Publications by authors named "Jonathan M Zenilman"

105 Publications

Transfusing convalescent plasma as post-exposure prophylaxis against SARS-CoV-2 infection: a double-blinded, phase 2 randomized, controlled trial.

Clin Infect Dis 2022 May 17. Epub 2022 May 17.

Department of Pathology, Northshore University Health System, Evanston, Illinois, USA.

Background: The efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection.

Methods: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed COVID-19 in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection.

Results: 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 RT-PCR positivity. Of the remaining 168 participants, 12/81 (14·8%) CCP and 13/87 (14·9%) control recipients developed SARS-CoV-2 infection; 6 (7·4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25·3 vs. 25·2 days; p = 0·49) and COVID-19 (26·3 vs. 25·9 days; p = 0·35) was similar for both groups.

Conclusions: Administration of high-titer CCP as post-exposure prophylaxis, while appearing safe, did not prevent SARS-CoV-2 infection.
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http://dx.doi.org/10.1093/cid/ciac372DOI Listing
May 2022

Randomized controlled trial transfusing convalescent plasma as post-exposure prophylaxis against SARS-CoV-2 infection.

medRxiv 2021 Dec 14. Epub 2021 Dec 14.

Background: The efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. We hypothesized that CCP might prevent infection when administered before symptoms or laboratory evidence of infection.

Methods: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed COVID-19 in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was development of SARS-CoV-2 infection.

Results: 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for SARS-CoV-2 RT-PCR positivity at screening. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. There were 28 adverse events in CCP and 58 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs. 25.2 days; p=0.49) and COVID-19 (26.3 vs. 25.9 days; p=0.35) were similar for both groups.

Conclusion: In this trial, which enrolled persons with recent exposure to a person with confirmed COVID-19, high titer CCP as post-exposure prophylaxis appeared safe, but did not prevent SARS-CoV-2 infection.

Trial Registration: Clinicaltrial.gov number NCT04323800 .
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http://dx.doi.org/10.1101/2021.12.13.21267611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8687473PMC
December 2021

Comparative performance of multiplex salivary and commercially available serologic assays to detect SARS-CoV-2 IgG and neutralization titers.

J Clin Virol 2021 12 9;145:104997. Epub 2021 Oct 9.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Oral fluid (hereafter saliva) offers a non-invasive sampling method for detection of SARS-CoV-2 antibodies. However, data comparing performance of salivary tests against commercially-available serologic and neutralizing antibody (nAb) assays are lacking. This study compared the performance of a laboratory-developed multiplex salivary SARS-CoV-2 IgG assay targeting antibodies to nucleocapsid (N), receptor binding domain (RBD) and spike (S) antigens to three commercially-available SARS-CoV-2 serologic enzyme immunoassays (EIAs) (Ortho Vitros, Euroimmun, and BioRad) and nAb. Paired saliva and plasma samples were collected from 101 eligible COVID-19 convalescent plasma (CCP) donors >14 days since PCR+ confirmed diagnosis. Concordance was evaluated using positive (PPA) and negative (NPA) percent agreement, and Cohen's kappa coefficient. The range between salivary and plasma EIAs for SARS-CoV-2-specific N was PPA: 54.4-92.1% and NPA: 69.2-91.7%, for RBD was PPA: 89.9-100% and NPA: 50.0-84.6%, and for S was PPA: 50.6-96.6% and NPA: 50.0-100%. Compared to a plasma nAb assay, the multiplex salivary assay PPA ranged from 62.3% (N) and 98.6% (RBD) and NPA ranged from 18.8% (RBD) to 96.9% (S). Combinations of N, RBD, and S and a summary algorithmic index of all three (N/RBD/S) in saliva produced ranges of PPA: 87.6-98.9% and NPA: 50-91.7% with the three EIAs and ranges of PPA: 88.4-98.6% and NPA: 21.9-34.4% with the nAb assay. A multiplex salivary SARS-CoV-2 IgG assay demonstrated variable, but comparable performance to three commercially-available plasma EIAs and a nAb assay, and may be a viable alternative to assist in monitoring population-based seroprevalence and vaccine antibody response.
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http://dx.doi.org/10.1016/j.jcv.2021.104997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502080PMC
December 2021

Sexually Transmitted Infections Treatment Guidelines, 2021.

MMWR Recomm Rep 2021 07 23;70(4):1-187. Epub 2021 Jul 23.

These guidelines for the treatment of persons who have or are at risk for sexually transmitted infections (STIs) were updated by CDC after consultation with professionals knowledgeable in the field of STIs who met in Atlanta, Georgia, June 11-14, 2019. The information in this report updates the 2015 guidelines. These guidelines discuss 1) updated recommendations for treatment of Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis; 2) addition of metronidazole to the recommended treatment regimen for pelvic inflammatory disease; 3) alternative treatment options for bacterial vaginosis; 4) management of Mycoplasma genitalium; 5) human papillomavirus vaccine recommendations and counseling messages; 6) expanded risk factors for syphilis testing among pregnant women; 7) one-time testing for hepatitis C infection; 8) evaluation of men who have sex with men after sexual assault; and 9) two-step testing for serologic diagnosis of genital herpes simplex virus. Physicians and other health care providers can use these guidelines to assist in prevention and treatment of STIs.
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http://dx.doi.org/10.15585/mmwr.rr7004a1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344968PMC
July 2021

The Experience of 2 Independent Schools With In-Person Learning During the COVID-19 Pandemic.

