The essential oil of Melaleuca alternifolia incorporated into hydrogel induces antimicrobial and anti-inflammatory effects on infected wounds by Staphylococcus aureus.

Staphylococcus aureus is one of the most common bacterial isolates found in wounds. Thus, innovative dressings, such as hydrogels, are interesting vehicles for incorporating bioactive compounds like those from Melaleuca alternifolia essential oil (MaEO). In this study, we evaluated the antimicrobial and anti-inflammatory potential of MaEO incorporated into an alginate and chitosan hydrogel for treating wounds infected by S. aureus. The hydrogel incorporated with MaEO 1% (HMa 1%) was homogeneous with a bright pale-yellow color and the characteristic smell of Melaleuca. The incorporation of MaEO 1% does not affect the stability of the hydrogel, which was stable up to 90 days of storage. The Scanning electron microscopy analysis revealed that hydrogels showed irregular surfaces and interconnected porous structures with accumulations of oil crystals distributed throughout the formulation. HMa 1% has a high moisture content (95.1%) and can absorb simulated wound fluid. Regarding the antimicrobial effects, HMa 1% reduced the growth of S. aureus ATCC 6538 in both in vitro conditions and in an ex vivo model of wounds using porcine skin. In addition, the dairy topical treatment of murine skin lesions with HMa 1% induced a significant reduction of the wound area, inflammation score, and bacterial load, as well as tissue re-epithelialization and modulation of inflammatory mediators. Therefore, hydrogel incorporated with MaEO 1% has excellent potential to be used in the pharmacotherapy of infected wounds.

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Over the past few decades, complementary and alternative treatments have become increasingly popular worldwide. The purported therapeutic characteristics of natural products have come under increased scrutiny both in vitro and in vivo as part of efforts to legitimize their usage. One such product is tea tree oil (TTO), a volatile essential oil primarily obtained from the native Australian plant, Melaleuca alternifolia, which has diverse traditional and industrial applications such as topical preparations for the treatment of skin infections. Its anti-inflammatory-linked immunomodulatory actions have also been reported. This systematic review focuses on the anti-inflammatory effects of TTO and its main components that have shown strong immunomodulatory potential. An extensive literature search was performed electronically for data curation on worldwide accepted scientific databases, such as Web of Science, Google Scholar, PubMed, ScienceDirect, Scopus, and esteemed publishers such as Elsevier, Springer, Frontiers, and Taylor & Francis. Considering that the majority of pharmacological studies were conducted on crude oils only, the extracted data were critically analyzed to gain further insight into the prospects of TTO being used as a neuroprotective agent by drug formulation or dietary supplement. In addition, the active constituents contributing to the activity of TTO have not been well justified, and the core mechanisms need to be unveiled especially for anti-inflammatory and immunomodulatory effects leading to neuroprotection. Therefore, this review attempts to correlate the anti-inflammatory and immunomodulatory activity of TTO with its neuroprotective mechanisms.

Diagnosis and treatment of filamentary keratitis in a patient with Demodex infestation--an overlooked risk factor: a case report.

BACKGROUND: Filamentary keratitis is an ocular condition that is tricky to handle for the difficulty to find the underlying cause. Here we report a case of filamentary keratitis associated with Demodex infestation which highlights the importance of Demodex mites as an easily-overlooked risk factor. CASE PRESENTATION: A 63-year-old woman had recurrent symptoms of foreign body sensation and sometimes painful feelings in her left eye soon after her surgical correction of ptosis in this eye. She was then diagnosed as conjunctivitis and given antibiotic eye drops. After one week, the patient complained of aggravation of symptoms with small corneal filaments in the left eye under slit-lamp examination. Despite the removal of filaments and addition of topical corticosteroids and bandage contact lenses, the patient's condition persisted with enlarged filaments and severe ocular discomfort. 3 days later, eyelashes with cylindrical dandruff were noticed and Demodex infestation was confirmed by microscopic examination of these eyelashes at our clinic this time. She was asked to use tea tree oil lid scrub twice daily. After 3 weeks, her filamentary keratitis was resolved with a dramatic improvement in symptoms and signs. And no recurrence of filamentary keratitis was noticed during the one-year follow-up. CONCLUSIONS: In this case, filamentary keratitis was resolved only with treatment of Demodex infestation while conventional treatment failed. Considering the fact that Demodex infestation is a common but easily overlooked condition, it may be suggestive to take Demodex infestation into account as a risk factor of filamentary keratitis, especially in refractory cases.

