TogaviridaeTogaviridaeSection of Microbiology and Section of Microbiology and ParasitologyParasitology

Togaviruses

(+)sense RNA Viruses

Family Genus Type Species Hosts

Togaviridae

Alphavirus Sindbis virus Vertebrates

Rubivirus Rubella virus

Vertebrates

Togaviridae1. Alphavirusa) Sindbisb) Semliki Forestc) Venezuelan equine encephalitisd) Eastern equine encephalitise) Western equine encephalitisf) Chikungunya

2. Rubivirus a) Rubella virus (German

Measles)

Togavirus: Togavirus: morphologmorphologyy

Toga: from Latin toga “cloak”

Capsid: 40-70 nm diameter– Enveloped; Spherical– Icosahedral

nucleocapsid– Comprised of

multimers of 1 gene product

Envelope-Envelope-– Tightly bound to Tightly bound to

capsidcapsid– 2 peplomers: E1 2 peplomers: E1

and E2 are and E2 are responsible for responsible for viral specificityviral specificity

– Envelope Envelope acquired by acquired by buddingbudding

TogavirusesTogaviruses

Genome : Genome : positive sense, single stranded positive sense, single stranded RNARNAthat is 10,000-12,000 that is 10,000-12,000 nucleotides long long• The 5'-terminus carries a The 5'-terminus carries a methylated nucleotide

cap and the 3'-terminus has a cap and the 3'-terminus has a polyadenylated tail tail• ~11.7kb, 4-8% total weight of particle~11.7kb, 4-8% total weight of particle• Nonstructural proteins encoded at the 5' endNonstructural proteins encoded at the 5' end• Togaviridae make use of a Togaviridae make use of a subgenome strategy strategy

to synthesize viral proteinsto synthesize viral proteins

The (+) sense genomic RNA ('49S' = 11.7kb) acts directly as mRNA partially translated (5' end) to produce nonstructural proteins these proteins are responsible for replication, forming a complementary (-) strand template for further (+)strand synthesis

2 species of (+) RNA are synthesized:a. full length genomic RNA b. sub-genomic mRNA ('26S' = 4.1kb) – Translation of the newly

synthesized sub-genomic RNA results in production of structural proteins

Assembly occurs at the cell surface

envelope is acquired as the virus buds from the cell

ReplicationReplication

AlphavirusesAlphaviruses

Togaviridae: Togaviridae: AlphavirusAlphavirus genusgenus

Important members Virus propertiesChikungunya virus,Eastern equine encephalitis virus,Mayaro virus, O’Nyongnyong virus,Ross River virus,Semilki Forest virus,Sindbis virus,Venezuelan equine encephalitis virus.Western equine encephalitis virus

• Spherical, 70 nm in diameter• Nucleocapsid has 42 capsomeres• Genome: (+) sense ss RNA, 9.7-11.8kb in size• Enveloped• Replication: cytoplasm• Assembly: budding through host cell membrane

Togaviridae: AlphavirusTogaviridae: Alphavirus Consists of about 30 Consists of about 30

viruses; 70 nm diameterviruses; 70 nm diameter Genome: single-stranded, + Genome: single-stranded, +

sense RNA (single 42S sense RNA (single 42S strand of approximately 4 x strand of approximately 4 x 106 daltons that is capped 106 daltons that is capped and polyadenylated)and polyadenylated)

icosahedral nucleocapsid icosahedral nucleocapsid enclosed in a lipid-protein enclosed in a lipid-protein envelopeenvelope– The single capsid protein (C The single capsid protein (C

protein) has a molecular protein) has a molecular weight of approximately weight of approximately 30,000 daltons30,000 daltons

Envelope: contains 2 Envelope: contains 2 glycoproteinsglycoproteins

establish persistent infections establish persistent infections in mosquitoes and are in mosquitoes and are transmitted between transmitted between vertebrates by mosquitoes vertebrates by mosquitoes and other blood-feeding and other blood-feeding arthropodsarthropods

Distribution: worldwideDistribution: worldwide Inactivated by acid pH, heat, Inactivated by acid pH, heat,

lipid solvents, detergents, lipid solvents, detergents, bleach, phenol, 70% alcohol bleach, phenol, 70% alcohol and formaldehydeand formaldehyde

Alphavirus Alphavirus structurestructure Envelope: lipid bilayer derived Envelope: lipid bilayer derived

from the host cell plasma from the host cell plasma membrane membrane – contains 2 viral glycoproteins (E1 contains 2 viral glycoproteins (E1

and E2) of molecular weights of and E2) of molecular weights of 48,000 to 52,000 daltons. 48,000 to 52,000 daltons.

