Noma: a neglected scourge of children in sub-Saharan Africa.

Noma: a neglected scourge of children in sub-Saharan Africa C.O. Enwonwu1 Poverty is the single most important risk indicator for noma (cancrum oris), a severe gangrene of the soft and hard tissues of the mouth, face, and neighbouring areas. The risk factors associated with an increased probability of noma developing include the following: malnutrition, poor oral hygiene, and a state of debilitation resulting from human immunodeficiency virus (HIV) infection, measles, and other childhood diseases prevalent in the tropics. There are many similarities between noma and necrobacil- losis of the body surface of wallabies (Macropus reforgriseus), and it is proposed that noma results from oral contamination by a heavy load of Bacteroidaceae (particularly Fusobacterium necrophorum) and a consortium of other microorganisms. These opportunistic pathogens invade oral tissues whose defences are weakened by malnutrition, acute necrotizing gingivitis, debilitating conditions, trauma, and other oral mucosal ulcers. The current escalation in the incidence of noma in Africa can be attributed to the worsening economic crisis in the region, which has adversely affected the health and well-being of children through deteriorating sanitation, declining nutritional status and the associated immunosuppres- sion, and increased exposure to infectious diseases. Prevention of noma in Africa will require measures that address these problems, and most importantly, eliminate faecal contamination of foods and water supplies. Introduction Noma (from the Greek nomen, "to devour") is a severe gangrene of the soft and hard tissues of the mouth, face, and neighbouring areas. This disease, also known as "cancrum oris", was described by Tourdes in 1848 as a "gangrenous affection of the mouth, especially attacking children in whom the constitution is altered by bad hygiene and serious ill- ness, especially from the eruptive fevers, beginning as an ulcer of the mucous membrane with oedema of the face, extending from within out, rapidly des- troying the soft parts and the bone, and almost always quickly fatal..." (1). This description is still very accurate today, except for the markedly reduced mortality rate resulting from the timely administra- tion of appropriate antibiotic therapy. Survivors of the disease may exhibit facial mutilation, impaired growth of the facial skeleton, nasal regurgitation of food, leakage of saliva, defective speech, and chew- ing difficulties. Reconstructive surgery of the resulting deformity is very costly, and the results are often less than satisfactory in terms of improvement in the patient's quality of life. I Professor of Biochemistry, University of Maryland, 666 W. Bal- timore Street, Baltimore, MD 21201, USA; Formerly: Director, Nigerian Institute for Medical Research, Yaba, Nigeria. Requests for reprints should be sent to Professor Enwonwu at the Univer- sity of Maryland. Reprint No. 5631 Noma was well known in Europe and North America some centuries ago (1), but today is virtual- ly nonexistent in developed countries. In marked contrast, the disease is still frequently seen in devel- oping countries, especially in sub-Saharan Africa, where it occurs almost exclusively among poor chil- dren, usually aged 3-10 years (1-7). More ominous are recent data from WHO that suggest an escalating increase in the incidence of noma in developing countries, particularly in several famine-stricken parts of Africa (M.H. Leclercq, personal communica- tion, 1994). In November 1992, WHO underscored the urgency of the situation by initiating a global information campaign on noma. Also in 1992, the WHO/Federation Dentaire Intemationale (FDI) Joint Working Group on Intemational Collaboration for Oral Health Research identified the disease as a major problem that would most benefit from shared intemational research, resources, and expertise (8). This view was reaffirmed on World Health Day 1994 (M.H. Leclercq, personal communication, 1994). Some workers hold that noma begins as a pur- plish-red spot or indurated papule on the alveolar margin, most frequently in the premolar-molar region (1). The papule breaks down into an ulcer, which then extends to the labiogingival fold and onto the mucosal surfaces of the cheeks and lips (1, 2, 4, 9). Other workers maintain that noma of the face (cancrum oris) always starts as acute necrotizing gin- givitis (ANG), a severe, painful form of gingivitis characterized by bleeding and necrosis of the inter- Bulletin of the World Health Organization, 1995, 73 (4): 541-545 © World Health