Correlation of severity & clinical outcomes of COVID-19 with virus variants: A prospective, multicentre hospital network study.

BACKGROUND OBJECTIVES: The clinical course of COVID-19 and its prognosis are influenced by both viral and host factors. The objectives of this study were to develop a nationwide platform to investigate the molecular epidemiology of SARS-CoV-2 (Severe acute respiratory syndrome Corona virus 2) and correlate the severity and clinical outcomes of COVID-19 with virus variants. METHODS: A nationwide, longitudinal, prospective cohort study was conducted from September 2021 to December 2022 at 14 hospitals across the country that were linked to a viral sequencing laboratory under the Indian SARS-CoV-2 Genomics Consortium. All participants (18 yr and above) who attended the hospital with a suspicion of SARS-CoV-2 infection and tested positive by the reverse transcription-PCR method were included. The participant population consisted of both hospitalized as well as outpatients. Their clinical course and outcomes were studied prospectively. Nasopharyngeal samples collected were subjected to whole genome sequencing to detect SARS-CoV-2 variants. RESULTS: Of the 4972 participants enrolled, 3397 provided samples for viral sequencing and 2723 samples were successfully sequenced. From this, the evolution of virus variants of concern including Omicron subvariants which emerged over time was observed and the same reported here. The mean age of the study participants was 41 yr and overall 49.3 per cent were female. The common symptoms were fever and cough and 32.5 per cent had comorbidities. Infection with the Delta variant evidently increased the risk of severe COVID-19 (adjusted odds ratio: 2.53, 95% confidence interval: 1.52, 4.2), while Omicron was milder independent of vaccination status. The independent risk factors for mortality were age >65 yr, presence of comorbidities and no vaccination. INTERPRETATION CONCLUSIONS: The authors believe that this is a first-of-its-kind study in the country that provides real-time data of virus evolution from a pan-India network of hospitals closely linked to the genome sequencing laboratories. The severity of COVID-19 could be correlated with virus variants with Omicron being the milder variant.

Genomic analysis unveils genome degradation events and gene flux in the emergence and persistence of S. Paratyphi A lineages.

Paratyphoid fever caused by S. Paratyphi A is endemic in parts of South Asia and Southeast Asia. The proportion of enteric fever cases caused by S. Paratyphi A has substantially increased, yet only limited data is available on the population structure and genetic diversity of this serovar. We examined the phylogenetic distribution and evolutionary trajectory of S. Paratyphi A isolates collected as part of the Indian enteric fever surveillance study "Surveillance of Enteric Fever in India (SEFI)." In the study period (2017-2020), S. Paratyphi A comprised 17.6% (441/2503) of total enteric fever cases in India, with the isolates highly susceptible to all the major antibiotics used for treatment except fluoroquinolones. Phylogenetic analysis clustered the global S. Paratyphi A collection into seven lineages (A-G), and the present study isolates were distributed in lineages A, C and F. Our analysis highlights that the genome degradation events and gene acquisitions or losses are key molecular events in the evolution of new S. Paratyphi A lineages/sub-lineages. A total of 10 hypothetically disrupted coding sequences (HDCS) or pseudogenes-forming mutations possibly associated with the emergence of lineages were identified. The pan-genome analysis identified the insertion of P2/PSP3 phage and acquisition of IncX1 plasmid during the selection in 2.3.2/2.3.3 and 1.2.2 genotypes, respectively. We have identified six characteristic missense mutations associated with lipopolysaccharide (LPS) biosynthesis genes of S. Paratyphi A, however, these mutations confer only a low structural impact and possibly have minimal impact on vaccine effectiveness. Since S. Paratyphi A is human-restricted, high levels of genetic drift are not expected unless these bacteria transmit to naive hosts. However, public-health investigation and monitoring by means of genomic surveillance would be constantly needed to avoid S. Paratyphi A serovar becoming a public health threat similar to the S. Typhi of today.

Validated In Silico Model for Biofilm Formation in Escherichia coli.

Using Escherichia coli as the representative biofilm former, we report here the development of an in silico model built by simulating events that transform a free-living bacterial entity into self-encased multicellular biofilms. Published literature on ∼300 genes associated with pathways involved in biofilm formation was curated, static maps were created, and suitably interconnected with their respective metabolites using ordinary differential equations. Precise interplay of genetic networks that regulate the transitory switching of bacterial growth pattern in response to environmental changes and the resultant multicomponent synthesis of the extracellular matrix were appropriately represented. Subsequently, the in silico model was analyzed by simulating time-dependent changes in the concentration of components by using the R and python environment. The model was validated by simulating and verifying the impact of key gene knockouts (KOs) and systematic knockdowns on biofilm formation, thus ensuring the outcomes were comparable with the reported literature. Similarly, specific gene KOs in laboratory and pathogenic E. coli were constructed and assessed. MiaA, YdeO, and YgiV were found to be crucial in biofilm development. Furthermore, qRT-PCR confirmed the elevation of expression in biofilm-forming clinical isolates. Findings reported in this study offer opportunities for identifying biofilm inhibitors with applications in multiple industries. The application of this model can be extended to the health care sector specifically to develop novel adjunct therapies that prevent biofilms in medical implants and reduce emergence of biofilm-associated resistant polymicrobial-chronic infections. The in silico framework reported here is open source and accessible for further enhancements.

Comparison of efficacy of a 7-day versus a 14-day course of intravenous antibiotics in the treatment of uncomplicated neonatal bacterial sepsis: study protocol of a randomized controlled non-inferiority trial.

BACKGROUND: Neonatal sepsis is a global public health problem. There is no consensus regarding the optimum duration of antibiotics for culture-proven neonatal sepsis. Published randomized controlled trials (RCTs) comparing shorter versus longer courses of antibiotics provide low-quality evidence with serious risk of bias. We hypothesized that among neonates with uncomplicated culture-proven sepsis, antibiotic duration of 7 days is not inferior to 14 days. METHODS: This is a multi-centric, parallel-group, stratified, block-randomized, active-controlled, non-inferiority trial with outcome assessment blinded. Stratification is by center and birth weight. Neonates weighing ≥1000 g at birth, with blood-culture-proven sepsis (barring Staphylococcus aureus and fungi), without conditions warranting > 14 days antibiotics, and who clinically remit, are enrolled in the RCT on day 7 of administration of sensitive antibiotics. They are randomly allocated to no further antibiotics (intervention arm: total 7 days) or 7 more days of the same antibiotics (control arm: total 14 days). Allocation is concealed by opaque, sealed envelopes. The primary outcome is "definite or probable relapse" within 21 days after antibiotic completion. Secondary outcomes include definite and probable relapses at various timepoints until day 35 post-randomization, secondary infections, and adverse events. The neonatologist adjudicating probable relapses and lab personnel are blinded. Three hundred fifty subjects will be recruited in each arm, assuming a non-inferiority margin of 7%, one-sided alpha error 5%, and power of 90%. Analysis will be per protocol and by intention-to-treat. An independent Data Safety Monitoring Board monitors adverse events and will perform one interim analysis when 50% of expected primary outcomes have occurred or 50% of subjects have completed follow-up, whichever is earlier. O'Brien-Fleming criteria will be used to stop for mid-term benefit and Pocock's to stop for mid-term harm. A priori subgroup analyses are planned by birth weight categories, gram-stain status of pathogens, and radiological pneumonia. DISCUSSION: This trial will provide evidence to guide practice regarding optimum duration of antibiotics for culture-proven neonatal bacterial sepsis. If a 7-day regime is proved to be non-inferior to a 14-day regime, it is likely to reduce hospital stay, costs, adverse effects of drugs, and nosocomial infections. TRIAL REGISTRATION: Clinical Trials Registry India CTRI/2017/09/009743 . Registered on 13 September 2017.

