Post-exposure Prophylaxis Regimens Research Articles

A phase 2b, Randomized, double blinded comparison of the safety and efficacy of the monoclonal antibody mixture SYN023 and human rabies immune globulin in patients exposed to rabies

BackgroundSYN023 is an anti-rabies monoclonal antibody mixture administered as part of post-exposure prophylaxis regimens. The rabies virus neutralizing antibody (RVNA) concentration generally accepted as an adequate immune response to vaccination is ≥ 0.5 IU/mL. MethodsWithin 54 h of potential rabies exposure, 448 patients in two risk substrata of WHO Category III exposure were randomized to receive either 0.3 mg/kg SYN023 or 0.133 mL/kg human rabies immunoglobulin (HRIG) injected in and around the wound site(s) plus a course of rabies vaccination. Patients were followed for safety and absence of rabies for ≥ 365 days. ResultsGMT RVNA was higher with SYN023 throughout the 2-week post-treatment period. In the primary analysis group (n = 368), 99.4 % of SYN023 recipients versus 4.5 % of HRIG recipients had protective RVNA levels on Day 4. On Day 8, 98.1 % SYN023 versus 12.2 % HRIG recipients were protected. The SYN023:HRIG ratio of geometric mean titer of RVNA (RVNA GMTs) on Day 8 (19.42) exceeded the 10 % superiority margin (P < 0.0001) indicating higher Day 8 RVNA with SYN023. On Day 99, the SYN023:HRIG RVNA GMT ratio (0.66) was below the non-inferiority margin of 20 % (P = 0.9485) suggesting some moderation of vaccine immune response by SYN023 relative to HRIG. The ratio of percent SYN023:HRIG recipients achieving RVNA ≥ 0.5 IU/mL on Day 99 (0.98) met the non-inferiority margin of 20 % (P = 0.013) indicating anti-rabies immune response with SYN023 was non-inferior to HRIG despite this effect. There were no probable/confirmed rabies cases in any patient. Study regimens were well tolerated. ConclusionsSYN023 provided higher RVNA than HRIG soon after rabies exposure. By Day 99 post-treatment, GM RVNA with SYN023 was lower than HRIG, however, the percent of SYN023 recipients with a protective response was not inferior at this time point. No rabies cases were reported in the study. The SYN023 safety profile was acceptable.ClinicalTrials.gov ID: NCT03961555.

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.

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®). 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. 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. In a simulated PEP setting, PVRV-NG2 + HRIG showed comparable immunogenicity and safety to current standard-of-care vaccines. NCT03965962.

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

BackgroundLeprosy 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.MethodsThe 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.DiscussionPast 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 registrationNL7022 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

Real-world evidence of rabies post-exposure prophylaxis in Serbia: Nation-wide observational study (2017–2019)

BackgroundRabies remains a deadly zoonotic disease, primarily prevalent in Eastern European countries, with a significant global burden in Asia and Africa. Post-exposure prophylaxis (PEP) is critical to prevent clinical rabies. Serbia, a country with a relatively low animal rabies incidence, has been implementing a 4-dose Essen PEP regimen for 13 years. This real-world study aimed to assess the effectiveness of the 4-dose Essen regimen, considering demographic and clinical factors, after WHO Category III exposure. MethodThe study included 601 patients who received the 4-dose Essen PEP and 79 who received an additional 5th dose. ResultsAge emerged as a critical factor influencing seroconversion rates after the 4-dose regimen, with older individuals exhibiting lower RVNA titers. Logistic regression indicated a 3.18% decrease in seroconversion odds for each added year of age. The Cox proportional hazards mixed model highlighted age-related risks, with age groups 45–60 and 75–92 at the highest risk of non-seroconversion. Human Rabies Immune Globulin (HRIG) administration was associated with lower RVNA values after the 4-dose regimen, suggesting interference with vaccine immunogenicity among people who received larger doses of HRIG. ConclusionsThis study provides valuable real-world evidence for rabies PEP in a non-homogeneous population with potential comorbidities. The results underscore the importance of optimizing PEP strategies, particularly in older individuals, and reconsidering HRIG dosing to improve seroconversion rates.

