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Measles
Measles also known as
rubeola, is a disease caused by a virus , specifically a paramyxovirus of the genus Morbillivirus.
Measles is spread through respiration (contact with fluids from an infected person's nose and mouth, either directly or through aerosol transmission),
and is highly contagious—90% of people without immunity sharing a house with an infected person will catch it. Airborne precautions should be taken for
all suspected cases of measles.
The incubation period usually lasts for 4–12 days (during which there are no symptoms). Infected people remain contagious from the appearance of the
first symptoms until 3–5 days after the rash appears.
Reports of measles go as far back to at least 600 B.C. however, the first scientific description of the disease and its distinction from smallpox is
attributed to the Persian physician Ibn Razi (Rhazes) 860-932 who published a book entitled "Smallpox and Measles" (in Arabic: Kitab fi al-jadari
wa-al-hasbah). In 1954, the virus causing the disease was isolated from an 11-year old boy from the US, David Edmonston, and adapted and propagated
on chick embryo tissue culture. To date, 21 strains of the measles virus have been identified. Licensed vaccines to prevent the disease became
available in 1963.
German measles is an unrelated condition caused by the rubella virus.
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Symptoms
The classical symptoms of measles include a fever for at least three days, and the three Cs—cough, coryza (runny nose) and conjunctivitis (red
eyes). The fever may reach up to 104° Fahrenheit/ 40° Celsius. Koplik's spots seen inside the mouth are pathognomonic (diagnostic) for measles
but are not often seen, even in real cases of measles, because they are transient and may disappear within a day of arising.
The characteristic measles rash is classically described as a generalized, maculopapular, erythematous rash that begins several days after the fever
starts. It starts on the head before spreading to cover most of the body, often causing itching. The rash is said to "stain", changing colour from
red to dark brown, before disappearing.
Diagnosis and Treatment
Clinical diagnosis of measles requires a history of fever of at least three days together with at least one of the three Cs. Observation of Koplik's
spots is also diagnostic of measles.
Alternatively, laboratory diagnosis of measles can be done with confirmation of positive measles IgM antibodies or isolation of measles virus RNA from
respiratory specimens. In cases of measles infection following secondary vaccine failure IgM antibody may not be present. In these cases serological
confirmation may be made by showing IgG antibody rises by Enzyme immunoasay or complement fixation.
Positive contact with other patients known to have measles adds strong epidemiological evidence to the diagnosis.
There is no specific treatment or antiviral therapy for uncomplicated measles. Most patients with uncomplicated measles will recover with rest and
supportive treatment.
Some patients will develop pneumonia as a sequela to the measles. Histologically, a unique cell can be found in the paracortical region of hyperplastic
lymph nodes in patients affected with this condition. This cell, known as the Warthin-Finkeldey cell, is a multinucleated giant with eosinophilic
cytoplasmic and nuclear inclusions.
Virology
Measles virus (MV) is an enveloped, nonsegmented negative-stranded RNA virus of the Paramyxoviridae family.
Transmission
The measles is a highly contagious airborne pathogen which spreads primarily via the respiratory system. The virus is transmitted in respiratory
secretions, and can be passed from person to person via aerosol droplets containing virus particles, such as those produced by a coughing patient.
Once transmission occurs, the virus infects the epithelial cells of its new host, and may also replicate in the urinary tract, lymphatic system,
conjunctivae, blood vessels, and central nervous system.
Humans are the only known natural hosts of measles, although the virus can infect some non-human primate species.
Complications
Complications with measles are relatively common, ranging from relatively mild and less serious diarrhea, to pneumonia and encephalitis (subacute
sclerosing panencephalitis), corneal ulceration leading to corneal scarring. Complications are usually more severe amongst adults who catch the
virus.
The fatality rate from measles for otherwise healthy people in developed countries is low: approximately 1 death per thousand cases. In underdeveloped
nations with high rates of malnutrition and poor healthcare, fatality rates of 10 percent are common. In immunocompromised patients, the fatality rate
is approximately 30 percent.
