Rubella is an acute viral disease often affecting
susceptible children and young adults worldwide.
Although it causes only a mild clinical illness in these
groups, its public health importance is due to the
teratogenic potential of the virus resulting in congenital
rubella syndrome (CRS). From just before conception
through the first 8–10 weeks of gestation, rubella
infection of the pregnant woman can result in multiple
fetal abnormalities in up to 90% of cases, and may result
in miscarriage or stillbirth. CRS defects can affect any
organ system, including ophthalmic, auditory, cardiac,
neurologic, hepatic and haemotologic. After 18 weeks
of gestation, the risk of CRS is low. The most common
defects of CRS are hearing impairment and deafness, eye
defects (cataracts, congenital glaucoma or pigmentary
retinopathy) and cardiac defects. Infected infants can
shed high amounts of rubella virus from body secretions
for up to one year, thus potentially causing outbreaks.
2. Introduction
Congenital rubella syndrome [CRS]
• Congenital Infections
• Caused by Rubella Virus
Infection of nonimmune pregnant
• Spontaneous Abortion
• Stillbirth/Fetal Death
• Birth of an Infant with CRS
3. Introduction
Before Introduction of Vaccine
• Incidence of CRS: 0.1–0.2/1000 live births during endemic periods
• ̴̴0.8–4/1000 live births during rubella epidemics
As per WHO Global Estimates [2008]
• Rubella a leading cause of congenital anomalies
• Highest CRS burden in developing world
• Southeast Asia [~48%] & Africa [~38%]
• ~300 babies are born worldwide with CRS every day
4. Introduction
Pre-vaaccination Era
• Incidence of CRS: >1000 newborn per year
• ~192/100,000 live births per year
As on 3 August 2018 [WHO Data]
• Successfully controlled rubella & CRS
• Achieved 97% reduction of rubella cases [against a target of 95%]
5. Introduction
Exact estimates are not available
1%–15% of all infants suspected to have intrauterine infection had laboratory
evidence of CRS
6 – 47% of School girls aging 11-18 are susceptible to Rubella Infection
7. Introduction
Rubella [German Measles]
• Prodromal symptoms
• Lymphadenopathy
• Brief appearance of an exanthem
• First on face and spreads down
• Usually lasts ≤ 3 days
• Mostly Mild, Self-limiting Measles-like Disease
• Threat When Nonimmune Pregnant Get Infection Especially In First Trimester
8. Pathogenesis
Obscured due to lack of suitable animal model
Are based on microscopic analyses of aborted infected fetuses
Two possible mechanisms
• A direct cytopathic effect, which may involve rubella virus-induced apoptosis
• A virus-induced inhibition of cell division
9. Pathogenesis
Cellular damage in multiple sites, with non-inflammatory necrosis
• Eyes, Heart, Brain, & Ears
RV-induced cataractous eye lenses from first-trimester fetuses revealed
• Pyknotic Nuclei, Cytoplasmic Vacuoles, & Inclusion Bodies
• Retarded Lens Development
10. Pathogenesis
Necrosis in endothelial cells within the blood vessels lining the heart
• Thrombosis of small vessels & necrosis of surrounding tissue
• Destruction of myocardium
Necrosis of cerebral blood vessels
• Ischemic brain damage
Damage to the epithelium of the cochlear duct
• Deafness
13. Teratogenecity
Infection in first 12 weeks of pregnancy
• CRS [90%], with almost a 100% risk of congenital defects
From 13 to 17 weeks
• Risk is about 60% with risk of defects about 50%
From 18 to 24 weeks
• Risk is about 25%, with hardly any risk of congenital defects
14. Clinicopathological Defects
Abnormality Common/Uncommon Early/Delayed
General
IUGR Common Early
Prematurity, Stillbirth, Abortion Uncommon Early
CVS
PDA, Pulmonary artery stenosis Common Early
Coarctation of the aorta, Myocarditis, Septal defects Uncommon Early
Ear
Hearing loss Common Early/Delayed
Eye
Cataract, Retinopathy, Microphthalmia Common Early
Cloudy cornea [With Spontaneous Resolution] Uncommon Early
Glaucoma Uncommon Early/Delayed
15. Clinicopathological Defects
Abnormality Common/Uncommon Early/Delayed
Skin
Blueberry muffin spots, Chronic rubelliform rash Uncommon Early
Dermatoglyphic abnormalities Common Early
Lungs
Interstitial pneumonia Uncommon Delayed
Liver
Hepatosplenomegaly Common Early
Hepatitis, Jaundice Uncommon Early
Bone Uncommon Early
Radiographic lucencies Common Early
Large anterior fontanel, Micrognathia Uncommon Early
16. Clinicopathological Defects
Abnormality Common/Uncommon Early/Delayed
Immune system
Hypogammaglobulinemia Uncommon Delayed
Lymphadenopathy, Thymic hypoplasia Uncommon Early
Blood
Anemia, Hemolytic anemia, Altered blood group expression Uncommon Early
CNS
Meningoencephalitis, Microcephaly, Intracranial
Calcifications, Hypotonia
Uncommon Early
Encephalographic abnormalities Common Early
Mental retardation, Behavioral disorders, Speech defects Common Delayed
Autism, Chronic progressive panencephalitis Uncommon Delayed
