Clinical Topic A-Z Clinical Speciality

Measles

Measles
D008457Measles
D008459Measles virus
Child healthInfections and infestations
2013-08-01Last revised in August 2013

Measles - Summary

Measles is a highly contagious airborne infection caused by a morbillivirus of the paramyxovirus family. It is spread by coughing or sneezing, close personal contact, or direct contact with nasal or throat secretions. Nearly all susceptible people (primarily children) who come into contact with the virus become infected, but once infected lifelong immunity develops.

Although endemic in the UK in the past, measles has become relatively rare since the introduction of measles immunization. However, in recent years, the infection has become more prevalent due to a failure of uptake of vaccination.

The main complications of measles are of the respiratory tract or central nervous system and include:

Otitis media (7–9% of children).

Pneumonia (1–6% of children.

Febrile convulsions (about 1 in 200 children).

Encephalitis (about 1 in 1000 children).

Subacute panencephalitis (a rare but serious complication affecting about 1 in 25,000 people with measles).

Measles tends to be more severe in adults, who have more complications than children; about 3% of adults require hospitalization. Measles in pregnancy may result in miscarriage, premature birth, and low birthweight.

Measles is usually a self-limiting condition; symptoms usually resolve over the course of about a week. Prodromal symptoms include cough, coryza, conjunctivitis with fever, and the appearance of the rash (with or without Koplik's spots) are highly suggestive of measles.

Other infections that are commonly misdiagnosed as measles include:

Parvovirus B19, the virus that causes fifth disease (erythema infectiosum, also known as slapped cheeks syndrome) that usually affects young children.

Streptococcal infection can cause skin reactions with a similar appearance to measles, but sore throat is usually the most prominent symptom.

Herpes virus type 6 (roseola infantum).

If a diagnosis of measles is considered likely, it is essential to notify the local Health Protection Unit (HPU), and it may be necessary to confirm the infection through laboratory investigation.

Paracetamol or ibuprofen provide symptomatic relief.

People with measles should stay away from school or work for 4 days after the initial development of the rash, and avoid contact with susceptible people (people who are not fully immunized through vaccination or natural exposure, infants, pregnant women, or immunosuppressed people).

Further advice should be obtained from the local HPU regarding the management of people who are immunosuppressed, pregnant women, and infants.

Admission may be necessary if the person develops a serious complication of measles, for example:

Pneumonia.

Neurological problems, such as febrile convulsions in children, or encephalopathy.

Have I got the right topic?

0months3060monthsBoth

This CKS topic covers the management of acute measles and postexposure prophylaxis for measles.

This CKS topic does not cover the prevention of measles with the combined measles, mumps, and rubella (MMR) vaccine. This is covered in a separate CKS topic on Immunizations - childhood.

There is a separate CKS topic on Rubella.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.

How up-to-date is this topic?

How up-to-date is this topic?

Changes

Last revised in August 2013

August 2013 — reviewed. A literature search was conducted in July 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. No major changes to recommendations have been made.

Previous changes

February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic [NICE, 2013a].

October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic [NPC, 2012].

July 2011 — minor update. More recent prevalence data from the Health Protection Agency added [HPA, 2011]. Issued in September 2011.

July 2011 — minor update. More exact paracetamol dosing for children has been introduced by the Medicines and Healthcare products Regulatory Agency [MHRA, 2011]. Prescriptions have been updated to reflect the revised dosing. Issued in July 2011.

May 2011 — minor update. The 2010/2011 QIPP options for local implementation have been added to this topic [NPC, 2011]. Issued in June 2011.

June 2010 — minor update to incorporate the latest recommendations from the Health Protection Agency [HPA, 2010b]. Issued in June 2010.

July to November 2009 — this is a new CKS topic. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

Update

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 July 2013.

HTAs (Health Technology Assessments)

No new HTAs since 1 July 2013.

Economic appraisals

No new economic appraisals relevant to England since 1 July 2013.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analyses since 1 July 2013

Primary evidence

No new randomized controlled trials published in the major journals since 1 July 2013.

New policies

No new national policies or guidelines since 1 July 2013.

New safety alerts

No new safety alerts since 1 July 2013.

Changes in product availability

No changes in product availability since 1 July 2013.

Goals and outcome measures

Goals

To determine the likelihood of measles based on clinical features, immunization history, and contact with measles infection

To notify the Health Protection Unit (HPU) of all cases of suspected measles

To confirm measles through laboratory testing

To give people with measles (or their carers) self-care advice

To encourage uptake of the combined measles, mumps, and rubella (MMR) vaccine where appropriate

To appropriately refer susceptible immunosuppressed people and pregnant women for specialist management

QIPP — Options for local implementation

QIPP — Options for local implementation

Non-steroidal anti-inflammatory drugs (NSAIDs)

Review the appropriateness of NSAID prescribing widely and on a routine basis, especially in people who are at higher risk of both gastrointestinal (GI) and cardiovascular (CV) morbidity and mortality (e.g. older patients).

