1. Togavirus: Rubella Longster Kemngang
Rubella virus particles on a cellular surface

2. https://online.epocrates.com, 12 March 2015
Clinical Vignettes
A 25-year-old man presents with a 3-day history of low-grade fever, malaise, headache, and aching knees. That morning he developed a rash on his face, which has now spread to his chest and arms. image His physical exam is notable for mild conjunctival injection, mild bilateral posterior auricular lymphadenopathy, and a discrete erythematous papular rash on his face, trunk, and upper arms. The patient is from Mexico, has lived in the US for 6 months, and is unaware of his immunization status. He reports that a coworker with whom he had close contact had a similar rash last week.
A 2820-gram (6lbs 2 oz) female infant is born to a 22-year old primigravidas mother at approximately 38 weeks' gestation following an uncomplicated pregnancy. The baby has mild hepatosplenomegaly, numerous purplish firm nonblanching skin nodules, scattered petechiae, and a grade 3 continuous murmur audible at the left infraclavicular area. The baby's mother immigrated from Liberia during the sixth month of her pregnancy; she cannot recall having been immunized in childhood.
primigravida —> first born
12 March 2015

4. Rubella Rubivirus Togaviridae : Rubivirus : Rubella/German Measles
DISEASE: GERMAN MEASLES (“3 DAY MEASLES”)
Enveloped Icosahedral Capsid Positive Single Stranded RNA
Rubella virus is the only member of the genus of Rubivirus and belongs to the family of Togaviridae
The physicians who found it were german, so german measles
The virus is covered by a lipid membrane (viral envelope), derived from the host cell membrane. There are prominent "spikes" (projections) of 6 nm composed of the viral envelope proteins E1 and E2 embedded in the membrane.
The E1 glycoprotein is considered immunodominant in the humoral response induced against the structural proteins and contains both neutralizing and hemagglutinating determinants. E1 and E2 are targeting to the golgi apparatus. packaging and resembling proteins —> duh. E1 is targeting to rubella by addition of the GPI anchor
Rubivirus

5. Virus Replication Cycle
attachment, penetration, uncoating, replication, assembly, and release.
The E1 glycoprotein is considered immunodominant in the humoral response induced against the structural proteins and contains both neutralizing and hemagglutinating determinants. E1 and E2 are targeting to the golgi apparatus. packaging and resembling proteins —> duh. E1 is targeting to rubella by addition of the GPI anchor

6. Acquired Rubella Host : Humans Virus enters body via respiratory route
a) replicates asymptomatically in URT in the nasopharyngeal mucosa
b) gains access to lymphatic system and subsequently enters bloodstream
2 week incubation period (12-18 days)
transmitted by breathing in droplets that are sprayed into the air when an infected person sneezes, coughs or talks.
Carrier is infectious for 7 days before appearance of rash and for 5-7 days after the appearance of the rash(2,3). Transmission requires close person-to-person contact(7).
Medscape, 2015

7. Clinical Presentation
Rubella production in the pharynx precedes the appearance of symptoms and continues through the course of the disease.
Fever and rash occur later. Patients are infectious for 7 days before and after rash appears.
The onset of lymphadenopathy coincides with viremia
The person is infectious as long the virus is produced in the pharynx.
Rash is the first symptoms to appear. Rash appears 2 weeks after infection
The rash, if it occurs at all, occurs after the incubation period and begins on the face, lasting between 12 hours and 5 days. 
Carrier is infectious for 7 days before appearance of rash and for 5-7 days after the appearance of the rash
Following respiratory transmission of rubella virus, replication of the virus is thought to occur in the nasopharynx and regional lymph nodes. A viremia occurs 5 to 7 days after exposure with spread of the virus throughout the body.

8. Signs and Symptoms 70% of Adults:
non-confluent —> there are not running together but they are fine, discrete erythematous rash
The rash appears first on face and neck, then spread to the trunk and limbs
The rash also fades after 48 hours or less
Arthralgia or arthritis may occur in up to 70% of adult women who contract rubella, but it is rare in children and adult males. Fingers, wrists, and knees are often affected. Joint symptoms tend to occur about the same time or shortly after appearance of the rash and may last for up to 1 month; chronic arthritis is rare.
Rare complications can include encephalitis in less than 1/5,000 cases, neuritis, orchitis, and panencephalitis.  
Rash: maculopapular, non-confluent
Rash extends from face to the trunk and limb
70% of Adults:
Lymphoadenopathy (retroauricular and suboccipital), arthritis and arthralgias (adults)
Mild Disease Signs/Symptoms:
Fever
Postauricular adenopathy
Lymphadenopathy
Arthralgias
Fine truncal rash that starts at the head and moves down

9. Rubella Disease Timeline
Prodrome — early symptom that may indicate the start of the disease
Rubella production in the pharynx precedes the appearance of symptoms and continues through the course of the disease.
The onset of lymphadenopaathy coincides with viremia
Fever and rash occur later days later post viremia. And the only last about 48 hours maximum
The person is infectious as long the virus is produced in the pharynx. We see that the virus remains in the pharynx the longest. So the symptoms can disappear but the pharynx still is carrying the virus
Children and Adults: symptoms include low grade fever, sore throat, rash, and lymphoadenopathy. In extremely young children there is usually no prodrome. That is because it is usually congenital and pasted through the mother.People are usually infectious one week before the appearance of the rash to one week after the rash disappears. 

