Diagnostic Utility of Galactomannan Enzyme Immunoassay in Invasive Aspergillosis in Pediatric patients with Hematological Malignancy.

OBJECTIVE: This study aims to determine the diagnostic utility of galactomannan enzyme immunoassay (GM EIA) in invasive aspergillosis (IA) in children with hematological malignancy (high risk population) in terms of sensitivity, specificity, negative predictive value (NPV) and positive predictive values (PPV) at various cut offs while validating the revised EORTC/MSG 2019 criteria in order to obtain the best cut-off. MATERIAL AND METHODS: For 100 pediatric patients, serum and respiratory samples were collected. Clinical, mycological workup (potassium-hydroxide mount, fungal culture) and GM EIA was done to classify proven, probable, and possible IA as per EORTC-MSG guidelines,2019. Sensitivity, specificity, PPV and NPV were calculated of GM indices at cut-off 0.5, 0.7 and 1, and validated with revised EORTC -MSG, 2019. RESULTS: Of 100 patients enrolled, 75 were diagnosed with ALL, 14 with AML, two with Hodgkin's, three had non-Hodgkin lymphoma, and six had undifferentiated leukemia. With routine mycological findings, 51 were classified as probable IA, 11 as possible IA, and 38 as no IA. Aspergillus flavus was the most prevalent on culture (56.9%, 29/51) followed by A. fumigatus (29%, 15/51) A. niger (7.8%, 4/51), A. terreus (3.9%, 2/51) and A. nidulans (2%, 1/51). GM EIA demonstrated sensitivity 82.3%, specificity 97.4%, PPV 98.1%, and NPV 77.1% at cut-off 0.67 when comparing probable/possible IA v/s no IA groups. The GM EIA had the best sensitivity (82.4%), specificity (81.8%), PPV (95.5%), and NPV (50%) at cut off 0.78 when the probable IA group was compared to the possible IA. Seven patients succumbed of whom 5 had GMI ≥ 2. CONCLUSION: This study deduces the optimal cut-off for serum GM EIA to be 0.67 obtained by ROC analysis when comparing possible and probable IA versus no IA and reinforces the definition of probable category of EORTC-MSG criteria, 2019. At 0.5 ODI the sensitivity (87.1%) and NPV (80.5%) are high, thus making it the most suitable cut-off for detecting true positive and ruling out IA respectively, in pediatric patients with hematological malignancy. GM EIA when performed adjunctive to clinico-radiological findings can prove to be screening, diagnostic and prognostic test for IA in pediatric hematological malignancy patients.

Battling the emerging epidemic of rhino-orbital-cerebral mucormycosis (ROCM) in COVID-19 pandemic: an interventional study.

PURPOSE: The most recent challenge being faced by the healthcare system during the worldwide COVID-19 pandemic is increase in the incidence rate of coinfection or superinfection; one of the most fatal being mucormycosis. This study aimed to estimate the risk factors, symptoms and signs, treatment outcome and prognosis of COVID-19-associated mucormycosis (CAM) patients. METHODS: This is an interventional study of 35 patients diagnosed and managed as CAM at a tertiary care centre in New Delhi, India. RESULTS: The mean age of patients was 40.45 ± 6 years with a male preponderance. CAM did not affect healthy individuals; the major risk factors included diabetes in 65.7% and injudicious steroid use in 51.4% patients. Orbital/facial edema was the most common presenting symptom (25.7%) as well as sign (28.57%). 68.5% patients were stage 3 (involvement of orbit) at presentation; 33.3% showed medial wall involvement. Treatment included intravenous Amphotericin and oral Posaconazole in all patients, paranasal sinus (PNS) debridement in 94.2%, orbital exenteration was done in 8 patients. Adjuvant retrobulbar Amphotericin B injection was administered in 12 patients with radiological resolution seen in 50% after 1 cycle. In patients with Stage 4 disease who underwent exenteration along with PNS debridement, survival rate was 100% at 30 days, and disease reduction occurred in 87.5% patients (P < 0.01). Overall, 68.5% responded to therapy, 8.5% showed progression and mortality rate was 22.85%, at a mean follow up period of 59.5 days. CONCLUSION: A multidisciplinary and aggressive approach is essential in the management of CAM patients.