J Sch Health 2021 05 25;91(5):347-355. Epub 2021 Mar 25.

Professor, Infectious Diseases Division-JHBMC, Johns Hopkins University School of Medicine, 5200 Eastern Avenue, Baltimore, MD, 21224., USA.

Background: In 2020, US schools closed due to SARS-CoV-2 but their role in transmission was unknown. In fall 2020, national guidance for reopening omitted testing or screening recommendations. We report the experience of 2 large independent K-12 schools (School-A and School-B) that implemented an array of SARS-CoV-2 mitigation strategies that included periodic universal testing.

Methods: SARS-CoV-2 was identified through periodic universal PCR testing, self-reporting of tests conducted outside school, and contact tracing. Schools implemented behavioral and structural mitigation measures, including mandatory masks, classroom disinfecting, and social distancing.

Results: Over the fall semester, School-A identified 112 cases in 2320 students and staff; School-B identified 25 cases (2.0%) in 1400 students and staff. Most cases were asymptomatic and none required hospitalization. Of 69 traceable introductions, 63 (91%) were not associated with school-based transmission, 59 cases (54%) occurred in the 2 weeks post-thanksgiving. In 6/7 clusters, clear noncompliance with mitigation protocols was found. The largest outbreak had 28 identified cases and was traced to an off-campus party. There was no transmission from students to staff.

Conclusions: Although school-age children can contract and transmit SARS-CoV-2, rates of COVID-19 infection related to in-person education were significantly lower than those in the surrounding community. However, social activities among students outside of school undermined those measures and should be discouraged, perhaps with behavioral contracts, to ensure the safety of school communities. In addition, introduction risks were highest following extended school breaks. These risks may be mitigated with voluntary quarantines and surveillance testing prior to reopening.
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http://dx.doi.org/10.1111/josh.13008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251146PMC
May 2021

Comparative performance of multiplex salivary and commercially available serologic assays to detect SARS-CoV-2 IgG and neutralization titers.

medRxiv 2021 Feb 1. Epub 2021 Feb 1.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Oral fluid (hereafter saliva) offers a non-invasive sampling method for the detection of SARS-CoV-2 antibodies. However, data comparing performance of salivary tests against commercially-available serologic and neutralizing antibody (nAb) assays are lacking. This study compared the performance of a multiplex salivary SARS-CoV-2 IgG assay targeting antibodies to nucleocapsid (N), receptor binding domain (RBD) and spike (S) antigens to three commercially-available SARS-CoV-2 serology enzyme immunoassays (EIAs) (Ortho Vitros, Euroimmun, and BioRad) and nAb. Paired saliva and plasma samples were collected from 101 eligible COVID-19 convalescent plasma (CCP) donors >14 days since PCR+ confirmed diagnosis. Concordance was evaluated using positive (PPA) and negative (NPA) percent agreement, overall percent agreement (PA), and Cohen kappa coefficient. The range between salivary and plasma EIAs for SARS-CoV-2-specific N was PPA: 54.4-92.1% and NPA: 69.2-91.7%, for RBD was PPA: 89.9-100% and NPA: 50.0-84.6%, and for S was PPA: 50.6-96.6% and NPA: 50.0-100%. Compared to a plasma nAb assay, the multiplex salivary assay PPA ranged from 62.3% (N) and 98.6% (RBD) and NPA ranged from 18.8% (RBD) to 96.9% (S). Combinations of N, RBD, and S and a summary algorithmic index of all three (N/RBD/S) in saliva produced ranges of PPA: 87.6-98.9% and NPA: 50-91.7% with the three EIAs and ranges of PPA: 88.4-98.6% and NPA: 21.9-34.4% with the nAb assay. A multiplex salivary SARS-CoV-2 IgG assay demonstrated comparable performance to three commercially-available plasma EIAs and a nAb assay, and may be a viable alternative to assist in screening CCP donors and monitoring population-based seroprevalence and vaccine antibody response.
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http://dx.doi.org/10.1101/2021.01.28.21250717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852272PMC
February 2021

Outcomes of Nursing Home COVID-19 Patients by Initial Symptoms and Comorbidity: Results of Universal Testing of 1970 Residents.

J Am Med Dir Assoc 2020 12 14;21(12):1767-1773.e1. Epub 2020 Oct 14.

Department of Medicine-Infectious Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Objective: Clinical implications of asymptomatic cases of the novel coronavirus disease 2019 (COVID-19) in nursing homes remain poorly understood. We assessed the association of symptom status and medical comorbidities on mortality and hospitalization risk associated with COVID-19 in residents across 15 nursing homes in Maryland.

Design: Retrospective cohort study.

Setting And Participants: 1970 residents from 15 nursing home facilities with universal COVID-19 testing in Maryland.

Methods: We used descriptive statistics to compare baseline characteristics, logistic regression to assess the association of comorbidities with COVID-19, and Cox regression to assess the association of asymptomatic and symptomatic COVID-19 with mortality and hospitalization. We assessed the association of comorbidities with mortality and hospitalization risk. Symptom status was assessed at the time of the first test. Maximum follow-up was 94 days.

