Rabies Virus

Classification

General Characteristics and Epidemiology

Basic features of rabies virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology

• Taxonomy:
  • Family: Rhabdoviridae
  • Genus: Lyssavirus
• Midsize:
  • 180 nm long
  • 75 nm wide
• RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure genome Genome The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics:
  • Single-stranded
  • Linear
  • Negative-sense
• Structure:
  • Bullet-shaped
  • Helical Helical Computed tomography where there is continuous x-ray exposure to the patient while being transported in a spiral or helical pattern through the beam of irradiation. This provides improved three-dimensional contrast and spatial resolution compared to conventional computed tomography, where data is obtained and computed from individual sequential exposures. Computed Tomography (CT) ribonucleoprotein core
  • Enveloped
  • Glycoprotein spikes on the virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology surface
• Carries RNA-dependent RNA polymerase RNA-dependent RNA polymerase An enzyme that catalyses rna-template-directed extension of the 3′- end of an RNA strand by one nucleotide at a time, and can initiate a chain de novo. Virology (RDRP)

Associated disease

Rabies virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology causes the disease rabies.

Epidemiology

• Rabies is present in nearly every country.
  • Developing countries are more affected:
    • Asia ASIA Spinal Cord Injuries
    • Africa
    • Latin America
  • Animal vaccinations in the United States and Europe have largely eliminated rabies in domestic animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic. 
• Approximately 59,000 deaths each year worldwide
• 2–3 cases per year in the United States
• Children (boys > girls) are 4 times as likely as adults to get rabies.

Pathogenesis

Reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli

Mammalian species serve as hosts. In the United States, these may include:

• Bat
• Skunk
• Raccoon
• Fox
• Mongoose
• Coyote
• Wolf
• Unvaccinated dogs

Transmission

Human infection is almost always due to a bite by an infected mammal.

• Most common: saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy of infected animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic
• Rare:
  • Organ transplant
  • Transplacental
  • Inhalation of aerosolized virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology

Host risk factors

Susceptibility to lethal infection is related to:

• Animal species
• Viral variant
• Inoculum concentration
• Location of exposure
  • Head and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess bite versus distal body part
  • Amount of innervation at the bite site
• Severity of exposure
• Host immune status

Viral replication cycle

• Rabies virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology binds to receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors on outside host cells → enters host cells by the endosomal transport pathway 
• ↓ pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance in the endosome Endosome Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. Hepatitis C Virus causes membrane fusion → viral genome Viral genome The complete genetic complement contained in a DNA or RNA molecule in a virus. Virology reaches the cytosol Cytosol A cell’s cytoskeleton is a network of intracellular protein fibers that provides structural support, anchors organelles, and aids intra- and extracellular movement. The Cell: Cytosol and Cytoskeleton → viral RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure uncoats in the cytoplasm of infected cells 
• Genome Genome The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription by a virion-associated RDRP →  viral RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure is translated into viral proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis 
• Replication occurs with synthesis Synthesis Polymerase Chain Reaction (PCR) of positive-stranded RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure templates for the production of negative-stranded RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure.
• Virions are assembled → virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology buds from the cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane

Pathophysiology

• Inoculation → virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology has predilection for neural tissue → enters local motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology and sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology nerves
• Travels via peripheral nerves Peripheral Nerves The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. Nervous System: Histology → migrates to the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy → brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
• Mechanism for encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis is unclear.
• Spreads back through peripheral nerves Peripheral Nerves The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. Nervous System: Histology → disseminates to other parts of the body

Clinical Presentation

5 general stages are recognized in humans: incubation → prodrome Prodrome Symptoms that appear 24–48 hours prior to migraine onset. Migraine Headache → acute neurologic period → coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma → death

Incubation

• Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables from 10 days–2 years, but usually 20–90 days
• Shorter in children and with bites closer to the CNS

Prodrome Prodrome Symptoms that appear 24–48 hours prior to migraine onset. Migraine Headache

• Prodromal period lasts 0–10 days.
• Symptoms are nonspecific
  • General malaise Malaise Tick-borne Encephalitis Virus
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
  • Sore throat Sore throat Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis
  • Cough
  • Dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
  • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways or paresthesias Paresthesias Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. Posterior Cord Syndrome at the bite site

Acute neurologic period

Acute neurologic period lasts 2–7 days.

