New Findings from 2003-2004!
The efficacy of two rabies post-exposure vaccines was compared within the model system of BALB/c mice. Mice in both treatment groups were exposed to rabies virus. One group was then vaccinated with rabies DNA vaccine, which consists of direct injection of a vector that expresses an antigen similar to rabies. The aim of a DNA vaccine is to stimulate the immune system against the viral antigen before the rabies virus has had a chance to replicate. The other group of mice was vaccinated with five injections of cell culture-derived rabies vaccine at days 0, 3, 7, 14, 28 respective to infection, which is the vaccination protocol currently recommended by the World Health Organization (WHO.) This study showed that, while both vaccination regimens triggered antibody production against rabies, the single injection of DNA vaccine was able to prevent rabies in 53% of the infected mice, whereas the 5 injections of cell culture-derived vaccine prevented rabies in only 40% of the mice. The findings suggest that the new technology of DNA vaccination is very promising.
(Bahloul, C, Ahmed, SBH, B-chir, BI, Karmachi, H, Hayouni, EA, Dellagi, K. "Post-exposure therapy in mice against experimental rabies: a single injection of DNA vaccine is a effective as five injections of cell culture-derived vaccine." Vaccine 22 (2003) 177-184.)
In March, 2003 a previously healthy 25 year old man from Virginia died and was post-mortally diagnosed with rabies. Upon genetic sequencing the rabies virus variant in his blood was found to be highly associated with the rabies virus that infects raccoons. This is the first known case of rabies transmission from raccoon to human within the United States. His illness had lasted 3 weeks before his death. The diagnosis of rabies had been considered by his doctors, but discarded after a review of the history and signs and symptoms.
(Silverstein, MA, Salgado, CD, Bassin, S, Bleck, TP, Lopes, MB, Farr, BM, Jenkins, SR, Sockwell, DC, Marr, JS, and Miller, GB. "First Human Death Associated with Raccoon Rabies -- Virginia, 2003. MMWR. Nov. 14, 2003. 52(45);1102-1103.)
Because rabies is frequently passed to humans by way of canines, mass vaccination of canines is important in order to prevent human rabies, particularly in poor regions where post-exposure treatment is of limited availability or feasibility. A study was conducted in order to assess the rate of canine vaccination that could be achieved through vaccination campaigns. Three test zones were chosen within N'Djamena, Chad. In zone 1 1.1% of dogs were ownerless, in zone 2 7.6% of dogs were ownerless, and in zone 3 10.6% of dogs were ownerless. It was hypothesized that zone 1 would achieve the highest rate of canine vaccination, followed by zone 2. In fact, the study showed that 87% of dogs in zone 1 were vaccinated, 71% of dogs in zone 2 were vaccinated, and 64% of dogs in zone 3 were vaccinated. Therefore, the study concluded that the vaccination effort was effective and ethical in all three study zones and therefore should be recommended throughout N'Djamena.
(Kayali, U., Mindekem, R, Yemadji, N, Vounatsou, P., Kaninga, Y., Ndoutamia, A.G., and Zinsstag, J. "Coverage of pilot parenteral vaccination campaign against canine rabies in N'Djamena, Chad." Bulletin of the World Health Organization. 2003, 81 (10) 739-745.)
A new vector has been engineered which is capable of efficient gene transfer to the central and peripheral nervous system. High-titer equine infectious anemia virus (EIAV), a lentivirus, was pseudotyped with envelop glycoproteins from four virus independently: 1) vesicular stomatitis virus (VSV), 2) various strains of rabies virus, 3) Mokala virus, and 4) lymphocytic choriomeningitis virus (LCMV.) Vectors were directly injected into striatum or spinal cord of adult rats, and muscle of neonatal mice. The lentivirus vectores pseudotyped with VSV and rabies viruses ERA and CVS were strongly transduced in the striatum. ERA and CVS vectors also demonstrated retrograde transport into distal neurons. These results suggest new, promising designs for therapeutic strategies for neurological disease.
(Wong, L, Azzouz, M, Walmsley, LE, Askham, Z, Wilkes, FJ, Mitrophanous, KA, Kingsman, SM, and Mazarakis, ND. "Transduction Patterns of Pseudotyped Lentiviral Vectors in the Nervous System." Molecular Therapy, vol. 9, no. 1, January 2004, 101-111.)
A new reagent was discovered that can be used to inactivate the rabies virus in vitro, without affecting the antigenicity of the virus. This will improve diagnostic lab techniques for rabies, because the previously recommended inactivating agent was both very expensive and potentially carcinogenic. Specifically, ascorbic acid used at concentration .5mg/ml with 5 microg/ml copper sulfate completely inactivate rabies virus within 72 hours. The virus retains antigenicity and potency.