Comparison of the effect of tea tree oil eye gel with standard treatment in patients with anterior blepharitis: An open-label clinical trial.

Purpose: Daily cleansing of eyelids is very important to carry out a successful blepharitis treatment. However, there are no therapeutic guidelines for blepharitis. The aim was to compare the symptomatic relief of anterior blepharitis using Blephamed eye gel, a cosmetic product, versus standard treatment. Methods: The study was a prospective, interventional open label clinical trial at a university-based hospital. The test population was subjects aged 18-65 years who presented with mild to moderate anterior blepharitis. Eyelid hygiene was applied twice a day. At each visit, a detailed assessment of symptomatology was carried out. A two-way repeated measure mixed model ANOVA was used to compare two groups by time. Results: In total, 61 patients with mean age of 60.08 ± 16.69 years were enrolled in the study including 30 patients in standard group and 31 patients in Blephamed group. Two groups did not differ in terms of age (P = 0.31) and eye laterality (P = 0.50). The baseline scores of erythema, edema, debris, and symptoms as well as total score were similar between two groups (all P values >0.50). Two groups became different for all these parameters at day 45 (all P values <0.001). Significant interaction was detected between time and intervention groups for all severity parameters of blepharitis as well as total score (all P values <0.001). Conclusion: Eyelid hygiene with Blephamed more significantly decreased symptoms of anterior blepharitis compared to standard treatment.

Effectiveness of aroma-Tea Tree Oil and Eucalyptus oil in alleviating COVID-19 vaccine discomfort side effects.

CONTEXT: Aromatherapy is considered a mild and non-invasive complementary treatment to relieve post-vaccination discomforts. There have been no studies that examine the use of aroma-Tea Tree oil and Eucalyptus oil to relieve the discomfort side effects related to COVID-19 vaccines. OBJECTIVE: This study examined the use of two aroma-essential oils to relieve discomfort side effects of COVID-19 vaccination. DESIGN: The study used experimental design to match two groups of participants. SETTING: The participants' home. PARTICIPANTS: Adults who had not yet been vaccinated against COVID-19 but were planning to receive it were recruited. The current study included 87 control participants matched to 83 experimental participants. INTERVENTION: The participants in the experimental group used Tea tree and Eucalyptus while the control group did not. MAIN OUTCOME MEASURES: A questionnaire was used to collect data on the topical and systematic symptoms related to COVID-19 vaccines. Both groups were asked to complete the online questionnaire and report their health status 24 h (T1) and 48 h (T2) after vaccination. RESULTS: The results revealed a statistically significant difference between the groups in swelling, injection side pain, lump, fever, and muscle ache (p = .05, 0.04, <0.00, 0.02, 0.02, respectively) for T1; but for T2, a significant difference between the two groups was found only in lump and fever (p = .05, 0.03). Aroma-Tea Tree oil and Eucalyptus oil may be recognized and accepted by more people worldwide to provide a safe and healthy option not only for post-vaccination care but also to relieve pain, fever, and skin lumps associated with other diseases or conditions.

Comparison of tea tree oil 5%, tea tree oil 10%, and nystatin inhibition zones against vaginal Candida isolates in pregnancy.