Azaindole Based Potentiator of Antibiotics against Gram-Negative Bacteria.

We discovered azaindole-based compounds with weak innate activity that exhibit substantial potentiation of antibacterial activities of different antibiotics, viz., rifampicin, erythromycin, solithromycin, and novobiocin in Gram-negative bacteria. In the presence of the azaindole derivatives, these antibiotics exhibited submicromolar minimum inhibitory concentrations (MICs) against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. The fold improvements in MIC of these antibiotics that were otherwise weak or inactive on their own against these bacteria were also observed against drug-resistant clinical isolates. Our studies indicate that this selective potentiation is probably through destabilization of the outer membrane's integrity, known to be regulated by the lipopolysaccharides (LPS). Thus, the azaindole based compounds described here open opportunities for those antibiotics that are otherwise ineffective due to LPS mediated entry barriers in Gram-negative bacteria.

Structure and function relationship of OqxB efflux pump from Klebsiella pneumoniae.

OqxB is an RND (Resistance-Nodulation-Division) efflux pump that has emerged as a factor contributing to the antibiotic resistance in Klebsiella pneumoniae. OqxB underwent horizontal gene transfer and is now seen in other Gram-negative bacterial pathogens including Escherichia coli, Enterobacter cloacae and Salmonella spp., further disseminating multi-drug resistance. In this study, we describe crystal structure of OqxB with n-dodecyl-ß-D-maltoside (DDM) molecules bound in its substrate-binding pocket, at 1.85 Å resolution. We utilize this structure in computational studies to predict the key amino acids contributing to the efflux of fluoroquinolones by OqxB, distinct from analogous residues in related transporters AcrB and MexB. Finally, our complementation assays with mutated OqxB and minimum inhibitory concentration (MIC) experiments with clinical isolates of E. coli provide further evidence that the predicted structural features are indeed involved in ciprofloxacin efflux.

Ileal Perforation and Enteric Fever: Implications for Burden of Disease Estimation.

BACKGROUND: Ileal perforation occurs in about 1% of enteric fevers as a complication, with a case fatality risk (CFR) of 20%-30% in the early 1990s that decreased to 15.4% in 2011 in South East Asia. We report nontraumatic ileal perforations and its associated CFR from a 2-year prospective enteric fever surveillance across India. METHODS: The Surveillance for Enteric Fever in India (SEFI) project established a multitiered surveillance system for enteric fever between December 2017 and March 2020. Nontraumatic ileal perforations were surveilled at 8 tertiary care and 6 secondary care hospitals and classified according to etiology. RESULTS: Of the 158 nontraumatic ileal perforation cases identified,126 were consented and enrolled. Enteric fever (34.7%), tuberculosis (19.0%), malignancy (5.8%), and perforation of Meckel diverticulum (4.9%) were the common etiology. In those with enteric fever ileal perforation, the CFR was 7.1%. CONCLUSIONS: Enteric fever remains the most common cause of nontraumatic ileal perforation in India, followed by tuberculosis. Better modalities of establishing etiology are required to classify the illness, and frame management guidelines and preventive measures. CFR data are critical for comprehensive disease burden estimation and policymaking.

Cost of Illness Due to Severe Enteric Fever in India.

BACKGROUND: Lack of robust data on economic burden due to enteric fever in India has made decision making on typhoid vaccination a challenge. Surveillance for Enteric Fever network was established to address gaps in typhoid disease and economic burden. METHODS: Patients hospitalized with blood culture-confirmed enteric fever and nontraumatic ileal perforation were identified at 14 hospitals. These sites represent urban referral hospitals (tier 3) and smaller hospitals in urban slums, remote rural, and tribal settings (tier 2). Cost of illness and productivity loss data from onset to 28 days after discharge from hospital were collected using a structured questionnaire. The direct and indirect costs of an illness episode were analyzed by type of setting. RESULTS: In total, 274 patients from tier 2 surveillance, 891 patients from tier 3 surveillance, and 110 ileal perforation patients provided the cost of illness data. The mean direct cost of severe enteric fever was US$119.1 (95% confidence interval [CI], US$85.8-152.4) in tier 2 and US$405.7 (95% CI, 366.9-444.4) in tier 3; 16.9% of patients in tier 3 experienced catastrophic expenditure. CONCLUSIONS: The cost of treating enteric fever is considerable and likely to increase with emerging antimicrobial resistance. Equitable preventive strategies are urgently needed.