Results: Among the 1970 residents (mean age 73.8, 57% female, 68% black), 752 (38.2%) were positive on their first test. Residents who were positive for COVID-19 and had multiple symptoms at the time of testing had the highest risk of mortality [hazard ratio (HR) 4.44, 95% confidence interval (CI) 2.97, 6.65) and hospitalization (subhazard ratio 2.38, 95% CI 1.70, 3.33), even after accounting for comorbidity burden. Cases who were asymptomatic at testing had a higher risk of mortality (HR 2.92, 95% CI 1.95, 4.35) but not hospitalization (HR 1.06, 95% CI 0.82, 1.38) compared with those who were negative for COVID-19. Of 52 SARS-CoV-2-positive residents who were asymptomatic at the time of testing and were closely monitored for 14 days at one facility, only 6 (11.6%) developed symptoms.

Conclusions And Implications: Asymptomatic infection with SARS-CoV-2 in the nursing home setting was associated with increased risk of death, suggesting a need for closer monitoring of these residents, particularly those with underlying cardiovascular and respiratory comorbidities.
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http://dx.doi.org/10.1016/j.jamda.2020.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556822PMC
December 2020

Desperate Times: Protecting the Public From Research Without Consent or Oversight During Public Health Emergencies.

Ann Intern Med 2020 12 27;173(11):926-928. Epub 2020 Jul 27.

Johns Hopkins School of Medicine and Johns Hopkins University, Baltimore, Maryland (H.M.L., M.S., R.G.B., D.E.F., B.H., C.W.H., E.V.J., R.D.M., P.R., J.M.Z.).

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http://dx.doi.org/10.7326/M20-4631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401979PMC
December 2020

Trichomonas vaginalis infection and prostate-specific antigen concentration: Insights into prostate involvement and prostate disease risk.

Prostate 2019 10 2;79(14):1622-1628. Epub 2019 Aug 2.

Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.

Background: The protist Trichomonas vaginalis causes a common, sexually transmitted infection and has been proposed to contribute to the development of chronic prostate conditions, including benign prostatic hyperplasia and prostate cancer. However, few studies have investigated the extent to which it involves the prostate in the current antimicrobial era. We addressed this question by investigating the relation between T. vaginalis antibody serostatus and serum prostate-specific antigen (PSA) concentration, a marker of prostate infection, inflammation, and/or cell damage, in young, male, US military members.

Methods: We measured T. vaginalis serum IgG antibodies and serum total PSA concentration in a random sample of 732 young, male US active duty military members. Associations between T. vaginalis serostatus and PSA were investigated by linear regression.

Results: Of the 732 participants, 341 (46.6%) had a low T. vaginalis seropositive score and 198 (27.0%) had a high score, with the remainder seronegative. No significant differences were observed in the distribution of PSA by T. vaginalis serostatus. However, slightly greater, nonsignificant differences were observed when men with high T. vaginalis seropositive scores were compared with seronegative men, and when higher PSA concentrations were examined (≥0.70 ng/mL). Specifically, 42.5% of men with high seropositive scores had a PSA concentration greater than or equal to 0.70 ng/mL compared with 33.2% of seronegative men (adjusted P = .125).

Conclusions: Overall, our findings do not provide strong support for prostate involvement during T. vaginalis infection, although our suggestive positive findings for higher PSA concentrations do not rule out this possibility entirely. These suggestive findings may be relevant for prostate condition development because higher early- to mid-life PSA concentrations have been found to predict greater prostate cancer risk later in life.
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http://dx.doi.org/10.1002/pros.23886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715535PMC
October 2019

Standards for Treatment and Control Regimens in Therapeutic Trials for Gonorrhea: Lessons From a "Failed" Trial.

Sex Transm Dis 2019 05;46(5):287-289

Division of Infectious Diseases, Department of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, MD.

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http://dx.doi.org/10.1097/OLQ.0000000000000994DOI Listing
May 2019

Risk of Gonococcal Infection During Vaginal Exposure is Associated With High Vaginal pH and Active Menstruation.

Sex Transm Dis 2019 02;46(2):86-90

Department of Laboratory Medicine, University of California San Francisco CA.

Background: An understanding of the biological reasons why 25% to 35% of women resist infection during vaginal intercourse with a man infected with Neisseria gonorrhoeae could lead to novel control measures. We sought modifiable biological bases for infection resistance by comparing women in the same core-mixing group who did or did not become infected after sexual exposure.

Methods: We enrolled 61 female contacts of index men with gonorrhea seen at Baltimore City Health Department clinics from January 2008 through May 2012. Exposure and sexual practices and histories, co-infections, physical signs on exam, patient symptom report, and menstrual history were collected.

Results: Thirty-eight (62.3%) of the exposed women developed cervical infections. Multiple logistic regression found that a vaginal pH of 4.5 or higher at presentation to clinic was significantly associated with gonococcal infection (adjusted odds ratio, 5.5; P = 0.037) in women who presented within one menstrual cycle, 35 days. In this group of women, there was a significant association between acquiring an N. gonorrhoeae cervical infection and sexual exposure during menstruation (adjusted odds ratio 12.5; P = 0.05).

