Assessing the Safety of a Novel Monoclonal Antibody Cocktail for Postexposure Prophylaxis in Category III Animal Exposures.

Background: TwinRab™ is a novel life-saving biological containing two monoclonal antibodies (docaravimab and miromavimab) essential for all age victims of category III animal exposures. It effectively neutralizes rabies and similar viruses at the exposure site until the body generates vaccine-induced antibodies. This postmarketing surveillance study assesses the safety of TwinRab™ in current postexposure prophylaxis (PEP) use and aims to reinforce its safety data for future applications. Methods: The prospective, open-label observational study was conducted on patients with the World Health Organization category III animal exposures at a government hospital in a northern region of India, by a suspected rabid animal. The study protocol included administering TwinRab™ (40 IU/kg) and a full course of anti-rabies vaccination as PEP. Results: Out of 405 participants, 404 completed the study as per the protocol. Adverse events (AEs) occurred in 12.35% of cases, with 9.88% local AEs (primarily pain and tenderness) and 2.47% systemic AEs (fever, malaise, and myalgia). All AEs were mild and resolved without complications. Most participants (88.9%) and investigators (89.1%) rated TwinRab™'s tolerability as excellent. Conclusion: The present study demonstrates the evidence of a satisfactory safety profile along with better tolerability of TwinRab™ (40 IU/kg) for category III animal exposures and supports its continued usage.

Post-Marketing Surveillance of the World's First Novel Cocktail of Rabies Monoclonal Antibodies: TwinRab™ in Real \-World Setting.

Rabies presents with a high fatality rate, which imposes a significant global public health challenge, and therefore the use of post-exposure prophylaxis (PEP) is crucial for prevention. Monoclonal antibodies (mAbs) have emerged as a promising substitute for rabies immunoglobulins (RIGs) due to their high efficacy and standardized manufacturing process. A prospective, open-label, post-marketing surveillance study (PMS) was conducted at Byramjee Jeejeebhoy Medical College (BJMC), Pune. The study included patients aged more than 2 years who had recently sustained Category III-suspected rabid animal bite exposures. These patients were administered TwinRabTM at a dosage of 40 IU/kg in and around the wound as intralesional transfer, along with the anti-rabies vaccine (ARV). Adverse events (AEs) grading was performed with reference to the Food and Drug Administration (FDA) toxicity grading. In this study, 215 subjects received the TwinRabTM mAb with a 100% completion rate. Out of 215 patients, three (1.3%) patients in the range of 18 to 65 years of age showed solicited local AEs, which were resolved after the appropriate treatment intervention, but causality assessment was non-assessable. The overall tolerability assessment showed positive ratings from doctors (91.63%) and patients (67.91%) for the mAb cocktail. The PMS demonstrated the safety of TwinRabTM in patients who experienced Category III-suspected rabid animal bites, thereby supporting its potential as an alternative option for post-exposure prophylaxis in the management of animal bites for the prevention of rabies.

Typhoid Conjugate Vaccine: A Boon for Endemic Regions.

Typhoid fever has the highest disease burden in countries in low- and middle-income countries, primarily located in Asia and Sub-Saharan Africa. Previous typhoid vaccines such as the live attenuated typhoid (Ty21a) vaccine and Vi (virulence) capsular polysaccharide vaccine had the limitation that they could not be administered with other standard childhood immunizations and were ineffective in children under two years of age. To address these shortcomings of the previous vaccines, typhoid conjugate vaccines (TCVs) were developed and prequalified by the World Health Organization. Cross-reacting material and tetanus toxoid are widely used as carrier proteins in TCVs. According to various studies, TCV has higher efficacy, has a more extended protection period, and is safe and immunogenic in infants as young as six months. This review article aims to comprehensively appraise the data available on TCVs' efficacy, duration of protection, safety, and immunogenicity in endemic regions.

Real-World Safety of TwinRab, the World's First Novel Cocktail of Rabies Monoclonal Antibodies, in a Clinical Setting.

OBJECTIVES: Every year, 18,000-20,000 people die from rabies in India, with children younger than the age of 15 accounting for 30%-60% of all cases. Wound cleaning, vaccination, and rabies immunoglobulin (RIG) administration are all part of treatment. TwinRabTM, a unique combination of two monoclonal antibodies (mAbs), docaravimab and miromavimab, effectively neutralizes rabies and rabies-like viruses. We conducted this study to evaluate the safety of the cocktail in patients infected with category-III animal bites according to WHO guidelines. METHODS: This open-label observational study was conducted in patients with WHO category-III animal bites by suspected rabid animals. All participants were screened, enrolled, and were administered the TwinRabTM manufactured by Zydus Lifesciences Ltd. at the rate of 40 IU/kg by infiltration in and around the wound along with anti-rabies vaccine (ARVs). Participants were assessed at various intervals, and any adverse events (AEs) were documented and reported to the sponsor within 24 hours. RESULT: The study enrolled 401 participants, 55.61% (n = 223) male, whose median age was 34 years. Adults made up 69.83% (n = 280) of the participants. The most exposed sites were the lower parts of the body (60.6%, n = 243); 99.75% (n = 400) of the population showed normal cardiovascular, gastrointestinal, and central nervous systems. After seven days of the last postexposure prophylaxis (PEP) dose, 9.98% of the total study population experienced 80 mild local solicited AEs and were assessed and treated. CONCLUSION: The study concluded that TwinRabTM when given in a 40 IU/kg dose with Essen or the updated Thai Red Cross Vaccine regimen, provides safe and effective rabies prophylaxis in WHO category III patients exposed to suspected rabied animal bites.

