Bats have been proposed as major reservoirs for diverse emerging infectious viral diseases, with rabies being the best known in Europe. However, studies exploring the ecological interaction between lyssaviruses and their natural hosts are scarce. This study completes our active surveillance work on Spanish bat colonies that began in 1992. Herein, we analyzed ecological factors that might affect the infection dynamics observed in those colonies. Between 2001 and 2011, we collected and tested 2,393 blood samples and 45 dead bats from 25 localities and 20 bat species. The results for dead confirmed the presence of EBLV-1 RNA in six species analyzed (for the first time in Myotis capaccinii). Samples positive for European bat lyssavirus-1 (EBLV-1)-neutralizing antibodies were detected in 68% of the localities sampled and in 13 bat species, seven of which were found for the first time (even in Myotis daubentonii, a species to date always linked to EBLV-2). EBLV-1 seroprevalence (20.7%) ranged between 11.1 and 40.2% among bat species and seasonal variation was observed, with significantly higher antibody prevalence in summer (July). EBLV-1 seroprevalence was significantly associated with colony size and species richness. Higher seroprevalence percentages were found in large multispecific colonies, suggesting that intra- and interspecific contacts are major risk factors for EBLV-1 transmission in bat colonies. Although bat-roosting behavior strongly determines EBLV-1 variability, we also found some evidence that bat phylogeny might be involved in bat-species seroprevalence. The results of this study highlight the importance of life history and roost ecology in understanding EBLV-1-prevalence patterns in bat colonies and also provide useful information for public health officials.

Our previous studies indicated that recombinant rabies viruses (rRABV) expressing chemokines or cytokines (including GM-CSF) could enhance the immunogenicity by recruiting and/or activating dendritic cells (DC). In this study, bacterial flagellin was cloned into the RABV genome and recombinant virus LBNSE-Flagellin was rescued. To compare the immunogenicity of LBNSE-Flagellin with recombinant virus expressing GMCSF (LBNSE-GMCSF), mice were immunized with each of these rRABVs by intramuscular (i.m.) or oral route. The parent virus (LBNSE) without expression of any foreign molecules was included for comparison. The i.m.-immunized mice were bled at three weeks after the immunization for the measurement of virus neutralizing antibody (VNA) and then challenged with 50 LD50 challenge virus standard (CVS-24). Orally immunized mice were boosted after three weeks and then bled and challenged one week after the booster immunization. It was found that both LBNSE-GMCSF and LBNSE-Flagellin recruited/activated more DCs and B cells in the periphery, stimulated higher levels of adaptive immune responses (VNA), and protected more mice against challenge infection than the parent virus LBNSE in both the i.m. and the orally immunized groups. Together, these studies suggest that recombinant RABV expressing GM-CSF or flagellin are more immunogenic than the parent virus in both i.m. and oral immunizations.

SESSION TYPE: Critical Care Student/Resident Case Report Posters IIPRESENTED ON: Tuesday, October 23, 2012 at 01:30 PM - 02:30 PM

INTRODUCTION:

Rabies is a zoonotic disease caused by a bullet shaped virus, which is transmitted via saliva of infected animals, usually a bat in USA [2]. The virus enters the CNS, causing an acute encephalomyelitis, which is almost uniformly fatal. The disease is preventable if exposure to the virus is promptly followed by wound cleaning, administration of rabies immunoglobulin and vaccination.