If initiating an NSAID is obligatory, use ibuprofen (1200 mg per day or less) or naproxen (1000 mg per day or less).

Review patients currently prescribed NSAIDs. If continued use is necessary, consider changing to ibuprofen (1200 mg per day or less) or naproxen (1000 mg per day or less).

Review and, where appropriate, revise prescribing of etoricoxib to ensure it is in line with MHRA advice and the NICE clinical guideline on osteoarthritis [CSM, 2005; NICE, 2008].

Co-prescribe a proton pump inhibitor (PPI) with NSAIDs for people with osteoarthritis, rheumatoid arthritis, or low back pain (for people over 45 years) in accordance with NICE guidance [NICE, 2008; NICE, 2009a; NICE, 2009b].

Take account of drug interactions when co-prescribing NSAIDs with other medicines (see Summaries of Product Characteristics). For example, co-prescribing NSAIDs with ACE inhibitors or angiotensin receptor blockers (ARBs) may pose particular risks to renal function; this combination should be especially carefully considered and regularly monitored if continued.

[NICE, 2013a]

Background information

Definition

What is it?

Measles is a highly contagious infection caused by a morbillivirus of the paramyxovirus family. It infects nearly all susceptible people (primarily children) who come into contact with it, but once infected the person develops lifelong immunity.

Measles is an airborne infection that is spread by coughing or sneezing, close personal contact, or direct contact with nasal or throat secretions.

Measles has an incubation period of about 10 days, with a further 2–4 days of prodromal symptoms (including coryza, fever, cough, and conjunctivitis) before the characteristic skin rash develops. The person usually feels most ill on the first or second day of the rash.

The person is infectious several days before and after the onset of the rash, but most infectious during the late prodromal phase when cough and coryza are at their peak.

[Gershon, 2010; PHE, 2013a]

Prevalence

How common is it?

Measles has been endemic in the UK in the past, but it has become relatively rare since the introduction of measles immunization. However, in recent years, the infection has become more prevalent due to a failure of uptake of vaccination.

Before the introduction of the measles vaccine in 1968, annual notification of measles infection in England and Wales varied between 160,000 and 800,000, with peaks every 2 years. By 1980, uptake of the measles vaccine was insufficient to cause 'herd immunity', and notifications remained relatively high at 50,000–100,000 per year [PHE, 2013a].

When the combined measles, mumps, and rubella (MMR) vaccine was introduced in 1988 and coverage exceeded 90%, notifications fell substantially [HPA, 2009b]. However, uptake of the MMR vaccine fell in the 2000s due to unfounded fears about a possible association with bowel disease and autism, and in 2006 there was a sharp increase in measles, with 3705 notifications and 739 confirmed cases in England and Wales [HPA, 2009b].

In 2010, there were 374 confirmed measles cases in England and Wales. Between January and May 2011, 496 cases were confirmed, with almost half of cases occurring in unvaccinated people aged between 5 and 19 years [HPA, 2011].

Epidemiological data shows that in the years 2006–2007 the UK had the third-highest incidence of measles in Europe [Muscat et al, 2009].

The highest number of laboratory confirmed cases of measles in England and Wales, since enhanced surveillance started in 1994, was in 2012 with 1920 laboratory confirmed cases [PHE, 2013b]

There was 258,000 measles deaths worldwide in 2011, however, measles vaccination have resulted in a 71% drop in measles deaths between 2000 and 2011 [WHO, 2013].

Complications

What are the complications?

The main complications of measles are of the respiratory tract or central nervous system.

Respiratory complications are usually due to bacterial superinfection, and include:

Otitis media (7–9% of children).

Pneumonia (1–6% of children).

Central nervous system complications include:

Febrile convulsions (about 1 in 200 children).

Encephalitis (about 1 in 1000 children).

Subacute panencephalitis is a rare but serious complication affecting about 1 in 25,000 people with measles, but is up to 16 times more common in children who contract measles at a very young age (less than 1 year of age). Subacute panencephalitis occurs a median of 7 years after exposure to the virus, although it may occur as late as three decades afterwards, and is invariably fatal.

Diarrhoea affects about 8% of children, but is not usually severe enough to cause problems.

Measles tends to be more severe in adults, who have more complications than children; about 3% of adults require hospitalization. The most common complications, reported in one large case series of 3220 adults, were bacterial superinfection of the respiratory tract (30%), sinusitis (25%), otitis media (29%), and laboratory evidence of hepatitis (31%) [Gershon, 2010].

Measles in pregnancy may result in miscarriage, premature birth, and low birthweight [Ornoy and Tenenbaum, 2006].

[Gershon, 2010; CDC, 2012; PHE, 2013a]

Prognosis

What is the prognosis?

Most people with measles make a full recovery after around 7–10 days of symptoms. Cough may persist longer, and the illness may last for up to 21 days in people who are immunocompromised.