Encephalitic form (most common):

• Hyperactivity Hyperactivity Attention Deficit Hyperactivity Disorder and agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus
• Altered mental status Altered Mental Status Sepsis in Children
  • Confusion
  • Hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia
• Pharyngeal muscle spasms Spasms An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. Ion Channel Myopathy
  • Hydrophobia 
  • Aerophobia
  • Choking
  • Coughing
• Nuchal rigidity Nuchal Rigidity Meningitis
• Muscle fasciculations Fasciculations Involuntary contraction of the muscle fibers innervated by a motor unit. Fasciculations may be visualized as a muscle twitch or dimpling under the skin, but usually do not generate sufficient force to move a limb. They may represent a benign condition or occur as a manifestation of motor neuron disease or peripheral nervous system diseases. Polyneuropathy and contractions
  • Facial grimacing
  • Back and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess hyperextension
• Increased deep tendon reflexes Deep Tendon Reflexes Neurological Examination
• Autonomic instability
  • Hypersalivation
  • Sweating
  • Lacrimation
  • Pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities dilation
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
  • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
• Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures

Paralytic form:

• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
• Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
• Ascending, flaccid paralysis
• Muscle fasciculations Fasciculations Involuntary contraction of the muscle fibers innervated by a motor unit. Fasciculations may be visualized as a muscle twitch or dimpling under the skin, but usually do not generate sufficient force to move a limb. They may represent a benign condition or occur as a manifestation of motor neuron disease or peripheral nervous system diseases. Polyneuropathy
• Absent deep tendon reflexes Deep Tendon Reflexes Neurological Examination
• Bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess dysfunction

Coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma

• Unresponsive
• Periods of rapid, irregular breathing
• Apnea
• Paralysis

Death

• Death usually occurs 2–14 days after 1st symptoms appear.
• Often results from:
  • Respiratory arrest
  • Uncontrolled seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Cardiac arrhythmias

Diagnosis and Management

Diagnosis

The diagnosis should be suspected in cases of unexplained viral encephalitis Viral encephalitis Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of togaviridae infections; herpesviridae infections; adenoviridae infections; flaviviridae infections; bunyaviridae infections; picornaviridae infections; paramyxoviridae infections; orthomyxoviridae infections; retroviridae infections; and arenaviridae infections. Encephalitis with a history of an animal bite. 

Diagnostic methods:

• Antibody titers
• PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) to detect viral RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure
• Isolation of virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology ( viral culture Viral culture West Nile Virus)
• Immunofluorescent staining of biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma specimens for viral antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination

Specimens that can be tested:

• Saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy
• CSF
• Serum
• Tissue ( skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions from the nape of the neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess or brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification)

Management

There is no effective treatment for symptomatic rabies, and few patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship survive.

• Palliative care
• Life support measures can prolong the clinical course but rarely affect the outcome.

Prevention

Prevention is the mainstay of care.

• Vaccinate susceptible species (dogs and cats).
• Preexposure prophylaxis Prophylaxis Cephalosporins with rabies vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination is indicated for:
  • Travel to endemic areas
  • Veterinarians
  • Animal handlers
• Postexposure prophylaxis Prophylaxis Cephalosporins:
  • Local wound cleaning
  • Human rabies immune globulin (HRIG)
    • Given only once to previously unvaccinated people.
    • Provides immediate antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions
    • Inject as much as possible at the bite site (infiltrate into the wounds).
    • Remaining volume should be injected IM at a site distant from vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination administration
  • Rabies vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination:
    • 1st dose given as soon as possible after exposure. 
    • Additional doses are given on days 3, 7, and 14 after the 1st vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination.

