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Rubella Virus

Rubella (also known as German 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 or three-day 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) is caused by a single-stranded, positive-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 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 of the Matonaviridae family and the Rubivirus genus. Rubella only infects humans and spreads prenatally via vertical transmission Vertical transmission The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. Congenital TORCH Infections or postnatally via droplet contact. Congenital Congenital Chorioretinitis rubella is particularly devastating and is associated with a classic triad of symptoms: cataracts, cardiac defects, and deafness. Infection in children and adults may be mild and present with constitutional symptoms Constitutional Symptoms Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis along with a viral exanthem Exanthem Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke's disease), fifth (erythema infectiosum), and sixth (exanthema subitum) numeric designations survive as occasional synonyms in current terminology. Varicella-Zoster Virus/Chickenpox resembling 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. Diagnosis is made clinically and confirmed with serum 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 detection and serologic studies. Treatment is supportive and may be targeted depending on the organ system involved. Prevention is achieved through childhood 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 with 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, 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, and rubella ( MMR MMR A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the base pair mismatch and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. Lynch syndrome) 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.

Last updated: Dec 12, 2023

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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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

Serotypes, lineages, and strains:

  • Matonaviridae family: Rubella is the only matonavirus using humans as the sole, natural host.
  • Rubivirus genus: Rubella 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 is the only member of the Rubivirus genus.
  • Serotype:
    • A serotype is defined by the number and type of surface antigens a microorganism possesses.
    • Only 1 genetically stable rubella serotype has been identified. 
  • Lineage:
    • A lineage is a collection of variants defined by novel mutations delineating a specific genetic line 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.
    • At least 3 distinct lineages have arisen from the single rubella serotype.
  • Strain:
    • A strain is a lineage acquiring new properties as a result of the mutations defining the lineage.
    • Multiple strains of the rubella 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 characterized by different antigenicities, which are the ability of antigens to bind BIND Hyperbilirubinemia of the Newborn to antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination 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 an antibody or T cell.

Rubella virion

Structure:

  • Spherical
  • 40–80 nm in diameter
  • The lipoprotein 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 contains 2, spike-forming, membrane glycoproteins Glycoproteins Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. Basics of Carbohydrates:
    • E1 E1 An aromatized C18 steroid with a 3-hydroxyl group and a 17-ketone, a major mammalian estrogen. It is converted from androstenedione directly, or from testosterone via estradiol. In humans, it is produced primarily by the cyclic ovaries, placenta, and the adipose tissue of men and postmenopausal women. Noncontraceptive Estrogen and Progestins mediates viral hemagglutination and neutralization.
    • E2 has 2 subtypes:
      • E2a and E2b
      • E2 glycoprotein variations confer the differences between rubella strains.
    • Spikes also contain 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 epitopes Epitopes Sites on an antigen that interact with specific antibodies. Vaccination, which cause RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology to clump together (hemagglutination).
  • A 30–35 nm electron-dense core:
    • Positive-sense, single-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
    • 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 protein C surrounds 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.

Rubella 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

  • Only a single, stable rubella serotype has been identified.
  • Very little variation between strains of rubella 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 
  • Suggestive of a low rate of mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations during viral replication
  • The strains are readily identified worldwide, which suggests constant cocirculation of lineages.
Electron micrograph of rubella virus

Electron micrograph of virions of the rubella virus

Image: “This transmission electron microscopic (TEM) image revealed the presence of rubella virus virions” by CDC. License: Public Domain

Epidemiology and Pathogenesis

Epidemiology

  • 1964–1965: Over 12 million cases of rubella and 20,000 cases of congenital Congenital Chorioretinitis rubella are recorded in the United States.
  • 1969: 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 introduced in the United States → cases dropped to 0.5 cases per 100,000
  • 1990–1991: resurgence outbreaks Outbreaks Sudden increase in the incidence of a disease. The concept includes epidemics and pandemics. Influenza Viruses/Influenza in California and Pennsylvania
  • 2004: rubella eliminated from the United States due to 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, 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, rubella ( MMR MMR A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the base pair mismatch and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. Lynch syndrome) 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
  • 2018: 14,621 cases globally
  • 2019: 168 countries with established 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 programs

