World health organization regional office for the western pacific regional guidelines

Adding rubella vaccine

Adding rubella vaccine to the immunization schedule is simple: change from measles vaccine to measles-rubella vaccine (MR) or measles-mumps-rubella vaccine (MMR).

The 2003 UNICEF price for a 10-dose vial of measles, MR, and MMR is US$1.21, $4.80, and $12.40, respectively. The UNICEF supplied MMR has Urabe strain mumps, which is known to have an increased risk of aseptic meningitis in about 1 in 10,000 recipients. (Several countries in the Region MMR with the Jeryl-Lynn strain mumps vaccine, which does not cause aseptic meningitis.) The rubella component does not cause any vaccine reactions apart from joint pains in adults.

The added cost and complication with mumps vaccine means that MR vaccine will be the preferred choice in the poorest countries. Measles and rubella are higher priorities than mumps control, because of its lower disease burden.⁶ However, WHO recommends the use of MMR for countries that have the capacity and resources to control all three diseases, as the mumps disease burden is not trivial (encephalitis, deafness, and other complications including the risk of testicular cancer).

In the current market, the price of rubella vaccine on its own is greater than for MR. Rubella vaccine on its own would also require additional injections and/or visits, and is therefore not recommended.

MR vaccine is likely to be the preferred way to introduce rubella in most countries that have not yet done so. MMR is also acceptable, but adds substantial costs.

Timing and number of doses

MR may be given from age 9 months or later. The timing of the first dose will be determined by measles epidemiology. WHO recommends measles vaccine at age 9 months, even though efficacy is lower than if given at 12 months, because when measles is common there are many children under one who get measles, and this age group has the highest mortality.

As countries move towards elimination and measles is no longer common, there are advantages to giving the first dose at age 12 months, because of the greater vaccine efficacy – even though it means that infants remain unprotected for longer.

Unless measles is endemic, the first dose of MR vaccine should be at age 12 months.

A single dose of measles vaccine has around 85% efficacy if given at 9 months of age, rising to 95% efficacy if given at 15 months. Because measles is so infections it is recommended that a second dose of vaccine be given at least one month after the first dose. A second dose (given at the age of 12 months or older) results in 99% of recipients being protected.

Rubella vaccine failure is lower (only 2 to 5%) – even when given at nine months.⁷ Rubella is also less infectious than measles. A single dose of rubella would be adequate, but it is operationally simpler for the immunization programme to use the same vaccine for both doses of measles. The second dose of rubella vaccine will also protect those who failed to be protected by the first.

A second dose is needed for measles, but not necessarily rubella; two doses of MR are operationally simpler and preferred (if affordable).

The second dose can be given at any time, but at least one month after the first dose.

Action for all countries

The Western Pacific Region has resolved to eliminate measles, and to “use measles elimination and hepatitis B control strategies to strengthen EPI and other public health programmes, such as prevention of congenital rubella syndrome” [WPR/RC54.R3]. Therefore, all countries should:

• 
  incorporate rubella surveillance (including laboratory confirmation) as part of their measles (acute febrile rash {AFR}) surveillance system.
  
• 
  assess the burden of rubella disease so as to help make informed decisions
  
• 
  consider adding rubella vaccine as part of the measles elimination programme
  

Incorporating rubella with measles surveillance

The Western Pacific Regional resolution included a resolve “to develop or strengthen measles surveillance systems and laboratory confirmation of cases” [WPR/RC54.R3].

Patients with acute febrile rash (AFR) who are suspected of having measles need laboratory tests to confirm the diagnosis. Those who are negative for measles should be tested for rubella. Thus, rubella surveillance can easily build on the requirements of measles surveillance.

All countries should include:

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  Rubella IgM testing for suspected measles (or febrile rash) cases if measles–negative.
  
• 
  Routine analysis of rubella cases as part of the measles (AFR) surveillance system
  

Laboratory network

Establishing a formalized laboratory network and ensuring that all samples are tested or confirmed in an appropriate network laboratory will enable reliable laboratory testing. A laboratory network allows standardised testing and reporting structures to be developed and establishment of a strong environment of quality assurance and referral procedures.

The WHO Measles Laboratory Network currently consists of 671 laboratories globally that test for rubella as well as measles to confirm the diagnosis in cases of rash and fever. The network consists of three tiers of laboratories (Global Specialized, Regional reference and National). Some countries are also establishing sub-national laboratories.

Estimating rubella disease burden

In countries without immunization programmes rubella epidemics occur every 5 to 9 years, with additional rubella cases during the inter-epidemic periods. There will be between 10 and 40 cases of CRS per 10,000 births from an epidemic, but many less between epidemics. An overall estimate of CRS burden (without immunization) is thus between 1 and 10 cases per 10,000 births.

Because of the substantial costs and difficulties in assessing disease burden, some countries (that do not have existing CRS surveillance) may choose to make the decision about rubella vaccine, based on the likely estimated incidence of between 1 and 10 cases per 10,000 births.

Countries with no CRS surveillance have these options for assessing CRS burden:

1. 
   Use existing data in the literature (or the estimated incidence as above)
   
2. 
   Conduct a serosurvey (including in pregnant women)
   
3. 
   Conduct retrospective study for CRS – using hospitalisation data, or data on blindness and/or deafness
   

A decision based on likely incidence of disease can be strengthened with data from neighbouring countries. In the case of the Pacific island countries, large rubella epidemics have been documented to occur six-yearly in Tonga and Samoa. However, CRS surveillance has not yet identified the CRS burden in these countries, highlighting the challenge of undertaking CRS surveillance. However, in both Tonga and Samoa there was also an important additional burden form rubella encephalitis.

A serosurvey can establish the age-profile of immunity, and hence the likelihood of CRS cases. A serosuvey will require a study protocol, ethical clearance, informed consent for the participants, as well as actions to be taken in relation to advising the individuals who were negative. Alternatively, a convenience sample may be undertaken using the residual sera of bloods taken for other purposes; however this would still require a proper protocol, and the testing undertaken by a laboratory with the appropriate quality control (or part of the Measles Laboratory Network).

Retrospective identification of cases from hospital data has been used to identify cases.⁸ In addition, data on the incidence (by year of birth) of new cases of deafness and blindness can identify possible rubella outbreak years and also give an indication of CRS burden. The retrospective surveillance is also complex, but can be achieved much faster than prospective CRS surveillance.

Establishing CRS surveillance

The primary disease burden from rubella is from CRS. Establishing surveillance for CRS is not straightforward and requires considerable resources. Even then, many cases of CRS may be missed – because of failure to present to health services or lack of clinical and/or laboratory expertise needed to detect them. For example, in Costa Rica there were no notifications of CRS from 1992, but active search at the National Children’s Hospital for the period 1996-2000 identified 49 CRS cases.⁹

CRS surveillance is important for monitoring the impact of immunization, as well as for estimating disease burden. However, the challenges of establishing CRS surveillance should not delay implementing rubella immunization. But, it is essential to have access to laboratory tests for rubella, and to have at least one major hospital site that can monitor for CRS cases by testing the blood of infants with defined congenital defects. Annex 3 provides guidance on establishing CRS surveillance, and gives an indication of the resources that will be needed.