However, people can die as a result of measles:

About 1 child in 5000 who contracts measles will die of the disease.

Respiratory complications are responsible for 60% of deaths in infants with measles.

Central nervous system complications are the main cause of death in older children.

[Gershon, 2010; PHE, 2013a]

Diagnosis

Diagnosis of measles

Clinical diagnosis

How should I clinically diagnose measles?

Consider a diagnosis of measles in people presenting with a rash, fever, and other symptoms suggestive of measles.

Following assessment, if a diagnosis of measles is considered likely, it is essential to notify the local Health Protection Unit (HPU), and it may be necessary to confirm the infection through laboratory investigation.

Check the person's immunization history and whether they have previously had measles.

Measles is very unlikely in people who have been fully immunized, or who have previously had measles (although the history may be unreliable).

The group most at risk is likely to be younger people (less than 30 years of age) who have not received the combined measles, mumps, and rubella (MMR) vaccine (or single vaccine equivalent).

Determine whether the person has had significant contact with a possible case of measles.

Significant contact means being in the same room for 15 minutes or more, or face-to-face contact.

Consider contacting the HPU to find out if there are any localized outbreaks of measles.

Enquire if the person has recently travelled to a country where measles is endemic (particularly Asia or Africa).

Ask about the presence of prodromal symptoms.

The prodromal phase occurs 10–14 days after contracting the infection, and lasts for 1–4 days before the rash becomes apparent.

Prodromal symptoms are similar to those of other upper respiratory tract infections (increasing fever, malaise, loss of appetite, cough, rhinorrhoea, and conjunctivitis).

Koplik's spots may appear towards the end of the prodromal phase and are highly suggestive of measles. These consist of blue-grey specks on a red base on the buccal mucosa, and have been likened to grains of sand or salt.

Examine the rash for characteristic features.

The rash usually develops 2–4 days after prodromal symptoms. It appears on the face first (when other symptoms tend to be at their most severe, including fever [39–40°C]), before descending down the body to the trunk and extremities, and forming on the palms and soles last, over the course of about 4 days.

The rash is erythematous and maculopapular, and may become confluent as it progresses, particularly on the face and neck. The rash peels off or fades after it has been present on an area for about 5 days, with the total duration of rash being about 1 week, after which time the person should feel better.

Consider a different cause for the rash if the person is likely to have immunity to measles, clinical features are atypical, there is no history of contact with measles or travel to measles-endemic countries, and there are no local outbreaks.

Basis for recommendation

Basis for recommendation

Immunization status and measles

Measles is unlikely in people who are fully immunized or who have previously contracted the infection.

Vaccination with one dose of the combined measles, mumps, and rubella (MMR) vaccine confers about 90% immunity. However, vaccination with two doses of the MMR vaccine, as indicated by the UK Childhood Immunization Programme, is thought to confer close to 100% lifelong immunity [PHE, 2013a].

Contracting measles once confers lifelong immunity [Gershon, 2010].

In the UK, seroprevalence studies indicate that less than 1% of people born before 1970, and less than 10% of people born between 1970 and 1980, are antibody-negative to measles [HPA, 2009a].

This suggests that the people most likely to present with measles are younger people who have not received the MMR vaccine and who have not been previously exposed to the virus (which is likely, as measles has become much less prevalent since the introduction of the MMR vaccine).

Clinical features of measles

The clinical features of measles are described in the textbook Principles and practice of infectious diseases [Gershon, 2010] and in guidelines from the World Health Organization [WHO, 2013].

Although measles causes a characteristic rash, clinical examination alone is not sufficient for diagnosis. Observational studies have shown the need for laboratory confirmation in highly immunized populations such as the UK [Ramsay et al, 2002].

Other causes of rash and fever are more common in younger children, so confirmation of the diagnosis is considered essential [Ramsay et al, 2002].

Differential diagnosis

What else may cause a measles-like rash?

Prodromal symptoms of cough, coryza, conjunctivitis with fever, and the appearance of the rash (with or without Koplik's spots) is highly suggestive of measles. Other causes of rash are much more likely in people who have previously had measles or who have been fully immunized.

Other infections that are commonly misdiagnosed as measles include:

Parvovirus B19, the virus that causes fifth disease (erythema infectiosum, also known as slapped cheeks syndrome) that usually affects young children. This is a mild self-limiting illness that, in addition to a bright red rash on the cheeks, may cause a red, lacy rash on the rest of the body which can be mistaken for measles. However, fever is not usually a defining feature.

Streptococcal infection can cause skin reactions with a similar appearance to measles, but sore throat is usually the most prominent symptom.

Herpes virus type 6 (roseola infantum), enterovirus, and adenovirus are rarer viral infections that should be considered.

Rubella presents with a rash of pink, discrete macules that coalesce as they develop. The rash usually starts behind the ears and on the face, and then spreads to the trunk and the extremities (similar to measles). However, the infection is generally mild, and the person does not present with high fever. Rubella is now increasingly rare because of the combined measles, mumps, and rubella (MMR) vaccine.

