Human Rabies Immunoglobulin Research Articles

Adherence to guideline recommendations for human rabies immune globulin patient selection, dosing, timing, and anatomical site of administration in rabies postexposure prophylaxis

ABSTRACTRabies is a fatal disease that mandates proper prophylaxis after a rabies virus exposure to prevent death. This study evaluated adherence to Centers of Disease Control and Prevention (CDC) recommendations for rabies immune globulin (IG) patient selection, dosing, timing of administration, and anatomical site of administration for rabies postexposure prophylaxis. This retrospective, cross-sectional study included patients who received at least one dose of rabies IG or rabies vaccine at a multi-hospital health system from January 2015 through June 2018. This study included 246 patients, and all of them received at least one dose of rabies vaccine. Two patients had a history of rabies vaccination, did not have an indication for rabies IG, and appropriately did not receive additional rabies IG. Rabies IG was administered to 91% (223 of 244) of patients with an indication. Of 223 patients who received rabies IG, 219 (98%) received doses within 10% of 20 IU/kg of body weight, and all 223 (100%) received rabies IG within 7 days of the first rabies vaccine administration. Only 56% (96 of 170) of patients with a wound that could be infiltrated with rabies IG actually received rabies IG via infiltration into and around the wound. This multi-hospital health system study demonstrated high adherence to guideline recommendations for rabies IG patient selection (91%), dosing (98%), and timing (100%). However, only 56% of eligible patients received rabies IG infiltration at wound sites as recommended by guidelines.

Comparison of SYN023 to Human Rabies Immune Globulin in Post Exposure Prophylaxis of Rabies

Comparison of SYN023 to Human Rabies Immune Globulin in Post Exposure Prophylaxis of Rabies

A Phase 3, Randomised, Open-Label, Non-Inferiority Trial Evaluating Anti-Rabies Monoclonal Antibody Cocktail (Twinrab <sup>TM</sup>) Against Human Rabies Immunoglobulin (HRIG)

Background: Rabies is a zoonotic disease caused by RNA (ribonucleic acid) viruses of the genus, Lyssavirus of the family, Rhabdoviridae. Limited supply, cost and potential for severe adverse effects observed with the blood derived rabies immunoglobulin products has led to the search for alternative therapies. To address this issue, Cadila Healthcare Ltd. in collaboration with the World Health Organization (WHO) has developed an anti-rabies monoclonal antibody cocktail based product. Methods: This was a phase 3, randomized, multi-centric, open-label, comparator-controlled, non-inferiority trial conducted in 308 patients with WHO category III suspected rabies exposures. Patients meeting the eligibility criteria were assigned to one of the two treatment arms, TwinrabTM or Human rabies immunoglobulin (HRIG; Imogam® Rabies-HT), in a ratio of 1:1. The study drug was administered to patients on Day 0. Five doses of rabies vaccine were also administered (Day 0, 3, 7, 14 and 28) to all the patients following the WHO Essen Schedule. The primary endpoint was the difference in responders [assessed as Rapid Fluorescent Focus Inhibition Test (RFFIT) titre ≥0·5 IU/mL on Day 14] in the TwinrabTM arm as compared to the HRIG arm. Findings: Three hundred and eight patients were randomized; 130 (90·28%) patients in the TwinrabTM arm and 134 (94·37%) patients in the HRIG arm had an RFFIT titre ≥0·5 IU/ml in the per-protocol (PP) population. The Geometric Mean of RFFIT titre in the same population on Day 14 was 4·38 and 4·85 IU/mL respectively, in the TwinrabTM and the HRIG arms. In the modified intent to treat (mITT) population on Day 14, there were 133 (89·86%) responders in the TwinrabTM arm and 137 (90·73%) responders in the HRIG arm. There were no deaths or any other serious adverse events reported during the study period in any of the treatment arms. Interpretation: This study confirmed that TwinrabTM is non-inferior to HRIG in terms of providing an unbroken window of protection as assessed by RFFIT titers up to Day 84. This trial also establishes the safety of TwinrabTM in patients with WHO category III suspected rabies exposures. Trial Registration: CTRI/2017/07/009038. Funding Statement: This trial was sponsored and funded by CHL., Ahmedabad, India. Declaration of Interests: All authors declared no competing interests. Ethics Approval Statement: Written informed consent was given by all study subjects and by parents/legal guardians in cases of children. The consent process was audio-visually recorded at the time of screening for all subjects, as per the local regulations. This trial was initiated after obtaining the approvals of Ethics Committees (ECs), Drugs Controller General of India (DCGI) (dated 17 March 2017) and registering the trial with the Clinical Trial Registry of India (CTRI). This trial was conducted in accordance with the applicable local regulations.

