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The COVID-19 pandemic is a global health crisis that poses a great challenge to the public health system of affected countries. Safe and effective vaccines are needed to overcome this crisis. Here, we develop and assess the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine in rhesus macaques. Twenty macaques were divided into four groups of five animals each. One group was administered a placebo, while three groups were immunized with three different vaccine candidates of BBV152 at 0 and 14 days. All the macaques were challenged with SARS-CoV-2 fourteen days after the second dose. The protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd-week post-immunization. Viral clearance was observed from bronchoalveolar lavage fluid, nasal swab, throat swab and lung tissues at 7 days post-infection in the vaccinated groups. No evidence of pneumonia was observed by histopathological examination in vaccinated groups, unlike the placebo group which exhibited interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. This vaccine candidate BBV152 has completed Phase I/II (NCT04471519) clinical trials in India and is presently in phase III, data of this study substantiates the immunogenicity and protective efficacy of the vaccine candidates., SARS-CoV-2 vaccines are needed to fight the pandemic. Here, authors show protective efficacy and immunogenicity of the inactivated SARS-CoV-2 vaccine BBV152 in rhesus macaques. This vaccine is currently in clinical development.

Vaccines remain the key protective measure to achieve herd immunity to control the disease burden and stop COVID-19 pandemic. We have developed and assessed the immunogenicity and protective efficacy of two formulations (1mg and 2mg) of ZyCoV-D (a plasmid DNA based vaccine candidates) administered through Needle Free Injection System (NFIS) and syringe-needle (intradermal) in rhesus macaques with three dose vaccine regimens. The vaccine candidate 2mg dose administered using Needle Free Injection System (NFIS) elicited a significant immune response with development of SARS-CoV-2 S1 spike region specific IgG and neutralizing antibody (NAb) titers during the immunization phase and significant enhancement in the levels after the virus challenge. In 2 mg NFIS group the IgG and NAb titers were maintained and showed gradual rise during the immunization period (15 weeks) and till 2 weeks after the virus challenge. It also conferred better protection to macaques evident by the viral clearance from nasal swab, throat swab and bronchoalveolar lavage fluid specimens in comparison with macaques from other immunized groups. In contrast, the animals from placebo group developed high levels of viremia and lung disease following the virus challenge. Besides this, the vaccine candidate also induced increase lymphocyte proliferation and cytokines response (IL-6, IL-5).The administration of the vaccine candidate with NFIS generated a better immunogenicity response in comparison to syringe-needle (intradermal route). The study demonstrated immunogenicity and protective efficacy of the vaccine candidate, ZyCoV-D in rhesus macaques.

The COVID-19 pandemic is a global health crisis that has severely affected mankind and posed a great challenge to the public health system of affected countries. The availability of a safe and effective vaccine is the need of the hour to overcome this crisis. Here, we have developed and assessed the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152) in rhesus macaques (Macaca mulata). Twenty macaques were divided into four groups of five animals each. One group was administered a placebo while three groups were immunized with three different vaccine candidates at 0 and 14 days. All the macaques were challenged with SARS-CoV-2 fourteen days after the second dose. The protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd-week post-immunization. Viral clearance was observed from bronchoalveolar lavage fluid, nasal swab, throat swab, and lung tissues at 7 days post-infection in the vaccinated groups. No evidence of pneumonia was observed by histopathological examination in vaccinated groups, unlike the placebo group which showed features of interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. Data from this study substantiate the immunogenicity of the vaccine candidates and BBV152 is being evaluated in Phase I clinical trials in India (NCT04471519).

