12. Measles

Mortality and morbidity

From 2000 to 2016, the annual reported measles incidence decreased by 75 percent worldwide, from 146 to 35 cases per million population, due to increased vaccine coverage.[14] Annual worldwide estimated measles deaths was 89,780 in 2016, representing an 84 percent decline since 2000.[15]

However, there was a worldwide increase in disease during 2019. Over 1.3 million confirmed and suspected cases of measles were reported to WHO from 187/194 member states, resulting from multiple outbreaks, including in the previously measles-free Americas.[16]

Although measles mortality rates have fallen significantly,[17] measles remains an important vaccine-preventable cause of death among children throughout the world, particularly in low-income countries in Africa and Asia. The disease is highly infectious in non-immune communities, with epidemics occurring approximately every second year. During 2019, the countries with the highest number of cases were Philippines, Madagascar, India, Ukraine, the Nigeria and Brazil.[16] The incidence rate in Samoa was almost 10 times that observed in New Zealand (4525 versus 476 per million population). In Samoa, around 1.5 percent of cases died and one-third were hospitalised (there were 83 deaths, 5,707 cases and 1,868 hospitalised as of 20 January 2020).[18]

Measles elimination

When a country is verified by the Measles Regional Verification Commission as having eliminated measles, it means that the country interrupted transmission of the endemic strain of circulating measles virus for a period of 36 months. Importations of measles virus may have occurred during this period, but circulation of the imported strains of measles virus was interrupted within 12 months of the importation.[19]

In May 2012 the 194 member states of the World Health Assembly endorsed the Global Vaccine Action Plan 2011–2020,[20] which aimed to eliminate measles in at least four WHO regions by 2015 and in five WHO regions by 2020. In September 2016, the Region of the Americas was the first WHO region to be declared free of endemic measles and New Zealand was verified as having eliminated measles in 2017.

Disappointingly, no region has sustained measles elimination. Measles cases were reported to have climbed by 300 percent globally in the first three months of 2019.[21] For example, four European countries (Albania, Czechia, Greece and the UK) lost measles elimination status and the US reported it highest number of cases in 25 years.[22] Global coverage for the first measles vaccine dose has stalled at 85 percent and for the second doses at 67 percent, falling short of the 95 percent required to prevent outbreaks.[21]

Measles vaccine was introduced in in New Zealand in 1969 and moved to a two-dose schedule (as a combined MMR vaccine) in 1992. Measles became a notifiable disease in 1996. The two-dose schedule at ages 15 months and 4 years was introduced in 2001 (see Appendix 1 for more information about the history of the Schedule) and was changed in 2020 to 12 months and 15 months following the 2019 outbreaks.

Historical holes in coverage, due to a combination of issues including historically low immunisation coverage in the childhood programme, unfounded vaccine safety concerns at the turn of the 21st century, changes to the schedule for MMR dose 2 from age 11 years to 4 years and compromised vaccine due to lack of adequate cold chain processes prior to 2004 have meant that young adults and adolescents (ages 15–30 years), in particular, are under immunised against measles.[23]

Prior to the introduction of two-dose MMR schedule, measles epidemics occurred in 1991 (the number of cases was estimated to be in the tens of thousands) and 1997 (when 2,169 cases were identified). In 2019, nine outbreaks occurred, six were linked to imported cases from the Philippines, Japan, Thailand, Australia and Singapore. In 2019, 2,213 cases were notified, of which 775 were hospitalised (ESR, 8 June 2020). The worst affected district was Counties Manukau, which had 1,174 cases, many of whom were of Māori and Pacific ethnicity, children too young to be immunised and unimmunised young adults.[24]

Importation of measles by non-immune people who had travelled overseas was also linked to the smaller measles outbreaks in New Zealand in 2009, 2011, 2014 and 2016 (see Figure 12.1; see also section 12.5.5).

Figure 12.1: Number of measles notifications by month reported, January 2009 to December 2019

The measles vaccine is only available as one of the components of MMR. This vaccine is a freeze-dried preparation containing live attenuated measles, mumps and rubella viruses.

Funded vaccine

Other vaccines

M-M-R II (MSD) was the funded vaccine prior to the 1 July 2017 Schedule change. It contains a attenuated line of measles virus derived from Enders’ attenuated Edmonston strain; the Jeryl Lynn (B level) strain of mumps virus; and the Wistar RA 27/3 strain of live attenuated rubella virus.