The only proteins in the The only proteins in the envelopes of alphaviruses are the envelopes of alphaviruses are the viral glycoproteins, each viral glycoproteins, each anchored in the lipid at or near anchored in the lipid at or near their C-terminus. their C-terminus.

On the virion surface, E1 and E2 On the virion surface, E1 and E2 are closely paired, and together are closely paired, and together form trimers that appear as form trimers that appear as "spikes" in an orderly array. "spikes" in an orderly array.

Alphaviruses: : replicationreplication Genomic length and subgenomic mRNAs are Genomic length and subgenomic mRNAs are

produced during transcriptionproduced during transcription The genomic length transcript produces a The genomic length transcript produces a

precursor polyprotein encoding the nonstructural precursor polyprotein encoding the nonstructural proteins needed for viral replication. proteins needed for viral replication.

The subgenomic mRNAs encodes structural The subgenomic mRNAs encodes structural proteinsproteins

The proteins are elaborated by posttranslational The proteins are elaborated by posttranslational cleavagecleavage

Alphaviruses replicate in the cytoplasm and Alphaviruses replicate in the cytoplasm and mature by budding nucleocapsids through the mature by budding nucleocapsids through the plasma membraneplasma membrane

Genomic organization of alphaviruses

nonstructural proteins (nsP) are translated from the genomic RNA as a polyprotein that is processed into 4 proteins by a viral protease present in nsp2.

structural proteins are translated from a subgenomic 26SmRNA as a polyprotein that is processed by a combination of viral and cellular proteases into a capsid protein (C), 3 envelope glycoproteins (E3, E2, and E1), and a membrane-associated protein named 6K

Cap An

cap An

Subgenomic 26S mRNA

Genome RNA

nsP1 nsP2 nsP3 nsP4

C E3 E2 6K E1

Alphavirus: functions of nonstructural Proteins

nsP1nsP1: synthesis of minus strand RNA: synthesis of minus strand RNA nsP2nsP2: regulation of minus strand synthesis; : regulation of minus strand synthesis;

initiation of subgenomic RNA synthesis; initiation of subgenomic RNA synthesis; processing of the NS polyprotein  processing of the NS polyprotein  

nsP3: nsP3: unknown unknown  nsP4: nsP4: viral polymeraseviral polymerase

capsid E3 E2 6k E1Function

Forms nucleocapsid

Contains signal sequence for protein translocation; ultimate function unknown (not present in all mature alphaviruses)

Surface glycoprotein; interacts with host receptors, functions in attachment

May act as signal sequence; important in virus assembly and budding.

Surface glycoprotein

Structural Proteins: alphaviruses

Multiplication Multiplication Genomic RNA serves as Genomic RNA serves as

mRNA for nonstructural mRNA for nonstructural proteins (e.g., RNA-proteins (e.g., RNA-dependent RNA dependent RNA polymerase) which are polymerase) which are encoded in the 5' two-encoded in the 5' two-thirds of the genome. thirds of the genome.

Complementary RNA, Complementary RNA, made from genomic made from genomic RNA, serves as a RNA, serves as a template for progeny template for progeny genomic RNA. genomic RNA.

A subgenomic mRNA A subgenomic mRNA representing the 3' representing the 3' one-third of the one-third of the genome encodes the genome encodes the structural proteins.structural proteins.

Lifecycle: Alphavirus1. Virus attaches to host receptors though E2 glycoprotein

endocytosed into vesicles in the host cell. 2. Fusion of virus membrane with the vesicle membrane

nucleocapsid released into the cytoplasm uncoating RNA genome is released

3. Positive-sense genomic ssRNA used as the messenger RNA for the translation of the nonstructural proteins (p270 and p230 polyproteins.)

4. A negative-sense complementary ssRNA is synthesized using the genomic RNA as a template.

5. New genomic RNA is synthesized using the negative-sense RNA as a template. A subgenomic RNA (26S RNA) containing the last third of the genome

is also synthesized.

