Abnormal Development - Rubella Virus
|Embryology - 27 Feb 2017 Expand to Translate|
|Google Translate - select your language from the list shown below (this will open a new external page)|
العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt These external translations are automated and may not be accurate. (More? About Translations)
|Educational Use Only - Embryology is an educational resource for learning concepts in embryological development, no clinical information is provided and content should not be used for any other purpose.|
- 1 Introduction
- 2 Some Recent Findings
- 3 Virus Structure
- 4 Vaccination
- 5 WHO Rubella Information
- 6 Rubella History
- 7 Congenital Rubella Syndrome Abnormalities
- 8 References
- 9 External Links
- 10 Glossary Links
Rubella virus (Latin, rubella = little red), also known as "German Measles" (due to early citation in German medical literature), infection during pregnancy can cause congenital rubella syndrome (CRS) with serious malformations of the developing fetus. The type and degree of abnormality relates to the time of maternal infection.
Rubella peaked in 1964 and 1965, when 12.5 million cases were reported (USA). As a result, 20,000 babies were born with birth defects, 6,200 babies were stillborn, and an estimated 5,000 births were aborted, both naturally and assisted. At that time no treatment by vaccination existed and this only became available in 1969. The disease was dangerous because in children it was almost unnoticable and pregnant women often did not know that they had been exposed. Initial vaccination strategies varied between countries, in the United States infants were first to be vaccinated, while in the United Kingdom adolescent girls were first to be vaccinated.
Pregnancy effects of measles results in a higher risk of premature labor, spontaneous abortion, low-birth-weight, and possibly rare cases of birth defects with no definable pattern of malformation.
Children infected with rubella before birth (a condition known as congenital rubella) are at risk for the following: growth retardation; malformations of the heart, eyes, or brain; deafness; and liver, spleen, and bone marrow problems.
The complete genomic sequence of Rubella is now known. Rubella is a 9755 bp single stranded RNA positive-strand virus with no DNA stage (Togaviridae; Rubivirus) encoding nonstructural protein, capsid protein, glycoproteins E1 and E2. (More? Rubella Genome)
Tinycc Rubella Virus page - http://tiny.cc/Rubella_Virus
|Viral Links: TORCH Infections | Cytomegalovirus | Hepatitis Virus | HIV | Parvovirus | Polio Virus | Rubella Virus | Chickenpox | Lymphocytic Choriomeningitis Virus | Zika Virus | Vaccination | Environmental|
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
N D Carvalho, R Z Mendonça, M I Oliveira, S P Curti, T F Barbosa, P E Silva, N N Taniwaki, M Tonelotto, D N S Giovanni, R H P Moraes, C A Figueiredo Antiviral activity of hemolymph of Podalia against rubella virus. Cytotechnology: 2016; PubMed 27896559
Manoel Sarno, Marcelo Aquino, Kleber Pimentel, Renata Cabral, Gisela Costa, Fernanda Bastos, Carlos Brites Progressive lesions of Central Nervous System in microcephalic fetuses with suspected congenital Zika virus syndrome. Ultrasound Obstet Gynecol: 2016; PubMed 27644020
Manon Vouga, David Baud Imaging of congenital Zika virus infection: the route to identification of prognostic factors. Prenat. Diagn.: 2016; PubMed 27481629
Use Zika to renew focus on birth-defect research. Nature: 2016, 535(7610);8 PubMed 27383948
Alexandre Yazigi, Aurelia Eldin De Pecoulas, Christelle Vauloup-Fellous, Liliane Grangeot-Keros, Jean-Marc Ayoubi, Olivier Picone Fetal and neonatal abnormalities due to congenital rubella syndrome: a review of literature. J. Matern. Fetal. Neonatal. Med.: 2016;1-14 PubMed 27002428
Jayakrishnan Thayyil, Vidya Kuniyil, Anitha P Moorkoth, Bhaskar Rao, Paramasivam Selvam Prevalence of rubella-specific IgG antibodies in unimmunized young female population. J Family Med Prim Care: 2017, 5(3);658-662 PubMed 28217601
Mariam M Mirambo, Said Aboud, Uwe Groß, Mtebe Majigo, Martha F Mushi, Stephen E Mshana Rubella Seromarkers and Determinants of Infection among Tanzanian Children and Adolescents in Prevaccination Era: Are We in the Right Track? Int J Prev Med: 2017, 8;3 PubMed 28217265
D Zhang, G Lin, L Yi, M Hao, G Fan, X Yang, R Peng, J Ding, K Zhang, R Zhang, J Li External Quality Assessment for Rubella Virus RNA Detection Using Armored RNA in China. Clin. Lab.: 2017, 63(2);399-405 PubMed 28182341
Cristina Caroça, Vera Vicente, Paula Campelo, Maria Chasqueira, Helena Caria, Susana Silva, Paulo Paixão, João Paço Rubella in Sub-Saharan Africa and sensorineural hearing loss: a case control study. BMC Public Health: 2017, 17(1);146 PubMed 28143602
Raye-Ann deRegnier 50 Years Ago in The Journal of Pediatrics: Cerebral Lesions in Congenital Rubella Syndrome. J. Pediatr.: 2017, 181;111 PubMed 28129869
Lineage: Viruses; ssRNA viruses; ssRNA negative-strand viruses; Mononegavirales; Paramyxoviridae; Paramyxovirinae; Morbillivirus; Measles virus
- ssRNA; linear; Length: 15,894 nt Measles virus, complete genome
- virus replication involves a viral RNA-dependent RNA polymerase (vRdRp), using as a template a nucleocapsid (NC) made of a single strand of RNA in tight complex with the nucleoprotein (N).