Two quadrivalent measles, mumps, rubella and varicella vaccines (MMRV: see chapter 24) are also registered but not currently available in New Zealand:

• Priorix-Tetra (GSK) contains n the Schwarz measles, RIT 4385 mumps, Wistar RA 27/3 rubella and Oka/Merck varicella-zoster virus strains.
• ProQuad (MSD) contains Enders’ attenuated Edmonston (Moraten) measles virus strain, Wistar RA 27/3 rubella virus, Jeryl Lynn mumps virus and live varicella virus vaccines (Oka/Merck).

Measles vaccines are highly efficacious, and immunisation programmes have controlled measles to the point of elimination in many populations.[26] Outbreaks and epidemics continue to occur where low immunisation rates and/or sufficient numbers of susceptible members of communities are present. A 2012 Cochrane review of the safety and effectiveness of MMR concluded that a single dose of MMR is at least 95 percent effective in preventing clinical measles and 92 percent effective in preventing secondary cases among household contacts aged 6 months and older.[27] This was a systematic review of clinical trials and studies, which involved approximately 14.7 million children.

Seroconversion to all three viruses of MMR occurs in 85–100 percent of recipients. ‘Primary vaccine failure’ refers to the lack of protective immunity despite vaccination. It is due to failure of the vaccine to stimulate an immune response. This occurs in 5–10 percent of recipients after the first dose and is rare after a second dose. More than 99 percent of people who receive two MMR doses (given at least four weeks apart, with the first dose given after age 12 months) develop serologic evidence of immunity to measles.[9] Two doses are required for measles control and elimination in populations.[9] The second MMR dose is not a booster: it is given to increase vaccine efficacy to 98 percent and address primary vaccine failure.

Measles vaccination may have nonspecific effects, reducing mortality from other infectious diseases. Infection with the measles virus causes immune memory loss and predispose people to opportunistic infections for more than three years.[5, 7, 8] Population-level data from the UK, US and Denmark indicates that when measles was common, measles virus infections could have been implicated in as many as half of all childhood deaths from infectious disease.[8] The reduction in measles infections is suggested to be the main factor in reducing overall childhood infectious disease mortality after the introduction of vaccination.

Duration of immunity

Even though antibody levels decline over time, secondary vaccine failure (ie, vaccine failure due to waning of protective immunity) has been documented for measles but remains rare.[28] There were three cases in the recent New Zealand outbreak with documented secondary vaccine failure but no transmission was recorded from these cases. Breakthrough cases, as a result of secondary vaccine failure, appear to be attenuated and less likely to be hospitalised.[29]

In Finland in 1982 a cohort was recruited at the start of the national MMR vaccination programme to study the persistence of vaccine-induced antibodies. By the mid-1990s Finland had eliminated measles, mumps and rubella, and there was little opportunity for natural boosting to occur. The follow-up of this cohort has shown that while antibodies wane over time, 20 years after the second MMR dose, 95 percent of people remained seropositive for measles.[30] The antibody avidity also decreased by 8 percent for measles.[31] Waning of both the concentration and the avidity of antibodies might contribute to measles infections occurring in individuals who have received two doses of MMR. Waning in immunity was suggested in a small proportion of vaccinated cases (less than 1 percent) in the 31–42 year age group reported in an outbreak in Berlin.[32]

Transport according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017 (2nd edition).

Store at +2°C to +8°C. Do not freeze.

MMR must be reconstituted only with the diluents supplied by the manufacturer. Use MMR as soon as possible after reconstitution. If storage is necessary, reconstituted vaccine can be stored at +2°C to +8°C for up to eight hours.

The dose of MMR is all of the reconstituted vaccine (approximately 0.5 mL) administered by intramuscular injection, or subcutaneous injection if indicated (see section 2.2.3).

Co-administration with other vaccines

MMR can be given concurrently with other vaccines, as long as separate syringes are used, and the injections are given at different sites. If not given concurrently, live vaccines should be given at least four weeks apart. (See also section 2.2.7 for information about multiple injections at the same visit.) Note that TST/Mantoux testing for tuberculosis must be deferred by at least four weeks after MMR if not given concurrently (see section 12.6.2).

Interchangeability

The two brands of MMR (Priorix and M-M-RII) may be used interchangeably for completion of a course.[33]

A two-dose MMR vaccination schedule (with appropriate documentation) is recommended irrespective of a history of measles, mumps or rubella infection or measles immunisation. A clinical history does not reliably indicate immunity. Positive serology for measles cannot be used as a proxy for mumps or rubella immunity. There are no known ill effects from vaccinating children, even if they have had serologically confirmed infection with any of the viruses.