Differential Diagnosis

• Bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis: acute infection of the meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges: Anatomy. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, nuchal rigidity Nuchal Rigidity Meningitis, and rapid clinical deterioration. A lumbar puncture Lumbar Puncture Febrile Infant is performed to make the diagnosis. Unlike with viral meningitis Viral meningitis Viral infections of the leptomeninges and subarachnoid space. Togaviridae infections; flaviviridae infections; rubella; bunyaviridae infections; orbivirus infections; picornaviridae infections; orthomyxoviridae infections; rhabdoviridae infections; arenaviridae infections; herpesviridae infections; adenoviridae infections; JC virus infections; and retroviridae infections may cause this form of meningitis. Clinical manifestations include fever, headache, neck pain, vomiting, photophobia, and signs of meningeal irritation. Meningitis, CSF studies will show a turbid fluid, low glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance, and high WBC with neutrophil predominance. Gram stain Gram stain Klebsiella and culture will determine the causative bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology. Treatment includes antibiotics and corticosteroids Corticosteroids Chorioretinitis.
• Herpes simplex Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. Congenital TORCH Infections encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis: severe CNS infection caused by herpes simplex Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. Congenital TORCH Infections viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship develop rapid onset of fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, altered level of consciousness Altered Level of Consciousness Intracerebral Hemorrhage, focal neurologic deficits Neurologic Deficits High-Risk Headaches, and seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures. The diagnosis is confirmed with PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) testing of CSF. MRI may show hyperintense Hyperintense Magnetic Resonance Imaging (MRI) lesions in the temporal lobes. IV acyclovir Acyclovir A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Herpes Zoster (Shingles) is the treatment of choice.
• Tick-borne encephalitis Tick-borne encephalitis Encephalitis caused by neurotropic viruses that are transmitted via the bite of ticks. In europe, the diseases are caused by encephalitis viruses, tick-borne, which give rise to russian spring-summer encephalitis, central european encephalitis, louping ill encephalitis, and related disorders. Powassan encephalitis occurs in north america and russia and is caused by the powassan virus. Aseptic meningitis and rarely encephalitis may complicate colorado tick fever which is endemic to mountainous regions of the Western United States. Tick-borne Encephalitis Virus virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology: member of the genus Flavivirus Flavivirus A genus of flaviviridae containing several subgroups and many species. Most are arboviruses transmitted by mosquitoes or ticks. The type species is yellow fever virus. Tick-borne Encephalitis Virus transmitted primarily by Ixodes ticks Ticks Blood-sucking acarid parasites of the order ixodida comprising two families: the softbacked ticks (argasidae) and hardbacked ticks (ixodidae). Ticks are larger than their relatives, the mites. They penetrate the skin of their host by means of highly specialized, hooked mouth parts and feed on its blood. Ticks attack all groups of terrestrial vertebrates. In humans they are responsible for many tick-borne diseases, including the transmission of rocky mountain spotted fever; tularemia; babesiosis; african swine fever; and relapsing fever. Coxiella/Q Fever. Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship infected with with tick-borne encephalitis Tick-borne encephalitis Encephalitis caused by neurotropic viruses that are transmitted via the bite of ticks. In europe, the diseases are caused by encephalitis viruses, tick-borne, which give rise to russian spring-summer encephalitis, central european encephalitis, louping ill encephalitis, and related disorders. Powassan encephalitis occurs in north america and russia and is caused by the powassan virus. Aseptic meningitis and rarely encephalitis may complicate colorado tick fever which is endemic to mountainous regions of the Western United States. Tick-borne Encephalitis Virus virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology are asymptomatic; however, symptomatic individuals may experience a biphasic illness Biphasic illness Lymphocytic Choriomeningitis Virus. After recovering from nonspecific symptoms, patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship can develop neurologic manifestations, such as meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis, encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis, or meningoencephalitis Meningoencephalitis Encephalitis. Serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus or PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) can confirm the diagnosis. Management is supportive. 
