2 Oral infectious diseases – Reflections after 50 years of experience in dentistry

Gunnar Dahlén

My experiences after nearly 50 years of employment in the same dental faculty are summarized. After graduation in 1972 I have been working continuously in oral microbiology research and education. During a period of 10 years I worked concomitantly clinically as a dentist (mostly in the Swedish Public Dental Health system “Folktandvården” but also in private practice for a couple of years). In addition, I have had commitments as the associate Dean for Academic Affairs during 8 years and as the Dean during 8 years. The Dental Faculty merged with the Medical Faculty and another five institutions into a Health Science Faculty, the Sahlgrenska Academy in 2004 

 The rise and fall of a dental faculty

As a graduated from one of the world-leading dental institutions, I had experienced an educational system that was characterized by research. Research activity was a priority in the new dental university from its start in 1968. Most of the professors were recruited from other Swedish dental universities, a number of “hungry” and career seeking research leaders like Jan Lindhe, Bo Krasse, Birgit Thilander, Gunnar E Carlsson, Lars Hollender and Bengt Magnusson (in pedodontics) just to mention some. Accordingly, they recruited assistants (Associate and Assistant Professors and PhD students) to teach, many of which later reached international reputation such as Anders Hugosson, Sture Nyman, Douglas Bratthall, Hans-Göran Gröndahl, Gunnar Bergenholtz and Anders Linde. No, Anders Linde was not my teacher – he was my good friend and my classmate after two years of studies in chemistry at the university. Anders and his father in law, Alf Öhman, both inspired me toward dental education and to research in odontology.  We started the dental education together in one of the first classes at the new dental faculty. Per-Ingvar Brånemark was a medical doctor and had a position at the Department of Anatomy at the Medical Faculty but financed on Dental Grant money, contributed to the international status of the Dental Faculty/ Institution at University of Gothenburg that it still has today (at least in some ranking lists).

Political decisions and changes within dental research and education systems as well as in dentistry have led to changes and threats for the dental schools through the years.

One strong concern was the dramatic increase of dental graduates and dentists in Sweden that took place during the 70-ties. All four of the Swedish dental schools expanded (In fact Stockholm had two dental schools during a period of 5-6 years). The priority in the dental faculties/schools went from research to education. The politicians did not realize that an overproduction of dentists was around the corner, until it was too late. Fear from overproduction of dentists has been an issue for the dental association and an intense debate occurred already in the 1930ies. The dental association has always had a fear of too many dentists – and has therefore rung the alarm bell frequently – so frequently that no one listened when the overproduction became a reality. The overemployment of dentists occurred in the mid 80ties along with a simultaneously dramatic caries decline among children throughout the country. The same situation occurred in other Nordic countries and closing dental universities became a reality in Finland. The Swedish government thought that just producing enough number on the national level could fill vacant positions in dentistry in the northern part of the country. But newly graduated dentists had no plans to move to the rural areas, but chose other European countries (Sweden became a member of EU in 1995). Many dental graduates even choose other professions or stayed unemployed rather than to move to low paid jobs in the middle of nowhere. This was a gigantic miscalculation that led to a remarkable reduction of dental student applications. The dental schools in Gothenburg and Malmö were threatened to close and Malmö was in fact closed for applications and intake of students during 7 years.

An interesting discussion took place in the 80ies when it came to the dimensions of the dental schools. The number of dentists was >9 000, which implied 1 dentist per <1000 inhabitants (Sweden had at that time 9 million inhabitants). That was far too low – 1 dentist per 1500 should give a more balanced situation, and 7000 was set as a goal. Concomitantly, a goal was also set for the increasing number of Dental hygienists to 2 000, with the vision to reach the same number as the number of dentists in the future. In addition to that, the number of specialists (postgraduates) also increased. Consequently, we will face an overproduction of dental care again in a near future.

In 1989 another big change took place for dental education and research in the Swedish dental schools by the decision that clinical practice and patient care should not be a governmental responsibility.  The clinical practice for dental students should instead be organized and governed by the Public Dental Health (Folktandvården, FTV) in each province with a dental school, similar to how the medical education was organized in the hospitals (Swedish “university” hospitals are owned and run by the province not by the universities).  FTV in Gothenburg and Umeå agreed to this arrangement, which would guarantee enough patients with a broad spectrum of dental treatment needs to be presented to the dental students in their clinical training program. That was a good thought. For this commitment, FTV recieved “intruder money” – a special grant from the government to finance the increasing costs that followed the dental education and practice in the FTV clinics. That was a less good thought –all clinical teachers (instructors) now became employed by the FTV and not by the university. The Faculty (and University) was now in charge of only 50% of the governmental grant for dental research and education. The other 50% went directly to FTV. The clinics become renovated for millions. The clinical “teachers” only did clinical work (as instructors and with own patient care) and did not participate in any university or academic business. Patient care became priority and not the education at the clinics.  For the teachers, research became something that could be done on spare time. The medical faculty has the same system but here 20% of the “intruder money” or governmental money to the hospitals is located for “educational matters” at the hospital and 80% for clinical research. In dentistry it came to be the opposite. There was a fundamental miscalculation of what the costs in fact are for a 5-year dental education of each student in comparison to a medical student. But from 120 students yearly in the 70ties, the dental school had in 1995 an intake of only 40 new students per year. Less number of students means less money and consequently fewer teachers were needed. Teachers were fired and the academic activities were reduced to a minimum. It was impossible to defend our independence, as a separate Dental Faculty, and it became my commitment as the last dean to merge the Dental Faculty into the Health Science Faculty (Sahlgrenska Academy).

