A Three-Step Multimodal Biofilm-Focused Protocol in Complex Acute and Chronic Wounds: Clinical Outcomes from ICU Real-World Patients

The presence of biofilms in chronic non-healing wounds, has been identified through in vitro model and in vivo animal data. However, human chronic wound studies are under-represented and generally report low sample sizes. For this reason we sought to ascertain the prevalence of biofilms in human chronic wounds by undertaking a systematic review and meta-analysis. Our initial search identified 554 studies from the literature databases (Cochrane Library, Embase, Medline). After removal of duplicates, and those not meeting the requirements of inclusion, nine studies involving 185 chronic wounds met the inclusion criteria. Prevalence of biofilms in chronic wounds was 78.2 % (confidence interval [CI 61.6-89, p<0.002]). The results of our meta-analysis support our clinical assumptions that biofilms are ubiquitous in human chronic non-healing wounds.

The potential impact of biofilm on healing in acute and chronic wounds is one of the most controversial current issues in wound care. A significant amount of laboratory-based research has been carried out on this topic, however, in 2013 the European Wound Management Association (EWMA) pointed out the lack of guidance for managing biofilms in clinical practice and solicited the need for guidelines and further clinical research. In response to this challenge, the Italian Nursing Wound Healing Society (AISLeC) initiated a project which aimed to achieve consensus among a multidisciplinary and multiprofessional international panel of experts to identify what could be considered part of 'good clinical practice' with respect to the recognition and management of biofilms in acute and chronic wounds. The group followed a systematic approach, developed by the GRADE working group, to define relevant questions and clinical recommendations raised in clinical practice. An independent librarian retrieved and screened approximately 2000 pertinent published papers to produce tables of levels of evidence. After a smaller focus group had a multistep structured discussion, and a formal voting process had been completed, ten therapeutic interventions were identified as being strongly recommendable for clinical practice, while another four recommendations were graded as being 'weak'. The panel subsequently formulated a preliminary statement (although with a weak grade of agreement): 'provided that other causes that prevent optimal wound healing have been ruled out, chronic wounds are chronically infected'. All members of the panel agreed that there is a paucity of reliable, well-conducted clinical trials which have produced clear evidence related to the effects of biofilm presence. In the meantime it was agreed that expert-based guidelines were needed to be developed for the recognition and management of biofilms in wounds and for the best design of future clinical trials. This is a fundamental and urgent task for both laboratory-based scientists and clinicians.

Chronic wounds, and among these infected diabetic foot ulcers, are a worldwide problem. The poor treatment outcomes result in high healthcare costs, amputations, a decreased quality of life, and an increased mortality. These outcomes are influenced by several factors, including biofilm formation. A biofilm consists of pathogenic bacteria that are encased in an exopolysaccharide layer and communicate through secretion of signaling molecules. Bacteria that live in a biofilm are refractory to host responses and treatment. We performed a nonsystematic review of the currently published to-date medical biofilm literature. The review summarizes the evidence of biofilm in chronic wounds, the role of biofilm in wound healing, detection of biofilm, and available antibiofilm treatments. Articles containing basic science and clinical research, as well as systematic reviews, are described and evaluated. The articles have variable levels of evidence. All articles have been peer reviewed and meet the standards of evidence-based medicine. Both animal and human studies have identified biofilm in chronic wounds and have suggested that healing might be influenced by its presence. A promising development in biofilm detection is rapid molecular diagnostics combined with direct microscopy. This technique, rather than classic culture, might support individualized treatment in the near future. A wide range of treatments for chronic wounds also influence biofilm formation. Several agents that specifically target biofilm are currently being researched. Biofilm formation has a substantial role in chronic wounds. Several diagnostic and therapeutic methods against biofilm are currently being developed.

Chronic wounds including diabetic foot ulcers, pressure ulcers, and venous leg ulcers are a worldwide health problem. It has been speculated that bacteria colonizing chronic wounds exist as highly persistent biofilm communities. This research examined chronic and acute wounds for biofilms and characterized microorganisms inhabiting these wounds. Chronic wound specimens were obtained from 77 subjects and acute wound specimens were obtained from 16 subjects. Culture data were collected using standard clinical techniques. Light and scanning electron microscopy techniques were used to analyze 50 of the chronic wound specimens and the 16 acute wound specimens. Molecular analyses were performed on the remaining 27 chronic wound specimens using denaturing gradient gel electrophoresis and sequence analysis. Of the 50 chronic wound specimens evaluated by microscopy, 30 were characterized as containing biofilm (60%), whereas only one of the 16 acute wound specimens was characterized as containing biofilm (6%). This was a statistically significant difference (p<0.001). Molecular analyses of chronic wound specimens revealed diverse polymicrobial communities and the presence of bacteria, including strictly anaerobic bacteria, not revealed by culture. Bacterial biofilm prevalence in specimens from chronic wounds relative to acute wounds observed in this study provides evidence that biofilms may be abundant in chronic wounds.

