Fungal Genetics, HIV & Mycoses Epidemiology in Kenya

FUNGAL GENETICS, KENYA EPIDEMIOLOGY & LABORATORY BIOSAFETY --- A. FUNGAL GENETICS### Basic Concepts Genetics — the discipline that explains how information needed to reproduce an organism is stored within it, and how that information may change and be reassorted before passing to the next generation. Genetic information (genome): Maintained as long, linear sequences of nucleotide base pairs making up DNA molecules Order of bases = genetic code → specifies amino acid sequences for all proteins Long DNA molecules incorporating thousands of base pairs = chromosomes Prokaryotes vs Eukaryotes: Prokaryotes (bacteria) — genome contained in a single chromosome in the cytoplasm Eukaryotes — genome contained in two or more chromosomes within a nucleus Eukaryotic plants and animals are basically diploid — nuclei contain two matched sets of chromosomes (one from male gamete, one from female gamete) Each chromosome has a paired counterpart; most genes have a counterpart called an allele on the paired chromosome — alleles affect the same characters but not necessarily in the same way --- Fungal Genome — Haploidy- The vast majority of fungi are haploid — nuclei contain a single set of chromosomes This is a key difference from most other eukaryotes (which are diploid) Advantages of haploidy for genetic studies: No competing alleles Every gene is potentially capable of being expressed in the phenotype (physical manifestation) Absence of masking (no dominant/recessive relationships) makes genetic analysis much easier This is why fungi like Neurospora crassa and Saccharomyces cerevisiae are invaluable model organisms in genetics research --- B. FUNGAL DISEASE EPIDEMIOLOGY IN KENYA### Background- Kenya is a developing country with a high rate of tuberculosis (TB) and a moderate HIV infection burden Both TB and HIV predispose patients to opportunistic fungal infections Sub-Saharan Africa is the epicentre of HIV/AIDS — main fungal infections include: - Respiratory fungal infections Eye (ocular) fungal infections Dermatological fungal infections Cryptococcal meningitis — most significant Burden of Fungal Infections in KenyaTotal estimated HIV-positive population in Kenya: 1,400,000 (2012 data) Infection Total Burden Rate per 100,000 --- --- --- Oral candidiasis 306,000 769 Oesophageal candidiasis 114,000 286 Recurrent vaginal candidiasis 594,660 2,988 Candidaemia 1,990 5 ABPA 17,696 44 SAFS (Severe Asthma with Fungal Sensitization) 23,359 58 Chronic pulmonary aspergillosis 12,927 32 Invasive aspergillosis 11,900 29 Cryptococcal meningitis 17,000 43 Pneumocystis pneumonia 1,712,676 4,302 Fungal keratitis 80 0.2 Tinea capitis 239 0.6 Total burden estimated 3,186,766 — Key observations: Pneumocystis pneumonia has the highest total burden Oral and vaginal candidiasis are the most common mucosal infections Cryptococcal meningitis remains a major killer in HIV/AIDS patients Most infections are driven by the HIV/AIDS burden --- Emerging and Re-emerging Fungal DiseasesKey factors driving emergence and re-emergence of fungal diseases: HIV/AIDS pandemic — massive increase in immunocompromised population Increased use of immunosuppressive therapy — transplants, cancer chemotherapy, biologics Antifungal resistance — especially in Candida and Aspergillus species Climate change — expanding geographic range of fungi like Coccidioides and Cryptococcus gattii Increased travel and globalisation — spread of endemic mycoses to non-endemic regions Candida auris — emerging multidrug-resistant yeast; nosocomial outbreaks worldwide; resistant to multiple antifungal classes; difficult to identify with standard methods Mucormycosis — re-emerged significantly during COVID-19 pandemic particularly in diabetic patients on corticosteroids --- C. MYCOLOGY LABORATORY BIOSAFETY### Why Biosafety MattersSafety in the mycology laboratory is crucial because of: Potentially pathogenic fungi being studied Hazardous nature of reagents, flames, glassware and procedures Risk of laboratory-acquired infections (LAIs) Senior supervisory staff must develop biosafety guidelines for all workers. --- Key Terminology Term Definition --- --- Bio-risk Any harm where the source is a biological material Bio-risk assessment Analysis of the severity and frequency of exposure to harm Bio-risk management Identification of bio-risks and steps towards control and mitigation --- Five Steps of Risk Assessment- Identify potential hazards Decide who is at risk Assess likelihood of harm Implement adequate precautions Manage risks and hazardous situations --- Pre-Analytical Phase Hazards Risk factors: Patients with active, latent, chronic or undiagnosed infections are sources of disease Sample collection, handling and transport must be done carefully Best practices: Only trained staff (phlebotomist, nurse, doctor) should collect samples — to avoid needlestick and prick injuries Always perform skin scrapings and nail drilling in an isolated room — to avoid creating contaminated aerosols Staff mu