Search Results (56)

Background: Since the introduction of Pasteur’s rabies vaccine in 1885, rabies prophylaxis and post-exposure prophylaxis (PEP) have been widely administered globally under the recommendation of the World Health Organization (WHO). However, 124 documented cases of PEP failure had been reported worldwide between 1980 and 2023. Additionally, sporadic media reports from China showed occasional PEP failures between 2017 and 2024. Rabies remains a serious public health problem in over 150 countries and regions. Methods: In this review, we summarize PEP procedures recommended by the Advisory Committee on Immunization Practices (ACIP) and the WHO. We also analyze potential contributing factors to PEP failure, propose a concept of circulating antibodies, and discuss their roles in PEP. Furthermore, we summarize key guidelines for clinical trial design from the U.S. Food and Drug Administration (FDA) and China’s Center for Drug Evaluation (CDE), as well as the latest developments in monoclonal antibody (cocktail) therapies. Results: Adherence to core PEP practices, such as wound cleansing, infiltration of wounds with immunoglobulin (mAbs), and administration of vaccines, and broader societal involvement are crucial for preventing rabies infection in most cases. For high-risk exposures or immunocompromised individuals, the provision of circulating antibodies through high-dose human rabies immune globulin (HRIG) or mAbs is of utmost importance for preventing PEP failure. Conclusions: Early, high-concentration circulating antibodies are important for preventing PEP failure. Addressing the global issue of rabies requires involvement of the entire society. Only through collective efforts can we tackle this neglected disease and achieve WHO’s goal of “zero by 30”. Full article

Background: Many new mRNA-based vaccine candidates in liquid mRNA-LNP formulations are under development; however, their stability limitations necessitate frozen storage, posing a significant challenge for long-term storage and transportation. Methods: In this study, an mRNA-LNP rabies vaccine, ABO1005, was prepared, freeze-dried and stored at 2–8 °C for 12-month storage stability evaluation. The immunogenicity, vaccine potency (the NIH method), and protective efficacy of ABO1005 were assessed in mice or dogs and compared to a commercialized inactivated vaccine. Results: Research conducted in mice indicated that the lyophilized vaccine exhibited comparable immunogenicity to its liquid form counterpart. Furthermore, the vaccine candidate elicited a robust humoral response lasting at least 175 days, and the specific antibody titers were not affected by the pre-administration of hyperimmune serum. In comparison to the commercialized inactivated vaccine (HDCV or PVRV), ABO1005 elicited significantly higher levels of humoral and cellular immunity. Vaccine potency testing (NIH) revealed that the potency of ABO1005 at 15 μg/dose was 8.85 IU/dose, which is substantially higher than the standard required for the lot release of rabies vaccines for current human use. In a post-exposure prophylaxis (PEP) study in Beagle dogs, the lyophilized vaccine provided 100% protection for dogs following a two-dose regimen (D0-D7), whereas commercially approved inactivated vaccine offered 83% protection. After storage at 2–8 °C for 12 months, no notable changes were observed in the particle size, encapsulation efficiency, and integrity of mRNA or in the immunogenicity of the lyophilized vaccine. Conclusions: This study successfully developed a formulation and process of freeze-drying for a rabies mRNA vaccine, paving the way for future lyophilized mRNA vaccine development. Full article

Rabies, a viral encephalitis caused by rabies virus (RABV), is 100% fatal upon the onset of symptoms. Effective post-exposure prophylaxis (PEP) measures are available, but they are often difficult to access in low-income countries. WHO estimates about 59,000 deaths due to rabies globally, and the majority are contributed by developing countries. Hence, developing drugs for the treatment of post-symptomatic rabies is an urgent and unmet demand. It is worth noting that previous efforts regarding antiviral strategies, such as small-interfering RNA, antibodies and small-molecule inhibitors, against the rabies virus have failed to show efficacy in pre-clinical studies, especially when the virus has reached the central nervous system (CNS). Therefore, drug repurposing seems to be an alternative tool for the development of new anti-rabies drugs. We validated and used a high-throughput, FITC-conjugated antibody-based flow cytometry assay to expedite the identification of repurposable new drug candidates against the RABV. The assay was validated using ribavirin and salinomycin as reference compounds, which showed EC50 values of 10.08 µM and 0.07 µM, respectively. We screened a SelleckChem library comprising 3035 FDA-approved compounds against RABV (CVS-11) at 10 µM concentration. Five compounds (clofazimine, tiamulin, difloxacin, harringtonine and homoharringtonine) were active against RABV, with greater than 90% inhibition. Homoharringtonine (HHT) identified in the present study is active against laboratory-adapted RABV (CVS-11) and clinical isolates of RABV, with an average EC50 of 0.3 µM in both BHK-21 and Neuro-2a cell lines and exhibits post-entry inhibition. Full article

