Measles

by Kenneth Lyen

INTRODUCTION

In 2000, public health officials declared that measles had been eliminated from the USA, stating that there was no continuous transmission of measles during the previous 12 months, and the few reported cases were largely overseas patients. Similarly, from 2013 to 2015, there was a significant drop in the number of new cases of measles in Europe. The fall in new cases of measles was so dramatic in England that the World Health Organization declared England to be measles-free in 2017.

Unfortunately, this was overoptimistic. The number of reported cases of measles shot up in 2019. The World Health Organisation has announced that globally the number of cases in the first three months of 2019 has jumped 300 percent compared to the same period last year.

What happened? But first, let us examine the clinical manifestations of measles in some detail.

SYMPTOMS

Measles is a highly infectious viral illness characterised by fever, generalised skin rash, often accompanied by a cough, runny nose and watery red eyes. The symptoms can be divided into three stages:

First Stage

The first symptoms are those of high fever, cough and runny nose (coryza) and red eyes (conjunctivitis). There may be vague symptoms of malaise, tiredness, loss of appetite, aches and pains, and occasionally the eyes are sensitive to bright lights (photophobia). The cough, corya and conjunctivitis form the classic triad of the “3 C’s”.

Second Stage

In the early phase of the illness, two or three days after the initial symptoms, there are small discrete white spots inside the mouth, often located in the inner cheeks. These were first described by Henry Koplik, and American physician, in 1896, and these white spots are referred to as Koplik spots. They are highly diagnostic of measles.

Third Stage

Some three to five days after the fever, a rash will appear, starting on the face and spreading throughout the body. It consists of a patchy flat reddish rash (macule) and in the middle is a slightly raised spot (papule). The rash lasts around 5-7 days, and fades into copper-brown patches before disappearing.

Measles Illustration 3 Straits Times.jpg

INFECTIVITY

Measles is most contagious about 4 days before the onset of the rash, and continues to be infective for 4 or 5 days after that. The incubation period is usually around 10 to 12 days.

CAUSE

Measles is caused by a virus which is airborne and can easily be spread from one person to another. When an infected person coughs or sneezes the virus is discharged into the air, and anybody nearby can inhale the virus into the nose, throat and lungs. The virus can remain active and contagious in the air for around 2 hours. In addition to the airborne route, measles can also be spread by direct contact with infected saliva and nasal discharge.

MEASLES VIRUS

This is an RNA virus belonging to the morbillivirus genus which is part of the paramyxovirus family. Man is the only natural host for this virus. There are no animal reservoirs.

People who are at special risk for measles include children, especially those who are too young to be vaccinated. Children with vitamin A deficiency are also more vulnerable. Those who have immunodeficiency, either from receiving immunosuppressants for cancer or autoimmune disease, or those carrying the human immunodeficiency virus (AIDS) are more susceptible to measles.

MECHANISM OF INFECTION

The measles virus has a protein called haemagglutinin or H-protein which binds to a receptor on the host cell surface. Cells lining the nose, throat or lungs are the first point of contact. There are a few receptor proteins on the cell surface, including CD46, CD150, and Nectin-4. By binding to one of these receptors, the virus becomes attached to the cell. The next step requires another protein which the measles virus also possesses, namely a fusion protein. With this fusion protein, the virus can enter the cell. It remains a mystery why our cells have evolved this binding and fusion to take place, because in so doing it allows the invading virus to enter the cell and to replicate.

After entering the cell, the measles virus, a single stranded RNA molecule, has to transform from a negative sense to a complementary strand or positive sense RNA. The latter acts like messenger RNA, and this transformation requires the help of RNA polymerase. Now the virus is able to replicate. The host cell not only replicates the viral RNA, but also makes H-proteins and fusion proteins. The completed virus then exits the cell where it is taken up by dendritic cells that carries it to lymph nodes where it continues its spread through the blood stream.

LABORATORY DIAGNOSIS

BLOOD ANTIBODY ASSAY

Immunoglobulin M (IgM)

The sandwich-capture IgM antibody assay is the quickest and most accurate way of diagnosing acute measles. However, the IgM may not be detectable during the first 2 days of rash, so there is a possibility of a false negative if blood is taken too early. It is recommended that blood be taken on the third day of the rash or later to avoid a false-negative IgM result.

Immunoglobulin G (IgG)

The IgG antibody test is only reliable if a 4-fold rise in antibody titre can be demonstrated by obtaining two blood samples taken 14 days apart. The first blood sample should ideally be drawn 7 d after the onset of the skin rash.

A single blood sample showing raised IgG levels is not necessarily diagnostic of acute measles, because the level may be due to a previous infection, vaccination, or due to maternal antibodies in young infants.

Throat and Nasal Swab for Viral Culture

Throat and nasal swabs are taken and placed in a special culture medium and sent to the laboratory to culture the measles virus. Less commonly, urine samples can also be sent for viral culture.

