Immunogenicity and efficacy of non-adjuvant tissue culture-based rabies vaccine produced in Ethiopia

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 100yrs. These vaccines have now been superseded in purity, potency, immunogenicity and safety. The efficacy and immunogenicity of inactivated tissue culture rabies 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 90 days. On the day 90 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 and 90. Geometric mean titers were equal to 1.59, 1.73, 2.19, 3.58, 3.17 and 3.35 IU/ml respectively. All dogs showed VNA titers higher than the 0.5 IU/ml mandated WHO recommended threshold. All vaccinated dogs, survived the challenge. In contrast, 83.3% of dogs in the control (non-vaccinated group), developed rabies and died. This study indicated that cell culture-based anti-rabies developed inhouse, with no adjuvant is efficacious and immunogenic

Novel Vaccines to Human Rabies

Rabies, the most fatal of all infectious diseases, remains a major public health problem in developing countries, claiming the lives of an estimated 55,000 people each year. Most fatal rabies cases, with more than half of them in children, result from dog bites and occur among low-income families in Southeast Asia and Africa. Safe and efficacious vaccines are available to prevent rabies. However, they have to be given repeatedly, three times for pre-exposure vaccination and four to five times for post-exposure prophylaxis (PEP). In cases of severe exposure, a regimen of vaccine combined with a rabies immunoglobulin (RIG) preparation is required. The high incidence of fatal rabies is linked to a lack of knowledge on the appropriate treatment of bite wounds, lack of access to costly PEP, and failure to follow up with repeat immunizations. New, more immunogenic but less costly rabies virus vaccines are needed to reduce the toll of rabies on human lives. A preventative vaccine used for the immunization of children, especially those in high incidence countries, would be expected to lower fatality rates. Such a vaccine would have to be inexpensive, safe, and provide sustained protection, preferably after a single dose. Novel regimens are also needed for PEP to reduce the need for the already scarce and costly RIG and to reduce the number of vaccine doses to one or two. In this review, the pipeline of new rabies vaccines that are in pre-clinical testing is provided and an opinion on those that might be best suited as potential replacements for the currently used vaccines is offered

Tobramycin: efficacy of intensive therapy

One of the leading cause of the decrease of treatment efficacy in patient with community-acquired infections in the intensive care department is a spread of antibiotic resistance in main causative agents. Among Gram-negative microorganisms Pseudomonas aeruginosa is one of the leading causative agents, that is related to health service. A review of foreign and domestic literature concerning tobramycin – systemic form use in the current medical practice in the conditions of increasing resistance of microorganisms to the most broad-spectrum antibiotics is presented in the article. Pharmacokinetic and pharmacodynamic characteristics of tobramycin are described, results of clinical trials, that demonstrate an efficacy of its use in the combination with other antibiotics in the life-threatening infections caused by Gram-negative microorganisms are presented in the article.</jats:p

