Biomedical subjects
Publications and source records attributed to C O Enwonwu.
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 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.
Fungal infections have gained considerable importance over the last decade as a result of significant increase in the incidence of opportunistic and systemic candidosis. Although Candida albicans is the predominant causative agent of candidosis, particularly oral disease, recently an epidemiological trend has been observed where other less pathogenic species of Candida, including the newly characterized species Candida dubliniensis, are emerging as significant opportunistic pathogens. The present study aimed to screen for the presence of C. dubliniensis and to compare the recovery of yeast species from 30 seemingly healthy and 30 HIV-positive children in the United States, as well as from 64 malnourished Nigerian children. Oral samples were cultured for fungal growth, and all germ tube and chlamydospore positive isolates were tested for ability to grow at 45 degrees C to differentiate between C. albicans and C. dubliniensis. All isolates were speciated based on colony color production on CHROMagar medium and sugar assimilation profiles. Among the 30 HIV-positive children, 15 (50%) were positive for fungus; 12 were positive for C. albicans, with one of the latter also positive for Candida glabrata, and three were found to harbor C. dubliniensis. Among the 30 non-HIV-positive children, five C. albicans and four C. dubliniensis isolates were recovered. No C. dubliniensis isolates were recovered from the Nigerian group. However, eight other different yeast species were recovered from 31 (48.4%) of the 64 Nigerian children sampled, with six of them growing a combination of species. In comparing the data from the Nigerian and United States children, the frequency of yeasts in the malnourished Nigerian group was considerably higher. The most striking difference between the two groups was in the variety of the usually less encountered and less pathogenic yeast species recovered from the Nigerian population. The findings support previously reported observations that there may be intrinsic differences between different populations sampled and that malnutrition might favor the presence of yeast species other than C. albicans.
Good dietary practices and optimal nutritional status promote growth and tissue development, as well as feature prominently in the prevention of diseases. Malnutrition (particularly protein-energy malnutrition, which invariably involves concurrent deficiencies of the antioxidant micronutrients) promotes salivary gland hypofunction, impaired immunity, and an early shift in the oral microbial ecology toward a preponderance of anaerobic organisms. The immune suppression, which includes impaired cytokine function as well as diminished acute-phase response to infections, impacts negatively on the natural history of inflammatory periodontal diseases. The pathogenesis of oral cancer is influenced by deficiencies of antioxidant nutrients, and there is evidence for diminished DNA methylation, disruption of DNA integrity, and increased DNA damage in folate deficiency.
Severe falciparum malaria, with its associated hyperpyrexia, distorts plasma levels of large neutral amino acids (NAA) and consequently, brain uptake of individual NAA. Since brain levels of NAA determine cerebral synthesis of monoamines (serotonin, histamine, catecholamines), we measured plasma concentrations of NAA, and also plasma histamine (Hm) in children with falciparum malaria and in uninfected controls. Malaria elicited a marked (P < 0.025) increase in plasma histidine (His) with a 5-fold significant (P < 0.001) elevation in histamine, as well as a 2.5-fold increase (P < 0.005) in plasma phenylalanine (Phe), with no changes in the other NAA. Using kinetic parameters of NAA transport at human blood-brain barrier (BBB), we showed that malaria significantly altered calculated brain uptake of His (+30%), Phe (+96%), Trp (-30%) and Ile (-27%), with no change in the other NAA, compared with controls. Our data suggested enhanced cerebral synthesis of Hm with impaired production of serotonin and the catecholamines in the patients, and therefore, the need to evaluate the encephalopathy in severe malaria within the context of abnormalities in metabolism of Hm and other monoamines resulting from imbalance in plasma levels of the large neutral amino acids. Of clinical relevance also is the impaired inactivation of increased brain Hm by antimalarials such as the widely used aminoisoquinolines leading to elevated brain levels of imidazole-4-acetic acid (IAA), a potent inducer of a sleep-like state often accompanied by seizures, analgesia, decreased blood pressure and other effects.
