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Antibody response of cattle to vaccination with commercial modified live rabies vaccines in Guatemala

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... In Latin America, due to attacks of bats, rabies is a significant problem, especially in cattle; many countries tend to vaccinate cattle but with an inadequate response from owners. In Guatemala, cattle vaccination coverage was estimated to be 11% [34]. In Latin America (e.g., Guatemala), vampire bat control activities (poisoning or culling) are used to control rabies in cattle, besides vaccination of cattle, although it is not widely used due to high cost [34]. ...
... In Guatemala, cattle vaccination coverage was estimated to be 11% [34]. In Latin America (e.g., Guatemala), vampire bat control activities (poisoning or culling) are used to control rabies in cattle, besides vaccination of cattle, although it is not widely used due to high cost [34]. In Morocco, free annual rabies vaccination campaigns for dogs are practiced; nevertheless, only around 6% vaccination coverage rate is achieved. ...
... In Euro-Asia and Europe, until 2001, cattle were the first rabies affected species in the Russian Federation, second in Belarus [35], the first one in Lithuania, the second one in Latvia, and the third after dogs and cats in Estonia [36]. In Guatemala, 154 cattle rabies due to vampire bat bites were reported (reviewed by [34]). In the United States, Canada, and Mexico, few cases were reported in cattle [53]. ...
Chapter
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Rabies is a lethal zoonotic encephalomyelitis and a major challenge to public and animal health. Livestock are affected by rabies mostly through bites of rapid dogs or wildlife carnivore\'s species. They are considered as ‘dead-end’ hosts that do not transmit the virus. Rabies in livestock has been endemic in many developing countries for many years and diagnosed through clinical signs and dog-biting history. An introduction on rabies situation in farm animals will be given then subchapters including `rabies in bovines, rabies in small ruminants, rabies in swine and rabies in camelids. In each subchapter we shall discuss, epidemiology, modes of transmission, diagnosis and prevention and control measures.
... RVNAs have been reported in apparently healthy and unvaccinated non-human primates, opossums and wild canids [10,[13][14][15][16] and following experimental infections of laboratory animals [17]. Abortive infections also occur in humans with routine contacts with rabies reservoirs [18][19][20][21] and in cattle bitten by vampire bats [22]. ...
... Sera were tested for RVNA using the rapid fluorescent focus inhibition test (RFFIT) [40]. All samples were screened for the presence of RABV using a 1:5 dilution of serum [22]. Samples with 100% neutralization of the virus at 1:5 were considered seropositive. ...
... We found that unvaccinated cattle, goats and sheep that are regularly bitten by vampire bats produce detectable levels of RVNAs and remained healthy for at least two years after sampling. RVNAs were previously reported in 12% of cattle that were bitten by vampire bats in two farms of Guatemala [22]. Our results confirm similar levels of seroprevalence (11% in cattle) in a larger geographic area in Peru. ...
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Rabies virus infections normally cause universally lethal encephalitis across mammals. However, ‘abortive infections’ which are resolved prior to the onset of lethal disease have been described in bats and a variety of non-reservoir species. Here, we surveyed rabies virus neutralizing antibody titers in 332 unvaccinated livestock of 5 species from a vampire bat rabies endemic region of southern Peru where livestock are the main food source for bats. We detected rabies virus neutralizing antibody titers in 11, 5 and 3.6% of cows, goats and sheep respectively and seropositive animals did not die from rabies within two years after sampling. Seroprevalence was correlated with the number of local livestock rabies mortalities reported one year prior but also one year after sample collection. This suggests that serological status of livestock can indicate the past and future levels of rabies risk to non-reservoir hosts. To our knowledge, this is the first report of anti-rabies antibodies among goats and sheep, suggesting widespread abortive infections among livestock in vampire bat rabies endemic areas. Future research should resolve the within-host biology underlying clearance of rabies infections. Cost-effectiveness analyses are also needed to evaluate whether serological monitoring of livestock can be a viable complement to current monitoring of vampire bat rabies risk based on animal mortalities alone.