Aim: The objective was to do a comparative study and to evaluate the outcome in overall acceptance for correction of residual facial deformity with autogenous graft versus porous polyethylene implants. Materials and Methods: A total of 16 patients in the age group of ≥15 years irrespective of sex, caste, religion, and socioeconomic status presenting with signs and symptoms of residual facial deformities and who were declared fit for surgery were included in the study. The study patients were further divided into two groups, of eight each. Deformity correction using autogenous grafts was performed in Group A and using high-density polyethylene (HDPE) alloplastic implants was performed in Group B. During the follow-up period, patients' and doctor rating of overall acceptance between autogenous and alloplastic (HDPE) bone grafts was recorded on 100-mm visual analog scale (VAS) on the 2nd day and 7th day and at 3, 6, and 12 weeks. Results: The unpaired t-test is used for evaluation. VAS score at all the follow-up periods above stated was significantly higher in alloplastic group than in the autogenous group for both in patients and doctor evaluation. Conclusion: From the present study, it can be concluded that porous HDPE implants are an effective alternative to autogenous grafts in accordance of overall acceptance for correction of residual facial deformity when proper case selection, exclusion of negative prognostic factors, and meticulous surgical procedure are followed.

Background: Systemic steroids are the cornerstone of therapy in allergic bronchopulmonary aspergillosis(ABPA) but are associated with adverse effects. Itraconazole(ITZ) is proposed as an effective yet safer alternative. Aims: To evaluate the effectiveness of ITZ in comparison to systemic steroids in the management of ABPA. Methods: ABPA patients diagnosed between 2010-16 were administered oral ITZ or deflazacort(DFZ) and were followed every 3 months with serial total and specific IgE antibodies, chest x-ray; symptom control, time to remission, exacerbations and time to exacerbations were noted. Results: 172 patients were enrolled, 45 received ITZ(group A) and 106 received DFZ(group B). Both groups were homogenous with regards to their baseline characteristics (P 0.9999) achieved remissions and at a similar time (7.7±0.7 vs 7.5±0.4months respectively;P=0.77). Also, an equal number exacerbated (57.5 vs 51.7% respectively;P=0.57) within 6 months (4.4±0.7 vs 5.7±0.5 respectively;P=0.13) after stopping therapy. However patients in group A suffered more exacerbations (1.2±0.1 vs 1.05±0.03months;P=0.048) subsequently. Conclusions: ITZ and DFZ are equally effective in ABPA when administered for a similar duration to effect a disease remission. While neither drug is superior in preventing or delaying exacerbations of the disease, steroids may have the advantage of producing lesser subsequent exacerbations in comparison to ITZ.

Background: Invasive aspergillosis (IA) is now recognized in immunocompetent patients too with outbreaks known to occur in hospitals during civil work Aims: To identify characteristics and outcomes of patients who developed IA and correlate aerial spore counts and molecular types of Aspergillus isolates with possible role of civil work in nosocomial infection Methods: Patients diagnosed in 2010-16 were enrolled. Clinical data and outcome were noted. Those with nosocomial infection, defined as IA diagnosed 2days after admission served as cases. Annual incidence of IA and spore counts were calculated. Environmental and clinical Aspergillus isolates were characterized by microsatellite typing (STR) to determine possible source of infection Results: IA was observed in 50cases. Civil work was done in 2011,2014-16. Incidence of IA correlated with greater spore counts (r=0.942). COPD was commonest risk factor. None were immunocompromised. Further, 77% of those admitted required ICU care. Cases stayed longer in wards than controls(12.4±9.4vs0.8±0.8days, p=0.000) before diagnosing IA and received therapy later(7.8±7.8vs3.3±3.5days, p=0.011). 64.4% patients succumbed to IA. Both groups were similar in terms of age, sex, risk factors, serology, radiology, treatment outcomes Although no environmental A. Fumigatus isolate shared the same STR type as patient isolates, similar STR types were observed among patients suggesting common source of infection Conclusion: Civil work in augments Aspergillus spore count, increasing the incidence of IA in admitted immunocompetent patients with prolonged fungal exposure. No difference is seen in the natural history of IA with respect to source of infection.

