Rubella

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]

Synonyms: German measles; 3 day measles

Rubella is a common childhood infection usually with minimal systemic upset although transient arthropathy may occur in adults. Serious complications are very rare. If it were not for the effects of transplacental infection on the developing fetus, rubella is a relatively trivial infection.

The clinical picture resembling rubella was described for the first time in 1814 and its role in causing congenital anomalies was identified in 1942. The virus was isolated for the first time in 1962 by two independent groups in tissue culture.

The pathophysiology of rubella is not completely understood. Viral replication in the respiratory epithelium occurs following transmission of the virus via contact with droplet secretions from an infected person. Viremia subsequently ensues, with the onset of the rubella rash occurring at the peak of viremia.

The disease is caused by rubella virus, a togavirus that is enveloped and has a single-stranded RNA genome.^[1] The virus is transmitted by the respiratory route and replicates in the nasopharynx and lymph nodes. The virus is found in the blood 5 to 7 days after infection and spreads throughout the body. It is capable of crossing the placenta and infecting the fetus.^[2]

Rubella infection must be differentiated from diseases presenting with features of skin rash, fever and lymphadenopathy such as measles, coxsackievirus infection and infectious mononucleosis.

In the United States, endemic rubella virus transmission has been eliminated since 2001. From 2004 to 2013, 10 cases of rubella infection were diagnosed in the immigrants.

The risk factors predisposing for rubella infection include: contact with infected patient and not receiving immunization according to the standard schedule.

There are no standard screening test recommended for rubella infection, however pregnant women with suspected rubella infection must be investigated to confirm the diagnosis to prevent fetal anomalies.

Rubella is transmitted by direct contact and presents with a fever, rash and lymphadenopathy. It is usually a self limiting infection and resolves without any complications. Few patients might develop complications such as arthritis which needs symptomatic treatment. The prognosis is good in adults with complete resolution of symptoms in a week.

Patients with rubella infection present with a fever, skin rash and cervical lymphadenopathy. Malaise and anorexia precede the development of fever and rash.

Rubella infection in adults presents with low grade fever and a maculopapular rash starting on the face and spreads caudally. Cervical lymphadenopathy is present in majority of the patients.

All patients with suspected rubella infection must be investigated further to confirm the diagnosis. Serological tests to look for the presence of rubella specific IgG antibodies and IgG avidity and RT-PCR should be done to confirm the diagnosis.

There is no specific antiviral therapy for rubella infection. Symptomatic therapy and reporting the infection to local disease control agencies is recommended.

Surgical intervention is not recommended for the management of rubella infection.

Rubella infections are prevented by active immunization programs using live, disabled virus vaccines. Two live attenuated virus vaccines, RA 27/3 and Cendehill strains, are effective in the prevention of adult disease

All the patients with confirmed rubella infection must be vaccinated. Pregnant women should be vaccinated after delivery of the baby.^[3]

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]

The clinical picture resembling rubella was described for the first time in 1814 and its role in causing congenital anomalies was identified in 1942. The virus was isolated for the first time in 1962 by two independent groups in tissue culture.

• 1814, George Maton, first recognized that a mild illness characterized by rash, lymphadenopathy, and little or no fever.^[1]
• In 1866, Henry Veale named the disease rubella.^[1]
• In 1942, Norman Gregg reported the birth defects in a pregnant woman infected with rubella in the first trimester.^[1]
• Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century.^[2]
• In 1962, rubella virus was isolated in tissue culture.^[1]
• In 1972, there was an rubella epidemic in Israel, affecting 11.8 per thousand live births.^[3][4]
• In May 2012, 194 countries at the World Health Assembly adopted the Global Vaccine Action Plan to eliminate measles and rubella in at least five WHO regions by the end of 2020. 53 member states of the WHO region still did not reach the goal for elimination of rubella to date.^{[5][6][7][8][9]}
• Between September 2011 and December 2012, an epidemic of rubella infection occurred in Romania affecting 24,627 people.^[10]

The “rubella umbrella” campaign urged parents to have their children immunized from this viral infection. Rubella, or more commonly referred to as the German measles, is a mild childhood illness that can pose a serious threat to a fetus, if the mother contracts the illness during pregnancy. More than 20,000 babies were born with congenital rubella syndrome (CRS) during an outbreak of rubella in 1964-65. This epidemic cost the country an estimated $1.5 billion. The rubella vaccine was first licensed in the U.S. in 1969.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Fatimo Biobaku M.B.B.S [2], Aravind Kuchkuntla, M.B.B.S[3]

The pathophysiology of rubella is not completely understood. Viral replication in the respiratory epithelium occurs following transmission of the virus via contact with droplet secretions from an infected person. Viremia subsequently ensues, with the onset of the rubella rash occurring at the peak of viremia.^[1][2]

• Rubella is transmitted primarily through direct or droplet contact with nasopharyngeal secretions of infected persons.
• Humans are the only natural host.
• Rubella infection usually occur during late winter and early spring.
• The average incubation period of rubella virus is 17 days, with a range of 12 to 23 days.
• People infected with rubella are most contagious when the rash is erupting.

