Norman Customized
Australian bat lyssavirus (ABLV) is a recently emerged rhabdovirus of the genus lyssavirus considered endemic in Australian bat populations that causes a neurological disease in people indistinguishable from clinical rabies. There are two distinct variants of ABLV, one that circulates in frugivorous bats (genus Pteropus) and the other in insectivorous microbats (genus Saccolaimus). Three fatal human cases of ABLV infection have been reported, the most recent in 2013, and each manifested as acute encephalitis but with variable incubation periods. Importantly, two equine cases also arose recently in 2013, the first occurrence of ABLV in a species other than bats or humans. Similar to other rhabdoviruses, ABLV infects host cells through receptor-mediated endocytosis and subsequent pH-dependent fusion facilitated by its single fusogenic envelope glycoprotein (G). Recent studies have revealed that proposed rabies virus (RABV) receptors are not sufficient to permit ABLV entry into host cells and that the unknown receptor is broadly conserved among mammalian species. However, despite clear tropism differences between ABLV and RABV, the two viruses appear to utilize similar endocytic entry pathways. The recent human and horse infections highlight the importance of continued Australian public health awareness of this emerging pathogen.
Rabies virus (RV) phosphoprotein P is an interferon (IFN) antagonist counteracting transcriptional activation of type I IFN (K. Brzózka, S. Finke, and K. K. Conzelmann, J. Virol 79:7673-7681, 2005). We here show that RV P in addition is responsible for preventing IFN-α/β- and IFN-γ-stimulated JAK-STAT signaling in RV-infected cells by the retention of activated STATs in the cytoplasm. Expression of IFN-stimulated response element- and gamma-activated sequence-controlled genes was severely impaired in cells infected with RV SAD L16 or in cells expressing RV P protein from transfected plasmids. In contrast, a recombinant RV expressing small amounts of P had lost the ability to interfere with JAK-STAT signaling. IFN-mediated tyrosine phosphorylation of STAT1 and STAT2 was not impaired in RV P-expressing cells; rather, a defect in STAT recycling was suggested by distinct accumulation of tyrosine-phosphorylated STATs in cell extracts. In the presence of P, activated STAT1 and STAT2 were unable to accumulate in the nucleus. Notably, STAT1 and STAT2 were coprecipitated with RV P only from extracts of cells previously stimulated with IFN-α or IFN-γ, whereas in nonstimulated cells no association of P with STATs was observed. This conditional, IFN activation-dependent binding of tyrosine-phosphorylated STATs by RV P is unique for a viral IFN antagonist. The 10 C-terminal residues of P are required for counteracting JAK-STAT signaling but not for inhibition of transcriptional activation of IFN-β, thus demonstrating two independent functions of RV P in counteracting the host's IFN response.
On June 22, 2014, a middle-aged male worker suffered a laceration to his right thumb from a cutter knife. The wound was 1.5 cm in length, and was accompanied by minimal bleeding. Once cleaned, disinfected, and sutured, the wound was dressed with gauze. As part of the treatment the patient received an administration of tetanus antitoxin. On July 6, the sutures were removed, and it was observed that the wound was healing well and subsequently redressed with gauze. On July 7, a relative of the man was bitten on the right calf by a stray dog at a highway service station. When he assisted his relative, the man’s gauze was contaminated with the relative’s blood. The gauze was immediately discarded, but he did not seek further medical attention or receive a rabies vaccination. On Sept. 1, he began to experience nighttime agitation and sleep disturbance. On Sept. 9, he suffered from right upper extremity parasthesia in the form of crawling and stinging sensations. On Sept. 10, he experienced more severe symptoms including photophobia, hydrophobia, anemophobia, pharyngeal muscle spasms, excessive sweating, salivation, chest tightness, irritability, and delirium. He was transferred to our hospital and rabies was suspected based on clinical presentation. The patient was isolated in a quiet single room and advised to avoid light and stimulation; sedation was also provided. Saliva samples of the patient were collected and tested by the State Key Lab of Diagnosis and Treatment of Infectious Diseases (Hangzhou, China), and a nested reverse transcription-polymerase chain reaction (RT-PCR) confirmed the presence of rabies virus RNA (Fig. 1). The reverse transcription-polymerase chain reaction (RT-PCR) kit for the detection of rabies virus RNA was purchased from TaKaRa Biotechnology Co., Ltd. (Dalian, China). The patient markedly deteriorated after admission, and experienced lapses in consciousness and convulsions. At 1:00 p.m. on Sept. 11, he suffered cardiac and respiratory arrest, and then died after attempts at resuscitation proved unsuccessful. In contrast, the relative who was bitten by the rabid dog received timely inoculation with the rabies vaccine and suffered no complications.