Conclusions: Modification of vaginal pH could be explored as novel strategy for reducing the risk of N. gonorrhoeae infections in women.
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http://dx.doi.org/10.1097/OLQ.0000000000000926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892601PMC
February 2019

Sustained influence of infections on prostate-specific antigen concentration: An analysis of changes over 10 years of follow-up.

Prostate 2018 09 30;78(13):1024-1034. Epub 2018 May 30.

Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.

Background: To extend our previous observation of a short-term rise in prostate-specific antigen (PSA) concentration, a marker of prostate inflammation and cell damage, during and immediately following sexually transmitted and systemic infections, we examined the longer-term influence of these infections, both individually and cumulatively, on PSA over a mean of 10 years of follow-up in young active duty U.S. servicemen.

Methods: We measured PSA in serum specimens collected in 1995-7 (baseline) and 2004-6 (follow-up) from 265 men diagnosed with chlamydia (CT), 72 with gonorrhea (GC), 37 with non-chlamydial, non-gonococcal urethritis (NCNGU), 58 with infectious mononucleosis (IM), 91 with other systemic or non-genitourinary infections such as varicella; and 125-258 men with no infectious disease diagnoses in their medical record during follow-up (controls). We examined the influence of these infections on PSA change between baseline and follow-up.

Results: The proportion of men with any increase in PSA (>0 ng/mL) over the 10-year average follow-up was significantly higher in men with histories of sexually transmitted infections (CT, GC, and NCNGU; 67.7% vs 60.8%, P = 0.043), systemic infections (66.7% vs 54.4%, P = 0.047), or any infections (all cases combined; 68.5% vs 54.4%, P = 0.003) in their military medical record compared to controls.

Conclusions: While PSA has been previously shown to rise during acute infection, these findings demonstrate that PSA remains elevated over a longer period. Additionally, the overall infection burden, rather than solely genitourinary-specific infection burden, contributed to these long-term changes, possibly implying a role for the cumulative burden of infections in prostate cancer risk.
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http://dx.doi.org/10.1002/pros.23660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690490PMC
September 2018

A Phase 1 Pharmacokinetic and Safety Study of Extended-Duration, High-dose Cefixime for Cephalosporin-resistant Neisseria gonorrhoeae in the Pharynx.

Sex Transm Dis 2018 10;45(10):677-683

Clinical RM, Inc, Hinckley.

Background: There are no fully oral recommended treatment regimens for gonorrhea. Inadequately treated pharyngeal gonococcal infections are a likely reservoir for transmission and development of antimicrobial resistance. We sought to determine an oral cefixime dosing regimen that would theoretically treat pharyngeal infections by gonococci with minimum inhibitory concentrations 0.5 μg/mL.

Methods: We conducted an open-label, nonrandomized, phase I pharmacokinetic and safety study of cefixime in 25 healthy male and female volunteers divided into 4 dosing cohorts (cohort A, 400 mg; cohort B, 800 mg; cohort C, 1200 mg; and cohort D, 800 mg every 8 hours × 3 doses [total dose 2400 mg]) with a target serum concentration of at least 2.0 μg/mL for more than 20 hours. Cefixime concentrations from serum and pharyngeal fluid were determined with use of a validated liquid chromatography-tandem mass spectrometry assay. Safety measures included laboratories, physical examinations, and symptom diaries.

Results: None of the single-dose regimens attained the target concentration; however, 50% of subjects in cohort D attained the target concentration. Variation in absorption and protein binding contributed to differences in concentrations. Pharyngeal fluid concentrations were negligible. The single-dose regimens were well tolerated; the multidose regimen resulted in mild to moderate gastrointestinal symptoms in 43% of subjects.

Conclusions: None of the dosing regimens achieved the target concentration. However, the proposed theoretical target was extrapolated from penicillin data; there are no empirically derived pharmacokinetic/pharmacodynamic criteria for pharyngeal gonorrhea. Under alternative cephalosporin-specific therapeutic goals, the multidose regimen may be effective, although the absence of cefixime in pharyngeal fluid is concerning. A clinical trial evaluating efficacy and defining pharmacokinetic/pharmacodynamic outcomes may be warranted.
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http://dx.doi.org/10.1097/OLQ.0000000000000844DOI Listing
October 2018

Insight into infection-mediated prostate damage: Contrasting patterns of C-reactive protein and prostate-specific antigen levels during infection.

Prostate 2017 May 12;77(13):1325-1334. Epub 2017 Jul 12.

Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.

Background: To investigate mechanisms underlying our previous observation of a large rise in serum prostate-specific antigen, a marker of prostate pathology, during both sexually transmitted and systemic infections, we measured serum high-sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation, in our previous case-control study of young, male US military members and compared our findings to those for PSA.

Methods: We measured hsCRP before and during infection for 299 chlamydia, 112 gonorrhea, and 59 non-chlamydial, non-gonococcal urethritis (NCNGU) cases; before and after infection for 55 infectious mononucleosis (IM) and 90 other systemic/non-genitourinary cases; and for 220-256 controls.

Results: Only gonorrhea cases were significantly more likely to have a large hsCRP rise (≥1.40 mg/L or ≥239%) during infection than controls (P < 0.01). However, gonorrhea, IM, and other systemic/non-genitourinary cases were more likely to have a rise of any magnitude up to one year post-diagnosis than controls (p = 0.038-0.077).

