Mumps Virus

Enveloped RNA Viruses

• Paramyoxviruses include Mumps and Measles viruses.

Mumps Virus

• Mumps is an acute contagious disease characterized by enlargement of one or both salivary glands.
• Mostly a mild childhood disease.
• In adults, it can cause complications like meningitis which is most common.
• Over one-third of all mumps infections are asymptomatic.
• Mumps occurs endemically worldwide
• Cases appear throughout the year in hot climates and peak in the winter and spring in temperate climates.
• Infection of children, with the highest incidence in children ages 5-9 years.
• Outbreaks occur where crowding favors dissemination of the virus.
• In children younger than 5 years, mumps may commonly cause upper respiratory tract infection without parotitis.
• Mumps is quite contagious; most susceptible individuals in a household will acquire infection from an infected member.
• The virus is transmitted by direct contact, airborne droplets, or fomites contaminated with saliva.
• Closer contact is necessary for transmission compared to measles or varicella.
• About one-third of infections with mumps virus are inapparent.
• Patients can transmit the virus inapparent, and individuals with subclinical mumps acquire immunity.
• The overall mortality rate for mumps is low (one death per 10,000 cases), mostly caused by encephalitis.
• The incidence of mumps and associated complications has declined markedly since introduction of the live-virus vaccine.
• Humans are are the only natural hosts for mumps.
• Primary replication occurs in nasal or upper respiratory tract epithelial cells.
• Viremia then disseminates the virus to the salivary glands and other major organ systems.
• Involvement of the parotid gland is not obligatory in the infectious process.
• The incubation period may range from 2 to 4 weeks but is typically about 14–18 days and is shed in the saliva from about 3 days before to 9 days after the onset of salivary gland swelling.
• About one-third of infected individuals do not exhibit obvious symptoms but are capable of transmitting infection.
• Difficult to control transmission due to variable incubation periods, presence of virus in saliva before symptoms, and many asymptomatic but infectious cases.
• The central nervous system is also commonly infected, even without parotitis.
• At least 1/3 of all mumps infections are subclinical, including the majority in children < 2 years.
• Swelling of the salivary glands is the most characteristic feature of symptomatic cases, happening in about 50% of patients.
• A prodromal period of malaise and anorexia is followed by rapid enlargement of parotid glands, as well as other salivary glands.
• Gland enlargement is associated with pain.
• CNS involvement is common (10-30% of cases).
• Mumps causes aseptic meningitis and is more common among males than females.
• The mortality rate from mumps encephalitis is about 1%.
• Pancreatitis is reported in about 4% of cases.
• Immunity is permanent after a single infection.
• There is only one antigenic type of mumps virus, which does not exhibit significant antigenic variation.
• Passive immunity is transferred from mother to offspring, so it is rare to see mumps in infants younger than 6 months.
• The diagnosis of typical cases can usually be made on the basis of clinical findings.
• In cases without parotitis, the laboratory can be helpful in establishing the diagnosis via Nucleic Acid Detection by RT-PCR, Isolation and Identification of Virus, and Serology (antigen and antibody).
• There is no specific therapy.
• Immunization with attenuated live mumps virus vaccine is the best way to reduce rates of mumps-associated morbidity and mortality.
• Attempts to minimize viral spread during an outbreak by using isolation procedures are ineffective because of the high incidence of asymptomatic cases.
• Students and health care workers should be excluded from school and work until 5 days after parotitis onset.
• Mumps vaccine produces a subclinical, noncommunicable infection.
• It's available combined with measles and rubella (MMR) live-virus vaccines produce antibodies to each of the viruses in 78-95% of vaccines.
• There is no increased risk of aseptic meningitis after MMR vaccination.

