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Vaccine 29 (2011) 65–69

Contents lists available at ScienceDirect

Vaccine

journa l homepage: www.e lsev ier .com/ locate /vacc ine

ragmatic management of programmatic vaccination errors—Lessons learnt fromncidents in London

aura Craiga,∗, David Ellimanb, Rachel Heathcockc, Deborah Turbittd, Barry Walshe,atasha Crowcrofta,f

Immunisation, Hepatitis and Blood Safety Department, Health Protection Agency’s Centre for Infections, 61 Colindale Avenue, London, United KingdomCommunity Child Health Department, Great Ormond Street Hospital for Children, 3rd Floor, 21-27 Lambs Conduit Street, London, United KingdomSouth East London Health Protection Unit, 1, Lower Marsh, London, United KingdomNorth East and North Central London Health Protection Unit, 7th Floor, Holborn Gate, 330 High Holborn, London, United KingdomSouth West London Health Protection Unit, Ground Floor, Building 15, Springfield University Hospital, 61 Glenburnie Road, Tooting, London, United KingdomSurveillance and Epidemiology, Ontario Agency for Health Protection and Promotion and the University of Toronto, Department of Laboratory Medicine and Pathobiology and Dallaana School of Public Health, Toronto, Ontario, Canada

r t i c l e i n f o

rticle history:eceived 3 May 2007eceived in revised form0 September 2010ccepted 7 October 2010vailable online 30 October 2010

a b s t r a c t

Correct storage, handling and administration of vaccines are vital components of a successful immunisa-tion programme. However, with the large number of different healthcare professionals now involved indelivering the vaccine programme on a daily basis, it is inevitable that programmatic errors will occur.Decisions as to how best to rectify these errors can be difficult however, as often they are unprecedentedand there may be no hard evidence on which to base their management. These decisions must therefore

eywords:accine errorsevaccinationdverse reactions

be based on what is known and any available previous experience. They also often take place in an envi-ronment of concern about litigation and liability which puts pressure on health care workers to take adefensive or conservative approach. Management decisions may ultimately also have to be a pragmaticchoice based on the individual situation and what is deemed to be the best way to minimise adversereactions, ensure patients are adequately protected and maintain public confidence in the immunisationprogramme. Here, we describe our experiences of managing vaccine programmatic errors and some of

had t

the many factors that we

. Introduction

With the growing awareness of clinical governance issues andreater use of clinical audit in recent years, the Health Protec-ion Agency (HPA) is increasingly being asked for advice on howo respond to the various errors in vaccine storage, preparationnd administration that have come to light as a result. Decisionss to the best way to deal with these programmatic errors in vacci-ation programmes can be difficult however, because the adverse

ncident is often unique and there are no clinical trial results avail-ble to provide evidence on which to base management decisions.he decisions made as to how to manage these incidents thereforeave to be based upon previous experience of similar incidents, any

urrently existing knowledge and general vaccination principles.

Here we describe four different adverse events which occurredn the primary care setting, had similar features, and illustrate somef the many considerations that have to be taken into account when

∗ Corresponding author. Tel.: +44 020 8327 7680; fax: +44 020 8200 7868.E-mail address: Laura.Craig@HPA.org.uk (L. Craig).

264-410X/$ – see front matter © 2010 Elsevier Ltd. All rights reserved.oi:10.1016/j.vaccine.2010.10.014

o consider.© 2010 Elsevier Ltd. All rights reserved.

such incidents arise. The experiences, the management approachchosen and the outcome achieved may provide helpful informationfor those dealing with similar incidents in the future.

2. Methods

The authors led, or were involved in advising in one or more ofthe incidents discussed here. Each incident is described separatelyfollowed by an outline of its management.

3. Results

3.1. Incident 1

An individual who had been working as a practice nurse for 15years was found to be unqualified during the checking process for

a new job. Amongst their duties at the five practices at which theyworked was administering routine and travel immunisations. Theyhad never attended an immunisation training or update course.

An incident team was convened to decide whether re-vaccination of children who had been seen by the unqualified

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ractice nurse was necessary. Consideration was given to assess-ng the individual’s competence through interview and practicalssessment, but this was not possible because of legal restrictions.hrough discussion with the practice nurses’ colleagues, many ofhom had received vaccinations from the nurse themselves, the

eam established that the individual’s vaccine technique appearedo be credible and therefore it was felt probable that vaccinesiven by this nurse were likely to have been effective. However,ecause this could not be confirmed, and because the primary carerganisation was concerned to do everything possible to avoid anyisk to patients as a result of the incident, it was felt that offer-ng a booster dose to those who received their primary schedulerom this nurse would be advantageous. Patients and parents wereontacted and offered revaccination. Reassurance and reinforce-ent of the positive benefits of vaccination using Department ofealth immunisation leaflets was also provided. A question andnswer sheet was produced and a helpline was provided by NHSirect. Dedicated clinics were set up and staffed by school and otherurses.