Evaluation of Antimicrobial Susceptibility Profile in Salmonella Typhi and Salmonella Paratyphi A: Presenting the Current Scenario in India and Strategy for Future Management.

BACKGROUND: Systematic studies to estimate the disease burden of typhoid and paratyphoid in India are limited. Therefore, a multicenter study on the Surveillance of Enteric Fever in India was carried out to estimate the incidence, clinical presentation, and antimicrobial resistance (AMR) trend. The data presented here represent the national burden of AMR in Salmonella Typhi and Salmonella Paratyphi A. METHODS: Antimicrobial susceptibility testing was performed for S. Typhi and S. Paratyphi A (n = 2373) isolates collected prospectively during a 2-year period from November 2017 to January 2020. RESULTS: Of 2373 Salmonella isolates, 2032 (85.6%) were identified as S. Typhi and 341 (14.4%) were S. Paratyphi A. Approximately 2% of S. Typhi were multidrug-resistant (MDR), whereas all 341 (100%) of S. Paratyphi A isolates were sensitive to the first-line antimicrobials. Among 98% of ciprofloxacin nonsusceptible isolates, resistance (minimum inhibitory concentration [MIC] >0.5 µg/mL) was higher in S. Typhi (37%) compared with S. Paratyphi A (20%). Azithromycin susceptibility was 99.9% and 100% with a mean MIC of 4.98 µg/mL for S. Typhi and 7.39 µg/mL for S. Paratyphi A respectively. Ceftriaxone was the only agent that retained 100% susceptibility. Moreover, beta-lactam/beta-lactamase inhibitors showed potent in vitro activity against the study isolates. CONCLUSIONS: Data obtained from this systematic surveillance study confirms the declining trend of MDR Salmonella isolates from India. The higher prevalence of ciprofloxacin nonsusceptibility enforces to limit its use and adhere to the judicious usage of azithromycin and ceftriaxone for enteric fever management.

Pathogen genomic surveillance of typhoidal Salmonella infection in adults and children reveals no association between clinical outcomes and infecting genotypes.

BACKGROUND: India is endemic for enteric fever, and it is not known whether the variations in clinical manifestations between patients are due to host, environmental or pathogen factors.Blood culture surveillance was conducted at St. John's Medical College Hospital, Bangalore, between July 2016 and June 2017. Clinical, laboratory and demographic data were collected from each case, and bacterial isolates were subjected to whole genome sequencing. Comparative analysis between adults and paediatric patients was carried out to ascertain differences between adult and paediatric disease. RESULTS: Among the 113 cases of blood culture-confirmed enteric fever, young adults (16-30 years) and children < 15 years accounted for 47% and 37% of cases, respectively. Anaemia on presentation was seen in 46% of cases, and 19% had an abnormal leucocyte count on presentation. The majority received treatment as inpatients (70%), and among these, adults had a significantly longer duration of admission when compared with children (p = 0.002). There were atypical presentations including arthritis, acute haemolysis and a case of repeated typhoid infection with two separate S. Typhi genotypes. There was no association between infecting genotype/serovar and treatment status (outpatient vs inpatient), month of isolation, duration of admission, patient age (adult or child), antimicrobial susceptibility, Widal positivity or haematologic parameters. CONCLUSIONS: Amidst the many public health concerns of South India, enteric fever continues to contribute substantially to hospital burden with non-specific as well as uncommon clinical features in both paediatric and adult populations likely driven by host and environmental factors. Robust clinical surveillance as well monitoring of pathogen population structure is required to inform treatment and preventive strategies.