Following confirmation of the presence of biofilms in chronic wounds, the term biofilm became a buzzword within the wound healing community. For more than a century pathogens have been successfully isolated and identified from wound specimens using techniques that were devised in the nineteenth century by Louis Pasteur and Robert Koch. Although this approach still provides valuable information with which to help diagnose acute infections and to select appropriate antibiotic therapies, it is evident that those organisms isolated from clinical specimens with the conditions normally used in diagnostic laboratories are mainly in a planktonic form that is unrepresentative of the way in which most microbial species exist naturally. Usually microbial species adhere to each other, as well as to living and non-living surfaces, where they form complex communities surrounded by collectively secreted extracellular polymeric substances (EPS). Cells within such aggregations (or biofilms) display varying physiological and metabolic properties that are distinct from those of planktonic cells, and which contribute to their persistence. There are many factors that influence healing in wounds and the discovery of biofilms in chronic wounds has provided new insight into the reasons why. Increased tolerance of biofilms to antimicrobial agents explains the limited efficacy of antimicrobial agents in chronic wounds and illustrates the need to develop new management strategies. This review aims to explain the nature of biofilms, with a view to explaining their impact on wounds.

Case 5: non-healing traumatic wound.

Case 6: ureteral cutaneous fistula.

The adverse impact of chronic wounds is felt worldwide. The concerns for advanced wound care product are progressively increasing due to factors such as value for money spent in wound care products. Acute and Chronic wounds are managed in most health facilities in Ghana with sodium chloride (0.9%) infusion solution and povidone iodine fortified with metronidazole solution. The procedure is usually done by the nurse cleaning the wound with the saline solution wet gauze or cotton and then covered with the povidone iodine wet gauze for acute and chronic wounds. For chronic infected wounds, the wound is usually cleaned with saline solution and covered with wet gauze saline or currently with neomycin wound care spray or powdered antibiotics applied on the wounds. But it is popular as many wounds are covered with povidone iodine after wound cleaning in wound care practices in Ghana. Despite all these efforts, many wounds, especially chronic type wounds take a very long time to heal or sometimes fails to heal which reduce the quality of life of the people suffering from the menace. When it happens in this way, many resort to the use of local remedies to cause the wounds to heal but no avail, especially in Ghana where advanced treatment is scare. It is against this background that focal research in wound care was done in Ghana to come out with an innovative pharmaceutical wound care product effective for chronic and acute wounds healing to improve the quality of life of people as global burden of wounds escalates. In a Blind Observational Study for a period of five years in Ghana to observe the wound care products efficacy to heal wounds especially chronic types, the objective of the study was to examine a new product efficacy in chronic wound healing in the targeted population of patients with wounds. A product that has dual purpose of wound care as a cleaning and application agent, also has unique product pharmaceutical characteristics. A scalable, easy- to- use, multi-purpose, multi-use and cost-effective product, able to address the barriers or problems of wounds healing. The areas of consideration as far as wound care are concerned included: The study also sought to observe the product ability to control wound pains, control wound bleeding, control and prevent wound infection, remove wound debris, remove wound exudates effecting wounds healing at reduced healing time and with minimal scar in varied targeted patients’ population. Again, to observe the product with outcome of which to mitigate the long-term effect of chronic wounds like recurrent hospitalizations, financial burden, amputations, deformity, and frequent visit to hospital for wound care. One product, 9G Wound Solution (a cleaning and application product) manufactured by Pat J Health Company Limited, Ghana, was effective in wounds healing, especially, effective chronic wounds healing. The product was used to subject varied patients’ population with wounds on randomized basis, for wound care, and through observation the direct short, intermedial and long-term outcomes recorded of product effectiveness recorded. The outcome reported included control of wound pains, control of wound odor, control of bleeding, control of wound infection, removal of wounds exudates, removal of wound debris and ultimately reduced wound healing time to prevent wounds complications like amputations. The study was progressively extended across 10 regions in Ghana to cover 500 patient population with varied wounds. Patients’ population included those with Diabetic ulcers, Burns, pressure ulcers, venous ulcers, herpes zoster skin ulcers, Perineum wounds, Surgical abdomen-pelvic wounds, Traumatic wounds, Buruli Ulcers, gas gangrene wounds, and Mouth ulcers. The outcome of using the new wound care product were directly observed for the study period. By this observational study, the new product was observed to be superior to the controls as this product was able to heal 99% patients who had wounds, especially chronic wounds for many years, including 20years-old wound at reduced healing rate with no reoccurrence within the study period. The product scientifically readily released to the wound environment modulators capable to address the problems or barriers of wounds and simultaneously promoting modulators effective for wound healing. The product was not only effective in chronic wound healing at reduced time but also controlled wound pains shortly, controlled wound odor shortly, stopped wound bleeding, fought and controlled wound infection. However, using the product needed change of wound dressing every two days. The long-term effect of the product on target population not conclusively observed within the period of the research. We need to continuously observe the reported long-term effect of the product efficacy.

