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 I 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.
References
1.
Adekeye EO, Ord RA (1983). Cancrum oris: principles of management of reconstructive surgery. I Maxillofac Surg1:160-170.
2.
Adelsberger L. (1945). Medical observations in Auschwitz concentration camp. Lancet1:317-320.
3.
Adolph HP, Yugueros P., Woods JE (1996). Noma: a review. Ann Plast Surg37:657-668.
Alleyne GAO, Hay RW, Picou DI (1977). Protein energy malnutrition, London: Edward Arnold, pp. 54-103.
6.
Amoako KK, Goto Y., Misawa N., Xiu DL, Shinjo T. (1997). Interactions between Fusobacterium necrophorum hemolysin, erythrocytes and erythrocyte membranes. FEMS Microbiol Lett150:101-106.
7.
Bader-Meunier B., Pinto G., Tardieu M., Pariente D., Bobin S., Dommerques JP (1994). Mastoiditis, meningitis and venous sinus thrombosis caused by Fusobacterium necrophorum. Eur J Ped153:339-341.
8.
Bakaletz LO (1995). Viral potentiation of bacterial superinfection of the respiratory tract. Trends Microbiol3:110-114.
9.
Balows A, Dehaan RM, Dowell VR Jr, Guze LB, editors (1975). Anaerobic bacteria: role in disease. American Lecture Series in Microbiology no. 940. Proceedings of the International Conference on Anaerobic Diseases. 2nd ed. Springfield, IL: Charles C. Thomas, pp. 140-165.
10.
Barmes DE, Enwonwu CO, Leclercq MH, Bourgeois D., Falkler WA (1997). The need for action against oro-facial gangrene (noma). Trop Med Int Health2:1111-1114.
11.
Barrios TJ, Aria AA, Brahney C. (1995). Cancrum oris in an HIV-positive patient. J Oral Maxillofac Surg53:851-855.
12.
Beck, MA (1996). The role of nutrition in viral disease. J Nutr Biochem7:683-690.
13.
Beck MA ( 1998). The influence of antioxidant nutrients on viral infection. Nutr Rev56:S140-S146.
14.
Beisel WR (1996). Nutrition and immune function: overview. I Nutr126:2611S-2615S.
15.
Berg A. ( 1992). Sliding toward nutritional malpractice: time to reconsider and redeploy. Am I Clin Nutr57:3-7.
16.
Berg JN, Loan RW ( 1975). Fusobacterium necrophorum and Bacteroides melaninogenicus as etiologic agents in foot rot in cattle. Am J Vet Res36:1115-1122.
17.
Beveridge WIB (1934). A study of twelve strains of Bacillus necrophorus with observations on the oxygen intolerance of the organism. J Pathol Bacteriol38:467-491.
18.
Bhaskaram P. (1995). Measles and malnutrition. Indian J Med Res102:195-199.
19.
Boppana SB (1996). Cytokines in infectious diseases. Indian J Pediatr63:447-452.
20.
Chan M. ( 1990). Vitamin A and measles in the Third World children. Br Med J301:1230-1231.
21.
Chandra RK (1991). Nutrition and immunity: lessons from the past. Am J Clin Nutr53:1087-1101.
Claesson R., Edlund M.-B, Persson S., Carlsson J. (1990). Production of volatile sulfur compounds by various Fusobacterium species. Oral Microbiol Immunol5:137-142.
24.
Clerici M., Bevilacqua M., Vago T., Villa ML, Shearer GM, Norbiato G. (1994). An immunoendocrinological hypothesis of HIV infection. Lancet343:1552-1553.
25.
Coates BH (1826). Description of the gangrenous ulcers of the mouths of children. North Am Med Surg2:1-24.
26.
Contreras A., Falkler WA Jr, Enwonwu CO, Idigbe EO, Savage KO, Afolabi MB, et al. (1997). Human herpesviridae in acute necrotizing ulcerative gingivitis in children in Nigeria. Oral Microbiol Immunol12:259-265.
27.
Coyle-Dennis JE, Lauerman JH (1978). Biological and biochemical characteristics of Fusobacterium necrophorum. Am J Vet Res39:1790-1793.
28.
