Modulation of autophagy and mTOR signaling pathway genes in respiratory epithelium by respiratory syncytial virus (RSV) in children suffering from acute lower respiratory tract infections.

The study was planned to carry out the molecular characterization of the respiratory syncytial virus (RSV) circulating strains and to elucidate the gene expression of autophagy and mammalian target of rapamycin (mTOR) signaling pathways in children with acute lower respiratory tract infection (ALRTI). Nasopharyngeal aspirate (NPA) samples (n = 145) from children suffering from ALRTI were subjected to the detection of RSV. Of them, 31 RSV positive strains were subjected for sequencing. Semi-quantitative gene expression analysis for mTOR signaling and autophagy pathway genes was performed in respiratory tract epithelial cells using 25 RSV positive cases, and 10 age and sex matched healthy control subjects. Five representative genes were selected for each pathway and subjected to SYBR green real-time polymerase chain reaction. RSV was positive in 69 (47.6%) samples and the representative (n = 31) RSV strains belonged to RSV-A. Thirty-one strains of RSV-A on phylogenetic analysis clustered with the novel ON1 genotype having 72 bp nucleotide duplicationby targeting the ecto-domain portion of the G gene. Further, the stains belonged to lineage 1 (51.6%), followed by lineage 3 (29%) and lineage 2 (19.4%). Autophagy gene expression analysis revealed significant upregulation in NPC1 and ATG3 autophagy genes. mTOR, AKT1, and TSC1 genes of the mTOR pathway were significantly downregulated in RSV positive patients. Thus, RSV infection inducing autophagy pathway genes (NPC1 and ATG3) and suppressing mTOR signaling pathway genes (AKT1, mTOR, and TSC1) to possibly evade the host immune system through dysregulating these pathways for its way of survival within the host.

Avian influenza revisited: concerns and constraints.

Avian influenza (AVI) is being known for its pandemic potential and devastating effects on poultry and birds. The AVI outbreaks in domesticated birds are of concern because the Low pathogenic avian influenza virus (LPAI) tends to evolve into a High pathogenic avian influenza virus (HPAI) resulting in the rapid spread and significant outbreak in poultries. The containment should be rapid and stringent precautions should be taken in handling the infected poultry cases or infected materials. In general, AVI viruses do not replicate efficiently in humans, indicating that transmitting these viruses to humans directly is a very rare preference. However, the HPAI ability to the cross-species barrier and infect humans has been known for H5N1 and H7N9. Recently, the world's first human case of transmission of the H5N8 strain from the avian species to humans has been documented. In this recent scenario, it is worth discussing the strain variations, disease severity, economic loss, and effective controlling strategies for controlling avian influenza.

Impact of Recent SARS-CoV-2 Infection on the Course and Severity of Dengue in Children: A Prospective Observational Study from North India.

In 2020, a considerable overlap occurred between the COVID-19 pandemic and seasonal dengue transmission in India. This study aimed to evaluate the effects of acute or recent infection with SARS-CoV-2 on the course and outcomes of dengue fever in children. We prospectively enrolled 44 children with a clinical and laboratory diagnosis of dengue fever. Assessment of acute and recent SARS-CoV-2 infection was done using reverse transcription-polymerase chain reaction and IgG antibody through ELISA. Children were grouped based on evidence of SARS-CoV-2 exposure and clinical severity, and outcomes were compared. The median age of the study cohort was 96 months (interquartile range [IQR]: 69-129 months). Fever (98%), vomiting (78%), abdominal pain (68%), hepatomegaly (68%), and edema (32%) were the common features. About two-thirds (N = 30) had severe dengue; 20 (45%) had dengue shock. Liver dysfunction (58%) and acute kidney injury (25%) were other major organ dysfunctions. Nineteen (43%) children stayed in the pediatric intensive care unit for a median duration of 5 days (IQR: 2-11 days). None had acute SARS-CoV2 infection; however, IgG against SARS-CoV-2 was detected in 15 (34%) cases. Children with recent exposure to SARS-CoV-2 showed a trend toward a lower incidence of acute kidney injury, fewer organ dysfunctions, and a lower frequency of invasive ventilation. Four children (9%) died; none of the deaths were in the SARS-CoV-2-exposed group. The present study exposes preliminary evidence that dengue fever might follow a less severe course in children with recent exposure to SARS-CoV-2 infection. However, it is pertinent to understand the antigenic similarity and cross-protective antibody response between the two viruses and their clinical relevance.

Rapid antigen detection kit for the diagnosis of SARS-CoV-2 - are we missing asymptomatic patients?