Market mapping and landscape analysis of human rabies biologicals in India.

Rabies vaccines and immunoglobulins are lifesaving in humans following animal exposures. These biologicals should continuously be available throughout the year to prevent and eliminate human rabies by 2030. The present study aimed at assessing availability of different kinds of human rabies biologicals in the country and undertaking market mapping and landscape analysis of human rabies biologicals in India. The study comprising both quantitative and qualitative approach was conducted from May to November 2017 as a part of the Indian multicentric rabies survey by Association for Prevention and Control of Rabies in India. All stakeholders (agencies/personnel) associated with rabies biologicals were the study units/participants. Required data were generated through brainstorming sessions with key stakeholders; reviewing of databases/existing literature; conducting in-depth surveys; interviewing; focused group discussions, etc. Two types of cell culture rabies vaccines are available in the country manufactured by different pharmaceutical companies; most of the vaccines are indigenously produced and the market size of the rabies vaccines is about INR 125 crores with highest sales in the northern region followed by South. Likewise, there are 2 types of immunoglobulin available, i.e., equine rabies immunoglobulins (RIGs), which are indigenously produced and human RIGs, which are imported. The market value of RIGs is about INR 83 crores. A novel rabies monoclonal antibody is also been marketed in the country from November 2017. There are many lacunas in the market availability of rabies biologicals in different parts of the country; therefore, a significant expansion/shift in focus must be considered, through rigorous strategic planning process.

Safety of new indigenous human Rabies Monoclonal Antibody (RMAb) for Post Exposure Prophylaxis

Background: WHO recommended development of Rabies Monoclonal Antibodies (RMAb) to overcome the problems associated with rabies immunoglobulin for post exposure prophylaxis against rabies in all category III exposures. A new indigenous RMAb has been manufactured and marketed in India. The present study was conducted to monitor the post marketing clinical use of RMAb for post exposure prophylaxis. Aims & Objectives: To assess the safety of human rabies monoclonal antibodies for post exposure prophylaxis. Material & Methods: A comparative study between the new RMAb and the previously established rabies immunoglobulins was conducted at anti-rabies clinic in a Medical college Hospital, Bangalore from January to June, 2018. All the animal bite victims with category III exposure were included in the study. The details regarding their socio demographic profile, characteristics of exposure, post exposure prophylaxis provided and any adverse drug reactions following administration of RMAb were recorded. Results: The study included 397 subjects with category III exposure; 142 in RMAb group, 243 in equine rabies immunoglobulin group & 12 in human rabies immunoglobulin group. Majority of the study subjects were males & aged between 1 – 85 years. All the subjects were provided post exposure prophylaxis as recommended by WHO. There were no immediate adverse drug reactions; however, 8% of the subjects had delayed ADRs such as pain at the site of infiltration (4.2%), swelling (2.1%) and wound infection (0.7%); which resolved without any complications. Conclusion: The new indigenous human RMAb is safe for post exposure prophylaxis against rabies.

