ARCHIVED - Canada Communicable Disease Report

Statement on the recommended use of pneumococcal 23-valent polysaccharide vaccine in homeless persons and injection drug users

Preamble

The National Advisory Committee on Immunization (NACI) provides the Public Health Agency of Canada with ongoing and timely medical, scientific and public health advice relating to immunization. The Public Health Agency of Canada acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge and is disseminating this document for information purposes. People administering the vaccine should also be aware of the contents of the relevant product monograph(s). Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) of the Canadian manufacturer(s) of the vaccine(s). Manufacturer(s) have sought approval of the vaccine(s) and provided evidence as to its safety and efficacy only when it is used in accordance with the product monographs. NACI members and liaison members conduct themselves within the context of the Public Health Agency of Canada’s Policy on Conflict of Interest, including yearly declaration of potential conflict of interest.

Introduction

As a result of outbreaks of invasive pneumococcal disease (IPD) among non-elderly adults with a history of homelessness and/or illicit drug use in urban centres in western Canada during 2006-2007, the National Advisory Committee on Immunization (NACI) reviewed the options for expanding the risk groups for which 23-valent pneumococcal polysaccharide vaccine (PPV- 23) is recommended. The recommendations in this statement deal specifically with these groups and present the available data on their risk of IPD. As well, there is a brief discussion of the delivery of vaccine programs to these populations.

For the purposes of this statement, homeless persons are defined as those individuals living in insecure housing either transiently or chronically. In the literature, there are a number of terms used to describe individuals who use drugs, for example “injection drug users”, “intravenous drug users” or “illicit drug users”. Each study defines which substances are included and the definition used; data are presented as described in the primary studies. For these recommendations, “illicit drug use” refers to both crack cocaine use and injection drug use.

Prior NACI recommendations

Current recommendations are that PPV-23 should be given to all persons > 65 years of age and individuals ≥ 5 years of age at high risk of IPD; children between the ages of 2 and 5 at high risk of IPD should receive conjugate pneumococcal vaccine followed by PPV-23 in order to increase the serotype coverage; PPV-23 should be given to high-risk individuals with co-morbid conditions, such as sickle cell disease and other sickle cell hemoglobinopathies, other types of functional or anatomic asplenia, HIV infection, immunocompromising conditions, pulmonary disease, diabetes, liver cirrhosis, chronic renal disease, cerebrospinal fluid leaks or cochlear implants; individuals with risk factors such as alcoholism and smoking should also receive PPV- 23. For more detailed information related to the use of pneumococcal vaccines, dosing and contraindications, readers are referred to the Canadian Immunization Guide(1).

Literature review

A literature review was conducted using the Medline database from 1 January, 1966, to 1 February 2008. All articles available in English, of any study design, were retrieved using the following MeSH subject headings: Streptococcus pneumoniae, pneumococcal infections, pneumococcal vaccines, risk factors, substance abuse, intravenous or homeless persons. The results are presented below.

Homeless populations

Homeless populations have high rates of a variety of respiratory infections, including S. pneumoniae^(2-4). In a 2000-2002 study of adults ≥ 17 years of age presenting to six hospitals and one emergency department in Edmonton, the attack rate for bacteremic pneumococcal pneumonia was 266.7 per 100,000 person-years among homeless persons, compared with 9.7 per 100,000 person-years overall. However, homelessness was not predictive of bacteremic pneumococcal pneumonia after adjustment for other factors, including smoking status⁽⁵⁾. A recent study using population-based adult surveillance data in Toronto found that IPD, defi ned as isolation of the organism from a sterile site, was more common among homeless individuals, at a rate of 273 per 100,000 per year, than their housed counterparts (9.0 per 100,000 per year)⁽⁶⁾.

Overcrowded shelters and pneumococcal carriage rates among shelter residents as high as 60% can facilitate disease transmission and outbreaks^(7,8). Four clusters or outbreaks of pneumococcal disease occurring in homeless shelters have been described in the literature (Table 1). Risk factors in these pneumococcal outbreaks included alcoholism and age < 65 years^(8,10). Lifetime rates of alcoholism among homeless persons are estimated at about 60%, and alcohol problems are approximately 6 to 7 times higher than in the general population. Homeless persons also suffer disproportionately from other chronic conditions against which vaccination with PPV-23 is recommended, such as chronic obstructive pulmonary disease⁽²⁾.

