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Parainfluenza Virus

Human parainfluenza 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 (HPIVs) are 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 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 of the family Paramyxoviridae Paramyxoviridae A family of spherical viruses, of the order mononegavirales, somewhat larger than the orthomyxoviruses, and containing single-stranded RNA. Subfamilies include paramyxoviridae and pneumovirinae. Respiratory Syncytial Virus and the genus Paramyxovirus Paramyxovirus Mumps Virus/Mumps. Human parainfluenza 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 the 2nd most common cause of lower respiratory disease in children, after 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. Upper 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, including croup Croup Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup, are caused by HPIVs as well, but to a lesser extent. Management of HPIV 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 relies on supportive care, racemic 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, and steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors.

Last updated: Oct 5, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Classification

Rna viruses flowchart classification

RNA virus identification:
Viruses can be classified in many ways. Most viruses, however, will have a genome formed by either DNA or RNA. RNA genome viruses can be further characterized by either a single- or double-stranded RNA. “Enveloped” viruses are covered by a thin coat of cell membrane (usually taken from the host cell). If the coat is absent, the viruses are called “naked” viruses. Viruses with single-stranded genomes are “positive-sense” viruses if the genome is directly employed as messenger RNA (mRNA), which is translated into proteins. “Negative-sense,” single-stranded viruses employ RNA dependent RNA polymerase, a viral enzyme, to transcribe their genome into messenger RNA.

Image by Lecturio. License: CC BY-NC-SA 4.0

General Characteristics

Structure

  • Genus Paramyxovirus Paramyxovirus Mumps Virus/Mumps (now split into Respirovirus and Rubulavirus)
  • Subfamily Paramyxovirinae
  • Family Paramyxoviridae Paramyxoviridae A family of spherical viruses, of the order mononegavirales, somewhat larger than the orthomyxoviruses, and containing single-stranded RNA. Subfamilies include paramyxoviridae and pneumovirinae. Respiratory Syncytial Virus
  • 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 that 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 within virions

Clinically relevant species

  • The family Paramyxoviridae Paramyxoviridae A family of spherical viruses, of the order mononegavirales, somewhat larger than the orthomyxoviruses, and containing single-stranded RNA. Subfamilies include paramyxoviridae and pneumovirinae. Respiratory Syncytial Virus consists of 3 genera:
    • Paramyxovirus Paramyxovirus Mumps Virus/Mumps: includes the parainfluenza 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 (Respirovirus) 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 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 (Rubulavirus) 
    • Pneumovirus Pneumovirus A genus of the family paramyxoviridae (subfamily pneumovirinae) where the human and bovine virions have neither hemagglutinin nor neuraminidase activity. Respiratory syncytial virus, human is the type species. Respiratory Syncytial Virus: 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 RSV Respiratory syncytial virus (RSV) is an enveloped, single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae and the genus Orthopneumovirus. Two subtypes (A and B) are present in outbreaks, but type A causes more severe disease. Respiratory syncytial virus causes infections of the lungs and respiratory tract. Respiratory Syncytial Virus)
    • 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: 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 Paramyxoviridae A family of spherical viruses, of the order mononegavirales, somewhat larger than the orthomyxoviruses, and containing single-stranded RNA. Subfamilies include paramyxoviridae and pneumovirinae. Respiratory Syncytial Virus 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.
  • Human parainfluenza 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 (HPIVs) are currently divided into 5 serotypes on the basis of antigenic and genetic characteristics: 
    • HPIV-1
    • HPIV-2
    • HPIV-3
    • HPIV-4a
    • HPIV-4b
  • The serotypes are classified into 2 different genera: 
    • Respirovirus (HPIV-1 and HPIV-3) 
    • Rubulavirus (HPIV-2 and HPIV-4)
Structure parainfluenza virus

The tertiary structure of human parainfluenza virus type 3

Image: “Fusion glycoprotein trimer, Human parainfluenza virus 3 (hPIV3)” by Yin et al. License: CC BY 4.0

