Herpesvirus-Bacteria pathogenic interaction in juvenile (aggressive) periodontitis. A novel etiologic concept of the disease.

Localized juvenile (aggressive) periodontitis starts at puberty in otherwise healthy individuals and involves the proximal surfaces of permanent incisors and first molars. The disease destroys a sizeable amount of periodontal bone within a few months despite minimal dental plaque and gingival tissue inflammation. Cytomegalovirus and Epstein-Barr virus, as well as the two main periodontopathic bacteria Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, are linked to juvenile periodontitis. Juvenile periodontitis-affected teeth show cementum hypoplasia. We hypothesize that an active herpesvirus infection, at the time of root formation, hampers cementum formation and, at puberty, herpesvirus reactivation triggers an upgrowth of bacterial pathogens which produce rapid periodontal destruction on teeth with a defective periodontium. A pathogenic interaction between active herpesviruses and bacterial pathogens can potentially explain the etiology and incisor-first molar destructive pattern of juvenile periodontitis. Effective treatment of juvenile periodontitis may target the herpesvirus-bacteria co-infection.

Concise evaluation and therapeutic guidelines for severe periodontitis: A public health perspective.

The main goal of periodontology is to prevent and arrest gingivitis and periodontitis to avoid tooth loss and focal infection of periodontal origin. Periodontal scaling or flap surgery of moderate-to-severe periodontitis have shortcomings, most likely because removal of herpesviruses and bacterial pathogens in deep periodontal lesions and the adjacent inflamed gingiva requires systemic antimicrobial treatment (or gingivectomy). Valacyclovir (1000 mg twice daily on day 1, and 500 mg twice daily on day 2 and on day 3) is a potent anti-herpesvirus agent. Antibiotic combinations against bacterial pathogens include amoxicillin-metronidazole (250 mg of each, thrice daily for 4 days; for systemically healthy adults) and ciprofloxacin-metronidazole (500 mg of each, twice daily for 4 days; for immunosuppressed individuals and patients exposed to contaminated water and poor sanitation). Supportive antiseptic treatment may consist of 0.1%-0.2% sodium hypochlorite (regular household bleach) as cooling spray in ultrasonic scalers, flosser fluid in oral irrigators, and mouthrinse in patient self-care. The anti-infective treatment described here helps control cases of severe periodontitis and constitutes an exceedingly inexpensive alternative to conventional (mechanical) periodontal therapy.

A bibliometric analysis of periodontology.

This bibliometric study assessed periodontal/implant articles that were part of the five most-cited dental articles in each of the years 2005-2019. Periodontal/implant articles made up one to four articles in each of 14 years and totaled 40% of the yearly five most-cited dental articles. The three core periodontal journals (Journal of Clinical Periodontology, Journal of Periodontology, and Periodontology 2000) increased ~50%-100% in Journal Impact Factor from 2005 to 2015 and were among the 10 most-cited dental journals in the 2015-2019 period. The Journal of Clinical Periodontology and Periodontology 2000 were in several years assigned the highest Journal Impact Factor in dentistry. In summary, periodontal journals continue to publish high-impact articles that are relevant for both oral health care and medicine.

Human and herpesvirus microRNAs in periodontal disease.

Periodontitis is a multi-etiologic infection characterized clinically by pathologic loss of the periodontal ligament and alveolar bone. Herpesviruses and specific bacterial species are major periodontal pathogens that cooperate synergistically in producing severe periodontitis. Cellular immunity against herpesviruses and humoral immunity against bacteria are key periodontal host defenses. Genetic, epigenetic, and environmental factors are modifiers of periodontal disease severity. MicroRNAs are a class of noncoding, gene expression-based, posttranscriptional regulatory RNAs of great importance for maintaining tissue homeostasis. Aberrant expression of microRNAs has been associated with several medical diseases. Periodontal tissue cells and herpesviruses elaborate several microRNAs that are of current research interest. This review attempts to conceptualize the role of periodontal microRNAs in the pathogenesis of periodontitis. The diagnostic potential of salivary microRNAs is also addressed. Employment of microRNA technology in periodontics represents an interesting new preventive and therapeutic possibility.

