MEASLES

Last updated: 24 October 2008

1. Summary

Public health priority

• Urgent.

• Laboratory confirmation should be sought in all sporadic cases.
• Cases should not attend school/preschool/child care/work from onset of symptoms to 4 days after onset of rash and should stay home (unless isolated in hospital). Cases should avoid contact with susceptible persons.

• Recommend either immunisation or normal human immunoglobulin to defined contacts where indicated.
• Exclude unimmunised contacts from school/preschool/child care.
• Ask contacts to be alert for signs and symptoms of measles and advise those who develop symptoms to call ahead before seeking medical advice (so as to avoid common waiting areas in doctors' rooms or Emergency Departments [EDs]), and to telephone the local Public Health Unit.
• Ask hospital EDs, GPs, school principals and child care directors to notify new cases promptly.

2. The disease

Infectious agents
The measles virus, a member of the genus Morbillivirus (paramyxovirus).

Mode of transmission
Measles is transmitted by airborne droplets and direct contact with discharges from respiratory mucous membranes of infected persons and less commonly by articles freshly soiled with nose and throat secretions. It is highly infectious.

Timeline
The incubation period is variable, about 10 days (varying from 7 to 18) to the onset of fever and about 14 days to the onset of the rash.

Infectious period
A rule of thumb is that measles is infectious 5 days before, to 4 days after, the appearance of the rash. However in cases with a clear history of time of onset of prodromal illness, the infectious period should be considered commencing 24 hours prior to the onset of prodromal symptoms.

Clinical presentation
The disease is characterised by a prodrome that usually lasts 2 to 4 days and includes fever followed by conjunctivitis, coryza and cough. Koplik spots may be present on the buccal mucosa. A characteristic maculopapular rash appears about 2 to 7 days after the onset of the prodrome, and begins on the face or upper neck, spreads to become generalised and lasts 4 to 7 days. The rash is not itchy. Cases are usually miserable, and complications such as middle ear infection, bronchopneumonia and encephalitis can follow. Infection in pregnancy can be severe for the woman and can result in increased risk of premature labour or spontaneous abortion. Although there is no association with congenital abnormalities, congenital measles infection can occur if the infection is contracted late in pregnancy. Prophylaxis and specialist care are required in these cases.

3. Risk assessment

Routine prevention activities
Measles vaccine, as MMR, is currently recommended as part of the National Immunisation Program schedule for all children at ages 12 months and 4 years. However in the future the 9th edition of The Australian Immunisation Handbook (in press) will recommend MMR at ages 12 months and 18 months.

Persons considered susceptible to measles are those who were born in or after 1966 who have neither serological evidence of measles immunity nor documented evidence of receiving two doses of measles containing vaccine. Two doses of MMR, given at least 4 weeks apart, are recommended for susceptible persons.

Threat and vulnerability
Until the mid 1960s, most Australian children were infected with wild measles. With increasing uptake of measles vaccine since the 1960s, the introduction of a 2-dose schedule in 1980s, and the school-based national Measles Control Campaign in the 1990s, transmission of measles was interrupted throughout Australia by the late 1990s. The Australian Childhood Immunisation Register (ACIR) and its related incentives for GPs and parents have improved immunisation rates in recent years to 94% of 2 year olds and 89% of 6 year olds in 2007. Serological surveys indicate that immunity is high (98%) in people born before 1968 due to exposure to wild measles, but lower (89%) in people born 1974-1980 due to less frequent exposure to wild virus or vaccine. Although measles is no longer endemic in Australia, measles continues to circulate internationally ensuring that it will be reintroduced from time to time, with the potential to cause small to moderate outbreaks. The risk of outbreaks may increase in the future as the pool of susceptible people grows.

Risk mitigation
Achieving and maintaining high rates of immunity to measles throughout the population is the mainstay of measles control in Australia, both through routine immunisation of children, and the promotion of immunisation in people born in or after 1966. Control of measles outbreaks relies on an effective and sensitive surveillance system to identify cases early and allow public health control measures, including case isolation, contact tracing and protection, and promotion of immunisation in susceptible groups.

4. Surveillance objectives

• To identify cases and their contacts in order to prevent further spread
• To monitor the epidemiology of measles in Australia and so inform the development of better prevention strategies
• To monitor progress towards regional measles elimination targets
• To monitor maintenance of Australia's measles-free status.