PURPOSE: To determine the utility, diagnostic accuracy, sensitivity, specificity, and negative predictive value of the laboratory based Covid-19 antigen detection test (Coris Bio- Concept, Gembloux, Belgium) for the diagnosis of SARS-CoV-2 in a tertiary care hospital among symptomatic and asymptomatic patients. METHODS: The nasopharyngeal swab samples were collected from the symptomatic patients and their contacts. The diagnostic accuracy of this antigen kit was determined in comparison to SARS-CoV-2 real-time reverse transcriptase (RT-PCR). RESULTS: A total of 825 patients fulfilling the inclusion criteria were included in the study; RT-PCR and antigen detection was performed simultaneously for 484 samples to determine the sensitivity and specificity of the test. The overall specificity and sensitivity was 99.32% and 71.96% respectively. Also, 3.7% of the asymptomatic patients who were negative by RAT were detected positive by RT-PCR. CONCLUSION: This rapid antigen test (RAT) was sensitive in the symptomatic patients presenting during the initial phase of the illness. Since, majority of the SARS-CoV-2 patients are asymptomatic and considering the huge population, the testing strategy formulated by Indian Council of Medical Research (ICMR) at the national level was cost effective. Thus, Ag-RDTs could play a pivotal role in early diagnosis, policy making and surveillance of the SARS-CoV-2.

Multi-Organ Involvement in COVID-19: Beyond Pulmonary Manifestations.

Coronavirus Disease 19 (COVID-19), due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become an on-going global health emergency affecting over 94 million cases with more than 2 million deaths globally. Primarily identified as atypical pneumonia, it has developed into severe acute respiratory distress syndrome (ARDS), a multi-organ dysfunction with associated fatality. Ever since its emergence, COVID-19 with its plethora of clinical presentations has signalled its dynamic nature and versatility of the disease process. Being a disease with droplet transmission has now assumed the proportion of a suspected airborne nature which, once proved, poses a Herculean task to control. Because of the wide distribution of the human angiotensin-converting enzyme-2 (hACE2) receptors, known for its transmission, we envisage its multiorgan spread and extensive disease distribution. Thus, an extensive review of the extrapulmonary organotropism of SARS-CoV-2 with organ-specific pathophysiology and associated manifestations like dermatological complications, myocardial dysfunction, gastrointestinal symptoms, neurologic illnesses, hepatic and renal injury is needed urgently. The plausible mechanism of site-specific viral invasion is also discussed to give a comprehensive understanding of disease complexity, to help us to focus on research priorities and therapeutic strategies to counter the disease progression. A note on the latest advancements in vaccine research will enlighten the scientific world and equip it for better preparedness.

Evaluation of various risk factors associated with multidrug-resistant organisms isolated from diabetic foot ulcer patients.

AIMS: Diabetic foot ulcer is a dreaded complication of diabetes. Diabetic foot ulcer patients are often infected with multidrug resistant organism (MDRO) due to chronic course of the wound, inappropriate antibiotics treatment, frequent hospital admission, neuropathy, nephropathy, and peripheral vascular disease. MATERIALS AND METHODS: This prospective study was conducted in our 750 bedded hospital for a period of 6 months. The present study was undertaken to isolate various MDRO methicillin resistant Staphylococcus aureus; Gram-negative bacteria producing enzymes such as extended spectrum beta-lactamases (ESBL), Amp C, Carbapenamases; Pseudomonas and Acinetobacter species producing metallo-beta-lactamases (MBL). In addition we attempted to identify risk factors for association of diabetic foot ulcer and MDRO. RESULTS: A total of 149 bacterial isolates were identified. Of the total isolates 73.2% were Gram-negative and remaining 26.8% were Gram-positive bacteria. Among Enterobacteriaceae 59% were ESBL producers and 48% were Amp C producers. In addition, 41.5% of the isolates produced both ESBL and Amp C and 13.4% were carbapenem resistant Enterobacteriaceae. Among 20 Pseudomonas and Acinetobacter isolates, 5 were MBL producers (25%). Furthermore, in the study, 56% of patients with diabetic foot ulcer harbored MDRO. The risk of multidrug-resistant infection is significantly more in patients having diabetes duration >20 years and size of ulcer more than 4 cm2. CONCLUSION: The detection of MDRO in patients of diabetic foot ulcer changes the treatment strategies limits the antimicrobial options and causes higher complications among them.

Phenotypic and genotypic characterization of carbapenem resistance mechanisms in Klebsiella pneumoniae from blood culture specimens: A study from North India.

