Point-of-Care: A Novel Approach to Periodontal Diagnosis

*Nancy Srivastava and Shivendra Rana*

## **Abstract**

Being one of the prevalent oral diseases, periodontal disease is marked by the presence of gingival inflammation and periodontal tissue destruction. Recently, there is a paradigm shift in the understanding of periodontal disease; it is now believed to be episodic in nature, showing periods of activity and inactivity. Thereby, posing a challenge for clinicians to diagnose this. Conventional diagnostic methods basically measure past tissue destruction, arising the need for new diagnostic methods that should be able to detect active sites of destruction, predict future progression, and determine the response to the therapy thus, leading to early diagnosis and better cure for the patient. One such advance is the development of point-of-care devices, which are rapid chair-side testing methods. These devices are already in use in healthcare services, a common example being home-used pregnancy test strips. This point-ofcare technology is now expanding its arms in periodontics as well, thus simplifying diagnosis and improving the therapeutic outcomes of the patient. In light of the above facts, this chapter throws light on periodontal diagnosis and various commercially available point-of-care devices.

**Keywords:** biomarkers, genetic testing, antigen-antibody reaction, gingivitis, body fluids

## **1. Introduction**

Oral cavity is the home of numerous microorganisms. Exposed to the outer environment, the oral mucosa is under continuous attack from various pathogens. The immune inflammatory response, which arises due to these pathogens, causes inflammation [1].

Periodontitis, the inflammation of periodontium, is one of the leading oral problems affecting the world. And like any other disease, the earlier it is diagnosed, the better is the prognosis [2].

Traditionally, periodontitis has been diagnosed by probing depth, bleeding on probing, or bone loss by radiographs [3, 4]. All these procedures tell us only the destruction caused by the disease till date and reflect only the clinical phenotype and not the biological phenotype. Knowledge about biologic phenotypes helps in assessing the burden of microbial and inflammatory load, which further affects the progression of periodontitis [1].

With advances in sciences, it has become known that diagnostic processes need to reveal much more than just the disease. It needs to help in locating the sites of active


### **Table 1.**

*Table showing various available point-of-care devices [10].*

disease, susceptibility of the patient to disease, future progression of the disease, long-term maintenance, patient response, and microbial challenge [5–7].

Point-of-care (POC) testing can be defined as testing performed close to the patient at the time care is required. POC can revolutionize both periodontal diagnostic and therapy. These tests rely on the detection of a plethora of biomarkers of disease activity. These markers present in saliva, gingival crevicular fluid (GCF), plaque, or living tissue are quantifiable and indicate health and disease [8, 9]. This chapter covers all the latest POC diagnostics available (**Table 1**), which detect markers for periodontal diseases.

## **2. Point-of-care diagnostics**

A good diagnostic marker should always have high specificity and sensitivity [11]. Saliva and GCF are vehicles with great potential to be used in diagnostic tests for various diseases. They are easy to collect and are rich in locally or systemically derived biomarkers of periodontal diseases [10].

### **2.1 Saliva**

Saliva is a bio-fluid that is very useful and easily accessible and can be used to monitor oral and systemic health (**Table 2**) [8]. Most of the biomarkers found in


### **Table 2.**

*demonstrating the biomarkers present in saliva [10].*

blood are also present in saliva (**Table 3**). Moreover, unlike blood, it does not clot or easily spreads infections. However, a disadvantage of saliva is the lower concentration of biomarkers in comparison to serum, thus requires the test to be highly sensitive [12]. Moreover, saliva is also influenced by environmental and psychological factors.

## *2.1.1 Biochemical tests done on saliva*

## *2.1.1.1 Oral fluid nano sensor test (OFNASET)*

It is an ultrasensitive and ultraspecific automated electrochemical detection system for salivary proteins and nucleic acids. This test is an oral cancer screening device that is developed by the University of California, Los Angeles (UCLA) collaborative oral fluid diagnostic research laboratory, led by Dr. David Wong [8, 13]. Four salivary mRNA biomarkers (SAT, ODZ, IL-8, and IL-1b) and two salivary proteomic biomarkers (thioredoxin and IL-8) are detected in the system [14].

### *2.1.1.2 Electronic test chip*

This microchip-based detection system is used for measuring analytes (acids, bases, electrolytes, and proteins) in the solution phase. Antigen-antibody reactions


### **Table 3.**

*Commercially available salivary point-of-care diagnostics [10].*

take place on the interior surface of microspheres. The microspheres, increase the surface area and thus, makes it more efficient than ELISA, where the reactions take place on a single layer on the bottom of the well [15].

## *2.1.1.3 OraQuick*

It is the first FDA-approved oral swab in-home test for HIV-1 and HIV-2. It is a stick-like device with a fabric swab and provides results within 20 minutes [14].

## *2.1.1.4 Integrated microfluidic platform for oral diagnostics (IMPOD)*

This kit rapidly measures MMP-8 a biomarker for detection of periodontal disease in saliva and other biomarkers by electrophoretic immunoassay [14].