After the millennium, FTV faced an increasing need again for more dentists and requested the government to increase the grants. As a consequence, the number of students has increased again and the intake is presently 95 new students per year, which means we are back almost at the same level as 40 years ago. The circle is closed.

Dental education

The gap in the collaboration between the Dental Institution and FTV has continuously increased. The University and the Public Dental Service are two organizations working toward different goals and the gap between them is now wide and deep. The Institution is even more vulnerable this time due to a weakness in research. The dental institution might even be closed in 5-10 years time, unless dental education and research will become an entire academic mission within the university as it was 50 years ago. There must also be a fundamental change is how the dental profession looks upon itself and why we are doing what we do. Dentistry is a medical discipline and education should be based on medical and health science principles and dental students should become dental (oral) doctors not just “producers of dental care”. Oral health efforts should go hand in hand with efforts in general health. In my 50 years of experience in dentistry I have seen a move from biology to technology in both research and education. Material science has totally dominated the IADR meetings the last couple of decades. Consequently, less education in biology and basic medicine in the current dental curriculum, which is a consequence of the priority for training in clinical dentistry. The newly graduates should not become a financial burden to their clinics. It is remarkable that it needs to be pointed out that the mouth is a part of the body or that the oral health conditions in the oral cavity mirrors that of general health. In a time where the periodontal disease, caries and endodontic infections, oral mucosal lesions are associated with a number of systemic diseases and focal infections again has become a hot topic it seems to be apparent that students should have a solid background in biology and basic medicine within their dental education. That “chance” will never come back after graduation, while various postgraduate programs and clinical courses are numerous. As long as there are separate organizations, educational, financial and insurance systems as well as attitudes between dentistry and medicine is a fact, dentistry will fade away on its own apart from medicine. Dentistry will become a paramedical activity with focus on restorative and esthetical activities rather than to control or treatment of oral diseases.

Oral microbiology in the dental education

Oral microbiology serves as a good example for what has happened in dental education the last 50 years. Fifty years ago the microbiological research was dominated by the search for the microorganisms that specifically caused the main dental diseases, caries and periodontitis. Both diseases have passed through different stages (hypothesis) through the years as basis for research and these hypotheses have been used as paradigms for the role of bacteria in dental diseases. A lot of good research has been conducted but so far not reached the end of the line. The non-specific, the specific, the modified non-specific, the ecological and lately keystone hypothesis are still debated and all of them are more or less attractive and relevant but still they are hypotheses (1). The new technologies using sequence methods (microbiome studies) have discovered an enormous number of “new” species and certainly have directed us from specificity to diversity. The variation between sites, individuals and populations is a never-ending story. At the same time this complexity has made microbiology difficult to grasp even for a microbiologist. Microbiology has never been popular among students and only few have asked for learning more microbiology once they have graduated from the dental school. Separate Oral Microbiology departments have successively disappeared in several countries or merged into the medical microbiology in others. But medical microbiology departments have unfortunately little knowledge of the oral microbiology or oral/dental diseases. We have seen the same trend within many dental faculties and departments of Oral Pathology (once the crown in dentistry) that have now totally disappeared from the dental arena. The Laboratory of Oral Microbiology, at the dental school in Gothenburg has since 50 years tried to support dental clinicians with oral microbiological diagnostic service (2). This activity was appreciated in the 70-ties and 80-ties when the specific plaque hypothesis was the paradigm. Later when it became clear that these “pathogens” could be found also in obvious healthy individuals as well, the clinicians lost interest. Microbiology became increasingly complex and the interpretation of microbial analyses was too difficult to manage. There were no obvious benefits for the therapist to know some microbiology in the treatment of the patients. The treatment strategy was the same anyway and microbiological risk evaluation for dental diseases was uncertain.

Oral microbiology in dental research

I am grateful for the opportunity of becoming a microbiologist educated by Åke Möller, a classical researcher always looking for the truth with an extreme patience. He may not have reached the international reputation he deserved, but became famous for his thesis of 375 pages on “how to take the appropriate microbiological sample from the root canal” (3). His life´s ambition was to expose the role of microorganisms in endodontic infections and how to carry out the most efficient root canal treatment. The ultimate goal for him in endodontic treatment was to reach a root canal free from microorganisms before the permanent root filling was performed. In a series of endodontic microbiological investigations on monkeys Åke Möller and Lars Fabricius made some outstanding studies (4-7). I learned that endodontic infections were polymicrobial, mostly anaerobic infections, organized and regulated as a football team with defenders and forwards of which one or two (usually anaerobes) sometimes had a key role as scorers (8). Single bacterial species rarely caused problems – they may survive but seldom grow if they are entombed in dentine tubules or the apical labyrinth with no access to nutrients. I learned that microorganisms should not be regarded as independent “LEGO-pieces”, but as living creatures, which interact with each other and with the host in an interplay regulated by environmental factors. Lack of nutrients is not equivalent to death to microorganism; they simply turn into a dormant state. They can survive for years in a root canal after a permanent root filling. The last couple of heroic experimental endodontic experiments clearly showed the importance of persistent bacteria in endodontic failures (9,10). Further, these studies on monkeys showed the importance of Gram-negative anaerobes in pathology and development of apical periodontitis and the ecological principles that regulate survival and growth of bacteria when an infection is induced and its progress (11). These are the same principles that may be applied also for marginal periodontitis.

