Safety and immunogenicity of a single dose of Tdap compared to Td in pregnant women in Mali and 3 its effect on infant immune responses: a single-centre, randomised, double-blind, active-controlled phase 2 study.

Background: While maternal pertussis vaccination is a strategy to reduce infant morbidity, safety and immunogenicity data are limited in sub-Saharan Africa. We aimed to evaluate the safety of a single dose of tetanus, diphtheria and acellular pertussis vaccine (Tdap) vaccine compared to tetanus and diphtheria vaccine (Td) vaccine in pregnant women in Bamako, Mali and to assess the pertussis toxin (PT) antibody response at birth. Methods: In this phase 2, single-centre, randomised, double-blind, active-controlled study, from 23 January 2019 to 10 July 2019, healthy 18-39 year old women in the second trimester of a singleton pregnancy were randomised 2:1 to receive Tdap or Td. Blood was tested for serum immunoglobulin G (IgG) against PT and other vaccine antigens using a qualified Meso Scale Discovery multiplex immunoassay. The co-primary objectives evaluated safety and birth anti-PT levels. Infant immune responses to whole-cell pertussis vaccine (DTwP) were assessed. Statistical analysis was descriptive. This trial is registered with clinicaltrials.gov, NCT03589768. Findings: 133 women received Tdap and 67 received Td, with 126 and 66 livebirths, respectively. In the Tdap group, 22 serious adverse events (SAEs) including one maternal death occurred in 20 participants (15·0%), with 10 SAEs in 10 participants (14·9%) in the Td group. Among infants, 18 events occurred among 13 participants (10.3%) and 8 SAEs in 6 participants (9.1%), including three and two infant deaths, occurred in Tdap and Td groups, respectively. None were related to study vaccines. Anti-PT geometric mean concentration (GMC) at birth in the Tdap group was higher than in the Td group (55.4 [46.2-66.6] IU/ml vs 7.9 [5.4-11.5] IU/ml). One month after the third dose of DTwP, the GMC in infants born to mothers in the Tdap group were lower compared to the Td group (20.2 [13.7-29.9] IU/ml vs 77.2 [32.2-184.8] IU/ml). By 6 months of age, the anti- PT GMCs were 17.3 [12.8-23.4] IU/ml and 67.1 [35.5-126.7] IU/ml in Tdap and Td groups, respectively. At birth, anti-tetanus toxin (TT) GMCs were higher in infants in the Td vs Tdap group (5.9 [5.0-7.0] IU/ml vs 4.1 [3.5-4.8] IU/ml). Anti-diphtheria toxin GMCs were similar in both groups. Interpretation: Tdap administered to pregnant women in Mali is safe and well-tolerated. Infants of mothers who received Tdap were born with high PT and protective anti-TT antibody levels. By six months of age, after primary vaccination, the PT levels were lower in the Tdap group compared to the Td group. The blunted immune responses to primary DTwP vaccination in the Tdap infant group warrant further study. Funding: This project was funded by National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), under contract numbers 75N93021C00012 (The Emmes Company), and HHSN27220130000221 (University of Maryland, Baltimore). Dr. Susana Portillo was supported by NIH award no. T32AI007524. NIAID, NIH provided Tdap vaccine (BOOSTRIX).

Evaluating the Efficacy of Eradicating Gardnerella vaginalis Vaginal Colonization With Amoxicillin: A Randomized, Double-Blind, Phase 2 Study.

BACKGROUND: Research suggests that Gardnerella vaginalis (GV) is the keystone pathogen in bacterial vaginosis (BV). Knowledge gaps exist regarding the role of GV eradication in the development of BV. This study was designed to test the hypothesis that vaginal colonization with GV could be eradicated by treatment of women without BV with amoxicillin, a drug highly active against GV. If GV is necessary for the development of BV, then eradication of GV may prevent the development of BV. METHODS: We conducted a randomized control trial of amoxicillin 500 mg twice daily versus placebo for 7 days in women aged 18 to 45 years without vaginitis who screened positive for vaginal colonization with GV by quantitative polymerase chain reaction. Test-of-cure visit for GV was conducted at day 21. RESULTS: One hundred seventy-two women met preliminary criteria and were screened for enrollment. Ninety-seven GV-positive women were randomized to receive amoxicillin versus placebo. Eradication of GV occurred in 21% of women randomized to amoxicillin versus 16% on placebo (P = 0.757). In the 4 weeks between screening and test-of-cure visit, 16 of 92 (17%) of participants developed Nugent scores greater than 3 with 8 of 92 (9%) having BV. All of these were in participants in whom GV was not eradicated (P = 0.035). CONCLUSIONS: The study failed to show a benefit of treatment with amoxicillin to eradicate GV. No participants in whom GV was eradicated had progression to abnormal vaginal flora during the study period.

Doxycycline Versus Azithromycin for the Treatment of Rectal Chlamydia in Men Who Have Sex With Men: A Randomized Controlled Trial.

