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Adverse reaction potential of three measles-mumps-rubella combination vaccines



In a recent issue of the Revista Panamericana de Salud Pública/Pan American Journal of Public Health, Santos et al. (1) reported meticulous data on adverse reactions attributable to three different measles-mumps-rubella (MMR) combination vaccines. Their findings would certainly guide public health administrators and clinicians all over the world to offer the least-toxic vaccine combinations. Nevertheless, before these data are extrapolated and applied in the field, it would be better if the potency of different combination vaccines in the field were also addressed. Lyophilized lots of measles vaccines have to be constantly maintained at a cold temperature. Reconstituted measles vaccine undergoes a 50% loss of potency after exposure to 22 °C–25 °C for only 1 hour. Furthermore, its exposure to a temperature above 37 °C leads to inactivation within 1 hour (2).

Field evaluations of storage facilities and potency of measles vaccines designated for use in the Brazilian Immunization Program have been alarming (3, 4). During the early 1990s, measles vaccine titers in 100% of vaccine samples in public health units in Niterói and São Gonçalo, two municipalities in the state of Rio de Janeiro, were under the minimal recommended potency (3). Four years later, in 55.2% of the vaccine lots at the respective public health units in Niterói the titers were under the minimum recommended potency (4).

Storage of measles vaccine lots in government and private sector facilities at temperatures higher than the ones stipulated has been documented in both developing and industrialized countries. Several studies, for example, have looked at the case of Nigeria (5, 6). In two government-recognized vaccination centers in the city of Ibadan the quality of measles vaccines offered to vaccinees was inadequate. At the Adeyo Maternity Centre in Lagos the vaccine titer was less than 102 50% tissue culture infective dose in 5 of the 7 lots examined, and the resultant seroconversion rate was 26%. However, in the Institute of Child Health in Lagos, vaccine titers were low in only 4 of the 16 lots assayed, and 64% of the vaccine recipients had seroconverted. In the states of Lagos, Osun, and Oyo, vaccine potency was adversely affected at two levels, that of the local government area cold stores and that of the vaccination centers.

Nor is the situation in a highly developed country such as the United States of America perfect at all times. Inadvertent exposures to temperatures outside the ones stipulated were reported with refrigerators in pediatric offices and clinics in the city of Los Angeles, California (7). Other research, in the state of Georgia, found a variety of problems with the refrigerators or freezers used to store vaccines in the offices of private physicians who immunize children (8). The temperature inside the refrigerator exceeded 8 °C in 22% of the Georgia offices, and it was above 9 °C in 4.5% of them. The refrigerator temperature was lower than 1 °C in 14.9% of the refrigerators. There was no thermometer to monitor the true refrigerator temperature in 6.9% of the offices.

Irrespective of the individual vaccine components in combined measles-mumps-measles vaccines (1), only robust vaccine lots would offer an efficient armory. Whether they are subcutaneous or aerosol, future MMR vaccines should be designed to resist extended power outages. Power outages such as the ones that the state of California suffered in January 2001 are alarming. Similar episodes are not unlikely elsewhere, and they would be best addressed through the use of stabilized vaccines.


Subhash C. Arya
Nirmala Agarwal
Sant Parmanand Hospital
18 Alipore Road
Delhi-110054, India



1. Santos BA dos, Ranieri TS, Bercini M, Schermann MT, Famer S, Mohrdieck R. An evaluation of the adverse reaction potential of three measles-mumps-rubella combination vaccines. Rev Panam Salud Publica 2002;12(4):240–246.

2. Australia, National Health and Medical Research Council. The Australian immunization handbook. 6th ed. Canberra: Australian Government Publishing Service; 1997.

3. Oliveira SA, Homma A, Mahul DC, Loureiro ML, Camillo-Coura L. Avaliação das condições de estocagem da vacina contra o sarampo nas unidades sanitarias dos municipios de Niterói e São Gonçalo, estado do Rio de Janeiro. Rev Inst Med Trop Sao Paulo 1991;33(4):313–318.

4. Oliveira SA, Loureiro ML, Kiffer CR, Maduro LM. Re-evaluation of the basic procedures involved in the storage of measles vaccine in public health units of the municipality of Niterói, State of Rio de Janeiro, Brazil. Rev Soc Bras Med Trop 1993;26(3):145–149.

5. Onoja AL, Adu FD, Tomori O. Evaluation of measles vaccination programme conducted in two separate health centers. Vaccine 1992;10:49–52.

6. Adu FD, Adedeji AA, Esan JS, Odusanya OG. Live viral vaccine potency: an index for assessing the cold chain system. Public Health 1996;110(6):325–330.

7. Bishai DM, Bhatt S, Miller LT, Hayden GF. Vaccine storage practices in pediatric offices. Pediatrics 1992;89:193–196.

8. Bell KN, Hogue CJR, Manning C, Kendal A. Risk factors for improper vaccine storage and handling in private office providers. Pediatrics 2001;107(6):85–89.


Organización Panamericana de la Salud Washington - Washington - United States