Rabies immunoglobulin human 500unit solution for injection vials

OBJECTIVES: To evaluate the immunogenicity and safety of an anti-rabies monoclonal antibody (mAb), ormutivimab, compared with human rabies immunoglobulin (HRIG). METHODS: This phase III trial was designed as a randomized, double-blind, non-inferiority clinical trial in patients aged ≥18 years with suspected World Health Organization category Ⅲ rabies exposure. The participants were randomized 1:1 to ormutivimab and HRIG groups. After thorough wound washing and injection of ormutivimab/HRIG on day 0, the vaccination was administered on days 0, 3, 7, 14, and 28. The primary endpoint was the adjusted geometric mean concentration (GMC) of rabies virus-neutralizing activity (RVNA) on day 7. The endpoint of safety included the occurrence of adverse reactions and serious adverse events. RESULTS: A total of 720 participants were recruited. The adjusted-GMC of RVNA (0.41 IU/ml) on day 7 in ormutivimab group was not inferior to that in the HRIG group (0.41 IU/ml), with ratio of adjusted-GMC of 1.01 (95% confidence interval: 0.91, 1.14). The seroconversion rate of the ormutivimab group was higher than that of the HRIG group on days 7, 14, and 42. Most local injection sites and systemic adverse reactions reported from both groups were mild to moderate in severity. CONCLUSION: ormutivimab + vaccine can protect victims aged ≥18 years with category Ⅲ suspected rabies exposure as a component of postexposure prophylaxis. ormutivimab has a weaker influence on the immunity response of rabies vaccines. CLINICAL TRIALS REGISTRATION: ChiCTR1900021478 (the Chinese Clinical Trial Registry of World Health Organization).

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Rabies is a major cause of human death in many developing countries. There is a worldwide shortage of human and equine rabies immune globulin. The WHO recommends combined administration of rabies vaccine and rabies immune globulin to patients after exposure. The implementation of post exposure prophylaxis by vaccination and specific immunoglobulin therapy are largely hampered by its high cost. The equine rabies immunoglobulin is less expensive than human rabies immunoglobulin, and is used for rabies post-exposure prophylaxis in developing countries.
 Equine rabies immunoglobulin is a F(ab)2 with high specific activity, purity, and safety. Healthy horses are immunized with a rabies vaccine. Crude plasma is collected and immunoglobulin is converted into F(ab)2 fragments by pepsin digestion. The F(ab)2 fragments are purified using caprylic acid precipitation followed by ultrafiltration.
 Keywords: Rabies, Equine rabies immunoglobulin (ERIG), Human rabies immunoglobulin (HRIG), IgG, Caprylic acid, Pepsin.

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Background: The incidence of rabies is equally more in children < 15 year of age i.e. 35.3% as found in the APCRI-WHO Survey in India. Out of the two alternatives (Equine Rabies Immunoglobulin: ERIG and Human Rabies Immunoglobulin: HRIG) for treatment for Category III animal bites, HRIG is invariably the preferred intervention mounting to exorbitantly high economic burden. There is paucity of studies comparing their safety profiles especially in children. Methods: A hospital-based observational study was conducted at the Anti-rabies Clinic of SCBMCH, Cuttack, Odisha from March to April 2019. The enrolment of patients was done in two months period from 1st March to 30th April 2019 and all these patients were followed up for a period of one month till 31st May 2019. New Category III animal bite cases in <15 years of age, taking ERIG and HRIG comprised of two groups A and B, respectively. They were followed up on their subsequent visits on 3rd, 7th and 28th days of treatment to study any local and systemic reactions. Chi square test/ Fischer exact test/ Mann Whitney test were applied to compare the outcomes. Result: Mean age in ERIG (Group A) is 9.84 (±3.9) years and for HRIG (Group B) is 7.1 (±4.1) years and mean weight for ERIG group is 27.63 (±12.4) kg and HRIG group is 24.2 (±23.8) kg. The total amount of immunoglobulin administered was 3.6 (±1.6) ml in ERIG (Group A) and 2.5 (±1.34) ml in HRIG (Group B). Any type of local reaction was seen in 42% cases in Group A (ERIG) and in only 5% cases in Group B (HRIG). Pain, itching, local swelling, oedema, and tenderness were more marked in Group A (ERIG) but were not found to be statistically significant in all cases. These local reactions were managed symptomatically with medications like analgesics and anti-histaminic. Similarly Systemic reactions in form of arthralgia, fever, malaise and generalized rash were also more observed in Group A (ERIG) which could be managed symptomatically with same medications. Conclusion: Safety profiles (in terms of local and systemic reactions) of ERIG and HRIG were comparable in children below 15 years of age. The minor side effects of ERIG can easily be managed by readily available drugs like analgesics and antihistaminics in the ARV OPD itself. How to cite this article:Debta SP, Behera TR, Routray D. Comparison of Safety Profile of Equine and Human Rabies Immunoglobulin in Children below 15 Years, in a Tertiary Care Hospital of Odisha - an Observational Study. J Commun Dis 2020; 52(2): 7-12. DOI: https://doi.org/10.24321/0019.5138.202012

