Antivirals for post-exposure prophylaxis of influenza: a systematic review and network meta-analysis.

BACKGROUND: Antiviral post-exposure prophylaxis with neuraminidase inhibitors can reduce the incidence of influenza and the risk of symptomatic influenza, but the efficacy of the other classes of antiviral remains unclear. To support an update of WHO influenza guidelines, this systematic review and network meta-analysis evaluated antiviral drugs for post-exposure prophylaxis of influenza. METHODS: We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Global Health, Epistemonikos, and ClinicalTrials.gov for randomised controlled trials published up to Sept 20, 2023 that evaluated the efficacy and safety of antivirals compared with another antiviral or placebo or standard care for prevention of influenza. Pairs of reviewers independently screened studies, extracted data, and assessed the risk of bias. We performed network meta-analyses with frequentist random effects model and assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. The outcomes of interest were symptomatic or asymptomatic infection, admission to hospital, all-cause mortality, adverse events related to antivirals, and serious adverse events. This study is registered with PROSPERO, CRD42023466450. FINDINGS: Of 11 845 records identified by our search, 33 trials of six antivirals (zanamivir, oseltamivir, laninamivir, baloxavir, amantadine, and rimantadine) that enrolled 19 096 individuals (mean age 6·75-81·15 years) were included in this systematic review and network meta-analysis. Most of the studies were rated as having a low risk of bias. Zanamivir, oseltamivir, laninamivir, and baloxavir probably achieve important reductions in symptomatic influenza in individuals at high risk of severe disease (zanamivir: risk ratio 0·35, 95% CI 0·25-0·50; oseltamivir: 0·40, 0·26-0·62; laninamivir: 0·43, 0·30-0·63; baloxavir: 0·43, 0·23-0·79; moderate certainty) when given promptly (eg, within 48 h) after exposure to seasonal influenza. These antivirals probably do not achieve important reductions in symptomatic influenza in individuals at low risk of severe disease when given promptly after exposure to seasonal influenza (moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir might achieve important reductions in symptomatic zoonotic influenza in individuals exposed to novel influenza A viruses associated with severe disease in infected humans when given promptly after exposure (low certainty). Oseltamivir, laninamivir, baloxavir, and amantadine probably decrease the risk of all influenza (symptomatic and asymptomatic infection; moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir probably have little or no effect on prevention of asymptomatic influenza virus infection or all-cause mortality (high or moderate certainty). Oseltamivir probably has little or no effect on admission to hospital (moderate certainty). All six antivirals do not significantly increase the incidence of drug-related adverse events or serious adverse events, although the certainty of evidence varies. INTERPRETATION: Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir probably decreases the risk of symptomatic seasonal influenza in individuals at high risk for severe disease after exposure to seasonal influenza viruses. Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir might reduce the risk of symptomatic zoonotic influenza after exposure to novel influenza A viruses associated with severe disease in infected humans. FUNDING: World Health Organization.

Immunogenicity and Safety of a Purified Vero Rabies Vaccine-Serum Free, Compared With 2 Licensed Vaccines, in a Simulated Rabies Post-Exposure Regimen in Healthy Adults in France: A Randomized, Controlled, Phase 3 Trial.

