How does the measeles virus form?

How does the measeles virus form?

We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

I would like to understand how (if possible) the measles virus could start to infect a population that was theoretically isolated from any other population group. Put another way, can the measles virus develop within a person without external influence/inputs?

The question could be rephrased

Can a measle virus be created anew and not via reproduction from another virus?

The answer to which is "no".

The falsified idea that new life forms can jump pop up out of nowhere is called spontaneous generation. Spontaneous generation do not occur.

Note however that sometimes it may look like as if a new epidemic came from nowhere. The reasons is due to natural reservoir.

A natural reservoir or nidus (the latter from the Latin word for "nest") is the long-term host of a pathogen of an infectious disease.

An asymptotic carrier can be used as a natural reservoir

An asymptomatic carrier (healthy carrier or just carrier) is a person or other organism that has contracted an infectious disease, but who displays no symptoms.

These reservoirs can keep the viruses (or other pathogens) alive in while from the outside it looks like the disease has been eradicated. At some point the virus can spread again making it feel like it came out of nowhere.

[… ] my confusion is on how a population gets the first instance

There is no clear first instance. Modern day measle viruses evolved from an ancestor that was not the modern day measles. Just like there was no sudden first human (or any other species). There were just ancestors that evolved to become what we now call modern day humans.

You might want to have a look at an intro course to evolutionary biology such as understanding evolution by UC Berkeley for example.

Developmental Aspects of Pagetic Osteoclasts

MVNP Downregulation of FoxO3 and Sirt1 also Increase IL-6

MVNP also was demonstrated to increase NFκB activity by downregulating expression of Sirtuin 1 (Sirt1), a class III protein deacetylase that targets acetylated NFκB and negatively regulates its activity [31] . MVNP decreases Sirt1 by triggering increased phosphorylation of Forkhead-box class O3 (FoxO3), resulting in decreased FoxO3 protein stability and decreased transcription of its target gene Sirt1 in OCL precursors and NIH3T3 cells. Several protein kinases have been reported to downregulate FoxO3 stability through phosphorylation, including AKT, ERK1/2, IKKβ, and IKKε [50–52] . It’s not yet known which, if any, of these are triggered by MVNP to phosphorylate FoxO3. However, TBK1 overexpression in TRAP-TBK1 BMM was sufficient to decrease Sirt1 mRNA (unpublished data), suggesting that activated TBK1 may phosphorylate FoxO3. Wang et al. [31] showed that NIH3T3 cells stably transduced with MVNP (MVNP-NIH3T3) demonstrated higher IL-6 promoter luciferase reporter activity than NIH3T3 cells transduced with empty vector (EV-NIH3T3), and ectopic expression of Sirt1 significantly decreased both the basal and MVNP-stimulated IL-6 promoter activity. Further, resveratrol, a Sirt1 gene activator, suppressed the high level of IL-6 mRNA in MVNP-NIH3T3 cells. Significantly, resveratrol inhibited OCL differentiation of BMM from both wild-type and MVNP mice. Strikingly, at a resveratrol dose that had little effect on wild-type OCL differentiation, the enhanced MVNP OCL differentiation was suppressed to wild-type levels. Higher resveratrol doses then suppressed wild-type and MVNP OCL differentiation to similar levels. Hence, MVNP acts via two pathways to increase IL-6 expression ( Fig. 4.2 ).

Where did viruses come from?

Tracing the origins of viruses is difficult because they don't leave fossils and because of the tricks they use to make copies of themselves within the cells they've invaded. Some viruses even have the ability to stitch their own genes into those of the cells they infect, which means studying their ancestry requires untangling it from the history of their hosts and other organisms. What makes the process even more complicated is that viruses don't just infect humans they can infect basically any organism&mdashfrom bacteria to horses seaweed to people.

Still, scientists have been able to piece together some viral histories, based on the fact that the genes of many viruses&mdashsuch as those that cause herpes and mono&mdashseem to share some properties with cells' own genes. This could suggest that they started as big bits of cellular DNA and then became independent&mdashor that these viruses came along very early in evolution, and some of their DNA stuck around in cells' genomes. The fact that some viruses that infect humans share structural features with viruses that infect bacteria could mean that all of these viruses have a common origin, dating back several billion years. This highlights another problem with tracing virus origins: most modern viruses seem to be a patchwork of bits that come from different sources&mdasha sort of "mix and match" approach to building an organism.

The fact that viruses like the deadly Ebola and Marburg viruses, as well as the distantly related viruses that cause measles and rabies, are only found in a limited number of species suggests that those viruses are relatively new&mdashafter all, those organisms came along somewhat recently in evolutionary time. Many of these "new" viruses likely originated in insects many million years ago and at some point in evolution developed the ability to infect other species&mdashprobably as insects interacted with or fed from them.

HIV, which is thought to have first emerged in humans in the 1930s, is another kind of virus, known as a retrovirus. These simple viruses are akin to elements found in normal cells that have the ability to copy and insert themselves throughout the genome. There are a number of viruses that have a similar way of copying themselves&mdasha process that reverses the normal flow of information in cells, which is where the term "retro" comes from&mdashand their central machinery for replication may be a bridge from the original life-forms on this planet to what we know as life today. In fact, we carry among our genes many "fossilized" retroviruses&mdashleft over from the infection of distant ancestors&mdashwhich can help us trace our evolution as a species.

Then there are the viruses whose genomes are so large that scientists can't quite figure out what part of the cell they would have come from. Take, for instance, the largest-ever virus so far discovered, mimivirus: its genome is some 50 times larger than that of HIV and is larger than that of some bacteria. Some of the largest known viruses infect simple organisms such as amoebas and simple marine algae. This indicates that they may have an ancient origin, possibly as parasitic life-forms that then adapted to the "virus lifestyle." In fact, viruses may be responsible for significant episodes of evolutionary change, especially in more complex types of organisms.

