Showing papers by "Charles E. Rupprecht published in 2018"

Oral vaccination of dogs: a well-studied and undervalued tool for achieving human and dog rabies elimination.

Abstract: The mass vaccination of dogs is a proven tool for rabies prevention. Besides parenteral delivery of inactivated vaccines, over the past several decades, several self-replicating biologics, including modified-live, attenuated and recombinant viruses, have been evaluated for the oral vaccination of dogs against rabies. Vaccines are included within an attractive bait for oral consumption by free-ranging dogs. Due to the high affinity between dogs and humans, such biologics intended for oral vaccination of dogs (OVD) need to be efficacious as well as safe. Baits should be preferentially attractive to dogs and not to non-target species. Although many different types have been evaluated successfully, no universal bait has been identified to date. Moreover, high bait acceptance does not necessarily mean that vaccine efficacy and programmatic success is predictable. The use of OVD in the laboratory and field has demonstrated the safety and utility of this technology. Within a One Health context, OVD should be considered as part of a holistic plan for the global elimination of canine rabies.

Rabies in the Caribbean: A Situational Analysis and Historic Review

Abstract: Rabies virus is the only Lyssavirus species found in the Americas. In discussions about rabies, Latin America and the Caribbean are often grouped together. Our study aimed to independently analyse the rabies situation in the Caribbean and examine changes in rabies spatiotemporal epidemiology. A questionnaire was administered to the 33 member countries and territories of the Caribbean Animal Health Network (CaribVET) to collect current data, which was collated with a literature review. Rabies was endemic in ten Caribbean localities, with the dog, mongoose, and vampire bat identified as enzootic reservoirs. The majority of animal cases occurred in Puerto Rico, the Dominican Republic, and Haiti, while human cases only consistently occurred in the latter two areas. Rabies vaccination was conducted for high-risk animal populations with variable coverage, and rabies diagnostic capacities varied widely throughout the region. Illegal importation and natural migration of animals may facilitate the introduction of rabies virus variants into virus-naive areas. Passive surveillance, together with enhanced methods and serological screening techniques, can therefore be of value. The insularity of the Caribbean makes it ideal for conducting pilot studies on reservoir host population management. Best practice guidelines developed for these reservoir hosts can be individually modified to the epidemiological status and available resources within each locality.

Cost-effectiveness of dog rabies vaccination programs in East Africa.

Abstract: Background Dog rabies annually causes 24,000–70,000 deaths globally. We built a spreadsheet tool, RabiesEcon, to aid public health officials to estimate the cost-effectiveness of dog rabies vaccination programs in East Africa. Methods RabiesEcon uses a mathematical model of dog-dog and dog-human rabies transmission to estimate dog rabies cases averted, the cost per human rabies death averted and cost per year of life gained (YLG) due to dog vaccination programs (US 2015 dollars). We used an East African human population of 1 million (approximately 2/3 living in urban setting, 1/3 rural). We considered, using data from the literature, three vaccination options; no vaccination, annual vaccination of 50% of dogs and 20% of dogs vaccinated semi-annually. We assessed 2 transmission scenarios: low (1.2 dogs infected per infectious dog) and high (1.7 dogs infected). We also examined the impact of annually vaccinating 70% of all dogs (World Health Organization recommendation for dog rabies elimination). Results Without dog vaccination, over 10 years there would a total of be approximately 44,000–65,000 rabid dogs and 2,100–2,900 human deaths. Annually vaccinating 50% of dogs results in 10-year reductions of 97% and 75% in rabid dogs (low and high transmissions scenarios, respectively), approximately 2,000–1,600 human deaths averted, and an undiscounted cost-effectiveness of $451-$385 per life saved. Semi-annual vaccination of 20% of dogs results in in 10-year reductions of 94% and 78% in rabid dogs, and approximately 2,000–1,900 human deaths averted, and cost $404-$305 per life saved. In the low transmission scenario, vaccinating either 50% or 70% of dogs eliminated dog rabies. Results were most sensitive to dog birth rate and the initial rate of dog-to-dog transmission (Ro). Conclusions Dog rabies vaccination programs can control, and potentially eliminate, dog rabies. The frequency and coverage of vaccination programs, along with the level of dog rabies transmission, can affect the cost-effectiveness of such programs. RabiesEcon can aid both the planning and assessment of dog rabies vaccination programs.

