1. O. O’Brien, C. Sadlier, C. Dowling, A. Carr, C. Bergin, C. Bannan
Optimising prevention of pneumococcal infection in HIV-infected patients
A Clinical Audit of Pneumococcal Vaccine Uptake in St. James’s Hospital
O. O’Brien, C. Sadlier, C. Dowling, A. Carr, C. Bergin, C. Bannan
26/11/2016
Good afternoon, everyone.
My name is Oisín – I’m a medical student from Trinity College and I undertook a research elective here in the GUIDE clinic over the summer.
I worked with Ciaran Bannan and Miriam Coghlan, looking at health outcomes for HIV/HCV co-infected patients receiving interferon-free therapies.
However, during my time here I also carried out an audit of pneumococcal vaccination rates amongst patients these co-infected patients. 1

2. IPD in St. James’s Hospital
IPD Incidence = 283/100,000 HIV+ patients vs 12/100,000 for all patients
212 cases of IPD in total presented to SJH between 2006 – 2015:
47 (22%) episodes occurred in 42 HIV-infected adults
46 = bacteraemia of respiratory origin
1 = meningitis
Risk factors included:
IV Drug Use = 36/42 (86%)
Hepatitis C = 31/41 (76%)
Overall mortality post-IPD = 7/47 (15%) HIV+ patients vs 7% of all cases
13/42 (31%) had received PPV23, compared to
2% of non-HIV IPD cases
84% of total HIV-infected cohort
8/13 (62%) infected with a PPV23 serotype
Now I’d like to draw your attention to some recent statistics for St. James’s Hospital specifically.
Corinna Sadlier and others recently conducted a study looking at the factors associated with IPD in HIV-infected adults
In the 8 years between , there were 186 recorded cases of IPD in this hospital
Just under a quarter of these episodes occurred in 41 HIV-infected adults
Two of the main IPD risk factors identified for this subgroup were Intravenous Drug Use (in 85% of patients) and HCV Co-infection (76%)
15% of the patients with HIV who had IPD died following the disease
It is interesting to note that 12 of the infected patients had been previously immunised with 23-Valent Pneumococcal Polysaccharide Vaccine, 7 of which had been infected with a serotype covered by the vaccine
To me, this suggests that PPV23 alone is insufficient to protect against pneumococcal infection
The authors concluded that “[Early studies of the conjugate vaccine] indicate a more immunogenic and durable response” compared to PPV23 and “HIV-infected IVDUs represent a group that should be prioritised” for this vaccine.
HPSC (2016)
Sadlier et al. (2016)

3. NIAC Guidelines Pneumococcal Vaccination is indicated for:
Chapter 16: Pneumococcal Infection (since January 2014)
Pneumococcal Vaccination is indicated for:
Routine Childhood Immunisation
PCV for all children <2 years
Routine Adult Immunisation
PPV for all adults ≥65 years
Clinical Risk Groups
Groups with a higher risk of IPD than the general population
Now I’d like to go through the national guidelines for pneumococcal vaccination, which can be found in Chapter 16 of this document prepared by the National Immunisation Advisory Committee.
According to this document, the indications for pneumococcal vaccination are as follows:
Routine immunisation with PCV13 for all children under 2 years of age
Routine immunisation with PPV23 for all adults 65 or over
In addition, immunisation of clinical risk groups (i.e. people who do not fall into either of the above age brackets, but have a higher risk of IPD than the general population)
For today I’d like to just focus on the latter…

4. High Risk Groups High Risk = PCV + PPV
“Early studies of PCV13 indicate a more immunogenic and durable response” and “HIV-infected IDUs represent a group that should be prioritised”.
High Risk = PCV + PPV
…Because groups considered “high risk” include immunosuppressive conditions (such as HIV)
These patients (that fall into “Group A” of this table) are particularly susceptible, require maximum protection against IPD, and therefore should receive both PCV13 and PPV23
Patients over the age of 5 should receive 1 dose of PCV13 (or 2 if there’s reason to believe their immune response may be blunted) followed by 1 dose of PPV at least 2 months afterwards. 4

5. Vaccination Schedule
If PCV is given first, wait 2 months before giving PPV
If the patient has already received PPV, wait 1 year before giving PCV
A PPV Booster should be given 5 years after first dose if:
Patient’s antibodies are likely to decline more rapidly (e.g. HIV) OR
Patient is ≥65 and was <65 at time of first dose
Those who received one dose of PPV at age 65 or older do not require any further dose regardless of immune status.
Here’s a bit more detail on the correct timing of the vaccinations:
Like I just said, if PCV is given first, you must wait 2 months before giving PPV23
However, if the order is reversed and the patient has already received PPV23 before PCV13, you must wait 1 year before giving PCV13
5 years after administering PPV, a booster should be given in the following two cases:
The patient’s antibodies are likely to decline more rapidly (such as in the case of HIV)
The patient is now 65 or older, but was younger than 65 at the time of their first PPV vaccine
(However, any patients that received their first dose of PPV at the age of 65 or beyond should not be given a booster regardless of their immune status)

