Impact and cost-effectiveness of short-course tuberculosis preventive treatment for household contacts and people with HIV in 29 high-incidence countries: a modelling analysis.

BACKGROUND: Guidelines and implementation of tuberculosis preventive treatment (TPT) vary by age and HIV status. Specifically, TPT is strongly recommended for people living with HIV/AIDS (PLWHA) and household contacts younger than 5 years but only conditionally recommended for older contacts. Cost remains a major barrier to implementation. The aim of this study was to evaluate the cost-effectiveness of TPT for household contacts and PLWHA. METHODS: We developed a state-transition model to simulate short-course TPT for household contacts and PLWHA in 29 high-incidence countries based on data from previous studies and public databases. Our primary outcome was the incremental cost-effectiveness ratio, expressed as incremental discounted costs (2020 US$, including contact investigation costs) per incremental discounted disability-adjusted life year (DALY) averted, compared with a scenario without any TPT or contact investigation. We propagated uncertainty in all model parameters using probabilistic sensitivity analysis and also evaluated the sensitivity of results to the screening algorithm used to rule out active disease, the choice of TPT regimen, the modelling time horizon, assumptions about TPT coverage, antiretroviral therapy discontinuation, and secondary transmission. FINDINGS: Between 2023 and 2035, scaling up TPT prevented 0·9 (95% uncertainty interval 0·4-1·6) people from developing tuberculosis and 0·13 (0·05-0·27) tuberculosis deaths per 100 PLWHA, at an incremental cost of $15 (9-21) per PLWHA. For household contacts, TPT (with contact investigation) averted 1·1 (0·5-2·0) cases and 0·7 (0·4-1·0) deaths per 100 contacts, at a cost of $21 (17-25) per contact. Cost-effectiveness was most favourable for household contacts younger than 5 years ($22 per DALY averted) and contacts aged 5-14 years ($104 per DALY averted) but also fell within conservative cost-effectiveness thresholds in many countries for PLWHA ($722 per DALY averted) and adult contacts ($309 per DALY averted). Costs per DALY averted tended to be lower when compared with a scenario with contact investigation but no TPT. The cost-effectiveness of TPT was not substantially altered in sensitivity analyses, except that TPT was more favourable in analysis that considered a longer time horizon or included secondary transmission benefits. INTERPRETATION: In many high-incidence countries, short-course TPT is likely to be cost-effective for PLWHA and household contacts of all ages, regardless of whether contact investigation is already in place. Failing to implement tuberculosis contact investigation and TPT will incur a large burden of avertable illness and mortality in the next decade. FUNDING: Unitaid.

An artificial intelligence platform provides an accurate interpretation of esophageal motility from Functional Lumen Imaging Probe Panometry studies.

BACKGROUND: Functional lumen imaging probe (FLIP) Panometry is performed at the time of sedated endoscopy and evaluates esophageal motility in response to distension. This study aimed to develop and test an automated artificial intelligence (AI) platform that could interpret FLIP Panometry studies. METHODS: The study cohort included 678 consecutive patients and 35 asymptomatic controls that completed FLIP Panometry during endoscopy and high-resolution manometry (HRM). "True" study labels for model training and testing were assigned by experienced esophagologists per a hierarchical classification scheme. The supervised, deep learning, AI model generated FLIP Panometry heatmaps from raw FLIP data and based on convolutional neural networks assigned esophageal motility labels using a two-stage prediction model. Model performance was tested on a 15% held-out test set (n = 103); the remainder of the studies were utilized for model training (n = 610). KEY RESULTS: "True" FLIP labels across the entire cohort included 190 (27%) "normal," 265 (37%) "not normal/not achalasia," and 258 (36%) "achalasia." On the test set, both the Normal/Not normal and the achalasia/not achalasia models achieved an accuracy of 89% (with 89%/88% recall, 90%/89% precision, respectively). Of 28 patients with achalasia (per HRM) in the test set, 0 were predicted as "normal" and 93% as "achalasia" by the AI model. CONCLUSIONS: An AI platform provided accurate interpretation of FLIP Panometry esophageal motility studies from a single center compared with the impression of experienced FLIP Panometry interpreters. This platform may provide useful clinical decision support for esophageal motility diagnosis from FLIP Panometry studies performed at the time of endoscopy.