Transmission

  • Respiratory droplets Droplets Varicella-Zoster Virus/Chickenpox:
    • Direct or droplet contact with respiratory secretions of infected patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
    • 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 replicates in the cells of the respiratory tract.
    • Viral shedding Viral shedding The expelling of virus particles from the body. Important routes include the respiratory tract, genital tract, and intestinal tract. Hepatitis A Virus from the respiratory tract may continue for up to 6 weeks after the initial infection.
    • Relatively low infectivity and 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
  • Vertical (mother to child):
    • During the 1st 3–4 months of 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 as one of the TORCH ( toxoplasmosis Toxoplasmosis Toxoplasmosis is an infectious disease caused by Toxoplasma gondii, an obligate intracellular protozoan parasite. Felines are the definitive host, but transmission to humans can occur through contact with cat feces or the consumption of contaminated foods. The clinical presentation and complications depend on the host’s immune status. Toxoplasma/Toxoplasmosis, other agents, rubella, cytomegalovirus Cytomegalovirus CMV is a ubiquitous double-stranded DNA virus belonging to the Herpesviridae family. CMV infections can be transmitted in bodily fluids, such as blood, saliva, urine, semen, and breast milk. The initial infection is usually asymptomatic in the immunocompetent host, or it can present with symptoms of mononucleosis. Cytomegalovirus, 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) 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:
      • TORCH 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 may also include HIV HIV Anti-HIV Drugs or syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis
      • Constitute the most common 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 spread via vertical transmission Vertical transmission The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. Congenital TORCH Infections
    • May occur during 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

Pathogenesis

Prenatal:

  • Direct viremia Viremia The presence of viruses in the blood. Erythema Infectiosum via placental transmission
  • Outcome depends on gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care and is likely due to immature fetal host defenses.
  • Risk of infection and associated congenital Congenital Chorioretinitis defects decreases with gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care:
    • 40%–60% chance if the mother is infected during the 1st 2 months of gestation
    • 30%–35% chance during the 3rd month of gestation
    • 10% chance during the 4th month of gestation
  • Virions may affect virtually any fetal organ system.

Postnatal:

Postnatal primary 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 with rubella undergo a sequential Sequential Computed Tomography (CT) pathogenic process:

  1. Inoculation through the respiratory tract
  2. Attachment to respiratory tract cell membranes (entry of the virion into the host cell occurs via transportation into endosomes)
  3. Multiplication in host cell cytoplasm over 2–3 weeks
  4. Exocytosis Exocytosis Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. The Cell: Cell Membrane via an unclear mechanism
  5. Infiltration of local lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy, causing constitutional symptoms Constitutional Symptoms Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis and lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy
  6. Development of viremia Viremia The presence of viruses in the blood. Erythema Infectiosum ( 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 is detected in the blood and respiratory secretions)
  7. Multiplication in the cells of other organs
  8. Development 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 and rash Rash Rocky Mountain Spotted Fever (rubella-specific 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 detected in the blood)
  9. Before rash Rash Rocky Mountain Spotted Fever resolution, disappearance of detectable 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 the blood as the 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 surge
  10. 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 confer future immunity, but reinfection can occur.