Ascorbic acid is preferentially concentrated in the hypothalamus, pituitary and adrenal glands. Its level in the acini of salivary glands is relatively high. We therefore hypothesized that ascorbate may have a role in salivary gland function. Ascorbate-deficient guinea pigs had lower stimulated whole salivary flow rates than well-fed, age-matched controls (P: < 0.005). Total salivary protein concentration was also markedly (P: < 0.005) reduced in the deficient guinea pigs. SDS-PAGE and densitometric quantification of protein bands confirmed significant reduction in specific salivary proteins (e.g., amylase, proline-rich proteins) in the saliva samples of malnourished guinea pigs. Some protein bands not seen in control saliva were detected in the saliva of malnourished guinea pigs. Ascorbate deficiency also produced a significant (P: < 0.005) reduction in the ss-adrenergic receptor density (subtype 1; 95 +/- 19 fmol/mg protein compared with 179 +/- 27 fmol/mg protein for the controls). No significant difference was observed between the two groups with respect to the ss-adrenergic receptor subtype 2. Additionally, ascorbate-deficient guinea pigs had significantly lower muscarinic-cholinergic receptor densities (50 +/- 5 vs. 74 +/- 8 fmol/mg protein for controls). Our data support the conclusion that diminished membrane receptors might impair the capacity of the transmembrane signaling system, resulting in salivary gland hypofunction in ascorbate-deficient guinea pigs. Without implying extrapolation of our findings in experimental animals to humans, it is perhaps relevant that many conditions often associated with salivary gland hypofunction in humans (e.g., smoking or drug ingestion) deplete cellular ascorbate.
A previous study demonstrated the presence and possible involvement of Fusobacterium necrophorum in the pathogenesis of noma lesions of children living in agricultural and herding villages in northwestern Nigeria. In order to determine if F. necrophorum was part of the oral flora of malnourished children with no noma lesions, a study of the fusobacteria present in the oral cavities of 30 children, 2-6 years of age in Sokoto State, was undertaken. Swabs taken of the oral cavity were cultured on selective fusobacteria medium using conventional anaerobic microbiological techniques. F. nucleatum was recovered from each child and F. necrophorum was isolated from the oral cavity of only one child. The presence of F. nucleatum and the lack of F. necrophorum, except in one case, suggests that the latter is not normal flora in the children at risk for noma. F. necrophorum, a putative trigger organism for noma may gain a foothold only when certain staging conditions (i.e., lowered host resistance and/or oral lesion) are present.
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.
OBJECTIVE: The aim of this study was to assess dental caries status and treatment needs in The Gambia for the purpose of national planning. MATERIALS AND METHODS: 1,235 subjects were obtained with a multi-stage stratified random sampling technique. Clinical examinations were carried out using the criteria suggested in WHO Basic Methods (WHO 1987). The WHO J2 software programme was used for data analysis. RESULTS: More than half of the subjects had caries. Mean DMFT increased from 1.7 in the 7-year-old group to 8.8 in 65-99-year-olds. Mean DT peaked at 5.1 in the 30-34-year-old group before declining to 3.2 among the 65-99-year-olds. Mean filled teeth (FT) was zero in all ages. Missing teeth (MT) increased from 0.1 in 13-year-olds to 5.6 among the 65-99-year group. Mean DMFT was 2.3, 2.8, and 6.6 in 12-year-olds, 15-year-olds and 35-44-year-olds respectively. Unmet treatment need (DT/DMFT) was 90-100% in subjects below 25 years. Need for dental extraction increased from 15% to 63% in 65-99-year-olds. Between 0.3 and 2.8 teeth required extraction, and 46-79% of subjects needed conservative treatment. Dental auxiliaries should be trained to carry out extractions and fillings using the atraumatic restorative treatment (ART).