Pathogenesis

Transmission

  • Humans are the only 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.
  • Transmission occurs mainly via airborne respiratory droplets Droplets Varicella-Zoster Virus/Chickenpox that come into contact with the mucous membranes 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.
  • Direct contact with infected fomites Fomites Inanimate objects that carry pathogenic microorganisms and thus can serve as the source of infection. Microorganisms typically survive on fomites for minutes or hours. Common fomites include clothing, tissue paper, hairbrushes, and cooking and eating utensils. Adenovirus is also a frequent route of transmission.
  • Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period: 2–4 days

Virulence Virulence The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its virulence factors. Proteus factors

HPIVs have 6 main 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:

  • Hemagglutinin-neuraminidase (HN): located on the viral surface, responsible for viral attachment and cell entry
  • Fusion protein Fusion protein Proteins that catalyze membrane fusion. Measles Virus: located on the viral surface, responsible for fusion to the host cell and cell entry
  • Matrix protein: located in the viral envelope Envelope Bilayer lipid membrane acquired by viral particles during viral morphogenesis. Although the lipids of the viral envelope are host derived, various virus-encoded integral membrane proteins, i.e. Viral envelope proteins are incorporated there. Virology, responsible for viral assembly
  • Nucleoprotein: located in the nucleocapsid, forms part of 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 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 complex
  • Phosphoprotein: located in the nucleocapsid, forms part of 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 complex
  • Large protein: located in the nucleocapsid, forms part of 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 complex

Replication cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation

  1. Viral replication occurs after entry into a host cell by attachment and fusion with the host’s cellular membrane and is aided by HN and fusion protein Fusion protein Proteins that catalyze membrane fusion. Measles Virus.
  2. The viral nucleocapsid enters the host cell cytoplasm.
  3. Genomic 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 occurs in the cytoplasm via 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 (large protein).
  4. The translation Translation Translation is the process of synthesizing a protein from a messenger RNA (mRNA) transcript. This process is divided into three primary stages: initiation, elongation, and termination. Translation is catalyzed by structures known as ribosomes, which are large complexes of proteins and ribosomal RNA (rRNA). Stages and Regulation of Translation and synthesis Synthesis Polymerase Chain Reaction (PCR) of the 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 are performed by the host’s ribosomes Ribosomes Multicomponent ribonucleoprotein structures found in the cytoplasm of all cells, and in mitochondria, and plastids. They function in protein biosynthesis via genetic translation. The Cell: Organelles.
  5. 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 Positive-sense antigenome A complementary template strand used to construct negative-sense RNA. Respiratory Syncytial Virus, 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, which is then associated with the nucleoprotein.
  6. The 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 packaged into nucleocapsids and transported to the plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products membrane for assembly and budding Budding Mycology
  7. Alternatively, 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 can also be used for subsequent rounds of 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 and replication.

Pathophysiology

HPIVs cause 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 airway Airway ABCDE Assessment through the up-regulation Up-Regulation A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (gene expression regulation), mRNAs, and proteins. Pharmacokinetics and Pharmacodynamics of inflammatory cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response, including:

  • Interferon α (IFN-α) 
  • Interleukins Interleukins Interleukins are a type of cytokines (signaling proteins) that communicate messages between different parts of the immune system. The majority of interleukins are synthesized by helper CD4 T lymphocytes along with other cells such as monocytes, macrophages, and endothelial cells. Interleukins (IL-2, IL-6)
  • Tumor necrosis factor Tumor necrosis factor Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor Necrosis Factor (TNF) α (TNF-α)

Virus-specific IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions 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 mediate the release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of histamine in the respiratory tract, contributing to the symptoms and pathogenesis of croup Croup Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup.

Risk factors

  • 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 state
  • Malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries
  • Overcrowding, such as in nursing facilities and daycare centers
  • Vitamin A Vitamin A Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Fat-soluble Vitamins and their Deficiencies deficiency
  • Lack of 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

Diseases Caused by Human Parainfluenza Viruses

Human parainfluenza 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 mainly limited to the respiratory tract. These 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 have been associated with every type of upper and lower respiratory tract illness. The serotypes can cause illnesses that vary in severity.

