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Adv Dent Res 19:139-145, April, 2006
© 2006 SAGE Publications

(B2) Periodontal Diseases and Other Bacterial Infections

Presented at the Fifth World Workshop on Oral Health and Disease in AIDS, Phuket, Thailand, July 6–9, 2004, sponsored by Prince of Songkla University, Thailand, the International Association for Dental Research, the World Health Organization, the NIDCR/National Institutes of Health, USA, and the University of California-San Francisco Oral AIDS Center.

M. Umadevi1, O. Adeyemi2, M. Patel3, P.A. Reichart4 and P.G. Robinson5,*

1 Department of Oral and Maxillofacial-Pathology, Ragas Dental College and Hospital, Chennai, India
2 School of Public Health, University of the Witwatersrand, Johannesburg, South Africa
3 Department of Clinical Microbiology and Infectious Diseases, University of the Witwatersrand, Faculty of Health Sciences, South Africa
4 Department of Oral Surgery and Dental Radiology, Center for Dental Medicine, Charité, University of Medicine Berlin, Berlin, Germany; and
5 Dental Public Health, School of Clinical Dentistry, Claremont Crescent, Sheffield S10 2TA, UK

Correspondence: * corresponding author, peter.g.robinson{at}sheffield.ac.uk


   Abstract
TOP
 Abstract
Introduction
 List of Questions
 Answers to Questions
 Summary
 Suggestions for Future Research
 References
 
The workshop addressed the following questions with respect to periodontal diseases and bacterial infections seen in HIV infection: (1) What is linear gingival erythema? Is it prevalent only in HIV disease? A crude Delphi technique was used to ascertain whether LGE existed, but a consensus could not be reached. It was agreed that a diagnosis of LGE should be considered only if the lesion persists after removal of plaque in the initial visit. (2) Do periodontal pockets contribute to viremia in HIV infection? At present, the data are not available to answer this question. (3) Do anti-viral drugs reach the sulcular fluid in significant concentrations? No one at the workshop was aware of data that could answer this question. (4) Does concurrent tuberculosis infection modify the oral manifestations of HIV infection? Though analysis of data from the developing countries does suggest an association between tuberculosis and oral candidiasis, more data and multivariate analysis considering immunosuppression as a confounding factor are necessary, for any conclusions to be derived. (5) What pathogens are involved in periodontal diseases in HIV infection? Periodontal disease may be initiated by conventional periodontal pathogens. But the progression and tissue destruction depend upon the presence of typical and atypical micro-organisms, including viruses, their by-products, increased secretion of potentially destructive inflammatory mediators, and overwhelming host response. (6) How can we diagnose the diseases seen in HIV infection? The answer can be obtained only with data from controlled and blinded studies. It is necessary to design collaborative multi-center longitudinal studies. The results obtained from such large sample sizes can contribute eventually to interpretation of the outcome.

Key Words: Oral • HIV • linear gingival erythema • periodontitis • bacterial • tuberculosis


   Introduction
TOP
 Abstract
 Introduction
List of Questions
 Answers to Questions
 Summary
 Suggestions for Future Research
 References
 
Knowledge concerning the varied nature, clinical and biological significance, and management of oral disease found in HIV infection has grown in concert with the huge body of work on the AIDS epidemic (Hodgson al., 2006). This report of the workshop on periodontal diseases, gingivitis, and other bacterial infections discusses the responses to questions considered by the workshop and then focuses on the outcome of the discussion.

Periodontal diseases form an important part of the constellation of oral manifestations of HIV infection (EC-Clearinghouse, 1993) as lesions strongly associated with the infection. As a microbial disease affecting the hard and the soft tissues of the oral cavity, periodontal diseases acquire a unique status in the diversity of their manifestations, having implications not only for oral health but also on systemic health. Other bacterial infections are placed in the group of lesions less commonly associated with HIV.

