Responding to the post-pandemic crisis: post-exposure prophylaxis for TB.
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ABSTRACT:
SUBMITTER: Heffernan C
PROVIDER: S-EPMC9423019 | biostudies-literature | 2022 Sep
REPOSITORIES: biostudies-literature
Publications
Responding to the post-pandemic crisis: post-exposure prophylaxis for TB.
Heffernan C C Savić R M RM Long R G RG Raviglione M C MC Ferrara G G
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 20220901 9
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Project description:BackgroundWith the rise of the second pandemic wave of the novel influenza A (H1N1) virus in the current season in the Northern Hemisphere, pandemic plans are being carefully re-evaluated, particularly for the strategic use of antiviral drugs. The recent emergence of oseltamivir-resistant in treated H1N1 patients has raised concerns about the prudent use of neuraminidase inhibitors for both treatment of ill individuals and post-exposure prophylaxis of close contacts.MethodsWe extended an established population dynamical model of pandemic influenza with treatment to include post-exposure prophylaxis of close contacts. Using parameter estimates published in the literature, we simulated the model to evaluate the combined effect of treatment and prophylaxis in minimizing morbidity and mortality of pandemic infections in the context of transmissible drug resistance.ResultsWe demonstrated that, when transmissible resistant strains are present, post-exposure prophylaxis can promote the spread of resistance, especially when combined with aggressive treatment. For a given treatment level, there is an optimal coverage of prophylaxis that minimizes the total number of infections (final size) and this coverage decreases as a higher proportion of infected individuals are treated. We found that, when treatment is maintained at intermediate levels, limited post-exposure prophylaxis provides an optimal strategy for reducing the final size of the pandemic while minimizing the total number of deaths. We tested our results by performing a sensitivity analysis over a range of key model parameters and observed that the incidence of infection depends strongly on the transmission fitness of resistant strains.ConclusionOur findings suggest that, in the presence of transmissible drug resistance, strategies that prioritize the treatment of only ill individuals, rather than the prophylaxis of those suspected of being exposed, are most effective in reducing the morbidity and mortality of the pandemic. The impact of post-exposure prophylaxis depends critically on the treatment level and the transmissibility of resistant strains and, therefore, enhanced surveillance and clinical monitoring for resistant mutants constitutes a key component of any comprehensive plan for antiviral drug use during an influenza pandemic.
| S-EPMC2794871 | biostudies-literature
Project description:The incidence of human immunodeficiency virus (HIV) infection continues to rise among core groups and efforts to reduce the numbers of new infections are being redoubled. Post-exposure prophylaxis (PEP) is the use of short-term antiretroviral therapy (ART) to reduce the risk of acquisition of HIV infection following exposure. Current guidelines recommend a 28-day course of ART within 36-72 hours of exposure to HIV. As long as individuals continue to be exposed to HIV there will be a role for PEP in the foreseeable future. Nonoccupational PEP, the vast majority of which is for sexual exposure (PEPSE), has a significant role to play in HIV prevention efforts. Awareness of PEP and its availability for both clinicians and those who are eligible to receive it are crucial to ensure that PEP is used to its full potential in any HIV prevention strategy. In this review, we provide current evidence for the use of PEPSE, assessment of the risk of HIV transmission, indications for PEP, drug regimens, and management of patients started on PEP. We summarize national and international guidelines for the use of PEPSE. We explore the place of PEP within the wider strategy of reducing HIV incidence rates in the era of treatment as prevention and pre-exposure prophylaxis. We also consider the implications of recent data from interventional and observational studies demonstrating significant reductions in the risk of HIV transmission within a serodiscordant relationship if the HIV-positive partner is taking effective ART upon PEP guidelines.
