Alternative routes of measles immunization: a review

Measles is one of the major causes of childhood mortality in developing countries, despite current prevention of over 2 million child deaths each year by measles vaccination programmes. New strategies, such as mass campaigns, and possibly new preparations of measles vaccines, may facilitate further progress in controlling the disease and improving the prospects for its ultimate eradication. To evaluate the potential for non-percutaneous routes of vaccine administration to improve control, we reviewed studies of serological responses to measles vaccine after intradermal, conjunctival, oral, aerosol and intranasal administration. The response to intradermal vaccination exceeded percutaneous results in only one of eight instances in five studies where such comparisons could be made, often producing substantially lower seroresponses. Further, intradermal administration using a needle and syringe is more difficult than subcutaneous vaccination. After oral administration of vaccine, less than 50% of children seroconverted in three small studies. Intranasal administration has not yet been studied extensively, but it may be susceptible to interference by upper respiratory infections. Seroconversion after conjunctival administration was very variable, and this route was difficult practically in young children. In infants below 9 months of age, aerosol administration of vaccine resulted in 80% or better seroresponse in seven of nine trials, with the Edmonston-Zagreb strain in standard titre doses consistently producing better results than the Schwarz strain. However, seroresponses after subcutaneous administration clearly exceeded those from aerosols of the same vaccine in four of six comparisons. Several trials noted practical difficulties in aerosol administration in young infants. In contrast, older seronegative children generally responded well to aerosol administration of vaccine (above 90% and often 100% seroresponse), regardless of vaccine strain and often with surprisingly low estimated retained doses. In each of three studies where it was possible to compare the same vaccines given percutaneously and by aerosol to seropositive children, better seroresponses followed aerosols. In older children, aerosols of the Edmonston-Zagreb strain also rather consistently provided better seroresponses than aerosols of the Schwarz strain, with the most notable differences in seropositive children. Thus, with the possible exception of very young infants, the aerosol route is promising and offers several theoretical and practical advantages as well. Further randomized trials should be conducted to evaluate comparative responses to aerosolized, intranasal, and subcutaneous vaccine, especially in those age ranges targeted for mass campaigns (most commonly 9 months to 15 years). The development of improved technology for aerosol delivery of measles vaccine would greatly advance the potential for wide scale use of this route, especially in mass campaigns in low income countries.