Purification and characterization of a hemocyanin with lectin-like activity isolated from the hemolymph of speckled shrimp, Metapenaeusmonoceros.

Lectins or agglutinins are mainly proteins or glycoproteins, reported to uphold an ability to agglutinate the red blood cells (RBCs) with a known sugar specificity in a diverse group of organisms. In the present study, we purified a hemocyanin (named as MmHc) from a shrimp, Metapenaeus monoceros by size-exclusion chromatography. Further characterization revealed that the purified MmHc showed hemagglutination activity that was found to be specifically inhibited by Lewis B and Lewis Y tetrasaccharides. The MmHc displayed two oligomers of molecular weight approximately ∼78 and ∼85 kDa in SDS-PAGE. The native molecular mass of MmHc was found to be ∼457 kDa as determined by size-exclusion chromatography which indicated that the purified MmHc is an oligomeric protein. MmHc showed a maximum activity within pH 7.0-8.0, while a wide range of temperature stability was observed between 4 to 55 °C, however, it did not show any dependency on metal ions for binding. Subsequently, the analysis of the peptides by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) identified the purified MmHc as shrimp hemocyanin showing significant similarity to the hemocyanin of Penaeus vannamei. The results of multiple sequence alignment and detailed analysis of the molecular interactions predicted by AutoDock suggested that besides the oxygen carrier function, this MmHc may have multiple roles and can interact well with the Lewis Y antigen through a typical sugar binding motif containing the similar hydrophilic amino acids as the conserved residues.

Evaluation of biodentine pulpotomy in caries-exposed symptomatic vital mature permanent teeth in 9‒13-year-old children: A 24-month clinico-radiographic observation.

Background: The present study evaluated the clinical and radiographic outcomes of Biodentine pulpotomy for 24 months in symptomatic vital mature permanent teeth with caries exposure. Methods: Seventy-three patients with a chief complaint of spontaneous pain in permanent teeth were screened. Finally, 47 mature permanent teeth underwent a Biodentine pulpotomy procedure. Clinical evaluation of 47 teeth was carried out at 1, 3, 6, 9, 12, and 24 months and radiographic evaluations were made at 6, 12, and 24 months. The success of Biodentine pulpotomy was evaluated using Pearson's chi-square test. The significance level was determined at P<0.05. Results: At 24 months, the clinical and radiographic success rate was 97.78%, with only one clinical failure at 9 months. Conclusion: The clinical and radiographic success of Biodentine pulpotomy was high (97.78%). Thus, Biodentine pulpotomy can be an alternative to root canal treatment (RCT) in symptomatic vital mature permanent teeth.

Vaccine innovation prioritisation strategy: Findings from three country-stakeholder consultations on vaccine product innovations.

As part of the Vaccine Innovation Prioritisation Strategy (VIPS), three immunization-stakeholder consultations were conducted between September 2018 and February 2020 to ensure that countries' needs drove the prioritization of vaccine product innovations. All consultations targeted respondents with immunization program experience. They included: (1) an online survey to identify immunization implementation barriers and desired vaccine attributes in three use settings, (2) an online survey to identify and evaluate the most important immunization challenges for ten exemplar vaccines, and (3) in-depth interviews to better understand the perceived programmatic benefits and challenges that could be addressed by nine innovations and to rank the innovations that could best address current challenges. The first consultation included responses from 442 participants in 61 countries, representing 89% of the 496 respondents who correctly completed at least one section of the online survey. For facility-based settings, missed opportunities for vaccination due to reluctance to open multidose vaccine vials was the barrier most frequently selected by respondents. In community-based (outreach) and campaign settings, limited access to immunization services due to geographic barriers was most frequently selected. Multidose presentations with preservative or single-dose presentations were most frequently selected as desired vaccine attributes for facility-based settings while improved thermostability was most frequently selected for outreach and campaign settings. The second online survey was completed by 220 respondents in 54 countries. For the exemplar vaccines, vaccine ineffectiveness or wastage due to heat or freeze exposure and missed opportunities due to multidose vial presentations were identified as the greatest vaccine-specific challenges. In-depth interviews with 84 respondents in six countries ranked microarray patches, dual-chamber delivery devices, and heat-stable/controlled temperature chain qualified liquid vaccines as the three innovations that could have the greatest impact in helping address current immunization program challenges. These findings informed the VIPS prioritization and provided broader application to designing immunization interventions to better meet country needs.