INTRODUCTION: Vulvovaginal candidiasis (VVC) in pregnancy frequently develops into recurrent infections. Clinical study suggests that conventional topical treatments for VVC are not always enough to eradicate Candida spp. from the vaginal microenvironment. This study aimed to evaluate the antifungal activity of tea tree oil (TTO) 5% and TTO 10% against Candida species causing VVC in pregnancy. METHODOLOGY: In vitro experimental study was conducted in the Mycology Laboratory at Dermatovenereology Outpatient Clinic Dr. Soetomo General Hospital Surabaya. Eighteen isolates of Candida species were isolated from the vaginal thrush of 15 pregnant women diagnosed with VVC from March to May 2021. Antifungal susceptibility of TTO 5% and TTO 10% was evaluated by the disc diffusion method, with the inhibitory zone diameter as the main outcome. RESULTS: The mean inhibitory zone diameter of TTO 5%, TTO 10%, and nystatin against all Candida spp. was 7.26 mm, 8.64 mm, and 25.57 mm, respectively (p < 0.001). The mean inhibitory zone diameter of TTO 5%, TTO 10%, and nystatin tend to be larger in C. albicans compared to the non-albicans, but the difference is not significant. Nystatin displayed the largest mean inhibitory zone diameters compared to TTO 5% and TTO 10% (p < 0.001) in all Candida species. Increased concentration from TTO 5% to TTO 10% resulted in a slight increment in the mean inhibitory zone diameters in all-Candida species (p = 0.001). CONCLUSIONS: Tea Tree Oil displayed antifungal activity against Candida species causing VVC in pregnancy. Further studies are required to investigate optimal TTO concentrations as a VVC treatment in pregnancy.

The healing effect of topical tea tree oil on pressure ulcers in a rat model.

Objective: The effects of topical tea tree oil (TTO) on the healing of pressure ulcers (PUs) in an animal model was evaluated. Method: To induce PUs, ischaemia-reperfusion cycles were performed by the external application of magnetic plates, with an ischaemic period of eight hours and a reperfusion period of 16 hours. Male and female Wistar rats were divided into three equally sized groups (n=20): one group received topical glycerin twice daily, another group received topical 10% (volume/volume (v/v)) TTO in glycerin twice daily; and the remaining group was untreated. The animals were assessed after one, four, seven and 14 cycles of ischaemia-reperfusion by thermal camera imaging, and then euthanised and sampled to investigate the degree of inflammation, collagen synthesis and apoptosis in the PUs. Results: Although topical glycerin alone suppressed local inflammation and apoptosis, this suppressive effect was accentuated at all timepoints by the application of topical TTO + glycerin. Similarly, an increase in collagen synthesis was observed in the glycerin group and this was accentuated by TTO at all timepoints. Parallel to the histological findings, the local temperature had decreased significantly on days 4 and 7 for both treatment groups (glycerin and TTO+glycerin). Conclusion: In this study, treatment with 10% (v/v) TTO in glycerin effectively suppressed skin inflammation and apoptosis, while it increased collagen synthesis during PU formation.

Role of Blepharoexfoliation in Demodex Blepharitis: A Randomized Comparative Study.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of blepharoexfoliation in the treatment of Demodex blepharitis. METHODS: Patients with microscopically approved Demodex blepharitis were enrolled. Patients in the treatment group were treated once with in-office blepharoexfoliation (BlephEx LLC; Franklin, TN) using tea tree oil 2% shampoo, followed by eyelid scrubs with tea tree oil 2% shampoo twice a day for 8 weeks. Patients in the control group were treated with the same protocol, except for the in-office sham blepharoexfoliation procedure. As the main outcome measurement, the changes in the severity of symptoms [Ocular Surface Disease Index (OSDI) score] were compared. The changes in Demodex count and meibomian gland dysfunction (MGD) severity were compared as the secondary outcome measurements. RESULTS: Eighty-one patients (36 male and 45 female) were included. The mean age of the patients was 53.56 ± 8.13 years. The mean baseline OSDI score was 33.30 ± 11.80. The mean baseline Demodex count was 4.84 ± 1.49. The Demodex count at the baseline visit was moderately correlated with the baseline OSDI score (R = 0.526, P = 0.011) and baseline MGD severity ( P = 0.02). At the 8-week visit, the OSDI score was 22.62 ± 8.23 and 27.09 ± 9.11 in the blepharoexfoliation and control groups, respectively ( P = 0.016). At the 8-week visit, the Demodex count was 2.6 ± 1.08 and 3.03 ± 1.27 in the treatment and control groups, respectively ( P = 0.025). MGD improved in both groups ( P = 0.84). In the blepharoexfoliation group, the change in the OSDI score was moderately correlated with the baseline OSDI score (R = 0.611, P = 0.01). CONCLUSIONS: One session of blepharoexfoliation, followed by manual eyelid scrubs was more effective than eyelid scrubs alone in reducing patients' symptoms and Demodex count.