Compatible co-administration of BioThrax® vaccine and ciprofloxacin—Results of a randomized open-label drug-vaccine interaction trial

The recommended treatment for post-exposure prophylaxis (PEP) following known/suspected exposure to Bacillus anthracis involves immunization with anthrax vaccine adsorbed (AVA, i.e., BioThrax® vaccine) and a course of antimicrobial therapy. A drug-vaccine interaction clinical trial was conducted to determine whether this combined treatment might modify antimicrobial exposure or vaccine immunogenicity.A Phase 2, randomized, open-label, multi-center trial involving 154 healthy adult participants was completed to evaluate the effect of AVA immunization (three doses administered subcutaneously (SC) at weeks 0, 2 and 4) on the pharmacokinetics (PK) of ciprofloxacin, as well as the effect of ciprofloxacin administration (500 mg po bid) on the immunogenicity of AVA. PK parameters were derived using noncompartmental analysis of ciprofloxacin serum concentrations. Immunogenicity was assessed using a toxin neutralizing antibody (TNA) assay resulting in 50 % neutralization factor (NF50) values. Safety was assessed via reports of adverse events (AEs), clinically significant changes in laboratory parameters and vital signs, and collection of solicited local and systemic reactogenicity reactions.Statistical analyses of the steady state (SS) and single dose PK parameters Cmax and AUC0-–12h indicated that the AVA PEP regimen did not significantly modify ciprofloxacin exposure. Comparison of the geometric mean TNA NF50 values between participants receiving AVA + ciprofloxacin and those receiving AVA alone showed that the combined treatment was non-inferior to AVA alone. The trial met all prospectively defined success criteria for the primary PK endpoint and for the secondary PK and immunogenicity endpoints. There were no deaths, SAEs or AEs leading to drug discontinuation or study withdrawal during the trial.Overall, concomitant administration of ciprofloxacin and AVA produced no significant changes in the PK profile of ciprofloxacin nor in the immunogenicity of AVA. Furthermore, this trial demonstrated that the co-administration of ciprofloxacin and AVA was well tolerated in healthy adult participants.

Post-Exposure Prophylaxis for Varicella-Zoster Virus Exposure in High-Risk Children.

Post-exposure prophylaxis (PEP) with varicella immunoglobulin is recommended to minimize risk of varicella complications for high-risk children. However, providers frequently use alternatives like acyclovir or intravenous immunoglobulin. A retrospective cohort study was conducted of PEP for varicella in children from January 2009 to December 2019. Data were provided by 47 children's hospitals who participate in the Pediatric Health Information Systems database. Patients with clinical encounters for varicella exposure were reviewed. Choice of varicella PEP regimens, including differences by underlying condition and institution, and incidence of varicella disease were determined. A total of 1704 patients with first clinical encounters for varicella met inclusion criteria. Of these patients, 509 (29.9%) were prescribed PEP after varicella exposure, and 65 (3.8%) ultimately had a subsequent encounter for varicella disease. Of 509 patients who received PEP, acyclovir was most frequently prescribed (n = 195, 38.3%), followed by varicella immunoglobulin (n = 146, 28.7%), IVIG (n = 115, 22.6%), and combination therapy (n = 53, 10.4%). The highest proportion of varicella immunoglobulin use (10/20, 50%) was amongst children with diagnoses of rheumatological/gastrointestinal conditions. The highest proportion of acyclovir use (29/684, 4.2%) was amongst children with diagnoses of oncology/stem cell transplant conditions. The proportion of patients who subsequently had clinical encounters for varicella disease was highest for Acyclovir (30/195, 15.4%) followed by varicella immunoglobulin (5/146, 3.4%), combination therapy (2/53, 3.8%), and intravenous immunoglobulin alone (0/115) (P < .0001). Varicella PEP in high-risk children was highly varied among children's hospitals. In our dataset, use of acyclovir was associated with a higher rate of subsequent encounters for Varicella disease.