Ectopic localization of matrix metalloproteinase-9 in chronic cutaneous wounds

The incidence, cost, morbidity, and mortality associated with non-healing of chronic skin wounds are dramatic. With the increasing numbers of people with obesity, chronic medical conditions, and an increasing life expectancy, the healthcare cost of non-healing ulcers has recently been estimated at $25 billion annually in the United States. The role played by bacterial biofilm in chronic wounds has been emphasized in recent years, particularly in the context of the prolongation of the inflammatory phase of repair. Rapid high-throughput genomic approaches have revolutionized the ability to identify and quantify microbial organisms from wounds. Defining bacterial genomes and using genetic approaches to knock out specific bacterial functions, then studying bacterial survival on cutaneous wounds is a promising strategy for understanding which genes are essential for pathogenicity. When an animal sustains a cutaneous wound, understanding mechanisms involved in adaptations by bacteria and adaptations by the host in the struggle for survival is central to development of interventions that favor the host. Characterization of microbiomes of clinically well characterized chronic human wounds is now under way. The use of in vivo models of biofilm-infected cutaneous wounds will permit the study of the mechanisms needed for biofilm formation, persistence, and potential synergistic interactions among bacteria. A more complete understanding of bacterial survival mechanisms and how microbes influence host repair mechanisms are likely to provide targets for chronic wound therapy.

Despite the extensive arsenal of antibacterial drugs and the diversity of new wound treatment technologies, it is fair to say that the problem of wound infection has not lost its relevance. As a rule, in patients with concomitant diseases (obesity, diabetes, sensory neuropathies, autoimmune diseases, etc.), the healing of wound defects is prolonged, which makes them especially vulnerable to infections. Wound infection is one of the decisive factors in the pathogenesis of chronic wounds associated with an increase in the number of multiresistant bacterial strains. Two most common wound pathogens are Pseudomonas aeruginosa and Staphylococcus aureus. Wound healing is mediated not only by complex coordinated cellular mechanisms, but also by the impact of the wound microbiome. Objective. Analysis of the mechanisms of pathogenicity and intermicrobial interactions of P. aeruginosa and S. aureus as a significant “instrument” of wound infection to identify priority strategies for antimicrobial therapy (combination antibacterial drugs, phage therapy, use of antimicrobial peptides etc.). Material and methods. A search and analysis of scientific literature for 2018­2025 was performed in the information resources PubMed, eLIBRARY.RU, Europe PMC, Web of Science, CyberLeninka. The search queries included the following combinations of words: for Russian­language publications chronic wound infection; biofilms in chronic wounds, pathophysiological mechanisms of wound healing; for English­language publications chronic wound infection, biofilms in chronic wounds, pathophysiological mechanisms of wound healing, chronic wound infection bacteria, acute and chronic wounds, P. aeruginosa, S. aureus, mechanisms of pathogenicity, virulent properties. Results and discussion. The review summarizes and presents the mechanisms of initiation of wound infection, determinants of virulence, pathogenicity, antibiotic resistance of P. aeruginosa and S. aureus, immune evasion strategies and features of intermicrobial interactions. Conclusions. Wound infections pose a significant global threat due to high rates of morbidity and mortality. P. aeruginosa and S. aureus remain the most common pathogens causing wound infections and form mixed biofilms that hamper their susceptibility to both antimicrobials and the host immune system. Both types of bacteria secrete a broad spectrum of virulence factors, including toxins and enzymes that facilitate their attachment to the wound surface and suppress the host immune response, leading to further tissue damage. Moreover, the spatial organization formed by these pathogens can influence their virulence properties and is key to understanding bacterial interactions within polymicrobial biofilms. Currently, combination antibacterial drugs, phage therapy, antimicrobial peptides, etc. are used to solve the problem of the growth of multidrug­resistant strains.

