Usefulness of White Blood Cell Count (WBCC) During Infection: a Comparison Between Hospitalized Geriatric and Young Groups.
Conditions: White Blood Cells Engulfing Red Blood Cells
Sponsor: Universitair Ziekenhuis Brussel

 
 
 
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Usefulness of white blood cell count in the diagnosis of infection: 
comparison between young and geriatric hospitalized groups. 
20/02/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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Protocol Clinical Trial 
 
Abstract 
Title of the project 
Usefulness of white blood cell count (WBCC) during infection: a comparison between 
hospitalized geriatric and young groups. 
 
Objective of the study 
In the general population, increased WBCC and neutrophil count are widely used as markers 
for infection during inflammatory states 1. However, 32% of geriatric patients with an 
infection do not develop an increase in WBCC 2. The hypothesis is that with inflammation, 
geriatric patients have a misadapted response of the immune system (IS) 3. 
Our recent retrospective study 4 has shown that total and differential WBCC were not 
correlated with infection in a geriatric hospitalized population. Therefore, WBCC does not 
seem to be a reliable marker for infection in geriatric hospitalized patients. The 
neutrophil/lymphocyte ratio, and CRP, seem to be better markers.  
We propose to investigate this hypothesis prospectively and assess the role of aging and 
chronic diseases (such as cardiovascular diseases (CVD) and risk factors (CVRF) 5, 
cytomegalovirus (CMV) infection 6, periodontitis 7, onychomycosis 8 ) in this process and 
assess the role of a geriatric assessment. 
To assess the usefulness of WBCC in the diagnosis of infection in geriatric patients and to 
address the contribution of ongoing chronic co-morbidities and age to WBCC-kinetics during 
an acute inflammatory syndrome, we will compare young and geriatric hospitalized patients 
with an inflammatory syndrome with and without infection. 
 
 
 

 
 
 
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Investigator(s) 
Hanne Maes (student master geneeskunde VUB) = principal investigator  
Prof. Dr. Nathalie Compté (geriatrics UZ Brussel) = promotor  
Prof. Dr. Bert Bravenboer (geriatrics UZ Brussel) = head of department 
Prof. Dr. Tony Mets 
 
Sponsor  
No sponsor 
 
Departments/laboratories involved in the study 
UZ Brussels geriatrics department 
UZ Brussels emergency department 
UZ Brussels rheumatology department, pneumology department, endocrinology department 
UZ Brussels central laboratory  
 
Introduction 
In the general population, increased white blood cell count (WBCC) and neutrophils are 
widely used as markers for bacterial infection during inflammatory states 1. However, 32% of 
geriatric patients with infection do not get an increase in WBCC during infection 2. The 
hypothesis is that with inflammation, geriatric patients get a misadapted response of the 
immune system (IS) 3. 
Ageing is associated with immune dysfunction. Older people have a decreased phagocytosis 
and chemotaxis by neutrophils 9, a decreased T-cell activation by dendritic cells, a decreased 
response of the innate immune system during Toll-like receptor stimulation 10, a decrease 
number of naive B- and T-cells 11, an increase number of memory B- and T-cells 12, increased 
presence of monoclonal Ab (MGUS) 13, and an increase in exhausted, senescent T-cells 14. 
This remodeling of the immune system could lead to a higher prevalence of infection, auto-
immune diseases, and cancer in geriatric patients 12. Ageing is also associated with low-grade 
inflammation: a process called inflammaging 15. The origin of inflammaging is multifactorial 
and is associated with cardiovascular risk factors (CVRF) and diseases (CVD) 5, chronic 
cytomegalovirus (CMV) infection 6, periodontitis 7, onychomycosis 8, microbiota changes 16, 
increased intestinal permeability 17 and senescent cells 14. 
Inflammaging is associated with the geriatric syndrome and mortality but also with 
centenarians and longevity 18. The inflammaging process seems to be a result of an adaptation 
to encountered stressors during life: the immunobiography of the individual. The 
immunobiography of the patients could influence the function of the IS leading to a well-

 
 