Specialty pharmacy interventions benefit patients receiving HIV postexposure prophylaxis

BackgroundSpecialty pharmacies service many different complex disease states that require high-cost medication, including the treatment of patients prescribed human immunodeficiency virus postexposure prophylaxis (PEP). PEP requires time-sensitive initiation and patient counseling for therapeutic efficacy. ObjectiveThis study aimed to examine all PEP referrals received at a specialty pharmacy and demonstrate how they aided in interventions including assisting in obtaining financial assistance, making clinical interventions, and offering counseling to patients. MethodsThis is an observational retrospective chart review of patients who received PEP from one specialty pharmacy. All patients who filled PEP at the pharmacy between January 1, 2017, and July 1, 2022, were included. Information was collected from documentation provided in the electronic medication record used by the pharmacy. The PEP regimen prescribed were raltegravir (RAL) + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and dolutegravir (DTG) + FTC/TDF. ResultsA total of 52 patients were treated with PEP during the measurement period. Patients who received a PEP regimen of RAL + FTC/TDF experienced a total cost savings of $1692.60 and $218.40 for those who were fully insured and uninsured, respectively. Patients who received a PEP regimen of DTG + FTC/TDF experienced a total cost savings of $676.20 and $2725.50 for those who were fully insured and uninsured, respectively. Counseling by a pharmacist was offered to all patients and 74.5% of patients accepted. Pharmacists made clinical interventions on 29.4% of PEP referrals. ConclusionPEP medications are expensive and time sensitive and can require clinical interventions and specific patient counseling. This study indicates that specialty pharmacies can provide and ensure access to care in the areas of financial assistance, patient counseling, and clinical interventions.

Rabies experts on demand: A cross-sectional study describing the use of a rabies telehealth service.

Rabies expert on demand (REOD) telehealth service is provided by the U.S. Centers for Disease Control and Prevention (CDC) to assist public health practitioners, health providers, and the public to interpret national and international rabies prevention guidelines. REOD is staffed by subject matter experts of the CDC Poxvirus and Rabies Branch to assess each unique situation and provide evidence-based guidance to stakeholders. This study aims to describe the utilization of a rabies telehealth system and provide insight into common consultations. A cross-sectional study of the nature of inquiries to REOD was done using the data collected from September 1, 2017 to September 30, 2021. An inquiry tracking form and Microsoft Access database were developed to document all inquiries received. Inquired ones were summarized to determine the frequency of inquiries by month, category, and location. Over a 49-month period, REOD received 5228 inquiries. Peak inquiries (n = 108) occurred during August 2019. The most frequent inquiries received pertained to risk assessment and management of rabies exposures (n = 1109), requests for testing assistance (n = 912), consultation for suspected human rabies (n = 746), rabies exposures and post-bite treatment occurring internationally (n = 310), and consultation for deviations in the recommended pre- and postexposure prophylaxis regimen (n = 300). REOD is a global resource for consultation related to managing rabies exposures, diagnostic issues, and rabies control strategies. REOD is a regularly utilized CDC service, as the demand for up-to-date rabies guidance remains high. REOD fulfills a critical role for the interpretation and consultation on rabies prevention guidelines to stakeholder.

Active safety surveillance of rabies monoclonal antibody and rabies vaccine in patients with category III potential rabies exposure.