Epigenetic alterations induced by aflatoxin B1: An in vitro and in vivo approach with emphasis on enhancer of zeste homologue-2/p21 axis.

The potent environmental toxicant aflatoxin B1 (AFB1), is a group I carcinogen reported to induce the expression of many cancer associated proteins. Epigenetic alterations such as DNA methylation and histone modifications play vital role in AFB1-mediated carcinogenesis. These epigenetic modifications may result in the recruitment of specific proteins and transcription factors to the promoter region and regulate gene expression. Here we show that AFB1, at lower concentrations (100 and 1000 nM) induced proliferation in L-132 and HaCaT cells with activation of the Akt pathway, which ultimately steered abnormal proliferation and transmission of survival signals. We demonstrated a significant reduction in the expression of p21 with a remarkable increase in the expression of cyclin D1 that correlated with increased methylation of CpG dinucleotides in p21 proximal promoter, while cyclin D1 promoter remained unmethylated. The chromatin immunoprecipitation results revealed the enrichment of DNMT3a and H3K27me3 repressive marks on the p21 proximal promoter where EZH2 mediated H3K27me3 mark enhanced the binding of DNMT3a at the promoter and further contributed to the transcriptional inactivation. The overall study provided the novel information on the impact of AFB1 on p21 inactivation via EZH2 and promoter methylation which is known to be a vital process in proliferation. Furthermore, AFB1 induced the expression of EZH2 analogue protein E(z), cyclin D1 analogue cyclin D and decreased the expression of p21 analogue Dacapo in Drosophila melanogaster. Interestingly, the aggressiveness in their expression upon re-exposure in successive generations suggested first hand perspectives on multigenerational epigenetic memory.

Primary Plasma Cell Leukemia: A Retrospective Study of a Rare Disease From Tertiary Cancer Centre From India.

Plasma cell leukemia (PCL) is an aggressive rare leukemic variant of multiple myeloma (MM). We aim to present 4 years data on clinical profile and treatment outcomes of Primary PCL (PPCL) patients treated at tertiary care cancer centre from Northern India. To analyse response and safety profile of a PPCL with or without stem cell transplantation. Retrospectively reviewed and analysed PPCL patient's data at our centre from January-2013 to June-2017. Total 11 PPCL patients diagnosed among 240 MM patients during study period. Eight were males. Only 10 patients were started on treatment. Four (n = 4/10) patients underwent stem cell transplantation. Overall response rate was 70% (n = 7). Eleven culture positive bacterial infections (bloodstream = 2, urinary tract = 3; pulmonary = 6) were recorded. Four patients had fungal infections. One patient had Herpes Zoster infection. Relapse rate of entire cohort was 50% (n = 5). Median PFS and OS of entire cohort was 11 months (95% confidence interval 6.3-15.6) and 21 months (95% C.I. 1-49.8) respectively. The estimated PFS and OS at 1 year of transplanted versus nontransplanted patients were 71% + 24% versus 0% (P = 0.96) and 71% + 24% versus 15% + 19% (P = 0.234) respectively. Treatment with PIs + IMAs followed by transplants (single/double) might improve depth and duration of remission and OS. Patients should be treated with indefinite maintenance therapy to control disease.

Outcome of Philadelphia Positive Acute Lymphoblastic Leukemia With or Without Allogeneic Stem Cell Transplantation in a Retrospective Study.