The HIV-associated periodontal lesions accepted by the EC-Clearinghouse (1993) include:

  1. linear gingival erythema (LGE), a non-plaque-induced gingivitis exhibiting a distinct erythematous band of the marginal gingiva, with either diffuse or punctuate erythema of the attached gingiva; and
  2. necrotising periodontal diseases, which are sub-classified as necrotizing ulcerative gingivitis (NUG), necrotizing ulcerative periodontitis (NUP), and necrotizing stomatitis (NS). NUG involves destruction of one or more inter-dental papillae and is limited to the marginal gingiva. NUP extends beyond the papillae and marginal gingivae, causing loss of periodontal attachment, possibly exposing bone. When the necrosis extends beyond the periodontium into the mucosa and osseous tissue, it results in NS. These three conditions appear to be different stages of the same disease. The only distinction appears to be their severity, and there are case reports of NUG that has progressed to NS (Williams et al., 1990; Patton and McKaig, 1998; Robinson et al., 1998).

Chronic periodontitis has also been reported with an increased rate of attachment loss or exacerbated periodontitis (Yeung et al., 1993). Periodontitis has a multifactorial initiation, development, and progression. With the discovery of the emerging risk factors, inflammatory responses, and genetic regulators of these responses, any factors associated with periodontitis could be a common underlying risk factor rather than a causal factor (Nunn, 2003). Risk factors for periodontitis in HIV-positive patients are age, smoking, viral load, micro-organisms (viz., Fusobacterium nucleatum, Prevotella intermedia, Actinobacillus actinomycetocomitans), enzymes (viz., GCF neutrophil elastase and beta glucuronidase) (Barr et al., 1992; Robinson et al., 1996; Alpagot et al., 2004; Umadevi et al., 2006).

It is increasingly accepted that these conditions are the same diseases as seen in non-HIV-infected populations, the initiation, progression, and presentation of which may be modified by HIV infection (Armitage, 1999).

The previous workshop on periodontal diseases in HIV-infected individuals (Robinson et al., 2002) considered the following questions, which were based on the existing knowledge from the then-published data. The questions were: (i) To what extent are specific periodontal changes associated with HIV infection? (ii) Are conventional periodontal diseases modified by HIV infection? (iii) If the above exist, are they consistent between geographical and transmission groups? (iv) Has the epidemiology of these periodontal diseases changed with the advent of new therapies in HIV infection? (v) What pathogens are involved in periodontal diseases seen in HIV infection? (vi) Which management protocols are suitable for the periodontal diseases seen in patients with HIV infection?

The limitations that initiated these questions were those concerning clinical measures and indices used to establish the diagnosis of periodontitis, study design, the necessity to distinguish severity and extent of the disease, and the representation and analysis of the data. It was suggested that future research should be based on standardized approaches, measures, and analytic strategies to enhance the comparability of data. A clear list of possible explanatory variables, potential confounding factors which would help in inclusion of these data, was also proposed (Robinson et al., 2002).

The workshop concluded that none of the questions could be answered, but it identified potential research avenues. It agreed that periodontal diseases associated with HIV are similar to or modified presentations of diseases seen in the non-infected population. The need to clarify the types and the natural history of the diseases seen in these patients with the availability of more information regarding periodontal diseases in general was stressed. To confirm the existence of LGE as a distinct entity, the group felt that primary data from well-designed clinical studies were essential, and that further research should identify and distinguish the factors involved in the initiation and progression of NUG, NUP, and NS. They were of the opinion that greater knowledge was needed in understanding the significance of periodontal diseases among people with HIV in the developing countries, especially in Africa. This information would determine which periodontal lesions most needed treatment in resource-poor regions of the world.

There are contradicting reports on the prevalence of periodontal diseases among HIV-positive patients from developing countries. In a descriptive study of 500 patients in Nigeria, the prevalence of NUG and NUP was reported as 2% each (Anteyi et al., 2003), whereas in a study of 156 Zimbabwean patients, the combined prevalence of NUG and NUP was 8.3% (Chidzonga, 2003). In another study, of 101 Cambodian HIV-positive patients, 28% presented with ’necrotizing gingivo-periodontitis’ (Reichart et al., 2003). In a cross-sectional study from Thailand, HIV-associated periodontal diseases were reported among 15% and 14% of the study population in Northern and Southern Thailand, respectively (Kerdpon et al., 2004).

In a cross-sectional study of 1000 patients from Chennai, South India, HIV-associated periodontal disease was not recorded, but the prevalence of conventional gingivitis (CG, defined as distinctive, dusky red, cyanosed free gingiva, the presence of bleeding on probing and/or spontaneous bleeding) was 72%, and that of conventional periodontitis (CP, defined as the presence of pockets > 4 mm in one or more sites) was 33% (Ranganathan et al., 2004).

