There have been numerous prior studies of invasive pneumococcal disease (IPD) ranging from those with small numbers that are rich in clinical detail to those that are very large and are focused on the intended and unintended consequences of vaccination but lack necessary clinical details [
Cases of IPD were defined as per the national case definition of isolation of
Research nurses collected sociodemographic, clinical, functional, and laboratory data using a standardized case report form (CRF). The research nurses received training on data collection prior to the start of the study. In addition to the CRF, standard operating procedures documents, definitions, drug classification, and underlying illness categorization were part of their working documents. With respect to underlying illnesses, if the attending physician recorded such an illness it was accepted as such. From September 2012 through the end of the study December 31, 2014, additional data were collected for a substudy examining cardiac events during the hospital stay. Our study received approval from the institutional research review committees of the Alberta Health Regions as well as the University of Alberta ethics review board.
For comparison purposes some characteristics of the Alberta population were obtained from the Alberta Ministry of Health interactive website [
Two thousand four hundred and thirty-five patients with a mean age of 54.2 years had IPD over the 15 years of the study. Across all age groups, males were more likely to have IPD than females. Other sociodemographic features of the study population are given in Table
Sociodemographic and lifestyle features in 2435 adults with invasive pneumococcal disease.
Number | Percent | |
---|---|---|
Number studied | 2435 | 100 |
Number of males | 1380 | 56.7 |
Mean age (SD) | 54.2 (17.8) | |
Aboriginal (first nations) | 312 | 12.8 |
To hospital by ambulance | 1098 | 45.1 |
Admission status | ||
Never seen at a hospital | 3 | 0.1 |
Outpatient only with visits for IV antibiotics | 10 | 0.4 |
Emergency Room only | 229 | 9.4 |
Inpatient | 2193 | 90.1 |
Residence prior to admission | ||
Home | 1960 | 80.5 |
Homeless, no shelter | 98 | 4.0 |
Homeless, shelter | 86 | 3.5 |
Lodge/group home | 119 | 4.9 |
Continuing care facility | 60 | 2.5 |
Subacute care | 7 | 0.3 |
Functional status in the week prior to admission | ||
Fully functional | 2078 | 85.4 |
Walking with assistance | 302 | 12.4 |
Wheelchair | 37 | 1.5 |
Bedridden | 18 | 0.7 |
Smoker, current | 1104 | 45.3 |
Alcohol, excess use | 620 | 25.5 |
Illicit drug use | 482 | 19.8 |
Occupations of 581 patients with IPD compared with Alberta population 2015 working in these occupations.
Occupation | IPD | Alberta population, % | |
---|---|---|---|
Number | % | ||
Accommodation, food services | 37 | 6.3 | 6.5 |
Agriculture | 22 | 3.7 | 2.2 |
Business | 17 | 2.9 | 3.4 |
Construction | 147 | 25.3 | 11.0 |
Education | 35 | 6.0 | 6.7 |
Finance, real estate | 79 | 13.5 | 4.4 |
Forestry, mining, oil, and gas | 44 | 7.5 | 6.4 |
Health care | 20 | 3.4 | 11.7 |
Professional, science, teacher | 15 | 2.4 | 7.8 |
Transportation | 30 | 5.1 | 5.9 |
Utilities | 3 | 0.5 | 0.7 |
Comorbid illnesses were common, being present in 98.9% (Table
Comorbid illnesses in 2435 patients with invasive pneumococcal disease.
Number | Percent | |
---|---|---|
Any underlying disease | 2409 | 98.9 |
Selected underlying diseases | ||
Epilepsy | 136 | 5.6 |
Alzheimer’s disease | 83 | 3.4 |
Stroke | 106 | 4.4 |
Hypertension | 622 | 25.5 |
Heart failure | 156 | 6.4 |
Previous myocardial infarction | 168 | 6.9 |
Atrial fibrillation | 128 | 5.3 |
Anemia | 167 | 6.9 |
Insulin dependent diabetes mellitus | 87 | 3.6 |
Hepatitis C | 307 | 12.6 |
Cirrhosis | 151 | 6.2 |
HIV/AIDS | 117 | 4.8 |
Asplenia | 37 | 1.5 |
Rheumatoid arthritis | 56 | 2.3 |
Asthma | 266 | 10.9 |
Chronic obstructive pulmonary disease | 441 | 18.6 |
Cancer within thepast 5 years | 307 | 12.6 |
Lung cancer | 53 | 2.1 |
Multiple myeloma | 42 | 1.7 |
Chronic lymphocytic leukemia | 19 | 0.7 |
Lymphoma | 17 | 0.7 |
Acute leukemia | 5 | 0.2 |
Solid organ transplant | 14 | 0.6 |
No underlying disease | 26 | 1.1 |
One underlying disease | 2121 | 87.1 |
Two underlying diseases | 256 | 10.5 |
Three underlying diseases | 32 | 1.3 |
The manifestations of IPD are presented in Table
Manifestations of invasive pneumococcal disease among 2435 patients.