- negative-strand genome contains six transcription units encoding the N, phospho (P), matrix (M), fusion (F), hemagglutinin (H), and large (L) or polymerase protein.
- each N protein binds to 6 nucleotides.
- the N polymer entirely covers the 15,894-nucleotide genome.
- 23 known measles genotypes.
Model of cell virus RNA accumulation
The following 5 -step model has been described for cell virus accumulation following hours post-infection (hpi)
- 0 to ~5 hpi - incoming viral RNA-dependent RNA polymerase (vRdRp) initiated primary transcription from every gene with no detectable lag phase.
- ~5 to ~12 hpi - mRNA accumulates exponentially.
- ~12 to ~24 hpi - mRNAs, genomes, and antigenomes accumulate exponentially because of the increase of both newly available template and vRdRp.
- ~24 to ~30 hpi - genomes and antigenomes continue to accumulate exponentially at the same rate, whereas the accumulation of the transcripts slows down.
- 30+ hpi - genome and antigenome accumulation slows down, and the cell content in viral transcripts tends to decrease.
Japan - first introduced to Japan in 1966 and adopted in the national regular immunization program from 1978.
WHO Rubella Information
- Causative agent - Virus
- Reservoir - Humans
- Spread - Close respiratory contact and aerosolized droplets
- Transmission period - A few days before to seven days after rash; up to one year of age in congenitally infected
- Subclinical infection - Common
- Duration of natural immunity - Lifelong
- Risk factors for infection (for unvaccinated individuals) - Highly transmissible; crowding; low socioeconomic status
- Case-fatality rate - Less than 0.1 percent (dependent on care)
- Vaccine (number of doses); route - Rubella (one or two); subcutaneous
- Vaccine efficacy - 95 percent (at 12 months and up)
- Duration of immunity after primary series - Lifelong in most; presumed rare cases of waning immunity after one dose, not two
- Schedule - First dose at 12 to 15 months; when given, a second dose with measles vaccine
- Status as of the end of 2001 - 110 countries in 2003
- Comments - Lower efficacy when maternal antibody present
The World Health Organization recommends that the combination measles-rubella or measles-mumps-rubella vaccines be introduced only after careful evaluation of public health priorities within each country and following the establishment of an adequate program for measles control as demonstrated by high coverage rates as part of a well-functioning childhood immunization program.
Sources: WHO 2002, 2004.
Norman Gregg (1892-1966) was a Sydney ophthalmologist who in 1941 identified the link between maternal rubella infection and developmental abnormalities (atypical congenital cataracts, congenital heart defects, infants small-for-gestational age) initially in his own practice. This had coincided with a rubella epidemic that occurred between 1940 to 1941.
- Links: Norman Gregg
United States first licensed live, attenuated rubella vaccines introduced.
United States Elimination of rubella and congenital rubella syndrome, 1969-2004
- 1969 - First official recommendations are published for the use of rubella vaccine. Vaccination is recommended for children aged 1 year to puberty.
- 1978 - Recommendations for vaccination are expanded to include adolescents and certain adults, particularly females.
- 1981 - Recommendations place increased emphasis on vaccination of susceptible persons in training and educational settings.
- 1984 - Recommendations are published for vaccination of workers in daycare centres, schools, colleges, companies, government offices, and industrial sites. Providers encouraged to conduct prenatal testing and postpartum vaccination of susceptible women. Recommendations for vaccination are expanded to include susceptible persons who travel abroad.
- 1990 - Recommendations include implementation of a new 2-dose schedule for measles-mumps-rubella vaccine.
Rubella and measles elimination in the Americas
In 2014 a Philippines measles outbreak of over 50,000 cases occurred. Travellers to and from the Philippines during this period led to an increase in cases occurring in other countries. For example, the USA experienced the highest number of measles cases CDC had reported in 20 years, over 600, many of the people who got measles last year were linked to travelers who had gotten measles from the Philippines.
