Research Articles (Medical Bioscience)

Permanent URI for this collection

https://hdl.handle.net/10566/77

Browse

Now showing 1 - 10 of 10

Candida antifungal drug resistance in sub-Saharan African populations: A systematic review
(Science Navigation Group, 2017) Africa, Charlene W.J.; Abrantes, Pedro Miguel dos Santos
BACKGROUND: Candida infections are responsible for increased morbidity and mortality rates in at-risk patients, especially in developing countries where there is limited access to antifungal drugs and a high burden of HIV co-infection. OBJECTIVES: This study aimed to identify antifungal drug resistance patterns within the subcontinent of Africa. METHODS: A literature search was conducted on published studies that employed antifungal susceptibility testing on clinical Candida isolates from sub-Saharan African countries using Pubmed and Google Scholar. RESULTS: A total of 21 studies from 8 countries constituted this review. Only studies conducted in sub-Saharan Africa and employing antifungal drug susceptibility testing were included. Regional differences in Candida species prevalence and resistance patterns were identified. DISCUSSION: The outcomes of this review highlight the need for a revision of antifungal therapy guidelines in regions most affected by Candida drug resistance. Better controls in antimicrobial drug distribution and the implementation of regional antimicrobial susceptibility surveillance programmes are required in order to reduce the high Candida drug resistance levels seen to be emerging in sub-Saharan Africa.
A comparison of susceptibility patterns of oral Candida isolates from South African and Cameroonian HIV- positive populations
(The International Association for Dental Research (IADR), 2012) Abrantes, Pedro Miguel dos Santos; McArthur, Carole P.; Africa, Charlene W.J.
METHOD: In this study, Candida isolates were collected from the oral mucosa of 128 South African and 126 Cameroonian HIV-positive patients, by scraping the mouths of consenting patients using sterile cotton swabs. Ethics clearance for this project was granted by the University of the Western Cape. Confirmation of Candida species was done by growth on differential media, Gram staining and microscopy. The isolates were grown on selective media and differentiated using two commercial chromogenic agars and Tomato (V8) agar. Changes in colony colour, morphology and pseudohyphae/chlamydospore expression could then be observed, allowing for species differentiation. Isolates were also examined for antifungal susceptibility patterns using the TREK system. RESULT: The results from this study suggest that the prevalence of Candida species varies according to geographical region and HIV-subtype. Discrepancies in antifungal drug susceptibility patterns were also observed in the two populations. CONCLUSION: The emerging drug-resistance raises the need for increased species prevalence surveillance, as this information can have clinical implications in the choice of more appropriate and effective patient treatment.
Drug susceptibility profiles of Candida species isolated from the oral mucosa of HIV-positive West African patients using the TREK Sensititre system
(2013) McArthur, Carole P.; Abrantes, Pedro Miguel dos Santos; Awasom, Charles; Ayuk, L.; Africa, Charlene W.J.
BACKGROUND: Candida infections are a common cause of death in immunocompromised patients. The prevalence and anti-mycotic drug susceptibility profiles of Candida species from Cameroon in Africa are unavailable. This study was prompted by an increasing incidence of treatment failure. Drug susceptibility profiles, necessary to improve treatment outcomes, is particularly important in countries where the sale of antimicrobials and antifungals is uncontrolled and resistance may emerge due to the indiscriminate use. OBJECTIVE: The goal of this study was to characterize and determine drug susceptibility of oral Candida species in Cameroonian patients with HIV/AIDS. MATERIALS AND METHODS: Candida species were isolated from the oral cavity of 126 HIV-positive patients attending a local HIV/AIDS clinic in the Cameroon. Drug susceptibility to azoles and echinocandins was determined using the commercial TREK Sensititre® YeastOne™ platform that provides the minimal inhibitory concentration of amphotericin B, 5-flucytosine, anidulafungin, caspofungin, micafungin, fluconazole, itraconazole, posaconazole, and voriconazole. RESULTS: Ninety two isolates identified were Candida albicans. Remaining isolates were C. glabrata (24), C. tropicalis (4), C. krusei (3), C. parapsilopsis/lusitanreae/keyfr (2), and one isolate was C. dubliniensis. More than 50% of C. albicans isolated were resistant to azoles but 115 Candida species (87%) were susceptible to amphotericin B. Twenty one of the twenty four C.glabrata identified (88%) were resistant to micafungin. The majority of Cameroonian Candida species were sensitive to flucytosine (5-FC) (95%) and echinocandins (79%). CONCLUSIONS: The report of azole resistance in all Candida species isolated from immunocompromised patients in Cameroon is a new and important observation. We found the approach using a broad screening platform an effective means to obtain data rapidly. We propose confirmation of these data and regional surveillance of Candida species in other areas in Cameroon and surrounding countries to develop an effective public health management and treatment strategy.
HIV/Candida co-infection in Sub-Saharan African women on ART
(Infectious Diseases Society of Southern Africa, the Sexually Transmitted Diseases Society of Southern and the Public Health Association of South Africa., 2013) Abrantes, Pedro Miguel dos Santos; Africa, Charlene W.J.
