National Measles Guidelines

Overview

This Guidelines summary of the UK Health Security Agency (UKHSA)'s guidance on measles highlights the key points for primary care. 

See the full guideline for further information and recommendations on international surveillance standards, measles Immunoglobulin (Ig) G testing of contacts, urgent IgG testing of contacts, risk assessment and public health management, case management and post-exposure prophylaxis for immunosuppressed and immunocompetent vulnerable patients, dosage and administration of Immunoglobulins, acute hospital settings, educational settings, and international travel.

Epidemiological Parameters

• A good understanding of the transmission parameters of measles is important to undertake an appropriate risk assessment
• The incubation period is typically around 10–12 days from exposure to onset of symptoms, but can vary from 7 to 21 days
• The period of infectiousness generally starts from 4 days before the rash and lasts up to 4 days after the onset of rash
• The transmission route of measles is mostly airborne by droplet spread or direct contact with nasal or throat secretions of infected persons. Much less commonly, measles may be transmitted by articles freshly soiled with nose and throat secretions, or through airborne transmission with no known face-to-face contact
• Measles is extremely infectious, with a basic reproduction number (R0) estimated to be around 15–20 (that is, on average, there will be 15–20 individuals infected from a single case in a totally susceptible population). The secondary attack rate is highest among close unimmunised contacts, particularly household contacts
• Vaccine effectiveness: based on available evidence, vaccination with one dose of the measles, mumps, and rubella (MMR) vaccine is at least 95% effective in preventing clinical measles and 92% effective in preventing secondary cases among household contacts
• In settings with high rates of close interpersonal contacts, such as large households or school settings, controlling measles outbreaks requires a high coverage of two doses of MMR.

Clinical Presentation of Primary Measles Infection

Figure 1 in the full guideline shows the clinical course of primary measles infection and its main symptoms.

• Measles starts with a 2–4 day illness (‘prodromal phase’) before the rash appears, which typically includes high fever, coryzal symptoms, cough, and conjunctivitis. The latter is a more specific symptom that differentiates measles from many other causes of influenza-like illness
• Symptoms typically peak on the first day of the rash
• Fever typically increases during the prodromal phase, peaks (generally >39°C) around the rash onset, and will gradually decrease after that
• The maculopapular rash generally starts on the face and behind the ears. The number of lesions/spots generally increases in the first 2–3 days, and their distribution expands further to the face, trunk, and can sometimes be generalised. Lesions can become confluent, particularly on the face and the trunk. The rash is red, blotchy, maculopapular (that is, nonvesicular), not itchy, and generally lasts for 3–7 days, fading gradually
• Koplik spots may appear around the time of the rash, usually 1 day before, and last for 2–3 days after the rash appears. These are small spots with white or bluish-white lesions, of about 2–3 mm in diameter, on an erythematous base on the buccal mucosa. These can be confused with other lesions in the mouth and therefore their suspected presence is an unreliable marker for measles
• Several other common rash illnesses have a similar clinical presentation, although the combination of rash, fever, coryzal symptoms, and conjunctivitis is almost unique to primary measles infection
• Rash illnesses including roseola (HHV6 infection), fifth disease (parvovirus B19 infection), and scarlet fever can be indistinguishable based on clinical features alone, particularly in children, and clinical diagnosis is often unreliable
• The timing and nature of symptoms is often helpful in the differential diagnosis. For example, while symptoms, including fever, peak with the onset of rash in measles, in roseola the onset of rash generally coincides with clinical improvement. See the full guideline for a summary of the clinical features of each of these conditions.

Complications of Primary Measles Infection

• The most frequent complications include viral pneumonitis and otitis media, as well as diarrhoea
• Measles infection often leads to a temporary reduction in immune responses in the few weeks following infection, which may increase the risk of severe secondary bacterial and viral infections
• Tracheobronchitis (‘measles croup’) and pneumonia due to secondary bacterial infection are frequent complications of measles
• Encephalitis occurs more rarely, in about 0.05%–0.1% of measles cases
• Subacute sclerosing panencephalitis (SSPE) is a very rare but very severe complication, occurring in about 0.01% of cases
• Immunosuppressed individuals are at higher risk than immunocompetent individuals of developing prolonged and severe measles, and of suffering complications. Viral pneumonitis is the most frequent severe complication, which generally develops within 2 weeks of symptom onset
• Measles can be particularly debilitating in very young infants and adults, who are more likely to develop complications and require hospitalisation
• Measles can be severe in pregnant women and leads to an increased risk of prematurity and fetal loss, although there is no evidence that it leads to congenital defects.