Organization 1995 541 C.O. Enwonwu proximal papillae (4-6, 9). The early features of can- crum oris include soreness of the mouth, a swollen, tender, painful lip or cheek, a foul-smelling purulent discharge, and a bluish-black discoloration of the skin in the affected area (1, 2). The gangrene, once started, establishes itself rapidly, often in a matter of days, but remains remarkably well demarcated. Fol- lowing separation of the soft tissue slough, seques- tration of the exposed bone and teeth occurs rapidly. In developing countries, noma is a neglected health problem that robs many children, particularly in Africa, of their future. In this review, widely held views on the cause of noma are reappraised in the light of recent observations. Also, a readily testable hypothesis is proposed, which suggests that in the presence of certain specific microorganisms any oral mucosal ulcer, and not only ANG, is potentially capable of evolving into cancrum oris in a malnour- ished, immunosuppressed child Risk factors for noma An important risk indicator for noma in African chil- dren is poverty (1, 9). The known risk factors asso- ciated with an increased probability of the disease developing in a given individual include malnutrition (particularly protein-energy malnutrition and vita- min A deficiency), poor oral hygiene, and a state of debilitation, often resulting from malaria, measles, and other childhood diseases prevalent in the tropics (1, 2, 6, 10, 11). The general hypothesis is that the interaction and/or increased virulence of certain spe- cific microorganisms in the periodontal/oral mucosal environment of a susceptible host is an essential pre- requisite for the genesis of noma. It has been suggested that ANG (12) is an important antecedent lesion of noma (1-5). Contrary to the situation in industrialized countries, where ANG is found mainly among young adults (12, 13), in developing countries it occurs almost exclusively among socioeconomically disadvantaged children (1, 2, 10). Recent hospital-based studies in Nigeria sug- gest that the incidence of ANG is increasing among children (2, 14, 15). The etiology of this condition is still poorly defined, with the suspected predisposing factors including stress, poor oral hygiene, malnutri- tion, and impaired immune function (12, 15, 16). In recent years, there has been a global increase in the incidence of ANG associated with human immuno- deficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (17, 18). The reported frequency of ANG among those infected with HIV varies from 4.3% to 16.0% (17-19). None the less, in both HIV- positive and HIV-negative individuals, only a very small number of ANG cases evolve into noma (2, 6, 10, 17, 20), suggesting that in this potential risk group, one or more unidentified factors are necessary for its occurrence. Consistent with this is the obser- vation made by Pindborg et al. that noma could occur in South Indian children without any evidence of pre-existing ANG (20). Similarly, not all debili- tated malnourished children with poor oral hygiene develop noma (6, 9, 10, 20). Reappraisal of the etiology of noma The remarkable speed with which noma establishes itself, and the very marked foul odour associated with it, suggest that a collagenase-type of enzyme, usually elaborated by anaerobic microorganisms is involved. Noma may therefore be a polymicrobial infection caused by Bacteroidaceae (particularly Fusobacterium necrophorum and Prevotella melani- nogenica) and a consortium of other organisms. F. necrophorum, a Gram-negative, nonspore-forming, nonmotile, strictly anaerobic pleomorphic organism, produces a leukocidin, as well as butyric acid as the main metabolic end-products (21). Bacteroides spp. produce a wide range of destructive metabolites, e.g., collagenase, fibrinolysin, endotoxin, hydrogen sulfide, indole, ammonia, fatty acids, proteases ca- pable of degrading the immunoglobulins and comple- ment factors, as well as substances inhibiting neutro- phil chemotaxis (21, 22). F. necrophorum could be the key microorganism in causing noma. Its infectivity is markedly enhanced by the simultaneous presence of other bacteria, ranging from strict aerobes to facultative and strict anaerobes (23), including Cory- nebacterium pyogenes, Pseudomonas aeruginosa, F. nucleatum, Escherichia coli, P. melaninogenica, Bacteroides fragilis, Bacillus cereus and Staphylo- coccus aureus (23). In instances when noma-like lesions have occurred in stressed, malnourished non- human primates, the key anaerobes isolated have been Bacteroides spp. and Fusobacterium spp., with P. aeruginosa