Illicit drug use

It is difficult to delineate the risk of pneumococcal disease associated specifically with the use of illicit drugs, as these individuals often have other co-morbid conditions such as HIV infection. As well, the type of drug use varies. The increased risk of bacterial pneumonia and IPD among HIV-infected individuals, whether or not they use illicit drugs, is well-established^(11-18), and persons with HIV infection are already a target group recommended by NACI for pneumococcal vaccine⁽¹⁾. Few studies have assessed the risk of IPD among persons who use illicit drugs without HIV infection (Table 2). In two studies, the incidence of pneumococcal pneumonia ranged from 1.2 to 3.4 per 1,000 person-years among HIV-negative persons who use illicit drugs, which was slightly higher than reported rates in the general population (0.5 to 1.0 per 1,000 person-years) but much lower than among HIV-positive persons who use illicit drugs (19 to 35 per 1,000 person-years)^(11,14). Among persons who use drugs and were attending a health service in Amsterdam, there was no increased risk of self-reported pneumonia among HIV-negative persons who injected drugs during the follow-up period as compared with those who did not inject drugs⁽¹³⁾.

Data from the surveillance of IPD in the United States (U.S.) show that injection drug use does not appear to additionally predispose these individuals to serotypes that are more commonly found in adults with HIV (6A, 6B, 9N, 9V, 18C, 19A, 19F and 23F)⁽¹⁹⁾, antibiotic-resistant forms of pneumococci⁽¹⁹⁾ or death from IPD⁽²⁰⁾. One study demonstrated that injection drug users had twice the risk of recurrent IPD than non-users after adjustment for HIV status and other underlying conditions⁽²⁰⁾. Persons who use injection drugs also represented approximately one-quarter of recurrent episodes of IPD in US Active Bacterial Core (ABC) Surveillance in 1998, but the potential correlation of a history of injection drug use with other underlying conditions that may be associated with recurrent disease was not assessed⁽²¹⁾.

Surveillance data show that there is signifi cant overlap between persons who use illicit drugs and the target groups recommended to receive pneumococcal vaccine. In a 2001-2003 study of adult IPD patients from six ABC Surveillance sites, 95% of 38 current injection drug users and 89% of 105 former injection drug users had a pneumococcal vaccine indication recommended by the US Advisory Committee on Immunization Practices (ACIP)⁽²²⁾. Multi-centre enhanced surveillance of 3,031 injection drug users in Canadian cities showed that 95% reported smoking in the previous 6 months, 13% were HIV-positive, and 40% reported unstable housing⁽²³⁾.

Table 1. Clusters or outbreaks of pneumococcal disease associated with residing in a homeless shelter

Delivering immunization programs to homeless persons and/or those who use illicit drugs

As many homeless persons and persons who use illicit drugs may not have a regular source of health care, alternative strategies for reaching these populations may be necessary. For example, mass immunization campaigns have been conducted in Vancouver’s Downtown Eastside (DTES), which has a population characterized by poverty, crowded housing, homelessness, poor nutrition and hygiene, and chronic illness. There are an estimated 12,000 injection drug users residing in the DTES. Pneumococcal immunization campaigns were conducted in November 1999 (7,575 doses), November 2000 (1,086 doses) and June 2002 (1,205 doses); influenza, hepatitis A and hepatitis B vaccines were also offered during some or all of these campaigns. Sites visited included single room occupancy hotels, soup kitchens and food banks, community agencies, fixed-site needle exchanges, drop-in centres, pubs, medical clinics, parks, streets and alleys. Vaccine was provided to persons who were eligible according to NACI recommendations. Few adverse events were officially reported despite the fact that some recipients had likely received a previous dose(24,25). Adverse events related to multiple pneumococcal vaccines have not been studied adequately to determine the risk it may pose to individuals. Compared with the year preceding the November 1999 campaign, during the year after it there was a significant decrease in the number of emergency department visits for pneumonia (863 and 646 visits respectively; p < 0.001). Rates of hospital admission for pneumonia through the local emergency department also decreased, by 25%(26).