In modern era, with tremendous competition, long working hours and more demanding workstyle, nearly every profession is associated with some or the other health hazards. These may develop and progress rapidly or in a gradual way but ultimately add up unwanted morbidities and in long run affects the production and work output. Unfortunately, doctors and other health professionals who look after the health of society, are not the exceptions to this rule and depending upon their specialty, they have to face some or the other health issues. This article highlights some important though underestimated health issues among radiologists and some remedies. It aims to sensitize radiologists about such health issues so that they can take timely remedial measures before it is really late.

The small airways, once regarded as the silent zone in the air conducting system of the lungs are now known to be one of the initial sites of involvement in diseases like asthma and Chronic Obstructive Pulmonary Disease (COPD). Identification of the involvement of distal airways in these diseases is often difficult to assess, clinically as well as by conventional pulmonary function tests and therefore, usually remains undiscovered in early stages. Early recognition of their involvement in asthma and COPD and timely management may reduce long term morbidity in these conditions. This article aims to highlight the relatively lesser recognized facts about small airways involvement in asthma and COPD and role of imaging and newer modalities for detection.

Contains fulltext : 137490.pdf (Publisher’s version ) (Closed access) Candida auris is a recently described rare agent of fungemia. It is notable for its antifungal resistance. A total of 15 C. auris isolates, originating from seven cases of fungemia, three cases of diabetic gangrenous foot, and one case of bronchopneumonia from a tertiary care hospital in south India, were investigated. All of the 15 isolates were identified by sequencing and 14 of these along with 12 C. auris isolates previously reported from two hospitals in Delhi, north India, two each from Japan and Korea were genotyped by amplified fragment length polymorphism (AFLP). In vitro antifungal susceptibility testing (AFST) was done by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. Candida auris isolates were misidentified as Candida haemulonii by VITEK. All were resistant to fluconazole [geometric mean minimum inhibitory concentration (MIC) 64 mug/ml] and 11 isolates were resistant to voriconazole (MIC >/=1 mug/ml). Forty-seven percent of the C. auris isolates were resistant to flucytosine (MIC >/=64 mug/ml) and 40% had high MIC (>/=1 mug/ml) of caspofungin. Breakthrough fungemia developed in 28.6% of patients and therapeutic failure in 4 (66.7%) patients. Interestingly, the 26 Indian C. auris isolates from north and south India were clonal and phenotypically and genotypically distinct from Korean and Japanese isolates. The present study demonstrates that C. auris is a potential emerging pathogen that can cause a wide spectrum of human mycotic infections. The prevalence of a C. auris endemic clonal strain resistant to azoles and other antifungals in Indian hospitals with high rates of therapeutic failure in cases of fungemia is worrisome.

Considering the growing need to identify alternative bio-nutritional sources, wild edible leaves consumed in forest zone of Uttarakhand, India were evaluated for their nutritive value in order to prioritize edible wild plant suitable for domestication. The result showed significance of wild plant species as important source of nutrient for rural poor people. The nutritional value of leaves of wild plant Urtica ardence were evaluated in terms of protein, carbohydrate, fat, fiber content, vitamin content, reducing sugars and minerals. Urtica ardence had a significant level of above nutrients and therefore was identified as promising specie for promotion as backyard planting especially farming systems suffering from crop loss, food shortage and chronic malnutrition.