As one of the few microbiologist at the Dental Faculty, I became involved in several collaborations with other researchers in endodontology, periodontology, oral medicine and oral surgery. This contributed to my broad knowledge of the entire oral microbiota. Endodontic infections were still my main research area and my thesis was on the importance of Lipopolysaccharides (endotoxins) from Gram-negative root canal bacteria for development and maintenance of apical periodontitis (12).

My research took a new direction towards periodontal disease when Jörgen Slots became the professor in Oral Microbiology in Gothenburg in 1984. He was strong enough to confront periodontal colleagues that some microorganisms are more important than others for the cause of infections while the majority of the plaque bacteria should be regarded as “innocent bystanders”.  He was one of the front figures for the “specific plaque hypothesis” that was formulated by Walter Loesche in 1976 (13). Periodontitis should be seen as an infection caused by “periodontal pathogens” and should be treated as an infection similar to ear and throat infections or pneumonia i.e. with antibiotics. Many studies were conducted with the aim to show the importance of some putative periodontal pathogens, started with 3 “major pathogens” e.g. Actinobacillus actinomycetemcomitans (later renamed to Aggregtibacter actinomyctemcomitans), Porphyromonas gingivalis and Prevotella intermedia (the latter two representing “black-pigmented Gram-negative rods”) (14,15).  In longitudinal clinical studies together with Sture Nyman, Stefan Renvert and others, we tried to predict further periodontal progression using microbiological parameters (16,17). A negative prediction was clearly found, but the positive prediction was limited. The list of “putative pathogens” expanded (18) and later 17 species or phylotypes was associated with periodontitis in a literature review (19). The specific plaque hypothesis was thereby more or less dead.

Examples of oral infectious diseases are dental caries, endodontic infection, periodontal disease and peri-implantitis. They are all plaque-mediated diseases, underlining the many different pathways bacteria may follow to grow in different ecological environments, such as on teeth, at or below the gingival or mucosal margin. Bacteria progress by way of sudden bursts of activity, somewhat resembling earthquakes. We can ascertain where they hit but not when; thus oral diseases are largely unpredictable. Clinical signs and symptoms of the disease follow the ‘burst’ and guide us to the pathological site. The “burst theory” was introduced in periodontology by Sig Socransky and Jan Lindhe (20) in order to explain that periodontitis did not progress continuously and not in a similar fashion in sites and individuals. The bursts coincided with an increased metabolic activity and growth, sometimes manifested in acute exacerbation, with attraction of neutrophils, clinically visible as pus and abscess formation and often symptoms (swelling, pain, and tender regional lymphnodes). Persisting bacteria with low metabolic activity, which characterize chronic infections, maintain a low-grade inflammation characterized by healing and repair (granulation tissue) and infiltration by lymphocytes and plasma cells. Chronic infections are usually quiet processes. Acute (exacerbating) and chronic forms exist for both apical and marginal periodontitis and do not represent a certain microbial composition but are genuinely associated with the metabolic activity and growth of bacteria (21).

Jörgen Slots also introduced me to the Danish research group organized by Ole Fejerskov and Vibeke Baelum at Aarhus University, and Firoze Manji at KEMRI, Kenya and their field research in Kenya. They all become my close friends and the participation in these studies became a real eye-opener for me. I came to see an oral disease pattern and efforts with a priority of pain relief and extractions rather than fillings, which was quite different from my experience from the well-organized Swedish dental service. The first two papers disclosed that “putative periodontopathogens” could be found in similar counts also on adults with apparently no periodontitis and on the dorsum of the tongue as well as in the subgingival plaque (22,23). The paper was not well recognized by colleagues since it was based on “Africans with poor oral hygiene”, so what else could be expected? This research group (now also including Panos Papapanou, who became senior researcher at the department and also a close friend) conducted similar studies on big cohorts of adult Chinese and Thai and obtained essentially similar clinical and microbiological results (24,25).  The “periodontopathogens” were more prevalent and in higher numbers in subjects with periodontitis than healthy/gingivitis – thus they were associated with the disease and pathological pockets. But the question if they could cause the disease was not answered. On the contrary, it was found that the immune response, measured as the IgG antibody activity against 18 different bacteria, was only weakly correlated with disease severity, bacterial colonization patterns or bacterial load. On the other hand a very strong correlation of the IgG antibody activity was obtained between the “periodontopathogens” and “early plaque colonizers” supporting the concept that both bacterial groups represent ordinary oral commensals. The variation in antibody activity across individuals was largely a result of inherent differences in individuals´ ability to mount responses, rather than being related to their periodontal status (26).