BACKGROUND: A next-generation Vero cell rabies vaccine (PVRV-NG2) was developed using the same Pitman-Moore strain as in the licensed purified Vero cell vaccine (PVRV; Verorab) and the human diploid cell vaccine (HDCV; Imovax Rabies®). METHODS: This dual-center, modified, double-blind, phase 3 study evaluated the immunogenic non-inferiority and safety of PVRV-NG2 with and without concomitant intramuscular human rabies immunoglobulin (HRIG) versus PVRV + HRIG and HDCV + HRIG in a simulated post-exposure prophylaxis (PEP) regimen. Healthy adults ≥18 years old (N = 640) were randomized 3:1:1:1 to PVRV-NG2 + HRIG, PVRV + HRIG, HDCV + HRIG, or PVRV-NG2 alone (administered as single vaccine injections on days [D] 0, D3, D7, D14, and 28, with HRIG on D0 in applicable groups). Rabies virus neutralizing antibodies (RVNA) titers were assessed pre- (D0) and post-vaccination (D14, D28, and D42) using the rapid fluorescent focus inhibition test. Non-inferiority, based on the proportion of participants achieving RVNA titers ≥0.5 IU/mL (primary objective), was demonstrated if the lower limit of the 95% CI of the difference in proportions between PVRV-NG2 + HRIG and PVRV + HRIG/HDCV + HRIG was >-5% at D28. Safety was assessed up to 6 months after the last injection. RESULTS: Non-inferiority of PVRV-NG2 + HRIG compared with PVRV + HRIG and HDCV + HRIG was demonstrated. Nearly all participants (99.6%, PVRV-NG2 + HRIG; 100%, PVRV + HRIG; 98.7%, HDCV + HRIG; 100%, PVRV-NG2 alone) achieved RVNA titers ≥0.5 IU/mL at D28. Geometric mean titers were similar between groups with concomitant HRIG administration at all time points. Safety profiles were similar between PVRV-NG2 and comparator vaccines. CONCLUSIONS: In a simulated PEP setting, PVRV-NG2 + HRIG showed comparable immunogenicity and safety to current standard-of-care vaccines. CLINICAL TRIALS REGISTRATION: NCT03965962.

Postexposure prophylaxis for occupational exposure to selected pathogens for healthcare personnel.

PURPOSE OF REVIEW: Timely postexposure prophylaxis is important after an occupational exposure. Here we review select organisms, exposure opportunities in the healthcare setting, and postexposure prophylaxis regimens. RECENT FINDINGS: Needlestick injuries pose a risk of exposure to bloodborne pathogens, such as HIV, Hepatitis B, and Hepatitis C. Risk mitigation strategies should be reexamined in light of newer vaccines and therapeutics. Increased vaccine hesitancy and vaccine denialisms may foster the re-emergence of some infections that have become extremely uncommon because of effective vaccines. With increasing occurrences of zoonotic infections and the ease of global spread as evidenced by COVID-19 and mpox, healthcare exposures must also consider risks related to emerging and re-emerging infectious diseases. SUMMARY: Early recognition and reporting of occupational exposures to pathogens with available postexposure prophylaxis is key to mitigating the risk of transmission. Providers should be able to evaluate the exposure and associated risks to provide prompt and appropriate postexposure prophylaxis.

One-dose intradermal rabies booster enhances rabies antibody production and avidity maturation.

The incidence of rabies in Thailand reached its peak in 2018 with 18 human deaths. Preexposure prophylaxis (PrEP) vaccination is thus recommended for high-risk populations. WHO has recently recommended that patients who are exposed to a suspected rabid animal and have already been immunized against rabies should receive a 1-site intradermal (ID) injection of 0.1 mL on days 0 and 3 as postexposure prophylaxis (PEP). In Thailand, village health and livestock volunteers tasked with annual dog vaccination typically receive only a single lifetime PrEP dose and subsequent boosters solely upon confirmed animal bites. However, the adequacy of a single PrEP dose for priming and maintaining immunity in this high-risk group has not been evaluated. Therefore, our study was designed to address two key questions: (1) sufficiency of single-dose PrEP-to determine whether a single ID PrEP dose provides adequate long-term immune protection for high-risk individuals exposed to numerous dogs during their vaccination duties. (2) Booster efficacy for immune maturation-to investigate whether one or two additional ID booster doses effectively stimulate a mature and sustained antibody response in this population. The level and persistence of the rabies antibody were determined by comparing the immunogenicity and booster efficacy among the vaccination groups. Our study demonstrated that rabies antibodies persisted for more than 180 days after cost-effective ID PrEP or the 1st or the 2nd single ID booster dose, and adequate antibody levels were detected in more than 95% of participants by CEE-cELISA and 100% by indirect ELISA. Moreover, the avidity maturation of rabies-specific antibodies occurred after the 1st single ID booster dose. This smaller ID booster regimen was sufficient for producing a sufficient immune response and enhancing the maturation of anti-rabies antibodies. This safe and effective PrEP regimen and a single visit involving a one-dose ID booster are recommended, and at least one one-dose ID booster regimen could be equitably implemented in at-risk people in Thailand and other developing countries. However, an adequate antibody level should be monitored before the booster is administered.

