Lessons from measles vaccination in developing countries.

Difficulties in reaching and sustaining high enough coverage combined with the need to delay vaccination until most infants have lost maternal antibodies make it hard to control measles with standard titres of measles vaccine. Maternal antibodies are no longer a factor in infants after 9 months in developing countries and after 15 months in developed countries. It would be good to have a vaccine which is effective in younger infants in order to protect them before they are exposed to natural measles infection. Attendance at vaccination sessions also tends to fall as children grow older. Since the Edmonston-Zagreb vaccine proved immunogenic in high concentration at ages 4-6 months in several countries, the World Health Organization in 1989 recommended using it in countries where measles before the age of 9 months is a major cause of death. A shortage of high-titre vaccines, however, led to delays in implementing this recommendation. The recommendation was subsequently rescinded after data from 3 countries with high background infant mortality revealed increased overall mortality among children receiving high-titre vaccines at 4-6 months compared with recipients of standard titre vaccines at age 9-10 months. This effect would probably not have been detected had the trials not been carried out with long-term mortality as an end point. These findings realerted the scientific community and funding agencies to measles, sparked the development and implementation of new technological approaches to develop measles vaccines which may be effective in the first few months of life, and prompted public health authorities to adopt new strategies. For now, early schedules of 2 vaccine doses given in the 1st year of life have been recommended in developing country populations at risk of measles morbidity and mortality before 9 months of age. Even though a recent analysis by Aaby et al. found that mortality declines unexpectedly with standard titre vaccine before 9 months of age, the relative efficacy and safety of this double-dose approach has yet to be formally tested. The finding of excess mortality after high-titre vaccines has also focused attention on immune function after measles and measles vaccines. It is suspected that high-titre vaccines cause long-term disruption of immune function, including an imbalance in the type of helper T cell response. Aaby et al. also suggest that standard-titre vaccines reduce overall mortality by general immunostimulation. The authors conclude by urging that vaccinations be introduced only after rigorous trials have been conducted with mortality as an end point.