6. Structural proteins (p130 polyprotein) are translated from the 26S subgenomic RNA.

7. Capsid protein cleaved autocatalytically from the p130 polyprotein; remainder of the polyprotein moves into the ER membrane

Post-translational modifications (glycosylation and acylation) and further cleavage occurs, yielding four separate proteins (E3, E2, 6K, and E1).

8. Membrane-embedded proteins move to the surface of the cell virus assembly occurs

C-terminal region of the E2 protein interacts with the nucleocapsid; the N-terminal region of E2 interacts with E1 to give heterodimer "spikes“ these spikes associate in trimers to give larger spike formations

assembled virions are released from the cell

Envelope proteins formed by posttranslational cleavage Envelope proteins formed by posttranslational cleavage are glycosylated and translocated to the plasma are glycosylated and translocated to the plasma membrane. membrane.

Virion formation occurs by budding of preformed Virion formation occurs by budding of preformed icosahedral nucleocapsids through regions of the plasma icosahedral nucleocapsids through regions of the plasma membrane containing E1 and E2 glycoproteinsmembrane containing E1 and E2 glycoproteins

virus Clinical syndrome vector host distributionEEE encephalitis mosquit

obirds Americas

WEE encephalitis mosquito

birds North America

VEE Febrile illness, encephalitis

mosquito

Rodents, horses

Americas

Chikungunya

Febrile illness, rash, arthralgia

mosquito

Primates, humans

Africa, India, Southeast asia

Mayaro Febrile illness, rash, arthralgia

mosquito

Primates, humans

South America, Trinidad

Onyongnyong

Febrile illness, rash, arthralgia

mosquito

primates

Africa

Ross river

Febrile illness, rash, arthralgia

mosquito

Mammals, humans

Australia, Pacific

SIndbis Febrile illness, rash, arthralgia

mosquito

birds N. europe, Africa, Asia, Australia

Semliki forest

Febrile illness, rare encephalitis

mosquito

birds Africa

Alphavirus: main host are domesticated and wild animals. virus is taken up in the animal host's blood by mosquitoes

– virus replicates within the mosquito vector before it is introduced into a human host through mosquito bite.

virus is introduced into the capilarriesreplicates in the vasular endothelium spread to other target tissues including muscles, joints, skin, and brain

PathogenesisPathogenesis transmitted via infected mosquitoestransmitted via infected mosquitoes

– Virus is transmitted from the salivary glands of the Virus is transmitted from the salivary glands of the mosquito to the bloodstream of the vertebrate host. mosquito to the bloodstream of the vertebrate host.

– Virus travels to the skin and reticuloendothelial Virus travels to the skin and reticuloendothelial system (spleen and lymph nodes), where the system (spleen and lymph nodes), where the primary infection occurs primary infection occurs then viraemia follows then viraemia follows systemic infectionsystemic infection

– Can involve CNS (esp. encephalitis), skin/bone Can involve CNS (esp. encephalitis), skin/bone marrow/blood vessels (haemorrhagic fevers)marrow/blood vessels (haemorrhagic fevers)

Infection with seroconversion in the absence of clinical Infection with seroconversion in the absence of clinical disease is common, but disease can be incapacitating disease is common, but disease can be incapacitating and, in cases of encephalitis, occasionally fataland, in cases of encephalitis, occasionally fatal

Virus is eliminated by the immune system but arthritis Virus is eliminated by the immune system but arthritis or central nervous system impairment may persist for or central nervous system impairment may persist for weeks.weeks.

Alphaviruses: Host Defenses Initial resistance is conferred by Initial resistance is conferred by

nonspecific defenses such as interferon. nonspecific defenses such as interferon. Antibodies are important in recovery Antibodies are important in recovery

and resistanceand resistance– T-cell responses are also involved. T-cell responses are also involved.

Lasting protection is generally Lasting protection is generally restricted to the same alphavirus and is restricted to the same alphavirus and is associated with, but not solely associated with, but not solely attributable to, the presence of attributable to, the presence of neutralizing antibodies. neutralizing antibodies.