From January 1 to January 28, 2015, 84 people from 14 states were reported to have measles. Most of these cases are part of a large, ongoing outbreak linked to an amusement park in California. On January 23, 2015, CDC issued a Health Advisory to notify public health departments and healthcare facilities about this multi-state outbreak and to provide guidance for healthcare providers nationwide. For more information see CDC Press Briefing Transcript: Measles in the United States, 2015, January 29, 2015.
Congenital Rubella Syndrome Abnormalities
The following are some examples of abnormalities associated with Congenital Rubella Syndrome (CRS).
- sensorineural deafness
- mental retardation
- (rare) progressive rubella panencephalitis
- patent ductus arteriosis
- atrial septal defect
- ventricular septal defect
- peripheral pulmonic stenosis
- insulin dependent diabetes mellitus
- general growth retardation
- radiolucent bone disease
- heamatologic abnormalities (thrombocytopenia, purpura)
- Makiko Egashira Chiba, Masatoshi Saito, Nobuaki Suzuki, Yoshinobu Honda, Nobuo Yaegashi Measles infection in pregnancy. J. Infect.: 2003, 47(1);40-4 PubMed 12850161
- G Dominguez, C Y Wang, T K Frey Sequence of the genome RNA of rubella virus: evidence for genetic rearrangement during togavirus evolution. Virology: 1990, 177(1);225-38 PubMed 2353453
- Nathaniel Lambert, Peter Strebel, Walter Orenstein, Joseph Icenogle, Gregory A Poland Rubella. Lancet: 2015; PubMed 25576992
- Centers for Disease Control and Prevention (CDC) Rubella and congenital rubella syndrome control and elimination - global progress, 2000-2012. MMWR Morb. Mortal. Wkly. Rep.: 2013, 62(48);983-6 PubMed 24304830 | MMWR Morb Mortal Wkly Rep.
- Irene Barrabeig, Nuria Torner, Ana Martínez, Gloria Carmona, Pilar Ciruela, Joan Batalla, Josep Costa, Sergi Hernández, Luis Salleras, Angela Domínguez, Rubella Surveillance Group of Catalonia Results of the rubella elimination program in Catalonia (Spain), 2002-2011. Hum Vaccin Immunother: 2013, 9(3);642-8 PubMed 23299566
- No authors listed Controlling rubella and preventing congenital rubella syndrome – global progress, 2009 Wkly Epidemiol Rec. 2010 Oct 15;85(42):413-8. PMID20949700 | PDF
- Matthew E Oster, Tiffany Riehle-Colarusso, Adolfo Correa An update on cardiovascular malformations in congenital rubella syndrome. Birth Defects Res. Part A Clin. Mol. Teratol.: 2010, 88(1);1-8 PubMed 19697432
- Jennifer Rota, Luis Lowe, Paul Rota, William Bellini, Susan Redd, Gustavo Dayan, Rob van Binnendijk, Susan Hahné, Graham Tipples, Jeannette Macey, Rita Espinoza, Drew Posey, Andrew Plummer, John Bateman, José Gudiño, Edith Cruz-Ramirez, Irma Lopez-Martinez, Luis Anaya-Lopez, Teneg Holy Akwar, Scott Giffin, Verónica Carrión, Ana Maria Bispo de Filippis, Andrea Vicari, Christina Tan, Bruce Wolf, Katherine Wytovich, Peter Borus, Francis Mbugua, Paul Chege, Janeth Kombich, Chantal Akoua-Koffi, Sheilagh Smit, Henry Bukenya, Josephine Bwogi, Frederick Ndhoga Baliraine, Jacques Kremer, Claude Muller, Sabine Santibanez Identical genotype B3 sequences from measles patients in 4 countries, 2005. Emerging Infect. Dis.: 2006, 12(11);1779-81 PubMed 17283637 | Emerg Infect Dis.
- Sébastien Plumet, W Paul Duprex, Denis Gerlier Dynamics of viral RNA synthesis during measles virus infection. J. Virol.: 2005, 79(11);6900-8 PubMed 15890929 | PMC1112129
- Gregg N. McA. Congenital cataract following German measles in the mother. Trans Ophthalmol Soc Aust 1941;3:35–46. | N M Gregg Congenital cataract following German measles in the mother. 1941. Epidemiol. Infect.: 1991, 107(1);iii-xiv; discussion xiii-xiv PubMed 1879476 | PMC2272051
- Weller, T. H., and Neva, F. A. Propagation in tissue culture of cytopathic agents from patients with rubella-like illnes . Proc. Soc. Exper. Biol. & Med. 111:215–225, 1962.
