RUBELLA

Titiek Djannatun
Bagian Mikrobiologi Universitas YARSI
 Rubella
History
1881 Rubella accepted as a distinct disease
1941 Associated with congenital disease (Gregg)
1961 Rubella virus first isolated
1967 Serological tests available
1969 Rubella vaccines available
 Characteristics of Rubella
• RNA enveloped virus, member of the
togavirus family

• Spread by respiratory droplets.

• In the prevaccination era, 80% of women

were already infected by childbearing age.
Morphology Virus
 Rubella (German Measles)

Campak german/Campak 3 harian demam akut  ruam kulit dan

limphadenopati auricular posterior dan sub ocipital pada anak dan
remaja
Infeksi Ibu hamil  abnormalitas pada janin  Malformasi kongenital,
retardasi mental
Virus : Familia  Togaviridae
Genus  Rubivirus
ss RNA, berenvelope
Hospes  Hanya manusia
Virus teratogenik
Infeksi  Anak, dewasa (Post natal)
kongenital
Sekresi  Respirasi, urine
Replikasi  Pada fase Prodomal (1 minggu setelah ruam keluar)
Subklinik  Beberapa minggu virus terdeteksi di nasofaring
 PATHOGENESIS OF RUBELLA

SITE OF VIRUS RESULT COMMENT

GROWTH
Respiratory tract Virus Shedding but symptoms Patient Infectious 5 days before to 3
minimal ( Mild sore throath, Coryza, days after symptoms
Cough)
Skin Rash Often fleeting, atypical:
Immunopathology involved (Ag-Ab
Complexes)
Lymph nodes Lymphadenopathy More common in posterior triangle of
neck or behind ear

Joints Mild Arthralgia, Arthritis Immunopathology involved

(Circulating immune complexes)

Placenta/Fetus Placentitis, Fetal damage Congenital Rubella

Viral Pathogenesis
Rubella Pathogenesis
Viral Pathogenesis
 Clinical Features
• maculopapular rash
• lymphadenopathy
• fever
• arthropathy (up to 60% of cases)
Rash of Rubella
 GEJALA KLINIS
POST NATAL :
Masa inkubasi  2-3 minggu
Infeksi virus pada mukosa saluran pernafasan atas  Jaringan limfoid
(replikasi pada limfonodi servikal)  Viremia (5-7 hari)  RES  Epitel
permukaan tubuh (Kulit, Saluran pernafasan, conjunctiva (Replikasi
fokal)

Simptom awal  Malaise, Mild Fever, SoreThroath, Limfadenopati

aurikular posterior dan suboksipital

Rash/Pink makula papular  Wajah  Badan Ekstremitas (Advancing

dan resolving  3 days

KOMPLIKASI  Arthralgia, arthritis, encephalitis  Banyak pada dewasa

 GEJALA KLINIS
KONGENITAL :
Ibu dapat tanpa gejala viremia  infeksi placenta dan janin (IgG ibu
tidak dapat melewati placenta)  infeksi sel janin (efek teratogenik)
Ibu hamil (3-4 bln pertama) yang terdeteksi virus selalu menyebabkan
infeksi janin  infeksi virus pada sel janin sebabkan efek teratogenik

Infeksi virus dalam rahim menyebabkan neonatus terinfeksi (kronis).

Virus dapat terdeteksi saat bayi lahir padasekresi faring dan berbagai
organ, cairan serebrospinal, urin, rectal swab. Ekskresi berlangsung 12-18
bulan setelah kelahiran

Infeksi pada 1ST trimester pertama  kematian janin, aborsi spontan,

bayi lahir dengan BB rendah

BAYI  abnormalitas jantung, lesi okuler, tuli, retardasi fisik/mental,

Anemia, Hepatitis, Pneumonia, Corditis, infeksi tulang
Risks of rubella infection during pregnancy

Preconception minimal risk

0-12 weeks 100% risk of fetus being congenitally infected

resulting in major congenital abnormalities.
Spontaneous abortion occurs in 20% of cases.