6. HIV+ 6 (Chapter 16, NIAC Immunisation Guidelines)
This is the flowchart for deciding if a booster dose of PPV23 should be given.
In the case of individuals infected with HIV, a first vaccination is indicated and so is a booster after 5 years
The only exemption from the booster is if the patient was aged 65 or over when they received their first dose
(Chapter 16, NIAC Immunisation Guidelines) 6

7. Audit
Now, having gone through those guidelines for vaccinating HIV patients against pneumococcus, I’ll discuss the clinical audit I performed to see how the vaccination practices in the GUIDE Clinic compared to standard.

8. Methods
A list was compiled of HIV/HCV co-infected patients who have attended the clinic (co-infection and IDU identified as risk factors for IPD)
Immunisation records were accessed to determine if patients had received PCV, PPV or PPV Booster.
Dates of patients’ vaccinations were recorded in an Excel spreadsheet (anonymised and encrypted).
Data Analysis was performed in Excel to see if vaccination schedules were consistent with NIAC Guidelines.
Initial Audit = July 2015
1 Year Follow-Up = August 2016
I conducted this audit in July 2015 during my elective placement here.
A list was compiled of 204 patients attending the clinic who are co-infected with HIV and Hepatitis C
The department’s immunisation records for these patients were made available to me
For each patient, I recorded any documented reports of them having received PCV13, PPV23 or an additional PPV booster
I also recorded the dates that these vaccinations were given (and other relevant details such as the patient’s age at time of vaccination)
These data were transferred into an Excel spreadsheet (which was anonymised, encrypted and stored here on the hospital system)
I then analysed this data in Excel, comparing dates of birth and dates of vaccinations to determine whether patients received their vaccines and, if so, whether they were given at appropriate times as per the NIAC schedule 8

9. Population N = 204 HIV/HCV co-infected High Risk of IPD
76% Male, 24% Female
Ages years (Mean = 45, IQR = 39-50)
Retrospective analysis was performed on a population of 204 patients.
These patients were selected based on their diagnosis of both HIV and Hepatitis C – a group with a high risk of contracting IPD
76% of the patients were male
The average age was 45, with half falling somewhere between 39-50 9

10. PPV23 (“Pneumovax”) Uptake
23 (11%) received no vaccine
90 (44%) only received the first dose
56 (27%) did not receive a booster at 5 years
34 (17%) are too early to receive a booster
91 (45%) received a booster
6 (3%) received a booster before 5 years
54 (26%) received a booster at 5 years
31 (15%) received a booster after 5 years
Here are the results regarding Pneumovax uptake (which I’ll try to explain as clearly as possible):
In the absence of any documented contraindications, it was assumed that all patients should have received PPV23
In reality, 181 (89%) had received at least one dose – meaning that 11% had not yet received a vaccine at the time of the study
Only 147 of these patients were eligible for a booster, and 91 (62%) of them had received it – meaning that 38% of those eligible had failed to receive a booster
Of the 204 patients eligible for Pneumovax:
181 (89%) received at least one dose.
Of the 147 patients eligible for a Booster:
91 (62%) received it.
54 (37%) received it at the right time. 10

11. PCV13 (“Prevnar”) Uptake
Yes
8 (3.9%)
Here are the results regarding Prevnar uptake:
Of the 204 patients for whom PCV13 is recommended, only 8 (4%) had been documented as receiving it.
All 8 patients who received PCV13 had also received PPV23