The fact that the periodontopathogens were present also in periodontally healthy adults was a concern for many researcher and clinicians in the 90ies. Socransky formulated the “colored complexes” model in order to explain the occurrence of certain bacterial clusters in periodontitis and periodontal progression (27). Thus the red and orange complexes were statistically more common in disease than in healthy and the green and yellow complexes were more common in periodontal healthy individuals and sites. It became a paradigm for how presence of various bacteria should be interpreted and a huge number of confirmations were published worldwide. In a series of publications using factor analysis it was suggested that many bacteria that shared similar characteristics (i.e. proteolytic activity, anaerobes, ammonia production etc.) and covariate with the ecology, consequently cluster together (28-30). This points to the composition and the dysbiosis that occur in periodontitis lesions are primarily ecologically driven (31). The role of bacteria in periodontitis and periodontal progression is still unclear. The model formulated in 1998 by Kornman and Page is still the explanatory model for periodontitis today (32). The microbial challenge by growth and dysbiosis that takes place in the gingival pocket induce an inflammatory reaction in the host tissues. The magnitude of the host response is influenced by environmental and acquired risk factors (e.g. smoking and systemic diseases such as diabetes) or by genetic risk factors. The net outcome or magnitude of the inflammatory (immune) response is dependent on the subject and genetic factors, which determines the degree of susceptibility for the disease progression. It is commonly found that around 10% of the populations worldwide have severe (advanced) periodontitis at 50 years and with a risk of loosing teeth before they die. It is tempting to argue that this group is the ”susceptible” one for periodontitis. It is also a model that diminishes the role of specific bacteria in the periodontal progression, although the later “key-stone hypothesis” is an attempt to restore the impact of certain bacteria in periodontitis. Keystone pathogens can trigger inflammation when they are present in low numbers. P. gingivalis is an example of a keystone pathogen (33).

The specific plaque hypothesis – is it still valid?

Regarding most oral infectious disease as endogenous polymicrobial infections, the value of the specific plaque hypothesis might be difficult to defend. But like in most football teams one player specifically can make a difference, not always but often. That is also typical for many mixed infections, that they usually have a heterogeneous composition but some bacteria occur more frequently than others. They have characteristics (virulence factors) that make them more competitive and give them a key role in the infection process.

A actinomycetemcomitans was the first bacteria recognized as the specific pathogen in localized juvenile periodontitis (now included in the periodontal diagnosis “aggressive periodontitis”). The pathogenicity of this bacterial species is linked to the very specific factor, a leukotoxin, with a similar effect as leukotoxin from some other classical pathogens (Staph aureus and Fusobacterium necrophorum). The interest in A. actinomycetemcomitans increased further, when a highly toxic clone of this species (called JP2) was detected in an Afro-American girl with severe periodontal breakdown. A deletion in the promotor gene for the leukotoxin, make the production of the toxin unregulated. Later studies (34) confirmed that the clone JP2 was found only in individuals with a West-African origin. Höglund-Åberg and coworkers were able in a 2-year longitudinal study on 400, 12-17 years old children in Ghana to predict severe periodontal progression in those with the JP2 clone at baseline (35). The JP2 clone has now been found also in non-African individuals and other highly toxic clones have been detected also in non-African populations e.g. Thailand. While the prevalence of juvenile periodontitis among Caucasians is 1-2%, the prevalence in Ghana is 24%, implicating that the susceptibility for periodontitis in various populations is highly different along with a colonization of different clones of A. actinomycetemcomitans. Studies on prevalence and distribution of principle periodontal pathogens worldwide presents distinct patterns in various populations as well as genetic variants within specific species (36). Interestingly, in an ongoing study on Somali immigrants in the city of Trollhättan, Sweden a high prevalence (approximately 12%) of periodontitis in 12-17 year-olds is revealed. The association with A. actinomycetemcomitans was weak and other bacteria seemed to prevail. The higher prevalence of periodontal disease among certain immigrant groups constitutes a big challenge for the future of Swedish dental health care, which have to deal with a quite new dental disease panorama. If so, future efforts in oral health need to include the significant risk for periodontitis in children. The specific plaque hypothesis seems to be valid at least for some virulent clones of some principle periodontal pathogens such as A. actinomycetemcomitans.

Are caries and periodontitis contrasting diseases?

