Noma (cancrum oris): questions and answers

Noma (cancrum oris) is an infectious disease which destroys the oro-facial tissues and other neighboring structures in its fulminating course. It affects predominantly children aged 2-16 years in sub-Saharan Africa where the estimated frequency in some communities may vary from one to seven cases per 1000 children. The key risk factors are poverty, malnutrition, poor oral hygiene, deplorable environmental sanitation, close residential proximity to livestock, and infectious diseases, particularly measles. Malnutrition acts synergistically with endemic infections in promoting an immunodeficient state, and noma results from the interaction of general and local factors with a weakened immune system as the common denominator. Acute necrotizing gingivitis (ANG) is considered the antecedent lesion. Current studies suggest that evolution of ANG to noma requires infection by a consortium of microorganisms with Fusobacterium necrophorum and Prevotella intermedia as the suspected key players. Without appropriate treatment, mortality rate is 70-90%. Survivors suffer the two-fold affliction of oro-facial disfigurement and functional impairment. Reconstructive surgery of the resulting deformity is time-consuming and financially prohibitive for the victims who are poor.     

Infectious oral necrosis (cancrum oris) in Nigerian children: a review

The devastating orofacial gangrenous disease known as cancrum oris (noma) is still commonly seen in underprivileged Nigerian children. These children are usually victims of such stressors as chronic malnutrition, numerous endemic communicable diseases and severe adverse physical conditions which may lead to depletion of their adaptive resources or produce physiological maladaptation to additional stressors. Measles is the most common infection preceding the development of noma in Nigerian children. Acquired immunodeficiency as well as the impaired endocrine balance of the chronically malnourished permits, for example, widespread infection with the measles virus. Anergy resulting from the combination of malnutrition and measles virus infection promotes selective overgrowth and invasion by an infective consortium consisting of anaerobic organisms and other species capable of elaborating necessary growth factors for the former. Because of the pre-existing depletion of adaptive physiologic resources in the malnourished child, the infection is not readily contained locally as necrotizing ulcerative gingivitis but instead spreads rapidly to the next naturally occurring anatomical barriers. This is then followed by continuing necrosis and possible sequestration as exemplified by noma.     

Noma (cancrum oris) associated with oral myiasis in an adult

Noma is a devastating oro-facial necrotic condition affecting debilitated subjects. Oral myiasis is an infectious disease caused by deposition of larval flies in oral wounds and lesions. Oro-facial noma-myiasis association has not been previously reported in the literature. The aim of this paper is to report a case of noma associated with myiasis in a 65-year-old Brazilian male.     

The surgical management of extra-articular ankylosis in noma patients

Extraarticular ankylosis occurs frequently in children suffering from noma sequelae. Over 20 years of operating on these patients, we observed high recurrence of mouth opening limitation. We therefore progressively changed our surgical strategy. This retrospective study compares the impact of different parameters (types of surgery, noma type, physiotherapy compliance, age and sex) on immediate and long-term mouth opening. It includes a series of 121 patients with extraarticular ankylosis operated on between 1990 and 2015. Soft tissue reconstruction evolved from local and pedicled flaps to large free flaps. Mouth opening was performed by bone-bridge excision, sometimes associated to contralateral coronoidectomy. Mouth opening technique including bilateral coronoidectomy with free flap reconstruction was the only independent factor for significantly better immediate mouth opening with a mean increase of 8.7 mm [95% confidence interval (CI) 4.3–13.1, P < 0.001) and this effect was maintained in the 3 years of follow-up. Another positive factor related to long-term results was excellent physiotherapy, while noma type 4 was a negative factor. Recurrence remains problematic in the management of noma sequelae. If physiotherapy and long-term follow-up cannot be offered, patients should not be operated on, because if limitation of mouth opening recurs, oral feeding may become impossible when a facial defect has been reconstructed.     

Noma (cancrum oris) in the South African context

Noma (cancrum oris) is a destructive necrotising disease affecting orofacial tissues predominantly of malnourished young children. It is characterised by a rapid acute onset which usually starts in the mouth, spreads intra‐orally destroying soft tissue and bone and progresses to perforate the facial skin, causing disfigurement. Polybacterial anaerobic infection is critical too, but is not alone sufficient for the initiation of noma. Cofactors, first and foremost malnutrition, but also systemic viral and bacterial infections are crucial to the development of noma. A patient with necrotising stomatitis or noma must be admitted to hospital for antibiotic treatment, fluid and electrolytes as well as nutritional supplementation and general supportive treatment. The epidemiology of noma in the South African population is unknown, and the clinicopathological features are poorly characterised. Although worldwide there is no evidence that HIV infection is a strong risk factor for noma, HIV infection may play a substantial role in the pathogenesis of noma in South Africa.     