Background Itraconazole (ITZ) is an alternative to steroids in the treatment of allergic bronchopulmonary aspergillosis (ABPA) but therapeutic drug monitoring (TDM) is warranted due to erratic absorption and early relapse. Aim To correlate serum ITZ levels with clinical outcomes in ABPA. Methods ITZ capsules 400mg/day for 6 months were administered as monotherapy to 30 consecutive patients in stage 4/5 of ABPA between Jan913 to Jun913. High-performance liquid chromatography was done on serum samples collected after 2-4 weeks to measure concentrations of ITZ and its active metabolite hydroxy-ITZ (OHITZ); ITZ levels of >2mg/L were considered adequate. Total and Aspergillus species specific IgE, leucocyte count (TLC), eosinophil count (AEC) and precipitins were recorded before and thereafter. Any relapse was noted till 2 years. Results Mean serum concentration of ITZ and OHITZ was 0.79±0.2 and 1.2±0.3mg/L respectively. Total IgE (9.9±1.4 vs 6.5±1.2×10 3 IU/mL), specific IgE (42.98±3.9 vs 34.1±4.8KUA/L), TLC (10.6±0.6 vs 9.7±0.7×10 3 cells/µL) and AEC (1.0±0.1 vs 0.6±0.09×10 3 cells/µL) reduced significantly. Remission was achieved in 64% but 52% relapsed after 3months. Serum ITZ and OHITZ levels correlated negatively with total IgE, specific IgE, TLC, AEC, relapse and time to relapse but only those between ITZ (r=0.049) and OHITZ (r=0.039) with duration to relapse were significant. Adequacy of ITZ and OHITZ significantly related with remissions(P=0.039). Conclusion ITZ monotherapy is effective in treating ABPA therefore TDM should be routinely undertaken. Adequate serum drug levels imply remissions but do not correlate well with markers of disease severity. Relapse may be prevented by prolonged drug use.

Background: Chronic pulmonary aspergillosis (CPA) is still under-diagnosed in high tuberculosis (TB) burden areas like India where similar clinical presentation and disregard for underlying risk factors lead to its misdiagnosis as the latter. Aim: To evaluate patient characteristics and treatment outcomes in CPA patients Methods: Consecutive patients with a differential diagnosis of CPA enrolled from Jan. 2012-Dec. 2013 were administered oral itraconazole (ITZ) or voriconazole. Weight, BMI, haemoglobin (Hb), total leucocyte count (TLC), specific IgG, precipitins, CRP, sputum fungus and radiology were followed till 2 years after the end of treatment. Negative specific IgG was taken as end-point of therapy. Results: CPA was diagnosed in 24(70.5%) patients including 10 CCPA, 9 CNPA, 3 CFPA and 2 simple aspergilloma. Mean age was 47.2±10.9years. Average 2.1 risk factors were present per patient; TB was the commonest risk factor (29.3%) but ABPA, sarcoidosis and diabetes mellitus were significantly associated with development of CPA. Cavitation was noted in 29% and aspergilloma in 12%. Specific IgG and serum precipitins were raised in 79% and CRP 92%. A. fumigatus was isolated in 80%. Both drugs exerted similar but significant improvements in weight (51.8±7 vs 56.3±8 Kg), BMI (18.7±3.1 vs 20.3±3.0 Kg/m 2 ), Hb (11.3±1.9 vs 12.3±1.7 g/dL), TLC (10.2±3.1 vs 7.9±2.6×10 3 /µL), precipitins and specific IgG (69.1; 26.5-84.2 vs 29.6; 0-39.3 MgA/L). Two cases on ITZ relapsed at 12 months; no deaths were reported. Conclusions: CPA should be investigated in patients with multiple risk factors. Triazole antifungals are effective in treatment. Specific IgG titers can be used to assess disease activity and response to treatment.

Aspergillus is a large genus of saprophytic fungi which are present everywhere in the environment. However, in persons with underlying weakened immune response this innocent bystander can cause fatal illness if timely diagnosis and management is not done. Chest infection is the most common infection caused by Aspergillus in human beings. Radiological investigations particularly Computed Tomography (CT) provides the easiest, rapid and decision making information where tissue diagnosis and culture may be difficult and time-consuming. This article explores the crucial role of CT and offers a bird's eye view of all the radiological patterns encountered in pulmonary aspergillosis viewed in the context of the immune derangement associated with it.

Several high energy physics and neutrino physics experiments worldwide require large-size RPCs to cover wide acceptances. The muon tracking systems in the Iron calorimeter (ICAL) experiment in the India based Neutrino Observatory (INO), India and the near detector in Deep Underground Neutrino Experiment (DUNE) at Fermilab are two such examples. A single gap bakelite RPC of dimension 240 cm × 120 cm, with gas gap of 0.2 cm, has been built and tested at Variable Energy Cyclotron Centre, Kolkata, using indigenous materials procured from the local market. No additional lubricant, like oil has been used on the electrode surfaces for smoothening. The chamber is in operation for > 365 days. We have tested the chamber for its long term operation. The leakage current, bulk resistivity, efficiency, noise rate and time resolution of the chamber have been found to be quite stable during the testing peroid. It has shown an efficiency > 95% with an average time resolution of ~ 0.83 ns at the point of measurement at ~ 8700 V throughout the testing period. Details of the long term performance of the chamber have been discussed.