CASE PRESENTATION:

A 24 year old male sought treatment for right hand numbness, dysphagia and vomiting for 5 days. He had history of dog bite in his hand 6 months ago while working in South East Asia and reported receiving a series of Immunoglobulin vaccine after the bite. The dog was killed and tested negative for rabies. On the day of presentation patient developed hydrophobia, aerophobia and copious salivary secretions followed by extreme agitation. CT head was normal, while CSF showed lymphocytic pleocytosis. He had a normal physical examination but was intubated for respiratory distress. Due to strong suspicion of rabies, Milwaukee protocol was started before the diagnosis was made. It included inducing therapeutic coma with midazolam, fentanyl and ketamine, along with antiviral drugs and supportive care, until the native immune response matured [1]. Patient developed bradycardia and raised ICP, which was managed by transvenous pacemaker, and ventriculostomy drains respectively. On the 3rd day nuchal skin biopsy, saliva and serum PCR tested positive for rabies. Daily saliva and CSF samples were checked for antibody titers against the virus. Hypothermia protocol was started for neuroprotection despite of which he developed Central Diabetes Inspidus, which was treated with vasopressin. Later on he developed ARDS leading to refractory hypoxia, for which Extra Corporeal Membranous Oxygen (ECMO) was started. It had to be weaned off in 4 days because of persistent thrombocytopenia. Rising titer of protective antibody were detected for the first time on day 12 but patient developed huge intracerebral bleed with mass effect, which was not amenable for surgical treatment. He was made comfort care by the family and ultimately died.

DISCUSSION:

This case warns the intensivists about the development of Multi Organ Dysfunction during the clinical course of rabies and requirement of multiple sub- specialties in its management. There is no known therapy for rabies and new approaches need to be developed in light of multiple failures of the Milwaukee protocol [2].

CONCLUSIONS:

As one of the oldest and deadliest infectious diseases, rabies is long overdue for development of a successful treatment.1) Aramburo A, Willoughby RE, Bollen AW, Glaser CA, Hsieh CJ, Davis SL, Martin KW, Roy-Burman A. Failure of the Milwaukee protocol in a child with rabies. Clin Infect Dis. 2011 Sep;53(6):572-42) Jackson AC. Rabies in the critical care unit. Can J Neurol Sci. 2011 Sep;38(5):689-95: diagnostic and therapeutic approaches.DISCLOSURE: The following authors have nothing to disclose: Dilpreet Kaur, Birendra SahNo Product/Research Disclosure InformationSUNY Upstate Medical University, Syracuse, NY.

SESSION TYPE: Critical Care Student/Resident CasesPRESENTED ON: Monday, October 22, 2012 at 01:45 PM - 03:00 PM

INTRODUCTION:

We report a case of a 24 year-old male US Army soldier who presented with aerophobia, hydrophobia and ataxia - eight months after being bit by a feral dog in Afghanistan. He did not receive effective post exposure prophylaxis(PEP) for rabies however[1].

CASE PRESENTATION:

The diagnosis of rabies was ultimately confirmed as viral antigens were detected on a nuchal skin biopsy. Furthermore, rabies viral RNA were detected in saliva, csf, and in the cornea as well. Immediately, we initiated an experimental protocol for rabies[2]. 5 days into the treatment, acute hypoxic respiratory failure developed. Despite the use of conventional ventilatory support or high-frequency oscillator ventilation with and without nitrogen oxide, the Pa02/Fi02 ratio continued to decrease. A chest x-ray revealed bilateral interstitial infiltrates. All cultures were negative. Moreover, the patient remained afebrile and without an elevated white blood cell count. A bedside echo was performed and showed a hyperdynamic LV without signs of diastolic dysfunction. The diagnosis of severe acute respiratory distress syndrome(ARDS) was made. In this setting of refractory hypoxemia, we recommended the initiation of extracorporeal membrane oxygenation(ECMO)[3]. Oxygen saturations gradually improved. The patient was kept on ECMO for 5 days with a successful wean and ultimately placed on assist control ventilation. Unfortunately, on day-13 of the hospital course, our patient developed an inoperable intracerebral hemorrhage and care was withdrawn in the setting of a poor prognosis.

DISCUSSION:

Rabies, a zoonotic disease with the highest case fatality rate of any infectious disease, presents as a challenge to health care professionals worldwide. Once symptoms develop, the management is largely supportive. The ultimate goal at this stage is to support the patient long enough until they can develop antibodies towards the virus. As a result, Intensivists have a vital role to play in managing complications such as severe ARDS that may ensue in human rabies.