Serum Sickness in Patients Receiving Equine Rabies Immunoglobulin

Background: Equine Rabies Immunoglobulin (ERIG) is being used for treatment of category-III animal bite cases. ERIG is economical as compared to Human Rabies Immunoglobulin (HRIG) and hence more affordable to patients in developing countries, like India. Despite high degree of purification, there are reported cases of serum sickness like reactions, anaphylaxis, and other allergic reactions following ERIG administration. Serum sickness is a type III or immune-complex-mediated hypersensitivity reaction that results from the injection of heterologous or foreign protein or serum. Because of fear of side effects (including serumsickness- like reaction) following ERIG, the use of ERIG is minimal among doctors. Objective: (1) To assess the incidence of serum sickness following the administration of ERIG. (2) To see the clinical features of serum sickness. Methods: This is a hospital-based cross-sectional study carried out in the ARV OPD of SCB Medical College, Cuttack, Odisha, India. All patients who received ERIG between September 2016 and December 2016 were included in the study. Side effects were monitored during the subsequent follow-up visits. Results: Out of 1548 category-III animal bite cases who received ERIG, 3.1% developed serum-sickness-like reactions, which manifested as rashes in 97.82%. Most of them had symptoms after seventh day following ERIG administration. Symptomatic relief with oral antihistamines like Cetirizine, Levocetirizine in 60% of cases and Inj. Avil (chlorpheniramine maleate) in 17% was achieved, and only one case required shortcourse corticosteroids. Conclusion: Despite 3.1% of serum sickness cases reported in our present study, the safety of ERIG has been proved and serum sickness can be managed with oral analgesics and antihistamines. Hence ERIG should be encouraged among doctors for use in category-III animal bite patients to prevent rabies.

Combination therapy of rabies-infected mice with inhibitors of pro-inflammatory host response, antiviral compounds and human rabies immunoglobulin

Recent studies demonstrated that inhibitors of pro-inflammatory molecular cascades triggered by rabies infection in the central nervous system (CNS) can enhance survival in mouse model and that certain antiviral compounds interfere with rabies virus replication in vitro. In this study different combinations of therapeutics were tested to evaluate their effect on survival in rabies-infected mice, as well as on viral load in the CNS. C57Bl/6 mice were infected with Silver-haired bat rabies virus (SHBRV)-18 at virus dose approaching LD50 and LD100. In one experimental group daily treatments were initiated 4 h before-, in other groups 48 or 96 h after challenge. In the first experiment therapeutic combination contained inhibitors of tumour necrosis factor-α (infliximab), caspase-1 (Ac-YVAD-cmk), and a multikinase inhibitor (sorafenib). In the treated groups there was a notable but not significant increase of survival compared to the virus infected, non-treated mice. The addition of human rabies immunoglobulins (HRIG) to the combination in the second experiment almost completely prevented mortality in the pre-exposure treatment group along with a significant reduction of viral titres in the CNS. Post-exposure treatments also greatly improved survival rates. As part of the combination with immunomodulatory compounds, HRIG had a higher impact on survival than alone. In the third experiment the combination was further supplemented with type-I interferons, ribavirin and favipiravir (T-705). As a blood-brain barrier opener, mannitol was also administered. This treatment was unable to prevent lethal consequences of SHBRV-18 infection; furthermore, it caused toxicity in treated mice, presumably due to interaction among the components. In all experiments, viral loads in the CNS were similar in mice that succumbed to rabies regardless of treatment. According to the findings, inhibitors of detrimental host response to rabies combined with antibodies can be considered among the possible therapeutic and post-exposure options in human rabies cases.

In Vivo Efficacy of a Cocktail of Human Monoclonal Antibodies (CL184) Against Diverse North American Bat Rabies Virus Variants.

Following rabies virus (RABV) exposure, a combination of thorough wound washing, multiple-dose vaccine administration and the local infiltration of rabies immune globulin (RIG) are essential components of modern post-exposure prophylaxis (PEP). Although modern cell-culture-based rabies vaccines are increasingly used in many countries, RIG is much less available. The prohibitive cost of polyclonal serum RIG products has prompted a search for alternatives and design of anti-RABV monoclonal antibodies (MAbs) that can be manufactured on a large scale with a consistent potency and lower production costs. Robust in vitro neutralization activity has been demonstrated for the CL184 MAb cocktail, a 1:1 protein mixture of two human anti-RABV MAbs (CR57/CR4098), against a large panel of RABV isolates. In this study, we used a hamster model to evaluate the efficacy of experimental PEP against a lethal challenge. Various doses of CL184 and commercial rabies vaccine were assessed for the ability to protect against lethal infection with representatives of four distinct bat RABV lineages of public health relevance: silver-haired bat (Ln RABV); western canyon bat (Ph RABV); big brown bat (Ef-w1 RABV) and Mexican free-tailed bat RABV (Tb RABV). 42–100% of animals survived bat RABV infection when CL184 (in combination with the vaccine) was administered. A dose-response relationship was observed with decreasing doses of CL184 resulting in increasing mortality. Importantly, CL184 was highly effective in neutralizing and clearing Ph RABV in vivo, even though CR4098 does not neutralize this virus in vitro. By comparison, 19–95% survivorship was observed if human RIG (20 IU/kg) and vaccine were used following challenge with different bat viruses. Based on our results, CL184 represents an efficacious alternative for RIG. Both large-scale and lower cost production could ensure better availability and affordability of this critical life-saving biologic in rabies enzootic countries and as such, significantly contribute to the reduction of human rabies deaths globally.