The PEP++ study protocol: a cluster-randomised controlled trial on the effectiveness of an enhanced regimen of post-exposure prophylaxis for close contacts of persons affected by leprosy to prevent disease transmission.

BACKGROUND: Leprosy is an infectious disease with a slow decline in global annual caseload in the past two decades. Active case finding and post-exposure prophylaxis (PEP) with a single dose of rifampicin (SDR) are recommended by the World Health Organization as measures for leprosy elimination. However, more potent PEP regimens are needed to increase the effect in groups highest at risk (i.e., household members and blood relatives, especially of multibacillary patients). The PEP++ trial will assess the effectiveness of an enhanced preventive regimen against leprosy in high-endemic districts in India, Brazil, Bangladesh, and Nepal compared with SDR-PEP. METHODS: The PEP++ study is a cluster-randomised controlled trial in selected districts of India, Brazil, Bangladesh, and Nepal. Sub-districts will be allocated randomly to the intervention and control arms. Leprosy patients detected from 2015 - 22 living in the districts will be approached to list their close contacts for enrolment in the study. All consenting participants will be screened for signs and symptoms of leprosy and tuberculosis (TB). In the intervention arm, eligible contacts receive the enhanced PEP++ regimen with three doses of rifampicin (150 - 600 mg) and clarithromycin (150 - 500 mg) administered at four-weekly intervals, whereas those in the control arm receive SDR-PEP. Follow-up screening for leprosy will be done for each individual two years after the final dose is administered. Cox' proportion hazards analysis and Poisson regression will be used to compare the incidence rate ratios between the intervention and control areas as the primary study outcome. DISCUSSION: Past studies have shown that the level of SDR-PEP effectiveness is not uniform across contexts or in relation to leprosy patients. To address this, a number of recent trials are seeking to strengthen PEP regimens either through the use of new medications or by increasing the dosage of the existing ones. However, few studies focus on the impact of multiple doses of chemoprophylaxis using a combination of antibiotics. The PEP++ trial will investigate effectiveness of both an enhanced regimen and use geospatial analysis for PEP administration in the study communities. TRIAL REGISTRATION: NL7022 on the Dutch Trial Register on April 12, 2018. Protocol version 9.0 updated on 18 August 2022 https://www.onderzoekmetmensen.nl/en/trial/23060.

Safety and adherence of bictegravir/emtricitabine/tenofovir alafenamide for HIV post-exposure prophylaxis among adults in Guiyang China: a prospective cohort study.

BACKGROUND: The effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens. METHODS: In this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG). RESULTS: The PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events. CONCLUSIONS: BIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391 ).

Spatial accessibility and inequality analysis of rabies-exposed patients to rabies post-exposure prophylaxis clinics in Guangzhou City, China.

BACKGROUND: The incidence of rabies exposure is high and increasing in China, leading to an urgent demand of rabies post-exposure prophylaxis (PEP) clinics for the injured. However, the spatial accessibility and inequality of rabies-exposed patients to rabies PEP clinics is less known in China. METHODS: Based on rabies exposure data, PEP clinic data, and resident travel origin-destination (OD) matrix data in Guangzhou City, China, we first described the incidence of rabies exposure in Guangzhou from 2020 to 2022. Then, the Gaussian two-step floating catchment area method (2SFCA) was used to analyze the spatial accessibility of rabies-exposed patients to rabies PEP clinics in Guangzhou, and the Gini coefficient and Moran's I statistics were utilized to evaluate the inequality and clustering of accessibility scores. RESULTS: From 2020 to 2022, a total of 524,160 cases of rabies exposure were reported in Guangzhou, and the incidence showed a significant increasing trend, with an average annual incidence of 932.0/100,000. Spatial accessibility analysis revealed that the overall spatial accessibility scores for three scenarios (threshold of driving duration [d0] = 30 min, 45 min, and 60 min) were 0.30 (95% CI: 0.07, 0.87), 0.28 (95% CI: 0.11, 0.53) and 0.28 (95% CI: 0.14, 0.44), respectively. Conghua, Huangpu, Zengcheng and Nansha districts had the higher accessibility scores, while Haizhu, Liwan, and Yuexiu districts exhibited lower spatial accessibility scores. The Gini coefficient and Moran's I statistics showed that there were certain inequality and clustering in the accessibility to rabies PEP clinics in Guangzhou. CONCLUSIONS: This study clarifies the heterogeneity of spatial accessibility to rabies PEP clinics, and provide valuable insights for resource allocation to achieve the WHO target of zero human dog-mediated rabies deaths by 2030.

