OrthomyxovirusesOrthomyxoviruses (Influenza virus) (Influenza virus)

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► In 1918 children would skip rope to the In 1918 children would skip rope to the rhyme*:rhyme*:

I had a little bird, I had a little bird, Its name was Enza. Its name was Enza. I opened the window, I opened the window, And in-flu-enza. And in-flu-enza.

* * Taken from Crawford, Richard, "The Spanish Flu," Taken from Crawford, Richard, "The Spanish Flu," Stranger Stranger Than Fiction: Vignettes of San Diego HistoryThan Fiction: Vignettes of San Diego History San Diego San Diego Historical Society, 1995 Historical Society, 1995

The influenza pandemic of 1918-1919 The influenza pandemic of 1918-1919 killed more people than the World War I killed more people than the World War I (WWI), at somewhere between 50 and (WWI), at somewhere between 50 and 100 million people. This was caused by 100 million people. This was caused by

the deadly strain subtype H1N1 influenza the deadly strain subtype H1N1 influenza type A virus. It has been cited as the type A virus. It has been cited as the

most devastating epidemic in recorded most devastating epidemic in recorded world history. More people died of world history. More people died of

influenza in a single year than in four-influenza in a single year than in four-years of the Black Death Bubonic Plague years of the Black Death Bubonic Plague

from 1347 to 1351. from 1347 to 1351.

Orthomyxoviruses Orthomyxoviruses

►Major cause of respiratory disease. Major cause of respiratory disease. Influenza (flu) can cause mild to severe Influenza (flu) can cause mild to severe illness, and has been responsible for millions illness, and has been responsible for millions of deaths worldwide.of deaths worldwide.

► ss negative-sense RNA. The antisense RNA ss negative-sense RNA. The antisense RNA genome occurs in eight separate segments genome occurs in eight separate segments containing 10 genes. containing 10 genes.

► The envelope contains viral haemagglutinin The envelope contains viral haemagglutinin (HA) and neuraminidase (NA) proteins.(HA) and neuraminidase (NA) proteins.

►Genetic reassortment of Genetic reassortment of InfluenzavirusInfluenzavirus is is common. The segmented viral genome common. The segmented viral genome allows a mixture of genome segments from allows a mixture of genome segments from two strains, when a single cell is infected by two strains, when a single cell is infected by 2 different strains.2 different strains.

Influenza virusInfluenza virus

ClassificationClassification

► Antigenic differences exhibited by two of the internal Antigenic differences exhibited by two of the internal structural proteins: nucleocapsid (NP) and matrix (M) structural proteins: nucleocapsid (NP) and matrix (M) proteins, are used to divide influenza viruses into proteins, are used to divide influenza viruses into types Atypes AC. NP antigens are stable and exhibit no C. NP antigens are stable and exhibit no serologic cross reactivity.serologic cross reactivity.

► Surface glycoproteins: Surface glycoproteins: HAHA and and NANA, are used to , are used to subtype the viruses. These two antigens are variable. subtype the viruses. These two antigens are variable. These Ags are responsible for immunity to infection.These Ags are responsible for immunity to infection.

► So far, 15 subtypes for HA (H1-H15); and So far, 15 subtypes for HA (H1-H15); and 9 subtypes for NA (N1-N9) have been recovered 9 subtypes for NA (N1-N9) have been recovered from birds, animals and humans.from birds, animals and humans.

► In humans, there are In humans, there are 4 HA4 HA (H1-3,H5) and (H1-3,H5) and 2 NA2 NA (N1-2). (N1-2).

Function of HAFunction of HA

►Haemagglutinin = agglutinate Haemagglutinin = agglutinate erythrocytes under certain conditions.erythrocytes under certain conditions.

►HA binds virus particles to susceptible HA binds virus particles to susceptible cells, and is the major Ag against cells, and is the major Ag against neutralising Abs.neutralising Abs.

Function of NAFunction of NA

► Functions at the end of viral replication cycle. It is a Functions at the end of viral replication cycle. It is a sialidasesialidase that removes sialic acid from that removes sialic acid from glycoconjugates.glycoconjugates.

