Mucormycosis: A Rare disease to Notifiable Disease

Abstract

Mucormycosis is the third most frequent invasive mycosis, following candidiasis and aspergillosis. It is frequently neglected due to its rare occurrence; but recently attend the status of notifiable disease due to its higher incidence in both developed and developing nations. India has received global notice since its estimated instances were greater than the global estimated figures. Mucormycosis has several clinical manifestations, including rhino-orbital-cerebral (ROCM), pulmonary, gastrointestinal, cutaneous, renal, and diffuse Mucormycosis. ROCM is the most frequent clinical manifestation in India, although pulmonary mucormycosis is prevalent worldwide. This review also discusses host defenses, pre disposing risk factors and fungal virulence factors that impair host's ability to prevent fungus invasion and disease establishment. The diagnosis of the disease depends on clinical interventions, histological or microbiological procedures along with molecular methods to obtain timely results. But there are still unmet challenges for rapid diagnosis of the disease. Treatment of the disease is achieved by multimodal approaches such as reversal of underlying predisposing factors, rapid administration of antifungals in optimal doses and surgical procedures to remove infected tissues. Liposomal Amphotericin B, Posaconazole and Isavuconazoles are preferred as the first line of treatment procedures. clinical trials. Different studies have improved the existing drug and under clinical trials while several studies predicted the new potential targets as CotH and Ftr1 as shown in infection and in vitro models. Therefore, current scenario demands a multidisciplinary approach is needed to investigate the prevalence, pathogenesis which is highly important for the advancement of rapid diagnosis and effective treatment.

Keywords: India; Mucorales; Mucormycosis; Notifiable disease.

Fig. 1

Illustration of COVID associated mucormycosis cases in different states and UTs of India as on Nov 2021. Source: Government of India Ministry of Health and Family Welfare

Fig. 2

Major clinical representaions of Mucormycosis: Pulmonary, Rhinoorbito-cerebral, cutaneous, gastrointestinal and disseminated mucormycosis(Upper Panel). Lower panel displays potential risk factors that associated with development of mucormycosis including the existence of underlying diseases such as renal insufficiency, diabetes mellitus, and haematological malignancies. Voriconazole, broad-spectrum antibiotics, and steroids have all been linked to an increased risk of mucormycosis. Furthermore, a rise in blood iron levels, neutropenia, and immunosuppressive therapies such as stem cell therapy and organ transplant render people more susceptible to Mucormycosis

Fig. 3

Pathogenesis of Mucormycosis. It depicts the difference of Mucorales invasion in healthy individual in comparison to patients with underlying disease conditions or immunocompromised population. A. displays the healthy individual with no sign of disease. (i) First with the exposure to the spores of Mucorales to host; macrophages getting activated and phagocytosed the spores. The germination process recruits neutrophils and kills the Mucorales. (ii) Bood vessels showing no sign of invasion with active immune system, maintained blood glucose, balanced acid base system and well-proportioned Fe pool with active transferrin system. B. Explains the tissue invasion due to mucormycosis in presence of different predisposing factors. (i) Exposure of spores to the unhealthy or immunocompromised individual. Due to lack of active immune system, the spores getting germinated and invade into the endothelium. (ii) In presence of high glucose concentration; iron binding proteins and storage proteins get glycated and become non-functional. When there is acidosis, the pH is disturbed, and the functionality of transferrin is also affected. Increase in the Fe pool does augment growth and germination. The CotH present on the spores get interacted to over expressed GRP78 and helps in tissue invasion. Siderophore mediated transport of Fe is increased in deferoxamine treated individuals. The expression of Ftr1 and Fob1/2 is increased to assimilate Fe to grow and invade. Further growth of Mucorales cause thrombosis and tissue necrosis