A vero cell-based inactivated Rabies Vaccine (Rabivax-S) and Rabies Human Monoclonal Antibody (Rabishield) have been approved since 2016. A post-marketing surveillance was conducted in India from 2020 to 2021 to gather real world safety data on Rabivax-S and Rabishield. This was non-interventional active surveillance in patients with category III potential rabies exposure who were administered a post-exposure prophylaxis (PEP) regimen (Rabishield and Rabivax-S) by their healthcare providers (HCPs) as per the dosages and regimens mentioned in the package insert approved by the Indian regulators. The approved schedule for PEP was local infiltration of Rabishield on Day 0 and five doses of Rabivax-S on Day 0, 3, 7, 14, and 28 (Intramuscular route, IM) or four doses of Rabivax-S on Day 0, 3, 7, and 28 (Intradermal route, ID). The primary objective of this surveillance was to generate real-world evidence on the safety and tolerability of Rabishield and Rabivax-S. All patients enrolled in the surveillance were required to report any adverse events (AEs) occurring up to Day 31 after initiation of PEP (administration of Rabishield and the first dose of Rabivax-S) to their HCP. A total of 1000 patients with category III potential rabies exposure were enrolled across India. 991 patients received the PEP regimen with IM Rabivax-S while 9 received a PEP regimen with the ID regimen. While 32% of the patients were <12 years of age, 11.8% were ≥12 to <18 years of age and 56.2% were ≥18 years of age. The entire PEP regimen was completed by 97.3% of the enrolled patients. A total of 69 AEs were reported in 64 patients. Out of these, 49 AEs in 47 patients were assessed as causally related to the study products (26 with Rabishield and 23 with Rabivax-S). The majority of the AEs were mild and all recovered without any sequelae. One serious adverse event (SAE) of fracture of the hand was reported which was not related to either Rabishield or Rabivax-S. No case of rabies was reported. Rabishield and Rabivax-S have an excellent safety profile and are well tolerated. No participant developed rabies during 31 day follow up. The PMS was funded by Serum institute of India Private Limited which is the manufacturer of the study products.

Side-by-side Comparative Study of the Immunogenicity of the Intramuscular and Intradermal Rabies Post-exposure Prophylaxis Regimens in a Cohort of Suspected Rabies Virus Exposed Individuals.

All World Health Organization (WHO) pre-qualified rabies vaccines for humans are inactivated tissue culture rabies virus formulations produced for intramuscular (IM) administration. Due to costs and vaccine shortage, dose-saving intradermal (ID) administration of rabies post-exposure prophylaxis (PEP) is encouraged by WHO. This study compared the immunogenicity of the ID 2-site, 3-visit Institut Pasteur Cambodge (IPC) PEP regimen to the IM 1-site, 4-visit 4-dose Essen regimen using Verorab vaccine (Sanofi). The development of neutralizing antibodies (nAbs) and T cell response was assessed in 210 patients with a category II or III animal exposure in a rabies-endemic country. At day 28, all participants developed nAbs (≥0.5 IU/mL), irrespective of PEP scheme, age, or administration of rabies immunoglobulin. T cell response and nAb titers were similar for both PEP schemes. This study demonstrated that the 1-week ID IPC regimen is as effective as the 2-week IM 4-dose Essen regimen in inducing an anti-rabies immune response under real-life PEP.

Cost analysis of implementation of a population level rabies control programme for children in India

BackgroundRabies is an endemic and major public health problem in India. This paper reports cost of implementation of various Pre-Exposure Prophylaxis (PrEP) and Post-Exposure Prophylaxis (PEP) strategies at programmatic level to avert rabies deaths in children in India. MethodsThe cost of implementation of various PrEP + PEP and PEP only regimens recommended by WHO and national guidelines was calculated separately for the first year of implementation for children in the age group of 0–5 years (U-5) and 5–15 years (U-15). The cost was calculated at the level of health facility from government's perspective considering the implementation of the strategies under National Rabies Control Program. All costs were converted into 2020 Indian National Rupee and International Dollars' value using implicit price deflators for Purchasing Power Parities. Base case, scenario and one-way sensitivity analyses were conducted. ResultsThe cost of implementation of PrEP regimen is several times higher than all other PEP regimens in children in the age groups of 0–5 years and 5–15 years for the first year of implementation. However, the study also reported use of intradermal route of vaccination and local infiltration of ERIG in wounds only as a cost-saving approach to prevent rabies deaths in children in situations where PEP only strategies are implemented. ConclusionsThere is a need to conduct primary studies in order to obtain data for cost of implementation of shorter regimens in real-time settings.