It is fully accepted that caries and periodontitis are plaque-mediated diseases. Dental plaque has been regarded like a two-sided coin but looked upon since the early 70ies (the Borderline conferences) only at one side at the time. Caries and calculus are clearly contrasting biochemical processes, resulting in increased demineralization at low pH (caries) and increased mineralization at high pH (calculus). Both processes are due to bacterial metabolic activity, growth and production of metabolic waste products (acids, ammonia, hydrogen sulfide, nitrite). The bacteria are consequently dependent on access of nutrients. The dental plaque bacteria (predominantly facultative anaerobic streptococci) at rest uses saliva constituents (mainly glycoproteins) for a comparably weak metabolism, production of waste products such as weak acids and ammonia and with a pH slightly below 7.0 (37). Intake of sugars (sucrose, glucose, fructose and more) gives an immediate plaque pH drop and returns to baseline after approximately 30 minutes according to classical Stephan curve (38). How deep the pH can drop is dependent on host factors, bacterial composition and how well the bacteria in the plaque are adapted to the diet (e.g. sugar). Subgingival bacteria at gingivitis are associated to the proteolytic metabolism that prevails in the gingival crevice. Increased gingival inflammation leads to increased gingival exudate, which contains proteins, peptides and amino acids but no sugars. Ammonia is a major waste product and pH is slightly above 7.0. The alkaline environment, which is characteristic for the gingival pocket, disfavors sugar dependent acidogenic bacteria (streptococci and lactobacilli) but favors proteolyic and anaerobic bacteria. The two main metabolic pathways of the dental plaque are thus regulated by the pH and anaerobiosis.

 Thanks to Dr Narong Suksuart, former Dean at the Faculty of Dentistry, Prince of Songkla University (PSU), Hat Yai, Thailand and later advisor and organizer of Mobile Dental Teams by Princess Mother Medical Volunteer Foundation, Bangkok, a study series was initiated after a visit to the Karen Hill tribes of Northern Thailand and the observation that the adult population had a very low caries experience. This was confirmed in a study (39), which showed that most of the adults had all their teeth remaining, 50% were caries free (DMFT=0) and the whole study group had a mean DMFT of 2.1. The betel chewing habit, although some antibacterial effect by the betel nut extract was noted on oral bacteria in vitro, did not explain the low caries experience.  The low caries experience was instead suggested to be due to almost no intake of refined sugar products. On the other hand the intake of fruit (glucose, fructose) and other carbohydrate containing products was regular but took place only 2-3 times per day. The adults had a poor oral hygiene and lots of plaque, calculus and a general appearance of gingivitis with Bleeding on Probing (BoP) > 90% of the dental sites. Pathological pocketing on the other hand was infrequent and only a limited number of the examined adults had advanced periodontal breakdown (40).

Using a chair-side strip method (41) plaque pH was evaluated in dental plaque of Karen adults and children after sucrose. The results indicated a low acid production and in the magnitude of caries free Swedish dental students (42).

With a similar chair-side for measuring urease activity (46) the Karen population had, compared to Swedish adults, a significantly higher activity in the lower anterior sites compared to molar sites and upper anterior sites, which coincide with the fact that the lower anterior sites generally show less caries but more supragingival calculus than other dental sites (43). Calculus was regularly registered among children (13-15 yrs of age) and frequently also among younger children (6-8 yrs).  Calculus is very seldom registered in Swedish children before puberty.

The proteolytic activity was estimated in the subgingival plaque using a simple chair-side method, which determines the net production of hydrogen sulfide (44,45).  It was concluded that the hydrogen sulfide production mirrors the capacity of the plaque and the total presence of cysteine degrading bacteria and therefore correlates to the total anaerobic and proteolytic microbiota and presence of inflammation (gingivitis) rather than periodontitis.

I have spent one month annually as a visiting professor and gained a fruitful collaboration with Professor Rawee Teanpaisan at Department of Stomatology, PSU. In view of the low caries but high calculus prevalence among Thai schoolchildren, a study was conducted to contrast individuals with presence of caries with those with presence of calculus (46). However no significant pattern was found on the individual level but the study was repeated on site level (47). We found that the mandibular anterior site 31m, had a higher baseline pH (resting pH) than other sites and showed a significant increase in pH compared to other sites when exposed to urea. In this dental region, no caries lesions were found. It may be speculated that the South-East Asian populations per se may have an inherent physiology (higher saliva/exudate content of urea) and/or develop a plaque microbiota due to limited exposure for sugars especially sucrose, that differs them from that of the Swedish. Thus this population may thereby be at a lower risk for caries.

The periodontal conditions and the subgingival microbiota in the Karen population were similar to that found for same age groups of a rural population in Southern Thailand (25,40). Notably, in adults, the older (13-15 yrs) and younger children (6-8 yrs) the anaerobes (Fusobacterium spp. and Prevotella spp. and Actinomyces spp. outnumbered the streptococci. This composition is probably due to the poor oral hygiene that results in plaque accumulation and maturation with longstanding gingivitis and a concomitant low and/or infrequent glycolytic activity and acid production. The continuous presence of plaque with low degree of “disturbing” factors (frequent food intake and oral hygiene procedures) allows for plaque maturation and a low Eh favoring the anaerobes (dysbiosis) not only in subgingival plaque but also in the supragingival (interproximal) plaque.

In conclusion, future research on oral infectious diseases is expected to focus more on bacterial function than compositions and numbers – or as Takahashi (48) put it: From “Who are they?” to “What are they doing?”. Functional expression of dental plaque microbiota will become a new research avenue for research of the role of bacteria in oral infectious diseases (49).

Treatment of oral infectious diseases from an ecological perspective. What can we expect in the future?