Tea tree oil, a vibrant source of neuroprotection via neuroinflammation inhibition: a critical insight into repurposing Melaleuca alternifolia by unfolding its characteristics / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Over the past few decades, complementary and alternative treatments have become increasingly popular worldwide. The purported therapeutic characteristics of natural products have come under increased scrutiny both in vitro and in vivo as part of efforts to legitimize their usage. One such product is tea tree oil (TTO), a volatile essential oil primarily obtained from the native Australian plant, Melaleuca alternifolia, which has diverse traditional and industrial applications such as topical preparations for the treatment of skin infections. Its anti-inflammatory-linked immunomodulatory actions have also been reported. This systematic review focuses on the anti-inflammatory effects of TTO and its main components that have shown strong immunomodulatory potential. An extensive literature search was performed electronically for data curation on worldwide accepted scientific databases, such as Web of Science, Google Scholar, PubMed, ScienceDirect, Scopus, and esteemed publishers such as Elsevier, Springer, Frontiers, and Taylor & Francis. Considering that the majority of pharmacological studies were conducted on crude oils only, the extracted data were critically analyzed to gain further insight into the prospects of TTO being used as a neuroprotective agent by drug formulation or dietary supplement. In addition, the active constituents contributing to the activity of TTO have not been well justified, and the core mechanisms need to be unveiled especially for anti-inflammatory and immunomodulatory effects leading to neuroprotection. Therefore, this review attempts to correlate the anti-inflammatory and immunomodulatory activity of TTO with its neuroprotective mechanisms.

Adjunctive Agent for Treating Scabies: In vitro Killing Activity of Permethrin and Tea Tree Oil on Sarcoptes scabiei Collected from Patients

Objective: Recently, there has been a serious increase in cases of scabies. The number of patients who do not benefit from the current treatment agents is also quite high. There are publications showing that scabies mites are permethrin-resistant and ivermectin. The treatment with scabicides usually lasts for several hours and usually the treatment is repeated for at least another time, which reduces the patient's compliance with the treatment, especially in pediatric patients where the toxic effects of the products are more pronounced. Therefore there is a need for treatment modalities that are less toxic to humans. To observe the in vitro effect of tea tree oil (TTO) on S. scabiei and to compare it with those of permethrin. Methods: Scabies specimens were removed from the patient and examined using a digital microscope. Parasites that were not damaged during sampling, and showed full motion were included in the study. No treatment was applied to the patients before removal of the mites. A total of 40 parasites were included in the study, with 10 parasites in each group. Immersion oil was applied to the control group, 5% permethrin to the first treatment group, while 5% and 25% TTO were used for the second and third study groups. Results: The mean survival time (ST) of scabies mites in the 5% permethrin group was 350±31.3 min, while this for 5% TTO group 180±15.1 min and 120±13.3 min in the 25% TTO group. The mean ST of the sarcoptes in the control group was 2.820±90 min. The mean ST between the control, permethrin and TTO groups was statistically significant (p=0.03). ST between 5% and 25% TTO groups was also statistically significant (p=0.04). There were no statistical differences between permethrin and 5% or 25% TTO. Conclusion: TTO has an acaricidal effect on S. scabiei. Although not used as the treatment of choise, it can be used as a supportive agent. Since it shows an acaricidal effect within a short time, it could be used as a shampoo or shower gel to enhance the acaricidal activity of another scabicide.

Recent Evidence of Tea Tree Oil Effectiveness in Blepharitis Treatment.