Clinical Presentation

Congenital Congenital Chorioretinitis rubella

  • Congenital Congenital Chorioretinitis rubella syndrome with the classic triad:
    • Cataracts
    • Cardiac defects
    • Deafness
  • Congenital Congenital Chorioretinitis rubella infection (broader term to encompass all possible signs and symptoms of infection):
    • Ocular: cataracts, microphthalmia, glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma, and retinitis
    • Cardiovascular: patent ductus arteriosus Ductus arteriosus A fetal blood vessel connecting the pulmonary artery with the descending aorta. Patent Ductus Arteriosus (PDA), atrial septal defect Atrial Septal Defect Atrial septal defects (ASDs) are benign acyanotic congenital heart defects characterized by an opening in the interatrial septum that causes blood to flow from the left atrium (LA) to the right atrium (RA) (left-to-right shunt). Atrial Septal Defect (ASD), ventricular septal defect Ventricular Septal Defect Tetralogy of Fallot, and pulmonary artery Pulmonary artery The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. Lungs: Anatomy stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS)
    • Central nervous system Central nervous system The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. Nervous System: Anatomy, Structure, and Classification: intellectual disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment, meningoencephalitis Meningoencephalitis Encephalitis, microcephaly Microcephaly A congenital abnormality in which the cerebrum is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (desk reference for neuroscience, 2nd ed. ). Fetal Alcohol Spectrum Disorder, and progressive rubella panencephalitis (rare)
    • Other: growth retardation Growth Retardation Failure of a fetus to attain expected growth. Fetal Alcohol Spectrum Disorder, radiolucent Radiolucent An object of low density that is permeable to X-rays (looks black) X-rays bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types disease, hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus, thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia, pneumonitis Pneumonitis Human Herpesvirus 6 and 7, diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus, thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel’s thyroiditis). Thyroiditis, petechiae Petechiae Primary Skin Lesions, and purpura (a “blueberry muffin rash Rash Rocky Mountain Spotted Fever” due to extramedullary hematopoiesis Extramedullary Hematopoiesis Primary Myelofibrosis in the 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)

Postnatal rubella

  • Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period of 2–3 weeks (may ultimately be asymptomatic (50% of cases))
  • Symptoms:
    • 1–2 weeks after exposure: 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, malaise Malaise Tick-borne Encephalitis Virus, myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus, lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy, myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus, and arthralgias
    • Up to 1 week after initial symptoms:
      • 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 and maculopapular Maculopapular Dermatologic Examination rash Rash Rocky Mountain Spotted Fever
      • Exanthem Exanthem Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke’s disease), fifth (erythema infectiosum), and sixth (exanthema subitum) numeric designations survive as occasional synonyms in current terminology. Varicella-Zoster Virus/Chickenpox: begins on the face and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, spreads caudally
      • Resembles the exanthem Exanthem Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke’s disease), fifth (erythema infectiosum), and sixth (exanthema subitum) numeric designations survive as occasional synonyms in current terminology. Varicella-Zoster Virus/Chickenpox of 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
Exanthem of rubella virus infection

Typical exanthem of rubella infection:
Spread and distribution are similar to measles, however, the lesions are less intensely red and less confluent.

Image: “This photograph shows the appearance of the German measles (rubella) rash.” by Parker N et al. License: CC BY 4.0, cropped by Lecturio.

Diagnosis, Management, and Prevention

Diagnosis

Diagnosis is made clinically and confirmed with serum 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 detection and serologic studies. 

  • Congenital Congenital Chorioretinitis infection commonly involves a triad of cataracts, cardiac defects, and deafness, which are detected in the newborn Newborn An infant during the first 28 days after birth. Physical Examination of the Newborn period.
  • Congenital Congenital Chorioretinitis infection can be confirmed in a newborn Newborn An infant during the first 28 days after birth. Physical Examination of the Newborn by viral detection from cord blood, nasopharyngeal secretions, or urine.
  • Congenital Congenital Chorioretinitis infection is more commonly confirmed using RT-PCR RT-PCR A variation of the pcr technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard pcr protocols. Polymerase Chain Reaction (PCR) to detect rubella 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 in the amniotic fluid Amniotic fluid A clear, yellowish liquid that envelopes the fetus inside the sac of amnion. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (amniocentesis). Placenta, Umbilical Cord, and Amniotic Cavity prior to birth.
  • 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 can also be detected from nasopharyngeal secretions of pregnant patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.
  • For postnatal cases, rubella-specific 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 can be detected using enzyme immunoassay Enzyme immunoassay HIV Infection and AIDS as early as 4 days after the rash Rash Rocky Mountain Spotted Fever onset.