Scenario of HIV infection in Pakistan

Human immunodeficiency virus (HIV) infection, which was previously lethal, has evolved into a chronic disease that may be treated and well-managed. HIV levels in the bloodstream may become undetectable with antiretroviral therapy (ART). All those providing care for people living with HIV should be aware of the risk factors, transmission, diagnosis, and treatment, acute HIV infection, possible opportunistic infections, and malignancies. Preexposure and postexposure prophylaxis regimens allow for preventive treatment. Home healthcare specialists can help people follow their drug schedules, assess the effectiveness of their treatments, and identify HIV problems and ART side effects. The ability to support, inform, and counsel people living with HIV and their families is most crucial [1].&#x0D; Approximately 38.9 million people worldwide were living with HIV, 25.4 million had access to antiretroviral therapy (ART), 1.7 million had just recently contracted the virus, and 690,000 had passed away from AIDS-related illnesses, according to a Joint United Nations Program on HIV/AIDS 2020 report. Although Pakistan's national HIV/AIDS control program was established in 1987, the number of new HIV/AIDS cases has been rising quickly ever since. In Pakistan, 160,000 people were living with HIV/AIDS as of 2018, yet only 10% of them were receiving ART. 3 Increasing people with HIV/AIDS' access to ART has a number of positive effects, including delaying the advancement of the disease, extending life expectancy, and enhancing people's quality of life and mental health [2].&#x0D; "More than 1,000 new HIV cases are reported each month from all four provinces, including the capitol city Islamabad, Azad Kashmir, and Gilgit Baltistan. This demonstrates unequivocally that homosexuals, persons who inject drugs, male, female, and transgender sex workers, and other critical demographics are now spreading HIV to the broader community. During the final 10 months of 2022, 9,773 people in Pakistan had HIV tests that were positive, casting significant doubt on HIV preventive and control initiatives and amply demonstrating the spread of HIV from important populations to the general public. New HIV infections account for a sizable portion of low-risk males, females, and clients of critical communities, showing an increase in HIV transmission to bridging populations [3].&#x0D; The increased rate of HIV in Pakistan pose a risk to a healthy population, blood recipients etc. Therefore, surrounding communities should also be checked for HIV. The government should direct public education campaigns in coordination with NGOs. To prevent any future epidemics, barbers and unlicensed health professionals in remote regions should receive training.

Survival of 21 Dogs after Post-exposure Prophylaxis using Intra-dermal Rabies Vaccine in the Pre-scapular Region and Emergency Use of Expired Equine Rabies Immunoglobulin for Local Wound Infiltration in Victims of a Rabid Dog Bite using One Health Approach

