Noma: neglected, forgotten and a human rights issue

Noma, an orofacial gangrene and opportunistic infection, affects primarily malnourished children living in extreme poverty. Neglected, forgotten, unknown by most health workers, noma results in death, disfigurement and disability of some of the world's most vulnerable children. Noma is a biological indicator of multiple human rights violations, including the right to food. International support and national attention in countries with noma are lacking. The end of neglect of noma can lead to the elimination of this horrific childhood diseas

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 identifi ed no specifi c single bacterial or viral pathogen in cases. Interpretation Noma is associated with indicators of severe poverty and altered oral microbiota. The predominance of specifi c bacterial commensals is indicative of a modifi cation 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

Noma is a devastating gangrenous disease that leads to severe facial disfigurement, but its cause remains unknown. It is associated with high morbidity and mortality and affects almost exclusively young children living in remote areas of developing countries, particularly in Africa. Several factors have been linked to the disease, including malnutrition, immune dysfunction, lack of oral hygiene, and lesions of the mucosal gingival barrier, particularly the presence of acute necrotizing gingivitis, and a potentially non-identified bacterial factor acting as a trigger for the disease. This study assessed the total bacterial diversity present in 69 oral samples of 55 children in Niger with or without acute noma or acute necrotizing gingivitis using culture-independent molecular methods. Analysis of bacterial composition and frequency showed that diseased and healthy site bacterial communities are composed of similar bacteria, but differ in the prevalence of a limited group of phylotypes. We failed to identify a causative infectious agent for noma or acute necrotizing gingivitis as the most plausible pathogens for both conditions were present also in sizeable numbers in healthy subjects. Most likely, the disease is initiated by a synergistic combination of several bacterial species, and not a single agent

NOMA: A Preventable “Scourge” of African Children

Noma is a serious orofacial gangrene originating intraorally in the gingival-oral mucosa complex before spreading extraorally to produce a visibly destructive ulcer. Although cases of noma are now rarely reported in the developed countries, it is still prevalent among children in third world countries, notably in sub-Sahara Africa, where poverty, ignorance, malnutrition, and preventable childhood infections are still common. This review summarizes historical, epidemiological, management, and research updates on noma with suggestions for its prevention and ultimate global eradication. The global annual incidence remains high at about 140,000 cases, with a mortality rate exceeding 90% for untreated diseases. Where the patients survive, noma defects result in unsightly facial disfigurement, intense scarring, trismus, oral incompetence, and social alienation. Although the etiology has long been held to be infectious, a definitive causal role between microorganisms cited, and noma has been difficult to establish. The management of noma with active disease requires antibiotics followed by reconstructive surgery. Current research efforts are focused towards a comprehensive understanding of the epidemiology, and further elucidation of the microbiology and pathogenesis of noma

Acute periodontal lesions

This is a review and update on acute conditions affecting the gingival tissues, including abscesses in the periodontium, necrotizing periodontal diseases, and other acute conditions that cause gingival lesions with acute presentation, such as infectious process not associated with oral bacterial biofilms, muco-cutanenous disorders, and traumatic and allergic lesions. A periodontal abscess is clinically important since it is a relatively frequent dental emergency, it can compromise the periodontal prognosis of the affected tooth, and because bacteria within the abscess have been identified, mainly by the type of etiology, and there are clear diffrences between those affecting a previously existing periodontal pocket ahd those affecting healthy sites. Therapy for this acute condition consists of drainage and tissue debridement, with individual evaluation of the need for systemic antimicrobial therapy. the definitive treatment of the pre-existing condition should be accomplished after the acute phase is controlled. Necrotizing periodontal disease (NPD) present three typical clinical features : papilla necrosis, gingival bleeding, and pain. Although the prevalence of these diseases is not high, their importance is clear, since they represent the most severe conditions associated with dental biofilm, with very rapid tissue destruction. In adittion to bacteria, the etiology of NPD includes numerous factors that alter the host response and predispose to these diseases, including HIV infection, malnutrition, stress, and tobacco smoking. The treatment consists of superficial debridement, careful mechanical oral hygiene, rinsing with chlorhexidine, and daily re-evaluation. Systemic antimicrobials may be used adjunctively in severe cases or in non-responding conditions and the best option is metronidazole.Once the acute disease is under control, definitive treatment should be provided, including the adequate therapy for the pre-existing gingivitis or periodontitis. Among other acute conditions affecting the periodontal tissues, but not caused by the microorganisms present in oral biofilms , are infectious diseases, muco-cutaneous diseases and traumatic or allergic lesions. In most cases, the gingival envolvement is not severe, though they are common and may prompt a dental emergency visit. These conditions may the direct result of a trauma or the consequence of the breaking of vesicles and bullae. A proper differential diagnosis is important for an adequate management of the case

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease