Lec 22 Mumps, Measles & Rubella PDF

OUTLINE # MEASLES, MUMPS, AND RUBELLA I. MEASLES A. General Features B. Structures C. Viral Replication D. Pathogenesis E. Clinical Presentation F. Diagnosis G. Epidemiology H. Treatment II. MUMPS A. General Characteristics B. Structure C. Spikes D. Epidemiology E. Clinical Presentation F. Pathoge...

OUTLINE # MEASLES, MUMPS, AND RUBELLA I. MEASLES A. General Features B. Structures C. Viral Replication D. Pathogenesis E. Clinical Presentation F. Diagnosis G. Epidemiology H. Treatment II. MUMPS A. General Characteristics B. Structure C. Spikes D. Epidemiology E. Clinical Presentation F. Pathogenesis G. Complications H. Laboratory Diagnosis I. Treatment and Prevention III. RUBELLA A. General Features B. Structure C. Epidemiology D. Pathogenesis E. Clinical Presentations F. Diagnosis G. Treatment and Prevention IV. REVIEW QUESTIONS V. APPENDIX 1 1 1 1 2 2 2 4 4 5 6 6 6 6 6 7 7 7 8 8 8 8 8 9 9 9 10 10 11 12 MEASLES ● ‘Measles’ – derived from a Middle English word, ‘Maseles’ ● Morbilli (genus Morbillivirus) is a diminutive of morbus, a disease which signifies a minor disease ● Highly contagious, viral infection ○ In 1980, before widespread vaccination, measles caused an estimated 2.6 million deaths each year ● Remains one of the leading causes of death among young children globally despite the availability of safe and effective vaccine ○ An estimated of 164,000 people died from measles in 2008, mostly children under the age of 5 ● Family: Paramyxovirus or Paramyxoviridae ○ Normally grows in cells that line the back of the throat and lungs ● It is a human disease and is not known to occur in animals GENERAL FEATURES ● Family Paramyxoviridae, subfamily Paramyxovirinae, genus Morbillivirus ● Also called Rubeola ● Negative ssRNA, enveloped, helical nucleocapsid ● Transmitted by respiratory secretions ○ Spread by coughing and sneezing via close personal contact or direct contact with the respiratory secretions Figure 1. Measles virus, SSPE 1/1000 cases, electron micrograph, measles virions[Lacuna, 2023] ● Other characteristics: ○ One serotype ■ Only a single serotype restricted to human infections is recognized ○ Humans as only natural host ○ Maybe related to other animal strains ■ Canine distemper and rinderpest in cattle ■ Seals, dolphins, horses ■ Can cause serious disease in natural species ○ Subtle antigenic and genetic variations among wild type of measles strains occur ■ Determined by sequencing analysis enabling more precise epidemiologic tracking of outbreaks and their origins ■ Such ongoing molecular surveillance is extremely important in determining whether significant antigenic drifts evolve over time STRUCTURE ● Measles virus encodes at least 6 virion structural proteins ● Structural Proteins ○ Proteins complexed with the viral RNA ■ Nucleoprotein (N) ● Forms helical nucleocapsid ● Major internal protein ■ Viral Polymerase Protein (P and L) ● Involved in viral polymerase activity and functions in transcription and RNA replication ■ Envelope ● H protein ○ Hemagglutinin ○ Type of glycoprotein projections (peplomers) ○ Mediates absorption to cell surfaces ● F protein ○ Fusion ○ Type of glycoprotein projections (peplomers) ○ Hemolysis ○ Mediates cell fusion, hemolysis, and viral entry to the cell ● M protein ○ Matrix ○ Plays a key role in viral assembly ○ The receptor for measles virus is CD-46 or Membrane Cofactor Protein ■ Regulator for complement activation ■ Virus attaches to CD-46 Figure 2. Structure of measles virus[Lacuna, 2023] PH152: MICROBIO | GROUP D & E: Beltran, Bernal, Bustos, Cruz, Manuel, Morales, Panganiban, Parallag 1 VIRAL REPLICATION ● Virus attachment, penetration & uncoating, and transcription & translation → RNA replication and maturation ● Cellular receptor: CD-46 molecule ○ Bind certain components of the complement 1. Virus attachment, penetration, and uncoating ○ Virus attaches to host cell via the H glycoprotein (although the viral attachment protein has hemagglutinating activity, it lacks neuraminidase) ○ Hemagglutinin agglutinates RBC; most important virulence factor needed to bind to the respiratory mucosal receptors and induce viral entry ○ Fusion protein (at neutral pH of the extracellular environment) allows release of viral nucleocapsid directly into the cell ○ Fusion protein facilitates uptake of the virion ○ RNA carries the information needed to make new virus cells 2. Transcription, translation, and RNA replication ○ The mRNA is made in the cytoplasm by viral RNA polymerase ○ The viral protein is synthesized in the cytoplasm ○ P and L proteins are responsible for viral genome replication ○ Regards termination signals within the gene boundaries which negates the possibility of gene reshuffling ○ Penetration occurs ○ Inside the cytoplasm, there is disassembly and replication 3. Maturation ○ Budding from the cell surface ○ Intranuclear inclusions due to the F protein ○ F protein will cause fusion of adjacent cell membranes (syncytium formation with the cytoplasmic inclusions) ○ The measles virus replication in tissue culture and certain organs of the intact organism is characterized by the formation of giant multinucleated cells (syncytium formation), resulting from the action of the viral spike F protein ○ Budding and maturation reflects sites of viral synthesis ■ Have been found to be recognizable nucleocapsid and viral proteins ○ After maturation, it will be released outside of the cell, infect another cell and repeat the replication process there ● Virus is shed from nasopharynx during prodrome until 3 to 4 days after onset of rash ● Measles virus infection causes a generalized immunosuppression marked by a decrease in the delayed type hypersensitivity ● Interleukin production and antigen specific lymphoproliferative responses persist for weeks to months after acute infection ● Immunosuppression may predispose individuals to secondary opportunistic infections (complications, bacterial infections, or other viral infections), particularly bronchopneumonia, a major cause of measles-related mortality among young children. CLINICAL PRESENTATION ● Incubation period: 10 to 12 days ● Prodromal ○ Period between the appearance of initial symptoms and the full development of rash or fever ● Appearance of rashes is the characteristic sign of measles ○ Can be inhibited by the immunoglobulin ○ Manifestations: ■ High fever ■ Cough, coryza, and conjunctivitis ■ Koplik’s spot ● Appearance of Maculopapular Rash ○ Begins on face and head and spreads rapidly to trunk and limbs within 24 to 48 hours ○ Manifestation of generalized infection ○ Can rise sharply at 40℃ ○ In every case, bronchitis, pneumonitis with cough and crackles in the chest if evident ○ Occasionally, diarrhea in the early stages indicates inflammatory lesions of the gut ○ Within 2 to 3 days of the onset, the rash starts to fade and temperature subsides ● Recovery in 10-14 days ○ Desquamation of skin Figure 4. Koplik’s Spot [Lacuna, 2023] Figure 3. Measles replication[Lacuna, 2023] PATHOGENESIS ● Infection is transmitted via respiratory droplets (respiratory transmission) which can remain active and