Rabies Biologics Research Articles

Lack of documentation in animal bite cases and its impact on rabies biologicals utilization.

Rabies has significant health and economic consequences for both humans and animals. Annually, India witnesses 17.4 million dog bites, yet only 3 million individuals receive post-exposure prophylaxis (PEP). There is a shortage of anti-rabies vaccine in India as quoted in many news reports. In India, lack of documentation of previous vaccination against animal bites is there, hence resulting in the re-administration of the anti-rabies vaccine, leading to a significant biological loss (anti-rabies vaccine). A cross-sectional, retrospective study was conducted. Data was collected, and analyzed from June 2021 to June 2023 a period of 2 years. Majority of the patients reported within the first 24 hours after being bitten while approximately one-third reported after 24 hours. Majority were Category 3 bites and unprovoked. Males, lower-middle class, and bites on lower extremities were common among 4291 patients attending the clinic. Out of 217 re-exposure cases, 185 did not have any documentation regarding their previous treatment of animal bites. Among 4291 patients attending the clinic, majority were Category 3 bites on the lower extremities. 85.25% of re-exposure cases had to be administered a full course of treatment due to a lack of documentation leading to rabies as a biological wastage. This avoidable wastage can be a resource for treating more patients.

IJCM_280A: A prospective study on safety and clinical efficacy of rabies biologicals in paediatric patients with category III animal exposure

Background: Rabies remains a significant public health concern worldwide, particularly among paediatric populations who are vulnerable to animal exposures. This prospective study aimed to assess the safety and clinical efficacy of rabies biologicals in pediatric patients following Category III animal exposures. Objectives: 1. To describe the post exposure prophylaxis provided to the animal bite victims at the anti rabies clinic. 2. To asses the safety and clinical efficacy of currently available rabies biologicals for post exposure prophylaxis. Methodology: A prospective study was undertaken enrolling 289 pediatric patients fulfilling eligibility criteria who presented with Category III animal exposures at the anti-rabies clinic of KIMS Hospital and Research Centre, Bangalore. All the subjects received rabies biologicals as per NCDC guidelines. The details pertaining to socio demographic profile, biting animal, characteristics of wound, details of post exposure prophylaxis provided were recorded. All the study subjects were followed up for immediate and delayed adverse events. Subsequently, all were followed up for 6 months to demonstrate the clinical efficacy of PEP. Results: The mean age of study subjects was 9.4 years and most of them (43%) were going to school. Dog was the predominant biting animals (96.6%) with most bites were abrasions (45%), mainly on the lower limbs (42%). Single RmAb was the most commonly administered passive immunization (67%) and PVRV was the predominant vaccine (65%). Adverse events following post-prophylaxis were primarily local, predominantly pain (13.2%) and there were no systemic events. All the subjects were alive and healthy at the end of 6 months following PEP. Conclusion: This study contributes valuable insights into the safety and clinical efficacy of rabies biologicals in a pediatric cohort following Category III animal exposures, supporting the continued use of these biologicals in pediatric patients.

Rabies post-exposure prophylaxis delivery to ensure treatment efficacy and increase compliance

ObjectivesSince rabies is lethal once symptoms appear, its prevention including community awareness, mass dog vaccination and post-exposure prophylaxis (PEP) is crucial. Although safe and potent rabies vaccines have long been available, the global rabies burden is still high and access to adequately-delivered PEP remains challenging. Here we offer healthcare providers up-to-date, simple, exhaustive, visual guidance on how to perform PEP steps correctly. ProtocolPEP consists of 1) washing the wound with water and soap for 15 min, 2) assessing the need for rabies biologicals based on specific criteria; 3) administering, if required, rabies immunoglobulin or monoclonal antibodies deep in and around all wounds; 4) starting, if necessary, the WHO-recommended intradermal 1-week vaccination regimen; 5) informing patients adequately throughout the PEP process to increase compliance and avoid dangerous misconceptions about animal bite treatment and rabies risk. DiscussionThe intradermal 1-week vaccination regimen recommended by WHO is as safe as other regimens but carries important cost-, dose- and time-sparing benefits. As fundamental as the correct administration of rabies biologicals is clear doctor-patient communication and sharing of up-to-date knowledge among healthcare professionals. ConclusionsThis resource will help ensuring that no life is lost to rabies, an incurable yet preventable disease.

