Viral Infections: Measles

Viral Infections: Measles

• Measles virus is a single-stranded, lipid-enveloped RNA virus belonging to the Paramyxoviridae family and Morbillivirus genus.
• Hemagglutinin (H) and fusion (F) proteins are the two most important structural proteins in inducing immunity.
• Neutralizing antibodies target H protein, and the antibodies to the F protein limit the virus proliferation during infection.
• Entry occurs via the respiratory tract or conjunctivae, through contact with suspended large or small-droplet aerosols.
• Patients are infectious from 3 days before to 4-6 days after the rash onset.
• Histology reveals intracellular edema and dyskeratosis associated with epidermal syncytial giant cell formation with up to 26 nuclei.
• Lymphoid hyperplasia is prominent in lymphoreticular tissue.
• Fusion of infected cells results in multinucleated giant Warthin-Finkeldey cells, pathognomonic for measles, containing up to 100 nuclei, cytoplasmic and intranuclear inclusions.
• Measles consists of the incubation period, prodromal illness, exanthematous phase, and recovery.
• Primary viremia disseminates the virus to the reticuloendothelial system.
• Secondary viremia spreads the virus to body surfaces.
• Koplik spots, enanthem, are pathognomonic and appear 1-4 days before the rash.
• Symptoms intensify for 2-4 days until the first day of the rash, then subside.
• The rash fades over about 7 days similarly as it evolved, at times leading to desquamation of the skin.
• Cough is the longest-lasting symptom, persisting up to 10 days.
• A subclinical form may occur in individuals with passively acquired antibodies and recipients of blood products.
• Those with inapparent or subclinical measles do not shed the virus or transmit infection to household contacts.
• Children who received formalin-inactivated measles vaccines showed a more severe form called atypical measles.
• Identification of immunoglobulin M (IgM) antibody in serum is the most convenient way to provide Serologic confirmation.
• IgM antibodies appear 1-2 days after the rash onset and remain detectable around 1 month.
• Complications are largely attributable to the effects of the virus on the respiratory tract and immune system.
• Morbidity and mortality are highest in patients aged <5 years (especially <1 year) and >20 years.
• Demonstration of a fourfold rise in IgG antibodies in acute and convalescent specimens collected 2-4 weeks later may also give serologic confirmation.
• Pneumonia is the most common cause of measles death.
• Giant cell pneumonia may be caused directly by measles or as superimposed bacterial infection.
• Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus are common bacterial pathogens.
• The final common pathway to a fatal outcome following severe measles pneumonia is often the development of bronchiolitis obliterans.
• Acute otitis media is the most common complication.
• Encephalitis is a postinfectious, immunologically mediated process, not directly effected by the virus.
• In rare cases, hemorrhagic measles or "black measles" manifests as hemorrhagic skin eruption and is often fatal.
• Antiviral therapy is ineffective in measles.
• Vitamin A treatment is recommended for children 6 months-2 years hospitalized with measles and its complications (like croup, pneumonia, and diarrhea). -It is also recommended for children >6 months with measles not already receiving Vitamin A with risk factors like immunodeficiency, Vitamin A deficiency, impaired intestinal absorption, malnutrition or recent immigration from high-mortality areas.
• A single dose of 200,000 IU orally is administered for children ≥1 year, 100,000 IU for children 6 months-1 year, and 50,000 IU for infants <6 months.
• The dose should be repeated the next day and again 4 weeks later for children with ophthalmologic evidence of Vitamin A deficiency.
• Patients shed measles virus from 7 days after exposure to 4-6 days after the onset of rash.
• Measles vaccine is available as a monovalent preparation or combined with rubella (MR) or measles-mumps-rubella (MMR) vaccine, the latter being recommended.
• The current recommendation gives the first dose at 12-15 months followed by a second dose at 4-6 years.
• The vaccine is effective if given within 72 hours of exposure, and immune globulin may be given up to 6 days after to prevent/modify infection.
• Immune globulin is indicated for susceptible household contacts, ages <6 months, pregnant women, and immunocompromised persons.
• Subacute sclerosing panencephalitis (SSPE) is a chronic complication of measles with delayed onset and a nearly always fatal outcome.
• SSPE results from persistent infection with altered measles virus harbored intracellularly in the CNS for years.
• After 7-10 years, the virus regains virulence and attacks CNS cells that once protected it.
• SSPE pathogenesis remains enigmatic.
• Clinical manifestations begin insidiously 7-13 years after measles infection.
• Subtle behavioral changes or school performance issues appear (irritability, reduced attention span, temper outbursts).
• The hallmark of stage two is massive myoclonus.
• Stage three is defined by involuntary movements disappearing, replaced by choreoathetosis, immobility, dystonia, and lead-pipe rigidity as a result of destruction of deeper centers in the basal ganglia.
• Stage four is characterized by loss of the critical centers that support breathing, heart rate, and blood pressure.
• SSPE diagnosis happens through documentation of a compatible clinical course and at least 1 of 3 supporting findings: (1) measles antibodies detected in CSF, (2) characteristic electroencephalographic findings, and (3) isolation of virus/viral antigen from brain tissue.
• CSF analysis reveals normal cells but elevated IgG and IgM antibody titers in dilutions >1:8.
• Electroencephalographic patterns are normal in stage 1, but in the myoclonic phase, suppression-burst episodes are sometimes seen.
• Most die within 1-3 years of onset from infection or loss of autonomic control mechanisms.