Manifestation | Number | Percent |
---|---|---|
Bacteremia | 2325 | 95.5 |
Bacteremia source unknown | 316 | 12.9 |
Pneumonia | 2009 | 82.2 |
Meningitis | 120 | 4.9 |
Cellulitis | 65 | 2.7 |
Sinusitis | 44 | 1.8 |
Septic arthritis | 40 | 1.6 |
Peritonitis | 39 | 1.6 |
Otitis media | 38 | 1.6 |
Endocarditis | 26 | 1.0 |
Pericarditis | 20 | 0.8 |
The complications and outcomes from IPD are shown in Table
Complications/outcomes of invasive pneumococcal disease among 2435 patients.
Complication | Number | Percent |
---|---|---|
Altered mental status | 1039 | 42.7 |
Intensive care admission | 618 | 25.4 |
Respiratory failure requiring | ||
Mechanical ventilation | 547 | 22.5 |
Pleural effusion | 846 | 34.7 |
Chest tube | 255 | 10.5 |
Aspiration | 179 | 7.4 |
Empyema | 175 | 7.2 |
Renal failure requiring dialysis | 99 | 4.1 |
Congestive heart failure | 90 | 3.7 |
Myocardial infarction | 78 | 3.2 |
Cardiac arrest | 70 | 2.8 |
New onset seizures | 67 | 2.8 |
Upper GI bleed | 64 | 2.6 |
Liver failure | 62 | 2.5 |
Lower GI bleed | 31 | 1.2 |
New onset stroke | 28 | 1.1 |
Pulmonary embolus | 11 | 1.3 |
|
|
|
Transferred to another acute care facility after admission | 275 | 11.6 |
Remained in acute care facility after infection cured | 149 | 6.1 |
Discharged home on antibiotics | 1370 | 56.3 |
Home care following discharge | 288 | 11.8 |
The substudy (
Cardiac events and investigations 871 patients with IPD.
Event or investigation | Number | Percent |
---|---|---|
Atrial fibrillation | 109 | 12.5 |
Myocardial infarction | 15 | 1.7 |
Asystole | 13 | 1.5 |
Ventricular tachycardia > 30 sec | 5 | 0.5 |
|
||
Cardiology consultation | 60 | 6.8 |
Coronary angiogram | 9 | 1 |
Echocardiogram | 210 | 24.1 |
Tricuspid regurgitation | 114 | 54.3 |
Mitral regurgitation | 112 | 53.3 |
Aortic regurgitation | 25 | 11.9 |
Valve vegetation | 5 | 2.3 |
Ejection fraction | ||
≥50% | 170 | 80.7 |
40–45% | 23 | 10.9 |
30–35% | 6 | 2.8 |
20–25% | 5 | 2.3 |
<20% | 8 | 3.8 |
Table
Selected
Serotype | Number | Percent |
---|---|---|
1 | 28 | 1.1 |
3 | 161 | 6.6 |
4 |
219 | 9.0 |
5 | 242 | 9.9 |
6A | 51 | 2.1 |
6B |
42 | 1.7 |
7F | 129 | 5.3 |
9V |
64 | 2.6 |
14 |
92 | 3.8 |
18C |
39 | 1.6 |
19A | 113 | 4.6 |
19F |
53 | 2.2 |
23F |
45 | 1.8 |
2 | 1 | 0.04 |
8 | 193 | 7.9 |
9N | 65 | 2.7 |
10A | 17 | 0.7 |
11A | 80 | 3.3 |
12F | 70 | 2.9 |
15B | 15 | 0.6 |
17F | 27 | 1.1 |
20 | 93 | 3.8 |
22F | 176 | 7.2 |
32F | 0 | 0 |
33F | 45 | 1.8 |
16F | 33 | 1.4 |
23A | 39 | 1.6 |
23B | 30 | 1.2 |
16F | 33 | 1.4 |
The first 13 serotypes are in PCV-13 and first 23 in PPV-23.
