Nervous Tissue Vaccine Research Articles

Health professionals KAP study on rabies exposure assessment and NTV administration in Ethiopia

Background: Globally, it’s estimated 60,000 human deaths occur due to rabies with 95% of cases occurring in Africa and Asia. Annually, thousands of people are infected with rabies in Ethiopia and more than 2700 people die. In Ethiopia, the neural-based vaccine has been used since the 1950’s. Due to the old method of production, low immunogenicity and vaccine associated adverse events, WHO discourage the use of this vaccine and recommend replacing it with a safe and effective modern cell culture vaccine. There was no specific guidelines and training for this vaccine and health professional mismanage the nerve tissue vaccine (NTV) with cell culture vaccine resulting in vaccination failure. This study identifies professional knowledge, attitude and practice (KAP), vaccine related adverse events and the burden of rabies cases in humans. Methods: Data were collected from health professionals in selected health facilities using structured questionnaire to identify the level of KAP. Results: The study identified overall gaps in the professionals KAP as below standard which is not more than 25%. The majority of the respondents (97%) reported vaccine associated local adverse events followed by 20% systemic complications during vaccination. Only 2.4% of the respondents reported post-vaccine complications. Rabies cases in humans at those covered health facilities were reported to be 32 during the one-year study period with an average of two cases at each facility. Conclusions: Gaps identified in the professional KAP result indicate the need to provide specific training based on standard guidelines. Generally, the study indicates the need to strengthen rabies prevention and control efforts through inter-sectoral collaboration, and facilitating the establishment of facility-based rabies palliative care centers. In addition, it is recommended to work on technology transfer to replace old method of NTV production with safe and effective modern cell culture based anti-rabies vaccine production for effective rabies PEP.

Dog demography, rabies awareness and dog bite cases in Bishoftu town, Ethiopia

Rabies is a zoonotic viral disease that affects humans and animals and dogs are the primary source of infection. Information on domestic dog populations is vitally important for rabies control. The present study is to assess the demography of dogs, the incidence of dog bites, and the knowledge, attitude, and practice (KAP) of the communities concerning rabies in Bishoftu town. Cross-sectional household surveys were conducted from April to June 2021 involving a questionnaire survey and collection of retrospective patient records from healthcare facilities. A total of 244 respondents were interviewed using a structured questionnaire format to determine their KAP about rabies and dog ownership. Data on the incidence of dog bites and suspected cases of rabies from November 2019 to June 2021 were retrieved from the records of four health centers in Bishoftu town. In interviewed households (HH) 51.2 % owned at least one dog with a dog: human ratio of 1:9 and 1.54 dogs/household. In the participating households, 71% of dogs had been vaccinated against rabies. Almost all, 99% of the respondents had heard of rabies and identified the mode of transmission of rabies. However, 61.8%, had a moderate level of knowledge and 59.8% had an intermediate level of attitude, and 64.3% satisfactory level of appropriate rabies prevention practices score. There was a statistically significant association between knowledge score and age, occupation, and source of information as well as attitude score with age and source of information (p<0.05). Respondents who attend higher education were more likely to have higher practice scores in the prevention of rabies (p <0.05). There were significant correlations among the participant’s knowledge, attitude, and practice (p<0.01). A total of 612 victims were registered and received the post-exposure vaccine in Bishoftu over two years (2019 to 2021). We identified critical knowledge gaps related to factors influencing rabies prevention and control. The veterinary and public health sectors should play an important role in educating and raising community awareness. Moreover, the production and use of the banned nerve tissue vaccine in the public health sector in Ethiopia need attention.

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.

Pregnant with puppies

In New Delhi, some migrants from central-eastern India espouse a belief in ‘puppy pregnancy’, or the notion that after being bitten by a dog its puppies are conceived within the abdomen and their growth leads to an awful death. This article suggests that this belief is related to the widespread fear of rabies. This lethal infectious disease causes one-half of deaths in India, leaving behind grief-stricken families and shocked communities. This rabies-related shock results not only from the disease per se but also from the long, painful, and disturbing post-bite vaccination prophylaxis, using a nervous tissue vaccine, in which bite victims receive fourteen distressing injections in the abdomen in the hope of saving them from death. I propose here that dread of this vaccination may have stimulated, within an already fertile cultural milieu, the belief in this unnatural, animal pregnancy.