- P D PARKMAN, E L BUESCHER, M S ARTENSTEIN Recovery of rubella virus from army recruits. Proc. Soc. Exp. Biol. Med.: 1962, 111;225-30 PubMed 13941530 | see PMC1926918
- T H WELLER, C A ALFORD, F A NEVA RETROSPECTIVE DIAGNOSIS BY SEROLOGIC MEANS OF CONGENITALLY ACQUIRED RUBELLA INFECTIONS. N. Engl. J. Med.: 1964, 270;1039-41 PubMed 14122801
- Elimination of rubella and congenital rubella syndrome--United States, 1969-2004. Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep. 2005 Mar 25;54(11):279-82. PMID 15788995 | MMWR Morb Mortal Wkly Rep.
- Progress Report: Elimination of Rubella and CRS in the Americas, 2007 Powerpoint slide on Elimination of Rubella and Congenital Rubella Syndrome in the Americas: Progress Report. Pan American Health Organization World Health Organization.
- Imran Jivraj, Chris J Rudnisky, Emmanuel Tambe, Graham Tipple, Matthew T S Tennant Identification of ocular and auditory manifestations of congenital rubella syndrome in mbingo. Int J Telemed Appl: 2014, 2014;981312 PubMed 25525427 | PMC4262751 | Int J Telemed Appl. 2
- Medical Microbiology. 4th edition. Baron S, editor. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 55 Togaviruses: Rubella Virus | Chapter 54Alphaviruses (Togaviridae) and Flaviviruses (Flaviviridae) | Table 55-1 Abnormalities Associated with Congenital Rubella Syndrome | Figure 55-3 Incidence rates of rubella USA 1966-1993
- Molecular Biology of the Cell. 4th edition. Alberts B, Johnson A, Lewis J, et al. New York: Garland Science; 2002. Viruses Exploit Host Cell Machinery for All Aspects of Their Multiplication
- Disease Control Priorities in Developing Countries. 2nd edition. Jamison DT, Breman JG, Measham AR, et al., editors. Washington (DC): World Bank; 2006. Chapter 20Vaccine-preventable Diseases
- Antenatal Care: Routine care for the healthy pregnant woman. NICE Clinical Guidelines, No. 62. National Collaborating Centre for Women's and Children's Health (UK). London: RCOG Press; 2008 Mar. 10.8. Rubella
M De Santis, A F Cavaliere, G Straface, A Caruso Rubella infection in pregnancy. Reprod. Toxicol.: 2006, 21(4);390-8 PubMed 16580940
Kihei Terada Rubella and congenital rubella syndrome in Japan: epidemiological problems. Jpn. J. Infect. Dis.: 2003, 56(3);81-7 PubMed 12944671
Yan Feng, Sabine Santibanez, Hazel Appleton, Yiyu Lu, Li Jin Application of new assays for rapid confirmation and genotyping of isolates of rubella virus. J. Med. Virol.: 2011, 83(1);170-7 PubMed 21108356
Graham Tipples, Joanne Hiebert Detection of measles, mumps, and rubella viruses. Methods Mol. Biol.: 2011, 665;183-93 PubMed 21116802
M J Binnicker, D J Jespersen, J A Harring Multiplex detection of IgM and IgG class antibodies to Toxoplasma gondii, rubella virus, and cytomegalovirus using a novel multiplex flow immunoassay. Clin. Vaccine Immunol.: 2010, 17(11);1734-8 PubMed 20861325
Juan Fontana, Carmen López-Iglesias, Wen-Ping Tzeng, Teryl K Frey, José J Fernández, Cristina Risco Three-dimensional structure of Rubella virus factories. Virology: 2010, 405(2);579-91 PubMed 20655079
Stanley A Plotkin The history of rubella and rubella vaccination leading to elimination. Clin. Infect. Dis.: 2006, 43 Suppl 3;S164-8 PubMed 16998777
External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.
- The Australian Immunisation Handbook 10th edition (updated June 2015) – Rubella http://www.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part4~handbook10-4-18
- World Health Organization (WHO)
- WHO position paper on rubella vaccines (2011). Weekly Epidemiological Record, No. 29, 2011, 86, 301–316 http://www.who.int/wer/2011/wer8629.pdf Webpage
- WHO-recommended surveillance standard of rubella and congenital rubella syndrome | PDF
- Surveillance guidelines for measles, rubella and congenital rubella syndrome in the WHO European Region | Surveillance Guidelines for Measles, Rubella and Congenital Rubella Syndrome in the WHO European Region (PDF)
- CDC Rubella (German Measles, Three-Day Measles) | About Rubella
- Merck MMR Vaccine (PDF)
- Pan American Health Organization - Rubella
- International Committee on Taxonomy of Viruses
- A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols
Cite this page: Hill, M.A. 2017 Embryology Abnormal Development - Rubella Virus. Retrieved February 27, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Rubella_Virus
- © Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G