Early meningococcal disease may present with a measles-like rash, but becomes purpuric in later stages, and does not fade when a glass is pressed against it.

Other causes of rash:

That are accompanied with systemic lymphadenopathy — include Kawasaki disease, infectious mononucleosis (reaction with ampicillin), brucellosis, cytomegalovirus, HIV, syphilis, toxoplasmosis, and reaction to antiepileptic drugs.

That are not accompanied by lymphadenopathy — include adverse drug reactions, enterovirus, echovirus, coxsackievirus, infectious hepatitis, and rat bite fever (Spirillum minus).

Basis for recommendation

Basis for recommendation

Information on the differential diagnosis is based on expert opinion from a review on measles [Burnett and Krusinski, 2007].

An observational study examined the cause of illness in 195 children from England presenting with a measles-like rash [Ramsay et al, 2002]. The investigators found:

No cause could be identified in most of the children (52%).

Parvovirus B19 was the most common single cause of rash that could be identified (17%).

Streptococcus was the only bacterial cause identified (group A accounting for 15%; and group C for 3%).

Less common pathogens included human herpes virus type 6 (6%), enterovirus (5%), and adenovirus (4%).

None of the children had measles or rubella.

Management

Management

Scenario: Management : covers the management of measles, including notification and confirmation and the management of contacts.

Scenario: Management

Scenario: Management of measles

0months3060monthsBoth

Management of healthy people

How should I manage suspected measles in an otherwise healthy person?

If there is any suspicion of measles infection, immediately notify the local Health Protection Unit (HPU). Measles is a notifiable disease.

Ask the HPU about the need for a testing kit and the testing schedule. Usually, an immediate oral fluid sample will be required for serological and/or viral RNA testing.

Advise the person (or their carer):

That measles is usually a self-limiting condition, but is likely to cause unpleasant symptoms including rash, fever, malaise, cough, and conjunctivitis. These will usually resolve over the course of about a week, with the person making a full recovery after about 10 days.

To rest, drink adequate fluids, and take paracetamol or ibuprofen for symptomatic relief (aspirin should be avoided in children younger than 16 years of age).

To stay away from school or work for 4 days after the initial development of the rash, and avoid contact with susceptible people (that is, people who are not fully immunized through vaccination or natural exposure, infants, pregnant women, or immunosuppressed people).

Provide written advice about measles — a fact sheet (pdf) for school children is available from the Health Protection Agency.

Advise the person or carer to seek urgent medical advice if they develop:

Shortness of breath or pleuritic chest pain, or if they start to cough up blood (haemoptysis).

Febrile convulsions or altered consciousness (for example lethargy or confusion).

Consider contacting the person about a week after the rash to ensure that symptoms have resolved or are resolving adequately.

When the person has sufficiently recovered from the acute symptoms, encourage them to undergo any outstanding vaccinations if applicable (see the CKS topic on Immunizations - childhood).

Antibiotics are not recommended for the prevention of secondary bacterial infections.

Acute interventions, such as antiviral drugs, human normal immunoglobulin, or vitamin A are not recommended for the treatment of measles in otherwise healthy people.

For the management of pregnant women or immunocompromised people, see Pregnant women and Immunosuppressed people.

Virus Reference Department

Virus Reference Department

The Virus Reference Department of the Health Protection Agency (HPA) is responsible for diagnostic tests for measles in the UK.

For more information, see www.hpa.org.uk, or telephone 020 8327 6017.

Basis for recommendation

Basis for recommendation

These recommendations are based on advice from the Department of Health, the Health Protection Agency (HPA), and the World Health Organization (WHO) [HPA, 2010a; HPA, 2010b; PHE, 2013a; WHO, 2013].

Notification

Laboratory confirmation of measles is necessary for surveillance purposes rather than management of the individual (which it does not usually directly impact). Most people with clinically-diagnosed measles are not subsequently confirmed to have measles.

Between 1994 and 1995, a UK surveillance study found that only 3.7% (126 of 3442) of people with clinically-diagnosed measles cases were confirmed to have measles by laboratory investigation [Ramsay et al, 1997].

An observational study in England found that measles was not the cause of measles-like rash in any of the 195 children studied [Ramsay et al, 2002].

However, the likelihood of measles being confirmed increases during outbreaks and epidemics [PHE, 2013a]. This likelihood has now increased because of the low uptake of the combined measles, mumps, and rubella (MMR) vaccine [Chief Medical Officer et al, 2008].

Prognosis

The natural history of measles is described in the textbook Principles and practice of infectious diseases [Gershon, 2010]. For most people, measles is a self-limiting but unpleasant illness.

Self-care advice

Adequate fluid intake should be maintained when symptoms of upper respiratory tract infection are present, to replace fluid lost by fever, sweating, and nasal discharge. However, there have been no controlled trials confirming the benefit of this [Guppy et al, 2011].