5. Data management

• Suspected, probable and confirmed cases should be entered onto the notifiable diseases database, ideally within 1 working day following notification. The date of onset is the onset of illness, not of the rash.
• Enter information on viral typing (if done) on notifiable diseases database within 3 working days of receipt of results.
• Cases subsequently shown not to have measles should be removed from notifiable diseases database within 1 working day.

6. Communications

As soon as is practicable and ideally within 1 working day following notification:

• Notify the State/Territory Communicable Diseases Branch (CDB) of the case's age, sex, date of onset, vaccination history, laboratory status, likely source of infection, other people at risk of infection and follow up action taken.
• The State/Territory CDB should notify the case details and response plan to the CDNA secretariat.
• Where there are cases or contacts among people from overseas, the State/Territory CDB should notify the Commonwealth Department of Health and Ageing's National Incident Room (via Health Ops) who will comply with the International Health Regulations reporting requirements.
• For outbreaks with the potential to involve multiple jurisdictions, the State/Territory CDB should liaise with the chair of CDNA and determine whether an urgent teleconference should be convened.

7. Case definition

Confirmed case
A confirmed case requires either:

1. laboratory definitive evidence, OR
2. clinical evidence AND epidemiological evidence.

Laboratory definitive evidence
At least one of the following:

1. Isolation of measles virus, OR
2. Detection of measles virus by nucleic acid testing, OR
3. Detection of measles virus antigen, OR
4. IgG seroconversion or a significant increase in antibody level or a fourfold or greater rise in titre to measles virus EXCEPT if the case has received a measles-containing vaccine 8 days to 8 weeks before testing. (NOTE: paired sera must be tested in parallel), OR
5. Detection of measles virus-specific IgM antibody confirmed in an approved reference laboratory EXCEPT if the case has received a measles-containing vaccine 8 days to 8 weeks before testing. Note that where a local laboratory uses the Dade Behring EIA (thought to be the most reliable commercial test available for measles IgM antibodies), further confirmation is not required.

Clinical evidence
An illness characterised by all of the following:

1. A generalised maculopapular rash lasting three or more days, AND
2. Fever (at least 38°C if measured) at the time of rash onset, AND
3. Cough, OR coryza OR conjunctivitis OR Koplik spots, at the time of rash onset.

1. Contact between two people involving a plausible mode of transmission at a time when:
   • one of them is likely to be infectious (approximately five days before to four days after rash onset), AND
   • the other has an illness that starts within 7 to 18 (usually 10) days after this contact, AND
2. At least one case in the chain of epidemiologically linked cases (which may involve many cases) has laboratory definitive evidence of measles.

Probable case
A probable case requires laboratory suggestive evidence AND clinical evidence.

Laboratory suggestive evidence
Detection of measles specific IgM antibody other than by an approved reference laboratory EXCEPT if the case has received a measles-containing vaccine 8 days to 8 weeks before testing.

Clinical evidence
Same as for confirmed case.

Suspected case
A suspected case requires clinical evidence only.

Clinical evidence
Same as for confirmed case.

8. Laboratory testing

Since recent MMR immunisation affects some laboratory tests, the results should be interpreted in the context of the clinical findings. The clinical diagnosis of measles may be confused with other diseases such as rubella, roseola, scarlet fever, human parvovirus infection, enterovirus, adenovirus, HIV, Kawasaki disease and some arboviral infections, so laboratory definitive evidence should be sought for all sporadic suspected cases.

Testing guidelines
Public Health Laboratory Network (PHLN) provides information on the laboratory diagnoses of measles. This is available at: http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-phln-pubs-measles.htm

For sporadic cases:

• Patients seen within 1 week of onset of rash should have respiratory and urine samples collected for direct detection (immunofluorescence or PCR) and culture, and clotted blood collected for serology (also see Case investigation below).
• Patients seen between 1 week and 3 weeks after the onset of rash should have clotted blood collected for serology and a respiratory and/or urine sample for PCR.
• Patients seen more than 3 weeks after onset of rash should only have clotted blood collected for serology.

In an established outbreak, laboratory confirmation by isolation or measles antigen/genome detection should be obtained on at least two cases, but may not be necessary for cases who meet the clinical case definition and have a clear epidemiological link to a confirmed case. Serological confirmation is encourage for these cases.