INTRODUCTION: Sub-Saharan Africa has 23.5 million cases of HIV and is home to 92% of the world’s HIV-positive pregnant women of whom 24% die of pregnancy related complications. Oral candidiasis is a common condition in HIV-AIDS patients, caused by commensal yeasts which may colonise the mucous membranes of the mouth causing morbidity due to several factors including immunosuppression, smoking, poor nutrition and the use of antibiotics. Methods: One hundred and ninety-four South African and Cameroonian HIV-positive women participated in the study. Only subjects who had white pseudomembranous plaque on the tongue or visible oral candidiasis were included. Samples were collected by scraping the patient’s oral mucosa and tongue with a sterile swab. Candida species were differentiated using selective and chromogenic media and their susceptibility to antifungal drugs was tested using the TREK Sensititre system. Results and conclusion: One hundred and ninety-six isolates, representative of six Candida species were identified. C. albicans was the predominating species, with C. glabrata and C. dubliniensis being the more frequent of the non-albicans isolates. Azole drug resistance patterns were very high for C. albicans, while C. glabrata showed high resistance patterns to echinocandins drugs. The duration of ART could be associated with the presence of different Candida species but no concrete conclusions could be drawn concerning HIV/Candida co-infection when controlling for other risk factors such as HIV stage, pregnancy, age and treatment for tuberculosis. This may be a cause for concern, particularly in the case of pregnancy, where co-infection may pose a risk for maternal morbidity and mortality.
HPLC-MS identification and expression of Candida drug-resistance proteins from African HIV-infected patients
(AIMS Press, 2021-09-10) Abrantes, Pedro Miguel dos Santos; Fisher, Randall; Bouic, Patrick J D; McArthur, Carole P; Fielding, Burtram C; Africa, Charlene Wilma Joyce
The objective of this study was to elucidate the proteomic mechanisms of drug resistance in HIV-infected African patients. Cell membrane fractions from forty oral Candida isolates isolated from African HIV-positive patients were analysed using HPLC-MS with the aim of identifying proteins associated with their pathogenicity and drug resistance. Heat shock proteins that mediate the fungicidal activity of salivary peptides were found in all tested Candida fractions, with pH-responsive proteins associated with increased pathogenicity only being present in the three most commonly isolated species. ABC multidrug transporter efflux pumps and estrogen binding proteins were only found in C. albicans fractions, while ergosterol biosynthesis proteins were identified in four species. The combination of various adherence, invasion, upregulation and efflux pump mechanisms appear to be instrumental for the Candida host colonization and drug resistance emergence in HIV-infected individuals.
K21 compound, a potent antifungal agent: Implications for the treatment of fluconazole-resistant HIV-associated Candida species
(Frontiers, 2019-05-24) John, Cathy Nisha; Abrantes, Pedro Miguel dos Santos; Prusty, Bhupesh; Ablashi, Dharam; Africa, Charlene Wilma Joyce
Background/objectives: With mucocutaneous candidiasis being highly prevalent in HIV patients, the emergence of fluconazole-resistant Candida species forms a major challenge in treating and eradicating these infections. The objective of this study was to establish the antifungal activity of K21, a membrane-rupturing antimicrobial compound derived from a silica quaternary ammonium compound (SiQAC) with tetraethoxysilane (TEOS). Methods: The study sample included 81 Candida species of which 9 were type strains and 72 were clinical isolates. Minimum inhibitory concentrations, synergy, fractional inhibitory concentration index (FICI) and time kill assays were determined by broth microdilution. Electron microscopy (EM) was used to determine the qualitative changes brought about after treatment with K21. Results: K21 inhibited the growth of all fluconazole-resistant and susceptible Candida strains with only 2 hours of exposure required to effectively kill 99.9% of the inoculum, and a definite synergistic effect observed with a combination of K21 and fluconazole. EM demonstrated the presence of two forms of extracellular vesicles indicative of biofilm formation and cell lysis. Conclusion: The study established the efficacy of K21 as an antifungal agent and with fluconazole-resistant candidiasis on the increase, the development of K21 can provide a promising alternative to combat acquired drug resistance.
Measuring Streptococcus mutans, Streptococcus sanguinis and Candida albicans biofilm formation using a real-time impedance-based system
(Elsevier, 2019-12-20) Abrantes, Pedro Miguel dos Santos; Africa, Charlene Wilma Joyce
Candida albicans and streptococci are amongst the most common fungal and bacterial organisms present in the oral cavity, with a growing body of evidence implicating C. albicans in increased caries severity and in the formation of the cariogenic biofilm. However, the interactive mechanisms between cariogenic streptococci and Candida are yet to be elucidated. In this study, the real-time biofilm formation of C. albicans, S. mutans and S. sanguinis was assessed individually and in combination using the xCELLigence system, an impedance-based microbial biofilm monitoring system. The impedance signal was the highest for C. albicans, followed by S. mutans and S. sanguinis. Although the streptococcal mixed adhesion was found to follow a similar trend to that of S. sanguinis, the introduction of C. albicans resulted in higher adhesion patterns, with the combined growth of S. sanguinis and C. albicans and the combination of all three species resulting in higher biofilm formation than any of the individual organisms over time. This study, the first to use impedance for real-time monitoring of interkingdom biofilms, adds to the body of evidence that C. albicans and oral streptococcal adhesion are interlinked and suggests that interkingdom interactions induce changes in the oral biofilm dynamics over time.