A country classification system to inform rabies prevention guidelines and regulations.

Assessing the global risk of rabies exposure is a complicated task requiring individual risk assessments, knowledge of rabies epidemiology, surveillance capacity and accessibility of rabies biologics on a national and regional scale. In many parts of the world, availability of this information is limited and when available is often dispersed across multiple sources. This hinders the process of making evidence-based health and policy recommendations to prevent the introduction and spread of rabies. CDC conducted a country-by-country qualitative assessment of risk and protective factors for rabies to develop an open-access database of core metrics consisting of the presence of lyssaviruses (specifically canine or wildlife rabies virus variants or other bat lyssaviruses), access to rabies immunoglobulins and vaccines, rabies surveillance capacity and canine rabies control capacity. Using these metrics, we developed separate risk scoring systems to inform rabies prevention guidance for travelers and regulations for the importation of dogs. Both scoring systems assigned higher risk to countries with enzootic rabies (particularly canine rabies), and the risk scoring system for travelers also considered protective factors such as the accessibility of rabies biologics for post-exposure prophylaxis. Cumulative scores were calculated across the assessed metrics to assign a risk value of low, moderate or high. A total of 240 countries, territories and dependencies were assessed, for travelers, 116 were identified as moderate to high risk and 124 were low or no risk; for canine rabies virus variant importation, 111 were identified as high-risk and 129 were low or no risk. We developed a comprehensive and easily accessible source of information for assessing the rabies risk for individual countries that included a database of rabies risk and protective factors based on enzootic status and availability of biologics, provided a resource that categorizes risk by country and provided guidance based on these risk categories for travelers and importers of dogs into the United States.

Rabies Elimination in Rural Kenya: Need for Improved Availability of Human Vaccines, Awareness and Knowledge on Rabies and Its Management Among Healthcare Workers.

BackgroundIn Africa, rabies causes an estimated 24,000 human deaths annually. Mass dog vaccinations coupled with timely post-exposure prophylaxis (PEP) for dog-bite patients are the main interventions to eliminate human rabies deaths. A well-informed healthcare workforce and the availability and accessibility of rabies biologicals at health facilities are critical in reducing rabies deaths. We assessed awareness and knowledge regarding rabies and the management of rabies among healthcare workers, and PEP availability in rural eastern Kenya.MethodologyWe interviewed 73 healthcare workers from 42 healthcare units in 13 wards in Makueni and Kibwezi West sub-counties, Makueni County, Kenya in November 2018. Data on demographics, years of work experience, knowledge of rabies, management of bite and rabies patients, and availability of rabies biologicals were collected and analyzed.ResultsRabies PEP vaccines were available in only 5 (12%) of 42 health facilities. None of the health facilities had rabies immunoglobulins in stock at the time of the study. PEP was primarily administered intramuscularly, with only 11% (n = 8) of the healthcare workers and 17% (7/42) healthcare facilities aware of the dose-sparing intradermal route. Less than a quarter of the healthcare workers were aware of the World Health Organization categorization of bite wounds that guides the use of PEP. Eighteen percent (n = 13) of healthcare workers reported they would administer PEP for category I exposures even though PEP is not recommended for this category of exposure. Only one of six respondents with acute encephalitis consultation considered rabies as a differential diagnosis highlighting the low index of suspicion for rabies.ConclusionThe availability and use of PEP for rabies was sub-optimal. We identified two urgent needs to support rabies elimination programmes: improving availability and access to PEP; and targeted training of the healthcare workers to improve awareness on bite wound management, judicious use of PEP including appropriate risk assessment following bites and the use of the dose-sparing intradermal route in facilities seeing multiple bite patients. Global and domestic funding plan that address these gaps in the human health sector is needed for efficient rabies elimination in Africa.

