Jesse D. Blanton

Estimating the global burden of endemic canine rabies.

Background Rabies is a notoriously underreported and neglected disease of low-income countries. This study aims to estimate the public health and economic burden of rabies circulating in domestic dog populations, globally and on a country-by-country basis, allowing an objective assessment of how much this preventable disease costs endemic countries. Methodology/Principal Findings We established relationships between rabies mortality and rabies prevention and control measures, which we incorporated into a model framework. We used data derived from extensive literature searches and questionnaires on disease incidence, control interventions and preventative measures within this framework to estimate the disease burden. The burden of rabies impacts on public health sector budgets, local communities and livestock economies, with the highest risk of rabies in the poorest regions of the world. This study estimates that globally canine rabies causes approximately 59,000 (95% Confidence Intervals: 25-159,000) human deaths, over 3.7 million (95% CIs: 1.6-10.4 million) disability-adjusted life years (DALYs) and 8.6 billion USD (95% CIs: 2.9-21.5 billion) economic losses annually. The largest component of the economic burden is due to premature death (55%), followed by direct costs of post-exposure prophylaxis (PEP, 20%) and lost income whilst seeking PEP (15.5%), with only limited costs to the veterinary sector due to dog vaccination (1.5%), and additional costs to communities from livestock losses (6%). Conclusions/Significance This study demonstrates that investment in dog vaccination, the single most effective way of reducing the disease burden, has been inadequate and that the availability and affordability of PEP needs improving. Collaborative investments by medical and veterinary sectors could dramatically reduce the current large, and unnecessary, burden of rabies on affected communities. Improved surveillance is needed to reduce uncertainty in burden estimates and to monitor the impacts of control efforts.

Oral rabies vaccination in North America: opportunities, complexities, and challenges.

Steps to facilitate inter-jurisdictional collaboration nationally and continentally have been critical for implementing and conducting coordinated wildlife rabies management programs that rely heavily on oral rabies vaccination (ORV). Formation of a national rabies management team has been pivotal for coordinated ORV programs in the United States of America. The signing of the North American Rabies Management Plan extended a collaborative framework for coordination of surveillance, control, and research in border areas among Canada, Mexico, and the US. Advances in enhanced surveillance have facilitated sampling of greater scope and intensity near ORV zones for improved rabies management decision-making in real time. The value of enhanced surveillance as a complement to public health surveillance was best illustrated in Ohio during 2007, where 19 rabies cases were detected that were critical for the formulation of focused contingency actions for controlling rabies in this strategically key area. Diverse complexities and challenges are commonplace when applying ORV to control rabies in wild meso-carnivores. Nevertheless, intervention has resulted in notable successes, including the elimination of an arctic fox (Vulpes lagopus) rabies virus variant in most of southern Ontario, Canada, with ancillary benefits of elimination extending into Quebec and the northeastern US. Progress continues with ORV toward preventing the spread and working toward elimination of a unique variant of gray fox (Urocyon cinereoargenteus) rabies in west central Texas. Elimination of rabies in coyotes (Canis latrans) through ORV contributed to the US being declared free of canine rabies in 2007. Raccoon (Procyon lotor) rabies control continues to present the greatest challenges among meso-carnivore rabies reservoirs, yet to date intervention has prevented this variant from gaining a broad geographic foothold beyond ORV zones designed to prevent its spread from the eastern US. Progress continues toward the development and testing of new bait-vaccine combinations that increase the chance for improved delivery and performance in the diverse meso-carnivore rabies reservoir complex in the US.

Enzootic rabies elimination from dogs and reemergence in wild terrestrial carnivores, United States.

Independent enzootics in wild terrestrial carnivores resulted from spillover events from long-term enzootics associated with dogs.

Rabies surveillance in the United States during 2009.