and S. aureus as the predominant aerobes (3, 24). F. necrophorum occurs in cases of foot rot in many domestic animals (21), as a commensal in the gut of herbivores (25), in human and animal faecal remains (25), and has been cultured occasionally from periodontal lesions (26). It has very little ability to invade intact epithelium, and infection usually arises from contamination of damaged mucous membrane or skin (23, 25). In many ways noma is similar to necrobacillosis of the body surface of wallabies (Macropus reforgri- seus), which is characterized by a purulent, necro- WHO Bulletin OMS. Vol 73 1995542 Noma: a neglected scourge of children in sub-Saharan Africa tizing lesion often affecting the periodontal tissues, maxilla, mandible, face, hind limbs and gastrointes- tinal tract (25, 27-29). It is a polymicrobial infection, F. nucleatum being the commonest organism isolated, often in pure culture (28). In a series of 27 wallabies with necrobacillosis, 14 were affected in the face; F. nucleatum and various Bacteroides spp. were the predominant organisms, occuring in 69% and 48%, respectively, of the facial lesions (30). Rosen has noted that in kangaroos, the microorgan- isms associated with necrobacillosis, especially F. nucleatum, are opportunistic pathogens that can only invade oral tissues if there is local weakening of defences resulting from abrasions, debilitating condi- tions, or trauma that may be a consequence of the eruption of molar teeth (27). It is also relevant that outbreaks of necrobacillosis in wild kangaroos in Australia occur during unusually prolonged droughts when the animals tend to congregate around water holes and there is heavy faecal contamination of arti- ficial feeding areas (27, 28). Also, more deaths from necrobacillosis occur among wallabies in severely cold weather when daily food supplements are need- ed to make good any deficits in natural feeding (25). There are similarities between noma and tropical skin ulcer, a painful, disabling condition occurring on the lower legs and feet of impoverished children in developing countries (31), and believed to result from faecal contamination of abrasions on the skin (32). F. nucleatum (31) and F. necrophorum (33) are reported to play a key role in causing tropical ulcer, and both these microorganisms have common anti- gens (26). Discussion For diseases such as noma, with multiple risk fac- tors, testing for the etiologic role of individual fac- tors is usually inadequate unless interactive associa- tions between factors are considered. The most commonly reported illness preceding noma in Afri- can children is measles (1, 2), an infection that is not only immunosuppressive but which also elicits marked reduction in food intake (34) as well as sig- nificantly impairing mobilization of vitamin A from hepatic stores (35). The interactions between malnutrition and measles, even when the former is moderate or incipient, are greater and have far more serious consequences than for other infectious dis- eases of childhood (35, 36) Malnourished African children who suffer a severe attack of measles are prone to develop deep, erosive ulcers of the mouth and eyes (37). Similarly, protein-energy malnutrition and/or vitamin A deficiency can cause progressive damage to mucosal tissues, including oral mucosa (35, 36). Thus, malnutrition acting in concert with an infection such as measles can readily lower the resistance of oral mucosa to colonization and inva- sion by the potential pathogens of noma. A number of ecological and behavioural vari- ables intensify the risk of oral and gastrointestinal diseases in impoverished sub-Saharan African com- munities (38). These include poor food supply and preservation, reliance on inadequate and often heavi- ly contaminated water supplies, close proximity of livestock to humans, earth-floored residential units, and very poor disposal of human and animal faeces (3, 38, 39). Over the last decade, malnutrition has remained stable in South America, decreased in Asia and Central America, but has increased in sub- Saharan Africa as a result of long-term decline in food supplies (40). The International Monetary Fund (IMF), as part of its lending policies, has imposed structural adjustments on the economies of most African countries (41, 42). The resulting economic crisis is adversely affecting the health and well-being of children by causing increasingly overcrowded living conditions, deteriorating sanitation, declining nutritional status, and increased exposure to infec- tious diseases. Malnutrition in sub-Saharan Africa is now severe and getting worse in