Comparative analysis of airway invasive aspergillosis and endobronchial spread of tuberculosis on high resolution computed tomography.

The presence of tree-in-bud (T-I-B) pulmonary opacities on high resolution computed tomography (HRCT) in tuberculosis endemic areas is frequently regarded as a sine qua non for endobronchial tuberculosis (TB). That is not always the case, however. They can also be found in immunocompromised non-neutropenic patients with airway invasive aspergillosis (IA). Understanding the differences between the two conditions is thus critical for making an accurate diagnosis. This research aims to pinpoint those distinguishing characteristics. The study defines the distribution and morphology of T-I-B opacities and other ancillary pulmonary findings in the two conditions by performing a retrospective analysis of HRCT features in 53 immunocompromised patients with lower respiratory tract symptoms, 38 of whom were positive for TB on BAL fluid analysis and 15 confirmed IA by Galactomannan method. While the global distribution of T-I-B opacities affecting all lobes favoured TB (p=0.002), the basal distribution overwhelmingly favoured IA (p<0.0001). Morphologically, dense nodules with discrete margins were associated with TB, whereas nodules with ground-glass density and fuzzy margins were associated with IA. Clustering of nodules was observed in 18 TB patients (p=0.0008). Cavitation was found in 14 (36.84%) of TB patients but not in any of the IA patients. Peri-bronchial consolidation was found in seven (46.67%) of the IA cases and four (10.53%) of the TB cases (p=0.005, 0.007). The presence of ground-glass opacity and bronchiectasis did not differ significantly between the two groups. Not all T-I-B opacities on HRCT chest in immunocompromised patients in endemic TB areas should be reported as tubercular. Immunocompromised non-neutropenic patients with airway IA can be identified earlier with tree-in-bud opacities on HRCT chest, even in the absence of a nodule with halo, resulting in earlier and more effective management.

Characteristics, outcome and risk factors for mortality of paediatric patients with ICU-acquired candidemia in India: A multicentre prospective study.

BACKGROUND: The epidemiology, clinical profile and outcome of paediatric candidemia vary considerably by age, healthcare settings and prevalent Candida species. Despite these differences, few comprehensive studies are undertaken. This nationwide study addresses this knowledge gap. METHODS: 487 children who contracted ICU-acquired candidemia at 23 Indian tertiary care centres were assessed for 398 variables spanning demography, clinical characteristics, microbiology, treatment and outcome. RESULTS: Both neonates (5.0 days; range = 3.0-9.5) and non-neonatal children (7.0 days; range = 3.0-13.0) developed candidemia early after ICU admission. Majority of neonates were premature (63.7%) with low birthweight (57.1%). Perinatal asphyxia (7.3%), pneumonia (8.2%), congenital heart disease (8.4%) and invasive procedures were common comorbidities, and antibiotic use (94.1%) was widespread. C tropicalis (24.7%) and C albicans (20.7%) dominated both age groups. Antifungal treatment (66.5%) and removal of central catheters (44.8%) lagged behind. Overall resistance was low; however, emergence of resistant C krusei and C auris needs attention. The 30-day crude mortality was 27.8% (neonates) and 29.4% (non-neonates). Logistic regression identified admission to public sector ICUs (OR = 5.64), mechanical ventilation (OR = 2.82), corticosteroid therapy (OR = 8.89) and antifungal therapy (OR = 0.22) as independent predictors of 30-day crude mortality in neonates. Similarly, admission to public sector ICUs (OR = 3.62), mechanical ventilation (OR = 3.13), exposure to carbapenems (OR = 2.18) and azole antifungal therapy (OR = 0.48) were independent predictors for non-neonates. CONCLUSIONS: Our findings reveal a distinct epidemiology, including early infection with a different spectrum of Candida species, calling for appropriate intervention strategies to reduce candidemia morbidity and mortality. Independent factors identified in our regression models can help tackle these challenges.

Disseminated Emergomyces pasteurianus Infection in India: A Case Report and a Review.