Animal Bite Management Facilities in aRural Area Near Bangalore

Background Rabies is almost always fatal but being a 100 preventable disease treatment for the prevention of rabies in humans exposed to rabies should begin promptly after the exposure. The vast majority of rabies deaths 84 occur in rural areas. There are various reasons contributing to it and non-availability of health care facilities for animal bite management in these areas is one among them.Methodology The study was conducted in the villages near Bangalore over a period of six months. All the health care facilities in the study area were visited and data was collected regarding the availability and storage of rabies biological by personal interview of the health personnel in charge of these health centres using a check list and also by observation of the storage of rabies biologicals in these health care facilities.Results Both government and private health care facilities in the study area lacked adequate resources for animal bite management.Conclusion The study showed that the health care facilities lacked training and resources for animal bite management in the rural area near Bangalore.

2013~New Horizon With Rabies Biologicals

Prevention is the only way out to stop death from Rabies, not the treatment of the same to cure the diseased. The only communicable ailment having 100% mortality depicts almost full preventive protection on the other side of the coin. The age old nerve tissue vaccine below the belly--dermis is ultimately history and almost half – a – dozen ultramodern Anti- rabies biological are on the cards now-a-days. Justified usage of them and social alertness reflecting the health consciousness of the civilization should improve the quality of human existence on the planet – let this be the theme of life in every sunrise to be seen. This Endeavour aims to reflect the light of management system of Anti-rabies prophylaxis with the most modern tools.

Rabies vaccine and immunoglobulin supply and logistics: Challenges and opportunities for rabies elimination in Kenya

Prompt provision of post-exposure-prophylaxis (PEP) including vaccines and rabies immunoglobulin (RIG) to persons bitten by suspect rabid dogs is a key strategy to eliminating human deaths from dog-mediated rabies in Kenya by 2030. We assessed the availability, forecasting and supply chain logistics for rabies PEP in Kenya, compared with the system used for vaccines in the expanded program of immunization (routine vaccines). Semi-structured questionnaires capturing data on forecasting, procurement, distribution, cold chain and storage, monitoring and reporting for routine vaccines and rabies vaccines and RIG were administered to 35 key personnel at the national, county, sub-county and health facility levels in five counties. Results showed large variability in PEP availability (stockouts ranged from 3 to 36 weeks per year) with counties implementing rabies elimination activities having shorter stockouts. PEP is administered intramuscularly using the 5-dose Essen regimen (day 0, 3, 7, 14 and 28). PEP costs to bite patients were reported to range from 10 to 15 US dollars per dose; RIG was seldom available. A less robust supply and logistics infrastructure is used for rabies PEP compared to routine vaccines. Forecasting and monitoring mechanisms for rabies PEP was poor in the study counties. The supply of vaccines from the national to the sub-national level is mainly through two government agencies and a private agency. Since government decentralization, the National Vaccine and Immunization Program has remained as the main supplier of the routine vaccines, playing a lesser role in the supply of rabies biologicals. Adoption of the dose-saving intradermal route for PEP administration, reduction of PEP costs to patients, and placing rabies vaccines within the routine vaccines supply and logistics system would significantly improve PEP availability and accessibility to persons at risk of rabies; a critical step to achieving elimination of human deaths from rabies.