Measles vaccine is recommended as MMR at age 12 and 15 months. Two doses of measles vaccine are recommended because nearly all the approximately 5 percent who fail to be protected by the first dose will be protected by the second.[9] The second dose of measles vaccine can be given as soon as four weeks after the first dose.

MMR vaccination when aged under 12 months

A dose of MMR (called MMR0 [zero]) may be recommended for infants aged 4 months to under 12 months during measles outbreaks for pre-exposure prophylaxis (for post-exposure prophylaxis and HNIG use see section 12.8). These children still require a further two doses of MMR at ages 12 months (given at least four weeks after previous dose) and 15 months because their immune response and long-term protection from measles is less when the vaccine is given at a younger age.[34, 35] Any recommendations in this regard will be made by the local medical officer of health and Health New Zealand | Te Whatu Ora based on local epidemiology.

The first dose of MMR is scheduled and recommended at age 12 months, if infants are given MMR from age 11 months in other circumstances, they are considered to have been given MMR1 and therefore only need one further dose, ideally given at age 15 months. To optimise early protection, dose two can be given from age 12 months, at least four weeks later. For toddlers and children older than 15 months, give both doses of MMR four weeks apart.

Note:

• For infants born to mothers who received immunomodulatory biologic agents in pregnancy, see precautions section 12.6.2 and section 4.2.5.
• Some immigrant children may have received a measles-containing vaccine when aged under 12 months.

Two doses of documented MMR (at least four weeks apart) are recommended and funded for any child, adolescent or adult who is known to be susceptible to one or more of the three diseases.

A second dose of MMR should be given at least four weeks after MMR1 to all children who are older than 15 months but have not yet received their second MMR dose (ie, those who would have been due their second dose at age 4 years).

Adults born from 1 January 1969

All individuals born in 1969 or later who have documented evidence of two doses of MMR given after age 12 months or who have serological evidence of protection for measles are considered immune to measles.

Some adults may have received one dose of measles-containing vaccine and one dose of MMR or MR during one of the catch-up campaigns (eg, the 1997 campaign, when all those aged up to 10 years were offered MMR, or from international schedules). They will have therefore received the recommended two doses of measles vaccine, but only one of mumps and rubella vaccines. While the main reason for a two-dose MMR schedule is to protect against measles, two doses of all three antigens is recommended and funded. These individuals can receive a second dose of MMR (ie, a third dose of measles vaccine) without any concerns. It is important that women of childbearing age are immune to rubella (see chapter 21).

All persons born from 1 January 1969 with only one documented dose of prior MMR should receive a further dose of MMR; if there are no documented doses of prior MMR or documented evidence of immunity, then two doses should be administered, at least four weeks apart.

Occupational risk groups

Certain occupational groups are at increased risk of exposure to measles; particularly those who travel frequently, such as military personnel and cruise ship staff and aircrew (in this case MMR is funded for those eligible for New Zealand health services). See Table 4.9 for details of relevant occupational groups.

Contacts of immunocompromised individuals

In general, MMR is contraindicated in immunocompromised individuals (see section 4.2.5). These people can be partially protected from exposure to infection by ensuring that all their close contacts, including hospital staff and family members, are fully immunised (this is funded), including hospital staff and family members, through cocoon strategies. There is no risk of transmission of MMR vaccine viruses from a vaccine recipient to an immunocompromised individual. See section 12.7.2.

See also ‘Vaccination of close contacts of immunocompromised individuals’ in section 4.3.1 for general vaccination information for contacts of immunocompromised individuals.

(Re)vaccination before or following immunosuppression

MMR is funded to be given at least 28 days before planned immunosuppression.

For vaccination or revaccination following immunosuppression (funded), it is important to be sure that the individual is immunocompetent enough to safely receive the vaccine.

HIV infection

Discuss vaccination of individuals with HIV infection with their specialist (see ‘HIV infection’ in section 4.3.12).

