Noma (cancrum oris).

Noma is an opportunistic infection promoted by extreme poverty. It evolves rapidly from a gingival inflammation to grotesque orofacial gangrene. It occurs worldwide, but is most common in sub-Saharan Africa. The peak incidence of acute noma is at ages 1-4 years, coinciding with the period of linear growth retardation in deprived children. Noma is a scourge in communities with poor environmental sanitation. It results from complex interactions between malnutrition, infections, and compromised immunity. Diseases that commonly precede noma include measles, malaria, severe diarrhoea, and necrotising ulcerative gingivitis. The acute stage responds readily to antibiotic treatment. The sequelae after healing include variable functional and aesthetic impairments, which require reconstructive surgery. Noma can be prevented through promotion of national awareness of the disease, poverty reduction, improved nutrition, promotion of exclusive breastfeeding in the first 3-6 months of life, optimum prenatal care, and timely immunisations against the common childhood diseases.

Inflammatory cytokine profile and circulating cortisol levels in malnourished children with necrotizing ulcerative gingivitis.

Necrotizing ulcerative gingivitis (NUG), a periodontal disease traditionally associated with stressful lifestyles in young adults in developed countries, is very prevalent in socioeconomically deprived Nigerian children. Random incident cases (153) of NUG, along with their neighborhood village counterparts of comparable age and without NUG, as control, were recruited for this study. Anthropometric evaluation revealed widespread malnutrition and poor health in both groups of children, with more severe stunting in NUG cases. The poor nutritional status of the village children, with and without NUG, was also confirmed by markedly reduced levels of circulating micronutrients. Compared with the neighborhood children, NUG victims showed significant (p < 0.05 or < 0.001) increases in serum levels of interleukin (IL)-8 (+ 233%), IL-18 (+ 30%), IL-6 (+ 190%), IL-1beta (+ 341%), IL-10 (+ 186%), with a small decrease in interferon (IFN)-gamma (-19%) and nonsignificant increases in soluble tumor necrosis factor (TNF) receptors (sTNFR-p55, p75). Associated with NUG was a significant, 38% (p < 0.05) increase in plasma cortisol above the already high levels observed in the neighborhood village children, as well as some micronutrient deficiencies. The findings suggest that NUG is associated with dysregulated cytokine production, with a complex interplay of elevated levels of pro- and anti-inflammatory mediators. Such changes may serve as the common link between the seemingly unrelated risk conditions (e.g. stressful life styles, smoking, microbial infections, diabetes, malnutrition, alcoholism) traditionally implicated in the genesis of NUG, and all known to promote an increase in the blood level of cortisol, as well as a Th(1) to Th(2) cytokine shift.

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.

Temporal relationship between the occurrence of fresh noma and the timing of linear growth retardation in Nigerian children.

BACKGROUND: Fresh noma (cancrum oris) occurs predominantly in children <4 years of age. The key risk factors are poverty, malnutrition and infections. Evolution from an intraoral inflammation to a grotesque oro-facial gangrene is very rapid. OBJECTIVE: We assessed potential relationship between the occurrence of fresh noma and linear growth retardation (LGR) which is prevalent in deprived Third World infants/children between ages 3 and 30 months. LGR is attributed to malnutrition and chronic immunostimulation by environmental antigens. DESIGN: Anthropometric evaluation of children (n = 91) with fresh noma, ages 0-8 years, in relation to US National Center for Health Statistics Reference values was carried out. Age-matched noma-free, poor village children (n = 151) from similar communities as noma cases, and elite urban children (n = 132) served as control groups. Heights and weights were measured and the height for age (HAZ), weight for age (WAZ) and weight for height (WHZ) scores calculated as indices of stunting, underweight and wasting respectively. Serum level of interleukin (IL)-18, a multifunctional cytokine, was also measured. RESULTS: In the age groups 0-4 and 4-8 years, the percentages of noma children <-2.0SD were 91% and 67% respectively. The corresponding values for the village children were 37% and 24% and significantly different (P < 0.001) from the noma group. Only 7% of the elite children aged 4-8 years were stunted. Low body weight and wasting were prominent features of village and noma groups, but more marked in the latter. Associated with noma was a profound increase (P < 0.001) in IL-18 in comparison with urban controls, and a 34% non-statistically significant increase relative to the village control group. Among other functions, IL-18 induces several pro-inflammatory cytokines and the matrix metalloproteinases, influences long bone growth, and consequently may be relevant to growth retardation seen in poor village children and noma victims. CONCLUSION: These results suggest that occurrence of fresh noma was probably programmed very early in life by malnutrition and chronic infections resulting from replacement of breast milk with contaminated, inferior substitutes. Although not investigated, we speculate that children with fresh noma might also be victims of intrauterine growth retardation as noma is most prevalent during the infantile phase of child growth which starts at mid-gestation and tails off at 4 years.