At the end of the day, however, despite all of their common features and unique abilities to copy and spread their genomes, the origins of most viruses may remain forever obscure.

  • Worldwide distribution, outbreaks in 2-3 years
  • Measles virus is extremely infectious, most children contract the clinical disease on exposure
  • Transmitted via respiratory droplets produced by sneeze or cough during prodromal period or direct contact with nasal or throat secretions from an infected person, which continues up to few days after the rash appears.
  • Less commonly, it is spread by airborne aerosolised droplet nuclei or by indirect contact with freshly contaminated articles.
  • More serious outcomes in malnurished children, people with deficient cell-mediated immunity.
  • Measles virus invades the cells lining the upper respiratory tracts i.e respiratory epithelium of the nasopharynx and spreads to the regional lymph nodes
  • After 2-3 days of replication in these sites, a primary viraemia widens the infection to the reticuloendothelial system where further replication takes place.
  • Secondary viraemia occurs and the virus enters skin, conjunctivae, respiratory tract and other organs, including the spleen, thymus, lung, liver, and kidney and further replication occurs.
  • Appearances of rash (cytotoxic T cells attacks measles virus-infected vascular endothelial cells in the skin).
  • Formation of Multinucleated giant cells.


Measles is a common infection in children and is spread by the respiratory route. It is characterized by a prodromal illness of fever, coryza, cough, and conjunctivitis followed by appearance of a generalized maculopapular rash. Measles virus (MeV) infects approximately 30 million people annually, with a mortality of 197,000, mainly in developing countries [1]. In the prevaccine era, more than 90% of 15-year-old children had a history of measles [2]. Measles remains a major cause of mortality in children, particularly in areas with inadequate vaccination and medical care.

MeV infection can confer lifelong immunity [3, 4], and there is no animal reservoir or evidence of latent or common persistent infection except for subacute sclerosing panencephalitis (SSPE). Therefore, maintenance of MeV in a population requires constant supply of susceptible individuals. If the population is too small to establish continuous transmission, the virus can be eliminated [5]. Mathematical analyses have shown that a naïve population of 250,000-500,000 is needed to maintain MeV [6–8]. This is approximately the population of the earliest urban civilizations in ancient Middle Eastern river valleys around 3000-2500 BCE [6, 9, 10]. Historically, the first scientific description of measles-like syndrome was provided by Abu Becr, known as Rhazes, in the 9 th century. However, small pox was accurately described by Galen in the 2 nd second century whereas measles was not. Epidemics identified as measles were recorded in the 11 th and 12 th centuries [9–11].

MeV is a member of the genus Morbillivirus, which belongs to the family Paramyxoviridae[12]. In addition to MeV, Morbillivirus includes dolphin and porpoise morbillivirus, canine distemper virus, phocid distemper virus, peste des petits ruminants virus, and rinderpest virus (RPV) [12, 13]. Genetically and antigenetically, MeV is most closely related to RPV, which is a pathogen of cattle [12, 14]. MeV is assumed to have evolved in an environment where cattle and humans lived in close proximity [11]. MeV probably evolved after commencement of livestock farming in the early centers of civilization in the Middle East. The speculation accords with mathematical analyses as mentioned above [6, 9, 10].

Molecular clock analysis can estimate the age of ancestors in evolutionary history by phylogenetic patterns [15, 16]. The basic approach to estimating molecular dates is to measure the genetic distance between species and use a calibration rate (the number of genetic changes expected per unit time) to convert the genetic distance to time. Pomeroy et al. showed that "Time to the Most Recent Common Ancestor" (TMRCA: the age of the sampled genetic diversity) of the current MeV circulating worldwide is recent, i.e., within the last century (around 1943) [17]. Nevertheless, the time when MeV was introduced to human populations has not been investigated until date. In the present study, we performed molecular clock analysis on MeV to determine the time of divergence from RPV, suggesting the evolutionary path of the virus.

MeV sequences were downloaded from GenBank and aligned using ClustalW. Additional file 1 includes a list of accession numbers for sequences used in this study. Sequences of the hemagglutinin (H) and nucleocapsid (N) genes collected worldwide between 1954 and 2009 were used. The H and N genes were selected for analyses since their sequences are registered commonly. Sequences associated with the persistent disease manifestation SSPE were removed because these were expected to exhibit different evolutionary dynamics [18]. To avoid weighting specific outbreaks, we also excluded sequences that had been collected at the same time and place and that were genetically similar to each other. Consequently, the final data sets comprised 149 taxa with an alignment length of 1830 bp for the H gene and 66 taxa with an alignment length of 1578 bp for the N gene.

To determine the divergence time between MeV and RPV, sequences of peste des petits ruminants virus [GenBank: FJ750560 and FJ750563] were used to define the root of divergence between MeV and RPV.

The rates of nucleotide substitutions per site and TMRCA were estimated using the Bayesian Markov chain Monte Carlo (MCMC) method available in the BEAST package [19, 20]. This method analyzes the distribution of branch lengths among viruses isolated at different times (year of collection) among millions of sampled trees. For each data set, the best-fit model of nucleotide substitution was determined using MODELTEST [21] in HyPhy [22]. All models were compared using Akaike's Information Criterion. For both the H and N genes, the favored models were closely related to the most general GTR + Gamma + Inv model. Statistical uncertainty in parameter values across the sampled trees was expressed as 95% highest probability density (HPD) values. Runs were carried out with chain lengths of 100 million and the assumption of an 'exponential population growth' using a 'relaxed (uncorrelated lognormal) molecular clocks' [23]. All other parameters were optimized during the burn-in period. The output from BEAST was analyzed using the program TRACER BEAST analysis was also used to deduce the maximum a posteriori (MAP) tree for each data set, in which tip times correspond to the year of sampling.

