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• Guest speaker Dr Dora Corzo-Leon </aside>

Mucorales

• Mucorales is a large group (’order’) of ubiquitous, environmental moulds that cause the devastating invasive fungal infection, mucormycosis
• Mucormycosis is a rapidly progressive infection, characterised by angioinvasion and tissue necrosis - it is the most acute and fulminant fungal infection known
• Due to limited diagnostics and treatment options, mortality exceeds 50%
• WHO high-priority fungal pathogen

Taxonomy

• The pathogenic moulds that cause mucormycosis are in the fungal order Mucorales and the fungal kingdom Mucormycota
• Diverse group consisting of different genera - the most common causative species include:
  • Rhizopus arrhizus var*. arrhizus (syn R. oryzae), R. arrhizus* var. delemar, R. microsporus
  • Rhizomucor pusillus
  • Cunninghamella bertholletiae
  • Apophysomyces variabilis
  • Saksenaea vasiformis
  • *Lichtheimia (*ex-Absidia) corymbifera, L. rasmosa
  • Mucor circinelloides, M. velutinosus
  • Syncephalastrum recemosum
  • Actinomucor elegans

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Nomenclature is tricky and confusing - time to be de-mythed:

• The disease mucormycosis as often mistakenly referred to as “black fungus” - these fungi are not black - they have clear hyphae - but cause invasive disease with black, necrotic tissue if affecting the skin or sinuses
• The fungal kingdom ‘Mucormycota’ used to be called ‘Zygomycota’ → mucormycosis is still commonly called ‘zygomycosis’
• The group of fungi that cause mucormycosis are often mistakenly referred to as ‘Mucor’ - this is only one of the many genera of fungi that cause mucormycosis - the correct term is ‘Mucorales’ or mucoraceous moulds </aside>

Epidemiology

• Mucorales are ubiquitous environmental fungi - found worldwide, commonly on decaying organic matter - fungal spores are small and easily aerosolised and dispersed
• Cause invasive, opportunistic infection immunocompromised patients when spores are inhaled, inoculated or ingested from the environment
• Invasive disease may also occur in previously immunocompetent individuals in the context of burns / trauma
• Global and national incidence rates are relatively unknown - lack of surveillance of invasive fungal infections
• Trends over the last 10 years show a rising incidence

Clinical

| Site | Rhino-orbito-cerebral > Pulmonary > Cutaneous > Gastrointestinal Disseminates in approximately 25% (usually by contiguous spread) | | --- | --- | | Risk Factors | Haemopoietic / solid organ transplant Haematological malignancy Prolonged neutropenia Poorly controlled diabetes mellitus Prolonged corticosteroid use Desferrioxamine therapy Iron overload states Trauma / burns COVID-19 infection → >47,000 cases of COVID-19 associated mucormycosis in India 2021 | | Pathogenesis | (i) Fungal spores are inhaled / inoculated into skin abrasions / ingested
(ii) Immunocompetent host: spores are phagocytosed (macrophages and neutrophils) (iii) Defects in cellular immunity / immune system overwhelmed → spores germinate → hyphae invade tissues → angioinvasion → hyphae grow along blood vessel → thrombosis, tissue infarction and necrosis These fungi grow rapidly → rapid disease progression Fungal growth is further favoured by hyperglycaemia, acidosis, iron overload states | | Clinical syndromes | Rhino-orbital-cerebral disease

• Most commonly seen in diabetic patients (especially with ketoacidosis)
• Follows inhalation of spores into the sinuses
• Characterised by infarction of tissues of the nasopharynx and orbit - direct invasion of the CNS may occur
• Symptoms: facial and / or eye pain, black eschar on nasal mucosa / palate, orbital cellulitis, proptosis, conjunctival swelling, cranial nerve defects, retinal artery thrombosis and visual impairment

Pulmonary disease

• Occurs most frequently in neutropenic patients
• Symptoms: initially non-specific with fever, breathlessness and cough → progresses to haemoptysis and severe haemorrhage pulmonary vascular invasion and infarction occurs
• Radiological findings: segmental consolidation, occasional cavitation

Cutaneous

• Initial inoculation is associated with trauma, burns, insect bites - outbreaks have been associated with non-sterile dressings
• Necrotic lesions develop following vascular invasion and progressively extend to involve deeper tissues penetration if not recognised.

Gastrointestinal

• Rare - associated with severe malnutrition, particularly children, and GI diseases that disrupt the GI mucosa - occurs following ingestion of fungal elements
• Clinical picture mimics intra-abdominal abscess - abdominal pain, fever, nausea, vomiting
• Rapidly fatal - usually diagnosed at autopsy

Other:

• Endocarditis, osteomyelitis, renal infection, allergic sinusitis |