Alphaviruses: Epidemiology maintained in nature by mosquito-vertebrate-maintained in nature by mosquito-vertebrate-

mosquito cyclesmosquito cycles

Restricted interactions between viruses, vector Restricted interactions between viruses, vector species, and vertebrate hosts tend to confine species, and vertebrate hosts tend to confine the geographic spread of alphavirusesthe geographic spread of alphaviruses

Occasionally, a virus may escape its usual ecological Occasionally, a virus may escape its usual ecological niche and cause widespread epizootics (Venezuelan niche and cause widespread epizootics (Venezuelan equine encephalitis virus) or urban epidemics equine encephalitis virus) or urban epidemics (chikungunya virus)(chikungunya virus)– Human infections are seasonal and are acquired in endemic Human infections are seasonal and are acquired in endemic

areas. areas.

Epidemiology Epidemiology EEE virus: fresh water EEE virus: fresh water

swamps in the eastern USswamps in the eastern US– causes sporadic equine & rare causes sporadic equine & rare

human caseshuman cases Small human outbreaks may Small human outbreaks may

occuroccur – Since Since Culiseta melanura Culiseta melanura

mosquitoes usually do not feed mosquitoes usually do not feed on humans, transmission to on humans, transmission to horses and humans is horses and humans is potentiated when less fastidious potentiated when less fastidious AedesAedes species feed upon an species feed upon an adequate natural reservoir of adequate natural reservoir of infected birds. infected birds.

WEE virus (widespread in WEE virus (widespread in the US and Canada)the US and Canada)– outbreaks of equine and outbreaks of equine and

human disease in western human disease in western and southwestern states. and southwestern states.

– principal vector: principal vector: Culex Culex tarsalis tarsalis ,a common ,a common mosquito, especially in mosquito, especially in irrigated regionsirrigated regions

VEE virus: VEE virus: Eight or more antigenic subtypesEight or more antigenic subtypes– Can be transmitted by at least 10 different species of mosquitoes, Can be transmitted by at least 10 different species of mosquitoes,

including including CulexCulex and and AedesAedes species species– Birds do not seem to play an important reservoir role in nature. Birds do not seem to play an important reservoir role in nature. – Enzootic subtypes of relatively low equine virulence exist in South and Enzootic subtypes of relatively low equine virulence exist in South and

Central America and Florida.Central America and Florida.

Epidemiology Epidemiology Chikungunya virusChikungunya virus

– exists in Africa in a forest cycle involving baboons and exists in Africa in a forest cycle involving baboons and other primates and forest species of mosquitoesother primates and forest species of mosquitoes

– can also be transmitted in a human-mosquito-human can also be transmitted in a human-mosquito-human cycle by cycle by Aedes aegyptiAedes aegypti

massive epidemics in Africa, India, and Southeast Asiamassive epidemics in Africa, India, and Southeast Asia– is endemic throughout much of south and Southeast is endemic throughout much of south and Southeast

AsiaAsia Mayaro virusMayaro virus

– This antigenically similar virus exists in the Amazon This antigenically similar virus exists in the Amazon Basin. Basin.

– Its cycle involves new world primates and Its cycle involves new world primates and hematophagous mosquitoes; causes outbreaks of human hematophagous mosquitoes; causes outbreaks of human disease through exposure to the forest cycle. disease through exposure to the forest cycle.

Ross River virusRoss River virus– is endemic in Australia and has spread in epidemic form is endemic in Australia and has spread in epidemic form

to several islands of the Western Pacific.to several islands of the Western Pacific.

Epidemiology Epidemiology O’nyong nyong virus

– Found in Africa – Vectors:mosquitos - Anopheles spp. , A. funestus, A.

gambiae

Semliki forest virus: – isolated from mosquitoes in the Semliki Forest,

Uganda; pathogenic for laboratory animals and man

Sindbis virus– Common in Africa, Asia, Australia, Middle East,

Eastern Europe, Scandinavia and the Commonwealth of Independent States

– transmitted by a mosquito vector

Alphavirus: clinical Alphavirus: clinical manifestationsmanifestations

alphaviruses can cause various alphaviruses can cause various syndromes, ranging from benign febrile syndromes, ranging from benign febrile illnesses to severe systemic diseases with illnesses to severe systemic diseases with hemorrhagic manifestations or major hemorrhagic manifestations or major organ involvement. organ involvement.

The neurotropic alphaviruses can produce The neurotropic alphaviruses can produce severe destructive central nervous severe destructive central nervous system disease with serious sequelae. system disease with serious sequelae.