Conclusions: These findings, which differ from those for PSA, suggest distinct mechanisms of elevation for hsCRP and PSA, and support both direct (eg, prostate infection) and indirect (eg, systemic inflammation-mediated prostate cell damage) mechanisms for PSA elevation. Future studies should explore our PSA findings further for their relevance to both prostate cancer screening and risk.
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http://dx.doi.org/10.1002/pros.23392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578879PMC
May 2017

Safety, Tolerability, Systemic Exposure, and Metabolism of CRS3123, a Methionyl-tRNA Synthetase Inhibitor Developed for Treatment of Clostridium difficile, in a Phase 1 Study.

Antimicrob Agents Chemother 2017 08 25;61(8). Epub 2017 Jul 25.

Johns Hopkins University, Baltimore, Maryland, USA.

causes antibiotic-associated diarrhea and is a major public health concern. Current therapies disrupt the protective intestinal flora, do not reliably prevent recurrent infections, and will be decreasingly effective should less susceptible strains emerge. CRS3123 is an oral agent that inhibits bacterial methionyl-tRNA synthetase and has potent activity against and aerobic Gram-positive bacteria but little activity against Gram-negative bacteria, including anaerobes. This first-in-human, double-blind, placebo-controlled, dose escalation study evaluated the safety and systemic exposure of CRS3123 after a single oral dose in healthy adults. Five cohorts of eight subjects each received CRS3123 or placebo in a 3:1 ratio. Doses for the respective active arms were 100 mg, 200 mg, 400 mg, 800 mg, and 1,200 mg. Blood and urine were collected for pharmacokinetic analysis. CRS3123 concentrations were measured with validated LC-MS/MS techniques. There were no serious adverse events or immediate allergic reactions during administration of CRS3123. In the CRS3123-treated groups, the most frequent adverse events were decreased hemoglobin, headache, and abnormal urine analysis; all adverse events in the active-treatment groups were mild to moderate, and their frequency did not increase with dose. Although CRS3123 systemic exposure increased at higher doses, the increase was less than dose proportional. The absorbed drug was glucuronidated at reactive amino groups on the molecule, which precluded accurate pharmacokinetic analysis of the parent drug. Overall, CRS3123 was well tolerated over this wide range of doses. This safety profile supports further investigation of CRS3123 as a treatment for infections. (This study has been registered at ClinicalTrials.gov under identifier NCT01551004.).
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http://dx.doi.org/10.1128/AAC.02760-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527627PMC
August 2017

Semen says: assessing the accuracy of adolescents' self-reported sexual abstinence using a semen Y-chromosome biomarker.

Sex Transm Infect 2017 03 4;93(2):145-147. Epub 2016 May 4.

Behavioural Sciences and Health Education, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.

Objective: Researchers often assess condom use only among participants who report recent sexual behaviour, excluding participants who report no recent vaginal sex or who did not answer questions about their sexual behaviour, but self-reported sexual behaviour may be inaccurate. This study uses a semen Y-chromosome biomarker to assess semen exposure among participants who reported sexual abstinence or did not report their sexual behaviour.

Methods: This prospective cohort study uses data from 715 sexually active African-American female adolescents in Atlanta, surveyed at baseline, 6 months and 12 months. Participants completed a 40 min interview and were tested for semen Y-chromosome with PCR from a self-administered vaginal swab. We predicted Y-chromosome test results from self-reported sexual behaviour using within-subject panel regression.

Results: Among the participants who reported abstinence from vaginal sex in the past 14 days, 9.4% tested positive for semen Y-chromosome. Among item non-respondents, 6.3% tested positive for semen Y-chromosome. Women who reported abstinence and engaged in item non-response regarding their sexual behaviour had respectively 62% and 78% lower odds of testing positive for Y-chromosome (OR 0.38 (0.21 to 0.67), OR 0.22 (0.12 to 0.40)), controlling for smoking, survey wave and non-coital sexual behaviours reported during abstinence.

Conclusions: Adolescents who report sexual abstinence under-report semen exposure. Research should validate self-reported sexual behaviour with biomarkers. Adolescents who engage in item non-response regarding vaginal sex test positive for semen Y-chromosome at similar rates, which supports the practice of grouping non-respondents with adolescents reporting abstinence in statistical analysis.

Trial Registration Number: NCT00633906.
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http://dx.doi.org/10.1136/sextrans-2016-052605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097018PMC
March 2017

Infectious mononucleosis, other infections and prostate-specific antigen concentration as a marker of prostate involvement during infection.

Int J Cancer 2016 May 21;138(9):2221-30. Epub 2016 Jan 21.

Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD.