Public Health
Measles is a significant infectious disease because, while the rate of complications is not high, the disease itself is so infectious that the sheer
number of people who would suffer complications in an outbreak amongst non-immune people would quickly overwhelm available hospital resources. If
vaccination rates fall, the number of non-immune persons in the community rises, and the risk of an outbreak of measles consequently rises.
In developed countries, most children are immunized against measles at the age of 18 months, generally as part of a three-part MMR vaccine (measles,
mumps, and rubella). The vaccination is generally not given earlier than this because children younger than 18 months usually retain anti-measles
immunoglobulins (antibodies) transmitted from the mother during pregnancy. A "booster" vaccine is then given between the ages of four and five.
Vaccination rates have been high enough to make measles relatively uncommon. Even a single case in a college dormitory or similar setting is often met
with a local vaccination program, in case any of the people exposed are not already immune. In developing countries, measles remains common.
Unvaccinated populations are at risk for the disease. After vaccination rates dropped in northern Nigeria in the early 2000s due to religious and
political objections, the number of cases rose significantly, and hundreds of children died. A 2005 measles outbreak in Indiana was attributed to
children whose parents refused vaccination. In the early 2000s the MMR vaccine controversy in the United Kingdom regarding a potential link between
the combined MMR vaccine (vaccinating children from mumps, measles and rubella) and autism prompted a comeback in the measles party, where parents
deliberately infect the child with measles to build up the child's immunity without an injection. This practice poses many health risks to the child,
and has been discouraged by the public health authorities. Scientific evidence provides no support for the hypothesis that MMR plays a role in
causing autism. Declining immunisation rates in the UK are the probable cause of a significant increase of cases of measles, 2006 being the highest
on record, and 2007 already showing an increase on the previous year.
According to the World Health Organization (WHO), measles is a leading cause of vaccine preventable childhood mortality. Worldwide, the fatality rate
has been significantly reduced by partners in the Measles Initiative: the American Red Cross, the United States Centers for Disease Control and
Prevention (CDC), the United Nations Foundation, UNICEF and the World Health Organization (WHO). Globally, measles deaths are down 60 percent, from
an estimated 873,000 deaths in 1999 to 345,000 in 2005. Africa has seen the most success, with annual measles deaths falling by 75 percent in just 5
years, from an estimated 506,000 to 126,000.
The joint press release by members of the Measles Initiative brings to light another benefit of the fight against measles: "Measles vaccination campaigns
are contributing to the reduction of child deaths from other causes. They have become a channel for the delivery of other life-saving interventions,
such as bed nets to protect against
malaria, de-worming medicine and vitamin A supplements. Combining measles immunization with other health interventions
is a contribution to the achievement of Millennium Development Goal Number 4: a two-thirds reduction in child deaths between 1990 and 2015."
Worldwide MMR Eradication
Most recently, in 2007, the country Japan has become a nidus for the Measles. Japan has suffered a record number of cases, and a number of universities
and other institutions in the country have closed in an attempt to contain the outbreak.
In the 1990s, the governments of the Americas, along with the Pan American Health Organization, launched a plan to eradicate Measles, Mumps, and
Rubella from the region.
Indigenous measles has been eliminated in North, Central, and South America; the last endemic case in the region was reported on November 12,
2002.
Outbreaks are still occurring, however, following importations of measles viruses from other world regions. For example, in June 2006, there was an
outbreak in Boston which resulted from a resident who had recently visited India. In 2005, there was an outbreak in a non-immunized population
in Indiana and Illinois, transmitted by an Indiana girl who visited Romania without being vaccinated. In Michigan in the fall of 2007, a confirmed
case of measles occurred in a girl who had been vaccinated and who apparently contracted it overseas. There were at least 6 other suspected cases,
all among children who had been vaccinated.
There are also plans underway to eliminate Rubella from the region by 2010. As of 2006, endemic cases were still being reported in Bolivia, Brazil,
Colombia, Guatemala, Mexico, Peru, and Venezuela, they are currently vaccinating Dominican Republic.