## *2.1.2 Microbiological tests done on saliva*

## *2.1.2.1 My periopath*

My periopath is a commercially available POC device produced by oral DNA labs. It detects the pathogens causing periodontal disease in saliva samples. This test uses DNA polymerase chain reaction to detect the type and concentration of bacteria present in the salivary samples [16].

## *2.1.2.2 OMNIgene*

This kit provides results in a short period and also these results can be mailed or faxed to the clinician. It can identify pathogens by either DNA probe or RNA probe. By DNA probes, it identifies *Porphyromonas gingivalis, Prevotella intermedia, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Eikenella corrodens, Campylobacter rectus, Bacteroides forsythus,* and *Treponema denticola* [17]. By RNA probe, it identifies *Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema forsythia,* and *Treponema denticola* [16]*.*OMNIgene-ORAL is a commercial POC device produced by DNA Genotek company.

## **2.2 Gingival crevicular fluid (GCF)**

GCF is a body fluid derived from serum, leukocytes, and cells of periodontium and oral microflora [18]. Its composition is influenced by both external environment and body physiology [19]. Therefore, GCF contains a variety of potential markers derived from the host and bacteria from supragingival and subgingival plaque (**Table 4**). These biomarkers can be categorized as (i) inflammatory and immune products, (ii) bacterial enzymes, (iii) host-derived enzymes, (iv) tissue breakdown products, and (v) bone-specific proteins.

The biomarkers in GCF provide information regarding inflammation, loss of bone, patient susceptibility, detection of periodontal disease, prognosis of disease, and onset of disease (**Table 5**) [20, 21]. The disadvantages of GCF are that it requires multiple samples of individual tooth sites and extreme lab processing [22]. Moreover, the collection of samples is difficult, and easy contamination of GCF can occur [23]. This makes GCF a difficult medium for chair-side diagnosis.


### **Table 4.**

*Biomarkers in gingival crevicular fluid [10].*


### **Table 5.**

*Commercially available kits using GCF for detecting host-derived enzymes [10].*

### *2.2.1 Biochemical tests done on GCF*

### *2.2.1.1 Periogard*

It detects aspartate aminotransferase (AST), which is released on cell death due to periodontal diseases (**Figure 1**) [24]. Thus, periogard can easily locate sites with active disease processes [25]. The only disadvantage is the numerous steps required and difficulty in colour measurement [26].

**Figure 1.** *Principle of periogard.*

## *2.2.1.2 Pocket watch*

Pocket watch also analyzes AST levels but through a different method. AST acts as a catalyst in the exchange of an amino group of cysteine sulfuric acid by α-ketogluteric acid to produce β-sulfinyl pyruvate in the presence of pyridoxal phosphate. Inorganic sulfite is released by the spontaneous decomposition of glutamate β-sulfinyl pyruvate. These sulfite ions produced react with malachite green to convert it into a colorless form, thereby showing the pink-colored rhodamine B dye. Thus, the rate of conversion assesses the AST concentration [27].

## *2.2.1.3 Periocheck*

It detects neutral proteases in GCF, such as elastases, proteinases, and collagenases, and is a FDA-approved rapid chair-side test (**Figure 2)** [28].

## *2.2.1.4 Prognostik*

It was developed in 1993 and helped in identifying active sites by measuring elevated MMP (**Figure 3)**. MMPs are host-derived proteinases, which play a major role in periodontitis and dental peri-implant health and disease. MMPs, such as elastases, are released by the lysosomes of polymorphonuclear leukocytes [29].

## *2.2.1.5 MMP dipstick*

MMP dipstick detects MMP-8, which differentiates sites having healthy gingiva, gingivitis, and periodontitis [30].

### **Figure 2.**

*Principle of periocheck.*

### **Figure 3.**

*Principle of prognostik.*


### **Table 6.**

*Biomarkers present in dental biofilm [10].*

## *2.2.1.6 Plaque*

Numerous studies have detected pathogens in dental plaque causing periodontal diseases (**Table 6**). Numerous commercially available kits have emerged, which detect these pathogens and help in diagnosis and treatment (**Table 7**) [10].


### **Table 7.**

*Other commercially available kits for detecting bacterial protease [10].*

## *2.2.2 Microbial tests done on plaque*

## *2.2.2.1 Perioscan (BANA)*

It basically detects trypsin-like proteins, which are produced by various periopathogens, such as *P. gingivalis*, *T. denticola,* and *T. forsythia* (**Figure 4)** [31]. A major disadvantage of perioscan is that it cannot differentiate among these bacteria. Moreover, it cannot detect non-trypsin-like enzymes, thus limiting the number of pathogens [32].

## *2.2.2.2 Evalusite*

This kit uses membrane-based enzyme immunoassay and can detect *A. actinomycetemcomitans, P. gingivalis, and P. intermedia* (**Figure 5)**. The major limitation is the ability to detect only these three pathogens. Moreover, the detection is done by assessing the change in color, which is always subjective and varies from person to person [24].