Evaluation of Vietnam’s post-exposure prophylaxis delivery system, 2017

BackgroundCanine-mediated human rabies deaths typically occur in poor and rural populations with limited access to rabies biologics: vaccine and immunoglobulin. A critical aspect of reducing rabies deaths is understanding how these countries procure, deliver, and forecast rabies biologics. Vietnam is one of the few endemic countries where biologics is widely available. However, a formal evaluation of its current rabies biologics distribution system has not been conducted. MethodsIn 2017, we conducted a formal evaluation of Vietnam’s rabies biologics distribution system. Our goals were (1) to identify centers providing rabies biologics (2) identify costs to the patient and centers and (3) assess the rabies biologic procurement and delivery system at eligible district and provincial centers (provides and orders biologics for itself and other centers directly from the manufacture). To conduct the formal evaluation, we developed a standardized survey that was distributed to centers. ResultsOf the 780 designated rabies biologics centers in Vietnam, 659 (84%) of them provide rabies immunoglobulin (eRIG), vaccine, or both. Of the 177 eligible centers, 90% (160) responded to the survey. The average costs to patients were $8.45 (range: 5.43–12.77) for one dose of IM injection, $13.90 (range: 11.86–16.71) for domestic eRIG, and $23 (21.11–27.11) for imported eRIG. Respondents reported experiencing delays in receiving vaccine in 50 centers and eRIG in 14 centers within the past year. Respondents stated their top three challenges in providing biologics were: delays or shortages from manufactures, lack of funds to pay for biologics, and the high cost of biologics. Conclusions and relevanceDespite the wide availability of biologics in Vietnam, more work is needed to provide affordable and reliable supply of biologics to patients. This includes the expansion of ID injection use throughout the country to lower vaccine demand, and decrease the costs to centers and patients. Furthermore, a more coordinated effort to share biologics among centers, possibly through a more centralized system at the provincial level may alleviate delays and shortages.

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.

Assessment of procurement, distribution, availability, and utilization of rabies biologicals for postexposure prophylaxis in seven states of India.

To achieve the elimination of dog-mediated human rabies by 2030, all bite victims shall have access to life-saving rabies biologicals across the country. The information on procurement, distribution, availability, and utilization of rabies biologicals for postexposure prophylaxis is insufficient. The objective of the study is to assess the demand, procurement, distribution, availability, storage, and utilization of rabies biologicals and to appraise the monitoring and reporting of rabies biologicals at all the levels. A multicentric survey was conducted from July to December 2017 in seven regional representative states across the country. The survey team visited the offices in-charge for logistics of rabies biologicals at the survey states and districts; information was collected using structured pro formas and perusing relevant records. District vaccine stores and health institutions in urban and rural areas were visited to assess the availability and stock-outs of rabies biologicals. Procurement, distribution, and availability of rabies biologicals grossly vary between states, since it is the state subject. In Gujarat, both vaccines and immunoglobulins were available even at the Primary Health Centre level; paradoxically, there was a scarcity of both at the district level in Manipur. Immunoglobulins were used only in nine of the surveyed 27 government health-care facilities (33.3%) and two of the eight private facilities (25%). The cold chain facility for storage of rabies biologicals was satisfactory; however, the monitoring and reporting of rabies biologicals were not complete. The procurement, distribution, availability, and utilization of rabies biologicals were not universal across the states. Frequent shortages of supply have to be improved to attain universal coverage.

Background paper for developing a policy for the use of rabies biologicals and vaccination of humans in India

National Rabies Control Programme, India, is in operation since 2012-2013 without much impact due to poor funding and no set policy for the rabies prevention and control. An effort was made to develop a draft policy paper which can help the Government of India to develop a national rabies vaccination policy for humans and for achieving the goal of zero dog-mediated human rabies deaths by the year 2030. A technical stakeholders meeting was held under the chairmanship of the Drug Controller General of India at New Delhi in December 2017 to discuss the problems and solutions for providing essential rabies postexposure prophylaxis (PEP). The following problems and dilemmas were identified: frequent shortages of life-saving rabies vaccines and rabies immunoglobulin for PEP; as rabies vaccines are mostly procured by the state governments that often face resource crunch and hurdles in logistics within the states; production levels of rabies biologicals in the public sector are low; and the export of rabies biologicals from the private sector needs to be critically evaluated in the context of frequent stock-outs in the domestic market and also the national vaccine security.

Facilities and services of postexposure prophylaxis in anti-rabies clinics: A national assessment in India.