The Bayesian approach assumed varied rates by branch. Using the Bayesian estimate, our analysis derived a mean evolutionary rate of 6.02 × 10 -4 substitutions/site/year for the N gene and 6.44 × 10 -4 substitutions/site/year for the H gene (Table 1). Based on this approach by analyses for the N gene, 1921 was estimated to be the TMRCA of the current MeV (Figure 1). Date of divergence between MeV and RPV was 1171. Analyses for the H gene yielded similar results the TMRCA of the current MeV was 1916. 1074 was estimated to be the date of divergence between MeV and RPV.

In order to ensure your immune system is top-top, make sure you have all the necessary immunizations. Adults often forget to refresh vaccinations they had when they were young. Check if you need booster shots for tetanus, diphtheria, whooping cough, polio, hepatitis, pneumococcus, meningitis, measles, mumps, rubella, the flu and others. Be sure to talk to your doctor!

Viruses and bacteria don't stand a chance with a strong immune system

Measles Virus (Rubeola)

Measles is caused by Rubeola virus, which belongs to the Paramyxovirus family.

Measles is an acute systemic viral infection with fever, respiratory involvement and symptoms, and a rash. Measles can cause serious complications and even fatalities. Infection confers lifelong immunity. Measles is highly contagious and vaccine preventable. Until recently, it had become rare in the United States. Parental fear of vaccinating children has led to an increase in susceptibles, a decrease in herd immunity, and a rise in the number of reported cases in the United States.

What is the best treatment?

Supportive measures, such as antipyretics and fluids, are used for treatment of measles, because no specific antiviral therapy is available. Antitussives may be used to suppress cough.

Bacterial superinfections, such as pneumonia and otitis media, should be treated with appropriate antimicrobials. Prophylactic antibiotics, however, should not be given. Children with measles should be administered Vitamin A once daily for 2 days. Children older than 12 months of age should receive 200,000 IU, infants 6-12 months of age should receive 100,000 IU, and babies less than 6 months old should be given 50,000 IU. For malnourished children with signs of Vitamin A deficiency, a third dose should be given after 2-4 weeks.

Although ribavirin intravenously or by aerosol has been used to treat measles, no formal studies have been conducted, so its efficacy against measles is unproven.

The safest and most successful approach to measles is prevention. Measles vaccine is usually given as the combination measles, mumps, and rubella (MMR) vaccines. Currently, 2 doses are usually administered, usually at 12-15 months of age (in outbreaks, vaccine can be given after 6 months of age.). The second dose is usually given at the start of school, but can be administered sooner. The minimum interval between doses is 1 month.

There are no issues of anti-infective resistance.

How do patients contract this infection, and how do I prevent spread to other patients?

Measles is one of the most contagious diseases known it is spread by the airborne route from respiratory secretions from infected individuals. There is a prodrome, very much like a rhinovirus “cold,” with some cough, lasting about 3 days. The prodrome is followed by fever and gradual development of rash. Measles is most contagious just before rash onset and during the first few days after the rash appears. The presence of Koplik spots on the buccal mucosa is pathognomonic of measles. Complications of measles, including pneumonia and encephalitis, occur in roughly 1 per 1000-2000 cases complications and severe measles are more frequent in immunocompromised patients. More common, less severe complications include otitis media and croup.

Measles usually occurs in winter and early spring in countries with temperate climates. The incubation period is 8-12 days, with an average of 10 days.

Worldwide, there were for many years 1 million annual deaths from measle, although this has recently decreased in 2013 146,000 were reported to WHO. Measles is an enormous problem in developing countries, where infections often occur in very young children with immature immune systems, many of whom are also malnourished, which further impairs their immune response to the virus.

Live attenuated measles vaccine was licensed in the United States in 1963. Prior to that, an estimated 500,000 annual cases occurred in the United States. In 1991, a two dose schedule in infancy and early childhood was instituted because of the recognition of a vaccine failure rate of about 5% after 1 dose. Between 2000 and 2007, there were less than 100 annual cases in the United States. Measles became no longer endemic in the United States molecular studies showed all cases to be due to imported measles from Europe, Asia, and the Middle East.

Beginning in 2008, an increase in measles began to occur in the United States. Many cases were related to travel in European and Asian countries, where there were many unvaccinated individuals. For a disease as contagious as measles, a very high rate of immunization (about 95%) is required to provide successful herd immunity. The increase in measles therefore was mainly ascribed to the failure of many parents to immunize their healthy infants, mainly from fear that MMR might be a cause of autism. Others refused vaccination, citing philosophical or religious objections. As many of 15 studies worldwide have failed to demonstrate a causal relationship between MMR vaccine and autism.

Today, cases of measles are on the increase in the United States, with reported mini-epidemics among unvaccinated and too-young-to-be-vaccinated children. In 2014, a record 667 cases of measles were reported in 27 states, the highest number of cases in many years. Most of the cases were unvaccinated.

Largely due to refusal of parents to immunize their children. In 2013, 11 measles outbreaks in the US were reported by the CDC, and in 2014 23 outbreaks were reported. In December 2015 an outbreak began at a large California amusement park, leading to 111 reported measles cases in 7 states, Mexico and Canada. There were no fatalities, but a number of patients were hospitalized.