Background: Sexual assault victims involving penetration are at risk of contracting human immunodeficiency virus (HIV). Post-exposure prophylaxis (PEP) can effectively prevent HIV infection if initiated promptly within 72 h following exposure and adhered to for 28 days. Nonetheless, therapeutic adherence amongst sexual assault victims is low. Victim-centered care, provided by specially trained forensic nurses and midwives, may increase adherence. Methods: We conducted a retrospective case–control study to evaluate the impact of sexual assault center (SAC)—centered care on adherence to PEP compared to care received in the emergency department (ED). Data from January 2011 to February 2022 were reviewed. Multivariable logistic regression analysis was employed to determine the association between centralized specific care for sexual assault victims and completion of the 28-day PEP regimen. The secondary outcome assessed was provision of psychological support within 5 days following the assault. Results: We analyzed 856 patients of whom 403 (47.1%) received care at a specialized center for sexual assault victims. Attendance at the SAC, relative to the ED, was not associated with greater probability of PEP completion both in the unadjusted (52% vs. 50.6%; odds ratio [OR]: 1.06, 95% CI: 0.81 to 1.39; p = 0.666) and adjusted (OR: 0.81, 95%CI 0.58–1.11; p = 0.193) analysis. The care provided at the SAC was associated with improved early (42.7% vs. 21.5%; p < 0.001) and delayed (67.3% vs. 33.7%; p < 0.001) psychological support. Conclusions: SAC-centered care is not associated with an increase in PEP completion rates in sexual assault victims beyond the increase associated with improved access to early and delayed psychological support. Other measures to improve PEP completion rates should be developed. What is already known on this topic—Completion rates for HIV post-exposure prophylaxis (PEP) among victims of sexual assault are low. Specialized sexual assault centers, which provide comprehensive care and are distinct from emergency departments, have been suggested as a potential means of improving treatment adherence and completion rates. However, their actual impact on treatment completion remains unclear. What this study adds—This study found that HIV PEP completion rates in sexual assault victims were not significantly improved by centralized care in a specialized sexual assault center when compared to care initiated in the emergency department and continued within a sexually transmitted infection clinic. However, linkage to urgent psychological and psychiatric care was better in the specialized sexual assault center. How this study might affect research, practice or policy—Healthcare providers in sexual assault centers should be more aware of their critical role in promoting PEP adherence and improving completion rates. Policymakers should ensure that measures aimed at improving HIV PEP outcomes are implemented at all points of patient contact in these centers. Further research is needed to assess the cost-effectiveness of specialized sexual assault centers. Full article

Background/Objective: Needlestick injuries (NSIs) are a significant source of bloodborne infections among nurses. This study aimed to assess the prevalence, contributing factors, and awareness of post-exposure prophylaxis (PEP) among Estonian nurses. Methods: This prospective cross-sectional study was conducted using an electronic questionnaire in September 2024. Results: The majority of the 211 nurses participating in this study were females aged 21 to 75 years. Notably, 57.1% (n = 109, aged 43.9 ± 12.2) had experienced an NSI in the past decade. Most injuries occurred during sharps’ disposal (33%) and with syringe needles (72%). Among those injured, 84% washed the area with water and soap, 80% used alcohol-based disinfectants, and 69% reported the incident. However, 20.6% did not report due to perceived insignificance or lack of follow-up actions. Additionally, 14.7% were unaware of the reporting requirement, and 8.8% did not know who to report to. Conclusions: Improved training and reporting practices are essential to reduce NSIs among nurses. Full article