► Facilitates release of virus particles from infected cell Facilitates release of virus particles from infected cell surfaces during the budding process. And prevent self-surfaces during the budding process. And prevent self-aggregation of virions by removing sialic acid residues aggregation of virions by removing sialic acid residues from viral glycoproteins. Also may help the virus to from viral glycoproteins. Also may help the virus to slide through the mucin layerslide through the mucin layer in resp T to reach the in resp T to reach the target epithelial cells.target epithelial cells.

Influenza virus ReplicationInfluenza virus ReplicationExpert Reviews in Molecular Medicine 2001 Cambridge University PressExpert Reviews in Molecular Medicine 2001 Cambridge University Press

► (a) The virus binds to cell-surface sialic acid receptors on the (a) The virus binds to cell-surface sialic acid receptors on the surface of the host cell and (b) is internalised into endosomes, surface of the host cell and (b) is internalised into endosomes, by receptor-mediated encytosis. (c) Fusion btw viral envelope by receptor-mediated encytosis. (c) Fusion btw viral envelope and cell membrane, and uncoating events, (d) Low pH is and cell membrane, and uncoating events, (d) Low pH is required by the virus-mediated membrane fusion to release of required by the virus-mediated membrane fusion to release of the viral genome (RNPs) into the cytoplasm. The vRNPs are then the viral genome (RNPs) into the cytoplasm. The vRNPs are then imported into the nucleus for (e) replication. (f) mRNAs are imported into the nucleus for (e) replication. (f) mRNAs are produced from viral nucleocapsids. Positive-sense viral produced from viral nucleocapsids. Positive-sense viral messenger RNAs (mRNAs) are exported out of the nucleus into messenger RNAs (mRNAs) are exported out of the nucleus into the cytoplasm for (g) protein synthesis. Cellular functions are the cytoplasm for (g) protein synthesis. Cellular functions are more involved. more involved. Protein synthesis requires cellular Protein synthesis requires cellular transcripts and RNA polymerase II, which explains why transcripts and RNA polymerase II, which explains why influenza virus is inhibited by drugs that block cellular influenza virus is inhibited by drugs that block cellular transcriptiontranscription. (h) Some of the proteins are imported into the . (h) Some of the proteins are imported into the nucleus to assist in viral RNA replication and (i) vRNP assembly, nucleus to assist in viral RNA replication and (i) vRNP assembly, which also occur in the nucleus. (j) Late in infection, the vRNPs which also occur in the nucleus. (j) Late in infection, the vRNPs form and leave the nucleus, and (k) progeny viruses assemble form and leave the nucleus, and (k) progeny viruses assemble and (l) bud from the plasma membrane. and (l) bud from the plasma membrane.

► The sites of action of anti-viral drugs are shown in red, italic text. The sites of action of anti-viral drugs are shown in red, italic text. Abbreviations used: cRNA (+), positive-sense complementary Abbreviations used: cRNA (+), positive-sense complementary RNA; HA, haemagglutinin; M1, matrix protein; M2, tetrameric ion RNA; HA, haemagglutinin; M1, matrix protein; M2, tetrameric ion channel; mRNA (+), positive-sense messenger RNA; NA, channel; mRNA (+), positive-sense messenger RNA; NA, neuraminidase; NP, nucleoprotein; NS1, a non-structural protein, neuraminidase; NP, nucleoprotein; NS1, a non-structural protein, NS2, a viral protein; pols, polymerases; vRNA (-), negative-sense NS2, a viral protein; pols, polymerases; vRNA (-), negative-sense genomic RNA genomic RNA

Pathogenesis & PathologyPathogenesis & Pathology

► Spreads from person to person by airborne Spreads from person to person by airborne droplets, or contaminated hands and surfaces.droplets, or contaminated hands and surfaces.