The CDC has released data on measles activity in the United States from January May in 2015. (MMWR April 17, 2015 / 64(14)373-376) It seems that in 2016, the incidence of measles in the US has declined, with less than 50 reported cases in the first half of the year, but final figures will not be available until at least next year.

A death from measles in the United States, was reported July 2, 2015, the first in many years.

Measles cases today are mostly ascribed to reluctance of some parents to vaccinate their children for fear of harm from the vaccine, and importations of measles cases from other countries where vaccination is not practiced.

Measles in hospitalized patients requires strict isolation with proper hand-washing, gowns, masks, and gloves. Hospitalized patients should be in a negative pressure room, if possible. Airborne transmission precautions are indicated until 4 days after rash onset in otherwise healthy patients and for the duration of illness in the immunocompromised. The incubation period is 8-12 days after exposure. Measles cases should be reported to the local Department of Health.

Vaccination of healthy children is highly recommended and, in most states, is required for entry into daycare and/or school. Two doses are administered at 1 year and 4-6 years of age, usually as MMR or the varicella vaccine-containing MMRV. Although MMRV is not licensed for individuals older than 13 years of age, MMR can be administered to adolescents and adults. Second doses of measles-containing vaccines should be at least 1 month apart. Healthy child or adult susceptibles should also be immunized. Exposure to measles in the unvaccinated is not a contraindication to immunization control of epidemics in schools or other institutions is by immunization. During an outbreak, infants as young as 6 months of age can be vaccinated such children should eventually receive a total of three doses of measles vaccine. Health care workers should be required to demonstrate proof of measles immunity before being hired.

Adverse events after measles vaccine include fever up to 39.4°C in 5-15% of those vaccinated, occurring between 1 and 2 weeks after MMR. Transient measles-like rash occurs in 5% of those vaccinated. Transient thrombocytopenia and anaphylaxis occur rarely. Measles vaccine considered to be extremely safe.

What host factors protect against this infection?

Although pre-formed antibodies are useful for passive immunization and play a significant role in preventing recurrent infections, cellular immunity appears more important in host defense against measles than humoral immunity. In general, CD4 T-cells help to control the virus by secretion of cytokines, whereas CD 8 T-cells directly eliminate cells infected with measles virus. Some CD4 T-cells are also cytotoxic for measles virus infected cells.

Unvaccinated patients at high risk to develop severe measles include infants younger than 6 months of age and immunocompromised individuals, such as those with congenital or acquired defects in cellular immunity, as well as children being treated for malignant disease or following transplantation. Such individuals should receive passive immunization after a recognized exposure. Exposed HIV-infected children should receive passive immunization whether or not they were immunized.

Passive immunization is accomplished with Immune Globulin (IG) within 6 days after exposure. The dose is 0.25 mL/kg IM (immunocompromised children require double that dose) the maximum dose is 15 mL. Passive immunization is not required for healthy household members who have received at least 1 dose of vaccine. For patients who receive intravenous immune globulin (IGIV) regularly, IG is not given unless it is more than 3 weeks since the IVIG was administered.

What are the clinical manifestations of infection with this organism?

Measles disease is the main manifestation of infection with rubeola virus. Patients with the prodrome of measles have non-specific respiratory symptoms for about 3 days. Koplik spots appear during and following this prodrome. In the next phase, patients complain of influenza-like symptoms, such as fever, cough, conjunctivitis, and coryza. After a few more days, the typical maculopapular, erythematous, non-pruritic rash begins on the head and face and progresses down the body. Rash first appears behind the ears and on the hairline. The rash, which blanches on pressure, appears last on the extremities, including the palms and soles. The rash may become confluent, especially on the face and neck. It clears first on the face and then on the body. Involved skin may desquamate (except on the palms and soles) during the healing phase. The rash lasts about 5 days the patient usually feels worst on the first or second day after rash onset.

Differentiation between measles and Kawasaki disease in children may be difficult, but it is clinically important because there is a specific treatment for Kawasaki disease (IV immunoglobulin). Children with Kawasaki disease are usually young (<2 years of age), have fever longer than 5 days, do not have Koplik’s spots, are often of Asian heritage, usually have a history of measles immunization, have swollen hands and feet, and often have prominent cervical lymph nodes.

Because the rash of measles is immunologically mediated, immunocompromised patients, including those with HIV infection, may have measles with no rash and may present with unexplained encephalitis. Immunocompromised patients may also have poor antibody responses to measles. When measles is suspected in such a patient, RT-PCR on body fluids or tissues becomes extremely important to rule in the diagnosis of measles.

Although measles in pregnancy does not cause congenital abnormalities, the disease may be more severe in pregnant women, especially in the last trimester, than in women who are not pregnant. Maternal measles early in pregnancy may result in fetal loss. In general, as with many so called childhood infections, measles is more severe in adults than in children. Measles in newborn infants of women with measles at delivery may also be a severe illness.

Possibly because measles virus induces a period of immunosuppression, tuberculosis may be aggravated in patients with measles. A positive tuberculin test in a patient with measles may revert to negative for a month or so after recovery from measles,

In addition to Kawasaki syndrome, other illnesses included in the differential diagnosis of measles include rubella scarlet fever roseola infectious mononucleosis infections with rickettsiae, enteroviruses, and adenoviruses Parvovirus B19 meningococcal infection toxic shock syndrome mycoplasma infections and drug eruptions.

There is no definitive evidence to implicate measles in Crohn’s disease, systemic lupus erythematosis (SLE), multiple sclerosis, or Paget’s disease of bone.

What common complications are associated with infection with this pathogen?

