scholarly journals LB-17. Efficacy of Hydroxychloroquine (HCQ) for Post-exposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Blinded, Randomized, Controlled Trial

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S851-S852
Author(s):  
Elizabeth R Brown ◽  
Anna Bershteyn ◽  
Helen C Stankiewicz Karita ◽  
Christine Johnston ◽  
Lorna Thorpe ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Controlled Trial ◽  
Panel Member ◽  
Control Group ◽  
Post Exposure Prophylaxis ◽  
Research Support ◽  
Double Blind ◽  
Post Exposure ◽  
Exposure Prophylaxis ◽  
Close Contacts

Abstract Background Prevention interventions for coronavirus disease (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), are currently limited to non-pharmaceutical strategies. Observational and laboratory data suggested that hydroxychloroquine (HCQ) had biologic activity against SARS-CoV-2. A blinded trial of HCQ in persons with confirmed exposure and virologic and clinical endpoints is needed. Methods We conducted a national, householdrandomized, double-blind, controlled trial of HCQ post-exposure prophylaxis, with entirely remote study procedures. We enrolled close contacts exposed to persons with SARS-CoV-2 infection in the past 96 hours. Participants were randomized to either HCQ (400 mg daily for three days followed by 200 mg daily for eleven days) or ascorbic acid (500 mg followed by 250 mg daily), as a placebo-equivalent control. Participants self-collected mid-turbinate swabs daily (days 1–14) for SARS-CoV-2 PCR testing. The primary outcome was PCR-confirmed, incident SARS-CoV-2 infection among persons SARS-CoV-2 negative at enrollment. Symptoms were assessed using criteria from the US CDC. Results From March-August 2020, 623 households were randomized; 311 households (381 participants) to the HCQ group and 312 households (400 participants) to the control group. Ninety- one percent of participants were retained up to day 14 and 9,595 of 10,588 (91%) of swabs were tested. Among participants who were SARS-CoV-2 negative at baseline (n=626/781, 80%), the cumulative incidence of SARS-CoV-2 was 14.5% (95% CI: 11.6–17.4) and the cumulative incidence of COVID-19 symptoms was 11.6% (95% CI: 8.9–14.2) at day 14. By day 14, there was no difference between the HCQ group and control group in SARS-CoV-2 acquisition (46 vs. 43 events, aHR= 0.99, 95% CI 0.64–1.52, p=0.95) or symptomatic disease (40 vs. 32 events, aHR= 1.23, 95% CI: 0.76–1.99, p=0.40). The adverse event frequency was similar between groups (59 [15.5%] participants in the HCQ and 45 [11.3%] in the control group, p=0.092). Cumulative incidence of RT-PCR-confirmed SARS-CoV-2 infection among close contacts of diagnosed cases, by study group Conclusion This randomized, double-blind, controlled trial among persons with recent exposure and high incidence of SAR-CoV2 provides strong evidence that HCQ post-exposure prophylaxis did not prevent SARS-CoV-2 infection or modify clinical disease. Disclosures Anna Bershteyn, PhD, Bill and Melinda Gates Foundation (Grant/Research Support)Gates Ventures (Consultant)National Institutes of Health (Grant/Research Support) Kristopher M. Paolino, MD, MTM&H, Nothing to disclose Raphael J. Landovitz, MD, MSc, Gilead (Advisor or Review Panel member)Merck (Advisor or Review Panel member)Roche (Other Financial or Material Support, Speaker Honoraria) Anna Wald, MD, MPH, Aicuris (Individual(s) Involved: Self): Consultant; Gilead (Individual(s) Involved: Self): Consultant; GlaxoSmithKline (Individual(s) Involved: Self): Scientific Research Study Investigator; Merck (Individual(s) Involved: Self): DSMB participation; provision of vaccine for a study, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Scientific Research Study Investigator; X-Vax (Individual(s) Involved: Self): Consultant Helen Y. Chu, MD MPH, Cepheid (Grant/Research Support)Ellume (Grant/Research Support)Glaxo Smith Kline (Consultant)Merck (Consultant)Sanofi-Pasteur (Grant/Research Support)

scholarly journals Laninamivir octanoate for post-exposure prophylaxis of influenza in household contacts: a randomized double blind placebo controlled trial