| S-EPMC4216036 | biostudies-other
Project description:From a healthcare perspective, infection due to the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and the ensuing syndrome called COVID-19 (coronavirus disease 2019) represents the biggest challenge the world has faced in several decades. Particularly worrisome are the high contagiousness of the virus and the saturation of hospitals' capacity due to overwhelming caseloads. Non-pharmaceutical interventions such as quarantine and inter-personal distancing are crucial to limiting the spread of the virus in the general population, but more tailored interventions may be needed at an individual level on a case-by-case basis. In this perspective, the most insidious situation is when an individual has contact with a contagious subject without adequate protection. If rapidly recognized afterwards, this occurrence may be promptly addressed through a post-exposure chemoprophylaxis (PEP) with antiviral drugs. This strategy has been implemented for other respiratory viruses (influenza above all) and was successfully used in South Korea among healthcare workers against the Middle East respiratory syndrome (MERS) coronavirus, by providing people who were exposed to high-risk contacts with lopinavir-ritonavir plus ribavirin. Initial experiences with the use of hydroxychloroquine to prevent COVID-19 also seem promising. Post-exposure chemoprophylaxis might help mitigate the spread of SARS-CoV-2 in the current phase of the COVID-19 pandemic.
| S-EPMC7312384 | biostudies-literature
Project description:HIV infection in HCW is an occupational hazard requiring policy decisions by the health care administrators. In this article we have outlined a post exposure prophylaxis protocol following HIV exposure in HCWs. By determining the HIV status code of the source and the HIV exposure code of the HCWs, recommendations for PEP are forwarded. Occupational exposures should be considered urgent medical and surgical concerns to ensure timely administration of PEP. At the end, an algorithm is provided to guide exposed health-care workers in deciding when to consider PEP.
| S-EPMC5532134 | biostudies-other
Project description:ObjectivesSexual assault (SA) is recognized as a public health problem of epidemic proportions. Guidelines recommend the administration of post-exposure prophylaxis (PEP) after an SA. However, few data are available about the feasibility of this strategy, and this study was conducted to assess this.MethodsWe conducted a retrospective, longitudinal, observational study in SA victims attending the Hospital Clinic in Barcelona from 2006 to 2015. A total of 1695 SA victims attended the emergency room (ER), of whom 883 met the PEP criteria. Five follow-up visits were scheduled at days 1, 10, 28, 90 and 180 in the out-patient clinic. The primary endpoint was PEP completion rate at day 28. Secondary endpoints were loss to follow-up, treatment discontinuation, occurrence of adverse events (AEs) and rate of seroconversion.ResultsThe median age of participants was 25 years [interquartile range (IQR) 21-33 years] and 93% were female. The median interval between exposure and presentation at the ER was 13 h (IQR 6-24 h). The level of risk was appreciable in 47% (n = 466) of individuals. Of 883 patients receiving PEP, 631 lived in Catalonia. In this group, the PEP completion rate at day 28 was 29% (n = 183). The follow-up rate was 63% (n = 400) and 38% (n = 241) at days 1 and 28, respectively. Treatment discontinuation was present in 58 (15%) of 400 patients who attended at least the day 1 visit, the main reason being AEs (n = 35; 60%). AEs were reported in 226 (56%) patients, and were mainly gastrointestinal (n = 196; 49%). Only 211 (33%) patients returned for HIV testing at day 90. A single seroconversion was observed in a men who have sex with men (MSM) patient at day 120.ConclusionsFollow-up and compliance rates in SA victims were poor. In addition, > 50% of the patients experienced AEs, which were the main reason for PEP interruption. Strategies to increase follow-up testing and new better tolerated drug regimens must be investigated to address these issues.