The reliability of serological and direct detection tests for asymptomatic contacts is unknown. Testing of asymptomatic contacts is not recommended.

Measles serology

• An IgM response will be present in approximately 75% of measles cases 3 days after rash onset, rising to approach 100% after 7 days. A measles IgG antibody test should preferably be performed together with the IgM assay to aid interpretation.
• Measles-specific IgM is a sensitive and specific marker of recent measles infection, but can also be detected for 1 to 2 months following immunisation.
• A negative result does not rule out a diagnosis of measles if the sample was taken earlier than 72 hours after onset of the rash. When no measles IgM or IgG antibody is detected in a sample collected within 3 days of rash onset from a suspected case of measles, repeat testing is recommended after 7 days. (Alternatively, a measles PCR could be requested upon the sample - see below.)
• False positive measles IgMs can also occur, and if suspected, the IgM test should be repeated. For sporadic cases, results should be confirmed, ideally by a reference laboratory using the Dade Behring assay.
• Where a false negative or false positive IgM result is suspected, testing for measles specific IgG seroconversion by EIA on paired sera collected 10-14 days apart is helpful.
• Testing paired sera using the complement fixation test (which expresses results in titres) may also be helpful, especially in cases with a history of measles vaccination.
• A 5 mL tube of clotted blood is the preferred specimen for serological testing.

Measles culture and immunofluorescence

• Measles virus may be identified by cell culture from blood, conjunctival swab, throat swab, nasopharyngeal swab or aspirate if taken within 5 days of the onset of the rash, and from urine for up to 10 days after the onset of rash. Antigen testing by immunofluorescence may also be performed on respiratory or urine samples collected during the prodrome or in the first few days after rash onset. Any isolate or immunofluorescence positive material should be referred to the Victorian Infectious Diseases Reference Laboratory (VIDRL) for genotyping. These samples may allow epidemiological identification of a measles importation source.
• Nasopharyngeal aspirates or nasopharyngeal swabs are the preferred sample for antigen detection by immunofluorescence and culture. Throat swabs or nasal washes are suitable for culture but not for immunofluorescence. The swabs should be placed immediately after collection into viral transport medium, and all these samples should be transported at 4°C.

Measles PCR

• Respiratory specimens and early catch urine (collected up to 3 weeks after onset of the rash) or sera collected early in the illness can be referred to an approved reference laboratory for measles PCR on an urgent basis if necessary. The PHU should facilitate communication with and between the laboratories involved concerning collection of suitable specimens and transport arrangements.
• Nasopharyngeal aspirates or nasopharyngeal swabs are the preferred sample for nucleic acid detection by PCR. Throat swabs or nasal washes are also suitable for PCR. A dry sterile swab of the nasal passage combined with a similar swab from the back of the throat is the recommended specimen for detection of viral nucleic acid (PCR). Swabs should be cotton, rayon or dacron-tipped, plastic-coated or aluminium shafted swabs. They should be placed into viral transport medium. Samples should be stored and transported at 4°C. If arrival at the testing laboratory will be delayed more than 72 hours then, if possible samples should be frozen at -70°C and transported on dry ice. Do not freeze at -20°C.
• Early catch urine samples should be stored and transported at 4°C. If arrival at the testing laboratory will be delayed more than 72 hours then, if possible samples should be frozen at -70°C and transported on dry ice. Do not freeze at -20°C.
• Heparinised blood for PCR should be stored and transported at room temperature.

The effect of recent vaccination

• Vaccine-induced "measles" is a modified form of measles occurring 5-12 days after measles vaccination. It is not transmissible and should NOT be classified as measles.
• Serologically-diagnosed cases who received a measles-containing vaccine 8 days to 8 weeks before testing may be classified as confirmed measles ONLY if they are also epidemiologically linked to a confirmed case.

9. Case investigation

Response times
Investigation
On same day of notification of a suspected, probable or confirmed case, begin follow-up investigation using the Measles Investigation Form.