Kuduz Riskli Temas Sonrası Başvuran Çocuk Olguların ve Profilaksi Uygulamalarımızın Geriye Dönük Değerlendirilmesi

Objective: The aim of the study was to assess epidemiological and anti-rabies vaccination status in children in our hospital. Material and Methods: We retrospectively analyzed the clinical data of the patients who presented to our clinic with complaint of animal bite between January 2015 and December 2017. Results: A total of 162 children presenting with animal bites were included in this study. The mean age was 9±4.8 years and 66.1% of the patients were boys. Most (53.1%) of the patients were injured by cats and 14.8% of the animals were vaccinated. In the study group, 61.1% of the patients had category III contact and 38.9% had category II contact. The wound was in the upper limbs in 59.3% of the patients, the head and neck in 21% and the lower limbs in 19.8%. Lesions were on the bare skin in 66.7% of the cases and 86% of the patients presented to our clinic without previous wound care. Only an antiseptic solution was used in 79.3% of the patients who had received wound care before admission. The vaccination rate was 95.1% and human rabies immune globulin was used in 46.9% of the patients. Conclusion: The outcome of an animal bite can be fatal. The only preventive and curative measures are anti-rabies vaccination and the use of human rabies immunoglobulin. Education of the population and health professionals is therefore crucial to ensure 100% compliance with appropriate management.

Consumption of human rabies immunoglobulin (HRIG) for major animal bites in government hospitals of Sri Lanka.

Abstract Introduction:Rabies still remains as a significant public health problem in Sri Lanka. Published data related to the usage of human rabies immunoglobulins (HRIG) which is an expensive biological used for post exposure prophylaxis and the types of animal bites are limited. This study was designed to analyze the consumption of HRIG for major animal bites in government hospitals of Sri Lanka. Methods: A audit was carried out at the rabies unit in the Medical Research Institute (MRI) on the use of HRIG from 1st of January to 31st of December 2012 . Data was extracted from scrutinizing the forms sent to the Rabies Unit following the administration of HRIG by the government hospitals which administer HRIG. Results:1896, 2160, 2186 patients have received HRIG during 2010, 2011and 2012 respectively. The number of patients treated without adhering to the rabies treatment protocol issued by the ministry of health also has inreased over the same period of time. Each year around 60% of total HRIG has been used for stray dog and cat bites, 24% for domestic animal and 17% for wild animal bites. Conclusions and recommendations:Annual consumption as well as the misuse of HRIG has increased from 2010 to 2012. Effective methods to control stray dogs and cats and the concept of responsible pet ownership should be encouraged. Medical officers in rabies treatment units should be trained on adherence to government protocol for anti rabies post exposure therapy.

A randomized non-inferiority clinical study to assess post-exposure prophylaxis by a new purified vero cell rabies vaccine (Rabivax-S) administered by intramuscular and intradermal routes

BackgroundRabies is a 100% fatal disease but preventable with vaccines and immunoglobulins. We have developed a new purified vero cell rabies vaccine (Rabivax-S) and evaluated its safety and immunogenicity in post-exposure prophylaxis by intramuscular (IM) and intradermal (ID) routes. MethodsThis was a randomized active-controlled non-inferiority study in 180 individuals (age 5years and above) with suspected rabies exposure (90 each with WHO Category II and Category III exposures). The participants received either Rabivax-S (1mL IM; five doses), Rabivax-S (0.1mL ID; eight doses) or purified chick embryo cell vaccine (PCEC, Rabipur®) (1mL IM; five doses). The IM doses were given on Day 0, 3, 7, 14 and 28 while the ID doses were given on days 0, 3, 7 and 28. Category III patients also received a human rabies immunoglobulin (HRIG) on Day 0. Adverse events (AEs) were recorded with diary cards till day 42. Rabies neutralizing antibody levels were measured on day 0, 7, 14, 28 and 42. ResultsIn both the category II and III patients, the geometric mean concentration (GMC) ratios of Rabivax-S IM and Rabivax-S ID groups to PCEC IM were more than 1, thus proving the non-inferiority. GMCs were similar or higher in Rabivax-S groups at all the time points. Seroresponse against rabies (RFFIT titre⩾0.5IU/mL) was achieved in all participants. Mostly mild local and systemic adverse events were reported across the three groups and all resolved without sequelae. ConclusionsRabivax-S was well tolerated and showed immunogenicity comparable to a licensed rabies vaccine by both IM and ID routes in post-exposure prophylaxis.Registry No.: CTRI/2012/11/003135