► Viral NA lowers the viscosity of the mucous film in Viral NA lowers the viscosity of the mucous film in the resp T, exposing the cellular surface receptors the resp T, exposing the cellular surface receptors and promoting the spread of virus-containing fluid and promoting the spread of virus-containing fluid to lower resp T. Within short time, many resp cells to lower resp T. Within short time, many resp cells are infected and eventually killed.are infected and eventually killed.

► Interferon is effective against influenza virus and Interferon is effective against influenza virus and attributes to host recovery.attributes to host recovery.

► Influenza infections cause cellular destruction and Influenza infections cause cellular destruction and desquamation of superficial mucosa of the desquamation of superficial mucosa of the respiratory tract but do not affect the basal layer of respiratory tract but do not affect the basal layer of epithelium. Viral damage in the epith lowers its epithelium. Viral damage in the epith lowers its resistance to resistance to secondary bacterialsecondary bacterial invaders esp invaders esp staphylococci, streptococci and staphylococci, streptococci and Haemophilus Haemophilus influenzaeinfluenzae..

Antigenic Drift & ShiftAntigenic Drift & Shift

► Antigenic variants confer selective advantage Antigenic variants confer selective advantage over the parental virus in the presence of Ab over the parental virus in the presence of Ab against the original strain.against the original strain.

► The 2 surface Ags undergo The 2 surface Ags undergo antigenic antigenic variationvariation independent of each other. independent of each other.

► Antigenic drift = Antigenic drift = MinorMinor changes, a changes, a gradual gradual change in antigenicity due to change in antigenicity due to point mutationspoint mutations that affect major antigenic sites on the that affect major antigenic sites on the glycoprotein.glycoprotein.

► Antigenic shift = Antigenic shift = MajorMajor changes, an changes, an abrupt abrupt change due to change due to genetic reassortmentgenetic reassortment with an with an unrelated strain, which results in the unrelated strain, which results in the appearance of a new subtype. appearance of a new subtype.

Clinical findingsClinical findings

► Uncomplicated InfluenzaUncomplicated Influenza : Abrupt symptoms : Abrupt symptoms include chills, headache, dry cough, include chills, headache, dry cough, muscular aches. These may be induced by muscular aches. These may be induced by influenza A or B. In contrast, influenza C influenza A or B. In contrast, influenza C causes a common cold illness, Coryza.causes a common cold illness, Coryza.

► PneumoniaPneumonia : complications occur only in the : complications occur only in the elderly and debilitated. Influenza infection elderly and debilitated. Influenza infection enhances the susceptibility of patients to enhances the susceptibility of patients to bacterial superinfectionbacterial superinfection, due to loss of ciliary , due to loss of ciliary clearance, dysfunction of phagocytic cells.clearance, dysfunction of phagocytic cells.

► Reye’s SyndromeReye’s Syndrome : an acute encephalopathy : an acute encephalopathy of children and adolescents (2-16yrs)of children and adolescents (2-16yrs)

Immunity Immunity ► Is long-lived and Is long-lived and subtypesubtype specific. specific.► Abs to Abs to HAHA and NA are important. Resistance to and NA are important. Resistance to

initiation of infection is related to Ab vs. HA, whereas initiation of infection is related to Ab vs. HA, whereas severity of disease and ability to transmit virus to severity of disease and ability to transmit virus to contacts are associated with Abs vs. NA.contacts are associated with Abs vs. NA.

► Local secretory IgA Abs is probably important in Local secretory IgA Abs is probably important in preventing infection. Serum Abs are also protective preventing infection. Serum Abs are also protective and persist for years. Abs modify the course of illness and persist for years. Abs modify the course of illness – person with low titres of Abs may experience mild – person with low titres of Abs may experience mild form of illness.form of illness.

► Cell-mediated immune response is probably Cell-mediated immune response is probably important for clearance of an infection. Cytotoxic T important for clearance of an infection. Cytotoxic T lymphocyte response is cross-reactive ie. able to lyse lymphocyte response is cross-reactive ie. able to lyse cells infected by any subtype of virus, and is directed cells infected by any subtype of virus, and is directed against both internal proteins (NP, M) and the surface against both internal proteins (NP, M) and the surface glycoproteins.glycoproteins.