Philadelphia positive ALL (Ph + ALL) is an aggressive leukemia associated with lower remission rates and poor survival. Current treatment approach for Ph + ALL is chemotherapy along with TKI and CNS directed therapy followed by Allogeneic stem cell transplantation (Allo-SCT). To analyze outcome of Ph + ALL with or without Allo-SCT in the era of universal TKI uses. Retrospectively reviewed medical records of 267 patients who were diagnosed and treated for ALL during study period at our centre. Fifty-one Ph + ALL patients (males = 31, females = 20) out of a total of 267 ALL patients were eligible for the study. Post induction 48 patients achieved complete remission while 1 died during induction. Forty-six patients received further treatment with TKI + CNS directed therapy and thereafter the consolidation therapy with Allo-SCT (n = 16) or chemotherapy + TKI (n = 30).Overall mortality was 7/51 (13.9%) (6/16 transplant related mortalities due to GVHD and infections and 1 induction death). Fifteen out of 46 patients (32.6%) had relapse (1/10 relapse after Allo-SCT vs. 14/24 after chemotherapy) on or after consolidation therapy. At a median follow-up of 17.5 months (2-58 months) of cohort, the median EFS was 22 months (95% CI 10.4-33.5 months). The estimated 4 year EFS and PFS in Allo-SCT versus chemotherapy only group was 36.0 ± 17.9 versus 27.3 ± 9.1% (p = 0.21) and 75 ± 21.7 versus 34.1 ± 10.9% (p = 0.02) respectively. Allo-SCT groups has a better progression free survival than chemotherapy group only. Preventing treatment related mortality can further improve outcome after Allo-SCT Ph + ALL.

Aflatoxin-induced upregulation of protein arginine methyltransferase 5 is mediated by protein kinase C and extracellular signal-regulated kinase.

Aflatoxins are fungal metabolites classified into four major groups such as B1, B2, G1, and G2. These natural aflatoxins are designated as group I carcinogen by the International Agency for Research on Cancer. Among these, the aflatoxin B1 is more potent. Protein arginine methyltransferase 5, an epigenetic modulator, emerged as an oncoprotein, is overexpressed in diverse forms of cancers. The present study aims to explore the AFB1-mediated overexpression of PRMT5. The AFB1 at nanomolar concentrations increased the cell viability, as well as the expression of PRMT5 and its binding partner methylosome protein 50 level significantly in L-132 and HaCaT cells. The knockdown of PRMT5 by its siRNA is attenuated by AFB1, thus substantiating AFB1-mediated PRMT5 overexpression. The PKC isoform-specific inhibitor study revealed direct relation with PKCα and an inverse relation with PKCδ. The analysis of mitogen-activated protein kinase pathway revealed reduced p38 phosphorylation with increased phosphorylation of ERK1/2 upon exposure to AFB1. The combination of MEK and PKC inhibitors with AFB1 treatment revealed that PKCα activates downstream kinase ERK which leads to overexpression of PRMT5. In summary, we propose that PKCα and extracellular signal-regulated kinases are conjointly involved in the induction of PRMT5 upon AFB1 exposure.

Aflatoxin B1 induced multiple epigenetic modulators in human epithelial cell lines.

The compulsive and insidious secondary metabolite aflatoxin B1, produced by the opportunistic fungi Aspergillus flavus, upholds a distinguished place in midst of the toxicants causing fatal hazards to humans. Aflatoxins alter the function of host cells by inducing multiple effects through genetic and non-genetic pathways. Epigenetic mechanisms drag major attention towards finding novel and new mechanisms involved in this process. Our present work intends to study the functional expression profile of multiple epigenetic regulators. AFB1 modulates multiple epigenetic regulators like DNA methyltransferases (DMNTs), histones modifying enzymes and polycomb proteins. AFB1 upregulates the expression of DNMTs at gene and protein level in a dose dependent manner. It reduced the histone acetyl transferase (HAT) activity significantly with a remarkable increase in histone deacetylase (HDAC) activity along with an induction in expression of HDACs gene and protein in a dose dependent manner. The gene and protein expression of polycomb repressor proteins B cell specific moloney murine leukemia virus integration site 1 (BMI-1) and enhancer of zeste homolog 2 (EZH2) was significantly over expressed with enhanced trimethylation of H3K27 and ubiquitination of H2AK119. In summary, our results show impact of aflatoxin B1 on multiple epigenetic modulations known to be pivotal in oncogenic processes.