contagious either airborne or on surfaces up to 2 hours ● Initial infection via replication occur locally in tracheal and bronchial epithelial cells ● Replication at the nasopharynx will cause the primary viremia ○ Primary viremia: 2 to 4 days after exposure ■ After 2 to 4 days, measles virus infects local lymphatic tissues carried by pulmonary macrophages → amplification of measles virus in medial lymph nodes → disseminates to various organs prior to the appearance of rash (indication of secondary viremia) ● Further replication, there will be a secondary viremia with subsequent spread to other tissues ○ Secondary viremia: 5 to 7 days after exposure with spread to other tissues ● Replication of virus at the nasopharynx and regional lymph nodes PRODROMAL ● Period of infection to the appearance of the rash which is about 2 weeks or less by a few days ● Lasts for 2 or 3 days ● Characterized by: ○ Fever ○ Sneezing ○ Coughing and coryza ■ intense inflammatory reaction of the mucosa of the respiratory tract ○ Running nose (and eyes) ○ Redness of the eyes ○ Koplik’s spots ■ Pathognomonic for measles ● Found in the buccal mucous membrane adjacent to the molar teeth ● Resembles grain of salt just beneath the mucosa ○ Lymphopenia ■ low levels of lymphocytes in the blood PH152:MICROBIO | GROUP D & E: Beltran, Bernal, Bustos, Cruz, Manuel, Morales, Panganiban, Parallag 2 APPEARANCE OF RASH ● Light pink or dull red, discrete maculopapules that coalesce to form blotches ○ May have a purpuric appearance if severe ● Starts on the head, spreads progressively to the trunk, down the limbs in the next 2 days ● Becomes brownish in 5 to 10 days ● Skin returns to normal afterward ○ No scarring Figure 8. 9-month-old with low grade fever and rash [Lacuna, 2023] Figure 5. Appearance of Rash [Lacuna, 2023] EXANTHEM PERIOD ● Maculopapular rash ○ Not due to the cytopathic effect of the virus but due to the interaction of immune T cells with virus-infected cells in the small blood vessels. ■ Reaction of the cytotoxic T cells against the viral antigen appearing in the skin cells ○ Is also a result of antigen-antibody complexes formed on the capillary endothelium with consequent cell damage, vasodilation, and leakage of the plasma ○ Rash is a clear sign that a satisfactory immune response is in progress and recovery is on the way conversely ○ The absence of rash, common in immunodeficient patients, is a bad prognostic sign as it indicates that no immune response is fighting off the infection ■ Giant cell pneumonia may occur often many weeks after the acute infection. Virus is widespread in the skin but disappears quickly with the onset of the rash and appearance of circulating antibodies ○ Circulating antibodies are detectable ○ Viremia disappears ○ Fever falls Figure 6. Exanthem Period [Lacuna, 2023] Figure 7. 5-year-old with fever and rash [Lacuna, 2023] Figure 9. 10-month-old with high grade fever, purulent conjunctivitis, cough and rash [Lacuna, 2023] ATYPICAL/MODIFIED MEASLES ● Occurs in partially immune persons ● Infants with residual maternal antibody ○ Mild signs and symptoms ● Prolonged incubation period ● Prodromal symptoms diminished ● Koplik spots usually absent ● Rash is mild COMPLICATIONS ● Most measle-related deaths are caused by complications ● More common in children <5 or adults >20 ● As high as 10% of measles cases result in death among populations with high levels of malnutrition and lack of adequate health care ● ↑ cases in developing countries due to ill management ○ Pneumonia ■ In giant cell pneumonia, life-threatening infections occasionally seen in immunodeficient children ○ Conjunctivitis ○ Blindness ○ Otitis media ○ Diarrhea - dehydration ○ Encephalitis - brain swelling ■ Post-infection encephalitis occurs in 1/1000 cases ○ SSPE - subacute sclerosing panencephalitis ■ Rare complication ■ Characterized by the onset of behavioral and intellectual deterioration and seizures years after an acute infection ● Progressive mental deterioration, involuntary movements, muscular rigidity, and coma ■ Mean incubation period: 10.8 years ■ Progressive degenerative CNS disease that can result from a persistent measles infection ■ Characterized by the onset of behavioral and intellectual deterioration and seizures years after an acute infection ● Loss of intellectual capacity before motor activity ● Also causes progressive mental deterioration, involuntary movements, muscular rigidity, and coma ■ Occurs 4 to 17 years after ■ Due to a defective form of measles virus in the brain cell ● Not able to produce M protein and was not released (only hid in the cell) ■ Not common now due to vaccines PH152:MICROBIO | GROUP D & E: Beltran, Bernal, Bustos, Cruz, Manuel, Morales, Panganiban, Parallag 3 NOTE It is highly recommended for individuals to be vaccinated for measles since it can lead to serious complications that may only be manifested after years of an acute infection (around 10 years after) IMMUNITY ● Natural infection confers lifelong immunity ● Presence of humoral antibodies indicates immunity ○ In the skin, measles cause inflammation in the capillary producing IgM (short-lived), IgA (short-lived), and IgG (lifetime) antibodies and appear at the same time with the rash ■ First two antibodies may appear in the first months, while the latter persists for life ● During the acute phase, replication of virus within monocytes and other WBC depresses cell-mediated response to other antigens ○ Cytotoxic T lymphocyte, specifically directed against measles and protein in infected cells, are important in the recovery process and also provide protection against subsequent infection ■ Averts infection by acting on the M protein ● Cellular immunity important for recovery and protection ● Patients with defective cell-mediated immunity do not develop rashes ● Infection causes immune suppression ● Cause of serious secondary infections DIAGNOSIS SUMMARY OF DIAGNOSIS LABORATORY DIAGNOSIS CLINICAL DIAGNOSIS ● Serology(ELISA) ● Look for characteristic signs ○ Atypical measles of measles ○ IgM ○ Maculopapular rash ● Immunofluorescence ○ Koplik’s spots ○ atypical measles ○ Cough, coryza, ○ large numbers of giant conjunctivitis cells – bad prognosis LABORATORY DIAGNOSIS ● Serology (ELISA) ○ Done in cases of atypical measles (usually seen in hospitals) ○ Most widely used laboratory technique ○ Straight-forward ○ Not tedious to use compared to isolation and genetic determination ○ Detects IgM or four-fold increase in antibody ■ IgM is the first antibody that appears in an acute infection ■ Four-fold rise is an indicative of a viral disease NOTE: Isolation and genetic determination of the virus can also be performed, but is usually only utilized when new serotypes or strains of the virus are suspected. EPIDEMIOLOGY ● Distribution: worldwide ● Highly infectious ● Habitat: human ● Transmission: Respiratory droplets ● Incidence: Sporadic outbreaks ● Mortality: increase in < 1-year-old and malnourished ● Communicability: 4 days before and after onset of rash ○ Some references say 4-7 days before and after the onset of rash OVERVIEW ● Becomes endemic only in countries