Rubella
Introduction
- Rubella
(German measles): viral illness, mild/self-limited in children, but devastating
in pregnancy →
congenital rubella syndrome (CRS).
- Transmission:
respiratory droplets, contagious 1 wk before–2 wk after rash.
- Vaccine-preventable
(MMR/MMRV).
Epidemiology
- Declared
eliminated in US (2004), Americas (2015), but sporadic
outbreaks still occur.
- Global
burden: ~100,000 infants/year born with CRS.
- Vaccine
coverage (2023): ~71% worldwide; > 80%
coverage ↓ CRS
significantly.
- Outbreaks:
occur in susceptible groups (e.g., Japan 2012–2014, 2018 → mainly adult males missed
by selective vaccination program).
Virology & Pathogenesis
- Family
Matonaviridae, genus Rubivirus.
- Single-stranded
RNA virus; proteins C, E1, E2 (E1/E2 = antigenic glycoproteins).
- Replication:
respiratory epithelium →
lymph nodes → viremia
(day 5–7) → systemic
spread.
- Rash
coincides with immune response (neutralizing Ab).
Clinical Manifestations
Children
- Rash:
pink, pinpoint maculopapular →
starts on face →
trunk →
extremities, spreads in 24 hr, lasts ~3 days (→ “3-day measles”).
- Posterior
auricular, suboccipital, posterior cervical LAD (classic, 5–8 days).
- Mild
fever, ± conjunctivitis, ± Forchheimer spots (soft palate).
- Usually
mild/subclinical.
Adults
- More
symptomatic than children.
- Arthralgia/arthritis:
up to 70% of adult women; knees, wrists, fingers (can last weeks).
- ±
Conjunctivitis, orchitis, testalgia.
Congenital rubella syndrome (CRS)
- Classic
triad: sensorineural deafness, cardiac defects (PDA, PS), ocular
defects (cataracts, retinopathy).
- Also
microcephaly, intellectual disability (ID), hepatosplenomegaly, bone
lesions.
Complications
- Rare
in postnatal infection, but include:
- Thrombocytopenic
purpura / hemorrhagic complications (~1:3000).
- Encephalitis
(~1:6000; usually good prognosis, but can be fatal).
- Progressive
rubella panencephalitis: rare, devastating.
- CRS =
major cause of morbidity/mortality.
Diagnosis
- Initial
test: Rubella IgM (EIA)
- Detectable
> day 4 after rash, persists 6–8 wk.
- Early
test (< 3 days) may be negative →
repeat in 2–4 wk.
- False
positives: parvovirus B19, RF, heterophile Ab.
- RT-PCR
(NP/throat swab, urine): sensitive in early infection (< 3 days
after rash).
- IgG
seroconversion (4-fold rise, acute vs convalescent).
- IgG
avidity: low = recent infection; high = past infection/reinfection.
- Culture:
rarely used (epidemiology).
Differential Diagnosis
- Viral
exanthems: measles (fever, 3C’s, Koplik spots), parvovirus B19,
roseola, EBV, enterovirus.
- Bacterial:
scarlet fever.
- Other:
toxoplasmosis, drug eruption, Kawasaki disease.
Treatment
- Supportive
only: antipyretics, hydration, symptomatic for rash/arthralgia.
- No
specific antiviral available.
- All
confirmed cases → report
to public health.
Prevention & Control
- Vaccination
(MMR/MMRV):
- US
schedule: 2 doses (12–15 mo, 4–6 yr).
- 1
dose seroconversion ≈ 95%.
- Goal:
prevent congenital rubella.
- Isolation:
droplet precautions ×7 days after rash onset.
- Exposed
contacts:
- Immune
→ no action.
- Non-immune
→ vaccinate (unless
pregnant or immunocompromised); exclude from outbreak settings until 21
days after last case.
- Immune
globulin PEP: not recommended (ineffective, does not prevent CRS).
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✅ Key Clinical Pearls
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Rubella in Pregnancy
Introduction
- Rubella
= self-limited viral infection (Matonaviridae, Rubivirus).
- มนุษย์เป็น reservoir เดียว → droplet
transmission จาก nasopharyngeal secretions.
- ปกติอาการไม่รุนแรงในผู้ใหญ่ → แต่เสี่ยงรุนแรงมากต่อ fetus
(Congenital Rubella Syndrome; CRS).
- Obstetric
care: routine screening IgG immunity ทุกคนตั้งครรภ์.
Clinical Manifestations in Pregnancy
- Maternal
infection:
- Asymptomatic
25–50%.
- Prodrome:
low-grade fever, conjunctivitis, coryza, sore throat, LAD (suboccipital,
postauricular, cervical), ± Forchheimer spots.