While some smaller organizations have proposed a global MMR eradication, none is likely to take place until, at least, after the worldwide eradication
of Poliomyelitis.
(adapted from Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Measles)
Heterologous Prime-Boost Strategy to Immunize Very Young Infants against Measles: Pre-clinical Studies in Rhesus Macaques
Authors: Pasetti MF, Resendiz-Albor A, Ramirez K, Stout R, Papania M, Adams RJ, Polack FP, Ward BJ, Burt D, Chabot S, Ulmer J,
Barry EM, Levine MM.
[1] 1Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA [2] 2Department of Pediatrics, University of
Maryland School of Medicine, Baltimore, Maryland, USA.
Infants in developing countries are at high risk of developing severe clinical measles if they become infected during the "window of vulnerability"
(age 4-9 months), when declining maternal antibodies do not protect against wild virus, yet impede successful immunization by attenuated measles
vaccine. We developed two Sindbis replicon-based DNA vaccines expressing measles virus hemagglutinin and fusion protein with the goal of priming young
infants to respond safely and effectively to subsequent boosting with attenuated measles vaccine. Intradermal prime with DNA vaccines by needle-free
injection followed by aerosol or parenteral boost with licensed measles vaccine was well tolerated by juvenile and young infant rhesus macaques, and
protected against clinical measles and viremia on wild-type virus challenge. A proteosome-measles vaccine administered alone (three doses) or as a boost
following DNA vaccine priming was also safe and protective. These promising results pave the way for clinical trials to assess this prime-boost
strategy. Clinical Pharmacology & Therapeutics advance online publication 31 October 2007. doi:10.1038/sj.clpt.6100420.
Journal: Clin Pharmacol Ther. 2007 Oct 31
Adapted from PubMed; click here to access full journal article.
An Immunocompetent Murine Model for Oncolysis with an Armed and Targeted Measles Virus
Authors: Ungerechts G, Springfeld C, Frenzke ME, Lampe J, Parker WB, Sorscher EJ, Cattaneo R.
Molecular Medicine Program and Virology and Gene Therapy Track, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
An immunocompetent model is required to test therapeutic regimens for clinical trials with the oncolytic measles virus (MV). Toward developing this
model, a retargeted MV that enters murine colon adenocarcinoma cells forming tumors in syngeneic C57BL/6 mice was generated. Since MV infection tends
to be less efficient in murine than in human cells, the targeted virus was also armed with the prodrug convertase, purine nucleoside phosphorylase
(PNP), and named MV-PNP-antiCEA. We have shown before that in cultured cells, infection with this virus activated the prodrug,
6-methylpurine-2'-deoxyriboside (MeP-dR), causing extensive cytotoxicity. When injected intratumorally (IT), MV-PNP-antiCEA inhibited subcutaneous
tumor growth marginally, but subsequent administration of the prodrug enhanced the oncolytic effect. Systemic delivery of MV-PNP-antiCEA alone had
no substantial oncolytic effects, but in combination with the prodrug it was therapeutic, revealing synergistic effects between virus and prodrug.
Immunosuppression with cyclophosphamide (CPA) retarded the appearance of MV neutralizing antibodies and enhanced oncolytic efficacy: survival was 100%,
with 9 out of 10 animals going into complete remission. This immunocompetent murine model facilitates the testing of therapeutic regimens for clinical
trials.Molecular Therapy (2007) 15 11, 1991-1997. doi:10.1038/sj.mt.6300291.
Journal: Mol Ther. 2007 Nov;15(11):1991-7. Epub 2007 Aug 21
Adapted from PubMed; click here to access full journal article.
The Impact of a Physical Geographic Barrier on the Dynamics of Measles
Authors: Vora A, Burke DS, Cummings DA.