Development and validation of a quantitative competitive ELISA for potency testing of equine anti rabies sera with other potential use

In case of a bite by a rabies infected animal, the World Health Organisation recommends a prophylactic treatment including the administration of Human Rabies Immunoglobulins (HRIGs) or highly purified F(ab′)2 fragments produced from Equine Rabies Immunoglobulin (F(ab′)2 – ERIGs). According to international regulation, quality control of F(ab′)2 – ERIGs lots requires potency testing by the in vivo Mouse Neutralisation Test (MNT) prior marketing. However, the strategy of the 3Rs (Reduce, Refine, Replace) for animal testing required by the European Directive encourages the replacement of the in vivo potency test by an in vitro assay. In this context, a competitive ELISA method (c-ELISA) has been developed by the Agence Nationale de Sécurité du Médicament et des Produits de Santé where F(ab′)2 – ERIGs are in competition with a monoclonal antibody recognizing the trimeric native form of the rabies glycoprotein. After a full validation study, the c-ELISA has been applied to commercial batches of F(ab′)2 – ERIGs. A correlation study with the MNT demonstrated a similarity between the two methods (r=0.751). Moreover, the c-ELISA method which does not need any species specific reagent has been applied to HRIGs potency testing as an alternative method to Rapid Fluorescent Focus Inhibition Test (RFFIT), thus avoiding the handling of live rabies virus in BSL3 containment. In conclusion, the c-ELISA has shown its potential to replace MNT and possibly RFFIT for the quantification of rabies immunoglobulin. After optimisation it may be used for the quantification of rabies immunoglobulin in any animal species, notably for rabies immunogenicity assay in mice.

Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis.

Currently available rabies post‐exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad‐spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non‐RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20–RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post‐vaccination antibody response.

Reduction in Corticosteroid Use Among Patients Receiving Omalizumab in Real World Settings: A Systematic Literature Review of Non-Randomized Studies

Sarah W. Spriet, DO, Taylor A. Banks, MD, Cecilia Mikita, MD, MPH, FAAAAI; Walter Reed National Military Medical Center, Bethesda, MD. RATIONALE: Rabies post-exposure treatment is a medical necessity. Two rabies vaccines are available in the United States; purified chick embryo cell culture vaccine (PCECV, RabAvert ) and gelatin-free human diploid cell vaccine (HDCV, Imovax ). We report a case of PCECV-triggered anaphylaxis. METHODS: After clinical evaluation, patient and a volunteer control underwent skin prick and intradermal testing to the rabies vaccines, vaccine components, and rabies immunoglobulin. Vaccine challenge was then performed. RESULTS: A healthy 15 year old male presented to the Emergency Department after a live bat was found in his home, captured, and found to have rabies.Mucousmembrane exposure could not be ruled out and human rabies immunoglobulin (ImogamRabies – HT ) and PCECVwere administered. Within minutes, he developed dyspnea, stridor and generalized hives. Symptoms resolved within one hour after treatment with antihistamines and IV corticosteroids and he was referred to AllergyImmunology. On day 3 post-exposure, patient and control underwent skin prick testing to undiluted PCECV, egg, gelatin, HDCVand Imogam. Skin prick was positive to PCECV and gelatin. Intradermal testing (IDT) using 0.02 mL of 1:100 dilution to HDCV and Imogam was negative. IDT using 0.02 mL of 1:10 dilution was negative to Imogam, positive to HDCV; however, considered an irritating dose given identical results in control. Patient tolerated a 10/90 challenge to HDCV and completed post-exposure series using this vaccine. CONCLUSIONS: Skin test results and successful challenge to HDCV suggest gelatin allergy. Awareness of the potential for IgE-mediated reactions to rabies vaccine is important. Challenge to HDCV should be considered in select patients.