Measles Virus

• Acute, highly infectious disease, with fever, respiratory symptoms, and a maculopapular rash (after the patient is no longer infectious).
• Complications are common and may be quite serious.
• Vaccine introduction has dramatically reduced the incidence of this disease.
• Measles is still a leading cause of death of young children in many developing countries.
• The key epidemiologic features of measles: highly contagious, single serotype, no animal reservoir, and lifelong immunity after infection.
• Prevalence and age incidence are related to population density, economic and environmental factors, and vaccine use.
• Transmission occurs mainly via the respiratory route, by inhalation of large droplets of infected secretions.
• Fomites appear to not play a significant role.
• Transplacental transmission is possible when measles occurs during pregnancy.
• Measles cases occur throughout the year in temperate climates; epidemics tend to occur in late winter and early spring.
• It is endemic throughout the world; before vaccination, epidemics recurred every 2-3 years.
• The severity of an epidemic is a function of the number of susceptible individuals.
• When the disease is introduced into isolated communities where it has not been endemic, an epidemic builds rapidly and attack rates are almost 100%.
• Mortality may be as high as 25% across all age groups in this scenario.
• In industrialized countries, measles occurs in childen, and it commonly infects younger children in developing countries.
• Measles rarely causes death in healthy people in developed countries.
• In malnourished children in developing countries, measles is a leading cause of infant mortality.
• Those with immunologic disorders are at risk of severe or fatal measles.
• In 2005, the WHO estimated 30–40 million measles cases and 530,000 deaths annually worldwide.
• The WHO established plan in 2005 to reduce measles mortality.
• Measles deaths were estimated to be reduced by more than 75% between 2000 and 2008 thanks to vaccination programs.
• Hard-fought gains can be lost without sustained attention and outbreaks still occur where children are unvaccinated.
• There were more than 140,000 measles deaths globally in 2018, mostly among children under five.
• Measles elimination is threatened because the disease has resurged in multiple countries per WHO in 2018.
• There were 5000 measles cases have been recorded in Egypt in 2015, compared to 1740 cases in the same period in 2014.
• In 2018, Measles deaths in Egypt reached 141, or 0.03% of total deaths, according to the latest WHO data.
• To sustain measles transmission elimination, vaccine coverage rates need to exceed 90%.
• Infants less than 1 year old are at particular risk for severe complications where the first dose of vaccine is given at 12-15 months.
• Gaining access to the human body via the respiratory tract, the virus multiplies locally and then spreads to the regional lymphoid tissue, where it continues to multiply.
• Primary viremia disseminates the virus, followed by secondary viremia.
• The secondary viremia seeds the epithelial surfaces of the body, including the skin, respiratory tract, and conjunctiva, where focal replication occurs.
• Measles can replicate in lymphocytes, which aids in dissemination throughout the body.
• Multinucleated giant cells with intranuclear inclusions are seen in lymphoid tissues throughout the body.
• These occur during the incubation period, which typically lasts 8-15 days but may last up to 3 weeks in adults.
• Patients are contagious during prodromal phase (2-4 days) and the first 2-5 days of the rash
• Virus is present in tears, nasal and throat secretions, urine, and blood.
• The characteristic maculopapular rash appears around day 14 and circulating antibodies become detectable, viremia disappears, and fever falls.
• The rash is a result of interaction of immune T cells with virus-infected cells in blood vessels and lasts about 1 week, but those with defective cell-mediated immunity do not develop a rush.
• CNS involvement is common.
• Infections in nonimmune hosts are almost always symptomatic.
• Measles has an incubation period of 8-15 days from exposure to rash.
• The prodromal phase has fever, sneezing, coughing, running nose, redness of the eyes, Koplik spots, and lymphopenia.
• Cough reflects reaction involving the mucosa of the respiratory tract.
• Conjunctivitis is commonly associated with photophobia.
• Koplik spots are small, bluish white ulcerations on the buccal mucosa opposite molars.
• Have giant cells and viral antigens and appear slightly before the rash.
• The fever and cough persist until the rash appears and then subside within 1-2 days.
• The rash starts on the head then spreads progressively to the chest, trunk, and limbs.
• Begins light pink, becomes brownish in 5–10 days, and fading rash resolves with desquamation.
• Modified measles occurs in partially immune persons.
• The incubation period is prolonged, symptoms are diminished, Koplik spots are absent, and the rash is mild.
• Otitis media is the most common complication of measles
• Pneumonia caused by secondary bacterial infection is the most common life-threatening complication.
• It occurs in fewer than 10% of cases in developed countries but is much more frequent in developing countries.
• Pulmonary complications account for more than 90% of measles-related deaths; viral pneumonia fatalities is rare
• Complications involving the CNS are serious.
• Infection confers lifelong immunity; most so-called second attacks represent errors in diagnosis.
• The presence of humoral antibodies indicates immunity.
• Measles immune responses are involved in disease pathogenesis.
• Local inflammation causes prodromal symptoms, and specific cell-mediated immunity plays a role in rash development.
• Measles infection causes immune suppression, primarily in the cell-mediated arm, but affects all components, leading to secondary infections and potentially persisting for months.
• Typical measles is reliably diagnosed on clinical grounds, but lab diagnoses are needed in cases of atypical measles.
• Measles antigens can be detected directly in epithelial cells from secretions and urine.
• Antibodies to nucleoprotein are useful because it is the most abundant viral protein.
• Detection of viral RNA by RT-PCR is a sensitive method for measles diagnosis.
• Nasopharyngeal and conjunctival swabs, blood samples, respiratory secretions, and urine collected from a patient during the febrile period are the proper sources for viral isolation.
• Cytopathic effects can be used to detect infections.
• Vitamin A treatment in developing countries has decreased mortality and morbidity.
• Measles virus is susceptible in vitro to inhibition by ribavirin, but clinical benefits have not been proved.
• Vaccination has been available, but the failure to vaccinate children and cases of vaccine failure have kept it from being eliminated.
• 94% of children aged 12-23 had received measles vaccinations in 2017.
• From 2008 to 2009 in Egypt, there was a 53% increase from 2007 where 95% of children had been vaccinated.
• Mild reactions occur in 2-5% of vaccines, but there is little/no virus excretion and no transmission.
• Antibody titers tend to be lower than after natural infection, but studies have shown that vaccine-induced antibodies persist for up to 33 years, indicating that immunity is likely lifelong.
• All children, health care workers, and international travelers are recommended to be vaccinated.
• Contraindications to vaccination: pregnancy, allergy to eggs or neomycin, immune compromise, and recent administration of immunoglobulin.
• Quarantine is ineffective against measles because transmission occurs during the prodromal phase.