On November 9, 2009, a Michigan hospital informed CDC of suspected rabies in a man aged 55 years. The patient reportedly had awakened with a bat on his arm 9 months earlier but had not sought medical evaluation. He went to a local emergency department (ED) on October 30 and soon after was hospitalized; he died 12 days later. On November 14, CDC confirmed infection with a rabies virus variant that commonly infects the silver-haired bat (Lasionycteris noctivagans) (Figure). This report summarizes the patient's clinical course and the associated public health investigation. The report highlights the importance of public awareness of rabies, particularly among persons who might be at risk for wildlife exposures. Persons who experience contact with a bat and cannot confidently rule out a bite or scratch should seek prompt medical attention.
Case Report
On October 30, the man went to a local ED after 10 days of pain and progressive numbness in the left hand and arm and pain in his lower neck and upper back. The patient had sought treatment for these symptoms from a chiropractor several times during the preceding 6 days. Although the back pain had improved, the numbness and tingling had worsened, and he was experiencing weakness in his left hand and arm. A neurologic examination revealed normal strength and sensation of his lower extremities. His right arm showed normal strength, but the left hand showed no grip, and the patient could only lift his left arm a few inches. The patient was afebrile, and his blood pressure was normal when he arrived at the ED. A complete blood count and routine chemistries were normal except for an elevated white blood cell count of 15,300/µL (normal: 3,600--10,000/µL) and elevated glucose of 155 mg/dL (normal: 70--99 mg/dL). A computed tomography scan of the brain without contrast revealed a cavernous sinus larger on the left than on the right and an area of slightly decreased density in the right basal ganglion and paraventricular areas.
During the ED evaluation, the patient's breathing became labored, and he had difficulty with respiratory secretions. He was placed on ventilation and transferred to a nearby tertiary-care facility. At the time of intubation, the anesthesiologist noted that the procedure was easy to perform because of lack of muscle tone in the patient's pharynx.
On admission to the tertiary-care facility, respiratory failure secondary to cerebral vascular accident or acute idiopathic demyelinating polyradiculoneuropathy (AIDP or Guillain-Barré syndrome) were the chief diagnoses considered. Findings from magnetic resonance imaging were unremarkable. Electromyography showed mild decreased conduction velocities and multiple absent F waves. Thereafter, AIDP was suspected, and intravenous immunoglobulin therapy was begun. The patient's sedation was lightened to conduct physical examinations.
During the first 2 days of hospitalization, the patient experienced progressive weakness, initially on the left side. He was able to respond to verbal commands and, according to the neurologist who evaluated him, his random eye movements were normal. On November 1, the patient's mental status appeared to improve, as sedation was lightened with the hope of removing him from the ventilator. However, over the next few days, his upper extremity weakness progressed to involve the right side, and lower extremity weakness was noted, demonstrating areflexia and a lack of response to plantar stimulation. Some nystagmus on far horizontal gaze to either side also was noted as a new development. On November 3, the patient became quadriplegic but could move his eyes to the right and left on request. Analysis of his cerebrospinal fluid (CSF) revealed several abnormal values: protein of 109 mg/dL (normal: 10--55 mg/dL); glucose of 92 mg/dL (normal: 45--75 mg/dL); and a white blood cell count of 243 cells/µL (normal: <5 cells/µL) with a differential of 80% lymphocytes, 18% monocytes, and 2% segmented neutrophils. A Gram stain and culture were negative.
On November 4, the patient had an acute change in his neurologic status, including twitching of the left foot, more marked nystagmus, and slightly asymmetric pupils. Based on the results of the CSF analysis, the working diagnosis was changed to meningoencephalitis, and an infectious disease consultation was sought. The CSF was further analyzed for Borrelia burgdoferi and the following viruses: West Nile, St. Louis encephalitis, California Group, Eastern equine encephalitis, Western equine encephalitis, measles, mumps, herpes simplex virus 1 and 2, enteroviruses, varicella-zoster, cytomegalovirus, lymphocytic choriomeningitis virus, adenovirus, and influenza. All tests were negative. Antiviral treatment with acyclovir was begun. The patient's electroencephalogram showed marked deterioration from previous studies, indicating severe encephalopathy.