Background and Aim: This systematic scoping review examines rabies-related incidents, interventions, and post-exposure immunoprophylaxis in the Arabian Gulf region and Saudi Arabian Peninsula. Methods: A comprehensive literature search was conducted in databases including PubMed, Scopus, WoS, MedLine, and Cochrane Library up to July 2024. Studies were included discussing the reported cases of rabies that received the PEP in all countries of the Arabian Gulf, their epidemiological data, the received schedules of vaccination, and their safety. The search was done by using the following terminologies: rabies vaccine, rabies human diploid cell vaccine, vaccine, Saudi Arabia, Bahrain, Iraq, Kuwait, Oman, Qatar, United Arab Emirates, Southwest Asia, Iran, West Asia, Western Asia, Persian Gulf, Arabian Gulf, Gulf of Ajam, Saudi Arabian Peninsula, and The Kingdom of Saudi Arabia. Results: The systematic scoping review included 36 studies, synthesizing findings from diverse research designs, including large-scale cross-sectional studies and case reports, spanning nearly three decades. Findings indicated that young males in urban areas are most at risk for animal bites, predominantly from domestic dogs and cats. While post-exposure prophylaxis (PEP) was generally administered within recommended timeframes, vaccination completion rates varied. Conclusions: The review highlighted gaps in public awareness about rabies risks and prevention. Vaccine safety profiles were generally favorable, with mostly mild-to-moderate side effects reported. The study underscores the need for enhanced public health education, standardized PEP protocols, and a One Health approach to rabies prevention. Full article

Rabies remains a significant public health and economic concern in Kazakhstan, particularly in rural livestock-farming communities. This study aimed to assess the knowledge, attitudes, and practices (KAPs) related to rabies among livestock farmers in the Aktobe and Oral regions of West Kazakhstan. A cross-sectional survey was conducted between April and August 2022, involving 688 randomly selected participants. The data were collected through structured interviews and analyzed using descriptive and inferential statistics. The findings revealed that 89% of respondents were aware of rabies, yet significant knowledge gaps existed regarding clinical signs, transmission, and prevention. While 87% recognized the importance of rabies vaccination in dogs, 81% were unaware of pre-exposure prophylaxis (PrEP) for cattle, and 72% lacked knowledge of PrEP for humans. Awareness of the post-exposure prophylaxis (PEP) regimen was significantly higher in the Aktobe region (p < 0.002). Attitudinal differences were observed, with the Oral region participants exhibiting more favorable perceptions of rabies control programs (p < 0.01). Additionally, the χ² test revealed that the proportion of female respondents (p < 0.02), those with school-aged dependents (p < 0.003), respondents owning both exotic and indigenous cattle breeds (p < 0.002), and those possessing more than five cattle (p < 0.025) was statistically different in the Oral region. Practices such as free grazing, lack of protective equipment use, and improper carcass disposal were identified as potential risk factors for rabies transmission. This study highlights the need for targeted educational initiatives to improve rabies awareness and promote safer livestock management practices. Enhancing veterinary surveillance, strengthening community engagement, and expanding vaccination efforts could mitigate rabies transmission risks. Full article

In 2021, the World Health Organization (WHO) recommended scaling up leprosy prevention activities, including chemoprophylaxis, as one of the pillars of their ‘Towards Zero Leprosy’ strategy. This recommendation was primarily based on a 57% overall reduction in leprosy incidence among contacts who received chemoprophylaxis in the COLEP study conducted in Bangladesh. Since this landmark study, further research on the efficacy, feasibility, and implementation of leprosy chemoprophylaxis has been conducted. Additionally, concerns have been raised regarding the strength of evidence supporting the overall benefit of chemoprophylaxis and the potential for propagation of drug resistance in M. leprae strains. This literature review presents the current evidence for the efficacy and safety of rifamycin-based chemoprophylaxis in preventing clinical disease, and the feasibility of implementing chemoprophylaxis programmes. Post-exposure prophylaxis (PEP) has a reported efficacy of 45–80%, depending on the degree of case contact, the classification of the index case, the selected chemoprophylaxis regimen, the geographical setting, childhood BCG coverage and the implementation approach. As an intervention, it appears to be feasible, cost-effective, and acceptable to patients, contacts, and healthcare staff, with minimal harm. Implementation strategies need to be tailored to specific epidemiological and sociocultural settings for maximal benefit. Further research is required to optimise PEP regimens and strategies in various epidemiological settings and to assess the impact of these programmes on the susceptibility profile of local M. leprae strains. Full article