Information from GP electronic clinical systems was made avail-ble to determine which children required re-immunisation. 659hildren were invited for immunisation at 12 clinic sessions. 115hildren attended for reimmunisation. Information on the extrammunisations given was recorded in the personal child healthecord and Child Health Information System (CHIS). Informationas given in a press statement advising anyone who was concerned

o seek advice from their GP.A small number of the parents were angry about the incident.

here were no post immunisation adverse events reported by thehildren’s parents.

.2. Incident 2

A practice nurse was found to have been mixing MenC withTP-Hib for infant primary vaccination over a period of 12 months.his affected 33 infants who had received one (18 infants), two (9nfants) and three (6 infants) doses given in this way. In addition,arents of eight infants had been given the oral polio vaccine (usedt the time of this incident) to take home and administer later in theay. The pharmaceutical company that produced the MenC vaccinead no data on vaccine efficacy when mixed in this way. Parents ofhe children affected were provided with information and offeredsingle additional dose of each vaccine. These were given as sepa-

ate injections (as DTP-Hib and MenC) at least 1 month after the lastrimary vaccination. Two dedicated clinic sessions were providedt different premises from the one where the practice nurse hadorked. Twenty-two children attended for the additional doses.

As in Incident 1, parents expressed their dismay and anger athe situation and there were no reports of adverse reactions fromny of the children who received additional vaccinations.

.3. Incident 3

Following Incident 2, the Regional Director of Public Health con-acted London Immunisation Co-ordinators to warn them about theossibility of such events occurring in their areas.

Subsequently, a GP was found to have been mixing some or allaccines together ‘out of kindness’ to patients. The GP had beenixing MMR and DTP together as well as MenC and DTP. The GP

lso gave all vaccines into the gluteal region. In addition, the vaccineridge for the practice was a domestic fridge which was not being

onitored at all.Vaccination was suspended at the surgery pending the arrival

f a new vaccine fridge. Once this was in place, a practice nurse wasrovided to deliver further immunisations. An incident team wasstablished to review the management of affected patients.

9 (2011) 65–69

A local helpline was set up and run by the PCT nursing staff.Children who might have been immunised incorrectly were iden-tified from clinical records and invited to attend a clinic forre-vaccination. Attempts were made to trace families that had leftthe practice and a letter sent to their new GP requesting that fur-ther vaccination be provided. Three special clinics were providedat which the parents could discuss the issues and have single addi-tional boosters of affected vaccines. Information was translated intolocally prevalent languages and an interpreter was provided at theclinic.

It was difficult to identify who had received the mixed vaccinessince the site of immunisation was not recorded. Practice nurseshad to make several visits in some instances to determine whethera patient might have received a mixed vaccine. For a few patients,records could not be found at the practice and these patients weretherefore invited to one of the clinics.

A total of 109 families who were still registered with the practicewere contacted. Of these families, 14 (13%) called the helpline and36 (33%) patients attended one of three clinics. A further 49 familieshad moved away, of whom 8 could not be traced and the GPs of 15did not respond to the letter from the PCT. Letters were sent to theGPs of the remaining 24 children, advising them of the need for anyfurther immunisations.

3.4. Incident 4

A routine audit carried out in a health centre by the PCT com-munity services pharmacist found that temperature recordings in avaccine fridge had been 0 ◦C on a number of occasions. The practicehad been following the local cold chain policy in that the daily fridgetemperatures were being recorded, however no action was takenwhen temperatures were found to be outside the recommended2–8 ◦C range. The staff member whose responsibility it was to moni-tor the fridge understood their task was to record the temperatures,but not to report any deviations from normal.

An incident team was set up and, on investigation, it was foundthat 19 children had received one or more primary immunisationdoses with vaccines potentially stored at low temperatures. In viewof the possibility that the vaccines could have frozen, thus affect-ing their potency, it was decided to offer reimmunisation to the 19children. Those children who had received one dose of affected vac-cines were offered a further MenC and Hib vaccination in additionto ensuring that their primary course was completed. Those chil-dren who had received two doses of affected vaccines were offeredtwo doses of MenC and Hib vaccines and an additional DTaP.

