Respiratory Syncytial Virus

Classification

General Characteristics

Taxonomy and structure

• Genus Pneumovirus 
• Family Paramyxoviridae
• Single-stranded, linear, negative-sense 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
• Enveloped 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
• Large 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) capsid Capsid The outer protein protective shell of a virus, which protects the viral nucleic acid. Capsids are composed of repeating units (capsomers or capsomeres) of capsid proteins which when assembled together form either an icosahedral or helical shape. Virology 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 in virion

Basic features

• Absence of hemagglutinin Hemagglutinin Agents that cause agglutination of red blood cells. They include antibodies, blood group antigens, lectins, autoimmune factors, bacterial, viral, or parasitic blood agglutinins, etc. Measles Virus
• Consists of 2 serotypes
• Limited to the respiratory tract
• Two subtypes (A and B) are present in outbreaks Outbreaks Sudden increase in the incidence of a disease. The concept includes epidemics and pandemics. Influenza Viruses/Influenza; type A causes more severe disease.

Clinically relevant species

• The Paramyxoviridae family consists of 3 genera:
  • Paramyxovirus Paramyxovirus Mumps Virus/Mumps, which includes the parainfluenza and mumps Mumps Mumps is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. Mumps is typically a disease of childhood, which manifests initially with fever, muscle pain, headache, poor appetite, and a general feeling of malaise, and is classically followed by parotitis. Mumps Virus/Mumps 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 
  • Orthopneumovirus, which includes the respiratory syncytial 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 (RSV)
  • Morbillivirus Morbillivirus A genus of the family paramyxoviridae (subfamily paramyxovirinae) where the virions of most members have hemagglutinin but not neuraminidase activity. All members produce both cytoplasmic and intranuclear inclusion bodies. Measles virus is the type species. Measles Virus, which includes the measles Measles Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles 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
• The Paramyxoviridae family causes 30%–40% of all acute respiratory infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease in infants and children.

Pathogenesis

Transmission and replication cycle

Transmission: 

Respiratory droplets Droplets Varicella-Zoster Virus/Chickenpox from an infected individual come into contact with the mucosa of the eyes, mouth, or nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose and Nasal Cavity: Anatomy of another individual.

Replication cycle:

• Once an individual is exposed, there is a fusion of the viral and host cell membranes.
  • The viral surface glycoproteins Surface glycoproteins Glycoproteins found on the membrane or surface of cells. Human Herpesvirus 8 F and G control viral attachment and the initial stages of infection.
  • The viral nucleocapsid and polymerase enter the host cell cytoplasm.
• 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 transcribes the viral genome Viral genome The complete genetic complement contained in a DNA or RNA molecule in a virus. Virology into mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure, which is translated by host 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.
• The 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 polymerase synthesizes a positive-sense antigenome, a complementary template strand used to construct negative-sense 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.
• The resultant 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 packaged into nucleocapsids and transported to the plasma membrane Plasma 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 for assembly and budding Budding Mycology.

Natural reservoirs

• Humans
• Cattle
• Sheep
• Goats

Pathophysiology

• The infection spreads within the respiratory tract, without systemic spread.
• RSV spreads by cell-to-cell transfer along intracytoplasmic bridges (syncytia) from the upper to the lower respiratory tract (the terminal bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy)
• Lytic viral replication causes epithelial cell sloughing → exposing nociceptive nerve fibers Nerve Fibers Slender processes of neurons, including the axons and their glial envelopes (myelin sheath). Nerve fibers conduct nerve impulses to and from the central nervous system. Nervous System: Histology → stimulating the cough reflex
• Influx of PMNs into the airway Airway ABCDE Assessment → replaced by lymphomononuclear infiltration of the peribronchiolar tissue and increased microvascular permeability → submucosal edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema and swelling Swelling Inflammation
• Mucous secretions increase in quantity and viscosity → widespread mucous plugging

Diseases Caused by Respiratory Syncytial Virus

Although RSV is limited to the respiratory tract, it can manifest as illnesses of varying severity depending on the individual’s age and state of the immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs.