Case Report
On October 30, the man went to a local ED after 10 days of pain and progressive numbness in the left hand and arm and pain in his lower neck and upper back. The patient had sought treatment for these symptoms from a chiropractor several times during the preceding 6 days. Although the back pain had improved, the numbness and tingling had worsened, and he was experiencing weakness in his left hand and arm. A neurologic examination revealed normal strength and sensation of his lower extremities. His right arm showed normal strength, but the left hand showed no grip, and the patient could only lift his left arm a few inches. The patient was afebrile, and his blood pressure was normal when he arrived at the ED. A complete blood count and routine chemistries were normal except for an elevated white blood cell count of 15,300/µL (normal: 3,600--10,000/µL) and elevated glucose of 155 mg/dL (normal: 70--99 mg/dL). A computed tomography scan of the brain without contrast revealed a cavernous sinus larger on the left than on the right and an area of slightly decreased density in the right basal ganglion and paraventricular areas.
During the ED evaluation, the patient's breathing became labored, and he had difficulty with respiratory secretions. He was placed on ventilation and transferred to a nearby tertiary-care facility. At the time of intubation, the anesthesiologist noted that the procedure was easy to perform because of lack of muscle tone in the patient's pharynx.
On admission to the tertiary-care facility, respiratory failure secondary to cerebral vascular accident or acute idiopathic demyelinating polyradiculoneuropathy (AIDP or Guillain-Barré syndrome) were the chief diagnoses considered. Findings from magnetic resonance imaging were unremarkable. Electromyography showed mild decreased conduction velocities and multiple absent F waves. Thereafter, AIDP was suspected, and intravenous immunoglobulin therapy was begun. The patient's sedation was lightened to conduct physical examinations.
During the first 2 days of hospitalization, the patient experienced progressive weakness, initially on the left side. He was able to respond to verbal commands and, according to the neurologist who evaluated him, his random eye movements were normal. On November 1, the patient's mental status appeared to improve, as sedation was lightened with the hope of removing him from the ventilator. However, over the next few days, his upper extremity weakness progressed to involve the right side, and lower extremity weakness was noted, demonstrating areflexia and a lack of response to plantar stimulation. Some nystagmus on far horizontal gaze to either side also was noted as a new development. On November 3, the patient became quadriplegic but could move his eyes to the right and left on request. Analysis of his cerebrospinal fluid (CSF) revealed several abnormal values: protein of 109 mg/dL (normal: 10--55 mg/dL); glucose of 92 mg/dL (normal: 45--75 mg/dL); and a white blood cell count of 243 cells/µL (normal: <5 cells/µL) with a differential of 80% lymphocytes, 18% monocytes, and 2% segmented neutrophils. A Gram stain and culture were negative.
On November 4, the patient had an acute change in his neurologic status, including twitching of the left foot, more marked nystagmus, and slightly asymmetric pupils. Based on the results of the CSF analysis, the working diagnosis was changed to meningoencephalitis, and an infectious disease consultation was sought. The CSF was further analyzed for Borrelia burgdoferi and the following viruses: West Nile, St. Louis encephalitis, California Group, Eastern equine encephalitis, Western equine encephalitis, measles, mumps, herpes simplex virus 1 and 2, enteroviruses, varicella-zoster, cytomegalovirus, lymphocytic choriomeningitis virus, adenovirus, and influenza. All tests were negative. Antiviral treatment with acyclovir was begun. The patient's electroencephalogram showed marked deterioration from previous studies, indicating severe encephalopathy.
A 6-year-old boy from India developed an atypical form of rabies following a stray dog bite and as a consequence of not receiving the standard World Health Organization recommended post-exposure prophylaxis for category III wounds. Serial rising rabies virus neutralizing antibody titres in serum and cerebrospinal fluid by rapid fluorescent focus inhibition test helped confirm the diagnosis of rabies. The child has survived for 4 months since the onset of illness, albeit with neurological sequelae.
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