The human oral phageome.

Oral bacteriophages (or phages), especially periodontal ones, constitute a growing area of interest, but research on oral phages is still in its infancy. Phages are bacterial viruses that may persist as intracellular parasitic deoxyribonucleic acid (DNA) or use bacterial metabolism to replicate and cause bacterial lysis. The microbiomes of saliva, oral mucosa, and dental plaque contain active phage virions, bacterial lysogens (ie, carrying dormant prophages), and bacterial strains containing short fragments of phage DNA. In excess of 2000 oral phages have been confirmed or predicted to infect species of the phyla Actinobacteria (>300 phages), Bacteroidetes (>300 phages), Firmicutes (>1000 phages), Fusobacteria (>200 phages), and Proteobacteria (>700 phages) and three additional phyla (few phages only). This article assesses the current knowledge of the diversity of the oral phage population and the mechanisms by which phages may impact the ecology of oral biofilms. The potential use of phage-based therapy to control major periodontal pathogens is also discussed.

Life-threatening pathogens in severe/progressive periodontitis: Focal infection risk, future periodontal practice, role of the Periodontology 2000.

Severe/progressive periodontitis is associated with cardiovascular disease, cancer, Alzheimer's disease, and dozens of other serious diseases. Herpesviruses are implicated in severe periodontitis and in specific subsets of each of the above systemic diseases. That both periodontitis and herpesviruses are linked to the same nonoral diseases is consistent with a systemic pathogenic role of periodontal herpesviruses. Effective control of periodontitis-related systemic diseases requires collaboration between dentistry and medicine. Periodontology has emerged as an important preventive medical discipline, and periodontal teaching and practice need to adjust accordingly.

Primer on etiology and treatment of progressive/severe periodontitis: A systemic health perspective.

Periodontology is an infectious disease-based discipline. The etiopathology of progressive/severe periodontitis includes active herpesviruses, specific bacterial pathogens, and proinflammatory cytokines. Herpesviruses and periodontopathic bacteria may interact synergistically to produce periodontal breakdown, and periodontal herpesviruses may contribute to systemic diseases. The infectious agents of severe periodontitis reside in deep pockets, furcation lesions, and inflamed gingiva, sites inaccessible by conventional (purely mechanical) surgical or nonsurgical therapy but accessible by systemic antibiotic treatment. This brief overview presents an effective anti-infective treatment of severe periodontitis, which includes systemic chemotherapy/antibiotics against herpesviruses (valacyclovir [acyclovir]) and bacterial pathogens (amoxicillin + metronidazole or ciprofloxacin + metronidazole) plus common antiseptics (povidone-iodine and sodium hypochlorite) and select ultrasonic scaling. The proposed treatment can cause a marked reduction or elimination of major periodontal pathogens, is acceptably safe, and can be carried out in minimal time with minimal cost.

Herpesvirus-bacteria synergistic interaction in periodontitis.

The etiopathogenesis of severe periodontitis includes herpesvirus-bacteria coinfection. This article evaluates the pathogenicity of herpesviruses (cytomegalovirus and Epstein-Barr virus) and periodontopathic bacteria (Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis) and coinfection of these infectious agents in the initiation and progression of periodontitis. Cytomegalovirus and A. actinomycetemcomitans/P. gingivalis exercise synergistic pathogenicity in the development of localized ("aggressive") juvenile periodontitis. Cytomegalovirus and Epstein-Barr virus are associated with P. gingivalis in adult types of periodontitis. Periodontal herpesviruses that enter the general circulation may also contribute to disease development in various organ systems. A 2-way interaction is likely to occur between periodontal herpesviruses and periodontopathic bacteria, with herpesviruses promoting bacterial upgrowth, and bacterial factors reactivating latent herpesviruses. Bacterial-induced gingivitis may facilitate herpesvirus colonization of the periodontium, and herpesvirus infections may impede the antibacterial host defense and alter periodontal cells to predispose for bacterial adherence and invasion. Herpesvirus-bacteria synergistic interactions, are likely to comprise an important pathogenic determinant of aggressive periodontitis. However, mechanistic investigations into the molecular and cellular interaction between periodontal herpesviruses and bacteria are still scarce. Herpesvirus-bacteria coinfection studies may yield significant new discoveries of pathogenic determinants, and drug and vaccine targets to minimize or prevent periodontitis and periodontitis-related systemic diseases.