Rabies is a 100% fatal zoonotic disease and is preventable through timely and adequate Post-Exposure Prophylaxis (PEP). World Organization for Animal Health (WOAH) haven’t issued any guidelines for PEP for rabies in animals, still in certain Indian states like Himachal Pradesh (HP) PEP regimen with active immunization on 0,3,7,14 and 28 days mostly by Intramuscular Rabies Vaccine (IMRV) is being followed. Recently in Rampur Bushahar, a suspected rabid dog later laboratory confirmed had bitten 21 dogs, 2 cows, and 2 men. We employed PEP in animals using Raksharab vaccine intra-dermally (IDRV) (0.2 ml, pre-scapular region) on days 0, 3,7,14, and 28 along with only local wound infiltration of eRIG in 8 out of 11 bitten dogs with Category III exposure. Furthermore, 3 noncooperative dogs with Category III exposure were given IMRV (1ml) on day 0,3,7,14,28 with only wound infiltration of eRIG. 2 Cows were administered 0.2 ml IDRV in the skin at the middle of the neck with only wound infiltration of eRIG. Human bite victims also received 0.1 ml IDRV at 2 sites in the deltoid region on days 0,3, and 7 along with wound infiltration of eRIG at the nearby health center. Serum samples were collected for Rapid Fluorescent Focus Inhibition Test (RFFIT) for estimation of Rabies Vaccine Neutralizing Antibody (RVNA) titer after day 14 for 8 dogs, 2 cows, and human bite victims, and all had RVNA titer &gt;0.5 IU/ml on day 14 except one in IMRV group. None of the bitten victims had clinical manifestations of rabies even after 1 year of follow-up. This indicates wound infiltration with eRIG along with the vaccine could be a life-saving protocol. Also using expired eRIG in emergencies was safe and life saving in animals. Expired eRIG used was later tested and was found to be potent.

A Cost-Effectiveness Analysis of Pre-Exposure Prophylaxis to Avert Rabies Deaths in School-Aged Children in India.

Children contribute to one-half of the total painful rabies mortalities in India. The state-of-the-art rabies mortality averting strategies need exploration for the effective implementation of pre-exposure prophylaxis (PrEP) in India. This study reports on the economic evaluation of various PrEP and post-exposure prophylaxis (PEP) strategies to avert rabies mortalities in school-aged children in India. A decision tree model has been developed for children in the age group of 5-15 years to evaluate various PrEP + PEP and PEP only regimens. The 2-site intradermal regimen administered on day zero and seven was chosen as the intervention [PrEP (I)]. ICER was calculated from the quasi-societal and quasi-health systems' perspectives for the base case analysis, along with one-way sensitivity, and scenario analyses for each regimen. The incremental DALYs averted per million population with the implementation of PrEP (I) ranged between 451 and 85,069 in 2020. The ICER was reported in the range of USD 384-352/DALY averted (non-dominant) in comparison to PEP regimens from a quasi-societal perspective. PrEP (I) is reported to be 'very cost effective' in comparison with PEP regimens from the quasi-societal and quasi-health systems' perspectives and reduce deaths by up to 89.9%. This study concludes that the PrEP (I) regimen is a cost-effective and life-saving strategy to avert painful mortalities due to rabies in school-aged children in India.

Impact of the switch from four to three intradermal rabies post-exposure prophylaxis sessions in patients bitten by dogs: A cost-consequence analysis from the patients' perspective

The annual incidence of rabies deaths has been estimated in Cambodia at nearly 5.8/100,000 person-years. The cost of post exposure prophylaxis (PEP) and travel is potentially a significant barrier for exposed patients and their families, although safety nets are in place to provide the prophylaxis at no cost for low-income families. A decision-tree model was built to estimate changes in the costs from the patients' perspective and the survival outcomes of the Institut Pasteur du Cambodge (IPC) rabies PEP regimen after the switch from the Thai Red Cross (TRC) rabies PEP regimen in patients exposed to WHO category II or III bites by dogs. Derived from the IPC database, data included the trajectory of 203,497 patients, 1412 called-back patients and economic data on 201 patients. Uncertainty was addressed using one-way and probabilistic sensitivity analyses. Compared to the TRC regimen, the IPC regimen was cheaper and equally effective in patients with category II bites. In patients with category III bites, the IPC regimen was cheaper and its modeled probability of survival was 0.04% (95% CI, −0.12%; 0%) lower than the TRC regimen. However, the mortality rate was very low and the causes of death were uncertain. The data available may have lacked power to be able to statistically significantly tell apart the difference between genuine PEP failure and incorrect PEP administration, in the three versus the four-PEP sessions.