Response procedure
Case investigation
The response to a notification will normally be carried out in collaboration with the case's health carers. Regardless of who does the follow-up, PHU staff should ensure that action has been taken to:

• Seek the doctor's permission to contact the case or the relevant care-giver
• Find out what the case or relevant care-giver has been told what the diagnosis is before beginning the interview
• Review case and contact management
• Review the measles vaccination status of the case
• Confirm the onset date and symptoms of the illness. For a suspected or probable case, ensure that the clinical evidence is consistent with the case definition. If not, consider rejecting the diagnosis (particularly if the case is age-appropriately vaccinated and there is no epidemiological link to another case)
• Confirm results of relevant pathology tests, or recommend that the tests be done. The choice of tests depends on the time since rash onset (see testing guidelines, above). Check with the State/Territory reference laboratory first, but this usually requires:
  • 5 mL of blood (EDTA tube at room temperature)
  • nose/throat aspirates or swabs (transferred immediately into viral transport media) kept at 4ºC and transported to the reference laboratory within 72 hours of collection
  • 10 mL urine in a sterile container at 4ºC and transported to the reference laboratory within 72 hours of collection
• Ensure that laboratories send copies of these results to the PHU
• Any isolate or PCR or immunofluorescence positive material should be referred to VIDRL for genotyping.

Case treatment
Supportive only.

Education
The case or relevant caregiver should be informed about the nature of the infection and the mode of transmission. By the time the case of measles is identified and notified, the case may already have transmitted the virus to other susceptible people. The case should be advised to stay at home in isolation while infectious and to avoid contact with susceptible people (see below) and immunosuppressed people.

Isolation and restriction
Exclude cases from work, school, preschool or child care and advise to stay in isolation (and specifically advise against interaction with susceptible people) until 4 days after the onset of the rash.
When measles is suspected, hospitalised cases should be kept in strict respiratory isolation (and preferably in a negative pressure room) until 4 days after the onset of the rash. Only healthcare workers who are immune should care for these patients.

When a case is isolated at home he or she should not mix with people who may be susceptible. For example, the household should not have visitors while the case is infectious.

Active case finding
Alert local doctors and laboratories in the areas where the measles case may have acquired the infection or was infectious to the possibility of further cases and ask them to report cases to the PHU promptly. Consider the need for a media alert to assist in case finding. Contacts (see below) who develop symptoms should be asked to inform the PHU as well as to seek medical advice.

10. Control of environment

None routinely required.

11. Contact management

Identification of contacts
Since measles is transmitted by airborne means, anyone who has shared the same air for any length of time with a case while the latter was infectious can be defined as a contact. In general, contacts may be prioritised in the following order, although it will not always be feasible for the PHU to identify individuals and arrange prophylaxis for them. In unclear or unusual situations, contact management should be discussed with State/Territory CDB.

Contact definition
Contacts include (in priority order for prophylaxis):

• All household members
• All people sleeping overnight in the same room as the case (for example, in a hospital, boarding school or military barracks)
• All children and adults at family day care, child care, preschool, school or other educational setting who share a classroom with the case
• People who stayed in a waiting area at the same time as the case (for example, patients in a health care facility's waiting room and any people accompanying these patients) and people who waited in the waiting area or who were seen in the same consultation room up to 2 hours after the case left
• All work colleagues of the case who share the same work area
• Others who attend or work in the same educational institution as the case, and may have spent time in the vicinity of the case, but do not share a classroom (for example, a high school, college, lecture theatre block)
• Passengers on an aeroplane who were seated in the same row and two rows in front of and behind a case ¹
• For others who cannot be individually identified but who may have been present in the general area where the case was known to be (for example, cinemas, shopping centres, aeroplane flights and restaurants) consideration should be given to the need to provide notices, or media informing them of their possible exposure.

A person considered susceptible to measles is someone who cannot provide acceptable presumptive evidence of immunity to measles. A person can be considered to have acceptable presumptive evidence of immunity to measles if they meet one of the following criteria:

• Persons born during or since 1966 who have documented evidence of receiving 2 doses of a measles-containing vaccine when both doses have been given at >= 12 months of age and at least 4 weeks apart (unless serological evidence indicates otherwise)
• Persons born before 1966 (unless serological evidence indicates otherwise)
• Documented evidence of immunity
• Documented laboratory definitive evidence of prior measles.

