Antifungal Drug Use for Onychomycosis.

BACKGROUND: Onychomycoses are fungal nail infections affecting predominantly toenails, and mainly caused by dermatophyte fungi, molds and some Candida species. Nail infections can be mild with purely cosmetic implications, but they can also negatively influence quality of life. The deep-seated nature of fungi within the nail plate, prolonged treatment, poor patient adherence, frequent recurrences, and development of resistance to various antimicrobial agents make onychomycosis difficult to successfully treat. AREAS OF UNCERTAINTY: When and how should clinicians prescribe systemic and topical antifungal drugs for onychomycosis? DATA SOURCES: A narrative review was undertaken of the current literature identified in Medline, Scopus, CINAHL, the Cochrane library, and Google Scholar. RESULTS: Treatment is often lengthy and requires persistence and patient education. Definitive mycological diagnosis, and an individualized evaluation of risks and benefits of different treatments are imperative before initiating therapy. The choice of treatment can be influenced by the age and general health of the patient, the causative organism, the number of affected nails, and the extent of nail involvement. Oral antifungals offer greater likelihood of a cure than topicals, but oral therapy carries greater risks and requires closer monitoring. Oral terbinafine is the treatment of choice, followed by itraconazole pulse regimen. The newly approved topical agents, efinaconazole and tavaborole, were superior to placebo in clinical trials and appear to produce slightly improved mycological cure rates compared to previous topicals, but further direct comparisons are needed. CONCLUSIONS: The treatment of onychomycosis can be challenging, as most therapeutic options are lengthy, expensive and potentially unsuccessful.

Antiparasitic Activity of Tea Tree Oil (TTO) and Its Components against Medically Important Ectoparasites: A Systematic Review.

Ectoparasites are pathogens that can infect the skin and cause immense pain, discomfort, and disease. They are typically managed with insecticides. However, the fast-emerging antimicrobial resistance and the slow rate of development of new bio-actives combined with environmental and health concerns over the continued use of neurotoxic insecticides warrant newer and alternative methods of control. Tea tree oil (TTO), as an alternative agent, has shown remarkable promise against ectoparasites in recent studies. To our knowledge, this is the first systematic review to assess preclinical and clinical studies exploring the antiparasitic activity of TTO and its components against clinically significant ectoparasites, such as Demodex mites, scabies mites, house dust mites, lice, fleas, chiggers, and bed bugs. We systematically searched databases, including PubMed, MEDLINE (EBSCOhost), Embase (Scopus), CENTRAL, Cochrane Library, CINAHL, ScienceDirect, Web of Science, SciELO, and LILACS in any language from inception to 4 April 2022. Studies exploring the therapeutic activity of TTO and its components against the ectoparasites were eligible. We used the ToxRTool (Toxicological data reliability assessment) tool, the Joanna Briggs Institute (JBI) critical appraisal tools, and the Jadad scale to assess the methodological qualities of preclinical (in vitro and in vivo) studies, non-randomised controlled trials (including cohort, case series, and case studies), and randomised controlled trials, respectively. Of 497 identified records, 71 studies were included in this systematic review, and most (66%) had high methodological quality. The findings of this review revealed the promising efficacy of TTO and its components against ectoparasites of medical importance. Most importantly, the compelling in vitro activity of TTO against ectoparasites noted in this review seems to have translated well into the clinical environment. The promising outcomes observed in clinical studies provide enough evidence to justify the use of TTO in the pharmacotherapy of ectoparasitic infections.

Treatment Guidelines for PTSD: A Systematic Review.