Although Epstein-Barr virus has been detected in prostate tissue, no associations have been observed with prostate cancer in the few studies conducted to date. One possible reason for these null findings may be use of cumulative exposure measures that do not inform the timing of infection, i.e., childhood versus adolescence/early adulthood when infection is more likely to manifest as infectious mononucleosis (IM). We sought to determine the influence of young adult-onset IM on the prostate by measuring prostate-specific antigen (PSA) as a marker of prostate inflammation/damage among U.S. military members. We defined IM cases as men diagnosed with IM from 1998 to 2003 (n = 55) and controls as men without an IM diagnosis (n = 255). We selected two archived serum specimens for each participant, the first collected after diagnosis for cases and one randomly selected from 1998 to 2003 for controls (index), as well as the preceding specimen (preindex). PSA was measured in each specimen. To explore the specificity of our findings for prostate as opposed to systemic inflammation, we performed a post hoc comparison of other infectious disease cases without genitourinary involvement (n = 90) and controls (n = 220). We found that IM cases were more likely to have a large PSA rise than controls (≥ 20 ng/mL: 19.7% versus 8.8%, p = 0.027; ≥ 40% rise: 25.7% versus 9.4%, p = 0.0021), as were other infectious disease cases (25.7% versus 14.0%, p = 0.020; 27.7% versus 18.0%, p = 0.092). These findings suggest that, in addition to rising because of prostate infection, PSA may also rise because of systemic inflammation, which could have implications for PSA interpretation in older men.
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http://dx.doi.org/10.1002/ijc.29966DOI Listing
May 2016

Sexually Transmitted Diseases and Travel: From Boudoir to Bordello.

Microbiol Spectr 2015 Oct;3(5)

Johns Hopkins Bayview Medical Center, Division of Infectious Diseases, MFL Center Tower, Baltimore, MD 21224.

Travel has historically been an important risk factor for acquisition of sexually transmitted infections (STIs). Travel is often associated with a sense of adventure, periods of loneliness, and exploration away from one's home environment-which often form a milieu in which sexual activity can occur with new partners. Survey data clearly demonstrate that out-of-country travel is associated with recruitment of new sex partners and increased STI risk. Pretravel counseling to prevent STI risk is variable, and there is little evidence that it modifies risk behavior. Some travel occurs specifically for sexual purposes, such as the sexual tourism junkets to Southeast Asian destinations which became popular during the 1980s or the more recent rise in the popularity of circuit parties for men who have sex with men. Some travel situations pose particularly high risks. For example, military deployments and assignments to work camps such as those for oil extraction occur in the context of large groups of individuals of reproductive age, often predominantly males, exposed to high levels of stress in unfamiliar environments. Additionally, over the past decade, the Internet has dramatically changed the ability to identify sexual partners while traveling.
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http://dx.doi.org/10.1128/microbiolspec.IOL5-0011-2015DOI Listing
October 2015

Phase 1 clinical trials of DAS181, an inhaled sialidase, in healthy adults.

Antiviral Res 2015 Nov 25;123:114-9. Epub 2015 Sep 25.

Clinical RM, Inc., Hinckley, OH, United States.

DAS181, (study drug, Fludase®) was developed for treatment of influenza and parainfluenza infections. Delivered by inhalation, DAS181 cleaves sialic acid receptors from respiratory epithelial cells. Treatment of influenza for three days with DAS181 reduced viral shedding. To increase deposition in the upper airways and decrease systemic absorption, the particle size was increased to 10μm. We conducted two Phase I trials with three cohorts, randomized 2:1, active drug to placebo. The initial cohort got a single 20mg dose of DAS181, or placebo; the second, 20mg DAS181 or placebo for 10days, and the third got 20mg of DAS181 or placebo for 3days. Formulations differed slightly in their excipients. Subjects in the 1- and 3-day cohorts completed dosing without serious adverse events. Two subjects in the 10-day cohort stopped at Day 9 after developing respiratory and systemic symptoms, and a third experienced a decrease in FEV1 (Forced Expiratory Volume in 1s) after the 9th dose and a further decline after the 10th dose. Plasma DAS181, in the 10-day cohort, peaked and began falling before the last dose. Antibodies, predominately IgG with neutralizing activity, were detected in 15/18 subjects by Day 30. The highest IgG concentrations were in the 10-day cohort. The respiratory adverse events occurring after seven days and rapid drug clearance during continued dosing are consistent with the induction of DAS181 antibodies. This could preclude use of this medication for longer than seven days or for repeated courses. (These studies have been registered at ClinicalTrials.gov under registration Nos. NCT 00527865 and NCT 01651494.).
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http://dx.doi.org/10.1016/j.antiviral.2015.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639451PMC
November 2015

Prevalence of Implanted Medical Devices in Medicine Inpatients.

J Patient Saf 2018 09;14(3):153-156

Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD.

Implanted medical devices (IMDs) are extremely common, yet they are not systematically documented on hospital admission. Through structured patient interviews, we determined the prevalence of IMDs in hospital inpatients. Using medical record review, we evaluated the sensitivity of the medical record reporting of IMDs on an academic medical inpatient service. Fifty-eight percent of 191 interviewees reported 1 or more IMDs. Participants who reported greater than 1 IMD were older and had more frequent hospitalizations. The most common devices reported were surgical mesh, screws, plates, or wires (n = 47); intravascular stents (n = 25); and prosthetic joint replacements (n = 17). Forty-six patients (24%) reported greater than 1 IMD that had not been recorded in their admission history and physical examination. The prevalence of IMDs in hospitalized patients is high and underestimated in the medical record and may have significant implications for patient care.
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http://dx.doi.org/10.1097/PTS.0000000000000187DOI Listing
September 2018

Biochemical association of metabolic profile and microbiome in chronic pressure ulcer wounds.

PLoS One 2015 15;10(5):e0126735. Epub 2015 May 15.