School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
SUMMARY Spatial-temporal patterns of measles incidence reflect the spatial distribution of human hosts. The heterogeneous spatial distribution of
communities has been shown to introduce spatially dependent temporal lags in the timing of measles incidence. Incidence patterns reflect internal
dynamics within a community and coupling of communities through the movement of infectious individuals. The central role of human movement in coupling
dynamics in separate communities suggests that physical geographic barriers to movement should reduce spatial-temporal correlation. We examine measles
dynamics in Maryland and Pennsylvania during the period of 1917-1938. The central feature of interest is the Chesapeake Bay, which separates Maryland
into two distinct regions. We find that correlation of measles incidences in communities separated by the bay is reduced compared to communities not
separated by the bay, suggesting the bay acted as a barrier to human movement during this time sufficient to decouple measles dynamics in Maryland
counties.
Journal: Epidemiol Infect. 2007 Jul 30;:1-8
Adapted from PubMed; click here to access full journal article.
A Vectored Measles Virus Induces Hepatitis B Surface Antigen Antibodies while Protecting Macaques Against Measles Virus Challenge
Authors: del Valle JR, Devaux P, Hodge G, Wegner NJ, McChesney MB, Cattaneo R.
Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Hepatitis B virus (HBV) acute and chronic infections remain a major worldwide health problem. Towards developing an anti-HBV vaccine with single-dose
scheme potential, we engineered infectious measles virus (MV) genomic cDNAs with a vaccine strain background and expression vector properties.
Hepatitis
B surface antigen (HBsAg) expression cassettes were inserted into this cDNA and three MVs expressing HBsAg at different levels generated. All vectored
MVs, which secrete HBsAg as subviral particles, elicited humoral responses in MV-susceptible genetically modified mice. However, small differences in
HBsAg expression elicited vastly different HBsAg antibody levels. The two vectors inducing the highest HBsAg antibody levels were inoculated into
rhesus monkeys (Macaca mulatta). After challenge with a pathogenic MV strain (Davis87), control naive monkeys showed a classic measles rash and high
viral loads. In contrast, all monkeys immunized with vaccine or a control nonvectored recombinant vaccine or HBsAg-expressing vectored MV remained
healthy, with low or undetectable viral loads. After a single vaccine dose, only the vector expressing HBsAg at the highest levels elicited protective
levels of HBsAg antibodies in two of four animals. These observations reveal an expression threshold for efficient induction of HBsAg humoral immune
responses. This threshold is lower in mice than in macaques. Implications for the development of divalent vaccines based on live attenuated viruses are
discussed.
Journal: J Virol. 2007 Oct;81(19):10597-605. Epub 2007 Jul 18.
Adapted from PubMed; click here to access full journal article.
Assessing Participation Bias in a Population-Based Study of Measles-Mumps-Rubella Vaccine Immunity in Children and Adolescents Aged 12-18
Authors: St Sauver JL, Jacobsen SJ, Jacobson RM, Vierkant RA, Ovsyannikova IG, Dhiman N, Poland GA.
Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, MN 55905, USA.
The purpose of our study was to determine whether specific characteristics were associated with study participation in a group of children residing
in Olmsted County, MN. We compared 346 participants and 848 non-participants from a study examining associations between human leukocyte antigen gene
variants and immunity following measles-mumps-rubella (MMR) vaccination by demographic characteristics, MMR vaccination history and length of time in
the Olmsted County health care system. We also compared the frequency and reasons for health care visits between participants and non-participants by
comparing diagnostic codes for all visits that had occurred between 1999 and 2001. Characteristics were compared using chi-square and t-tests, followed
by multivariable logistic regression. Study participants were more likely to be white/Caucasian, to have received their first MMR vaccination at a
younger age, and to have had more health care visits (especially for acute respiratory illnesses, vaccinations, or other acute conditions such as
fainting and headaches) than study non-participants. These results suggest that frequent use of local health care systems by children and parents
may increase comfort levels with local physicians and physician researchers, thereby improving participation rates in research studies among these
populations. However, special efforts may be necessary to improve research participation among children who are infrequent users of the health care
systems of interest.
Journal: Paediatr Perinat Epidemiol. 2007 Jul;21(4):376-84.
Adapted from PubMed; click here to access full journal article.
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