At the same referral center, in a subsequent cohort of another 700 HIV patients, the prevalence of conventional gingivitis was 69% and that of conventional periodontitis was 29%. There was no case of HIV-associated periodontal disease. In this group of patients, those who presented with oral candidiasis were 1.4 times more likely to have conventional gingivitis (CI 1.1–1.9, p < 0.01) and 1.7 times more likely to have conventional periodontitis (CI 1.3–2.2, p < 0.01). Periodontitis was 1.6 times (95% CI 1.29–1.98, p < 0.01) more frequent in smokers than in non-smokers. There was a significant difference between the median CD4 counts in patients with conventional gingivitis (230) and those without (320), but this difference was not observed in periodontitis. The high prevalence of these lesions in the normal population limits the significance of occurrence of these lesions in the study population. Larger case-control studies are necessary to understand the significance of the lesions (Umadevi et al., 2006).

Periodontitis was prevalent in the entire sample of 61 HIV patients in a study in Kenya (Butt et al., 2001). The authors recommended that early detection is mandatory to prevent the morbidity arising from such commonly occurring lesions. However, this conclusion needs to be supported by data on the effectiveness of treatments for the condition before it can be implemented.

It is evident from the literature that both HIV-associated periodontal diseases and conventional periodontal diseases are prevalent in developing countries. For further understanding of the importance of these periodontal diseases in the HIV population, the term ’periodontal disease’ should not be used singularly. As the last workshop concluded, more careful specification of the type of disease under discussion would facilitate research of the epidemiology and management of these lesions (Robinson et al., 2002; Johnson, 2004).


   List of Questions
TOP
 Abstract
 Introduction
 List of Questions
Answers to Questions
 Summary
 Suggestions for Future Research
 References
 
With this background, the Workshop on Periodontal Disease, Gingivitis, and Other Bacterial Infections (Clinical/Basic Science) considered the following questions:

  1. What is linear gingival erythema? Is it prevalent only in HIV disease?
  2. Do periodontal pockets contribute to viremia in HIV infection?
  3. Do anti-viral drugs reach the sulcular fluid in significant concentrations? Is this important in view of our present understanding of the periodontal tissues?
  4. What pathogens are involved in periodontal disease in HIV infection?
  5. How can we diagnose the diseases seen in HIV infection?
  6. Does concurrent tuberculosis infection modify the oral manifestations of HIV infection?

An earlier question on the possible role of cytokines in the immunopathogenesis of bacillary angiomatosis was not addressed, owing to the paucity of literature on this condition in the mouth.


   Answers to Questions
TOP
 Abstract
 Introduction
 List of Questions
 Answers to Questions
Summary
 Suggestions for Future Research
 References
 
Question 1. What is linear gingival erythema? Is it prevalent only in HIV disease?
The EC-Clearinghouse describes linear gingival erythema as a distinct, fiery, red band along the margin of the gingiva. The amount of erythema is disproportionately intense for the amount of plaque seen. No ulceration is present, and there is no evidence of pocketing/attachment loss. Apparently, LGE does not respond to routine plaque control measures (Winkler et al., 1988).

Recent studies reported the prevalence of LGE ranges between 2 and 25% (Martinez-Canut et al., 1996; Arendorf et al., 1997, 1998; Fonseca et al., 2000; Schoen et al., 2000; Flaitz et al., 2001; Khongkunthian et al., 2001; Nittayananta et al., 2001; Kamiru and Naidoo, 2002; Anteyi et al., 2003). This diversity of findings indicates a need for the calibration of examiners and more stringent application of the diagnostic criteria. Studies attempting to ascertain whether LGE is seen only in HIV infection require HIV-negative controls and, ideally, blinding of examiners to subjects’ HIV status. Earlier large controlled-prevalence studies of periodontal health in adults with HIV infection (Grbic et al., 1995; Robinson et al., 1996) found the prevalence of LGE to be similar in infected and non-infected patients. These findings illustrate that CG is commonly misdiagnosed as LGE.