Assessment of 200 pediatric patients exposed to rabies risk.

Rabies is still an important health problem particularly in underdeveloped or developing countries. In this study, the aim was to investigate demographic characteristics and vaccination schedules of cases suspected of having rabies and admitted to the Pediatric Emergency Clinic of our hospital, which serves as one of the Rabies Vaccination Centers in our province. In our study, medical records of 200 patients admitted to the Pediatric Emergency Clinic with suspicion of risk of contact with the rabies virus were retrospectively analyzed. Of those 200 cases, rabies risk was found to be greater in the 5-9 year old group. There was a history of having been bitten by dogs in 68.5% of cases, cat scratch in 29.5%, and contact with other animals in 2%. While 76% of animals were stray animals, only 11% of them had an owner and had been vaccinated, and were under supervision. Rabies vaccination only had been administered to 42.5% of admitted patients, tetanus and rabies vaccination to 51.5%, tetanus; rabies vaccination and human rabies immune globulin were administered to 6%. Post-exposure prophylaxis was found to have been given as recommended to 83.5% of cases. Rabies remains an important public health problem in developing countries Like ours. We consider that public awareness should be raised; local authorities should devote efforts to control stray animals and supervise such services, and updated guidance and training should be provided to the concerned health staff to reduce the risk of rabies.

Evaluación de 200 pacientes pediátricos expuestos al riesgo de contraer rabia

Rabies is still an important health problem particularly in underdeveloped or developing countries. In this study, the aim was to investigate demographic characteristics and vaccination schedules of cases suspected of having rabies and admitted to the Pediatric Emergency Clinic of our hospital, which serves as one of the Rabies Vaccination Centers in our province. In our study, medical records of 200 patients admitted to the Pediatric Emergency Clinic with suspicion of risk of contact with the rabies virus were retrospectively analyzed. Of those 200 cases, rabies risk was found to be greater in the 5-9 year old group. There was a history of having been bitten by dogs in 68.5% of cases, cat scratch in 29.5%, and contact with other animals in 2%. While 76% of animals were stray animals, only 11% of them had an owner and had been vaccinated, and were under supervision. Rabies vaccination only had been administered to 42.5% of admitted patients, tetanus and rabies vaccination to 51.5%, tetanus; rabies vaccination and human rabies immune globulin were administered to 6%. Post-exposure prophylaxis was found to have been given as recommended to 83.5% of cases. Rabies remains an important public health problem in developing countries Like ours. We consider that public awareness should be raised; local authorities should devote efforts to control stray animals and supervise such services, and updated guidance and training should be provided to the concerned health staff to reduce the risk of rabies.

Rabies Vaccine and Rabies Immunoglobulin in Cambodia: Use and Obstacles to Use

Authorities have pledged to eliminate canine rabies by 2020 in Cambodia, a country with a very high rabies burden. Logistic and financial access to timely and adequate postexposure prophylaxis (PEP) is essential for preventing rabies in humans. We undertook a survey of the few identified sites where PEP rabies vaccination and rabies immunoglobulin (RIG) are available in Cambodia. We examined the Rabies Prevention Center at Institut Pasteur du Cambodge (rpc@ipc) database and rpc@ipc order forms for 2012 to assess vaccine and RIG use. We conducted a rapid internet survey of centers that provide rabies vaccine and RIG in Cambodia, other than rpc@ipc. The cost of a full course of intramuscular or intradermal PEP in Cambodia, with and without RIG, was also estimated. Rabies vaccination is free of charge in one foundation hospital and is accessible for a fee at Institut Pasteur du Cambodge (IPC), some institutions, and some Cambodian private clinics. In 2012, 27,500 rabies vaccine doses (0.5 mL) and 591 equine RIG doses were used to provide intradermal PEP to 20,610 persons at rpc@ipc following animal bites. Outside of rpc@ipc, an estimated total of 53,400 vaccine doses and 200 RIG doses were used in Cambodia in 2012. The wholesale cost of full rabies PEP was estimated at 50% to 100% of a Cambodian farmer's monthly wage. Local populations and travelers cannot be sure to locally access adequate and timely PEP due to high costs and low access to RIG. Travelers to high-endemic areas such as Cambodia are strongly encouraged to undergo pre-exposure vaccination or seek expert advice, as per World Health Organization (WHO) recommendations. State-subsidized, pre-positioned stocks of human vaccine and RIG in bite management centers would extend the rabies prevention centers network. Support from Institut Pasteur du Cambodge for staff training, cold chain, and quality control would contribute to reducing the risk of rabies deaths in Cambodia.