Several alphaviruses (chikungunya, Several alphaviruses (chikungunya, Mayaro, and Ross River) cause painful Mayaro, and Ross River) cause painful arthritis that persists for weeks or months arthritis that persists for weeks or months after the initial febrile illness.after the initial febrile illness.

Alphavirus: clinical Alphavirus: clinical manifestationsmanifestationsHuman illness disease patterns. Human illness disease patterns. Chikungunya virus is the prototype for those Chikungunya virus is the prototype for those

causing an acute (3- to 7-day) febrile illness with causing an acute (3- to 7-day) febrile illness with malaise, rash, severe arthralgias, and malaise, rash, severe arthralgias, and sometimes arthritis. sometimes arthritis.

O'nyong'nyong, Mayaro, and Ross River O'nyong'nyong, Mayaro, and Ross River viruses, which are closely related (antigenically) viruses, which are closely related (antigenically) to chikungunya virus, cause similar or identical to chikungunya virus, cause similar or identical clinical manifestationsclinical manifestations

Sindbis viruses cause similar but milder Sindbis viruses cause similar but milder diseases known as Ockelbo (in Sweden), diseases known as Ockelbo (in Sweden), Pogosta (Finland), or Karelian fever (Russia). Pogosta (Finland), or Karelian fever (Russia).

Alphavirus: clinical Alphavirus: clinical manifestationsmanifestations

viremia coincident with abrupt onset of fever, viremia coincident with abrupt onset of fever, chills, malaise, and joint aches. chills, malaise, and joint aches. – viremia subsides in 3 to 5 days, and antiviral antibodies viremia subsides in 3 to 5 days, and antiviral antibodies

appear in the blood within 1 to 4 days of the onset of appear in the blood within 1 to 4 days of the onset of symptomssymptoms

A macular-papular rash typically develops around A macular-papular rash typically develops around the third to fifth day of illness, when the patient is the third to fifth day of illness, when the patient is defervescing.defervescing.

migratory arthralgia (characteristic feature), migratory arthralgia (characteristic feature), involves mainly the small joints involves mainly the small joints – occurs more prominently in adults than children. occurs more prominently in adults than children. – severe cases: joints are swollen and tendersevere cases: joints are swollen and tender

Alphavirus: Diagnosis Alphavirus: Diagnosis

Diagnosis is suggested by clinical Diagnosis is suggested by clinical evidence and by known risk of exposure evidence and by known risk of exposure to virus. to virus. Confirmation is typically by virus Confirmation is typically by virus isolation and identification, or by a isolation and identification, or by a specific rise in IgG antibody, or the specific rise in IgG antibody, or the presence of IgM antibody. presence of IgM antibody.

–isolating virus from the blood during the viremic isolating virus from the blood during the viremic phase phase

detection of viral RNA (e.g. using polymerase detection of viral RNA (e.g. using polymerase chain reaction, PCR) or proteins (e.g., chain reaction, PCR) or proteins (e.g., immunohistochemistry) in frozen or fixed immunohistochemistry) in frozen or fixed tissues. tissues.

Alphavirus:Alphavirus: Control Control Disease surveillance and virus activity in natural hosts Disease surveillance and virus activity in natural hosts

are used to determine whether control measures will are used to determine whether control measures will be undertaken to reduce populations of vector be undertaken to reduce populations of vector mosquitoes or to vaccinate hosts, especially horses. mosquitoes or to vaccinate hosts, especially horses. – These measures include control of larvae and adult These measures include control of larvae and adult

mosquitoesmosquitoes Human vaccines, where available, are used only in Human vaccines, where available, are used only in

individuals at particularly high risk of exposure, such individuals at particularly high risk of exposure, such as laboratory workers.as laboratory workers.

RubivirusRubivirus

RubivirusRubivirus 3 major virion 3 major virion

polypeptides : C and polypeptides : C and envelope GP E1 and E2.envelope GP E1 and E2.