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The main objective of the present research was to review the studies that look into ways of improving production of anti-rabies immunoglobulin in terms of bioethical principles: ensuring patients’ right to receive quality pharmaceutical care, and compliance with the 3R principles. At the same time, compliance with bioethical principles should contribute to the improvement of production technology and the product quality, which is especially important for antirabies immunoglobulin due to the existing high demand for it. The paper analyses the current trends in avoidance of animal use in the production of rabies immunoglobulin. It summarises the main methods of production of serum products for post-exposure prophylaxis of rabies. The example of heterologous rabies immunoglobulin is used to substantiate the need to improve quality control of drugs by following the 3R principles. The paper highlights the potential use of cell cultures for determination of rabies immunoglobulin specific activity. The authors formulated the objectives that include development and use of pyrogen detection methods which do not involve animal use and are consistent with the current pharmacopoeial standards. They assessed the possibility and feasibility of removing Abnormal Toxicity Test for heterologous rabies immunoglobulin in accordance with the current international trends. The formulated objectives imply optimisation of production of heterologous rabies immunoglobulin in Russia in order to improve the quality of antirabies measures. The objectives include higher production volumes to ensure the availability of the product to patients, reduction of the product reactogenicity by using cell-culture technologies for obtaining rabies antigen, as well as development and implementation of in vitro test methods for product quality control in terms of Specific activity, Pyrogenicity, and Abnormal toxicity

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Novel lyssaviruses, the causative agents of rabies, continue to be described mostly due to increased surveillance in bat hosts. Biologicals for the prevention of rabies in humans have, however, remained largely unchanged for decades. This study aimed to determine if commercial rabies immunoglobulin (RIG) could neutralize diverse lyssaviruses. Two commercial preparations, of human or equine origin, were evaluated against a panel consisting of 13 lyssavirus species. Reduced neutralization was observed for the majority of lyssaviruses compared to rabies virus and was more evident for lyssaviruses outside of phylogroup I. Neutralization of more diverse lyssaviruses only occurred at very high doses, except for Ikoma lyssavirus, which could not be neutralized by the RIG evaluated in this study. The use of RIG is a crucial component of rabies post-exposure prophylaxis and the data generated here indicate that RIG, in its current form, will not protect against all lyssaviruses. In addition, higher doses of RIG may be required for neutralization as the genetic distance from vaccine strains increases. Given the limitations of current RIG preparations, alternative passive immunization options should be investigated.

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Background: Ensuring the uninterrupted availability of the anti-rabies vaccine (ARV) and rabies immunoglobulin (RIG) in health facilities is crucial to achieve the global target of zero dog-mediated human rabies deaths by 2030. This study aimed to estimate the availability of ARV and RIG across health facilities in India. Methods: We conducted a nationwide health facility-based, cross-sectional study across 60 districts selected by multistage probability sampling from 15 Indian states. In each district, we selected nine health facilities. We interviewed staff involved in the rabies control program in each of the selected health facilities, and abstracted and physically validated information on the availability of ARV and RIG. Findings: Of the 534 health facilities surveyed, 467 (87.5%) were public sector health facilities. ARV was available in 372 (79.7%, 95% CI: 75.7%-83.2%) public sector health facilities, ranging from 60.0% to 93.2% in different geographic regions. Availability of ARV was lowest in Urban Primary Healthcare Centres (UPHCs) (58.9%, 95% CI: 45.0%-71.9%). RIG was available in 95 (20.3%, 95% CI: 16.8%-24.3%) public sector health facilities, with the highest availability in southern states (27/88, 30.7%). The availability of RIG ranged from 1.8% (95% CI: 16.8%-24.3%) in UPHCs to 69.2% (95% CI: 48.2%-85.7%) in medical college hospitals. Interpretation: Considerable geographic and facility-level variations exist in the availability of ARV and RIG across India. Bridging the gap in the availability of ARV and RIG should be prioritised to achieve the goal of zero-dog-mediated human rabies deaths by 2030. Funding: Indian Council of Medical Research.

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