Viral Infections: Rubella

• Rubella virus, also German measles or 3-day measles, belongs to the Togaviridae family.
• It is a single-stranded RNA virus with a lipid envelope and 3 structural proteins.
• The Rubella enzyme immunosorbent assay tests for IgM as a supportive measure.
• The period of highest communicability is 5 days before to 6 days after the rash appearance.
• Chronicity is the most distinctive feature of congenital rubella.
• The first manifestation is a rash.
• Forchheimer spots are tiny, rose-colored lesions on the soft palate.
• The rash fades as it extends to the rest of the body
• Encephalitis is the most common complication of postnatal rubella.
• Nerve deafness is the single most common finding in congenital rubella syndrome (CRS).
• Salt-and-pepper retinopathy is the most common ocular abnormality.
• Patients must be isolated for 7 days after the rash onset.
• Immune globulin is not recommended.
• The MMR vaccine is available for Rubella.
• Deafness is seen In 67% of children with congenital rubella syndrome following maternal rubella.
• Ocular issues, specifically cataracts, are seen in 71% and retinopathy in 29% of reported cases.
• Heart disease is seen in 48% of children with congenital rubella syndrome following maternal rubella specifically patent ductus arteriosus (78%), right pulmonary artery stenosis (70%), left pulmonary artery stenosis(56%), and valvular pulmonic stenosis (40%).
• Low birthweight is seen in 60% of children with maternal rubella.
• Psychomotor retardation is seen in 45% of children with congenital rubella syndrome following maternal rubella.
• Neonatal pupura is seen in 23% of children with congenital rubella syndrome following maternal rubella..
• Death is seen in 35% of children with congenital rubella syndrome following maternal rubella.

Viral Infections: Mumps

• Mumps is characterized by fever, bilateral or unilateral parotid swelling and tenderness, as well as frequent meningoencephalitis and orchitis.
• Mumps virus belongs to the Paramyxoviridae family and the Rubulavirus genus.
• It is a single-stranded pleomorphic RNA virus encapsulated in a lipoprotein envelope with possessing seven structural proteins.
• The two surface glycoproteins, HN (hemagglutinin-neuraminidase) and F (fusion), mediate the absorption of and penetration into host cells, respectively.
• The virus appears in saliva from up to 7 days before and 7 days after parotid swelling onset.
• The period of maximum infectiousness is 1-2 days before and 5 days after parotid swelling onset.
• Mumps virus targets the salivary glands, central nervous system (CNS), pancreas, testes, and, to an extent, thyroid, ovaries, heart, kidneys, liver, and joint synovia.
• The incubation period ranges from 12-25 days, but is usually 16-18 days.
• The typical patient presents with a 1-2 day prodrome of fever, headache, vomiting, and achiness.
• Parotitis appears unilaterally at first, then bilaterally in ~70% of cases.
• Parotid swelling peaks in ≈3 days, and then gradually subsides over 7 days.
• Confirmation is made by evaluating elevated serum amylase.
• The virus can be isolated from upper respiratory tract secretions, cerebral spinal fluid, or urine during the acute illness.
• A significant increase in serum mumps immunoglobulin G (IgG) antibody between acute and convalescent serum specimens is detected via complement fixation, neutralization hemagglutination, or enzyme immunoassay (EIA) tests, the latter establishing the diagnosis.
• Purulent parotitis, often caused by Staphylococcus aureus, is unilateral and extremely tender with elevated white blood cell counts, and may involve purulent drainage from Stensen duct.
• The most common complications are meningitis (with or without encephalitis) and gonadal involvement.
• Maternal infection with mumps during the 1st trimester results in increased fetal wastage.
• Mumps virus is neurotropic and is thought to enter the CNS via the choroid plexus, infecting choroidal epithelium and ependymal cells, both of which can be found in CSF along with mononuclear leukocytes.
• Symptomatic CNS involvement occurs in 10-30% of infected individuals, and CSF pleocytosis is found in 40-60% of patients suffering mumps parotitis.
• Meningoencephalitis commonly manifests 5 days following the parotitis.
• In adolescent and adult males, orchitis is second only to parotitis as a common finding.
• Orchitis is often bilateral in ≤30% of cases.
• Testes atrophy may occur; however, sterility is rare, even with bilateral involvement.
• Pancreatitis may occur with or without parotid involvement.
• Management should reduce pain associated with meningitis/orchitis and encourage adequate hydration.
• Immunization with the live mumps vaccine is the primary method of prevention.
• Administered as part of the MMR 2-dose vaccine schedule, with the 1st dose at 12-15 months and the 2nd at 4-6 years of age.
• Acceptable presumptive evidence of immunity consists of 1 of 4 criteria: (1) documentation of adequate vaccination, (2) laboratory evidence of immunity, (3) birth before 1957, and (4) documentation of physician-diagnosed mumps.