Haemagglutinin (E1)Haemagglutinin (E1)– E1 is an envelope proteins E1 is an envelope proteins

responsible for viral hemagglutination responsible for viral hemagglutination and neutralizationand neutralization

enveloped,Ss (+) RNA enveloped,Ss (+) RNA genomegenome

replication includes replication includes early (nonstructural) early (nonstructural) and late (structural) and late (structural) protein synthesisprotein synthesis

replicate in the replicate in the cytoplasm and bud from cytoplasm and bud from the plasma membranethe plasma membrane

Rubella Virus ( German measles )Rubella Virus ( German measles ) Latin “ little red”Latin “ little red” enveloped virus must stay wet enveloped virus must stay wet inactivated by drying, soap, inactivated by drying, soap,

detergentsdetergents respiratory virusrespiratory virus does not cause readily detectable does not cause readily detectable

cytopathologycytopathology

Rubella virusRubella virusPathogenesisPathogenesis Virus infects URT Virus infects URT spreads to local LN spreads to local LNviremia viremia

infection of other tissues and characteristic mild rashinfection of other tissues and characteristic mild rashImmune response :Immune response : Penetrates the natural defenses of the nasopharynx Penetrates the natural defenses of the nasopharynx

and lungand lung– Antibody generated blocks viremic spread of the Antibody generated blocks viremic spread of the

virusvirus Viral replication continue until cleared by CMI or Viral replication continue until cleared by CMI or

limited by interferonlimited by interferon Only 1 serotype; Lifelong immunityOnly 1 serotype; Lifelong immunity Rubivirinae lack animal reservoirs Communicability: 7 days before to 5-7 days after rash onsetCommunicability: 7 days before to 5-7 days after rash onset

- Infants with CRS may shed virus for a year or more- Infants with CRS may shed virus for a year or more

RubellaRubellamild disease in children and adults, but can mild disease in children and adults, but can cause devastating problems if it infects the cause devastating problems if it infects the fetus, especially if infection is in the fetus, especially if infection is in the first first few weeks of pregnancyfew weeks of pregnancy

Congenital InfectionCongenital Infection (+) rubella infection in pregnant (+) rubella infection in pregnant womenwomen alter normal growth, mitosis and alter normal growth, mitosis and chromosomal structure chromosomal structure congenital congenital rubella syndrome (CRS)rubella syndrome (CRS)

RubellaRubellaClinical syndromes :Clinical syndromes : I.P. 12-21 daysI.P. 12-21 days Children : benign 3 day rash and Children : benign 3 day rash and swollen glandsswollen glands Adults : arthralgia, arthritis, Adults : arthralgia, arthritis, thrombocytopenia, postinfectious thrombocytopenia, postinfectious encephalitisencephalitis

Rubella Clinical FeaturesRubella Clinical Features Incubation period 14 days (range 12-23 days)Incubation period 14 days (range 12-23 days)

Prodrome of low grade feverProdrome of low grade fever

Lymphadenopathy in second weekLymphadenopathy in second week

Maculopapular rash 14-17 days after exposureMaculopapular rash 14-17 days after exposure

RUBELLARUBELLA

Murray et al. Medical Microbiology

Congenital Rubella Congenital Rubella SyndromeSyndrome severe bilateral

deafness severe bilateral

visual defects cataract corneal opacity

RubellaRubellaCongenital Rubella Syndrome: Congenital Rubella Syndrome:

triad : abnormalities of the eyes, ears triad : abnormalities of the eyes, ears and heartand heart eyes : cataract, microophthalmia, glaucoma, eyes : cataract, microophthalmia, glaucoma, pigmentary retinopathypigmentary retinopathy ears : bilateral or unilateral sensorineural ears : bilateral or unilateral sensorineural

deafnessdeafness heart : PDA, PA and valvular stenosis,VSDheart : PDA, PA and valvular stenosis,VSD

RubellaRubellaClinical syndromes :Clinical syndromes : CNS : microcephaly, psychomotor CNS : microcephaly, psychomotor retardation, behavioral retardation, behavioral disordersdisorders persistent infection : progressive persistent infection : progressive rubella subacute rubella subacute panencephalitispanencephalitis

Congenital Rubella Congenital Rubella SyndromeSyndrome

a) infection of fetus during first trimester of pregnancyb) at least 20% of infants have severe birth defects

i. neurosensory deafnessii. blindness (total or partial; cataracts are especially common)iii. congenital heart disease iv. microcephaly with mental retardation

c) other symptoms associated with CRSi. bone translucency and retarded growthii. hepatosplenomegalyiii. Intrauterine growth retardation

d) 10 -20% of babies with CRS die within 1 yeare) 20 % will develop insulin dependent diabetes

mellitus as young adultsf) CRS babies continue to shed Rubella virus from their

throats for several months up to a year after birth and pose a serious risk to pregnant women.