## *2.2.2.3 Perio 2000*

Similar to perioscan, this kit detects *P. gingivali, P. intermedia,* and *T. forsythia.* It measures volatile sulfide compounds (VSCs), which are produced by bacteria after

**Figure 4.** *Principle of perioscan.*

### **Figure 5.** *Principle of evalusite.*

degrading the serum proteins (cysteine and methionine), and displays it digitally. The main advantage is that there is no need to collect GCF as the probe tip can be inserted directly into the gingival sulcus.

## *2.2.2.4 Toxicity prescreening assay (TOPAS)*

It directly detects bacterial toxins and bacterial proteins in GCF. Thus, it is able to locate active disease sites. It is a chair-side test kit that shows results by changing color intensity according to toxin concentration in the GCF [33].

## *2.2.3 Genetic tests*

## *2.2.3.1 MyperioID*

MyperioID does not identify any pathogens, but basically provides genetic susceptibility of the patient to periodontal diseases [16].

## *2.2.3.2 Periodontitis susceptibility trait test*

The periodontitis susceptibility trait test (PST) is the test that identifies the genetic predisposition of the patient for periodontitis. It detects polymorphism in IL-1 gene, which has been linked with periodontal diseases [17].

## **2.3 Diagnostics-lab-on-chip**

Lab-on-chip is a newer generation of POC technology still undergoing development [14]. It basically integrates and automates all the complexities of a laboratory procedure onto a computer chip [28]. This technology will thus measure multiple biomarkers in a small sample of plaque, GCF, or saliva [13, 16]. It will omit all the requirements of heavy expensive equipment or trained lab technicians. The result will be chair-side, instant, and not subjective.

## **3. Advantages of POC**

It increases patient cooperation as no blood is drawn from the patient. Cost and inventory for shipping samples to a centralized laboratory are reduced. Large populations can be screened. Treatment can be started immediately as results are obtained rapidly. It requires lesser training and resources than current diagnostic methods. Patients with higher risk can be recognized and treated.

## **4. Disadvantages of POC**

The use of POC diagnostics in periodontal surveillance looks promising; however, in the clinical setting, these approaches suffer from various obstacles. These tests still need validation and acceptance by dentists. Cost-effectiveness of the procedure and kit is another concern. Finally, the clinician needs to be abreast with the knowledge of diagnosis, disease risks, and prevention before diagnostics may be integrated into routine clinical periodontal practice.

## **5. Conclusion**

The cornerstone for a successful periodontal treatment is an accurate initial diagnosis. The current existing diagnostic methods suffice the purpose but cannot achieve any more goals than this. Knowledge of patient susceptibility and active disease sites are desired by any clinician from the diagnostic methods. With the introduction of new chair-side test kits, which use the host and bacterial markers of periodontal disease, monitoring of specific sites is now possible. The various oral fluids easily available for test are under great amount of research and investigation. Though with various challenges, saliva, GCF, and plaque are promising mediums to be used for periodontal diseases. One of the latest clinical applications of POCT is in the detection of the SARS-CoV-2 virus. Although SARS-CoV-2 RNA detection in nasopharyngeal swabs is reported to be the gold standard method but it is an invasive method, and therefore uncomfortable for the patient. Due to the limitations of this method, saliva is now suggested to be a better alternative because it is easy to collect the sample and is not uncomfortable for the patient [34]. SpeciMAX is the commercially available saliva collection kit for the detection of SARS-CoV-2 virus.

The need of an hour is to develop POC devices for diseases, such as cancer and hyperthyroidism, so that these can be detected with the help of biomarkers at home leading to their early diagnosis and effective intervention at right time.

*Point-of-Care: A Novel Approach to Periodontal Diagnosis DOI: http://dx.doi.org/10.5772/intechopen.107517*

## **Author details**

Nancy Srivastava1 \* and Shivendra Rana<sup>2</sup>

1 Department of Periodontics, NIMS Dental College and Hospital, Jaipur, Rajasthan, India

2 Department of Oral and Maxillofacial Pathology, Rajasthan Dental College, Jaipur, Rajasthan, India

\*Address all correspondence to: dr.nancy15@gmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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## *Edited by Gokul Sridharan*

Periodontology is a specialized branch of dentistry that deals with the health and diseases of the periodontium, which is the supportive tissue surrounding the teeth. Periodontal diseases are common oral diseases that can affect the teeth and supporting structures, and maintaining a healthy periodontium is essential for preserving the integrity of dentition. Advances have been made in the pathophysiology, classification, diagnosis, and management of periodontal diseases over the years. This book aims to provide researchers and clinicians who deal with periodontal diseases with an overview of the latest insights regarding the periodontium and periodontal disease.

## *Sergio Alexandre Gehrke, Dentistry Series Editor*

Published in London, UK © 2023 IntechOpen

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Periodontology - New Insights

IntechOpen Series

Dentistry, Volume 13

Periodontology

New Insights

*Edited by Gokul Sridharan*