EpidemiologyEpidemiology

► Periodic outbreaks appear because of Periodic outbreaks appear because of antigenic changes in one or both surface antigenic changes in one or both surface glycoproteins of the virus.glycoproteins of the virus.

►Only influenza A viruses circulate in animals Only influenza A viruses circulate in animals and avians. Antigenic shift ?and avians. Antigenic shift ?

► The recent strain in avian influenza A virus The recent strain in avian influenza A virus (H5N1) in 1997, reported in Hong Kong. The (H5N1) in 1997, reported in Hong Kong. The source was domestic poultry. At present, source was domestic poultry. At present, there is no vaccine against this strain.there is no vaccine against this strain.

Prevention & Control by Prevention & Control by VaccinesVaccines

► A) A) Inactivated Viral VaccinesInactivated Viral Vaccines::► Parenteral use;usually contain 1 or 2 type A and a Parenteral use;usually contain 1 or 2 type A and a

type B viruses, isolated from previous winter’s type B viruses, isolated from previous winter’s outbreaks.outbreaks.

► Strains are grown in embryonated eggs and the Strains are grown in embryonated eggs and the virus is harvested from egg allantoic fluid.virus is harvested from egg allantoic fluid.

► Vaccines are either whole virus (WV), subvirion Vaccines are either whole virus (WV), subvirion (SV), or surface Ag (SAg) preparations. (SV), or surface Ag (SAg) preparations. WV=contains intact, inactivated virus; SV=purified WV=contains intact, inactivated virus; SV=purified virus disrupted with detergents; SAg contains virus disrupted with detergents; SAg contains purified HA and NA glycoproteins. purified HA and NA glycoproteins.

► Sometimes called “flu shot” or “flu jab”.Sometimes called “flu shot” or “flu jab”.

Prevention & Control by Prevention & Control by VaccinesVaccines

► B) Live Attenuated Influenza VaccineB) Live Attenuated Influenza Vaccine► Contains live but attenuated (weakened) vaccine. It Contains live but attenuated (weakened) vaccine. It

is sprayed into nostril.is sprayed into nostril.

► For both types of vaccines, it will take up to 2 For both types of vaccines, it will take up to 2 weeks to develop protection after vaccination.weeks to develop protection after vaccination.

► The synthetic drugs amantadine and rimantadine The synthetic drugs amantadine and rimantadine hydrochloride effectively prevent infection and hydrochloride effectively prevent infection and illness caused by type A, but not by type B, viruses. illness caused by type A, but not by type B, viruses. The drugs interfere with virus uncoating and The drugs interfere with virus uncoating and transport by blocking the transmembrane M2 ion transport by blocking the transmembrane M2 ion channel (see fig of replication). channel (see fig of replication).

ParamyxoviruseParamyxovirusess

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ParamyxovirusesParamyxoviruses

► The World Health Organisation (WHO) The World Health Organisation (WHO) estimates that acute respiratory infections and estimates that acute respiratory infections and pneumonia are responsible every year worlwide pneumonia are responsible every year worlwide for the deaths of 4 million children under 5 for the deaths of 4 million children under 5 years of age.years of age.

► Paramyxoviruses are the major respiratory Paramyxoviruses are the major respiratory pathogens in this age group.pathogens in this age group.

► Reinfections are common throughout childhood. Reinfections are common throughout childhood. ► All members of the Paramyxoviridae family All members of the Paramyxoviridae family

initiate infection via the resp T.initiate infection via the resp T.► Transmission is by person-to-person contact or Transmission is by person-to-person contact or

by large-droplet aerosols.by large-droplet aerosols.

General StructureGeneral Structure

► Enveloped. Viral Enveloped. Viral genome is linear, genome is linear, negative sense ss negative sense ss RNA. Non-segmented RNA. Non-segmented genome, hence all genome, hence all members are members are antigenically stable. antigenically stable.

► Haemagglutinin Haemagglutinin glycoprotein HN glycoprotein HN proteins are important proteins are important for viral attachment.for viral attachment.