The rabies postexposure prophylaxis (PEP) is provided through anti-rabies clinics in the country. It was considered important to assess their facilities under a nationwide multi-centric survey. The objective of this study is to assess the facilities available for PEP at the anti-rabies clinics and to ascertain the PEP provided at the anti-rabies clinics. The cross-sectional assessment was made from May 2017 to January 2018 in selected seven states of India. Thirty-five anti-rabies clinics from both Government and private; urban and rural areas from the states were assessed by an expert team using a pretested checklist for facilities and services available for PEP. On an average, 10 new animal bite cases were attended at each anti-rabies clinic per day. The cold chain facilities for rabies biologicals were satisfactory. The facilities for wound washing (54.3%) and the use of antiseptics to animal bite wounds were not adequate. Rabies vaccines were administered by intramuscular in 54.3% and by intradermal route in 45.7% of the cases. The vaccine stock-outs were reported only in the government sector (18.5%). The type of rabies immunoglobulin (RIG) used was equine (63.2%) and human (36.8%); given free of cost in 40% of Anti rabies clinics. The local wound infiltration of RIG was in practice at 58.6% of anti-rabies clinics. The stock-out of RIG was more in private (50%) hospitals than in Government (40.7%) hospitals. The facilities available for PEP at the anti-rabies clinics were inadequate and have to be improved across the country.

Modelling to inform prophylaxis regimens to prevent human rabies

BackgroundThe Strategic Advisory Group of Experts (SAGE) Working Group on rabies vaccines and immunoglobulins was established in 2016 to develop practical and feasible recommendations for prevention of human rabies. To support the SAGE agenda we developed models to compare the relative costs and potential benefits of rabies prevention strategies. MethodsWe examined Post-Exposure Prophylaxis (PEP) regimens, protocols for administration of Rabies Immunoglobulin (RIG) and inclusion of rabies Pre-Exposure Prophylaxis (PrEP) within the Expanded Programme on Immunization (EPI). For different PEP regimens, clinic throughputs and consumables for vaccine administration, we evaluated the cost per patient treated, costs to patients and potential to treat more patients given limited vaccine availability. ResultsWe found that intradermal (ID) vaccination reduces the volume of vaccine used in all settings, is less costly and has potential to mitigate vaccine shortages. Specifically, the abridged 1-week 2-site ID regimen was the most cost-effective PEP regimen, even in settings with low numbers of bite patients presenting to clinics. We found advantages of administering RIG to the wound(s) only, using considerably less product than when the remaining dose is injected intramuscularly distant to the wound(s). We found that PrEP as part of the EPI programme would be substantially more expensive than use of PEP and dog vaccination in prevention of human rabies. ConclusionsThese modeling insights inform WHO recommendations for use of human rabies vaccines and biologicals. Specifically, the 1-week 2-site ID regimen is recommended as it is less costly and treats many more patients when vaccine is in short supply. If available, RIG should be administered at the wound only. PrEP is highly unlikely to be an efficient use of resources and should therefore only be considered in extreme circumstances, where the incidence of rabies exposures is extremely high.

Global characteristics of the rabies biologics market in 2017

In 2017, the World Health Organization, the World Organisation for Animal Health, the Food and Agriculture Organization of the United Nations and the Global Alliance for Rabies control developed a strategic plan to end human rabies deaths by 2030.A survey for manufacturing capacity and product characteristics of rabies biologics was conducted to inform this process. Twenty-three of 42 manufacturers, responded, giving a market capacity for 2017 of 90 million vials for human vaccines, 2.5 million vials for rabies immunoglobulins, 2 million vials for monoclonal antibodies and 181 million vials for dog vaccines.Production capacity could be increased by many manufacturers but was limited by country demand, lack of long-term planning and restricted market expansion. Should countries implement national rabies elimination programmes where biologic needs are forecasted and production lead times respected, manufacturers can meet future supply needs towards global elimination of human dog-mediated rabies deaths.

Retrospective Cohort Study to Assess the Risk of Rabies in Biting Dogs, 2013⁻2015, Republic of Haiti.