Molecular characterization of carbapenem-resistant Acinetobacter baumannii strains from a tertiary care center in South India / Caracterización molecular de cepas de Acinetobacter baumannii carbapenem-resistante en un centro de atención terciaria en el sur de la India

Objectives: Carbapenem resistantAcinetobacter baumannii is an important therapeutic and infection control challenge worldwide. In this study, we investigated the prevalence and distribution of molecular mechanisms of resistance among carbapenem resistant A. baumannii species at a tertiary care setting in South India. Materials and Methods: A total of 89 non-duplicate clinical isolates of carbapenem-resistantA. baumannii were collected from critical care units of St. John's Medical College Hospital, Bengaluru, India. Polymerase chain reaction (PCR) was performed to detect blaOXA type carbapenemase blaOXA-51-like, blaOXA-23-like, blaOXA-24-like and bla OXA-58-like, MBL genes blaNDM, blaIMP, and blaVIM genes. Molecular typing of carbapenem-resistant A. baumannii strains was performed by using Rep-PCR. Results: Eighty-seven of the isolates were found to carry the blaOXA-51 gene and 81 (91%) isolates were found to have blaOXA-51-like gene and blaOXA-23, gene. The bla OXA-24 like gene was detected in two isolates of which one also carried blaOXA-51 like and one isolate carried blaVIM coding gene. The prevalence of blaNDM, blaIMP, bla VIM genes was 12(13%),14 (16%) and 57(64%) respectively. Cluster analyses revealed a 90% similarity and were divided into 5 clusters. Most of the isolates containing carbapenemases coding genes grouped under cluster A, C and UC. Considerable heterogeneity was observed within UC cluster indicating circulation of multiple strains of A. baumannii within our institution. Conclusions: Carbapenemase coding blaOXA-23, blaOXA-24 and blaOXA-51 -like were more common than blaVIM and blaNDM. The presence of blaNDM with other genes coding for carbapenemases indicate the ability of the strains to acquire novel genes despite having its share of the blaOXA like carbapenemase.

Objetivos: El Acinetobacter baumannii resistente a Carbapenem es un reto importante en todo el mundo para su tratamiento y para el control de infecciones hospitalarias. Nosotros estudiamos la prevalencia y los mecanismos de resistencia en aislados de un centro de atención terciario, en el sur de la India Materiales y Métodos: Se estudiaron 89 aislados clínicos de A. baumannii recolectados en unidades de cuidado crítico del Hospital St. John's Medical College en Bengaluru, India. Se realizó amplificación por PCR (Reacción en Cadena de Polimerasa) y luego tipificación molecular con la técnica Rep-PCR (PCR de elementos repetitivos palindromicos) para detectar los genes de carbapenemasa blaOXA, blaOXA-51, blaOXA-23, blaOXA-24, blaOXA-58, MBL, blaNDM, blaIMP y blaVIM. Resultados: Se encontraron 87 aislados que llevaban el gen blaOXA-51 y de ellos en 81 (91%) se encontró blaOXA-51 y blaOXA-23. El blaOXA-24 se detectó en dos aislados de los cuales uno de ellos llevaba blaOXA-51 y otro blaVIM. Los genes blaNDM, blaIMP y blaVIM se encontraron en 12 (13%),14 (16%) y 57(64%) de los aislados, respectivamente. El análisis de agrupamiento reveló un 90% de similitud entre los aislados y que podían asignarse a 5 agrupamientos. La mayoría de aislados llevaban genes de carbapenemasas de los grupos A, C y UC. Se observó mucha heterogeneidad dentro del agrupamiento UC indicando que existe circulación de múltiples cepas de A. baumannii dentro de nuestra institución. Conclusiones: Las carbapenemasas que codifican para blaOXA-23, blaOXA-24 y blaOXA-51 son más comunes que blaVIM y blaNDM en nuestra institución. La presencia de NDM con otros genes codificando para carbapenemasas indica la capacidad que tienen este tipo de aislados para adquirir nuevos genes a pesar de contar con blaOXA.