BACKGROUND: Emergence of carbapenem resistance among Enterobacteriaceae in different geographical regions is of great concern as these bacteria are easily transmissible among patients. Carbapenem-resistance in Enterobacteriaceae is due to production of carbapenemases of various classes and hyper production of the ESBLs (Extended spectrum beta lactamases) and Amp C beta lactamases with reduced cell wall permeability mechanisms. Phenotypic detection and differentiation is important for proper infection control and appropriate patient management. This study was done to know the prescence of various beta lactamases and carbapenemases with other mechanisms of resistance in Klebsiella pneumoniae isolates. MATERIALS AND METHODS: 50 non-duplicate carbapenem resistant isolates of Klebsiella pneumoniae from blood culture specimens were included and various mechanisms of resistance were studied based on phenotypic and genotypic methods. RESULTS: Out of 50 isolates, 39 (78%) of K. pneumoniae isolates were Extended Spectrum Beta Lactamase (ESBL) producers based on CLSI guidelines. All 50 showed positive Modified Hodge Test (MHT) and 32 showed Metallo Beta Lactamase (MBL) by Combined Disc Test (CDT). Four isolates showed AmpC production with porin loss. None of the isolates showed Class A KPC production by CDT. In our study all the 10 isolates evaluated by genotypic technique produced CTX-M group 1 enzyme by multiplex PCR. Seven out of 10 strains which showed positive MBL results were positive for NDM. CONCLUSIONS: Carbapenems are often considered last resort antibiotics in the treatment of infections due to multidrug-resistant organisms. It is therefore mandatory to maintain the clinical efficacy of carbapenems by early detection of various enzymes. For routine clinical laboratories both phenotypic and genotypic tests need to be followed to detect various mechanisms of carbapenem resistance and this is of epidemiological relevance also.

Biomedical waste management in India: Critical appraisal.

The safe and sustainable management of biomedical waste (BMW) is social and legal responsibility of all people supporting and financing health-care activities. Effective BMW management (BMWM) is mandatory for healthy humans and cleaner environment. This article reviews the recent 2016 BMWM rules, practical problems for its effective implementation, the major drawback of conventional techniques, and the latest eco-friendly methods for BMW disposal. The new rules are meant to improve the segregation, transportation, and disposal methods, to decrease environmental pollution so as to change the dynamic of BMW disposal and treatment in India. For effective disposal of BMWM, there should be a collective teamwork with committed government support in terms of finance and infrastructure development, dedicated health-care workers and health-care facilities, continuous monitoring of BMW practices, tough legislature, and strong regulatory bodies. The basic principle of BMWM is segregation at source and waste reduction. Besides, a lot of research and development need to be in the field of developing environmental friendly medical devices and BMW disposal systems for a greener and cleaner environment.

Citrobacter freundii as a cause of acute suppurative thyroiditis in an immunocompetent adult female.

Acute suppurative thyroiditis (AST) is an uncommon condition, in the patients with preexisting thyroid disease or immunosuppression. The most common cause of AST is bacterial, and the most common bacteria are Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Klebsiella species. Due to various complications such as septicemia, septic thrombophlebitis, necrotizing mediastinitis, or pericarditis, prompt diagnosis and treatment are the keys to reduce mortality and morbidity. Here, we describe a case of a 40-year-old female with AST caused by Citrobacter freundii. This is the first case report of isolation of this bacterium from AST in the world. It is important to differentiate AST from subacute thyroiditis, which is far more frequent and runs a more prolonged course. Various risk factors which predispose to this condition include structural abnormality in the thyroid gland or thyroid disease and immunocompromised state. The route of infection may be either hematogenous or lymphatic seeding. With the increase in number of immunocompromised patients, the cases of AST will increase.

Lactobacillus coryniformis Causing Pulmonary Infection in a Patient with Metastatic Small Cell Carcinoma: Case Report and Review of Literature on Lactobacillus Pleuro-Pulmonary Infections.

Lactobacilli are normal commensals of the gastrointestinal and female genital tract. Due to its low virulence these bacteria are known to cause opportunistic infections. They cause mostly bacteraemia with or without endocarditis and rarely cause pleuro-pulmonary infection. We report a case of Lactobacillus coryniformis pleuro-pulmonary infection and review 14 previously reported cases of lactobacilli causing pleuro-pulmonary infections. Our patient had small cell carcinoma with metastasis. All the 14 cases had pre-existing risk factors like immunosuppresion, cancer or chronic disease. There was no consensus on choice of antimicrobial agents to be used. Different species of lactobacilli were involved. Available susceptibility data showed that lactobacilli species were more susceptible to ampicillin, erythromycin, gentamycin, and clindamycin and decreased to ceftriaxone, ciprofloxacin and trimethoprim-sulphamethoxazole. Isolation of Lactobacillus species from a case of pleuro-pneumonia infection could be a marker of poor long-term prognosis. The diagnosis of these infections requires both microbiologist and clinical correlation to rule out contamination.