Pregnant with puppies: the fear of rabies in the slums of New Delhi, India

In New Delhi, some migrants from central-eastern India espouse a belief in ‘puppy pregnancy’, or the notion that after being bitten by a dog its puppies are conceived within the abdomen and their growth leads to an awful death. This article suggests that this belief is related to the widespread fear of rabies. This lethal infectious disease causes one-half of deaths in India, leaving behind grief-stricken families and shocked communities. This rabies-related shock results not only from the disease per se but also from the long, painful, and disturbing post-bite vaccination prophylaxis, using a nervous tissue vaccine, in which bite victims receive fourteen distressing injections in the abdomen in the hope of saving them from death. I propose here that dread of this vaccination may have stimulated, within an already fertile cultural milieu, the belief in this unnatural, animal pregnancy.

Clinical study on rabies prone animal bite

Introduction: Rabies is almost invariably fatal zoonotic disease, it can be prevent well with proper management of wound and rabies prophylaxis. This study aims to describe the pattern of rabies prone animal bite, to observe the trends of management and relationship with socioeconomic condition of victims.Method : This is an observational study. Data was collected from patients presenting with animal bite or attendants on structured case record form at Infectious Disease Hospital, Dhaka and emergency department of Mitford Hospital from 1st to 27th February 2010. Patients with category II &III bite were followed up 3 months over phone to observe the outcome.Results: A total 235 animal bite victims attending at Infectious Disease Hospital and Mitford Hospital were enrolled in study. Young patients, around 49.79% population within 18 years age group; male (82.98%) was more affected and mostly from low socioeconomic condition. Dog bite (91.06%) was predominant by stray dogs (94.89%) Exposure was mainly bite (83.82%), which were unprovoked (95.75%) and category – III(86.81%). Local wound care was minimal (wash with soap – 28.93%) and use of nerve tissue and cell culture vaccination was 81.70% and 18.29% respectively.Conclusion : Predominant rabies prone animal bite is stray dog. Victims after bite took ineffective nerve tissue vaccine while missing important rabies immunoglobulin due to economic constraints. The prevention of animal bite need to be addressed for prevention of rabies in Bangladesh.Bangladesh J Medicine Jan 2018; 29(1) : 26-30

Development of In-vitro Assays to Estimate Rabies Viral Protein in Vaccine Preparation

Vaccine against rabies is prepared by cell culture technology and these vaccines are free from many side effects when compared to nerve tissue vaccines. The vaccine production is a continuous process involving propagation of virus, harvesting, concentration, inactivation, purification and formulation with preservatives. The quantification of viral protein in the intermediate biological product is an in-process quality control test to reduce the product loss during various process of vaccine manufacturing. The conventional in-vivo & in-vitro tests employed for the quantification of rabies viral protein are time consuming, laborious and requires laboratory animals. In this study, we attempted to develop in-house serological methods such as sandwich ELISA, Dot Blot for the detection and quantification of rabies antigen in the intermediate biological material during vaccine preparation. The hyper immune sera was prepared by immunizing two animal models i.e. Guinea Pigs and rabbits with standard Rabies antigen. The sera samples were purified by saturated ammonium sulphate precipitation and further by G50 gel column. The anti-rabies antibody titre in the purified preparation was estimated using Rapid Fluorescent Focus Inhibition Test (RFFIT). National Reference Rabies Vaccine received from Central Drug Laboratory, Kasauli was used to prepare the local reference standard and it was included in the in-house serological methods to validate the assay. Our in-house tests are found to be simple, rapid and cost effective and require less time when compared to in-vivo animal challenge and cell culture based in-vivo tests.

Importance to Vaccination Against Rabies in Travellers to Areas of Risk

A patient returned from Algeria showing a grade III wound (WHO standard) produced by a dog bite, was treated with rabies nerve tissue vaccines (NTVs) lacked the rabies immunoglobin, and developed a visible local reaction to the vaccine. The last WHO position paper (2010) recommends replacing nerve-tissue vaccines with CCVs. The nerve tissue vaccines induce more-severe adverse reaction sand are less immunogenic than CCVs. It should be assessed in travellers to areas of risk, pre-exposure vaccination, and eliminated the need to the use of rabies globulin post exposition, and avoid as much as possible the use of of nerve-tissue vaccines.