Necrotizing ulcerative gingivitis and cancrum oris (noma) in Ibadan, Nigeria

This study analyzed 58 cases of necrotizing ulcerative gingivitis (NUG) and 5 cases of cancrum oris among children who sought treatment at the Ibadan University College Hospital, Dental Centre in a 1-year period. The peak occurrence of NUG was among 4- and 5-year old children and 84.5% of them were in the 2 to 7 years age range. Seventy-two percent presented in the rainy season with positive history of recent febrile illness in 55 cases. There was no statistically significant association of NUG and rainy season. Possible predisposing factors in NUG and cancrum oris such as malnutrition, infectious childhood diseases, HIV infection, and immune compromise are discussed. It is suggested that children at risk should be advised to maintain good oral hygiene, adequate nutrition, and proper medical care.     

甲壳胺影响细菌硫化氢代谢产物的研究

目的:观察甲壳胺对口腔细菌硫化氢产物的影响,评价甲壳胺的抗口臭作用.方法:选择3种口腔主要产臭菌:牙龈卟啉单胞菌、中间普氏菌、具核梭杆菌,分别接种于不含药物的液体培养基、含1%甲壳胺的液体培养基和含0.2%洗必泰溶液的液体培养基中,厌氧培养后,用硫化物测量仪分析3个菌种硫化氢代谢产物的变化.结果:3种细菌在不含药物的试管中有大量硫化氢生成,含1%甲壳胺的实验组和含0.2%洗必泰溶液的对照组试管中检测出硫化氢的量明显降低(P＜0.05).结论:甲壳胺能有效抑制产臭菌异味产物--硫化氢,实验为甲壳胺抗口臭的临床应用提供了可靠的实验依据.     

Lipopolysaccharides from periodontal pathogens prime neutrophils for enhanced respiratory burst: differential effect of a synthetic lipid a Precursor IVA(LA-14-PP)

When neutrophils are incubated with bacterial lipopolysaccharide (LPS), they become primed for enhanced release of superoxide anion (O₂⁻) in response to stimulation by FMLP. We investigated the human neutrophil-priming activity of LPS from the periodontal pathogens, Porphyromonas gingivalis (Pg) , Prevotella intermedia (Pi) and Actinobacillus actinomycetemcomitans (Aa) in comparison with that of LPS from Escherichia coli (E. coli) . The optimum conditions for LPS to prime neutrophils were assessed for every LPS and found to be as follows: Neutrophils were incubated with LPS in the presence of 10% heat-inactivated plasma and 1 mM EDTA at 37°C for 30 min and then stimulated with 1 μM FMLP at 37°C for 7 min. Under these conditions, half-maximum priming was observed at 6.2 ng/ml Pg -LPS, 45 ng/ml Pi -LPS, 1.5 ng/ml Aa -LPS and 1.5 ng/ ml E. coli -LPS. The priming activity of each LPS was neutralized by polymyxin B. Anti-CD14 monoclonal antibody inhibited priming by all LPS. The priming by Aa -LPS and E. coli -LPS was inhibited by LA-14-PP, a synthetic lipid A precursor IV_A, but that by Pg -LPS and Pi -LPS was not. Priming by tumor necrosis factor alpha was not affected by polymyxin B, anti-CD14 antibody or LA-14-PP. Gelation of Limulus amebocyte lysate occured at 10 pg/ml Pg -LPS, 30 pg/ml Pi -LPS, 3 pg/ml Aa -LPS and 3 pg/ml E. coli -LPS. Thus LPS from different periodontal pathogens primed neutrophils with different efficacy. The difference in the sensitivity to LA-14-PP among the four LPS tested raises the possibility that the mechanism of host response to Pg -LPS or Pi -LPS may be different from that to Aa -LPS or E . coli -LPS.     

Cancrum oris (noma): Level of education and occupation of parents of affected children in Nigeria.

A total of 173 cancrum oris patients who were brought by their parents to the University College Hospital, Ibadan, Nigeria, were analyzed. Ninety-one (52.6%) were males and 82 (47.4%) females. Their ages ranged from 1.5 to 11 years with a mean of 4.36 (standard deviation 2.13) years. One hundred and twenty-one (69.9%) and 52 (30.1%) were from monogamous and polygamous family respectively. The average number of children per family was 7.0. The number of parents with no formal education was 148 (85.5%) and 98.3% were low-income earners. The relationships between occupation, income and educational status were highly significant. This study suggests that apart from poverty, large family units and low educational status of parents are contributing factors in the aetiology of cancrum oris.     