#71 Post-Exposure Prophylaxis for Varicella-Zoster Virus Exposure in High-Risk Children

Abstract Background Despite universal childhood vaccination, Varicella-Zoster virus (VZV) remains a cause of severe infection following varicella exposure for immunocompromised children and high-risk infants. Post-exposure prophylaxis (PEP) is recommended to minimize this risk; however, providers may not consistently administer Varicella-specific immune globulin (VariZIG) as recommended in guidelines or may choose alternative regimens. The purpose of this study was to determine patterns of PEP for Varicella-Zoster Virus (VZV) at children’s hospitals. Method Using the Pediatric Health Information Systems database, clinical encounters with the ICD-9/10 codes for VZV exposure from 2009-2019 were reviewed. Only the first VZV exposure encounter for a given patient in the study period was included. Patients receiving prophylaxis or intravenous immunoglobulin (IVIG) within 30 days of the index encounter were also excluded. Presence of chronic illness or conditions at risk of progression to severe varicella disease was identified by reviewing ICD-9/10 codes for encounters in the prior 12 months. Choice and timing of PEP regimen exposure were identified, classified into the following categories: VZIG, intravenous immunoglobulin (IVIG), acyclovir, or combination prophylaxis. Clinical encounters for subsequent varicella disease within 30 days of exposure were recorded. Results There were 1770 children with first clinical encounters for VZV during the study period of which, 66 were excluded due to recent prior receipt of anti-viral therapy or IVIG. Of these 1704 children, 509 (29.9%) were prescribed PEP after VZV exposure, while 65 (3.8%) ultimately developed VZV disease. Of patients who received PEP, acyclovir was most frequently prescribed (n=195, 38.3%), divided between administration between1-4 days (n=132), 5-10 days (n=19), and both time periods (n=44), post-exposure. The proportion who received the other regimens was VariZIG (n=146, 28.7%), IVIG (n=115, 22.6%), and combination therapy (n=53, 10.4%). From 2009-2019, the proportion of children receiving acyclovir declined from 56% to 36%, VariZIG increased from 10 to 15%, IVIG decreased from 32 to 7%, while a similar percentage (8-9%) received a combination of Acyclovir and IG. The proportion of patients who subsequently had clinical encounters for varicella disease was highest for Acyclovir (30/195, 15.4%) followed by VariZIG (5/146, 3.4%), combination therapy (2/53, 3.8%), and IVIG alone (0/115). (p&amp;lt;0.0001). Of the 65 patients that developed VZV disease, 24/65 (36.9%) had at least one high-risk condition. Conclusion Varicella PEP in high-risk children was highly varied among children’s hospitals and often diverged from guideline recommendations. Use of acyclovir was associated with a higher rate of breakthrough infection. More consistent use of guideline-recommended agents like VariZIG may lead to less varicella disease and complications in high-risk children.

Post-Exposure Prophylactic Vaccination against Rabies: A Systematic Review

Post-exposure prophylaxis (PEP) is an effective method for preventing rabies, a highly fatal infection in exposed persons. Malaysia is currently using the purified Vero cell rabies vaccine (PVRV). Nonetheless, there are other commercially available vaccine types and regimens. This systematic review aimed at comparing the effectiveness of the different PEP vaccines, regimens and routes of administration among Asian populations. We systematically reviewed the PubMed and Web of Science databases for articles reporting on the effectiveness of PEP vaccination against rabies among Asian populations between 2015 and 2019. Our search identified 11 relevant studies. Majority of study either used PCECV or PVRV type of vaccine, with different regimes and method. All are non-inferior to the other. Most of the studies recorded adequate response by Day 14 of vaccination. Nonetheless, the intradermal (ID) vaccination used minimal volume of vaccine used in all settings, thus cost less and the concurrent administration of RIG to the wound(s) doesn't affect the RVNA GMT response. PCECV, using either the Essen or Zagreb regimen, might be a useful alternative for the healthy population in the context of PVRV shortage, especially during an outbreak. Use of the Zagreb or Thai Red Cross (TRC) regimens can be considered (either PVRV or PCECV), as both demonstrate good immunogenic outcomes in Asian populations.