Live Vaccine and Varicella Postexposure Prophylaxis in Pediatric Liver Transplant Recipients: A Survey of Practice in Australia and New Zealand.

BACKGROUND: Administration of live vaccines following liver transplant (LT) has historically not been recommended due to concerns regarding risk of vaccine-attenuated disease. However, there is evidence suggesting that in select transplant recipients live vaccinations can be administered safely. Studies in other regions have indicated that despite this evidence many clinicians remain hesitant to administer live vaccinations. METHOD: A REDCap survey was distributed to gastroenterologists, pediatricians, and infectious diseases physicians at pediatric centers across Australia and New Zealand via email between September and November 2023. The survey included a series of questions regarding live vaccine and varicella postexposure prophylaxis (PEP) practices in pediatric LT recipients and barriers to live vaccine administration in this cohort. RESULTS: There was a total of 16 responses to the survey, from 10 different pediatric centers, including 10/11 pediatric gastroenterology centers and all four pediatric LT centers in the region. Only 31% (5/16) of respondents (from 3/10 different centers) offer live vaccines. The main barrier to live vaccine administration was clinician reluctance and the main reason for not offering live vaccines was insufficient safety data. Sixty-nine percent (11/16) of respondents take vaccination status and/or serology into account when deciding whether to offer varicella PEP to this cohort. Respondents universally offer varicella zoster immunoglobulin as PEP, though 31% (5/16) also offer antiviral medication. CONCLUSIONS: Many clinicians in our region remain hesitant to provide live vaccines to pediatric LT recipients, with concerns regarding insufficient safety data. Updated local guidelines may help to address this.

Rabies post-exposure prophylaxis in the emergency department.

STUDY OBJECTIVES: Rabies is a zoonotic single-stranded RNA lyssavirus that can cause acute infections of the central nervous system (CNS) including encephalomyelitis, encephalitis, and meningoencephalitis that is progressively fatal. Rabies is more common in developing countries, but approximately 23,000 people in the United States (US) are estimated to have been exposed or to have received post exposure prophylaxis (PEP) yearly. Nebraska Medicine follows the Advisory Committee on Immunization Practices (ACIP) guidelines for the vaccination series, as well as the 20 units/kg administration of immunoglobulin (RIG). Nebraska Medicine Medical Center (NMC) and Bellevue Medical Center (BMC) treat the scheduling of the complete rabies vaccine series differently. At both campuses, patients receive their immunoglobulin and first vaccine in the Emergency Department (ED). At NMC, patients are scheduled to receive the remainder of their vaccination series at the outpatient infusion center by the ED pharmacist. At BMC, the subsequent vaccinations are given as "Nurse Only" return visits to the ED. The objective of this study was to compare patient compliance of two different processes for follow-up rabies vaccine series completion. This project's primary aim was to determine the rate of patient compliance for follow up rabies vaccine doses. The secondary aims of this project were to determine if there was a difference in patient follow-up compliance between the two campuses, patient specific factors that impact compliance, and potential cost savings if a dose rounding protocol for RIG was utilized. METHODS: This retrospective chart review was completed as a quality improvement project. Data from patients who had received either rabies immunoglobulin and/or a rabies vaccine, were >18 years of age, and were not admitted were collected for a 3-year period from July 1, 2019, to June 30, 2022. Data were abstracted from the patient's EMR (electronic medical records) using a SQL (Structured query language) query of pre-identified data elements. When unable to abstract with SQL query, data elements were manually abstracted. All data abstracted was collated and descriptive analysis performed. RESULTS: A total of 723 individual encounters were identified during the study period. After combining rabies series for each individual patient, 173 unique patients remained. After exclusions were applied, 143 patients were included: 104 patients from NMC, and 39 from BMC. For the primary outcome, appropriate completion between the two campuses was 78.3%. When comparing the two campuses, completion rates were higher at NMC (82% vs. 69%), although not statistically significant (p = 0.12). Appropriate completion of vaccine series was statistically significant for both payor and exposure type. Application of a dose rounding policy with those >45 kg, rounding to the nearest vial, as well as rounding down if at the midpoint interval, 56 fewer vials would have been used between the two campuses. This would have resulted in a potential cost savings of $57,928.64 over the study period.