Comparative mitogenicity and polyclonal B cell activation capacity of eight oral or nonoral bacterial lipopolysaccharides in cultures of spleen cells from athymic (nu/nu-BALB/c) and thymic (BALB/c) mice

Optimal stimulatory doses of purified phenol-water extracted lipopolysaccharides (LPS) from 5 selected strains of 3 putative periodontopathogens (Fusobacterium nucleatum, Prevotella intermedia, and Veillonella), 3 strains of 2 nonoral bacterial species (Bacteroides fragilis and Salmonella enteritidis), and pokeweed mitogen (PWM) induced significantly higher maximum mitogenic responses and polyclonal Ig production in cultures of unfractionated spleen cells from nu/nu-BALB/c (nude) than from BALB/c (normal) mice. Compared with PWM, the LPS were stronger mitogens showing relative mitogenic capacities: B. fragilis LPS greater than F. nucleatum LPS greater than S. enteritidis LPS, Veillonella LPS, and P. intermedia LPS. B. fragilis LPS was the most and S. enteritidis LPS the least effective polyclonal B cell activator of total Ig, IgG2a, IgG2b, IgG3, IgA, and IgM secretion. IgG1 was not detected. P. intermedia LPS was the strongest IgA inducer. Kinetic observations indicated mitogenic responses and polyclonal B cell activation in a close sequential order in nude and normal cells. The LPS were potent Ag- and T cell-independent polyclonal B cell activators and LPS of subgingival plaque bacteria may therefore play a nonspecific role in the pathogenesis of periodontal diseases.     

几株口腔厌氧菌胞外膜泡,外膜蛋白复合物的提取

采用盐析、超滤、超速离心等方法提取并比较了５种口腔常见厌氧菌（ＰｇＷ５０，Ｐｇ３８１，ＰｅＡＴＣＣ３５４０６，ＰｉＡＴＣＣ２５２６１，ＰｍＡＴＣＣ２５８４５）的胞外膜泡（ＥＣＶ）、外膜蛋白复合物（ＯＭＰＣ），结果显示：二种提取物外观性状均较好，呈淡灰色，其中ＰｇＷ５００ＯＭＰＣ的湿沉淀有一定粘度。ＥＣＶ的提取率由高至低分别为：ＰｇＷ５０（１９．８４ｍｇ／Ｌ）、Ｐｇ３８１（１８．７５ｍｇ／Ｌ）、Ｐｅ（１５．６５ｍｇ／Ｌ）、Ｐｍ（９．６０ｍｇ／Ｌ）、Ｐｉ（７．４０ｍｇ／Ｌ）；ＯＭＰＣ提取率分别为：ｐｇＷ５０（８７．３６ｍｇ／Ｌ）、Ｐｇ３８１（７２．５６ｍｇ／Ｌ）、Ｐｉ（５７．４０ｍｇ／Ｌ）Ｐｍ（４１．２８ｍｇ／Ｌ）、Ｐｅ（３２．７６ｍｇ／Ｌ）．在ＥＣＶ的提取中，采用超滤和超离心法提取ＥＣＶ的量要高于盐析法，表明营养条件不是细菌ＥＣＶ形成的决定因素。     

Fusobacterium nucleatum GroEL induces risk factors of atherosclerosis in human microvascular endothelial cells and ApoE(-/-) mice

Infection and inflammation are risk factors in the initiation and progression of atherosclerosis. Periodontitis is one of the most prevalent chronic inflammations of the oral cavity, and has been reported to be associated with systemic disease. In this study, we evaluated whether the heat-shock protein GroEL of Fusobacterium nucleatum, one of the most prevalent bacteria in periodontitis, induces factors that predispose to atherosclerosis in human microvascular endothelial cells (HMEC-1) and apolipoprotein E-deficient (ApoE(-/-)) mice. GroEL induced the expression of chemokines such as monocyte chemoattractant protein-1 and interleukin-8 as well as cell adhesion molecules, such as intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin. GroEL induced the activity of tissue factor and reduced the activity of the tissue factor pathway inhibitor. Foam cell formation was induced by GroEL. GroEL-injected ApoE(-/-) mice showed significant atherosclerotic lesion progression compared with control mice. Serum levels of risk factors for atherosclerosis such as interleukin-6, C-reactive protein, and low-density lipoprotein were increased in GroEL-injected ApoE(-/-) mice compared with control mice, whereas serum levels of high-density lipoprotein were decreased. We could detect significantly higher levels of anti-F. nucleatum GroEL antibody in serum and F. nucleatum DNA in gingival crevicular fluid from patients with periodontitis than in that from healthy subjects. Our results indicate that the host response to the GroEL of periodontal pathogens like F. nucleatum may be a mechanism involved in atherosclerosis, supporting the association of periodontitis and systemic infection.     