Letters and information were sent to parents, a helpline was setup staffed by health visitors and paediatricians and arrangementswere made to reimmunise in a PCT clinic. GPs of the affected chil-dren were informed of the incident and follow up arrangements.

Nineteen parents responded with 15 children being reimmu-nised in the dedicated clinics and four who had moved outside thearea being reimmunised by their new GP.

No adverse reactions were reported. Parental responses weregenerally understanding of the situation. However parents of twochildren were very angry and one of these reacted aggressivelyusing threatening language to staff.

4. Discussion

The main considerations that arise following the discovery of a

vaccine incident are how efficacious the vaccines given will havebeen and whether revaccination is necessary. If revaccination isconsidered, would it be more harmful than beneficial? What willthe public response to the incident be and what are the implicationsfor the surgery or Primary Care Trust involved?

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.1. Assessing vaccines involved in incidents

Given the risk of local reactions, which for some vaccines withigher reactogenicity profiles is greater than others, it is importanto try to establish as far as possible, whether vaccines involved inntoward incidents really are likely to have been rendered sub-otent or ineffective. With some of the incidents described above,uch as where the vaccinator’s immunisation practice and tech-ique was questionable but un-assessable, and in the cases wherehe vaccines were incorrectly mixed, this was not possible. Inddition, testing the potency of vaccines involved in incidents isime-consuming and may be inconclusive. Therefore, in many inci-ents, such as where the cold chain has not been maintained, somestablished basic principles must be used.

.2. Cold chain

Exposing or storing vaccines for relatively short periods atemperatures above 8 ◦C should have limited effect on most inacti-ated vaccines. The World Health Organisation guidance on vaccinetability [1] indicates that exposure to temperatures above theecommended range of 2–8 ◦C does not cause immediate loss ofotency but is likely to shorten the shelf-life. Therefore in prac-ices with a fairly quick vaccine turnaround time from arrival inhe surgery to delivery to the patient, there should be very lim-ted loss of potency and to recommend revaccination may not beeemed necessary.

What is of more concern however, is where individuals haveeceived a whole course of potentially heat rendered sub-potentaccine (such as where storage problems were prolonged orurnover of vaccines slow). In both this case, and where a vaccineas lost potency due to freezing (as many vaccines, particularlyhose containing adjuvant, will do when subject to temperatureselow 0 ◦C), a booster dose or doses would be actively recom-ended.It is important to acknowledge that health care providers and

accine manufacturers tend to err on the side of caution and forany incidents this tends to lead to a conservative approach. Itould be helpful to have more published data and clear statements

rom vaccine manufacturers on the known stability of currentlysed vaccines in order to determine what action to take when vari-tions in storage temperatures occur. However, the authors haveirect experience of the difficulty in achieving agreement on anyuch guidance because of perceived issues of liability.

In recent years, more data on vaccine stability is beginning tomerge. Had this information been known at the time of dealingith the cold chain incident described here (incident 4), a differentanagement approach may have been taken.

.3. Serological testing

On discovering an adverse incident, the question as to whetherlood tests can be carried out to establish vaccine efficacy is oftensked. In general however, serological testing is not helpful invaluating whether or not vaccines have worked. This is becauselthough for some antigens (diphtheria, tetanus, hepatitis B) pro-ective antibody levels have been defined, for many vaccines, theres no data on the serological levels that would be expected at anyiven time from vaccination that correlates with life long pro-ection. In other words, although it can be established whether aerson who has received vaccine of uncertain efficacy has protec-

ive antibody levels (above a minimum cut off) on the day of testing,r whether they are as high as another person who was vaccinatedppropriately, the duration of time for which they can rely on beingrotected in the future cannot be determined. In addition, the levelf antibody considered to be protective for many diseases is based

9 (2011) 65–69 67

on laboratory models and may be somewhat arbitrary [2]. Finally,a blood test is often far more distressing for a child and their par-ents than a repeat immunisation and, if they are found not to beprotected, they will need yet another injection.

4.4. Risk of adverse reactions

Consideration must therefore be given as to the likelihood of anadverse reaction in a person who is given an extra dose or dosesof a vaccine to compensate for any doses given that are deemed tohave possibly been ineffective.

For live vaccines, the rate of adverse reactions falls with increas-ing number of doses because the antibodies that are produced inresponse to an initial dose or doses of vaccine neutralise the livevaccine virus in subsequent doses.

In contrast, increasing rates of adverse reactions are frequentlyseen with increasing number of doses of inactivated vaccinesbecause the antibodies produced in response to an initial dose ordoses of vaccine react with the antigen in subsequent doses, pro-ducing a local inflammatory reaction.