12. Integrated Vaccine Unit as a Model of Care
Sadlier et al. (2014)
Integrated Vaccine Unit as a Model of Care
The Integrated Vaccine Unit was established in the GUIDE Clinic in 2002
Consists of:
Vaccine Nurse
Data Manager
Pharmacist
Vaccine Subgroup Committee
Strategies employed:
SMS texting
Personal Vaccine Passports
Reminders announcing availability
of seasonal influenza vaccine
Factors affecting uptake:
“In the 2012/2013 active attending cohort
(n=1645) IDU was associated with
non-receipt of influenza vaccine
(67% vs 82%, p<0.01)”
At this point I think it would be worth mentioning the Integrated Vaccine Unit as a Model of Care
This unit was established in the GUIDE Clinic in 2002 and consists of:
Vaccine Nurse
Data Manager
Pharmacist
Vaccine Subgroup Committee
Strategies employed by the unit have included:
An SMS texting service for notifying patients
Personal Vaccine Passports as a form of documentation
Reminders announcing availability of seasonal influenza vaccine
This graph shows the increases in uptake of seasonal influenza and Pneumovax vaccines since the vaccine unit was established:
Between , influenza vaccine uptake has increased from 47% to 80% and pneumovax uptake has increased from 34% to 84%
Corinna Sadlier and others (who prepared this data) also investigated the possible factors influencing vaccine uptake.
They found that IV drug use was associated with non-receipt of influenza vaccine.
Progress in vaccine coverage, 2003 vs 2012:
Influenza = 47% vs 80% (p<0.01)
Pneumovax = 34% vs 84% (p<0.01)

13. Proposals
The next step in the process is to decide what measures need to be implemented.
As I said, it is not clear to me what the underlying cause is, but I think the solution should take into account both patients and staff
The following are just examples of measures that were mentioned in the literature regarding vaccine uptake 13

14. For Patients
Raise Public Awareness with an advertising campaign (e.g. posters)
Educate Patients by counselling them on the importance of vaccines
Improve Access with home visits; convenient transport and clinic hours
(Busy clinics – perhaps make more rooms available to facilitate consultations?)
Encourage Adherence with reminders before next appointment
Utilise Inpatient Admissions as opportunities to vaccinate patients who do not reliably attend clinic
It’s possible that patients are not getting their vaccines because they’re not engaging with the service.
Raising public awareness of the importance of pneumococcal vaccines could be achieved with an advertising campaign (such as posters within the GUIDE Clinic).
During consultations, staff members could educate patients on the importance of keeping up to date with their vaccinations
Although I don’t really know how feasible it may be, another possible approach could be improving patient access to services. (home visits or special transport arrangements may not be on the table, but there may be ways to reduce the workload in busy clinics so that patients get a 20 minute consultation where their vaccination status can be reviewed)
Another possibility would be an automated notification system (such as a text message or service) to remind patients to attend appointments.
And lastly, inpatient admissions should be utilised as opportunities to vaccinate patients who may not otherwise engage with the service 14

15. For Staff Emphasise Importance of vaccination in management protocols
Update Staff on pneumococcal vaccine guidelines
Ensure Availability of vaccination schedules in clinic
(i.e. hard copy or electronic access to national guidelines)
Incentivise staff vigilance towards vaccine provision
(electronic prescribing records could be used to monitor adherence to guidelines)
Electronic Notifications to remind staff when a vaccine is due
Standardise Documentation of vaccines in electronic patient records
Staff members can also play a part in improving adherence rates:
Emphasising the importance of pneumococcal vaccines in management protocols for patients with HIV
Organising sessions like this one to keep staff up to date on the current guidelines
Ensure the availability of the relevant flowcharts in clinic rooms (either on a poster or on the computer desktop)
Perhaps it may be worthwhile to use electronic records to monitor staff adherence to guidelines
If it turns out that some staff are forgetting to follow up on a patient’s vaccinations, it may be feasible to set up an electronic notification system to remind them when a vaccine is due
And finally, this may be facilitated by establishing a standardised format for documenting vaccinations in the electronic patient records 15

16. 1 Year Follow-Up

17. Improving Vaccine Uptake
Measures implemented:
Reminder s circulated to staff re: Pneumococcal vaccines
Staff re-educated on updated immunisation guidelines
Immunisation flowchart made clearly visible in clinic rooms
Automated notifications in Electronic Patient Records
Public Awareness Campaign (posters & leaflets)
SMS reminders for patients
Immediate signs of improvement:
In 12 months preceding these measures, 50 PCV doses were given (in the total HIV+ cohort)
In 3 months following these measures, ~350 PCV doses were given (in the total HIV+ cohort)
Reflected in follow-up audit…
Once viable proposals have been accepted, the next step will be to implement them.
I was very happy to receive an from Corinna updating me on the work that has been done since I left in July.
Some measures have already been implemented…
And there are already signs of improvement
I hope that this trend will be reflected when I conduct another audit next summer.