Transmission of Primary Measles

• A patient with suspected measles should be advised to isolate and in particular to avoid contact with immunosuppressed individuals and other vulnerable people (such as pregnant women and infants) while potentially infectious
• Individuals with primary measles infection are infectious from about 4 days before rash onset until 4 full days after the rash appears
• Generally, secondary transmission is higher among close contacts, such as household members and non-household members with whom prolonged contact has occurred—such as students in the same classroom
• Where a large group of people have been exposed but the level of contact cannot be defined at an individual basis, it may be appropriate to initiate a mass communication, for example using approaches such as email, text messaging, or posters to 'warn and inform' those who may have been exposed.

Breakthrough Measles (Reinfection)

• The term ‘breakthrough measles’ (previously referred to as ‘reinfection’, or secondary vaccine failure) is used to describe a confirmed case of measles in someone who developed immunity to measles, either from natural measles or from prior receipt of measles-containing vaccine, typically 6–30 years after infection or immunisation
• Cases of breakthrough measles are generally mild; conjunctivitis is generally absent and the rash may not follow typical progression
• The illness tends to be of shorter duration, and the infectivity of these cases is much lower and transient, unlike primary measles infection.

Rash Illness 10–12 Days Post-MMR

• MMR is an attenuated vaccine, and some individuals develop a rash 10–12 days post vaccination
• Individuals may have a mild fever but are otherwise well
• Measles virus can be detected in oral fluid samples and mouth and throat swabs
• Standard polymerase chain reaction (PCR) cannot distinguish between vaccine and wild-type measles and so sample should be sent to Virus Reference Department for either their measles-vaccine-specific PCR assay or formal genotyping.

Surveillance of Measles

• Measles is a notifiable disease under the Health Protection (Notification) Regulations (England) 2010
• Health protection teams should work with local partners to raise awareness of measles among health professionals in order to facilitate early recognition, diagnosis, and reporting
• Notification of the local health protection team (HPT) fulfils the physician’s responsibility to notify the local authority proper officer
• Physicians managing the case should inform the HPT by phone as soon as is reasonably practical.

Laboratory Surveillance

• When a suspected case of measles is reported and/or notified to the local HPT, the HPT should arrange for an oral fluid (OF) kit to be sent directly to the case (or their parent/guardian), or via their GP
• Samples should be taken as soon as possible after measles is suspected, and posted or couriered back to the Virus Reference Department, UKHSA Colindale, where they are tested for anti-measles IgM, measles IgG, and/or measles RNA. Results are reported back to the patient's GP and to the local HPT. All relevant OF kit documents can be found online.

Types of Sample

• For World Health Organization purposes, a measles antibody test is required to exclude measles
• In the UK, OF is the optimal sample for measles surveillance
• In the absence of an OF sample, serum and a mouth swab should be sent to the Virus Reference Department instead
• It is important to note that OF samples cannot be used to assess the immune status of vulnerable contacts, and serum should be used instead.

Oral Fluid

• OF, also known as gingival crevicular fluid, is the optimal sample for measles surveillance and should be taken from all suspected cases regardless of any other samples that may have already been taken, including when other laboratory methods have not confirmed measles
• Testing for IgM on OF is more sensitive and more specific than serum, particularly in the first few days after the rash, as IgM antibodies are positive in >50% of samples on day 1 of the rash, and in over 90% by day 3 of the rash. For OF samples taken within 7 days of onset of disease, the Virus Reference Department also performs PCR analysis for RNA detection.

Serum

• Serum samples can be used for IgM/IgG detection through enzyme immunoassays, preferably using a mu capture assay for detecting IgM
• Serum is the most appropriate sample to assess the immune status of contacts
• Serum can be used to confirm breakthrough measles (reinfection) by detection of high-avidity measles IgG
• Serum is generally not suitable for PCR detection and viral typing
• Serum cannot be used to distinguish wild-type measles from vaccine-derived measles following recent vaccination.