Outbreak of S. pneumoniae serotype 5 in urban centres in western Canada, 2006-2007

From 2005 to 2007, outbreaks of IPD caused by S. pneumoniae serotype 5 (ST5) occurred in western Canada, particularly Alberta and British Columbia (B.C.). Two outbreaks occurring in Vancouver and Calgary are presented in further detail here.

Alberta

From 2000 to 2004, between 0 and three cases of ST5 IPD were reported annually to Alberta Health and Wellness, accounting for < 1% of reported cases of IPD in the province. In 2005, with earliest reported onset dates in February, the number of ST5 IPD cases in Alberta increased to 40 (10% of 383 cases of IPD, all serotypes). The increase continued dramatically throughout 2006, when there were 204 cases of ST5 IPD (38% of 539 total cases of IPD). In 2007 there were an additional 220 cases (37% of 597 total IPD cases) reported. Cases have been reported in all nine regional health authorities, most occurring in Calgary and Edmonton (K. Simmonds, Alberta Health and Wellness, 12 March, 2008, personal communication).

Analysis of IPD cases compiled by the Calgary Area S. pneumoniae Epidemiology Research (CASPER) surveillance system in 2006-2007 found that ST5 IPD cases had clinical presentations and multiple risk factors that differed from those of other IPD (non-ST5) cases that occurred in persons ≥ 16 years. Compared with non-ST5 IPD cases, they were more likely to have empyema (20% vs 9%, odds ratio [OR] 2.5, 95% confi dence intervals [CI] 1.4 to 4.6) and to have a chest tube inserted (19% vs 9%, OR 2.5, 95% CI 1.3 to .8); there was also a trend towards lower mortality (2% vs 9%, OR 0.3, 95% CI 0.06 to 1.13). Multivariate analysis found that ST5 IPD cases were significantly more likely to be aged 16 to 64 years (98% vs 66%, OR 9.5, 95% CI 2.2 to 41.4), homeless (63% vs 12%, OR 3.5, 95% CI 1.8 to 6.6) and users of illegal drugs (57% vs 11%, OR 6.5, 95% CI 3.6 to 12.0)(27) . In August 2006, the Alberta PPV-23 high-risk immunization program was expanded province-wide to include homeless/ disadvantaged individuals. The immunization program was also expanded to explicitly include those with hepatitis C virus infection, which was previously included under chronic liver disease. Regional health authorities have since been immunizing these groups. In addition, a targeted immunization campaign in Calgary homeless shelters took place from 19 to 22 December, 2006, to increase uptake in this population.

Vancouver, British Columbia

Invasive disease due to ST5 was also previously uncommon in B.C. (one case per year in 2004 and 2005). In August 2006, an increase in IPD cases was detected at St. Paul’s Hospital, which serves Vancouver’s DTES. Forty-six cases of IPD were admitted in November, compared with the usual monthly admissions of 0 to 10 cases. Hospital admissions peaked in December 2006. Between 1 August, 2006, and 12 March, 2007, there were 163 cases of ST5 reported to the BC Centre for Disease Control, including 125 cases from Vancouver and 27 cases from Fraser Health Authority, and at least three deaths. Most cases (78%) reported living in or being exposed to Vancouver’s DTES (J. Dhaliwal, BC Centre for Disease Control, 23 March, 2007, personal communication). Of the cases of serotype 5, 25.6% were homeless individuals. Frequenting or living in the DTES was also used as an indication of unstable housing. In univariate analysis, exposure to DTES was statistically signifi cant (OR 10.25, 95% CI 4.07-25.8, p < 0.001), but once other factors were controlled for it was no longer significant (OR 7.79, 95% CI 0.91-66.8, p = 0.06). Multivariate analysis identified only crack cocaine use as a risk factor (OR 12.4, 95% CI 2.22- 69.5, p < 0.01) (R. Gustafson, 1 February, 2008, personal communication).