A bibliometric analysis of Periodontology 2000.

The continually high impact factor of Periodontology 2000 (7.861 for 2018), the level of which is unprecedented among dental journals, prompted the present bibliometric analysis of the Journal. Since the inception of Periodontology 2000 in 1993 and until July 2019, the top 100 most-cited articles have received a total of 21,276 (Web of Science), 23,009 (Elsevier's Scopus), and 43,518 (Google Scholar) citations. The citations of the 100 most-cited articles were found to vary from 118 to 827 (Web of Science), 10 to 1069 (Scopus), and 15 to 2028 (Google Scholar). Three articles had more than 600 (Web of Science) citations, 5 had between 400 and 600 citations, 25 had between 200 and 400 citations, and 67 had between 100 and 200 citations. The first authors of the 100 most-cited articles were based in the USA (51%), Switzerland (14%), and Australia (10%). The 5 dental institutions with the most frequently cited articles were The Forsyth Institute, USA (9 articles), The University of Queensland, Australia (8 articles), University of Bern, Switzerland (7), University of Texas Health Science Center at San Antonio, USA (6 articles), and University of Washington, USA, and Temple University School of Dentistry, USA (5 articles each). The likely reason for the high impact factor of Periodontology 2000 is publication of insightful and timely review articles produced by eminent researchers and clinicians from a wide range of dental institutions and countries.

Focal infection of periodontal origin.

Periodontology has evolved from a predominantly mechanical to a sophisticated infectious disease-based discipline. Research has paved the way for a greater understanding of the periodontal microbiome, improvement in periodontal diagnostics and therapies, and the recognition of periodontitis being associated with more than 50 systemic diseases. The etiopathology of progressive periodontitis includes active herpesviruses, specific bacterial pathogens, and proinflammatory immune responses. This article points to a role of periodontal herpesviruses in the development of systemic diseases and proposes treatment of severe periodontitis not only to avoid tooth loss, but also to reduce the risk for systemic diseases. An efficient, safe, and reliable anti-infective treatment of severe periodontitis is presented, which targets both herpesviruses and bacterial pathogens and which can be carried out in minimal time with minimal cost.

Periodontal herpesvirus morbidity and treatment.

Four billion individuals worldwide have a history of periodontitis, with the poorest people in society most affected. Periodontitis can lead to unsightly drifting of teeth and tooth loss that may interfere with the wellbeing of daily living and has also been linked to at least 57 medical diseases and disabilities. The etiology of severe periodontitis includes active herpesviruses, specific bacterial pathogens, and destructive immune responses, but herpesviruses seem to be the major pathogenic determinant. Periodontal herpesviruses that disseminate via the systemic circulation to nonoral sites may represent a major link between periodontitis and systemic diseases. Current treatment of periodontitis focuses almost exclusively on bacterial biofilm and will require revision. Periodontal therapy that targets both herpesviruses and bacterial pathogens can provide long-term clinical improvement and potentially reduces the risk of systemic diseases. Molecular diagnostic tests for periodontal pathogens may enable early microbial identification and preemptive therapy. This review details an efficient and reliable anti-infective treatment of severe periodontitis that can be carried out in minimal time with minimal cost.

Periodontitis: facts, fallacies and the future.