The purpose of our study is to see how beneficial is tea tree oil (TTO) for treating chronic blepharitis topically, with a focus on the Demodex mite. To discover all possibly relevant published papers, an accurate Pubmed database search analysis of the current literature was undertaken from 2012 to December 2021. Fourteen papers dealing with the use of TTO to treat chronic blepharitis have been found. The effectiveness of TTO treatment was tested in vitro by 4 authors and in vivo by 10 authors. All studied confirmed efficacy of TTO treatment, even cyclic, on Demodex mite blepharitis. TTO can be used for lid scrubs, facial cleanser, eyelid patch, eyelid gel, eyelash shampoo or, more commonly, as TTO impregnated eyelid wipes. The scientific evidence of TTO for chronic blepharitis treatment gives a lot of confidence for the progress that this treatment may have in the future clinical practice.

The use of Dalmatian pyrethrum daisy and an excipient in the treatment of seborrheic dermatitis.

The active ingredients of the Pyretrin-D trichological cosmetic series, namely benzyl benzoate, Dalmatian pyrethrum daisy, Cistus incanus, tea tree oil and geranium oil, almond acid and arginine were tested in respect to the treatment of seborrheic dermatitis. The paper describes the application of Dalmatian pyrethrum daisy and the excipient. Methods and devices used to confirm the effectiveness of the tested formulations included the TrichoScope Polarizer Dino-Lite (MEDL4HM) and the scanning electron microscope (SEM).

The comparative in vitro killing activity of tea tree oil versus permethrin on Demodex folliculorum of rosacea patients.

BACKGROUND: Demodex mites have been implicated in several cutaneous disorders compelling the research efforts for effective anti-Demodex therapy. OBJECTIVE: Compare the survival time (ST) of Demodex folliculorum exposed to six different concentrations of tea tree oil (TTO) versus a positive control (permethrin 5%) and a negative control (immersion oil) group. MATERIALS AND METHODS: The wastes of rosacea patients' standardized superficial skin biopsy samples were recruited for the trial. The primary outcome measure of this study was the survival time, defined as the period between the exposure of study agents to the complete cessation of Demodex movements. RESULTS: All differences between the mean survival times of 2.5% (54.0 ± 6.1), 5% (39.0 ± 3.9), 10% (22.0 ± 2.5), 25% (13.0 ± 2.5), 50% (7.8 ± 0.6), and 100% TTO (3.3 ± 1.3) were significant (p < 0.05). The ST of the negative control group was 196.0 ± 23.6 min. The ST of permethrin 5% was 12.5 ± 1.9 that did not show a statistically significant difference from the ST of TTO 25% (p = 0.628). CONCLUSION: The survival times of the six different TTO groups confirmed a dose-related pattern, all of which had survival times shorter than the negative control (immersion oil). TTO 25% had comparable efficacy to the positive control agent (permethrin 5%).

Update on the Management of Demodex Blepharitis.

ABSTRACT: Demodex blepharitis is a common ophthalmologic disease that is often overlooked in the workup of blepharitis. Demodex infestation occurs in both symptomatic and asymptomatic individuals at similar rates; consequently, its role in the development of blepharitis has not been well elucidated. Two species have been confirmed to inhabit the human eyelid- Demodex folliculorum and Demodex brevis. These species differ in their preferred location of infestation, with D. folliculorum occupying the base of the eyelash and D. brevis inhabiting the meibomian glands, contributing to anterior and posterior Demodex blepharitis, respectively. A clinical index of suspicion must be developed from the history when blepharitis, conjunctivitis, or keratitis in adults and blepharoconjunctivitis or chalazia in children are resistant to treatment. The diagnosis can be strongly suspected by the presence of cylindrical dandruff at the base of the eyelash and confirmed by light microscopy of an epilated lash or by in vivo confocal microscopy. No cure is currently available. Management most frequently includes topical tea tree oil and its active ingredient terpinen-4-ol, both of which have produced good clinical outcomes. Topical tea tree oil is typically applied by a professional due to risk of toxicity. Several second-line treatment options have been studied, including ivermectin, metronidazole, selenium sulfide, microblepharoexfoliation, and lid hygiene. Novel, targeted therapies such as TP-03 (Tarsus Pharmaceuticals) are also currently being investigated in phase 2b/3 clinical trials. The purpose of this review purpose is to characterize Demodex blepharitis in detail, including its historical perspective and various classifications, and describe the latest diagnostic and management strategies.