2013 ◽  
Vol 19 (4) ◽  
pp. 740-749 ◽  
Author(s):  
Seizaburo Kashiwagi ◽  
Akira Watanabe ◽  
Hideyuki Ikematsu ◽  
Shinichiro Awamura ◽  
Takako Okamoto ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Post Exposure Prophylaxis ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Post Exposure ◽  
Household Contacts ◽  
Exposure Prophylaxis

scholarly journals Adverse reactions associated with a Fuenzalida-Palacios rabies vaccine: a quasi-experimental study

2004 ◽  
Vol 37 (1) ◽  
pp. 7-9 ◽  
Author(s):  
Rosuita Fratari Bonito ◽  
Neide Mattar de Oliveira ◽  
Sérgio de Andrade Nishioka
Keyword(s):  
Experimental Study ◽  
Adverse Reactions ◽  
Signs And Symptoms ◽  
Rabies Vaccine ◽  
Control Group ◽  
Post Exposure Prophylaxis ◽  
Post Exposure ◽  
Quasi Experimental ◽  
Group A ◽  
Exposure Prophylaxis

The Fuenzalida-Palacios rabies vaccine has been used in South America for rabies post-exposure prophylaxis. To determine the frequency of adverse reactions associated with this vaccine compared to a control group a quasi-experimental study was carried out in Uberlândia, Brazil, from May 1997 to April 1998. Victims of bites or other injuries by dogs or other mammals and who received or not post-exposure prophylaxis with Fuenzalida-Palacios rabies vaccine were compared as to the occurrence of a list of signs and symptoms. Out of 2,440 victims of bites and other injuries from dogs and other mammals 2,114 participated in the study; 1,004 of them provided follow-up information within 10 to 15 days. Headache and pain at the injection sites were the most commonly found symptoms (125/1,000). No neuroparalytic event was detected. Patients who were given Fuenzalida-Palacios rabies vaccine and those who were not had similar incidences of symptoms (risk ratios close to 1). Regarding the occurrence of adverse reactions, Fuenzalida-Palacios rabies vaccine is a valid alternative for rabies post-exposure prophylaxis.

scholarly journals Countering the rise of syphilis: A role for doxycycline post-exposure prophylaxis?

2021 ◽  
pp. 095646242110424
Author(s):  
Nguyen K Tran ◽  
Neal D Goldstein ◽  
Seth L Welles
Keyword(s):  
Cumulative Incidence ◽  
Population Level ◽  
Limited Attention ◽  
Post Exposure Prophylaxis ◽  
Adherence Level ◽  
Sexual Minority Men ◽  
Post Exposure ◽  
Syphilis Screening ◽  
Minority Men ◽  
Exposure Prophylaxis

Doxycycline post-exposure prophylaxis (PEP) holds the potential to mitigate increasing rates of syphilis among sexual minority men (SMM) in the US yet has received limited attention. Since evaluation of this intervention in actual populations is not currently feasible, we used agent-based models (ABM) to assess the population-level impact of this strategy. We adapted ABM of HIV and HPV transmission, representing a population of 10,230 SMM in Philadelphia, Pennsylvania, US. Parameter inputs were derived from the literature, and ABM outputs during the pre-intervention period were calibrated to local surveillance data. Intervention scenarios varied doxycycline uptake by 20, 40, 60, 80 and 100%, while assuming continued condom use and syphilis screening and treatment. Under each intervention scenario, we incorporated treatment adherence at the following levels: 0, 20, 40, 60, 80 and 100%. Long-term population impact of prophylactic doxycycline was measured using the cumulative incidence over the 10-year period and the percentage of infections prevented attributable to doxycycline at year 10. An uptake scenario of 20% with an adherence level of 80% would reduce the cumulative incidence of infections by 10% over the next decade, translating to 57 fewer cases per 1000 SMM. At year 10, under the same uptake and adherence level, 22% of infections would be prevented due to doxycycline PEP in the instances where condoms were not used or failed. Findings suggest that doxycycline PEP will have a modest impact on syphilis incidence when assuming a reasonable level of uptake and adherence. Doxycycline PEP may be most appropriate as a secondary prevention measure to condoms and enhanced syphilis screening for reducing infections among SMM.