Prophylaxis
Susceptible contacts should be provided with either MMR vaccine or normal human immunoglobulin (NHIG) according to:

• time elapsed since exposure to an infectious case. Where there has been ongoing exposure (such as with household contacts) the time since exposure should be calculated from the first contact during the infectious period;
• age;
• previous MMR vaccination history; and
• current pregnancy or immunosuppression.

Tables 1 and 2 (Post exposure guidelines for exposures that have occurred within 144 hours) are provided in the appendix for this purpose.

NB: MMR and varicella vaccines should be delayed for 5 months after administration of NHIG to prevent measles.

Not infrequently, contacts may believe that they have been vaccinated but do not have the necessary documentation to prove vaccination readily available. If time allows, it may be possible, on a case-by-case basis, to determine whether individual contacts are susceptible by requesting measles IgG serology.

However, this is quite impractical on any large scale, so pragmatic decisions have to be made. If within 72 hours of exposure to a case, MMR vaccine should be given to those with an uncertain history of measles vaccination (Table 1). However, beyond 72 hours, it may be quite impractical to use NHIG on any large scale, but should always be considered for immunosuppressed individuals and for pregnant women who cannot provide evidence of either immunisation or immunity.

In settings with large numbers of individuals with uncertain vaccination histories (e.g., in high schools, in company workers) it is reasonable to recommend prompt MMR vaccination, even if it is >72 hours after the exposure. In this circumstance, it cannot be assured that further cases of measles will not occur (as someone may already be incubating the disease), but the liberal use of MMR should further reduce the likelihood of further ongoing transmission of the measles virus.

Education
Advise susceptible contacts (or parents/guardians) of the risk of infection and counsel them to watch for signs or symptoms beginning 7 to 18 days after the first contact with an infectious case (or longer if the contact received NHIG). They should avoid contact with other susceptible people and immunosuppressed people during this period. If symptoms develop, they should also be advised to call ahead before visiting doctors' rooms, hospital EDs or pathology services so as to avoid mixing with other people, and to telephone the local PHU if measles is suspected.

Advise the case's doctor that all people who used the same waiting room area or consultation room up to two hours following the case's departure require immediate assessment and prophylaxis if susceptible. Similarly, inform the relevant Infection Control Officer if the case has been in hospital while infectious (see below).

A sample script and "Measles: information for contacts" factsheet can be found in the appendix.

Isolation and restriction
Children who are enrolled in primary school, preschool or child care should be excluded as follows:

• Susceptible contacts should be excluded until 14 days after the onset of the rash in the last case occurring at the facility. However they may return if vaccinated within 72 hours of first exposure to an infectious case or if they receive NHIG within 144 hours of exposure.
• Immunosuppressed children or staff should be excluded (regardless of their measles vaccination status) until 14 days after the onset of the rash in the last case occurring at the facility. Exclusion is advised for their own safety even if they receive NHIG.

Susceptible contacts in high school should be advised to stay away until 14 days after the onset of the rash in the case. They may return if vaccinated within 72 hours of first contact with an infectious case or if they receive NHIG within 144 hours of exposure.

12. Special situations

Since the transmission of measles frequently occurs before diagnosis, the spread of the disease can be facilitated wherever susceptible individuals gather in groups.

Cases among children or staff at school or in child care
In addition to routine case and contact management, ask about possible cases occurring among attendees or employees within the previous 18 days. Daily surveillance to detect possible cases may be needed and should be considered for 18 days after the last infectious case attended. All suspected cases should be investigated and measures taken to minimise or eliminate secondary transmission from these cases.

Parents and staff should be provided with information about the disease and its prevention. Written information such as a fact sheet is recommended, but an information meeting for parents may also be useful (see appendix for sample letters to parents). Vaccination of all susceptible contacts should be recommended. Consider holding an immunisation clinic at the facility.