Item does not contain fulltext A rare case of allergic bronchopulmonary mycosis (ABPM), caused by Alternaria alternata, is reported in an immunocompetent resident of Delhi. Her complaints included a generalized, urticarial skin rash and occasional pain in the right lower chest. Her differential count showed eosinophils, 22%; absolute eosinophil count (AEC), 2400 cells/mul; and total IgE, 4007 IU/ml. The computerised tomogram (CT) scan of her thorax showed an enhancing lesion with surrounding ground glass haziness in the right lower lobe. Histopathologic examination of the resected lung revealed a necrotizing granulomatous inflammation, parenchymal infiltration by eosinophils, lymphocytes, neutrophils, plasma cells and some exudative bronchiolitis suggestive of ABPM. Observation of KOH wet mounts of repeat sputum and BAL samples demonstrated the presence of septate, brownish hyphae and cultures of these specimens yielded A. alternata (identified by sequencing of the ITS region). Her serum showed a three-fold higher specific IgE to A. alternata antigens than control levels, and the type I cutaneous hypersensitivity response to antigens of A. alternata was strongly positive. She was treated successfully with oral glucocorticoids and itraconazole. To our knowledge, ABPM due to Alternaria alternata has not been reported previously. 01 november 2012

Atopic patients with chronic obstructive pulmonary disease (COPD) demonstrate more severe symptoms than their non-atopic counterparts. Also, Aspergillus hypersensitivity is known in COPD. However, allergic sensitisation to non-Aspergillus fungi has never been studied in COPD patients. To evaluate the prevalence of fungal sensitisation and its impact on the clinical presentation and outcome of COPD patients. Sensitisation to 17 fungi was studied in 55 COPD patients through skin prick tests, fungus-specific IgE, precipitating antibodies, total IgE and eosinophil counts. The clinical symptoms of patients were monitored thorough a patient-administered questionnaire. Overall, 5.4% (n = 3) of COPD patients were fungus sensitive. The sensitisation was noted to Alternaria alternata and Schizophyllum commune in two patients each, whereas another was sensitive to A. tamarii, Rhizopus spp. and Aspergillus fumigatus. Eosinophils were higher in fungus-sensitised patients (P = 0.001 vs. 0.003). No differences were noted in the clinical presentation of patients sensitised to fungi compared to those not sensitised to fungi or non-atopic. Although low, fungal sensitisation occurs in COPD but it is not limited to Aspergilli alone. Fungus-sensitised patients exhibit greater eosinophilia, implying more severe inflammation. Thus, such patients should be followed up regularly to recognise clinical worsening or development of ABPM.

Penicillium species are ubiquitously present in the environment and are usually considered as laboratory contaminants or non-pathogenic. Among Penicillium species Penicillium marneffei is the only dimorphic member, which is an established agent of invasive mycoses in immunocompromised and immunocompetent patients [1, 2]. However, invasive fungal infections due to Penicillium species other than P marneffei such as Penicillium chrysogenum [3, 4], Penicillium citrinum [5], Penicillium decumbens [3, 6], Penicillium piceum [7, 8], Penicillium commune [9], and Penicillium purpurogenum [3] have also been rarely reported. The reduced susceptibility of these species to voriconazole, which is often the first-line therapy for invasive mold infections, is particularly worrisome [10, 11]. In this study, we report 3 rare cases of opportunistic fungal infection caused by voriconazole-resistant Penicillium oxalicum in patients with acute myeloid leukemia (AML), diabetes mellitus (DM), and chronic obstructive pulmonary disease (COPD), while on voriconazole therapy for 3–6 weeks.