Department of Chemistry and Biochemistry, Montana State University, Bozeman, Montana, United States of America.

Chronic, non-healing wounds contribute significantly to the suffering of patients with co-morbidities in the clinical population with mild to severely compromised immune systems. Normal wound healing proceeds through a well-described process. However, in chronic wounds this process seems to become dysregulated at the transition between resolution of inflammation and re-epithelialization. Bioburden in the form of colonizing bacteria is a major contributor to the delayed headlining in chronic wounds such as pressure ulcers. However how the microbiome influences the wound metabolic landscape is unknown. Here, we have used a Systems Biology approach to determine the biochemical associations between the taxonomic and metabolomic profiles of wounds colonized by bacteria. Pressure ulcer biopsies were harvested from primary chronic wounds and bisected into top and bottom sections prior to analysis of microbiome by pyrosequencing and analysis of metabolome using 1H nuclear magnetic resonance (NMR) spectroscopy. Bacterial taxonomy revealed that wounds were colonized predominantly by three main phyla, but differed significantly at the genus level. While taxonomic profiles demonstrated significant variability between wounds, metabolic profiles shared significant similarity based on the depth of the wound biopsy. Biochemical association between taxonomy and metabolic landscape indicated significant wound-to-wound similarity in metabolite enrichment sets and metabolic pathway impacts, especially with regard to amino acid metabolism. To our knowledge, this is the first demonstration of a statistically robust correlation between bacterial colonization and metabolic landscape within the chronic wound environment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0126735PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433261PMC
March 2016

Negative pressure wound therapy technologies for chronic wound care in the home setting: A systematic review.

Wound Repair Regen 2015 Jul-Aug;23(4):506-17. Epub 2015 Jul 31.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

The use of negative pressure wound therapy (NPWT) is increasing in both the inpatient and outpatient settings. We conducted a systematic review on the efficacy and safety of NPWT for the treatment of chronic wounds in the home setting. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature, up to June 2014. Two independent reviewers screened search results. Seven studies met our criteria for inclusion. Six of the studies compared NPWT devices to other wound care methods and one study compared two different NPWT technologies. Data were limited by variability in the types of comparator groups, methodological limitations, and poor reporting of outcomes. We were unable to draw conclusions about the efficacy or safety of NPWT for the treatment of chronic wounds in the home setting due to the insufficient evidence. Consensus is needed on the methods of conducting and reporting wound care research so that future studies are able inform decisions about the use of NPWT in the home environment for chronic wounds.
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http://dx.doi.org/10.1111/wrr.12295DOI Listing
June 2016

Editorial commentary: persistent gonococcal DNA: artifact or real? Further insights into the biology of a remarkable pathogen.

Clin Infect Dis 2015 Feb 3;60(4):564-5. Epub 2014 Nov 3.

Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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http://dx.doi.org/10.1093/cid/ciu876DOI Listing
February 2015

Interplay between the temporal dynamics of the vaginal microbiota and human papillomavirus detection.

J Infect Dis 2014 Dec 18;210(11):1723-33. Epub 2014 Jun 18.

Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland.

Background: We sought to describe the temporal relationship between vaginal microbiota and human papillomavirus (HPV) detection.

Methods: Thirty-two reproductive-age women self-collected midvaginal swabs twice weekly for 16 weeks (937 samples). Vaginal bacterial communities were characterized by pyrosequencing of barcoded 16S rRNA genes and clustered into 6 community state types (CSTs). Each swab was tested for 37 HPV types. The effects of CSTs on the rate of transition between HPV-negative and HPV-positive states were assessed using continuous-time Markov models.

Results: Participants had an average of 29 samples, with HPV point prevalence between 58%-77%. CST was associated with changes in HPV status (P<.001). Lactobacillus gasseri-dominated CSTs had the fastest HPV remission rate, and a low Lactobacillus community with high proportions of the genera Atopobium (CST IV-B) had the slowest rate compared to L. crispatus-dominated CSTs (adjusted transition rate ratio [aTRR], 4.43, 95% confidence interval [CI], 1.11-17.7; aTRR, 0.33, 95% CI, .12-1.19, respectively). The rate ratio of incident HPV for low Lactobacillus CST IV-A was 1.86 (95% CI, .52-6.74).

Conclusions: Vaginal microbiota dominated by L. gasseri was associated with increased clearance of detectable HPV. Frequent longitudinal sampling is necessary for evaluation of the association between HPV detection and dynamic microbiota.
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http://dx.doi.org/10.1093/infdis/jiu330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296189PMC
December 2014

Effect of lubricants and a vaginal spermicide gel on the detection of prostate specific antigen, a biomarker of semen exposure, using a quantitative (Abbott ARCHITECT) assay.

Contraception 2014 Feb 12;89(2):134-8. Epub 2013 Nov 12.

CONRAD, Eastern Virginia Medical School (EVMS), Arlington, VA 23501, USA.

Objectives: Little is known about the effects of commonly used lubricants on detection of biomarkers of semen exposure. We investigated the in vitro effect of Gynol®, K-Y Jelly®, Replens®, Astroglide®, Carbopol, and Silicorel on quantitative detection of prostate specific antigen (PSA).