Factors Limiting the Appropriate Use of Rabies Post-exposure Prophylaxis by Health Professionals in Brazil.

Post-exposure prophylaxis (PEP) is necessary to prevent the fatal onset of rabies but requires optimization to avoid overuse in populations at risk of rabies. In Brazil, the incidence of dog bites remains high, with almost half of dog-bite patients not receiving the PEP recommended by the Ministry of Health guidelines between 2008 and 2017. In this study, we aimed to identify the factors that limit the appropriate prescribing of PEP by interviewing health professionals responsible for PEP administration and completion of the ‘Information System on Diseases of Compulsory Declaration’ (SINAN) form reporting human anti-rabies care for patients seeking health care after a dog bite. We conducted 147 questionnaires (45 questions each) in three Brazilian states (i.e., Rio Grande do Sul, Santa Catarina, Rio Grande do Norte) including questions related to the criteria used by professionals to classify a dog as “suspect” or “rabid”, knowledge on PEP prescription guidelines, SINAN and communication with veterinarians. Our analyses showed that most health professionals delivering PEP in these three states struggle to identify a rabies “suspect” dog according to the Ministry of Health guidelines, and to indicate the adequate PEP regimen, with only 11% of professionals prescribing the appropriate PEP under various dog-bite patient scenarios. PEP knowledge score was higher among professionals trained on PEP guidelines and working in facilities with the highest incidence of dog bites. In contrast, PEP knowledge scores did not vary significantly between states, and were not correlated to the professional's level of experience, the number of colleagues available at the health unit or the professional's confidence on prescribing appropriate PEP. Our results suggest that knowledge gaps in PEP administration among health professionals of Brazil can be reduced by implementing training programs to differentiate among rabies risk scenarios, prescribe the corresponding appropriate PEP and improve communication between health and veterinary authorities.

Safety and Tolerability of Once Daily Coformulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide for Postexposure Prophylaxis After Sexual Exposure.

Antiretroviral post-exposure prophylaxis (PEP) is recommended to prevent HIV infection after a high-risk exposure, but current regimens have presented challenges in tolerability, regimen completion, and potential drug-drug interactions. Because coformulated bictegravir, emtricitabine, and tenofovir alafenamide [BIC/FTC/tenofovir alafenamide (TAF)] is effective for HIV treatment, it was evaluated for use for PEP. Boston community health center. Individuals accessing PEP were enrolled in an open-label study of coformulated BIC/FTC/TAF, taken as one pill daily for 28 days. Pearson's χ2 and Fisher's exact tests were used to assess whether BIC/FTC/TAF differed with respect to side effects and regimen completion rates compared with historical PEP regimens. Between August, 2018 and March, 2020, 52 individuals enrolled in the study. Most identified as cisgender gay (67.3%) or bisexual (11.5%) men, but 7.7% identified as cisgender heterosexual men and 3.8% cisgender heterosexual women. The most common regimen side effects were nausea or vomiting (15.4%), fatigue (9.6%), and diarrhea/loose stools (7.7%), which were less common than historical controls using other PEP regimens, including those containing other integrase strand transfer inhibitors. Only 1 participant discontinued the regimen because of fatigue, and all other side effects were self-limited. Almost all participants (90.4%) completed the indicated regimen, which was a higher completion rate compared with earlier PEP regimens, and none became HIV-positive. BIC/FTC/TAF coformulated as a single daily pill was found to be safe, well-tolerated, and highly acceptable when used for PEP, and compared more favorably than historical PEP regimens used at an urban health center.

PEP for HIV prevention: are we missing opportunities to reduce new infections?

PEP for HIV prevention: are we missing opportunities to reduce new infections?