pregnancy and infant outcomes. The role of combined maternal STIs in HIV mother-to-child transmission (MTCT) was evaluated in mother-infant pairs from NICHD HPTN 040. Urine samples from HIV-infected pregnant women during labor were tested by polymerase chain reaction (PCR) for CT, NG, and CMV. Infant HIV infection was determined by serial HIV DNA PCR testing. Maternal syphilis was tested by VDRL and confirmatory treponemal antibodies. A total of 899 mother-infant pairs were evaluated. Over 30% had at least one of the following infections (TP, CT, NG, and/or CMV) detected at the time of delivery. High rates of TP (8.7%), CT (17.8%), NG (4%), and CMV (6.3%) were observed. HIV MTCT was 9.1% (n = 82 infants). HIV MTCT was 12.5%, 10.3%, 11.1%, and 26.3% among infants born to women with CT, TP, NG or CMV respectively. Forty-two percent of HIV-infected infants were born to women with at least one of these 4 infections. Women with these infections were nearly twice as likely to have an HIV-infected infant (aOR 1.9, 95% CI 1.1-3.0), particularly those with 2 STIs (aOR 3.4, 95% CI 1.5-7.7). Individually, maternal CMV (aOR 4.4 1.5-13.0) and infant congenital CMV (OR 4.1, 95% CI 2.2-7.8) but not other STIs (TP, CT, or NG) were associated with an increased risk of HIV MTCT. HIV-infected pregnant women identified during labor are at high risk for STIs. Co-infection with STIs including CMV nearly doubles HIV MTCT risk. CMV infection appears to confer the largest risk of HIV MTCT. NCT00099359.

To the Editor: In the review article by Stafford et al. (Jan. 18 issue), 1 the description of therapy for congenital syphilis omitted a discussion of the Jarisch–Herxheimer reaction, which was described independently by Jarisch and Herxheimer after treating syphilis with mercury. 2,3 Fever, rigors, hypotension, and worsening of skin lesions are typical clinical findings and may follow therapy for any spirochetal infection. With the current alarming increases in the incidence of syphilis, it is imperative that clinicians appreciate this reaction and not call it an “allergy to penicillin.” Indeed, the only reaction a neonate can have to penicillin is the Jarisch–Herxheimer . . .

One dose of benzathine penicillin G (BPG) has been recommended for HIV-infected patients with early syphilis (primary, secondary, and early latent syphilis) in the sexually transmitted diseases treatment guidelines, but clinical data to support such a recommendation are limited. We prospectively observed the serological response to 1 or 3 weekly doses of BPG in HIV-infected adults who sought treatment of early syphilis at 8 hospitals around Taiwan. Rapid plasma reagin (RPR) titers were followed every 3-6 months after treatment. The serological response was defined as a 4-fold or greater decline in RPR titers at 12 months of treatment. The missing values were treated by following the last-observed-carried-forward principle. We hypothesized that 1 dose was non-inferior to 3 weekly doses of BPG with the non-inferiority margin for the difference of serological response set to 10%. Between 2007 and 2012, 573 patients completed at least 12 months of follow-up: 295 (51.5%) receiving 1 dose of BPG (1-dose group) and 278 (48.5%) 3 doses (3-dose group). Overall, 198 patients (67.1%; 95% confidence interval [CI], 61.4-72.5%) in the 1-dose group achieved serological response at 12 months, as did 208 patients (74.8%; 95% CI, 69.3-79.8%) in the 3-dose group (one-sided 95% CI of the difference, 15.1%). In the multivariate analysis, secondary syphilis (adjusted odds ratio [AOR], 1.90; 95% CI 1.17-3.09), RPR titer ≥32 (AOR, 1.93; 95% CI, 1.38-2.69), and 3 doses of BPG (AOR, 1.68; 95% CI, 1.20-2.36) were independently associated with a serological response. The time to the first episode of treatment failure was 1184 (standard deviation [SD], 70.5) and 1436 (SD, 80.0) days for 1- and 3-dose group, respectively. Single-dose BPG resulted in a higher serological failure rate and shorter time to treatment failure than 3 weekly doses of BPG in the treatment of early syphilis in HIV-infected patients.

This randomized trial involving patients with early syphilis in Tanzania found that treatment with 2 g of azithromycin led to cure rates that were similar to those for penicillin G benzathine at both nine months (97.7 percent and 95.0 percent, respectively) and six months (85.5 percent and 81.5 percent, respectively). This single-dose, oral regimen may be particularly useful in settings in which there are shortages of sterile equipment and trained personnel. In 328 patients with early syphilis in Tanzania, treatment with 2 g of azithromycin led to cure rates that were similar to those for penicillin G benzathine at both nine months and six months. A single intramuscular injection of 2.4 million units (MU) of penicillin G benzathine is the recommended therapy for early syphilis. 1 Major advantages of this regimen are its low cost and absence of problems related to poor adherence, whereas disadvantages include pain associated with large-volume (4 ml), deep, intramuscular injections; the relatively high prevalence of self-reported penicillin allergy in some settings; and the need for injection equipment and medically trained personnel, which may be lacking in countries with few health resources. In addition, there are risks of transmission of blood-borne infections, such as human immunodeficiency virus (HIV), if injection equipment is . . .