BACKGROUND: The aim of this review was to assess the quality of international treatment guidelines for post-traumatic stress disorder (PTSD), and identify differences between guideline recommendations, with a focus on the treatment of nightmares. METHODS: Guidelines were identified through electronic searches of MEDLINE, CINAHL, PubMed, Embase and Science Direct, as well as web-based searches of international guideline repositories, websites of psychiatric organisations and targeted web-searches for guidelines from the three most populous English-speaking countries in each continent. Data in relation to recommendations were extracted and the AGREE II criteria were applied to assess for quality. RESULTS: Fourteen guidelines, published between 2004-2020, were identified for inclusion in this review. Only five were less than 5 years old. Three guidelines scored highly across all AGREE II domains, while others varied between domains. Most guidelines consider both psychological and pharmacological therapies as first-line in PTSD. All but one guideline recommended cognitive behavioural therapy (CBT) as first-line psychological treatment, and selective serotonin reuptake inhibitors (SSRIs) as first-line pharmacological treatment. Most guidelines do not mention the targeted treatment of nightmares as a symptom of PTSD. Prazosin is discussed in several guidelines for the treatment of nightmares, but recommendations vary widely. Most PTSD guidelines were deemed to be of good quality; however, many could be considered out of date. Recommendations for core PTSD symptoms do not differ greatly between guidelines. However, despite the availability of targeted treatments for nightmares, most guidelines do not adequately address this. CONCLUSIONS: Guidelines need to be kept current to maintain clinical utility. Improvements are most needed in the AGREE II key domains of 'applicability', 'rigour of development' and 'stakeholder involvement'. Due to the treatment-resistant nature of nightmares, guideline development groups should consider producing more detailed recommendations for their targeted treatment. More high-quality trials are also required to provide a solid foundation for making these clinical recommendations for the management of nightmares in PTSD.

Clinical interventions for tungiasis (sand flea disease): a systematic review.

Tungiasis (sand flea disease) is an epidermal parasitic skin disease occurring in resource-limited communities. There is no standard treatment for tungiasis, and available treatment options are scarce. To our knowledge, this is the first systematic review aimed to assess randomised controlled trials (RCTs) investigating interventions for tungiasis. We systematically searched databases including MEDLINE (EBSCOhost), CENTRAL, CINAHL, PubMed, Web of Science, SciELO, LILACS and Embase (Scopus) for RCTs in any language, from inception of the databases until June 12, 2021. RCTs exploring preventive and therapeutic interventions for tungiasis were eligible. We used the revised Cochrane Collaboration's risk of bias tool to assess the risk of bias and Jadad scale to quantify the methodological quality of the RCTs. Of the 1839 identified records, only eight RCTs involving 808 participants were included, and several methodological deficiencies were identified in most of the trials. Trial interventions included: oral drugs niridazole and ivermectin and topical interventions of ivermectin lotion, metrifonate lotion, thiabendazole lotion, thiabendazole ointment, dimeticones (NYDA), and a neem seed and coconut oils-based mixture for treatment and coconut oil-based lotion (Zanzarin) for prevention. The coconut oil-based lotion for prevention and dimeticones for treatment of tungiasis have displayed the most promise. Most of the RCTs included in this study had low methodological quality. There is a clear unmet need for high-quality RCTs examining safe and effective prevention and treatment alternatives of tungiasis in endemic settings.

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.

Challenges and Opportunities in the Management of Onychomycosis.

Onychomycosis is an increasingly common fungal nail infection, chiefly caused by dermatophyte fungi. The disease is notoriously difficult to treat due to the deep-seated nature of fungi within the nail plate, prolonged treatment requirements, poor patient adherence and frequent recurrences. Given the poor efficacy of currently available topical and systemic therapies, there is a renewed interest in exploring alternative treatment modalities for onychomycosis. Natural therapies, physical treatments and various combination therapies have all shown potential for the management of onychomycosis, though research on many of these methods is still in preliminary stages. Further large, well-designed, randomised controlled trials are necessary to confirm the efficacy of these novel treatments in order to make formal recommendations regarding their use in the management of onychomycosis.

Fake News: Medicines Misinformation by the Media.

Mainstream broadcasting media is a potentially powerful avenue for disseminating wellness education. For example, it can be used for community-based risk management, including preparing for pandemic events. The media can have a considerable positive impact on the public by increasing their health knowledge, changing attitudes and intentions, and influencing health behavior. However, although the broadcasting media can usefully convey prosocial, healthy messages, there is also a risk of propagating incorrect and antisocial, poor public health information.

Treatment of scabies using a tea tree oil-based gel formulation in Australian Aboriginal children: protocol for a randomised controlled trial.

