Gargi Rai

Subcutaneous mycoses caused by Rhytidhysteron species in an immunocompetent patient

Subcutaneous mycoses are chronic fungal infections of the skin and subcutaneous tissues caused by variety of fungal agents and usually occur following trauma with vegetative matter. We report a case of subcutaneous mycoses caused by rare fungus belonging to the genus Rhytidhysteron, in an immunocompetent male who presented with a subcutaneous nodule on left foot. This unusual species was identified and confirmed by molecular methods.

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]-1β, IL-2, IL-4, IL-6, IL-17, IL-21, IL-27, TGF-β) 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-1β, IL-17, IL-21, and TGF-β 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.

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

Abstract 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.

Phenotypic and functional profile of Th17 and Treg cells in allergic fungal sinusitis

&NA; Interleukin‐17 producing T helper (Th17) and regulatory T cells (Treg) cells have been identified to play a critical role in atopic inflammation. However, conflicting reports on the role of Th17/Treg cells in allergic fungal rhinosinusitis (AFRS) patients of different ethnicities has mystified its pathogenesis. To better understand the pathophysiological mechanisms involved in AFRS, we conducted a prospective, analytical, case‐control study involving 40 confirmed immunocompetent AFRS patients and 20 healthy controls. The distribution of Th17 and Treg cells in PBMC, intracellular mRNA expression of retinoid orphan nuclear receptor (ROR&ggr;t) in Th17 and forkhead transcription factor (FoxP3) in Treg cells, and serum cytokine levels were investigated. Aspergillus flavus was identified from majority (85%) of patient tissue biopsies. Total serum IgE level along with cytokines IL‐17, IL‐21, IL‐1&bgr; and TGF‐&bgr; were comparatively elevated in AFRS. Nevertheless, IL‐2 and IL‐10 were reduced. Higher percentages of CD3+CD4+ T cells in AFRS with increased expression of CD161 and/or IL‐23R markers were observed. Though, lower percentages of CD4+CD25+ Treg cells with elevated expression of GITR were patent. Transcription factor ROR&ggr;t mRNA was upregulated, whereas FoxP3 mRNA was downregulated in AFRS patients. This inclination of Th17/Treg balance towards Th17, and the proposed role of Tregs on Th1 and Th2 cells in AFRS, directed us to conclude that Aspergillus infestation may lead to development of atopy and immunological dysbalance inciting a Th17 driven response, thereby, promoting aggravation of nasal polyposis. The observation may provide new insight into the molecular mechanisms leading to revision of the classical paradigm. HighlightsAspergillus flavus acts as the predominant etiological agent in allergic fungal rhinosinusitis in Indian population.Aspergillus infection leads to atopy and immunological dysbalance.Immunological dysbalance incites a Th17 driven response, thereby, promoting aggravation of nasal polyposis.

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.

FcɛR1α gene polymorphism shows association with high IgE and anti-FcɛR1α in Chronic Rhinosinusitis with Nasal Polyposis

Despite large number of investigations, the etiology of chronic rhinosinusitis (CRS) remains unclear. Several factors are likely involved in its onset. The genetic susceptibility of IgE‐responsiveness likely caused by polymorphism(s) in high affinity receptor for IgE (FcɛR1α) gene can help in understanding the pathophysiology of CRS with nasal polyposis (CRSwNP). A population‐based case‐control association analysis was conducted to assess the risk of CRSwNP conferred by single nucleotide polymorphisms (SNPs) in FcɛR1α gene in a North Indian cohort. Two promoter and three exonic regions of FcɛR1α gene were amplified and sequenced to investigate five SNPs: rs2427827, rs2251746, rs2298804, rs2298805, and rs2269718. BLAST analysis and subsequent multiple alignments, with known sequences available in the NCBI database, were performed. Total serum IgE and FcɛR1α antibody levels were estimated. Patient IgE level of 461.22 ± 436.43 in comparison to 83.62 ± 58.043 IU/mL in controls (P < 0.0001), and FcɛR1α antibody level of 292.38 ± 115.27 in comparison to 160.56 ± 105.9 in controls (P < 0.0001), depicts their highly significant associations with CRSwNP disease. However, no SNP showed evidence of association with CRSwNP; although relatively higher Odds ratios were observed with rs2427827, rs2251746, and rs2298804. Patient stratification revealed a significant association (P < 0.05) of rs2427827 SNP with high IgE level CRSwNP patients. Nonetheless, we found no SNP associated with low serum IgE level patients. SNP (rs2427827) in the FcɛR1α gene region and high IgE levels may confer susceptibility to CRSwNP in north Indian population. However, further studies including larger sample size, gene‐gene, and gene‐environment interactions are required for its elucidation.

Candida auris in critically ill patients: Emerging threat in intensive care unit of hospitals

Candida auris has emerged as the multi-drug resistant non-albican candida species in critically ill patients admitted to intensive care units (ICU) causing bloodstream and other infections. It has often been misidentified as Candida famata, Candida sake, Rhodotorula glutinis, or Saccharomyces cerevisiae and Candida haemulonii by automated identification systems. We, in this study, discuss three patients who acquired Candida auris infection after 15 to 20days of their stay in medical ICU. Medical equipment, use of multiple antibiotics, and poor hand hygiene are the most probable predisposing factors attributing to its colonization at multiple anatomical sites leading to bloodstream infection. Candida auris might substantially contaminate the environment of colonized or infected patients making its eradication difficult. Patient screening for Candida auris, especially during prolonged ICU stays, along with strict infection prevention and control strategies needs to be adopted to break its persistence.

Serum Interleukin-6 Levels in Children with Febrile Seizures

ObjectivesTo compare levels of Interleukin-6 (IL-6) in children with febrile seizures and febrile controls.MethodsStudy conducted in a tertiary-care hospital in Northern India from November 2013 to April 2015, enrolling 160 children (80 each with febrile seizures and febrile controls), aged 6–60 months. Serum IL-6 estimated by ELISA method. Iron study done as per standard technique. All the cases of febrile seizure were followed up at 1 week, 3 months and 6 months for recurrence of seizures.ResultsThe mean serum IL-6 levels in children with febrile seizures was 62.0 (63.9) pg/mL and febrile controls was 86.9 (70.6) pg/mL (P=0.025).ConclusionSerum IL-6 levels were significantly lower in children with febrile seizures as compared to febrile controls.

Challenges in culture-negative cases of Madurella mycetomatis: A case report re-accentuating PCR as an essential diagnostic tool

Identification of dematiaceous fungi responsible for black-grain mycetoma has remained cumbersome and time consuming for years leading to delayed diagnosis and thereby increased agony to patients. Moreover, difficult morphology of some of these fungi demanding enough expertise for species identification in addition to culture-negativity has often led to misdiagnosis and hence inapt treatment to the patients. We report the identification of Madurella mycetomatis from culture-negative black granules discharged from foot nodular lesions of a 27 years old male using PCR followed by sequencing of the internal transcribed spacer region. The patients lesions were successfully treated using a combination of itraconazole (200mg) and terbinafine (250mg), confirming our diagnosis. Our case study proves the clinical value of PCR as the best, rapid and accurate diagnostic method for the identification of Madurella mycetomatis and related fungi, particularly in culture-negative cases.