Mouth Swabs

• Mouth swabs can be used for PCR if collected within 6 days of the onset of rash, but need to be collected by a healthcare professional
• A negative PCR result does not exclude a diagnosis of measles
• Mouth swabs can be used to distinguish between wild-type virus and vaccine in someone who has recently been vaccinated
• Mouth swabs cannot be used for measles IgM/IgG testing and cannot be used to distinguish between a primary infection and a breakthrough measles (reinfection).

Throat Swabs or Nasopharyngeal Aspirate

• Such samples can be used for PCR if collected within 6 days of the onset of rash, but need to be collected by a healthcare professional
• A negative PCR result does not negate a diagnosis of measles, especially in the absence of a test for cellular RNA
• Nose swabs and eye swabs are not suitable for measles testing.

Urine

• Urine samples can be highly variable and are therefore not advised for measles testing in the UK.

EDTA Blood

• Samples can be used for testing for measles IgM and IgG, although serum samples are generally preferable.

Collection of Samples

• Kits for collecting OF samples are available through the local HPT. It is important that the sample is collected according to the instructions
• The swab needs to be rubbed along the gum line for 2 minutes
• If young children chew on the swab while the sample is being collected it should not compromise the sample collection. Sputum samples are not suitable for testing
• OF samples sent for measles IgM testing are also tested for total IgG as an indication of whether the sample is suitable for testing
• If the total IgG is less than 1 mg/l, then this indicates a poor-quality sample and the test may need to be repeated. If OF collection kits are not available, then a serum sample plus mouth swab can be taken instead (and sent to the Virus Reference Department)
• A mouth swab should be collected by rubbing the swab along the gum line and then over the tongue
• A serum or OF sample is required for distinguishing a primary infection from breakthrough measles (reinfection)
• Note: any viral swab may be used for measles PCR testing.

Laboratory Definitions

• Laboratory-confirmed case of measles: a suspected case with evidence of laboratory confirmation of acute measles infection (that is, measles IgM in blood or OF in the absence of recent vaccination, or confirmed wild-type measles RNA in any clinical specimen)
• Presumed primary infection: a laboratory-confirmed case with no evidence of two doses of measles-containing vaccine
• Presumed breakthrough measles (reinfection):detection of measles virus RNA in a suspected case of measles with mild or atypical symptoms and a reliable history of having received two doses of measles-containing vaccine. Breakthrough measles can be confirmed by detection of high-avidity measles IgG in serum or high levels of measles-specific IgG in OF. Measles IgM in serum may be negative.

Assessment of the Index Case

• When measles is not endemic, the positive predictive value of a clinical diagnosis is generally poor. In the absence of laboratory results, the likelihood of measles will therefore depend upon an assessment of the epidemiological features
• Case management should commence based on this assessment, without waiting for the results of laboratory testing (even when requested urgently).

Case Management Definitions

• The HPT should conduct a public health risk assessment for ever suspected case of measles reported by a clinician in order to decide on management
• Each case should be promptly investigated and classified according to laboratory results, clinical features, and epidemiological features.

Patient Information Required for Assessment of Suspected Measles Cases

• Demographic details
  • name
  • gender
  • date of birth
  • date, address, NHS number
  • contact details
• Clinical and laboratory features
  • signs and symptoms: collect information on signs and symptoms, and importantly the onset dates of rash
  • laboratory results: document the type of tests conducted and results
• Individual epidemiological features
  • travel: any travel within and outside the UK during the incubation period, with an assessment of whether travel was in an area where measles is known to be circulating
  • ethnic and cultural or religious background: obtain details on the patient’s ethnicity, and importantly, assess whether the patient is a member of an under-vaccinated population group (for example, Charedi Orthodox Jewish community, Steiner community)
  • immunisation history: any known vaccination history or history of measles; if not known, ask where the patient was born and grew up to help assess the likelihood of vaccination and/or natural exposure
  • epidemiological link: assess if there has been a known epidemiological link with another laboratory or epidemiologically confirmed case.

Table 1: Case Definitions for Measles

Table 2: Clinical Features of Measles

Local Transmission

• To ensure that true cases are not missed, there should be a very low threshold for OF testing and all suspected measles cases should be tested irrespective of whether they meet the clinically compatible criteria.