• West Nile virus West Nile Virus West Nile virus is an enveloped, positive-sense, single-stranded RNA virus of the genus Flavivirus. Birds are the primary hosts and the disease is most often transmitted by Culex mosquitoes. Most people infected with West Nile virus are asymptomatic. Some patients develop West Nile fever (a self-limited, febrile illness) and a very small proportion of patients develop West Nile neuroinvasive disease. West Nile Virus: member of the genus Flavivirus Flavivirus A genus of flaviviridae containing several subgroups and many species. Most are arboviruses transmitted by mosquitoes or ticks. The type species is yellow fever virus. Tick-borne Encephalitis Virus transmitted by Culex mosquitoes. Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship infected with West Nile virus West Nile Virus West Nile virus is an enveloped, positive-sense, single-stranded RNA virus of the genus Flavivirus. Birds are the primary hosts and the disease is most often transmitted by Culex mosquitoes. Most people infected with West Nile virus are asymptomatic. Some patients develop West Nile fever (a self-limited, febrile illness) and a very small proportion of patients develop West Nile neuroinvasive disease. West Nile Virus are asymptomatic. A very small proportion of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship develop neuroinvasive disease Neuroinvasive disease West Nile Virus, which includes meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis, encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis, and acute flaccid paralysis Acute flaccid paralysis West Nile Virus. The diagnosis is confirmed with serum or CSF serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus or PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR). Management is supportive. 
• Saint Louis encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology: member of the genus Flavivirus Flavivirus A genus of flaviviridae containing several subgroups and many species. Most are arboviruses transmitted by mosquitoes or ticks. The type species is yellow fever virus. Tick-borne Encephalitis Virus transmitted by Culex mosquitoes. Symptomatic individuals may have varied presentations, with flu-like symptoms Flu-Like Symptoms Babesia/Babesiosis, aseptic meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis, encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis, or meningoencephalitis Meningoencephalitis Encephalitis. Diagnosis is confirmed with serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus. Management is supportive.
• Equine encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology: members of the family Togaviridae Togaviridae A family of RNA viruses, mainly arboviruses, consisting of two genera: alphavirus (group A arboviruses), and rubivirus. Virions are spherical, 60-70 nm in diameter, with a lipoprotein envelope tightly applied to the icosahedral nucleocapsid. Rubella Virus. The equine encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology are mosquito-borne arboviruses Arboviruses Arthropod-borne viruses. A non-taxonomic designation for viruses that can replicate in both vertebrate hosts and arthropod vectors. Included are some members of the following families: arenaviridae; bunyaviridae; reoviridae; togaviridae; and flaviviridae. Encephalitis that can cause minor viral illness or encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis (in severe cases). Diagnosis is by CSF evaluation, serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus, or PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR). Management is supportive.
• Guillain-Barré syndrome Guillain-Barré syndrome Guillain-Barré syndrome (GBS), once thought to be a single disease process, is a family of immune-mediated polyneuropathies that occur after infections (e.g., with Campylobacter jejuni). Guillain-Barré Syndrome ( GBS GBS An acute inflammatory autoimmune neuritis caused by t cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. Polyneuropathy): acute, rapidly progressive, acquired inflammatory neuropathy Neuropathy Leprosy that can be triggered by infectious pathogens. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship develop progressive, symmetric muscle weakness and sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology loss. Unlike rabies, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever is rare in GBS GBS An acute inflammatory autoimmune neuritis caused by t cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. Polyneuropathy. The diagnosis is clinical. A lumbar puncture Lumbar Puncture Febrile Infant will show a normal cell count and elevated protein. Management requires intensive care support, IV immune globulin, and plasma exchange Plasma exchange Removal of plasma and replacement with various fluids, e.g., fresh frozen plasma, plasma protein fractions (ppf), albumin preparations, dextran solutions, saline. Used in treatment of autoimmune diseases, immune complex diseases, diseases of excess plasma factors, and other conditions. Thrombotic Thrombocytopenic Purpura.