scholarly journals Three-day regimen of oseltamivir for post-exposure prophylaxis of influenza in hospital wards: a study protocol for a prospective, multi-center, single-arm trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nobuhisa Ishiguro ◽  
Yoichi M. Ito ◽  
Sumio Iwasaki ◽  
Miki Nagao ◽  
Hideki Kawamura ◽  
...  
Keyword(s):  
Clinical Trials ◽  
University Hospital ◽  
Infection Prevention And Control ◽  
Post Exposure Prophylaxis ◽  
University Hospitals ◽  
Once Daily ◽  
Post Exposure ◽  
Link Type ◽  
Exposure Prophylaxis ◽  
Close Contacts

Abstract Background In a previous retrospective observational study, a 3-day regimen of oseltamivir as post-exposure prophylaxis (PEP) for preventing transmission of influenza in wards was shown to be comparable to 7- to 10-day regimens provided index cases were immediately separated from close contacts. In order to confirm the efficacy of a 3-day regimen, we started to conduct a prospective, multi-center, single-arm trial. Methods This study is a prospective, multi-center, single-arm study designed by the Sectional Meeting of Clinical Study, Japan Infection Prevention and Control Conference for National and Public University Hospitals. Index patients with influenza are prescribed a neuraminidase inhibitor and are discharged immediately or transferred to isolation rooms. The close contacts are given oseltamivir as 75 mg capsules once daily for adults or 2 mg/kg (maximum of 75 mg) once daily for children for 3 days as PEP. All close contacts are monitored for development of influenza for 7 days after starting PEP. Discussion A 3-day regimen of oseltamivir as PEP has advantages over 7- to 10-day regimens in terms of costs, medication adherence and adverse effects. Trial registration The Institutional Review Board of Hokkaido University Hospital for Clinical Research, 015-0518, registered on November 11, 2016. UMIN Clinical Trials Registry, UMIN000024458, disclosed on October 31, 2016. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027881. Japan Registry of Clinical Trials, jRCTs011180015, disclosed on March 14, 2019. https://jrct.niph.go.jp/latest-detail/jRCTs011180015

scholarly journals Daily Lactobacillus Probiotic versus Placebo in COVID-19-Exposed Household Contacts (PROTECT-EHC): A Randomized Clinical Trial

2022 ◽  
Author(s):  
Paul E Wischmeyer ◽  
Helen Tang ◽  
Yi Ren ◽  
Lauren Bohannon ◽  
Zeni E Ramirez ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Lactobacillus Rhamnosus ◽  
The United States ◽  
Post Exposure Prophylaxis ◽  
Event Analysis ◽  
Double Blind ◽  
Intention To Treat ◽  
Tract Infections ◽  
Exposure Prophylaxis ◽  
Vaccine Availability

Background: The COVID-19 pandemic continues to pose unprecedented challenges to worldwide health. While vaccines are effective, supplemental strategies to mitigate the spread and severity of COVID-19 are urgently needed. Emerging evidence suggests susceptibility to infections, including respiratory tract infections, may be reduced by probiotic interventions. Therefore, probiotics may be a low-risk, widely implementable modality to mitigate risk of COVID-19 disease, particularly in areas with low vaccine availability and/or uptake. Methods: We conducted a randomized, double-blind, placebo-controlled trial across the United States testing the probiotic Lactobacillus rhamnosus GG (LGG) as post-COVID-19-exposure prophylaxis. We enrolled individuals > 1 year of age with a household contact with a recent (≤ 7 days) diagnosis of COVID-19. Participants were randomized to receive daily LGG or placebo for 28 days. Stool was collected to evaluate the microbiome. The primary outcome was development of symptoms of illness compatible with COVID-19 within 28 days. Findings: We enrolled 182 COVID-19-exposed participants. Intention-to-treat analysis showed that participants randomized to LGG were less likely to develop symptoms versus those randomized to placebo (26.4% vs. 42.9%, p=0.02). Further, LGG was associated with a statistically significant reduction in COVID-19 diagnosis (log rank p=0.049) via time-to-event analysis. Overall incidence of COVID-19 diagnosis was not significantly different between LGG (8.8%) and placebo (15.4%) (p=0.17). LGG was well-tolerated with no increased side effects versus placebo. Interpretation: These findings suggest that LGG probiotic may protect against the development of COVID-19 infection and symptoms when used as post-exposure prophylaxis within 7 days after exposure. Funding: This work was supported by a grant from the Duke Microbiome Center to A.D.S. and P.E.W. and private philanthropic donations to A.D.S. DSM/iHealth donated the LGG and placebo for the trial but had no role in its design, conduct, analysis, or writing. Trial registration: NCT04399252

