RUBELLA

TITIEK DJANNATUN

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 subooipital 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 (POSTNATAL)

KONGENITAL

SEKRESI RESPIRASI, URINE

REPLIKASI Pada FASE PRODROMAL (1 MINGGU STLH RUAM KLR)

SUBKLINIK BBRP MINGGU VIRUS TERDETEKSI DI NASOFARING

PATHOGENESIS OF RUBELLA

SITE OF VIRUS

GROWTH

RESULT COMMENT

RESPIRATORY

TRACT

VIRUS SHEDDING BUT SYMPTOMS

MINIMAL ( MILD SORE THROATH,

CORYZA, COUGH)

PATIENT INFECTIOUS 5 DAYS

BEFORE TO 3 DAYS AFTER

SYMPTOMS

SKIN RASH OFTEN FLEETING, ATYPICAL:

IMMUNOPATHOLOGY INVOLVED (Ag-

Ab COMPLEXES)

LYMPH NODES LYPHADENOPATHY 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 JAR LIMFOID (replikasi pada limfonodi servikal) Viremia (5-7 hari) RES EPITEL PERMUKAAN TBH (KULIT, SAL NAFAS, CONJUNCTIVA (REPLIKASI FOKAL))

SIMPTOM AWAL MALAISE, MILD FEVER, SORE THROATH, Limfadenopati aurikular posterior dan suboksipital

RASH/PINK MAKULA PAPULAR WAJAH BADAN EKSTREMITAS (ADVANCING & 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

DIAGNOSA, 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 AGLUTINATION 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

ORGANISM(S)

Measles virus (Rubeola) Rubella virus Parvovirus B 19 Human Herpesvirus 6 or

7

MOST COMMON

MODES OF

TRANSMISSION

DROPLETS CONTACT DROPLETS CONTACT

DROPLETS CONTACT,

DIRECT CONTACT

?

VIRULENCE FACTORS SYNCYTIUM

FORMATION, ABILITY

TO SUPPRESS CMI

IN FETUSES :

INHIBITION OF

MITOSIS, INDUCTION

OF APOPTOSIS, &

DAMAGE TO

VASCULAR

ENDOTHELIUM

- ABILITY TO REMAIN

LATENT

CULTURE/ DIAGNOSIS

ELISA FOR IgM,

ACUTE/CONVALESCEN

T IgG

ACUTE IgM,

ACUTE/CONVALESCEN

T IgG

USUALLY DIAGNOSIS

CLINICALLY

USUALLY DIAGNOSIS

CLINICALLY

PREVENTION LIVE ATTENUATED

VACCINE (MMR)

LIVE ATTENUATED

VACCINE (MMR)

- -

TREATMENT

NO ANTIVIRALS, VIT A,

AB FOR SECONDARY

BACTERIAL

INFECTIONS

-

-

-

DISTINGUISHING

FEATURE OF THE

RASHES

STAR ON HEAD,

SPREADS TO WHOLE

BODY, LAST OVER A

WEEK

MILDEER RED RASH,

LASTS

APPROXIMATELY 3

DAYS

SLAPPED-FACE RASH FIRST, SPREAD TO

LIMBS & TRUNK, TENDS

TO BE CONFLUEENT

RATHER THAN DISTINCT

BUMPS

HIGH FEVER

PRECEDES RASH

STAGE RASH NOT ALWAYS PRESENT

MEASLES (RUBEOLA)

PENYEBAB KEMATIAN 1 MILLION ANAK DI NEGARA BERKEMBANG

1963/1964 TERSEDIA VAKSIN MMR

VIRUS : FAMILIA PARAMYXOVIRUS

GENUS MORBILLIVIRUS

SS RNA

TIDAK ADA HEWAN RESERVOAR

BAHAN PEMERIKSAAN DARAH (HARI KE 3 STLH ONSET), SALIVA

VIRUS TIDAK BISA 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 Kopliks spot

Manifestasi selanjutnya pada kulit

PATOGENESA

VIRUS MUKOSA SAL PERNAFASAN SEL TRACHEA & BRONCHIALIS SISTEM LIMFATIK (REPLIKASI) PEMBULUH DARAH (VIREMIA) KULIT & BBRP ORGAN

MEMBENTUK GIANT CELL

IMUNITAS AB, CMI

GEJALA : SORE THROATH, BATUK KERING, SAKIT KEPALA, CONJUNCTIVITIS, LIMPHADENOPATI, FEVER

AWAL LESI ORAL (KOPLIKS SPOT) MACULOPAPULAR EXANTHUM (ULCERASI PTH KEBIRUAN, KCL PD MUKOSA BUCCAL BLAWANAN DG GERAHAM BWH, BERISI GIANT CELL & AG VIRUS ERUPSI PADA KEPALA MENYEBAR KE BADAN & EKSTREMITAS

ANAK LARYNGITIS, BRONCHOPNEUMONIA, INFEKSI SEKUNDER BAKTERI (H. influenzae, S. pneumoniae) SBBK INF TELINGA & SINUS

ANAK DG LEUKEMIA PNEUMONIA

Measles Pathogenesis

PATOGENESA

FASE PRODROMAL (2-4 HARI) VIRUS TERDPT DI AIR MATA, SEKRESI HIDUNG, TENGGOROK, URINE, DARAH

RUAM KULIT HARI KE 14 INTERAKSI SEL T DG 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 PRODROMAL : 2-4 HARI, FASE ERUPSI : 5-7 HARI

KOMPLIKASI SERIUS SSPE (SUBACUTE SCLEROSIS PENENCEPHALITIS)

DEG NEUROLOGIS CORTEX CEREBRI, BATANG OTAK, WHITE MATTER)

IBU HAMIL KEGUGURAN, BAYI DENGAN BB RENDAH

KERUSAKAN OTAK EPILEPSI

KULTUR, DIAGNOSA, PENCEGAHAN & TERAPI

ELISA IgM (CURRENT INFECTION)

HARI KE 14 TITER IgG MENINGKAT

PREVENTIF VAKSINASI MMR (MEASLES, MUMPS, RUBELLA) PD ANAK UMUR 12-15 BLN, BOOSTER SBLM MSK SEKOLAH PROTEKSI SELAMA 20 TAHUN

VAKSIN TIDAK UNTUK IBU HAMIL

TERAPI : OBAT- OBAT UNTUK HILANGKAN GEJALA

ANTIBIOTIK CEGAH INFEKSI SEKUNDER

VIT A MENINGKATKAN PERTAHANAN MUKOSA

CLINICAL IMPACT OF MEASLES

SITE OF VIRUS

GROWTH

WELL-NOURISHED

CHILD,GOOD MEDICAL CARE

MALNOURISHED

CHILD,GOOD MEDICAL

CARE

LUNG TEMPORARY RESPIRATORY ILNESS LIFE-THREATENING PNEUMONIA

EAR OTITIS MEDIA QUITE COMMON OTITIS MEDIA MORE COMMON, MORE

SEVERE

ORAL MUCOSA KOPLIKS SPOT SEVERE ULCERATING LESSIONS

CONJUNCTIVA CONJUNCTIVITIS 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 OF THOSE INFECTED

MAJOR CAUSED OF DEATH IN

CHILDHOOD (ESTIMATED ONE

MILLION DEATHS/YEAR WORLDWIDE)