Noma in an HIV infected patient in Guinea-Bissau: a case report.

BACKGROUND: Noma is a multifactorial and multibacterial opportunistic infection that initially causes necrotic gingivitis but rapidly spreads to the nearby orofacial tissue resulting in sloughing and severe deformation of the facial structures. The majority of cases are seen in young children under the age of 6 years. Noma is strongly associated with poverty, malnutrition and immunosuppression, and is often preceded by severe systemic infections such as measles and malaria. Only few cases of noma infection in adults have been described. CASE REPORT: We present here a case report with a 32-year-old Guinean woman who was diagnosed with noma infection and on that occasion discovered that she was HIV-1 seropositive. After treatment with amoxicillin/clavulanic acid and metronidazole for her noma infection the woman was transferred to the national hospital where antiretroviral treatment was initiated. CONCLUSION: Noma is an opportunistic infection and immunodeficiencies such as HIV should always be suspected when presenting in an adult patient.

Acute necrotic stomatitis (noma) associated with methicillin-resistant Staphylococcus aureus infection in a newly acquired rhesus macaque (Macaca mulatta).

BACKGROUND: A newly acquired rhesus macaque was suffering from rapid destruction of the left cheek caused by necrotizing stomatitis. METHODS: To restore reconstructive surgery and intensive care with antibiotics, wound protection, wound healing agents, and debridement were applied. RESULTS: Staphylococcus aureus and Enterococcus faecalis were isolated from the culture of the lesion, and the antibiotic susceptibility test revealed methicillin-resistant Staphylococcus aureus infection. Vancomycin and ampicillin-sulbactam effectively treated the bacterial infections, and reconstructive surgery was performed once the infection was cleared. Topical application of recombinant human epidermal growth factor (rhEGF) was useful to treat exposed wound of the noma lesion. CONCLUSIONS: Simian noma associated with methicillin-resistant Staphylococcus aureus (MRSA) had not previously been reported in non-human primates. Although noma associated with MRSA is hard to cure because of its rapid and destructive progress, the aggressive therapy used in this study led to the successful resolution of an acute necrotic stomatitis lesion in a rhesus macaque.

Noma (cancrum oris) in human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV and AIDS): clinical experience in Zimbabwe.

PURPOSE: This retrospective study describes the clinical features and management of noma (cancrum oris) in patients with HIV and AIDS. PATIENTS AND METHODS: Records of 48 consecutive patients with noma (cancrum oris) seen between July 2002 and November 2006 were reviewed for age, gender, clinical features, and management. Other reports on noma in HIV and AIDS in Zimbabwe were also reviewed. RESULTS: There were 48 patients included; 35.4% (n = 17) were males, of which 64.7% (n = 11) were children (16 years and younger) and 35.3% (n = 6) were adults; 64.6% (n = 31) were females, out of which 87.1% (n = 27) were children and 12.9% (n = 4) were adults. The average age was 14.2 years (range, 3 to 30 years) for males and 9.2 years (range, 1 to 36 years) for females. The average age for the entire group was 11 years (range, 1 to 36 years). All patients were HIV-positive by the ELISA method. Only 13 patients had CD4 cell and CD8 cell count obtained, ranging from 10 to 594 cells/microL with a CD4/CD8 ratio ranging from 0.02 to 0.45. Only 5 patients had microbiologic investigations conducted, isolating Staphylococcus aureus, Klebsiella species, group D Streptococcus, and group B hemolytic Streptococcus. Isolated cheek defect (37.5%) was most common, followed by the type I and type IV defect (25% each). Administration of antibiotics, nutritional support, wound debridement, and sequestrectomy were conducted before definitive reconstructive surgery. Facial reconstruction was performed using distant and local advancement flaps. No bony reconstruction was performed. Satisfactory results were achieved with minimal infection and flap breakdown. Follow-up was difficult; patients were lost to follow-up within 6 to 12 months after surgery. CONCLUSION: Noma cases are on the increase in line with the current HIV and AIDS epidemic. Female children appear to be more commonly affected than their male counterparts. Reconstructive surgery is possible in patients with low CD4/CD8 ratios because of HIV infection.