Evaluation of the fusion partner cell line SPYMEG for obtaining human monoclonal antibodies against influenza B virus.

Influenza B virus has been known to infect humans and other animals, including seals. Vaccination efficacy varies across seasons. Human monoclonal antibodies (mAbs) can be useful for developing novel vaccines, guided by epitope analysis, and can be used therapeutically. Hybridoma technology has been used to make mAbs. Here we evaluated SPYMEG as a fusion partner cell line for human mAb generation specific to influenza B hemagglutinin (HA). SPYMEG is a human/murine myeloma partner cell line that has previously been used to generate human mAbs that recognize the HA of influenza A and B viruses. Peripheral blood mononuclear cells were obtained from 16 volunteers, previously vaccinated with the 2014-2015 trivalent seasonal influenza vaccine, and were fused with SPYMEG to yield hybridomas. The resulting hybridomas were screened for antigen-specific antibody secretion and cloned by limiting dilution. We obtained 32 stable clones secreting anti-influenza B HA human IgG, although most of these clones were obtained from one volunteer (SeaV-29) who had a robust immune response. We conclude that SPYMEG is a good fusion partner cell line, although cloning by limiting dilution may lead to significant loss of hybridomas.

Diversity of antigenic mutants of influenza A(H1N1)pdm09 virus escaped from human monoclonal antibodies.

Since the 2017 Southern Hemisphere influenza season, the A(H1N1)pdm09-like virus recommended for use in the vaccine was changed because human, but not ferret, sera distinguish A(H1N1)pdm09 viruses isolated after 2013 from the previously circulating strains. An amino acid substitution, lysine to glutamine, at position 166 (H3 numbering) in the major antigenic site of HA was reported to be responsible for the antigenic drift. Here, we obtained two anti-A(H1N1)pdm09 HA monoclonal antibodies that failed to neutralize viruses isolated after 2013 from a vaccinated volunteer. Escape mutations were identified at position 129, 165, or 166 in the major antigenic site of HA. Competitive growth of the escape mutant viruses with the wild-type virus revealed that some escape mutants possessing an amino acid substitution other than K166Q showed superior growth to that of the wild-type virus. These results suggest that in addition to the K166Q mutation that occurred in epidemic strains, other HA mutations can confer resistance to antibodies that recognize the K166 area, leading to emergence of epidemic strains with such mutations.

Opportunistic Microorganisms in Oral Cavity According to Treatment Status in Head and Neck Cancer Patients.

INTRODUCTION: Cancer patients receiving chemotherapy and/or radiation therapy are prone to many predisposing factors like immunosuppression, imbalance in the oral flora, hypo-salivation and local tissue damage. Therefore, considered to be at higher risk for oral bacterial and fungal infection than the general population. AIM: To study oropharyngeal flora in head and neck cancer patients under treatment and to correlate their incidence according with Chemotherapy cycles and Radiochemotherapy. MATERIALS AND METHODS: Total 110 patients were selected for study, those were further divided into two groups, group I under Chemotherapy (CT) - 55 patients and group II under Radiochemotherapy (RCT) - 55 patients and 50 healthy individuals were taken as control. Saliva sample was collected from control and study group and inoculated on Blood agar, MacConkey agar and Sabouraud's Dextrose Agar (SDA). The identification of bacterial and fungal isolates was done by standard microbiological methods and result was calculated according to cycles of Chemotherapy and Radiochemotherapy combined. Significant differences between patients were tested using the Chi-square test or Fisher's exact test. A p-value less than 0.05 was considered as statistically significant. RESULT: There were 149 culture isolates from 110 patient in which Gram Negative Bacilli (GNB) found in 63.6%, Candida spp. in 50%, Staphylococcus aureus in 8% and Normal commensal of oral cavity in 13.6% patients in study group and this was higher than control group and this difference was statistically significant in relation to all isolates individually. Relatively more microorganism were isolated during RCT (56%) in compare to CT alone (44%), among GNB- Pseudomonas (27.7%,32.3%) and Klebsiella (25%,29.4%) were most frequently isolated during CT, RCT respectively. Candida spp. were more commonly isolated from patient on RCT (63.6%) than CT (36.3%) when compared to control group (20%) among which C. tropicalis was more prevalent species. Both GNB & Candida spp. were more commonly isolated in later chemotherapy cycles (CT4, CT5 CT6). CONCLUSION: Colonisation of Gram negative bacilli & Candida spp. is directly related to number of chemotherapy cycles and combined cancer therapy. Hence, prophylactic medication for these two organisms should be incorporated along with cancer therapy.

