Measles, in spite of available vaccination, remains a heavy public health burden worldwide especially in developing countries with 30-40 million cases occuring annually. In 2002, there were an estimated 610 000 deaths due to measles worldwide, 540 000 of them in children under the age of five, representing 30-40% of the burden of vaccine-preventable diseases in childhood. Measles may be ultimately responsible for more child deaths than any other single agent because of complications from pneumonia, diarrhoea and malnutrition. Measles is also the major cause of preventable blindness in the world, affecting the same disadvantaged populations.

Of the deaths attributable to measles, 98% occur in developing countries, where vitamin A deficiency is common. Case-fatality rates in these countries are usually estimated to be in the range 1-5% but may reach 10-30% in some situations. Specific goals for reduction in measles mortality and morbidity were set by the World Heath Assembly in 1989 and the Word Summit for Children in 1990, as major steps towards the eventual eradication of the disease. Subsequently, target dates of 2000, 2007 and 2010 for its elimination were established for the Region of the Americas, the European Region and the Eastern Mediterranean Region respectively. The aim in the African Region, the South-East Asia Region and Western Pacific Region is to reduce measles mortality.

Several strategies are now developed to increase coverage of immunization including a two-dose schedule, mopping up strategies, supplementary immunization strategies such vitamin A supplementation, one-round national and regional mass immunizations, and development of high-quality case-based measles surveillance supported by regional measles laboratory.

Vaccine

Measles vaccination is one of the most cost effective health interventions available and one of the most powerful tools for providing health equity to poor children. It is cost-effective to improve routine measles vaccination, as preliminary estimates suggest that the cost per life-year gained for expanding measles coverage from 50% to 80% is US$ 2.53 in areas with high disease incidence and high measles case-fatality ratios. Measles vaccine is highly effective, safe and inexpensive. With US$ 0.15 for one measles vaccine dose, children in developing countries can survive exposure to measles without sequelae. However, coverage with measles vaccine is low in many countries due to limited resources. Coverage could be greatly enhanced if the method of administration could be simplified. Current measles vaccination requires injection with a needle and syringe. The drawbacks of the needle and syringe technology are as follows:

• it requires highly skilled personnel to administer the vaccine;
• it is associated with a risk of transmitting blood-borne diseases such as hepatitis and HIV if syringes and needles are re-used. This risk can be minimized if auto-disable syringes are used; and
• injection may be painful and present a risk of infection if a proper technique is not used.

As the natural route of infection for measles virus is the respiratory tract, administration of live attenuated measles vaccine through the respiratory tract has been investigated as an alternative to injection. Early studies have shown fewer acute adverse events following aerosol vaccination, as compared to conventional parenteral vaccine. Aerosolized vaccine is immunogenic and affective in seronegative and seropositive children. More than 4 million children were vaccinated with aerosolized measles vaccine in mass immunization campaigns in Mexico with good public acceptance. Aerosol vaccination can be performed by non-medical staff with some training. As aerosol vaccination uses the same vaccine formulation as parenteral vaccination, most cold chain procedures are identical. Now that the development of a respiratory route of administration is so promising for measles vaccine, WHO has convened a Product Development Group (PDG) to identify critical licensure steps, define clinical trials strategies and assist in protocol design, identify sites for clinical trials and ensure adequate implementation, monitoring and documentation of good practice. Following the current work plan aerosolized measles vaccine could be licensed in 2007 and introduced in practical use in 2009. This project is managed as a partnership between WHO, CDC and the American Red Cross, with funding from the Bill & Melinda Gates Foundation.

In addition, studies are in progress to develop new measles vaccine effective for immunization of infants before 6-months of age. Indeed, infants are refractory to conventional measles vaccines in the presence of maternal anti-measles antibodies. To reach this objective several technologies are currently being tested including DNA vaccines, bacterial vectors, viral vectors (e.g. adenoviruses, poxviruses, alpha viruses) or ISCOMS.