Measles overview

# Overview
Measles is a disease caused by the Morbillivirus. It is transmitted into the respiratory by contact with infected fluids. Incubation lasts for 4-12 days, during which patients are asymptomatic. Symptomatic onset includes the appearance of a distinct rash. Infected people remain contagious from 5 days before appearance to until 4 days after.

# Historical Perspective
The measles virus was isolated in cell culture in 1954, by Jhon F. Enders and Thomas C. Peebles. This was the first step that allowed the development of a successful vaccine, licensed 9 years later, in 1963. To date, 21 strains of the measles virus have been identified.

# Pathophysiology
Measles is caused by a nonsegmented negative-stranded RNA virus of the Paramyxoviridae family, genus Morbillivirus. The primary site of infection is the respiratory epithelium of the nasopharynx and it is transmitted in respiratory secretions, via aerosol droplets containing virus particles.

# Differentiating Measles from other Diseases
Measles is a disease characterized by the classical clinical triad of cough, coryza and conjunctivitis. In most cases the presentation is classical and the diagnosis can be sufficiently made clinically. However, in a few cases certain other diagnostic possibilities must be kept in mind. These include other viral exanthams such as erythema infectiosum, other maculopapular rashes etc. Also, in areas where killed vaccines are used, the probability of atypical measles with fever, conjunctivitis, pneumonitis and rash must be kept in mind. It is worthwhile to consider Kawasaki's disease, rubella, dengue, systemic lupus erythematosus and serum sickness while considering the diagnosis of measles.

# Epidemiology and Demographics
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.

# Risk Factors
Measles is a disease with very low incidence in the developed world. Lack of vaccination against measles is one of the biggest risk factors that predisposes measles spread. In developed countries like USA, most cases are attributed to unvaccinated or incompletely vaccinated travelers from other parts of the world. Primary vaccine failure occurs in approximately 5% of individuals vaccinated with a single dose of vaccine at 12 months of age or older and also predisposes an individual to the risk of developing measles.

# Natural History, Complications and Prognosis
Measles spreads through the air by breathing, coughing or sneezing. It is so contagious that any child who is exposed to it and is not immune will probably get the disease. The virus lives in the mucus in the nose and throat of the infected person. When that person sneezes or coughs, droplets spray into the air. The virus can live on infected surfaces for up to 2 hours and spreads so easily that people who are not immune will probably get it when they come close to someone who is infected. Measles is a disease of humans.
Complications with measles are relatively common, ranging from relatively mild and less serious diarrhea, to pneumonia and encephalitis (subacute sclerosing panencephalitis - SSPE). Complications are usually more severe amongst adults who catch the virus.
Measles itself is unpleasant, but the complications are dangerous. Six to 20 percent of the people who get the disease will get an ear infection, diarrhea, or even pneumonia. One out of 1000 people with measles will develop inflammation of the brain, and about one out of 1000 will die.

# Diagnosis

## Diagnostic Criteria
A measles case is confirmed in a person with febrile rash illness and laboratory confirmation or a direct epidemiologic link to a confirmed case.

## History and Symptoms
The symptoms of measles generally begin about 7-14 days after a person has been infected. Clinical diagnosis of measles requires a history of fever of at least three days together with at least one of the three Cs cough, coryza (runny nose) and conjunctivitis (red eyes). Observation of Koplik's spots is also a characteristic finding in measles.  The fever may reach up to 104 F/ 40 C.

## Physical Examination
Measles is a condition, that is best diagnosed clinically based on a constellation of signs and symptoms. Fever, rash and conjunctivitis are 3 major physical findings that must be looked out for, while making the diagnosis of measles.

## Laboratory Findings
Laboratory confirmation is essential for all sporadic measles cases and all outbreaks. Detection of measles-specific IgM antibody and measles RNA by real-time polymerase chain reaction (RTPCR) are the most common methods for confirming measles infection. Healthcare providers should obtain both a serum sample and a throat swab (or nasopharyngeal swab) from patients suspected to have measles at first contact with them. Urine samples may also contain virus, and when feasible to do so, collecting both respiratory and urine samples can increase the likelihood of detecting measles virus. 

## Chest X Ray
A chest X-ray can be used to diagnose pneumonia, which is one of the complications of measles.   The chest x-ray findings in patient with measles will be a patchy consolidation of lung lobes and poorly define nodules. 

## Other Diagnostic Studies
Other diagnostic tests include Vero/hSLAM cells for isolation of measles virus and genetic and sequencing analysis.

# Treatment

## Medical Therapy
Despite the efforts made in the past years to develop a treatment regimen for measles, there is still no specific antiviral therapy for uncomplicated cases of measles, however, some drugs such as ribavirin and interferon- have been used in the more severe cases of the condition, notably for cases of infection of the CNS by the virus. Yet, there is evidence that the administration of two doses of vitamin A in children, under the age of two, was associated with a reduced risk of morbidity and mortality from the disease. For most patients with measles, the standard treatment is focused on supportive care.

## Primary Prevention
Ever since the introduction of the measles vaccine, there has been a marked reduction of the incidence of this disease in the population. The widespread use of measles vaccine has led to a greater than 99% reduction in measles cases in the United States, when compared with the non vaccine era. Therefore the most effective way of preventing measles is with active immunization provided by this vaccine, which is often incorporated with the rubella and/or mumps vaccines, in the MMR vaccine, in countries where these illnesses represent a problem. Unfortunately, measles is still a common disease in developing countries, where the virus is highly contagious and is able to spread across large areas, where vaccination is not common.

## Cost-Effectiveness of Therapy
Although there is still no specific antiviral treatment for measles, attending to the considerable decrease in morbidity and mortality of measles in the United States, with the introduction of measles vaccine, it may be considered that prevention of measles by vaccination shows cost-effectiveness.

## Future or Investigational Therapies
Despite the impact of primary prevention with vaccination in the incidence of measles there is still no specific antiviral treatment for the disease once it develops. Most developing countries are still severely affected by the high incidence of this conditions, in part due to the absence of an adequate vaccination system. Therefore, it is essential the role of research in developing a more adequate approach to the disease, once it is established. Also, the development of easier and less expensive ways of bringing the vaccine to populations in developing countries would greatly contribute to a potential eradication of measles.