First case report of Providencia Rettgeri neonatal sepsis.

BACKGROUND: Providencia are gram negative motile rods and is a member of the Enterobacteriaceae family. It consists of five species, namely Providencia alcalifaciens, Providencia rustigianii, Providencia stuartii, Providencia rettgeri and Providencia heimbachae. These are opportunistic pathogens and leads to infections in immunocompromised host. Providencia rettgeri has been associated with the nosocomial infections of the urinary tract and infections of wounds, burns and blood. Providencia rettgeri is very rare cause of neonatal sepsis and we report first case of neonatal late onset sepsis secondary to it. CASE PRESENTATION: A term male infant presented on day 4 of post-natal life with the complaint of decreased appetite, fast respiration and lethargy. The clinical examination showed features of sepsis and shock with chest radiogram showing pneumonia. The infant was started on invasive ventilation, intravenous fluids, antibiotic and inotropes. The blood culture was suggestive of multi-drug resistant P. rettgeri. The antibiotics were changed according to organism antibiotic susceptibility pattern and infant gradually improved and was discharged successfully. CONCLUSION: Providencia rettgeri is a very rare organism to cause neonatal sepsis. The management involves early diagnosis, treatment with appropriate antibiotics and finding the source of infection.

CD24 and Nanog expression in Stem Cells in Glioblastoma: Correlation with Response to Chemoradiation and Overall Survival

Background and aim: Glioblastoma (GBM) is one of the most common and aggressive brain tumors with a median survival of 12-14 months. The aim of present study was to evaluate the gene expression profile of stem cell markers Nanog and CD24 in GBM and to determine its relationship to outcome in terms of treatment response and overall survival. Material and methods: This was a retrospective as well as retrospective study which included 51 histologically confirmed cases of GBM. Expression of CD24, and Nanog was evaluated by RT-PCR. Control tissue included debrided brain tissue from open head injury cases. All cases of GBM underwent total surgical resection and subsequently chemotherapy. Immediate treatment response was evaluated at 3 months using Response Evaluation Criteria In Solid Tumors (RECIST) guidelines and overall survival was measured at 36 months. Result: As compared to control gene, expression of CD24 and Nanog was seen to be unregulated to 24.5% and 31.7% respectively. However, the difference in mean expression of cases and controls was not statistically significant. Correlation between expressions of these two markers was also not statistically significant. On univariate cox regression analysis, cases with >2 fold expression of CD24 and Nanog had significantly poor survival as compared to those with <2 fold expression. On multivariate analysis > 2 fold CD24 expression had a statistically significant correlation with poor survival. Conclusion: An overexpression of CD24 by more than two fold was associated with poor overall survival in GBM. Poor survival may be related to increased "stemness" of tumour cells. Targeted therapy inclusive of drugs targeting stem cells directly or indirectly may be a promising therapeutic option.

Water deficit-induced oxidative stress affects artemisinin content and expression of proline metabolic genes in Artemisia annua L.