Azelaic acid and Melaleuca alternifolia essential oil co-loaded vesicular carrier for combinational therapy of acne.

Aim: Azelaic acid (AzA), a comedolytic, antibacterial, anti-inflammatory anti-melanogenic agent, prescribed against acne vulgaris is safe on skin. Its combination with another widely used anti-acne agent, tea tree oil (EO) whose delivery is limited by volatility, instability and lipophilicity constraints was attempted. Method: Solvent injection was used to prepare AzA-EO integrated ethosomes. Result: Ethosomes were transformed into carbopol hydrogel, which exhibited pseudo-plastic properties with appreciable firmness, work of shear, stickiness and work of adhesion. The hydrogel showed better permeation and retention characteristics vis-a-vis commercial formulation (AzidermTM), when evaluated in Wistar rat skin. Further, ethosome hydrogel composite was better tolerated with no side effects. Conclusion: The findings suggests that the aforementioned strategy could be a potential treatment used for acne management.

Comparação da ação entre o antifúngico fluconazol e o óleo essencial de Melaleuca Alternifolia sobre amostras de leveduras do gênero Candida / Comparison of the action between the antifungal fluconazole and the essential oil of Melaleuca Alternifolia on samples of yeasts of the genus Candida

As onicomicoses são doenças causadas por fungos que acometem a pele, unhas e pelos, existindo diferentes formas clínicas e ocasionado por diversos agentes etiológicos. Os agentes causadores mais frequentes das onicomicoses são classificados como dermatófitos, não dermatófitos e leveduras. Dentre as leveduras destaca-se os fungos do gênero Candida, caracterizada como leveduriforme, em condições normais se apresentam como colonizantes, comensais e são consideradas oportunistas. A Candida albicans é a levedura mais comum de ser encontrada e está possui relatos de resistência ao fluconazol. A presença desta resistência representa um grande desafio terapêutico, pela escassez de alternativas no tratamento. Por conta disso muitas pessoas acabam optando por métodos alternativos para o controle deste tipo de infecção, um exemplo seria a aplicação de óleos essenciais naturais puros com ação combatente de microrganismos. O óleo essencial de Melaleuca, teve atividade antifúngica relatada por vários estudos usando diversas combinações de compostos originados da planta, mas sua aplicação mais comum é do óleo puro diluído. Porém os estudos aprofundando do quanto este composto possui de ação bactericida e antifúngica, comparados a medicamentos sintéticos, são escassos, mas sabe-se que com o uso frequente e correto do óleo ocasiona uma ação satisfatória. Objetivo geral foi descrever o efeito do óleo de Melaleuca sobre amostras de Candida albicans (ATT 90028) e Candida krusei (ATT 6258) comparando ao uso de Fluconazol.Método: Foi desenvolvida uma pesquisa qualitativa de caráter exploratório do uso tópico do óleo de Melaluca sobre Candida albicans (ATT 90028) e Candida krusei (ATT 6258) comparando com o antifúngico Fluconazol em método de difusão de disco.Os halos formados nos testes foram positivos para o Fluconazol, já para o óleo essencial de Melaleuca não constatando que a comparação por igual não é válida.

Onychomycosis are diseases caused by fungi that affect the skin, nails and hair, with different clinical forms and caused by different etiological agents. The most frequent causative agents of onychomycosis are classified as dermatophytes, non-dermatophytes and yeasts. Among the yeasts, the fungi of the genus Candida stand out, characterized as yeast, under normal conditions they present themselves as colonizers, commensals and are considered opportunistic. Candida albicans is the most common yeast to be found and has been reported to be resistant to fluconazole. The presence of this resistance represents a major therapeutic challenge, due to the scarcity of alternatives in the treatment. Because of this, many people end up opting for alternative methods to control this type of infection, an example would be the application of pure natural essential oils with microorganism-fighting action. Melaleuca essential oil has had antifungal activity reported by several studies using various combinations of compounds originating from the plant, but its most common application is as a diluted pure oil. However, the in-depth studies of how much this compound has bactericidal and antifungal action, compared to synthetic drugs, are scarce, but it is known that with the frequent and correct use of the oil it causes a satisfactory action. General objective was to describe the effect of Melaleuca oil on samples of Candida albicans (ATT 90028) and Candida krusei (ATT 6258) comparing to the use of Fluconazole. Method: A qualitative exploratory research was carried out on the topical use of Melaluca oil on Candida albicans (ATT 90028) and Candida krusei (ATT 6258) comparing it with the antifungal Fluconazole in a disc diffusion method. The halos formed in the tests were positive for Fluconazole, as for the essential oil of Melaleuca, not finding that the comparison is not valid.