18. PPV23 (“Pneumovax”) Uptake (n=204)

19. PCV13 (“Prevnar”) Uptake (n=204)
3.9%

20. Limitations Weaknesses: Strengths: Some data may be missing
Patients unaccounted for
Vaccines given at other centres (absence of “vaccine passport”)
Failure to record vaccinations
Results do not clarify the cause(s) of suboptimal uptake
Results clearly identify room for improvement in an important aspect of care for high risk patient group
Patients all attend the same clinic (so should be relatively easy to target and improve uptake)
Admittedly, there are significant weaknesses with this work:
I can’t exclude the possibility that some important data is missing. There may be HIV/HCV co-infected patients whose records were not available. It is certainly possible that additional vaccines were given and documented at other centres (perhaps by a GP or as an inpatient at another hospital). And I also can’t rule out the possibility that more vaccinations were in fact given on site, but did not appear in the records.
Another shortcoming is the fact that the data collected don’t really indicate what is causing suboptimal vaccination rates
On the other hand, I think this audit has at least been successful in identifying an important aspect of care for a high risk patient group that can be improved.
Even if the data gathered were not fully reflective of the actual vaccination rates, they may still suggest room for improvement in how vaccinations are documented.
On an optimistic note, this patient cohort attend the same clinic and are in contact with the same members of staff so, now that the issue has been identified, I hope that it will be relatively easy to target these patients and implement measures to improve their vaccine uptake.

21. Conclusions
IPD is a significant cause of morbidity and mortality in HIV-infected individuals, particularly in those with IV drug use and HCV co-infection.
All HIV+ patients should receive both PCV13 and PPV23 vaccines.
Of 204 HIV/HCV co-infected adults attending the GUIDE Clinic:
89% received PPV23, but only 62% of those eligible received a booster
Only 4% received PCV13
Measures were taken to improve provision by staff, uptake by patients, and adherence to guidelines regarding schedules and precautions.
Improvements seen after 1 year:
PPV23 uptake increased from 89%  91%
PCV13 uptake increased from 4%  54%
In summary:
IPD is a significant cause of morbidity and mortality in HIV- infected individuals, particularly in those with IV drug use and HCV co-infection.
All HIV patients should receive both PCV13 and PPV23 vaccines.
Of 204 HIV/HCV co-infected adults attending the GUIDE Clinic:
89% received PPV23, but only 62% of those eligible received a booster
Only 4% received PCV13
Measures should be taken to improve vaccine provision by staff, vaccine uptake by patients, and adherence to guidelines regarding schedules and precautions.
Re-Audit to be performed in Summer 2016

22. Future Work
Extension of audit to all HIV+ patients attending SJH (& nationally)
Re-evaluation of epidemiology of IPD in 2018
Evaluation of implementation of national immunisation guidelines

23. Acknowledgements
C. Sadlier
C. Bergin
- C. Dowling
A. Carr
- C. Bannan

24. Thank You Any Questions? 24 Before I finish I would like to thank:
Ciaran and Miriam for all of their help and guidance during my elective
Corinna Sadlier for providing me with details of her previous vaccine work
The members of the vaccine team who helped me source the audit data from patient records
Professor Bergin for organising my elective in the first place and making sure it was as useful and enjoyable as I could have hoped
And not least, I’d like to thank you all for your time and I’d be happy to answer any questions you may have 24

25. References
Royal College of Physicians of Ireland. “Clinical Practice Audit for Professional Competence.” (Revised 1st May 2015)
Hibberd PL. “Pneumococcal immunization in HIV-infected adults.” In: UpToDate (Accessed on September 7th 2015)
National Immunisation Advisory Committee. “Pneumococcal infections.” Chapter 16, Immunisation Guidelines for Ireland (Updated August 2015)
Lynch JP & Zhanel GG. (April 2009). “Streptococcus pneumoniae: epidemiology, risk factors, and strategies for prevention.” In: Seminars in respiratory and critical care medicine (Vol. 30, No. 2, pp ).
Hirschtick RE, Glassroth J, Jordan MC, Wilcosky TC, Wallace JM, Kvale PA, ... & Hopewell PC. (1995). “Bacterial pneumonia in persons infected with the human immunodeficiency virus.” New England Journal of Medicine, 333(13),
Health Protection Surveillance Centre. “Invasive Pneumococcal Disease in Ireland: Quarters 3-4, 2015 & Annual Data provisional”. (19th April 2016)
Sadlier C, O'Connell S, Kelleher M, Bergin C. “Incidence and risk factors for invasive pneumococcal disease (IPD) in HIV-infected individuals ” (April 2016) HIV Medicine  (Vol. 17, pp ).
Sadlier C, Rock C, Kelleher M, Bergin C. “Factors Associated with Invasive Pneumococcal Disease in HIV-infected Adults in the Era of HAART.” (May 2015). Infectious Diseases Society of Ireland 8th Annual Scientific Meeting.
Sadlier C, Carr A, Kelly S, O’Dea S, Bergin C. “Integrated vaccine unit as a model of care for vaccine delivery in a HIV-infected cohort.” (2014)