On this basis, the risks of reactions associated with giving addi-tional doses of live vaccines is small but the risk of giving additionaldoses of inactivated vaccines is slightly greater.

4.5. Reaction to additional doses

The UK immunisation schedule has fewer doses of tetanusand diphtheria toxoid-containing vaccines in early childhood thanmany other countries where a booster in the second year of lifeis the norm yet additional adverse events are not reported. Thisprovided reassurance in recommending in these incidents, that anextra dose of DTP in the pre-school years could be given withoutputting a child at significant risk of adverse reactions. It is reassur-ing to note that in all of the incidents described, no adverse eventsfollowing re-immunisation were reported.

However, these incidents occurred at a time when the infantimmunisation schedule included whole cell pertussis vaccine. In re-vaccinating affected children, acellular pertussis (aP) vaccine wasrecommended in order to reduce rates of local reaction [3]. Withthe change to exclusive use of aP in the UK infant schedule from2004 however, a new concern with offering additional doses of thisvaccine must now be considered.

Reports from the UK, America and Australia indicate that ratesof reactions to aP boosters are higher in children who were primedwith an acellular vaccine than those who were primed with a wholecell vaccine [4–6] and that the incidence of adverse local reactionsto aP-containing vaccines increases with further doses. Some ofthese reactions are very large and involve swelling of the wholelimb or blistering at the injection site. It is important that parentsare informed about the possibility of a local reaction occurring andboth they and healthcare professionals need to know that this is arecognised phenomenon and does not contraindicate further dosesof aP vaccine [4].

Our experience in incidents where reimmunisation has beenrecommended is that no serious adverse events have occurred andvaccine reactions have not been reported. It has not been possibleto formally assess reactions following reimmunisation as health-care workers involved in reimmunisation have expressed concernsthat it would undermine parents’ confidence if they felt that theirchild was being followed up because the risk of adverse reactionswas unknown.

4.6. Informing patients

Having made the decision to offer revaccination, con-sideration must be given as to how patients should be

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nformed and how to offer and organise reimmunisation inuch a way as to maximise uptake and minimise anxiety andnger.

With the increasing awareness of the moral and legal require-ent to inform the public about potential hazards to their health

7], careful consideration should be given as to effective risk com-unication following vaccine incidents. There is now, rightly, more

f an onus on informing the public when things have gone wrongnd ensuring that patients are given sufficient and appropriatenformation so that they can make an informed decision as to

hether to be revaccinated and what the risks of doing or notoing this are. One of the difficulties in the incidents described washe paucity of information on which to make decisions. The effectsn the potency of the vaccines involved and the risk of adverseeactions were not quantifiable. Communication with the public isherefore more difficult than in most other look back situations.triking the right balance between conveying this to the publicn a way that does not affect their confidence in vaccines and yet

akes them take the incident seriously enough that they attend foreimmunisation is challenging.

In each of the incidents described above, letters and Q&A sheetsere provided to patients and parents that gave comprehensive,onest, clear and consistent information which communicated thealance of risks of revaccination versus risks of not being ade-uately protected. Efforts were made to use appropriate languagend consideration was given as to the most suitable and effectiveays to inform patients through means appropriate to the local

ommunity, such as local radio stations and newspapers.The response to vaccine incidents may vary considerably

epending on the characteristics of the local community. In somereas, the local population may be highly engaged and vocal andatients may become quite inflamed in response to an incident

nvolving immunisation. Reimmunisation clinic staff need to berepared and supported to respond to this.

In other areas however, such as Incident 3, there is a pooresponse when reimmunisation is offered. Some of the variationay be related to differences in local cultures, languages and lit-

racy. For this reason, careful consideration needs to be given toroviding written information in appropriate languages and inter-reting services. In addition, reimmunisation clinics need to beexible and consideration should be given to offering clinics ateekends and evenings. They should be staffed by well-trained,

onfident, competent and knowledgeable staff who have access ton expert so that any questions can be rapidly and effectively dealtith and maximum use of the opportunity to reimmunise thoseho present is taken.

Local areas may also vary in the mobility of the population. It isoncerning that 8 children could not be traced at all in Incident 3, anssue which has implications for other areas such as child protec-ion. It is important that efforts are made to contact patients whoave moved away and to inform their new GP of the reimmunisa-ion recommendations. Patient tracing services should be used toocate affected patients. If the new country-wide NHS informationtrategy [8] is fully implemented, tracing these patients in futurencidents should hopefully become easier.