Antibody Response of Dogs to Ethiorab Rabies Vaccine

Rabies is 100% fatal, but it is preventable. More than 95% of human rabies cases occur in improperly treated individuals. This is partly due to the fact that modern post-exposure rabies prophylaxis is expensive and therefore not readily available in many endemic regions. Nervous tissue vaccine has been in use for more than 100 yrs. These vaccines have now been superseded in purity, potency, immunogenicity and safety. The efficacy and immunogenicity of inactivated tissue culture vaccine, produced in Ethiopia was evaluated. Twelve experimental dogs from local breed were duly conditioned during a quarantine period and assigned to two groups randomly. Animals in group I (cases) were vaccinated subcutaneously with 1 ml of our experimental vaccine. Dogs in group II served as non-vaccinated controls. The immune response of each dog was monitored for 120 days. On the day 120 after final sampling, all dogs were challenged in the masseter muscle with a rabies street virus of canine origin. To evaluate the titer of the rabies virus neutralizing antibodies (VNA), sera were analyzed by Fluorescent Antibody Virus Neutralization (FAVN) Test. Geometric Mean Titers (GMT) to rabies virus was determined at days 7, 15, 21, 30, 60, 90 and 120. Geometric mean titers were equal to 1.59, 1.73, 2.19, 3.58, 3.17, 3.35 and 3.56 IU/ml respectively. All dogs showed VNA titers higher than the 0.5 IU/ml mandated WHO recommended threshold. 83.3% vaccinated dogs, survived the challenge virus. In contrast, all dogs in the control (non-vaccinated group), developed rabies and died. This study indicated cell culture-based anti-rabies vaccine manufactured in Ethiopia is efficacious and immunogenic.

Rabies in South Asia: Fighting for Elimination

South Asia is regarded as the hot spot for the tourist and travelers. Unfortunately, three big countries (India, Pakistan and Bangladesh) of this region belong to top five rabies endemic countries of the world. Around 55,000 people die of rabies every year globally and 45% of them belong to South and South East Asia. Countries are now working on the elimination of rabies by the year 2020. Elimination of animal rabies is the pivotal of controlling human rabies. Dog (primary source) registration, population control and mass vaccination are the different ways of eliminating animal rabies. Pre (for risk groups including travelers) and post-exposure vaccine is the core for controlling human rabies. Post-exposure vaccine consists of nerve tissue vaccine and tissue culture vaccine. Due to low antigenicity and post-vaccine neurological complications all countries of South Asia except Pakistan have phased out the production and use of nerve tissue vaccine. To reduce the cost intramuscular regimen is now largely replaced by intradermal regimen and equine rabies immunoglobulin will probably replace human immunoglobulin in future for category III animal bite. 'SAARC' took initiatives for rabies elimination through 'SAARC development fund' which would hopefully play a vital role in regional collaboration to make the region rabies free.

Epidemiology of animal bites and other potential rabies exposures and anti-rabies vaccine utilization in a rural area in Southern Ethiopia.

The presented report describes the epidemiology of potential rabies exposures and examines the utilization of anti-rabies vaccine in a rural area of Ethiopia during a period of 43 months. A total of 683 persons (51.1% females, 73% children) with animal- related bites were included in the retrospective, registry-based study. The most common site of exposure was the leg (66.8%). In children under 8 years of age the face was more often involved than in adults (9.5% vs. 4.8%; p=0.03). The main type of exposure was a bite with bleeding (66.3%) followed by contamination of mucous membranes with saliva (19.7%). The primary sources were dogs (93.4%) followed by cats (2.6%). Children under 15 years were more likely to be exposed to dogs (94.9%) than adults (88.7%) (p=0.01). The most common way of coming in contact with animals was 'walking by' (83.9%). Children came in contact with animals while 'playing with' (10.7%) more often than adults (1.1%) (p<0.001). All the patients received an anti-rabies nervous-tissue vaccine, 99% of whom completed the vaccination course. Animal bites continue to be a problem in rural Ethiopia, mainly among children. Efforts to protect children against animal bites must be of paramount importance in preventing rabies in this population.

Production of Cell Culture Based Anti- rabies Vaccine in Ethiopia

Prevention and control of rabies in the world will require international efforts to increase the availability and use of high quality cell-culture rabies vaccines for use in human and veterinary. An important aspect of activities to ensure such availability is transfer of technologies to developing countries for production of these vaccines. Methods for Rabies Virus manipulation have changed fundamentally from random attenuation to defined modifications. In 2001, WHO issued a resolution for the complete replacement of nerve tissue vaccines by 2006 with cell-culture rabies vaccines. However, sheep brain derived Fermi type rabies vaccine is still being manufactured and utilized for the majority of exposed patients in Ethiopia. Therefore, production of a safer and effective cell culture based anti-rabies vaccine is needed. Currently the Ethiopian government has heavily invested in upgrading the facilities required to produce a rabies vaccine in keeping with WHO recommendation. Rabies virus suspensions were obtained from vero cells cultivated on roller bottles after infection with the Pasteur virus strain (PV) and Evelyn Rokitniki Abelseth (ERA). Initially the titer of the obtained virus and multiplicity of infection of the viruses had to be optimized; therefore in rabies virus infected cultures, higher virus yields was obtained when infected with 0.001ERA virus/cell and incubated at 37°C in 5% CO2 for 96hr and 0.01PV/cell incubated at 37°C in 5% CO2 for 48hr. Based on the results it is conclude that, ERA virus 0.001ID/cell with incubation period of 96h and was selected as best titer for rabies vaccine production.