The complication of acute encephalitis occurs in 1/1000-2000 measles patients. Symptoms of encephalitis usually develop during the first week after rash onset. Abnormal electroencephalograms may occur in 50% of essentially asymptomatic children during measles convalescence, suggesting, however, that measles infection of the brain is not uncommon. Measles encephalitis ranges from mild to severe. Survivors frequently have neurologic sequelae. Because measles encephalitis is thought to result from infection of the central nervous system (CNS), steroids are not recommended for its treatment.

Pneumonia and otitis media accompanying measles may be due to primary viral infection or bacterial superinfection. It appears that measles virus suppresses cell-mediated immune responses, which may explain why secondary bacterial infections occur. In addition, neutropenia may accompany measles. Pneumonia is a common reason for death in infants who contract measles. In teenagers dying of measles, the cause is likely due to encephalitis.

Bacterial superinfections of the respiratory tract are common complications and can usually be treated successfully with appropriate antimicrobials.

A rare fatal complication, subacute sclerosing panencephalitis (SSPE), with an incubation period as long as 10 years, occurs mainly in children who had measles when they were younger than 2 years of age. These children present with gradual onset of behavioral and intellectual deterioration, with seizures, eventually progressing to coma and death. There is no treatment. The pathogenesis is thought to be from a persistent measles-related virus infection in the brain despite a vigorous immune response to the virus. The incidence of SSPE in the United States declined dramatically after the widespread use of measles vaccine, but increased after the increased number of cases in the early 1990s. There is only 1 case on record of SSPE caused by the vaccine-type virus. Most cases of SSPE in the United States today are seen in children who immigrated to the United States from countries where measles vaccine is not used. SSPE can be diagnosed by unusually high levels of measles antibodies in cerebrospinal fluid (CSF) and serum.

Rarely, myocarditis and pericarditis, as well as thrombocytopenic purpura, occur during measles.

In immunocompromised patients, two severe complications of measles are giant cell (primary) pneumonia and measles encephalitis. This form of encephalitis appears somewhat between acute encephalitis in non-immunocompromised patients and SSPE. The incubation period is variable encephalitis may occur as long as 6 months after measles onset. Seizures are often the presenting symptom. Other manifestations include paralysis, coma, and slurred speech the outcome is usually fatal within weeks to a few months.

Atypical measles is an unusual form of the infection that usually appears in adults who received the inactivated (“killed”) measles vaccine as children. Use of this vaccine was discontinued in 1968. This vaccine did not induce long-term immunity to measles but did provide partial immunity manifested as hypersensitivity to the virus when the person vaccinated was exposed to natural measles.

In atypical measles, the rash begins on the extremities and progresses towards the trunk. The rash may itch and also have a vesicular component. Nodular pneumonia may be seen, along with hepatosplenomegaly, neurological symptoms, such as weakness and paresthesias, and high fever. Koplik spots are rare. These patients are not contagious to others. Antibody titers are usually quite high, which suggests this diagnosis. The illness may be prolonged but is self-limited. Fatalities are exceedingly rare.

How should I identify the organism?

Measles can often be diagnosed clinically, especially if Koplik spots are noted. White or bluish Koplik spots first appear on the mucosa opposite the lower molar teeth and, with time, spread to the entire buccal mucosa.

In the laboratory, the diagnosis can be made by virus isolation, performed using peripheral blood mononuclear cells (PBMC), nasal washings, broncholavage samples, or available tissues in the instance of fatalities. For virus isolation, primary human or monkey kidney cells are mainly used. It is also possible to demonstrate measles antigens or RNA in infected tissues. Multinucleated giant cells in PBMC or other tissues or secretions stained with Wright’s stain or hematoxylin and eosin reveal Warthin-Finkeldey cells, which are pathognomonic of measles. These cells are the result of cell fusion. Multinucleated giant cells may originate from lymphoid (classical Warthin-Finkeldey cells) or epithelial cells.

Because virus isolation is difficult and expensive, it has been largely supplanted by polymerase chain reaction (PCR) for diagnosis. PCR for measles virus is commercially available and is also performed by many local health departments. Detection of measles virus RNA by RT-PCR is thought to be highly sensitive and specific, although studies of sensitivity and specificity are not yet available. Measles RNA may be persistent for long periods of time in certain tissues and may not necessarily indicate replication of the virus. Nucleotide sequencing that can differentiate between vaccine and wild type virus is available through local health departments.

The presence of IgM antibodies to measles virus in a single blood specimen is considered diagnostic. IgM may not be detectable until well into the development of the rash, so two determinations may be necessary if the first is negative and measles is still suspected. Measles IgM persists for about 1 month after rash onset. A four-fold increase in IgG antibody titer in acute and convalescent blood specimens is diagnostic of measles.

How does this organism cause disease?

Measles virus enters the body at the respiratory tract using the signaling lymphocyte activation molecule (SLAM) receptor and is thought to multiply first in lymphoid cells. Attenuated measles vaccine strains also utilize another cellular receptor, CD46. The virus then invades epithelial cells in many organs, as well as the respiratory tract. In the respiratory tract, progeny is released into the airway, enabling transmission of the virus to others by the airborne route. Infection of the respiratory tract sets the stage for cough, coryza, croup, bronchiolitis, otitis media, and pneumonia. Damage to the respiratory tract, such as loss of cilia and immunosuppression and neutropenia caused by the virus, may predispose to severe complications, such as pneumonia. Secondary bacterial infection is also facilitated by these transient abnormalities in host defense.