Receipt of MMR, on time at age 12 and 15 months, is recommended for asymptomatic children who are not severely immunocompromised. MMR is recommended for all HIV-positive individuals aged from 12 months, whether they are symptomatic or asymptomatic, if their CD4+ lymphocyte level is over 15 percent or CD4+ lymphocyte count is at least 200 cells/mm³. Administration of MMR with CD4+ counts below these recommended levels has been associated with vaccine-related pneumonitis (from the measles component).[9]

MMR is contraindicated during pregnancy. Pregnancy should be avoided for four weeks after MMR vaccination.[1, 9]

After delivery

If MMR and Rhesus anti-D IG are required after delivery, both the vaccine and anti-D IG may be given at the same time, in separate sites with separate syringes. The vaccine may be given at any time after the delivery. Anti-D IG does not interfere with the antibody response to the vaccine, but whole blood transfusion does inhibit the response in up to 50 percent of vaccine recipients (see section A6.4.1).

MMR can be given to breastfeeding women.

(See also sections 4.1.3, 12.6.1 and 21.5.3.)

International travel is an important factor in reintroducing measles into New Zealand. To avoid importing measles to New Zealand, vaccination with MMR is recommended for all children aged 12 months and older and adults travelling overseas if they have not previously been adequately vaccinated (see Appendix 2 for planning catch-up immunisations). Infants aged from 4 months can receive a dose of MMR if they are travelling to a country with an active measles outbreak. These children will still require two doses from age 12 months to be fully immunised.

Measles remains endemic in many countries, including areas in Europe, Asia, the Pacific and Africa, and outbreaks are ongoing worldwide. A high rate of measles incidence was reported in the Philippines during 2019 and early 2020.[36] During January to October 2019, 52 (64 percent) out of 81 imported measles cases in the US were residents returning from travel abroad and 73 (90 percent) were unvaccinated or had unknown vaccination status. Eight outbreaks (85 percent of cases of the resulting 1,259 cases) were associated with unvaccinated close-knit populations, such as the Orthodox Jewish community in New York; these began from two single imported cases.[37] Travel was also linked to the measles outbreaks in New Zealand in 2011, 2014, 2016 and 2019.

The general contraindications that apply to all immunisations are relevant to MMR (eg, children with an acute febrile illness should have their immunisation deferred).

Anaphylaxis following a previous dose of MMR or any of the vaccine components is a contraindication to a further dose of MMR. Individuals who have anaphylaxis after receiving MMR should be serologically tested for immunity and referred to, or discussed with, a specialist if they are non-immune to rubella or measles.

MMR is contraindicated for:

• those with proven anaphylaxis to the vaccine or vaccine component (eg, neomycin)
• immunocompromised individuals (ie, those with significantly impaired cell-mediated immunity, such as those with untreated malignancy, type 1 interferon receptor (IFNAR) signalling pathway defects, or altered immunity as a result of drug therapy, including high-dose steroids, or receiving high-dose radiotherapy) (see section 4.2.5)
• individuals who have received another live vaccine, including BCG, within the previous 4 weeks unless given concurrently (for BCG, see chapter 23)
• pregnant women – pregnancy should be avoided for four weeks after immunisation[1, 9] see section 21.5.3)
• individuals who have received IG or a blood transfusion during the preceding 11 months (see Table A6.1 in Appendix 6 for the length of time to defer measles vaccine after specific blood products)
• those with severe immune deficiency from HIV, because vaccine-related pneumonitis (from the measles component) has been reported[9] – discuss vaccination of individuals with HIV infection with their specialists.

Note: Inadvertent immunisation with a rubella-containing vaccine in early pregnancy is no longer considered an indication for termination of pregnancy. There have been no cases of teratogenic damage from vaccine virus despite intensive surveillance in the US, the UK and Germany.[38]

Children with a history of seizures should be given MMR, but the parents/guardians should be warned that there may be a febrile response. In the case of children with current ITP, the timing of vaccination should be discussed with their specialist.

Women of childbearing age should be advised to avoid pregnancy for the next four weeks after MMR vaccination (see section 21.5.3).[1, 9]

Measles vaccination may temporarily suppress tuberculin skin test (TST/Mantoux) reactivity, so if required, a TST should be placed on the same day as MMR vaccination or be postponed for four to six weeks after vaccination.[9] TST is not a prerequisite for measles vaccination. An individual with active TB should be established on treatment before administering MMR.

For infants aged under 12 months, please discuss immunomodulatory therapies taken during pregnancy with infant’s mother or specialist, or contact IMAC before administration of MMR0. See section 4.2.5.