To evaluate the anti-inflammatory property of the different extract of bark of Juglans regia , family Juglandaceae is a deciduous tree. Its fruits are consumed as food, which are rich in unsaturated fatty acids. Walnut leaf has been widely used in traditional medicine for the treatment of skin inflammations and ulcers and for its antidiarrheic, antihelmintic, antiseptic and astringent properties. The present study aimed at the evaluation of anti-inflammatory property of the aqueous, chloroform and alcoholic extracts of the bark by in vitro methods. In vitro method was estimated by human red blood cell membrane stabilization (HRBC) method. Results showed significant anti-inflammatory property of the different extracts tested. The aqueous extract at a concentration of 200 mg/ml. showed potent activity on comparing with the standard drug diclofenac sodium. Key words: Juglans regia , HRBC, Inflammation and dicloenac.

Introduction: The loss of body mass leading to cachexia is known to exist in chronic obstructive pulmonary disease (COPD). However, the role of body composition in asthmatics has not been widely explored. Materials and Methods: Body weight (BW), body mass index (BMI), percentage of ideal BW (PIBW), fat mass (FM), fat free mass index (FFMI), and midthigh cross-sectional were evaluated in COPD (n = 40) and asthma (n = 40) and compared with 20 healthy controls. Socioeconomic status served as a marker of dietary adequacy. Results: Weight (P < 0.001), BMI (P < 0.01), FMI (P < 0.05), and FFMI (P < 0.001) differed significantly among socioeconomic classes. Significant intergroup differences of weight and FFMI in the upper (P < 0.05) and BMI and PIBW in the upper-middle class (P < 0.05) were seen. BW in COPD was lower than bronchial asthma (BA) (P < 0.001) and controls (P < 0.001). BMI in COPD was lower than BA (P < 0.000) as were PIBW (P < 0.000) and FM (P < 0.001), whereas neither study group differed from controls. FFMI in COPD was lower than BA (P < 0.004) and controls (P < 0.01). No parameter differed between BA and control groups. Comparing by severity of airflow obstruction, all parameters were reduced in COPD, but statistical significance (P < 0.05) was noted for BMI and FFMI in mild/moderate cases and weight, BMI, PIBW, and FM in severe/very severe cases. No significant differences were noted when assessed with respect to severity of either disease. Correlations were noted between FFMI and post bronchodilator forced expiratory volume in the 1 st second (FEV) 1 (r = 0.342) and weight and post bronchodilator FEV 1 (r = 0.322) in COPD. Conclusion: COPD produces malnutrition with regards to both fat and fat free components, irrespective of the severity of the disease, whereas asthma bears no such association.

Allergic bronchopulmonary aspergillosis (ABPA) is known to complicate asthma and cystic fibrosis, but an association of ABPA with chronic obstructive pulmonary disease (COPD) has also been found lately. The mechanism through which ABPA operates is still an enigma. With the discovery of ABPA in COPD, interest in the theory that asthma and COPD could share a common etiology has been rekindled. Herein, we present the case of a 60-year-old male, diagnosed case of COPD, who reported exacerbations during the monsoons, which mandated frequent courses of systemic steroids. He was diagnosed to have co-existing ABPA based on positive skin tests to Aspergillus niger, A. flavus, A. fumigatus, and A. tamarii and raised serum total IgE and specific IgE against Aspergillus spp. His CT scan showed centrilobular and panacinar emphysema along with central bronchiectasis. The spirometry showed a significant response to bronchodilators. The patient fulfilled all the minimal essential requirements for the diagnosis of ABPA, except asthma. The patient responded well to systemic steroids. This report makes an important observation that species of Aspergillus other than A. fumigatus could be instrumental in causing ABPA in patients with COPD, unlike that seen in asthma. The possible etiologic mechanisms underlying the development of ABPA in COPD and also the evolution of ABPA from its serological to bronchiectasis variant are discussed in this report.