Dack GM, Dragstedt LR, Johnson R., McCullough NB (1938). Comparison of Bacterium necrophorum from ulcerative colitis in man with strains isolated from animals. J Infect Dis62:169-180.
29.
Dawson J. (1945). Cancrum oris. Br Dent J79:151-157.
30.
DeOnis M., Monteiro C., Akre J., Clugston G. (1993). The worldwide magnitude of protein-energy malnutrition: an overview from the WHO global database on child growth. WHO Bull71:703-712.
31.
Diefenbach A., Schindler H., Rollinghoff M., Yokoyama WM, Bogdan C. (1999). Requirement for type 2 NO synthase for Il-12 signaling in innate immunity. Science284:951-955.
32.
Doulos NL, Constantopoulos A., Litsios B. (1987). Effect of ascorbic acid on guinea pig adrenal adenylate cyclase activity and plasma cortisol. I Nutr117:1108-1114.
33.
Eckstein A. (1940). Noma. Am J Dis Child59:219-237.
34.
Editorial (1997). A good turn for Africa, please. Lancet349:69.
Enwonwu CO (1972). Epidemiological and biochemical studies of necrotizing ulcerative gingivitis and noma (cancrum oris) in Nigerian children. Arch Oral Biol17:1357-1371.
37.
Enwonwu CO (1985). Infectious oral necrosis (cancrum oris) in Nigerian children. Community Dent Oral Epidemiol13:190-194.
38.
Enwonwu CO (1994). Cellular and molecular effects of malnutrition and their relevance to periodontal disease. J Clin Periodontol21:643-657.
39.
Enwonwu CO (1995). Noma: a neglected scourge of children in sub-Saharan Africa. WHO Bull73:541-545.
40.
Enwonwu CO, Falkler WA Jr, Idigbe EO, Afolabi MB, Ibrahim M., Onwujekwe D., et al. (1999). Pathogenesis of cancrum oris (noma): confounding interactions of malnutrition with infection. Am J Trop Med Hyg60:223-232.
41.
Fales WH, Warner IF, Teresa GW (1977). Effects of Fusobacterium necrophroum leukotoxin on rabbit peritoneal macrophages in vitro. Am J Vet Res38:491-495.
42.
Falkler WA Jr, Enwonwu CO, Idigbe EO (1999). Isolation of Fusobacterium necrophorum from noma (cancrum oris). Am J Trop Med Hyg60:150-156.
43.
Fifis T., Costopoulos C., Vaughan JA (1996). Evidence for phospholipase B activity in Fusobacterium necrophorum cultures and its association with hemolysin/leucocidin activities. Vet Microbiol49:219-233.
44.
Finegold SM (1977). Anaerobic bacteria in human disease. New York: Academic Press, pp. 102-446.
45.
Finegold SM, Strong CA, McTeague M., Marina M. (1993). The importance of black-pigmented Gram-negative anaerobes in human infections. FEMS Immun Med Microbiol6:77-82.
46.
Finnie EO (1976). Necrobacillosis in kangaroos. In: Wildlife diseases. Page LA, editor. Proceedings of the 3rd International Wildlife Diseases Conference, Munich, 1975. New York; Plenum Press. p. 511.
47.
Frisken KW, Higgins T., Palmer JM (1990). The incidence of periodontopathogenic microorganisms in young children. Oral Microbiol Immunol5:43-45.
48.
Garcia MM, Charlton KM, McKay KA (1975a). Characterization of endotoxin from Fusobacterium necrophorum. Infect Immun11:371-379.
49.
Garcia MM, Alexander DC, McKay KA (1975b). Biological characterization of Fusobacterium necrophorum cell fractions in preparation for toxin and immunization studies. Infect Immun11:609-616.
50.
Gazi MI, Cox SW, Clark DT, Eley BM ( 1997). Characterization of protease activities in Capnocytophaga spp., Porphyromonas gingivalis, Prevotella spp., Treponema denticola and Actinobacillus actinomycetemcomitans. Oral Microbiol Immunol12:240-248.
51.
Gharbia SE, Haapasalo M., Shah HN, Kotiranta A., Lounatmaa K., Pearce MA, et al. (1994). Characterization of Prevotella intermedia and Prevotella nigrescens isolates from periodontic and endodontic infections. J Periodontol65:56-61.