Pre-exposure and postexposure prophylaxis access in rural versus urban pharmacies in Georgia and Pennsylvania.

BACKGROUND: Pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) prevent HIV among individuals at high risk for acquisition. Pre-existing structural barriers to PrEP/PEP access among rural patients may be exacerbated further if pharmacies do not keep PrEP/PEP in stock, constituting a significant barrier to mitigating the HIV epidemic. OBJECTIVES: To compare PrEP/PEP availability for same-day pickup in rural vs urban Georgia and Pennsylvania pharmacies. METHODS: We conducted a cross-sectional simulated patient caller study, calling pharmacists in Georgia and Pennsylvania to see whether PrEP/PEP was available for same-day pickup. We identified retail pharmacies through state pharmacy boards and categorized rurality using state-based definitions. We used multivariable logistic regression to assess PrEP availability by rurality and Ending the HIV Epidemic (EHE) designation, accounting for chain pharmacy status and county-level racial composition. RESULTS: Among 481 pharmacies contacted (304 in Pennsylvania and 177 in Georgia), only 30.77% had PrEP for same-day pickup and only 10.55% had PEP for same-day pickup. PrEP availability did not differ significantly by state. Urban pharmacies had 2.02 (95% CI: 1.32-3.09) greater odds of PrEP same-day availability compared to rural pharmacies. Pharmacies in EHE counties had 3.45 (95% CI: 1.9-6.23) times higher odds of carrying PrEP compared to non-EHE counties. CONCLUSIONS: Pharmacies were unlikely to carry PrEP or PEP. Pharmacies in rural compared to urban, and non-EHE compared to EHE locations were less likely to carry PrEP. Addressing pharmacy barriers to PrEP/PEP may enhance access to HIV prevention for those living at high risk of HIV.

Telemedicine in Post-Exposure Prophylaxis to Biological Material During the COVID-19 Pandemic: Impact on Care and Outcome Indicators.

Introduction: The restrictions on face-to-face care for exposure to biological material during the COVID-19 pandemic required alternatives to maintain outpatient assistance. This study evaluated the impact of telemedicine on care and outcome indicators of a reference service for exposure to biological material during the COVID-19 pandemic. Methods: This pre- and post-study compared the effectiveness of telemedicine in the Hospital Correia Picanço in Recife (Pernambuco, Brazil) before (August 2018 to January 2019 [P1]) and during the COVID-19 pandemic (August 2020 to January 2021 [P2]). Individuals above 18 years old exposed to biological material who sought the service during P1 or P2 were included in the study. Results: A total of 4,494 cases were assessed (1,997 in P1 and 2,497 in P2), mostly because of sexual exposure (62.3%). The mean age was 32.2 ± 9.2 years, most individuals were male (64.9%), originated from Recife (56.6%), and the education level was up to 12 years (53.7%). P2 presented 43% more attendances and shorter intervals between the exposure and first attendance (51%), first testing (28%), and discharge (10%) than P1 (p < 0.05), and cases had no difference in discharge rate (p = 0.339). Cases of sexual exposure had the highest dropout rate in both periods. Conclusion: Telemedicine maintained similar outcomes to face-to-face care and improved the indicators, increasing the mean monthly attendance and reducing the time between exposure and follow-up.

[From HIV screening to diagnosis : indications, tests, and post-exposure prophylaxis]. / Du dépistage au diagnostic du VIH : indications, tests et prophylaxie postexposition.

Despite the substantial national resources invested in the fight against HIV to achieve its elimination, its incidence has remained stable in recent years. In 2022, the FOPH estimated that 7% of people living with HIV in Switzerland remained undiagnosed, underlining the potential for improving screening. The aim of this article is to present the process of HIV screening and diagnosis in clinical practice, adapted to the Federal Office of Public Health (FOPH) national strategy, and including the different indications for screening, the interpretation of available tests, and the place of post-exposure prophylaxis (PEP).