Honey is a viscous, supersaturated sugar solution derived from nectar gathered and modified by the honeybee, Apis mellifera. Honey has been used since ancient times as a remedy in wound care. Evidence from animal studies and some trials has suggested honey may accelerate wound healing. The objective was to determine whether honey increases the rate of healing in acute wounds (burns, lacerations and other traumatic wounds) and chronic wounds (venous ulcers, arterial ulcers, diabetic ulcers, pressure ulcers, infected surgical wounds). We searched the Cochrane Wounds Group Specialised Register (May 2008), CENTRAL (May 2008) and several other electronic databases (May 2008). Bibliographies were searched and manufacturers of dressing products were contacted for unpublished trials. Randomised and quasi randomised trials that evaluated honey as a treatment for any sort of acute or chronic wound were sought. There was no restriction in terms of source, date of publication or language. Wound healing was the primary endpoint. Data from eligible trials were extracted and summarised using a data extraction sheet by one author and independently verified by a second author. 19 trials (n=2554) were identified that met the inclusion criteria. In acute wounds, three trials evaluated the effect of honey in acute lacerations, abrasions or minor surgical wounds and nine trials evaluated the effect the honey in burns. In chronic wounds two trials evaluated the effect of honey in venous leg ulcers and one trial in pressure ulcers, infected post-operative wounds, and Fournier's gangrene respectively. Two trials recruited people with mixed groups of chronic or acute wounds. The poor quality of most of the trial reports means the results should be interpreted with caution, except in venous leg ulcers. In acute wounds, honey may reduce time to healing compared with some conventional dressings in partial thickness burns (WMD -4.68 days, 95%CI -4.28 to -5.09 days). All the included burns trials have originated from a single centre, which may have impact on replicability. In chronic wounds, honey in addition to compression bandaging does not significantly increase healing in venous leg ulcers (RR 1.15, 95%CI 0.96 to 1.38). There is insufficient evidence to determine the effect of honey compared with other treatments for burns or in other acute or chronic wound types. Honey may improve healing times in mild to moderate superficial and partial thickness burns compared with some conventional dressings. Honey dressings as an adjuvant to compression do not significantly increase leg ulcer healing at 12 weeks. There is insufficient evidence to guide clinical practice in other areas.

Despite a growing consensus that biofilms contribute to a delay in the healing of chronic wounds, conflicting evidence pertaining to their identification and management can lead to uncertainty regarding treatment. This, in part, has been driven by reliance on in vitro data or animal models, which may not directly correlate to clinical evidence on the importance of biofilms. Limited data presented in human studies have further contributed to the uncertainty. Guidelines for care of chronic wounds with a focus on biofilms are needed to help aid the identification and management of biofilms, providing a clinical focus to support clinicians in improving patient care through evidence-based medicine. A Global Wound Biofilm Expert Panel, comprising 10 clinicians and researchers with expertise in laboratory and clinical aspects of biofilms, was identified and convened. A modified Delphi process, based on published scientific data and expert opinion, was used to develop consensus statements that could help identify and treat biofilms as part of the management of chronic nonhealing wounds. Using an electronic survey, panel members rated their agreement with statements about biofilm identification and treatment, and the management of chronic nonhealing wounds. Final consensus statements were agreed on in a face-to-face meeting. Participants reached consensus on 61 statements in the following topic areas: understanding biofilms and the problems they cause clinicians; current diagnostic options; clinical indicators of biofilms; future options for diagnostic tests; treatment strategies; mechanical debridement; topical antiseptics; screening antibiofilm agents; and levels of evidence when choosing antibiofilm treatments. This consensus document attempts to clarify misunderstandings about the role of biofilms in clinical practice, and provides a basis for clinicians to recognize biofilms in chronic nonhealing wounds and manage patients optimally. A new paradigm for wound care, based on a stepped-down treatment approach, was derived from the consensus statements.