13-16 weeks deafness and retinopathy 15%

after 16 weeks normal development, slight risk of deafness

and retinopathy
 Congenital Rubella Syndrome
Classical triad consists of cataracts, heart defects, and sensorineural deafness.
Many other abnormalities had been described and these are divided into
transient, permanent and developmental.

Transient low birth weight, hepatosplenomegaly, thrombocytopenic purpura

bone lesions, meningoencephalitis, hepatitis, haemolytic anemia
pneumonitis, lymphadenopathy

Permanent Sensorineural deafness, Heart Defects (peripheral pulmonary stenosis,

pulmonary valvular stenosis, patent ductus arteriosus, ventricular
septal defect) Eye Defects (retinopathy, cataract, microopthalmia,
glaucoma, severe myopia) Other Defects (microcephaly, diabetes
mellitis, thyroid disorders, dermatoglyptic abnormalities

Developmental Sensorineural deafness, Mental retardation, Diabetes Mellitus,

thyroid disorder
Congenital Rubella Syndrome
 Prevention (1)
Antenatal screening

• All pregnant women attending antenatal clinics are

tested for immune status against rubella.

• Non-immune women are offered rubella

vaccination in the immediate post partum period.
 Prevention (2)
• Since 1968, a highly effective live attenuated vaccine has
been available with 95% efficacy
• Universal vaccination is now offered to all infants as part
of the MMR regimen in the USA, UK and a number of
other countries.
• Some countries such as the Czech Republic continue to
selectively vaccinate schoolgirls before they reach
childbearing age.
• Both universal and selective vaccination policies will work
provided that the coverage is high enough.
 Laboratory Diagnosis
Diagnosis of acute infection
• Rising titres of antibody (mainly IgG) - HAI, EIA
• Presence of rubella-specific IgM - EIA

Immune Status Screen

• HAI is too insensitive for immune status screening
• SRH, EIA and latex agglutination are routinely used
• 15 IU/ml is regarded as the cut-off for immunity
DIAGNOSIS, KULTUR, PENCEGAHAN, TERAPI

SPESIMEN  Swabtenggorok/nasofaring (3-4 hari setelah

gejala), Urine, cairan tubuh (Bayi)
KULTUR  Jaringan kera ( BSC-1, Vero), jaringan kelinci (RK-
13, SIRC), jaringan ginjal kera hijau  CPE 
immunofluorescein (3-4 hari pasca inokulasi)
SEROLOGI  HI, ELISA, Latex Alutination  IgM (terdeteksi
2 minggu setelah muncul ruam, menetap kurang dari 6
minggu)  IgG (kekebalan seumur hidup)
PENCEGAHAN  Vaksin MMR
TERAPI  Penyakit ringan  Sembuh sendiri Tidak ada
terapi khusus
 Typical Serological Events following acute
rubella infection

Note that in reinfection, IgM is usually absent or only present transiently at a low level
 MACULOPAPULAR RASH DISEASES
DISEASE MEASLES RUBELLA FIFTH DISEASE ROSEOLA
Causative Measles virus (Rubeola) Rubella virus Parvovirus B 19 Human Herpesvirus 6
Organism(S) or 7

Most common Droplets contact Droplets contact Droplets contact , ?

modes of Direct contact
transmission

Virulence factors Syncytium formation, In fetuses : Inhibition - Ability to remain

ability to suppress CMI of mitosis, Induction latent
of apoptosis, and
damage to vascular
endothelium

Culture/ Diagnosis ELISA for IgM, Acute IgM, Usually diagnosis Usually diagnosis
Acute/Convalescent Acute/Convalescent clinically clinically
IgG IgG

Prevention Live Attenuated Live Attenuated - -

Vaccine (MMR) Vaccine (MMR)

Treatment No antivirals, Vitamin A, - - -

Ab for secondary
bacterial Infections

Distinguishing Star on head, spreads Mildeer red rash, ‘Slaped-Face’ Rash High fever precedes
feature of the to whole body, last over Lasts Approximately first, spread to limbs rash stage – rash not
rashes a week 3 days and trunk, Tends to be always present
conflueent rather than
distinct bumps
 MEASLES (RUBEOLA)