Rabies Virus

• A preventable acute viral disease of the CNS that is almost always fatal.
• It is a zoonotic virus disease usually transmitted to humans from the bite of a rabid animal.
• Despite the small number of human cases, it is a major public health problem due to its prevalence among animal reservoirs.
• The main reservoir includes dogs and stray cats.
• Wild carnivores like foxes and wolves carry and transmit rabies.
• Bats are another key reservoir.
• After inoculation, it may replicate locally but then travel within neurons to the brain
• Once in the brain, it replicates primarily in the gray matter.
• Rabies virus can enter the nervous system and progressive encephalitis develops.
• The virus then spreads through peripheral nerves to the salivary glands, leading to further transmission through a bite from an infected animal.
• Susceptibility to infection and incubation period depending on the host's age, immune status, inoculum amount, laceration severity, and the distance entry point to the central nervous system.
• There is a higher attack rate and shorter incubation period in persons bitten on the face or head.
• There is lowest mortality in those bitten on the legs.
• Incubation period is 1-8 weeks and may range up to several months or even years following exposure.
• 3 phases are Prodromal, acute neurological (mania), and coma (convulsive seizures/coma and death).
• The major cause of death is respiratory paralysis.
• Clinical illness may start with an abnormal sensation at the bite site, then progress to a fatal encephalitis and neuronal degeneration.
• Symptoms include hallucinations, seizures, weakness, mental dysfunction, paralysis, coma, and death.
• Classical rabies is hydrophobia: the patient's painful inability to swallow liquids (pharyngeal spasms).
• Death is unavoidable once symptoms begin.
• To diagnose a rabid animal, detection of Negri bodies in cytoplasm of brain cells, identify virus antigens using immunofluorescence or through RT-PCR from saliva.
• Inoculation of the virus from the animal brain and saliva into mice will results in death.
• Post rabies, there is no effective treatment.
• For prophylaxis, a killed vaccine is available but it can cause an adverse reaction.
• There are two vaccine formulations approved by the FDA.
• Pre-exposure prophylaxis is indicated for high-risk individuals, like veterinarians.
• Management of a person bitten by an animal involves wound care such as washing with soap & water, alcohol and tincture iodine.
• If available, the animal should be kept under observation for 10 days post bite.
• Rabies is excluded, If the animal survives this period, or in which case symptoms appear if found to be rabid.
• Post-exposure immunization depends on the site and severity of the bite and availability of the suspected animal.
• If the animal is proved to be rabid, there is no further management necessary when the bite is peripheral, an animal is available, and survived for 10 days.
• Immunization is given when the animal is not available or with a severe bite.
• Human rabies immunoglobulin (HRIG) provides immediate protection.
• Rabies vaccine is given on the day of exposure and then again on days 3, 7, and 14.
• Vaccination of domestic animals, controlling and removing stray animal poulations as well as vaccination of specific groups are methods for rabies.