During 2009, 49 states and Puerto Rico reported 6,690 rabid animals and 4 human rabies cases to the CDC, representing a 2.2% decrease from the 6,841 rabid animals and 2 human cases reported in 2008. Approximately 92% of reported rabid animals were wildlife. Relative contributions by the major animal groups were as follows: 2,327 (34.8%) raccoons, 1,625 (24.3%) bats, 1,603 (24.0%) skunks, 504 (75%) foxes, 300 (4.5%) cats, 81 (1.2%) dogs, and 74 (1.1%) cattle. Compared with 2008, numbers of rabid raccoons and bats that were reported decreased, whereas numbers of rabid skunks, foxes, cats, cattle, dogs, and horses that were reported increased. Fewer rabid raccoons, compared with 2008, were reported by 12 of the 20 eastern states where raccoon rabies is enzootic, and number of rabid raccoons decreased by 2.6% overall nationally. Despite a 10% decrease in the number of rabid bats that were reported and a decrease in the total number of bats submitted for testing, bats were the second most commonly submitted animal, behind cats, during 2009. The number of rabid skunks that were reported increased by 0.9% overall. The proportion of rabid skunks in which infection was attributed to the raccoon rabies virus variant decreased from 473% in 2008 to 40.9% in 2009, resulting in a 12.7% increase in the number of rabid skunks infected with a skunk rabies virus variant. The number of rabid foxes increased 11.0% overall from the previous year. Four cases of rabies involving humans were reported from Texas, Indiana, Virginia, and Michigan. The Texas case represented the first presumptive abortive human rabies case, with the patient recovering after the onset of symptoms without intensive care. The Indiana and Michigan cases were associated with bat rabies virus variants. The human rabies case in Virginia was associated with a canine rabies virus variant acquired during the patients travel to India.

Burden of encephalitis-associated hospitalizations in the United States, 1998–2010

Objective: To estimate the burden of encephalitis-associated hospitalizations in the United States for 1998–2010. Methods: Using the Nationwide Inpatient Sample, a nationally representative database of hospitalizations, estimated numbers and rates of encephalitis-associated hospitalizations for 1998–2010 were calculated. Etiology and outcome of encephalitis-associated hospitalizations were examined, as well as accompanying diagnoses listed along with encephalitis on the discharge records. Total hospital charges (in 2010 US dollars) were assessed. Results: An estimated 263,352 (standard error: 3,017) encephalitis-associated hospitalizations occurred in the United States during 1998–2010, which corresponds to an average of 20,258 (standard error: 232) encephalitis-associated hospitalizations per year. A fatal outcome occurred in 5.8% (95% confidence interval [CI]: 5.6%–6.0%) of all encephalitis-associated hospitalizations and in 10.1% (95% CI: 9.2%–11.2%) and 17.1% (95% CI: 14.6%–20.0%) of encephalitis-associated hospitalizations in which a code for HIV or a tissue or organ transplant was listed, respectively. The proportion of encephalitis-associated hospitalizations in which an etiology for encephalitis was specified was 50.3% (95% CI: 49.6%–51.0%) and that for which the etiology was unspecified was 49.7% (95% CI: 49.0%–50.4%). Total charges for encephalitis-associated hospitalizations in 2010 were an estimated

Rabies surveillance in the United States during 2010

2.0 billion. Conclusions: Encephalitis remains a major public health concern in the United States. Among the large number of encephalitis-associated hospitalizations for which an etiology is not reported may be novel infectious and noninfectious forms of encephalitis. Associated conditions such as HIV or transplantation increase the risk of a fatal outcome from an encephalitis-associated hospitalization and should be monitored.

Rabies surveillance in the United States during 2011

During 2010, 48 states and Puerto Rico reported 6,154 rabid animals and 2 human rabies cases to the CDC, representing an 8% decrease from the 6,690 rabid animals and 4 human cases reported in 2009. Hawaii and Mississippi did not report any laboratory-confirmed rabid animals during 2010. Approximately 92% of reported rabid animals were wildlife. Relative contributions by the major animal groups were as follows: 2,246 raccoons (36.5%), 1,448 skunks (23.5%), 1,430 bats (23.2%), 429 foxes (6.9%), 303 cats (4.9%), 71 cattle (1.1 %), and 69 dogs (1.1 %). Compared with 2009, number of reported rabid animals decreased across all animal types with the exception of a 1 % increase in the number of reported rabid cats. Two cases of rabies involving humans were reported from Louisiana and Wisconsin in 2010. Louisiana reported an imported human rabies case involving a 19-year-old male migrant farm worker who had a history of a vampire bat (Desmodus rotundus) bite received while in Mexico. This represents the first human rabies case reported in the United States confirmed to have been caused by a vampire bat rabies virus variant. Wisconsin reported a human rabies case involving a 70-year-old male that was confirmed to have been caused by a rabies virus variant associated with tri-colored bats (Perimyotis subflavus).

Raccoon Rabies Virus Variant Transmission Through Solid Organ Transplantation

During 2011, 49 states and Puerto Rico reported 6,031 rabid animals and 6 human rabies cases to the CDC, representing a 1.9% decrease from the 6,153 rabid animals and 2 human cases reported in 2010. Approximately 92% of reported rabid animals were wildlife. Relative contributions by the major animal groups were as follows: 1,981 raccoons (32.8%), 1,627 skunks (27.0%), 1,380 bats (22.9%), 427 foxes (7.1%), 303 cats (5.0%), 65 cattle (1.1%), and 70 dogs (1.2%). Compared with 2010, there was a substantial increase in the number of rabid skunks reported. Six cases of rabies involving humans were reported from California, Massachusetts, New Jersey, New York, and South Carolina. Three cases reported from Massachusetts, New Jersey, and New York were determined to be a result of canine rabies virus variants acquired outside the United States.