10. Most common congenital manifestations
Congenital TORCHES
Most common congenital manifestations
Toxoplasma gondii
Other (varicella-zoster, parvovirus B19)
Rubella
CMV
HIV
Herpes simplex virus-2
Syphilis
microbes that pass from mother to fetus. transmission is transplacental in most cases or via delivery . esp in the HSV-2. non specific abnormalities.
Infection with rubella virus is most severe in early gestation. The virus may affect all organs and cause a variety of congenital defects.
Infection may lead to fetal death, spontaneous abortion, or premature delivery.

11. Congenital Rubella Crosses placenta when mother has acute infection.
The earlier the fetus is infected -> more serious disease.
May result in serious congenital abnormalities
Intrauterine growth retardation
Hepatosplenomegaly
Cataracts
Mental retardation
Sensorineural hearing loss
Heart- Patent ductus arteriosis
Pulmonary stenosis
Thrombocytopenic purpura
The severity of the effects of rubella virus on the fetus depends largely on the time of gestation at which infection occurs.
As many as 85% of infants infected in the first trimester of pregnancy will be found to be affected if followed after birth.
While fetal infection may occur throughout pregnancy, defects are rare when infection occurs after the 20th week of gestation. The overall risk of defects during the third trimester is probably no greater than that associated with uncomplicated pregnancies.
Congenital infection with rubella virus can affect virtually all organ systems. Deafness is the most common and often the sole manifestation of congenital rubella infection, especially after the fourth month of gestation. Eye defects, including cataracts, glaucoma, retinopathy, and microphthalmia may occur. Cardiac defects such as patent ductus arteriosus, ventricular septal defect, pulmonic stenosis, and coarctation of the aorta are possible. Neurologic abnormalities, including microcephaly and mental retardation, and other abnormalities, including bone lesions, splenomegaly, hepatitis, and thrombocytopenia with purpura may occur.
* In Pediatrics , these is a classic triad for the congenital manifestations
blueberry muffin rash —distrubuted purpura—bleeding under the skin .3-1cm (skin lesions are sites of extra medullary hematopoesis—> differential. This rash is seen in CMV and Rubella.
Cataracts
Classic triad:
PDA
Cataracts, and deafness
+/- “blueberry muffin” rash
Blueberry Muffin Rash
PDA

12. Pattern of Viral Excretion and Infant’s Antibody
Response in Congenital Rubella
viral excretion (+)
Transplacental infection of the fetus occurs during viremia. Fetal damage occurs through destruction of cells as well as mitotic arrest.
The risk of severe disease in neonates is the highest if the mother is infected within the first few weeks of pregnancy and declines as the pregnancy progresses. So here we see that during the first trimester, the mother has the virus and IgM is fighting the infection. By birth, the mother has IgG fighting off the infection and the child’s IgM is high as the longevity pairing up with the longevity of the infection due to the time the virus occurred in the mother. Viremia, 1st trimested.
Virus from congenital infections persists after birth.
Those with congenital infections can infect others after birth for several months. The virus occurs in naso-pharyngeal secretions, urine and feces.

13. Clinical Laboratory Findings/Diagnosis
Isolation of rubella virus from clinical specimen (e.g., nasopharynx, urine)
Positive serologic test for rubella IgM antibody
Significant rise in rubella IgG by any standard serologic assay (e.g., enzyme immunoassay)
Treatment: No treatment, just supportive care
Prevention: MMR vaccine (Measles/Mumps/Rubella)

14. Treatment, Prevention & Control
MMR vaccine: live attenuated virus
Measles/Mumps/Rubella
Dramatic decline in the incidence of the disease since introduction of vaccine
Periodic epidemics affect unvaccinated populations. 
Pro — induces strong, often life-long immunity
Con — may revert to virulent form
USA Vaccination schedule: at months and at 4 to 6 years
Immunize at 9 months in endemic areas
Administer 1 dose of MMR vaccine to infants aged 6 through 11 months before departure from the United States for international travel
Efficiency: 95% lifelong immunization with a single dose
live attenuated vaccine —> the microorganism loses its pathogenicity but retains capacity for transient growth within the inoculated host. the vaccine mainly induces a cellular response
Rubella vaccine is very safe. Most adverse reactions reported following MMR vaccination (such as fever and rash) are attributable to the measles component. The most common complaints following rubella vaccination are fever, lymphadenopathy, and arthralgia. These adverse reactions only occur in susceptible persons and are more common in adults, especially in women.
Joint symptoms, such as arthralgia (joint pain) and arthritis (joint redness and/or swelling), are associated with the rubella component of MMR. Arthralgia and transient arthritis occur more frequently in susceptible adults than in children and more frequently in susceptible women than in men. Acute arthralgia or arthritis is rare following vaccination of children with RA 27/3 vaccine. By contrast, approximately 25% of susceptible postpubertal females develop acute arthralgia following RA 27/3 vaccination, and approximately 10% have been reported to have acute arthritis-like signs and symptoms. Rarely, transient peripheral neuritic complaints, such as paresthesias and pain in the arms and legs, have been reported.
Rubella Vaccine
Vaccine Trade Name Licensure
HPV-77:DE Meruvax
HPV-77:DK Rubelogen
GMK-3:RK Cendevax
RA 27/3* Meruvax II
*Only vaccine currently licensed in U.S.
CDC, 2015