More recently, a study of 291 women attending ante-natal clinics in Johannesburg, South Africa, found significant differences between HIV-positive and -negative women in the occurrence of LGE (4% and 0.7%, respectively), NUG (24.3% and 0.7%), and NUP (4.3% and 0%) (Adeyemi et al., 2006). While necrotizing diseases are associated with HIV (Robinson et al., 1996) and are unlikely to be misdiagnosed, LGE may be confused with CG.

During the course of the workshop, several participants expressed the view that LGE does exist in non-HIV-infected population, others felt that it was specific to HIV infection, and a sizable proportion felt that the disease may not exist at all in adults. Some participants stressed the paucity of data, the lack of well-described cases of this disease, and the danger of misdiagnosis. They went on to propose that the association of this condition with HIV be reconsidered at future consensus conferences, perhaps by Delphi techniques.

For the time being, then, the uncertainty regarding the clinical diagnosis of LGE is still present. To overcome this difficulty, it is emphasized that a diagnosis of LGE should be given only if the resistance to plaque removal over subsequent visits is documented. The same criterion should be followed when a diagnosis of LGE is considered in a non-HIV-infected population. It is the responsibility of the physician to confirm or rule out a diagnosis of LGE when suspecting its presence, for it may be a clinical manifestation of the underlying immunosuppression.

Questions 2 and 3. Do periodontal pockets contribute to viremia in HIV infection? Do anti-viral drugs reach the sulcular fluid in significant concentrations? Is this important in view of our present understanding of the periodontal tissues?
The dentogingival epithelial surface (DGES) is comprised of the sulcular and junctional epithelium present in health, as well as any intervening pocket epithelium present in periodontitis. Individuals without periodontitis have a typical DGES of 5 cm2. In patients with periodontitis, the mean DGES ranges between 8 cm2 and 20 cm2 (Hujoel et al., 2001). Accompanying this increase of the DGES in periodontal disease, there is an increase in the excretion of mononuclear-cell-enriched GCF.

Human viruses have been identified in GCF from periodontal pockets (Parra and Slots, 1996; Chebbi et al., 1997). Some investigations have assessed HIV viral burden in oral fluids by means of HIV RNA quantification (Phillips et al., 1994; Barr et al., 1996; Liuzzi et al., 1996).

Of most interest is the work by Shugars et al.(2000), who quantified HIV-1 RNA in saliva and plasma of 40 HIV-seropositive adults. Many (42%) of their subjects had detectable salivary HIV-1 RNA, which highly correlated with plasma viral levels, and HIV-associated periodontal disease. In particular, LGE, severe gingival inflammation, and absence of anti-retroviral therapy were associated with high salivary titers. A hyper-excretory status has also been defined as a fourfold or higher viral load in saliva compared with that in plasma (Shugars et al., 2001). They also postulated that a high salivary viral load may increase the local inflammatory responses that, in turn, may create a local environment that favors the establishment of acute periodontal lesions.

This group suggested that the contribution of periodontal disease to viral load appears to be greater than that of local mucosal disease. They further speculated that pro-inflammatory cytokine responses generated from acute periodontal conditions may further enhance viral shedding in the oral cavity. If confirmed, this idea may have important clinical implications, signifying systemic pathological consequences of gingival and periodontal inflammation, which were hitherto considered as a self-contained infection.

It has also been reported that mononuclear cells present in GCF and harboring pro-viral HIV-1 DNA would represent a possible source of HIV-1 in the presence or absence of local bleeding, especially in persons with advanced HIV infection and presenting with periodontal disease with associated loss of clinical attachment (Maticic et al., 2000).

The present literature confirms the presence of HIV-1 RNA in saliva and pro-viral HIV-1 DNA in the mononuclear cell infiltrate. There has also been consideration of salivary viral load as a potential marker for monitoring anti-retroviral therapy. But there are no studies considering whether periodontal pockets contribute to viremia in HIV infection, and whether anti-viral drugs reach the sulcular fluid in significant concentrations. Knowledge pertaining to these questions will contribute to our present understanding of the implications of periodontal diseases in HIV infection.

Overall, though analysis of the available data indicates that HIV has been detected in saliva and GCF, there is no body of literature that could convincingly answer the above two questions.