Measles virus spreads to many organs via lymphocytes and monocytes by cell-associated viremia. The virus multiplies in lymphoid organs and tissues, such as thymus, spleen, lymph nodes, and tonsils, as well as the skin, lung, gastrointestinal tract, and liver tissues. The hallmark of infection is the multinucleated giant cell. The onset of clinical disease corresponds to activation of adaptive immune responses, with activation, as well as immunosuppression, which probably accounts for the many infectious complications of measles.

Presumably, many of the symptoms are the result of tissue destruction, such as cilia, by the virus directly and also possibly due to cytokine release.

Measles vaccine has been exonerated as causal of autism by numerous studies, as well as the recently published Report of the Institute of Medicine “Adverse Effects of Vaccines: Evidence and Causality.”

WHAT’S THE EVIDENCE for specific management and treatment recommendations?

Afzal, MA, Ozoemena, LC, O’Hare, A, Kidger, KA, Bentley, ML, Minor, PD. “Absence of detectable measles virus genome sequence in blood of autistic children who have had their MMR vaccination during the routine childhood immunization schedule of UK”. J Med Virol. vol. 78. 2006. pp. 623-30.

Angel, JB, Walpita, P, Lerch, RA. “Vaccine-associated measles pneumonitis in an adult with AIDS”. Ann Intern Med. vol. 129. 1998. pp. 104-6.

Arenz, S, Fischer, R, Wildner, M. “Measles outbreak in Germany: clinical presentation and outcome of children hospitalized for measles in 2006”. Pediatr Infect Dis J. vol. 28. 2009. pp. 1030-2.

Atmar, RL, Englund, JA, Hammill, H. “Complications of measles during pregnancy”. Clin Infect Dis. vol. 14. 1992. pp. 217-26.

Bellini, WJ, Icenogle, J, Murray, PR, Baron, E, Jorgensen, J, Landry, M, Pfaller, M. “Measles and Rubella virus”. Manual of clinical microbiology. 2007. pp. 1378-83.

Betta Ragazzi, SL, De Andrade Vaz-de-Lima, LR, Rota, P. “Congenital and neonatal measles during an epidemic in Sao Paulo, Brazil in 1997”. Pediatr Infect Dis J. vol. 24. 2005. pp. 377-8.

Chen, SY, Anderson, S, Kutty, PK. “Health care-associated measles outbreak in the United States after an importation: challenges and economic impact”. J Infect Dis. vol. 203. 2011. pp. 1517-25.

Forni, AL, Schluger, NW, Roberts, RB. “Severe measles pneumonitis in adults: evaluation of clinical characteristics and therapy with intravenous ribavirin”. Clin Infect Dis. vol. 19. 1994. pp. 454-62.

Gerber, JS, Offit, PA. “Vaccines and autism: a tale of shifting hypotheses”. Clin Infect Dis. vol. 48. 2009. pp. 456-61.

Gremillion, DH, Crawford, GE. “Measles pneumonia in young adults. An analysis of 106 cases”. Am J Med. vol. 71. 1981. pp. 539-42.

Griffin, DE, Knipe, D, Howley, P. “Measles virus”. 2007. pp. 1551-85.

Hussey, GD, Klein, M. “A randomized, controlled trial of vitamin A in children with severe measles”. New Eng J Med. vol. 323. 1990. pp. 160-4.

Krasinski, K, Borkowsky, W. “Measles and measles immunity in children infected with human immunodeficiency virus”. JAMA. vol. 261. 1989. pp. 2512-6.

La Boccetta, AC, Tornay, AS. “Measles encephalitis. Report of 61 cases”. Am J Dis Child. vol. 107. 1964. pp. 247

Ma, SJ, Li, X, Xiong, YQ, Yao, AL, Chen, Q. “Combination Measles-Mumps-Rubella-Varicella Vaccine in Healthy Children: A Systematic Review and Meta-analysis of Immunogenicity and Safety”. Medicine. vol. 94. 2015. pp. e1721

McHale, P, Keenan, A, Ghebrehewet, S. “Reasons for measles cases not being vaccinated with MMR: investigation into parents' and carers' views following a large measles outbreak”. Epidemiology and infection. vol. 144. 2016. pp. 870-875.

“Measles—United States, January—May 20, 2011”. MMWR. vol. 60. 2011. pp. 666-8.

Parker, AA, Staggs, W, Dayan, GH. “Implications of a 2005 measles outbreak in Indiana for sustained elimination of measles in the United States”. N Engl J Med. vol. 355. 2006. pp. 447-55.

Parker Fiebelkorn, A, Redd, SB, Gallagher, K. “Measles in the United States during the postelimination era”. J Infect Dis. vol. 202. 2010. pp. 1520-8.

Rota, PA, Liffick, SL, Rota, JS. “Molecular epidemiology of measles viruses in the United States, 1997-2001”. Emerg Infect Dis. vol. 8. 2002. pp. 902-8.

Schuchat, A, Fiebelkorn, AP, Bellini, W. “Measles in the United States since the Millennium Perils and Progress in the Postelimination Era”. Microbiology spectrum 4 2016.

Smith, PJ, Marcuse, EK, Seward, JF, Zhao, Z, Orenstein, WA. “Children and Adolescents Unvaccinated Against Measles: Geographic Clustering, Parents' Beliefs, and Missed Opportunities”. Public health reports. vol. 130. 2015. pp. 485-504.

Sotir, MJ. “Measles in the 21st Century, a Continuing Preventable Risk to Travelers: Data From the GeoSentinel Global Network”. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. vol. 62. 2016. pp. 210-212.

Sugerman, DE, Barskey, AE, Delea, MG. “Measles outbreak in a highly vaccinated population, San Diego, 2008: role of the intentionally undervaccinated”. Pediatrics. vol. 125. 2010. pp. 747-55.