with populations large enough to provide a continuing supply of susceptible children ○ Communities confined in small spaces. ● Dies out until a fresh importation causes a major epidemic ○ However, outbreaks may occur, if there is a re-emergence of a new susceptible group of children ○ Without intervention, herd immunity is achieved when the majority of susceptible hosts have already contracted the disease (Batch Trans, 2024) ● Before widespread use of vaccines in developed countries, endemic infections punctuate every two to three years that attack the 3-5-year-old cohort. ○ Because of vigorous vaccination campaigns, epidemics are rarely seen in USA and European countries. ● In third world countries, measles still has a high incidence in infants <2 years old with more severe clinical manifestations (i.e. blindness) with a high fatality rate of 3-6%. ○ This is due to the lack of vigorous vaccination programs and campaigns (Batch Trans 2024). The average re-emergence case of measles is every 2 to 3 years. Over 1 million malnourished children die of measles each year in developing countries. In order to explain its prevalence, it is important to investigate two possible factors: (1) acquiring the infection at a younger age and (2) poorly nourished (Lacuna, 2023) REASONS FOR MEASLES RESURGENCE ● Failure to vaccinate the susceptible population. ● Suboptimal vaccination coverage. ● Underserved populations with limited healthcare access, healthcare facilities, and conflict-affected areas. ● Delayed or suboptimal supplementary immunization activities. ● Controversy over vaccine safety, religious or philosophical objections to vaccination. SITUATION IN THE PHILIPPINES ● Comparing the cases in 2018 to 2019, a sudden surge in the number of reported measle cases can be observed in the succeeding year (See Figure 10). ● Based on Figure 11, NCR has one of the highest reported cases (over 740) due to its crowded population ● Immunofluorescence ○ Also done for atypical measles ○ Detect a large number of giant cells CLINICAL DIAGNOSIS ● In day-to-day practice, clinical diagnosis is more commonly utilized compared to laboratory diagnosis. ○ If the rash is typical, confirmation tests are no longer done for clinical diagnosis ● Look for characteristic signs of measles: ○ Maculopapular rash ○ Koplik’s spots ○ Cough, coryza, conjunctivitis Figure 10. Measles cases by region, Philippines, Feb. 2018 vs Feb 2019 (Table)[Lacuna, 2023] PH152:MICROBIO | GROUP D & E: Beltran, Bernal, Bustos, Cruz, Manuel, Morales, Panganiban, Parallag 4 ○ The first 2 doses are appropriate for age, then a third age-specific dose given 2-4 weeks later. Figure 11. Measles cases by region, Philippines, Feb. 2018 vs Feb 2019 (heat map)[Lacuna, 2023] (See Appendix for Enlarged Image) Figure 12. Measles cases, deaths, and case fatality rate, Philippines, Jan. 26-Feb. 18, 2019[Lacuna, 2023] (See Appendix for Enlarged Image) ● Since the declaration of an outbreak in five regions on the 11th of February 2019, a surge in the number of measles cases has been observed. This is caused by the rapid spread of the disease, which is highly contagious ○ Highly contagious = rapid increase in the cases TREATMENT ● No antiviral drugs recommended. Supportive care is emphasized. ○ Address fever with analgesics (i.e. pain reliever) ● Vitamin A supplements ○ Given because children in developing countries are malnourished and have vitamin deficiencies ○ 2 doses given 24 hours apart (Recommended by WHO) ○ Can help prevent eye damage and blindness ○ Reduces mortality by 50% ● Post exposure prophylaxis for unvaccinated contacts ○ Should be considered in unvaccinated contacts ○ Need for timely tracing of contacts ○ Should be priority ○ Measles vaccine - within 3 days ○ Human immunoglobulin - within 6 days ■ Those sufficient to modify but not complement measles is valuable for protecting debilitated or immune deficient children exposed to infection ■ To reduce the complications and modify the symptoms of measles ■ Ex: A child who is immune deficient or is exposed to measles must be given post-exposure prophylaxis immunoglobulin VITAMIN SUPPLEMENTATION ● The World Health Organization recommends all children diagnosed with measles should receive vitamin A supplementation ● Infants younger than 6 months ○ 50,000 IU/day PO for 2 doses ● Age 6-11 months ○ 100,000 IU/day PO for 2 doses ● Older than 1 year ○ 200,000 IU/day PO for 2 doses ● Children with clinical signs of vitamin A deficiency MEASLES VACCINE ● Live attenuated vaccine ○ Recommended age for vaccination depends on local epidemiology ○ Studies have shown higher circumvention rates and effectiveness if delayed until all maternal antibodies are lost which is until 12 months ○ In most developing countries where there are high attack and serious disease among infants, early vaccination is necessary, despite long seroconversion rates following vaccination at this age group ● Early immunization can start at 6 to 9 months (Batch Trans 2024) ○ For highly endemic countries: 9 months ○ In times of outbreak it can be given as early as 6 months ● Children are given a booster vaccine at 12 to 15 months ○ Two doses is recommended, as 15% of vaccinated children fail to develop immunity from the 1st dose ○ In some cases (i.e. outbreak in minority groups), booster vaccines are given at the age of 3 to 5 years (In the US, 11 to 12 years old) LINKING MMR VACCINE WITH AUTISM “Vaccination became a setback in the UK where fraud data were attempting to show that the vaccine virus was associated with autism (large impact of vaccination program). However, there is no sound evidence of an association, but parental confidences are seriously undermined.” (Lota, 2023) ● Passive transfer of maternal antibodies interferes with immune response by neutralization ○ It is recommended to be given after maternal antibodies wane or neutralize ○ Given at 9 - 12 months old VACCINE INDICATIONS AND SCHEDULE ● Highly endemic countries ● 1st dose = 9-12 months ○ Outbreaks = given as young as 6 months ● General Recommendation (not endemic areas) ○ 1st dose = 12 months of age or older ○ 2nd dose = 4-6 years old ○ For MMR = may be given as soon as 1 month after the first dose ○ For MMRV = minimum interval bet doses is 3 months *Modern attenuated vaccines are very effective with mumps and vaccines at ages 13-15 months (no risk of neutralization by maternal antibodies) - preparation is simplified by the fact that there is only one virus serial type or marked antigen variation EARLY TWO-DOSE MEASLES SCHEDULE ● WHO recommends vaccination at 9 months in countries with: ○ High transmission rate of measles in young infants ○ High case fatality rates during the first year of life ○ Any measles containing vaccine given at age <12 months should be revaccinated with 2 doses of MMR vaccine ○ Booster given at 4-6 years old is given to prevent outbreak in school age children PH152:MICROBIO | GROUP D & E: Beltran, Bernal, Bustos, Cruz, Manuel, Morales, Panganiban, Parallag 5 MUMPS GENERAL CHARACTERISTICS SPIKES ● Contain ssRNA (-) surrounded by two glycoprotein envelopes ● First viral envelope glycoprotein: mediates neuraminidase and hemagglutination activity (houses Hemagglutinin Neuraminidase or HN protein) HEMAGGLUTINATION ● Involved in binding of virus to a cell ● Agglutinates cells of many species ● Hemagglutination of avian cells is widely used in the diagnostic methods of mumps Figure 13. Mumps [Lacuna, 2023 ● Etymology ○ The name probably originates from an old word meaning “to mope” Figure 14. A girl moping due to mumps as described by Hippocrates [Lacuna, 2023) ○ One of the first infections to be recognized and was described by Hippocrates as early as the fifth century BC ■ He described it as an epidemic disease of swelling of the ear and large swelling of the testes ● Taxonomy ○ Family of Paramyxoviridae ○ Subfamily of Paramyxovirinae ○ Genus Rubulavirus ○ Mumps disease ● What is it? ○ Acute, self-limited, systemic, viral illness characterized by the swelling of one or more salivary glands, typically the parotid glands ○ Also called infectious parotitis ○ Primarily affects the salivary glands ○ Mostly a mild childhood disease ● If you are a healthy individual that is not immunocompromised, most likely you will not develop this disease STRUCTURE ● Second viral envelope glycoprotein: responsible for the lipid membrane fusion to the host cell (houses F protein) ○ Promotes fusion of plasma membranes and viral envelope ○ Facilitates virus entry to the cytoplasm where viral replication occurs ○ Reaction with F protein inhibits hemolysis due to neutralization caused by mumps virus ○ Crucial in determining the spread of the virus in a cell population and in the body ● M protein: forms a structure which underlies the viral envelope ○ Important for assembly of the virions during the replicative cycle THE GENOME ● Has 16,000 nucleotides ● Contains the following peptides (aside from the HN): ○ L (Large polymerase) ○ Three fusion proteins: ■ NP (Nucleocapsid Protein matrix): codes 4 nonstructural proteins (C,V,W,I) which plays a central role in the encapsidation, transcription, and replication of the viral RNA; Most abundant protein of the virion and of the infected cell ■ P (Phosphoprotein): Important in RNA synthesis ■ SH (Unknown function) Figure 16. Genome of Mumps Figure 15. Structure of Mumps ● ● ● ● NEURAMINIDASE ● Its presence differentiates mumps from measles virus ● Mediates in the attachment of the virion to target cells via receptor molecules of the cell which contains sialic acid SS RNA, helical nucleocapsid Enveloped One serotype Spikes ○ HN protein ○ M protein [Lacuna, 2023) [Lacuna, 2023) EPIDEMIOLOGY ● Sole Reservoir: Humans ● Transmission: Person-to-Person (respiratory droplets, saliva, direct contact, fomites) ● Infectivity: High ○ Outbreaks in institutions, where there is often close contact between people, are common ○ Often infectious before symptoms become apparent ● Distribution: Worldwide ○ Mainly affects people aged <15 years ○ Thrive in temperate climates ○ Sporadic cases occur all year round ○ Cases are highest in winter for countries with seasons ○ No seasonal variation in tropical countries (possible all throughout the year) ○ Rare in countries using MMR vaccine ● Communicability: 3 days before or 4 days after active infection ● Immunity: Lifelong ○ Antibodies in order of appearance: IgM → IgA → IgG PH152:MICROBIO | GROUP D & E: Beltran, Bernal, Bustos, Cruz, Manuel, Morales, Panganiban, Parallag 6 ○ Cellular Mediated Immunity (CMI) is responsible and most important in recovery process, as with measles CLINICAL PRESENTATION ● Flu-like illness with localization to salivary glands ● Eventual involvement of other organs ● About ⅓ of cases may be subclinical ● Incubation period may take 14 to 18 days ● Onset of the virus may be marked by: ○ Malaise and Fever within 24 hours ○ Painful enlargement of one or both parotid glands ■ Other salivary glands are less often affected ■ In most cases, swelling subsides after a few days and recovery is uneventful PATHOGENESIS ORCHITIS / OOPHORITIS ● Orchitis: Inflammation of the testes ○ Can rarely cause sterility ○ Develops in about 20% of males who contract mumps after the age of puberty (postpubertal) ● May develop in the absence of preceding parotitis ● Pain and swelling of one or both testicles 4-5 days after the onset of parotitis ○ Pain is severe enough to demand strong analgesics ○ There is often an accompanying general reaction with high temperature and headache ● Symptoms often subside after 3-6 days ● Some degree of testicular atrophy follows in about 30% of cases ● Oophoritis: Inflammation of the ovaries ○ Does not have serious long term effects PANCREATITIS ● Does not have serious long term effects Figure 17. Pathogenesis flow chart of Mumps [Lacuna, 2023) ● Mumps is transmitted via droplets or direct contact ● Primary site of replication is the epithelium of the upper respiratory tract (eyes) ● First infected cells form the primary focus from which the virus spreads to local lymphoid tissues or lymph nodes ○ Further multiplication within this restricted area result eventually in the primary viremia, during which the virus spreads to distant sites ○ The parotid gland is usually involved, but the CNS, testes or epididymis, pancreas, or ovaries may also be involved ● A few days after the onset of clinical parotitis, the virus can be isolated from blood indicating virus multiplication in the target organs ○ Leads to secondary viremia ● As a result, virus may spread to various target organs ○ Virus is excreted in the urine in infectious form starting at anytime during the 2 weeks following the onset of clinical disease, also called viruria COMPLICATIONS MENINGITIS ● Approximately 1- 10% develop meningitis ● Incidence of aseptic meningitis is higher after mumps than after any other acute viral infection of childhood ● Rarely fatal ○ Almost always resolves without sequelae ○ Post-infection encephalitis is more serious and carries an appreciable mortality TINNITUS AND DEAFNESS ● A residual complication in a small percentage of cases ● Tinnitus: “Ringing in the ears” ○ Hearing sounds that come from inside your body, rather than from an outside source ○ May be dizzying LABORATORY DIAGNOSIS VIRUS ISOLATION ● Can be isolated using cell cultures or embryonated eggs (via egg inoculation) ○ From various cell lines such as monkey kidney cells identified by heme adsorption or heme agglutination inhibition (HEp2 cells) ○ Cell lines like human or monkey cells should be maintained or kept alive (as virus only replicates in living cells/tissues) ● Observe for Little Cytopathic Effects (CPE) ○ Signifies presence of virus ○ Virus will not be identified unless hemadsorption or hemagglutination inhibition are performed (due to the H protein in the viral structure) ● Samples: throat swab, urine, saliva from affected gland, CSF ● Not for routine diagnosis due to tedious nature ○ Usually used for investigation, especially if disease is not yet known or mutation is suspected, or for research purposes (i.e. looking for cures) ● Requires good laboratory ○ Prone to contamination ○ Cells can die, killing the virus as well ● Diagnostic in CSF ● Herringbone zipper-like appearance