... The number of bovine rabies outbreaks reported here correspond with a Brazilian study which showed that vampire attacks occurred more frequently in areas of forest fragments close to cattle grazing areas (Gomes et al. 2010). Furthermore, a study in Guatemala reported that vampire bats are highly territorial with respect to feeding grounds and likely to visit the same cattle pastures, and even the same animals, frequently (Gilbert et al. 2015). ...
... In the past, such data collection was difficult and labor intensive, however, new surveillance software should help remedy this situation. Reports have been made of problems with cold storage and transportation of samples throughout Latin America (Gilbert et al. 2015), and it is likely that such issues also occurred during the early years of rabies surveillance covered here. In addition, it would be ideal to confirm all suspected rabies cases in individual animals by laboratory analysis and perform a phylogenetic sequence analysis for each outbreak. ...
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This is the first comprehensive epidemiological analysis of rabies in Costa Rica. We characterized the occurrence of the disease and demonstrated its endemic nature in this country. In Costa Rica, as in other countries in Latin America, hematophagous vampire bats are the primary wildlife vectors transmitting the rabies virus to cattle herds. Between 1985 and 2014, a total of 78 outbreaks of bovine rabies was reported in Costa Rica, with documented cases of 723 dead cattle. Of cattle outbreaks, 82% occurred between 0 and 500 meters above sea level, and seasonality could be demonstrated on the Pacific side of the country, with significantly more outbreaks occurring during the wet season. A total of 1588 animal samples, or an average of 55 samples per year, was received by the veterinary authority (SENASA) for rabies diagnostic testing at this time. Of all samples tested, 9% (143/1588) were positive. Of these, 85.6% (125/1588) were from cattle; four dogs (0.3% [4/1588]) were diagnosed with rabies in this 30-year period. Simultaneously, an extremely low number (n = 3) of autochthonous rabies cases were reported among human patients, all of which were fatal. However, given the virus' zoonotic characteristics and predominantly fatal outcome among both cattle and humans, it is extremely important for healthcare practitioners and veterinarians to be aware of the importance of adequate wound hygiene and postexpositional rabies prophylaxis when dealing with both wild and domestic animal bites.
... Successful pre-exposure vaccination of cattle against rabies using inactivated commercial rabies vaccines is well documented (Carneiro et al., 1955;Blancou et al., 1984;Silvonen et al., 1994;Benisek et al., 2000;Anderson et al., 2014;Gilbert et al., 2015). Rabies cases reported in vaccinated cattle are most often related to product use variables including wide-ranging immunization protocols and booster recommendations (Rodrigues da Silva et al., 2000;Albas et al., 1998;Filho et al., 2012). ...
... This study supports previously published reports that cattle respond well to commercially available rabies vaccines and are capable of producing long lasting serum antibody levels indicative of protection after at least two vaccinations (Carneiro et al., 1955;Blancou et al., 1984;Silvonen et al., 1994;Benisek et al., 2000;Anderson et al., 2014;Gilbert et al., 2015). Further, these results support current recommendations for use of Rabisin in cattle under a protocol that calves receive their first vaccination when they are older than 4 months but less than 9 months. ...
... Rabies is one of the oldest worldwide infectious diseases with highest mortality rate of all known diseases which cause roughly 59,000 deaths every year according to the World Health Organization [1][2][3]. This fatal disease is caused by the rabies virus (RABV), a non-segmented negative-strand RNA virus from the Rhabdoviridae family, Mononegavirales order, Lyssavirus genus, is responsible for this lethal illness [4][5][6]. ...
Article
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Vaccination is the most feasible way of preventing rabies, an ancient zoonosis that remains a major public health concern globally. However, administration of inactivated rabies vaccination without adjuvants is always inefficient and necessitates four to five injections. In the current study, we explored the adjuvant characteristics of cordycepin, a major bioactive component of Cordyceps militaris, to boost immune responses against a commercially available rabies vaccine. We found that cordycepin could stimulate stronger phenotypic and functional maturation of dendritic cells (DCs). For animal experiments, mice were immunized 3 times with rabies vaccine in the presence or absence of cordycepin at 1-week interval. Analysis of T cell differentiation and serum antibody isotypes showed that humoral immunity was dominant with a Th2 biased immune response. These results were also supported by the raised ratio of follicular helper T cells (TFH) and germinal center B cells (GCB). Thus, titer of rabies virus neutralizing antibody (RVNAb) and rabies virus-specific memory B cells were both raised as a result. Furthermore, administration of cordycepin did not cause pathological phenomena or body weight loss. The findings indicate that cordycepin could be used as a promising adjuvant for rabies vaccines to get a higher range of protection without any side effects.