Water stress is one of the most critical abiotic stresses that restricts growth, development, and alters physiological and biochemical mechanisms of plant. The effects of long-term water shortage-induced oxidative stress on morphophysiological parameters, proline metabolic genes, and artemisinin content were studied in Artemisia annua L. under greenhouse conditions. Plant growth, biomass accumulation, relative water content, and chlorophyll content were reduced under drought. Leaf water potential ranged from -0.3248 MPa to -1.22 MPa in stress conditions. Increased levels of proline accumulation, protein concentration, and lipid peroxidation were detected in water-stressed plants. Stage-dependent increases in activity of antioxidants including superoxide dismutase, ascorbate peroxidase, glutathione reductase, monodehydroascorbate reductase, and dehydroascorbate reductase were observed. The expression of proline biosynthetic genes including pyrroline-5-carboxylase synthase1, 1-pyrroline-5-carboxylase synthase2, and 1-pyrroline-5-carboxylase reductase was induced, while the ornithine aminotransferase transcript showed a variable response and the expression of proline catabolic genes including proline dehydrogenase1, proline dehydrogenase1, and proline 5-carboxylate dehydrogenase was reduced by water stress. Our results indicate that the glutamine pathway is predominant under drought stress in A. annua and a reduction of catabolic gene expression is adopted as a defense strategy in adverse conditions. Higher expression of biosynthetic genes and lower expression of catabolic genes at the preflowering stage confirmed the important role of proline in flower development. Artemisinin content decreased owing to water stress, but the slightly higher amounts were detected in leaves of severely stressed plants compared with moderately stressed plants. The artemisinin content of A. annua might be regulated by controlling irrigation regimes.

Ralstonia picketti neonatal sepsis: a case report.

BACKGROUND: Ralstonia genus are gram negative bacillus and includes four bacteria namely Ralstonia picketti, Ralstonia Solanacearum, Ralstonia insidiosa and Ralstonia mannitolilytica. These are opportunistic pathogens and cause infections in immunocompromised host. The sources of infection are usually contaminated solutions and water. The majority of the reported cases are caused by R. picketti. It is very rare cause of neonatal sepsis with less than twenty cases reported in literature till date. CASE PRESENTATION: A late preterm male infant, Indian race was admitted to the neonatal intensive care unit for respiratory distress developing soon after birth. The infant was managed with respiratory support and gradually infant improved and diagnosis of transient tachypnea of newborn was made. At age of 84 h of postnatal life, the infant developed features of neonatal sepsis and investigations were suggestive of sepsis. The infant was started on intravenous antibiotic, multiple vasopressors and steroids. The blood culture showed growth of multi-drug resistant R. picketti. The antibiotics were changed as per sensitivity pattern and infant was discharged in good condition and was accepting breast feeding at the time of discharge. There was also no other case of R. picketti in the nursery during the same time period. CONCLUSION: Ralstonia picketti is an uncommon cause of neonatal sepsis and usually source of infection are contaminated solutions and medical products. The management involves early detection, treatment with appropriate antibiotics and doing surveillance culture to identify the possible source of infection.

Leminorella sepsis in very low birth weight neonate as cause of neonatal mortality.

Leminorella is a member of Enterobacteriaceae family and was known previously as Enteric Group 57. Based upon genetic differences using DNA hybridization, it has three taxa: Leminorella grimontii, Leminorella richardii, and Leminorella sp. strain 3. The third one is similar biochemically to the L. grimontii strains. The generic name has been derived on the name of a French microbiologist, Leon Le Minor. The biochemical properties includes being facultative anaerobes, growth on sheep blood, TSI, and MacConkey agar; hydrogen sulfide producer, l-arabinose fermenter, and tyrosine hydrolyzer; and are negative for d-mannose fermentation, urea, and lipase. They usually infect in adulthood and result in urinary tract infection, surgical site infection, bacteremia, peritonitis, respiratory tract infection, and soft tissue infection. We report the first case of L. grimontii sepsis in a very low birth weight neonate that died because of neonatal sepsis.

Empedobacter brevis Meningitis in a Neonate: A Very Rare Case of Neonatal Meningitis and Literature Review.

Empedobacter brevis is gram-negative bacilli that belongs to Flavobacteriaceae family. It was previously known with name of Flavobacterium breve. The reservoir of these bacteria is soil, plants, water, food, hospital water sources, including incubators, sinks, faucets, tap water, hemodialysis systems, saline solutions, and other pharmaceutical solutions. We report a case of term female newborn, admitted with complaint of respiratory distress developing soon after birth and developed clinical features of sepsis at age of 92 hours of postnatal life. The sepsis screen was positive and blood culture and cerebrospinal fluid showed growth of Empedobacter brevis that was resistant to multiple antibiotics. The neonate was treated with appropriate antibiotics and was discharged successfully. The novelty of the case report is that this is the first case report of neonatal sepsis caused by Empedobacter brevis.