In response to the outbreak, pneumococcal immunization campaigns were launched targeting indigent persons and those who use illicit drugs in affected urban areas. In November and December 2006, teams of outreach nurses from Vancouver Coastal Health conducted PPV-23 immunization of more than 4,000 people in the inner city by targeting shelters, food banks and other community locations. Immunization of indigent persons and persons who use illicit drugs in regions adjacent to Vancouver has also been accelerated.

Table 2. Pneumococcal disease among people who use illicit drugs

Recommendations

In summary, there is evidence from cohort studies, cross-sectional surveys, outbreak investigations and case reports that homeless persons have a higher incidence of IPD than the general population. Also, a high proportion of these individuals have co-morbidities or risk factors that would make them eligible for pneumococcal immunization. Homeless persons living in shelters may be at additional risk of outbreaks of pneumococcal disease because of the crowded living conditions and high carriage rates. For endemic disease, there are methodological difficulties in determining whether homelessness is causally linked to IPD. It is recognized that homelessness may be a confounder, that is, it refl ects the presence of other risk factors that are disproportionately present in homeless individuals and contribute to IPD rather than being an independent risk factor. From the Calgary and Vancouver outbreak data presented above, there is evidence that homelessness is an independent risk factor for serotype 5 IPD. There is limited evidence that persons who use illicit drugs are at increased risk of pneumococcal disease. The increased risk may be due to the strong correlation of crack cocaine drug use with underlying conditions such as smoking and HIV infection.

NACI therefore recommends the following:

• The 23-valent pneumococcal polysaccharide vaccine should be provided to persons who are homeless.
• Individuals who use illicit drugs should also be considered for vaccination with 23-valent polysaccharide pneumococcal vaccine.

Considerations for future research:

• Creative solutions need to be developed to delivering pneumococcal vaccine to eligible individuals at homeless shelters, needle exchange programs and/or other sites where there are homeless populations and people who use illicit drugs in order to improve vaccine coverage rates in these populations.
• Further research should be done in these populations to address programmatic issues such as the following:
  • evaluation of vaccine programs for homeless persons and illicit drug users in Vancouver, Calgary and Toronto
  • tracking of immunization status among those with varied contact with health care providers, which may include the use of immunization registries
  • further determination of the risk of adverse events if multiple doses of vaccine are given understanding the dynamics of homelessness in Canada as it relates to the delivery of effective and efficient immunization services to at-risk individuals
  • effective and efficient means to deliver vaccination programs to homeless persons.