Blood, Nasal Swab or Urine for Polymerase Chain Reaction (PCR)

The most accurate diagnosis of measles is the polymerase chain reaction (PCR) which identifies the RNA sequence of the measles virus. This can be detected in blood, nasopharyngeal and urine samples. The diagnosis is quite fast, and very accurate.

Chest Xray

A chest Xray should be ordered if measles pneumonia is suspected. Measles pneumonia is common.

Lumbar Puncture for Cerebrospinal IgG antibody to Measles

Patients suspected of having subacute sclerosing panencephalitis (SSPE) should have cerebrospinal fluid taken and measles antibodies assayed. The earliest this can be done is 3 weeks after the onset of symptoms. The diagnosis is confirmed when very high levels of measles antibodies are detected.

Electroencephalogram (EEG)

This should be ordered if subacute sclerosing panencephalitis (SSPE) is suspected.

COMPLICATIONS

Measles can result in many potential complications. These commonly include diarrhoea and vomiting, middle ear infection (otitis media) resulting in earache and potential hearing impairment, eye infection (conjunctivitis) which is manifest as red teary eyes and can cause visual loss, inflammation of the throat and voice box (laryngitis), infection of the lungs (pneumonia, bronchitis and croup), high fever which may trigger a seizure (febrile fit).

Less common complications include infection of the liver (hepatitis), infection of the membrane lining the brain and spinal cord (meningitis), or infection of the nerve cells inside the brain (encephalitis). Pregnant mothers who get measles may miscarry their baby.

Another complication is damage to the optic nerve (optic neuritis) which can result in blindness.

Subacute Sclerosing Panencephalitis (SSPE)

A rare complication affecting about 1 in 10,000 cases of measles, is called subacute sclerosing panencephalitis (SSPE). This is manifest several years after the initial measles infection which had affected very young children under one year of age. It may come on insidiously with poor school performance, easy forgetfulness, distractibility, temper tantrums, lethargy, hallucinations, uncoordinated movements (ataxia), involuntary neuromuscular jerks (myoclonic seizures), and blindness. Unfortunately, nearly every patient who gets SSPE will die despite antiviral treatment with isoprinosine and interferon alpha.

The complications of measles are averted by preventing measles in the first place, and this is effectively achieved by vaccination.

TREATMENT OF MEASLES

There is no specific antiviral antibiotic treatment of measles. Fever can be treated with paracetamol and/or ibuprofen. If there is dehydration, give fluids. If the child is suspected of having vitamin A deficiency due to malnutrition, one should give vitamin A supplements.

PREVENTION

Vaccination is a safe and effective way of preventing measles. Currently measles is given together with mumps and rubella (German measles) in a combination known as MMR. It is recommended that two doses of MMR are given, the first at the age of one year, and the second dose given 3 months or more later.

In developing countries, the vaccine can be given to children under one year old,

Significant adverse reactions to vaccination are rare. The most common reactions are pain at the injection site and fever. Life-threatening side effects occur in less than one per million vaccinations (<0.0001%).

The MMR is a live weakened (attenuated) viral vaccine. Therefore, vaccination should not be given during pregnancy, and it is advisable to be vaccinated before contemplating pregnancy. Ideally the vaccine should be given at least 28 days before becoming pregnant.

Patients on immunosuppressants, such as steroids or anti-cancer drugs, should not be given the MMR vaccine. Patients who have serious immunodeficiency, including those who have the human immunodeficiency virus (HIV AIDS) should also not be given the vaccine. If the degree of immunodeficiency in a patient with HIV infection is mild, some doctors are willing to give the MMR vaccine can be given. However, it is important to discuss this with your doctor first.

In 1998 Andrew Wakefield and colleagues published a paper in the Lancet medical journal, incorrectly claiming that the MMR vaccine can cause autism spectrum disorder. This claim has been conclusively rejected by careful large-scale medical studies in many countries worldwide. Unfortunately the Lancet publication has provided fuel to a movement led by a group of parents who are against vaccinations. A significant number of parents have not had their infants vaccinated, and there have been outbreaks of measles leading to many deaths.

MEASLES HISTORY

CHINESE GOD OF MEASLES

Measles has been known for about 2,000 years or more. The Chinese god, Tcheng Chen is recognized as the god of measles.

TAOIST MONK KO HUNG (280-340)

The Taoist monk Ko Hung wrote several treatises on Chinese alchemy, and he was one of the first people to distinguish measles from smallpox.

PERSIAN PHYSICIAN MUHAMMAD AL-RHAZES (860-932)

In the 9th century AD, the Persian physician Muhammad Al-Rhazes wrote a book entitled “The Book of Smallpox and Measles” where he differentiated measles from smallpox.

SCOTTISH PHYSICIAN FRANCIS HOME (1719-1813)

In 1719, the Scottish physician Francis Home who was the first Professor of Materia Medica at the University of Edinburgh demonstrated in 1757 that measles was caused by an infectious agent. He was the first person to try to vaccinate against measles in 1758.

