Browsing by Author "Holmes, Haly Karen"

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    The effect of a combination therapy of Fluconazole and Amphotericin B on the growth and CDR1 gene expression of Candida glabrata
    (University of the Western Cape, 2020) Mohamed, Nada Abdelrahman Nurein; Holmes, Haly Karen
    Candida glabrata (C. glabrata/ Cg) is a pathogenic organism that is increasingly developing frank innate and acquired resistance to the most commonly used antifungal agents, namely, azole group of antifungals. Furthermore, C. glabrata-associated oropharyngeal infections affecting immunocompromised patients, are more difficult to treat and the development of resistance worsen the prognosis. Molecular studies related the emergence of resistance in C. glabrata to the upregulation of ATP-binding cassette (ABC) transporter genes, which work by reducing drug concentration within the cell via drug efflux mechanism, and among these genes, CgCDR1 is considered to play a major role in resistance development. Thus, in order to overcome this problem, several combinations of antifungal agents are being studied. Aim: To evaluate the effect of a combination therapy of fluconazole and amphotericin B on the growth and CDR1 gene expression of C. glabrata. Research design and methodology: This in-vitro study evaluated the effect of a combination therapy of fluconazole and amphotericin B on the growth of C. glabrata and related it to the expression of CgCDR1 resistance gene. C. glabrata was revived in brain heart infusion (BHI) broth and later inoculated onto agar plates. Following overnight incubation, 5 colonies were transferred using a sterile loop into 2 ml of phosphate buffered saline (PBS) solution to establish McFarland (Mcf) standard. Later, the solution was diluted by transferring 200 μL to 400 ml of yeast peptone dextrose (YPD) agar (flask 1). From (flask 1), 90 ml, 99 ml and 89 ml of inoculum were allocated into 3 separate flasks, into which 10 ml fluconazole, 1 ml amphotericin B and 11 ml combination (10 ml fluconazole + 1 ml amphotericin B) were added, respectively. The inoculums were left to settle for 20 minutes, then incubated at 37oC with serial dilutions carried after 30 minutes, 2, 4, 6 and 24 hours. From the 96-microtiter plate, 10 μL for each treatment arm and time interval were transferred from selected wells and onto 30 Casein-peptone Soymeal-peptone (CASO) agar plates, and incubated for 24 hours. After incubation, the number of colonies were counted using an automated colony counter, to establish colony forming unit (CFU)/ml. CgCDR1 gene expression was analyzed using real time polymerase chain reaction. After 6 hours of incubation, a sample was taken from each treatment arm, transferred into CASO agar plates and incubated for 24 hours at 37oC. After establishing Mcf, gene extraction and gene expression were carried out according to manufacturer’s instructions. Results and discussion: No significant difference between the effect of the combination and amphotericin B was evident regarding C. glabrata growth. However, the combination therapy was more effective against C. glabrata than fluconazole, with a marked decrease in candidal growth at 30 minutes and 6 hours. Furthermore, the expression of CgCDR1 gene at 6 hours contact time was more pronounced in the samples of C. glabrata treated with the combination therapy, compared to that of the monotherapy. Conclusion: The combination therapy had better effect on the growth of C. glabrata than fluconazole monotherapy. On the other hand, the expression of CgCDR1 was detected in the samples of C. glabrata treated with the combination therapy, suggesting the ability of the yeast to adapt and develop resistance in such environment.
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    Prevalence and distribution of HPV infection and subtypes in oral squamous cell carcinoma in Africa: A systematic review protocol
    (BMJ Publishing Group, 2021) Holmes, Haly Karen; Afrogeh, Amir; Adeola, Henry
    Human papillomavirus (HPV) is an established risk factor for oropharyngeal squamous cell carcinoma, regardless of a history of other known risk factors such as alcohol and tobacco. While cases of HPV-related oral squamous cell carcinoma (OSCC) are increasing in the USA, Europe and South Central Asian countries, little is known about the impact of the disease on the African continent. s We describe a protocol for a systematic review to synthesise the best current evidence to assess the disease burden in Africa. Electronic databases including EBSCOhost, MEDLINE, CINAHL, ACADEMIC SEARCH COMPLETE, ScienceDirect, Web of Science, Scopus, SciCENTRAL, Cochrane Library.
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    The prevalence and impact of oral lesions on the quality of life in persons with epidermolysis bullosa
    (2010) Holmes, Haly Karen; Stephen, L.X.G.