17. Clinicopathological Defects
Abnormality Common/Uncommon Early/Delayed
Endocrine glands
Diabetes mellitus Common Delayed
Hypothyroidism, Hyperthyroidism,Thyroiditis, Growth
hormone deficiency
Uncommon Delayed
Genitourinary system
Cryptorchidism, Polycystic kidney Uncommon Early
18. WHO Case Definition- Suspected Case
Any infant < 12 months of age that presents with any of the following:
• Congenital Heart Disease
• Suspicion of hearing impairment
• One or more of the following eye signs:
• Cataract
• Congenital glaucoma
• Pigmentary retinopathy
Any infant < 12 months of age in whom a health worker suspects CRS, even
without apparent signs of CRS, including maternal history of suspected or
confirmed rubella during pregnancy
19. WHO Case Definition- Final Classification
Depends, in part, on identifying Group A or Group B clinical signs of CRS :
Group A Group B
Cataract(s)
Congenital Glaucoma
Pigmentary Retinopathy
Congenital Heart Disease
Hearing Impairment
Purpura
Splenomegaly
Microcephaly
Developmental Delay
Meningoencephalitis
Radiolucent Bone Disease
Jaundice within the First 24H after birth
Using these Clinical Signs, final classifications are made
20. WHO Case Definition- Final Classification
Laboratory-confirmed CRS:
• A suspected CRS case with at least one sign from group A
• Meets the laboratory criteria for confirmation of CRS
Clinically Compatible CRS:
• A suspected CRS case without an adequate specimen
• At least two of the complications from group A OR
• One from group A and one from group B
21. WHO Case Definition- Final Classification
Congenital Rubella Infection [CRI]:
• An infant who has none of the clinical signs of CRS from group A
• Meets the laboratory criteria for CRS
Discarded:
• A suspected CRS case with an adequate specimen not meeting the laboratory-
confirmed case definition OR
• A suspected case without an adequate laboratory specimen and not meeting
the clinically compatible case definition
22. Laboratory Diagnosis
Specimen
• For Detection of IgM /IgG by ELISA
• Serum
• Specimens for viral detection by Viral Culture or RT-PCR
• Throat Swabs, Oral fluids, Nasopharyngeal Secretions
• Cataract Tissue, Urine, Dried Blood Spots
Congenital rubella syndrome (CRS) is one of the most devastating viral congenital infections caused by rubella virus. Infection of nonimmune pregnant females can result in spontaneous abortion, stillbirth/fetal death, or birth of an infant with CRS
As on 3 August 2018 that Nepal has successfully controlled rubella and congenital rubella syndrome. Nepal has achieved 97% reduction of rubella cases (against a target of 95%) compared to 2008. Nepal has achieved this goal two years ahead of the regional target year of 2020 and one year ahead of the national target of 2019
The outcome of fetal infection is dependent on the gestational timing of maternal rubella, but fetal infection can occur at any stage of pregnancy. In maternal infection after the first trimester, the frequency and severity of fetal damage decreases strikingly because the fetus is protected by the progressive development of fetal humoral and cell-mediated immune responses and by passive transfer of maternal antibodies. Also by this time the important phase of organogenesis is mostly complete
The outcome of fetal infection is dependent on the gestational timing of maternal rubella, but fetal infection can occur at any stage of pregnancy. In maternal infection after the first trimester, the frequency and severity of fetal damage decreases strikingly because the fetus is protected by the progressive development of fetal humoral and cell-mediated immune responses and by passive transfer of maternal antibodies. Also by this time the important phase of organogenesis is mostly complete
If an infant is < 1 month of age with a high suspicion of CRS and a negative IgM serology, then a second specimen should be collected after one month to retest for IgM, as IgM seropositivity can be delayed until after the first month of life (false-negative for ages < 1 month). For infants ≥ 6 months of age but < 12 months with an initial positive rubella IgG serology, a second serum specimen for IgG should be collected after one month and tested in parallel with the initial serum specimen to assess if there is a sustained rubella IgG response.
If an infant is < 1 month of age with a high suspicion of CRS and a negative IgM serology, then a second specimen should be collected after one month to retest for IgM, as IgM seropositivity can be delayed until after the first month of life (false-negative for ages < 1 month). For infants ≥ 6 months of age but < 12 months with an initial positive rubella IgG serology, a second serum specimen for IgG should be collected after one month and tested in parallel with the initial serum specimen to assess if there is a sustained rubella IgG response.