Treatment of oral infectious diseases is challenging by the fact that ecological principles needs to be considered. In periodontitis, periimplantatis, caries and mucosal infections, we are dealing with an open growth system not a closed, bacteria-free environment (as the dental root canal). Bacteria (and fungi) are always present and have the chance to become “opportunistic pathogens” more than once, meaning that treatment does not necessarily imply life-long oral health. Thus the rational goal is to seek to control the disease, not to cure it. A general principle to combat oral infectious diseases is to mechanically remove, debride or by surgery and drainage control the process by supporting the recovery as long as they are reversible (incipient caries and gingivitis).

Periodontitis and periimplantitis. Supragingival plaque control is the cornerstone of periodontal treatment because it establishes long-term periodontal stability and guarantees the long-term successful result of our professional intervention. The constant application of meticulous supragingival plaque control measures is more critical in the case of maintenance of patients because it will directly affect the result of our non-surgical and/or surgical periodontal treatment. If supragingival plaque is present after meticulous professional pocket debridement, a subgingival microbiota similar to that of the untreated periodontitis site is re-established within 4-6 weeks, posing the risk for recurrence of the disease.

Plaque control is the main option also for treatment of perimplantitis – although much more challenging due to the implant construction with threads of different designs, often a rough surface to enhance osseointegration, which impede the ability to detect and remove plaque under the mucosal margin. Suprastructures are commonly overextended for aesthetic reasons or constructed in a way that restricts access for oral hygiene.

The treatment goal for periodontitis and peri-implantitis should be directed against the factors that support the environmental change, bacterial growth and dysbiosis, namely gingival inflammation and deep pockets. Surgical pocket elimination would therefore be an option combined with plaque control and mechanical debridement; however, in reality we compromise with this goal for aesthical reasons (exposed root surfaces).

A number of alternatives (such as ultrasonication, laser, air-polishing, photodynamic therapy) to antimicrobial and mechanical means of eliminating dental plaque bacteria have been introduced in periodontal therapy.  They all may enhance the efficiency of the mechanical debridement performed by hand but are equally operator sensitive. The long-term clinical effectiveness of these alternatives remains controversial.

In vitro studies of antiseptics with regard to their antimicrobial effect have often been very promising but the in vivo clinical reality does not always correspond. They can provide supportive data to clinical investigations but cannot stand alone as proof of efficacy in vivo. Antiseptics are usually effective when used in closed systems such as the dental root canal, where highly efficient antiseptics e.g. sodium-hypochlorite, iodine solutions and chlorhexidine may be used in appropriate concentrations and for a prolonged time with low risk for toxic effects on vital tissues (only at the apex of the tooth).  In an open system and with presence of abundant of organic material, the antiseptics are rapidly bound and inhibited and the effect is of short duration. Antiseptic irrigation is used in periodontal therapy as adjunct to mechanical debridement. So, while the toxic effect on the surrounding periodontal tissues increases (compared to the root canal) the effect in periodontal therapy is only temporary.

Antibiotics seriously interfers with the microbiome and overuse of antibiotics is today a global concern when we face that a number of drawbacks overshadow the benefits. Superinfections and increased resistance have implied national programs, EU and WHO programs with the aim to use of antibiotics only when it is necessary. It is a misconception that antibiotics could be used as some kind of “disinfection agent” that kills the bacteria. Antibiotics target specific metabolic activities of the bacterial cells (cell-wall synthesis, protein synthesis or DNA/RNA synthesis) and consequently inhibit the bacterial growth.  Normally, antibiotics are used over the threshold of minimal inhibitory concentration for the target bacteria in the blood, which primarily means that the antibiotics stop the bacteria from growing but not necessarily kill them. Antibiotics are efficient in acute exacerbating processes where bacteria are rapidly growing and should be used if there is a risk for complications and systemic spread of the infection. In chronic infections and in microbial niches such as the dental plaque, where the bacteria are slowly growing or even dormant, the antimicrobial effect is reduced several hundred times. Although numerous studies have shown significant clinical improvements using systemic antibiotics as an adjunct to mechanical debridement, alone or in various combinations, the long-term effect is still not proven. Locally delivered antibiotics may have the advantage to limit the systemic side effects and the concentrations can be increased, but the effect is still only temporary in an open growth system. The poor long-term effect on the disease may therefore not justify the use of antibiotics in periodontal therapy.