Honey is a viscous, supersaturated sugar solution derived from nectar gathered and modified by the honeybee, Apis mellifera. Honey has been used since ancient times as a remedy in wound care. Evidence from animal studies and some trials has suggested that honey may accelerate wound healing. The objective was to determine whether honey increases the rate of healing in acute wounds (e.g. burns, lacerations) and chronic wounds (e.g. skin ulcers, infected surgical wounds). For this first update of the review we searched the Cochrane Wounds Group Specialised Register (searched 13 June 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 5); Ovid MEDLINE (2008 to May Week 5 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 12 June 2012); Ovid EMBASE (2008 to 2012 Week 23); and EBSCO CINAHL (2008 to 8 June 2012). Randomised and quasi-randomised trials that evaluated honey as a treatment for any sort of acute or chronic wound were sought. There was no restriction in terms of source, date of publication or language. Wound healing was the primary endpoint. Data from eligible trials were extracted and summarised by one review author, using a data extraction sheet, and independently verified by a second review author. We identified 25 trials (with a total of 2987 participants) that met the inclusion criteria, including six new trials that were added to this update. In acute wounds, three trials evaluated the effect of honey in acute lacerations, abrasions or minor surgical wounds and 12 trials evaluated the effect of honey in burns. In chronic wounds, two trials evaluated the effect of honey in venous leg ulcers, and single trials investigated its effect in infected post-operative wounds, pressure injuries, cutaneous Lieshmaniasis, diabetic foot ulcers and Fournier's gangrene. Three trials recruited people into mixed groups of chronic or acute wounds. Most trials were at high or unclear risk of bias. In acute wounds, specifically partial-thickness burns, honey might reduce time to healing compared with some conventional dressings (WMD -4.68 days, 95%CI -4.28 to -5.09 days), but, when compared with early excision and grafting, honey delays healing in partial- and full-thickness burns (WMD 13.6 days, 95% CI 10.02 to 17.18 days). In chronic wounds, honey does not significantly increase healing in venous leg ulcers when used as an adjuvant to compression (RR 1.15, 95% CI 0.96 to 1.38), and may delay healing in cutaneous Leishmaniasis when used as an adjuvant to meglumine antimoniate compared to meglumine antimoniate alone (RR 0.72, 95% CI 0.51 to 1.01). Honey dressings do not increase rates of healing significantly in venous leg ulcers when used as an adjuvant to compression. Honey may delay healing in partial- and full-thickness burns in comparison to early excision and grafting, and in cutaneous Leishmaniasis when used as an adjuvant with meglumine antimoniate. Honey might be superior to some conventional dressing materials, but there is considerable uncertainty about the replicability and applicability of this evidence. There is insufficient evidence to guide clinical practice in other types of wounds, and purchasers should refrain from providing honey dressings for routine use until sufficient evidence of effect is available.