Factors to Consider in the Risk Assessment

Factors Increasing the Risk of Exposure

• Membership of a community known to be more susceptible, for example, traveller community, Charedi Orthodox Jewish community, anthroposophical (Steiner) communities, local community with low MMR vaccination coverage
• Visited an area (local or international) where measles is known to be circulating, during the incubation period
• Attendance at large international mass gathering events, where substantial mixing occurs between individuals potentially travelling from areas where measles is circulating; this would include events such as music festivals.

Factors Favouring the Diagnosis of Primary Measles Infection

• Age: the likelihood of a suspected case being confirmed as measles is higher among adolescent and young adults. In infants and toddlers, measles-like clinical presentations due to other illnesses, such as roseola or scarlet fever, are common
• A lack of immunity or incomplete vaccination: the diagnosis is more likely if cases are unvaccinated or partially vaccinated, and have no prior history of measles infection.

Testing of the Index Case

• Regardless of any other testing performed, all cases should have OF samples taken and sent to the Virus Reference Department for exclusion/confirmation of the diagnosis.

OF Testing

• All suspected cases (including cases confirmed by local laboratory testing) require an OF sample to be sent for testing at the Virus Reference Department in Colindale
• Contacts of epidemiologically or laboratory-confirmed cases (by other methods) should be risk assessed and managed without awaiting the result of the OF test in the index case
• Immunosuppressed contacts of likely cases (including breakthrough measles [reinfection]) should be risk assessed and managed without awaiting the result of the OF test in the index case
• Where the case is considered unlikely, there have been no recent cases locally, and there has been no indication on notification that the case has clinically classical features, awaiting the results of a posted OF kit without further investigation is appropriate.

Urgent Testing

• Measles is a clinical diagnosis and, while all cases should be confirmed for surveillance purposes, urgent testing will only be necessary in certain circumstances and where results will be available in time to inform action
• All locally tested measles IgM and/or measles PCR positive samples should also be forwarded on to Colindale/the Virus Reference Department for further testing and characterisation.

Risk Assessment

• The risk assessment should take into account the clinical features, epidemiological features, vaccination history, and laboratory results to decide on the need for further testing and post-exposure prophylaxis of vulnerable contacts
• Algorithm 1 illustrates the principles of risk assessment and public health management.

Algorithm 1: Principles of Risk Assessment and Public Health Management

Management of Contacts and Post-Exposure Prophylaxis

For further information and recommendations on the risk assessment, susceptibility, and management of patients and contacts who are immunosuppressed or immunocompetent and vulnerable (pregnant women and infants), as well as on the dosage and administration of Immunoglobulins, refer to the full guideline.

Identification of Contacts

• The best way to protect individuals and to achieve measles elimination is with high vaccination coverage with two doses of MMR vaccine (≥95%)
• Where practicable, all contacts should be provided with information on symptoms of measles and advised to exclude themselves from schools or other settings if they develop symptoms
• Although post-exposure prophylaxis is of limited effectiveness, there may be an opportunity to offer some protection to exposed vulnerable contacts. This requires identification of contacts in the following order of priority:

1. immunosuppressed contacts
2. pregnant women and infants aged <12 months
3. healthcare workers
4. healthy contacts.

Defined Contacts

• Contact tracing should identify close contacts within the 8-day infectious period, from 4 full days before and until completion of 4 full days after rash onset

Immunosuppressed Individuals

• Any level of contact should trigger an assessment of an immunosuppressed individual, even if the index case is presumed to be breakthrough measles (reinfection)
• If immunosuppressed contacts are identified, assessment of their susceptibility and post-exposure prophylaxis should be considered without waiting for, or in parallel with, laboratory testing of the index case
• Inadvertent administration of MMR to an immunosuppressed individual should be risk assessed as a potential exposure to measles.

Vulnerable Immunocompetent Individuals (Infants, Pregnant Women)

• For immunocompetent vulnerable individuals (infants, pregnant women), local HPTs should prioritise contact tracing efforts to those most likely to have had close or prolonged exposure to a primary measles infection.

