Abnormal Development - Rubella Virus
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- 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.
L D Frenkel, F Gomez, F Sabahi The pathogenesis of microcephaly resulting from congenital infections: why is my baby's head so small? Eur. J. Clin. Microbiol. Infect. Dis.: 2017; PubMed 28980148
Yanna K M Nóbrega, Bruna C de Carvalho, Nadjar Nitz, Tamires E Vital, Franco B Leite, Inês J Sequeira, Elsa E Moreira, Juliana K B de Andrade, Lenora Gandolfi, Riccardo Pratesi, Mariana M Hecht Rubella Seropositivity in Pregnant Women After Vaccination Campaign in Brazil's Federal District. Viral Immunol.: 2017; PubMed 28972455
Nathalie Auger, Caroline Quach, Jessica Healy-Profitós, Anne-Marie Lowe, Laura Arbour Congenital microcephaly in Quebec: baseline prevalence, risk factors and outcomes in a large cohort of neonates. Arch. Dis. Child. Fetal Neonatal Ed.: 2017; PubMed 28676560
Adolfo Martinez-Palomo Revisiting Zika (and Rubella). J Public Health Policy: 2016, 37(3);273-276 PubMed 28615701
Juan B Yepez, Felipe A Murati, Michele Pettito, Carlos F Peñaranda, Jazmin de Yepez, Gladys Maestre, J Fernando Arevalo, Johns Hopkins Zika Center Ophthalmic Manifestations of Congenital Zika Syndrome in Colombia and Venezuela. JAMA Ophthalmol: 2017; PubMed 28418539
Iêda M Orioli, Helen Dolk, Jorge S Lopez-Camelo, Daniel Mattos, Fernando A Poletta, Maria G Dutra, Flavia M Carvalho, Eduardo E Castilla Prevalence and clinical profile of microcephaly in South America pre-Zika, 2005-14: prevalence and case-control study. BMJ: 2017, 359;j5018 PubMed 29162597
Progress in rubella and congenital rubella syndrome control and elimination – worldwide, 2000–2016. [Progrès réalisés pour combattre et éliminer la rubéole et le syndrome de rubéole congénitale dans le monde, 2000-2016.] Wkly. Epidemiol. Rec.: 2017, 92(46);707-15 PubMed 29148274
Gavin B Grant, Susan E Reef, Minal Patel, Jennifer K Knapp, Alya Dabbagh Progress in Rubella and Congenital Rubella Syndrome Control and Elimination - Worldwide, 2000-2016. MMWR Morb. Mortal. Wkly. Rep.: 2017, 66(45);1256-1260 PubMed 29145358
Eduardo Jucá, André Pessoa, Erlane Ribeiro, Rafaela Menezes, Saile Kerbage, Thayse Lopes, Luciano Pamplona Cavalcanti Hydrocephalus associated to congenital Zika syndrome: does shunting improve clinical features? Childs Nerv Syst: 2017; PubMed 29086073
Noriyuki Otsuki, Masafumi Sakata, Kyoko Saito, Kiyoko Okamoto, Yoshio Mori, Kentaro Hanada, Makoto Takeda Both sphingomyelin and cholesterol in the host cell membrane are essential for Rubella virus entry. J. Virol.: 2017; PubMed 29070689
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
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- 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
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Cite this page: Hill, M.A. 2017 Embryology Abnormal Development - Rubella Virus. Retrieved November 23, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Rubella_Virus
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