• Botulism Botulism Botulism is a rare, neuroparalytic syndrome caused by Clostridium botulinum (C. botulinum). A fatal neurotoxin (botulinum toxin) is released causing varying degrees of muscle paralysis and distinct clinical syndromes. The most common types of botulism are foodborne and infant. Botulism: rare, neuroparalytic syndrome caused by a neurotoxin released from Clostridium botulinum Clostridium botulinum A species of anaerobic, gram-positive, rod-shaped bacteria in the family clostridiaceae that produces proteins with characteristic neurotoxicity. It is the etiologic agent of botulism in humans, wild fowl, horses; and cattle. Seven subtypes (sometimes called antigenic types, or strains) exist, each producing a different botulinum toxin (botulinum toxins). The organism and its spores are widely distributed in nature. Clostridia. Botulism Botulism Botulism is a rare, neuroparalytic syndrome caused by Clostridium botulinum (C. botulinum). A fatal neurotoxin (botulinum toxin) is released causing varying degrees of muscle paralysis and distinct clinical syndromes. The most common types of botulism are foodborne and infant. Botulism presents with blurred vision Blurred Vision Retinal Detachment, respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure, and symmetric, descending flaccid paralysis. Unlike rabies, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever is absent. Diagnosis is made on clinical grounds and can be confirmed by the isolation of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology or toxins from stool, wound specimens, or food sources. Treatment requires prompt management of respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure, administration of antitoxin, and supportive care for paralysis.
• Tetanus Tetanus Tetanus is a bacterial infection caused by Clostridium tetani, a gram-positive obligate anaerobic bacterium commonly found in soil that enters the body through a contaminated wound. C. tetani produces a neurotoxin that blocks the release of inhibitory neurotransmitters and causes prolonged tonic muscle contractions. Tetanus: bacterial infection caused by Clostridium tetani Clostridium tetani The cause of tetanus in humans and domestic animals. It is a common inhabitant of human and horse intestines as well as soil. Two components make up its potent exotoxin activity, a neurotoxin and a hemolytic toxin. Tetanus, a gram-positive Gram-Positive Penicillins obligate anaerobic bacterium commonly found in soil that enters the body through a contaminated wound. Tetanus Tetanus Tetanus is a bacterial infection caused by Clostridium tetani, a gram-positive obligate anaerobic bacterium commonly found in soil that enters the body through a contaminated wound. C. tetani produces a neurotoxin that blocks the release of inhibitory neurotransmitters and causes prolonged tonic muscle contractions. Tetanus presents with lockjaw Lockjaw Spasmodic contraction of the masseter muscle resulting in forceful jaw closure. This may be seen with a variety of diseases, including tetanus, as a complication of radiation therapy, trauma, or in association with neoplastic conditions. Tetanus, neck stiffness Neck Stiffness Meningitis, opisthotonus Opisthotonus Tetanus, rigid abdomen, and severe, painful muscle spasms Spasms An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. Ion Channel Myopathy. Diagnosis is made on clinical grounds, as it is rarely possible to isolate the infectious agent from the wound. Tetanus Tetanus Tetanus is a bacterial infection caused by Clostridium tetani, a gram-positive obligate anaerobic bacterium commonly found in soil that enters the body through a contaminated wound. C. tetani produces a neurotoxin that blocks the release of inhibitory neurotransmitters and causes prolonged tonic muscle contractions. Tetanus is treated with antibiotic therapy and the human tetanus Tetanus Tetanus is a bacterial infection caused by Clostridium tetani, a gram-positive obligate anaerobic bacterium commonly found in soil that enters the body through a contaminated wound. C. tetani produces a neurotoxin that blocks the release of inhibitory neurotransmitters and causes prolonged tonic muscle contractions. Tetanus antitoxin.