in electron microscopy HEMADSORPTION Figure 18. Hemadsorption of erythrocytes onto cell surface of the cell sheet [Lacuna, 2023) Syncytial formation (type of CPE) caused by mumps virus and the hemadsorption of erythrocytes onto the surface of the cell sheet To determine the presence of a viral antigen, a known antibody is used to react SEROLOGY ● More widely used ○ It is not as tedious as cell culture ○ Unlike bacterial culture, viral culture must maintain cell lines (e.g. human cell, monkey cells, tissues) since viruses only replicates on living tissues or cells PH152:MICROBIO | GROUP D & E: Beltran, Bernal, Bustos, Cruz, Manuel, Morales, Panganiban, Parallag 7 ● Observe for the rise in antibody between acute and convalescent phase ● ELISA Test for specific IgM and complement fixation tests ○ Used to demonstrate a rise in a specific antibody titers or the presence of IgM class antibodies ● Complement fixation test employs ○ Soluble (S) antigen and viral (V) antigen prepared from the virions that was earlier frequently used as the most common test ○ Mumps V antigen consists predominantly of HN glycoprotein while Mumps S antigen is largely nucleoprotein (NP) ○ Antibody to S antigen develop early ○ Antibody to V antigen persists longer ● By measuring antibodies to the two antigens, it is possible to make a specific laboratory diagnosis early in the course of infection ● However, due to the reagent stability problems, it has been replaced by Enzyme-immunoassay (EIA) or ELISA ● Other tests: ○ Enzyme immuno-assay → most sensitive ○ Single radial hemolysis ○ Neutralization test ○ Hemagglutination inhibition ● Mumps antigen has also been demonstrated from saliva samples by immunofluorescence or EIA techniques ○ Allows easy processing of large number of samples RUBELLA HISTORY 1814 ● Described as distinct clinical entity in German literature 1941 ● Sir Norman Gregg described congenital rubella syndrome 1962 ● First isolated by Parkman and Weller GENERAL FEATURES ● Family: Togaviridae ● Genus: Rubivirus ● Genome: 10 kb ● Single positive strand RNA or (+)ssRNA ● Enveloped, pleomorphic with icosahedral nucleocapsid ● There is only one serotype ○ Important consideration both in epidemiology of rubella in making of vaccine ● Cause rubella and congenital rubella syndrome ● Easily inactivated by chemical agents, low pH, heat, and UV light ● One antigenic type ● Human are natural host PCR ● Can be used to detect viral mumps RNA and fosters a rapid confirmation for the diagnosis TREATMENT AND PREVENTION ● Supportive care ○ Lessen the symptoms ● Immunization ○ Passive - not effective ○ Active - live attenuated vaccine ■ E.g. Jeryl Lynn strain licensed in 1967 and Urabe strain ● Both highly effective ● But Urabe strain has an appreciable incidence of post-vaccination meningitis which has now been abandoned in the UK ● Jeryl Lynn strains are strains of mumps virus used in the Mumpsvax mumps vaccine made by Merck Co. ● Jeryl Lynn strain was named after Jeryl Lynn Hilleman. Jeryl’s father, Maurice Hillman, made the efforts to produced mumps vaccine for Merck ■ >97% develop seroconvert ● Seroconversion is the development of specific AB in blood or serum as a result of infection or immunization including vaccination ○ MR, MMR, MMRV ■ Where uptake rates are high, there have been substantial reductions in cases ○ Immunity lasts for 20 years RUBELLA ● Latin word rubellus - “reddish” ○ Refers to pink rash seen in patients ● Commonly known as German measles ○ First discovered in the 18th century as a mild illness ● Different from rubeola ○ Rubeola is measles, rubella is German measles ● Presentation of rash is almost similar to measles ○ Exanthem is also present ● Predominantly an infection of children causing a mild febrile illness ● Before, it was thought to be a variant of measles and scarlet fever Figure 19. Rubella under the microscope [Lacuna, 2023) STRUCTURE Figure 20. Rubella Structure [Lacuna, 2023) ● The outer envelope is made up of glycosylated lipoproteins or glycoproteins ○ Contains 2 virus-specific polypeptides, E1 and E2, and a host cell-derived lipid ● E1 and E2: these two envelope proteins comprise the spine 5-6 nm surface projections that are observed on the outer membrane of the rubella virus and are important for the virulence of the virus ● Spherical ○ Diameter of 50-70 nm ○ Has a central core or nucleocapsid ○ Covered externally by a lipid-containing envelope ○ The icosahedral nucleocapsid is composed of the polypeptide capsid (C) protein and a single-stranded RNA ■ The ssRNA is infective and replication occurs in the cytoplasm ○ 3 major virion polypeptides are C protein, E1, and E2 PH152:MICROBIO | GROUP D & E: Beltran, Bernal, Bustos, Cruz, Manuel, Morales, Panganiban, Parallag 8 COMPLICATIONS RUBELLA COMPLICATIONS Figure 21. Rubella [Lacuna, 2023) EPIDEMIOLOGY ● Reservoir: Human ● Transmission: ○ Respiratory ○ Transplacental ● Temporal pattern: Peak in late winter and spring ● Communicability: 7 days before and after onset ○ Infants may shed the virus for >1 year ● Respiratory secretions of an infected person are the primary vehicles for Rubella virus transmission ● 30% to 60% of Rubella infected susceptible persons develop clinically apparent disease ● Patients with primary acquired rubella infections are contagious from 7 days before to 7 days after the onset of rash ● Congenitally infected infants may spread the virus to others for 6 months or longer after birth ● CRS is the highest in Africa and Southeast Asia where the vaccination is the lowest ● The disease is preventable by vaccination PATHOGENESIS POSTNATAL RUBELLA PATHOGENESIS ● Respiratory transmission of virus ○ Virus is transmitted by aerosolized particles from the respiratory secretions of an infected individual 1. Rubella enters and infects the nasopharynx and lungs 2. Virus spreads to the lymph nodes and replicates in the reticuloendothelial system a. Primary Viremia: replication in nasopharynx and regional lymph nodes 3. Virus is carried in the blood and spreads to other tissues and skin a. Secondary Viremia: occurs 6-20 days after infection i. Rubella virus can be recovered from different body sites: lymph nodes, urine, CSF, conjunctival sac, breastmilk, synovial fluid, and lungs ii. Viremia peaks just before rash onset and disappears shortly after iii. Infected persons begin to shed virus from nasopharynx 3-8 days after exposure for 6-14 days after rash onset 4. If a pregnant woman without protective antibodies is infected, the virus can infect the placenta and spread to the fetus a. Classic triad of Rubella symptoms in affected neonates (CDC) i. Cataracts (eyes) ii. Deafness (ears) iii. Cardiac abnormalities (heart) Complications Frequency of Occurrence Arthralgia or arthritis Rare (children) Up to 70% (adult females) Thrombocytopenic purpura 1/3,000 cases Encephalitis 1/5,000 cases Neuritis Rare Orchitis Rare REINFECTION ● Usually asymptomatic and mild ● Natural infection is followed by a high level of protection ● Infections after second attacks of Rubella and immunization have been recorded and confirmed serologically ○ Lifelong immunity depends