The document describes investigating adverse events following immunization (AEFI). It provides an example of investigating convulsions reported in children after a measles campaign. The investigation found the convulsions were coincidental and not caused by the vaccine, as the first child had a history of prior convulsions. The report concludes it is important to properly investigate AEFIs to maintain confidence in immunization programs and determine if issues are related to vaccines, errors, or coincidences.

1. Respond Detect Report Investigate INVESTIGATING ADVERSE EVENTS FOLLOWING IMMUNIZATION AEFI

2. AEFI: An example of an AEFI investigation Background It is reported that following a measles campaign in a primary school in District X, several children had convulsions. It was widely rumoured that the measles injection was responsible for it One child had an attack of fit half an hour after the immunization. Following this three other children had fainting spells in the same class. All recovered spontaneously although the child who had the first convulsion took longer to recover. Also, the first child sustained a minor cut on the forehead from the fall Next day, five more children called in sick on grounds that they had also attacks of fits after the school

3. OVERVIEW Definitions Detecting and reporting AEFIs Conducting a case investigation Analysing and assessing AEFI data Taking action Measuring outcome

4. WHAT IS AN ADVERSE EVENT FOLLOWING IMMUNIZATION (AEFI)? A medical incident that takes place after an immunization, causes concern, and is believed to be caused by immunization Vaccine reaction - caused by vaccine’s inherent properties Programme error - caused by error in vaccine preparation, handling, or administration Coincidental - happens after immunization but not caused by it (a chance association) Injection reaction - anxiety or pain of injection not vaccine Unknown - cause cannot be determined

5. CLUSTER >=2 cases of the same adverse event following immunizations related in time, geography or in the vaccine administered Why is it important to monitor for clustering ?

6. POTENTIAL OBJECTIVES FOR IMMUNIZATION SAFETY SURVEILLANCE SYSTEM Detect, correct, and prevent programme errors Identify problems with vaccine lots or brand Prevent false blame from coincidental events Maintain confidence by properly responding to parent/community concerns while increasing awareness (public and professional) about vaccine risks Generate new hypotheses about vaccine reactions that are specific to the population Estimate rates of occurrence on AEFI in the local population, compared with trial and international data (particularly for new vaccines being introduced)

7. DETECTING AND REPORTING AEFIs

8. DETECTING AND REPORTING AEFIs Decide on WHICH events to be included in surveillance? WHO should be involved in detection? WHAT is the route of reporting? WHEN should AEFIs be reported? HOW should reporting occur? WHAT happens next?

9. AEFI Detection and reporting Every individual that administers an immunization injection should know about AEFI The following are events need to be reported and investigated immediately All deaths suspected to be related to immunization All hospitalisation suspected to be related to immunization Any event where vaccine quality is suspected

10. AEFI Detection and reporting The above basic categories act as “ trigger ” mechanisms for further course of action While minor events may be recorded and reported as a routine activity in monthly reports to be analysed only at periodic times, sudden, unexplained deaths or large scale hospitalisation or a cluster of events reported following immunisation warrants immediate investigation

11. Reporting of Severe AEFI

12. AEFI Investigation AEFI investigation will attempt to confirm or propose alternative diagnosis of the reported event identify the specifications of the vaccine incriminated examine the operational aspects of the programme identify whether it was an isolated event or a cluster of events and, if a cluster, where the immunization was given and what vaccines were used Preliminary investigation may be carried out by the local health worker, but serious AEFIs or clusters of AEFIs should be investigated from district or state/central level

13. AEFI Investigation Data on the patient(s); vaccine (lot number, expiry, manufacturer, lab results if any), storage, reconstitution practice, diluent used, general disease information in the area, similar disease episodes in unimmunized persons in the same locality, etc. should be collected Collect samples of vaccines and diluents used (make sure vaccine sample collected are kept in the cold chain)

14. FORMS USED FOR INVESTIGATION The reporting of the minor events is done on monthly basis in the form 9 of RCH The reporting for severe cases is done using First Information report (FIR) in 48 hrs Followed by Preliminary investigation report (PIR) within 7 days And a Final report in form of Detailed investigation report (DIR) within 90 days

15. AEFI: An example of an AEFI investigation Background It is reported that following a measles campaign in a primary school in District X, several children had convulsions. It was widely rumoured that the measles injection was responsible for it Hypothesis that the reported health event (convulsion) was an AEFI following measles vaccination Define the case You define your ‘case’ as any child in that primary school who received measles injection on that particular day and had convulsions .