- Rash:
maculopapular, face →
trunk → extremities,
lasts 1–3 days.
- Arthritis/arthralgia:
common (60–70% adult women).
- Maternal
complications (rare): thrombocytopenia, encephalitis, myocarditis,
hepatitis.
- Prognosis
for mother: ดี, self-limited.
Congenital Rubella Syndrome (CRS)
- Transmission:
maternal viremia →
placenta → fetal
hematogenous spread.
- Risk
of fetal infection:
- 1st
trimester: สูงสุด (< 81%).
- Late
2nd trimester: ~25%.
- 27–30
wks: ~35%.
- >
36 wks: almost 100% infection, แต่ risk of major
malformation ต่ำ.
- Risk
of congenital defects: essentially limited to < 16 wks
gestation.
- After
20 wks: almost no risk CRS, อาจมีแค่ IUGR.
- Manifestations:
spontaneous abortion, stillbirth, IUGR, CRS (hearing loss, CHD, cataracts,
intellectual disability).
- Reinfection:
rare CRS, reported only if infection < 12 wks GA.
Diagnosis
- Serology
(ELISA = standard):
- IgM:
acute infection (detectable > day 4 rash, persists 6–8 wk).
Beware false positives (RF, parvovirus).
- IgG:
immunity; acute infection = 4-fold rise.
- Culture:
throat, blood, urine, CSF (mostly surveillance).
- PCR:
sensitive, esp. CVS samples (10–12 wks GA). Better than amniotic fluid.
Detects rubella virus RNA before serology positive.
- Fetal
diagnosis: CVS PCR > amniotic fluid; fetal blood IgM often negative
despite infection.
- Ultrasound:
not sensitive except IUGR; must consider TORCH.
- CDC
caution: don’t use IgM alone for routine prenatal screening (false
positive common).
- IgG
avidity: distinguish recent vs past infection.
Treatment
- Maternal:
symptomatic only (acetaminophen).
- Complications:
steroids, platelet transfusion, supportive as indicated.
- Pregnancy
counseling:
- Infection
< 16 wks →
offer termination (high CRS risk).
- Infection
> 20 wks →
CRS risk negligible; counsel re IUGR/late effects.
- No
proven in utero treatment.
- Maternal
prognosis excellent; fetal prognosis depends on GA at infection.
Prevention
- Preconception
vaccination (MMR):
- Document
immunity before pregnancy.
- Avoid
conception 28 days post-vaccination.
- Live
vaccine contraindicated during pregnancy.
- Postpartum
vaccination:
- All
non-immune women should receive MMR before hospital discharge.
- Breastfeeding
not contraindicated.
- If
also received anti-D Ig, recheck immunity at 3 mo.
- Public
health: postpartum vaccination programs reduce seronegative
prevalence.
Postexposure Management
- Assess
immunity:
- Immune
→ no action.
- Non-immune
pregnant women →
counsel on risk, monitor serology.
- Serology
follow-up: baseline IgM/IgG →
repeat at 3–4 wk and 6 wk.
- Ig
prophylaxis: not recommended (fails to prevent CRS, complicates
diagnosis).
- Exposure
definition: direct contact 7 days before → 7 days after rash onset.
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✅ Key Clinical Pearls
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Congenital Rubella Infection (CRI) & Congenital
Rubella Syndrome (CRS)
Terminology
- CRI
= spectrum ของ intrauterine rubella infection → ตั้งแต่ miscarriage,
stillbirth, asymptomatic infection จนถึง congenital
anomalies
- CRS
= subset ของ CRI →
congenital anomalies ชัดเจน เช่น sensorineural
hearing loss (SNHL), congenital heart disease, cataracts, glaucoma
Epidemiology
- CRS rare
ในประเทศที่มี robust vaccination; eliminated
in Americas (2015).
- WHO
2022: 90% ประเทศมี RCV, coverage global = 27%
(low-income) → 93%
(high-income).
- CRS ส่วนใหญ่ใน resource-limited countries; immigrants ยังเป็น source ของ CRS ในประเทศพัฒนาแล้ว.
Pathogenesis
- Maternal
viremia → placenta → fetal vascular spread.
- Mechanisms:
- Virus-induced
inhibition of cell division →
organ hypoplasia.
- Direct
cytopathic effect & apoptosis →
selective organ injury.
- Timing
critical:
- < 8 wks GA →
heart & eye defects
- <
18 wks GA → hearing
loss
- 20
wks GA → defects
uncommon (อาจมีแค่ IUGR)
- Fetal
infection persists throughout gestation & after birth.
Immunology
- Fetus:
IgM detectable ~9–11 wks GA, maternal IgG transfer limited < 20
wks.