National Guideline of Rabies Prophylaxis-2010

Background: Rabies has been the subject of fear ever since the disease was recognized. Worldwide the number of deaths annually, due to rabies, is estimated to be between 35,000 to 50,000 approximately Rabies continues to be a major public health problem in Bangladesh killing an estimated 2000 people annually and 100,000 people receive post-exposure treatment in the country. In this regard the post-exposure treatment of animal bite cases is of prime importance. Materials and Methods: Communicable disease control(CDC) of, Directorate General of Health Services (DGHS) took the noble initiative to establish the national rabies elimination programme 2010 with an comprehensive approach of care for human and control of rabid animal. An expert group meeting for strategic plan and finalizing the guidelines for prevention and control of rabies cases was held in 2010, under CDC of DGHS to bring out uniformity in post-exposure treatment practices. . The participants in the meeting included practitioners managing anti-rabies clinics, laboratory medicine practitioners, policy makers, public health experts from both public and private sector. The guideline, which emerged out of consensus of expert groups, is summarized in this paper. Results: Until recently the Nervous Tissue Vaccine (NTV) was the mainstay for post-exposure prophylaxis in Bangladesh. As per WHO recommendations, the production and use of this reactogenic vaccine should be gradually phased out from our country. Modern, safe and effective anti-rabies Cell Culture Vaccines (CCVs) will be used for post-exposure prophylaxis in public sectors. The limitation is the high cost of this vaccine and also the cost and unavailability of Anti Rabies Immunoglobulin. WHO recommended the use of intra-dermal (ID) route of application of CCVs. Considering the recommendations of experts, results of clinical trials and international experience, experts of Bangladesh recommends ID regimen phase wise. In first phase, only Dhaka Infectious Disease Hospital will serve as Anti-rabies centre for ID regimen. After its successful implementation, ID regimen will spread out to Division and then to District level hospitals. National experts suggested and recommended the use of cost-effective vaccination schedules such as abbreviated multisite IM Zagreb protocol (4 dose, 3 visits) and updated Thai Red Cross (TRC) intradermal regimen(2-2-2-0-2) to phase out NTV and to make available modern rabies vaccine in public sector. Conclusion: This guideline will be extremely useful for the country to make rational use of modern rabies vaccine and phase out NTV by 2011. The guideline will be of immense use for better management of animal bite cases and availability and affordability of modern rabies vaccine will be of great help for physician to manage appropriately for preventing the deadly disease rabies. DOI: http://dx.doi.org/10.3329/jom.v12i2.7691 JOM 2011; 12(2): 153-159

Five-year (January 2004–December 2008) surveillance on animal bite and rabies vaccine utilization in the Infectious Disease Hospital, Dhaka, Bangladesh

The magnitude of animal bite and utilization of rabies vaccine was determined at the Infectious Disease Hospital, Dhaka, Bangladesh. From January 2004 to December 2008, 150,068 patients with animal bite visited the hospital, 86.2% and 13.8% of them received nerve tissue and tissue culture vaccine (TCV), respectively. Dog bite was most frequent, found in 90.7% cases. In 794 rabies cases only 24.4% had a history of post-exposure vaccination. Only a negligible number of patients received rabies immunoglobulin (RIG). To prevent further human deaths and economic losses intra-dermal TCV regime and equine RIG should be immediately introduced in Bangladesh.

Acute Demyelinating Encephalomyelitis Due to Neural Antirabies Vaccine

Rabies is highly endemic in India and seen with dog bites from rabid dogs. In India, nervous tissue vaccine is commonly used as it is inexpensive and freely available despite frequent neurological complications. Neurological complications seen with traditional vaccine are morbid and the medical community should switch over to the cell culture rabies vaccine in spite of the expense to prevent these complications with rabies vaccine.