This volume of Periodontology 2000 represents the 25th anniversary of the Journal, and uses the occasion to assess important advancements in periodontology over the past quarter-century as well as the hurdles that remain. Periodontitis is defined by pathologic loss of the periodontal ligament and alveolar bone. The disease involves complex dynamic interactions among active herpesviruses, specific bacterial pathogens and destructive immune responses. Periodontal diagnostics is currently based on clinical rather than etiologic criteria, and provides limited therapeutic guidance. Periodontal causative treatment consists of scaling, antiseptic rinses and occasionally systemic antibiotics, and surgical intervention has been de-emphasized, except perhaps for the most advanced types of periodontitis. Plastic surgical therapy includes soft-tissue grafting to cover exposed root surfaces and bone grafting to provide support for implants. Dental implants are used to replace severely diseased or missing teeth, but implant overuse is of concern. The utility of laser treatment for periodontitis remains unresolved. Host modulation and risk-factor modification therapies may benefit select patient groups. Patient self-care is a critical part of periodontal health care, and twice-weekly oral rinsing with 0.10-0.25% sodium hypochlorite constitutes a valuable adjunct to conventional anti-plaque and anti-gingivitis treatments. A link between periodontal herpesviruses and systemic diseases is a strong biological plausibility. In summary, research during the past 25 years has significantly changed our concepts of periodontitis pathobiology and has produced more-effective and less-costly therapeutic options.

Periodontal herpesviruses: prevalence, pathogenicity, systemic risk.

Periodontitis is an infectious/inflammatory disease characterized by the loss of periodontal ligament and alveolar bone. Herpesviruses are frequent inhabitants of periodontitis lesions, and the periodontopathogenicity of these viruses is the topic of this review. In 26 recent studies from 15 countries, subgingival cytomegalovirus, Epstein-Barr virus and herpes simplex virus type 1, respectively, yielded median prevalences of 49%, 45% and 63% in aggressive periodontitis, 40%, 32% and 45% in chronic periodontitis, and 3%, 7% and 12% in healthy periodontium. An active herpesvirus infection of the periodontium exhibits site specificity, is a potent stimulant of cellular immunity, may cause upgrowth of periodontopathic bacteria and tends to be related to disease-active periodontitis. Pro-inflammatory cytokines induced by the herpesvirus infection may activate matrix metalloproteinases and osteoclasts, leading to breakdown of the tooth-supportive tissues. The notion that a co-infection of herpesviruses and specific bacteria causes periodontitis provides a plausible etiopathogenic explanation for the disease. Moreover, herpesvirus virions from periodontal sites may dislodge into saliva or enter the systemic circulation and cause diseases beyond the periodontium. Periodontal treatment can diminish significantly the periodontal load of herpesviruses, which may lower the incidence and magnitude of herpesvirus dissemination within and between individuals, and subsequently the risk of acquiring a variety of medical diseases. Novel and more effective approaches to the prevention and treatment of periodontitis and related diseases may depend on a better understanding of the herpesvirus-bacteria-immune response axis.

Periodontal microbiology in Latin America.

This review article describes the microbiota associated with periodontal disease in Latin America. This vast territory includes 22 nations, which show great ethnic diversity, with large groups of White people, Black people, Mestizo people and Native people. Widespread poverty and limited access to education and health-care services, including periodontal care, are prominent predisposing factors for destructive periodontal disease in Latin America. Black people and Mestizo people seem to have particularly severe periodontal disease and are frequently colonized by the major periodontal pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. The 'red complex' bacterial pathogens and A. actinomycetemcomitans predominate in chronic and aggressive periodontitis, but gram-negative enteric rods and herpesviruses can also play important periodontopathic roles in Latin America. The key to minimizing the risk of periodontal disease is control of the pathogens, and new low-cost periodontal treatments deserve serious consideration in Latin America.

Sodium hypochlorite (dilute chlorine bleach) oral rinse in patient self-care.