| S-EPMC6916272 | biostudies-literature
Project description:ObjectivesThe objective was to perform a survey-based service evaluation of our telephone PrEP clinic (Tele-PrEP), which was instituted during the COVID-19 pandemic, to inform future service delivery.MethodsWe administered parallel, web-based, anonymous surveys to PrEP-users who had a Tele-PrEP appointment between 13.11.2020 and 17.12.2020 and all healthcare professionals (HCPs) conducting Tele-PrEP clinics. We used descriptive statistics to summarise demographic and qualitative data, and thematically categorised free text responses using the Framework for a Systems Approach to Healthcare Delivery.Results62/117 (53%) PrEP-users and 8/9 (89%) HCPs completed the surveys. Tele-PrEP was rated 'excellent' or 'good' by 61/62 (98%) PrEP-users. All HCPs felt that Tele-PrEP allowed them to assess patients safely and confidently. 10/62 (16%) PrEP-users and 1 (11%) HCP expressed a preference for face-to-face care. Using the Framework for a Systems Approach to Healthcare Delivery we identified key areas important to respondents who highlighted the rapid changes as a result of COVID-19, which required an increase in dedicated resources. HCPs valued teamwork, support/supervision and convenience in achieving quality care for the patient, who in turn, valued convenient, holistic and individualised management to meet their sexual healthcare needs.ConclusionTele-PrEP is feasible and acceptable. While most respondents rated the service highly, others identified a need/preference for face-to-face appointments.
| S-EPMC9189322 | biostudies-literature
Project description:Although the risk of a herpes B virus (Cercopithecine herpes virus 1) infection is low, the clinical course of the infectious disease is generally unfavourable. A high safety standard can be achieved if people with professional contact to primates apply proper organisational, technical and personal safety precautions. The risk can be considerably reduced if animal keepers, laboratory assistants and scientists receive adequate information about the pathology of herpes B virus and are well trained in the necessary procedures and the precautions. For this reason, comprehensive and regular training, information and instruction must be provided to all primate workers and to laboratory workers who come into contact with potentially infectious material. After potential contamination, the risk for the affected worker must be assessed immediately and post-exposure chemoprophylaxis performed if necessary. This necessitates internal risk assessment. An interdisciplinary group of experts has developed an action plan for Germany.
| S-EPMC2789725 | biostudies-literature
Project description:Background: Mitochondrial genome has been used across multiple fields in research, diagnosis, and toxicogenomics. Several compounds damage mitochondrial DNA (mtDNA), including biological and therapeutic agents like the human immunodeficiency virus (HIV) but also its antiretroviral treatment, leading to adverse clinical manifestations. HIV-infected and treated patients may show impaired mitochondrial and metabolic profile, but specific contribution of viral or treatment toxicity remains elusive. The evaluation of HIV consequences without treatment interference has been performed in naïve (non-treated) patients, but assessment of treatment toxicity without viral interference is usually restricted to in vitro assays. Objective: The objective of the present study is to determine whether antiretroviral treatment without HIV interference can lead to mtDNA disturbances. We studied clinical, mitochondrial, and metabolic toxicity in non-infected healthy patients who received HIV post-exposure prophylaxis (PEP) to prevent further infection. We assessed two different PEP regimens according to their composition to ascertain if they were the cause of tolerability issues and derived toxicity. Methods: We analyzed reasons for PEP discontinuation and main secondary effects of treatment withdrawal, mtDNA content from peripheral blood mononuclear cells and metabolic profile, before and after 28 days of PEP, in 23 patients classified depending on PEP composition: one protease inhibitor (PI) plus Zidovudine/Lamivudine (PI plus AZT + 3TC; n = 9) or PI plus Tenofovir/Emtricitabine (PI plus TDF + FTC; n = 14). Results: Zidovudine-containing-regimens showed an increased risk for drug discontinuation (RR = 9.33; 95% CI = 1.34-65.23) due to adverse effects of medication related to gastrointestinal complications. In the absence of metabolic disturbances, 4-week PEP containing PI plus AZT + 3TC led to higher mitochondrial toxicity (-17.9 ± 25.8 decrease in mtDNA/nDNA levels) than PI plus TDF + FTC (which increased by 43.2 ± 24.3 units mtDNA/nDNA; p < 0.05 between groups). MtDNA changes showed a significant and negative correlation with baseline alanine transaminase levels (p < 0.05), suggesting that a proper hepatic function may protect from antiretroviral toxicity. Conclusions: In absence of HIV infection, preventive short antiretroviral treatment can cause secondary effects responsible for treatment discontinuation and subclinical mitochondrial damage, especially pyrimidine analogs such as AZT, which still rank as the alternative option and first choice in certain cohorts for PEP. Forthcoming efforts should be focused on launching new strategies with safer clinical and mitotoxic profile.