Preventing rabies with the Verorab ® vaccine: 1985–2005 : Twenty years of clinical experience

Purified rabies vaccine cultured on Vero cells (Verorab, sanofi pasteur) is WHO-approved for pre- and post-exposure prophylaxis by intradermal and intramuscular routes. During 20 years of use, over 40 million doses of Verorab have been administered in more than 100 countries. No serious adverse event due to Verorab has been reported in clinical trials involving 3937 persons, and Verorab is better tolerated than human diploid cell vaccine (HDCV). Pre-exposure prophylaxis is confirmed immunogenic in 1437 subjects by all routes, with prompt responses following boosting; Verorab boosts effectively subjects pre-immunized with HDCV. Unlike HDCV, Verorab is not associated with post-boosting serum sickness. In the absence of data in immunodeficient/HIV-positive individuals, pre-exposure immunization is urged as early as possible. Essen, Zagreb, Thai Red Cross Intradermal (TRC-ID) and other post-exposure intramuscular and intradermal regimens are documented. Two thousand one hundred and eighty-three subjects received post-exposure prophylaxis, including 874 high risk, severe or confirmed rabid attacks. Co-administration of rabies immune globulin (RIG) does not affect neutralizing antibody levels when Essen or TRC-ID regimens are employed; levels are lower with the Zagreb regimen. Verorab has been administered safely and effectively post-exposure to 251 pregnant women, without any increase in congenital malformations or spontaneous abortions. From a pediatric perspective, safety and efficacy have been demonstrated in 759 children (0-15 years). Intradermal post-exposure Verorab is an effective and inexpensive option for developing countries. Inadvertent subcutaneous administration does not reduce immunogenicity. WHO already strongly recommends the replacement of nerve tissue vaccines with modern vaccines. Extensive clinical experience supports the use of Verorab for intramuscular and intradermal pre- and post-exposure prophylaxis, including in special situations.

Rabies control in South and Southeast Asia

We have the knowledge and tools to eliminate the threat of canine rabies but this disease, nevertheless, remains a public health threat in many parts of the world. Lack of motivation by governments, cultural issues and inadequate funding remain barriers. This is amazing since the number of human rabies deaths worldwide is greater than that from polio, meningococcal meningitis, Japanese encephalitis, yellow fever, SARS, bird flue and other scourges that attract more attention. Safe and effective vaccines are now widely available. Reduced dose effective and less expensive post-exposure vaccination regimens have helped eliminate nerve tissue vaccines in Thailand, Philippines and Sri Lanka. India and Pakistan, the major users of dangerous nerve tissue derived Semple type vaccine, are now considering following suite. Immediate wound care and prompt use of a potent vaccine will save a majority of infected persons. Rabies immunoglobulin, injected into and around bite wounds, provides added safety for the severely exposed. The high cost of rabies immunoglobulin and tissue culture vaccines are remaining barriers, but new manufacturers and the use of intradermal vaccination schedules can reduce costs. Ultimately, it is the need to control rabies in dogs that must occupy most of our attention. The tools are available, but attitudes must change before they can be applied. There have been many new developments since publication of the last WHO rabies expert committee report in 1992 [WHO Expert Committee on Rabies. Eighth Report. Tech Series 824. Geneva: World Health Organization; 1992 (new version in print)] and we will address those that have practical applicability.

Human rabies in India: epidemiological features, management and current methods of prevention.

In most endemic countries stray dogs are the main source of rabies infection in humans. In India 95-97% of rabies patients are infected by dogs. Most pet dogs do not regularly receive booster doses of vaccine. In Thailand, most rabies patients develop the disease within 1 month of exposure. Rabies immunoglobulin is costly and usually not available. So in India nervous tissue vaccine is commonly used--it is inexpensive and freely available despite frequent neurological complications. The cost of immunization by tissue culture vaccines may be reduced by nearly 60% by intradermal vaccination.

Viral encephalitis of public health significance in India: current status.

Japanese encephalitis (JE) and rabies are 2 viral encephalitis that are of public health importance in India. JE is a zoonosis with the primary cycle occurring in arthropods (mosquito vectors) and vertebrate animals (primarily the pig), man being only an incidental 'dead end' host. Out-breaks have been seen in most parts of India except the north west. The disease presents with a prodromal stage, an acute encephalitic stage with coma, convulsions and variable deficits and a convalescent stage. Diagnosis can be made by viral isolation from CSF or brain, or serologic tests such as haemagglutination inhibition test and IgM antibody capture ELISA in CSF and blood. There is no specific treatment. Mortality ranges from 20-50% and almost half the survivors have sequelae. The most effective control measure besides control of mosquitos is vaccination. A killed mouse brain vaccine is being prepared in India and is safe and effective but expensive. Rabies is a highly fatal encephalomyelitis primarily occurring in urban dogs and wild animals especially canines. It is endemic in India and affects an estimated 3 per 100,000 persons annually. The patient initially may display bizarre combative behaviour. The disease can be effectively prevented by post exposure vaccination. The nervous tissue vaccine is no longer recommended because of unacceptable neurotoxicity. Three cell culture vaccines are presently available with about equal efficacy.

Rabies

Rabies