We report here a case of disseminated Emergomyces pasteurianus infection from India in a patient with AIDS. The patient presented with weight loss, dyspnoea and multiple non-tender skin lesions over face, neck and chest over 3 months. The case was diagnosed by microscopy, histopathology of sample and isolation of fungus from skin lesion, breast nodule, bone marrow and sputum. The identification of the isolates was confirmed by sequencing internal transcribed spacer region of rDNA, beta-tubulin, actin and intein PRP8. The patient responded well to intravenous amphotericin B deoxycholate followed by itraconazole therapy.

Candida auris candidaemia in Indian ICUs: analysis of risk factors.

Objectives: To identify the risk factors associated with Candida auris candidaemia, as this fungus now poses a global threat. Methods: We performed a subgroup analysis of a previously reported study of 27 Indian ICUs. The clinical data of candidaemia cases due to C. auris and other Candida species were compared to determine significant risk factors associated with C. auris infection. Results: Of the 1400 candidaemia cases reported earlier, 74 (5.3%) from 19 of 27 ICUs were due to C. auris . The duration of ICU stay prior to candidaemia diagnosis was significantly longer in patients with C. auris candidaemia (median 25, IQR 12-45 days) compared with the non- auris group (median 15, IQR 9-28, P < 0.001). Based on logistic regression modelling, admission to north Indian ICUs [OR 2.1 (1.2-3.8); P = 0.012], public-sector hospital [OR 2.2 (1.2-3.9); P = 0.006], underlying respiratory illness [OR 2.1 (1.3-3.6); P = 0.002], vascular surgery [OR 2.3 (1.00-5.36); P = 0.048], prior antifungal exposure [OR 2.8 (1.6-4.8); P < 0.001] and low APACHE II score [OR 0.8 (0.8-0.9); P = 0.007] were significantly associated with C. auris candidaemia. The majority (45/51, 88.2%) of the isolates were clonal. A considerable number of isolates were resistant to fluconazole ( n = 43, 58.1%), amphotericin B ( n = 10, 13.5%) and caspofungin ( n = 7, 9.5%). Conclusions: Although C. auris infection has been observed across India, the number of cases is higher in public-sector hospitals in the north of the country. Longer stay in ICU, underlying respiratory illness, vascular surgery, medical intervention and antifungal exposure are the major risk factors for acquiring C. auris infection even among patients showing lower levels of morbidity.

Invasive pulmonary mycosis due to Chaetomium globosum with false-positive galactomannan test: a case report and literature review.

In this case, the authors report Chaetomium globosum as a cause of invasive pulmonary infection in a patient with Wegener's granulomatosis. Fungal hyphae (KOH and Calcofluor) were seen on direct microscopy of lung biopsy sample and bronchoalveolar lavage (BAL) sample. C. globosum isolated on culture clinched the diagnosis of invasive pulmonary infection by Chaetomium spp. A positive galactomannan of serum and BAL was repeatedly seen and was utilised for follow-up and as prognostic marker in patient management. The patient was successfully treated with liposomal amphotericin B followed by voriconazole. All the Chaetomium infections reported till date since 1980 are reviewed. Chaetomium spp. with its unique ecology has a hidden clinical potential to cause invasive mould infections.

Disseminated Emmonsia pasteuriana infection in India: a case report and a review.

We report here the first case of disseminated Emmonsia pasteuriana infection in a patient with AIDS in India. The patient presented with weight loss, dyspnoea, left-sided chest pain and multiple non-tender skin lesions over face and body for 3 months. Disseminated emmonsiosis was diagnosed on microscopic examination and fungal culture of skin biopsy and needle aspirate of lung consolidation. It was confirmed by sequencing internal transcribed spacer region of rDNA, beta tubulin, actin, and intein PRP8. The patient responded to amphotericin B and itraconazole therapy.

Subcutaneous Phaeohyphomycosis Caused by Pyrenochaeta romeroi in a Rheumatoid Arthritis Patient: A Case Report with Review of the Literature.