Objective: Evidence on long-term antibody persistence for the rabies vaccine administered using the four-dose Essen regimen is lacking. This study compared antibody persistence for the human diploid cell rabies vaccine (HDCV) administered using the four- versus five-dose Essen intramuscular regimen in post-exposure prophylaxis (PEP). Methods: This prospective cohort study enrolled patients vaccinated with the lyophilized HDCV for PEP who were grouped into four-dose and five-dose Essen groups. Rabies virus-neutralizing antibody (RVNA) detection was performed at 1 year or 3 years after initial vaccination. Results: In total, 180 and 184 patients were included in the four- and five-dose groups, respectively. The 1-year seroconversion (>0.5 IU/mL) rates were similar in the five-dose and four-dose Essen groups (99.2% vs. 98.3%, p = 0.662), as were the 3-year seroconversion rates (98.4% vs. 98.3%, p > 0.999). The median RVNA titer was significantly higher with the five-dose Essen regimen compared with the four-dose Essen regimen at 1 year (2.75 vs. 4.6 IU/mL, p = 0.002), and both groups had similar rates at 3 years (2.00 vs. 3.80 IU/mL, p = 0.443). Multivariable stepwise linear regression analysis showed that the five-dose Essen regimen was independently associated with higher serum RVNA titer compared to the four-dose Essen regimen (β = 0.175, p = 0.001), and 3 years after vaccination, was independently associated with a lower serum RVNA titer compared to 1 year (β = −1.06, p = 0.049). Conclusions: The four- and five-dose Essen regimens effectively produce durable immunogenicity, supporting the feasibility of implementing the four-dose Essen regimen for rabies immunization in China. Full article

The aim of this study was to analyze the predisposition and factors associated with the use of Post-Exposure Prophylaxis (PEP) for HIV in men who have sex with men (MSM). This was a cross-sectional study conducted in the city of Teresina, Piauí, Brazil, between January and July 2024. The study sample consisted of 320 MSM. A questionnaire consisting of 37 previously validated questions and a risk perception scale for HIV with eight questions were used. To explain which factors would be associated with predisposition to the use of PEP, a logistic regression analysis was applied with an odds ratio. The criterion for including variables in the logistic model was an association at the 20% level (p ˂ 0.20) in the bivariate analysis. Statistical significance in the final model was set at 5%. Although the vast majority of MSM reported a willingness to use PEP (94.4%), their knowledge about prophylaxis and their HIV risk perceptions were largely unsatisfactory. It was found that living alone reduces the chances of predisposition to PEP use by 75% (AOR = 0.25; p = 0.01), and using a condom during oral sex reduces the chances of predisposition to PEP use by 91% (AOR = 0.09; p < 0.001). In light of this, the importance of greater investments in health education actions that reinforce the mechanisms of HIV transmission, as well as the use of methods for its prevention, is highlighted. In addition, targeted interventions are needed to improve knowledge about PEP and HIV risk perception. Full article

Syphilis, a global healthcare burden, is a sexually transmitted infection caused by the spirochete Treponema pallidum, a spiral-shaped, Gram-negative obligate human pathogen. Despite its easy identification and treatability, the disease affects over 50 million people worldwide, with 8 million new cases in the 15–49 age group annually, as per the WHO 2024 report. If left untreated, syphilis progresses through its primary, secondary, latent, and tertiary stages, causing severe complications like neurosyphilis, congenital syphilis, and organ damage. The first-line treatment, penicillin, faces challenges, including logistical issues, shortages, allergic reactions, and patient non-compliance. Secondary treatment options are sparse, and there are reported cases of T. pallidum strains resistant to those antibiotics. The absence of an effective vaccine for syphilis has led to efforts to control its spread through sexual education, condom usage, and post-exposure prophylaxis with doxycycline, which raises concerns about antimicrobial resistance (AMR). The continued reliance on penicillin and the increasing rates of doxycycline post-exposure prophylaxis (DoxyPEP) use have both contributed to concerns about AMR development. Recent works pointing to emerging antibiotic resistance and treatment failures highlight the urgent need for new antibiotics to manage syphilis effectively and reduce dependency on penicillin. This review has focused on the shortcomings and limitations of penicillin treatment, recently identified antimicrobial-resistant strains of T. pallidum, and case studies where its application failed to treat the disease adequately. Full article

Over the past two decades, the global incidence of sexually transmitted infections (STIs) such as gonorrhea, chlamydia, and syphilis have increased significantly, particularly among cisgender men who have sex with men (MSM) and transgender women (TGW). This rise in STIs has spurred interest in new preventive measures, including doxycycline post-exposure prophylaxis (DoxyPEP). Clinical trials in the United States and France have demonstrated the effectiveness of DoxyPEP in reducing both chlamydia and syphilis incidence among MSM and TGW; although, its efficacy against gonorrhea remains limited, and it was further found to be ineffective among cisgender women in Kenya. Due to the promising results, the CDC and the German STI Society have incorporated DoxyPEP into their guidelines for specific high-risk groups. However, the broader implementation of DoxyPEP presents several challenges and ethical concerns. Key issues involve the potential development of antimicrobial resistance, particularly among common STI pathogens like C. trachomatis, M. genitalium, and N. gonorrhoeae, as well as other bacteria such as S. aureus and K. pneumoniae. Additionally, questions concerning equitable healthcare access, the potential impact on adherence to safer sex practices, and broader public health implications warrant careful consideration. Addressing these challenges necessitates a careful balance between the benefits and risks of DoxyPEP, as well as the implementation of strategies to mitigate negative outcomes while maximizing the impact on public health. Lastly, future research should explore the integration of DoxyPEP with other preventive strategies, such as vaccines, to enhance its effectiveness and reduce the global burden of STIs. Full article