A Perspective on Rabies in the Middle East-Beyond Neglect.

Abstract: Rabies is a neglected but preventable viral zoonosis that poses a substantial threat to public health. In this regard, a global program has been initiated for the elimination of human rabies caused by rabid dogs through the mass vaccination of canine populations. Geographic areas vary greatly towards attainment of this objective. For example, while dog-mediated and wildlife rabies have been largely controlled in major parts of the Americas and Western Europe, the Middle East still grapples with human rabies transmitted by unvaccinated dogs and cats. Rabies prevention and control in the Middle East is quite difficult because the region is transcontinental, encompassing portions of Africa, Asia, and Europe, while consisting of politically, culturally, and economically diverse countries that are often subject to war and unrest. Consequently, one over-riding dilemma is the misinformation or complete lack of rabies surveillance data from this area. This communication is an attempt to provide an overview of rabies in the Middle East, as a cohesive approach for the honing of disease management in each area, based on data compiled from multiple sources. In addition, the related regional transboundary movement of rabies was investigated through phylogenetic studies of available viral gene sequences. Thereafter, the epidemiological status of rabies was assessed for the region. Finally, localities were classified first by the Stepwise Approach towards Rabies Elimination framework and then categorized into four different groups based on management theme: “rabies free”; owned dog and domestic animal vaccination; community dog vaccination; and wildlife vaccination. The classification system proposed herein may serve as a baseline for future efforts. This is especially important due to the severe lack of rabies information available for the Middle East as a whole and a need for a comprehensive program focusing on the entirety of the region in light of renewed international commitment towards canine rabies elimination.

Field trials of ontario rabies vaccine bait in the northeastern usa, 2012–14

Abstract: In the US, rabies virus (RV) has been enzootic in raccoons (Procyon lotor) since the late 1940s. Oral rabies vaccination (ORV) was implemented in the 1990s to halt the spread of raccoon RV and continues to be used as a wildlife management tool. Our objective was to evaluate a recombinant human adenovirus–rabies virus glycoprotein vaccine in northern New York, Vermont, and New Hampshire over a 3-yr period, using changes in RV neutralizing antibody (RVNA) seroprevalence in raccoon populations as an immunologic index of ORV impact. Vaccine baits were distributed at 75 baits/km2 and 750-m flight-line spacing in the study area. Animal sampling occurred during 10-d intervals pre- and post-ORV during 2012–14 within eight study cells: four northern cells had a history of ORV with a different vaccine for 3 or more years prior and four southern cells were ORV naive. Baseline raccoon RVNA seroprevalence was 27.3% (n=1,079, 95% confidence interval [CI]: 24.8–30.1) before ORV in 2012. Raccoon RVNA seroprevale...

Additional Progress in the Development and Application of a Direct, Rapid Immunohistochemical Test for Rabies Diagnosis.

Abstract: Laboratory-based surveillance is fundamental to effective rabies prevention and control. The direct fluorescent antibody (AB) test (FAT) is the gold standard for rabies diagnosis. Recently, additional tests besides the FAT have been developed, such as the direct rapid immunohistochemical test (DRIT). In this study, our objective was to further refine technical aspects of the DRIT using a combination of two monoclonal ABs (MABs), 502 and 802, conduct additional testing among rabies reference laboratories using a diversity of animal species and rabies virus (RV) variants and compare the potential utility of the DRIT for end users via proficiency testing (PT) against the FAT. Considering the ideal molar ratios of biotin to AB in formulation of the DRIT conjugate, 3.9 was found to be superior to 7.4, for detection of RV antigens in the brain of a naturally infected raccoon. Optimization of the DRIT conjugate may also be dependent upon the apparent choice of specific viral antigens for testing, as a gray fox RV variant reacted less strongly than a raccoon RV variant in determining the working dilution of the MAB cocktail. Using the same MABs and protocol, the DRIT was compared to the FAT using more than 800 samples of mammalian brains, representative of more than 25 taxa, including in excess of 250 animal rabies cases from Europe and North America. Sensitivity was determined at 98% (96⁻100%, 95% CI) and specificity was calculated at 95% (92⁻96%, 95% CI). In a comparison among end users, PT of laboratory personnel resulted in values of 77⁻100% sensitivity and 86-100% specificity. Based upon these and previously reported results, the DRIT appears to be a suitable alternative to the FAT for use in lyssavirus diagnosis.