Background: In canine rabies endemic countries the World Health Organization recommends post-exposure prophylaxis (PEP) be initiated immediately after exposure to an animal suspected to have rabies. Limited capacity in low and middle income countries to assess biting animals for rabies may result in the over prescription of rabies biologics. Few guidelines exist to determine the risk of whether a dog that has bitten someone is rabid. Given PEP cost and access limitations in many countries, accurate and timely assessment of dogs that have bitten people may reduce unwarranted PEP use and improve healthcare seeking behaviors. Methods: Haiti’s animal rabies surveillance program utilizes veterinary professionals to conduct rabies assessments on reported biting dogs and records characteristics of the dog, health outcomes, and laboratory results in a national database. Characteristics of rabid dogs were assessed through a retrospective cohort study of biting dogs investigated during the period from January 2013–December 2015. 1409 biting dogs were analyzed; 1361 dogs that were determined to not have rabies were compared to 48 laboratory-confirmed rabid dogs. Rate ratios, sensitivity, specificity, positive predictive values, negative predictive values, likelihood ratios, quarantine survival of biting dogs, and a risk matrix were developed. Findings: The assessor’s determination that the animal likely had rabies was the most significant predictive factor for a rabid dog (RR = 413.4, 95% CI 57.33–2985, Sn = 79.17, Sp = 91.92). Clinical factors significantly associated with rabid dogs included hypersalivation, paralysis, and lethargy (RR = 31.2, 19.7, 15.4, respectively). Rabid dogs were 23.2 times more likely to be found dead at the time of the investigation compared to case negative dogs (95% CI 14.0–38.6). Rabid dogs were also significantly more likely to lack a history of rabies vaccination or be unowned (RR = 10.3 95% CI 2.5–42.3 and RR = 4.5 95% CI 2.0–10.1, respectively). Rabid dogs were four times more likely to have bitten multiple people (RR = 4.0 95% CI 1.9–8.3). Most rabid dogs died or were killed before quarantine (75%) and all died by day 3 of quarantine, compared to <1% of quarantined case-negatives. The greatest risk of death was predicted to be for persons bitten on the head or neck from symptomatic dogs. Bites from dogs deemed healthy by veterinary assessors and which were available for quarantine presented less than a 0.05% risk of rabies death to the victim. Conclusions: Vaccination of all persons exposed to a suspected rabid dog is a highly effective approach to minimize human rabies deaths. However, this may place undue financial burden on bite victims that have had a low-risk exposure and over-prescription may contribute to regional supply shortages. The results here indicate that in a low-resource country such as Haiti, a well-trained veterinary assessor can provide an accurate risk assessment of biting dogs based on a standard case investigation protocol. In canine rabies endemic countries with limited access to PEP, or where PEP costs may cause undue burden on bite victims, structured risk assessments by trained professionals may be a reliable method of triaging PEP for bite victims. Evaluating rabies risk through a matrix of bite location and risk factor in the dog presents a clear delineation of high and low risk encounters and should be used to develop data-derived PEP recommendations.

Costs Analysis of a Population Level Rabies Control Programme in Tamil Nadu, India

The study aimed to determine costs to the state government of implementing different interventions for controlling rabies among the entire human and animal populations of Tamil Nadu. This built upon an earlier assessment of Tamil Nadu's efforts to control rabies. Anti-rabies vaccines were made available at all health facilities. Costs were estimated for five different combinations of animal and human interventions using an activity-based costing approach from the provider perspective. Disease and population data were sourced from the state surveillance data, human census and livestock census. Program costs were extrapolated from official documents. All capital costs were depreciated to estimate annualized costs. All costs were inflated to 2012 Rupees. Sensitivity analysis was conducted across all major cost centres to assess their relative impact on program costs. It was found that the annual costs of providing Anti-rabies vaccine alone and in combination with Immunoglobulins was $0.7 million (Rs 36 million) and $2.2 million (Rs 119 million), respectively. For animal sector interventions, the annualised costs of rolling out surgical sterilisation-immunization, injectable immunization and oral immunizations were estimated to be $ 44 million (Rs 2,350 million), $23 million (Rs 1,230 million) and $ 11 million (Rs 590 million), respectively. Dog bite incidence, health systems coverage and cost of rabies biologicals were found to be important drivers of costs for human interventions. For the animal sector interventions, the size of dog catching team, dog population and vaccine costs were found to be driving the costs. Rabies control in Tamil Nadu seems a costly proposition the way it is currently structured. Policy makers in Tamil Nadu and other similar settings should consider the long-term financial sustainability before embarking upon a state or nation-wide rabies control programme.