15. Differential Dx Rubella: Enveloped Icosahedral Capsid Positive
Single Stranded RNA Measles: Paramyxoviruses Enveloped negative
linear non segmented helical Single
Stranded RNA
Rubella has NO desquamation (different from Measles)
Rash: maculopapular, non-confluent
(different from Measles: Rash presents last and spreads from head to toe. Koplik spots—not present in Rubella).
Crucial Symptom: Lymphoadenopathy (retroauricular and suboccipital), arthritis and arthralgias — 70% of Adults
viral exanthems —> a wide spread rash
measles —> triple C and P —-> cough, conjuctiva, coryza (runny nose) and photophobia … multinucleated giant cells and inclusion bodies but koplik spots are the definite diagnosis ..
rash measles —-> it appears in 1-2 days then leaves in 1-2 days so its hard to tell still —> desqaumation= to come off as flakes
rubella and measles are both rare in vaccinated children so independent of the “con” of the vaccine, the chances are you were not vaccinated.
In Exanthem Roseola: The rash begins as the fever goes away. There is a sudden "surprise" appearance of the rash after the fall of the fever. Numerous pale pink, almond-shaped macules appear on the trunk and neck. They become confluent, and then fade in a few hours to 2 days without scaling or pigmentation.vomiting, running nose, cough, and hepatomegaly
The hallmark of rubella is the generalized tender lymphadenopathy which involves all nodes, but which is most striking in the suboccipital, postauricular, and anterior and posterior cervical nodes. Swelling of the lymph nodes most prevalent at the time of appearance of the exanthem but may precede it by a week. The tenderness that accompanies this lymphadenopathy subsides rapidly, however the enlargement may last days or weeks.
Extend from face to the trunk and limb (different from Exanthem roseola: surprise “almond-shaped” macule rash post fever on the trunk and neck)
Viral exanthems : Varicella (VZV) , Rubella, Measles
Congenital:
Rubella and CMV are the only TORCH viruses that have been documented by
skin biopsies to cause dermal erythropoiesis
Parvo B19 (Slap cheek) no vaccine; EASY to mistake for rubella
Look for Anemia and NO Teratogenic properties if congenital in Parvo B19

16. https://online.epocrates.com, 12 March 2015
Clinical Vignettes
A 25-year-old man presents with a 3-day history of low-grade fever, malaise, headache, and aching knees. That morning he developed a rash on his face, which has now spread to his chest and arms. image His physical exam is notable for mild conjunctival injection, mild bilateral posterior auricular lymphadenopathy, and a discrete erythematous papular rash on his face, trunk, and upper arms. The patient is from Mexico, has lived in the US for 6 months, and is unaware of his immunization status. He reports that a coworker with whom he had close contact had a similar rash last week.
A 2820-gram (6lbs 2 oz) female infant is born to a 22-year old primigravidas mother at approximately 38 weeks' gestation following an uncomplicated pregnancy. The baby has mild hepatosplenomegaly, numerous purplish firm nonblanching skin nodules, scattered petechiae, and a grade 3 continuous murmur audible at the left infraclavicular area. The baby's mother immigrated from Liberia during the sixth month of her pregnancy; she cannot recall having been immunized in childhood.
12 March 2015

17. References http://www.cdc.gov/rubella/index.html
Chantler, J., Wolinsky, J. S., & Tingle, A. (2001). Rubella Virus. In D. M. Knipe, & P. M. Howley (Eds.), Fields Virology (4th ed., pp ).
Philidelphia: Lippincott Williams & Wilkins.
Edlich, R. F., Winters, K. L., Long, W. B.,3rd, & Gubler, K. D. (2005). Rubella and congenital rubella (German measles). Journal of Long-Term Effects of Medical Implants, 15 (3),
De Santis, M., Cavaliere, A. F., Straface, G., & Caruso, A. (2006). Rubella infection in pregnancy. Reproductive Toxicology (Elmsford, N.Y.), 21 (4), doi: /j.reprotox
Murray, Patrick R. PhD , Ken S. Rosenthal PhD. Medical Microbiology: with Student consult Online Access, 7e Paperback – November 28, 2012