Dr Natasa Jovanovic, Dr Hanna Tillly, Dr James Hatcher
Measles is a highly contagious viral disease. Before the measles vaccine was introduced in 1968 (followed by the combined measles, mumps and rubella ‘MMR’ vaccine in 1988), measles caused major epidemics and an estimated 2.6 million deaths each year worldwide. Unfortunately, in recent years widespread misinformation and anti-vaccination campaigns have seriously impacted the uptake of childhood vaccinations – and the last two decades have seen large-scale measles outbreaks across many countries.
Under the WHO Global Vaccine Action Plan, measles was one of the diseases targeted for elimination 2020. The number of reported cases and deaths from measles surged worldwide in 2019 despite a steady progress between 2010 and 2016. There are multiple explanations offered for the rise in numbers, however there is a discouraging theme. Immunisation rates for vaccine-preventable disease are lower than they should be.
“When rates of routine vaccination — children receiving all their shots on schedule, as a preventive measure rather than a reaction to an outbreak — start to fall, the first sign is usually a measles outbreak. In global-health security terms, these outbreaks are the proverbial canaries in the coal mine.”
Seth Berkley, CEO of global-health organisation Gavi, The Atlantic, 2015
It’s a busy winter morning in your waiting room; an anxious dad has brought nine-month-old Annie in with a rash. You recognise her as she had come in the evening before with a fever and cough. You’d examined Annie last night and noted that she had a red throat, conjunctivitis and cervical lymphadenopathy. Reassured that it was probably a viral URTI, you prescribed some antipyretics, advised dad to make sure Annie drank plenty of fluids and gave the usual safety net advice.
Why could they be back?!
Annie’s dad tells you that a couple hours after discharge, he noticed a rash behind Annie’s ears, around the neck and on her forehead. Annie has a few food allergies, so her dad assumed it was an allergic reaction and gave her some Piriton before bedtime. In the morning, she had a fever again and the rash had spread across Annie’s face, neck and down her arms.
Your differential diagnoses include viral exanthem or roseola, but you want to keep a closer eye on her, so you arrange for them to come back for a review tomorrow.
The next day, Annie still has a mild fever (fourth day) and her parents report that she is better in herself, but her rash has spread to the back, tummy and thighs. The rash has merged together into large pink areas on the face, but on the arms and legs it looks patchier.
Annie’s dad asks you if it could be measles.
- Measles is a single-stranded RNA virus.
- Transmission is via air-borne respiratory droplets, close personal contact or direct contact with nasal or throat secretions; viable virus can be suspended in the air up to two hours after an infected person leaves the room.
- The peak season for measles is late winter through early spring.
- Measles is highly transmissible. The Ro of measles (basic reproduction number) is one of the highest for all viral infections (between 12-18) and therefore needs a high immunisation rate to achieve herd immunity.
- Passive immunity from birth gradually disappears after the first 6 months of life.
- High risk groups include infants and young children, un-immunised and immunocompromised individuals.
- Children are contagious 4 days before the rash appears and up to 4 days afterward.
- Measles has a 90% attack rate – No, this isn’t power-up in a video game, it means that once exposed, roughly 9 out of 10 susceptible individuals will develop measles.
- Measles is a notifiable disease and must be reported within 24 hours of suspected diagnosis.
Clinical findings in classical measles
- Incubation stage: Children can be asymptomatic or have non-specific viral URTI type symptoms. The average incubation period is 10-12 days (range 7-21 days).
- Prodromal stage: This stage lasts 3-5 days. Malaise, high fevers and The Three C’s: “hacking cough”, coryza and non-purulent conjunctivitis with photophobia. Koplik spots (small, irregular, bluish-white spots on an erythematous background) can be found in the mouth, usually near the lower molars, 1 to 4 days before the rash appears and only last for 12 to 72 hours. Koplik Spots are pathognomonic of measles infection – they are easy to miss, you have to look for them!
- Rash stage: (remember, children are infectious from 4 days BEFORE the rash appears!) An erythematous maculopapular rash usually appears day 3 or 4 into the prodrome (around 14 days after exposure). It first appears behind the ears, the nape of the neck and on the forehead (often initially at the hairline) progressing down the body and legs. After 2-3 days the rash starts to resolve (from the head, down) changing to a purple/brown non-blanching rash. In severe cases, the rash can look haemorrhagic.
- Recovery: In uncomplicated measles, symptoms can last up to 10 days. Fever usually resolves by the 4th day of rash. As the rash clears, it leaves behind a desquamating hypopigmentation, lasting about a week. The cough can last up to 3 weeks and the child can still be lethargic for 2-6 weeks after infection.
What are the possible complications?
The acute measles infection can be bad on its own, but some of the complications are even more worrying. Measles can cause a profound transient immunosuppression, paving the way for opportunistic infections. Complications affect 10-20% of people in developed countries. Death occurs in 1-3 per 1000 cases and is highest in younger children and those who are immunosuppressed.
Respiratory complications: The most common complications are otitis media, pneumonitis, tracheobronchitis and most commonly pneumonia (the latter accounting for 60% of measles associated deaths. Bacterial secondary infection is often caused by Streptococcus pneumoniae, Haemophilus influenzae or Staphylococcus aureus. Young children can also develop concomitant viral infections, such as croup or bronchiolitis.
Neurological complications: Acute encephalitis occurs in 0.1% of measles cases. Symptoms start 2-6 days after the rash appears, with fever, headache, lethargy and changes in mental status. In most children the encephalitis is mild and self-limiting, but 1 in 10 children can develop progressive fatal disease within 24 hours. Some children suffer long-term neurological problems like seizures, hearing loss and developmental delay.