Factors for early death in rabies- the bitter truth.

Sir, Early death phenomenon in rabies reported by Sadeghi et al.[1] is informative and has long been recognized in patients whose incubation period is shorter than average in patients who were inadequately vaccinated with or without accompanying immunoglobulin and develop rabies.[2] However, we would like to recall other factors related to virus, patients, therapeutic agents, and care providers contributing to early death, so as to introduce appropriate measures to ensure quality in service and enforce patient safety. The high viral load inoculated at the site of bite, which infects motor endplates and motor axons without previous replication in the muscle and its virulence. Those related to patients are anatomical site of bite such as head and neck,[3] or bite in highly innervated areas such as fingers as noted in this case,[1] which has close proximity to central nervous system, and nonfeasibility to infiltrate adequate dose of human rabies immunoglobulin (HRIG). Next is the functional status of the immune system, which may be immune enhancement or “early death” phenomenon through B cells during the incubation period, and/or nonspecific immunosuppressive effect following rabies infection. Rabies nucleoprotein acts as a weak superantigen, and directly induces proliferation of human CD4 Th2 cells bearing the V8 TCR, which suppresses the immunity through polyclonal antibody response.[4] Matters related to therapeutic agents are questionable status of the potency of vaccine and HRIG, due to inherent technical constraints and electricity problems in countries such as India. Certain important factors related to health care providers are nonadherence to World Health Organization (WHO) postexposure prophylaxis protocol. Furthermore, health care providers should avoid prescribing antimalarials and other drugs that interfere with the effectiveness of rabies vaccine or HRIG. To overcome these, we need identification of other responsible factors so as to empower the health care providers for effective services and community health education.[5] Our motto shall be “no death due to rabies” through community education, early intervention, quality assurance of therapeutic agents, and adherence to WHO protocol.

Epidemiological characteristics of patients attending for rabies post-exposure prophylaxis at the infectious diseases hospital of lucknow, India.

Aims:The objective of the study was to assess epidemiological and anti-rabies vaccination status in animal bite patients attending the Infectious Diseases Hospital, Lucknow.Materials and Methods:A longitudinal survey was conducted in the Infectious Diseases Hospital of Lucknow from January to December 2013. During this duration a total of 390 patients presenting with animal bites were included.Results:A majority (63.3%) of patients were in the 16-59 years age group. 75% of patients had attended the IDH for rabies post-exposure prophylaxis (PEP) within 24 hours. The male to female ratio was 2.98:1. A majority (79.5%) of patients were injured by dogs. 9.0% patients were in close contact with rabies patient. On the basis of WHO classification, 4.2% of animal bite patients were placed in grade I, 88.2 in grade II and 7.6% in grade III. In 73.3% of patients wound were in lower limbs. Complete vaccination was found in 65.0% and the use of human rabies immune globulin was only in 11.1%.Conclusion:Outcome of an animal bite can be fatal. The only preventive/curative measure available is anti-rabies vaccination and the use of human rabies immune globulin, hence to assure 100% compliance for the same awareness campaign is required.

Australian bat lyssavirus: implications for public health.

Australian bat lyssavirus (ABLV) infection in humans is rare but fatal, with no proven effective therapy. ABLV infection can be prevented by administration of a post-exposure prophylaxis regimen of human rabies immunoglobulin and rabies vaccine. All Australian bats (flying foxes and microbats) should be considered to be carrying ABLV unless proven otherwise. Any bat-related injury (bite, scratch or mucosal exposure to bat saliva or neural tissue) should be notified immediately to the relevant public health unit - no matter how small the injury or how long ago it occurred. Human-to-human transmission of ABLV has not been reported but is theoretically possible. Standard infection control precautions should be employed when managing patients with suspected or confirmed ABLV infection.