Exploring the relationship between adipokines, cytokines, and Clostridium bacteria in the pathogenesis of cancrum oris
Abstract
Cancrum oris ( noma ) is a rapidly progressing, necrotizing orofacial infection that primarily affects malnourished chi l dren in impoverished regions. It begins as a gingival inflammation and advances to severe tissue destruction, often leading to facial disfigurement and high mortality rates. We i nvestigate the interplay of adipokines , cytokines, and Clostridium bacteria in the pathogenesis of cancrum oris to identify their roles in disease progression and potential therapeutic targets. This case-control study (September 1, 2024 – February 1, 2025) at Al- Habboubi Teaching Hospital and Nasiriyah General Hospital included 150 cancrum oris patients (60% males, 40% females) and 75 healthy controls. Clostridium spp. were isolated using b lood, MacConkey , an d anaerobic agar, id entified via biochemical tests, and quantified by colony counting. The study an a lyzed socio-demographic, adipokine , cytokine, bacterial load, hematological, and clinical parameters in cancrum oris patients and healthy controls. Patients had significantly lower socioeconomic status and higher malnutrition rates. Leptin and resistin were elevated, while adiponectin was reduced in patients. Cytokines (TNF-α, IL-6) were higher, while IL-10 was lower. Clostridium perfringens was significantly present in patients. Blood tests showed anemia, leukocytosis , and thrombocytosis . Oral ulceration (96%) and pain (89%) were the most severe symptoms. Cancrum oris is strongly associated with altered adipokine and cytokine levels, increased Clostridium perfringens load, and significant hematological changes, indicating immune dysregulation and severe infection. Elevated leptin and resistin suggest metabolic imbalance, while reduced adiponectin and IL-10 indicate impaired anti-inflammatory response, contributing to disease severity and tissue necrosis.References
Adesola, R. O., Ajibade, F. A., & Agaie, M. I. (2024). Noma (cancrum oris) in Africa: A newly added neglected tropical disease. Rare, 2, 100031.
Alasi, M. A., Aqyil, N. P., Oyeleke, A., Yahaya, M., Taiwo, A. O., & Legbo, J. N. (2024). Clinical presentation and treatment outcomes of necrotizing fasciitis: A prospective comparative study of children and adults in Sokoto. Journal of West African College of Surgeons, 15(1), 59–67.
Al-Mansoori, L., Al-Jaber, H., Prince, M. S., & Elrayess, M. A. (2021). Role of inflammatory cytokines, growth factors and adipokines in adipogenesis and insulin resistance. Inflammation, 45(1), 31–44.
Bala, M., Sulaiman, A. O., Taiwo, A. O., Braimah, R. O., Ibikunle, A. A., Bello, A. A., Abdulazeez, S. I., Olayemi, L. A., Jaafar, R., & Kaura, A. M. (2024). Demographic and socioeconomic determinants of noma (cancrum oris) and strategies to reverse the trend. Journal of Public Health and Primary Care, 5(2), 95–98.
Bhat, S. S., H. R., P., Koppolu, S., Ahmed, M. M., Nair, A. U., D., M., Nallathambi, N., S., Y., A., P., Prasad, R., & Mittal, G. (2024). Enhancing early detection of necrotizing soft tissue infections: The role of the laboratory risk indicator for necrotizing fasciitis (LRINEC) score. Cureus, 16(6), e61620.
Braun, U., Wiese, K. G., Merten, H.-A., & Timmermann, A. (2020). Anaesthetic care for noma (cancrum oris) – the disease, the airway and how to provide anaesthetic care without a clinical safety infrastructure. Trends in Anaesthesia and Critical Care, 31, 16–20.
Chukwuma, B. C., Mujtaba, B., Ibikunle, A. A., Taiwo, A. O., & Ogunsanya, A. (2021). Nutritional status and anemia in persons with cancrum oris. Nigerian Journal of Medicine, 30(6), 670–674.
Dominic, C., Farley, E., & Elkheir, N. (2021). More than 100 years of neglect: A bibliometric analysis of global research on noma (cancrum oris). Transactions of The Royal Society of Tropical Medicine and Hygiene, 116(5), 479–486.
Farley, E., Mehta, U., Srour, M. L., & Lenglet, A. (2021). Noma (cancrum oris): A scoping literature review of a neglected disease (1843 to 2021). PLoS Neglected Tropical Diseases, 15(12), e0009844.
Finegold, S. M., George, W. L., & Mulligan, M. E. (1985). Anaerobic infections part II. Disease-a-Month, 31(11), 1–97.
Fu, Y., Haider Rubio, A., Gscheider, C., Du Teil Espina, M., Flores Vallejo, R., van Dijl, J. M., & Gabarrini, G. (2022). Oral and dental infections: Bacteria. In: Rezaei, N. (Ed.). Encyclopedia of infection and immunity. Elsevier. Pp. 346–362.
Gebretsadik, H. G., & de Kiev, L. C. (2022). A retrospective clinical, multi-center cross-sectional study to assess the severity and sequela of noma / cancrum oris in Ethiopia. PLoS Neglected Tropical Diseases, 16(9), e0010372.