Erratum: Association of Hemorrhoid Vascular Injuries with Cigarette Smoking-An Evaluation with Interesting Prospects.

[This corrects the article DOI: 10.1055/s-0039-1700497.].

Persistent circulation of a fluoroquinolone-resistant Salmonella enterica Typhi clone in the Indian subcontinent.

BACKGROUND: The molecular structure of circulating enteric fever pathogens was studied using hospital-based genomic surveillance in a tertiary care referral centre in South India as a first genomic surveillance study, to our knowledge, of blood culture-confirmed enteric fever in the region. METHODS: Blood culture surveillance was conducted at St John's Medical College Hospital, Bengaluru, between July 2016 and June 2017. The bacterial isolates collected were linked to demographic variables of patients and subjected to WGS. The resulting pathogen genomic data were also globally contextualized to gauge possible phylogeographical patterns. RESULTS: Hospital-based genomic surveillance for enteric fever in Bengaluru, India, identified 101 Salmonella enterica Typhi and 14 S. Paratyphi A in a 1 year period. Ninety-six percent of isolates displayed non-susceptibility to fluoroquinolones. WGS showed the dominant pathogen was S. Typhi genotype 4.3.1.2 (H58 lineage II). A fluoroquinolone-resistant triple-mutant clone of S. Typhi 4.3.1.2 previously associated with gatifloxacin treatment failure in Nepal was implicated in 18% of enteric fever cases, indicating ongoing inter-regional circulation. CONCLUSIONS: Enteric fever in South India continues to be a major public health issue and is strongly associated with antimicrobial resistance. Robust microbiological surveillance is necessary to direct appropriate treatment and preventive strategies. Of particular concern is the emergence and expansion of the highly fluoroquinolone-resistant triple-mutant S. Typhi clone and its ongoing inter- and intra-country transmission in South Asia, which highlights the need for regional coordination of intervention strategies, including vaccination and longer-term strategies such as improvements to support hygiene and sanitation.

Association of Hemorrhoid Vascular Injuries with Cigarette Smoking-An Evaluation with Interesting Prospects.

Background Hemorrhoids are vascular structures in the anal canal which are seldom used to evaluate vascular diseases. Cigarette smoking is well-known to cause both arterial and venous vascular injuries. However, the impact of smoking on hemorrhoid vasculature is unknown. Objective Considering that vasculature in the hemorrhoids has the same anatomy and pathophysiology of vascular damage as other systemic vasculatures, we conducted this study to evaluate the relation between smoking and incidence of hemorrhoidal vascular injury. Design and Data Analysis Retrospective review of all the screening colonoscopies performed at our Department of Gastroenterology (predominantly serving urban minority population) over 3 years was conducted and patients with recorded smoking history were included in the study ( n = 242). Fisher's exact test with two-tailed p -value and odds ratio were used to evaluate for the association between smoking and incidence of hemorrhoids. Results We studied 242 subjects and found statistically significant association between smoking and hemorrhoids ( p < 0.05) with the risk of developing hemorrhoids among smokers being 2.4 times that of a nonsmoker. We further noted no significant difference in the incidence of hemorrhoidal vascular injuries between the past versus current smokers and male versus female smokers. Conclusion This is one of the first studies to establish an association between smoking and hemorrhoids. Our study shows that the hemorrhoidal vasculature is impacted by smoking similar to other vascular systems. This study sheds light on the possibility of evaluating hemorrhoids for clues of other systemic and gastrointestinal vascular damage. This correlation can add clinical value especially given the flexibility of assessing hemorrhoids as an outpatient in a cost effective and comfortable manner.

Decreasing Central Line-associated Bloodstream Infections Through Quality Improvement Initiative.