Rabies surveillance in the United States during 2008.

IMPORTANCE The rabies virus causes a fatal encephalitis and can be transmitted through tissue or organ transplantation. In February 2013, a kidney recipient with no reported exposures to potentially rabid animals died from rabies 18 months after transplantation. OBJECTIVES To investigate whether organ transplantation was the source of rabies virus exposure in the kidney recipient, and to evaluate for and prevent rabies in other transplant recipients from the same donor. DESIGN Organ donor and all transplant recipient medical records were reviewed. Laboratory tests to detect rabies virus-specific binding antibodies, rabies virus neutralizing antibodies, and rabies virus antigens were conducted on available specimens, including serum, cerebrospinal fluid, and tissues from the donor and the recipients. Viral ribonucleic acid was extracted from tissues and amplified for nucleoprotein gene sequencing for phylogenetic comparisons. MAIN OUTCOMES AND MEASURES Determination of whether the donor died from undiagnosed rabies and whether other organ recipients developed rabies. RESULTS In retrospect, the donors clinical presentation (which began with vomiting and upper extremity paresthesias and progressed to fever, seizures, dysphagia, autonomic dysfunction, and brain death) was consistent with rabies. Rabies virus antigen was detected in archived autopsy brain tissue collected from the donor. The rabies viruses infecting the donor and the deceased kidney recipient were consistent with the raccoon rabies virus variant and were more than 99.9% identical across the entire N gene (1349/1350 nucleotides), thus confirming organ transplantation as the route of transmission. The 3 other organ recipients remained asymptomatic, with rabies virus neutralizing antibodies detected in their serum after completion of postexposure prophylaxis (range, 0.3-40.8 IU/mL). CONCLUSIONS AND RELEVANCE Unlike the 2 previous clusters of rabies virus transmission through solid organ transplantation, there was a long incubation period in the recipient who developed rabies, and survival of 3 other recipients without pretransplant rabies vaccination. Rabies should be considered in patients with acute progressive encephalitis of unexplained etiology, especially for potential organ donors. A standard evaluation of potential donors who meet screening criteria for infectious encephalitis should be considered, and risks and benefits for recipients of organs from these donors should be evaluated.

Development of a GIS-based, real-time Internet mapping tool for rabies surveillance

During 2008, 49 states and Puerto Rico reported 6,841 cases of rabies in animals and 2 cases in humans to the CDC, representing a 3.1% decrease from the 7,060 cases in animals and 1 case in a human reported in 2007. Approximately 93% of the cases were in wildlife, and 7% were in domestic animals. Relative contributions by the major animal groups were as follows: 2,389 (34.9%) raccoons, 1,806 (26.4%) bats, 1,589 (23.2%) skunks, 454 (6.6%) foxes, 294 (4.3%) cats, 75 (1.1%) dogs, and 59 (0.9%) cattle. Compared with numbers of cases reported in 2007, numbers of cases reported in 2008 increased among cats, cattle, and skunks and decreased among dogs, raccoons, bats, and foxes. Numbers of rabid raccoons reported during 2008 decreased in 11 of the 20 eastern states where raccoon rabies was enzootic; overall number of rabid raccoons reported decreased by 8.6% during 2008, compared with 2007. On a national level, the number of rabies cases involving skunks increased by 7.7% during 2008, compared with the number reported in 2007; this was the first increase in the number of reported rabid skunks since 2006. The total number of cases of rabies reported nationally in foxes decreased 1.7% in 2008, compared with 2007. The 1,806 cases of rabies reported in bats represented a 6.7% decrease, compared with the number reported in 2007. One case of rabies in a dog imported from Iraq was reported at a quarantine station in New Jersey during 2008. Follow-up of potentially exposed animals in the same shipment did not reveal any secondary transmission. The United States remained free from dog-to-dog transmission of canine rabies virus variants. Total number of rabid dogs reported decreased 19.4% in 2008, compared with 2007. Two human rabies cases were reported from California and Missouri during 2008. The California case involved a recent immigrant from Mexico and was attributed to a newly identified rabies virus variant most likely associated with Mexican free-tailed bats. The case in Missouri was attributed to a rabies virus variant associated with eastern pipistrelle and silver-haired bats.