Inflammation limited to the gingival margin in a female adult African
To effectively manage those “difficult to explain” cases, periodontologists must embrace the shift to the measurement of periodontal inflammation through inflammatory markers and salivary metabolomics. The innovation of point-of-care kits makes this even more versatile in everyday management of inflammatory periodontal diseases. The neutrophil collagenase-2 (aMMP-8) is a promising point-of-care system in this regard.
4.3 Validity, Sensitivity, and Specificity of Neutrophil Collagenase-2 (aMMP-8) System
The long history of dependence on clinical measures of periodontal inflammation cannot be easily discarded. The gradual paradigm shift will be expedited by validating the claims of these novel systems and ascertaining their sensitivity, specificity, and reliability. Recently there are published studies, which have investigated the validity, sensitivity, specificity, reliability, and reproducibility of a novel point of care (aMMP-8 chairside test). The studies had satisfactory results concerning initial periodontitis in Caucasian adolescents as well as chronic periodontitis among nigerians [16, 17].
(a) Inflammation in a 16-year-old boy aMMP-8 test slightly positive. (b) PerioSafe—test analysis of negative (1) <20 ng/ml and positive (2) >20 ng/ml adolescent patient with initial periodontitis
With the high validity and reliability of the novel aMMP-8 chairside test being established, the applicability to general health parameters was investigated, namely, reproductive health parameters [21–23].
4.4 Justification for aMMP-8 Chairside Test in Reproductive Health Parameters
The possible link between chronic periodontitis and reproductive health parameters predates the present century. The concerns have existed for over one century. This was expressed by the early focal infection theory of Charles Rosenow in 1909 [24], the focal allergy theory of Berger’s in 1939 [25], and Slauk’s focal toxicosis theory of the 1940s [26]. The “premature birth” of those theories ensured their “early death,” but the ideas resurfaced almost half a decade later with concerns raised by the finding of Linossier and coworkers 1982 [27]. It was their isolation of sperm immobilizing factor from necrotic dental pulp which probably fueled the awakened interest within a few years. This time, the investigators were neither dentists nor periodontologists; they were in fact gynecologists –Bieniek and Riedel.
In 1986, Bieniek and Riedel [28] were curious about the finding of antibiotic-resistant bacteriospermia among patients with chronic periodontitis. This relationship between chronic periodontitis and fertility was again neglected until another decade with the landmark work of Offenbacher and colleagues linking preterm birth with chronic periodontitis in 1996 [29]. Later, Kavoussi and coworkers [30] reported links between chronic periodontitis and endometriosis in 2009 which was followed up by Kligner and coworkers who reported sperm motility in 2011 [31]. Hart in 2012 reported a link between delayed conception [32], while Oguz reported erectile dysfunction in relation to chronic periodontitis in 2013 [33].
These findings necessitated a search of the literature for associations between chronic periodontitis and specific reproductive parameters. The relationship between chronic periodontitis and reduced libido is unclear with possible mechanisms including the arginine link. A direct relationship exists between arginine—a direct nitrous oxide precursor—and libido in men and men and women [34, 35]. In men, arginine is required for achieving and maintaining penile erection making the enhancement of arginase activity by P. gingivalis of great importance [36, 37]. A critical biochemical pathway necessary for male sexual arousal is short-circuited by P. gingivalis [38]. The fact that salivary arginase activity increases in patients with chronic periodontitis while periodontal therapy reduces activity explains the link [39].
4.5 Effect of Chronic Periodontitis on Erectile Dysfunction and Sperm Count
The arginine link already explains partly the link between chronic periodontitis and erectile dysfunction which according to the American Sexual Health Association is the inability to maintain an erection suitable for intercourse [40]. Other mechanisms involved the effect of a proinflammatory state cause of host-derived mediators of chronic periodontitis. Prominent among these mediators is the proinflammatory state promoted by tumor necrosis factor-α (TNF-α) and interleukin (IL)-1 and IL-6 [41, 42] which promotes endothelial dysfunction and injury resulting in erectile dysfunction through the vasculogenic pathway [43, 44].