Caries treatment and control. Bacteria are essential but not sufficient to develop caries. The aetiology of caries is of low microbiological specificity. Consequently, measures directed to “putative pathogens” such as mutans streptococci will fail. To modulate the microbial ecology of caries by using relatively simple approaches such as diet control, oral hygiene and usage of fluoride leads to predictable and successful results. Diet control and selection of non-cariogenic foodstuffs modify the substrate and deprive the acidogenic and aciduric bacteria of harmful exogenous nutrients, which are critical for their survival and growth. Limiting the frequency of sucrose intake also reduces the time that the substrate is in the mouth. Mechanical removal of plaque from the tooth surface, by efficient oral hygiene measures, disrupts the biofilm, lowers the number of micro­organisms in contact with the tooth and maintains the ecological homeostasis despite environmental stresses. Introduction of alkaline generating substances (e.g. urea or arginine) in tooth-pastes and chewing gums, has been used in order to balance the acid production in the dental plaque after sugar exposure. Application of anti-plaque agents such as quaternary ammonium compounds, bisbiguinides (chlorhexidine), enzymes, metal salts, essential oils and plant extracts have been used, mostly as mouthwashes. The critical issue in combating caries effectively is that these substances retain their antimicrobial effect in an open growth system. The relatively short contact time between the inhibitor in the rinse and the mouth makes substantivity very important. A wide use (regular and longitudinal) may give both expected and unexpected ecological changes of the microbiota as wells as of the host, which carefully has to be investigated before we have the evidence for their benefits and wide use in combating the caries disease. I am sceptical to the existence of any such anti-plaque substance that has any substantial effect on the dental biofilm and without side effects. But if they are harmless like most other products we eat and drink, they can be used as refreshments.

Other approaches to modulate the flora and control caries, which seems more sophisticated and attractive in concept and delivery, are vaccine development and replacement therapy. Vaccination is no longer a topic under discussion, mainly because the long-term effect of altering the indigenous oral microbiota is highly unpredictable. Moreover, the epidemic character of caries has declined and no longer justifies the use of a vaccine as a caries prevention vehicle, given the substantially reduced prevalence of caries in western countries over the past several decades. Replacement therapy – currently named probiotic therapy – was another idea based on the possibility that indigenous antagonistic organisms could be exploited to block the major caries pathogens (also putative periodontal pathogens by the way). In this approach, a harmless effector strain is permanently implanted in the host’s microbiota. Once established, the presence of the effector strain prevents the colonisation or outgrowth of a particular strain, such as S. mutans in the case of caries. Neither immunisation nor replacement therapy, though they may sound promising, can guarantee elimination of the disease. They are directed specifically at mutans streptococci and, despite potential reduction of these species in caries, no clear ecological changes are triggered and caries may not necessarily be arrested. Caries control presupposes changing the pH balance from acidic to alkaline, which in turn slows down the growth and metabolism of cariogenic bacteria.

With the dynamic development of ‘functional food’ markets worldwide, the prebiotic concept has also been attractive in relation to the control of plaque-mediated diseases. Prebiotics are selectively fermented ingredients that allow specific changes both in the composition and the activity of the gastrointestinal microbiota that confer benefits on host well-being and health. Prebiotics cause their effects through the metabolism of the bacteria they promote. Within this concept, prebiotics in theory may have an effect on caries initiation and progression but there is still a long way to go from the laboratory to clinical trials to evaluate the potential effect in vivo. Research on prebiotics and oral health is still in its infancy.

Mucosal infections. The phylogenetic predominance of streptococci in the oral cavity is probably as old as the homo-sapiens itself and streptococci are the predominant oral bacteria in all populations world-wide.  Streptococci also occur in the mouth of many animals with a similarly mixed diet such as monkeys, dogs and cats. The oral cavity thus creates its own microbial unit and differs remarkably to close located areas such as lips/skin, nose, sinus, tonsils, pharynx and respiratory tract. The reason for this remarkable selection of microorganisms that colonizes the oral cavity is the enormous ecological pressure from exogenous microorganisms in food, drinks and contacts with the surroundings by kisses (other humans, pet animals etc), licking and biting on various items etc. means that only those microorganisms that are well accepted by the host and its receptors and are well adapted to the environment at various locations of the mouth will survive and colonize. In that perspective streptococci are outstanding. They are extremely efficient in adhesion, they are biochemically very active, producing both alkali and acids, can survive and grow in a wide pH span, they are facultative and they produce bacteriocins i.e. peptide molecules specifically against other bacterial species. Other bacteria that predominate oral biofilms are Neisseria, and Haemophilus species and anaerobic genera such as Veillonella, Prevotella and Fusobacterium. The complex biofilms that forms on the oral mucosa and teeth constitute the main host defense factor that protects us from colonization of “non-oral” pathogens or exogenous microorganism simply by competition. Accidentally or by changes in systemic (diseases and drugs) or local factors (mucosal lesions), the balance (homeostasis) between the microbiota and the host becomes destroyed, which favors the establishment of external bacteria and fungi and thereby creates a mucosal dysbiosis and a mucosal infection. They are classical opportunistic infections that are usually benign although they induce symptoms that sometimes can be quite uncomfortable. However, mucosal surface infections are usually non-invasive but may lead to serious consequences by transmission and spread to the respiratory system in hospitalized patients or patients with compromised respiratory system (intubation, respiratory diseases e.g. asthma and COPD). Most opportunistic infections are difficult to treat as long as the opportunistic factor prevails. Systemic treatment with antibiotics or antifungals has a limited effect on the mucosal infections due to difficulties to reach efficient concentrations. Mucosal infection should preferentially be treated by local medication (ointment, tablets or solutions) and symptomatically to prevent further spreading. Opportunistic infections with bacteria such as Staph aureus, enterococci and enteric rods are especially troublesome due to multi-drug resistance and that the efficient drugs may not be available. Presently, we have few, if any, suitable drugs for local application, and treatment of mucosal infections with these bacteria. Also for Candida species an increasing resistance is noticed (e.g. fluconazole) and an increasing resistance problems with treatment failures of yeast infections are to be expected in the future.