Infant with congenital rubella and "blueberry muffin" skin lesions.

This infant has the rash of congenital rubella (German measles). These infants are at great risk for severe mental retardation, deafness, blindness (atrophic eyes, cataracts and chorioretinitis) as well as congenital heart disease and other abnormalities.

Congenital rubella Congenital rubella with hemorrhagic with hemorrhagic lesions in the skin lesions in the skin

Baby born with rubella: Thickening of the lens of the eye that causes blindness (cataracts)

Rubella ComplicationsRubella ComplicationsArthralgia or arthritis

childrenadult female

Thrombocytopenic purpuraEncephalitisNeuritisOrchitis

rareup to 70%

1/3000 cases

1/6,000 casesrarerare

RubellaRubellaDiagnosis :Diagnosis :

ClinicalClinicalConfirmed : anti rubella specific Confirmed : anti rubella specific

IgMIgMRecent infection : 4 fold rise in Recent infection : 4 fold rise in specific IgG titerspecific IgG titerIsolation of rubella virus from clinical Isolation of rubella virus from clinical specimen (e.g., nasopharynx, urine)specimen (e.g., nasopharynx, urine)

RubellaRubella CDC Case CDC Case DefinitionDefinition

Acute onset of generalized Acute onset of generalized maculopapular rash, andmaculopapular rash, and

Temperature of >37.2 C (>99 F), if Temperature of >37.2 C (>99 F), if measured, andmeasured, and

Arthralgia or arthritis, or lymph-Arthralgia or arthritis, or lymph-adenopathy, or conjunctivitisadenopathy, or conjunctivitis

RubellaRubellaTreatment : SupportiveTreatment : Supportive

Prevention : live rubella vaccinePrevention : live rubella vaccine

Rubella VaccineRubella Vaccine CompositionComposition Live virus (RA 27/3 strain)Live virus (RA 27/3 strain)

EfficacyEfficacy 95% (Range, 90%-97%)95% (Range, 90%-97%)

Duration ofDuration ofImmunityImmunity LifelongLifelong

ScheduleSchedule >>1 Dose1 Dose

Should be administered with measles and mumps as Should be administered with measles and mumps as MMR MMR

Rubella Vaccine (MMR) Rubella Vaccine (MMR) IndicationsIndications

All infants >12 months of ageAll infants >12 months of age

Susceptible adolescents and adults Susceptible adolescents and adults without documented evidence of without documented evidence of rubella immunityrubella immunity

Emphasis on non-pregnant women of Emphasis on non-pregnant women of childbearing agechildbearing age

MMR Adverse ReactionsMMR Adverse Reactions FeverFever 5%-15%5%-15% RashRash 5%5% Joint symptomsJoint symptoms 25% 25% ThrombocytopeniaThrombocytopenia <1/30,000 doses <1/30,000 doses ParotitisParotitis rare rare DeafnessDeafness rare rare EncephalopathyEncephalopathy <1/1,000,000 doses <1/1,000,000 doses

Rubella Vaccine ArthropathyRubella Vaccine Arthropathy Acute joint symptoms in about 25% of Acute joint symptoms in about 25% of

susceptable adult womensusceptable adult women

Frank arthritis occurs in about 10%Frank arthritis occurs in about 10%

Rare reports of chronic or persistent symptomsRare reports of chronic or persistent symptoms

Population-based studies have not confirmed Population-based studies have not confirmed associationassociation

Severe allergic reaction to vaccine Severe allergic reaction to vaccine component or following prior dosecomponent or following prior dose

PregnancyPregnancy ImmunosuppressionImmunosuppression Moderate or severe acute illnessModerate or severe acute illness Recent blood productRecent blood product

MMR VaccineMMR VaccineContraindications and Contraindications and PrecautionsPrecautions

Vaccination of Women Vaccination of Women of Childbearing Ageof Childbearing Age

Ask if pregnant or likely to become so in Ask if pregnant or likely to become so in next 4 weeksnext 4 weeks

Exclude those who say "yes"Exclude those who say "yes"

For othersFor others– Explain theoretical risksExplain theoretical risks– VaccinateVaccinate