Pathogenesis of Parainfluenza Pathogenesis of Parainfluenza InfectionsInfections

► Parainfluenza virus replication in Parainfluenza virus replication in immunocompromised appears to be limited immunocompromised appears to be limited to respiratory epithelia. Viraemia is rare. The to respiratory epithelia. Viraemia is rare. The result is “common cold” syndrome.result is “common cold” syndrome.

► Infection may spread to larynx and upper Infection may spread to larynx and upper trachea, resulting in croup. Croup is trachea, resulting in croup. Croup is characterised by resp obstruction due to characterised by resp obstruction due to swelling of larynx and related structures.swelling of larynx and related structures.

► Viral shedding is about 1 week after onset of Viral shedding is about 1 week after onset of illness. Some immunocompromised children illness. Some immunocompromised children experience persistent shedding.experience persistent shedding.

Clinical findings & Lab Clinical findings & Lab diagnosisdiagnosis

► Primary infections in children usually result in Primary infections in children usually result in rhinitis, pharyngitis, often with fever.rhinitis, pharyngitis, often with fever.

► Severe illness associated with Parainfluenza Severe illness associated with Parainfluenza Type 3 may occur in infants.Type 3 may occur in infants.

► Common complication is Common complication is otitis mediaotitis media..► LabLab: Ag detection – immunofluorescence test; : Ag detection – immunofluorescence test;

isolation of virus-containing specimens; and isolation of virus-containing specimens; and serological by detecting specific IgM Ab.serological by detecting specific IgM Ab.

► Parainfluenza viruses are troublesome in Parainfluenza viruses are troublesome in hospitals. Contact isolation is necessary to hospitals. Contact isolation is necessary to prevent outbreaks.prevent outbreaks.

► Antiviral ribavirin is used to treat Antiviral ribavirin is used to treat immunocompromised with lower resp T immunocompromised with lower resp T disease.disease.

Respiratory Syncytial VirusRespiratory Syncytial Virus

► Most important causeMost important cause of lower resp T illness of lower resp T illness in in infantsinfants and young children. and young children.

► Replication occurs initially in epithelial cells of the Replication occurs initially in epithelial cells of the nasopharynx. Virus may spread into the lower resp nasopharynx. Virus may spread into the lower resp T and cause bronchiolitis and pneumonia.T and cause bronchiolitis and pneumonia.

► The incubation period between exposure and onset The incubation period between exposure and onset of illness is 3-5 days.of illness is 3-5 days.

► Viral shedding may persist 1-3 weeks in children; Viral shedding may persist 1-3 weeks in children; and 1-2 days only in adults.and 1-2 days only in adults.

► RSV initially replicates in epithelial cells of RSV initially replicates in epithelial cells of nasopharynx, which then migrates to the lower resp nasopharynx, which then migrates to the lower resp T and causes bronchiolitis and pneumonia. The T and causes bronchiolitis and pneumonia. The virus spreads both extracellularly and by fusion of virus spreads both extracellularly and by fusion of cells to form syncytia.cells to form syncytia.

TreatmentTreatment

► Treatment on supportive care (eg. removal of Treatment on supportive care (eg. removal of secretions, administration of Osecretions, administration of O22) )

► A promising means of protection is the A promising means of protection is the administration of RSV-enriched polyclonal administration of RSV-enriched polyclonal immunoglobulin (RSVIG) with monthly high-immunoglobulin (RSVIG) with monthly high-dose infusion. The maintenance of high-titer dose infusion. The maintenance of high-titer RSV neutralizing antibodies seems to RSV neutralizing antibodies seems to significantly decrease the incidence and significantly decrease the incidence and severity of respiratory syncytial virus illness in severity of respiratory syncytial virus illness in children at high risk.children at high risk.

► Ribavirin – in the US. Ribavirin – in the US. ► As yet, there is no safe and effective vaccine As yet, there is no safe and effective vaccine

against RSV.against RSV.