Diseases caused

• Infants:
  • Acute bronchiolitis Bronchiolitis Inflammation of the bronchioles. Pediatric Chest Abnormalities
  • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Acute otitis media Acute Otitis Media Acute otitis media is an infection in the middle ear characterized by mucosal inflammation and retention of fluid. The most common pathogens are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The condition can present with fever, otalgia, and diminished hearing. Acute Otitis Media
  • 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
• Immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis or elderly adults:
  • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Acute exacerbation of underlying chronic illness (e.g., chronic obstructive pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis ( COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD)), asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma, heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR))

Epidemiology

• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: affects 4 million–5 million children < 4 years of age per year
  • Primarily a disease of young infants and children
  • Peak incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency at 2–8 months of age
• > 125,000 patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with RSV infection are hospitalized annually in the United States.
• In mild presentations of RSV, there is an equal incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency among boys and girls.
• However, boys are 2 times more likely to require hospitalization Hospitalization The confinement of a patient in a hospital. Delirium because of RSV infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease.

Risk factors

• Premature infants Premature infants A human infant born before 37 weeks of gestation. Sudden Infant Death Syndrome (SIDS)
• Infants with chronic lung disease
• Children with congenital Congenital Chorioretinitis heart disease
• Low birth weight
• Maternal smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
• No breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding

Clinical presentation

• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus time: 4–5 days
• Upper respiratory tract infection
  • Cough
  • Rhinorrhea
• Lower respiratory tract infection
  • Tachypnea Tachypnea Increased respiratory rate. Pulmonary Examination
  • Intercostal and subcostal retractions
  • Cyanosis Cyanosis A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. Pulmonary Examination
  • Wheezing Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing and rales
  • 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
• Associated with otitis media, dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration, and apneic episodes

Diagnosis

• Laboratory studies are not typically indicated in well-appearing patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who are breathing room air, are well hydrated, and are feeding adequately. 
• RSV-specific diagnostic tests Diagnostic tests Diagnostic tests are important aspects in making a diagnosis. Some of the most important epidemiological values of diagnostic tests include sensitivity and specificity, false positives and false negatives, positive and negative predictive values, likelihood ratios, and pre-test and post-test probabilities. Epidemiological Values of Diagnostic Tests
  • Antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination detection (point-of-care testing)
  • Molecular probes ( 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) assays)
  • Culture
• Antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination detection (point-of-care testing)
• Molecular probes ( 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) assays)
• Culture
• Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests for suspicion of pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia

Management

Supportive care is the mainstay of therapy for RSV infection, including oxygenation and hydration. 

Pharmacologic therapy:

• Generally not recommended by the American Academy of Pediatrics but may be used in select cases.
• In select cases, beta-agonists ( albuterol Albuterol A short-acting beta-2 adrenergic agonist that is primarily used as a bronchodilator agent to treat asthma. Sympathomimetic Drugs), alpha-agonists ( epinephrine Epinephrine The active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. Sympathomimetic Drugs), or corticosteroids Corticosteroids Chorioretinitis may be used
• In patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with significant underlying risk factors (e.g., transplant patients Transplant patients Individuals receiving tissues or organs transferred from another individual of the same or different species, or from within the same individual. Human Herpesvirus 8), ribavirin Ribavirin A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. Antivirals for Hepatitis C is used.

Prophylaxis Prophylaxis Cephalosporins: palivizumab, FDA-approved for children at high risk for severe RSV disease

• Premature infants Premature infants A human infant born before 37 weeks of gestation. Sudden Infant Death Syndrome (SIDS) born at < 29 weeks, < 1 year of age
• Premature infants Premature infants A human infant born before 37 weeks of gestation. Sudden Infant Death Syndrome (SIDS) born at < 32 weeks, < 1 year of age with chronic lung disease
• In the 2nd year of life for children who need supplemental oxygen Supplemental Oxygen Respiratory Failure or long-term corticosteroid or diuretic therapy
• Children < 24 months who have significant congenital Congenital Chorioretinitis heart disease or pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension

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:

• Approved for individuals 60 years and older
• Under review for use during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care

Differential Diagnosis

Acute bronchiolitis Bronchiolitis Inflammation of the bronchioles. Pediatric Chest Abnormalities: respiratory condition caused by inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy. The majority of cases of acute bronchiolitis Bronchiolitis Inflammation of the bronchioles. Pediatric Chest Abnormalities are caused by RSV. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship usually present with upper respiratory symptoms, such as cough and congestion, and later develop lower respiratory signs, including 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, wheezing Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing, crackles, and hypoxia Hypoxia Sub-optimal oxygen levels in the ambient air of living organisms. Ischemic Cell Damage. Diagnosis is clinical, and treatment is directed at improving oxygenation and hydration. The disease is self-limiting Self-Limiting Meningitis in Children and has a good prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas with appropriate management.