Paracetamol and ibuprofen are recommended for the symptomatic relief of measles on the basis that they reduce fever and pain (including headache and myalgia).

The antipyretic and analgesic efficacy of paracetamol and ibuprofen have been confirmed by randomized controlled trials in several conditions, including other upper respiratory tract infections (influenza and the common cold) [Eccles, 2006].

The National Institute for Health and Care Excellence (NICE) recommends that antipyretic drugs 'should be considered in children with fever who appear distressed or unwell'. However, the routine use of antipyretic drugs to reduce temperature in children with no other symptoms or discomfort is not recommended [NICE, 2013b].

Aspirin is not usually recommended as it has a less favourable adverse effect profile. It is contraindicated in children younger than 16 years of age, because of the risk of Reye's syndrome [BNF for Children, 2013].

Guidance from the HPA states that children with suspected measles should be kept away from school or nursery for 4 days after the development of rash [HPA, 2010a], and this can reasonably be extrapolated to adults.

Follow up and further management

Follow up is not necessary, but may be considered to verify the person has recovered adequately.

Previously, follow up was required to allow for laboratory confirmation of measles using serology, which cannot be reliably performed for at least 1 week after symptoms of rash develop [Ramsay et al, 1997].

However, measles can now be detected immediately following outbreak of the rash (or during the prodrome) using polymerase chain reaction (PCR) techniques to detect viral RNA [Thomas et al, 2007].

People should be advised to seek urgent advice if they develop any symptoms of a complication of measles (see Admission and referral).

Pneumonia is usually caused by bacterial superinfection and affects about 1 in 20 children with measles [CDC, 2012]. It is the main cause of death from measles in infants [Gershon, 2010].

Encephalopathy affects about 1 child in every 1000 and is the main cause of death in older children [CDC, 2012].

Vaccination with the combined measles, mumps, and rubella (MMR) vaccine is recommended when the person has recovered, to provide future protection against mumps and rubella [PHE, 2013a].

Treatments not recommended

Antibiotics are not recommended for the prevention of secondary bacterial infections by experts because of the lack of good quality evidence to support their use in the UK population [PHE, 2013a; HPA, 2010b].

Although there is some evidence from randomized and quasi-randomized controlled trials suggests that antibiotics reduce the incidence of pneumonia in children following infection with measles these trials were either of poor methodological quality or were performed in developing countries, and cannot be generalized to the current UK population.

Vitamin A is not recommended. There is evidence from controlled trials that treatment with high-dose vitamin A is beneficial for people with measles [Yang et al, 2005], and the World Health Organization have estimated it can reduce mortality by up to 50% [WHO, 2013]. However, it is of no proven benefit in western countries where populations are well nourished.

Human normal immunoglobulin (HNIG) and measles vaccine are not recommended for the treatment of measles.

HNIG is not effective for the treatment of measles and is only recommended for postexposure prophylaxis of particularly vulnerable groups (for example some pregnant women and immunocompromised people) [HPA, 2009a].

By the time symptoms of measles present, it is too late to provide protection by immunizing the person. However, it is recommended that the person receives the MMR vaccine to protect against future mumps and rubella [PHE, 2013a].

Antiviral drugs are not recommended for the treatment of measles.

CKS found one small randomized controlled trial in 40 participants that studied the effectiveness of ribavirin for the treatment of measles. Although the authors stated that ribavirin shortened the duration of symptoms and reduced complications compared with placebo, interpretation of the results is difficult as the outcomes were not statistically analysed [Uylangco et al, 1981].

Ribavirin and other antiviral drugs are not licensed for the treatment of measles [BNF 65, 2013].

Management of contacts

How should I manage a person who has been in contact with possible measles?

Determine the person's immunization status and whether they have had significant contact with a possible case of measles.

Assume lack of immunity if the person has not been fully immunized (that is, they have not received two doses of the combined measles, mumps, and rubella [MMR] vaccine, or an equivalent vaccine) and has not previously had laboratory-confirmed measles.

Significant contact means being in the same room for 15 minutes or more, or face-to-face contact.

If the person is susceptible to measles infection, and is not immunosuppressed or pregnant, and has no other contraindications to the MMR vaccine:

Offer immediate vaccination. See the CKS topic on Immunizations - childhood for information on the MMR vaccine, including contraindications.

Ideally, the MMR vaccine should be given within 3 days of contact with a possible case of measles and should be repeated after a period of at least 1 month. For children younger than 13 months of age, two further doses will be required, in accordance with the Childhood Immunization Programme.

Contact the local Health Protection Unit for advice if the person is:

Immunosuppressed (even if they were previously fully immunized or have a history of laboratory-confirmed measles).

Pregnant (even if they are thought to be immune to measles, as investigation for contact with possible rubella or parvovirus B19 may be required).

Younger than 1 year of age.

Susceptible to measles infection but the MMR vaccine is contraindicated.