Malgré les ressources nationales considérables investies dans la lutte contre le VIH pour atteindre son élimination, son incidence est restée stable ces dernières années. En 2022, l'Office fédéral de la santé publique (OFSP) a estimé que 7 % des personnes vivant avec le VIH en Suisse n'étaient pas diagnostiquées, soulignant ainsi un potentiel d'amélioration du dépistage. L'objectif de cet article est de présenter le processus de dépistage et de diagnostic du VIH en pratique clinique, conformément à la stratégie nationale de l'OFSP. Il couvre les différentes indications au dépistage, l'interprétation des tests disponibles, ainsi que la place de la prophylaxie postexposition (PEP).

Fatal Human Rabies Infection With Suspected Host-Mediated Failure of Post-Exposure Prophylaxis Following a Recognized Zoonotic Exposure-Minnesota, 2021.

BACKGROUND: No human rabies post-exposure prophylaxis (PEP) failure has been documented in the United States using modern cell culture-based vaccines. In January 2021, an 84-year-old male died from rabies 6 months after being bitten by a rabid bat despite receiving timely rabies PEP. We investigated the cause of breakthrough infection. METHODS: We reviewed medical records, laboratory results, and autopsy findings and performed whole-genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close patient contacts. RESULTS: Rabies virus antibodies present in serum and cerebrospinal fluid were nonneutralizing. Antemortem blood testing revealed that the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, 3 (0.9%) warranted PEP. CONCLUSIONS: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture-based vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise.

Strategies to inTerrupt RAbies Transmission for the Elimination Goal by 2030 In China (STRATEGIC): a modelling study.

BACKGROUND: A global plan has been set to end human deaths from dog-mediated rabies by 2030 ("Zero-by-30"), but whether it could be achieved in some countries, such as China, remains unclear. Although elimination strategies through post-exposure prophylaxis (PEP) use, dog vaccination, and patient risk assessments with integrated bite case management (IBCM) were proposed to be cost-effective, evidence is still lacking in China. We aim to evaluate the future burdens of dog-mediated human rabies deaths in the next decade and provide quantitative evidence on the cost-effectiveness of different rabies-control strategies in China. METHODS: Based on data from China's national human rabies surveillance system, we used decision-analytic modelling to estimate dog-mediated human rabies death trends in China till 2035. We simulated and compared the expected consequences and costs of different combination strategies of the status quo, improved access to PEP, mass dog vaccination, and use of IBCM. RESULTS: The predicted human rabies deaths in 2030 in China will be 308 (95%UI: 214-411) and remain stable in the next decade under the status quo. The strategy of improved PEP access alone could only decrease deaths to 212 (95%UI: 147-284) in 2028, remaining unchanged till 2035. In contrast, scaling up dog vaccination to coverage of 70% could eliminate rabies deaths by 2033 and prevent approximately 3,265 (95%UI: 2,477-3,687) extra deaths compared to the status quo during 2024-2035. Moreover, with the addition of IBCM, the "One Health" approach through mass dog vaccination could avoid unnecessary PEP use and substantially reduce total cost from 12.53 (95%UI: 11.71-13.34) to 8.73 (95%UI: 8.09-9.85) billion US dollars. Even if increasing the total costs of IBCM from 100 thousand to 652.10 million US dollars during 2024-2035, the combined strategy of mass dog vaccination and use of IBCM will still dominate, suggesting the robustness of our results. CONCLUSIONS: The combined strategy of mass dog vaccination and IBCM requires collaboration between health and livestock/veterinary sectors, and it could eliminate Chinese rabies deaths as early as 2033, with more deaths averted and less cost, indicating that adding IBCM could reduce unnecessary use of PEP and make the "One Health" rabies-control strategy most cost-effective.

Neuroimmunology of rabies: New insights into an ancient disease.