 
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adapted response of the IS such as in centenarians, or to a mis-adapted response of the IS such 
as in geriatric patients 3. Consequently, the WBCC response in geriatric patients during 
infection could be wel or mis- adapted, depending on the immunobiography. 14 
An inflammatory state is characterized by an acute phase response with increased CRP, in 
both acute and chronic inflammation 19. A rise of CRP can point to an acute infection but also 
to an inflammatory disease such as CV diseases, autoimmune diseases, thrombosis, stroke, 
pulmonary embolism, …  
Our recent retrospective study from 2018 has shown that there was no correlation between 
total and differential WBCC and infection in a geriatric hospitalized population 4. Therefore, 
the WBCC does not seem to be a reliable marker for infection in geriatric hospitalized 
patients. The neutrophil/lymphocyte ratio and CRP appeared to be better markers. 
The aim of the present study is to assess the usefulness of WBCC in the diagnosis of infection 
in geriatric patients and to address the contribution of ongoing chronic co-morbidities and age 
to WBCC kinetics during an acute inflammatory syndrome. We shall compare young and 
geriatric hospitalized patients with an inflammatory syndrome with and without infection.    
 
Study design 
Observational prospective study 
 
The subjects 
Number of subjects 
200 subjects: 
Average value CRP: group 1: 55; group 2: 84 
Average standard deviation: 70.52 
Power 80%: 158 deelnemers 
Power 90%: 202 deelnemers 
alpha = 0.05 
2-sample T-test. 
 
Inclusion criteria 
Acute inflammation is defined as a CRP ≥ 10 mg/l. We will include 2 groups of participants: 
=> A) A group with an inflammatory syndrome and infection; infection being defined as: 
1. Viral infection confirmed by nasopharynx swab for: influenza, RSV, parainfluenza, 
rhinovirusses, coronavirusses. 

 
 
 
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2. Bacterial infection confirmed with positive blood culture, positive articular 
punction, positive expectorations, pneumonia on chest radiograph, or infection 
documented by abdominal imagery (CT or echo), a positive urine culture with a 
confirmed pyelonephritis with a renal echography or a DMSA scintigraphy or specific 
clinical symptoms for pyelonephritis and positive hemoculture.  A positive urine 
culture alone is not considered as urine infection because of the high prevalence of 
asymptomatic bacteriuria in geriatric patients.  
=> B) A group with inflammatory syndrome and inflammatory diseases without infection: 
defined as: 
1. Confirmed pulmonary embolism (PE) by CT or ventilation-perfusion scintigraphy 
2. Microcrystalline arthritis diagnosed by articular punction  
3. Crush syndrome or rhabdomyolyses defined by history of a fall and raised creatine 
kinase in blood sample. 
 
Exclusion criteria 
Immunosuppressive therapy (NSAIDs, corticosteroids, chemotherapy, immunotherapy), 
active cancer, antibiotics before admission, hematological diseases  
 
 
Replacement of subjects 
None. 
 
Restrictions and prohibitions for the subjects 
None. 

 
 
 
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Procedures 
A) Questionnaires:  
taken at UZ Brussels  
-Social: age, home, sex, marital status.  
-Clinical: smoking and alcohol habits, streptococcus pneumoniae and influenza vaccination 
status, allergies, BMI, medical history, current treatment, reason for current hospitalization.  
-Comprehensive geriatric assessment: 
-CIRS-G (Cumulative Illness Rating Score): to quantify disease burden. It rates each organ 
system on a scale of 0 to 4, and differentiates older adults with the highest risk of and severity 
of infection, from those with lower infection risk. 20 
-Katz scale (ADL: assessment of activities of daily living): It rates 6 tasks of daily living 
(bathing, dressing, toilet, transfer, continence and eating) on a scale from 1 to 4. A low score 
means absence of dependence, and a high score the maximum of dependence for the task. 21 
-MMSE (Mini Mental Status Examination): a 0-30 score of cognitive functions, <24/30 
meaning cognitive function impairment. 22 Patients with dementia: we will request approval to 
be included in the study to the family of the patients. 
-MUST (Malnutrition Universal Screening Tool): to assess nutritional status. It divides 
patients into 3 groups: A low risk of malnutrition (score 0). A medium risk of malnutrition 
(score 1): then it is recommended to observe the patient for dietary intake. A high risk of 
malnutrition (score ≥2): treat the malnutrition. 23  
-Questionnaire for periodontal health. The newly developed questionnaire produces a reliable 
assessment of the individual risk of periodontitis (total score) and the need for periodontal 
treatment as well as the differentiation between gingivits and peridontitis. 24 