Pyrenochaeta romeroi is a rare fungal agent of chronic, suppurative subcutaneous infections leading to mycetoma. It is an unusual cause of deep, non-mycetomatous infections. We herein present review of the literature along with a case of 61-year-old Indian female with rheumatoid arthritis who developed subcutaneous phaeohyphomycosis caused by Pyrenochaeta romeroi. It posed a diagnostic challenge, as the culture from fine-needle aspirate revealed a non-sporulating dematiaceous mould, which was the only supportive tool for its diagnosis and initiation of the therapy. However, it was the molecular sequencing which played the pivotal role in clinching the final aetiological diagnosis. To the best of our knowledge, this is the 20th case of Pyrenochaeta species infection occurring worldwide and first case report of subcutaneous phaeohyphomycosis caused by Pyrenochaeta romeroi in a rheumatoid arthritis patient.

Phaeohyphomycosis Due to Exophiala jeanselmei: An Emerging Pathogen in India--Case Report and Review.

We present a rare case of a 30-year-old woman who presented with a swelling on the lateral aspect of her left forearm, present since 6 months, adjacent to a 16-year-old burn scar. X-ray of elbow joint and forearm revealed the subcutaneous nature of the swelling. Giemsa and periodic acid-Schiff-stained smears and potassium hydroxide mount of fine-needle aspirate of the swelling revealed dematiaceous, branching, and septate fungal hyphae. Fungal culture of the aspirated pus showed growth of Exophiala jeanselmei. Histopathological examination revealed brown-coloured hyphae with foreign body giant cell reaction and palisading granulomas in the surrounding tissue. The patient was successfully treated with surgical excision of the swelling. All the cases of phaeohyphomycosis due to Exophiala spp. in India are also reviewed.

Pulmonary Cryptococcosis in HIV- sero-negative patients: case series from India.

Pulmonary cryptococcosis is likely to be misdiagnosed due to relatively non-specific clinical and radiological features. It is more frequently associated with immuno-suppressed conditions especially acquired immuno-deficiency syndrome (AIDS) and pulmonary tuberculosis (PTB). Four cases of pulmonary cryptococcosis were diagnosed over a period of eleven years. All patients in this case series were human immune-deficiency virus (HIV)-negative. The predisposing factors in these patients were diabetes mellitus (DM), acute lymphoblastic leukaemia (ALL), post-partum and pregnancy in one each of the patients. Relapse was seen in two cases. All the patients survived due to strict follow-up. Pulmonary cryptococcosis is common in non-AIDS patients and it warrants rapid diagnosis, treatment and follow-up to prevent relapse.

An Unusual Presentation of Disseminated Histoplasmosis: Case Report and Review of Pediatric Immunocompetent Patients from India.

Histoplasmosis is a progressive disease caused by dimorphic intracellular fungi and can prove fatal. Usually, it is present in immunocompromised individuals and immunocompetent individuals in the endemic zones. We report an unusual presentation of progressive disseminated histoplasmosis. The patient in the present case report was immunocompetent child and had fever, bone pains, gradual weight loss, lymphadenopathy and hepatosplenomegaly. Disseminated histoplasmosis (DH) was diagnosed on microscopic examination and fungal culture of bone marrow, blood, skin biopsy and lymph node aspirate. The patient died on seventh day of amphotericin B. In the absence of predisposing factors and classical clinical presentation of febrile neutropenia, lung, adrenal and oropharyngeal lesions, the disease posed a diagnostic challenge. Progressive disseminated histoplasmosis in children can be fatal despite timely diagnosis and therapy. In India, disseminated histoplasmosis is seen in immunocompetent hosts. All the pediatrics immunocompetent cases from India are also reviewed.

Tinea capitis caused by Microsporum canis: A case study of three family members in India, a non-endemic region.

INTRODUCTION: Tinea capitis, a common scalp infection primarily affecting children, is caused by keratinophilic dermatophytic fungi, notably Microsporum and Trichophyton species. Microsporum canis, primarily transmitted from cats and dogs to humans, is rarely reported in non-endemic regions like India. We report a cases involving three family members from Delhi, India, diagnosed with tinea capitis caused by Microsporum canis. The index case, a five-year-old boy, contracted the infection through contact with a cat, while his younger brother and sister acquired it through human-to-human transmission within the family. METHODS: Clinical examination, microscopic analysis, and molecular identification techniques confirmed the diagnosis. Antifungal susceptibility testing revealed sensitivity to itraconazole and terbinafine but resistance to griseofulvin. RESULTS: Treatment with oral terbinafine and topical ketoconazole cream led to successful outcomes for all three patients. Molecular typing confirmed clonality of the isolates, indicating human-to-human transmission. CONCLUSION: This case study underscores the significance of considering atypical sources of infection and human-to-human transmission in the diagnosis and management of tinea capitis caused by Microsporum canis in non-endemic regions. It emphasizes the necessity of thorough contact history assessment and appropriate antifungal therapy for effective control of the infection.

Disseminated histoplasmosis in an apparently immunocompetent individual from north India: a case report and review.

Mucocutaneous histoplasmosis is frequently reported in patients with acquired immune deficiency syndrome (AIDS), but it is rare in immunocompetent hosts. Disseminated histoplasmosis involving skin and larynx in a 50-year-old immunocompetent male is described from a non-endemic area in India. The infection appeared to be imported from Thailand. The patient responded very well to intravenous amphotericin B followed by itraconazole. A review of all cases of histoplasmosis occurring in immunocompetent patients from India is reported. Most cases are reported from the Gangetic plains. Adrenals are the most common organ involved in immunocompetent patients, but adrenal insufficiency is not common. Skin lesions and oral ulcers are seen in more than one-third of patients. Predisposing factors like exposure to birds, farming, mining, diabetes were observed in few patients.

Epidemiological and clinico-mycological profile of fungal wound infection from largest burn centre in Asia.

The current study was conducted to know the incidence, predisposing factors, spectrum, clinical profile and antifungal susceptibility (AFS) of fungal wound infection (FWI) in burn patients. Of a total of 71 patients, 20 (28.2%) emerged with the diagnosis of FWI. Fungal pathogens in this study were Candida tropicalis (14%), Candida parapsilosis (5.6%), Aspergillus niger (2.8%) and one each of Candida albicans (1.4%), Candida glabrata (1.4%), Syncephalestrum (1.4%) and Fusarium solani (1.4%). All patients with mould infections expired before the mycological culture results could be conveyed to clinicians. Of the yeasts isolated in the study, one each of C. tropicalis and C. albicans showed cross-resistance to azoles. All the moulds were susceptible to amphotericin B. This study depicted that fungal invasion is associated with a high mortality, burn size 30-60% and high incidence of inhalational injury. Fungal invasion was detected on an average of 14 days after injury. Association of use of four classes of drugs - aminoglycosides, imipenem, vancomycin and third generation cephalosporins and use of total parenteral nutrition was observed. Expedient laboratory diagnosis of FWI and appropriate systemic antifungal therapy guided by AFS may improve outcome for severely injured burn victims.

Cladophialophora carrionii: an aetiological agent of cutaneous chromoblastomycosis from a non-endemic area, North India.

We present a case of infection due to Cladophialophora carrionii, an agent of Chromoblastomycosis in a 37-year-old Indian male. The patient developed a nodule as the lateral malleolus of his left leg. The lesion was successfully treated with surgical excision. Histopathologically, pigmented organisms were readily identified in tissue sections, and the cultural characteristics were these of Cladophialophora carrionii.

Biomedical Waste and Solid Waste Management in the Time of COVID-19: A Comprehensive Review of the National and International Scenario and Guidelines.

Biomedical waste generated during the diagnosis, isolation, and treatment of coronavirus disease 2019 (COVID-19) patients can also be the source of new infections; hence, it needs special consideration. Previous guidelines for the management of biomedical waste need to be revisited as the majority of COVID-19 patients remain asymptomatic and reside in community. Personal protective equipment (PPE) like masks, hazmat suits, gloves, and visors are now being used by the public also. Thus, the general household waste and disposables now make an exponential increase in the waste that can be considered an environmental hazard. In this article, the authors have tried to present the problems arising from COVID-19 waste and the recommendations put forth by competent authorities both nationally and internationally on COVID-19 waste management. Furthermore, in all the guidelines, it is crucial that the COVID-19 waste management follows environmentally sound principles and practices of biomedical waste management, with safe work and infection-control practices. Segregation of COVID-19 waste at source, awareness, and precautions at all steps of the waste-cycle are the only way ahead in this crisis.

Current perspectives of biomedical waste management in context of COVID-19".

COVID-19 pandemic and it's consequent biomedical waste is an unprecedented challenge worldwide. Biomedical waste generated during COVID-19 patient isolation, testing and care needs special consideration as it challenges the previous notion that only 15-20% of waste can be considered infectious. With establishment of new home quarantine facility, isolation/quarantine centres the chances of general waste getting contaminated with biomedical waste has increased exponentially. Through this systematic review the authors searched for all possible queries raised by different researchers on COVID19 waste management on Pubmed. A summary of all the different issues unique to COVID19 waste was prepared. Guidelines, rules and recommendation given by national and international agencies published till date were taken into account while trying to answer all the above questions raised by different studies. The key step in COVID19 waste management is segregation of biomedical waste from solid waste. Waste generated from COVID19 patients is like any other infectious waste, therefore creating public awareness about the COVID19 waste hazards and segregation at source is highlighted in all guidelines as a recommendation. These guidelines for management of waste generated during diagnostics and treatment of COVID-19 suspected or confirmed patients, are required to be followed in addition to existing practices under regulation. BMWM in COVID-19 context is a public health concern and is both a legal and social responsibility for all stakeholders.

Phenotypic and molecular characterisation of Sporothrix globosa of diverse origin from India.

Sporotrichosis is one of the neglected tropical diseases causing subcutaneous chronic granulomatous lesion by thermally dimorphic fungi belonging to Sporothrix species. Sporothrix brasiliensis, Sporothrix mexicana and Sporothrix globosa are the common pathogenic species. In Asian countries, S. globosa constitutes nearly 99.3% of all Sporothrix species. We studied 63 cases of sporotrichosis of geographically diverse origin from India and Sporothrix isolates were characterised for its growth in different media, temperatures, ability to assimilate sugars and antifungal susceptibility profile. Molecular characterization was performed by sequencing of the calmodulin (CAL), beta tubulin (BT) and translational elongation factor 1-alpha (TEF-1α) and typing by fluorescent amplified fragment length polymorphism (FAFLP). In patients who presented with fixed (49.2%), lymphocutaneous lesions (23.8%), in 26.9% the details were not known, none had systemic dissemination. All the isolates tested were Sporothrix globosa and that could grow up to 35 °C and unable to grow at and beyond 37 °C. The assimilation of sucrose, ribitol and raffinose helps in identifying S. globosa. Sequences of CAL or BT or TEF-1α can differentiate S. globosa from other species in the complex. FAFLP results exhibited low genetic diversity. No correlation was noted between genotypes and clinical presentation, or geographic distribution. Itraconazole, terbinafine and posaconazole showed good in vitro antifungal activity against S. globosa whereas fluconazole and micafungin had no activity. S. globosa of Indian origin is relatively less pathogenic than other pathogenic Sporothrix species as it does not cause systemic dissemination and in the diagnostic laboratory, incubation of the cultures below 37 °C is essential for effective isolation.

Minimum inhibitory concentration of carbapenems and tigecycline against Salmonella spp.

Antimicrobial resistance in Salmonella spp. is of grave concern, more so in quinolone-resistant and extended-spectrum beta-lactamase (ESBL)-producing isolates that cause complicated infections. The MIC of azithromycin, ciprofloxacin, cefixime, cefepime, ceftriaxone, gatifloxacin, imipenem, levofloxacin, meropenem and ofloxacin (E-test strip) and tigecycline and faropenem (agar dilution) against 210 Salmonella spp. was determined. MIC(90) (defined as the antimicrobial concentration that inhibited growth of 90 % of the strains) of the carbapenems (imipenem and meropenem) for Salmonella Typhi and Salmonella Paratyphi A was 0.064 microg ml(-1). MIC(90) of faropenem was 0.25 microg ml(-1) for S. Typhi, S. Paratyphi A and Salmonella Typhimurium. The MIC(90) of azithromycin for all Salmonella spp. ranged from 8 to 16 microg ml(-1). Tigecycline showed an MIC(90) of 2 microg ml(-1) for S. Typhi, 1 microg ml(-1) for S. Paratyphi A and 4 microg ml(-1) for S. Typhimurium. We concluded that tigecycline and the carbapenems are likely to have roles in the final stage of treatment of quinolone-resistant and ESBL-producing multidrug-resistant salmonellae.