INTRODUCTION: In remote Aboriginal communities in Australia, scabies affects 7 out of 10 children before their first birthday. This is more than six times the rate seen in the rest of the developed world. Scabies infestation is frequently complicated by bacterial infection, leading to the development of skin sores and other more serious consequences, such as septicaemia and chronic heart and kidney diseases. Tea tree oil (TTO) has been used as an antimicrobial agent for several decades with proven clinical efficacy. Preclinical investigations have demonstrated superior scabicidal properties of TTO compared with widely used scabicidal agents, such as permethrin 5% cream and ivermectin. However, current data are insufficient to warrant a broad recommendation for its use for the management of scabies because previous studies were small or limited to in vitro observations. METHODS AND ANALYSIS: A pragmatic first trial will examine the clinical efficacy of a simple and low-cost TTO treatment against paediatric scabies and the prevention of associated secondary bacterial infections, with 1:1 randomisation of 200 participants (Aboriginal children, aged 5-16 years and living in remote Australia) into active control (permethrin 5% cream) and treatment (5% TTO gel) groups. The primary outcome for the study is clinical cure (complete resolution). Secondary outcome measures will include relief of symptoms, recurrence rate, adverse effects, adherence to treatment regimen and patient acceptability. ETHICS AND DISSEMINATION: The project has received approvals from the University of Canberra Human Research Ethics Committee (HREC 16-133), Wurli-Wurlinjang Health Service Indigenous subcommittee and the Aboriginal Medical Services Alliance Northern Territory reference group. The results of this study will be published in core scientific publications, with extensive knowledge exchange activities with non-academic audiences throughout the duration of the project. TRIAL REGISTRATION: ACTRN12617000902392; Pre-results.

Development of an allele-specific PCR for Escherichia coli B2 sub-typing, a rapid and easy to perform substitute of multilocus sequence typing.

We developed and validated an allele-specific PCR method for detecting the nine main Escherichia coli phylogroup B2 lineages involved in extra-intestinal infections, which could be used as a substitute for multilocus sequence typing in studies for which the greater resolution at the sequence type level is not needed.

The Clermont Escherichia coli phylo-typing method revisited: improvement of specificity and detection of new phylo-groups.

There is extensive genetic substructure within the species Escherichia coli. In 2000 a simple triplex PCR method was described by Clermont and colleagues that enables an E. coli isolate to be assigned to one of the phylo-groups A, B1, B2 or D. The growing body of multi-locus sequence data and genome data for E. coli has refined our understanding of E. coli's phylo-group structure and eight phylo-groups are now recognized: seven (A, B1, B2, C, D, E, F) belong to E. coli sensu stricto, whereas the eighth is the Escherichia cryptic clade I. Here a new PCR-based method is developed that enables an E. coli isolate to be assigned to one of the eight phylo-groups and which allows isolates that are members of the other cryptic clades (II to V) of Escherichia to be identified. The development of the method is described and the method is validated. Over 95% of E. coli isolates can be correctly assigned to a phylo-group. Two collections of human faecal isolates were screened using the new phylo-group assignment method demonstrating that about 13% of E. coli isolates belong to the newly described phylo-groups C, E, F and clade I.

Evolution of colicin BM plasmids: the loss of the colicin B activity gene.

Colicins, a class of antimicrobial compounds produced by bacteria, are thought to be important mediators of intra- and interspecific interactions, and are a significant factor in maintaining microbial diversity. Colicins B and M are among the most common colicins produced by Escherichia coli, and are usually encoded adjacently on the same plasmid. In this study, the characterization of a collection of E. coli isolated from Australian vertebrates revealed that a significant fraction of colicin BM strains lack an intact colicin B activity gene. The colicin B and M gene region was sequenced in 60 strains and it was found (with one exception) that all plasmids lacking an intact colicin B activity gene have an identical colicin gene structure, possessing a complete colicin B immunity gene and a 130 bp remnant of the B activity gene. A phylogenetic analysis of the colicin M and B operons and characterization of the plasmids suggested that ColBM plasmids with a truncated B activity gene have evolved on at least three separate occasions. Colicin B immunity was found to be non-functional in strains that have lost colicin B activity, and colicin M was still produced despite the absence of the SOS box believed to regulate its production in colicin BM strains. The presence of a remnant of the microcin V operon next to the truncated colicin B activity gene indicated that these plasmids evolved as a consequence of gene transfer between colicin BM and microcin V plasmids. We suggest that these transfer events most likely involved the transfer of some microcin V genes and associated virulence factors onto ColBM plasmids.