16. AEFI: example contd.. Case investigation Line list all children, with age & sex, who had received measles injection on that day Find those that reported to have had convulsions Find out all the details regarding the convulsions- onset time after immunization, manner of convulsion, recovery following the convulsion, concomitant medications, fever, any other health problems. Determine the quality of the vaccine (expiry, storage), reconstitution, diluent, injection process, etc. Take samples of the vaccine vials used for lab testing Scrutinise the stock entries, stock balance, etc.

17. AEFI: example contd.. One child had an attack of fit half an hour after the immunization. Following this three other children had fainting spells in the same class. All recovered spontaneously although the child who had the first convulsion took longer to recover. Also, the first child sustained a minor cut on the forehead from the fall Next day, five more children called in sick on grounds that they had also attacks of fits after the school

18. AEFI Data analysis Once the data is collected, it should be analysed as quickly as possible to determine whether the AEFI is Programme related (incorrect dose of vaccine, wrong site, wrong diluent, improper storage & handling, use of other medicines as diluent, etc.) Vaccine induced AEFI Coincidental AEFIs (caused by something other than vaccine or programme errors) Unknown Laboratory support If patient hospitalised, tests may confirm diagnosis Testing vaccines often yield doubtful answers Send case investigation report with vaccine for test

19. AEFI: example contd.. Data Analysis You find that the vaccine used has not expired, was well maintained in the cold chain, correct diluent was used, There was no evidence of contamination, the health workers always discarded reconstituted vaccine at the end of the session. The medical history showed that the fits which the other children had were mere fainting spells, lasting only for a few moment, with spontaneous recovery. No subsequent attacks occurred The index child had a true convulsion. No fever or other illnesses at that time.

20. AEFI: example contd.. However, going over the medical history of the child, the health worker recalled that last year the same child had an episode of convulsion for which he had provided treatment. He had advised that the parents should consult a medical or a neurological expert for further management. On questioning, it was found that the parents did not have the time or the money to do that and it was felt that it would resolve naturally

21. AEFI: example contd.. Conclusion From the available information, and based on the data analysis, you conclude that event was not an AEFI, but Coincidental. Following this, you will take time to explain to the parents, teachers and the community about the event, your investigation and your final conclusions.

22. AEFI Corrective and other actions Action must not wait for investigation to be completed Treat the patient(s) as the first response Communicate, inform the public, parents, media people on the event, actions being taken & next steps Once the investigation is completed, publicise the results Take corrective actions, where necessary Training of health workers & supervision to prevent avoidable AEFIs in future

23. AEFI Avoiding Programme Errors Use sterile needle & syringe for every injection Reconstitute only with specific diluent Discard reconstituted vaccines after six hours Do not store drugs & other medicines in the same fridge as the vaccines and diluents Train & supervise health workers to ensure safe injection practices Monitor, Investigate and Act when AEFIs occur

24. AEFI Evaluation Like any other surveillance systems, AEFI surveillance must also be evaluated periodically to examine its usefulness and to modify it if necessary Issues to consider when evaluating a surveillance system are timeliness, completeness, accuracy of the system swiftness with which response was effected when a trigger event was reported appropriateness of actions taken potential for strengthening of immunization system

25. IDENTIFYING CAUSE OF AEFI CLUSTER Yes Yes Yes Yes Yes Yes No No No No No No Programme error, coincidental or vaccine problem/ “unknown” Manufacturer error, batch problem, or transport/storage error Programme error Coincidental event Vaccine reaction Cluster of AEFIs All cases from only one facility (same lot used at others)? Coincidental event Programme error or vaccine problem All cases got same vaccine or lot? Known vaccine reaction? Similar illness in others who didn’t get vaccine? Similar illness in others who didn’t get vaccine? Rate of reaction within the expected rate?

26. CAUSALITY ASSESSMENT ? Adverse Event

27. CASE REPORTS - ONLY ONE PART Risk evaluation requires a 2x2 table of exposures and outcomes Case reports represent only one cell of table Risk of event from vaccine = a*d/b*c

28. CONCLUSIONS Immunization safety is likely to become increasingly important Need to develop system which detects investigates takes action (including communication) measures outcome of action