Therapeutic Potential of Tea Tree Oil for Tungiasis.

Tungiasis (sand flea disease) is a neglected tropical disease caused by penetration of female sand fleas, Tunga penetrans, into a person's skin usually in their feet. The disease inflicts immense pain and suffering on millions of people, particularly children. The condition is most prevalent in Latin America, the Caribbean, and sub-Saharan Africa. Currently, there is no standard drug treatment for tungiasis. The available treatment options are fairly limited and unrealistic to use in endemic areas; as a result, in desperation, the affected people do more harm to themselves by extracting the fleas with non-sterile instruments, further exposing themselves to secondary bacterial infections and/or transmission of diseases such as hepatitis B virus, hepatitis C virus, or HIV. This highlights the urgent need for simpler, safer, and effective treatment options for tungiasis. Tea tree oil (TTO) has long been used as an antiseptic with extensive safety and efficacy data. The evidence on parasiticidal properties of TTO against ectoparasites such as head lice, mites, and fleas is also compelling. The purpose of this review is to discuss the current tungiasis treatment challenges in endemic settings and highlight the potential role of TTO in the treatment of tungiasis.

Solubilización in vitro del aceite de árbol de té y primeros resultados de su efecto antifúngico en onicomicosis / Solubilization in vitro of tea tree oil and first results of antifungal effect in onychomycosis

Introducción: La onicomicosis por dermatofitos son la principal causa de alteración ungueal. Su abordaje terapéutico farmacológico tiene asociado bajas tasas de éxito, hepatotoxicidad, interferencia y baja adherencia al tratamiento. Por ello, nuestro objetivo fue valorar la efectividad in vitro del aceite esencial de árbol de té, para aportar alternativas menos nocivas en el abordaje terapéutico frente a los principales agentes causantes de estas infecciones. Material y métodos: Se aisló de fragmentos de uña con infección fúngica el Trichophyton rubrum y Trichophyton mentagrophytes. Posteriormente, se inocularon a una concentración de 3 x105 UFC/mL en agar patata con dextrosa y aceite esencial de árbol de té a diferentes concentraciones para evaluar su efecto mediante el recuento de unidades formadoras de colonia (UFC) y el crecimiento radial (CR). Resultados: Se obtuvo compromiso en el crecimiento de Trichophyton rubrum a concentraciones a partir de 0,04% del aceite esencial de árbol de té (p = 0,004). En el caso del Trichophyton mentagrophytes se obtuvo inhibición a partir de 0,02% (p = 0,017), e incluso la inhibición completa a una concentración final del aceite a 0,07%. Conclusiones: El aceite esencial de árbol de té inhibe el crecimiento in vitro de los hongos estudiados, pudiéndose considerar una alternativa menos nociva para el abordaje terapéutico de las onicomicosis.(AU)

Introduction: Onychomycosis is the main cause of nail alteration. Hepatotoxicity, interference and low adherence to pharmacological treatment are associated. Therefore, our objective was to assess the in vitro effectiveness of tea tree essential oil (less harmful) against main causative agents of these infections. Material and methods: Trichophyton rubrum and Trichophyton mentagrophytes were isolated and inoculated at a concentration of 3x105 CFU / mL in potato agar dextrose and tea tree essential oil at different concentrations to assess its effect by counting colony forming units and radial growth. Results: Trichophyton rubrum growth inhibition was obtained at concentrations higher than 0.04% of the essential tea tree oil (p = 0.004). In the case of Trichophyton mentagrophytes, inhibition was obtained at 0.02% (p = 0.017), and even complete inhibition at a final concentration of the oil at 0.07%. Conclusions: Tea tree essential oil inhibits the in vitro growth of the fungus and may be a less harmful alternative to the onychomycosis treatment.(AU)

Treatment of tungiasis using a tea tree oil-based gel formulation: protocol for a randomised controlled proof-of-principle trial.