Rabies is an ancient neuroinvasive viral (genus Lyssavirus, family Rhabdoviridae) disease affecting approximately 59,000 people worldwide. The central nervous system (CNS) is targeted, and rabies has a case fatality rate of almost 100% in humans and animals. Rabies is entirely preventable through proper vaccination, and thus, the highest incidence is typically observed in developing countries, mainly in Africa and Asia. However, there are still cases in European countries and the United States. Recently, demographic, increasing income levels, and the coronavirus disease 2019 (COVID-19) pandemic have caused a massive raising in the animal population, enhancing the need for preventive measures (e.g., vaccination, surveillance, and animal control programs), postexposure prophylaxis, and a better understanding of rabies pathophysiology to identify therapeutic targets, since there is no effective treatment after the onset of clinical manifestations. Here, we review the neuroimmune biology and mechanisms of rabies. Its pathogenesis involves a complex and poorly understood modulation of immune and brain functions associated with metabolic, synaptic, and neuronal impairments, resulting in fatal outcomes without significant histopathological lesions in the CNS. In this context, the neuroimmunological and neurochemical aspects of excitatory/inhibitory signaling (e.g., GABA/glutamate crosstalk) are likely related to the clinical manifestations of rabies infection. Uncovering new links between immunopathological mechanisms and neurochemical imbalance will be essential to identify novel potential therapeutic targets to reduce rabies morbidity and mortality.

A novel mRNA rabies vaccine as a promising candidate for rabies post-exposure prophylaxis protects animals from different rabies viruses.

Rabies, caused by the rabies virus (RABV), is the most fatal zoonotic disease. It is a neglected tropical disease which remains a major public health problem, causing approximately 59,000 deaths worldwide annually. Despite the existence of effective vaccines, the high incidence of human rabies is mainly linked to tedious vaccine immunisation procedures and the overall high cost of post-exposure prophylaxis. Therefore, it is necessary to develop an effective vaccine that has a simple procedure and is affordable to prevent rabies infection in humans. RABV belongs to the genus Lyssavirus and family Rhabdoviridae. Previous phylogenetic analyses have identified seven major clades of RABV in China (China I-VII), confirmed by analysing nucleotide sequences from both the G and N proteins. This study evaluated the immunogenicity and protective capacity of SYS6008, an mRNA rabies vaccine expressing rabies virus glycoprotein, in mice and cynomolgus macaques. We demonstrated that SYS6008 induced sufficient levels of rabies neutralising antibody (RVNA) in mice. In addition, SYS6008 elicited strong and durable RVNA responses in vaccinated cynomolgus macaques. In the pre-exposure prophylaxis murine model, one or two injections of SYS6008 at 1/10 or 1/30 of dosage provided protection against a challenge with a 30-fold LD50 of rabies virus (China I and II clades). We also demonstrated that in the post-exposure prophylaxis murine model, which was exposed to lethal rabies virus (China I-VII clades) before vaccination, one or two injections of SYS6008 at both 1/10 and 1/30 dosages provided better protection against rabies virus challenge than the immunization by five injections of commercial vaccines at the same dosage. In addition, we proved that SYS6008-induced RVNAs could neutralise RABV from the China I-VII clades. Finally, 1/10 of the dosage of SYS6008 was able to stimulate significant RABV-G specificity in the T cell response. Furthermore, we found that SYS6008 induced high cellular immunity, including RABV-G-specific T cell responses and memory B cells. Our results imply that the SYS6008 rabies vaccine, with a much simpler vaccination procedure, better immunogenicity, and enhanced protective capacity, could be a candidate vaccine for post-exposure prophylaxis of rabies infections.

Serum Sickness like Reaction Postequine Rabies Immunoglobulins.

A 30-year-old, previously healthy adult male received equine rabies immunoglobulins (Ig) (ERIG) along with anti-rabies vaccinations as per protocol for postexposure prophylaxis after an unprovoked rabid dog bite of grade three wound over the shin of the left lower limb. On the 8th day, he developed urticarial rashes beginning from the site of the wound, which gradually became a widespread maculopapular rash. Development of the rash was followed by low-grade fever, nonspecific arthralgias and soreness in the throat. A diagnosis of serum sickness-like illness was made based on history, temporal correlation of administration of ERIG and development of symptoms. He responded well to antihistaminic and a short course of injectable steroids. The purpose of this article is to increase awareness regarding the clinical presentation and management of this rare yet potentially curable adverse event if identified timely.

Knowledge, Attitude, and Practice (KAP) of post exposure prophylaxis for fifth year dental students at a private Egyptian university: a cross-sectional study.