Management and prevention

Treatment is supportive and targeted based on the organ system involved. Prevention is achieved through MMR MMR A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the base pair mismatch and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. Lynch syndrome or MMRV ( 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, 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, rubella, varicella) 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.

  • 1st dose at 12–15 months of age, 2nd dose at 4–6 years of age for either 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
  • Infection confers immunity; however, cases of reinfection have been documented.

Comparison of Common Childhood Rashes

Table: Comparison of common childhood rashes Rashes Rashes are a group of diseases that cause abnormal coloration and texture to the skin. The etiologies are numerous but can include irritation, allergens, infections, or inflammatory conditions. Rashes that present in only 1 area of the body are called localized rashes. Generalized rashes occur diffusely throughout the body. Generalized and Localized Rashes
Number Other names for the disease Etiology Description
1st disease 1st disease 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
  • 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
  • Rubeola Rubeola 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
  • 14-day measles 14-day 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
  • Morbilli Morbilli 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
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 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
  • Cough, coryza Coryza Inflammation of the nasal mucosa, the mucous membrane lining the nasal cavities. Rhinitis, conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis
  • Koplik’s spots (blue-white spots with a red halo) on the buccal membrane
  • Maculopapular Maculopapular Dermatologic Examination rash Rash Rocky Mountain Spotted Fever begins on the face and behind the ears → spreads to trunk/extremities
2nd disease
  • Scarlet Fever Scarlet fever Infection with group a Streptococci that is characterized by tonsillitis and pharyngitis. An erythematous rash is commonly present. Scarlet Fever
  • Scarlatina Scarlatina Infection with group a Streptococci that is characterized by tonsillitis and pharyngitis. An erythematous rash is commonly present. Scarlet Fever
Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus pyogenes
3rd disease
  • Rubella
  • German 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
  • 3-day 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
Rubella 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
  • Asymptomatic in 50% of cases
  • Fine macular rash Rash Rocky Mountain Spotted Fever on the face (behind the ears) → spreads to the neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, trunk, and extremities (spares palms/soles)
  • Forscheimer’s spots: Pinpoint red macules and petechiae Petechiae Primary Skin Lesions can be seen over the soft palate Soft palate A movable fold suspended from the posterior border of the hard palate. The uvula hangs from the middle of the lower border. Palate: Anatomy/ uvula Uvula A fleshy extension at the back of the soft palate that hangs above the opening of the throat. Peritonsillar Abscess.
  • Generalized tender lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy
4th disease
  • Staphylococcal scalded skin syndrome Staphylococcal Scalded Skin Syndrome Staphylococcal scalded skin syndrome (SSSS), also known as Ritter disease and staphylococcal epidermal necrolysis, is a toxin-mediated condition caused by Staphylococcus aureus. The exfoliative toxin produced disseminates and cleaves desmoglein 1 in the epidermis, causing separation and detachment of the skin. Staphylococcal Scalded Skin Syndrome (SSSS)
  • Filatow-Dukes’ disease
  • Ritter’s disease
Due to Staphylococcus aureus Staphylococcus aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. Brain Abscess strains that make epidermolytic (exfoliative) toxin
  • Some believe that 4th disease is a misdiagnosis and, thus, nonexistent.
  • The term was dropped in the 1960s and is only used for medical trivia today.
  • Begins with a diffuse erythematous rash Rash Rocky Mountain Spotted Fever that usually starts around the mouth → fluid-filled bullae Bullae Erythema Multiforme or cutaneous blisters → rupture and desquamate
  • Nikolsky’s sign: Applying pressure on the 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 with a finger (stroking) results in sloughing off of upper layers.
5th disease Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion infectiosum Erythrovirus or parvovirus B19 Parvovirus B19 Primate erythroparvovirus 1 (generally referred to as parvovirus B19, B19 virus, or sometimes erythrovirus B19) ranks among the smallest DNA viruses. Parvovirus B19 is of the family Parvoviridae and genus Erythrovirus. In immunocompetent humans, parvovirus B19 classically results in erythema infectiosum (5th disease) or “slapped cheek syndrome.” Parvovirus B19 (Primate erythroparvovirus Erythroparvovirus Parvovirus B19 1)
  • Facial erythema (“slapped-cheek” rash Rash Rocky Mountain Spotted Fever) that consist of red papules on the cheeks Cheeks The part of the face that is below the eye and to the side of the nose and mouth. Melasma
  • Begins on the face → spreads to the extremities → extends to trunk/buttocks
  • Initially confluent, then becomes net-like or reticular as it clears
6th disease
  • Exanthem Exanthem Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke’s disease), fifth (erythema infectiosum), and sixth (exanthema subitum) numeric designations survive as occasional synonyms in current terminology. Varicella-Zoster Virus/Chickenpox subitum
  • Roseola infantum Roseola infantum An acute, short-lived, viral disease of infants and young children characterized by a high fever at onset that drops to normal after 3-4 days and the concomitant appearance of a macular or maculopapular rash that appears first on the trunk and then spreads to other areas. It is the sixth of the classical exanthematous diseases and is caused by HHV-6. Human Herpesvirus 6 and 7
  • Rose rash Rash Rocky Mountain Spotted Fever of infants
  • 3-day 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
Human herpesvirus 6B or 7
  • Sudden onset of high 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
  • Nagayama spots: papular spots on the soft palate Soft palate A movable fold suspended from the posterior border of the hard palate. The uvula hangs from the middle of the lower border. Palate: Anatomy/ uvula Uvula A fleshy extension at the back of the soft palate that hangs above the opening of the throat. Peritonsillar Abscess
  • Rash Rash Rocky Mountain Spotted Fever begins as 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 resolves (the term “ exanthem Exanthem Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke’s disease), fifth (erythema infectiosum), and sixth (exanthema subitum) numeric designations survive as occasional synonyms in current terminology. Varicella-Zoster Virus/Chickenpox subitum” describes “surprise” of rash Rash Rocky Mountain Spotted Fever after the 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 subsides).
  • Numerous rose-pink, almond-shaped macules on the trunk and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess → sometimes spreads to face/extremities