Poorly Defined Contacts

• When the information provided cannot clearly define the level of contact but there are known immunosuppressed individuals involved, these should be managed as close contacts and rapidly assessed for post-exposure prophylaxis
• Where there is a defined list of contacts, but it is not clear if the group contains immunosuppressed individuals, an individual risk assessment is not practicable. In this situation, warn and inform letters or messaging should be issued to all potential contacts
• If there is no identifiable list of contacts at all, then other means of case-finding should be considered, such as writing to local healthcare providers, information leaflets or posters in public areas, and other communication activities as relevant to the setting.

Primary Care Settings

• All staff working in healthcare settings with any contact with patients (including ambulance drivers, receptionists) should have their immune status assessed and, if non-immune or unclear, offered MMR vaccination
• Infection prevention and control guidance for clinical settings can be found in the National infection prevention and control manual
• Whenever possible, signs should be placed in GP surgery waiting areas advising patients with any rash illness to report to reception
• Receptionists should know that any patients with fever and rash are potentially infectious and, ideally, should attend at the end of surgery to minimise the risk of transmission
• Where patients with a fever and rash attend when other patients are in the waiting room, they should be directed to a side room
• When a GP refers a suspected measles case to A&E or hospital, they should inform the hospital staff ahead of time, so that the case can be appropriately isolated on arrival
• When a likely case of measles is reported from primary care, the GP practice retains the lead responsibility for conducting a risk assessment in the setting itself. The HPT will be able to advise on infection control measures and if, for example, the patient was not isolated on arrival and exposed other patients in the waiting room, will be able to support risk assessment and advise on post-exposure measures as per current guidelines.

Considerations for Healthcare Workers

• All healthcare workers (including receptionists, ambulance workers) should have satisfactory evidence of protection against measles to protect both themselves and their patients. Satisfactory evidence of protection includes documentation of having received two or more doses of measles-containing vaccine and/or a positive measles IgG antibody test
• Healthcare workers (HCWs) who are exposed to a confirmed or likely case and do not have satisfactory evidence of protection should be excluded from work from the 5th day after the first exposure to 21 days after the final exposure
• If HCWs are tested rapidly after exposure, they can continue to work if found to be measles IgG positive within 7 days of exposure (as this is too early to be due to infection from the recent exposure)
• Where MMR vaccine is given post exposure, it is unlikely to prevent the development of measles but if the HCW remains symptom-free for at least 14 days after MMR vaccine was given, they can return at that stage
• HCWs with satisfactory evidence of protection can continue to work normally but should be advised to report to Occupational Health if they develop prodromal symptoms or a fever between 7 days after the first exposure and 21 days after the last exposure
• Exposed HCWs that develop fever or rash should be excluded from all work until 4 full days after onset of the rash. Those HCWs should be treated as an epidemiologically confirmed case and laboratory confirmation and notification should be sought in the usual way.

Outbreaks

• An outbreak is defined as two or more epidemiologically linked cases that occur within one incubation period of each other (that is, the second case occurs between 7 and 21 days of the first case)
• Although most outbreaks will occur within the household setting, an outbreak control team may need to be convened when transmission has occurred in other settings where a large number of people been exposed (for example, school outbreak) or where the population exposed may be more vulnerable (for example, hospital outbreak)
• An outbreak of measles in a prison setting will require close liaison with UKHSA and NHS Health and Justice leads.

Planning and Response

• HPTs should work with their local NHS England Screening and Immunisation teams to ensure that the necessary resources are available within their area to manage outbreaks. HPTs should know where to access urgent laboratory testing services (particularly measles IgG) and human normal Immunoglobulin (HNIG) supplies. Access to a small stock of MMR vaccine should be available by the next day, including at weekends, and HPTs should ensure they know which walk-in clinics or out-of-hours GP services are available at the weekend to enable prompt administration of MMR vaccine or HNIG if required
• When outbreaks occur in an institutional setting such as a school, university or place of detention, all individuals in the setting who are susceptible or incompletely vaccinated should be offered MMR vaccine promptly, even if direct contact with the index case has not occurred
• If an outbreak occurs in an institutional setting where vaccination coverage is known to be low, an urgent campaign should be considered. Vaccination of all susceptible students will limit the risk of tertiary transmission within the school setting. Commissioners should have contracts in place to provide support for vaccination campaigns in defined settings, such as schools, and providers should have arrangements in place to source MMR promptly for outbreak control.