Dear Sir Malaria with estimated annual global mortality from 700,000 to 2.7 million, caused by Plasmodium falciparum, the most deadly Plasmodium species prevails mainly in Africa (1,2). The pleomorphic clinical outcomes display a remarkable range of disease from acute primary stages to complicated clinical presentations, depending on the transmission intensity, age, immunity and genetic background of the affected individuals (3). Cerebral malaria (CM) is one of the manifestations of sever malaria with enormous morbidity and mortality worldwide. It affects approximately more than 500 million people annually, primarily in sub-Saharan Africa (WHO 2011). CM with the high case fatality rate remains one of the major causes of acquired disability throughout much of the tropical and subtropical world plagued by malaria (4,5). It imposes a substantial economic and palliative care and cost burden to households, which impedes economic development in countries with low national gross products. CM is characterised by a generalised systemic process with high overall level of cytokines related to predominant Th1 response. The shift of immune balance towards Th1 arm is simultaneous with under presentation of the Th2/T (reg) immune regulatory (5). Overproduction of Th1-related proinflammatory cytokines, mainly as interferon-γ, tumour necrosis factor-α (TNF-α), interleukin-1b (IL-1b) and IL-6 combined with underproduction of Th2-related anti-inflammatory cytokines, mainly as IL-10, IL-4 and transforming growth factor-β (TGF-β) is seen in CM (6,7). Raised levels of proinflammatory cytokines have been consistently observed in the cases affected with CM followed by schizont rupture (8). Th1-related proinflammatory cytokines modulate production of eicosanoides (prostaglandines and leukotrienes), thromboxane B2, 5-LOX, phospholipase A2, COX1 and COX2 in peripheral circulation (9). The balance between induced immune suppressive versus immune stimulating state by prostaglandins and leukotrines, respectively, is critical for development of CM (9). Finally, these excreted inflammatory mediators lead to the upregulation of intercellular adhesion molecule-1 (ICAM-1), nitric oxide (NO) production and immune proliferation within spleen (10,11). The pathological scenario evolved from these molecular events is enhanced vessel leakage following pronounced cytoadherence of parasitised erythrocytes and activated mononuclear cells to vascular endothelial cells (6). Preliminary animal and human investigations showed that prior infection with parasites such as Schistosoma hematonium, Ascaris lumbricoides and hookworms has been associated with reduced malaria severity in an age and dose-dependent manner (6,12). Pre-existing helmintic infection has been shown to exert 64% protection against murine CM (6). The suppression of both cellular and humoral immune responses essential for establishment and maintenance of coinfected parasites has been speculated as the main mechanism (13). This competitive parasitic milieu is owned by the influential effects of excessive production of IL-4 and IL-10 by stimulated Th2 lymphocytes and decreased Th1 responses (6). Decreased TNF-α production and IL-6 secretion could simply reflect amplified Th2 responses through non specific B lymphocyte presentation (13). This pattern of cytokine expression is also observed consistently in non CM (6). The induced CD23/NO pathway, increased immunoglobulin E concentrations, decreased ICAM-1 expression and cytoadherence of parasitised red blood cells exert additive effects in this context (12). Therefore, it is translated clinically that factors which alter the polarisation of naÏve T helper cells towards the Th2 phenotype can potentially improve disease profile. Several factors rather than pathogens can influence the host immune network particularly those causing chronic inflammation. Chronic non healing wounds, associated with arose chronic inflammatory state, alter the sum of Th1 versus Th2/T (reg) cytokines with promoted differentiation of precursor Th cells into the Th1 subset (14). Mutually, wounds might get chronic non healing state by standing in deteriorating Th1-dominant immune milieu. Complex inflammatory cascade in chronic non healing wounds is extensively characterised by suppression of IL-10, a prowound healing cytokine (14). Thus coexistence of persistent wounds might play a role in changing the clinical course of CM through elicited pathogenic Th1-type immune response. Lack of IL-10 predominance in chronic non healing wounds is such event seen in episodes of CM (6). The observed microcirculatory dysfunction and angiogenic failure in chronic non healing wounds is a favoured milieu for induction of CM's pathogenesis (15,16). Hence, non healing wounds would synergistically enhance load on immune system in CM. The possible influence of chronic wounds on the acquisition of immunity against CM would likely result in a higher rate of CM. This combination might confer lethality and exacerbation of symptoms. It needs to be determined at the population level whether patients with underlying chronic non healing wounds require a higher sequestered parasite biomass to develop CM or not. Each stage of wound carriage might play an important role in shaping the immunity against malaria and CM and this shared exposure should not be neglected simply. Both of these multifactorial diseases are largely seen in association with poor nutrition and socioeconomic status. The possible influence of chronic wounds on the immune response to malaria, parasite development and cytoadherence phenomena needs to be determined. Chronic non healing wounds continue to be a pandemic health problem (17). Animal studies would be of paramount value in this regard. Chronic wounds are major public-health problem in developing countries prone to CM: coendemic. The possibility that chronic non healing wounds could markedly affect the CM disease burden in malaria endemic area and their relevance to clinical disease deserves further investigations. Comparison between rate of CM resistance or tolerance between population widely devastated by chronic wounds and wound-free areas will illuminate the possible wound–CM interaction. Comparison of wound distribution among sites with peak occurrence of CM and variable malaria transmission intensities also seems helpful. This implies that treating one burden (wounds) could potentially relieve the other (CM), but it is not yet clinically proved. This would offer affordable means to roll back CM and its consequent complications and costs. If deleterious effects of concomitant non healing wounds on CM are confirmed, vigorous therapeutic measures for chronic wounds might become a priority in malaria endemic area before the progress towards CM. Perhaps, little paid attentions to the pre-existing non healing wounds merely before the onset of rainy seasons with the peak malaria transmissions would be of paramount impact on CM elimination. This seasonal attention to wounds or even every factor able to aggravate much of the hyperimmune responsiveness associated with CM expected to be economically more cost effective. The data regarding favoured season could be derived from district statistics and informed to resident clinicians. Considering the high prevalence of chronic non healing wounds in malaria endemic area as sub-Saharan Africa and the fatality rate of CM in this area, the fundamental practical implication of dewounding on the outcome of CM will be perceived easier. It is also convincible to address this hypothesis that wounds will get non healing fate in the cases experienced fatal CM. Mohaddeseh Behjati 1 The author declares no conflicts of interest.