. Preventing future incidents

.1. National guidelines

The common factor in all the incidents is that good practiceas not being followed – adequate training and supervision couldave prevented all of the incidents described above from occur-ing. These incidents illustrate the need to comply with nationalinimum standards in immunisation training [9], to provide good

9 (2011) 65–69

basic training and regular updates for all staff and to ensure thatstaff attend.

Following each of the incidents, changes to practice were madein the areas involved. These incidents and continued reporting ofadverse incidents in immunisation such as these to the HPA hasbeen the stimulus for production of guidance both for training [9]and for the management of vaccine incidents [10] in order bothto prevent such incidents from occurring and to try and ensureconsistency in approach when they do occur.

5.2. Use of audit

Cold chain audits are an excellent indicator of the quality ofprimary care immunisation services and often uncover multipleproblems. Thorough and regular audit of cold chain practice, train-ing and record keeping by PCTs may therefore also help to preventincidents from occurring or to detect them at an earlier stage, thusmaking them easier and less resource-costly to resolve.

Mistakes will continue to happen as long as human beings areinvolved in delivering immunisation programmes, but robust sys-tems can minimise both the likelihood of human error and itsimpact. Audit tools used at local level should regularly monitor thestandard of immunisation so that poor practice can be identifiedand rectified.

6. Conclusion

In all of the incidents it was not possible to define whether thechildren had been protected by the vaccines they had received.Since neither vaccine nor serological testing are usually helpful, themanagement of all the incidents therefore had to be based uponknowledge of the adverse events profile of the vaccines involvedin the incident and judgement of the balance of the risk of givingan additional dose of vaccine that might not be needed against therisk of leaving a person unprotected. We acknowledge that a con-servative approach was taken particularly in the first incident, butwe learnt with each incident to be more confident in the face ofpressure to re-vaccinate everyone. We hope that through sharingour experience others will be helped to manage similar incidents

The National Immunisation programme is one of the few activ-ities of the health service that promotes health rather than treatsdisease and is the most effective medical intervention there is toprotect health. However, when mistakes happen there is often apaucity of evidence on which to base action. A pragmatic approachis necessary, and open dialogue with parents and patients aboutthe advantages and disadvantages of different courses of action isessential. Our experience is that re-vaccination does not appear tocarry an excessive risk of local reactions and that the overwhelmingchallenge in inner-city populations is locating families and gettinghigh attendance at follow-up clinics, whilst maintaining confidencein immunisation programmes and putting measures in place toprevent further incidents from occurring.

Acknowledgements

The authors would like to acknowledge all the staff involved inhandling these incidents.

References

[1] World Health Organisation Department for Immunization, Vaccines and

Biologicals. Temperature sensitivity of vaccines. Geneva: World Health Organ-isation; 2006. Available from: http://www.who.int/vaccines-documents/DocsPDF06/847.pdf.

[2] Galazka AM. General immunology. Module 1. The immunological basis forimmunization series. WHO/EPI/93. 11. Geneva: World Health Organisation;1993.

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[9] Bedford H, Crowcroft N, Cummins A, Elliman D, Gibbons V, Lane L, et al. National

L. Craig et al. / Va

[3] Miller E. Overview of recent clinical trials of acellular pertussis vaccines. Bio-logicals 1999;27:79–86.

[4] MHRA/CHM. Local reactions associated with pre-school d/DTaP-IPV boosters. Curr Probl Pharmacovigalence 2006;31:5. Available at:http://www.mhra.gov.uk.

[5] Rennels MB, Deloria MA, Pichichero ME, Losonsky GA, Englund JA,Meade BD, et al. Extensive swelling after booster doses of acellularpertussis–tetanus–diphtheria vaccines. Pediatrics 2000;105(1):e12.

[6] Gold MS, Noonan S, Osbourn M, Precepa S, Kempe AE. Local reactions afterthe fourth dose of acellular pertussis vaccine in South Australia. Med J Aust2003;179(4):191–4.

[

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[7] Pencheon D, Guest C, Melzer D, Gray M. Oxford handbook of public healthpractice. 2nd ed. Oxford: Oxford University Press; 2006.

[8] Connecting for Health: National Programme for IT in the NHS. Available at:http://www.connectingforhealth.nhs.uk/ (accessed April 2007).

minimum standards for immunisation training. Health Protection Agency;2005.

10] Health Protection Agency.Investigation of a Cold Chain Incident. 2010.Available at: http://www.hpa.org.uk/web/HPAwebFile/HPAweb C/1267551139589.