Cyril O. Enwonwu

Prevalent Bacterial Species and Novel Phylotypes in Advanced Noma Lesions

ABSTRACT The purpose of this study was to determine the bacterial diversity in advanced noma lesions using culture-independent molecular methods. 16S ribosomal DNA bacterial genes from DNA isolated from advanced noma lesions of four Nigerian children were PCR amplified with universally conserved primers and spirochetal selective primers and cloned into Escherichia coli. Partial 16S rRNA sequences of approximately 500 bases from 212 cloned inserts were used initially to determine species identity or closest relatives by comparison with sequences of known species or phylotypes. Nearly complete sequences of approximately 1,500 bases were obtained for most of the potentially novel species. A total of 67 bacterial species or phylotypes were detected, 25 of which have not yet been grown in vitro. Nineteen of the species or phylotypes, including Propionibacterium acnes, Staphylococcus spp., and the opportunistic pathogens Stenotrophomonas maltophilia and Ochrobactrum anthropi were detected in more than one subject. Other known species that were detected included Achromobacter spp., Afipia spp., Brevundimonas diminuta, Capnocytophaga spp., Cardiobacterium sp., Eikenella corrodens, Fusobacterium spp., Gemella haemoylsans, and Neisseria spp. Phylotypes that were unique to noma infections included those in the genera Eubacterium, Flavobacterium, Kocuria, Microbacterium, and Porphyromonas and the related Streptococcus salivarius and genera Sphingomonas and Treponema. Since advanced noma lesions are infections open to the environment, it was not surprising to detect species not commonly associated with the oral cavity, e.g., from soil. Several species previously implicated as putative pathogens of noma, such as spirochetes and Fusobacterium spp., were detected in at least one subject. However, due to the limited number of available noma subjects, it was not possible at this time to associate specific species with the disease.

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.

Epidemiological and biochemical studies of necrotizing ulcerative gingivitis and noma (cancrum oris) in Nigerian children

Abstract Epidemiological and biochemical studies were carried out on Nigerian children during the period 1963–1965. The studies were undertaken to determine the role of oral hygiene and the major indices of socio-economic status in the patterns of distribution of necrotizing ulcerative gingivitis and the oro-facial lesion of noma. A total of 1068 children aged 0–10 yr and drawn from educated well-to-do familes, under-privileged village communities and patients hospitalized for treatment of malnutrition and/or cancrum oris formed the sample material. Necrotizing ulcerative gingivitis, which is very rarely seen in children in developed countries, was frequently encountered in Nigerian children and showed a peak age incidence around 2–6 yr. Necrotizing ulcerative gingivitis in Nigeria was found to be a disease of the low socio-economic group. While no case of the lesion was encountered in the high social class children, underprivileged Osegere village children with borderline malnutrition showed an incidence of 15 per cent, and the incidence rose to 27 per cent in hospitalized cases of severe protein-calorie malnutrition. All 69 cases of noma seen were miserably malnourished as revealed by biochemical, clinical and dietary evaluations. The low social group children had poor oral hygiene status compared with their well-fed high socio-economic group counterparts, but there was evidence from some cases of necrotizing ulcerative gingivitis and noma that the status of oral hygiene was not enough to explain the presence of these lesions in only the poor underprivileged communities. Findings of this study have been evaluated in light of the high physiological and metabolic activities of oral tissues and the importance of adequate supply of dietary nutrients for the maintenance of structural and functional integrity of oral tissues.

