Satellite Epidemic of Covid-19 Associated Mucormycosis in India: A Multi-Site Observational Study.

BACKGROUND: Sudden upsurge in cases of COVID-19 Associated Mucormycosis (CAM) following the second wave of the COVID-19 pandemic was recorded in India. This study describes the clinical characteristics, management and outcomes of CAM cases, and factors associated with mortality. METHODS: Microbiologically confirmed CAM cases were enrolled from April 2021 to September 2021 from ten diverse geographical locations in India. Data were collected using a structured questionnaire and entered into a web portal designed specifically for this investigation. Bivariate analyses and logistic regression were conducted using R version 4.0.2. RESULTS: A total of 336 CAM patients were enrolled; the majority were male (n = 232, 69.1%), literate (n = 261, 77.7%), and employed (n = 224, 66.7%). The commonest presenting symptoms in our cohort of patients were oro-facial and ophthalmological in nature. The median (Interquartile Range; IQR) interval between COVID diagnosis and admission due to mucormycosis was 31 (18, 47) days, whereas the median duration of symptoms of CAM before hospitalization was 10 (5, 20) days. All CAM cases received antifungal treatment, and debridement (either surgical or endoscopic or both) was carried out in the majority of them (326, 97.02%). Twenty-three (6.9%) of the enrolled CAM cases expired. The odds of death in CAM patients increased with an increase in HbA1c level (aOR: 1.34, 95%CI: 1.05, 1.72) following adjustment for age, gender, education and employment status. CONCLUSION: A longer vigil of around 4-6 weeks post-COVID-19 diagnosis is suggested for earlier diagnosis of CAM. Better glycemic control may avert mortality in admitted CAM cases.

Review on host-pathogen interaction in dermatophyte infections.

Dermatophytosis is a common superficial fungal infection of the skin and its appendages caused by dermatophytes. Recent times have witnessed a dynamic evolution of dermatophytes driven by their ecology, reproduction, pathogenicity and host immune response, influenced by population migration and socioeconomic status. Dermatophytes establish infection following successful adherence of arthroconidia to the surface of keratinized tissues. The proteolytic enzymes released during adherence and invasion not only ascertain their survival but also allow the persistence of infection in the host. While the cutaneous immune surveillance mechanism, after antigen exposure and presentation, leads to activation of T lymphocytes and subsequent clonal expansion generating effector T cells that differentially polarize to a predominant Th17 response, the response fails to eliminate the pathogen despite the presence of high levels of IFN-γ. In chronic dermatophytosis, antigens are a constant source of stimulus promoting a dysregulated Th17 response causing inflammation. The host-derived iTreg response fails to counterbalance the inflammation and instead polarizes to Th17 lineage, aggravating the chronicity of the infection. Increasing antifungal resistance and recalcitrant dermatophytosis has impeded the overall clinical remission. Human genetic research has the potential to generate knowledge to explore new therapeutic targets. The review focuses on understanding specific virulence factors involved in pathogenesis and defining the role of dysregulated host immune response against chronic dermatophytic infections for future management strategies.

Correction to: Whole genome sequences of two Trichophyton indotineae clinical isolates from India emerging as threats during therapeutic treatment of dermatophytosis.

[This corrects the article DOI: 10.1007/s13205-021-02950-1.].

Whole genome sequences of two Trichophyton indotineae clinical isolates from India emerging as threats during therapeutic treatment of dermatophytosis.

In the current study, we report the genome sequence of two different clinical isolates from India, Trichophyton indotineae UCMS-IGIB-CI12 and Trichophyton indotineae UCMS-IGIB-CI14. The resulting genome assembly achieved a 143-fold coverage in 824 contigs for T. indotineae UCMS-IGIB-CI12 and a 136-fold coverage in 904 contigs for T. indotineae UCMS-IGIB-CI14. Both the clinical isolates contain a c.1342G>A mutation corresponding to Ala448Thr amino acid substitution in erg1 and exhibit an intermittent drug response to terbinafine. Comparative genomics analysis with available genomes of Trichophyton interdigitale/Trichophyton mentagrophytes species complex revealed a similar genome architecture and identified large number of genes associated with virulence and pathogenicity, namely, lipases, proteases, LysM domain-containing factors, carbon metabolism enzymes and cytochrome P450 enzymes, in all the genomes. An analysis of single amino acid polymorphisms (SAPs) in the protein sequences of subtilisin and lipase enzyme families identified a higher frequency of SAPs in functionally important proteins, Sub3 and Sub6 and their possible use in multilocus phylogenetic analysis of T. interdigitale/T. mentagrophytes species complex. The whole genome sequences of T. indotineae clinical isolates provided in this report will, hence, serve as a key reference point for investigation of clinical strains and emerging drug resistance among dermatophytes originating from different parts of the world.

The interplay among Th17 and T regulatory cells in the immune dysregulation of chronic dermatophytic infection.

The delineation of the pathogenic interaction between the host skin immune responses and dermatophytes has remained indigent. The obscure enigma in host-dermatophyte immunopathogenic interactions is the T regulatory (Treg) and T-helper (Th) 17  cell role in maintaining immune homeostasis. We attempted to understand the regulation and recognition of lineage-specific response in chronic dermatophytic skin infection patients. The percentages of Th17 (CD4+CD161+IL23R+) and Treg (CD4+CD25+FoxP3+) cell subpopulations in the peripheral circulation of thirty chronic dermatophytic skin infection patients and twenty healthy individuals was determined. The serum cytokine levels were estimated for disease correlation. The mean duration of the disease was 10.68 ± 8.72 months, with Trichophyton mentagrophytes complex as the major pathogen. Total serum IgE level of patients was significantly higher compared to healthy controls (305 ± 117 vs 98.53 ± 54.55 IU/ml; p < 0.01). Expression of Th17 and Treg cell markers on CD4+ T cells was significantly elevated in patients than controls (p < 0.05). Comparatively, serum interleukin (IL)-4 and interferon (IFN)-γ levels were increased, with low IL-10 levels in patients. Our data envisages a complex immune dysfunction in chronic dermatophytosis, arising either as a result of dermatophyte exposure or paradoxical precedence of disease establishment. Designing new treatment strategies and preventing recurrences are challenges for future research.

Burden of Chronic Dermatophytosis in a Tertiary Care Hospital: Interaction of Fungal Virulence and Host Immunity.

Dermatophytosis is caused by keratinophilic dermatophytes and affects the superficial skin and its appendages. The nature of infection and response to treatment is influenced by host-pathogen factors like duration and severity of disease, prior drug history and type of causative organism. In our study, the burden of dermatophytosis affecting glabrous skin saw a rise in recalcitrant and reinfection cases with only 1.6% achieving complete cure. Chronicity of dermatophytic infection was reflected in the high serum IgE levels and immediate hypersensitivity reactions. Hence, it becomes pertinent for clinicians to identify the non-responders and modify therapy to achieve clinical cure with fungal clearance confirmed by mycological tools.

Candida auris colonization in an immunocompetent patient: A new threat in medical ICU.

Candida auris has become a great challenge in diagnostic, therapeutic and hospital environmental adaptation. With a prevalence of 5.3% in intensive care unit (ICU) acquired candidemia in India, its colonization is very rapid which hastens hospital transmission. Strict surveillance and preventive measures need to be adopted in ICU as it can persist on dry, inanimate object, prompt adaptation and antifungal resistance can pose a future threat of a new drug hospital acquired pathogen.