    Introduction:Hereditary Epidermolysis bullosa (EB) is a group of rare mechanobullous dermatological disorders in which blisters develop following gene mutations. These genes encode structural proteins that anchor the epidermis to the underlying dermis.There are four main types of Epidermolysis bullosa, with more than 20 subtypes. The medical, physical and psychosocial aspects of Epidermolysis bullosa are well documented (Lucky et al, 2005; Mellerio et al, 2005). Many studies have documented case reports of associated oral lesions (Silva et al, 2004; Pacheco and de Sousa Araugio 2008; Siqueira et al, 2008). However, no assessment of the impact of these oral lesions on the affected person's everyday life has been made. The morbidity of the oral lesions associated with EB is expected to have an impact on the quality of life of these patients.Aim:To assess the prevalence and impact of oral lesions on daily activities in persons with Epidermolysis bullosa in Cape Town, South Africa, utilizing the Oral Impact on Daily Performance (OIDP) measure. Research Design and Methodology A case-controlled, descriptive analysis of the way in which oral lesions impact on quality of life in persons with Epidermolysis bullosa was carried out using semi-structured interviews. Fourteen persons with a confirmed diagnosis of hereditary Epidermolysis bullosa who attended the dermatology clinics at the Red Cross and Groote Schuur hospitals participated in the study. The control group comprised eighteen persons closely matched for gender, age, and dental status. Three persons with EB were unavailable for inclusion in the study.Results and Discussion Fourteen persons with Epidermolysis bullosa and eighteen controls were included in the study. Epidermolysis bullosa Simplex comprised the largest sub-group (n=9). Two persons had Junctional Epidermolysis bullosa, two had recessive Dystrophic Epidermolysis bullosa and one person had Kindler syndrome. The oral manifestations observed were consistent with those reported in the literature(Chimenos et al, 2003; Silva et al, 2004; Pekinar et al, 2005). No significant oral lesions (other than tooth decay) were seen in persons in the Epidermolysis bullosa Simplex group. Oral ulcers, atrophy of the dorsal surface of the tongue and gingival erythema were seen in persons with Junctional Epidermolysis Bullosa. The two individuals with Dystrophic Epidermolysis bullosa had a maximal oral opening of 15mm and 24mm. Ankyloglossia, depapillation of the dorsal tongue, absence of palatal rugae and poor oral hygiene was seen in these two persons. The patient with Kindler syndrome presented with erythematous and inflamed gingiva and cratering in the maxillary anterior interdental area. The gingiva appeared desquamative, fragile and bled with even the slightest provocation. Healing peri-oral blisters and angular cheilitis was also seen. His mouth opening was restricted to a maximal oral aperture of 13mm and his tongue extrusion was limited to only the tip of the tongue passing over the lower anterior incisor teeth.Defects in the tooth enamel was recorded in both participants with Junctional Epidermolysis bullosa and one person with dystrophic Epidermolysis bullosa, as well as excessive occlussal tooth wear (attrition), which may have been secondary to enamel hypoplasia. The dental caries status of the Epidermolysis bullosa and control groups varied according to age. The dmf for persons with Epidermolysis bullosa (all of whom had Epidermolysis bullosa Simplex), was lower than in the control group. The DMF in EB persons (15.3) was higher than in the control group (10.1).Toothache and tooth decay were the most common perceived complaints in both the Epidermolysis bullosa and control participants, accounting for the high overall OIDP score in both groups (87.5%). No statistically significant difference was found between the two groups (85.7% and 88.9% for Epidermolysis bullosa and control group persons respectively).Conclusion:The results of the study show that oral lesions (particularly tooth decay and toothache) in persons with Epidermolysis bullosa do affect their daily activities and the impact thereof is high. Other oral manifestations, irrespective of the subtype, had little impact on the OIDP score. This may be because the EB persons become tolerant of and “learn to cope” with them.Recommendations:Epidermolysis bullosa is a rare condition and not all persons with EB will present with lesions. However, all health personnel (including oral health profession) must be cognizant of this condition, in order to manage these persons safely, without incurring harm inadvertently. Thus, the overall management of persons with Epidermolysis bullosa must encompass ways to minimize and prevent trauma; provide an optimum wound healing environment; provide pain management and judicious checks for the development of premalignant lesions. This necessitates a multidisciplinary and holistic approach, with emphasis on patient involvement. To this end, an oral health care programme should form an integral part of their management because of the risk of dental disease. Periodic recall visits will enable the monitoring of home care and minimize the need for advanced restorative procedures. In this way, one may reduce the impact any oral problems may have, so that they do not further influence the patients well being.
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    Treatment of oral fungal infections using photodynamic therapy: Systematic review and meta-analysis
    (Wiley Open Access, 2021) Roomaney, Imaan Amina; Holmes, Haly Karen; Engel, Mark M.
    This systematic review evaluated the evidence for the effectiveness of Photodynamic therapy (PDT) in treating oral fungal infections, as an alternative to conventional antifungal medications.Five randomized control trials (168 participants) comparing the treatment of oral fungal infections using met with our inclusion criteria. Clinical and microbiological improvement was assessed by random-effects meta-analysis. Methodological quality assessment and heterogeneity were performed using peer-reviewed criteria. PROSPERO registration: CRD42017076.