JOHN ENDERS (1897-1985) and THOMAS PEEBLES (1921-2010)

In 1954 the virus that causes measles was isolated in Boston, Massachusetts, by John Enders and Thomas Peebles.

EPIDEMIOLOGY

NOTABLE HISTORICAL OUTBREAKS OF MEASLES

HAWAII

In 1824, the king and queen of Hawaii visited London to seek an audience with King George IV. Both came down and died within a month, of measles. In 1848 an epidemic of measles swept through Hawaii killing around 10-33% of the population.

FIJI

In 1875, the British royal navy ship HMS Dido arrived in Fiji bringing King Cakobau and his two sons home after a state visit to Australia. Over the next 10 days, the royal family entertained chieftains and their entourage, many of whom came down with measles. An estimated total of about 40,000 people died, comprising one-third of the population of Fiji.

WORLD

Until recently, measles was under control in developed countries, but remains common in developing countries. The American CDC estimates that there are about 10 million children affected each year, and 110,000 children die from measles each year.

Worldwide, measles is the leading causes of blindness in the young, affecting some 15,000-60,000 cases of blindness per year. This is a fact often overlooked.

EUROPE

The World Health Organisation (WHO) has reported 34,300 cases of measles in Europe in the first two months of 2019, triple the 11,436 cases in same period in 2018. A total of 13 measles-related deaths were reported in Albania, Romania and Ukraine. Measles was declared eliminated from the USA in 2000, but 2019 there have been over 700 cases. Similarly, in 2017, the WHO declared the United Kingdom to have eliminated measles, but in 2019 there has been a resurgence with over 800 cases of measles diagnosed.

PHILIPPINES

There has been a spike of cases of measles in Southeast Asia. The Philippines reported over 31,000 confirmed cases from January to April 2019, causing 415 deaths.

According to the World Health Organization, the vaccination coverage of measles in the Philippines was already low at 80% in 2008, but has steadily fallen to below in 70% in 2017. An estimated 2.6 million Filipino children under the age of 5 years are not protected against measles.

INDONESIA

There has also been an increase in cases in Indonesia. This is attributed to the fake news propagated by the Muslim clerics who stated that the vaccine contained pork gelatin.

SAMOA (PACIFIC ISLAND)

The New York Times reported that in 2019 there was a measles epidemic affecting more than 5,600 cases, of which 81 people died; the population of Samoa is only 200,000. "For weeks, families have been holding burials all over the island nation. Funeral homes, used to handling the elderly, are preparing tiny coffins for the bodies of young children and babies, with many offering their services at no charge." The reason for the epidemic is due to the decline in the vaccination rate to about 30 percent in 2018. And the reason for this bottoming out is because of 2 deaths from a vaccine wrongly mixed with a muscle relaxant instead of sterile water by a nurse. The resulting scare fueled the anti-vaxxers, and many children did not get vaccinated.

Samoa measles 16 yr old sleeps in living

IS THE IMMUNIZATION GAP RESPONSIBLE FOR THE RISE IN MEASLES CASES?

Epidemiological evidence shows that herd immunity protects the general population when more than 95% are vaccinated. When the level drops to less than 80% there is a dramatic rise in the number of cases of measles.

The mortality rate of measles ranges from 0.2 per 100,000 population to 13.3 per 100,000. Poor living conditions, nutrition and health care contributes to the higher mortality.

FEAR OF VACCINATION

The fear of vaccination goes back a long way. The 1802 caricature painting by James Gillray depicts the early controversy surrounding Edward Jenner's vaccination theory.

There is no specific antiviral antibiotics for measles. Prevention is effective and side effects such as pain at the injection site and fever, are transient and mild. It is now firmly established that the MMR vaccine does not cause autism spectrum disorder.

If you have HIV AIDS or are treated with strong immunosuppressants, there may be a case for withholding vaccination. But for the general population, vaccination is safe and effective.

“MEASLY”

The word “measly” has a double meaning. On the one hand it refers to the feeling miserable, wretched. On the other hand it also means insufficient, inadequate, paltry, scanty, niggardly. If one applies the term to measles vaccination, both meanings are applicable. The inadequate vaccination rates results in epidemics of measles leading to misery and illness!

CONCLUSIONS

Measles is one of the most contagious common viral infections. It is spread by coughing and sneezing, and the virus can remain viable in the air for about 2 hours, even after the original patient has left the room. It is characterised by fever, cough, runny nose and red eyes, followed by a skin rash and small whitish spots in the inner cheeks. Common complications include diarrhoea, vomiting, laryngitis, and pneumonia. Uncommon complications include hepatitis, meningitis, encephalitis. A rare but fatal complication is subacute sclerosing panencephalitis where the brain is severely affected.

The incidence had been falling until recently. There is a resurgence of measles in the past few years due to the increasing number of unvaccinated individuals.

The balance between vaccination and not getting vaccinated for measles is heavily tipped in favour of vaccination. The evidence is overwhelming. With rare exceptions, vaccination saves lives. It is therefore highly recommended.

Kenneth Lyen

8 May 2019, Updated 23 July 2020