Pedro Miguel dos Santos Abrantes

Multi-drug resistant oral Candida species isolated from HIV-positive patients in South Africa and Cameroon.

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 9 antifungal drugs tested using the TREK™ YeastOne9 drug panel (Thermo Scientific, USA). Eighty-three percent (82.8%) of South African isolates were Candida albicans (106 isolates), 9.4% were Candida glabrata (12 isolates), and 7.8% were Candida dubliniensis (10 isolates). Of the Cameroonian isolates, 73.02% were C. albicans (92 isolates); 19.05% C. glabrata (24 isolates); 3.2% Candida tropicalis (4 isolates); 2.4% Candida krusei (3 isolates); 1.59% either Candida kefyr, Candida parapsilopsis, or Candida 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 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 2 countries. Regional surveillance of Candida species drug susceptibility should be undertaken to ensure effective treatment for HIV-positive patients.

Candida antifungal drug resistance in sub-Saharan African populations: A systematic review

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.

Proteomics of drug-resistant HIV-associated candidiasis

Proteomics of drug-resistant HIV-associated candidiasis 1Abrantes PMDS, 2Bouic PJD, 1Africa CWJ 1 Microbial Endogenous Infections Studies (MEnIS) Research Laboratories, Department of Medical Biosciences, University of the Western Cape, Cape Town, South Africa, 2Synexa Life Sciences, Cape Town, South Africa Introduction Results The isolated species included C. albicans (n=198), C. glabrata (n=36), C. dubliniensis (n=11), Candida tropicalis (n=4), Candida krusei (n=3) and either Candida kefyr, Candida parapsilopsis, or Candida lusitaneae (n=2), with Cameroonian patients harbouring double the species of their South African counterparts. Drug resistance to different classes of antifungals was found to be widespread, especially in the case of azole drugs. Fluconazole-resistant Candida isolates run on SDS-PAGE expressed proteins with molecular weights consistent with that of tropiase (a 24kDa acid proteinase enzyme associated with increased Candida virulence) and exoglucanase (a 44kDa protein involved in host cell surface adhesion). In the case of HPLC/MS, a much more detailed spectrum of fluconazole-resistance related proteins was identified, ranging from multi-drug resistance efflux transporter CDR1 and CDR2 proteins and the elucidation of Candida colonization mechanisms through the action of oxidoreductases that bind to mammalian estrogen, heat shock proteins that bind to human salivary peptides and mediate their fungicidal activity, pH-responsive proteins which may increase the pathogenic ability of the organisms and S(hydroxymethyl) glutathione dehydrogenase.

Drug susceptibility profiles of Candida species isolated from the oral mucosa of HIV-positive West African patients using the TREK Sensititre system

Poster presented at ASM2013, 113th General Meeting, American Society of Microbiology, 18-21 May, Denver, Colorado