Sodium hypochlorite (NaOCl), commonly known as "bleach," is widely accepted as being a safe and effective antiseptic against bacteria, fungi, and viruses. For over a century, bleach has been used to control or overcome infection in homes, hospitals, and even on battlefields, and in endodontics for disinfection of root canals. This paper reviews clinical studies on the efficacy of sodium hypochlorite oral rinse to combat dental plaque and gingival inflammation. Sodium hypochlorite is readily available as inexpensive household bleach, and we suggest that oral rinsing twice weekly with dilute bleach (0.25% sodium hypochlorite) constitutes a valuable adjunct to current methods of plaque removal.

Biology and pathogenesis of cytomegalovirus in periodontal disease.

Human periodontitis is associated with a wide range of bacteria and viruses and with complex innate and adaptive immune responses. Porphyromonas gingivalis, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, Treponema denticola, cytomegalovirus and other herpesviruses are major suspected pathogens of periodontitis, and a combined herpesvirus-bacterial periodontal infection can potentially explain major clinical features of the disease. Cytomegalovirus infects periodontal macrophages and T-cells and elicits a release of interleukin-1ß and tumor necrosis factor-α. These proinflammatory cytokines play an important role in the host defense against the virus, but they also have the potential to induce alveolar bone resorption and loss of periodontal ligament. Gingival fibroblasts infected with cytomegalovirus also exhibit diminished collagen production and release of an increased level of matrix metalloproteinases. This article reviews innate and adaptive immunity to cytomegalovirus and suggests that immune responses towards cytomegalovirus can play roles in controlling, as well as in exacerbating, destructive periodontal disease.

Elevated subgingival temperature infers high bacterial pathogen counts in severe periodontitis.

OBJECTIVES: Periodontal inflammation may be assessed by bleeding on probing and subgingival temperature. This pilot study evaluated the intrapatient relationship between subgingival temperature and selected bacterial groups/species in deep periodontal pockets with bleeding on probing. MATERIALS AND METHODS: In each of eight adults, an electronic temperature probe identified three "hot" pockets with elevated subgingival temperature and three "cool" pockets with normal subgingival temperature among premolars/molars with 6‒10 mm probing depths and bleeding on probing. Microbial samples collected separately from the hot and cool periodontal pockets were cultured for selected periodontal pathogens. RESULTS: Hot compared to cool periodontal pockets revealed significantly higher absolute and normalized subgingival temperatures and yielded higher mean proportions of Porphyromonas gingivalis (10.2% for hot vs. 2.5% for cool, p = 0.030) and total red/orange complex periodontal pathogens (48.0% for hot vs. 24.6% for cool, p = 0.012). CONCLUSIONS: Hot versus cool deep periodontal pockets harbored significantly higher levels of major periodontal pathogens. Subgingival temperature measurements may potentially be useful to assess risk of periodontitis progression and the efficacy of periodontal therapy.

Systemic ciprofloxacin treatment of multidrug-resistant Aggregatibacter actinomycetemcomitans in severe periodontitis.

An adult periodontitis patient treated with mechanical/surgical therapy experienced gingival necrosis and granulomas post-treatment. Aggregatibacter actinomycetemcomitans, a tissue-invasive pathogen, was recovered and multidrug-resistant but susceptible to ciprofloxacin. Systemic ciprofloxacin eliminated A. actinomycetemcomitans with marked clinical improvement. Ciprofloxacin may be prescribed for A. actinomycetemcomitans periodontal infection unresponsive to the common amoxicillin-metronidazole treatment.

Periodontology: past, present, perspectives.

Periodontitis is an infectious disease that affects the tooth-supporting tissues and exhibits a wide range of clinical, microbiological and immunological manifestations. The disease is associated with and is probably caused by a multifaceted dynamic interaction of specific infectious agents, host immune responses, harmful environmental exposure and genetic susceptibility factors. This volume of Periodontology 2000 covers key subdisciplines of periodontology, ranging from etiopathogeny to therapy, with emphasis on diagnosis, classification, epidemiology, risk factors, microbiology, immunology, systemic complications, anti-infective therapy, reparative treatment, self-care and affordability issues. Learned and unlearned concepts of periodontitis over the past 50 years have shaped our current understanding of the etiology of the disease and of clinical practice.