The pathophysiology of rubella infection is not fully understood.^[1] The pathophysiology of rubella infection involves the following processes:^[1][2][3]

• The transmission of infection is via person-person spread through droplets that are shed from respiratory secretions of infected persons.
• Viral replication occurs in the respiratory epithelium, with subsequent spread of the virus to the regional lymph nodes.
• Viremia ensues and subsequent seeding of viremia to multiple organs may occur (including the placenta in pregnant women, which results in congenital rubella syndrome).
• The onset of viremia is usually between 8-9 days after exposure, peaking at 10-17 days.
• The onset of rash often occurs 16-18 days after exposure (around the peak of viremia).
• Approximately 10 days after infection, viral shedding from the nasopharynx begins.
• Viral shedding may continue 1 week before the rash appears to about 5-14 days after the disappearance of the rash.
• The infected patient is contagious 5 days before the onset of the rash to 6 days after the appearance of the rash.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]

Rubella virus is a single stranded, positive sense RNA virus (ssRNA). It is the only member of the genus Rubivirus and belongs to the family of Togaviridae. Rubella virus is only known to infect humans, and it is responsible for causing the common childhood Rubella infection. Rubella infection is also known as German Measles or Three Day Measles. The most devastating consequence is when Rubella virus infects pregnant women during their first trimester, as it may result in congenital rubella syndrome in the newborn. Rubella infection has largely been eradicated in the developed world since the introduction of the MMR vaccine. However, it is still a challenge in many parts of the developing world due to cost and availability of the MMR vaccine.

The Rubella virus genome is composed of 9762 nucleotides and encodes 2 nonstructural polypeptides (p150 and p90) within its 5′-terminal two-thirds and 3 structural polypeptides (C, E2, and E1) within its 3′-terminal one-third. Both envelope proteins E1 and E2 are glycosylated. The Rubella virus has the highest concentration of G/C nucleotides of any RNA virus, with 69.5% of the genome consisting of those nucleotides. Rubella has been sequenced completely for three strains showing >95% homology between the three strains.

There are three sites that are highly conserved in Togaviruses:

• A stem-and-loop structure at the 5′ end of the genome
• A 51-nucleotide conserved sequence near the 5′ end of the genome and
• A 20-nucleotide conserved sequence at the subgenomic RNA start site. Homologous sequences are present in the rubella genome.
  

The genome encodes several non-coding RNA structures. Among those is the rubella virus 3′ cis-acting element, which contains multiple stem-loops and one of the stem-loop structures has been found to be essential for viral replication.

Rubella virus is an enveloped virus, circular or oval in shape and 60nm in diameter. The virion is composed of a capsid core containing a single copy of genomic RNA. The outer membrane is a lipid bilayer containing specialized glycoproteins (E1 and E2) believed to be responsible for attachment to host cells. It is also believed that a pH of 6.0 or less induces conformational changes in the glycoproteins making attachment of the viral envelope to host cells more likely. Rubella virus likely enters cells via endocytosis. Once in the cell a conformational change occurs in the capsid shell releasing the genetic information into the cell. Replication is slow with a latency period of 8-12 hours, with structural proteins appearing at 12-16 hours and peak viral 36-48 hours after infection. In volunteer subjects infected via aerosol, the characteristic rash typically appears 16-20 days from the time of exposure.

On the basis of differences in the sequence of the E1 protein, two genotypes have been described which differ by 8-10%. These have been subdivided into 13 recognised genotypes: 1a, 1B, 1C, 1D, 1E, 1F, 1G, 1h, 1i, 1j, 2A, 2B and 2C.

For typing, the WHO recommends a minimum window that includes nucleotides 8731 to 9469.

• Genotypes 1a, 1E, 1F, 2A and 2B have been isolated in China.
• Genotype 1j has only been isolated from Japan and the Philippines.
• Genotype 1E is found in Africa, the Americas, Asia and Europe.
• Genotype 1G has been isolated in Belarus, Cote d’Ivoire and Uganda.
• Genotype 1C is endemic only in Central and South America.
• Genotype 2B has been isolated in South Africa.
• Genotype 2C has been isolated in Russia.