OBJECTIVE: To study the impact of a quality improvement (QI) initiative using care bundle approach on Central-line associated bloodstream infections (CLABSI) rates. METHODS: A QI team for infection control in NICU was formed in a tertiary-care neonatal intensive care unit (NICU) from June 2015 to August 2016. Baseline data were collected over first 3 months followed by the intervention period of 1 year. Measures with respect to strengthening hand hygiene and central line bundle care were implemented during the intervention period. Audits assessing the compliance to hand hygiene and CLABSI bundle protocols were used as process indicators. Multiple PDSA cycles were used to strengthen the practices of proposed interventions, documentation of data and audits of the processes during the study period. RESULTS: The QI initiative achieved a 89% reduction in CLABSI from the baseline rate of 31.7 to 3.5 per 1000 line-days. The blood stream Infections reduced from 7.3 to 2.3 per 1000 patient-days. The overall mortality showed a reduction from 2.9% to 1.7% during the intervention period. There was a significant improvement in compliance with hand hygiene protocol and compliance with CLABSI protocols. CONCLUSION: This study demonstrated that simple measures involving hand hygiene and strengthening of the care bundle approach through quality improvement could significantly reduce the blood stream Infections and CLABSI rates.

Recurrent Peritoneal Pseudocyst: A Rare Complication of Peritoneal Dialysis.

An alarming 468,000 people are dependent on dialysis for their end-stage renal disease (ESRD) management in the United States alone. Peritoneal dialysis is a preferred type of dialysis over hemodialysis, considering its initial survival advantage, patient satisfaction, and cost-effectiveness. One of the rare complications of peritoneal dialysis is abdominal and peritoneal pseudocyst formation. Literature regarding the accurate medical management of such peritoneal pseudocysts is scarce. Adding to this, management of recurrent loculated, non-malignant peritoneal pseudocyst poses to be challenging especially when pseudocysts recur after the offending peritoneal dialysis catheter is removed. We report one such case of a patient with a history of ESRD managed on long-term peritoneal dialysis. He presented to the hospital with recurrent abdominal pain which was treated multiple times for spontaneous bacterial peritonitis. Due to recurrence, his peritoneal dialysis was discontinued and hemodialysis was initiated. While on hemodialysis and two years after peritoneal dialysis catheter removal, he presented with sudden onset abdominal distension. Imaging showed loculated peritoneal pseudocyst with multiple loculations. Standard recommendation of surgical removal of cyst could not be performed in this patient due to his coexisting medical co-morbidities. Interventional radiology (IR) guided cyst drainage was attempted but was limited due to multiple locutions. However, IR drainage proved to provide temporary relief and after repeated IR guided drainage, a temporary drainage tube was placed. This subsided the recurrence of fluid-filled pseudocysts and the patient improved. This case emphasizes the importance of follow up of patients who have been or currently are on peritoneal dialysis for early recognition of late-onset complications. Our case also shows the routine challenges faced by the clinician when rare complications arise and standard treatment options cannot be applied.

Streptococcus pneumoniae serotype prevalence and antibiotic resistance among young children with invasive pneumococcal disease: experience from a tertiary care center in South India.

INTRODUCTION: We performed a study to describe the clinical profile, antimicrobial susceptibility and prevalent serotypes of pneumococcal isolates from children with suspected invasive pneumococcal disease (IPD) admitted to a tertiary care hospital in South India. METHODS: Hospitalized children, ≤ 5 years with fever (>38 °C); increased respiratory rate or neurological symptoms were recruited, (as part of the Alliance for Surveillance of Invasive Pneumococci - ASIP - project) from January 2011 to March 2013. Identification of pneumococcal isolates from blood or cerebrospinal fluid samples was done by routine culture methods. Isolates were analyzed for antimicrobial susceptibility, and confirmed by serotyping (using Quellung's test) and multiplex PCR. RESULTS: Out of the 171 samples received in the lab, 17 grew pneumococci identified by standard methods. Fourteen of them were confirmed by multiplex PCR. Maximum recruitment was observed during the months of January and February (36.4%, 28.6%). The average age of affected subjects was 21 months. The common clinical presentation was pneumonia (42.8%). Two isolates belonging to the 19F and 19B serotypes were resistant to penicillin (on Etest). The observed serotype distribution was 6B and 19F (2 each), and 1, 2, 6A, 9V, 10A, 14, 15A, 19B, 21, 35F (1 each). The overall fatality rate was 14.3% (n=2); the S. pneumoniae isolates from these two patients belonged to the non-vaccine serotype 19B and vaccine serotype 19F and demonstrated in vitro resistance to penicillin and erythromycin. CONCLUSION: Our study demonstrates the presence of invasive pneumococcal disease among under-5-year-old children in India caused by serotypes that are in large part covered by available pneumococcal vaccines.