  • Serotypes 1 and 2: croup Croup Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup ( laryngotracheobronchitis Laryngotracheobronchitis Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup)
  • Serotype 3: acute bronchiolitis Acute bronchiolitis Acute bronchiolitis is a respiratory condition caused by inflammation of the bronchioles. The condition is a common cause of hospitalization in children in the United States, with the majority of cases caused by respiratory syncytial virus (RSV). Acute Bronchiolitis and 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
  • Serotype 4: mild cold-like syndrome
  • Rarely, HPIVs have been associated with febrile 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, viral 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, and 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.
Table: Diseases caused by HPIVs
Serotype Diseases caused Main clinical features
HPIV-1 and 2 Croup Croup Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup ( laryngotracheobronchitis Laryngotracheobronchitis Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup)
  • Infection of the lower respiratory tract
  • Mainly affects children 2–5 years of age
  • Clinical presentation:
    • 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
    • Coryza Coryza Inflammation of the nasal mucosa, the mucous membrane lining the nasal cavities. Rhinitis
    • Intercostal and subcostal retractions Subcostal retractions Respiratory Syncytial Virus
    • Tachypnea Tachypnea Increased respiratory rate. Pulmonary Examination
    • Irritability
    • “Seal bark” cough
    • Inspiratory stridor Stridor Laryngomalacia and Tracheomalacia
    • Tracheal swelling Swelling Inflammation with “ steeple sign Steeple Sign Pediatric Chest Abnormalities” on 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
HPIV-3 Acute bronchiolitis Acute bronchiolitis Acute bronchiolitis is a respiratory condition caused by inflammation of the bronchioles. The condition is a common cause of hospitalization in children in the United States, with the majority of cases caused by respiratory syncytial virus (RSV). Acute Bronchiolitis and 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
  • Mainly affects infants or 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/elderly patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Clinical presentation:
    • 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
    • Coryza Coryza Inflammation of the nasal mucosa, the mucous membrane lining the nasal cavities. Rhinitis
    • Tachypnea Tachypnea Increased respiratory rate. Pulmonary Examination
    • Coughing
    • 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
HPIV-4a and 4b Mild cold-like syndrome
  • May be asymptomatic
  • Clinical presentation:
    • Coryza Coryza Inflammation of the nasal mucosa, the mucous membrane lining the nasal cavities. Rhinitis
    • Nasal congestion
    • Mild cough

Epidemiology

  1. In the United States, by 1 year of age 50% of children and by age 6 almost all children have been infected with HPIV-3.
  2. 80% of children have 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 for HPIV-1 and HPIV-2 by age 10.
  3. Although HPIV-4 causes few clinical illnesses, 70%–80% of children have 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 by age 10.
  4. Morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status rates are higher in developing countries.

Diagnosis

  • Isolation and identification Identification Defense Mechanisms of 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 in cell culture
  • Direct detection of 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 in respiratory secretions by ELISA ELISA An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. St. Louis Encephalitis 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)
  • IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions 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
  • A significant increase in IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis 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 between collected paired serum specimens
  • X-rays X-rays X-rays are high-energy particles of electromagnetic radiation used in the medical field for the generation of anatomical images. X-rays are projected through the body of a patient and onto a film, and this technique is called conventional or projectional radiography. X-rays of the neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess or chest are important if epiglottitis Epiglottitis Epiglottitis (or “supraglottitis”) is an inflammation of the epiglottis and adjacent supraglottic structures. The majority of cases are caused by bacterial infection. Symptoms are rapid in onset and severe. Epiglottitis, croup Croup Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup, or 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 is suspected.
    • In croup Croup Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup, the “ steeple sign Steeple Sign Pediatric Chest Abnormalities” is seen on a 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; this formation is caused by subglottic swelling Swelling Inflammation with narrowing of the trachea Trachea The trachea is a tubular structure that forms part of the lower respiratory tract. The trachea is continuous superiorly with the larynx and inferiorly becomes the bronchial tree within the lungs. The trachea consists of a support frame of semicircular, or C-shaped, rings made out of hyaline cartilage and reinforced by collagenous connective tissue. Trachea: Anatomy.
    • In epiglottitis Epiglottitis Epiglottitis (or “supraglottitis”) is an inflammation of the epiglottis and adjacent supraglottic structures. The majority of cases are caused by bacterial infection. Symptoms are rapid in onset and severe. Epiglottitis, the “thumb sign” is seen on lateral neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess views; the condition is due to enlargement of the epiglottis Epiglottis A thin leaf-shaped cartilage that is covered with laryngeal mucosa and situated posterior to the root of the tongue and hyoid bone. During swallowing, the epiglottis folds back over the larynx inlet thus prevents foods from entering the airway. Larynx: Anatomy and ballooning Ballooning Varicella-Zoster Virus/Chickenpox of the hypopharynx.
Steeple sign

Chest X-ray showing subglottic stenosis, known as steeple sign (between red arrows)

Image: “Steeple sign” by Jayshil J. Patel, Emily Kitchin, and Kurt Pfeifer. License: CC BY 4.0

Management

Management depends on the severity of the disease.

