Information for health-care workers - managing adverse events
Real-life case histories from the field
Some vaccines used in immunization programmes, such as measles, BCG, and yellow fever, are provided in lyophilized (freeze-dried) form and must be reconstituted before use with a diluent provided by the manufacturer. There is an opportunity for programmatic errors to occur in the handling of the vaccine. Reconstituted vaccines should be discarded not longer than six hours after reconstitution or at the end of a vaccination session, whichever is earlier, and should NEVER be kept and used in a subsequent vaccination session. Several examples are presented below of adverse events reported to the WHO in the last two decades which have been attributed to errors in reconstitution and handling of lyophilized vaccines.
In 1987, four separate AEFI clusters were registered with three, two, five and four cases, respectively, of "collapse" that occurred up to five minutes following immunization with measles vaccine. All 14 cases presented with hypotonia; 11 became pale; seven cases had cyanosis, dyspnoea and increased saliva secretion; three patients had depressed respiration and one patient died; others recovered in less than one hour. All involved clinics were visited. In two of the clinics vials that contained succinyl choline (anectine) and pancuronium bromide (pavulon) were found stored with vials containing vaccine and diluent. Vials containing pavulon and diluent were the same size and shape; labels on a number of vials recovered could not be read. Infra-red spectrophotometry of the urine of one of the cases revealed a metabolite of succinyl choline and thin layer chromatographic analysis of vaccine from one of the implicated vials showed the presence of pavulon.
In one hospital in September 1992, five neonates collapsed a few minutes following immunization with BCG and OPV. Neonates were one day (1), two days (3) and five days (1) old. They had been vaccinated at the maternity ward with BCG and oral polio vaccine within a two- to five-minute period. The first vaccinated child collapsed three minutes after vaccination with cyanosis and apparent shock. The physician indicated that the child had had a cardiac arrest. He resuscitated the child with an intra-cardiac injection of adrenaline and intramuscular hydrocortisone. Subsequently, the other four neonates collapsed with similar symptoms. Three were resuscitated and one died.
The medical records of the mothers of the five neonates had no significant findings. All neonates were being breast fed. The nurse who gave the vaccines was a highly qualified nurse-midwife; however, she had been assigned only a month earlier to the maternity ward where BCG vaccines were given and may have needed more training in immunization practices. In the hospital clinic, the following drugs were found in the refrigerator in which vaccines were also kept: pancuronium chloride, suxamethonium bromide and insulin. All incriminated BCG ampoules had been emptied and no further analysis was done. The hypothesis was that the vaccine had been reconstituted with a muscle relaxant which caused the reactions.
Three infants died in early April, 1995 after administration of measles vaccine. Symptoms, developing within five hours post-immunization, were fever, rash, vomiting, and diarrhoea, described by the attending health worker as "toxic shock syndrome." Reconstituted vaccine was routinely kept until it was used, and syringes were never sterilized, but washed with ordinary water and wiped with cotton wool. No testing could be done.
Four children died and a fifth was hospitalized after receiving measles vaccine from the same vial in February 1995. Vaccine was not refrigerated, and was transported house to house for immunization. Reactions began four to five hours after vaccination, with vomiting, unconsciousness, and meningeal irritation. Penicillin-resistant Staphylococcus aureus was cultivated from the incriminated vial. The same lot of measles vaccine had been distributed in more than 50 000 multi-dose units in four different countries, without reports of adverse events.
In June 2003, three infants, aged nine to eleven months, died following routine measles immunization. The three infants developed convulsions and died within minutes of vaccination. Three more infants were given the same vaccine before health workers learnt about the deaths and stopped the vaccination session. These three infants developed milder symptoms but survived.
An investigation of the deaths revealed that Suxamethonium (a muscle relaxant) had been used to reconstitute the vial of measles vaccine used to vaccinate the six children. Further, the information provided suggested that a few days prior to the vaccination session, as a result of a power failure, several vials of vaccine and ampoules of diluent were transferred by a health worker from the vaccine refrigerator in the health centre to a pharmacy refrigerator where both Suxamethonium and Pitocin (Oxytocin) were in stock (incidentally these two drugs were noted to have “similar containers”). On the day of vaccination, the vaccines and diluent were transferred back to the vaccine refrigerator. This wrong practice of storing vaccines with other drugs (coupled with lack of proper training for and/or inattention by the health workers involved) subsequently led to the fatal use of Suxamethonium as a measles vaccine “diluent".