OBJECTIVE: The aim of the pathfinder survey was to assess the periodontal status and treatment needs in The Gambia. METHODS: A multistage stratified random sampling technique was used to obtain a sample of 1,235 (or 0.1% of the national population). The study was conducted according to the World Health Organisation's criteria (WHO, 1987). The WHO J2 software programme was used to analyse the data. RESULTS: Not more than 12% of subjects in any age group had healthy periodontal tissues. Two to three sextants were healthy among those under the age of 35 years. Shallow (4-5 mm) pockets were present in all ages. However, less than one sextant was involved among subjects younger than 25 years. Despite the high prevalence of pockets, few sextants were edentulous. The majority of subjects needed oral hygiene instructions and oral prophylaxis. Of the subjects between the ages of 8 and 29 years, 5-28% needed complex treatment in only half of a sextant. Similarly, 38% and 80% of older subjects needed complex treatment in 0.8-1.9 sextants. CONCLUSION: A national oral health plan in The Gambia should focus on health education and provision of oral prophylaxis by trained auxiliary health care workers. In conclusion, there is a need to develop a functional district oral health services system in The Gambia.
Brain monoamine levels may underlie aspects of the cerebral component of falciparum malaria. Since circulating amino acids are the precursors for brain monoamine synthesis, we measured them in malaria patients and controls. Malaria elicited significantly elevated plasma levels of phenylalanine, particularly in comatose patients, with the Tyr/Phe (%) ratio reduced from 83.3 in controls to 39.5 in infected children, suggesting an impaired phenylalanine hydroxylase enzyme system in malaria infection. Malaria significantly increased the apparent K(m) for Trp, Tyr and His, with no effect on K(m)(app) for Phe. Using the kinetic parameters of NAA transport at the human blood-brain barrier, malaria significantly altered brain uptake of Phe (+96%), Trp (-28%) and His (+31%), with no effect on Tyr (-8%), compared with control findings. Our data suggest impaired cerebral synthesis of serotonin, dopamine and norepinephrine, and enhanced production of histamine, in children with severe falciparum malaria.
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.
The microbiologic history of noma was reviewed. Studies have associated the disease process with large numbers of fusiform bacilli and spirochetal organisms. In order to study the microbiology of the staging and infection periods of noma 62 Nigerian children, aged 3-14 years, 22 children had acute necrotizing ulcerative gingivitis (ANUG) and were also malnourished, 20 exhibited no acute necrotizing ulcerative gingivitis but were malnourished and 20 were free of acute necrotizing ulcerative gingivitis and in good nutritional state) were evaluated for the presence of viruses and oral microorganisms. The ANUG cases in the malnourished children had a higher incidence of Herpesviridae, the main virus being detected was cytomegalovirus. There were more anaerobic microorganisms recovered, with Prevotella intermedia as the predominant isolate, in the malnourished children as compared to the healthy children. A study of the predominant microflora in active sites of noma lesions was carried out in eight noma patients, 3-15 years of age, in Sokoto State, northwestern Nigeria. Fusobacterium necrophorum was recovered from 87.5% of the noma lesions. Oral microorganisms isolated included Prevotella intermedia, alpha-hemolytic streptococci and Actinomyces spp. which were isolated from 75.0, 50.0 and 37.5% of the patients, respectively. Peptostreptococcus micros, Veillonella parvula, Staphylococcus aureus and Pseudomonas spp. were each recovered from one lesion. All strains were observed to be sensitive to all of the antibiotics tested with the exception of one strain of P. intermedia which showed resistance to penicillin. The pathogenic mechanisms of F. necrophorum as a trigger organism were discussed. The isolation from human noma lesions of F. necrophorum, a pathogen primarily associated with animal diseases, may have important etiologic and animal transmission implications.