52.
Ghosal SP, Gupta PC, Mukherjee AK (1978). Noma neonatorum: its aetiopathogenesis. Lancet2:289-290.
Grappin G., Dupiot M. (1978). Signes bucco-faciaux des maladies generales en milieu tropical. Odontostomatologie Trop1:7-28.
55.
Hagelskjaer L., Pedersen G. (1993). Fusobacterium necrophorum septicemia complicated by liver abscess. A case report. Acta Pathol Microbiol Immunol Scand101:904-906.
56.
Hicken F., Eldredge RB (1935). Acute myelogenous leukemia complicated by noma and streptococcal dermatitis. Am J Dis Child50:1455-1464.
57.
Hofstad T., Kristofferson T. (1971). Preparation and chemical characteristics of endotoxic lipopolysaccharide from three strains of Sphaerophorus necrophorus. Acta Pathol Microbiol Scand79(Sect B):385-390.
58.
Inoue T., Nakakouji M., Iwata H. (1994). Delayed-type hypersensitivity in mice experimentally infected with Fusobacterium necrophorum. J Vet Med Sci56:59-63.
59.
Jacob RA (1990). Assessment of human vitamin C status. J Nutr120:1480-1485.
60.
lansen H-J., Grenier D., Van der Hoeven IS (1995). Characterization of immunoglobulin G-degrading proteases from Prevotella imtermedia and Prevotella nigrescens. Oral Microbiol Immunol10:138-145.
61.
Jaya Rao KS (1982). Endocrines in protein-energy malnutrition. World Rev Nutr Diet39:53-84.
62.
Jelliffe DB (1952). Infective gangrene of the mouth (cancrum oris). Paediatrics9:544-550.
63.
Jimenez M., Baer PN ( 1975). Necrotizing ulcerative gingivitis in children: a 9 year clinical study. J Periodontol46:515-720.
64.
Johnson BD, Engel D. (1986). Acute necrotizing ulcerative gingivitis: a review of diagnosis, etiology and treatment. J Periodontol57:141-150.
65.
Johnson JL, Holdeman LV (1983). Bacteroides intermedius comb. nov. and descriptions of Bacteroides corporis sp. nov. and Bacteroides levii sp. nov. Int J Syst Bacteriol33:15-25.
66.
Jones-Carson J., Vazquez-Torres A., van der Heyde HC, Warner T., Wagner RD, Balish E. (1995). Gamma-delta T cell-induced nitric oxide production enhances resistance to mucosal candidiasis. Nature Med1:552-557.
67.
Juster-Reicher A., Mogilner BM, Levi G., Flidel O., Amitai M. (1993). Neonatal noma. Am J Perinatol10:409-411.
68.
Kanoe M., Abe K., Kai K., Blobel H. (1995). Dermonecrotic activity of a cell wall preparation from Fusobacterium necrophorum. Lett Appl Microbiol20:145-147.
69.
Karanas YL, Yim KK, Shuster BA, Lineaweaver WC (1995). Lemierre's syndrome: a case of postanginal septicemia and bilateral flank abscesses. Ann Plastic Surg35:525-528.
70.
Kornman KS, Loesche WJ (1980). The subgingival microbial flora during pregnancy. J Periodont Res15:111-122.
71.
Lemierre A. (1936). On certain septicemias due to anaerobic organisms. Lancet1:701-703.
72.
Limongelli WA, Clark MS, Williams AC (1976). Noma-like lesion in a patient with chronic lymphocytic leukemia. Oral Surg41:40-51.
73.
Listgarten MA (1965). Electron microscopic observations on the bacterial flora of acute necrotizing ulcerative gingivitis. J Periodontol36:328-339.
74.
Listgarten MA, Socransky SS (1964). Ultrastructural characteristics of a spirochete in the lesion of acute necrotizing gingivostomatitis. Arch Oral Biol9:95-96.
75.
Listgarten MA, Lewis DW (1967). The distribution of spirochetes in the lesion of acute necrotizing ulcerative gingivitis: an electron microscopic and statistical survey. J Periodontol38:379-386.
76.
Loesche WJ, Syed SA, Laughon BE, Stoll J. (1982). The bacteriology of acute necrotizing ulcerative gingivitis. J Periodontol53:223-230.