Mumps VirusMumps Virus

► Is an acute contagious disease Is an acute contagious disease characterised by non-suppurative characterised by non-suppurative enlargement of one or both enlargement of one or both salivary glands.salivary glands.

► Mostly causes mild childhood Mostly causes mild childhood disease, but in adults, disease, but in adults, complications inc meningitis and complications inc meningitis and orchitis are common. orchitis are common.

► More than 1/3 of mumps infections More than 1/3 of mumps infections are asymptomatic, but equally capable of are asymptomatic, but equally capable of transmitting the virus.transmitting the virus.

► Humans are the only natural hosts.Humans are the only natural hosts.

Pathogenesis & PathologyPathogenesis & Pathology► Primary replication occurs in nasal and upper resp T Primary replication occurs in nasal and upper resp T

epithelial cells epithelial cells viraemia viraemia salivary G & other salivary G & other organs (NB. Parotid G is not compulsory)organs (NB. Parotid G is not compulsory)

► Incubation period may range from 2-4 wks.Incubation period may range from 2-4 wks.► Virus shed in saliva from about 2 days before to 9 Virus shed in saliva from about 2 days before to 9

days after the onset of salivary G swelling.days after the onset of salivary G swelling.► It is difficult to control transmission since mumps is It is difficult to control transmission since mumps is

asymptomatic and has a variable incubation periods.asymptomatic and has a variable incubation periods.► Virus frequently infects kidneys, detectable in urine. Virus frequently infects kidneys, detectable in urine.

CNS is commonly infected and may be involved in the CNS is commonly infected and may be involved in the absence of parotitis.absence of parotitis.

► Testes and ovaries may be affected, esp after Testes and ovaries may be affected, esp after puberty. 20-50% of males infected with mumps virus puberty. 20-50% of males infected with mumps virus develop orchitis, and lack elasticity of the tunica develop orchitis, and lack elasticity of the tunica albuginea which prevents testis to swell. This results albuginea which prevents testis to swell. This results in pressure necrosis, but rarely results in sterility. 5 in pressure necrosis, but rarely results in sterility. 5 % of women develops mumps oophoritis.% of women develops mumps oophoritis.

Immunity vs. Mumps VirusImmunity vs. Mumps Virus

► Immunity is permanent after a single Immunity is permanent after a single infection.infection.

►Only one antigenic type of mumps virus.Only one antigenic type of mumps virus.►Abs develop against surface glycoproteins Abs develop against surface glycoproteins

and internal nucleocapsid protein.and internal nucleocapsid protein.► Interferon induced early in mumps Interferon induced early in mumps

infection. IgA secreted in nasopharynx.infection. IgA secreted in nasopharynx.►Passive immunity from motherPassive immunity from motheroffspring. offspring.

Hence, rare mumps in infants < 6 mth.Hence, rare mumps in infants < 6 mth.

DiagnosisDiagnosis

► Mumps virus is isolated Mumps virus is isolated from saliva, CSF, urine.from saliva, CSF, urine.

► Serology: detect mumps-Serology: detect mumps-specific IgM or IgG.specific IgM or IgG.

► Mumps primarily is an Mumps primarily is an infection of children 5-9 infection of children 5-9 yrs is the highest yrs is the highest incidence.incidence.

► Transmission by close Transmission by close contact eg. Crowded areas contact eg. Crowded areas (army camps).(army camps).

Treatment Treatment

►No specific therapy.No specific therapy.► Immunisation with attenuated live Immunisation with attenuated live

mumps virus vaccine to reducing mumps virus vaccine to reducing mumps-associated morbidity and mumps-associated morbidity and mortality.mortality.

► Isolation of infected subjects to prevent Isolation of infected subjects to prevent outbreak.outbreak.

►Mumps vaccine available in MMR Mumps vaccine available in MMR ((mmumps, umps, mmeasles and easles and rrubella). Produce ubella). Produce Abs to each viruses in ~95% vaccinees.Abs to each viruses in ~95% vaccinees.