Tatsuo, H, Ono, N, Tanaka, K, Yanagi, Y. “SLAM (CDw150) is a cellular receptor for measles virus”. Nature. vol. 406. 2000. pp. 893-7.

(Measles Cases and Outbreaks January 1 to May 16, 2014.)

Copyright © 2017, 2013 Decision Support in Medicine, LLC. All rights reserved.

No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. The Licensed Content is the property of and copyrighted by DSM.

The virus causes measles, a highly contagious disease transmitted by respiratory aerosols that triggers a temporary but severe immunosuppression. Symptoms include fever, cough, runny nose, inflamed eyes and a generalized, maculopapular, erythematous rash. The virus is spread by coughing and sneezing via close personal contact or direct contact with secretions.

Entry Edit

The measles virus has two envelope glycoproteins on the viral surface – hemagglutinin (H) and membrane fusion protein (F). These proteins are responsible for host cell binding and invasion. The H protein mediates receptor attachment and the F protein causes fusion of viral envelope and cellular membrane. Additionally, the F protein can cause infected cells to directly fuse with neighboring uninfected cells forming syncytia. Three receptors for the H protein have been identified to date: complement regulatory molecule CD46, the signaling lymphocyte activation molecule (SLAMF1) and the cell adhesion molecule Nectin-4. [2] For wild type and vaccine strains, extracellular domains of CD150 (SLAM or SLAMF1) [3] [4] and/or of nectin-4 (also called Poliovirus-Receptor-Like 4 (PVRL4)) [5] [6] mainly work as cell entry receptors. Minor fraction of wild type virus strains and all modern vaccine strains derived from the Edmonston strain also use CD46. [7] [8]

Genome replication and viral assembly Edit

Once the virus has entered a host cell, its strand of negative sense ssRNA (single stranded RNA) is used as a template to create a positive sense copy, using the RNA-dependent RNA polymerase that's included in the virion. Then this copy is used to create a new negative copy, and so on, to create many copies of the ssRNA. The positive sense ssRNA is then mass translated by host ribosomes, producing all viral proteins. The viruses are then assembled from their proteins and negative sense ssRNA, and the cell will lyse, discharging the new viral particles and restarting the cycle. [9]

The RNA genome of the virus codes 6 main proteins Nucleoprotein (N), Phosphoprotein (P), Matrix protein (M), Fusion protein (F), Hemagglutinin (H), and Large Protein (L), [10] which represents RNA dependent RNA polymerase (RdRp). The viral genome also codes two non-structural proteins C and V. These non-structural proteins are innate immunity antagonists they help the virus to escape host immune response. Inside the virion genomic RNA is forming complex with N, L and P proteins. N, P and M proteins regulate RNA synthesis by RdRp. The virus is enveloped by a lipid membrane and glycoproteins H and F are virion surface proteins that are associated with this lipid membrane.

The measles virus evolved from the now eradicated but formerly widespread rinderpest virus, which infected cattle. [11] Sequence analysis has suggested that the two viruses most probably diverged in the 11th and 12th centuries, though the periods as early as the 5th century fall within the 95% confidence interval of these calculations. [11]

Other analysis has suggested that the divergence may be even older because of the technique's tendency to underestimate ages when strong purifying selection is in action. [12] There is some linguistic evidence for an earlier origin within the seventh century. [10] [13] The current epidemic strain evolved at the beginning of the 20th century—most probably between 1908 and 1943. [14]

The measles virus genome is typically 15,894 nucleotides long and encodes eight proteins. [15] The WHO currently recognises 8 clades of measles (A–H). Subtypes are designed with numerals—A1, D2 etc. Currently, 23 subtypes are recognised. The 450 nucleotides that code for the C‐terminal 150 amino acids of N are the minimum amount of sequence data required for genotyping a measles virus isolate. The genotyping scheme was introduced in 1998 and extended in 2002 and 2003.

Despite the variety of measles genotypes, there is only one measles serotype. Antibodies to measles bind to the hemagglutinin protein. Thus, antibodies against one genotype (such as the vaccine strain) protect against all other genotypes. [16]

The major genotypes differ between countries and the status of measles circulation within that country or region. Endemic transmission of measles virus was interrupted in the United States and Australia by 2000 and the Americas by 2002. [17]

In the early stages of infection, the measles virus via CD150 (SLAMF1) receptor infects immune cells located in the host respiratory tract such as macrophages and dendritic cells. [18] [19] [20] They transmit the virus to the lymphoid organs, from which it spreads systemically. In the later stages of infection, the virus infects other immune cell types, including B cells [21] and T lymphocytes [22] also via SLAMF1 receptor. In addition, it infects epithelial cells located in the airways. These cells become infected via nectin-4 receptor and by cell to cell contacts with infected immune cells. The infection of epithelial cells allows the virus to be released via the airstream. [23] [24]

Measles Virus Antigens

The measles virus (MV or MeV) is a member of the genus Morbillivirus, which belongs to the family Paramyxoviridae. It is an enveloped (non-segmented), negative-sense and single-stranded RNA virus which targets human as its natural host (no animal reservoirs are reported up to now). Measles virus causes measles, an infection disease that targets on the respiratory system of humans. Measles is a highly contagious injection with multiple symptoms including cough, fever, runny nose, red eyes and generalized, maculopapular, erythematous rash. Measles affects more than 20 million people all over the world each year, mainly in developing areas in Asia and Africa. Mortality rate of measles infection is about 0.2%, but it can up to 10% for individuals who have malnutrition. Despite the fact that measles virus is serologically monotypic, eight clades of measles have been classified and are named from A to H. They are further catalogued into 23 sub types. Major genotype is different in different areas.