Multi-drug resistant (MDR) oral Candida species isolated from HIV-positive patients in South Africa and Cameroon
(Elsevier, 2014) Abrantes, Pedro Miguel dos Santos; McArthur, Carole P.; Africa, Charlene W.J.
Candida species are a common cause of infection in immune-compromised HIV-positive individuals, who are usually treated with the antifungal drug, fluconazole in public hospitals in Africa. However, information about the prevalence of drug resistance to fluconazole and other antifungal agents on Candida species is very limited. This study examined 128 Candida isolates from South Africa and 126 Cameroonian Candida isolates for determination of species prevalence and antifungal drug susceptibility. The isolates were characterized by growth on chromogenic and selective media and by their susceptibility to nine antifungal drugs tested using the TREK™ YeastOne9 drug panel (Thermo Scientific). Eighty three percent (82.8%) of South African isolates were C. albicans (106 isolates), 9.4% were C. glabrata (12 isolates) and 7.8% were C. dubliniensis (10 isolates). Of the Cameroonian isolates, 73.02% were C. albicans (92 isolates); 19.05% C. glabrata (24 isolates); 3.2% C. tropicalis (4 isolates); 2.4% C. krusei (3 isolates); 1.59% either C. kefyr, C. parapsilopsis or C. lusitaneae (2 isolates); and 0.79% C. dubliniensis (1 isolate). Widespread C. albicans resistance to azoles was detected phenotypically in both populations. Differences in drug resistance were seen within C. glabrata found in both populations. Echinocandin drugs were more effective on isolates obtained from the Cameroon than in South Africa. A multiple drug resistant (MDR) C. dubliniensis strain isolated from the South African samples was inhibited only by 5-flucytosine in vitro on the YO9 panel. Drug resistance among oral Candida species is common among African HIV patients in these two countries. Regional surveillance of Candida species drug susceptibility should be undertaken to ensure effective treatment for HIV-positive patients.
Proteomic mechanisms of drug resistance in Candida cell membrane fractions
(International Association for Dental Research, 2014) Abrantes, Pedro Miguel dos Santos; Bouic, Patrick J.D.; Africa, Charlene W.J.
INTRODUCTION: The African continent has the highest burden of HIV infection, accounting for approximately 65% of new infections globally. Oral candidiasis is a major cause of increased morbidity in HIV-infected individuals and is usually treated with fluconazole, an antifungal drug which interferes with ergosterol synthesis in the fungal cell membrane. The increased resistance of Candida species to antifungal drugs leads to treatment failure and an increase in untreatable Candida infections. OBJECTIVES/METHODS: Drug susceptibility patterns were determined for Candida species isolated from oral swabs of 254 patients from two HIV-positive African populations. Forty cell membrane fractions isolated from the clinical isolates were analyzed using High Performance Liquid Chromatography – Mass Spectrometry (HPLC-MS) and the results compared to the UniProt protein database for the identification of Candida peptides known to be involved in colonization and drug resistance strategies within the host. RESULTS: Fluconazole-susceptible and –resistant C. albicans isolates were found to express oxidoreductases that bind mammalian estrogens with high affinity. Peptides that confer resistance to formaldehyde were found in C. albicans, C. glabrata and C. dubliniensis in both susceptible and resistant cell fractions. Multidrug resistance proteins (CDR1 and CDR2) were seen in C. albicans cell fractions. CONCLUSION: The combination of different drug resistance mechanisms and binding abilities to salivary histatins and estrogen seem to be instrumental in the colonisation and retention of Candida in these immunocompromised patients. The results also suggest the presence of differences in efflux transporter protein expression in fluconazole-susceptible and –resistant isolates within the HIV population.
Strengths and limitations of different Chromogenic Media for the identification of Candida species
(Scientific & Academic Publishing, 2012) Messeir, Ilze; Abrantes, Pedro Miguel dos Santos; Africa, Charlene W.J.
The treatment of invasive candidiasis and other Candida infections with the appropriate antifungal agent is assisted by the identification of Candida isolates to the species level. Rapid and accurate methods of differentiation are therefore imperative if treatment is to be effective, particularly in HIV-positive patients and in pregnant mothers where intervention may be necessary to reduce the risk for preterm delivery. The time used for isolation, identification and detection of mixed cultures may be reduced with the help of available chromogenic media. In this study, five commercial chromogenic media were evaluated for the differentiation of Candida species. Six type-strains of Candida species were streaked onto each of five different chromogenic media and incubated for up to 4 days at the different temperatures recommended by the manufacturers. This comparative evaluation demonstrated the strengths and weaknesses of each medium employed and found CHROMagar™ Candida and Chromogenic Candida Agar to be the most effective for distinguishing between different Candida species.

Browse

Browsing by Author "Abrantes, Pedro Miguel dos Santos"

Results Per Page

Sort Options