Mild croup Croup Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup:

  • Supportive care
  • Cool blow-by oxygen mist
  • 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 control

Moderate croup Croup Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup:

  • Cool oxygen mist
  • Corticosteroids Corticosteroids Chorioretinitis for the airway Airway ABCDE Assessment 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
  • Racemic 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 with a nebulizer
  • IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids for hydration

Severe croup Croup Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup:

Clinical Relevance

  • Croup Croup Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup: also known as laryngotracheobronchitis Laryngotracheobronchitis Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup: Croup Croup Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup is a disease that leads to severe 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 upper airway Airway ABCDE Assessment, and it usually presents in children < 5 years of age. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship develop a hoarse, “seal-like” barking cough and inspiratory stridor Stridor Laryngomalacia and Tracheomalacia. Human parainfluenza 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 account for the majority of cases, followed by RSV RSV Respiratory syncytial virus (RSV) is an enveloped, single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae and the genus Orthopneumovirus. Two subtypes (A and B) are present in outbreaks, but type A causes more severe disease. Respiratory syncytial virus causes infections of the lungs and respiratory tract. Respiratory Syncytial Virus, adenovirus Adenovirus Adenovirus (member of the family Adenoviridae) is a nonenveloped, double-stranded DNA virus. Adenovirus is transmitted in a variety of ways, and it can have various presentations based on the site of entry. Presentation can include febrile pharyngitis, conjunctivitis, acute respiratory disease, atypical pneumonia, and gastroenteritis. Adenovirus, rhinovirus Rhinovirus Rhinovirus is an acid-labile, positive-sense RNA virus of the Picornavirus family. The virus, which causes the common cold, is most often acquired through the airway via the inhalation of aerosols containing rhinovirus and fomites. Rhinovirus, and enteroviruses. Croup Croup Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup is usually diagnosed clinically or with 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 imaging ( steeple sign Steeple Sign Pediatric Chest Abnormalities). Management consists of steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors and 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.
  • Acute bronchiolitis Acute bronchiolitis Acute bronchiolitis is a respiratory condition caused by inflammation of the bronchioles. The condition is a common cause of hospitalization in children in the United States, with the majority of cases caused by respiratory syncytial virus (RSV). Acute Bronchiolitis: 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 Acute bronchiolitis Acute bronchiolitis is a respiratory condition caused by inflammation of the bronchioles. The condition is a common cause of hospitalization in children in the United States, with the majority of cases caused by respiratory syncytial virus (RSV). Acute Bronchiolitis are caused by RSV RSV Respiratory syncytial virus (RSV) is an enveloped, single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae and the genus Orthopneumovirus. Two subtypes (A and B) are present in outbreaks, but type A causes more severe disease. Respiratory syncytial virus causes infections of the lungs and respiratory tract. Respiratory Syncytial Virus. 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-limited 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.
  • 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: infection of the lower respiratory tract that results in air sacs filling with fluid or pus. Symptoms 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 include cough with phlegm, 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, chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever, and difficulty breathing. For management of bacterial causes, antibiotics are indicated. Some forms 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 can be prevented by vaccines.

References:

  1. Ison, M. (2020). Parainfluenza viruses in adults. UpToDate. Retrieved February 8, 2021, from: https://www.uptodate.com/contents/parainfluenza-viruses-in-adults
  2. Munoz, F. (2020). Parainfluenza viruses in children. UpToDate. Retrieved February 8, 2021, from: https://www.uptodate.com/contents/parainfluenza-viruses-in-children#H14
  3. Parijua, S. (2020). Human parainfluenza viruses (HPIV) and other parainfluenza viruses treatment & management. Emedicine. Retrieved February 8, 2021, from: https://emedicine.medscape.com/article/224708-treatment#d9

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