Cases among staff or patients in a health care facility
For suspected, probable or confirmed cases among staff or patients in a health care facility, consult immediately with staff from infection control or staff health to institute a management plan appropriate to the facility. This should include procedures for:

• Defining and identifying contacts
• Informing contacts and organising management where appropriate
• Keeping infectious patients in respiratory isolation for 4 days after the appearance of the rash, and ensuring that susceptible individuals do not enter any room for 2 hours after an infectious case has used it. Susceptible people entering this room within the 2 hour period should be considered as contacts
• Ensuring that only staff who are immune provide direct care to infectious patients
• Vaccinating susceptible contacts (ie. those who do not have documentation of having received 2 doses of a measles-containing vaccine) among patients and staff.
  • Susceptible patients who are not vaccinated within 72 hours or do not receive NHIG within 144 hours of first exposure, should be isolated and discharged from hospital as soon as possible
  • Susceptible staff who are not vaccinated within 72 hours or receive NHIG within 144 hours of first exposure should be redeployed to duties not requiring direct patient care (for up to 14 days after the rash onset in the last case at the facility)
• Carrying out active surveillance for measles, where practical, among exposed inpatients, inpatients discharged before the diagnosis of the first case, staff, students, volunteers and visitors
• Investigating staff members presenting with prodromal symptoms and ensuring that the affected person stays away from work until 4 days have elapsed after the onset of the rash (or until a measles diagnosis is excluded)
• Reviewing staff health records to ensure that all have been protected in line with current recommendations.

Local transmission of measles
Where transmission of measles is identified within Australia, then additional control measures should be considered. Depending on the people affected and nature of the setting, control strategies may include:

• Epidemiological studies to determine risks for infection
• Additional alerts to doctors directly and to the wider community through the media

Key messages to be communicated usually include:

• Awareness of the signs and symptoms of measles
• Reviewing vaccination status and prompt MMR vaccination if necessary
• Early case finding and isolation
• Contact tracing
• Prophylaxis

13. Additional resources

• The Australian Immunisation Handbook
• Heymann DL, ed. Control of Communicable Diseases Manual

14. Jurisdiction specific issues (NSW)

Legislation
NSW Public Health Act 1991

Measles is to be notified by:

• medical practitioners and hospital CEOs on clinical suspicion
• laboratories on confirmation
• school principals and directors of child care facilities on receipt of a report that an attendee has measles.

Policies
Occupational Assessment, Screening & Vaccination Against Specified Infectious Diseases PD2007_006

Obtaining NHIG
NHIG is available through the Australian Red Cross Blood Service (ARCBS) during working hours by calling the Transfusion Medical Officer on 9229-4347, or the After Hours Medical Officer on call 9229 4444. ARCBS keeps a small stock of NHIG at its Clarence Street, Sydney and Newcastle Distribution Departments. These departments are not set up for public access. For individual doses, the ARCBS may provide NHIG from stock at a local hospital, issue stock direct or supply it via CSL, depending on the urgency.

For outbreaks, the PHU should discuss with ARCBS the number of potential patients involved and the best way to distribute the product according to whether a clinic will be set up or whether patients will be referred to individual GPs. If a clinic is planned, ARCBS will arrange for product to be transported to the site of clinic, but the PHU will need to ensure availability of suitable storage for the NHIG (e.g., the hospital blood bank or pharmacy). If it is planned to refer patients to individual GPs, a suitable central access point for NHIG will need to be identified (e.g., a local hospital blood bank or pharmacy). The PHU is responsible for notifying GPs on the process for accessing NHIG for their patients.

Small stocks of NHIG may be held at some hospitals including: Westmead, Wollongong, Gosford, John Hunter, Cessnock, Albury, Orange, Macksville, Port Macquarie, Lismore, Tamworth, Armidale, Narrabri, Wagga Wagga, Tumut, Griffith, Broken Hill, Hornsby and Sutherland.

Appendices

• Table 1. Post exposure guidelines - within 72 hours  /resources/publichealth/infectious/diseases/measles/post_exposure_guidelines_within_72hrs.pdf
• Table 2. Post exposure guidelines - 73 to 144 hours  /resources/publichealth/infectious/diseases/measles/post_exposure_guidelines_73_144hrs.pdf
• PHU Check list  /resources/publichealth/infectious/diseases/measles/measles_checklist.pdf
• Sample letters for child care, primary and high schools  /resources/publichealth/infectious/diseases/measles/sample_letters.doc
• Sample script: Waiting room contacts  /resources/publichealth/infectious/diseases/measles/sample_script.doc
• Measles Investigation Form  /resources/publichealth/infectious/diseases/measles/measles_form.pdf
• Factshest: Measles  /factsheets/infectious/measles.html
• Factsheet "Measles: Information for contacts"  /resources/publichealth/infectious/diseases/measles/measles_info_for_contacts.pdf