Stimulation of epithelial cell matrix metalloproteinase (MMP-2, -9, -13) and interleukin-8 secretion by fusobacteria

Background/aims:  Bacterial pathogens involved in periodontal diseases exert their destructive effects primarily by stimulating the host cells to increase their secretion of proinflammatory cytokines and matrix metalloproteinases (MMPs). This study aimed to determine the epithelial cell matrix metalloproteinase and interleukin-8 (IL-8) secretion upon exposure to fusobacteria.
Methods:  Eight different oral and non-oral Fusobacterium strains were incubated with HaCaT epithelial cells. Gelatin zymography and Western blot analysis were performed to detect collagenase 3 (MMP-13), gelatinase A (MMP-2), gelatinase B (MMP-9), and IL-8 secretion by epithelial cells.
Results:  All Fusobacterium strains, especially Fusobacterium necrophorum ATCC 25286, Fusobacterium nucleatum ATCC 25586, and Fusobacterium varium ATCC 51644, increased MMP-9 and MMP-13 secretion. Fusobacterium simiae ATCC 33568, and to a lesser extent F. nucleatum and F. necrophorum , increased epithelial MMP-2 secretion. F. nucleatum and F. necrophorum also increased IL-8 secretion. F. varium ATCC 27725, a strain that only weakly stimulated MMP production, strongly increased the IL-8 production, suggesting that their expression is differently regulated.
Conclusion:  We conclude that the pathogenic potential of fusobacteria may partly result from their ability to stimulate secretion of MMP-9, MMP-13, and IL-8 from epithelial cells.     

Stimulation of epithelial cell matrix metalloproteinase (MMP‐2, ‐9, ‐13) and interleukin‐8 secretion by fusobacteria

Background/aims: Bacterial pathogens involved in periodontal diseases exert their destructive effects primarily by stimulating the host cells to increase their secretion of proinflammatory cytokines and matrix metalloproteinases (MMPs). This study aimed to determine the epithelial cell matrix metalloproteinase and interleukin‐8 (IL‐8) secretion upon exposure to fusobacteria. Methods: Eight different oral and non‐oral Fusobacterium strains were incubated with HaCaT epithelial cells. Gelatin zymography and Western blot analysis were performed to detect collagenase 3 (MMP‐13), gelatinase A (MMP‐2), gelatinase B (MMP‐9), and IL‐8 secretion by epithelial cells. Results: All Fusobacterium strains, especially Fusobacterium necrophorum ATCC 25286, Fusobacterium nucleatum ATCC 25586, and Fusobacterium varium ATCC 51644, increased MMP‐9 and MMP‐13 secretion. Fusobacterium simiae ATCC 33568, and to a lesser extent F. nucleatum and F. necrophorum, increased epithelial MMP‐2 secretion. F. nucleatum and F. necrophorum also increased IL‐8 secretion. F. varium ATCC 27725, a strain that only weakly stimulated MMP production, strongly increased the IL‐8 production, suggesting that their expression is differently regulated. Conclusion: We conclude that the pathogenic potential of fusobacteria may partly result from their ability to stimulate secretion of MMP‐9, MMP‐13, and IL‐8 from epithelial cells.     

Microbial composition of monkey dental plaque (Macaca arctoides and Macaca fascicularis)

Abstract – The supragingival and subgingival dental plaque flora of Macaca arctoides and Macaca fascicularis monkeys were examined using mylar strip impressions, direct smears, and cuiture techniques. In smears, samples generally contained 40–50% cocci, 20–30% rods, 8–20% fusiform bacteria, and 4–5% each of filaments, vibrios and spirochetes. Differences in the ratios of the various bacterial groups related to age and sex were found. Several monkey bacterial species were similar to those in human dental plaque. The present results indicate that the Macaca female monkey can be a suitable animal model for the experimental studies of dental diseases.     

Detection of Eikenella corrodens and Actinobacillus actinomycetemcomitans by use of the polymerase chain reaction (PCR) in vitro and in subgingival plaque

Abstract The purpose of the present investigation was to identify 2 putative penodontal pathogens: Eikenella corrodens and Actinobacillus actinoinycetemcoiniiuns by polymerase chain reaction (PCR) in vilro and in subgingival plaque. On the basis of published sequences coding for 16S rRNA two primer pairs were designed which amplify a 410 bp sequence from E. corrodens DNA and a 547 bp fragment from A. actinomycetemcomitans DNA. respectively. As few as 50 cells could be detected from pure bacterial cultures. Each of the two primer pairs was found to be specific in that it did not give any amplification product neither with cell lysates from the respective alternative bacterium nor with lysates obtained from other putative periodontal pathogens and other bacteria. The PCR method developed turned out to be a simple, rapid and reliable diagnostic tool for the detection of the target microorganisms in clinical samples.