Тобрамицин: эффективность использования в интенсивной терапии

One of the leading cause of the decrease of treatment efficacy in patient with community-acquired infections in the intensive care department is a spread of antibiotic resistance in main causative agents. Among Gram-negative microorganisms Pseudomonas aeruginosa is one of the leading causative agents, that is related to health service. A review of foreign and domestic literature concerning tobramycin – systemic form use in the current medical practice in the conditions of increasing resistance of microorganisms to the most broad-spectrum antibiotics is presented in the article. Pharmacokinetic and pharmacodynamic characteristics of tobramycin are described, results of clinical trials, that demonstrate an efficacy of its use in the combination with other antibiotics in the life-threatening infections caused by Gram-negative microorganisms are presented in the article.Однією з провідних причин зниження ефективності лікування хворих з нозокоміальними інфекціями у відділеннях інтенсивної терапії є поширення резистентності провідних збудників до антибіотикотерапії. Серед грамнегативних мікроорганізмів Pseudomonas aeruginosa є однією з домінуючих збудників інфекцій, пов’язаних з наданням медичної допомоги. У статті наведено огляд зарубіжної та вітчизняної літератури використання тобраміцину – системної форми в сучасній клінічній практиці в умовах зростаючої резистентності мікроорганізмів до більшості антибіотиків широкого спектра дії. Описано фармакокінетичні та фармакодинамічні характеристики тобраміцину, а також наведено результати якісних клінічних досліджень, що демонструють ефективність його використання в комбінації з іншими антибіотиками при загрозливих інфекціях, викликаних грамнегативними мікроорганізмами.Одной из основных причин снижения эффективности лечения больных с нозокомиальными инфекциями в отделении интенсивной терапии является распространение резистентности к антибиотикотерапии у основных возбудителей. Среди грамотрицательных организмов Pseudomonas aeruginosa является одним из доминирующих возбудителей инфекции, связанных с предоставлением медицинской помощи. В статье приведен обзор зарубежной и отечественной литературы касательно использования тобрамицина – системной формы в современной клинической практике в условиях нарастающей резистентности микроорганизмов к большинству антибиотиков широкого спектра действия. Описаны фармакокинетические и фармакодинамические характеристики тобрамицина, а также приведены результаты качественных клинических исследований, которые демонстрируют эффективность его использования в комбинации с другими антибиотиками при угрожающих инфекциях, вызванных грамотрицательными микроорганизмам

Spatio-temporal Use of Oral Rabies Vaccines in Fox Rabies Elimination Programmes in Europe

In Europe, the elimination of wildlife rabies using oral rabies vaccination [ORV] of foxes for more than 30 years has been a success story. Since a comprehensive review on the scope of the different oral rabies vaccine baits distributed across Europe has not been available yet, we evaluated the use of different vaccine baits over the entire period of ORV [1978-2014]. Our findings provide valuable insights into the complexity of ORV programs in terms of vaccine related issues. More than 10 oral vaccines against rabies were used over the past four decades. Depending on many factors, the extent to which oral rabies virus vaccines were used varied considerably resulting in huge differences in the number of vaccine doses disseminated in ORV campaigns as well as in large spatial and temporal overlaps. Although vaccine virus strains derived from the SAD rabies virus isolate were the most widely used, the success of ORV campaigns in Europe cannot be assigned to a single oral rabies virus vaccine alone. Rather, the successful elimination of fox rabies is the result of an interaction of different key components of ORV campaigns, i.e. vaccine strain, vaccine bait and strategy of distribution

Rabies Vaccines for Wildlife

Since the first proof of principle experimental study in the 1970s, oral rabies vaccines have gained a great reputation in controlling and eliminating rabies in wildlife. Starting with classically attenuated virus vaccines derived from only a few virulent rabies virus field isolates, oral rabies vaccination (ORV) for the first time has offered new opportunities and opened new avenues worldwide in fighting this fatal zoonosis in particular in its canine wildlife reservoir hosts. Beyond classical approaches, biotechnological tools have been increasingly used to generate new oral rabies vaccines with the aim to improve safety, immunogenicity, and efficacy in the various canine wildlife reservoir species. While heterologous vector systems have been developed for expression of the immune-dominant glycoprotein (G) of rabies virus (RABV), recent advancements in recombinant DNA technology and virus reverse genetics helped facilitating vaccine development through targeted modifications and directed attenuation of rabies virus constructs. Unlike in humans, pets, and livestock, there is no alternative way yet to efficiently vaccinate canine wildlife reservoir hosts at a population level other than using modified live virus vaccines. In contrast to any other vaccines for veterinary use, next to safe and efficacious vaccine constructs, attractive species-specific baits, as well as a well-defined distribution system/strategy, are indispensable components of any oral rabies vaccine for wildlife. As baits play a decisive role for successful application in the field they are an integral part of the licensing procedure. This chapter summarizes the state-of-the-art information on oral rabies virus vaccines for wildlife and provides an outlook on the challenges of vaccine development for wildlife for the future