Filoviridae (Ebola Virus)

• Ebola causes zoonotic infections and It is highly communicable via exposure to blood or other body fluid
• First isolated from a patient with hemorrhagic fever in Zaire.
• Marked by widespread bleeding into the skin, mucous membrane, visceral organ, and GIT.
• Its immunosuppressive and has a mortality rate greater than 50%.
• The death thought to be due to visceral organ necrosis.
• There is no specific treatment.
• Strict barrier techniques are essential when caring for infected individuals.
• To prevent Ebola, avoid contact with the viruses, wash your hands frequently, avoid contact with infected people, and follow infection-control procedures.
• Specially organized and trained teams should bury remains using appropriate safety equipment, and bodies of those who have died are contagious.

Enveloped DNA Viruses: Poxviruses

• Variola virus (Smallpox)
• It was the 1st disease to be eliminated by vaccination.
• Vaccine was introduced in 2003 for military and medical personnel.
• Transmission is through inhalation or skin contact.
• Symptoms are fever, malaise, and rash.
  • Vaccination up to 4 days post-exposure can prevent/attenuate clinical symptoms.
  • Supportive care is treatment such as adequate fluid intake, relieving pain & fever and aggressive treatment of secondary infections
  • Antiviral therapy is experimental (Cidofovir).

Enveloped DNA Viruses: Herpesviridae

Herpes Simplex

• Transmission is by direct contact with virus in secretions.
• Two immunologic types: HSV1 and HSV2.
• HSV1 causes Herpes febrilis, Eczema Herpeticum, Gingivostomatitis, Keratoconjunctivitis, Meningoencephalitis and meningitis.
  • HSV2: Genital tract infections in women is associated with cervical carcinoma.
    • There is currently no specific cure.
    • Treatment focuses on getting rid of sores and limiting outbreaks, but in some cases, your sores will disappear without treatment.
    • Acyclovir, Famciclovir, and Valacyclovir are used for treatment to help infected individuals reduce the risk of spreading the virus and to lower the intensity & frequency of outbreaks.

Varicella Zoster Virus (Chickenpox)

• Transmission: easily spread from person to person by respiratory droplet and direct contact.
• Humans are the only natural host.
• Treatment: self limited but Acyclovir and interferon may be used.
• Prevention: live attenuated vaccine (optional).
• The US Food and Drug Administration (FDA) approved the Varizig (Cangene) in 2012, for reducing the severity of chickenpox infections (high-risk individuals when given within 4 days of exposure).

Non-Enveloped DNA Viruses: Adenoviruses

• These are icosahedral viruses that commonly cause respiratory tract infection, gastroenteritis, and conjunctivitis.
• Mode of transmission: droplet----respiratory; direct inoculation of contaminated objects with virus into eye------- ocular infections.
• They can be isolated easily from a large number of different species.
• Adenoviral vectors rapidly infect a broad range of human cells and yields high levels of gene transfer.
• They have low pathogenicity in humans.
• These vectors are relatively easy to manipulate using recombinant DNA techniques.