Interferon alpha receptor deficiencies

IFNAR deficiencies can increase the risk of severe reaction to some live viral vaccines, such as MMR.  These are extremely rare immune disorders that can result in a defective response to certain viruses, including measles and COVID-19.[39] If an older sibling or relative had a severe illness following MMR this should be discussed with immunisation specialists. If a child did not develop a serious illness in response to their first dose of MMR, it appears unlikely that they will have a serious reaction to their second MMR vaccine due to undiagnosed IFNAR1 deficiency. For more information see section 4.3.2.

The measles and mumps components of the MMR are manufactured in chick embryo cell culture, so there may be trace amounts of egg protein in the vaccine. Egg allergy, including anaphylaxis, is not a contraindication to measles-containing vaccines. Various studies have confirmed that children with egg allergy can be vaccinated safely.[9, 40, 41] Other components of the vaccine may be responsible for allergic reactions.[42] Individuals with egg allergy may therefore be safely vaccinated in primary care.[43]

Some children, around 5–15 percent, may experience fever of 39.4°C or more between 6 and 12 days after immunisation that generally lasts one to two days and is associated with a strong measles antibody response.[9, 44] Rash, often with atypical distribution, can occur in approximately 5 percent of vaccine recipients at the same interval post-vaccination: these individuals are not infectious to others.[9] Fevers, rashes and other systemic symptoms can occur coincidentally after vaccination due to common childhood infections and are not caused by the vaccine.[45]

Serological tests or PCR can be expected to be positive if performed during this time, so testing should not be routinely performed. During an outbreak, genotyping the sample can help to identify vaccine strain versus wild type disease.

The mumps vaccine may produce parotid and/or submaxillary swelling in about 1 percent of vaccine recipients, most often 10–14 days after immunisation.[46] The rubella vaccine can cause a mild rash, fever, joint pain and lymphadenopathy between one and three weeks after immunisation.[9, 47] There were no persisting sequelae associated with the administration of 3 million doses of MMR to 1.5 million children in Finland.[45, 48]

Temporally related reactions, including febrile seizures, nerve deafness, aseptic meningitis, encephalitis, rash, pruritus and purpura, may follow immunisation rarely; however, causality has not been established.[49]

Vaccine virus transmission

MMR vaccine viruses are regarded as being non-transmissible from vaccine recipients. Two historical, poorly documented case of transmission (of a rubella and a mumps vaccine strain) were reported from a vaccine that is no longer in production.[50] Following immunisation with both measles and rubella vaccines, live virus has been isolated rarely from pharyngeal secretions.[38, 51] There have been no confirmed cases of disease transmission from MMR vaccine viruses.

Idiopathic thrombocytopenic purpura

MMR is the only childhood vaccine with an elevated risk of ITP, which occurs in 1 in 25,000 to 40,000 people, 15 days to six weeks after immunisation.[9] ITP is mild and transient, resolving within six months in 93 percent of cases.[1, 52] If ITP occurs, measles, mumps and rubella serology should be measured, and if the individual is immune to all three infections, a second dose is not required. However, if the individual is susceptible to any of the three infections, a second dose should be administered.[53, 54, 55] The risk of thrombocytopenia is higher after the first dose of vaccine than after the second dose and is much rarer after vaccination than after wild-type infection.[9]

Over three decades, multiple published epidemiological studies in the UK,[56] Finland[57] and elsewhere[27] have confirmed that there is no link between MMR and the development of autism in young children (see section 3.2.4 for further discussion on this issue).

A single case of measles should be considered an outbreak and result in an appropriate outbreak response. Practitioners should have a low index of suspicion for notification, and all suspected clinical cases should be self-isolated immediately and notified to the medical officer of health.

The standard clinical case definition for measles is ‘an illness characterised by all of the following: generalised maculopapular rash, starting on the head and neck then spreading down and out and fading; fever (at least 38°C if measured) present at the time of rash onset; and cough and/or coryza and/or conjunctivitis and/or Koplik’s spots present at the time of rash onset’.

It is important that the diagnosis be laboratory confirmed, as many viral infections can mimic measles. 

For more details on case definition, diagnosis and management, refer to the ‘Measles’ chapter of the online Communicable Disease Control Manual.

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39. Bastard P, Hsiao K-C, Zhang Q, et al. A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes. J. Exp. Med, 2022. 219(6).
40. James JM, Burks AW, Roberson PK, et al. Safe administration of the measles vaccine to children allergic to eggs. New England Journal of Medicine, 1995. 332(19): p. 1262-6.
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