Historical, current and expected future occurrence of rabies in enzootic regions.

Abstract: Rabies is one of the oldest recorded pathogens, with the broadest distribution of any known viral zoonosis. Antarctica is believed to be free of all lyssaviruses, but no laboratory-based surveillance has taken place to support this supposition. Re-introduction of the disease is possible in Pacific Oceania, as evidenced by a historical outbreak in Guam and the translocation of rabid bats to Hawaii. Australia is the only inhabited continent with enzootic rabies, without the presence of rabies virus. Europe and North America have broken the cycle of dog-mediated rabies, with a few remaining focal points in Latin America and the Caribbean, but wildlife rabies predominates. The greatest burden resides in the 'Old World'. The elimination of human rabies mediated via dogs by 2030 in Africa, Asia and the Middle East will not be simple, rapid or inexpensive, but it may be achievable through the use of widely available tools and the application of lessons learned during the course of the 20th century.

Correction to: Oral vaccination of dogs: a well-studied and undervalued tool for achieving human and dog rabies elimination.

Abstract: The original article [1] contained an error in the Author details paragraph. “5Neglected Zoonotic Diseases, World Health Organization, Geneva, Switzerland” should be replaced by “5Le Grand-Saconnex, Switzerland”.

Rabies and Related Lyssaviruses

Abstract: 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.

Detection of rabies virus in organs unrelated to the central nervous system of experimentally-inoculated vampire bats

Abstract: The aim of this research was to detect rabies virus in peripheral tissues in captive vampires. Vampire bats were inoculated with 106 MICLD50 of homologous rabies virus. Bats displayed clinical signs of rabies beginning on d 8 until the 19th d post-inoculation (pi). Rabies virus antigens were found in the brain of all rabid bats. Viral RNA was detected in brain, salivary gland and tongue tissue by RT-PCR and nested PCR (nPCR). Viral genome was also detected in organs unrelated to the central nervous system. Rabies virus was not detected in saliva nor documented from any tissues without occurrence of viral antigens in the brain. Host humoral response was most pronounced via the induction of viral neutralizing antibodies (VNA) from d 8 to 20 pi, having a peak at d 14 with 0.9 IU. Antibody levels were variable, but tended to remain high after inoculation, showing significant differences to the negative control group (P=0.001). This research is one of the few recent studies focused upon Desmodus rotundus and contributes to the basic knowledge of rabies virus pathogenesis, which is required for an understanding of perpetuation in a major viral reservoir in Latin America.

Meeting the urgent need for rabies education in Haiti.

Abstract: The highest rate of human rabies deaths reported in the Americas is in Haiti, and most of these deaths result from rabies virus infections that occur after individuals are bitten by infected dogs and do not receive rabies post-exposure prophylaxis. One barrier to rabies prevention in Haiti is a lack of knowledge about this disease among healthcare professionals and community members. During the past 4 years, The US Centers for Disease Control and Prevention has collaborated with public health officials and partners to develop, test and refine educational materials aimed at filling this need for rabies education. This report summarizes the use of feedback from knowledge, attitudes and practises surveys; key informant interviews; and focus groups to develop culturally appropriate rabies prevention materials for community members, health officials, clinicians, laboratory professionals, veterinary professionals, government officials and national and local district leaders about ways to prevent rabies. These formative research methods were critically important in ensuring that the materials would be culturally appropriate and would stand the greatest likelihood of motivating Haitians to protect themselves from rabies. Centers for Disease Control and Prevention is using lessons learned in Haiti to develop and test materials in other countries with high rates of canine rabies.

Erratum: Rupprecht, C.E., et al. Additional Progress in the Development and Application of a Direct, Rapid Immunohistochemical Test for Rabies Diagnosis. Vet. Sci. 2018, 5, 59.

Abstract: Due to an error during production, the order in which Figure 1 and Figure 2 appear and the linking of the Figure 1 and Figure 2 captions in the Results section of the published paper [1] were incorrect A corrected version of the Figure order and associated captions is provided below[]