Histological Histological diagnosis:diagnosis:

Haemadsorption by Mumps virus

Large syncytia by Respiratory Syncytial virus

Measles (Rubeola) VirusMeasles (Rubeola) Virus

►Measles is an acute, highly infectious Measles is an acute, highly infectious disease characterised by fever, resp disease characterised by fever, resp symptoms and maculopapular rash.symptoms and maculopapular rash.

►Complications are common.Complications are common.►Although there is a vaccine, incidence is Although there is a vaccine, incidence is

low, but still a leading cause of death in low, but still a leading cause of death in young children in developing countries.young children in developing countries.

►Humans are the only host. Other Humans are the only host. Other animals can be experimentally infected.animals can be experimentally infected.

Pathogenesis & PathologyPathogenesis & Pathology

Virus enters resp T (and multiply locally)Virus enters resp T (and multiply locally)

Lymphoid tissues (more multiplication)Lymphoid tissues (more multiplication)

1° viraemia1° viraemia

ReticuloendothelialReticuloendothelial

2° viraemia2° viraemia epithelial surfaceepithelial surfaceSkin Skin resp Tresp T conjunctivaconjunctiva

Aids dissemination throughout body - seen as multinucleated giant cells

Pathogenesis Pathogenesis

► Rash appears at about day 14, just as Rash appears at about day 14, just as circulating Ab is detectable, viraemia circulating Ab is detectable, viraemia disappears and fever falls. Rash develops as disappears and fever falls. Rash develops as a result of interaction of immune T cells with a result of interaction of immune T cells with virus-infected cells in the small blood vessels virus-infected cells in the small blood vessels and lasts about 1 week. and lasts about 1 week. (Thus, patients with defective (Thus, patients with defective cell-mediated immunity will have no rash)cell-mediated immunity will have no rash)

► Brain/CNS infection is common. Complication Brain/CNS infection is common. Complication subacute sclerosing panencephalitis that subacute sclerosing panencephalitis that develops years after infection, caused by develops years after infection, caused by viruses remaining in the body. viruses remaining in the body.

► Viral replication is defective owing to the lack Viral replication is defective owing to the lack of production of one or more viral gene of production of one or more viral gene products, often matrix protein.products, often matrix protein.

Clinical FindingsClinical Findings

► Fever, sneezing, coughing, running nose and redness Fever, sneezing, coughing, running nose and redness of eyes; Koplik’s spots (small bluish-white ulcerations of eyes; Koplik’s spots (small bluish-white ulcerations on the buccal mucosa opposite lower molars) and on the buccal mucosa opposite lower molars) and lymphopenia.lymphopenia.

► Rash starts on head, spreads to the chest, trunk, Rash starts on head, spreads to the chest, trunk, lower limbs.lower limbs.

► Pneumonia – most common life-threatening Pneumonia – most common life-threatening complications of measles, by 2° bacterial infections.complications of measles, by 2° bacterial infections.

► More serious complications More serious complications acute encephalitis acute encephalitis► Subacute sclerosing panencephalitis occur insidiously Subacute sclerosing panencephalitis occur insidiously

5-15 yrs after case of measles, characterised by 5-15 yrs after case of measles, characterised by progressive mental deterioration, involuntary progressive mental deterioration, involuntary movements, muscular rigidity and coma. movements, muscular rigidity and coma.

ImmunityImmunity

►There is only one antigenic type, hence There is only one antigenic type, hence infection confers lifelong immunity.infection confers lifelong immunity.

►Patients with Ig-defective recover well, Patients with Ig-defective recover well, whereas cellular immune-deficiency do whereas cellular immune-deficiency do poorly.poorly.

►Abs to nucleoprotein is the most useful Abs to nucleoprotein is the most useful – the most abundant viral protein in – the most abundant viral protein in cells. cells.

Epidemiology and TreatmentEpidemiology and Treatment

► Transmission is predominantly via resp route. Transmission is predominantly via resp route. Haematogenous transplacental transmission Haematogenous transplacental transmission during pregnancy.during pregnancy.

► Continuous supply of susceptible individuals is Continuous supply of susceptible individuals is required for the virus to persist in a community.required for the virus to persist in a community.