BACKGROUND: Health care professionals including dental staff are at greater risk of occupational exposure to life threatened blood-borne pathogens. Occupational exposures will continue to occur despite improved techniques of prevention and using the post exposure prophylaxis (PEP) in these situations are of great importance. Therefore, the aim of this study was to assess the knowledge, attitude, and practice of post exposure prophylaxis for fifth year dental students at a private Egyptian university. METHODS: This cross-sectional study was conducted among 404 dental students in the fifth year at a private Egyptian university from July 2019 to March 2020. Data were collected using self-administrated questionnaires including personal information, knowledge, attitude, and practice questions. RESULTS: Our study showed that the total mean knowledge score was (0.45 ± 0.50), for attitude (0.70 ± 0.46), and that for practice (0.45 ± 0.50). There was no gender difference regarding PEP (P > 0.05). A total of 213 (47.5%) dental students believed that PEP should be indicated for any needlestick injury in the workplace. A number of 379 of the students (94%) chose "Yes" when asked if they thought PEP is important. While, 143 students (32.5%) were unaware of the existence of PEP service and protocol when asked about the reasons for not taking PEP after occupational exposure. CONCLUSIONS: Knowledge and practice of fifth year dental students at a private Egyptian university toward post exposure prophylaxis are not satisfactory. Awareness and curriculum modifications are important regarding PEP.

Standardizing HIV post-exposure prophylaxis in the emergency department following sexual assault.

OBJECTIVES: A standardized non-occupational post-exposure prophylaxis (nPEP) programme was implemented to improve guideline compliance for treatment of post-sexual assault patients within an emergency department (ED). METHODS: A single-centre, retrospective, observational study of adult patients evaluated in the ED for sexual assault was performed following nPEP programme implementation. A comprehensive nPEP programme consisting of a standardized order set, real-time multidisciplinary consultation, on-site pharmacy and close post-discharge follow-up was implemented between July 2017 and June 2018. Laboratory, treatment, vaccination, prescription and follow-up data during the pre- (July 2016 to June 2017) and post-intervention (July 2018 to August 2019) periods were compared. RESULTS: Of the 147 post-sexual assault patients included in this study (59 pre-intervention, 88 post-intervention), 133 (90.5%) were eligible for nPEP. Patient demographics and rate of those eligible for nPEP were similar in both cohorts. Antiretroviral therapy (ART) was offered (72.2% vs. 100%; p < 0.005) and ultimately prescribed (51.9% vs. 86.1%; p < 0.005) more frequently following nPEP programme implementation. Patients were more likely to have appropriate screening for renal function, liver function, pregnancy, syphilis, hepatitis B, hepatitis C and HIV in the post-intervention period (all p < 0.005). Hepatitis B vaccination was more commonly administered post-intervention (8.5% vs. 22.7%; p < 0.024). In-person 28-day follow-up was rare in both pre- (3.5%) and post-intervention (11.3%) cohorts (p = 0.278). CONCLUSIONS: Implementation of a comprehensive nPEP programme resulted in improved guideline compliance with more frequent and appropriate ART administration. Recommended screening laboratories and hepatitis B vaccinations were more commonly performed, but in-person follow-up remained low. The nPEP programmes should be implemented to standardize efforts that decrease the risk of HIV transmission.

Evidence of HIV pre-exposure or post-exposure prophylaxis (PrEP/PEP) among blood donors: a pilot study, England June 2018 to July 2019.

OBJECTIVE: Due to increased use of pre-exposure prohylaxis (PrEP) and its potential to affect HIV screening of blood donors, we undertook antiretroviral residual testing among HIV-negative male donors in England. METHODS: Residual plasma samples were obtainnd from 46 male donors confirmed positive for syphilis and 96 donors who were repeat reactive for HIV antibodies in screening but confirmed as HIV-negative by reference testing. These were tested for concentrations of tenofovir and emtricitabine by high-performance liquid chromatograhpy coupled with mass spectrometry. RESULTS: We found evidence of pre-exposure or post-exposure prophylaxis (PrEP/PEP) use in three male blood donors confirmed positive for syphilis (3 out of 46 screened, 6.5%). Two were estimated to have taken PrEP/PEP within a day of donating, and the third within 2 days. Two were new donors, whereas one had donated previously but acquired syphilis infection after his last donation. CONCLUSIONS: Our findings indicate that a small proportion of blood donors have not been disclosing PrEP/PEP use and therefore donating in non-compliance to donor eligibility criteria.