What have we learned and what about the future?

From the Swedish horizon we can summarize the situation in dentistry and the oral health in the population as follows. In a population of 10 millions, Sweden now have 7 000 general dentists, >1000 specialists (8 different specialist disciplines) and 4 000 dental hygienists. The Jönköping studies show the changes in oral health pattern that has occurred in adults from 1973 – 2013 (49-51). The frequency (among those under 70 years of age) of edentulous patients was reduced from 16% to 0.3% and those with implants increased from 0 to 0.4%.    Compared to 1973, the number of crowned teeth was lowered as well as endodontically treated teeth, the plaque index was lower, gingivitis was lower, periodontal probing depth > 4 mm was lower, bone loss was lower and number of patients that brush their teeth twice daily was 85% in 2013. Further, the studies report that the prevalence of periodontal health (in age 20-80 years) increased from 8% to 44% and the number subjects with gingivitis or moderate periodontal disease was reduced while the number with advanced periodontitis remained unchanged. Oral hygiene and periodontal health was improved significantly among adults (20-80 years olds) over 30 years (1973-2003). There was no single explanation to this improvement but it can be assumed that it was due to an increasing awareness of health and hygiene practice in the entire population as well as a result of introduction of dental hygienists and periodontal specialists during this period.

But what about the dentists in this context – do they contribute significantly to the increasing periodontal health? Periodontal treatment and prevention is carried out on two levels: 1) infection control, professional tooth cleaning and mechanical debridement – which usually is an issue for the dental hygienists. 2) When more advanced treatment procedures and treatment planning are needed it is assumed that this is mainly a matter for the specialists.  To the last category we can also include the increasing number of severe peri-implantitis cases. In conclusion, the dental hygienists and the specialists are needed in the future – but what about dentists? Are the dentists only for restorative dentistry – fillings, crown and bridge work, implants?

What about endodontics? Looking at the numbers of teeth with unacceptable root fillings, unacceptable coronary restorations or presence of apical periodontitis in the population of various countries, the picture is a nightmare (52-57).  Around 50% of root filled teeth has a periapical lesion, and 50-80 % of root-filled teeth have a technically poor endodontic filling together with a poor coronal restoration. All studies concern about the technical shortcomings but few studies discuss the basic problem of a persistent infection in combination with a poor aseptic management.  A comparison between 1973-2003 of root-filled teeth in Jönköping, Sweden, the frequency of technically adequate root fillings increased significantly from 1973 (23.7%) to 2003 (36.4%) without a concomitant improvement of the periapical status in root filled teeth over time (24.5% vs 24.6%) (58). This indicates that persistent infection of root canals still prevails at the same level. Dentists cannot do endodontics. What are we teaching our students? Should we leave all endodontics to the specialists?

Finally, Norderyd et al. (51) concluded from the Jönköping studies: The continuous improvement in oral health and the reduced need of restorative treatment will seriously affect the provision of dental health care and dental delivery system in a near future. It means that the need for restorative treatment, which dentists are good at and also get well paid for, is going to decline with an new risk for unemployment for many dentists unless there is a reduction of the number of students introduced into dental education also in Sweden.

Future perspective on dentistry and oral infectious diseases

  • The dental curricula and the dimension and organization of dental schools and the number of dentists, specialists, hygienists, dental therapists, dental nurses that are needed are very different from one country to another. It is not possible to give general views or recommendations here. It needs to be dimensioned and organized according to each country´s needs, economy and social structures.
  • Dentist education (and curricula) is an academic activity and dental schools should be dental faculties/institutions within a university. Teachers should have an academic degree. Sahlgrenska Academy has set the level that all teachers should have a PhD. Education and research should go hand in hand.
  • Dentistry (Odontology) is a medical discipline with oral cavity as its working target. Oral cavity is an ecological unit and to understand oral ecology in health and disease is essential for dental education. Education and curricula should give priority for biology and basic medicine. Dental training today is focused too much on practical skills rather than the academic.
  • We need to educate the dental students to be more critical to what they hear and read. In a world where almost everything can be published in some form, the students themselves need to select the true message from the false/fake (including disinformation).
  • We need to bridge the gap between the biology and the clinical practice. Do we have all the pieces in the puzzle of oral diseases´aethiology? Are caries and periodontitis contrasting? To what extent do oral infectious diseases give systemic effects and vice versa?
  • Are caries and periodontal disease the same diseases in all populations? Are caries and periodontal diseases distributed by normality – and some happens to be in the marginal 5-10% just by random?
  • Dental plaque bacteria – Who are they and what are they doing? Functional expression of dental plaque microbiota is the new research avenue?
  • Is there certain risk groups for caries and periodontitis and can we identify them?
  • The development of chair-side test for risk evaluation: blood tests, test of saliva and/or dental plaque at different sites (Biochemical, immunological, genetics, microbiological).
  • Is there a magic drug in treatment of caries and periodontitis? Probiotics and prebiotics?


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