Advise the person to seek medical advice if they develop symptoms of measles.

Ask them to telephone, if possible, before arriving at the surgery or A&E department, and/or advise the receptionist immediately on arrival that they may have measles.

Basis for recommendation

Basis for recommendation

This recommendation is based on guidance from Immunisation against infectious disease (the 'Green Book'), published by the Department of Health [PHE, 2013a], and Post exposure prophylaxis for measles: revised guidance published by the Health Protection Agency (HPA) [HPA, 2009a].

Measles vaccination

Vaccine-induced antibodies develop more rapidly than antibodies induced by natural infection, and it is believed that early vaccination with the combined measles, mumps, and rubella (MMR) vaccine following exposure to measles protects susceptible people.

Vaccination needs to be prompt, ideally within 3 days of exposure.

Vaccination after this period is still recommended, to provide future protection against mumps and rubella. There are no harms associated with immunizing people who have already contracted the illness or who have previously received the MMR vaccine.

Human normal immunoglobulin

Human normal immunoglobulin (HNIG) is not recommended in otherwise healthy people as evidence of its benefit is limited and it requires intramuscular administration. However, HNIG is recommended by the HPA for people who are immunosuppressed who are known or are likely to be antibody negative for measles, or for pregnant women who do not already have immunity to measles [HPA, 2009a].

Infants who are 12 months of age or younger may require treatment with HNIG or the MMR vaccine, depending on the immunization status of the mother. For further information, see Post exposure prophylaxis for measles: revised guidance, published by the Health Protection Agency [HPA, 2009a], and available to download at www.hpa.org.uk (pdf).

Symptomatic measles

It is important that, where possible, the receptionist is aware that the person waiting for medical attention may have measles, so that they can be directed to a side room, to prevent transmission to other patients in the waiting room [HPA, 2010b].

Pregnant women

How should I manage a pregnant woman with suspected measles, or possible exposure to measles?

Contact the local Health Protection Unit (HPU) for advice if the woman is pregnant and:

Has a measles-like rash, or

Has been in significant contact with a person suspected of having measles. Significant contact means being in the same room for 15 minutes or more, or face-to-face contact.

Management recommendations from the HPU may include serology testing for measles immunization status (immunoglobulin G antibodies), investigations for rubella or parvovirus B19, and/or administration of human normal immunoglobulin. For further information, see the guidelines on Rash illness in pregnancy (pdf) published by the Health Protection Agency.

Basis for recommendation

Basis for recommendation

These recommendations are based on Guidelines on the management of, and exposure to, rash illness in pregnancy (including consideration of relevant antibody screening programmes in pregnancy), published by the Public Health Laboratory Service (PHLS, now the Health Protection Agency [HPA]) [Morgan-Capner et al, 2002], and Post exposure prophylaxis for measles: revised guidance, published by the HPA [HPA, 2009a].

Measles is a potentially serious infection when it is acquired during pregnancy. Although the measles virus is not known to be teratogenic (unlike rubella), it has been associated with maternal hospitalization and death, miscarriage, premature birth, and low birthweight [Ornoy and Tenenbaum, 2006].

Most women of childbearing age will have full immunity against measles (acquired naturally or through the combined measles, mumps, and rubella [MMR] vaccine, or single vaccine equivalent). Confirmation of immunity through immunoglobulin G (IgG) antibody testing may be required [PHE, 2013a].

Human normal immunoglobulin (HNIG) may not prevent measles, and evidence is lacking on its benefit in terms of reducing intrauterine death or preterm pregnancy. However, HNIG may attenuate measles and reduce complications [Manikkavasagan and Ramsay, 2009].

Other viruses which may be confused with measles, such as rubella and parvovirus B19, can have potentially serious consequences for the fetus, and require specialist investigation if they are suspected [Morgan-Capner et al, 2002].

Immunosuppressed people

How should I manage an immunosuppressed person with suspected measles, or possible exposure to measles?

Contact the local Health Protection Unit (HPU) regardless of immunization status if the person is immunosuppressed and:

Has a measles-like rash, or

Has been in significant contact with a person who is suspected of having measles. Significant contact means being in the same room for 15 minutes or more, or face-to-face contact.

Management in secondary care may include serology testing for measles immunization status or administration of human normal immunoglobulin.

Definition of immunosuppressed people

Definition of immunosuppressed people

People who are immunosuppressed include those:

Being treated for malignant disease with immunosuppressive chemotherapy or generalized radiotherapy, and those who have received this within the past 6 months.

Who have received an organ transplant and are currently receiving immunosuppressive treatment.

Who have received a bone marrow transplant and are still considered to be immunosuppressed (including those within 12 months of finishing all immunosuppressive treatment, or longer for those who have developed graft-versus-host disease).