SSPE (subacute sclerosing panencephalitis) is a neurodegenerative disease that can present several years after a measles infection. It is very rare, only occurring in 1 in 25,000 cases. There is an insidious decline in motor and cognitive function with subtle mood disturbances, changes in behaviour and seizures. SSPE is invariably fatal within 6 to 9 months after the onset of symptoms. Patients with SSPE are not infectious.
Other complications include diarrhoea, transient hepatitis, thrombocytopenia, myocarditis.
What else could it be?
- Rubella, adenovirus, enterovirus, EBV, human herpesvirus-6 (HHV-6) and parvovirus can all present with similar symptoms
- Mycoplasma pneumoniae and Group A Streptococci can produce similar rashes
- Kawasaki disease – it is worth noting that there is a more prominent cough with measles, whereas Kawasaki typically presents with a very high CRP, neutrophilia and thrombophilia.
- Drug reactions
How is Measles diagnosed?
A good history and examination are often enough to make a clinical diagnosis. Measles is a notifiable disease and a suspected case should be reported as early as possible. Oral fluid samples are currently the optimal sample for measles surveillance and are used to test for anti-measles IgM, igG and/or measles RNA. Alternatively, serum AND mouth swabs can be sent instead.
● Measles IgM antibody – can be detected in oral fluid samples from the onset of viraemia and the rash. Levels peak at 2-3 weeks and can be present for up to 2 months. A positive IgM result indicates an acute infection. If there is a strong clinical suspicion and a negative IgM, repeat the test two days later.
● Measles IgG antibody – a fourfold or greater rise in IgG antibodies after 2 to 4 weeks can also be diagnostic.
Other findings can include high white cell count and very low lymphocyte count. Normal ESR and CRP.
What’s the treatment for measles?
Mostly, the management is supportive – bed rest, antipyretics and encouraging fluids. If you’re worried about sepsis and / or secondary bacterial infection, treat with antibiotics. Antivirals are sometimes used, in severe cases of measles or in children who are immunocompromised. The World Health Organisation recommends Vitamin A for all children, especially in developing countries, as Vitamin A deficiency is associated with increased mortality from various infectious diseases including measles.
Infection control measures – Any inpatient suspected of having measles should be in a negative-pressure respiratory isolation room and be nursed as per local air-bourne and contact isolation guidelines. Isolation is required for 4 days after the first appearance of the rash. Immunocompromised patients require isolation throughout the course of the illness.
Immunisation is the only effective way to prevent measles infections. A single dose of live attenuated vaccine protects 90-95% children who receive their first dose when they are over 12 months old. To achieve herd immunity, it is necessary to give two doses. When given to children < 12 months old, maternal antibodies can risk primary vaccine failure (up to 5% in infants), though vaccine effectiveness increases to 95% with a second dose. In the UK, the first dose is recommended between 12 and 13 months followed by a second preschool booster dose at 3 years plus.
The MMR vaccine can cause a fever and rash between 6-12 days afterwards and rarely, a transient thrombocytopenia. Several large and well-designed scientific studies have convincingly shown that there is no evidence that the measles vaccine causes autism.
The MMR is a live-attenuated vaccine, so it should not be given to pregnant women or people who are immunocompromised. It shouldn’t be given in babies under 6 months of age due to the interaction of the vaccine with maternal measles antibodies.
During a measles outbreak, vaccines can be given to babies over 6 months old if they have been in close contact with a measles case (or if they are travelling to a country with a high incidence of measles) following discussion with the local Health Protection Agency. Babies between 6 months and 1 years old who receive the vaccine in these circumstances, should still receive the routine doses as per the UK immunisation schedule.
Post-Exposure Prophylaxis (PEP)
Hospital and clinic waiting rooms pose a major risk for measles exposure. As well as close household contacts, staff and other patient contacts should be contact-traced and have a risk assessment to decide whether PEP is needed.
- Measles vaccine can provide protection against measles if it’s given within 72 hours of exposure. If exposure was more than 72 hours ago, IVIG can be considered between 4 to 6 days, though the evidence for this is limited
- If MMR is contraindicated intravenous normal human immunoglobulin (IVIG) should be given (ideally within 72 hours).
- To assure immunogenicity, measles vaccine must be deferred until 3-6months after immunoglobulin administration.
- Healthcare professionals should be screened for measles immunity and susceptible individuals vaccinated to prevent transmission of measles happening in the hospital environment.
- As neither immunoglobulin or vaccine are fully effective in preventing measles, exposed individuals who receive post-exposure treatments will still be an infection control risk, for example in health care settings and therefore should continue to follow infection control advice.
Variations to classical measles
Modified / Inapparent measles is a subclinical form of infection. It can happen in children with partial antibody protection, for example those who have received an improperly administered measles containing vaccine, have been passively immunised with immunoglobulin after exposure to the disease, or in babies under 9 months old with transplacental antibodies. They have milder symptoms and the diagnosis is often missed.
Atypical measles – A historical footnote! This disease was seen in some people who were given the killed measles vaccine in the 1960’s. A vesicular petechial rash, unlike typical measles, appeared distally and progressed upwards, with little involvement of the face and upper body. Most patients with atypical measles have pneumonia, often with pleural effusions. Since we now only use the live attenuated vaccine, ‘atypical measles’ is now rare.
Dr Natasa Jovanovic, (General) Paediatrician, Healthcare center Cacak, Serbia; Dr Hanna Tilly, Paediatric registrar, North Middlesex Hospital, London; senior review by Dr James Hatcher, Paediatric Infectious Diseases Consultant, Great Ormond Street Hospital, London