Evaluation of Rabies Biologics against Irkut Virus Isolated in China

An Irkut virus (IRKV) was recently isolated from a bat in China. The protective ability of rabies biologics available in the Chinese market and experimental biologics against the rabies virus (RABV) and IRKV were assessed in a hamster model via preexposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) experiments. The results demonstrated that a single dose of rabies vaccine did not induce adequate protection against IRKV infection. However, routine PrEP with three doses of vaccine induced complete protection against IRKV infection. Higher doses of RABV immunoglobulins and alpha interferon were required during PEP to protect hamsters against IRKV versus RABV infection. Experimental recombinant vaccines containing IRKV glycoproteins induced more-reliable protection against IRKV than against RABV infection. Those findings may be explained by limited cross-neutralization of these viruses (confirmed via in vitro tests) in conjunction with antigenic distances between RABV and IRKV. These results indicate that the development and evaluation of new biologics for PrEP and PEP are required to ensure sufficient protection against IRKV infection in China and other territories where this virus is present.

Analysis of the complete genome of the first Irkut virus isolate from China: Comparison across the Lyssavirus genus

The genome of Irkut virus, isolate IRKV-THChina12, the first non-rabies lyssavirus from China (of bat origin), has been completely sequenced. In general, coding and non-coding regions of this viral genome are similar to those of other lyssaviruses. However, alignment of the deduced amino acid sequences of the structural proteins of IRKV-THChina12 with those of other lyssavirus representatives revealed significant variability between viral species. The nucleoprotein and matrix protein were found to be the most conserved, followed by the large protein, glycoprotein and phosphoprotein. Differences in the antigenic sites in glycoprotein may result in only partial protection of the available rabies biologics against Irkut virus, which is of particular concern for pre- and post-exposure rabies prophylaxis.

Rabies vaccination for international travelers

Rabies prevention in travelers is a controversial issue. According to experts, the decision to vaccinate results from an individual risk assessment based on the duration of stay, the likelihood of engagement in at-risk activities, the age of the traveler, the rabies endemicity and access to appropriate medical care in the country of destination. However, no detailed information is available regarding the last two determinants in many regions. Twenty-two cases of rabies were reported in tourists, expatriates and migrant travelers over the last decade, including three cases following short-term travel of no more than two weeks. Studies on rabies post-exposure prophylaxis (PEP) in travelers show that overall, 0.4% (range 0.01-2.3%) of travelers have experienced an at-risk bite per month of stay in a rabies-endemic country, while 31% of expatriates and 12% of tourists were vaccinated against rabies before traveling. The main reason cited by travelers for not being vaccinated is the cost of the vaccine. The majority of patients who sustained a high risk injury was not vaccinated against rabies before traveling and were not properly treated abroad. From available studies, the following risk factors for injuries sustained from potentially rabid animals may be identified: traveling to South-East Asia, India or North Africa, young age, and traveling for tourism. The duration of travel does not appear to be a risk factor. It should be noted that "at-risk activities" have not been addressed in these studies. Detailed rabies distribution maps and information on the availability of rabies biologics are urgently needed in order to identify those travelers who need pre-travel vaccination. Meanwhile, cost-minimization of rabies pre-exposure vaccination may be achieved in several ways, notably by using the intra-dermal method of vaccination.