Receiving high-dose systemic steroids (until at least 3 months after treatment has stopped). For children, this includes those who have taken prednisolone, 2 mg/kg per day for at least 1 week or 1 mg/kg per day for 1 month (or equivalent doses). For adults, an equivalent dose is harder to define, but immunosuppression should be considered in those who have taken around 40 mg of prednisolone daily for more than 1 week.

Receiving immunosuppressive drugs (for example azathioprine, ciclosporin, methotrexate, cyclophosphamide, leflunomide, cytokine inhibitors), alone or in combination with lower doses of steroids, for at least 6 months after treatment.

With primary immunodeficiency (for example severe combined immune deficiency syndromes, Wiskott–Aldrich syndrome).

Who are immunosuppressed because of HIV infection.

Basis for recommendation

Basis for recommendation

These recommendations are based on guidance from Immunisation against infectious disease (the 'Green Book'), published by the Department of Health [PHE, 2013a], and Post exposure prophylaxis for measles: revised guidance, published by the Health Protection Agency [HPA, 2009a].

People who are immunosuppressed are at increased risk of complications and may require human normal immunoglobulin (HNIG), although there is only limited evidence of its efficacy in the postexposure prophylaxis of measles [HPA, 2009a].

For the purposes of primary healthcare professionals, the definition of immunosuppressed is as detailed in Chapter 6 of the 'Green Book' (see webarchive.nationalarchives.gov.uk for more information) [PHE, 2013a].

Not all people who are immunosuppressed using this definition will require HNIG. The decision on whether to use HNIG will be made by specialists in immunology, in line with advice from the UK Primary Immunodeficiency Network (UK PIN) [HPA, 2009a].

Admission and referral

Which people with suspected measles should be admitted or referred?

Seek advice from the local Health Protection Unit (or equivalent) if the person is:

Immunosuppressed .

Pregnant .

An infant who is 1 year of age or younger.

Contact the local hospital regarding appropriate isolation before admission.

Consider admission if the person develops a serious complication of measles, for example:

Pneumonia (characterized by laboured breathing, shortness of breath, pleuritic chest pain, and haemoptysis).

Neurological problems, such as febrile convulsions in children, or encephalopathy (for example presenting with altered consciousness).

Children with fever who are otherwise at serious risk. See the CKS topic on Feverish children - risk assessment.

Basis for recommendation

Basis for recommendation

These recommendations are in line with guidance from the Department of Health and the Health Protection Agency [HPA, 2010a; PHE, 2013a].

Measles can have serious consequences in people who are immunocompromised and in women who are pregnant. These groups may require admission for specialist assessment or administration of human normal immunoglobulin (HNIG) [Manikkavasagan and Ramsay, 2009].

About 1 in 5000 children in the UK die of complications associated with measles, and there should be a low threshold for admission if these are present [PHE, 2013a].

The National Institute for Health and Care Excellence has published a clinical guideline regarding the referral of children with fever [NICE, 2013b].

Evidence

Evidence

Supporting evidence

Evidence about the following interventions for the treatment or postexposure prophylaxis of measles has been reviewed.

Antibiotics should not be used in primary care for preventing the complications caused by measles (for example otitis media and pneumonia).

Human normal immunoglobulin is sometimes used in secondary care for the postexposure prophylaxis of measles in susceptible people.

For information on the evidence available for the effectiveness of the combined measles, mumps, and rubella (MMR) vaccine, see the Supporting evidence section on Vaccines for measles in the CKS topic on Immunizations - childhood.

Antibiotics

Evidence on antibiotics for preventing complications

Limited evidence from randomized and quasi-randomized controlled trials suggests that antibiotics reduce the incidence of pneumonia in children following infection with measles. However, these trials were either of poor methodological quality or were performed in developing countries, and cannot be generalized to the current UK population.

A Cochrane systematic review (search date: December 2007) identified seven controlled trials, with 1385 participants, investigating the effectiveness of antibiotics for preventing pneumonia and other complications caused by measles in children [Kabra and Lodha, 2013].

Five of the included trials were of poor methodological quality, conducted in western populations between 1939 and 1954. One trial of poor quality was conducted in India in 1967, and another trial of good quality was conducted in New Guinea in 2006.

Most (six out of seven) trials showed some benefit of antibiotics. However, meta-analysis of all the trials showed no significant reduction in pneumonia, with a rate of 1.9% in the antibiotic group compared with 6.0% in the control (placebo or no treatment) group (odds ratio [OR] 0.28, 95% CI 0.06 to 1.25).

When the single trial with conflicting results (conducted in 1942 using oral sulfathiazole) was removed from the meta-analysis, there was a significant reduction in the rate of pneumonia in favour of antibiotics (OR 0.17, 95% CI 0.05 to 0.65). This means 24 children would need to be treated with antibiotics for one child to avoid pneumonia (NNT 24).

Meta-analysis revealed no significant reduction of other complications.

The authors concluded that antibiotics could be of benefit in preventing complications of measles, but there was insufficient evidence from trials to give definitive guidance on the antibiotic regimen that should be used, and further study was needed.