Oro-Facial Gangrene (Noma/Cancrum Oris): Pathogenetic Mechanisms

Cancrum oris (Noma) is a devastating infectious disease which destroys the soft and hard tissues of the oral and para-oral structures. The dehumanizing oro-facial gangrenous lesion affects predominantly children ages 2 to 16 years, particularly in sub-Saharan Africa, where the estimated frequency in some communities varies from 1 to 7 cases per 1000 population. The risk factors are poverty, malnutrition, poor oral hygiene, residential proximity to livestock in unsanitary environments, and infectious diseases, particularly measles and those due to the herpesviridae. Infections and malnutrition impair the immune system, and this is the common denominator for the occurrence of noma. Acute necrotizing gingivitis (ANG) and oral herpetic ulcers are considered the antecedent lesions, and ongoing studies suggest that the rapid progression of these precursor lesions to noma requires infection by a consortium of micro-organisms, with Fusobacterium necrophorum (Fn) and Prevotella intermedia (Pi) as the suspected key players. Additional to production of a growth-stimulating factor for Pi, Fn displays a classic endotoxin, a dermonecrotic toxin, a cytoplasmic toxin, and a hemolysin. Without appropriate treatment, the mortality rate from noma is 70-90%. Survivors suffer the two-fold afflictions of oro-facial mutilation and functional impairment, which require a time-consuming, financially prohibitive surgical reconstruction.

Influence of socio-economic conditions on dental development in nigerian children

Abstract A joint dental, biochemical and nutritional study was carried out on Nigerian children from different socio-economic backgrounds. Timing of eruption of deciduous dentition and prevalence of enamel hypoplasia were recorded. Evaluation of findings in 872 children from the Yoruba community of Western Nigeria showed that physical development, as reflected in heights and body weights, was retarded in the underprivileged, malnourished village children compared with their counterparts from higher socio-economic homes. Eruption of the deciduous teeth demonstrated good correlation with changes in height and weight. Enamel hypoplasia was not seen in any of the well-fed children examined. In contrast, among 420 village children aged 0–4 yr, the prevalence of gross enamel hypoplasia of the deciduous teeth was 21 per cent. Hypoplastic defects of enamel involving the pre-natally formed parts of the deciduous dentition accounted for 72 per cent of the observed cases. No evidence emerged of a causal relationship between the enamel hypoplasia and past or present systemic conditions, including premature birth. The developing dental organ, like most other organs of the body, appears to be susceptible to factors associated with low socioeconomic status. Prominent among such factors in developing countries is severe malnutrition.

Bionutrition and Oral Cancer in Humans

Tobacco (smoking and smokeless) use and excessive consumption of alcohol are considered the main risk factors for oral cancer (ICD9 140-149). Conspicuous national and international variations in oral cancer incidence and mortality rates, as well as observations in migrant populations, raise the possibility that diet and nutritional status could be an important etiologic factor in oral carcinogenesis. As shown in this report, abuse of alcohol and tobacco has serious nutritional implications for the host, and generates increased production of reactive free radicals as well as eliciting immunosuppression. Maintenance of optimal competence of the immune system is critical for cancer surveillance. Active oxygen species and other reactive free radicals mediate phenotypic and genotypic alterations that lead from mutation to neoplasia. Consequently, the most widely used chemopreventive agents against oral cancer (e.g., vitamins A, E, C, and beta-carotene) are anti-oxidants/free radical scavengers. These anti-oxidants, both natural and synthetic, neutralize metabolic products (including reactive oxygen species), interfere with activation of procarcinogens, prevent binding of carcinogens to DNA, inhibit chromosome aberrations, restrain replication of the transformed cell, suppress actions of cancer promoters, and may even induce regression of precancerous oral lesions such as leukoplakia and erythroplakia. Malnutrition is characterized by marked tissue depletion of anti-oxidant nutrients, including GSH (gamma-glutamyl-cysteinyl-glycine), a key cellular anti-oxidant as well as a modulator of T-cell activation. GSH or its precursor cysteine inhibits activation of the nuclear transcription factor kB(NFkB), and has been shown to be protective against chemically induced oral cancer and leukoplakia. Alcohol-, tobacco-, and/or malnutrition-induced immunosuppression promotes impaired salivary gland function and oral mucosal immunity, a prominent reduction in the number of helper CD4 cells with less marked changes in number of suppressor T-cells, and depressed NK cell activity, among others. These suggest a breakdown in capacity or the malnourished to mount effective tumor surveillance. This review article underscores the compounding but important roles of nutritional/dietary factors in the long-established causal link between abuse of alcohol and tobacco (smoking and smokeless) and oral cancer.