... For cattle in rabies-endemic areas, such as Nigeria, pre-exposure prophylaxis against rabies is recommended (OIE, 2014). Cattle respond well to available rabies vaccines, producing long-lasting serum antibody levels indicative of protection after at least two vaccinations, with a priming dose given at or after six months of age and a subsequent booster given as late as three years after the initial one (Anderson et al., 2014;Gilbert et al., 2015;Yakobson et al., 2015). Furthermore, health promotion for preventing dog bites, dog vaccination, and human post-exposure prophylaxis is regarded as foundations of robust rabies control programmes worldwide (Okeme et al., 2020). ...
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This paper describes a case of rabies outbreak in a bull-calf which led to euthanasia following manifestation of clinical signs of the disease. Infection was confirmed using a rapid immunochromatographic test of the homogenates from brain tissues (the brain stem, hippocampus and cerebellum) sample. Exposure to rabies virus (RABV) had resulted due to an attack by a free-roaming dog (FRD). Mass vaccination campaigns against rabies and improving biosecurity measures to limit access of free-roaming dogs to farms can prevent the occurrence of RABV in dogs, livestock animals and personnel at risk in Nigeria.
... Also, in certain countries, physicians in areas with demonstrated rabies circulation in cattle [58], do not consider the importance of cycles where also canids are present, increasing the risk for humans (e.g. Colombia, Guatemala and Panama) [38,39]. ...
... A further challenge to the interpretation of rabies serology is that it is currently unknown whether antibodies from natural exposure confer protection to re-exposure [16]. There is limited evidence that previously unvaccinated seropositive individuals show an anamnestic response to vaccination consistent with immunity [15,23,38,55]. However, even in vaccinated individuals, serology status is not definitive proof of an effective immune response, and individuals with a detectable titre may still succumb to the disease [56]. ...
Article
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A number of mathematical models have been developed for canine rabies to explore dynamics and inform control strategies. A common assumption of these models is that naturally acquired immunity plays no role in rabies dynamics. However, empirical studies have detected rabies-specific antibodies in healthy, unvaccinated domestic dogs, potentially due to immunizing, non-lethal exposure. We developed a stochastic model for canine rabies, parameterised for Laikipia County, Kenya, to explore the implications of different scenarios for naturally acquired immunity to rabies in domestic dogs. Simulating these scenarios using a non-spatial model indicated that low levels of immunity can act to limit rabies incidence and prevent depletion of the domestic dog population, increasing the probability of disease persistence. However, incorporating spatial structure and human response to high rabies incidence allowed the virus to persist in the absence of immunity. While low levels of immunity therefore had limited influence under a more realistic approximation of rabies dynamics, high rates of exposure leading to immunizing non-lethal exposure were required to produce population-level seroprevalences comparable with those reported in empirical studies. False positives and/or spatial variation may contribute to high empirical seroprevalences. However, if high seroprevalences are related to high exposure rates, these findings support the need for high vaccination coverage to effectively control this disease.
... Bahloul and colleagues also found that dogs in field conditions showed higher antibody titres postvaccination than those kept under experimental conditions, potentially due to previous subclinical infection [30]. In cattle, Gilbert and colleagues also found that prevaccination RVNA was marginally associated with a stronger postvaccination response [104]. By contrast, a study of dogs in Thailand found no evidence of an anamnestic response, with seropositive results detected by an RFFIT suggested to be false positives [105]. ...