on the amount of antibodies developed ○ Importance of vaccination due to reinfection ● Pose little to no risk to fetus during early pregnancy due to absence of viremia in this stage ○ Uncommon to cause fetal infection and damage ● IgG antibody response is higher with equivocal IgM titer ○ Higher ability of IgG ○ IgM present due to the recent infection CLINICAL PRESENTATIONS CLINICAL FEATURES ● Incubation Period: 12-21 days ● Symptoms are often mild ○ 50% of infections are subclinical or asymptomatic ○ Mild clinical syndrome characterized by a generalized maculopapular rash and occipital lymphadenopathy ○ In most cases, symptoms may be hardly noticeable and the infection remains subclinical, thus, the only reliable evidence for prior infection with Rubella virus is a demonstration of the anti-Rubella antibodies ● Prodromal ○ Low grade fever ○ Malaise ○ Lymphadenopathy ○ Respiratory symptoms ● Maculopapular rash ○ 14-17 days after exposure ○ Often follows one day after onset ○ Rash progression: ■ From head to foot ■ Lasts 1-3 days ■ Sometimes face rash has already faded before it reaches lower extremities ○ Quite faint and most prominent in the head, neck, and trunk ● Lymphadenopathy ○ Start a week before rash and may last several weeks (usually 2 weeks) ○ Involves postauricular, posterior cervical, and suboccipital nodes ■ Most prominent in the postauricular and posterior cervical areas ● Other symptoms ○ Forschheimer spots ■ Fleeting enanthem (mucous membrane rash) observed in 20% of Rubella patients during prodromal period ■ Can be present in some patients during the initial phase of exanthem (skin rash) ■ Consists of pinpoint or larger petechiae usually occurring on the soft palate ○ Arthralgia ■ Most common complication ■ Overt arthritis which may affect the joints of fingers, wrists, elbows, knees, and ankles PH152:MICROBIO | GROUP D & E: Beltran, Bernal, Bustos, Cruz, Manuel, Morales, Panganiban, Parallag 9 ■ Joint problems occur most frequently in women, rarely last longer than a few days to 3 weeks ○ Other complications: Conjunctivitis, orchitis, thrombocytopenic purpura, encephalitis CONGENITAL RUBELLA SYNDROME ● During primary maternal infection (mother has no antibodies, immunization, and history of infection) ● Causes teratogenic effects when contracted especially during early weeks of gestation ○ Major complication of Rubella ○ Cell division slowing ○ Disordered cell differentiation ○ Damage to small blood vessels ● Virus can be transmitted from the mother to the fetus through the placenta ● Serious congenital effects include abortions, premature deliveries, and stillbirths ● Affects all organs of the fetus → variety of congenital effects ○ CDC Triad: cataract, deafness, cardiac abnormalities ○ Eye-related abnormalities: cataract, microphthalmia, glaucoma, retinopathy ○ Ear-related abnormalities: unilateral/bilateral sensorineural deafness ○ Heart-related diseases ■ Patent Ductus Arteriosus (PDA) ● Persistent opening between two major blood vessels from the heart ■ Pulmonary Atresia (PA) ● Due to abnormal development of fetal heart during first 8 weeks of pregnancy ■ Valvular Stenosis (VS) ● Narrowing of valve opening due to stiffening of heart valves ● Restricted blood flow ■ Ventricular Septal Defect (VSD) ● Hole in the septum that separates heart and ventricles ● Severity or damage to the fetus depends on gestational age ● >85% of infants affected during 1st trimester ● Most common manifestation ○ Intrauterine growth retardation ○ Deafness (may be the only abnormality) ● Other clinical features ○ Microcephaly ○ Mental retardation ○ Bone alterations ○ Liver and spleen damage ● May lead to persistent infection causing clinical problems later on in life ○ Diabetes mellitus, chronic thyroiditis, occasional development of progressive subacute panencephalitis in the second decade of life RISK TO FETUS ● Risk of structural abnormalities decreases with gestational age ○ Highest risk of malformations: 1st trimester ○ Risk of fetus after 20th week is greatly decreased and the risks are no greater than uncomplicated pregnancy ● First 8 weeks of pregnancy ○ Organogenesis period ○ Spontaneous abortion ○ Cardiac and eye defects ● First 12 weeks of pregnancy ○ Fetal infection ○ Rubella-induced sequelae ● 13th-20th week of pregnancy ○ Deafness and other hearing defects ○ Retinopathy without blindness DIAGNOSIS ● Unlike measles, clinical diagnosis is notoriously unreliable ● Laboratory investigation is necessary ○ More than 50% of infections are subclinical LABORATORY DIAGNOSIS ● Isolation from clinical specimen ○ Nasopharynx, urine, blood, CSF ○ Pharynx: 1 week before and 2 weeks after onset of rash ○ Unreliable and time consuming ■ Labor-intensive, not routinely used ● Serology ○ Method of choice ○ Total rubella antibody or rubella-specific IgG and IgM ○ Antibody titer compared between acute and convalescent serum specimens drawn 2-3 weeks apart ○ Significant rise (four-fold in a single serum sample or observation) in rubella IgG by any standard serologic assay ■ Enzyme immunoassay, HI (hemagglutination inhibition), IFA (immunofluorescence) ● PCR CONGENITAL RUBELLA SYNDROME ● Viral isolation preferred unlike in postnatal rubella ○ Rubella serology may be difficult to interpret after transplacental passage of rubella-specific maternal IgG antibody ○ Today, other methods may be used aside from cell culture ● Large amounts of virus is evident during first few months ● Highly infectious ● Specific IgM observed in less than 12 months ● Specific IgG observed at 9-12 months ● Detection in the placenta ○ Maternal IgM does not cross the placenta ■ Detection is diagnostic of intrauterine infection ○ IgG crosses the placenta ■ Detection does not mean infection ■ Has a half-life of 3-4 weeks in the infants ■ Persistence until 9-12 months is diagnostic ○ Persistent antibody presence for 3-4 weeks in infants implies rubella-caused complications TREATMENT AND PREVENTION TREATMENT ● Supportive measures ● No specific therapy for neither acquired nor congenital rubella infection CONTROL ● Passive Prophylaxis ○ Human immunoglobulin (not recommended for pregnant women) ○ Given when exposed individual is immunodeficient ● Active Immunization ○ Composition: Live virus (RA 27/3) strain attenuated by human diploid fibroblast cells ■ Available for routine immunization since 1969 ○ Immunogenicity and Efficacy: 95% protective Ab after 1st dose ○ Preparation: MR, MMR, MMRV ○ Duration of Immunity: Lifelong immunity ○ Virus can be shed from nasopharynx 18-25 days after vaccination but not infectious ○ Indications and Schedule: usually only one dose ■ 1st dose: same as measles ■ 2nd dose: produce immunity in those who failed to respond to 1st dose ○ Target groups: female adolescents, hospital personnel in high-risk settings ○ Recommended for: ■ Infants after first year of life ■ Other individuals with no history of immunization PH152:MICROBIO | GROUP D & E: Beltran, Bernal, Bustos, Cruz, Manuel, Morales, Panganiban, Parallag 10 ■ Those with lack of immunity by serologic testing ○ Contraindicated in many immunocompromised patients and in pregnancy ■ More than 200 reported accidental vaccinations in susceptible pregnant women with no apparent clinical adverse effect on fetus ■ Non-pregnant women recommended to avoid conception for at least 3 months after vaccination (due to live attenuated nature) ○ Vaccine has few complications and is effective in preventing congenital rubella → reduces the reservoir of the virus in the child population and ensures that women reaching child-bearing age are immune to rubella infection Figure 22. Rubella Treatment chart [Lacuna, 2023) PH152:MICROBIO | GROUP D & E: Beltran, Bernal, Bustos, Cruz, Manuel, Morales, Panganiban, Parallag 11 REVIEW QUESTIONS 1. It is a major cause of measles-related mortality among young children. A. Meningitis B. Thrombocytopenic purpura C. Bronchopneumonia D. Encephalitis 2. H and M proteins are the two types of glycoprotein projections (peplomers) in measles virus. H protein (Hemolysis) mediates cell fusion, hemolysis, and viral entry to the cell. A. The first statement is correct and the second statement is incorrect. B. The first statement is incorrect and the second is correct. C. Both statements are correct. D. Both statements are incorrect. 3. The characteristic sign of measles A. Fever B. Rashes C. Koplik’s Spot D. Cough 4. T/F. In the exanthem period of measles, the maculopapular rash is due to the cytopathic effect of the virus. 5. Pathognomonic for measles A. Fever B. Rashes C. Koplik’s Spot D. Cough 6. The serology test (ELISA) is able to IgA or two-fold increase. Immunofluorescence is also done for atypical measles and can detect small numbers of cells. E. The first statement is correct and the second statement is incorrect. F. The first statement is incorrect and the second is correct. G. Both statements are correct. H. Both statements are incorrect. 7. The following are characteristics of measles except: A. Maculopapular rash B. Coryza C. Forschheimer spots D. Koplik’s spots 8. The following are included in the treatment for measles except for: A. Vitamin A supplements B. Specific Therapy C. Measles vaccine D. All of the above are included in the treatment for measles. 9. Any measles-containing vaccine given at 4 to 6 years old should be revaccinated with 2 doses of MMR vaccine. Measles vaccine is a type of live attenuated vaccine that starts at 6 to 9 months of age. A. The first statement is correct and the second statement is incorrect. B. The first statement is incorrect and the second is correct. C. Both statements are correct. D. Both statements are incorrect. 10. The Urabe strain for Mumps vaccine has an appreciable incidence of post-vaccination meningitis. Mumps V antigen and S antigen both consist predominantly of nucleoprotein (NP). A. The first statement is correct and the second statement is incorrect. B. The first statement is incorrect and the second is correct. C. Both statements are correct. D. Both statements are incorrect. 11. Which of the following is NOT true regarding Rubella A. The disease is preventable by using vaccines B. Peaks at late winter and spring C. Also known as measles D. None of the above 12.T/F Active immunization for Rubella gives lifelong immunity to an individual. 13. Organogenesis period happens in what stage of pregnancy? A. First 8 weeks of pregnancy B. First 12 weeks of pregnancy C. 13th-20th week of pregnancy 14. The following are complications associated with mumps EXCEPT: A. Meningitis B. Tinnitus & Deafness C. Blindness D. Orchitis 15. This method of laboratory diagnosis can be used to detect viral mumps RNA and fosters a rapid confirmation for the diagnosis A. Virus Isolation B. Serology C. PCR D. None of the above 16. Which of the following does not belong to the classical triad of Rubella in infected neonates? A. Cataracts B. Congenital defects C. Cardiac abnormalities D. Two of the choices 18. Which heart-related disease in congenital rubella syndrome is due to the abnormal development of the fetal heart during the first 8 weeks of pregnancy? A. Patent Ductus Arteriosus B. Valvular Stenosis C. Ventricular Septal Defect D. Pulmonary Atresia 19. During primary viremia, the virus spreads and replicates in the blood. In secondary viremia, infected persons begin to shed the virus from the nasopharynx 6-14 days after exposure for 3-8 days after rash onset. A. The first statement is correct and the second statement is incorrect. B. The first statement is incorrect and the second is correct. C. Both statements are correct. D. Both statements are incorrect. 20. The presence of this component differentiates mumps from measles virus. A. H protein B. Neuraminidase C. L protein D. Nucleocapsid Answer Key 1. C 2. D (H and F proteins; H protein (Hemagglutinin) mediates absorption to cell surfaces) 3. B 4. F; not due to the cytopathic effect of the virus but due to interaction of immune T cells with virus-infected cells 5. C. 6. D (IgM or four-fold increase; large numbers of giant cells) 7. C 8. B 9. B 10. A (Mumps V antigen consists predominantly of HN glycoprotein while Mumps S antigen is largely nucleoprotein/NP) 11. C (Rubella is German measles, not measles which is Rubeola) 12. T 13. A 14. C; it is associated with measles 15. C 16. B 17. A 18. D 19. D 20. B PH152:MICROBIO | GROUP D & E: Beltran, Bernal, Bustos, Cruz, Manuel, Morales, Panganiban, Parallag 12 APPENDIX Figure 23. Measles Cases by Region, Philippines, 18 February 2018 vs 18 February 2019.[Lacuna, 2023] Figure 24. Measles cases, deaths, and case fatality rate, Philippines, Jan. 26 - Feb. 18, 2019 [Lacuna, 2023] PH152:MICROBIO | GROUP D & E: Beltran, Bernal, Bustos, Cruz, Manuel, Morales, Panganiban, Parallag 13 SUMMARY TABLE OF MEASLES, MUMPS AND RUBELLA Measles General Characteristics Epidemiology Structure Pathogenesis Diagnosis Mumps Rubella ● Family Paramyxoviridae, subfamily Paramyxovirinae, genus ● Family of Paramyxoviridae, Genus Rubulavirus ● Family Togaviridae, genus Rubivirus Morbillivirus ● Also called infectious parotitis ● Commonly known as German measles ● Also called Rubeola ● Acute, self-limited, systemic, vital illness characterized by the ● Single positive strand RNA or (+)ssRNA ● Negative ssRNA, enveloped, helical nucleocapsid swelling of one or more salivary glands, typically the ● Enveloped, pleomorphic with icosahedral nucleocapsid ● Only one serotype restricted to human infections parotid glands ● There is only one serotype ● Primarily affects the salivary glands ● Predominantly an infection of children ● Natural Host: Humans ● Sole Reservoir: Humans ● Transmission: Close personal contact or direct contact with ● Transmission: Person-to-Person (respiratory droplets, saliva, respiratory secretions direct contact, fomites) ● Infectivity: High ● Infectivity: High ● Distribution: Worldwide ● Distribution: Worldwide ● Incidence: Sporadic outbreaks ○ Mainly affects <15 years ● Mortality: increase in <1 year old and malnourished ○ Thrives in temperate climates ○ Sporadic cases ○ Countries with seasons: highest in winter ○ Countries with no seasonal variation: possible all throughout the year ● Communicability: 3 days before or 4 days after active infection ● Immunity: Lifelong ○ IgM → IgA → IgG ● Reservoir: Human ● Transmission: Respiratory and Transplacental ○ Primary vehicles: respiratory secretions of an infected person ● Temporal pattern: Peak in late winter and spring ● Communicability: 7 days before and after onset ○ Infants may shed the virus for >1 year ● Congenitally infected infants may spread the virus to others for 6 months or longer after birth ● The disease is preventable by vaccination ● Encodes at least 6 virion structural proteins ● Structural Proteins ○ Nucleoprotein (N) ○ Viral Polymerase Protein (P and L) ○ Envelope ■ H protein (Hemagglutinin) ■ F protein (Fusion) ■ M protein (Matrix) ● Receptor for measles virus: CD-46 or Membrane Cofactor Protein ● ● ● ● ● Outer envelope made up of glycoproteins ● Contains 2 virus-specific polypeptides, E1 and E2, and a host cell-derived lipid ● Spherical, diameter of 50-70 nm ● Has a central core or nucleocapsid ● Covered externally by a lipid-containing envelope ● The icosahedral nucleocapsid is composed of the polypeptide capsid (C) protein and a single-stranded RNA ● The ssRNA is infective and replication occurs in the cytoplasm ● 3 major virion polypeptides are C protein, E1, and E2 ● Transmission via respiratory droplets ● Replication of virus at the nasopharynx and regional lymph nodes ● Primary viremia: 2 to 4 days after exposure ● Secondary viremia: 5 to 7 days after exposure with spread to other tissues ● Generalized immunosuppression: decrease in the delayed type hypersensitivity ● Interleukin production and antigen specific lymphoproliferative responses ● Immunosuppression, predisposing individuals to secondary opportunistic infections ● Transmission via droplets or direct contact ● Primary site of replication: epithelium of the upper respiratory tract ● Infection of first cells → formation of the primary focus → virus spreads to local lymphoid tissues or lymph nodes → further multiplication & spreading to different sites → primary viremia ● Involvement of parotid gland (main) and CNS, testes or epididymis, pancreas, or ovaries ● Onset of clinical parotitis → isolation from blood after a few days (indicates virus multiplication in the target organs) → secondary viremia ● Viruria (anytime during the 2 weeks following the onset of clinical disease) ● Transmission via aerosols from respiratory secretions ● Site of replication: reticuloendothelial system (nasopharynx and regional lymph nodes) → Primary Viremia ● 6-20 days after infection, the virus is carried in the blood and spreads to other tissues and skin → Secondary Viremia ○ Different body sites: lymph nodes, urine, CSF, conjunctival sac, breastmilk, synovial fluid, and lungs ○ Viremia peaks just before rash onset and disappears shortly after ○ Infected persons shed virus from nasopharynx 3-8 days after exposure for 6-14 days after rash onset ● Infected pregnant woman (w/o protective antibodies) → virus can infect the placenta & fetus Laboratory Diagnosis ● Serology(ELISA) ● Immunofluorescence Laboratory Diagnosis ● Virus Isolation ○ Throat swab, urine, saliva from affected gland, CSF Clinical diagnosis is unreliable SS RNA, helical nucleocapsid Enveloped One serotype Spikes ○ HN protein (Hemagglutinin Neuraminidase) ○ M protein (Matrix) PH152:MICROBIO | GROUP D & E: Beltran, Bernal, Bustos, Cruz, Manuel, Morales, Panganiban, Parallag Laboratory Diagnosis 14 Treatment and Prevention Clinical Diagnosis ● Maculopapular rash ● Koplik’s spots ● Cough, coryza, conjunctivitis ○ Not for routine diagnosis ○ Tedious ● Serology ○ More widely used ○ ELISA Test for specific IgM and complement fixation tests ○ Used to demonstrate a rise in a specific antibody titers or the presence of IgM class antibodies between acute and convalescent phase ● PCR ● Isolation from clinical specimen ○ Nasopharynx, urine, blood, CSF ○ Unreliable and time consuming ● Serology ○ Method of choice ○ Total rubella antibody or rubella-specific IgG and IgM ● PCR Congenital Rubella Syndrome ● Viral isolation preferred ● Specific IgM observed in less than 12 months ● Specific IgG observed at 9-12 months ● Detection in the placenta ● Vitamin A Supplements ● Measles vaccine ● Early two–dose measles schedule ● Supportive care ● Immunization ○ Passive - not effective ○ Active - live attenuated vaccine ■ E.g. Jeryl Lynn strain and Urabe strain ● Urabe strain has an appreciable incidence of post-vaccination meningitis ● Jeryl Lynn strains used in the Mumpsvax mumps vaccine by Merck Co. ○ MR, MMR, MMRV ● Immunity lasts for 20 years Treatment ● supportive measures Control ● Passive Prophylaxis ○ Human immunoglobulin (not recommended for pregnant women) ● Active immunization ○ Live virus (RA 27/3) strain attenuated by human diploid fibroblast cells ○ Lifelong immunity ○ Usually only one dose ○ Target groups: female adolescents, hospital personnel in high-risk settings ○ Contraindicated in immunocompromised patients and in pregnancy SUMMARY TABLE FOR THE CLINICAL PRESENTATIONS OF MEASLES, MUMPS, AND RUBELLA Clinical Presentations Measles Mumps Rubella Incubation Period ● 10 to 12 days ● Recovery in 10 to 14 days desquamation of skin ● 14 to 18 days ● Recovery is uneventful, in most cases, swelling subsides after a few days ● 12-21 days Symptoms/ Clinical Features ● Prodromal ○ High fever ○ Cough ○ Coryza and conjunctivitis ○ Koplik’s spot ● Appearance of maculopapular rash ● Exanthem Period ○ Not due to cytopathic effect ● Atypical/Modified Measles ○ Partially immune persons (infants) ● Flu-like illness with localization to salivary glands ● Within 24 hours, onset may be marked by: ○ Malaise ○ Fever ○ Painful enlargement of one or both parotid glands ● Prodromal ○ Low grade fever ○ Malaise ○ Lymphadenopathy ○ Respiratory symptoms ● Maculopapular rash ○ 14-17 days after exposure ○ Often follows one day after onset ○ Rash progression ● Lymphadenopathy ○ Start a week before rash and may last several weeks (usually 2 weeks) ○ Involves postauricular, posterior cervical, and suboccipital nodes ● Other symptoms: ○ Forschheimer spots PH152:MICROBIO | GROUP D & E: Beltran, Bernal, Bustos, Cruz, Manuel, Morales, Panganiban, Parallag 15 ○ ○ ○ ○ ○ Arthralgia Conjunctivitis Orchitis Thrombocytopenic purpura Encephalitis Congenital Rubella Syndrome ● CDC Triad ● Eye-related abnormalities: cataract, microphthalmia, glaucoma, retinopathy ● Ear-related abnormalities: unilateral/bilateral sensorineural deafness ● Heart diseases ○ Patent Ductus Arteriosus (PDA) ○ Pulmonary Atresia (PA) ○ Valvular Stenosis (VS) ○ Ventricular Septal Defect (VSD) ● Most common manifestations ○ Intrauterine growth retardation ○ Deafness ● Other clinical features ○ Microcephaly ○ Mental retardation ○ Bone alterations ○ Liver and spleen damage Complications ● ● ● ● ● ● Conjunctivitis Blindness Otitis media Diarrhea Encephalitis SSPE ● ● ● ● Meningitis Tinnitus & Deafness Orchitis/Oophoritis Pancreatitis PH152:MICROBIO | GROUP D & E: Beltran, Bernal, Bustos, Cruz, Manuel, Morales, Panganiban, Parallag Fetus: Risk of gestational age ● ● ● ● ● structural abnormalities decreases with Arthralgia (most common) Thrombocytopenic purpura Orchitis Encephalitis Neuritis 16