BACKGROUND: Azithromycin and doxycycline are both recommended treatments for rectal Chlamydia trachomatis (CT) infection, but observational studies suggest that doxycycline may be more effective. METHODS: This randomized, double-blind, placebo-controlled trial compared azithromycin (single 1-g dose) versus doxycycline (100 mg twice daily for 7 days) for the treatment of rectal CT in men who have sex with men (MSM) in Seattle and Boston. Participants were enrolled after a diagnosis of rectal CT in clinical care and underwent repeated collection of rectal swabs for nucleic acid amplification testing (NAAT) at study enrollment and 2 weeks and 4 weeks postenrollment. The primary outcome was microbiologic cure (CT-negative NAAT) at 4 weeks. The complete case (CC) population included participants with a CT-positive NAAT at enrollment and a follow-up NAAT result; the intention-to-treat (ITT) population included all randomized participants. RESULTS: Among 177 participants enrolled, 135 (76%) met CC population criteria for the 4-week follow-up visit. Thirty-three participants (19%) were excluded because the CT NAAT repeated at enrollment was negative. Microbiologic cure was higher with doxycycline than azithromycin in both the CC population (100% [70 of 70] vs 74% [48 of 65]; absolute difference, 26%; 95% confidence interval [CI], 16-36%; P < .001) and the ITT population (91% [80 of 88] vs 71% [63 of 89]; absolute difference, 20%; 95% CI, 9-31%; P < .001). CONCLUSIONS: A 1-week course of doxycycline was significantly more effective than a single dose of azithromycin for the treatment of rectal CT in MSM. CLINICAL TRIALS REGISTRATION: NCT03608774.

Resistance-Guided Treatment of Gonorrhea: A Prospective Clinical Study.

BACKGROUND: Novel treatment strategies to slow the continued emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae are urgently needed. A molecular assay that predicts in vitro ciprofloxacin susceptibility is now available but has not been systematically studied in human infections. METHODS: Using a genotypic polymerase chain reaction assay to determine the status of the N. gonorrhoeae gyrase subunit A serine 91 codon, we conducted a multisite prospective clinical study of the efficacy of a single oral dose of ciprofloxacin 500 mg in patients with culture-positive gonorrhea. Follow-up specimens for culture were collected to determine microbiological cure 5-10 days post-treatment. RESULTS: Of the 106 subjects possessing culture-positive infections with wild-type gyrA serine N. gonorrhoeae genotype, the efficacy of single-dose oral ciprofloxacin treatment in the per-protocol population was 100% (95% 1-sided confidence interval, 97.5-100%). CONCLUSIONS: Resistance-guided treatment of N. gonorrhoeae infections with single-dose oral ciprofloxacin was highly efficacious. The widespread introduction and scale-up of gyrA serine 91 genotyping in N. gonorrhoeae infections could have substantial medical and public health benefits in settings where the majority of gonococcal infections are ciprofloxacin susceptible. CLINICAL TRIALS REGISTRATION: NCT02961751.

Associations with retinal vascular occlusions in a diverse, urban population.

PURPOSE: Retinal vascular occlusions can lead to sudden and permanent visual impairment or blindness. Few epidemiological studies on retinal vascular occlusions have been conducted, especially on diverse populations. METHODS: This is a retrospective case-control study of all incident retinal vascular occlusions occurring during a three and one-half year study period at Montefiore Medical Center, capturing all potential cases by diagnosis codes. Patients with retinal venous occlusions (RVO) and retinal arterial occlusions (RAO) were analyzed separately and compared to age-matched control groups. RESULTS: All potential charts (n = 700) were reviewed, confirming 214 RVO and 35 RAO incident cases. In multivariable analyses, RVO was associated with type 2 diabetes mellitus (OR 2.41, p < 0.001), history of cerebrovascular accident (OR 2.14, p = 0.011), hypertension (OR 1.83, p = 0.004), glaucoma (OR 6.91, p < 0.001), black race (OR 3.72, p < 0.001), and male gender (OR 2.19 p < 0.001). RAO was significantly associated with current and former smoking combined (OR 8.95, p = 0.021) and male gender (OR 2.56, p = 0.038). CONCLUSION: Cardiovascular risk factors and glaucoma are reaffirmed as significant predictors of retinal vascular occlusions in a diverse patient population. Retinal vascular occlusions are more common in certain races and ethnicities, and further study into this may help identify high-risk individuals based on demographics.

Case-Control Study of Herpes Simplex Eye Disease: Bronx Epidemiology of Human Immunodeficiency Virus Eye Studies.

PURPOSE: To determine whether human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS), diabetes mellitus, and atopic disease are associated with herpes simplex virus (HSV) eye disease and to examine the characteristics of patients with HIV infection and HSV eye disease. DESIGN: Retrospective case-control study. METHODS: A hospital-based control group was matched to outpatient visits from June 1, 2010, through May 31, 2014, at Montefiore Medical Center (Bronx, NY). Inclusion criteria were a diagnosis of HSV eye disease during the study period and residency in the Bronx. Associations evaluated included age, sex, HIV/AIDS, diabetes mellitus, and atopic disease. RESULTS: HSV eye disease was confirmed in 70 patients, who were compared with 280 controls. Patients with ocular HSV had a greater prevalence of HIV/AIDS compared with controls (8.6% and 2.9%, respectively). Using multivariate analysis to control for age and sex, atopic dermatitis [odds ratio (OR) 3.08, 95% confidence interval (CI), 0.84-11.20] and diabetes with chronic complications (OR 2.25, 95% CI, 0.91-5.61) approached significance, whereas HIV/AIDS (OR 3.37, 95% CI, 1.09-10.40), an age less than 45 years (OR 2.89, 95% CI, 1.54-5.41), and male sex (OR 1.85, 95% CI, 1.07-3.18) were significant. In patients with HIV infection and HSV eye disease, 3 of 6 (50%) had confirmed AIDS at the time of ocular HSV diagnosis. CONCLUSIONS: Patients with HIV infection have more than a 3-fold increased risk of developing ocular HSV.