Metabolic effects of acute measles in chronically malnourished Nigerian children.

We hypothesized that acute measles infection imposes severe metabolic demands on malnourished children. Nigerian rural communities, characterized by severe poverty and extensive malnutrition, served as site for this study. Sixty-five children (mean [+/-SD] age 2.67 +/- 1.96 years) with measles and a randomly selected equal number of children (age 2.83 +/- 1.23 years) from the same communities but measles-free were studied. Both groups were serologically negative for human immunodeficiency virus. The percentages of nonmeasles group who were underweight and wasted as exemplified by weight for age (WAZ) and weight for height (WHZ) scores less than -2.0 SD were 43% and 23%, respectively. Comparative values for the measles group (66% and 54% respectively) were significantly (P < 0.01 or 0.001) different. Compared to the controls, measles-infected children had significantly (P < 0.001) higher plasma cortisol level, marked hyporetinemia (plasma retinol 0.62 +/- 0.24 micromol/L) and prominent reduction (P < 0.002) in the sum of serum essential amino acids. Measles promoted a TH(1) to TH(2) cytokine shift, with severe depletion of plasma interleukin (IL)-12, a key cytokine in the development of cell mediated immunity. IL-6, a key stimulator of hepatic acute phase protein response, was prominently (P < 0.002) increased in plasma in measles-infected children. Glucocorticoids exert effects on cytokine expression, as well as on cytokine receptor expression and cytokine-regulated biological responses. They enhance synergistically, the effects of IL-1 and IL-6 type cytokines on many acute phase proteins. Because of the prominent increase in circulating level of cortisol in acute measles, glucocorticoid treatment for associated sepsis may pose serious problems. Additionally, glucocorticoids antagonize several effects of retinoids at cellular and transcriptional levels, thus suggesting that hypercortisolemia may increase the requirement for retinoids.

Nutrition and oral health in Africa.

Poverty, low birth weight, low life expectation at birth, widespread malnutrition, numerous endemic infections, little or no access to safe water, poor oral hygiene, deplorable environmental sanitation and political instability among other problems, characterise the lives of many Africans, particularly in sub-Saharan Africa. In African countries undergoing rapid urbanisation, health problems associated with undernutrition and overnutrition coexist, and these result from lifestyle changes which promote physical inactivity, increased consumption of fats and refined carbohydrates, as well as abuse of tobacco and alcohol. Thus, in several African countries, inflammatory oral diseases (e.g. periodontal diseases, acute necrotising gingivitis, noma) resulting from inappropriate interactions between microorganisms and the malnourished, immunocompromised host, have continued to pose serious health problems. There are suggestions of increasing incidence of squamous cell carcinoma, probably related to increased use of alcohol and tobacco, which elicit nutrient deficiencies and oxidative stress. Additionally, there is an increase in caries prevalence particularly in the poor urban areas. The latter is related not only to increased availability of refined sugars, but also to limited access to the caries preventive effects of fluorides. Good dietary practices through judicious combination of available foods should therefore feature prominently in the promotion of optimal oral health in Africa.

Nutrition and oral infectious diseases: state of the science.

Immunological competence and nutritional status are two of the most important determinants of morbidity and mortality. Oral diseases, particularly inflammatory periodontal lesions, are caused by viruses and specific periodontopathic bacteria. Paradoxically, the production of cytokines and oxidant molecules, which are supposed to be part of a highly effective mechanism for combating the periodontal pathogens, may damage the host. Malnutrition consistently impairs innate and adaptive defenses of the host, including phagocytic function, cell-mediated immunity, complement system, secretory antibody, and cytokine production and function. In protein-energy malnutrition, there are marked changes in the oral microbial ecology resulting in a preponderance of pathogenic anaerobic organisms, increased propensity of bacteria to bind to oral mucosal cells, attenuation of acute phase protein response, and dysfunction of the cytokine system. Cellular depletion of antioxidant nutrients promotes immunosuppression, accelerated replication rate of ribonucleic acid viruses, and increased disease progression. Therefore, malnutrition can intensify the severity of oral infections and may lead to their evolution into life-threatening diseases.