Rubella virus only infects humans and is spread from person to person through contact or from a cough or sneeze, as the virus lives in the mucus of an infected person. The virus can be transmitted up to a week before the rash appears and one to two weeks after. Rubella is also transmitted from an infected mother to her unborn child causing congenital rubella syndrome.

The rubella vaccine is included as a part of the common childhood vaccination known as MMR (Measles, Mumps, Rubella) vaccination. The Meruvax II or Rubella vaccination effectively prevents the disease after a single injection in humans 12 moths or older. While antibodies are usually developed after a single infection of the virus the vaccine is vital to prevent infection of expecting mothers who could pass on the virus to their unborn fetus. The vaccine is a freeze dried sample of the Wistar RA 27/3 strain of Rubella virus which when injected induces an immunity by causing a modified rubella infection. Rubella hemagglutinin antibodies are produced to prevent infection of wild rubella virus. Vaccination with MMR is a requirement in most states for children wishing to enter school. It is not yet clearly known if the immunity is permanent, however, it is known to last for at least 10 years.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Michael Maddaleni, B.S., João André Alves Silva, M.D. [2], Aravind Kuchkuntla, M.B.B.S[3]

Rubella infection must be differentiated from diseases presenting with features of skin rash, fever and lymphadenopathy such as measles, coxsackie virus infection and infectious mononucleosis.

Different rash-like conditions can be confused with rubella and are thus included in its differential diagnosis. The various conditions that should be differentiated from rubella include:^{[1][2][3][4][5][6][7]}

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]

In the United States, endemic rubella virus transmission has been eliminated since 2001. From 2004 to 2013, 10 cases of rubella infection was diagnosed in the immigrants.

Incidence

• In the United States, endemic rubella virus transmission has been eliminated since 2001.
• From 2004 to 2013, a median of 10 (range, 4–18) imported cases were reported annually in the United States, and 6 cases of congenital rubella syndrome were reported during the same period. The patients diagnosed with the infection are the immigrants.
• In 2013, 2 large outbreaks were reported in Poland and Japan; cases were mostly among adolescent boys and adult men, but pregnant women were also affected, and their children subsequently developed congenital rubella syndrome.^[1]

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]

The risk factors predisposing for rubella infection include: contact with infected patient and not receiving immunization according to the standard schedule.

The following risk factors predispose to get rubella infection: ^[1]

• Contact with infected patient
• Failure to get vaccinated
• Overcrowding^[2]
• Poor immune response to the vaccine^[3]
• Medical personnel^[4][5]

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Michael Maddaleni, B.S., Aravind Kuchkuntla, M.B.B.S[2]

There are no standard screening test recommended for rubella infection, however pregnant women with suspected rubella infection must be investigated to confirm the diagnosis to prevent fetal anomalies.^[1]

There is no screening test for rubella, however, if there is a high clinical suspicion of rubella infection during pregnancy, serum IgG and IgM antibodies against rubella may be ordered. Also, if a pregnant woman proves to be not immune aganist rubella, vaccination with MMR should be deferred till after delivery due to the theoretical teratogenic effects of the rubella vaccine.^[2][3][4]

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]

Rubella is transmitted by direct contact and presents with a fever, rash and lymphadenopathy. It is usually a self limiting infection and resolves without any complications. Few patients might develop complications such as arthritis which needs symptomatic treatment. The prognosis is good in adults with complete resolution of symptoms in a week.

Rubella is transmitted primarily through direct or droplet contact from nasopharyngeal secretions, and affects adolescents and adults.The onset of viremia is usually between 8-9 days after exposure, peaking at 10-17 days. The onset of rash usually occurs 16-18 days after exposure. Approximately 10 days after infection, viral shedding from the nasopharynx begins. The patient is most contagious 5 days before the onset of the rash to 6 days after the appearance of the rash. Majority of the patients are asymptomatic and few present with low grade fever, skin rash and cervical lymphadenopathy. Rubella is a self limiting condition and most patients have no sequalae but few patients develop arthritis.^[1]

• The most common complication of rubella in adults is the development of arthritis.
• The most serious complication of rubella is the transmission of infection to the fetus if the women is a pregnant at the time of infection. Infection of the fetus during gestation can result in congenital rubella syndrome.
• Rare complications of rubella include thrombocytopenic purpura and encephalitis.

Rubella is a self limiting condition and most patients have no sequelae and have good prognosis but few patients develop transient arthralgia.

Template:WH Template:WS