Susceptibility of invasive Neisseria meningitidis strains isolated in Germany to azithromycin, an alternative agent for post-exposure prophylaxis

2020 ◽  
Vol 75 (4) ◽  
pp. 984-987 ◽  
Author(s):  
Manuel Krone ◽  
Thiên-Trí Lâm ◽  
Ulrich Vogel ◽  
Heike Claus
Keyword(s):  
Neisseria Meningitidis ◽  
Post Exposure Prophylaxis ◽  
Broth Microdilution ◽  
Careful Monitoring ◽  
Post Exposure ◽  
Gradient Diffusion ◽  
Alternative Agent ◽  
Resistant Strains ◽  
Exposure Prophylaxis ◽  
Close Contacts

Abstract Background Post-exposure prophylaxis (PEP) for close contacts of invasive meningococcal disease (IMD) cases is recommended in most countries to avoid secondary cases by eradicating supposed meningococcal colonization. Currently, rifampicin, ciprofloxacin and ceftriaxone are recommended in many countries including Germany. Azithromycin has been shown to eradicate meningococcal colonization. Objectives To assess the azithromycin susceptibility of invasive Neisseria meningitidis isolates. Methods A subset of German invasive meningococcal isolates from 2006–18 was selected for this study. Azithromycin MIC was determined using broth microdilution and agar gradient diffusion. Results Azithromycin MICs as determined by broth microdilution ranged from <0.003 to 2 mg/L (median 0.50 mg/L, Q75 1 mg/L). All isolates were susceptible to azithromycin according to the CLSI breakpoint (95% CI 0.0%–1.5%). There was no significant correlation between MICs determined by broth microdilution and agar gradient diffusion. Nevertheless, the two methods were consistent regarding the categorization of all isolates as susceptible. Conclusions Azithromycin is an eligible antibiotic for PEP of IMD close contacts. It is approved for adults as well as children and may even be used in pregnancy. Because of easier application and lower toxicity, it might be an alternative to rifampicin and ciprofloxacin, as we found no resistant isolates. Since a gonococcal gene associated with elevated azithromycin MICs has been reported in N. meningitidis, careful monitoring of the emergence of resistant strains is nevertheless necessary for meningococci. Lack of concordance of MICs between broth microdilution and agar gradient diffusion needs to be considered.

scholarly journals 860. Immediate Access to Post-Exposure Prophylaxis (PEP) Through a 24/7 New York City PEP Hotline

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S20-S21
Author(s):  
Allison Glaser ◽  
Emma Kaplan-Lewis ◽  
Ana Ventuneac ◽  
Wyley Gates ◽  
Michael Cruz ◽  
...  
Keyword(s):  
New York ◽  
New York City ◽  
York City ◽  
Hiv Transmission ◽  
Clinical Care ◽  
Post Exposure Prophylaxis ◽  
Research Support ◽  
Post Exposure ◽  
Exposure Prophylaxis