Study Design: A predetermined concentration of each of the gels was added to serially diluted semen samples. Additionally, serial dilutions of each of the gels were added to three different semen dilutions (high, medium, or low). The resulting samples were tested for PSA on the Abbott ARCHITECT System.

Results: When using the Abbott ARCHITECT system, the only products that inhibited PSA detection were Gynol® and Replens®. The inhibition caused by Gynol® was dose-dependent, but that of Replens was dose-independent. K-Y Jelly®-spiked samples had higher PSA values than controls.

Conclusions: Caution is warranted when using the Abbott quantitative assay for PSA detection as a biomarker of semen exposure in settings where Gynol®, Replens® or K-Y Jelly® might also have been used. Neither Astroglide® nor Silicorel inhibited PSA detection. Additional studies evaluating other vaginal products, including microbicides, and their effects on other assays, are needed. In vivo studies will be especially important to optimize PSA detection from clinical samples.

Implications: Researchers should consider the potential for specific lubricants or any vaginal products to affect the particular assay used for semen biomarker detection. The Abbott ARCHITECT's total PSA assay should not be used with the product Replens. Caution is warranted when using the assay in settings where Gynol or K-Y jelly may have been used.
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http://dx.doi.org/10.1016/j.contraception.2013.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4554523PMC
February 2014

The legacy of sexually transmitted disease research: lessons from Guatemala and Dr. Thomas Parran: the American STD Association Distinguished Career Award Lecture.

Sex Transm Dis 2013 Dec;40(12):901-8

From the Division of Infectious Diseases, Johns Hopkins Bayview Medical Center, Baltimore, MD.

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http://dx.doi.org/10.1097/OLQ.0000000000000063DOI Listing
December 2013

Characterizing the temporal dynamics of human papillomavirus DNA detectability using short-interval sampling.

Cancer Epidemiol Biomarkers Prev 2014 Jan 15;23(1):200-8. Epub 2013 Oct 15.

Authors' Affiliations: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine; Institute for Genome Sciences; Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland; Department of Family Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan; and Perdana University Graduate School of Medicine, Serdang, Malaysia.

Background: Variable detection of human papillomavirus (HPV) DNA can result in misclassification of infection status, but the extent of misclassification has not been quantitatively evaluated.

Methods: In 2005-2007, 33 women of ages 22 to 53 years self-collected vaginal swabs twice per week for 16 consecutive weeks. Each of the 955 swabs collected was tested for 37 HPV types/subtypes. Assuming that a woman's underlying infection status did not change over the short study period, biases in prevalence estimates obtained from single versus multiple swabs were calculated. Using event history analysis methods, time to recurrent gain and loss of at least one HPV type was determined, separately. Baseline any-type and high risk-type HPV prevalence was 60.6% and 24.2%, respectively. Cumulative any-HPV and high-risk HPV prevalence over the 16-week period was 84.8% and 60.6%, separately.

Results: Overall, there were 319 events of detection and 313 events of loss of detection. Median times to a recurrent detection and loss of detection were 11 and seven days, respectively. Neither vaginal sex nor condom use during follow-up was associated with recurrent viral detection or loss of detection. Assuming the cumulative 16-week prevalence reflects the true prevalence of infection, the baseline any-HPV prevalence underestimated infection status by 24.2%, with a bootstrapped mean of 20.2% [95% confidence interval (CI), 8.9%-29.6%].

Conclusions: These findings suggest that a substantial proportion of HPV-infected women are misclassified as being uninfected when using a single-time DNA measurement.

Impact: Short-term variation in detectable HPV DNA needs to be considered while interpreting the natural history of infections using single samples collected at long intervals.
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http://dx.doi.org/10.1158/1055-9965.EPI-13-0666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947138PMC
January 2014

Detection of two biological markers of intercourse: prostate-specific antigen and Y-chromosomal DNA.

Contraception 2013 Dec 14;88(6):749-57. Epub 2013 Aug 14.

Department of Obstetrics and Gynecology, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Background: Although biological markers of women's exposure to semen from vaginal intercourse have been developed as surrogates for risk of infection or probability of pregnancy, data on their persistence time and clearance are limited.

Study Design: During 2006-2008, 52 couples were enrolled for three 14-day cycles of abstinence from vaginal sex during which women were exposed in the clinic to a specific quantity (10, 100 or 1000 μL) of their partner's semen. Vaginal swabs were collected before and at 1, 6, 12, 24, 48, 72 and 144 h after exposure for testing for prostate-specific antigen (PSA) and Y-chromosome DNA (Yc DNA).

Results: Immediately after exposure to 1000 μL of semen, the predicted sensitivity of being PSA positive was 0.96; this decreased to 0.65, 0.44, 0.21 and 0.07 at 6, 12, 24 and 48 h, respectively. Corresponding predicted sensitivity of being Yc DNA positive was 0.72 immediately postexposure; this increased to 0.76 at 1 h postexposure and then decreased to 0.60 (at 6 h), 0.63 (at 12 h), 0.49 (at 24 h), 0.21 (at 48 h), 0.17 (at 72 h) and 0.12 (at 144 h).

Conclusions: Overall findings suggest that PSA may be more consistent as a marker of very recent exposure and that Yc DNA is more likely to be detected in the vagina after 12 h postexposure compared to PSA.
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http://dx.doi.org/10.1016/j.contraception.2013.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845849PMC
December 2013
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