Worm Therapy as a Treatment for Diabetic Foot Ulcer: Lessons Learned From the Banks of the Nile

Abstract

Dear Editor The diabetic foot ulcer, or syndrome in a better word, is a terrible complications of diabetes. The increasing worldwide prevalence of diabetes is in parallel with increased rate of diabetic foot ulcers, which is the cause of 85% of lower leg amputations. This complex process imposes a great burden on both patients and nations. It is worth recalling that “every 30 seconds a lower limb is lost to diabetes” as mentioned by Linda Siminerio, Chair of the International Diabetic Federation (IDF) BRIDGES Review Committee. Patients lose more than a leg as their activity is affected. Despite the global prevalence of this disease, there are some ethnic differences. In Egypt, the prevalence of diabetic foot ulcer is reported by IDF to be 6.8%. This rate of prevalence is high in absolute terms but low compared with that in developed countries where 1 in every 6 patient with diabetes will conflict an ulcer during lifetime (IDF), or with North America, where foot complications account for 20% of diabetic-related admissions. It is believed that diabetic foot ulcers occur in almost 25% of the patients with diabetes. The above-mentioned prevalence of diabetic foot ulcer in Egypt has been attributed to the poor footwear, tinea pedis, thick nails, lack of appropriate education to 90% of the diabetic patients, and the lack of regular follow-up sessions with the doctors on account of lack of provision. This setting should increase the prevalence; hence Egypt, with 4.4 million cases from 246 million of diabetic patients in the world, is one of the top 10 countries conflicted with diabetes. Interestingly, this rate of diabetic foot ulcer is occurring against a background of low prevalence of neuropathy and peripheral arterial diseases. What possible explanation could there be? It is likely that an ulcerprotective factor may exist. Chronic helminthic infection is a common problem among in Egypt. This condition provides a modified microenvironment with the drift of immune balance toward Th2 cells and related cytokines. This selective suppression of Th1 responses by inhibition of tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12) and selective augmentation of Th2 responses by potentiation of TGFbeta and IL-10 are of great value in the process of wound healing. Dominant Th2 immune arm, induced by hormonal status, may also be one possible explanation for the lower prevalence of diabetic foot ulcers in women compared with that in men, ignoring the greater exposure to foot irritants in men. The Th2-oriented microenvironment is associated with the recruitment of cells attracted by the signals derived from Th2-related cytokines, such as fibrocytes. The recruited fibrocytes participate in wound healing, angiogenesis, and fiber production, which eventually afford a healing phenotype to the wound. Furthermore, chronic helminthic infection has been shown to be associated with increased concentration of adenosine, a purinergic intermediate metabolite, with great potency in induction and maintenance of the above mentioned favored skewness of the immune balance. The promoted wound healing in the case of topical administration of adenosine receptor agonists is another clue toward the importance of Th2-related cytokines in the process of wound healing. Interestingly, the increased production of adenosine has been shown in the mice infected with chronic New World Leishmania. This worm-induced purinergic alteration makes a Th2 focus within the infected host, which is involved in the establishment of immune suppression needed for further maintenance of helminthic infection. This antiinflammatory environment is against the pro-inflammatory environment that exists in the milieu of recalcitrant diabetic foot ulcers. Despite these immune modulatory effects, adenosine exerts other ulcer-protective roles, for example, vasodilatation, neuroprotection, anti-ischemic properties, and induction of angiogenesis. These properties may also explain the low prevalence of the main predisposing factors to diabetic foot ulcer among Egyptians: neuropathy and peripheral arterial diseases. Perhaps this common problem in developing countries affords a protective role for diabetic foot ulcer. The prevalence of chronic helminthic infection among diabetic patients is not clear, but a survey about the probable ulcer-protective role of the worms will get more insight Letter to the Editor