The study reported in this paper was carried out in the Northwestern and Southwestern regions of Nigeria, between October 1996 and April 1998. The study examined the possible contributory role of living conditions in the development of acute necrotizing gingivitis (ANG) or noma from oral lesions. Questionnaire data obtained from 42 fresh noma cases seen in the Northwest and four fresh cases seen in the Southwest were examined. In addition 46 cases of advanced ANG from the Southwest were included. The main focus was to compare some of the environmental living conditions of cases with advanced ANG and those with noma in these regions. All the noma and ANG cases were seen in children aged 2-12 years. The level of good oral hygiene practices and general environmental living conditions were significantly higher in the Southwest than in the Northwest. Data also showed that living in close proximity with livestock was significantly higher in the Northwest than in the Southwest (P < 0.05). The environmental living conditions of children in the Northwest were further compounded by poor sanitary faecal disposal practices as well as minimal access to potable water. The overall data indicated that living in substandard accommodations, exposure to debilitating childhood diseases, living in close proximity to livestock, poor oral hygiene, limited access to potable water and poor sanitary disposal of human and animal faecal waste could have put the children in the Northwest at higher risk for noma than the children in the Southwest. These could have been responsible for the higher prevalence of noma in the Northwest than in the Southwest.
A study of the predominant microflora in active sites of noma (cancrum oris) lesions was carried out in eight noma patients 3-15 years of age in Sokoto State in northwestern Nigeria. Paper point sampling and conventional anaerobic microbiologic techniques were used. Fusobacterium necrophorum was recovered from 87.5% of the noma lesions. Oral microorganisms included Prevotella intermedia, alpha-hemolytic streptococci, and Actinomyces spp. which were isolated from 75.0%, 50.0%, and 37.5% of the patients, respectively. Peptostreptococcus micros, Veillonella parvula, Staphylococcus aureus, and Pseudomonas spp. were each recovered from one lesion. The F. necrophorum and P. intermedia isolates were tested for antibiotic sensitivity to clindamycin, tetracycline, metronidazole, and penicillin using the E-test, and all strains were observed to be sensitive to all of the antibiotics tested with the exception of one strain of P. intermedia, which showed resistance to penicillin. The first reported isolation from human noma lesions of F. necrophorum, a pathogen primarily associated with animal diseases, may have important etiologic and animal transmission implications.
This study showed that impoverished Nigerian children at risk for cancrum oris (noma) had significantly reduced plasma concentrations of zinc (< 10.8 micromol/L), retinol (< 1.05 micromol/L), ascorbate (< 11 micromol/L), and the essential amino acids, with prominently increased plasma and saliva levels of free cortisol, compared with their healthy counterparts. The nutrient deficiencies, in concert with previously reported widespread viral infections (measles, herpesviruses) in the children, would impair oral mucosal immunity. We postulate, subject to additional studies, that evolution of the oral mucosal ulcers including acute necrotizing gingivitis to noma is triggered by a consortium of microorganisms of which Fusobacterium necrophorum is a key component. Fusobacterium necrophorum elaborates several dermonecrotic toxic metabolites and is acquired by the impoverished children via fecal contamination resulting from shared residential facilities with animals and very poor environmental sanitation.
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Herpesviruses have been implicated in the pathogenesis of human periodontitis. The present study investigated whether herpesviruses are present in the lesions of acute necrotizing ulcerative gingivitis. Sixty-two Nigerian children, aged 3-14 years, were studied. Twenty-two children had acute necrotizing ulcerative gingivitis and were also malnourished, 20 exhibited no acute necrotizing ulcerative gingivitis but were malnourished and 20 were free of acute necrotizing ulcerative gingivitis and in a good nutritional state. Polymerase chain reaction methods were used to determine the presence of human cytomegalovirus (HCMV), Epstein-Barr virus type 1 and type 2 (EBV-1, EBV-2), herpes simplex virus (HSV), human herpes virus 6 (HHV-6), human papilloma virus and human immunodeficiency virus type 1 in crevicular fluid specimens collected by paper points. Of the 22 acute necrotizing ulcerative gingivitis patients, 15 (68%) revealed viral infection and 8 (36%) viral coinfection. Thirteen (59%) acute necrotizing ulcerative gingivitis patients demonstrated HCMV, 6 (27%) EBV-1, 5 (23%) HSV and 1 (5%) HHV-6. Only 2 (10%) subjects from each group not affected by acute necrotizing ulcerative gingivitis showed viral presence, and no control subject revealed viral coinfection. These findings suggest that HCMV and possibly other herpesviruses contribute to the onset and/or progression of acute necrotizing ulcerative gingivitis in malnourished Nigerian children.