Article
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Rabies has been a widely feared disease for thousands of years, with records of rabid dogs as early as ancient Egyptian and Mesopotamian texts. The reputation of rabies as being inevitably fatal, together with its ability to affect all mammalian species, contributes to the fear surrounding this disease. However, the widely held view that exposure to the rabies virus is always fatal has been repeatedly challenged. Although survival following clinical infection in humans has only been recorded on a handful of occasions, a number of studies have reported detection of rabies-specific antibodies in the sera of humans, domestic animals, and wildlife that are apparently healthy and unvaccinated. These ‘seropositive’ individuals provide possible evidence of exposure to the rabies virus that has not led to fatal disease. However, the variability in methods of detecting these antibodies and the difficulties of interpreting serology tests have contributed to an unclear picture of their importance. In this review, we consider the evidence for rabies-specific antibodies in healthy, unvaccinated individuals as indicators of nonlethal rabies exposure and the potential implications of this for rabies epidemiology. Our findings indicate that whilst there is substantial evidence that nonlethal rabies exposure does occur, serology studies that do not use appropriate controls and cutoffs are unlikely to provide an accurate estimate of the true prevalence of nonlethal rabies exposure.
... A high frequency of abortive infection is clearly seen in the presence of antibodies in healthy bats [67][68][69] , spanning many species and geographic areas 52 . VNAs in non-bats are less well established but have been detected at varying levels in diverse reservoir and non-reservoir species, including human, cow and mongoose 45,[70][71][72] . These findings highlight major unanswered questions. ...
Article
Rabies is a lethal zoonotic disease that is caused by lyssaviruses, most often rabies virus. Despite control efforts, sporadic outbreaks in wildlife populations are largely unpredictable, underscoring our incomplete knowledge of what governs viral transmission and spread in reservoir hosts. Furthermore, the evolutionary history of rabies virus and related lyssaviruses remains largely unclear. Robust surveillance efforts combined with diagnostics and disease modelling are now providing insights into the epidemiology and evolution of rabies virus. The immune status of the host, the nature of exposure and strain differences all clearly influence infection and transmission dynamics. In this Review, we focus on rabies virus infections in the wildlife and synthesize current knowledge in the rapidly advancing fields of rabies virus epidemiology and evolution, and advocate for multidisciplinary approaches to advance our understanding of this disease.
... An example of the latter scenario was the single vaccinated case in 2012, in which the vaccine was administered less than one month prior to the development of clinical signs. In this case, the immune response would not have had sufficient time to produce adequate antibodies to combat natural infection considering the peak rabies viral neutralizing antibody response is typically 28 days post vaccination [58]. Vaccine efficacy may also be affected if vaccination regimes differ from the manufacturers' recommendations due to factors such as the interference of the immune response by maternal antibodies. ...
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Vampire bat-transmitted rabies was first recognized in Trinidad during a major outbreak reported in 1925. Trinidad is the only Caribbean island with vampire bat-transmitted rabies. We conducted a literature review to describe the changing epidemiology of rabies in Trinidad and give a historical perspective to rabies prevention and control measures on the island. The last human case of rabies occurred in 1937 and although no case of canine-transmitted rabies was reported since 1914, sporadic outbreaks of bat-transmitted rabies still occur in livestock to date. Over the last century, seven notable epidemics were recorded in Trinidad with the loss of over 3000 animals. During the 1950s, several measures were effectively adopted for the prevention and control of the disease which led to a significant reduction in the number of cases. These measures include: vampire bat population control, livestock vaccination, and animal surveillance. However, due to lapses in these measures over the years (e.g., periods of limited vampire control and incomplete herd vaccination), epidemics have occurred. In light of the significant negative impact of rabies on animal production and human health, rabies surveillance in Trinidad should be enhanced and cases evaluated towards the design and implementation of more evidence-based prevention and control programs.
Chapter
Rabies is a neglected viral zoonosis, with a substantial agricultural and public health burden. The most important and widely distributed member is the type species, rabies virus. Modern potent rabies virus vaccines should protect against all phylogroup I lyssaviruses throughout the world, including rabies virus. Most inactivated vaccines have contained adjuvants. During replication, viral products induce upregulation of host cellular processes to evade primary immune responses, which increases success for productive generation of viral progeny. Rabies vaccines for veterinary use are unique in a One Health context, considering that their use in domestic animals and wildlife provides an important public health benefit by creating a barrier between rabies virus reservoirs and human populations. Applications of rabies vaccination to livestock will vary, dependent in part upon life history stage, immunological status, and exposure circumstances. The most serious adverse events are vaccine‐associated rabies and vaccine failure.