The percentage of males with IPD at 56.7% was higher than the percentage of females. Despite the introduction of pneumococcal conjugate vaccines the rate of IPD among males remains higher than that among females especially in children and in adults aged 40–64 and >74 years [
People of Aboriginal descent were overrepresented in this study population at 12.8% whereas they constitute about 5.2% of the population of Alberta [
Almost half the patients with IPD required an ambulance to come to hospital. This is similar to what is observed at a tertiary care hospital in Halifax where 45% of the patients with all-cause pneumonia arrive by ambulance (Petrie D, personal communication). However 90% of our patients were admitted to hospital in sharp contrast to the rate of 47% admission rate for all-cause pneumonia in the Edmonton area but not surprising since most of these patients were bacteremic [
Residence at the time of admission may have implications for programs directed towards prevention of IPD in adults. Only 80% of our patients were living at home whereas 7.5% were homeless and 7.4% were in a group home setting. The rate of homelessness among patients with IPD is much higher than the 2.5% observed for patients with all-cause community-acquired pneumonia in the Edmonton area [
In terms of common lifestyle risk factors for IPD, almost half of the patients in our cohort were tobacco smokers. This contrasts with 28.3% of those with all-cause pneumonia in Edmonton requiring hospitalization and with a 28% smoking rate in the general population of Alberta [
Occupation may also be a risk factor for acquisition of IPD. Previously we found that welders were at increased risk for IPD with a rate of 22.7/100,000 versus 8.7/100,000 in the general adult population [
The vast majority (98.9%) of our patients had one or more comorbid illnesses. Moore et al. found that 76% of the adults with IPD in the USA had an indication for pneumococcal vaccination [
From 1935 to present, pneumonia has remained the major manifestation of IPD [
Almost half (43.7%) of the study population had alteration of mental status. This is much higher than the 11.5% rate among adults with all-cause pneumonia admitted to Edmonton hospitals [
Just over 1% of our patients had new onset stroke following admission to hospital. From 2.2 to 17% of all strokes have onset during hospitalization for a diagnosis or procedure other than stroke [
Pulmonary embolism occurred in 1.3% of our patients. Investigators from Taiwan found that patients with pneumococcal pneumonia were 1.97 times more likely to have a pulmonary embolus than age and sex matched controls without pneumonia [
Several of the complications that occurred were pneumonia specific. Thus decortication was necessary because of late stage empyema. Bronchopleural fistula is an uncommon complication that occurs because cavitating pneumonia results in a pneumothorax [
While necrotizing fasciitis is more commonly associated with Group A
Because of a growing literature on the cardiovascular sequelae of sepsis in general [
Table
A strength of this study is the detailed collection of data which allow for a full appreciation of the various epidemiological and clinical factors in IPD. This strength is also a weakness in that in some areas necessary data were not collected. However what the study does do is allow for the development of a standardized data collection instrument which can be used in all future such studies so that comparisons from study to study can be made. There are also several noteworthy limitations to our study. First and foremost, we do not have detailed immunization data for these patients. Second, comorbidities and complications were based on physician records and not necessarily standardized definitions. For example, serial troponins were not collected on all IPD patients nor were echocardiograms done on all patients. Third, biomarkers and measures of inflammatory response were not routinely collected. Fourth, we did not gather data on the few IPD patients that may not have been admitted to hospital. Last, our cohort, though population based, was drawn from the northern half of one province in Canada and some may be concerned that our results are not generalizable to other jurisdictions or nations.
In conclusion, IPD remains a serious infection in adults. Preventative measures to improve vaccination rates especially in the elderly and groups at higher risk that may be harder to reach as shown in this study are needed [
The funders had no role in the design of the study or data analysis and they have not seen the manuscript.
Other than the two research grants mentioned in the Acknowledgments, authors declare no conflicts of interest.
T. J. Marrie and G. J. Tyrrell designed the study, organized the data collection, and had full access to all of the data in the study. Dean T. Eurich conducted all analyses and had full access to the data. T. J. Marrie, G. J. Tyrrell, Dean T. Eurich, and Sumit R. Majumdar wrote the manuscript. All authors contributed to the interpretation of data, revising the manuscript for intellectual content, and approving the manuscript to be published.
This study was supported by a grant-in-aid from Pfizer, Canada, and Merck Canada Inc. Sumit R. Majumdar holds the Endowed Chair in Patient Health Management supported by the Faculties of Medicine and Dentistry and Pharmacy and Pharmaceutical Sciences at the University of Alberta. Dean T. Eurich is a Canada Research Chair supported by the Government of Canada. The authors wish to thank Ibrahim Quazi and Lilly Yusho for data management and Carol Mangan RN for data collection. They also thank the microbiology staff of hospitals in Northern Alberta for forwarding