Granular Cell Tumor of Rectum: A Very Rare Entity.

Granular cell tumors are predominantly benign, occurring more commonly in women, with about 10% developing in the gastrointestinal tract. Rectal location of this tumor is very rare. We herein report one such case of a 61-year-old man with granular cell tumor in the rectum who underwent endoscopic curative resection.

Invasive pneumococcal disease in children aged younger than 5 years in India: a surveillance study.

BACKGROUND: Invasive pneumococcal disease continues to be a major cause of morbidity and mortality among children younger than 5 years of age in India. We aimed to provide nationally representative data for the pattern of disease due to Streptococcus pneumoniae, trends in the serotype of invasive pneumococci, and invasive pneumococci antimicrobial resistance patterns, in India. METHODS: In this prospective hospital-based and retrospective laboratory-based surveillance study, we prospectively enrolled children aged younger than 5 years with suspected or proven invasive pneumococcal disease from 18 hospitals or institutional centres and retrospectively included laboratory-confirmed pneumococcal isolates from ten sentinel laboratories, together representing 11 states in India. Eligibility criteria were fever higher than 38°C without localising symptoms, clinical presentation of suspected meningitis or pneumonia, and evidence of radiographic pneumonia. We cultured blood and other normally sterile body fluids, reconfirmed and serotyped pneumococcal isolates, and established antimicrobial susceptibility using standard study protocols. FINDINGS: Between Jan 1, 2011, and June 30, 2015, we enrolled 4377 patients. Among 361 (8%) patients with culture-proven pneumococcal disease, all clinical data were known for 226 (63%); among these patients, 132 (58%) presented with pneumonia, 78 (35%) presented with meningitis, and 16 (7%) had other clinical conditions. 131 (3%) died overall and 29 (8%) patients with invasive pneumococcal disease died. Serotypes 14 (52 [14%] of 361), 1 (49 [14%]), 5 (37 [10%]), and 19F (33 [9%]) were the most common. Penicillin non-susceptibility occurred in isolates from 29 (8%) patients, co-trimoxazole resistance occurred in 239 (66%), erythromycin resistance occurred in 132 (37%), and chloramphenicol resistance occurred in 33 (9%). We found multidrug resistance in 33 (9%) of 361 patients. INTERPRETATION: The proportion of positive blood cultures, number of isolates, geographical representation, and data generated over the 4·5 years of the study are representative of data for most of India. Continued surveillance is warranted as the decision to introduce protein conjugated vaccine in India is made. FUNDING: GlaxoSmithKline India.

Mincle Signaling Promotes Con A Hepatitis.

Con A hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor that is critical in the immune response to mycobacteria and fungi but does not have a well-defined role in preclinical models of non-pathogen-mediated inflammation. Because Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con A hepatitis. Acute liver injury was assessed in the murine Con A hepatitis model using C57BL/6, Mincle(-/-), and Dectin-1(-/-) mice. The role of C/EBPß and hypoxia-inducible factor-1α (HIF-1α) signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con A hepatitis. Most significantly, Mincle deletion or blockade protected against Con A hepatitis, whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other C-type lectin receptors did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κß-related signaling intermediates C/EBPß and HIF-1α, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con A hepatitis and inhibition of both C/EBPß and HIF-1α reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation.