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.

Aetiology of hospital-acquired diarrhoea in under-five children from an urban hospital in East Delhi, India.

Background & objectives: Majority of the studies of hospital-acquired diarrhoea conducted in Western countries have focused on the detection of Clostridium difficile in stool samples. Limited Asian and Indian literature is available on hospital-acquired diarrhoea. This study was aimed to describe the aetiological profile for hospital-acquired diarrhoea in children aged below five years. Methods: One hundred children aged one month to five years who developed diarrhoea (≥3 loose stools for >12 h) after hospitalization for at least 72 h were enrolled. Children who were prescribed purgatives or undergoing procedures such as enema and endoscopy or those with underlying chronic gastrointestinal disorders such as celiac disease and inflammatory bowel disease were excluded from the study. Stool samples from the enrolled children were subjected to routine microscopic examination, modified Ziel-Nielson (ZN) staining for Cryptosporidium and culture for various enteropathogens. Multiplex PCR was used to identify the strains of diarrhoeagenic Escherichia coli. Rotavirus detection was done using rapid antigen kit. Toxins (A and B) of C. difficile were detected using enzyme immunoassay. Results: Of the 100 samples of hospital-acquired diarrhoea analysed, diarrhoeagenic E. coli (DEC) was found to be the most common organism, detected in 37 per cent of cases (enteropathogenic E. coli-18%, enterotoxigenic E. coli-8%, enteroaggregative E. coli-4% and mixed infections-7%). Cryptosporidium was detected in 10 per cent of cases. Rotavirus was detected in six per cent and C. difficile in four per cent of cases. Interpretation & conclusions: The findings of this study suggest that the aetiological profile of hospital-acquired diarrhoea appears to be similar to that of community-acquired diarrhoea, with DEC and Cryptosporidium being the most common causes. The efforts for the prevention and management of hospital-acquired diarrhoea should, thus, be directed towards these organisms.

In Situ Functionalization of Cellulose with Zinc Pyrithione for Antimicrobial Applications.

Considering the public health demands for stronger and effective personal protective clothing, herein, antimicrobial fabrics using a known bacteriostatic and fungistatic drug zinc pyrithione (ZPT) have been reported. ZPT was synthesized in situ on cellulosic fabric, viscose (VC), using a zinc metal precursor and 2-mercaptopyridine-N-oxide as a ligand (VC-ZPT). For comparison, viscose was also phosphorylated (VP) before in situ functionalization with ZPT (VP-ZPT). Both approaches provided adequate protection from microbes; however, functionalization of cellulose with phosphate (VP) resulted in the formation of a linking group between cellulose and ZPT, which exhibited better uniformity of ZPT over the fabric surface and higher durability to washing. The functionalization was confirmed by inductively coupled plasma mass spectroscopy (ICP-MS), scanning electron microscopy (SEM), and Raman spectroscopy. Further, the bonding of phosphate with ZPT was confirmed by 31P solid-state NMR. The physical properties, such as appearance, bending length, and mechanical strength, of the treated fabrics remained unchanged. The antimicrobial activities of VP-ZPT with VC-ZPT were studied against Escherichia coli, Staphylococcus aureus, and Candida albicans, which were found to be effective until 20 laundry cycles in VP-ZPT. Additionally, VP-ZPT samples exhibited poor adherence of bacteria on the fabric surface. The functionalized fabrics may find applications for topical skin diseases in reducing the necessity of repeated use of antibiotic ointments.

Gene expression profiling of protease and non-protease genes in Trichophyton mentagrophytes isolates from dermatophytosis patients by qRT-PCR analysis.

Trichophyton mentagrophytes secretes Metallocarboxypeptidase A and B of the M14 family as endoproteases and exoprotease. T. mentagrophytes produce Metalloprotease 3 and 4 which degrades the protein into the short peptides and amino acids. To understand the host fungal relationship and identification of such genes expressed during infection is utmost important. T. mentagrophytes encodes some proteins which are associated with the glyoxylate cycle. The glyoxylate cycle enzymes have been involving in virulence of dermatophytes and their up-regulation during dermatophytes growth on keratin. On comparing the expression level of virulence protease and non-protease genes, we observed, among exoprotease protease genes, Metallocarboxypeptidase B was strongly up regulated (134.6 fold high) followed by Metallocarboxypeptidase A (115.6 fold high) and Di-peptidyl-peptidases V (10.1 fold high), in dermatophytic patients as compared to ATCC strain. Furthermore, among endoprotease, Metalloprotease 4 was strongly up regulated (131.6 fold high) followed by Metalloprotease 3 (16.7 fold high), in clinical strains as compared to T. mentagrophytes ATCC strain. While among non-protease genes, Citrate Synthase was highly expressed (118 fold high), followed by Isocitrate Lyase (101.6 fold high) and Malate Synthase (52.9 fold high). All the studied virulence genes were considered the best suitable ones by geNorm, Best keeper, Norm Finder and Ref finder.

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.

Serum Cytokine Profile in Patients with Chronic Rhinosinusitis with Nasal Polyposis Infected by Aspergillus flavus.

BACKGROUND: Fungi, especially Aspergillus flavus, can cause chronic rhinosinusitis with nasal polyposis and modulate host innate immune components. The objective of this study was to examine the serum levels of T helper (Th) cell subset Th1, Th2, and Th17 cytokines and total IgE in patients having chronic rhinosinusitis with nasal polyposis and Aspergillus flavus infection. METHODS: A case-control study including 40 patients with chronic rhinosinusitis with nasal polyposis and 20 healthy controls was conducted. Aspergillus flavus infection was confirmed by standard potassium hydroxide (KOH) testing, culture, and PCR. Serum samples of all patients and controls were analyzed for various cytokines (interleukins [IL]-1ß, IL-2, IL-4, IL-6, IL-17, IL-21, IL-27, TGF-ß) and total IgE by ELISA. Data from patients with Aspergillus flavus infection and healthy volunteers were compared using the independent t-test and non-parametric Mann-Whitney U test. RESULTS: Aspergillus flavus infection was found in 31 (77.5%) patients with chronic rhinosinusitis with nasal polyposis. IL-1ß, IL-17, IL-21, and TGF-ß serum levels were significantly higher in these patients than in controls; however, IL-2, IL-4, IL-6, and IL-27 levels were lower. Compared with nine (22.5%) patients without Aspergillus flavus infection, IL-17 level was higher while IL-2 level was lower in patients with Aspergillus flavus infection. Total IgE was significantly higher in patients with Aspergillus flavus infection than in controls. CONCLUSIONS: High levels of IL-17 and its regulatory cytokines in patients with chronic rhinosinusitis with nasal polyposis infected by Aspergillus flavus raise a concern about effective disease management and therapeutic recovery. Surgical removal of the nasal polyp being the chief management option, the choice of post-operative drugs may differ in eosinophilic vs. non-eosinophilic nasal polyposis. The prognosis is likely poor, warranting extended care.

Sporadic occurrence of cryptococcal meningitis in HIV-seronegative patients: Uncommon etiology?

Cryptococcosis in HIV-seronegative patients is rarely reported from India. This prospective study was conducted to look for cryptococcal meningitis in HIV-seronegative individuals and compare their laboratory features to cryptococcal meningitis in HIV-seropositive patients. Cerebrospinal fluid was collected from 153 suspected cases of meningitis and subjected to India ink preparation, antigen detection, and culture. Nineteen samples tested positive for Cryptococcus neoformans infection. Seventeen and two patients were HIV reactive and nonreactive, respectively. In vitro susceptibility of C. neoformans isolates to fluconazole and amphotericin B was performed using standard broth microdilution method and E-test. Eighteen strains were susceptible to amphotericin B, while fluconazole was reported susceptible in 15 strains. Hence, index of suspicion of C. neoformans infection as possible cause of meningitis must be maintained even in HIV-negative patients. Use of amphotericin B for treating C. neoformans meningitis should be restricted to prevent any increase in resistance.

Interleukin-6-174G > C (rs1800795) polymorphism distribution and its association with rheumatoid arthritis: A case-control study and meta-analysis.

The association of interleukin-6 (IL-6)-174G > C (rs1800795) single nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) is a relevant issue because of conflicting and consensus lacking reports published in literature. We investigated IL-6-174G > C promoter polymorphism in 34 RA patients, attending a tertiary care hospital in north India. We also performed a meta-analysis, of the previously published studies reporting this genetic relationship, in overall population, and independently in Asian and Caucasian ethnicities to further elucidate this association. A total of 13 studies, including the current one, involving 3291 RA cases and 3812 controls were analyzed. Out of the 13 studies, 6 were from Asian, 6 from Caucasian and 1 from a mixed population. Our case-control study showed significant association of IL-6-174G > C SNP with increased RA risk: allelic (OR = 3.750, 95% CI = 1.800-7.813, p < 0.001); dominant (OR = 2.800, 95% CI = 1.167-6.721, p = 0.021); and recessive (OR = 36.72, 95% CI = 2.004-672.7, p = 0.015). The meta-analysis revealed the increased RA risk associated with IL-6-174G > C SNP in overall population: allelic (OR = 1.650, 95% CI = 1.169-2.329, p = 0.004); homozygous (OR = 1.380, 95% CI = 0.906-2.101, p = 0.133); heterozygous (OR = 1.559, 95% CI = 1.001-2.428, p = 0.049); dominant (OR = 1.663, 95% CI = 1.078-2.567, p = 0.022); and recessive (OR = 1.366, 95% CI = 0.964-1.935, p = 0.079). Subgroup analysis also showed this polymorphism to be associated with increased RA risk in Asian population: allelic (OR = 3.724, 95% CI = 1.361-10.190, p = 0.010); dominant (OR = 3.823, 95% CI = 1.320-11.074, p = 0.013); and recessive (OR = 4.357, 95% CI = 1.634-11.623, p = 0.003), but not in Caucasian population. This meta-analysis shows that IL-6-174G > C SNP is significantly associated with increased RA risk in overall, and specifically in Asian population.