►Measles is endemic worldwide. Epidemics recur Measles is endemic worldwide. Epidemics recur regularly every 2-3 years.regularly every 2-3 years.

► RxRx: live attenuated measles virus vaccine : live attenuated measles virus vaccine (monovalent or combination with rubella – (monovalent or combination with rubella – MMR).MMR).

► Vaccinees may experience mild clinical Vaccinees may experience mild clinical reactions, but no virus excretion and no reactions, but no virus excretion and no transmission.transmission.

Nipah Virus & Hendra VirusNipah Virus & Hendra Virus

► Zoonotic paramyxoviruses. Zoonotic paramyxoviruses. ► 1998-99: severe encephalitis in Malaysia by 1998-99: severe encephalitis in Malaysia by

Nipah virus. High mortality rate up to 70%. Nipah virus. High mortality rate up to 70%. Infection caused by direct viral transmission Infection caused by direct viral transmission from pigs to humans.from pigs to humans.

►Hendra virus is an equine virus.Hendra virus is an equine virus.► Fruit bats (flying foxes) are natural hosts for Fruit bats (flying foxes) are natural hosts for

both Nipah and Hendra viruses. both Nipah and Hendra viruses. ► Ecologic changes inc land use and animal Ecologic changes inc land use and animal

husbandry practices are probably the reason husbandry practices are probably the reason for the emergence of these two infectious for the emergence of these two infectious diseases.diseases.

Rubella/German MeaslesRubella/German Measles

► Is an acute febrile illness characterised Is an acute febrile illness characterised by a rash and lymphadenopathy that by a rash and lymphadenopathy that affects children and young adults. A affects children and young adults. A self-limiting illness.self-limiting illness.

► It is the mildest of common viral It is the mildest of common viral exanthems but infection during early exanthems but infection during early pregnancy may results in congenital pregnancy may results in congenital malformations and mental retardation.malformations and mental retardation.

►Rubella virus is a member of Rubella virus is a member of Togaviridae.Togaviridae.

Postnatal RubellaPostnatal Rubella

►Neonatal, children and adults may be Neonatal, children and adults may be infected whereby infections starts in upper infected whereby infections starts in upper resp T, and multiplication in cervical lymph resp T, and multiplication in cervical lymph nodes nodes viraemia. viraemia.

► Fever, malaise and a morbiliform rash. Rash Fever, malaise and a morbiliform rash. Rash starts on face, extends over trunk and starts on face, extends over trunk and extremities. But rarely lasts more than 3 extremities. But rarely lasts more than 3 days.days.

► Lab diagnosis is unreliable because similar Lab diagnosis is unreliable because similar symptoms are seen with other viruses.symptoms are seen with other viruses.

Congenital Rubella Congenital Rubella

► Occurs when maternal viraemia Occurs when maternal viraemia placenta and foetusplacenta and foetus► In infected foetus, growth rate is reduced, results in In infected foetus, growth rate is reduced, results in

deranged/hypoplastic organ development. The earlier deranged/hypoplastic organ development. The earlier in the pregnancy infection occurs, the greater the in the pregnancy infection occurs, the greater the damage to the foetus.damage to the foetus.

► Newborn will have cardiac abnormalities, deafness, Newborn will have cardiac abnormalities, deafness, rash, hepatosplenomegaly and jaundice. Rubella rash, hepatosplenomegaly and jaundice. Rubella panencephalitis (rare) in second decade of life. panencephalitis (rare) in second decade of life.

► ImmunityImmunity: IgG = maternal rubella Ab which lost after : IgG = maternal rubella Ab which lost after 6mths; IgM = diagnostic of congenital rubella, since 6mths; IgM = diagnostic of congenital rubella, since IgM does not cross placenta, so its presence concurs IgM does not cross placenta, so its presence concurs the IgM synthesis by infants in utero.the IgM synthesis by infants in utero.

► RxRx: No specific treatment. Best to prevent the : No specific treatment. Best to prevent the disease.disease.