77.
MacDonald JB (1962). On the pathogenesis of mixed anaerobic infections of mucous membranes. Ann R Coll Surg31:361-378.
78.
Malberger E. (1967). Acute infectious oral necrosis among young children in the Gambia, West Africa. I Periodont Res2:154-162.
79.
Marck KW, de Bruijn HP, Schmid F., Meixner J., Van Wijhe M., van Poppelen RHM (1998). Noma: the Sokoto approach. Eur J Plast Surg21:277-281.
80.
Meier CA (1996). Mechanisms of immunosuppression by glucocorticoids. Eur J Endocrinol10:134-150.
81.
Meis JF, Polder TW, van der Kar P., Hoogkamp-Korstanje JA (1993). Multiple brain abscesses and bacteremia in a child due to Fusobacterium necrophorum. Infection21:174-176.
82.
Melnick SL, Roseman JM, Engel D., Cogen RB (1988). Epidemiology of acute necrotizing ulcerative gingivitis. Epidemiol Rev10:191-211.
83.
Moore WEC (1993). Investigation of the influences of puberty, genetics and environment on the composition of subgingival periodontal floras. Infect Immun61:2891-2898.
84.
Morley D. (1969). Severe measles in the tropics. Br Med J1:297-300.
85.
Oliphant JC, Parsons R., Smith GR (1984). Aetiological agents of necrobacillosis in captive wallabies. Res Vet Sci36:382-384.
86.
Osuji OO (1990). Necrotizing ulcerative gingivitis and cancrum oris (noma) in Ibadan, Nigeria. J Periodontol61:769-772.
87.
Price SB, McCallum RE (1986). Enhancement of Bacteroides intermedius growth by Fusobacterium necrophorum. J Clin Microbiol23:22-28.
88.
Roberts DS (1967a). The pathogenic synergy of Fusiformis necrophorus and Corynebacterium pyogenes. 1. Influence of the leucocidal exotoxin of F. necrophorus. Br J Exp Pathol48:665-673.
89.
Roberts DS (1967b). The pathogenic synergy of Fusiformis necrophorus and Corynebacterium pyogenes. II. The response of F. necrophorus to a filterable product of C. pyogenes. Br J Exp Pathol48:674-679.
90.
Rotbarth HA, Levin MJ, Jones JF, Hayward AR, Allan J., McLane MF, et al. (1986). Noma in children with severe combined immunodeficiency. J Pedr109:596-600.
91.
Ruben MP, Miller M. (1964). Noma: its association with nutritional deprivation and physical debilitation. Oral Surg Oral Med Oral Pathol18:167-175.
92.
Sabiston CB Jr (1986). A review and proposal for etiology of acute necrotizing gingivitis. J Clin Periodontol13:727-734.
93.
Salmi AA (1997). Suppression of T-cell immunity after measles infection: is the puzzle solved? Trends Microbiol5:85-86.
94.
Sawyer DR, Nwoku AL, Rotimi VO, Hagen JC (1986). Comparison of oral microflora between well-nourished and malnourished Nigerian children. J Dent Child Nov/Dec:439-443.
95.
Scrimshaw NS (1975). Nutrition and infection. Prog Food Nutr Sci1:393-420.
96.
Seidenfeld SM, Sutker WL, Luby JP ( 1982). Fusobacterium necrophorum septicemia following oropharyngeal infection. J Am Med Assoc248:1348-1350.
97.
Selye H. (1953). Effect of cortisone and somatotrophic hormone upon the development of a noma-like condition in the rat. Oral Surg6:557-561.
98.
Sheiham A. (1966). An epidemiological survey of acute necrotizing gingivitis in Nigerians. Arch Oral Biol11:937-942.
99.
Shinjo T., Misawa N., Goto Y. ( 1996). Comparison of haemolytic acitivity between Fusobacterium necrophorum subsp. necrophorum and Fusobacterium necrophorum subsp. funduliforme in vitro and in vivo. Acta Pathol Microbiol Immunol Scand104:75-78.
100.
Simon PC, Stovell PL (1969). Diseases of animals associated with Sphaerophorus necrophorus: characteristics of the organisms. Vet Bull (London)39:311-315.