Question 4. What pathogens are involved in periodontal disease in HIV infection?
Bacteria, yeasts, and viruses may be present in the periodontal pockets of HIV-positive subjects. Which of these micro-organisms is/are pathogenic in people with HIV? This question can be considered in four parts:

  • "Do conventional periodontal pathogens cause periodontal disease in HIV-positive patients? If so, which bacteria are predominant? Are they more numerous in people with HIV? Does the genotype differ? Are these micro-organisms more virulent? Are combinations of periodontal pathogens important?
  • "Are atypical micro-organisms responsible for periodontal disease in HIV infection?
  • "Do viruses play a role in HIV-related periodontal diseases?
  • "Is the host response different at disease sites?

Conventional periodontal pathogens
Many species of the periodontal microflora found in sites with diseases associated with HIV are also found in non-HIV-infected individuals with classic periodontitis—in particular, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Actinobacillus actinomycetemcomitans, Eikenella corrodens, and Campylobacter rectus (Murray et al., 1988, 1989, 1991; Zambon et al., 1990; Rams et al., 1991; Moore et al., 1993; Tenenbaum et al., 1997; Teanpaisan et al., 2001; Tsang and Samaranayake, 2001; Patel et al., 2003). Severe immunosuppression favors the colonization by these species, as well as by species not commonly found in the subgingival microbiota (Goncalves et al., 2004).

Given the range of microbiological methods and the diversity of clinical presentations, it is not surprising that some studies have conflicting findings. P. gingivalis was present in the HIV-positive subjects more frequently and in higher numbers than in the HIV-negative patients with periodontitis (Chattin et al., 1999). A combination of certain periodontal pathogens may be responsible for chronic periodontitis seen in HIV-infected patients—for example, three combinations of periodontal pathogens (P. nigrescens and C. rectus; P. nigrescens and P. gingivalis; and P. nigrescens and T. denticola) were significantly associated with HIV-positive compared with HIV-negative patients (Patel et al., 2003).

We can also ask the question, are the same conventional periodontal pathogens present in a different genotypic form? One study has shown no difference in the genotype distribution of black-pigmented anaerobes in HIV-positive and HIV-negative subjects (Teanpaisan et al., 2001).

Regarding the measurement of virulence of bacteria, two studies (Mellanen et al., 1996, 1998) have shown increases in metalloproteinases, collagenase, and gelatinase in the gingival crevicular fluid and saliva of HIV-positive patients. However, the enzymes were of host origin. No research has looked at the virulence of periodontal pathogens in HIV-positive patients.

Atypical micro-organisms
Atypical or opportunistic micro-organisms have been isolated from HIV+ patients, including Clostridium difficile, Clostridium clostridiforme, Entamoeba gingivalis, Enterobacter species, Enterococcus faecalis, Enterococcus avium, Klebsiella species, Mycoplasma salivarium, Pseudomonas aeruginosa, and candida species (Murray et al., 1988; Zambon et al., 1990; Rams et al., 1991; Moore et al., 1993; Lucht et al., 1998; Chattin et al., 1999). The mere presence of these organisms among conventional periodontal pathogens cannot prove that they are responsible for periodontal disease in HIV-positive patients. A pathogenic role must be established.

Candida species and C. albicans are frequently found in HIV-positive individuals (Murray et al., 1988; Zambon et al., 1990; Moore et al., 1993; Brady et al., 1996; Chattin et al., 1999). The presence of C. albicans is strongly associated with gingival redness (Grbic et al., 1995; Robinson et al., 1996; Lamster et al., 1997, 1998) and with the incidence of NUG (Robinson et al., 1998). In a study of 54 HIV-positive patients, C. dublinienis was recovered from subgingival plaque samples from periodontal lesions in 48% of patients of the 82% who were positive for the yeast (Jabra-Rizk et al., 2001). A pathogenic role for candida in the progression of periodontal diseases cannot be ruled out, because it can invade periodontal soft tissues and could increase the severity of periodontal disease in HIV patients (Odden et al., 1994; Gomez et al., 1995).

Do viruses play a role?
The presence of HSV type I specific antigen in sulcular epithelial cells of patients undergoing periodontal treatment was noted as early as 1983 (Ehrlich et al., 1983). Later, Contreras and Slots showed that replication of HCMV can occur in periodontal sites (Contreras and Slots, 1998).