- After
birth: rubella IgM persists > 6 mo (บางรายนาน 1–2
yr); IgG สูงผิดปกติ.
- Tolerance:
บางราย antibody titers ↓
จน undetectable และไม่ boost หลัง vaccination.
- Risk
autoimmunity: DM type 1, thyroid disease ↑ (แต่ไม่ชัดเจน).
Clinical Features
Early manifestations (neonatal)
- Classic
triad CRS: SNHL (~2/3, bilateral), congenital heart disease (~½, esp.
PDA, pulm. stenosis), ocular defects (cataracts, retinopathy, glaucoma).
- อื่น ๆ: FGR, microcephaly, hepatosplenomegaly, jaundice,
blueberry muffin lesions, thrombocytopenia, myocarditis, interstitial
pneumonia, radiolucent bone lesions.
- Most
infants asymptomatic at birth, แต่ 70% develop
clinical features by age 5 yr.
- Severe
neonatal CRS → ↑ mortality (eg.
myocarditis, severe CNS, pneumonitis, hepatitis).
Late manifestations
- Hearing
loss (up to 80%, often progressive).
- Endocrine:
DM (~1% childhood, ↑
risk in adulthood), thyroid disease (~5%).
- Ocular:
pigmentary retinopathy (40–60%), cataracts, glaucoma, keratoconus, corneal
hydrops.
- Neurologic:
developmental delay, autism, CP, intellectual disability, progressive
rubella panencephalitis (rare, fatal).
- Cardiac/vascular:
progressive valvular stenosis, systemic HTN, vascular sclerosis.
- Immune
defects: IgG deficiency, recurrent infections.
- Prolonged
viral shedding: pharyngeal shedding up to 1 yr (20% infants), rarely
beyond 2 yr.
Evaluation
- Suspect
CRI/CRS if:
- Maternal
rubella during pregnancy
- Infant
with FGR, cataracts, CHD, hearing loss, blueberry muffin rash
- Work-up:
- Physical
exam
- CBC,
LFT, bilirubin
- LP,
neuroimaging
- Echo,
long bone X-ray
- Ophthalmologic
+ audiologic evaluation
- Rubella
serology
Diagnosis
- Within
1 yr of age (ก่อน vaccination):
- Rubella-specific
IgM (most useful <2 mo, may persist up to 12 mo).
- Persistence
of rubella IgG > expected maternal decay (normally 4–8× ↓ by 3 mo, disappear by 6–12
mo).
- Viral
culture (NP swab, blood, urine, CSF).
- PCR
(pharyngeal swab, urine, CSF, lens tissue).
- 1
yr: difficult; use IgG avidity, lymphocyte response, failure to
seroconvert after vaccine.
Differential Diagnosis
- Other
congenital infections (TORCH): toxoplasmosis, CMV, syphilis, Zika,
LCMV.
- Noninfectious:
genetic syndromes with SNHL, CHD, cataracts.
Management
- No
antiviral therapy.
- Supportive
& multidisciplinary care:
- Hearing
loss → early
intervention, hearing aids, cochlear implant if needed.
- Eye
disease → pediatric
ophthalmology, cataract/glaucoma surgery.
- CHD
→ standard cardiology
management.
- CNS
→ seizure mgmt,
developmental therapy.
- Endocrine
→ monitor & treat
DM, thyroid.
- Hematologic
→ thrombocytopenia
usually transient; treat if severe.
- Neonatal
jaundice → avoid
phototherapy if conjugated hyperbilirubinemia predominant.
Surveillance & Follow-up
- Lifelong
monitoring:
- Audiology:
neonatal, 24–30 mo, periodic per AAP.
- Vision:
routine + ophthalmology follow-up.
- Developmental
screening: ongoing.
- Cardiology:
even if initial negative (late stenosis possible).
- Endocrine:
DM, thyroid disease screening.
- Immunology:
check if recurrent infections.
Outcome
- Perinatal
mortality ↑ in severe
neonatal disease.
- Long-term
survivors → ↑ prevalence of SNHL, ocular
disease, CHD, endocrine and vascular disease.
- Progressive
rubella panencephalitis rare but fatal.
Prevention
- Universal
rubella vaccination = cornerstone.
- Prenatal
care: document immunity, vaccinate postpartum if seronegative.
- Infection
control:
- CRS
infants contagious until > 1 yr (unless 2 negative cultures/PCR
> 1 mo apart after 3 mo age).
- Hospitalized
infants: droplet precautions.
- Care
only by immune staff.
- Household
contacts: if vaccinated, no special restriction; counsel re risk to
pregnant visitors.
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✅ Key Clinical Pearls
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