Pro- versus anti-inflammatory cytokine profile in African children with acute oro-facial noma (cancrum oris, noma).

Fresh noma is a severe orofacial necrosis with an astonishingly rapid development. It is seen mainly in malnourished children less than 4 years old from developing countries. Cytokines play a central role in oral mucosal inflammation. We therefore studied the relevance of circulating cytokines to noma, and the key microorganisms associated with the lesion. Nigerian village children with acute noma (n=68) and their neighborhood village (n=63) as well as urban (n=45) counterparts of comparable age and free of overt infections were evaluated for serum cytokine levels by ELISA. Oral bacteria were studied by polymerase chain reaction. Evaluation of random cases of the village and noma children showed marked depletion (p<0.05 or 0.001) of the plasma antioxidant micronutrients (retinol, ascorbic acid, zinc) as well as albumin and blood hemoglobin in the latter, relative to the former group. Concentrations of the circulating, pro-inflammatory cytokines (IL-18, IL-6, IL-12, IL-8, IFN-gamma) and the soluble inhibitors (TNFR-p55, TNFR-p75 and IL-1ra) were significantly higher (p<0.01 or 0.001) in noma children than in the healthy urban children, but less so when compared to their neighborhood village counterparts. The increase in levels of the anti-inflammatory/regulatory cytokines (IL-4, IL-10 and TGF-beta) was less marked relative to the pro-inflammatory cytokines. Bacteria observed at the highest frequencies in noma lesions were P. intermedia (83%), T. forsythensis (83%), P. gingivalis (50%), C. rectus (50%) and T. denticola (50%). We conclude that noma is an immunopathological response to potent bacterial factors resulting in uncontrolled production of cytokines and possibly other, still unknown, inflammatory mediators.

Necrotizing ulcerative periodontal diseases in children and young adults in Medellín, Colombia, 1965--2000.

Previous findings that necrotizing ulcerative gingivitis (NUG) is a precursor to noma or cancrum oris were confirmed by the follow-up of these clinical conditions in a study of 45 Colombian patients: necrotizing ulcerative gingivitis (NUG, n = 29), necrotizing ulcerative periodontitis (NUP, n = 7) and noma (n = 9). Patients were diagnosed at the outpatient clinic of the School of Dentistry at the University of Antioquia, at the University Hospital Saint Vincent of Paul, at the Luz Castro de Gutierrez University Hospital, at the Red Cross Hospital and at the private office of one of the authors (Jiménez L., M) in Medellín, Colombia, from 1965 until 2000. Almost all the patients came from low socioeconomic groups and presented with predisposing and/or contributing factors, such as acute herpetic gingivostomatitis, measles, and leukemia (including acute lymphoblastic and chronic lymphoid leukemia). Malnutrition and poor oral hygiene were associated with the necrotizing process and favored progression from the gingiva to deeper periodontal tissues and other structures within the oral cavity or the facial tissues. No patients had human immunodeficiency virus (HIV) or AIDS, which makes these findings different from other reports. Noma can be prevented by vaccinating children against infectious diseases, by controlling malnutrition and by improving their oral hygiene. It is arrested by mechanical lesion debridement, improving oral hygiene and antibiotic therapy. Necrotizing ulcerative gingivitis may progress in some cases to ulcerative necrotizing stomatitis, necrotizing ulcerative periodontitis, and, finally, to noma. Microbial studies among new Colombian NUG, NUP and noma patients are necessary, using bacterial culturing and identification methods and molecular techniques such as PCR for viruses and bacteria, in order to establish the exact nature of these lesions.

[Noma/Cancrum oris: a neglected disease]. / La enfermedad de Noma/cancrum oris: una enfermedad olvidada.