Viral Infections: Nonpolio Enteroviruses

• Nonpolio Enteroviruses are non-enveloped, single-stranded, positive-sense viruses in the Picornaviridae ("small RNA virus") family.
• The viruses include the genera Rhinovirus and Hepatovirus, and Parechovirus, and contain related animal viruses.
• Humans are the only known reservoir for human enteroviruses.
• The incubation period is typically 3-6 days, but for acute hemorrhagic conjunctivitis, the incubation is 1-3 days.
• The development of circulating type-specific neutralizing antibodies serves as the most important immune defense, mediating prevention against and recovery from infection.
• The most common symptomatic manifestation across all forms is nonspecific febrile illnesses, especially in infants and young children.
• Hand-foot-and-mouth disease arises from coxsackievirus A16.
• Herpangina manifests with sudden fever onset, sore throat, dysphagia, and oral lesions.
• Epidemics of acute hemorrhagic conjunctivitis are caused primarily by enterovirus 70 and coxsackievirus A24/A24, spread by eye-hand-fomite-eye transmission.
• Enteroviruses account for approximately 25-35% of cases of myocarditis and pericarditis with proven cause.
• Enteroviruses account for the most cases of viral meningitis in mumps-immunized populations.
• Enteroviruses are also responsible for ≈10-20% of cases of encephalitis with an identified cause.
• Characteristic enterovirus infections include hand-foot-mouth disease, herpangina lesions, consistent seasonality, and known enterovirus exposure.
• Viral culture using a combination of cell lines is the gold standard for confirmation.
• In the absence of a proven antiviral agent for enterovirus infections, supportive care is the mainstay of treatment.

Viral Infections: Parvovirus B19

• Named Erythema infectiosum or fifth disease, this is caused by the human parvovirus, a single-stranded DNA virus.
• The viral exanthem is benign in healthy children.
• Erythrocyte stem cells are divided by the virus with cell death, which results in anemia.
• The initial stage typically is apparent by erythematous cheeks, appearing as a "slapped cheek" rash with circumoral pallor.
• The virus is sexually transmitted via respiratory secretions as well as through blood transfusions.
• The normal incubation period is typically 4 to 14 days but can, in rare cases, last for 21 days.
• In general, parvovirus B19 typically starts with a mild, nonspecific illness characterized by fever, fatigue, muscle aches, and headaches.
• Erythroid stem cells are produced by the virus, which replicates leading to cell death.
• As a result, Erythroid aplasia is an outcome and product of these occurrences.
• Some instances have shown the rash to occur 7 to 10 days later after the beginning of illness.
  • Erythema infectiosum presents itself through rash, low-grade/nonexistent fever, and at times mild conjunctivitis/pharyngitis.
  • An erythematous symmetric maculopapular truncal rash appears 1 to 4 days later, but after fading takes place, a distinguishing lacy reticulated rash that lasts 2 to 40 days may occur.
  • The truncal rash stage may be itchy, does not naturally peel when scratched, and can occur with exercise, bathing, or stress.
• In children who are erythrocytes, the body needs to maintain the shortened lifespan for the red blood cells via consistent function.
• Patients who become infected from parvovirus B19 may produce mild anemia and mild fever.
• There is no specific therapy and IV immunoglobulin may be used for immunocompromised people who have anemia.
• Parvovirus B19 is not teratogenic; however, in utero infection may result in hydrops fetalis and heart failure, and fetal death.
• 50% of women of childbearing age are affected by developing Parvovirus B19.
  • The greatest risk is if women encounter infected children aged 5 to 7. This often occurs at school, daycare, and/or at household.
  • Often, children, when displaying the described effects, are naturally noninfectious and are not advised to stay home from school,