Nitrogen Metabolism in Sickle Cell Anemia: Free Amino Acids in Plasma and Urine

Twenty-four hour urinary levels and fasting plasma concentrations of free amino acids (AA) were evaluated in adult sickle cell anemia (HbSS) and age-matched HbAA subjects with comparable daily energy (E) and protein (N) intake. HbSS elicited significant reduction in the sum of plasma indispensable (EAA) with no change in the dispensable (NAA) amino acids, resulting in a prominent (P less than 0.01) reduction in the EAA/NAA ratio from 71% to 55%. Arg (-38%), Leu (-32%), Val (-28%) and His (-32%) were among the AA most severely affected. Despite a twofold increase in 24-hour urine volume in HbSS compared with HbAA subjects, total urinary losses of EAA and NAA were markedly reduced in the former group, with Arg (-53%) and Gly (-56%) levels most prominently affected. Compared with HbAA controls, HbSS subjects showed a three-fourfold increase in 24-hour urinary orotate excretion that had no relationship to amount of N intake. The results indicated that adult subjects with HbSS, who consumed adequate N and E as per the RDA for healthy individuals, behaved like normal HbAA controls on a low protein diet. There was evidence that the HbSS subject might be in a precarious state with respect to sufficiency of several amino acids, particularly L-Arg, which is now classified as conditionally indispensable for the human.

Experimental protein-calorie malnutrition in rats: Biochemical and ultrastructural studies

Abstract Young rats (100–130 gm) fed a low-protein diet which simulates the protein value of diets eaten by children in areas where protein-calorie malnutrition is prevalent developed many of the features associated with kwashiorkor. Among the findings were marked loss in body weight, atrophy of many visceral organs, fatty liver, hypoproteinemia, edema, and profound changes in serum amino acid patterns. Associated with the alterations in serum amino acid levels were extreme disproportions in the fasting levels of amino acids in liver. This experimental model of rodent kwashiorkor showed marked reduction in liver protein and RNA contents, but DNA remained remarkably constant indicating loss of cellular contents rather than decrease in cell population. The decreased RNA content of the liver was consistent with the observations of massive breakdown of the membranes of the endoplasmic reticulum as well as the elevated activity of alkaline ribonuclease assayed in the absence of PCMB. The polysomes showed extensive disaggregation resulting in increased monomer and dimer peaks. The significance of these biochemical and anatomical changes as well as their possible relevance to kwashiorkor in children was discussed.

Rate of RNA turnover in rat liver in relation to intake of protein

Abstract The effect of dietary intake of protein on the turnover of liver RNA has been measured in rats by observing the rate of loss of label from liver ribosomal RNA over a period of several days after injection of 3 H-labeled orotic acid. Rats receiving a normal intake of protein showed fractional rates of RNA synthesis and degradation of about 20–25% daily. When rats were fed a diet free of protein, RNA breakdown was at first accelerated to over 40% per day. However, after 2 days on the protein-free diet the fractional rate of degradation fell to about 15% daily, and the rate of RNA synthesis to an even lower level, so that animals on this diet showed a continuous reduction in the RNA content of their livers. On the basis of the present and earlier studies, it is suggested that RNA turnover is regulated through changes in the population of free ribosomal subunits in the liver cytoplasm, the abundance of subunits being affected by amino acid supply.

Editorial: The need for action against oro‐facial gangrene (noma)

Oro-facial gangrene, also known 3 s cancrum oris or noma, i s a n infectious disease which destroys o ra l tissues, the palate, facial tissues and other neighbouring structures in i t s fdiiiinatiiig course (Tempest 1966). The v i c t ims of noma are mainly young children caught 111 the v ic ious cycle of extreme poverty, chronic malnutrition, a markedly impaired immune system and increased vulnerability to endemic bacterial and viral infections. Many people were scandalized when the ciiscnse reappeared in Europe during the Second World War, h u t we seem to he able to ignore i t when it wreaks havoc in developing countries hordering the Sahara Ilcscrt.