Noma is an aggressive orofacial gangrenous pathology that damages hard and soft tissues of the mouth and the face. Throughout the centuries it has been present around the globe, but nowadays it has practically disappeared from developed countries and mainly affects children from the most disadvantaged places, especially in Africa. Noma disease is a multifactorial process; malnutrition, debilitating diseases (bacterial or viral systemic diseases, HIV-associated immunosuppression, etc.) and intraoral infections are some of the factors implied. The characteristic tissue necrosis is produced by a polymicrobial infection. Fusobacterium necrophorum, Prevotella intermedia, Prevotella melaninogenica, Fusobacterium nucleatum, Bacteroides fragilis, Bacillus cereus, Trueperella pyogenes, spyrochetes, etc, are some of the species that have been isolated from the affected areas. Without treatment, noma is lethal in a short period of time, and the patients that survive show severe sequelae that hinder their life and interpersonal relationships. The aim of this paper is to unify the existing information and to promote wider knowledge and awareness among the population.

Noma Neonatorum From Multidrug-Resistant Pseudomonas aeruginosa: An Underestimated Threat?

We present the case of an extremely low birth weight infant with diffuse gingival noma, initially misdiagnosed as thrush. Multidrug-resistant Pseudomonas aeruginosa strain was cultured and treated with systemic and local colistin with complete healing. Noma neonatorum from multidrug-resistant pathogens may appear in neonatal intensive care units. Old antibiotics may help.Noma (cancrum oris) is a devastating gangrenous disease that leads to destruction of facial tissue with significant morbidity and mortality in children and young adults. Noma has virtually disappeared from Europe and North America, but it is still common among children and young adults in India, Africa, and South America. Noma is a polymicrobial opportunistic infection related to malnutrition and immune dysfunction. In the neonate, a similar but distinct condition, known as "noma neonatorum" was described in 1977, in which gangrenous lesions involve the mucocutaneous junctions of oral, nasal, and anal area, and, occasionally, the eyelids and the scrotum. The neonatal disease has been linked to Pseudomonas aeruginosa, prematurity, and low birth weight. There is no established treatment, and mortality is almost inevitable in the few reported cases. In this study, we present the first European case of noma neonatorum from a multidrug-resistant strain of P aeruginosa.

Necrotizing ulcerative gingivitis in children: a 9 year clinical study.

Twenty-eight children with ANUG and nine children with noma were studied over the past 9 years. It is concluded that these entities occur only in children from low socioeconomic groups and have a multifactorial etiology consisting of poor oral hygiene and malnutrition. In the case of noma, a prior infection with a viral agent or intestinal parasitism appears to be important predisposing factors.

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.

Report of an infant with noma (cancrum oris).

Noma (cancrum oris) is an infectious disease that destroys the oro-facial tissues and other neighboring structures in its fulminating course. The starting point of the disease is acute ulcero-necrotic gingivitis, which results in an extensive gangrenous plaque destroying all of the soft tissues of the face. It predominantly affects children aged 2-16 years and is primarily seen in areas where the socioeconomic standards are low and there is poor hygiene, as in developing countries. We discuss possible predisposing factors in cancrum oris such as malnutrition, infectious diseases, HIV infection, and immune compromise conditions. Poverty is the most important risk factor. We report the case of a 6-month-old child with noma and review the characteristic features of this disease.

Cancrum oris-like lesions.

Cancrum oris is predominantly seen in children in underdeveloped countries where widespread malnutrition, dehydration and epidemic infections are present. In the western world, it is sometimes found in immunosuppressed adults with predisposing conditions such as leukaemia and infection associated with malnutrition. Early diagnosis and an intensive therapeutic approach are the key to a favourable prognosis of noma-like necro-ulcerative lesions. The prognosis is significantly improved if the predisposing condition can be removed. Two cases are presented and the treatment is discussed.

Noma affected children from Niger have distinct oral microbial communities based on high-throughput sequencing of 16S rRNA gene fragments.