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The emergence of epidemics does not respond to random factors, but due to conditions of inequality, poverty and underdevelopment. The accumulation of variables that contribute the appearance of a large number of sick individuals, as well as the limited possibility of accessing treatments, respond to economic and technological factors, which determine the health status of the communities and their capacity to develop. Humanity as a species has been able to modify its environment to meet its requirements, and has formulated tools to deal epidemics throughout history, but there are still populations at risk by their socioeconomic status and poor access to appropriate hygienic-sanitary conditions, therefore, vulnerability analysis of societies to different epidemics must be carried out from the socioeconomic point of view.
Chapter
Rabies is a significant neglected vaccine-preventable disease that is global in distribution. Multiple biologics are utilized in routine prevention and control of this zoonosis. Currently, rabies vaccines are used to interrupt a productive viral encephalitis before or after pathogen exposure in humans and animals. In addition, rabies immune globulins are used as part of prophylaxis after human exposure to a known or suspect animal. Such rabid animals are diagnosed based upon antigenic detection in the brain by selective antibody conjugates. Although experimental proof of concept has been demonstrated in a variety of systems, to date no plant-produced biologics have been licensed for such applications in rabies surveillance, prevention or control. In addition, given the breadth of the host spectrum, there are multiple domestic and wild mammalian species that lack specific vaccines and the cross reactivity of existing products is limited by considerable viral diversity. Hence, if safe, effective and inexpensive biologics may be produced in plants, especially for oral delivery, there is a considerable global niche to fill within the realms of public health, veterinary medicine and conservation biology.
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A panel of 8 monoclonal antibodies to rabies glycoprotein antigen was used to characterize the modified-live virus vaccines marketed in the United States during the last 10 years. Thirteen of 14 rabies virus isolates from 11 dogs, 2 cats, and 1 fox suspected of developing vaccine-induced rabies were shown to have reactivity patterns that were identical to the vaccine administered. Reactivity patterns for 20 rabies isolates from human beings, wild animals, or domestic animals with no history of recent vaccination with modified-live virus rabies vaccine were different from those obtained for vaccines.
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Soluble glycoprotein (Gs), purified from virion-depleted, rabies-infected tissue culture fluid, was chemically and immunologically analyzed. A comparison of this antigen with the virion-associated glycoprotein showed that Gs lacks 58 amino acid residues from the carboxy terminus of the virion-associated glycoprotein. Analysis with monoclonal antibodies revealed that all the epitopes of the viral glycoprotein are also present in the soluble glycoprotein. However, when tested for its ability to protect mice against a lethal challenge infection with rabies virus, Gs in contrast to viral glycoprotein, showed no protective activity. These results suggest that the carboxy terminus of the rabies virus glycoprotein is necessary for its full protective activity even though this portion of the glycoprotein molecule does not contain any antigenic determinants.
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In a comparative study of two commercial baby hamster kidney rabies vaccines produced in Brazil, the authors were able to demonstrate the following: a) both vaccines provoked a high level of antibody response and protection against challenge in cattle b) in primary vaccination, at least, the addition of avridine (a synthetic lipoidal amine) enhances the immune response in terms of the level and persistence of antibody c) over 90% of cattle vaccinated with either vaccine were protected against experimental challenge one year after revaccination, and the antibody response profile indicated that these vaccines were capable of maintaining antibody titres above protective levels for more than two years after revaccination. On the basis of these results, the authors recommend optional revaccination of young animals (i.e. "primo-vaccinates") at six months of age. Thereafter, annual revaccination should be sufficient to ensure high levels of antibody between vaccination cycles.
Vampire bat and bovine paralytic rabies
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Baer, G.M., 1991. Vampire bat and bovine paralytic rabies. In: Baer, G.M. (Ed.), The Natural History of Rabies. CRC Press, Inc, Boca Raton, FL, pp. 389-403.
Bat rabies in guatemala Biology and control of the vam-pire bat The Natural History of Rabes
  • J A Ellison
  • A T Gilbert
  • S Recuenco
  • D Moran
  • D A Alvarez
  • N Kuzmina
  • D L Garcia
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