Background: The effectiveness of pre-exposure prophylaxis (PrEP) and non-occupational post-exposure prophylaxis (nPEP) in preventing HIV is well-established, yet their use in clinical practice remains low. Healthcare providers, especially those in primary and emergency care settings, play a crucial role in adopting and implementing these prevention strategies. We conducted a statewide survey with 519 healthcare providers in Texas to assess their knowledge, practices, and barriers related to prescribing PrEP and nPEP. Methods: The survey collected data on demographics, clinical experience, practice type, awareness of recommended guidelines, knowledge of PrEP and nPEP, prescribing practices, and challenges encountered to prescribe these medications. We used multiple regression analysis to identify factors associated with PrEP and nPEP prescribing behavior. Results: While most providers were familiar with CDC and/or USPSTF-recommended PrEP guidelines, fewer had adequate knowledge of nPEP. Key challenges identified by providers included concerns about cost (48%), limited time (40% for PrEP and 51% for nPEP), and insufficient education or training (40% for PrEP and 35% for nPEP). Providers who were more familiar with the recommended guidelines and had greater experience in sexual health assessment were more likely to prescribe both PrEP and nPEP. Conclusions: This study highlights the need for enhanced education and training to boost providers’ knowledge and confidence in prescribing PrEP and nPEP. It also underscores the importance of addressing cost-related barriers and simplifying care processes to better integrate these HIV prevention strategies into primary and emergency care settings. Full article

The World Health Organization is encouraging countries to include contact screening and single-dose rifampicin administration as preventive chemotherapy for contacts of leprosy patients in their leprosy control activities. However, no study has been conducted to assess the safety of SDR-PEP and the acceptability and feasibility of this intervention in Togo. To assess the safety of SDR-PEP, we used a cohort design, and for acceptability and feasibility, we used a mixed method, combining a quantitative study to assess the safety of SDR-PEP in a cohort of contacts from recently diagnosed leprosy patients followed by a qualitative study to identify the social, cultural, or institutional factors that would influence the adoption of single-dose rifampicin as post-exposure prophylaxis for contacts of leprosy patients in Togo. For the quantitative study, all identified index patients agreed to the disclosure of their status to their contacts and provided a list of their contacts. All the contacts found agreed to take part in the study, and an appointment was made for screening. However, some contacts were absent on the screening day for no reason. All eligible contacts agreed to take SDR and were followed up after taking the drug. No severe adverse events were reported during the follow-up. For the qualitative study, 72 interviews (66 semi-structured interviews and 6 focus groups) were carried out, and it emerged that, overall, opinions were favorable on the acceptability and feasibility of implementing single-dose rifampicin as post-exposure prophylaxis for contacts of leprosy patients in Togo. However, a number of conditions need to be considered for more effective results. Full article

Anthrax is a fatal zoonotic disease caused by exposure to Bacillus anthracis spores. The CDC’s guidelines divide anthrax treatment into three categories according to disease progression: post-exposure prophylaxis (PEP), systemic, and systemic with a suspicion of CNS infection. While the prognosis for PEP or the early treatment of systemic anthrax is very good, ingress of the bacteria into the CNS poses a substantial clinical challenge. Here, we use rabbits to test the efficacy of a combined treatment of meropenem and doxycycline, which is the first choice in the CDC recommendations for treating systemic patients with an indication of CNS infection. In addition, we test the efficacy of the first-generation cephalosporin, cefazolin, in treating different stages of the disease. We found that the combination of doxycycline and meropenem is highly effective in treating rabbits in our inhalation model. Cefazolin was efficient only for PEP or systemic-stage treatment and not for CNS-infected animals. Our findings support the CDC recommendation of using a combination of doxycycline and meropenem for systemic patients with or without indications of CNS infection. We found that cefazolin is a decent choice for PEP or early-stage systemic disease but recommend considering using this antibiotic only if all other options are not available. Full article