101.
Slots J. (1981). Enzymatic characterization of some oral and nonoral Gram-negative bacteria with the API ZYM system. J Clin Microbiol14:228-294.
102.
Slots J. (1986). Bacterial specificity in adult periodontitis-a summary of recent work. J Clin Periodont13:912-917.
103.
Slots J., Wikstrom M., Dahlen G. (1986). The occurrence of Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Bacteroides intermedius in destructive periodontal disease in adults. J Clin Periodontol13:570-577.
104.
Smith LDS (1975). The pathogenic anaerobic bacteria. 2nd ed. Springfield, IL: Charles C. Thomas, p. 359.
105.
Smith GR, Turner A., Cinderey R. (1986). Susceptibility of wallabies to Fusobacterium necrophorum. Vet Rec118:691-693.
106.
Sooriyamoorthy M., Gower DB (1989). Hormonal influences on gingival tissue relationships to periodontal disease. J Clin Periodontol16:201-208.
107.
Sundqvist G. (1976). Bacteriological studies of necrotic dental pulps (thesis). Umea, Sweden: Umea University7, pp. 1-94.
108.
Sung EC, Sung BY ( 1947). Some clinical observations concerning noma. Am J Orthod Oral Surg33:284-292.
109.
Taiwo JO (1993). Oral hygiene status and necrotizing ulcerative gingivitis in Nigerian children. J Periodontol63:1071-1074.
110.
Tan ZL, Nagaraja TG, Chengappa MM, Smith JS (1994). Biological and biochemical characterization of Fusobacterium necrophorum leukotoxin. Am J Vet Res55:515-521.
111.
Tan ZL, Nagaraja TG, Chengappa MM (1996). Fusobacterium necrophorum infections: virulence factors, pathogenic mechanism and control measures. Vet Res Commun20:113-140.
Thurnham DI (1997). Impact of disease on markers of micronutrient status. Proc Nutr Soc56:421-431.
114.
Van Oosten MAC, Mombelli A., Gusberti FA, Lang NP ( 1988). Black-pigmented Bacteroides and spirochetes in the subgingival microbiota of prepubertal school children. J Periodont Res23:199-203.
115.
Van Winkelhoff AJ Carlee AW, de Graaff J. (1985). Bacteroides endodontalis and other black-pigmented Bacteroides species in odontogenic abscesses. Infect Immun49:494-497.
116.
Vining RF, McGrinley RA (1985). Hormones in saliva. CRC Crit Rev Clin Lab Sci23:95-146.
117.
Wahren A., Bernholm K., Holme T. (1971). Formation of proteolytic activity in continuous culture of Sphaephorus necrophorus. Acta Pathol Microbiol Scand79(Sect B):391-398.
118.
Weaver GH, Tunnicliff R. (1907). Noma. I Infect Dis4:8-35.
119.
Wennstrom JL, Dahlen G., Svensson J., Nyman S. (1987). Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Bacteroides intermedius: predictors of attachment loss? Oral Microbiol Immunol2:158-163.
120.
Whittle HC, Greenwood BM (1977). Persistent measles infection in malnourished children. Br Med J1:1633-1635.
121.
Whittle HC, Sanderford Smith ), Kogbe OI, Dossetor J., Duggan NM (1979). Severe ulcerative herpes of mouth and eyes following measles. Trans R Soc Trop Med Hyg73:66-69.
122.
WHO (1994a). Delphi Expert Consultation. Is noma today a public health problem? Unpublished report. WHO/HQ, Division of Noncommunicable Diseases, Responsible Officer for Noma Project. Geneva, Switzerland: WHO.
123.
WHO (1994b). Press kit, World Health Day. WHO/HQ, Division of Noncommunicable Diseases, Responsible Officer for Oral Health Programme. Geneva, Switzerland: WHO.
124.
WHO (1996). The Leishmaniases and Leishmania/HIV co-infections. WHO-OMS Fact Sheet No. 116. Geneva, Switzerland: World Health Organization.
125.
Zambon JJ, Reynolds M., Fisher JG, Shlossman M., Dunford R., Genco RJ (1988). Microbiological and immunological studies of adult periodontitis in patients with non-insulin-dependent diabetes mellitus. I Periodont59:23-31.