Viral Infections: Herpesviruses

• Acyclovir, valacyclovir, and fanciclovir
• Reduce the transmission via caesarian section.
• The DNA encodes at least 84 proteins.
• The virus culture gold standard.
• PCR can be performed for the diagnosis.
• Inactivate components
• Recurrent HSV-1 Infections.
• The common site of herpes labiallis.
  • The vermillion border of the lip.
  • Mollaret meningitis

Viral Infections: Varicella-Zoster

• Varicella-Zoster is a herpesvirus.
• It is neurotropic human.
• It is DNA Enveloped with double-stranded.
• The distribution can be centripenal or central.
• Tzanck smear can allow for diagnosis.
• Foscarnet is used for treatment of acyclovir-resistant infections.
• Acyclovir is also used to treat Varicella-Zoster.
• Varicella vaccine is also an option
• Congenital Varicella Syndrome skin scarring, limb hypoplasia, and abnormalities can be adverse effects of infection.

Viral Infections: Epstein-Barr Virus

• The virus is a gamma-herpesvirus
• The virus can induce infectious mononucleosis
• The infection presents similarly to that of Glandular Fever
• The Classic Triad includes that of fatigue, atypical lymphocytes transformation, and general lymphadenopathy
• Epstein-Barr Virus was the first associated with viruses that induce malignancy
• LADS is 90%
• Classic physical examinations can reveal generalized LADS (90%), splenomegaly (50%), hepatomegaly (10%)
• Symptoms includes fever, generalized fatigue and swollen glands.
• The illness can be treated using ampicillin/amoxicillin
• The Gianotti-Crosti syndrome rashes in symmtery
  • This presents in the cheeks
  • Multiple erythematous papules

Viral Infections: Human Herpes Viruses 6 and 7

• Roseola is of the Roseolavirus type
• It is within the Betaherpesvirinae types of human herpesviruses
• It can integrate into chromosomes, and is also known as exanthem subitum or sixth disease
• Lower than average white blood cell counts with lymphocytes and neutrophils
• Abrupt onset of high fever
• Ulcers can be indicative of an infection
• The infection is high fever
• The main care to treat is supportive

Viral Infections: Respiratory Syncytial Virus

• Is a major cause of bronchiolitis and viral pneumonia in children
• This can be assessed for diagnostics.
  • Important diagnostics
• The Virus is an enveloped RNA genome with a single infection.
• Identification may present bacterial components from the infection.
• There are many stages that can be identified via imaging and assessments.

Viral Infections: Rotavirus

• Causes diarrhea and rotavirus spreads to 11 people cause the infection due to the fecal infection.
• There is a vaccine available
• Good hygiene to prevent it.

Viral Infections: Dengue fever

• Transmitted by Dengue mosquitoes after 3-4 days.
• Dengue virus is characterized by fever, rash, and muscle and joint pains.
• The hemorrhagic symptoms include Pancytopenia
  • Hemorrhage can result in increased fluid release.

Viral Infections: Rabies

• Bullet shaped single stranded RNA virus
• It's a vector for diseases, typically in dogs, with rates above 90% transmission
• The rabies virus is transmissible through saliva via bites, scratches
• People bitten by a rabid animal have 35-50% chance of contraction.
• Transmission is increased through open wounds.
• Post viral replication, muscle contraction will occur.
• Through replication, the infection will quickly infect the brain
• If left unattended for extended incubation periods and no exposure to rabies, head will express symptoms.
• Hydrophobia is the most commonly diagnosed symptom
• Diagnosis is through biopsies of skin and/or the brain if suspected.
• Through education, primary prevention starts against rabies.
• Nimodipine is recommended against rabies in some cases.