several countries (43). The most pressing health problem in such com- munities is therefore the well-known synergism of malnutrition and infection (36), as typified by noma. In rural and poor urban settings in Africa, sup- plies of water are often obtained from polluted streams and shallow underground wells; also, tradi- tional weaning foods are microbiologically hazard- ous, being heavily contaminated with faecal organ- isms (44, 45). Microbial contamination of foods in developing countries occurs more readily during the rainy season (45, 46); it is perhaps not fortuitous that the reported frequency of noma in Nigerian children is highest during the rainy season (1, 47). Prevention of noma depends on implementing measures aimed at eradicating malnutrition, improv- ing oral hygiene status, and minimizing damage to the oral mucosa, as well as avoiding contamination of the oral environment by a heavy load of Bacteroi- daceae, particularly F. necrophorum. Among vulner- able children, not only ANG but also other oral mucosal ulcers and traumatic lesions, including the trauma of tooth eruption, should be considered to be potentially capable of evolving into noma. An impor- tant public health measure that will help to contain the current upsurge of noma among sub-Saharan African children is the prevention of faecal contami- nation of water and weaning foods, carried out con- currently with reduction in host susceptibility through improved nutrition and oral hygiene practices. WHO Bulletin OMS. Vol 73 1995 543 C.O. Enwonwu Acknowledgements The author is supported, in part, by USPHS Research Grant DE-09653 awarded by the National Institutes of Health, Bethesda, MD. I thank Ms Teri Folks for her excel- lent secretarial assistance. Resume Le noma: un flMau neglige de l'enfance en Afrique subsaharienne La pathog6nie du noma (cancrum oris) - une gangrene grave des tissus mous et des os de la bouche, de la face et des r6gions adjacentes - est encore tres mal connue. Selon une hypothese g6nerale, une association d'un ou plusieurs micro- organismes sp6cifiques dans le milieu buccal/ p6riodontique d'un h6te receptif serait la condition indispensable a son apparition. La pauvret6 est un indicateur crucial du risque de noma dans les pays en developpement, la probabilit6 d'apparition de cette maladie aug- mentant en pr6sence des facteurs suivants: mal- nutrition, mauvaise hygiene buccale, gingivite ulc6ro-n6crotique, et etat d'affaiblissement dO au paludisme, a la rougeole, a l'infection par le VIH (virus de l'immunod6ficience humaine), et a d'au- tres maladies immunosuppressives pr6valentes dans les pays en d6veloppement les plus pau- vres. Neanmoins, seuls quelques rares sujets pre- sentant ces facteurs de risque font un noma. Dans cette breve mise au point, I'auteur fait observer que le noma partage de nombreuses caract6ristiques avec la n6crobacillose cutanee du wallaby (Macropus reforgriseus) et avance une hypothese 6tiologique faisant intervenir une conta- mination massive de la bouche par des Bacteroi- daceae (en particulier Fusobacterium necropho- rum et quelques Bacteroides spp.) et une association de divers autres micro-organismes qui concourent a renforcer leur infectiosit6. F. necro- phorum pourrait etre le micro-organisme c16 dans le processus d'apparition du noma. Tous ces agents pathogenes opportunistes envahissent les tissus de la bouche a la faveur d'une faiblesse locale des d6fenses due a la malnutrition, a des maladies d6bilitantes, a une gingivite ulc6ro- n6crotique et a d'autres ulc6rations et trauma- tismes buccaux. Chez des enfants sensibles, non seulement la gingivite ulc6ro-n6crotique mais aussi d'autres ulc6rations et l6sions traumatiques buccales sont consid6r6es comme susceptibles de conduire au noma. En Afrique, l'incidence du noma a augmente ces dernieres ann6es du fait de I'aggravation de la crise 6conomique, qui a eu des effets nocifs sur la sante et le bien-etre des enfants par une det6- rioration des conditions d'hygiene et de l'6tat nutri- tionnel, et par une exposition accrue aux maladies infectieuses. La prevention du noma chez les enfants africains repose sur la mise en ceuvre de mesures de sant6 publique appropri6es, afin d'ameliorer le niveau d'hygiene bucco-dentaire, de r6duire la malnutrition et les lesions de la mu- queuse buccale, de controler l'incidence et la gra- vit6 des maladies infectieuses et, surtout, d'6limi- ner la contamination f6cale des aliments et de l'eau. References 1. Tempest MN. Cancrum oris. British journal of sur- gery, 1966, 53: 949-969. 2. Enwonwu CO. 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