(Madhusudana, SN, Shamsundar, R, Seetharaman, S. "In vitro inactivation of rabies virus by ascorbic acid." Int J Infect Dis. 2004 Jan;8(1):21-5.)
An account of all rabies cases recorded in the United States in 2002 was published. A total of 7969 cases of non-human rabies were reported, and 3 cases of human rabies were reported. This was an increase of 7.2% from the number of rabies cases reported in 2001, which was 7436 cases of non-human rabies and 1 case of human rabies. All three people who were infected by rabies in 2002 had bat variants of the virus. The distribution of rabies between non-human species remained fairly constant, except that the instance of rabies in cats increased 10.7%, in cattle it increased 41.5%, in dogs it increased 11.24%, in sheep and goats it increased 400% (woah!), and in horses and mules it increased 13.7%.
(Krebs, JW, Wheeling, JT, and Childs, JE. "Rabies surveillance in the United States during 2002." J Am Vet Med Assoc. 2003 Dec 15;223(12):1736-48.)
Rabies virus has been used as a laboratory tool to study the architecture of cerebral cortex loops. In cebus monkeys, rabies virus was injected into the primary motor cortex (M1.) Four days later, the virus had traveled from that site to 'third-order' neurons in the basal ganglia. Specifically, those neurons were found in the external globus pallidus, striatum, subthalamic nucleus, ventral putamen. The external globus pallidus, striatum, and subthalamic nucleus were expected results because they have been shown, using conventional tracer, to be the terminations of M1. However, such methods demonstrated that the ventral putamen is not innervated by M1. Instead, the putamen is targeted by neurons coming from the amygdale. This suggests that the limbic system may influence motor output, and shows that the cerebral cortex has both open and closed loop architecture.
(Kelly, RM, Strick, PL. "Macro-architecture of basal ganglia loops with the cerebral cortex: use of rabies virus to reveal multisynaptic circuits." Prog Brain Res. 2004;143:449-59.)
A study was conducted to test the level of protection provided by three strains of rabies immunoglobin. The model system of the Syrian hamster was used. Two distinct batches of heat-treated equine rabies immunoglobulin (pERIG HT) were compared to each other and reference rabies immunoglobulin preparations (RIG) in hamsters that had been exposed to Ariana canine field strain of rabies. The first batch of pERIG HT provided only 53% protection from infection, while the second batch of pERIG HT and RIG provided 83-90% survival. The reason for the difference between supposedly identical batches has not been explained.
(Servat, A, Lutsch, C, Delore, V, Lang, J, Veitch, K, Cliquet, F. "Efficacy of rabies immunoglobulins in an experimental post-exposure prophylaxis rodent model." Vaccine 22 (2003) 244-249.)
Since 1981, both raccoon and skunk rabies have been on the rise. Analysis was conducted to map the spacial and temporal distribution of raccoon and skunt epizootics (the veterinary equivalents of epidemics.) It was found that the temporal patterns of raccoon rabies accurately predicts the pattern of skunk rabies, with a 1-month lag between the epizootics of the two species. This suggests that rabies virus is being passed at significant rates between raccoons and skunks.
(Guerra, MA, Curns, AT, Rupprecht, CE, Hanlon, CA, Krebs, JW, Childs, JE. "Skunk and raccoon rabies in the eastern United States: temporal and spatial analysis." Emerg Infect Dis. 2003 Sep;9(9):1143-50.)
A study was conducted to test whether chemokines or TRANCE, a survival factor for mature dendritic cells, act as adjuvants for rabies DNA vaccine. This research was based on the assumption that the number of antigen-presenting dendritic cells, as well as the duration of their antigen presentation, affects the degree of immune response. Neither the chemokines nor TRANCE enhanced the immune response when given with a DNA vaccine that encoded the full rabies glycoprotein. However, both cytokines and TRANCE did enhance the immune system when they were introduced with a DNA vaccine that expressed a truncated, and therefore secreted, version of the glycoprotein.
(Pinto, AR, Reyes-Sandoval, A, Ertl, HC. "Chemokines and TRANCE as genetic adjuvants for a DNA vaccine to rabies virus." Cell Immunol. 2003 Aug;224(2):106-13.)
Three cellular mechanisms that allow for the impressive neuroinvasivness of rabies virus have been identified in a study that compared a highly neuroinvasive strain of the virus to an attenuated, less invasive strain (PV.) The first identified mechanism is that the neuroinvasive strain avoids neuron death for infected neurons. Second, "protective" T cells that migrate to infection are killed. Third, inflammatory response is limited in the region of the infected neurons. This study suggest that each of those abilities contribute to rabies viruses invasiveness.
(Baloul, L, Lafon, M. "Apoptosis and rabies virus neuroinvasion." Biochimie. 2003 Aug;85(8):777-88.)
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