Some viruses (EBV-1 and HCMV) are present and are associated with periodontal pathogens in systemically healthy patients with gingivitis and mild to moderate periodontitis (Contreras et al., 1999). Similar co-infections may occur in HIV-positive patients, because viruses have been isolated from these patients (Contreras et al., 2001).

However, the periodontopathic role of viruses combined with periodontal pathogens needs further research. When the presence of viruses was compared in HIV-positive patients and HIV-negative patients, several human herpes viruses, especially EBV, HHV-6, were found to occur with higher frequency in subgingival specimens from periodontitis lesions in HIV-positive patients (Contreras et al., 2001). However, Mardirossian and colleagues showed that HHV-6 and HHV-7 occurred with similar frequency in both gingival biopsy and GCF specimens of HIV-positive and HIV-negative individuals, whereas HHV-8 was detected exclusively in HIV+ patients without KS (Mardirossian et al., 2000).

In conclusion, the presence of viruses in HIV-positive patients with periodontal lesions has been established, but the periodontopathic significance of this observation needs further investigation.

Host response
Interleukin (IL-1) and tumor necrosis factor (TNF) represent pro-inflammatory cytokines that stimulate several events that occur during periodontal disease. These include the induction of adhesion molecules and other mediators that facilitate and amplify the inflammatory response, the stimulation of matrix metalloproteinase, and bone resorption. The activity of these cytokines coincides with the critical events that occur during periodontal disease, namely, loss of attachment and bone resorption. In addition, the loss of fibroblasts that occurs during infection with periodontal pathogens is partly mediated by TNF.

Thus, much of the damage that occurs during periodontal tissue destruction can be attributed to IL-1 and TNF activity. This destruction may very well represent an overreaction of the host response to periodontal pathogens caused by excessive production of IL-1 and TNF (Graves and Cochran, 2003). In GCF of HIV-positive patients, the levels of IL-1β, IL-6, and TNF{alpha} were higher than in the GCF of HIV-negative patients. The levels were higher in deeper pockets than in shallow pockets (Grbic et al., 1997; Lamster et al., 1997, 1998; Baqui et al., 2000). This may explain the increased rate of attachment loss and tissue destruction seen in HIV-positive patients. Animal studies have confirmed the role of these pro-inflammatory cytokines (Delima et al., 2002). Another factor that may contribute to tissue destruction is excessive production of metalloproteinases, which are elevated in HIV-positive patients (Mellanen et al., 1998).

Although serum IgG levels of important periodontal pathogens are low in HIV-positive patients (Steinsvoll et al., 1997), there was no difference in IgG subclass specific antibody response to periodontopathic organisms (Yeung et al., 2002). This suggests that HIV-positive status does not impair humoral immune response to periodontopathic organisms.

Question 5. How can we diagnose the periodontal diseases seen in HIV infection?
A diagnosis is derived from the information obtained from the patients’ medical and dental histories, combined with findings from thorough oral examinations. The entire constellation of signs and symptoms associated with the disease or condition is taken into account before a diagnosis is reached (Armitage, 2004). The clinical presentation of periodontitis is due to inflammation and the pathology that results from the inflammation. Injury mediated by inflammation is a consequence of inability of the host to resolve the inflammation, and not the initial inflammation itself (Van Dyke and Serhan, 2003).

The altered immune response in HIV-positive patients is only a varied presentation of the normal, but is not in itself diagnostic. Moreover, there are no specific criteria to distinguish periodontal diseases occurring in HIV-positive from those in HIV-negative patients. It is now known that the lesions of NUP are commonly observed in individuals with systemic conditions including, but not limited to, HIV infection, severe malnutrition, and immmunosuppression (Corbet, 2004). It may be that periodontal diseases are associated with HIV, not because they are different, but because they are more common or more severe.

The post-HAART era may also witness changes in periodontal diseases. Ceballos-Salobrena and co-workers examined 154 AIDS patients receiving HAART and found a 30% decrease in prevalence of periodontal disease (Ceballos-Salobrena et al., 2000). In this context, prospective studies and case-control studies, in which the examiner is blinded to the HIV status of the patient being examined, in different population subgroups, are still required to answer this question.