INTRODUCTION: Tungiasis (sand flea disease or jigger infestation) is a neglected tropical disease caused by penetration of female sand fleas, Tunga penetrans, in the skin. The disease inflicts immense pain and suffering on millions of people, particularly children, in Latin America, the Caribbean and sub-Saharan Africa. Currently, there is no standard treatment for tungiasis, and a simple, safe and effective tungiasis treatment option is required. Tea tree oil (TTO) has long been used as a parasiticidal agent against ectoparasites such as headlice, mites and fleas with proven safety and efficacy data. However, current data are insufficient to warrant a recommendation for its use in tungiasis. This trial aims to generate these data by comparing the safety and efficacy of a 5% (v/w) TTO proprietary gel formulation with 0.05% (w/v) potassium permanganate (KMnO4) solution for tungiasis treatment. METHODS AND ANALYSIS: This trial is a randomised controlled trial (RCT) in primary schools (n=8) in South-Western Kenya. The study will include school children (n=88) aged 6-15 years with a confirmed diagnosis of tungiasis. The participants will be randomised in a 1:1 ratio to receive a 3-day two times a day treatment of either 5% TTO gel or 0.05% KMnO4 solution. Two viable embedded sandflea lesions per participant will be targeted and the viability of these lesions will be followed throughout the study using a digital handheld microscope. The primary outcome is the proportion of observed viable embedded sand fleas that have lost viability (non-viable lesions) by day 10 (9 days after first treatment). Secondary outcomes include improvement in acute tungiasis morbidities assessed using a validated severity score for tungiasis, safety assessed through adverse events and product acceptability assessed by interviewing the participants to rate the treatment in terms of effectiveness, side effects, convenience, suitability and overall satisfaction. ETHICS AND DISSEMINATION: The trial protocol has been reviewed and approved by the University of Canberra Human Research Ethics Committee (HREC-2019-2114). The findings of the study will be presented at scientific conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: Australian New Zealand Clinical Trials Registry (ACTRN12619001610123); PACTR202003651095100 and U1111-1243-2294.

Tea tree oil extract causes mitochondrial superoxide production and apoptosis as an anticancer agent, promoting tumor infiltrating neutrophils cytotoxic for breast cancer to induce tumor regression.

The antitumor activity of the tea tree oil (TTO) derived product, Melaleuca Alternifolia Concentrate (MAC) was characterized mechanistically at the molecular and cellular level. MAC was analyzed for its anticancer activity against human prostate (LNCaP) and breast (MCF-7) cancer cell lines growing in vitro. MAC (0.02-0.06% v/v) dose-dependently induced the intrinsic (mitochondrial) apoptotic pathway in both the LNCaP and MCF-7 cell lines, involving increased mitochondrial superoxide production, loss of mitochondrial membrane potential (MMP), caspase 3/7 activation, as well as the presence of TUNEL+ and cleaved-PARP+ cell populations. At concentrations of 0.01-0.04% v/v, MAC caused cell cycle arrest in the G0/1-phase, as well as autophagy. The in vivo anticancer actions of MAC were examined as a treatment in the FVB/N c-Neu murine model for spontaneously arising breast cancers. Intratumoral MAC injections (1-4% v/v) significantly suppressed tumor progression in a dose-dependent manner and was associated with greater levels of tumor infiltrating neutrophils exhibiting anticancer cytotoxic activity. Induction of breast cancer cell death by MAC via the mitochondrial apoptotic pathway was also replicated occurring in tumors treated in vivo. In conclusion, our data highlights the potential for the Melaleuca-derived MAC product inducing anticancer neutrophil influx, supporting its application as a novel therapeutic agent.