CONCLUSIONS:

Our case highlights the role of ECMO in treating severe ARDS secondary to rabies. To our knowledge, this is the first reported case of ECMO use in rabies and the longest any patient had lived with symptomatic dog rabies.1) Center of Disease and Control, "Use of a Reduced (4-Dose) Vaccine Schedule for Postexposure Prophylaxis to Prevent Human Rabies." Last modified April 22,2011. http://www.cdc.gov/rabies/resources/acip_recommendations.html2) Willoughby,R et. Al Survival after Treatment of Rabies with Induction of Coma, N Engl J Med2005; 352:2508-25143) Brodie,D; Bacchetta, M. Extracorporeal Membrane Oxygenation for ARDS in Adults N Engl J Med 2011 365: 1905-1914.DISCLOSURE: The following authors have nothing to disclose: Amritpal Nat, Ioana Amzuta, Waleed Javaid, Aravind Pothineni, Amit Sharma, Namita Sharma, Dana Savici, Gregory Fink, Amitpal NatNo Product/Research Disclosure InformationSUNY Upstate, Syracuse, NY.

Immune evasion by rabies virus depends on targeting of STAT1 and 2 proteins by the viral interferon-antagonist P-protein, but targeting of other STATs has not been investigated. Here, we find that P-protein associates with activated STAT3 and inhibits STAT3 nuclear accumulation and Gp130-dependent signaling. This is the first report of STAT3 targeting by the interferon-antagonist of a virus other than a paramyxovirus, indicating that STAT3 antagonism is important to a range of human pathogenic viruses.

Rabies is a devastating encephalitis caused by RNA viruses that use mammals as reservoirs. In the United States, most naturally acquired human cases have come from bats. The use of appropriate preexposure and postexposure prophylaxis can be nearly 100% effective. If prophylaxis is not used, or is implemented incorrectly, the patient may develop clinical rabies, which is almost universally fatal. All health care practitioners should be familiar with the appropriate evaluation of patients presenting with a possible rabies exposure and ensure that expeditious and appropriate prophylaxis is provided to help prevent the development of this lethal disease.

We conducted a study of the knowledge, attitudes and practices regarding dog bites among residents of a rural community in Bangladesh from September 2006 to February 2007 using face to face interviews with 1,973 adults from five villages. The mean age of the respondents was 34+/-16 years. Sixty-eight percent of subjects were female, 7.3% of respondents reported a history of dog bite in a family member; 10% had been bitten twice. Sixty-five percent of subjects were aware of rabies and 99.1% knew a dog bite was the cause of rabies. Seventy-one percent of subjects were aware of a rabies vaccine, 77.5% of respondents stated rabies can cause death. Ninty percent of dog bite victims received treatment by traditional healers, 25% were treated with a rabies vaccine and 2.1% of victims died. Greater awareness is needed in rural Bangladesh regarding prevention of rabies.

An epidemic of Chinese ferret badger-associated human rabies was investigated in Wuyuan county, Jiangxi province and rabies viruses isolates from ferret badgers in different districts in Jiangxi and Zhejiang provinces were sequenced with their nucleotides and amino acids and aligned for epidemiological analysis. The results showed that the human rabies in Wuyuan are only associated with ferret badger bites; the rabies virus can be isolated in a high percentage of ferret badgers in the epidemic areas in Jiangxi and Zhejiang provinces; the isolates share the same molecular features in nucleotides and have characteristic amino acid signatures, i.e., 2 sites in the nucleoprotein and 3 sites in the glycoprotein, that are distinct from virus isolates from dogs in the same region. We conclude that rabies in Chinese ferret badgers has formed an independent transmission cycle and ferret badgers may serve as another important rabies reservoir independent of dog rabies in China.