Penyebab kematian 1 million anak di negara berkembang

1963/1964  Tersedia vaksin MMR
Virus : Familia  Paramyxovirus
Genus  Morbilli virus
ss RNA
Tidak ada hewan reservoar
Bahan Pemeriksaan  Darah (Hari ke 3 setelah onset), saliva,
Virus tidak dapat dikultur
Transmisi  Droplets
Epidemik  Padat, imunitas rendah, malnutrisi, tidak tersedia medical
care
Infeksius  Periode inkubasi, fase prodomal, Skin rash
 Pathogenesis Measles/Rubeolla
• Virus  via blood vessel  body (sel
epitel permukaan  yang pertama adalah
sel epitel saluran pernapasan)
• Manifestasi awal pada mukosa 
Koplik’s spot
• Manifestasi selanjutnya  pada kulit
 PATOGENESIS
Virus  Mukosa saluran pernafasan  Sel trachea dan bronchialis 
Sistem limfatik (Replikasi)  Pembuluh darah (viremia)  Kulit dan
beberapa organ
Membentuk Giant cell
Imunitas  Ab, CMI
Gejala : Sore throath, batuk kering, sakit kepala, conjunctivitis,
limphadenopati, fever
Awal  Lesi oral (Koplik’s spot)  Maculapapular exanthum (Ulcerasi
putih kebiruan, kecil pada mukosa buccal berlawanan dengan geraham
bawah, berisi Giant cell dan antigen virus  Erupsi pada kepala 
Menyebar ke badan dan ekstremitas
Anak  Leryngitis, Bronchopneumonia, Infeksi sekunder bakteri (H.
influenzae, S. pneumoniae) sebabkan infeksi telinga dan sinus
Anak dengan leukemia  Pneumonia
Measles Pathogenesis
 PATOGENESIS
Fase prodomal (2-4 hari)  Virus terdapat di air mata, sekresi hidung,
tenggorok, urin, darah
Ruam kulit  Hari ke 14  Interaksi sel T dengan sel terinfeksi virus
pada pembuluh darah kecil  1 Minggu (Pada pasien CMI rusak  ruam
tidak timbul)  viremia  demam turun
Masa inkubasi  9-11 hari
Penyakit berlangsung 7-11 hari 
Prodomal : 2-4 hari
Fase erupsi : 5-7 hari
Komplikasi serius  SSPE (Subacute Sclerosis Panencephalitis)
Degenerasi neurologis  Cortex cerebri, batang otak, white matter)
Ibu hamil  Keguguran, Bayi dengan berat badan rendah
Kerusakan otak  Epilepsi
 KULTUR, DIAGNOSIS, PENCEGAHAN & TERAPI

ELISA  IgM (Current infection)

Hari ke 14  Titer IgG meningkat
Preventif  vaksinasi MMR (Measles, MUMPS, Rubella)
pada anak umur 12-15 bulan, booster sebelum masuk
sekolah  Proteksi selama 20 tahun
Vaksin tidak untuk ibu hamil
Terapi : Obat-obat untuk hilangkan gejala
Antibiotik  Cegah infeksi sekunder
Vitamin A  Meningkatkan pertahanan mukosa
 CLINICAL IMPACT OF MEASLES

SITE OF VIRUS GROWTH MALNOURISHED CHILD,GOOD

MEDICAL CARE

Lung Temporary respiratory ilness Life-Threatening Pneumonia

Ear Otitis media quite common Otitis media more common ,

more severe

Koplik’s Spot
Oral mucosa Severe ulcerating lessions
Conjunctivitis
Conjunctiva Severe corneal lessions,
secondary bacterial infection,
blindness may result
Skin Maculapapular rash Hemorrhagic rashes may occur
(Black measles)
Intestinal tract No lesions Diarrhae-exacerbates
malnutrition, halt growth, impairs
recovery
Urinary tract Virus detectable in urine No Known complications

Overall impact Serious disease in a small proportion Major caused of death in

of those infected childhood (Estimated one million
death/year worlwide)