Gezimu, W., Demeke, A., & Duguma, A. (2022). Noma – a neglected disease of malnutrition and poor oral hygiene: A mini-review. SAGE Open Medicine, 10, 20503121221098110.
Grobusch, M. P., Adegbite, B. R., & Ntoumi, F. (2024). Central Africa. In: Petersen, E., Chen, L. H., & Schlagenhauf, P. (Eds.). Routledge handbook of infectious diseases. Routledge, London. Pp. 83–96.
James, G., Chen, X., Diwan, A., & Hodges, P. W. (2020). Fat infiltration in the multifidus muscle is related to inflammatory cytokine expression in the muscle and epidural adipose tissue in individuals undergoing surgery for intervertebral disc herniation. European Spine Journal, 30(4), 837–845.
Karched, M., Bhardwaj, R. G., Qudeimat, M., Al-Khabbaz, A., & Ellepola, A. (2022). Proteomic analysis of the periodontal pathogen Prevotella intermedia secretomes in biofilm and planktonic lifestyles. Scientific Reports, 12, 5636.
Li, H., Wu, G., Zhao, L., & Zhang, M. (2021). Suppressed inflammation in obese children induced by a high-fiber diet is associated with the attenuation of gut microbial virulence factor genes. Virulence, 12(1), 1754–1770.
M’Bondoukwé, N. P., Moutongo, R., Gbédandé, K., Ndong Ngomo, J. M., Hountohotegbé, T., Adamou, R., Koumba Lengongo, J. V., Pambou Bello, K., Mawili-Mboumba, D. P., Luty, A. J. F., & Bouyou-Akotet, M. K. (2022). Circulating IL-6, IL-10, and TNF-alpha and IL-10/IL-6 and IL-10/TNF-alpha ratio profiles of polyparasitized individuals in rural and urban areas of gabon. PLoS Neglected Tropical Diseases, 16(4), e0010308.
O’Brien, N. (2019). G306(P). Noma (cancrum oris) in a child with severe acute malnutrition in Northern Nigeria. Archives of Disease in Childhood, 104(S2), A125.
Onu, J. U., Aluh, D. O., & Ononiwu, C. N. (2023). Psychosocial aspects of noma (cancrum oris) in Sub-Saharan Africa: A scoping review. Tropical Doctor, 53(4), 470–474.
Otto, W. R., Behrens, E. M., Teachey, D. T., Lamson, D. M., Barrett, D. M., Bassiri, H., Lambert, M. P., Mount, S., Petrosa, W. L., Romberg, N., Sullivan, K. E., Topjian, A. A., Fisher, B. T., & Kajon, A. E. (2020). Human adenovirus 7-associated hemophagocytic lymphohistiocytosis-like illness: Clinical and virological characteristics in a cluster of five pediatric cases. Clinical Infectious Diseases, 73(7), e1532–e1538.
Phillips, R. S., Enwonwu, C. O., & Falkler, W. A. (2005). Pro- versus anti-inflammatory cytokine profile in African children with acute oro-facial noma (cancrum oris, noma). European Cytokine Network, 16(1), 70–77.
Reethega, L., Ganapathy, D., Duraisamy, R., & Velayudhan, A. (2021). Current understanding on the manifestations of cancrum oris: A review. Natural Volatiles and Essential Oils, 8(4), 7242–7248.
Ren, Y., Zhao, H., Yin, C., Lan, X., Wu, L., Du, X., Griffiths, H. R., & Gao, D. (2022). Adipokines, hepatokines and myokines: Focus on their role and molecular mechanisms in adipose tissue inflammation. Frontiers in Endocrinology, 13, 873699.
Sambreen, Z., Asghar, M., Rehan, H., Geetha, K. D., & Zameer, A. (2024). System vaccinology: Applications, trends, and perspectives. i-Manager’s Journal on Life Sciences, 3(2), 42–59.
Schaller, M. (2009). Other bacterial infections. In: Burgdorf, W., Plewig, G., Wolff, H. H., & Landthaler, M. (Eds.). Braun-Falco’s dermatology. Springer, Cham. Pp. 140–165.
Schneiderman, P. I., & Grossman, M. E. (2022). The clinician’s guide to dermatologic differential diagnosis. Springer International Publishing, Cham.
Siffeti, H., Taylor, C., & Sina, C. (2021). Nutrition-related disorders. In: Schmidt, E. (Ed.). Diseases of the oral mucosa. Springer, Cham. Pp. 497–504.
Silva, K. N., Twaddell, W. S., Powers, D. B., Mackowiak, P. A., Frayha, N., & Silhan, L. L. (2011). A 40-year-old man with a perforated cheek. The American Journal of the Medical Sciences, 341(5), 399–403.
Taori, T., Wadher, B., Maheshwari, S., Mohod, S., & Dangore, S. (2024). Pharmacological management of oral lesion. International Arab Journal of Dentistry, 15(1), 184–198.
Todorov, I., Bliznakova, D., Madjova, C., Tonchev, T., & Gospodinova, M. (2015). Oral cavity changes in the course of infectious diseases, during childhood. Scripta Scientifica Medicinae Dentalis, 1(2), 7–16.
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