 
 
 
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-Grip strength: Inflammatory states in the elderly are also associated with a decrease in 
muscle strength and fatigue resistance, as seen at UZ Brussels by Bautmans et al. The reduced 
strength and fatigue resistance in geriatric patients with inflammation are significantly related 
with the concentration of circulating CRP levels. 25 In our study we will use the martin 
vigorimeter which is at our disposal at the geriatrics ward of UZ Brussels, to measure the 
patients’ grip strength and muscle fatiguability and determine which factors seem to 
contribute to a decrease in muscle strength (CRP, CVD, CVR, infection, periodontitis, CMV 
status, onychomycosis, age). We will use the Martin vigorimeter (Elmed, Addison, IL) to 
assess grip strength and fatiguibility. We will ask the patients to squeeze the rubber bulb of 
the vigorimeter as hard as possible in 3 consecutive attempts, to assess their grip strength. The 
highest score for each hand is recorded. Fatigue resistance will be assessed by asking the 
patient to squeeze the bulb of the vigorimeter as hard as possible and to maintain this pressure 
as long as possible; the time (seconds) until the pressure diminished to half of the maximal 
grip strength is recorded for each hand.25 26  
B) Collection of data from physical examination 
C) Clinical evaluation of onychomycosis of the toenails: We will perform a clinical 
examination of the toenails. Following parameters are found to be significantly related to 
positive mycology results in onychomycosis patients 8: scaling on one or both soles, white 
crumbly patches on the nail surface, and an abnormal colour of the nail.  
D) Follow up of bacterial and viral culture analyses  
Observational data from bacterial and viral samples during hospitatalization : 
1. Viral infection confirmed by nasopharynx swab for: influenza, RSV, parainfluenza, 
rhinovirusses, coronaviruses 
2. Bacterial infection confirmed with positive blood culture, positive articular punction, 
positive expectorations, pneumonia on chest radiograph, or infection documented by 
abdominal imagery (CT or echo), a positive urine culture with a confirmed pyelonephritis 
with a renal echography or a DMSA scintigraphy or specific clinical symptoms for 
pyelonephritis and positive hemoculture.  A positive urine culture alone is not considered as 
urine infection because of the high prevalence of asymptomatic bacteriuria in geriatric 
patients.  
 
E) Follow up of blood analyses:  
Observational data from blood samples during hospitalization: 
-Day 0 (at the emergency department): CRP, total and differential WBCC, renal function 
-Day 1: at hospitalization, within 24h of admission 

 
 
 
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- Geriatric patients: CRP, total and differential WBCC, renal function, hepatic function 
(transaminases), albumin, prealbumin, protein profile and monoclonal protein, vitamin 
B12, folic acid, hemoglobin, hematocrit, TSH, CMV-serology. 
- Young patients: CRP, total and differential WBCC, renal function, albumin, vitamin 
B12, folic acid, TSH, CMV-serology. 
-Day 3: CRP, total and differential WBCC. 
-Day 5: CRP, total and differential WBCC.  
 
Flowchart 
Questionnaires, blood samples: conducted by Hanne Maes. Supervising MD: Dr. Nathalie 
Compté, UZ Brussels. 
 
Randomisation/blinding 
Observational study, not applicable. 
 
Prior and concomitant therapy 
All medication can be continued during this study. 
 
Study analysis 
Statistical analysis 

 
 
 
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We will perform student t-tests or Mann-Whitney rank sum tests to compare geriatric/young 
patients with and without infection. To assess the contribution of age, comorbidities and 
geriatric syndrome in the kinetics of WBCC, we will perform univariate and multivariate 
analyses. 
 
Quality control and quality assurance 
/ 
Publication policy 
/ 
 

 
 
 
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