References

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2. Hwang SW. Homelessness and health. Can Med Assoc J 2001;164(2):229-33.
3. O’Connell JJ. Nontuberculous respiratory infections among the homeless. Semin Resp Infect 1991;6(4):247-53.
4. Park DR, Sherbin VL, Goodman MS et al. The etiology of community-acquired pneumonia at an urban public hospital: Influence of human immunodefi ciency virus infection and initial severity of illness. J Infect Dis 2001;184:268-77.
5. Shariatzadeh MR, Huang JQ, Tyrrell GJ et al. Bacteremic pneumococcal pneumonia: A prospective study in Edmonton and neighbouring municipalities. Medicine 2005;84(3):147-61.
6. Plevneshi A, Svoboda T, Armstrong I et al. Invasive pneumococcal disease in homeless adults in Toronto: Five years of population-based surveillance. 47th Annual Interscience Congress on Antimicrobial Agents and Chemotherapy, Chicago, September 2007.
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8. DeMaria A, Browne K, Berk SL et al. An outbreak of type 1 pneumococcal pneumonia in a men’s shelter. JAMA 1980;244(13):1446-49.
9. Mufson MA, Kruss DM, Wasil RE et al. Capsular types and outcome of bacteremic pneumococcal disease in the antibiotic era. Arch Intern Med 1974;134:505-10.
10. Birtles A, McCarthy N, Sheppard CL et al. Multilocus sequence typing directly on DNA from clinical samples and a cultured isolate to investigate linked fatal pneumococcal disease in residents of a shelter for homeless men. J Clin Microbiol 2005;43(4):2004-08.
11. Selwyn PA, Feingold AR, Hartel D et al. Increased risk of bacterial pneumonia in HIV-infected intravenous drugs users without AIDS. AIDS 1988;2:267-72.
12. Redd SC, Rutherford GW, Sande MA et al. The role of human immunodeficiency virus infection in pneumococcal bacteremia in San Francisco residents. J Infect Dis 1990;162:1012-17.
13. Mientjes GHC, Spijkerman JB, van Ameijden EJC et al. Incidence and risk factors for pneumonia in HIV infected and non-infected drug users. J Infect 1996;32:181-86.
14. Boschini A, Smacchia C, Di Fine M et al. Community acquired pneumonia in a cohort of former injection drug users with and without human immunodeficiency virus infection: incidence, etiologies, and clinical aspects. Clin Infect Dis 1996;23:107-13.
15. Hirschtick RE, Glassroth J, Jordan MC et al. Bacterial pneumonia in persons infected with the human immunodeficiency virus. N Engl J Med 1995;333(13):845-51.
16. Dworkin MS, Ward JW, Hanson DL et al. Pneumococcal disease among human immunodeficiency virusinfected persons: incidence, risk factors, and impact of vaccination. Clin Infect Dis 2001;32:794-800.
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19. Fry AM, Facklam RR, Whitney CG et al. Multistate evaluation of invasive pneumococcal diseases in adults with human immunodefi ciency virus infection: Serotype and antimicrobial resistance patterns in the United States. J Infect Dis 2003;188:643-52.
20. Nuorti JP, Butler JC, Gelling L et al. Epidemiologic relation between HIV and invasive pneumococcal disease in San Francisco County, California. Ann Intern Med 2000;132:182-90.
21. King MD, Whitney CG, Parekh F et al. Recurrent invasive pneumococcal disease: A population-based assessment. Clin Infect Dis 2003;37:1029-36.
22. Greene CM, Kyaw MH, Ray SM et al. Preventability of invasive pneumococcal disease and assessment of current polysaccharide vaccine recommendations for adults: United States, 2001-2003. Clin Infect Dis 2006;43:141-50.
23. Public Health Agency of Canada. I-Track: enhanced surveillance of risk behaviours among people who inject drugs: Phase I report, August 2006. Ottawa: Surveillance and Risk Assessment Division, Centre for Infectious Disease Prevention and Control, Public Health Agency of Canada, 2006.
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25. Buxton J, Weatherill S, Daly P. Influenza and pneumococcal immunization ‘blitz’ in an inner city area: Downtown Eastside of Vancouver, British Columbia. CCDR 2000;26(14):117-22.
26. Graftstein EJ, Daly PC, Buxton J et al. The effect of a community mass pneumococcal vaccination campaign. Acad Emerg Med 2001;8(5):492-93.
27. Twele L, Tyrell G, Vanderkooi OG et al. Outbreak of serotype 5 (ST5) invasive pneumococcal disease (IPD) in predominantly homeless middle-aged persons in Calgary, Canada. Poster presentation #L-1155 at 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, September 2007.

Members: Dr. J. Langley (Chairperson), Dr. B. Warshawsky (Vice-Chairperson), Dr. S. Virani (Executive Secretary), Dr. S. Dobson, Ms. A. Hanrahan, Dr. J. Kellner, Dr. K. Laupland, Dr. A. McGeer, Dr. S. McNeil, Dr. M.-N. Primeau, Dr. B. Seifert, Dr. D. Skowronski, Dr. B. Tan.

Liaison Representatives:Dr. B. Bell (CDC), Dr. P. Orr (AMMI Canada), Ms. K. Pielak (CNCI), Dr. S. Rechner (CFPC), Dr. M. Salvadori (CPS), Dr. D. Scheifele (CAIRE).

Ex-Officio Representatives: Ms. M. FarhangMehr (CIRID – Canadian Immunization Committee), Major P. Laforce (DND), Dr. B. Law (CIRID – Vaccine Safety), Dr. H. Rode (BGTD), Dr. M. Nsungu (FNIHB – Northern Intertribal Health Authority-Saskatchewan), as external expert.

†This statement was prepared by Ms. Christine Navarro, Dr. James D. Kellner and Dr. Shalini Desai, and approved by NACI.