| S-EPMC7264262 | biostudies-literature
Project description:This phase 3 trial assessed AZD7442 (tixagevimab/cilgavimab) for post-exposure prophylaxis against symptomatic coronavirus disease 2019 (COVID-19). Adults without prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or COVID-19 vaccination were enrolled within 8 days of exposure to a SARS-CoV-2-infected individual and randomized 2:1 to a single 300-mg AZD7442 dose (one 1.5-mL intramuscular injection each of tixagevimab and cilgavimab) or placebo. Primary end points were safety and first post-dose SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR)-positive symptomatic COVID-19 event before day 183. A total of 1121 participants were randomized and dosed (AZD7442, n = 749; placebo, n = 372). Median (range) follow-up was 49 (5-115) and 48 (20-113) days for AZD7442 and placebo, respectively. Adverse events occurred in 162 of 749 (21.6%) and 111 of 372 (29.8%) participants with AZD7442 and placebo, respectively, mostly mild/moderate. RT-PCR-positive symptomatic COVID-19 occurred in 23 of 749 (3.1%) and 17 of 372 (4.6%) AZD7442- and placebo-treated participants, respectively (relative risk reduction, 33.3%; 95% confidence interval [CI], -25.9 to 64.7; P = .21). In predefined subgroup analyses of 1073 (96%) participants who were SARS-CoV-2 RT-PCR-negative (n = 974, 87%) or missing an RT-PCR result (n = 99, 9%) at baseline, AZD7442 reduced RT-PCR-positive symptomatic COVID-19 by 73.2% (95% CI, 27.1 to 90.1) vs placebo. This study did not meet the primary efficacy end point of post-exposure prevention of symptomatic COVID-19. However, analysis of participants who were SARS-CoV-2 RT-PCR-negative or missing an RT-PCR result at baseline support a role for AZD7442 in preventing symptomatic COVID-19. Clinical Trials Registration. NCT04625972.
| S-EPMC10069855 | biostudies-literature
Project description:BackgroundA single administration of laninamivir octanoate, a long-acting neuraminidase inhibitor, has been proven to be effective in the treatment of influenza but not for post-exposure prophylaxis.MethodsWe conducted a double-blind, multicenter, randomized, placebo-controlled study to determine if a single administration of laninamivir octanoate 40 mg was superior to placebo for post-exposure prophylaxis. Eligible participants who had cohabited with an influenza patient within 48 hours of symptom onset were randomly assigned (1:1:1) to 1 of 3 groups: 40 mg of laninamivir octanoate single administration (LO-40SD), 20 mg of laninamivir octanoate once daily for 2 days (LO-20TD), or placebo. The primary efficacy endpoint was the proportion of participants who developed clinical influenza (defined as influenza virus positive, an axillary temperature >37.5°C, and at least 2 symptoms) over a 10-day period.ResultsA total of 803 participants were enrolled, with 801 included in the primary analysis. The proportions of participants with clinical influenza were 4.5% (12/267), 4.5% (13/269), and 12.1% (32/265) in the LO-40SD, LO-20TD, and placebo groups, respectively. A single administration of laninamivir octanoate 40 mg significantly reduced the development of influenza compared with placebo (P = .001). The relative risk reductions compared with the placebo group were 62.8% and 63.1% for the LO-40SD and LO-20TD groups, respectively. The incidence of adverse events in the LO-40SD group was similar to that of the LO-20TD and placebo groups.ConclusionsA single administration of laninamivir octanoate was effective and well tolerated as post-exposure prophylaxis to prevent the development of influenza.Clinical trials registrationJapicCTI-142679.
| S-EPMC4946013 | biostudies-literature