An earlier systematic review and analysis (search date: circa 1995) identified the six controlled trials described in the Cochrane systematic review up to that date [Shann, 1997]. The authors concluded that antibiotics should 'only be given if a child has clinical signs of pneumonia or other evidence of sepsis'.

Human normal immunoglobulin and vaccine

Evidence on human normal immunoglobulin and vaccine for postexposure prophylaxis of measles

There is no evidence from randomized controlled trials to confirm the efficacy of human normal immunoglobulin (HNIG) for the postexposure prophylaxis of measles. However, historical observational studies provide evidence suggesting HNIG is effective if administered early (within 3 days of exposure) and at a sufficient dose, although there are concerns that HNIG is not as effective today as it was in previous decades. There are no data to verify the effectiveness of measles vaccine used for postexposure prophylaxis.

A review published by the Health Protection Agency (HPA) summarized the available evidence for the effectiveness of HNIG when used for postexposure prophylaxis of measles [HPA, 2009a].

In an early controlled study (1945), HNIG or control was given to children of the same family that had been exposed to measles. In the control group, 43/46 (94%) children developed measles, compared with 18/62 (29%) in the HNIG group; this suggests a protective efficacy of 69%. In addition, in children who became infected, the illness was less severe in the HNIG group.

A large observational study in 891 participants in 1943 found that the infection rate of measles in susceptible people who had been exposed to the virus and then received HNIG was 41% in young children, 49% in older children, and 49% in adults, and there was evidence of a dose-response. All the participants who went on to develop measles had mild infection. A smaller observational study of 38 participants in 1960 found that 50% of disabled boys receiving HNIG did not develop measles infection.

Later observational studies suggest that delaying administration of HNIG reduces its effectiveness, with an estimated efficacy of 8% (95% CI 0 to 59) at 6 days postexposure.

There are concerns that because levels of measles antibody are lower in vaccine-induced immunity compared with naturally acquired immunity, the HNIG produced today may be less effective than is suggested by historical studies.

The HPA review found no evidence from controlled studies to confirm the efficacy of measles vaccine for the postexposure prophylaxis of measles; however it is likely to be low. One study from the 1990 US epidemic estimated the protective efficacy to be as low as 4% (95% CI 0 to 36). A UK-based case series found that, when given as postexposure prophylaxis, the combined measles, mumps, and rubella (MMR) vaccine offered no protection in four susceptible children exposed to measles in a nursery.

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on the primary care management of acute measles.

Search dates

August 2009 - July 2013

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

exp Measles/, exp Measles virus/, measles.tw

Table 1 . Key to search terms.
Search commands Explanation
/ indicates a MeSH subject heading with all subheadings selected
.tw indicates a search for a term in the title or abstract
exp indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree
$ indicates that the search term was truncated (e.g. wart$ searches for wart and warts)
Topic specific literature search sources

Health Protection Agency

World Health Organization

Sources of guidelines

National Institute for Health and Care Excellence (NICE)

Scottish Intercollegiate Guidelines Network (SIGN)

Royal College of Physicians

Royal College of General Practitioners

Royal College of Nursing

NICE Evidence

Health Protection Agency

World Health Organization

National Guidelines Clearinghouse

Guidelines International Network

TRIP database

GAIN

NHS Scotland National Patient Pathways

New Zealand Guidelines Group

Agency for Healthcare Research and Quality

Institute for Clinical Systems Improvement

National Health and Medical Research Council (Australia)

Royal Australian College of General Practitioners

British Columbia Medical Association

Canadian Medical Association

Alberta Medical Association

University of Michigan Medical School

Michigan Quality Improvement Consortium

Singapore Ministry of Health

National Resource for Infection Control

Patient UK Guideline links

UK Ambulance Service Clinical Practice Guidelines

RefHELP NHS Lothian Referral Guidelines

Medline (with guideline filter)

Driver and Vehicle Licensing Agency

NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

The Cochrane Library :

Systematic reviews

Protocols

Database of Abstracts of Reviews of Effects

Medline (with systematic review filter)

EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

NIHR Health Technology Assessment programme

The Cochrane Library :

NHS Economic Evaluations

Health Technology Assessments

Canadian Agency for Drugs and Technologies in Health

International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

The Cochrane Library :

Central Register of Controlled Trials

Medline (with randomized controlled trial filter)

EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Drug & Therapeutics Bulletin

Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

Department of Health

Health Management Information Consortium (HMIC)

Patient experiences

Healthtalkonline

BMJ - Patient Journeys

Patient.co.uk - Patient Support Groups

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

British National Formulary (BNF)

electronic Medicines Compendium (eMC)

European Medicines Agency (EMEA)

LactMed

Medicines and Healthcare products Regulatory Agency (MHRA)

REPROTOX

Scottish Medicines Consortium

Stockley's Drug Interactions

TERIS

TOXBASE

Micromedex

UK Medicines Information

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