Abstract Background Oral post-exposure prophylaxis (PEP) is effective in preventing HIV transmission. To minimize barriers to PEP for New York City (NYC) residents, the Institute for Advanced Medicine (IAM), Mount Sinai Health System, and the NYC Department of Health and Mental Health established a 24-hour 7-days PEP hotline to provide eligible callers with immediate access to PEP and follow-up clinical care. Methods Data from hotline callers (January to December 2017) was analyzed utilizing multivariable logistic regression to determine whether a call resulted in PEP access within 72 hours of exposure by sociodemographic variables and exposure characteristics. We describe transitions from PEP to PrEP (pre-exposure prophylaxis). Results The PEP hotline cohort (n = 1278) was 83% male, 11% female, 1% transgender; 66% LGBTQ and 20% heterosexual; 35% White, 15% Black, 9% Asian; 41% other/unknown; 25% Hispanic; mean age of 30 years (range 14–72). The majority of callers learned about the hotline by Internet search (59%). Mean exposure time prior to call was 31 hours with 57% within 24 hours. Exposures were 98% sexual; 73% anal sex (43% receptive; 30% insertive), 21% vaginal, and 6% other. 63% reported condomless sex and 29% condom failure. 15% of callers reported a partner with HIV. 35% of callers reported alcohol or recreational substances at the time of the exposure. Prior PEP and PrEP use was 20% and 9%, respectively. 91% of callers were eligible for PEP; 69% called afterhours and received a telephone PEP prescription, and 27% called during business hours and were directed to a clinic. Access to PEP within 72 hours of exposure occurred in 1,081 (93%) of eligible callers and within 36 hours in 68%. 90% of callers had confirmed follow-up clinic appointments. Of the 472 callers linked to care at the IAM, 89 (19%) transitioned to PrEP. Conclusion This unique program demonstrates a timely initiative to facilitate PEP access to a diverse cohort with the purpose of mitigating risk from potential exposure to HIV. Further investigation is needed to explore adherence to PEP, follow-up testing results, transitions to PrEP for prevention planning, and coordination of health care and substance use services. Disclosures E. Kaplan-Lewis, Viiv: Consultant, Consulting fee. J. Aberg, Gilead: Research Contractor, Research support. GSK: Research Contractor, Research support. ViiV: Research Contractor, Research support. A. Urbina, Theratechnologies: Scientific Advisor, Consulting fee. ViiV: Scientific Advisor, Consulting fee. Merck: Scientific Advisor, Consulting fee. Gilead: Scientific Advisor, Consulting fee.

scholarly journals Review: Insights on Current FDA-Approved Monoclonal Antibodies Against Ebola Virus Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Olivier Tshiani Mbaya ◽  
Philippe Mukumbayi ◽  
Sabue Mulangu
Keyword(s):  
Ebola Virus ◽  
Virus Disease ◽  
Controlled Trial ◽  
Post Exposure Prophylaxis ◽  
Post Exposure ◽  
Robust Immune Response ◽  
Critical Knowledge ◽  
Republic Of The Congo ◽  
Exposure Prophylaxis ◽  
The Impact

The unprecedented 2013-2016 West Africa Ebola outbreak accelerated several medical countermeasures (MCMs) against Ebola virus disease (EVD). Several investigational products (IPs) were used throughout the outbreak but were not conclusive for efficacy results. Only the Randomized Controlled Trial (RCT) on ZMapp was promising but inconclusive. More recently, during the second-largest Ebola outbreak in North Kivu and Ituri provinces, Democratic Republic of the Congo (DRC), four IPs, including one small molecule (Remdesivir), two monoclonal antibody (mAb) cocktails (ZMapp and REGN-EB3) and a single mAb (mAb114), were evaluated in an RCT, the Pamoja Tulinde Maisha (PALM) study. Two products (REGN-EB3 and mAb114) demonstrated efficacy as compared to the control arm, ZMapp. There were remarkably few side effects recorded in the trial. The FDA approved both medications in this scientifically sound study, marking a watershed moment in the field of EVD therapy. These products can be produced relatively inexpensively and can be stockpiled. The administration of mAbs in EVD patients appears to be safe and effective, while several critical knowledge gaps remain; the impact of early administration of Ebola-specific mAbs on developing a robust immune response for future Ebola virus exposure is unknown. The viral mutation escape, leading to resistance, presents a potential limitation for single mAb therapy; further improvements need to be explored. Understanding the contribution of Fc-mediated antibody functions such as antibody-dependent cellular cytotoxicity (ADCC) of those approved mAbs is still critical. The potential merit of combination therapy and post-exposure prophylaxis (PEP) need to be demonstrated. Furthermore, the PALM trial has accounted for 30% of mortality despite the administration of specific treatments. The putative role of EBOV soluble Glycoprotein (sGP) as a decoy to the immune system, the virus persistence, and relapses might be investigated for treatment failure. The development of pan-filovirus or pan-species mAbs remains essential for protection. The interaction between FDA-approved mAbs and vaccines remains unclear and needs to be investigated. In this review, we summarize the efficacy and safety results of the PALM study and review current research questions for the further development of mAbs in pre-exposure or emergency post-exposure use.

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