Background The infection rate of congenital syphilis is gradually increasing, the clinical manifestations of some children with congenital syphilis are abnormal liver function, which is given the clinical diagnosis of syphilitic hepatitis. At present, there are few studies on the clinical features of children with early congenital syphilis combined with syphilitic hepatitis, so we set out to do such a study. We compared the liver function indicators before and after the treatment of syphilis to find the clinical features that can provide guidance for clinical diagnosis and treatment. Methods This study collected clinical data on 51 children with early congenital syphilis combined with syphilitic hepatitis in Beijing Ditan Hospital, affiliated with Capital Medical University, between April 2014 and October 2019. We observed their age, gender, clinical symptoms, and physical symptoms, as well as the pregnancy and childbirth history of their mothers. We also compared the liver function indicators before and after the treatment of the syphilis and analyzed the children’s clinical features. Results The results of this study showed that the clinical manifestations in children with early congenital syphilis combined with syphilitic hepatitis were diverse. The most common clinical manifestation was anemia (56.9 %), followed by syphilitic rash (54.9 %), hands, feet, and whole-body peeling (35.3 %), and splenomegaly (29.4 %). Liver damage caused by a syphilis infection tends to result in elevated alanine aminotransferase, aspartate aminotransferase, and bilirubin, while albumin decreases. After the syphilis treatment, the liver function indexes were significantly improved compared with before treatment, and the difference was statistically significant (all p < 0.05). Conclusions A child with abnormal liver function, especially with anemia, skin rash, peeling, abdominal distension, and hepatosplenomegaly should be highly suspected of having a syphilis infection. Once the diagnosis is made, the appropriate standard penicillin treatment should be started as soon as possible to improve the condition and prognosis of the child.

The incidence of syphilis has increased steadily over the past 25 years. Undiagnosed cases have presumably increased in the same proportions, and rare complications are at particularly high risk of being unrecognised. A previously healthy 60-year-old man presented with rapidly progressive heart failure and severe aortic and mitral valve insufficiency, with direct valvular destruction and preservation of the aortic valve annulus and aortic root. Treponemal serology was reactive, with rapid plasma reagin titre of 1:128. The patient also had classic manifestations of tertiary syphilis: fusiform aneurysm of the aorta and meningovascular syphilis. He underwent bi-valvular and ascending aorta replacement, and the presence of Treponema pallidum was confirmed by specific immunohistochemistry and PCR in all tissues, including aortic and mitral valves, myocardium, and aorta. This case links T pallidum to infectious endocarditis with severe damage to both aortic and mitral valves, in addition to confirmed syphilitic myocarditis, a long-forgotten complication. It occurred 4 years after probable infection, long before what would be expected according to current understanding of its natural history. Syphilis serology should be considered in patients with culture-negative endocarditis as well as in those with heart failure or arrhythmias of unclear cause, especially in the presence of risk factors for syphilis. Syphilitic endocarditis and myocarditis are potentially lethal but treatable conditions.

Background The destruction of blood eye barrier and the administration of corticosteroid eyedrops after phacoemulsification surgery can lead to the replication of the local potential pathogens. With the rapid increase and popularization of cataract surgery, all kinds of rare postoperative complications have appeared. Here, we report a case of interstitial keratitis and secondary glaucoma after cataract surgery, which may be related to late congenital syphilis, which eventually led to blindness in the right eye. We hope that the timely report of this case will enable doctors to pay more attention to the possibility of potential pathogen replication after cataract surgery, and enable more patients to receive reasonable and effective treatment. Case presentation A 63-year-old female was referred to our clinic for investigation with a 1-week history of moderate pain in the right eye and ipsilateral headache in January 2020. She had cataract surgery on her right eye two years ago and on her left eye one year ago. The intraocular pressure (IOP) in the right eye was 43.2 mmHg and that in the left eye was 28.5 mmHg. Her right eye underwent medication, trabeculectomy and finally was subjected to ciliary body photocoagulation to control the IOP. The IOP of the left eye was well controlled by regular use of eye drops. In addition to the elevated IOP, the inflammation of the anterior segment and corneal stroma was found. Before cataract surgery, bilateral corneal opacities was revealed, but after cataract surgery, interstitial keratitis in both eyes was gradually aggravated, during the follow-up period from 2019 to 2021. She informed us that she had suffered from decreased vision in both eyes and was diagnosed with bilateral keratitis and congenital syphilis at the age of 20. In 2018, the serologic test for syphilis was positive in blood (Chemiluminescence analysis (CLIA): + ; Toluidine red unheated serum test (TRUST): + , titer was 1:1). However, four tests for TRUST were negative in 2019 and 2020, so she was not treated for syphilis. Conclusion This case of glaucoma and interstitial keratitis might be secondary to ocular inflammation caused by late congenital syphilis. The ocular inflammation and the activation of syphilis may be related to cataract surgery.

A 35-year-old man presented with patchy, irregular alopecia of the scalp and a faint, erythematous rash on his trunk and his arms and legs. A diagnosis of secondary syphilis was made.