References:

  1. Parkman PD. (1996). Togaviruses: Rubella Virus. In Baron S (Ed). Medical Microbiology. (4th ed). https://www-ncbi-nlm-nih-gov.online.uchc.edu/books/NBK8200/
  2. Frey TK. (1994). Molecular biology of rubella virus. Advances in virus research, 44, 69–160. https://doi-org.online.uchc.edu/10.1016/s0065-3527(08)60328-0
  3. CDC. Rubella. In: Epidemiology and Prevention of Vaccine-Preventable Diseases, 12th Ed, Atkinson W, Wolfe C, Hamborsky (Eds), Public Health Foundation, Washington, DC 2011.
  4. WHO fact sheet. Rubella. http://www.who.int/en/news-room/fact-sheets/detail/rubella
  5. Grant GB, Desai S, Dumolard L, Kretsinger K, & Reef SE. (2019). Progress Toward Rubella and Congenital Rubella Syndrome Control and Elimination – Worldwide, 2000-2018. MMWR. Morbidity and mortality weekly report, 68(39), 855–859. https://doi-org.online.uchc.edu/10.15585/mmwr.mm6839a5
  6. Miller S. (2015). Paramyxoviruses and Rubella Virus. In Brooks JE, et al. (Eds.), Jawetz, Melnick, & Adelberg’s Medical Microbiology. (27th ed). [VitalSource Bookshelf 9.4.3]. 
  7. Edwards MS. (2021). Rubella. UpToDate. Retrieved April 26, 2021, from https://www.uptodate.com/contents/rubella

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