Question 6. Does concurrent tuberculosis infection modify the oral manifestations of HIV infection?
Co-infection with Mycobacterium tuberculosis and HIV is responsible for one-third of all deaths due to AIDS (Murray, 2003). Nieto Garcia and colleagues stated that oral candidiasis is an early marker of TB and late marker of AIDS (Nieto Garcia et al., 1992). The advent of HIV infection has accelerated the spread of tuberculosis inexorably, while the multi-drug-resistant strains of the bacillus have hampered disease management (Samaranayake, 2002).

However, since both tuberculosis and oral candidiasis are caused by underlying immunosuppression, any observed relationship between them could be due to confounding rather than causal.

A determination of a causal role for tuberculosis in other oral opportunistic infections would require several avenues of research. Laboratory-based studies might indicate the biological plausibility of such a link, but patient-based and epidemiological research would require careful control of confounding via the design or analysis of studies.


   Summary
TOP
 Abstract
 Introduction
 List of Questions
 Answers to Questions
 Summary
Suggestions for Future Research
 References
 
With respect to each question, the workshop’s conclusions were as follows:

  1. What is linear gingival erythema? Is it prevalent only in HIV disease?
    A crude Delphi technique (used in consensus conferences) was used to ascertain whether participants thought LGE existed. No consensus could be reached. It was suggested that, for consistency and to prevent inter-observational variation, stringent diagnostic criteria be followed. A diagnosis of LGE could be made only after confirmation of the persistence of the lesion after plaque removal.
  2. Do periodontal pockets contribute to viremia in HIV infection?
    It is known from the literature that the saliva and GCF harbor HIV. At present, however, the data are not available to answer this question.
  3. Do anti-viral drugs reach the sulcular fluid in significant concentrations? Is this important in view of our present understanding of the periodontal tissues?
    No one at the workshop was aware of data that could answer these questions.
  4. What pathogens are involved in periodontal disease in HIV infection?
    NUG, NUP, and NS appear to have the same pathogens as the corresponding diseases in non-infected populations. HIV-related periodontitis seems to be a multifactorial, multimicrobial disease with no single organism being responsible. The disease may be initiated by conventional periodontal pathogens, but the progression and tissue destruction depend upon many factors, the most important being the overwhelming host response and increase in secretion of potentially destructive inflammatory mediators. This condition may also allow other opportunistic micro-organisms, including viruses, to become established and cause further destruction.
    The progression of periodontal disease and tissue destruction in the presence of HIV infection is dependent upon the presence of typical and atypical subgingival micro-organisms, including viruses, their by-products, and local inflammatory host response.
  5. How can we diagnose the diseases seen in HIV infection?
    The answer to this question can be obtained only after data are available from case-control studies with the examiners blinded to the HIV status of participants. It is believed that the clinical presentations of periodontal lesions in HIV-positive patients are similar to those in the non-infected population, though they may be modified by the extent of the underlying immunosuppression.
  6. Does concurrent tuberculosis infection modify the oral manifestations of HIV infection?
    Some data have been reported from developing countries suggesting an association between tuberculosis and oral candidiasis. Before any conclusions can be derived, more data and multivariate analysis considering immunosuppression as a confounding factor are necessary.


   Suggestions for Future Research
TOP
 Abstract
 Introduction
 List of Questions
 Answers to Questions
 Summary
 Suggestions for Future Research
References
 
Longitudinal studies should be undertaken to monitor the progression of the disease, and as many parameters as possible should be measured at each stage. Stringent uniform diagnostic criteria and presentation of the data and analysis should be the fundamental governing principle in periodontal research for extrapolation of the information thus obtained. The parameters should include probing depth, recession, percentage of radiographic bone loss, prevalence and number of periodontal pathogens, atypical micro-organisms, viruses, measurement of virulence factors, and host response. Collaborative multicentric studies should be designed to increase the sample size and interpret the outcomes.


   References
TOP
 Abstract
 Introduction
 List of Questions
 Answers to Questions
 Summary
 Suggestions for Future Research
 References
 

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Advances in Dental Research, Vol. 19, No. 1, 139-145 (2006)
DOI: 10.1177/154407370601900125
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