Colagar and coworkers reported a link between lipid peroxidation/decreasing total antioxidant capacity and low sperm count [45]. Raised levels of IL-6, a mediator of chronic periodontitis, are linked with lipid peroxidation explaining a possible link between chronic periodontitis and reduced sperm count [46].
Kligner and others reported an association sperm sub-motility and chronic periodontitis [31].
4.6 Association Between Periodontitis and Conception
Associations between endometriosis [30], pelvic inflammatory disease [47], and increased time to conception [32] have been reported in the literature. Chronic periodontitis influences pregnancy outcomes through two possible mechanisms, first a direct access by periopathogens and second by mediators of chronic inflammation [48]. F. nucleatum “a potential accessory pathogen” facilitates the colonization of periodontitis-associated bacteria [31] through a “gate opener” effect. Once it translocates to extraoral sites, the “potential accessory pathogen” of F. nucleatum changes into an “overt pathogen” status [49].
Evidence exists for the direct hematogenous spread of F. nucleatum found in the subgingival biofilm of a stillborn infant whose mother had pregnancy-associated gingivitis [50]. It also crossed the endothelium to access the fetal-placental compartment in experimental models using E-cadherin-binding FadA adhesin and TLR4-dependent necroinflammatory response [51]. P. gingivalis, probably the most important periopathogen, induces fetal loss through its cardiolipin-specific antibody production [50–52].
4.7 Emerging Racial Differences on Chronic Periodontitis and Pregnancy Outcomes
The literature appears indifferent and at best equivocal on the effect of race on chronic inflammation especially as it relates to periodontitis. African human umbilical vein endothelial cells showed greater oxidative stress and inflammation in vitro with higher nitrous oxide expression [53]. Some workers have reported a reduced inflammatory response among Africans due to “chronic conditioning or priming of innate immunity” leading to attenuated inflammatory responsiveness [54]. Africans put up a lower inflammatory response to endotoxin [55]. This, however, might not predict acute stress response in innate immunity-mediated diseases but might apply to acute inflammation rather than the chronic endotoxemia in periodontitis [55].
Interleukin-6 (IL-6) and interleukin-10 (IL-10) relationship is important in the pathogenesis and response level in chronic periodontitis [4]. Raised interleukin levels are not enough to explain levels of without a relatively low level of the anti-inflammatory IL-10 [4]. Raised IL-6 levels have been reported, but the same study failed to demonstrate racial differences in IL-10, TNF-α, and C-reactive protein [56]. Their finding partly explains the elevated aMMP-8 among nine of ten Nigerian pregnant women assessed with a novel aMMP-8 chairside test [21]. Since MMP activity increases in the prepartum period [57], raised MMP-8 levels are important for preterm birth. The findings of Nwhator and coworkers in 2015 [21] are therefore an important step toward understanding racial differences in preterm birth deserving further investigation.
The mechanisms mediating delayed conception and chronic periodontitis [21, 32] are unclear, and the dearth of literature on the topic is not surprising considering its novelty. However, a direct relationship exists between levels of tissue inhibitor of metalloproteinase (TIMP) and successful conception post-in vitro fertilization [58]. The likelihood of the reverse scenario, increased time to conception by raised MMP-8 levels, deserves further investigation. To further explore the mechanisms of association between reproductive health parameters and periodontitis , a novel aMMP-8 chairside test was employed amidst several clinical situations among men and women in Nigeria.
4.8 Role of aMMP-8 Chairside Test in Specific Periodontal Health Parameters
The widespread elevation of aMMP-8 among black pregnant Nigerians affecting almost 90% of women independent of demographics, educational level, and trimester was a surprising chance finding [21]. The workers further investigated the possible association between chronic periodontitis and increased time to conception among nonpregnant [22] fertility clinic attendees trying for pregnancy and 70 pregnant controls. The odds of increased time to conception were higher with suffering from periodontitis assessed with a novel qualitative aMMP-8 chairside test.
Comparing the aMMP-8 test and bleeding on probing (BOP) and periodontal pockets
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