We aim to understand the microbial ecology of noma (cancrum oris), a devastating ancient illness which causes severe facial disfigurement in>140,000 malnourished children every year. The cause of noma is still elusive. A chaotic mix of microbial infection, oral hygiene and weakened immune system likely contribute to the development of oral lesions. These lesions are a plausible entry point for unidentified microorganisms that trigger gangrenous facial infections. To catalog bacteria present in noma lesions and identify candidate noma-triggering organisms, we performed a cross-sectional sequencing study of 16S rRNA gene amplicons from sixty samples of gingival fluid from twelve healthy children, twelve children suffering from noma (lesion and healthy sites), and twelve children suffering from Acute Necrotizing Gingivitis (ANG) (lesion and healthy sites). Relative to healthy individuals, samples taken from lesions in diseased mouths were enriched with Spirochaetes and depleted for Proteobacteria. Samples taken from healthy sites of diseased mouths had proportions of Spirochaetes and Proteobacteria that were similar to healthy control individuals. Samples from noma mouths did not have a higher abundance of Fusobacterium, casting doubt on its role as a causative agent of noma. Microbial communities sampled from noma and ANG lesions were dominated by the same Prevotella intermedia OTU, which was much less abundant in healthy sites sampled from the same mouths. Multivariate analysis confirmed that bacterial communities in healthy and lesion sites were significantly different. Several OTUs in the Orders Erysipelotrichales, Clostridiales, Bacteroidales, and Spirochaetales were identified as indicators of noma, suggesting that one or more microbes within these Orders is associated with the development of noma lesions. Future studies should include longitudinal sampling of viral and microbial components of this community, before and early in noma lesion development.

[Evoluting form of cancrum oris, about 55 cases collected at the Academic Hospital Yalgado Ouedraogo of Ouagadougou]. / Le noma évolutif, à propos de 55 observations vues au centre hospitalier universitaire Yalgado Ouedraogo de Ouagadougou.

The cancrum oris is still an up to date disease in our environment. The death rate and the after effects of this disease make all together the main interest of this survey. In a retrospective survey carried out from January 2003 to December 2012, we colligated 55 cases of progressive cancrum oris followed at the stomatological and maxillofacial surgery at the Academic Hospital Yalgado OUEDRAOGO. On the epidemiological level, we noticed an impact of 5.5 cases per year. The average age of our patients was about 7.64 with a sex ratio of 1.03. Most of the patients were from an underprivileged family (96.4%). On the clinical level, we noticed that most of the patients consulted only after the gangrene had fallen (89.1%) and were seriously affected (67.3%) with a bad oral and dental hygiene (38.1%). The attacks were mainly jugal (25%) and labial (24.1%). The cancrum oris was in most of the cases associated to broncho pneumonitis, malaria and to HIV infection (31.37%). For the medical treatment, we focused on resuscitation, re nutrition, hydro electrolytic rebalancing and antibiotherapy. The surgical treatment was essentially made on the affected areas, controlled skinning and most often followed by sequestrectomy. 81.8% of the patients recovered completely from the infection, 60% had after effect injuries. We recorded a death rate of 14.5%. In order to overcome this disease we need both national and international support.

Microarray analysis of microbiota of gingival lesions in noma patients.

Noma (cancrum oris) is a gangrenous disease of unknown etiology affecting the maxillo-facial region of young children in extremely limited resource countries. In an attempt to better understand the microbiological events occurring during this disease, we used phylogenetic and low-density microarrays targeting the 16S rRNA gene to characterize the gingival flora of acute noma and acute necrotizing gingivitis (ANG) lesions, and compared them to healthy control subjects of the same geographical and social background. Our observations raise doubts about Fusobacterium necrophorum, a previously suspected causative agent of noma, as this species was not associated with noma lesions. Various oral pathogens were more abundant in noma lesions, notably Atopobium spp., Prevotella intermedia, Peptostreptococcus spp., Streptococcus pyogenes and Streptococcus anginosus. On the other hand, pathogens associated with periodontal diseases such as Aggregatibacter actinomycetemcomitans, Capnocytophaga spp., Porphyromonas spp. and Fusobacteriales were more abundant in healthy controls. Importantly, the overall loss of bacterial diversity observed in noma samples as well as its homology to that of ANG microbiota supports the hypothesis that ANG might be the immediate step preceding noma.

Risk factors for noma disease: a 6-year, prospective, matched case-control study in Niger.

BACKGROUND: Noma is a poorly studied disease that leads to severe facial tissue destruction in children in developing countries, but the cause remains unknown. We aimed to identify the epidemiological and microbiological risk factors associated with noma disease. METHODS: We did a prospective, matched, case-control study in Niger between Aug 1, 2001, and Oct 31, 2006, in children younger than 12 years to assess risk factors for acute noma. All acute noma cases were included and four controls for each case were matched by age and home village. Epidemiological and clinical data were obtained at study inclusion. We undertook matched-paired analyses with conditional logistic regression models. FINDINGS: We included 82 cases and 327 controls. Independent risk factors associated with noma were: severe stunting (odds ratio [OR] 4·87, 95% CI 2·35-10·09) or wasting (2·45, 1·25-4·83); a high number of previous pregnancies in the mother (1·16, 1·04-1·31); the presence of respiratory disease, diarrhoea, or fever in the past 3 months (2·70, 1·35-5·40); and the absence of chickens at home (1·90, 0·93-3·88). After inclusion of microbiological data, a reduced proportion of Fusobacterium (4·63, 1·61-13·35), Capnocytophaga (3·69, 1·48-9·17), Neisseria (3·24, 1·10-9·55), and Spirochaeta in the mouth (7·77, 2·12-28·42), and an increased proportion of Prevotella (2·53, 1·07-5·98), were associated with noma. We identified no specific single bacterial or viral pathogen in cases. INTERPRETATION: Noma is associated with indicators of severe poverty and altered oral microbiota. The predominance of specific bacterial commensals is indicative of a modification of the oral microbiota associated with reduced bacterial diversity. FUNDING: Gertrude Hirzel Foundation.

Bacterial diversity in oral samples of children in niger with acute noma, acute necrotizing gingivitis, and healthy controls.

BACKGROUND: Noma is a gangrenous disease that leads to severe disfigurement of the face with high morbidity and mortality, but its etiology remains unknown. Young children in developing countries are almost exclusively affected. The purpose of the study was to record and compare bacterial diversity in oral samples from children with or without acute noma or acute necrotizing gingivitis from a defined geographical region in Niger by culture-independent molecular methods. METHODS AND PRINCIPAL FINDINGS: Gingival samples from 23 healthy children, nine children with acute necrotizing gingivitis, and 23 children with acute noma (both healthy and diseased oral sites) were amplified using "universal" PCR primers for the 16 S rRNA gene and pooled according to category (noma, healthy, or acute necrotizing gingivitis), gender, and site status (diseased or control site). Seven libraries were generated. A total of 1237 partial 16 S rRNA sequences representing 339 bacterial species or phylotypes at a 98-99% identity level were obtained. Analysis of bacterial composition and frequency showed that diseased (noma or acute necrotizing gingivitis) and healthy site bacterial communities are composed of similar bacteria, but differ in the prevalence of a limited group of phylotypes. Large increases in counts of Prevotella intermedia and members of the Peptostreptococcus genus are associated with disease. In contrast, no clear-cut differences were found between noma and non-noma libraries. CONCLUSIONS: Similarities between acute necrotizing gingivitis and noma samples support the hypothesis that the disease could evolve from acute necrotizing gingivitis in certain children for reasons still to be elucidated. This study revealed oral microbiological patterns associated with noma and acute necrotizing gingivitis, but no evidence was found for a specific infection-triggering agent.

Neonatal noma.

Neonatal noma is a rare clinical syndrome affecting term and preterm infants. It causes gangrene of the orofacial tissues accompanied by sepsis and a high mortality rate. A preterm 35-week infant, severely growth retarded in utero, developed clinical signs of sepsis with ulcers all over the oral mucosa caused by local infection with Pseudomonas aeruginosa. The lesions healed with cicatricial sequelae of the mouth, sequestration of teeth, and retraction of perimandibular soft tissues.

Bacterial bone resorption in noma (gangrenous stomatitis).

Bone resorption (gangrenous stomatitis) was found to be associated with extensive bacterial colonization of mandibular bone in three separate cases of noma. Light and electron microscopy revealed a heterogeneous bacterial population with a long, filamentous, Gram-positive organism predominantly in direct contact with the resorbing bone front. The bone was completely denuded and no osteoclastic activity was observed. The highly regular arrangement of the filamentous organism along the resorbing bone and the absence of osteoclastic activity suggested that bone resorption in noma is mediated by bacterial action.