A review of safety and immunogenicity of a novel measles, mumps, rubella (MMR) vaccine.

Measles, mumps, and rubella (MMR) are highly infectious viral diseases affecting young children and have high secondary attack rates. Present MMR vaccines show consistent seroconversion rates for anti-measles and anti-rubella antibodies with variable responses for anti-mumps antibodies. Most common strains for MMR vaccines, currently available in India, are the Edmonston-Zagreb measles strain, Leningrad Zagreb (L-Z) mumps strain, and the RA 27/3 rubella strain. L-Z strain of mumps virus has been found to be associated with aseptic meningitis by different studies from different parts of the world including India. Recently, a novel freeze-dried MMR vaccine developed by Zydus Lifesciences (Zyvac MMR) contains Edmonston Zagreb measles strain, Hoshino mumps strain, and RA 27/3 rubella strain. The Hoshino strain is WHO approved and was found to induce interferon gamma production. This review article aims to provide a comprehensive appraisal of the data available on the safety and immunogenicity of the novel MMR vaccine.

Amino acids in post-stroke rehabilitation.

Objectives: Patients with stroke are prone to disability due to muscle hypercatabolism. We aim to review this concept based on available data on benefits of amino acid supplementation in post-stroke rehabilitation.Method: The search was performed on Medline and Embase in January 2019. Randomized controlled studies, observational studies and case reports conducted in the last 15 years on the supplementation of amino acids in post-stroke rehabilitation patients were included.Result: Amino acids prevent muscle hypercatabolism in post stroke patients by suppressing myofibrillar protein and skeletal muscle degradation. Stroke patients supplemented with amino acids led to an improvement of functional and physical performance.Discussion: Muscle protein hypercatabolism and sequestration of amino acids from skeletal muscles occur cyclically in post-stroke patients to counter each other. There is a resultant deficit of amino acids which is unmet. Amino acids have antiproteolytic effect. Its supplementation prevents muscle wasting and improves rehabilitation by promoting physical performance, muscle strength, mass, and function.

A comparative study of synbiotic as an add-on therapy to standard treatment in patients with aggressive periodontitis.

CONTEXT: The role of synbiotic in the management of aggressive periodontitis (AP) is not well established. AIM: We designed this study to evaluate the efficacy and safety of synbiotic as an add-on therapy in the management of AP. SETTINGS AND DESIGN: This was a randomized, double-blind, placebo-controlled study. MATERIALS AND METHODS: Sixty patients with AP were randomized to two groups of 30 each. Study group received standard treatment, i.e., scaling and root planing along with doxycycline 100 mg twice daily for the 1st day (loading dose) followed by 100 mg once daily for 1 week and synbiotic lozenge twice daily for 8 weeks, whereas control group received standard treatment for 1 week and placebo lozenge for 8 weeks. Clinical parameters were recorded at baseline, 4th, 8th, and 12th weeks. STATISTICAL ANALYSIS USED: Pearson's Chi-square test and one-way analysis of variance were used to analyze distribution of sex and age, respectively. Differences within the groups were analyzed by Student's paired t-test. Pearson's Chi-square test was applied to measure gingival bleeding index. RESULTS: On comparison at 12 weeks, there was a statistically significant reduction (P < 0.01) in probing depth, clinical attachment loss, oral hygiene index, and bleeding on probing in study group. No Adverse drug reactions were noted. CONCLUSION: Co-administration of synbiotic lozenge along with standard therapy is highly efficacious in improving periodontal health in patients with AP.

A study of promotional advertisements of drugs in a medical journal: an ethics perspective.

The study assessed 54 advertisements of 145 different drugs, published over one year (from December 2011 to November 2012) in an Indian medical journal, circulated widely mainly among general practitioners (GPs). The ethical guidelines of the World Health Organization (WHO) and Organisation of Pharmaceutical Producers of India (OPPI) for medicinal drug promotion were applied. The brand name was mentioned in all advertisements (100% compliance both with the WHO and OPPI criteria) and the names of the active ingredients were also mentioned in 128 (90.14%) advertisements. However, major adverse drug reactions were mentioned in only two advertisements (1.37%); precautions, contraindications and warnings in only two (1.37%); and major interactions in only one (0.68%). Only three advertisements (2.06%) were well substantiated with references. To ensure the ethical promotionof drugs among GPs, journals must introduce compulsory review and appraisal of promotional advertisements by a dedicated review board, including at least one member trained in pharmacology and one representative from the medical division of a pharmaceutical company.