Fig.1 Measles virus particle under electron microscopy

Two envelope glycoproteins were identified from the surface of measles virus: hemagglutinin (H) and membrane fusion protein (F). Both of them are critical for the binding between measles virus and host cells, and the invasion of measles virus. Three receptors from the surface of host cells have been found to bind with measles H protein: the signaling lymphocyte activation molecule (SLAM), the complement regulatory molecule CD46 and the cell adhesion molecule Nectin-4. Genomes of measles virus are covered by its capsid, which are constructed by the nucleocapsid protein N. Two other large proteins are identified as protein L and the phosphoprotein P. The protein L and phosphoprotein P are involved in the replication of measles viral genome and also play important roles in the expression of viral structural proteins.

After the entrance into the host cells, viral protein P and L will make a strand of viral RNA for the replication of viral genomes and expression of viral proteins. The viral RNA strand is complimentary to the genomic strand. The newly expressed viral proteins will be carried out with the association of protein P and L. The new viral genomes and proteins will proceed the self-assembly to form new measles virus particles and bud off from the cell membrane and steal part of the host cell membrane to construct its own envelopes.

Creative Diagnostics now can provide Measles virus antigens and proteins for different applications. Welcome to contact us for more details.

How measles causes the body to ‘forget’ past infections by other microbes

One of the most contagious human pathogens, the measles virus is dangerous enough by itself, with sometimes-fatal complications including pneumonia and brain inflammation. Two detailed studies of blood from unvaccinated Dutch children who contracted measles now reveal how such infections can also compromise the immune system for months or years afterward, causing the body to "forget" immunity it had developed to other pathogens in the past.

To what extent this "immune amnesia" increases illness and deaths from other infections isn't clear. But the results are another good reason to immunize children against the virus, the studies' authors and other infectious disease experts say. The findings are particularly sobering now that measles cases are increasing sharply—by more than 30% globally from 2017 to 2018—because of undervaccination and misguided vaccine safety concerns. "If we allow [measles] outbreaks to happen, we are knowingly creating pockets of people who are susceptible to other diseases as well," says Velislava Petrova at the Wellcome Sanger Institute in Hinxton, U.K., who led one study.

"These two studies provide further strong evidence for the highly immunosuppressive effects of measles infection and the power of measles vaccination to counter it," adds population biologist Bryan Grenfell of Princeton University, whose group in 2015 reported early evidence for the effect.

That finding was based on population data showing that mortality from other pathogens increases after a measles outbreak. Experiments in animals have also suggested the measles virus impairs immunity. So Petrova's group and another, headed by Stephen Elledge of Harvard University, decided to explore this phenomenon more closely in people. Both teams chose a well-known cohort of children from an Orthodox Protestant community in the Netherlands whose parents had opted out of all vaccines for their children for religious reasons.

Michael Mina, a Harvard virologist who also worked on the population study, teamed up with Elledge to analyze blood samples from 77 of the children before and after they became infected during a 2013 measles outbreak in the Netherlands. Tomasz Kula, a postdoc in Elledge's lab, had developed a technology called VirScan that enabled the team to test the antibodies in the infected children's blood against antibody targets representing most known human pathogenic viruses.

Before the children contracted measles, their blood contained antibodies to many common pathogens. "These were really healthy kids," Mina says. After the disease, the children lost, on average, about 20% of their antibody repertoire. Some fared much worse, losing more than 70% of their immunity to viral pathogens, the researchers report this week in Science. They did not see the effect in their controls: five unimmunized children who never contracted measles over the course of the study, as well as more than 100 other children and adults. They also saw no loss of antibodies in children after they received a vaccination against measles.

The diminished antibody shield means that after a case of measles, unvaccinated children become vulnerable again to viruses they had been exposed to in the past. For example, if a child had contracted mumps prior to having measles, they might be susceptible to mumps again. "It's like taking somebody's immune system and rewinding time, putting them at a more naïve state," Mina says.

To understand the effect, Petrova's group did a different analysis of blood from the Dutch children. The team went straight to the source of antibodies: B cells, which the measles virus is known to infect. They found that measles infection reduced the diversity of memory B cells, which "remember" past infections and are quick to fight any recurrence. The virus killed off B cells specific to other pathogens, allowing new, measles-specific memory B's to replace them.

Measles also decreased the diversity of another category of B cells: nonspecific naïve B cells in the bone marrow, which stand ready to fight unfamiliar infections. A measles infection left this cell repertoire "immature, similar to that of a fetus," says Petrova, whose study appeared this week in Science Immunology. Basically, the measles virus doesn't just delete immune memory—it makes it harder for the immune system to respond to new pathogens in the future.

"This [measles-induced immune amnesia] has never been characterized to the extent that they've done here," says Mark Slifka, an immunologist at Oregon Health & Science University in Portland. But its long-term significance is unclear, he says, noting that immunity naturally fades as the body destroys some antibodies to keep their numbers in check. "Hopefully these families will be willing to continue to be involved with the researchers," he says.

The only way to prevent measles from erasing immune memory, Mina says, is the obvious one: Prevent cases by vaccinating. In fact, Mina says, after a child has measles, physicians should consider revaccinating them against all common pathogens. "The Catch-22 is that [these children] are only getting measles because they're not vaccinated in the first place," he says.

On the other hand, says Jennifer Lighter, an infectious disease physician at New York University's Langone Health in New York City, "I think after you see your child that has measles, you wouldn't want your child to get other infections and to suffer needlessly."

Watch the video: Γιατρός στη Θεσσαλονίκη εναντιώνεται στο εμβόλιο της ιλαράς (May 2022).